Anti-oxidative and reno-restorative effects of physalis angulata (whole plant extract) in alloxan-induced diabetic male Wistar rats.

PubMed

Adewoye, E O; Oguntola, M A; Ige, A O

2016-05-01

Backgroiound: Hyperglycemia has been reported to increase protein glycation and generation of free radicals which predispose to diabetic renal dysfunction. Physalis ahgulata has been shown to have hypoglycacmic and anti-lipidemic properties but there is dearth of information regarding its effect on kidney functions in diabetes. This study investigated the anti-oxidative and reno-restorative effects of methanol extract of whole plant of Physalis angulata (MEPA) in alloxan-induced diabetic rats. Twenty male Wistar rats (150-180g) were randomly divided into four groups: Group 1 (control) received 0.2 ml distilled water, groups 2-4 were made diabetic by single intra-peritoneal dose of alloxan monohydrate (100mg/kg) and treated with 0.2 ml distilled water, 500 mg/kg MEPA and 150 mg/kg metformin respectively. All treatments were given orally for 14 days. Blood samples were collected from each animal through retro-orbital puncture. The serum obtained were analysed for fructosamine, glycated hemoglobin (HbAlc), creatinine and blood urea nitrogen (BUN). Kidney samples were harvested into cold phosphate buffer, homogenized and centrifuged at- 7500rpm for 15 minutes. The supernatant obtained was analyzed for malondialdehyde and superoxide dismutase (SOD) activities. Values were compared using ANOVA at P<0.05. The MEPA-treated groups showed significant decrease (P<0.05) in blood glucose, kidney weights, fructosamine,. HbAlc, malondialdehyde, creatinine and BUN, while the body weights and SOD significantly increased (P<0.05) compared to diabetic untreated group. Treatment with methanol extract of Physalis angulata (whole plant) reduced hyperglycemia, malondialdehyde and glycation end- products, which could have contributed to the development of diabetic nephropathy if diabetes is left untreated.

Rapid assessment of avoidable blindness and diabetic retinopathy in Republic of Moldova.

PubMed

Zatic, Tatiana; Bendelic, Eugen; Paduca, Ala; Rabiu, Mansour; Corduneanu, Angela; Garaba, Angela; Novac, Victoria; Curca, Cristina; Sorbala, Inga; Chiaburu, Andrei; Verega, Florentina; Andronic, Victoria; Guzun, Irina; Căpăţină, Olga; Zamă-Mardari, Iulea

2015-06-01

To evaluate the prevalence and causes of blindness and visual impairment, the prevalence of diabetes mellitus and diabetic retinopathy among people aged ≥50 years in the Republic of Moldova using Rapid Assessment of Avoidable Blindness plus Diabetic Retinopathy ('RAAB+DR') techniques. 111 communities of people aged ≥50 years were randomly selected. In addition to standard RAAB procedures in all people with diabetes (previous history of the disease or with a random blood glucose level >11.1 mm/L (200 mg/dL)), a dilated fundus examination was performed to assess the presence and the degree of diabetic retinopathy using the Scottish DR grading system. 3877 (98%) people out of the 3885 eligible people were examined. The prevalence of blindness was 1.4% (95% CI 1.0% to 1.8%). The major causes of blindness and severe visual impairment were untreated cataract (58.2%), glaucoma (10.9%), and other posterior segment causes (10.9%). The estimated prevalence of diabetes was 11.4%. Among all people with diabetes, 55.9% had some form of retinopathy, and sight threatening diabetic retinopathy affected 14.6%. The RAAB+DR survey in the Republic of Moldova established that untreated cataract is the major cause of avoidable blindness in rural areas. This needs to be tackled by expanding the geographical coverage of cataract surgical services. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The protective effect of 1alpha, 25-dihydroxyvitamin d3 and metformin on liver in type 2 diabetic rats.

PubMed

Elattar, Samah; Estaphan, Suzanne; Mohamed, Enas A; Elzainy, Ahmed; Naguib, Mary

2017-10-01

There is an accumulating evidence suggesting an immunomodulatory role of 1α,25(OH) 2 D3. Altered 1α,25(OH) 2 D3 level may play a role in the development of T2DM and contribute to the pathogenesis of liver diseases. Our study was designed to study and compare the effect of metformin and 1α,25(OH) 2 D3 supplementation on liver injury in type 2 diabetic rat. Sixty male Albino rats were divided into 5 groups; group 1: control rats. the remaining rats were fed high fat diet for 2 weeks and injected with streptozotocin (35mg/kg BW, i.p.) to induce T2DM and were divided into: group 2: untreated diabetic rats, group 3: diabetic rats treated by metformin (100mg/kgBW/d, orally), group 4: diabetic rats supplemented by 1α,25(OH) 2 D3 (0.5μg/kg BW, i.p.) 3 times weekly and group 5: supplemented by both 1α,25(OH) 2 D3 and metformin. Eight weeks later, serum glucose and insulin levels were measured, HOMA IR was calculated, lipid profile, Ca2+, ALT and AST were estimated. Liver specimens were taken to investigate PPAR-α (regulator of lipid metabolism), NF-κB p65, caspase 3 and PCNA (proliferating cell nuclear antigen) and for histological examination. The liver enzymes were elevated in the diabetic rats and the histological results revealed an injurious effect of diabetes on the liver. 1α,25(OH) 2 D3, metformin and both drugs treatment significantly improved liver enzymes as compared to the untreated rats. The improvement was associated with a significant improvement in the glycemic control, lipid profile and serum Ca2+ with a significant reduction in NF-κB p65 and caspase 3 and increased PPAR-α, and PCNA expression as compared to the untreated group. 1α,25(OH) 2 D3 induced a slightly better effect as compared to metformin. Both agents together had a synergistic action and almost completely protected the liver. Histological results confirmed the biochemical findings. Our results showed a protective effect of 1α,25(OH) 2 D3 and metformin on liver in diabetic rats as indicated by an improvement of the level of the liver enzymes, decreased apoptosis and increased proliferation and this was confirmed histologically, with modulating NFkB and PPAR-α. Both agents together had a synergistic effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of PRP and adipose tissue-derived keratinocytes on burn wound healing in diabetic rats

PubMed Central

Hosseini Mansoub, Navid; Gürdal, Mehmet; Karadadaş, Elif; Kabadayi, Hilal; Vatansever, Seda; Ercan, Gulinnaz

2018-01-01

Introduction: Diabetic burn wounds and ulcers are significant complications of diabetic patients. The aim of this study is to investigate the use of platelet rich-plasma (PRP) and/or keratinocyte-like cells (KLCs) in diabetic thermal wound rat model and to evaluate EGF, FGF-2, TGF-β1, COL1α2, MCP-1 and VEGF-α as wound healing markers at gene expression level. Method: In this study, we used adipose tissue as the source of mesenchymal stem cells (MSCs) and differentiated MSCs into KLCs. KLCs were characterized and transferred to the burn areas on the dorsum of streptozotocine (STZ)-induced diabetic rats. We prepared PRP from rat blood and evaluated its effect alone or in combination with KLCs. On 3rd, 7th, 10th and 14th days after treatment, wound areas were measured and biopsy samples were excised from the wound areas of the KLCs and/or PRP-treated and untreated diabetic rats to analyze gene expression levels of wound healing markers by qPCR. Results: We observed that, wound contraction started earlier in the PRP and/or KLCs-treated groups in comparison to the control group. However, PRP and KLCs when applied in combination showed additive affect in wound healing. In all groups treated with KLCs and/or PRP, the gene expression levels of evaluated growth factors and COL1α2 increased, while MCP-1 levels decreased when compared to the untreated diabetic rats. In addition, the most prominent difference in qPCR results belongs to combined PRP and KLCs-treated group. Conclusion: We demonstrated that applying PRP and KLCs in combination has a greater potential for treatment of diabetic burn wounds. PMID:29713597

Effects of Vernonia cinerea on reproductive performance in streptozotocin-induced diabetic rats.

PubMed

Pomjunya, Atchariya; Ratthanophart, Jasada; Fungfuang, Wirasak

2017-03-23

The present study investigated the effects of Vernonia cinerea (VC) on the reproductive function in streptozotocin (STZ)-induced diabetic male rats. Six-week-old male Sprague-Dawley rats were randomly divided into four groups: group 1, normal control rats; group 2, diabetic untreated rats; group 3, diabetic rats treated with VC (10 mg/kg); and group 4, diabetic rats treated with VC (40 mg/kg). Diabetes mellitus (DM) was induced by intraperitoneal injection of STZ (60 mg/kg). All animals were treated for 30 consecutive days. Body weight, blood glucose, food intake, epididymal sperm parameters, testicular microstructure and serum testosterone levels were evaluated. VC treatment significantly restored the sperm motility and testosterone concentration, and decreased the testicular histopathological changes in DM rats. Moreover, high-dose VC exhibited an antidibetic activity and significantly improved the sperm count. In conclusion, we found, for the first time, that administration of VC significantly restored the testicular function and testosterone concentration in diabetic male rats.

Effects of Vernonia cinerea on reproductive performance in streptozotocin-induced diabetic rats

PubMed Central

POMJUNYA, Atchariya; RATTHANOPHART, Jasada; FUNGFUANG, Wirasak

2017-01-01

The present study investigated the effects of Vernonia cinerea (VC) on the reproductive function in streptozotocin (STZ)-induced diabetic male rats. Six-week-old male Sprague-Dawley rats were randomly divided into four groups: group 1, normal control rats; group 2, diabetic untreated rats; group 3, diabetic rats treated with VC (10 mg/kg); and group 4, diabetic rats treated with VC (40 mg/kg). Diabetes mellitus (DM) was induced by intraperitoneal injection of STZ (60 mg/kg). All animals were treated for 30 consecutive days. Body weight, blood glucose, food intake, epididymal sperm parameters, testicular microstructure and serum testosterone levels were evaluated. VC treatment significantly restored the sperm motility and testosterone concentration, and decreased the testicular histopathological changes in DM rats. Moreover, high-dose VC exhibited an antidibetic activity and significantly improved the sperm count. In conclusion, we found, for the first time, that administration of VC significantly restored the testicular function and testosterone concentration in diabetic male rats. PMID:28190818

Prevention of retinal capillary basement membrane thickening in diabetic dogs by a non-steroidal anti-inflammatory drug.

PubMed

Gardiner, T A; Anderson, H R; Degenhardt, T; Thorpe, S R; Baynes, J W; Archer, D B; Stitt, A W

2003-09-01

To investigate the effect of treatment with the non-steroidal anti-inflammatory drug Sulindac on the early vascular pathology of diabetic retinopathy in the dog, and it's effect on recognised biochemical indices of hyperglycaemia-related pathophysiology. Experimental diabetes (streptozotocin/alloxan) was induced in 22 male beagle dogs and 12 of the animals were assigned at random to receive oral Sulindac (10 mg/kg daily). Age- and sex-matched control animals were maintained as non-diabetic controls. After 4 years, several morphological parameters were quantified in the retinal microvasculature of each animal group using an established stereological method. Also, the following diabetes-associated biochemical parameters were analysed: accumulation of advanced glycation end products (AGEs), red blood cell polyol levels and antioxidant status. Diabetes increased red blood cell sorbitol levels when compared to non-diabetic controls (p< or =0.05), however, there was no difference in sorbitol levels between the untreated and the treated diabetic animals. No significant differences were found in red blood cell myoinositol levels between the three groups of animals. Pentosidine and other AGEs were increased two- to three-fold in the diabetic animals (p< or =0.001) although treatment with Sulindac did not affect their accumulation in diabetic skin collagen or alter diabetes-induced rises in plasma malondialdehyde. Retinal capillary basement membrane volume was significantly increased in the untreated diabetic dogs compared to non-diabetic controls or Sulindac-treated diabetic animals (p< or =0.0001). This study has confirmed the beneficial effect of a non-steroidal anti-inflammatory drug on the early vascular pathology of diabetic retinopathy. However the treatment benefit was not dependent on inhibition of polyol pathway activity, advanced glycation, or oxidative stress.

Naringin Reduces Hyperglycemia-Induced Cardiac Fibrosis by Relieving Oxidative Stress

PubMed Central

Adebiyi, Olubunmi A.; Adebiyi, Oluwafeyisetan O.; Owira, Peter M. O.

2016-01-01

Introduction Hyperglycemia promotes myocardial fibrotic lesions through upregulation of PKC and p38 in response to redox changes. The effects of naringin on hyperglycemia-induced myocardial fibrotic changes and its putative effects on PKC-β and p38 protein expression in type 1 rat model of diabetes are hereby investigated. Methods Male Sprague-Dawley rats were divided into six groups I-VI. Groups I and II, were orally treated with distilled water {3.0 ml/kg body weight (BW)} and naringin (50 mg/kg BW), respectively. Groups III, IV, V and VI were rendered diabetic by a single intraperitoneal injection of streptozotocin (60 mg/kg, BW) and were similarly treated with subcutaneous insulin (8.0 I.U/kg BW, twice daily), naringin (50 mg/kg BW), distilled water (3.0 ml/Kg BW) and ramipril (3.0 mg/kg/BW), respectively. The animals were sacrificed after 56 days by halothane overdose; blood and heart samples removed for further analysis. Results The untreated diabetic rats exhibited significantly increased oxidative stress, NADPH oxidase activity, increased cardiac fibrosis, PKC-β and p38 mitogen activated protein kinase expression compared to controls. Naringin treatment significantly ameliorated these changes in diabetic rats compared to the untreated diabetic controls. Conclusions Naringin’s amelioration of myocardial fibrosis by modulating p38 and PKC-β protein expression possibly through its known antioxidant actions and may therefore be useful in retarding the progression of fibrosis in a diabetic heart. PMID:26967518

Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes.

PubMed

Muraleedharan, Vakkat; Marsh, Hazel; Kapoor, Dheeraj; Channer, Kevin S; Jones, T Hugh

2013-12-01

Men with type 2 diabetes are known to have a high prevalence of testosterone deficiency. No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy (TRT). We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone. A total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.81.3 S.D. years. mortality rates were compared between total testosterone 10.4nmol/l (300ng/dl; n=343) and testosterone 10.4nmol/l (n=238). the effect of TRT (as per normal clinical practise: 85.9% testosterone gel and 14.1% intramuscular testosterone undecanoate) was assessed retrospectively within the low testosterone group. Mortality was increased in the low testosterone group (17.2%) compared with the normal testosterone group (9%; P=0.003) when controlled for covariates. In the Cox regression model, multivariate-adjusted hazard ratio (HR) for decreased survival was 2.02 (P=0.009, 95% CI 1.2-3.4). TRT (mean duration 41.6±20.7 months; n=64) was associated with a reduced mortality of 8.4% compared with 19.2% (P=0.002) in the untreated group (n=174). The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 (95% CI 1.3-3.9, P=0.004). Low testosterone levels predict an increase in all-cause mortality during long-term follow-up. Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes.

Statin, testosterone and phosphodiesterase 5-inhibitor treatments and age related mortality in diabetes

PubMed Central

Hackett, Geoffrey; Jones, Peter W; Strange, Richard C; Ramachandran, Sudarshan

2017-01-01

AIM To determine how statins, testosterone (T) replacement therapy (TRT) and phosphodiesterase 5-inhibitors (PDE5I) influence age related mortality in diabetic men. METHODS We studied 857 diabetic men screened for the BLAST study, stratifying them (mean follow-up = 3.8 years) into: (1) Normal T levels/untreated (total T > 12 nmol/L and free T > 0.25 nmol/L), Low T/untreated and Low T/treated; (2) PDE5I/untreated and PDE5I/treated; and (3) statin/untreated and statin/treated groups. The relationship between age and mortality, alone and with T/TRT, statin and PDE5I treatment was studied using logistic regression. Mortality probability and 95%CI were calculated from the above models for each individual. RESULTS Age was associated with mortality (logistic regression, OR = 1.10, 95%CI: 1.08-1.13, P < 0.001). With all factors included, age (OR = 1.08, 95%CI: 1.06-1.11, P < 0.001), Low T/treated (OR = 0.38, 95%CI: 0.15-0.92, P = 0.033), PDE5I/treated (OR = 0.17, 95%CI: 0.053-0.56, P = 0.004) and statin/treated (OR = 0.59, 95%CI: 0.36-0.97, P = 0.038) were associated with lower mortality. Age related mortality was as described by Gompertz, r2 = 0.881 when Ln (mortality) was plotted against age. The probability of mortality and 95%CI (from logistic regression) of individuals, treated/untreated with the drugs, alone and in combination was plotted against age. Overlap of 95%CI lines was evident with statins and TRT. No overlap was evident with PDE5I alone and with statins and TRT, this suggesting a change in the relationship between age and mortality. CONCLUSION We show that statins, PDE5I and TRT reduce mortality in diabetes. PDE5I, alone and with the other treatments significantly alter age related mortality in diabetic men. PMID:28344753

Hypoglycemic and hypolipidemic effects of methanol seed extract of Citrus paradisi Macfad (Rutaceae) in alloxan-induced diabetic Wistar rats.

PubMed

Adeneye, A A

2008-01-01

Alcohol decoction of Citrus paradisi Macfad (Rutaceae) seed is reputed for the local management of array of human diseases including, anemia, diabetes mellitus and obesity by some Yoruba herbalists (SouthWest, Nigeria). Despite its historic use, scientific evaluation of its folkloric use in the management of diabetes mellitus is scarce. The present study was designed at investigating the glucose and lipid lowering effects of methanol seed extract of Citrus paradisi Macfad (MECP) in alloxan-induced diabetic rats. In addition, the phytochemical analysis of the extract was also conducted using standard procedures. Young adult, male, alloxan-induced diabetic rats were randomly divided into groups I - VI with 12 rats in each group. Group I rats were the normal untreated rats while group II rats served as the diabetic untreated rats while Rats in groups III - VI served as diabetic rats treated with 100, 300 and 600 mg/kg/day MECP and 20 mg/kg/ day metformin, respectively, for 30 days. On the 15th and respectively, 31st day, blood samples from the fasted rats were obtained for fasting plasma glucose (FPG), plasma triglycerides (TG), total cholesterol (TC), high density lipoprotein- cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c) and very low density lipoprotein-cholesterol (VLDL-c) from the sacrificed rats. Oral treatment with 100 - 600 mg/kg/day MECP, for 30 days, resulted in significant (p < 0.05, p < 0.01, p < 0.001) reductions in FPG, TG, TC, LDL-c, VLDL-c in the diabetic rats, effects which were comparable to that of metformin. The extract also caused significant (p < 0.05, p < 0.01) rise in HDL-c values in the alloxan diabetic rats. Phytochemical result showed the presence of alkaloids, flavonoids, cardiac glycosides, tannins and saponin in varying concentrations. The biological effects recorded for the extract could be due to any or a combination of these phytochemical constituents. Results of this study lend support to the traditional use of grapefruit seeds in the management of type 1 diabetic patients and may suggest a role in orthodox management of the disease.

The lesson of Monsieur Nouma: effects of a culturally sensitive communication tool to improve health-seeking behavior in rural Cameroon.

PubMed

Gessler, Noemi; Labhard, Niklaus Daniel; Stolt, Pelle; Manga, Engelbert; Balo, Jean-Richard; Boffolo, Adelaide; Langewitz, Wolf

2012-06-01

To test the effect of patient counseling using educational tools, on rates of return for follow-up in newly diagnosed hypertensive and/or diabetic patients in a rural African context. Free screening for hypertension and elevated blood glucose was offered in primary health care centers in central Cameroon during 9 campaigns of 3 days each. Individuals with untreated hypertension and/or diabetes were divided into 2 groups: a control group receiving counseling according to routine procedures, and an intervention group receiving counseling with different educational tools to explain the diagnosis and its implications to the patient. Prevalence of hypertension and/or diabetes in the screened population was 41%. At 3 months from screening, rates of return visits were higher in the intervention group than in the control group: 55/169 (32%) vs. 15/92 (16%), OR 2.4; 95%CI 1.3-4.7; p<0.001. Screening may identify untreated individuals efficiently. Rates of return visits after screening, although low in both groups, could be doubled by a short communication intervention. This study suggests that modest communication interventions, e.g., the application of educational tools, may bring important benefits and increase the effectiveness of public health measures to combat chronic diseases in settings of limited resources. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Are the new IADPSG criteria for gestational diabetes useful in a country with a very high prevalence?

PubMed

Minsart, Anne-Frederique; N'guyen, Thai-Son Pierre; Dimtsu, Hirut; Ratsimandresy, Rachel; Dada, Fouad; Ali Hadji, Rachid

2014-09-01

The International Association of Diabetes and Pregnancy Study Groups released new recommendations on screening methods and diagnostic criteria for gestational diabetes. The main objectives of the present study were to analyze characteristics of mothers who underwent the new screening test, and to assess the prevalence of gestational diabetes and related pregnancy complications such as the 5-minute Apgar score <7, in a urban maternity clinic in Djibouti. The effect of treating gestational diabetes was also evaluated. Totally, 231 mothers underwent the new screening test, and 106 were diagnosed as having gestational diabetes (45.9%). Mothers with gestational diabetes had an excess risk of low Apgar scores, even after adjustment for socio-economic and medical covariates, with an odds ratio of 6.34 (1.77-22.66), p value <0.005. Only 46.2% of mothers with gestational diabetes followed the recommendations regarding treatment. Among these patients, 18.6% of infants from untreated mothers had a 5-minute Apgar score <7, compared to 3.9% infants from treated mothers (p value = 0.017). After adjustment, untreated mothers still had a high excess risk of low Apgar scores, although non-significant, with an odds ratio of 4.67 (0.78-27.87), p value = 0.09. In conclusion, gestational diabetes is highly prevalent in Djibouti and is related to low Apgar scores.

The Effects of Creatine Monohydrate on Permeability of Coronary Artery Endothelium and Level of Blood Lipoprotein in Diabetic Rats.

PubMed

Rahmani, Asghar; Asadollahi, Khairollah; Soleimannejad, Kourosh; Khalighi, Zahra; Mohsenzadeh, Yosouf; Hemati, Ruhollah; Moradkhani, Atefeh; Abangah, Ghobad

2016-09-01

Creatine monohydrate has beneficial effects on serum glucose. This study aimed to investigate the effects of creatine on serum biochemical markers and permeability of coronary arteries among diabetic rats. 32 Wistar rats, which weighed 150-200 grams were randomly divided into 4 groups including: group I, control; group II, creatine monohydrate; group III, diabetic rats; and group IV, diabetic rats + creatine. Creatine monohydrate was applied by 400 mg/kg/daily for 5 months. Animals' weights and blood samples were taken before and after the study. Endothelial permeability rate was measured by Evans Blue method. Data were analysed by SPSS 16. At the end of fifth month, rats' weights in diabetic group under treatment with creatine, compared to those without, increased significantly (p<0.0001). Also, the serum levels of triglyceride (TG), cholesterol, glucose and low density lipoprotein (LDL)- cholesterol decreased significantly among those under treatment with creatine (p<0.05), but high density lipoprotein (HDL)- cholesterol increased significantly (p<0.002). Permeability rate of coronary arteries was reduced significantly in the diabetic group treated by creatine compared to untreated groups, closed to the intact group (p<0.001). Results of this study showed that creatine monohydrate caused an improvement of serum biochemical markers associated with diabetes and reduced the permeability rate of coronary arteries among diabetic rats. © 2016 by the Association of Clinical Scientists, Inc.

Metabonomics study of the therapeutic mechanism of fenugreek galactomannan on diabetic hyperglycemia in rats, by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

PubMed

Jiang, Wenyue; Gao, Lu; Li, Pengdong; Kan, Hong; Qu, Jiale; Men, Lihui; Liu, Zhiqiang; Liu, Zhongying

2017-02-15

Fenugreek is a traditional plant for the treatment of diabetes. Galactomannan, an active major component in fenugreek seeds, has shown hypoglycemic activity. The present study was performed to investigate the therapeutic mechanism underlying fenugreek galactomannan (F-GAL) in treating diabetes, using a metabonomics approach based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The F-GAL used for study was highly purified, and its yield, purity, and galactose/mannose ratio were characterized by capillary zone electrophoresis (CZE) and a modified phenol-sulfuric acid method. After treatment of streptozotocin (STZ)-induced diabetic rats with F-GAL for 28days, urine and serum samples were analyzed by UPLC-QTOF/MS. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were applied to distinguish the non-diabetic/untreated, diabetic/untreated, and diabetic/F-GAL-treated groups. Then, potential biomarkers were identified that may help elucidate the underlying therapeutic mechanism of F-GAL in diabetes. The results demonstrated that there was a clear separation among the three groups in the PCA model. Fourteen potential biomarkers were identified by OPLS-DA, and they were determined to be produced in response to the therapeutic effects of F-GAL. These biomarkers were involved in histidine metabolism, tryptophan metabolism, energy metabolism, phenylalanine metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism. In conclusion, our study demonstrates that a metabonomics approach is a powerful, novel tool that can be used to evaluate the underlying therapeutic mechanisms of herb extracts. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of low power density on wound healing in streptozotocin-induced diabetic rats

NASA Astrophysics Data System (ADS)

Lau, Pik Suan; Bidin, Noriah; Islam, Shumaila; Musa, Nurfatin; Zakaria, Nurlaily; Krishnan, Ganesan

2017-05-01

Photobiomodulation therapy (PBMT) is used for wound healing at two different power densities, i.e. 0.2 W cm-2 and 0.4 W cm-2, while maintaining the same fluence of 5 J cm-2. Forty-five streptozotocin (STZ)-induced diabetic rats were allocated into three groups: the untreated laser group (G0), 0.2 W cm-2 laser treated group (GL1), and 0.4 W cm-2 laser treated group (GL2). Six mm full thickness cutaneous wounds are created on the dorsal side of rats. A 808 nm diode laser irradiates the wound in GL1 and GL2 daily for 9 consecutive days. Groups GL1 and GL2 have the same total fluence but different power densities, 0.2 W cm-2 and 0.4 W cm-2, which results in stimulatory and inhibitory effects in wound healing, respectively. In group GL1, enhanced wound contraction and inflammation has been triggered at an earlier stage compared to the untreated laser group G0. Meanwhile, the laser treated group GL2 exhibits an escalated volume of inflammatory cells, and collagen synthesis is inhibited. Therefore, it can be concluded that PBMT has potential in promoting wound healing under the low power density (0.2 W cm-2) condition.

Diabetes induced renal urea transport alterations assessed with 3D hyperpolarized 13 C,15 N-Urea.

PubMed

Bertelsen, Lotte B; Nielsen, Per M; Qi, Haiyun; Nørlinger, Thomas S; Zhang, Xiaolu; Stødkilde-Jørgensen, Hans; Laustsen, Christoffer

2017-04-01

In the current study, we investigated hyperpolarized urea as a possible imaging biomarker of the renal function by means of the intrarenal osmolality gradient. Hyperpolarized three-dimensional balanced steady state 13 C MRI experiments alongside kidney function parameters and quantitative polymerase chain reaction measurements was performed on two groups of rats, a streptozotocin type 1 diabetic group and a healthy control group. A significant decline in intrarenal steepness of the urea gradient was found after 4 weeks of untreated insulinopenic diabetes in agreement with an increased urea transport transcription. MRI and hyperpolarized [ 13 C, 15 N]urea can monitor the changes in the corticomedullary urea concentration gradients in diabetic and healthy control rats. Magn Reson Med 77:1650-1655, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Effects of umbilical cord blood stem cells on healing factors for diabetic foot injuries.

PubMed

Çil, N; Oğuz, E O; Mete, E; Çetinkaya, A; Mete, G A

2017-01-01

The use of stem or progenitor cells from bone marrow, or peripheral or umbilical cord blood is becoming more common for treatment of diabetic foot problems. These cells promote neovascularization by angiogenic factors and they promote epithelium formation by stimulating cell replication and migration under certain pathological conditions. We investigated the role of CD34 + stem cells from human umbilical cord blood in wound healing using a rat model. Rats were randomly divided into a control group and two groups with diabetes induced by a single dose of 55 mg/kg intraperitoneal streptozocin. Scarred areas 5 mm in diameter were created on the feet of all rats. The diabetic rats constituted the diabetes control group and a diabetes + stem cell group with local injection into the wound site of 0.5 × 106 CD34 + stem cells from human umbilical cord blood. The newly formed skin in the foot wounds following CD34 + stem cell treatment showed significantly improvement by immunohistochemistry and TUNEL staining, and were closer to the wound healing of the control group than the untreated diabetic animals. The increase in FGF expression that accompanied the local injection of CD34 + stem cells indicates that FGF stimulation helped prevent apoptosis. Our findings suggest a promising new treatment approach to diabetic wound healing.

An in vivo and in vitro investigation of the effect of Aloe vera gel ethanolic extract using animal model with diabetic foot ulcer

PubMed Central

Daburkar, Mohan; Lohar, Vikram; Rathore, Arvind Singh; Bhutada, Pravin; Tangadpaliwar, Shrikant

2014-01-01

Aim: To examine the preventive effect of Aloe vera gel ethanolic extract using diabetic foot ulcer (DFUs) protocol in Wistar rats. Materials and Methods: Male Wistar rats were divided into untreated control (Group I), untreated DFUs (Group II), DFUs treated with A. vera gel ethanolic extract (Group III), DFUs treated with topical A. vera gel (Group IV), DFUs treated with A. vera gel ethanolic extract and topical A. vera gel (Group V). The rats in the treatment groups were daily administered the A. vera gel and ethanolic extract for 9 days. Fasting blood glucose levels and percentage of wound ulcer contraction were measured on day 3, 6, and 9. Statistical Analysis used: The results are expressed as a mean ± Standard Error Mean (SEM). Data were analyzed using one-way analysis of variance (ANOVA) after Newman–Keuls test. P < 0.05 were considered statistically significant in all cases. Results: Oral administration of A. vera gel ethanolic extract at a dose of 300 mg/kg body weight per day to diabetic rats for a period of 9 days resulted in a significant reduction in fasting blood glucose and a significant improvement in plasma insulin. Topical application of A. vera gel at a dose 30 mg/kg body weight per day to streptozotocin (STZ)-induced diabetic rats for a period of 9 days resulted in no change in blood glucose and plasma insulin. Oral administration as well as topical application of A. vera gel ethanolic extract and gel significantly reduced the blood glucose, improved the plasma insulin, and significantly increased DNA and glycosaminoglycans (GAGs) to improve the wound ulcer healing as well as the breaking strength on day 9. Conclusions: Present findings provide a scientific rationale for the use of A. vera gel ethanolic extract, and showed that the gel attenuated the diabetic foot wound in rats. PMID:25035641

Cannabidiol Arrests Onset of Autoimmune Diabetes in NOD Mice

PubMed Central

Weiss, Lola; Zeira, Michael; Reich, Shoshana; Slavin, Shimon; Raz, Itamar; Mechoulam, Raphael; Gallily, Ruth

2008-01-01

We have previously reported that cannabidiol (CBD) lowers the incidence of diabetes in young non-obese diabetes-prone (NOD) female mice. In the present study we show that administration of CBD to 11–14 week old female NOD mice, which are either in a latent diabetes stage or with initial symptoms of diabetes, ameliorates the manifestations of the disease. Diabetes was diagnosed in only 32% of the mice in the CBD-treated group, compared to 86% and 100% in the emulsifier-treated and untreated groups, respectively. In addition, the level of the proinflammatory cytokine IL-12 produced by splenocytes was significantly reduced, whereas the level of the anti-inflammatory IL-10 was significantly elevated following CBD-treatment. Histological examination of the pancreata of CBD-treated mice revealed more intact islets than in the controls. Our data strengthen our previous assumption that CBD, known to be safe in man, can possibly be used as a therapeutic agent for treatment of type 1 diabetes. PMID:17714746

A study on the protective effect of Cynodon dactylon leaves extract in diabetic rats.

PubMed

Karthik, D; Ravikumar, S

2011-04-01

To investigate the antidiabetic, antioxidant and hypolipidemic efficacy of Cynodon dactylon in diabetic rats. The experimental rats were randomly divided into three groups: Group I: control; Group II: Alloxan diabetic, untreated; and Group III: Alloxan diabetic treated with ethanolic extract of C. dactylon leaves (450 mg/kg·bw). Experimental diabetes was induced by alloxan in a single dose of 150 mg/kg·bw. A Significant diminution of fasting blood sugar level was observed and also significant increase in HDL and decrease (P<0.05) in cholesterol, triglyceride, LDL and VLDL were observed after 15 days of treatment. The investigation also revealed, the activities of AST, ALT, ALP, AP, LDH, and CPK (P<0.05) were decreased in the extract-supplemented group. The significant decrease in protein content and SOD, CAT, GPx, and GSH (P<0.05) activity and increase in LPO in plasma were found to be ameliorated after treatment. Our result supports the fact that administration of extract of C. dactylon leave is able to reduce hyperglycemia and hyperlipidemia risk and also reduced the oxidative stress in diabetic rats. Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

A highly successful and novel model for treatment of chronic painful diabetic peripheral neuropathy.

PubMed

Pfeifer, M A; Ross, D R; Schrage, J P; Gelber, D A; Schumer, M P; Crain, G M; Markwell, S J; Jung, S

1993-08-01

To investigate why, in spite of a vast variety of treatment agents, the alleviation of pain in patients with diabetic neuropathy is difficult. Previous studies have not used a treatment algorithm based on anatomic site and neuropathophysiological source of the neuropathic pain. A model that categorizes the types of pain into three groups (superficial, deep, and muscular) was applied in 75 diabetic patients with chronic (> 12 mo) painful distal symmetrical polyneuropathy in a controlled case series. Twenty-two patients were untreated and 53 patients were treated with imipramine +/- mexiletine for deep pain, capsaicin for superficial pain, and stretching exercises and metaxalone +/- piroxican for muscular pain. Each type of pain was scored separately on a scale of 0 (none) to 19 (worst), and the total of all three types was used as an index of overall pain. Ability to sleep through the night was scored by a scale of 1 (never) to 5 (always). No significant differences were observed in initial pain scores, sleep scores, demographics, biochemistries, or physical findings between the two groups. After 3 mo a significant improvement in scores was noted in the treated but not the untreated patients. In addition, a significant difference was found in the change of scores between the treated and untreated patients: total pain (-18 +/- 2 vs. 0 +/- 2), deep pain (-7 +/- 1 vs. 0 +/- 1), superficial pain (-5 +/- 1 vs. 0 +/- 1), muscular pain (-6 +/- 1 vs. 0 +/- 1), and sleep (1.2 +/- 0.2 vs. 0.2 +/- 0.2), all P < 0.0001. In treated patients 21% became pain-free (total pain < 2), 66% had improvement (decrease in total pain > 5, but not total elimination of painful symptoms), and 13% were considered treatment failures (a decrease in total pain of < or = 5). This compares with 0 (P < 0.02), 10 (P < 0.0001), and 90% (P < 0.0001), respectively, in the untreated patients. This study presents a new rationale and hypothesis for the successful treatment of chronic painful diabetic peripheral neuropathy. It uniquely bases the treatment algorithm on the types and sources of the pain.

Momordica charantia ointment accelerates diabetic wound healing and enhances transforming growth factor-β expression.

PubMed

Hussan, F; Teoh, S Lin; Muhamad, N; Mazlan, M; Latiff, A A

2014-08-01

Transforming growth factor-β (TGF-β) plays an important role in wound healing. Delayed wound healing is a consequence of diabetes, leading to high morbidity and poor quality of life. Momordica charantia (MC) fruit possesses anti-diabetic and wound healing properties. This study aimed to explore the changes in TGF-β expression in diabetic wounds treated with topical MC fruit extract. Fifty-six male Sprague-Dawley rats were divided into a normal control group and five diabetic groups of ten rats each. Intravenous streptozotocin (50mg/kg) was given to induce diabetes in the diabetic groups. Full thickness excision wounds were created on the thoracodorsal region of the animals, and these wounds were then treated with vehicle, MC powder, MC ointment and povidone ointment or ointment base for ten days. Wound healing was determined by the rate of wound closure, total protein content and TGF-β expression in the wounds, and histological observation. Diabetic groups showed delayed wound closure rates compared to the control group. The wound closure rate in the MC ointment group was significantly faster than that of the untreated diabetic group (p<0.05). The MC ointment group also showed intense TGF-β expression and a high level of total protein content. MC ointment has a promising potential for use as an alternative topical medication for diabetic wounds. This work has shown that it accelerates wound healing in diabetic rats, and it is suggested here that this occurs by enhancing TGF-β expression. Further work is recommended to explore this effect.

Effects of parathyroid hormone on cortical porosity, non-enzymatic glycation and bone tissue mechanics in rats with type 2 diabetes mellitus.

PubMed

Campbell, G M; Tiwari, S; Hofbauer, C; Picke, A-K; Rauner, M; Huber, G; Peña, J A; Damm, T; Barkmann, R; Morlock, M M; Hofbauer, L C; Glüer, C-C

2016-01-01

Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and the efficacy of bone-forming agents are unclear. We studied diabetes and parathyroid hormone (PTH) treatment effects on cortical porosity (Ct.Po), non-enzymatic glycation (NEG) and bone mechanics in Zucker diabetic fatty (ZDF) rats. Eleven-week old ZDF diabetic (DB) and non-diabetic (ND) rats were given 75μg/kg PTH (1-84) or vehicle 5days per week over 12weeks. The right femora and L4 vertebrae were excised, micro-CT scanned, and tested in 3-point bending and uniaxial compression, respectively. NEG of the samples was determined using fluorescence. Diabetes increased Ct.Po (vertebra (vert): +40.6%, femur (fem): +15.5% vs. ND group, p<0.05) but had no effect on NEG. PTH therapy reduced vertebral NEG in the ND animals only (-73% vs untreated group, p<0.05), and increased femoral NEG in the DB vs. ND groups (+63%, p<0.05). PTH therapy had no effect on Ct.Po. Diabetes negatively affected bone tissue mechanics where reductions in vertebral maximum strain (-22%) and toughness (-42%) were observed in the DB vs. ND group (p<0.05). PTH improved maximum strain in the vertebra of the ND animals (+21%, p<0.05) but did not have an effect in the DB group. PTH increased femoral maximum strain (+21%) and toughness (+28%) in ND and decreased femoral maximum stress (-13%) and toughness (-27%) in the DB animals (treated vs. untreated, p<0.05). Ct.Po correlated negatively with maximum stress (fem: R=-0.35, p<0.05, vert: R=-0.57, p<0.01), maximum strain (fem: R=-0.35, p<0.05, vert: R=-0.43, p<0.05) and toughness (fem: R=-0.34, p<0.05, vert: R=-0.55, p<0.01), and NEG correlated negatively with toughness at the femur (R=-0.34, p<0.05) and maximum strain at the vertebra (R=-0.49, p<0.05). Diabetes increased cortical porosity and reduced bone mechanics, which were not improved with PTH treatment. PTH therapy alone may worsen diabetic bone mechanics through formation of new bone with high AGEs cross-linking. Optimal treatment regimens must address both improvements of bone mass and glycemic control in order to successfully reduce diabetic bone fragility. This article is part of a Special Issue entitled "Bone and diabetes". Copyright © 2015 Elsevier Inc. All rights reserved.

Beneficial effects of Hibiscus rosa-sinensis L. flower aqueous extract in pregnant rats with diabetes.

PubMed

Afiune, Luana Alves Freitas; Leal-Silva, Thaís; Sinzato, Yuri Karen; Moraes-Souza, Rafaianne Queiroz; Soares, Thaigra Sousa; Campos, Kleber Eduardo; Fujiwara, Ricardo Toshio; Herrera, Emilio; Damasceno, Débora Cristina; Volpato, Gustavo Tadeu

2017-01-01

The Hibiscus rosa-sinensis flower is widely used in Brazilian traditional medicine for the treatment of diabetes and has shown antifertility activity in female Wistar rats. However, there is no scientific confirmation of its effect on diabetes and pregnancy. The aim of this study was evaluate the effect of aqueous extract of H. rosa-sinensis flowers on maternal-fetal outcome in pregnant rats with diabetes. Diabetes was induced by streptozotocin (STZ, 40 mg/kg) in virgin, adult, female Wistar rats. After diabetes induction, the rats were mated. The pregnant rats were distributed into four groups (n minimum = 11 animals/group): non-diabetic, non-diabetic treated, diabetic, and diabetic treated. Oral aqueous extract of Hibiscus rosa-sinensis was administered to rats in the treatment groups during pregnancy. At term pregnancy, maternal reproductive outcomes, fetal parameters, and biochemical parameters were analyzed. The non-diabetic treated group showed decreased high density lipoprotein cholesterol, increased atherogenic index (AI) and coronary artery risk index (CRI), and increased preimplantation loss rate compared to the non-diabetic group. Although treatment with H. rosa-sinensis led to no toxicity, it showed deleterious effects on cardiac and reproductive functions. However, the diabetic treated group showed increased maternal and fetal weights, reduced AI and CRI, and reduced preimplantation loss rate compared to the untreated diabetic group. Our results demonstrate beneficial effects of this flower only in pregnant rats with diabetes and their offspring. Although these findings cannot be extrapolated to human clinical use, they show that the indiscriminate intake of H. rosa-sinensis may be harmful to healthy individuals and its use should be completely avoided in pregnancy.

Beneficial effects of Hibiscus rosa-sinensis L. flower aqueous extract in pregnant rats with diabetes

PubMed Central

Afiune, Luana Alves Freitas; Leal-Silva, Thaís; Sinzato, Yuri Karen; Moraes-Souza, Rafaianne Queiroz; Soares, Thaigra Sousa; Campos, Kleber Eduardo; Fujiwara, Ricardo Toshio; Herrera, Emilio; Damasceno, Débora Cristina

2017-01-01

Purpose The Hibiscus rosa-sinensis flower is widely used in Brazilian traditional medicine for the treatment of diabetes and has shown antifertility activity in female Wistar rats. However, there is no scientific confirmation of its effect on diabetes and pregnancy. The aim of this study was evaluate the effect of aqueous extract of H. rosa-sinensis flowers on maternal-fetal outcome in pregnant rats with diabetes. Methods Diabetes was induced by streptozotocin (STZ, 40 mg/kg) in virgin, adult, female Wistar rats. After diabetes induction, the rats were mated. The pregnant rats were distributed into four groups (n minimum = 11 animals/group): non-diabetic, non-diabetic treated, diabetic, and diabetic treated. Oral aqueous extract of Hibiscus rosa-sinensis was administered to rats in the treatment groups during pregnancy. At term pregnancy, maternal reproductive outcomes, fetal parameters, and biochemical parameters were analyzed. Results The non-diabetic treated group showed decreased high density lipoprotein cholesterol, increased atherogenic index (AI) and coronary artery risk index (CRI), and increased preimplantation loss rate compared to the non-diabetic group. Although treatment with H. rosa-sinensis led to no toxicity, it showed deleterious effects on cardiac and reproductive functions. However, the diabetic treated group showed increased maternal and fetal weights, reduced AI and CRI, and reduced preimplantation loss rate compared to the untreated diabetic group. Conclusion Our results demonstrate beneficial effects of this flower only in pregnant rats with diabetes and their offspring. Although these findings cannot be extrapolated to human clinical use, they show that the indiscriminate intake of H. rosa-sinensis may be harmful to healthy individuals and its use should be completely avoided in pregnancy. PMID:28644857

Basal and glucagon-stimulated plasma C-peptide concentrations in healthy dogs, dogs with diabetes mellitus, and dogs with hyperadrenocorticism.

PubMed

Montgomery, T M; Nelson, R W; Feldman, E C; Robertson, K; Polonsky, K S

1996-01-01

Serum glucose and plasma C-peptide response to i.v. glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5, 10, 20, 30, and (for healthy dogs) 60 minutes after i.v. administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after i.v. glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after i.v. glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sampling times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .00l) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .01) in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, > 0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with the results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired beta-cell function (ie, diabetes mellitus), and dogs with increased beta-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of beta-cell loss in dogs with type-1 diabetes.

Impact of ellagic acid in bone formation after tooth extraction: an experimental study on diabetic rats.

PubMed

Al-Obaidi, Mazen M Jamil; Al-Bayaty, Fouad Hussain; Al Batran, Rami; Hussaini, Jamal; Khor, Goot Heah

2014-01-01

To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction. Twenty-four Sprague Dawley male rats weighing 250-300 g were selected for this study. All animals were intraperitoneally injected with 45 mg/kg (b.w.) of freshly prepared streptozotocin (STZ), to induce diabetic mellitus. Then, the animals were anesthetized, and the upper left central incisor was extracted and the whole extracted sockets were filled with Rosuvastatin (RSV). The rats were separated into three groups, comprising 8 rats each. The first group was considered as normal control group and orally treated with normal saline. The second group was regarded as diabetic control group and orally treated with normal saline, whereas the third group comprised diabetic rats, administrated with EA (50 mg/kg) orally. The maxilla tissue stained by eosin and hematoxylin (H&E) was used for histological examinations and immunohistochemical technique. Fibroblast growth factor (FGF-2) and alkaline phosphatase (ALP) were used to evaluate the healing process in the extracted tooth socket by immunohistochemistry test. The reactions of immunohistochemistry for FGF-2 and ALP presented stronger expression, predominantly in EA treated diabetic rat, than the untreated diabetic rat. These findings suggest that the administration of EA combined with RSV may have accelerated the healing process of the tooth socket of diabetic rats, after tooth extraction.

Inhibiting MicroRNA-503 and MicroRNA-181d with Losartan Ameliorates Diabetic Nephropathy in KKAy Mice.

PubMed

Zhu, XinWang; Zhang, CongXiao; Fan, QiuLing; Liu, XiaoDan; Yang, Gang; Jiang, Yi; Wang, LiNing

2016-10-22

BACKGROUND Diabetic nephropathy (DN) is the most lethal diabetic microvascular complication; it is a major cause of renal failure, and an increasingly globally prominent healthcare problem. MATERIAL AND METHODS To identify susceptible microRNAs for the pathogenesis of DN and the targets of losartan treatment, microRNA arrays were employed to survey the glomerular microRNA expression profiles of KKAy mice treated with or without losartan. KKAy mice were assigned to either a losartan-treated group or a non-treatment group, with C57BL/6 mice used as a normal control. Twelve weeks after treatment, glomeruli from the mice were isolated. MicroRNA expression profiles were analyzed using microRNA arrays. Real-time PCR was used to confirm the results. RESULTS Losartan treatment improved albuminuria and the pathological lesions of KKAy mice. The expression of 10 microRNAs was higher, and the expression of 12 microRNAs was lower in the glomeruli of the KKAy untreated mice than that of the CL57BL/6 mice. The expression of 4 microRNAs was down-regulated in the glomeruli of the KKAy losartan-treated mice compared to that of the untreated mice. The expression of miRNA-503 and miRNA-181d was apparently higher in the glomeruli of the KKAy untreated mice, and was inhibited by losartan treatment. CONCLUSIONS The over-expression of miR-503 and miR-181d in glomeruli of KKAy mice may be responsible for the pathogenesis of DN and are potential therapeutic targets for DN.

Transition metals and polyol pathway in the development of diabetic neuropathy in rats.

PubMed

Nakamura, Jiro; Hamada, Yoji; Chaya, Sadao; Nakashima, Eitaro; Naruse, Keiko; Kato, Koichi; Yasuda, Yutaka; Kamiya, Hideki; Sakakibara, Fumihiko; Koh, Naoki; Hotta, Nigishi

2002-01-01

The transition metal-catalyzed reaction is a major source of oxygen free radicals, which play an important role in vascular dysfunction leading to ischemia in diabetic tissues. The inhibition of polyol pathway hyperactivity has been reported to ameliorate neurovascular abnormalities in diabetic rats and has been proposed to improve the oxygen free radical scavenging capacity. The present study was conducted to compare the effect of a transition metal chelating agent, trientine (TRI), on diabetic neuropathy with that of an aldose reductase inhibitor, NZ-314 (NZ). Diabetic rats were divided into three groups: (1). untreated, (2). TRI-treated, and (3). NZ-treated. TRI (20 mg/kg) or NZ (100 mg/kg) was administered by gavage or chow containing NZ, respectively, for 8 weeks. Motor nerve conduction velocity (MNCV), coefficient of variation of the R - R interval on electrocardiogram (CVr-r), sciatic nerve blood flow (SNBF), platelet aggregation activities, and serum concentrations of malondialdehyde were measured. Untreated diabetic rats showed delayed MNCV, decreased CV(R-R), and reduced SNBF compared to normal rats. TRI or NZ completely prevented these deficits. Platelet hyperaggregation activities in diabetic rats were prevented by NZ, but not by TRI. Increased concentrations of malondialdehyde in diabetic rats were partially but significantly ameliorated by either TRI or NZ. These observations suggest that increased free radical formation through the transition metal-catalyzed reaction plays an important role in the development of diabetic neuropathy and that the preventive effect of an aldose reductase inhibitor on diabetic neuropathy may also be mediated by decreasing oxygen free radicals. Copyright 2002 John Wiley & Sons, Ltd.

Glycosylated hemoglobin concentrations in the blood of healthy dogs and dogs with naturally developing diabetes mellitus, pancreatic beta-cell neoplasia, hyperadrenocorticism, and anemia.

PubMed

Elliott, D A; Nelson, R W; Feldman, E C; Neal, L A

1997-09-15

To characterize glycosylated hemoglobin (GHb) concentrations in the blood of dogs with disorders that may affect serum glucose or blood GHb concentrations, and to determine whether changes in GHb concentration correlate with changes in control of diabetes in dogs. Prospective study. 63 healthy dogs, 9 dogs with anemia, 24 dogs with untreated hyperadrenocorticism, 12 dogs with pancreatic beta-cell neoplasia, 23 dogs with newly diagnosed diabetes mellitus, and 77 diabetic dogs treated with insulin. Control of diabetes in dogs treated with insulin was classified as good or poor on the basis of history, physical examination findings, changes in body weight, and measurement of serum glucose concentrations Sequential evaluations of control were performed and GHb concentration in blood was measured, by means of affinity chromatography, for 5 untreated diabetic dogs before and after initiating insulin treatment, for 10 poorly controlled diabetic dogs before and after increasing insulin dosage, and for 5 diabetic dogs before and after pancreatic islet cell transplantation. Mean (+/-SD) GHb concentration was 3.3 +/- 0.8% in the blood of healthy dogs. Compared with results from healthy dogs, mean GHb concentration was significantly lower in the blood of dogs with anemia and pancreatic beta-cell neoplasia and significantly higher in the blood of untreated diabetic dogs. Mean GHb concentration was significantly higher in the blood of 46 poorly controlled diabetic dogs, compared with 31 well-controlled diabetic dogs (7.3 +/- 1.8 vs 5.7 +/- 1.7%, respectively). Mean GHb concentration in blood decreased significantly in 5 untreated diabetic dogs after treatment (8.7 +/- 1.9 vs 5.3 +/- 1.9%). Mean GHb concentration in blood also decreased significantly in 10 poorly controlled diabetic dogs after control was improved and in 5 diabetic dogs after they had received a pancreatic islet cell transplant. Measurement of GHb concentration in blood may assist in monitoring control of diabetes in dogs.

Effects of the Hydroalcoholic Extract of Zingiber officinale on Arginase I Activity and Expression in the Retina of Streptozotocin-Induced Diabetic Rats.

PubMed

Lamuchi-Deli, Nasrin; Aberomand, Mohammad; Babaahmadi-Rezaei, Hossein; Mohammadzadeh, Ghorban

2017-04-01

Emerging evidence suggests that an increased arginase activity is involved in vascular dysfunction in experimental animals. Zingiber officinale Roscoe, commonly known as ginger, has been widely used in the traditional medicine for treatment of diabetes. This study aimed at investigating the effects of the hydroalcoholic extract of Z. officinale on arginase I activity and expression in the retina of streptozotocin (STZ)-induced diabetic rats. In this experimental study, 16 male Wistar rats weighing 200 - 250 g were assessed. Diabetes was induced via a single intraperitoneal injection of STZ (60 mg/kg body weight). The rats were randomly allocated into four experimental groups. Untreated healthy and diabetic controls received 1.5 mL/kg distilled water. Treated diabetic rats received 200, and 400 mg/kg of the Z. officinale extract dissolved in distilled water (1.5 mL/kg). Body weight, blood glucose and insulin concentration were measured by standard methods. The arginase I activity and expression were determined by spectrophotometric and western blot analysis, respectively. Our results showed that blood glucose concentration was significantly decreased in diabetic rats treated with the extract compared to untreated diabetic controls (P < 0.01). Treatment with 400 mg/kg of the extract reduced arginase I activity and expression (P < 0.05). A significant elevation in body weight was observed in diabetic rats treated with the extract. Serum insulin was significantly increased in diabetic rats treated with 400 mg/kg of the extract compared to diabetic controls (P < 0.05). Our results suggest that the Z. officinale hydroalcoholic extract may potentially be a promising therapeutic option for treating diabetes-induced vascular disorders, possibly through reducing arginase I activity and expression in the retina.

Effects of the Hydroalcoholic Extract of Zingiber officinale on Arginase I Activity and Expression in the Retina of Streptozotocin-Induced Diabetic Rats

PubMed Central

Lamuchi-Deli, Nasrin; Aberomand, Mohammad; Babaahmadi-Rezaei, Hossein; Mohammadzadeh, Ghorban

2017-01-01

Background Emerging evidence suggests that an increased arginase activity is involved in vascular dysfunction in experimental animals. Zingiber officinale Roscoe, commonly known as ginger, has been widely used in the traditional medicine for treatment of diabetes. Objectives This study aimed at investigating the effects of the hydroalcoholic extract of Z. officinale on arginase I activity and expression in the retina of streptozotocin (STZ)-induced diabetic rats. Methods In this experimental study, 16 male Wistar rats weighing 200 – 250 g were assessed. Diabetes was induced via a single intraperitoneal injection of STZ (60 mg/kg body weight). The rats were randomly allocated into four experimental groups. Untreated healthy and diabetic controls received 1.5 mL/kg distilled water. Treated diabetic rats received 200, and 400 mg/kg of the Z. officinale extract dissolved in distilled water (1.5 mL/kg). Body weight, blood glucose and insulin concentration were measured by standard methods. The arginase I activity and expression were determined by spectrophotometric and western blot analysis, respectively. Results Our results showed that blood glucose concentration was significantly decreased in diabetic rats treated with the extract compared to untreated diabetic controls (P < 0.01). Treatment with 400 mg/kg of the extract reduced arginase I activity and expression (P < 0.05). A significant elevation in body weight was observed in diabetic rats treated with the extract. Serum insulin was significantly increased in diabetic rats treated with 400 mg/kg of the extract compared to diabetic controls (P < 0.05). Conclusions Our results suggest that the Z. officinale hydroalcoholic extract may potentially be a promising therapeutic option for treating diabetes-induced vascular disorders, possibly through reducing arginase I activity and expression in the retina. PMID:28835766

Febuxostat ameliorates diabetic renal injury in a streptozotocin-induced diabetic rat model.

PubMed

Lee, Hong-Joo; Jeong, Kyung Hwan; Kim, Yang Gyun; Moon, Joo Young; Lee, Sang Ho; Ihm, Chun Gyoo; Sung, Ji Youn; Lee, Tae Won

2014-01-01

Oxidative stress and inflammation are known to play central roles in the development of diabetic nephropathy (DN). Febuxostat is a novel non-purine xanthine oxidase (XO)-specific inhibitor developed to treat hyperuricemia. In this study, we investigated whether febuxostat could ameliorate DN via renoprotective mechanisms such as alleviation of oxidative stress and anti-inflammatory actions. Male Sprague-Dawley rats were divided into three groups: a normal group, a diabetes group (DM group), and a febuxostat-treated diabetes group (DM+Fx group). We administered 5 mg/kg of febuxostat to experimental rats for 7 weeks and evaluated clinical and biochemical parameters and XO and xanthine dehydrogenase (XDH) activity in hepatic tissue. The degree of oxidative stress and extent of inflammation were evaluated from urine samples and renal tissue collected from each group. Diabetic rats (DM and DM+Fx groups) had higher blood glucose and kidney weight relative to body weight than normal rats. Albuminuria was significantly reduced in febuxostat-treated diabetic rats compared with untreated diabetic rats. Quantitative analysis showed that hepatic XO and XDH activities were higher in the DM groups, but decreased after treatment with febuxostat. Urinary 8-OHdG concentrations and renal cortical nitrotyrosine also indicated reduced oxidative stress in the DM+Fx group relative to the DM group. The number of ED-1-stained cells in the glomerulus and tubule of diabetic renal tissue decreased in febuxostat-treated diabetic rats relative to that of non-treated diabetic rats. Diabetic rats also expressed higher transcript levels of inflammatory genes (E-selectin and VCAM-1), an inflammation-induced enzyme (COX-2), and inflammatory mediators (ED-1 and NF-κB) than control rats; expression of these genes was significantly reduced by treatment with febuxostat. Febuxostat prevents diabetic renal injury such as albuminuria. This renoprotective effect appears to be due to attenuation of the inflammatory and oxidative effects of diabetes-induced renal damage through inhibition of XO and XDH activities. © 2014 S. Karger AG, Basel.

Epigallocatechin gallate attenuates ET-1-induced contraction in carotid artery from type 2 diabetic OLETF rat at chronic stage of disease.

PubMed

Matsumoto, Takayuki; Watanabe, Shun; Kawamura, Ryusuke; Taguchi, Kumiko; Kobayashi, Tsuneo

2014-11-24

There is a growing body of evidence suggesting that epigallocatechin gallate (EGCG), a major catechin isolated from green tea, has several beneficial effects, such as anti-oxidant and anti-inflammatory activities. However, whether treatment with EGCG can suppress the endothelin-1 (ET-1)-induced contraction in carotid arteries from type 2 diabetic rats is unknown, especially at the chronic stage of the disease. We hypothesized that long-term treatment with EGCG would attenuate ET-1-induced contractions in type 2 diabetic arteries. Otsuka Long-Evans Tokushima fatty (OLETF) rats (43 weeks old) were treated with EGCG (200 mg/kg/day for 2 months, p.o.), and the responsiveness to ET-1, phenylephrine (PE), acetylcholine (ACh) and sodium nitroprusside (SNP) was measured in common carotid artery (CA) from EGCG-treated and -untreated OLETF rats and control Long-Evans Tokushima Otsuka (LETO) rats. In OLETF rats, EGCG attenuated responsiveness to ET-1 in CA compared to untreated groups. However, EGCG did not alter PE-induced contractions in CA from OLETF rats. In endothelium-denuded arteries, EGCG did not affect ET-1-induced contractions in either the OLETF or LETO group. Acetylcholine-induced relaxation was increased by EGCG treatment in CA from the OLETF group. The expressions of ET receptors, endothelial nitric oxide synthase, superoxide dismutases, and gp91(phox) [an NAD(P)H oxidase component] in CA were not altered by EGCG treatment in either group. Our data suggest that, within the timescale investigated here, EGCG attenuates ET-1-induced contractions in CA from type 2 diabetic rats, and one of the mechanisms may involve normalizing endothelial function. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Protective effect of the daming capsule on impaired baroreflexes in STZ-induced diabetic rats with hyperlipoidemia.

PubMed

Ai, Jing; Wang, Li-Hong; Zhang, Rong; Qiao, Guo-Fen; Wang, Ning; Sun, Li-Hua; Lu, Guan-Yi; Sun, Chao; Yang, Bao-Feng

2010-12-22

The Daming capsule (DMC) is a traditional Chinese medicine used to treat hyperlipoidemia. Both clinic trials and studies on animal models have demonstrated that DMC is beneficial against diabetic symptoms. Impairment of the baroreflex can cause life-threatening arrhythmias and sudden cardiac death in patients with diabetes mellitus (DM). This study was designed to elucidate the effects of DMC on baroreflexes in streptozocin (STZ)-induced diabetic rats with hyperlipoidemia. Wistar rats were randomly divided into three groups: untreated controls, rats pretreated STZ and high lipids (a diabetes model or DM rats), and DM rats treated with DMC. The baroreflex sensitivity was examined during intravenous injection of phenylephrine (PE) or sodium nitroprusside (SNP) and quantified by the change in heart rate over the change in mean arterial blood pressure (ΔHR/ΔMABP). Morphological remodeling of baroreceptors was analyzed by transmission electron microscopy (TEM). The mRNA levels and expression of GluR2 and a GABAA receptor subunit were measured by quantitative RT-PCR and Western blotting. Compared to untreated DM rats, DMC significantly elevated the ratio of ΔHR/ΔMABP by enhancing the compensatory reduction in HR (-ΔHR) in response to PE-induced hypertension (+ΔMABP) (P < 0.05). In the presence of SNP, DMC increased the ΔMABP (P < 0.05). In addition, DMC markedly shortened the duration of blood pressure changes elicited by PE or SNP in DM rats compared to the untreated DM group (P < 0.05). Electron microscopy revealed disrupted myelin sheaths, swollen ER, and lysed mitochondria in the nucleus ambiguous (NAm) DM rats. These signs of neuropathology were largely prevented by treatment with DMC for 30 days. Treatment with DMC elevated both mRNA and protein level of GluR2 in the NAm of DM rats, but had no effect on GABAA receptor expression. The Daming capsule partially reversed the parasympathetic baroreflex impairment observed in STZ-induced diabetic rats with hyperlipoidemia. Treatment with DMC also prevented the degeneration of neurons and myelinated axons in the brain stem NAm and reversed the down-regulation of GluR2 mRNA. Rescue of NAm function may contribute to the medicinal properties of DMC in diabetic rats.

Microaneurysm turnover in diabetic retinopathy assessed by automated RetmarkerDR image analysis--potential role as biomarker of response to ranibizumab treatment.

PubMed

Leicht, Simon F; Kernt, Marcus; Neubauer, Aljoscha; Wolf, Armin; Oliveira, Carlos Manta; Ulbig, Michael; Haritoglou, Christos

2014-01-01

To evaluate the influence of a ranibizumab treatment on microaneurysm (MA) turnover in diabetic retinopathy. Sixty-nine eyes were included in this retrospective study. We compared a group of 33 eyes with ranibizumab treatment for diabetic macular edema to 36 eyes with nonproliferative diabetic retinopathy only. Nonmydriatic ultra-widefield scanning laser ophthalmoscopy (Optomap) images were obtained at a mean 4.76 ± 1.69 days prior to the first ranibizumab injection (baseline) and again 35.94 ± 2.44 days after the third consecutive injection in a 4-week interval. In untreated controls, images were obtained at baseline and 97.81 ± 3.16 days thereafter. Images were analyzed using the RetmarkerDR software (Critical Health SA, Coimbra, Portugal), and the turnover of MAs was documented and analyzed. Thereafter, MA turnover was correlated with central retinal thickness (CRT) as assessed by OCT. At baseline, patients in the treatment group had 5.64 ± 0.75 MAs. One month after 3 ranibizumab injections, measured MAs decreased to 4.03 ± 0.66. In the untreated control group, the initial number of 3.36 ± 0.6 MAs remained almost unchanged over 3-4 months (2.89 ± 0.57 MAs). Dynamic analysis showed that after ranibizumab treatment 3.06 ± 0.5 new MAs appeared, while 5.09 ± 0.79 disappeared. In the control group, 2.11 ± 0.4 new MAs appeared and 2.61 ± 0.48 disappeared. MA turnover was significantly higher with ranibizumab compared to the control group (8.15 ± 1.14 vs. 4.72 ± 0.81, p < 0.001). Consistently, CRT decreased from 444 to 330 µm in the ranibizumab group, while there was no change in the control group (291 vs. 288 µm). The treatment of macular edema using ranibizumab does not only reduce macular thickness, but also has an impact on the turnover of MAs in diabetic retinopathy. RetmarkerDR analysis showed that more pre-existent MAs disappeared than new MAs developed, and the absolute number of MAs also decreased. © 2014 S. Karger AG, Basel.

The Effect of Pycnogenol on Wound Healing in Diabetic Rats.

PubMed

Dogan, Elif; Yanmaz, Latif; Gedikli, Semin; Ersoz, Ugur; Okumus, Zafer

2017-04-01

Pycnogenol (PYC), an extract of pine bark, is known to have photoprotective, antimicrobial, antioxidant, and anti-inflammatory properties. An in vivo study was conducted to evaluate the effects of PYC treatment on wound healing in 48 adult male Sprague-Dawley rats, of which 24 were injected with a single dose of alloxan to induce diabetes. Three (3) excisional skin wounds (1.3 cm x 1.3 cm x 2 mm) were created in each healthy and diabetic animal. One (1) wound in each animal was left untreated, 1 was treated daily with a cleanser (ethacridine lactate) and covered with silver sulfadiazine (SSD), and 1 was treated with PYC powder (30 mg). After measuring wound size, 6 animals from both groups were sacrificed on days 3, 7, 14, and 21 and tissue samples were taken for histopathological evaluation of acute and chronic inflammation, granulation tissue, fibroblast maturation, collagen deposition, epithelialization, and neovascularization using a scoring system of 0 = none, 1 = mild, 2 = moderate, and 3 = abundant. Because the wounds created were not uniform in size within and among the animals, healing was expressed as a percentage of the initial wound size for each animal. Data were compared using 2-way analysis of variance; histopathological lesion scores were reported in median values in univariate analysis, with P <.05 denoting statistical significance. The mean initial wound surface area was 1.69 ± 0.44 cm². On day 21, the average reduction in wound size was lower in diabetic than in healthy rats (47.42% versus 50.91%, P <.0001) and, in both groups combined, the average reduction was 45.73% in untreated, 48.73% in cleanser/SSD-treated, and 58.03% in PYC-treated wounds (P <.0001). Wound size reduction was also significantly different between PYC and the cleanser/SSD treatment depending on the rats' health status (P <.0001): 49.68% and 47.84% using cleanser/SSD and 56.17% and 49.84% using PYC in healthy and diabetic rats, respectively. After 3 weeks, wound size for the healthy rats had decreased more than in the diabetic rats (mean 50.91% versus 47.42%). Although reepithelialization was complete in both groups by day 21, complete neovascularization was evident in the healthy rats but not in the diabetic rats. Overall, compared to the untreated control wounds, treatments with cleanser/SSD and PYC were equally effective in lowering acute and chronic inflammation scores on days 7 and 21. In diabetic rat wounds, collagen deposition and neovascularization scores were higher in wounds treated with PYC than cleanser/SSD-treated wounds (1.5 versus 1.0 and 2.0 versus 1.5, respectively). PYC appears to be a viable option to accelerate wound healing. Further in vivo and human research is warranted.

Impact of Ellagic Acid in Bone Formation after Tooth Extraction: An Experimental Study on Diabetic Rats

PubMed Central

Al-Obaidi, Mazen M. Jamil; Al-Bayaty, Fouad Hussain; Hussaini, Jamal; Khor, Goot Heah

2014-01-01

Objectives. To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction. Methods. Twenty-four Sprague Dawley male rats weighing 250–300 g were selected for this study. All animals were intraperitoneally injected with 45 mg/kg (b.w.) of freshly prepared streptozotocin (STZ), to induce diabetic mellitus. Then, the animals were anesthetized, and the upper left central incisor was extracted and the whole extracted sockets were filled with Rosuvastatin (RSV). The rats were separated into three groups, comprising 8 rats each. The first group was considered as normal control group and orally treated with normal saline. The second group was regarded as diabetic control group and orally treated with normal saline, whereas the third group comprised diabetic rats, administrated with EA (50 mg/kg) orally. The maxilla tissue stained by eosin and hematoxylin (H&E) was used for histological examinations and immunohistochemical technique. Fibroblast growth factor (FGF-2) and alkaline phosphatase (ALP) were used to evaluate the healing process in the extracted tooth socket by immunohistochemistry test. Results. The reactions of immunohistochemistry for FGF-2 and ALP presented stronger expression, predominantly in EA treated diabetic rat, than the untreated diabetic rat. Conclusion. These findings suggest that the administration of EA combined with RSV may have accelerated the healing process of the tooth socket of diabetic rats, after tooth extraction. PMID:25485304

Effect of Infrared Radiation on the Healing of Diabetic Foot Ulcer

PubMed Central

Hakim, Ashrafalsadat; Sadeghi Moghadam, Ali; Shariati, Abdalali; karimi, Hamid; Haghighizadeh, Mohamad Hossien

2016-01-01

Background Diabetic foot ulcer is a worldwide health care concern affecting tens of thousands of patients. If these ulcers left untreated, they can create severe complications. Objectives This study was designed to examine the effect of infrared radiation on the healing of diabetic foot ulcer. Patients and Methods This clinical trial was performed on 50 patients referred to Dr. Ganjavian hospital in Dezful city, Iran, with diabetic foot ulcer degree 1 and 2 (based on Wegener Scale). Sample size was determined based on relevant studies of the recent decade. Patients were classified into the intervention and control groups (n = 25 in each group) in terms of age, gender, degree of ulcer, ulcer site and body mass index. In this study, work progress was evaluated according to the checklist of diabetic foot ulcer healing evaluation. Results The results of the current study showed that there was a statistically significant difference in healing ulcers (P < 0.05) and mean healing time (P < 0.05) between the two groups. Conclusions Using the infrared plus routine dressing is more effective than using merely routine dressing. PMID:27942260

Type 2 Diabetes

MedlinePlus

... increasing dramatically among children, adolescents and younger adults. Prediabetes. Prediabetes is a condition in which your blood sugar ... enough to be classified as diabetes. Left untreated, prediabetes often progresses to type 2 diabetes. Gestational diabetes. ...

The Effects of Natural Clinoptilolite and Nano-Sized Clinoptilolite Supplementation on Glucose Levels and Oxidative Stress in Rats With Type 1 Diabetes.

PubMed

Hossein Nia, Behnoosh; Khorram, Sirous; Rezazadeh, Hassan; Safaiyan, Abdolrasol; Tarighat-Esfanjani, Ali

2018-02-01

Oxidative stress has a major role in development of diabetic complications. In this study we investigated whether clinoptilolite and nano-sized clinoptilolite could reduce hyperglycemia and oxidative stress in streptozotocin-induced diabetic rats and attempted to determine which intervention was more effective. Thirty-six rats were randomly allocated to 2 groups; 1 group was randomly chosen as a diabetic group and injected with streptozotocin (60 mg/kg body weight in 0.1 mol/L sodium citrate buffer, pH 4.5) to induce diabetes. Three days after diabetes induction, each group (diabetic group and nondiabetic group) was randomly divided into 3 subgroups of 6 animals each ([1] control, [2] 1% clinoptilolite/food, [3] 1% nano-sized clinoptilolite/food). Supplementation was continued for 28 days. Blood glucose was measured 3 times, at the beginning of the study and on the 14th and 28th days. Activity of antioxidant enzymes, including glutathione peroxidase and superoxide dismutase, and levels of total antioxidant capacity, as well as malondialdehyde, were evaluated. Blood glucose and malondialdehyde were significantly elevated, but there were no statistically significant changes in superoxide dismutase, glutathione peroxidase or total antioxidant capacity in diabetic rats. In diabetic rats treated with nano-sized clinoptilolite, blood glucose decreased to near normal levels (12.4 vs. 27.5 mmol/L). No significant changes were found in the other groups. None of the oxidative stress indices showed significant changes in either the treated or untreated rats. Nano-sized clinoptilolite exerted a hypoglycemic effect in streptozotocin-induced diabetic rats but had no significant influence on oxidative stress markers. Copyright © 2018. Published by Elsevier Inc.

Antidiabetic and Antioxidant Impacts of Desert Date (Balanites aegyptiaca) and Parsley (Petroselinum sativum) Aqueous Extracts: Lessons from Experimental Rats.

PubMed

Abou Khalil, Nasser S; Abou-Elhamd, Alaa S; Wasfy, Salwa I A; El Mileegy, Ibtisam M H; Hamed, Mohamed Y; Ageely, Hussein M

2016-01-01

Medicinal plants are effective in controlling plasma glucose level with minimal side effects and are commonly used in developing countries as an alternative therapy for the treatment of type 1 diabetes mellitus. The aim of this study is to evaluate the potential antidiabetic and antioxidant impacts of Balanites aegyptiaca and Petroselinum sativum extracts on streptozotocin-induced diabetic and normal rats. The influences of these extracts on body weight, plasma glucose, insulin, total antioxidant capacity (TAC), malondialdehyde (MDA) levels, and liver-pyruvate kinase (L-PK) levels were assessed. Furthermore, the weight and histomorphological changes of the pancreas were studied in the different experimental groups. The herbal preparations significantly reduced the mean plasma glucose and MDA levels and significantly increased the mean plasma insulin, L-PK, and TAC levels in the treated diabetic groups compared to the diabetic control group. An obvious increase in the weight of the pancreas and the size of the islets of Langerhans and improvement in the histoarchitecture were evident in the treated groups compared to untreated ones. In conclusion, the present study provides a scientific evidence for the traditional use of these extracts as antidiabetic and antioxidant agents in type 1 diabetes mellitus.

Short-term glycemic control is effective in reducing surgical site infection in diabetic rats.

PubMed

Kroin, Jeffrey S; Buvanendran, Asokumar; Li, Jinyuan; Moric, Mario; Im, Hee-Jeong; Tuman, Kenneth J; Shafikhani, Sasha H

2015-06-01

Patients and animals with diabetes exhibit enhanced vulnerability to bacterial surgical infections. Despite multiple retrospective studies demonstrating the benefits associated with glycemic control in reducing bacterial infection after cardiac surgery, there are fewer guidelines on the use of glycemic control for noncardiac surgeries. In the current study, we investigated whether long-term (begun 2 weeks before surgery) or immediate (just before surgery) glycemic controls, continued postoperatively, can reduce surgical site infection in type 1 diabetic-induced rats. Rats were injected with streptozotocin to induce type 1 diabetes. Four groups of animals underwent surgery and thigh muscle Staphylococcus aureus bacteria challenge (1 × 10 colony forming units) at the time of surgery. Group 1 diabetic rats received insulin treatment just before surgery and continued until the end of study (short-term glycemic control group). Group 2 diabetic rats received insulin treatment 2 weeks before surgery and continued until the end of study (long-term glycemic control). Group 3 diabetic rats received no insulin treatment (no glycemic control group). Group 4 nondiabetic rats served as a healthy control group. Rats were euthanized at 3 or 6 days after surgery. Blood glucose and muscle bacterial burden were measured at 3 or 6 days after surgery. Glycemic control was achieved in both long- and short-term insulin-treated diabetic rats. Compared with untreated diabetic rats, the bacterial burden in muscle was significantly lower in both groups of glycemic controlled diabetic rats at 3 (all P < 0.003) and 6 (all P < 0.0001) days after surgery. A short-term glycemic control regimen, initiated just before surgery and bacterial exposure, was as effective in reducing surgical site infection as a long-term glycemic control in type 1 diabetic rats. These data suggest that immediately implementing glycemic control in type 1 diabetic surgical patients before undergoing noncardiac surgery may decrease the risk of infection.

Naringin Mitigates Cardiac Hypertrophy by Reducing Oxidative Stress and Inactivating c-Jun Nuclear Kinase-1 Protein in Type I Diabetes.

PubMed

Adebiyi, A Olubunmi; Adebiyi, Oluwafeysetan O; Owira, Peter M O

2016-02-01

Cardiac hypertrophy (CH) in type 1 diabetes mellitus is attributed to increased oxidative stress-associated activation of c-Jun Nuclear Kinase (JNK). We investigated the effects of naringin on hyperglycemia-associated oxidative stress, activation of JNK-1, and CH. Male Sprague-Dawley rats (225-250 g) (n = 7) were divided into 6 groups. Groups I and II were orally treated with distilled water [3.0 mL/kg body weight/day (BW)] and naringin (50 mg/kg BW), respectively. Groups III-VI were rendered diabetic by a single intraperitoneal injection of 65 mg/kg BW of streptozotocin. Groups III, IV, and V were further treated with insulin (4.0 I.U, s.c, twice daily), naringin (50 mg/kg BW), and ramipril (3.0 mg/kg BW), respectively. After 56 days, the animals were sacrificed and then plasma and cardiac tissues obtained for further analysis. Naringin treatment of diabetic rats significantly reversed oxidative stress, lipid peroxidation, proteins oxidation, CH indices, and JNK protein activation compared with untreated diabetic animals. Our results do suggest that naringin mitigates CH by inhibiting oxidative stress leading to inactivation of JNK-1. Naringin supplements could therefore ameliorate CH in diabetic patients.

Summary of studies on the blue-green autofluorescence and light transmission of the ocular lens

NASA Astrophysics Data System (ADS)

Van Best, Jaap A.; Kuppens, Esmeralda V.

1996-07-01

This paper reviews previous work done to demonstrate the clinical relevance of the measurement of blue-green autofluorescence and light transmission of the ocular lens. These can be determined quantitatively with fluorophotometry in a few seconds. Autofluorescence and transmission values are determined in healthy volunteers, in patients with insulin-dependent diabetes mellitus, and in patients with untreated glaucoma or untreated ocular hypertension. The lens autofluorescence of healthy volunteers increased linearly and transmission decreased exponentially with age. Each year of diabetes induced an increase of autofluorescence equal to one extra year of age. Untreated glaucoma or ocular hypertension had no significant effect on lens autofluorescence and transmission. Increased autofluorescence and decreased transmission values in comparison with values of a healthy population are proved to be indicative for an increased risk of developing cataract and the clinical usefulness of these measures is demonstrated. Diabetes is a risk factor for developing cataracts while untreated glaucoma or ocular hypertension is not.

Effect of Ethanolic Leaf Extract of Senna Fistula on some Haematological Parameters, Lipid Profile and Oxidative Stress in Alloxan-induced Diabetic Rats.

PubMed

Ayinla, Tayo Maryam; Owoyele, Victor B; Yakubu, Toyin M

2015-12-20

Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. The disease is also known to adversely affect some haematological parameters and cause dyslipidemia. This study was designed to investigate the effect of chronic administration of ethanolic leave extract of Senna fistula on haematological values, oxidative stress and dyslipidemia in experimental diabetic rats. Twenty-four albino rats weighing 120-150 g were divided into 4 experimental groups of six rats each; control, diabetic untreated, diabetic treated with glibenclamide and diabetic treated with 100 mg/kg b.w of Senna fistula. Diabetes was induced by 100 mg/kg b.w. of alloxan monohydrates. The control and diabetic groups received normal saline while the diabetic treated groups were administered with 5mg/kg and 100mg/kg body weight of glibenclamide and ethanolic leaves extract of Senna fistula respectively for 28 days. At the end of experimental period blood samples were taken from the animals for the determination of Red blood cells (RBC), packed cell volume (PCV), Haemoglobin concentration (Hb), total cholesterol, triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL) and malondialdehyde (MDA), marker of lipid peroxidation. The result showed that in diabetic rats, PCV, RBC and Hb were decreased but the application of the extract increased the parameters. Similarly, the result showed a significant increase in total cholesterol, TG and LDL level of the diabetic group when compared with the control, glibenclamide and extract treated diabetic groups, however, there was no significant difference in HDL level in all the groups. The result also showed a significant decrease in elevated MDA of diabetic treated rats. These findings suggest that ethanolic leaves extract of Senna fistula might improve the diabetic induced disturbances of some haematological parameters, reduces the plasma lipid imbalances and decreases the production of free radicals associated with diabetes.

Angiotensin converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy

PubMed Central

Wysocki, Jan; Ye, Minghao; Khattab, Ahmed M.; Fogo, Agnes; Martin, Aline; David, Nicolae Valentin; Kanwar, Yashpal; Osborn, Mark; Batlle, Daniel

2016-01-01

Blockers of the renin-angiotensin system are effective in the treatment of experimental and clinical diabetic nephropathy. An approach different from blocking the formation or action of angiotensin II(1-8) that could also be effective involves fostering its degradation. Angiotensin converting enzyme 2 (ACE2) is a monocarboxypeptidase than cleaves angiotensin II (1-8) to form angiotensin (1-7). Therefore, we examined the renal effects of murine recombinant ACE2 in mice with streptozotocin-induced diabetic nephropathy as well as that of amplification of circulating ACE2 using minicircle DNA delivery prior to induction of experimental diabetes. This delivery resulted in a long-term sustained and profound increase in serum ACE2 activity and enhanced ability to metabolize an acute angiotensin II (1-8) load. In mice with streptozotocin-induced diabetes pretreated with minicircle ACE2, ACE2 protein in plasma increased markedly and this was associated with a more than 100-fold increase in serum ACE2 activity. However, minicircle ACE2 did not result in changes in urinary ACE2 activity as compared to untreated diabetic mice. In both diabetic groups, glomerular filtration rate increased significantly and to the same extent as compared to non-diabetic controls. Albuminuria, glomerular mesangial expansion, glomerular cellularity and glomerular size, were all increased to a similar extent in minicircle ACE2-treated and untreated diabetic mice, as compared to non-diabetic controls. Recombinant mouse ACE2 given for 4 weeks by intraperitoneal daily injections in mice with streptozotocin-induced diabetic nephropathy also failed to improve albuminuria or kidney pathology. Thus, a profound augmentation of ACE2 confined to the circulation failed to ameliorate the glomerular lesions and hyperfiltration characteristic of early diabetic nephropathy. These findings emphasize the importance of targeting the kidney rather than the circulatory renin angiotensin system to combat diabetic nephropathy. PMID:27927599

Angiotensin-converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy.

PubMed

Wysocki, Jan; Ye, Minghao; Khattab, Ahmed M; Fogo, Agnes; Martin, Aline; David, Nicolae Valentin; Kanwar, Yashpal; Osborn, Mark; Batlle, Daniel

2017-06-01

Blockers of the renin-angiotensin system are effective in the treatment of experimental and clinical diabetic nephropathy. An approach different from blocking the formation or action of angiotensin II (1-8) that could also be effective involves fostering its degradation. Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that cleaves angiotensin II (1-8) to form angiotensin (1-7). Therefore, we examined the renal effects of murine recombinant ACE2 in mice with streptozotocin-induced diabetic nephropathy as well as that of amplification of circulating ACE2 using minicircle DNA delivery prior to induction of experimental diabetes. This delivery resulted in a long-term sustained and profound increase in serum ACE2 activity and enhanced ability to metabolize an acute angiotensin II (1-8) load. In mice with streptozotocin-induced diabetes pretreated with minicircle ACE2, ACE2 protein in plasma increased markedly and this was associated with a more than 100-fold increase in serum ACE2 activity. However, minicircle ACE2 did not result in changes in urinary ACE2 activity as compared to untreated diabetic mice. In both diabetic groups, glomerular filtration rate increased significantly and to the same extent as compared to non-diabetic controls. Albuminuria, glomerular mesangial expansion, glomerular cellularity, and glomerular size were all increased to a similar extent in minicircle ACE2-treated and untreated diabetic mice, as compared to non-diabetic controls. Recombinant mouse ACE2 given for 4 weeks by intraperitoneal daily injections in mice with streptozotocin-induced diabetic nephropathy also failed to improve albuminuria or kidney pathology. Thus, a profound augmentation of ACE2 confined to the circulation failed to ameliorate the glomerular lesions and hyperfiltration characteristic of early diabetic nephropathy. These findings emphasize the importance of targeting the kidney rather than the circulatory renin angiotensin system to combat diabetic nephropathy. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Anti-diabetic potential of the essential oil of Pinus koraiensis leaves toward streptozotocin-treated mice and HIT-T15 pancreatic β cells.

PubMed

Joo, Hye-Eun; Lee, Hyo-Jung; Sohn, Eun Jung; Lee, Min-Ho; Ko, Hyun-Suk; Jeong, Soo-Jin; Lee, Hyo-Jeong; Kim, Sung-Hoon

2013-01-01

The metabolic syndrome creates risk factors for coronary heart disease, diabetes, fatty liver, obesity and several cancers. Our group has already reported that the essential oil from leaves of Pinus koraiensis SIEB (EOPK) exerted antihyperlipidemic effects by upregulating the low-density lipoprotein receptor and inhibiting acyl-coenzyme A, cholesterol acyltransferases. We evaluated in the current study the anti-diabetic effects of EOPK on mice with streptozotocin (STZ)-induced type I diabetes and on HIT-T15 pancreatic β cells. EOPK significantly protected HIT-T15 cells from STZ-induced cytotoxicity and reduced the blood glucose level in STZ-induced diabetic mice when compared with the untreated control. EOPK consistently and significantly suppressed the α-amylase activity in a dose-dependent manner and enhanced the expression of insulin at the mRNA level in STZ-treated HIT-T15 cells, while the expression of insulin was attenuated. EOPK also significantly abrogated the population of reactive oxygen species when compared to the untreated control in STZ-treated HIT-T15 cells. Furthermore, EOPK significantly reduce nitric oxide production, suppressed the phosphorylation of endothelial nitric oxide (NO) synthase and suppressed the production of vascular endothelial growth factor (VEGF) in STZ-treated HIT-T15 cells, implying its potential application to diabetic retinopathy. Overall, our findings suggest that EOPK had hypoglycemic potential by inhibiting reactive oxygene species (ROS), endothelial NO synthase (eNOS) and VEGF in STZ-treated mice and HIT-T15 pancreatic β cells as a potent anti-diabetic agent.

Effects of Linagliptin on Pancreatic α Cells of Type 1 Diabetic Mice.

PubMed

Zhang, Yanqing; Fava, Genevieve E; Wu, Meifen; Htun, Wynn; Klein, Thomas; Fonseca, Vivian A; Wu, Hongju

2017-10-01

The dipeptidyl peptidase-4 inhibitor linagliptin promotes β -cell survival and insulin secretion by prolonging endogenous glucagon-like peptide 1 (GLP-1) action and therefore helps to maintain normoglycemia in diabetic patients. The effect of linagliptin on glucagon-producing α cells, however, was not clear. In this study, we investigated whether linagliptin had any effects on α cells with regard to their proliferation and hormonal production using type 1 diabetes mouse models, including streptozotocin-induced and nonobese diabetes mice. After diabetes development, the mice were either untreated or treated with linagliptin or insulin for up to 6 weeks. Our results showed that linagliptin significantly increased circulating GLP-1 levels in both type 1 diabetes models, but therapeutic benefit was detected in nonobese diabetes mice only. Circulating C-peptide and glucagon levels (nonfasting) were not significantly altered by linagliptin treatment in either model. In addition, we found that linagliptin did not increase α -cell proliferation compared with the untreated or insulin-treated controls as assessed by in vivo 5-bromo-2'-deoxyuridine labeling assay. Finally, we examined whether linagliptin treatment altered GLP-1 vs glucagon expression in pancreatic α cells. Immunohistochemistry assays showed that linagliptin treatment resulted in detection of GLP-1 in more α cells than in control groups, suggesting linagliptin was able to increase intraislet GLP-1 presence, presumably by inhibiting GLP-1 degradation. In summary, this study indicates that linagliptin would not confer adverse effect on α cells, such as causing α cell hyperplasia, and instead may facilitate a blood glucose-lowering effect by increasing GLP-1 presence in α cells.

Relationship of clinical and microbiological variables in patients with type 1 diabetes mellitus and periodontitis.

PubMed

Sakalauskiene, Jurgina; Kubilius, Ricardas; Gleiznys, Alvydas; Vitkauskiene, Astra; Ivanauskiene, Egle; Šaferis, Viktoras

2014-10-08

The aim of the study was to analyze how metabolic control of type 1 diabetes is related to clinical and microbiological periodontal parameters. The study involved 56 subjects aged from 19 to 50 years divided into 2 groups: healthy subjects (the H group), and diabetic (type 1 diabetes) patients with chronic untreated generalized periodontitis (the DM group). The glycosylated hemoglobin value (HbA1c) was determined using the UniCel DxC 800 SYNCHRON System (Beckman Coulter, USA), and the concentration in blood was measured by the turbidimetric immunoinhibition method. A molecular genetic assay (Micro-IDent plus, Germany) was used to detect periodontopathogenic bacteria in plaque samples. Periodontitis was confirmed by clinical and radiological examination. Fusobacterium nucleatum, Capnocytophaga species, and Eikenella corrodens were the most frequently found bacteria in dental plaque samples (77.8%, 66.7%, and 33.4%, respectively), whereas Aggregatibacter actinomycetemcomitans was identified 40.7% less frequently in the DM group than in the H group. The strongest relationship was observed between the presence of 2 periodontal pathogens - F. nucleatum and Capnocytophaga spp. - and poorer metabolic control in type 1 diabetes patients (HbA1c) and all clinical parameters of periodontal pathology. Periodontal disease was more evident in type 1 diabetic patients, and the prevalence of periodontitis was greatly increased in subjects with poorer metabolic control.

Prevalence of depression and its associations with cardio-metabolic control in Aboriginal and Anglo-Celt patients with type 2 diabetes: the Fremantle Diabetes Study Phase II.

PubMed

Davis, Timothy M E; Hunt, Kerry; Bruce, David G; Starkstein, Sergio; Skinner, Timothy; McAullay, Daniel; Davis, Wendy A

2015-03-01

To determine the prevalence and associates of depression in Aboriginal and Anglo-Celt (AC) Australians with type 2 diabetes. Community-based patients were screened using the Patient Health Questionnaire (PHQ-9) as part of detailed assessment. The prevalence of any current depression, major depression and antidepressant use by racial group was compared after adjustment for age, sex, educational attainment and marital status. Multiple logistic regression was used to determine associates of current depression. The 107 Aboriginal participants were younger (mean±SD 54.3±11.8 vs. 67.2±10.6 years), less often male (34.6% vs. 50.9%) and married (39.3% vs. 61.7%), and more likely to smoke (44.6% vs. 8.1%) than the 793 AC subjects (P≤0.002). Fifty-two Aboriginal (48.5%) and 772 AC participants (97.4%) completed the PHQ-9; these Aboriginals had similar socio-demographic, anthropometric and diabetes-related characteristics to those without PHQ-9 data. A quarter of the Aboriginals had current depression vs 10.6% of ACs (P=0.16), 15.4% vs. 4.1% had major depression (P=0.029), and 68.8% vs. 29.7% had untreated depression (P=0.032). Compared with non-depressed participants, patients with current depression were younger and more likely to smoke, to be overweight/obese and to have worse glycaemic control (P≤0.024). Significant independent associates of current depression were educational attainment (inversely), smoking status, body mass index and fasting plasma glucose in the AC group and alcohol use in the Aboriginal group. Although prevalence of depression was not significantly increased in the Aboriginal patients, it was more likely to be major and untreated. Depression complicating type 2 diabetes is associated with adverse cardiovascular risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide 1.

PubMed

Yanay, Ofer; Moralejo, Daniel; Kernan, Kelly; Brzezinski, Margaret; Fuller, Jessica M; Barton, Randall W; Lernmark, Ake; Osborne, William R

2010-06-01

Type 1 diabetes (T1D) in both humans and BioBreeding (BB) rats is an autoimmune disease that results in complete destruction of islets and insulin dependency for life. Glucagon-like peptide 1 (GLP-1) promotes beta cell proliferation and neogenesis and has a potent insulinotropic effect. We hypothesized that the expression of GLP-1 before disease onset would increase islet mass, delay diabetes and prolong survival of BB rats. Vascular smooth muscle cells retrovirally transduced to secrete GLP-1 were seeded into TheraCyte encapsulation devices, implanted subcutaneously, and rats were monitored for diabetes. In untreated control rats, plasma GLP-1 levels were 34.5-39.5 pmol/l, whereas, in treated rats, plasma levels were elevated, in the range 90-250.4 pmol/l. Hypoglycemia was not detected and this was anticipated from the glucose-regulated action of GLP-1. Diabetes onset (mean + or - SEM) in untreated rats occurred at 56.5 + or - 0.6 days (n = 6) and, in GLP-1-treated rats, was delayed until 76.4 + or - 3.3 days (n = 5) (p < 0.001). After disease onset, untreated control rats showed a rapid weight loss and elevated blood glucose (>650 mg/dl) and did not survive beyond 11 days. At 5 days after diabetes onset, insulin-secreting islets were absent in untreated rats. By contrast, treated rats maintained weight for up to 143 days of age and showed insulin-secreting beta cells. Sustained GLP-1 expression delivered by encapsulated cells before diabetes onset in BB rats showed an improved clinical outcome, suggesting the potential for treating patients using long lasting GLP-1 analogs.

Antidiabetic and Antioxidant Impacts of Desert Date (Balanites aegyptiaca) and Parsley (Petroselinum sativum) Aqueous Extracts: Lessons from Experimental Rats

PubMed Central

Abou Khalil, Nasser S.; Abou-Elhamd, Alaa S.; Wasfy, Salwa I. A.; El Mileegy, Ibtisam M. H.; Hamed, Mohamed Y.; Ageely, Hussein M.

2016-01-01

Medicinal plants are effective in controlling plasma glucose level with minimal side effects and are commonly used in developing countries as an alternative therapy for the treatment of type 1 diabetes mellitus. The aim of this study is to evaluate the potential antidiabetic and antioxidant impacts of Balanites aegyptiaca and Petroselinum sativum extracts on streptozotocin-induced diabetic and normal rats. The influences of these extracts on body weight, plasma glucose, insulin, total antioxidant capacity (TAC), malondialdehyde (MDA) levels, and liver-pyruvate kinase (L-PK) levels were assessed. Furthermore, the weight and histomorphological changes of the pancreas were studied in the different experimental groups. The herbal preparations significantly reduced the mean plasma glucose and MDA levels and significantly increased the mean plasma insulin, L-PK, and TAC levels in the treated diabetic groups compared to the diabetic control group. An obvious increase in the weight of the pancreas and the size of the islets of Langerhans and improvement in the histoarchitecture were evident in the treated groups compared to untreated ones. In conclusion, the present study provides a scientific evidence for the traditional use of these extracts as antidiabetic and antioxidant agents in type 1 diabetes mellitus. PMID:27019854

[Evaluation of the burden of diabetes in Poland].

PubMed

Kissimova-Skarbek, K; Pach, D; Płaczkiewicz, E; Szurkowska, M; Szybiński, Z

2001-09-01

Burden of diabetes in terms of economic costs and life years lost due to premature deaths and disability in Poland is analyzed. This study calculates direct costs of type 1 and type 2 diabetes in Poland in 1998 and burden of diabetes in terms of years of life lost using Disability Adjusted Life Years (DALYs) measure within the Polish Multicenter Study of Diabetes Epidemiology (1998-1999). There is a consequent need to evaluate the burden of diabetes for the society and to develop affordable and cost-effective preventing strategies. The burden of diabetes is examined in terms of resources used by diabetic patients and time lost due to premature deaths and disability caused by diabetes. The profile of "a standard patient" (type 1 and type 2 diabetes) resource utilization is created using patient survey in Krakow. This includes main elements of cost associated with prevention, diagnosis and treatment: ambulatory care (visits); hospital care (bed/days and dialysis sessions); pharmaceuticals (goods consumed) and diagnosis (tests). This study calculates direct costs to the health sector of type 1 and type 2 diabetes in Poland 1998. Burden of diabetes in Poland in terms of time lost in 1998 is expressed in Disability Adjusted Life Years (DALYs) unit of measurement. DALY is a combination of two dimensions: YLL--number of years lost due to premature mortality; YLD--loss of healthy years due to disability caused by diabetes (with and without complications). The incidence approach is applied for the YLD caused by diabetes type 1 calculations by gender and age groups (0-29 years). Incidence rates are obtained from the prospective data collection [1, 2]. Other data as average age of onset, average duration of the disease (with or without complications), severity (age specific disability weight for treated or untreated forms of diabetes--with or without complications) are obtained from the GBD study for the Formerly Socialist Economies of Europe [9]. Discounting and age weighting procedure is applied. The prevalence approach is applied for YLD caused by diabetes type 2 calculations for treated and untreated forms of diabetes (with and without complications) by gender and age groups (35 years and more). Prevalence data are obtained from the Polish Multicenter Study on Diabetes Epidemiology. Age specific disability weights for treated or untreated forms of diabetes (with or without complication) are obtained from the GBD study for the Formerly Socialist Economies. Discounting procedure is not applied (duration of the disease is assumed 1 year). Years of Life Lost are calculated using Polish mortality data and life expectancy at the time of death in 1998. Cost of diabetes study is particularly useful in indicating the magnitude of the costs involved, which tend to be much higher than perceived by the general public. In 1998 the average diabetes type 1 patient's costs were 6.4 times and diabetes type 2 patient's costs 3 times higher than average public direct health care costs. The total costs of diabetes in Poland 1998 accounted for 9.3% of total public health care expenditures. The cost of diabetic patient's estimation indicates the potential benefits of effective medical interventions. Not only mortality rates should be taken into consideration in the creation of health policy and financial planning. Disability of the population is also an important factor, particularly in diseases which do not lead to fatalities. In 1998 112,584 DALYs (46% for males and 54% for females) were lost in Poland due to premature deaths and disability caused by diabetes. 72% of the total was due to disability. Secondary prevention is very important especially for diabetes type 2 patients. 95% of total time lost due to disability is caused by diabetes type 2. National burden of disease evaluation is helpful to develop a justifiable basis for setting priorities in purchasing and investing at central and local levels especially in prevention.

Featured Article: Inhibition of diabetic cataract by glucose tolerance factor extracted from yeast

PubMed Central

Cohen, Revital; Eliaz, Anat; Dovrat, Ahuva

2016-01-01

Diabetes leads to many complications; among them is the development of cataract. Hyperglycemia brings to increased polyol concentration in the lens, to glycation of lens proteins, and to elevated level of ROS (Reactive Oxygen Species) causing oxidative stress. The glucose tolerance factor (GTF) was found by several groups to decrease hyperglycemia and oxidative stress both in diabetic animals and humans. The aim of our study was to explore the damages induced by high glucose to the eye lens and to assess the protective effects of GTF both in vivo and in vitro. The in vivo study included control healthy rats, streptozotocin (STZ) diabetic untreated rats, and STZ diabetic rats orally treated with 15 doses of GTF. The diabetic untreated rats developed cataracts, whereas the development of cataract was totally or partially prevented in GTF treated animals. In vitro studies were done on bovine lenses incubated for 14 days. Half of the lenses were incubated in normal glucose conditions, and half in high glucose conditions (450 mg%). To one group of the normal or high glucose condition GTF was added. The optical quality of all the lenses was measured daily by an automated scanning laser system. The control lenses, whether with or without GTF addition, did not show any reduction in their quality. High glucose conditions induced optical damage to the lenses. Addition of GTF to high glucose conditions prevented this damage. High glucose conditions affected the activity of aldose reductase and sodium potassium ATPase in lens epithelial cell. Addition of GTF decreased the destructive changes induced by high glucose conditions. The amount of soluble cortical lens proteins was decreased and structural changes were detected in lenses incubated in high glucose medium. These changes could be prevented when GTF was added to high glucose medium. Our findings demonstrate the anticataractogenic potential of GTF. PMID:26825353

The effect of taurine and enriched environment on behaviour, memory and hippocampus of diabetic rats.

PubMed

Rahmeier, Francine Luciano; Zavalhia, Lisiane Silveira; Tortorelli, Lucas Silva; Huf, Fernanda; Géa, Luiza Paul; Meurer, Rosalva Thereza; Machado, Aryadne Cardoso; Gomez, Rosane; Fernandes, Marilda da Cruz

2016-09-06

Diabetes mellitus (DM) has been studied recently as a major cause of cognitive deficits, memory and neurodegenerative damage. Taurine and enriched environment have stood out for presenting neuroprotective and stimulating effects that deserve further study. In this paper, we examined the effects of taurine and enriched environment in the context of diabetes, evaluating effects on behaviour, memory, death and cellular activity. Eighty-eight Wistar rats were divided into 2 groups (E=enriched environment; C=standard housing). Some animals (24/group) underwent induction of diabetes, and within each group, some animals (half of diabetics (D) and half of non-diabetics (ND)/group) were treated for 30days with taurine (T). Untreated animals received saline (S). In total, there were eight subgroups: DTC, DSC, NDTC, NDSC, DTE, DSE, NDTE and NDSE. During the experiment, short-term memory was evaluated. After 30th day of experiment, the animals were euthanized and was made removal of brains used to immunohistochemistry procedures for GFAP and cleaved caspase-3. As a result, we observed that animals treated with taurine showed better performance in behavioural and memory tasks, and the enriched environment had positive effects, especially in non-diabetic animals. Furthermore, taurine and enriched environment seemed to be able to interfere with neuronal apoptosis and loss of glial cells, and in some instances, these two factors seemed to have synergistic effects. From these data, taurine and enriched environment may have important neurostimulant and neuroprotective effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Amelioration of Hyperglycaemia, Oxidative Stress and Dyslipidaemia in Alloxan-Induced Diabetic Wistar Rats Treated with Probiotic and Vitamin C

PubMed Central

Aluwong, Tagang; Ayo, Joseph O.; Kpukple, Alkali; Oladipo, Olusola Olalekan

2016-01-01

Clinical and experimental evidence suggests that hyperglycaemia is responsible for the oxidative stress in diabetes mellitus. The study was designed to investigate the comparative effects of probiotic and vitamin C (Vit-C) treatments on hyperglycaemia, oxidative stress and dyslipidaemia in alloxan-induced diabetic rats. Type 1 diabetes (T1DM) was induced in male Wistar rats by a single intraperitoneal (i.p.) injection of alloxan (150 mg/kg). Six groups of the animals received the following treatment regimens for four weeks: (1) Normal saline, per os; (2) alloxan (150 mg/kg, i.p.); (3) alloxan (150 mg/kg) + insulin (4 U/kg, subcutaneously); (4) alloxan (150 mg/kg) + probiotic (4.125 × 106 CFU/100 mL per os); (5) alloxan (150 mg/kg) + Vit-C (100 mg/kg, i.m.); (6) alloxan (150 mg/kg) + probiotic (4.125 × 106 CFU/100 mL per os) + Vit-C (100 mg/kg, intramuscularly). Probiotic + Vit-C decreased (p < 0.05) blood glucose concentration in diabetic treated group, when compared with the untreated diabetic group. Probiotic + Vit-C reduced malondialdehyde concentration, in the serum, brain and kidneys, respectively, but increased the activity of antioxidant enzymes. Probiotic and Vit-C may be more effective than Vit-C alone, in ameliorating hyperglycaemia, oxidative stress and dyslipidaemia in alloxan-induced diabetic rats. PMID:27164129

Amelioration of Hyperglycaemia, Oxidative Stress and Dyslipidaemia in Alloxan-Induced Diabetic Wistar Rats Treated with Probiotic and Vitamin C.

PubMed

Aluwong, Tagang; Ayo, Joseph O; Kpukple, Alkali; Oladipo, Olusola Olalekan

2016-05-05

Clinical and experimental evidence suggests that hyperglycaemia is responsible for the oxidative stress in diabetes mellitus. The study was designed to investigate the comparative effects of probiotic and vitamin C (Vit-C) treatments on hyperglycaemia, oxidative stress and dyslipidaemia in alloxan-induced diabetic rats. Type 1 diabetes (T1DM) was induced in male Wistar rats by a single intraperitoneal (i.p.) injection of alloxan (150 mg/kg). Six groups of the animals received the following treatment regimens for four weeks: (1) Normal saline, per os; (2) alloxan (150 mg/kg, i.p.); (3) alloxan (150 mg/kg) + insulin (4 U/kg, subcutaneously); (4) alloxan (150 mg/kg) + probiotic (4.125 × 10⁶ CFU/100 mL per os); (5) alloxan (150 mg/kg) + Vit-C (100 mg/kg, i.m.); (6) alloxan (150 mg/kg) + probiotic (4.125 × 10⁶ CFU/100 mL per os) + Vit-C (100 mg/kg, intramuscularly). Probiotic + Vit-C decreased (p < 0.05) blood glucose concentration in diabetic treated group, when compared with the untreated diabetic group. Probiotic + Vit-C reduced malondialdehyde concentration, in the serum, brain and kidneys, respectively, but increased the activity of antioxidant enzymes. Probiotic and Vit-C may be more effective than Vit-C alone, in ameliorating hyperglycaemia, oxidative stress and dyslipidaemia in alloxan-induced diabetic rats.

Application of platelet derived growth factor-BB and diabetic wound healing: the relationship with oxidative events.

PubMed

Gökşen, Sibel; Balabanlı, Barbaros; Coşkun-Cevher, Şule

2017-05-01

The reasons that cause delay in wound healing in diabetes are a decrease in the level of growth factors secretion, an increase in the destruction of growth factors and in oxidative stress. Platelet derived growth factor (PDGF) is one of the important growth factors that play a role in all phases of wound healing. This study investigates time-dependent effects of topically PDGF-BB administration on oxidative events on the healing of dorsolateral-excisional wounds in diabetic rats. Forty-two female Wistar-albino rats with streptozotocin-induced diabetes were divided into four groups: control group, untreated group, chitosan-treated group, chitosan + PDGF-BB-treated group. Two identical full-thickness excisional skin wounds were made under anaesthesia in all rats except for the control group. In the PDGF-BB-treated and chitosan-treated groups, the wounds were treated topically PDGF-BB (7 ng/mL, single daily dose) and blank chitosan gel (equal amount) after wounding, respectively. After these administrations, on day 3 and day 7 of wound healing, rats were sacrificed. Thiobarbituric acid reactive substances, glutathione, nitric oxide, ascorbic acid levels, and superoxide dismutase activity in wound tissues were spectrophotometrically measured. PDGF-BB administration significantly increased TBARS levels and non-enzymatic antioxidant levels in early phase of diabetic wound healing. PDGF-BB dramatically reduced NO x levels on day 3 and sharply increased NO x levels on day 7 of wound healing. Consequently, PDGF-BB administration can be effective on oxidative balance in the early phase of diabetic wound healing.

Serum uric acid change and modification of blood pressure and fasting plasma glucose in an overall healthy population sample: data from the Brisighella heart study.

PubMed

Cicero, Arrigo F G; Rosticci, Martina; Bove, Marilisa; Fogacci, Federica; Giovannini, Marina; Urso, Riccardo; D'Addato, Sergio; Borghi, Claudio

2017-06-01

Serum uric acid (SUA) is an emerging risk factor for incident hypertension and type 2 diabetes. It is less clear if changes in SUA are associated to different incidence in these main cardiovascular risk factors. From the cohort of the Brisighella Heart Study, we selected non-diabetic subjects that in 2008 were untreated with SUA-lowering drugs nor antihypertensive ones. Then we divided the subjects in four main groups: the ones that maintained their SUA level unchanged during the next 4 years, the ones that increased it >1 mg/dL without treatment, the ones that reduced it >1 mg/dL without drug treatment and the ones that reduced it >1 mg/dL with the continuous use of allopurinol. Compared with 2008, SBP significantly increased in subjects with worsened (and untreated) SUA level, while improved in subjects treated with allopurinol (p < 0.05). In 2012, subjects with worsened (and untreated) SUA level had a significantly higher SBP compared with subjects with unchanged SUA and those with SUA improved after allopurinol treatment (p < 0.05). An identical trend has been observed as it regards FPG. It seems that SUA improvement could positively influence the age-related worsening of SBP and FPG in general population. Key messages Serum uric acid (SUA) is an emerging risk factor for incident hypertension and type 2 diabetes. SUA improvement could positively influence the age-related worsening of SBP and FPG in general population.

DPP IV inhibitor treatment attenuates bone loss and improves mechanical bone strength in male diabetic rats.

PubMed

Glorie, Lorenzo; Behets, Geert J; Baerts, Lesley; De Meester, Ingrid; D'Haese, Patrick C; Verhulst, Anja

2014-09-01

Dipeptidyl peptidase IV (DPP IV) modulates protein activity by removing dipeptides. DPP IV inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. DPP IV substrates not only increase insulin secretion but also affect bone metabolism. In this study, the effect of DPP IV inhibitor sitagliptin on bone was evaluated in normal and streptozotocin-induced diabetic rats. This study included 64 male Wistar rats divided into four groups (n = 16): two diabetic and two control groups. One diabetic and one control group received sitagliptin through drinking water. Tibiae were scanned every 3 wk using an in vivo μCT scanner. After 6 and 12 wk, rats were euthanized for histomorphometric analysis of bone parameters. The mechanical resistance of femora to fracture was assessed using a three-point bending test, and serum levels of bone metabolic markers were measured. Efficient DPP IV inhibition was achieved in sitagliptin-treated groups. Trabecular bone loss, the decrease in trabecular number, and the increase in trabecular spacing was attenuated through sitagliptin treatment in diabetic rats, as shown by in vivo μCT. Bone histomorphometry was in line with these results. μCT analysis furthermore showed that sitagliptin prevented cortical bone growth stagnation in diabetic rats, resulting in stronger femora during three-point bending. Finally, the serum levels of the resorption marker CTX-I were significantly lower in sitagliptin-treated diabetic animals compared with untreated diabetic animals. In conclusion, sitagliptin treatment attenuates bone loss and increases bone strength in diabetic rats probably through the reduction of bone resorption and independent of glycemic management. Copyright © 2014 the American Physiological Society.

Examining a Bidirectional Association Between Depressive Symptoms and Diabetes

PubMed Central

Golden, Sherita Hill; Lazo, Mariana; Carnethon, Mercedes; Bertoni, Alain G.; Schreiner, Pamela J.; Roux, Ana V. Diez; Lee, Hochang Benjamin; Lyketsos, Constantine

2008-01-01

Context Depressive symptoms are associated with development of type 2 diabetes, but it is unclear whether type 2 diabetes is a risk factor for elevated depressive symptoms. Objective To examine the bidirectional association between depressive symptoms and type 2 diabetes. Design, Setting, and Participants Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000-2002 and followed up until 2004-2005. Main Outcome Measures Elevated depressive symptoms defined by Center for Epidemiologic Studies Depression Scale (CES-D) score of 16 or higher, use of antidepressant medications, or both. The CES-D score was also modeled continuously. Participants were categorized as normal fasting glucose (<100 mg/dL), impaired fasting glucose (100-125 mg/dL), or type 2 diabetes (≥126 mg/dL or receiving treatment). Analysis 1 included 5201 participants without type 2 diabetes at baseline and estimated the relative hazard of incidenttype2diabetesover3.2yearsforthosewithandwithoutdepressivesymptoms.Analysis 2 included 4847 participants without depressive symptoms at baseline and calculated the relative odds of developing depressive symptoms over 3.1 years for those with and without type 2 diabetes. Results In analysis 1, the incidence rate of type 2 diabetes was 22.0 and 16.6 per 1000 person-years for those with and without elevated depressive symptoms, respectively. The risk of incident type 2 diabetes was 1.10 times higher for each 5-unit increment in CES-D score (95% confidence interval [CI], 1.02-1.19) after adjustment for demographic factors and body mass index. This association persisted following adjustment for metabolic, inflammatory, socioeconomic, or lifestyle factors, although it was no longer statistically significant following adjustment for the latter (relative hazard, 1.08; 95% CI, 0.99-1.19). In analysis 2, the incidence rates of elevated depressive symptoms per 1000-person years were 36.8 for participants with normal fasting glucose; 27.9 for impaired fasting glucose; 31.2 for untreated type 2 diabetes, and 61.9 for treated type 2 diabetes. Compared with normal fasting glucose, the demographic–adjusted odds ratios of developing elevated depressive symptoms were 0.79 (95% CI, 0.63-0.99) for impaired fasting glucose, 0.75 (95% CI, 0.44-1.27) for untreated type 2 diabetes, and 1.54 (95% CI, 1.13-2.09) for treated type 2 diabetes. None of these associations with incident depressive symptoms were materially altered with adjustment for body mass index, socioeconomic and lifestyle factors, and comorbidities. Findings in both analyses were comparable across ethnic groups. Conclusions A modest association of baseline depressive symptoms with incident type 2 diabetes existed that was partially explained by lifestyle factors. Impaired fasting glucose and untreated type 2 diabetes were inversely associated with incident depressive symptoms, whereas treated type 2 diabetes showed a positive association with depressive symptoms. These associations were not substantively affected by adjustment for potential confounding or mediating factors. PMID:18560002

Oral Health Knowledge, Attitudes and Behaviors of Parents of Children with Diabetes Compared to Those of Parents of Children without Diabetes.

PubMed

Sohn, Hyun A; Rowe, Dorothy J

2015-06-01

To compare the oral health knowledge, attitudes, and behaviors of parents of children, aged 6 to 13, who have type 1 (insulin-dependent) diabetes to those of parents of similarly aged children without diabetes. The study population consisted of 46 parents of children with diabetes and 46 parents of children without diabetes from outpatient clinics, providing medical care to children with and without diabetes, respectively. After gaining permission of clinic directors, the investigator approached parents, who were waiting in the clinics' reception areas, to complete the 33-item survey. The survey included questions on socio-demographic characteristics, their child's oral hygiene practices, dental visits, dietary habits, their own oral health knowledge and attitudes, and their child's diabetic condition, when relevant. A Chi-square test was used to determine significant differences between responses of the two groups of parents. All parents approached completed the survey. Children with diabetes had significantly less frequent sugary drink consumption and less untreated dental caries than children without diabetes. The majority of parents of children with diabetes selected "don't know" for statements related to diabetes and oral health, whereas most parents of children without diabetes agreed with the statements, resulting in significant differences between groups. Most parents of children with diabetes considered these same statements important to them, while the importance to parents of children without diabetes was variable. To maintain their children's oral health, parents of children with diabetes must receive more education regarding the prevention and control of the oral complications of diabetes. Copyright © 2015 The American Dental Hygienists’ Association.

Anti-Diabetic Potential of Ocimum gratissimum Leaf Fractions in Fortified Diet-Fed Streptozotocin Treated Rat Model of Type-2 Diabetes

PubMed Central

Umar, Isamila A.; James, Dorcas B.; Inuwa, Hajiya M.

2017-01-01

Background: Ocimum gratissimum (OG) is used in the traditional management of diabetes in Nigeria. This study investigated the anti-diabetic potential of OG leaf fractions (OGLF) in a rat model of Type-2 diabetes (T2D). Methods: Methanol crude extract of OG leaf was fractionated with solvents of increasing order of polarity (n-hexane, chloroform, ethyl-acetate, n-butanol and water). The anti-diabetic potential of the fractions was evaluated in vivo. T2D was induced in Albino Wistar rats and treated with OGLF. Results: The T2D rats showed significant elevation in serum levels of fasting blood glucose (FBG), liver and kidney function biomarkers. At 4-week of intervention with OGLF, the untreated diabetic control group maintained severe hyperglycaemia in the presence of 61.7% serum insulin, 17.3% pancreatic β-cell function (HOMA-β) and 51.5% Insulin sensitivity. The glucose tolerance ability was enhanced in the n-butanol-fraction (OGb) treated group. With 74.8% available serum insulin and 38.6% improvement in insulin sensitivity, the OGb treated group had a 63.5% reduction in FBG and it was found to be most effective as it ameliorates a majority of the changes caused in the studied parameters in diabetic rats. Conclusions: The data from this study suggest that OGb fraction is a potential candidate for the development of an effective drug for the management of T2D. PMID:29019956

Anti-Diabetic Potential of Ocimum gratissimum Leaf Fractions in Fortified Diet-Fed Streptozotocin Treated Rat Model of Type-2 Diabetes.

PubMed

Okoduwa, Stanley I R; Umar, Isamila A; James, Dorcas B; Inuwa, Hajiya M

2017-10-11

Background : Ocimum gratissimum (OG) is used in the traditional management of diabetes in Nigeria. This study investigated the anti-diabetic potential of OG leaf fractions (OGLF) in a rat model of Type-2 diabetes (T2D). Method : Methanol crude extract of OG leaf was fractionated with solvents of increasing order of polarity ( n -hexane, chloroform, ethyl-acetate, n -butanol and water). The anti-diabetic potential of the fractions was evaluated in vivo. T2D was induced in Albino Wistar rats and treated with OGLF. Result : The T2D rats showed significant elevation in serum levels of fasting blood glucose (FBG), liver and kidney function biomarkers. At 4-weeks of intervention with OGLF, the untreated diabetic control group maintained severe hyperglycaemia in the presence of 61.7% serum insulin, 17.3% pancreatic β-cell function (HOMA-β) and 51.5% Insulin sensitivity. The glucose tolerance ability was enhanced in the n -butanol-fraction (OGb) treated group. With 74.8% available serum insulin and 38.6% improvement in insulin sensitivity, the OGb treated group had a 63.5% reduction in FBG and it was found to be most effective as it ameliorates a majority of the changes caused in the studied parameters in diabetic rats. Conclusions : The data from this study suggest that OGb fraction is a potential candidate for the development of an effective drug for the management of T2D.

N-acetylcysteine prevents nitrosative stress-associated depression of blood pressure and heart rate in streptozotocin diabetic rats.

PubMed

Nagareddy, Prabhakara Reddy; Xia, Zhengyuan; MacLeod, Kathleen M; McNeill, John H

2006-04-01

Previous studies have indicated that cardiovascular abnormalities such as depressed blood pressure and heart rate occur in streptozotocin (STZ) diabetic rats. Chronic diabetes, which is associated with increased expression of inducible nitric oxide synthase (iNOS) and oxidative stress, may produce peroxynitrite/nitrotyrosine and cause nitrosative stress. We hypothesized that nitrosative stress causes cardiovascular depression in STZ diabetic rats and therefore can be corrected by reducing its formation. Control and STZ diabetic rats were treated orally for 9 weeks with N-acetylcysteine (NAC), an antioxidant and inhibitor of iNOS. At termination, the mean arterial blood pressure (MABP) and heart rate (HR) were measured in conscious rats. Nitrotyrosine and endothelial nitric oxide synthase (eNOS) and iNOS expression were assessed in the heart and mesenteric arteries by immunohistochemistry and Western blot experiments. Untreated diabetic rats showed depressed MABP and HR that was prevented by treatment with NAC. In untreated diabetic rats, levels of 15-F(2t)-isoprostane, an indicator of lipid peroxidation increased, whereas plasma nitric oxide and antioxidant concentrations decreased. Furthermore, decreased eNOS and increased iNOS expression were associated with elevated nitrosative stress in blood vessel and heart tissue of untreated diabetic rats. N-acetylcysteine treatment of diabetic rats not only restored the antioxidant capacity but also reduced the expression of iNOS and nitrotyrosine and normalized the expression of eNOS to that of control rats in heart and superior mesenteric arteries. The results suggest that nitrosative stress depress MABP and HR following diabetes. Further studies are required to elucidate the mechanisms involved in nitrosative stress mediated depression of blood pressure and heart rate.

Butanol fraction of Parkia biglobosa (Jacq.) G. Don leaves enhance pancreatic β-cell functions, stimulates insulin secretion and ameliorates other type 2 diabetes-associated complications in rats.

PubMed

Ibrahim, Mohammed Auwal; Habila, James Dama; Koorbanally, Neil Anthony; Islam, Md Shahidul

2016-05-13

Ethnopharmacological surveys have reported that Parkia biglobosa (Jacq.) G. Don (Leguminosae) is among the plants commonly used in the traditional management of diabetes mellitus in Nigeria and Togo. This study investigated the anti-diabetic activity of the butanol fraction of P. biglobosa leaves (PBBF) in a type 2 diabetes (T2D) model of rats and a possible bioactive compound in the fraction. T2D was induced by feeding rats with a 10% fructose solution ad libitum for two weeks followed by an intraperitoneal injection of 40mg/kg body weight streptozotocin and the animals were orally treated with 150 and 300mg/kg BW of the PBBF for five days in a week. Another group of rats was non-diabetic but similarly administered with 300mg/kg BW of the PBBF. Food and fluid intakes, body weight changes and blood glucose levels were monitored during the experiment while other relevant diabetes-associated parameters were measured at the end of the experiment. The PBBF treatments significantly (P<0.05) decreased the blood glucose levels and improved the glucose tolerance ability compared to untreated diabetic rats. Furthermore, the treatments were found to improve pancreatic β cell function (HOMA-β), stimulate insulin secretions, decrease insulin resistance (HOMA-IR), restore liver glycogen, ameliorate serum dyslipidaemia and prevent hepatic and renal damages compared to untreated diabetic rats. Phytochemical analysis of the fraction led to the isolation of lupeol which inhibited α-glucosidase and α-amylase in non-competitive and uncompetitive inhibition patterns respectively. It was concluded that PBBF possessed remarkable anti-T2D activity which is mediated through modulation of β-cell function and stimulation of insulin secretion and the lower dose (150mg/kg BW) was found optimum for anti-T2D activity compared to the high dose (300mg/kg BW) in this study. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The effect of the Ras homolog gene family (Rho), member A/Rho associated coiled-coil forming protein kinase pathway in atrial fibrosis of type 2 diabetes in rats.

PubMed

Chen, Jinling; Li, Qingqing; Dong, Ruiqing; Gao, Huikuan; Peng, Hui; Wu, Yongquan

2014-09-01

Diabetes mellitus promotes atrial structural remodeling, thereby producing atrial arrhythmogenicity. Atrial arrhythmia can substantially increase the risk of premature death. The aim of this study was to investigate the role of Ras homolog gene family, member A (RhoA)/Rho associated coiled-coil forming protein kinase (ROCK) in atrial fibrosis in diabetic hearts, and the effects of fasudil hydrochloride hydrate on atrial fibrosis. An eight-week-old male Sprague-Dawley rat model of type 2 diabetes was established using a high-fat diet combined with streptozotocin [30 mg/kg, once, intraperitoneal (i.p.)]. Animals were randomly divided into three groups: Control rats, untreated diabetic rats that received vehicle, and treated diabetic rats that received Rho kinase inhibitor fasudil hydrochloride hydrate (10 mg/kg/day, i.p., for 14 weeks). The morphological features of atrial fibrosis were observed using Masson staining. The mRNA expression levels of RhoA, ROCK1, ROCK2, type-I and type-III procollagen were assessed with quantitative polymerase chain reaction. The protein levels of RhoA, ROCK1 and ROCK2 were evaluated using western blot analysis. The atria of untreated diabetic rats showed evident atrial fibrosis as compared to the control rats; the mRNA expression levels of RhoA, ROCK1, ROCK2, type-I and type-III procollagen were upregulated; and the protein levels of RhoA, ROCK1 and ROCK2 were increased. The treatment with fasudil hydrochloride hydrate significantly reduced atrial fibrosis, mRNA levels of RhoA, ROCK1, ROCK2, type-I and type-III procollagen, and the protein levels of RhoA, ROCK1 and ROCK2. The results suggested that RhoA/ROCK was involved in atrial fibrosis, and that fasudil hydrochloride hydrate ameliorates atrial fibrosis through the RhoA/ROCK pathway in rats with type 2 diabetes.

The importance of morphometric radiographic vertebral assessment for the detection of patients who need pharmacological treatment of osteoporosis among postmenopausal diabetic Korean women.

PubMed

Choi, Y J; Yang, S-O; Shin, C S; Chung, Y-S

2012-08-01

Many diabetic patients with vertebral fractures remain undiagnosed and untreated. We found that more than two-thirds of osteoporotic diabetic women could not be identified for pharmacological treatment according to the NOF guidelines if without radiographic vertebral assessment. This study shows the importance of radiographic vertebral assessment for identifying patients who need treatment for osteoporosis in diabetic women. Diagnosis of vertebral fracture (VF) is important for identifying patients who need pharmacologic therapy for osteoporosis. However, many patients with vertebral fractures remain undiagnosed and untreated. This study evaluated the number of patients with VFs who would be unrecognized as candidates for osteoporosis treatments according to the National Osteoporosis Foundation (NOF) Clinician’s Guidelines to the Treatment of Osteoporosis, among postmenopausal diabetic Korean women without spinal imaging. A total of 873 postmenopausal diabetic women were enrolled. Lateral plain radiographs of the thoracolumbar spine and total hip BMD were obtained. The Fracture Risk Assessment Tool (FRAX®) probability was computed using the algorithm available online at http://www.shef.ac.uk/FRAX (South Korea version). The subjects with and without VFs were classified into candidates for osteoporosis treatment [Tx+by NOF] and not candidates for osteoporosis treatment [Tx−by NOF] according to the NOF pharmacologic treatment guidelines, regardless of the presence of VFs. Forty-six percent of postmenopausal diabetic womenhad morphometric VFs. Among the subjects with morphometric VFs, only 2% of the patients had previously diagnosed VFs by medical doctors. In addition, 73.6% of the patients with VFs were not included in the [Tx+by NOF] group, given the assumption of no radiographic diagnosis of VFs. With regard to increased risk of VFs in postmenopausal Korean women with type 2 diabetes mellitus, radiographic vertebral assessment would be useful for the clinical identification of osteoporosis and fractures.

Investigation of the effects of the level of glycemic control on erectile function and pathophysiological mechanisms in diabetic rats.

PubMed

Cho, Sung Yong; Chai, Ji Sun; Lee, Sun Hee; Park, Kwanjin; Paick, Jae-Seung; Kim, Soo Woong

2012-06-01

Poor glycemic control is associated with erectile dysfunction (ED); however, differences in ED according to the level of glycemic control have been poorly investigated. The aim of this paper is to investigate the change in erectile function according to the level of glycemic control and to clarify the pathophysiological mechanism of diabetes-associated ED. Streptozotocin was injected into 55 male Sprague-Dawley rats classified into four groups: control (group 1), diabetes with multiple insulin injections (group 2), diabetes with a single injection (group 3), and untreated diabetes (group 4). Daily insulin injections in groups 2 and 3 were administered for 4 weeks after 10 weeks of diabetic induction. The main outcome measures are the anova or Kruskal-Wallis tests to evaluate glycosylated hemoglobin (HbA1c), testosterone levels, the ratios of intracavernosal pressure to mean arterial pressure (ICP/MAP), area under the ICP curve to MAP (AUC/MAP), and changes in cavernous tissue and protein expression related to Rho kinase and nitric oxide pathways. HbA1c levels were different between pairs of groups. Group 4 showed the lowest erectile parameters and group 2 showed near normal level. No differences in erectile parameters were found between groups 1 and 2 or between groups 3 and 4, except the ratio of AUC to MAP for group 1 was significantly higher than that of group 2 (20 Hz stimulation). Decrease in erectile function of group 2 was related to decreased expression of nitrergic nitric oxide synthase or decreased testosterone level compared with group 1. Groups 2 and 3 showed significant differences in erectile parameters, which were associated with difference in apoptotic index. Groups 3 and 4 showed no differences in erectile parameters, although these groups had significant differences in apoptotic index, smooth muscle component, and protein expression ratios of phosphorylated to total myosin phosphatase target subunit 1, endothelial nitric oxide synthase, and Akt. Improvement in glycemic control assists recovery from diabetes-associated ED; however, only tight glycemic control can provide recovery from ED to a near normal status. © 2012 International Society for Sexual Medicine.

Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus.

PubMed

Ezquer, Fernando; Giraud-Billoud, Maximiliano; Carpio, Daniel; Cabezas, Fabián; Conget, Paulette; Ezquer, Marcelo

2015-01-01

The aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and very low number of donor cells was found in the kidney of DM + MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected.

Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus

PubMed Central

Ezquer, Fernando; Giraud-Billoud, Maximiliano; Carpio, Daniel; Cabezas, Fabián; Conget, Paulette

2015-01-01

The aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and very low number of donor cells was found in the kidney of DM + MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected. PMID:26167475

Anti-diabetic effect of dietary mango (Mangifera indica L.) peel in streptozotocin-induced diabetic rats.

PubMed

Gondi, Mahendranath; Basha, Shaik Akbar; Bhaskar, Jamuna J; Salimath, Paramahans V; Rao, Ummiti J S Prasada

2015-03-30

In the present study, the composition of mango peel powder (MPP) collected from the mango pulp industry was determined and the effect of MPP on ameliorating diabetes and its associated complications was studied. Mango peel was rich in polyphenols, carotenoids and dietary fibre. Peel extract contained various bioactive compounds and was found to be rich in soluble dietary fibre. Peel extract exhibited antioxidant properties and protected against DNA damage. Therefore, the effect of peel on ameliorating diabetes was investigated in a rat model of diabetes. A significant increase in urine sugar, urine volume, fasting blood glucose, total cholesterol, triglycerides and low density lipoprotein, and decrease in high density lipoprotein were observed in the rats; however, these parameters were ameliorated in diabetic rats fed with diet supplemented with mango peel at 5% and 10% levels in basal diet. Treatment of diabetic rats with MPP increased antioxidant enzyme activities and decreased lipid peroxidation in plasma, kidney and liver compared to untreated diabetic rats. Glomerular filtration rate and microalbuminuria levels were ameliorated in MPP treated diabetic group. Mango peel, a by-product, can be used as an ingredient in functional and therapeutic foods. © 2014 Society of Chemical Industry.

Improvement of Insulin Secretion and Pancreatic β-cell Function in Streptozotocin-induced Diabetic Rats Treated with Aloe vera Extract

PubMed Central

Noor, Ayesha; Gunasekaran, S.; Vijayalakshmi, M. A.

2017-01-01

Background: Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. Plant extracts and their products are being used as an alternative system of medicine for the treatment of diabetes. Aloe vera has been traditionally used to treat several diseases and it exhibits antioxidant, anti-inflammatory, and wound-healing effects. Streptozotocin (STZ)-induced Wistar diabetic rats were used in this study to understand the potential protective effect of A. vera extract on the pancreatic islets. Objective: The aim of the present study was to evaluate the A. vera extract on improvement of insulin secretion and pancreatic β-cell function by morphometric analysis of pancreatic islets in STZ-induced diabetic Wistar rats. Materials and Methods: After acclimatization, male Wistar rats, maintained as per the Committee for the Purpose of Control and Supervision of Experiments on Animals guidelines, were randomly divided into four groups of six rats each. Fasting plasma glucose and insulin levels were assessed. The effect of A. vera extract in STZ-induced diabetic rats on the pancreatic islets by morphometric analysis was evaluated. Results: Oral administration of A. vera extract (300 mg/kg) daily to diabetic rats for 3 weeks showed restoration of blood glucose levels to normal levels with a concomitant increase in insulin levels upon feeding with A. vera extract in STZ-induced diabetic rats. Morphometric analysis of pancreatic sections revealed quantitative and qualitative gain in terms of number, diameter, volume, and area of the pancreatic islets of diabetic rats treated with A. vera extract when compared to the untreated diabetic rats. Conclusion: A. vera extract exerts antidiabetic effects by improving insulin secretion and pancreatic β-cell function by restoring pancreatic islet mass in STZ-induced diabetic Wistar rats. SUMMARY Fasting plasma glucose (FPG) and insulin levels were restored to normal levels in diabetic rats treated with Aloe vera extractIslets of pancreas were qualitatively and quantitatively restored to normalcy leading to restoration of FPG and insulin levels of diabetic rats treated with Aloe vera extractMorphometric analysis of pancreatic sections revealed quantitative and qualitative gain in terms of number, diameter, volume, and area of the pancreatic islets of diabetic rats treated with Aloe vera extract when compared to the untreated diabetic rats. Abbreviations Used: A. vera, FPG: Fasting plasma glucose, STZ: Streptozotocin, BW: Body weight PMID:29333050

Pivotal role of oxidative stress in tumor metastasis under diabetic conditions in mice.

PubMed

Ikemura, Mai; Nishikawa, Makiya; Kusamori, Kosuke; Fukuoka, Miho; Yamashita, Fumiyoshi; Hashida, Mitsuru

2013-09-10

Diabetic patients are reported to have a high incidence and mortality of cancer, but little is known about the linkage. In this study, we investigated whether high oxidative stress is involved in the acceleration of tumor metastasis in diabetic mice. Murine melanoma B16-BL6 cells stably labeled with firefly luciferase (B16-BL6/Luc) were inoculated into the tail vein of streptozotocin (STZ)-treated or untreated mice. A luciferase assay demonstrated that tumor cells were present largely in the lung of untreated mice, whereas large numbers of tumor cells were detected in both the lung and liver of STZ-treated mice. Repeated injections of polyethylene glycol-conjugated catalase (PEG-catalase), a long-circulating derivative, reduced the elevated fasting blood glucose levels and plasma lipoperoxide levels of STZ-treated mice, but had no significant effects on these parameters in untreated mice. In addition, the injections significantly reduced the number of tumor cells in the lung and liver in both untreated and STZ-treated mice. Culture of B16-BL6/Luc cells in medium containing over 45 mg/dl glucose hardly affected the proliferation of the cells, whereas the addition of plasma of STZ-treated mice to the medium significantly increased the number of cells. Plasma samples of STZ-treated mice receiving PEG-catalase exhibited no such effect on proliferation. These findings indicate that a hyperglycemia-induced increase in oxidative stress is involved in the acceleration of tumor metastasis, and the removal of systemic hydrogen peroxide by PEG-catalase can inhibit the progression of diabetic conditions and tumor metastasis in diabetes. Copyright © 2013 Elsevier B.V. All rights reserved.

Vascular mechanisms of cyanidin-3-glucoside response in streptozotocin-diabetic rats.

PubMed

Nasri, Sima; Roghani, Mehrdad; Baluchnejadmojarad, Tourandokht; Rabani, Tahereh; Balvardi, Mahboubeh

2011-09-01

Considering the high incidence of cardiovascular disorders in diabetes mellitus and some evidence on the antioxidant and antidiabetic potential of cyanidin-3-glucoside (C3G), this study was conducted to evaluate the possible beneficial effect of C3G administration on vascular reactivity of isolated thoracic aorta in diabetic rats and some of its underlying mechanisms. Male diabetic rats received C3G (10mg/kg; i.p.) on alternate days for 8 weeks one week after streptozotocin (STZ) diabetes induction. It was found out that treatment of diabetic rats with C3G exerted a hypoglycaemic effect and attenuated the increased malondialdehyde (MDA) content and reduced the activity of superoxide dismutase (SOD) in aortic tissue. Maximum contractile response of endothelium-intact aortic rings to phenylephrine (PE) was significantly lower in C3G-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine (ACh) was significantly higher in C3G-treated diabetic rats as compared to diabetic group. Chronic treatment with C3G may prevent some diabetes-related changes in vascular reactivity observed in diabetic rats directly and/or indirectly due to its hypoglycaemic effect and attenuation of lipid peroxidation and through endothelial-derived factors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Ocular pulse amplitude after panretinal photocoagulation in normotensive eyes with proliferative diabetic retinopathy.

PubMed

Bozic, Marija M; Karadzic, Jelena B; Kovacevic, Igor M; Marjanovic, Ivan S

2017-06-26

To assess the effect of panretinal laser photocoagulation on ocular pulse amplitude (OPA) in normotensive eyes with proliferative diabetic retinopathy. Prospectively, we performed unilateral argon laser panretinal photocoagulation (PRP) in 30 patients with diabetes mellitus type II and previously untreated bilateral proliferative diabetic retinopathy. Before and 7 and 30 days after the treatment, OPA was measured using dynamic contour tonometer. Compared with the untreated contralateral eyes, laser photocoagulation led to a reduction of OPA. Ocular pulse amplitude did not significantly differ in photocoagulated eyes 7 days after the treatment, but there was a significant difference in OPA 30 days after the treatment. The decrease in OPA values was 15% 7 days after PRP and 40% 30 days after PRP. Ocular pulse amplitude reduction after PRP indirectly informs us about choriocapillary closure, already reported in previous studies.

Treating fat grafts with human endothelial progenitor cells promotes their vascularization and improves their survival in diabetes mellitus.

PubMed

Hamed, Saher; Ben-Nun, Ohad; Egozi, Dana; Keren, Aviad; Malyarova, Nastya; Kruchevsky, Danny; Gilhar, Amos; Ullmann, Yehuda

2012-10-01

Bone marrow-derived endothelial progenitor cells are required for vascularization of a fat graft to form a functional microvasculature within the graft and to facilitate its integration into the surrounding tissues. Organ transplantation carries a high risk of graft loss and rejection in patients with diabetes mellitus because endothelial progenitor cell function is impaired. The authors investigated the influence of endothelial progenitor cell treatment on the phenotype and survival of human fat grafts in immunocompromised mice with experimentally induced diabetes mellitus. The authors injected 1 ml of human fat tissue into the scalps of 14 nondiabetic and 28 diabetic immunocompromised mice, and then treated some of the grafts with endothelial progenitor cells that was isolated from the blood of a human donor. The phenotype of the endothelial progenitor cell-treated fat grafts from the 14 diabetic mice was compared with that of the untreated fat grafts from 14 nondiabetic and 14 diabetic mice, 18 days and 15 weeks after fat transplantation. Determination of graft phenotype included measurements of weight and volume, vascular endothelial growth factor levels, vascular endothelial growth factor receptor-2, endothelial nitric oxide synthase, and caspase 3 expression levels, and histologic analysis of the extent of vascularization. The untreated grafts from the diabetic mice were fully resorbed 15 weeks after fat transplantation. The phenotype of endothelial progenitor cell-treated fat grafts from the diabetic mice was similar to that of the untreated fat grafts from the nondiabetic mice. Endothelial progenitor cell treatment of transplanted fat can increase the survival of a fat graft by inducing its vascularization and decreasing the extent of apoptosis.

Anti-diabetic effect of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) fruit acetone fraction in a type 2 diabetes model of rats.

PubMed

Mohammed, Aminu; Koorbanally, Neil Anthony; Islam, Md Shahidul

2016-03-02

In traditional medicine from West Africa, the fruit decoction of Xylopia aethiopica (Dunal) A. Rich. is widely used for the treatment of diabetes mellitus (DM) either alone or in combination with other plants. The present study is designed to investigate the anti-diabetic effects of X. aethiopica acetone fraction (XAAF) from fruit ethanolic extract in a type 2 diabetes (T2D) model of rats. T2D was induced in rats by feeding a 10% fructose solution ad libitum for 2 weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight) and the animals were orally treated with 150 or 300 mg/kg body weight (bw) of the XAAF once daily for four weeks. After 4 weeks study period, diabetic untreated animals (DBC) exhibited significantly higher serum glucose, serum fructosamine, LDH, CK-MB, serum lipids, liver glycogen, insulin resistance (HOMA-IR), AI, CRI and lower serum insulin, β-cell function (HOMA-β) and glucose tolerance ability compared to the normal animals. Histopathological examination of their pancreas revealed corresponding pathological changes in the islets and β-cells. These alterations were reverted to near-normal after the treatment of XAAF at 150 (DXAL) and 300 (DXAH) mg/kg bw with the effects being more pronounced in the DXAH group compared to the DXAL group. Moreover, the effects in the animals of DXAH group were comparable to the diabetic metformin (DMF) treated animals. In addition, no significant alterations were observed in non-diabetic animals treated with 300 mg/kg bw of XAAF (NXAH). The results of our study suggest that XAAF treatment showed excellent anti-diabetic effects in a T2D model of rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Investigation of the in vivo antioxidative activity of Cynara scolymus (artichoke) leaf extract in the streptozotocin-induced diabetic rat.

PubMed

Magielse, Joanna; Verlaet, Annelies; Breynaert, Annelies; Keenoy, Begoña Manuel Y; Apers, Sandra; Pieters, Luc; Hermans, Nina

2014-01-01

The in vivo antioxidant activity of a quantified leaf extract of Cynara scolymus (artichoke) was studied. The aqueous artichoke leaf extract (ALE), containing 1.5% caffeoylquinic acid with chlorogenic acid being most abundant (0.30%), and luteolin-7-O-glucoside as major flavonoid (0.15%), was investigated by evaluating the effect on different oxidative stress biomarkers, after 3 wk oral supplementation in the streptozotocin-induced diabetic rat model. Apart from two test groups (0.2 g ALE/kg BW/day and 1 g ALE/kg BW/day, where BW is body weight), a healthy control group, untreated oxidative stress group, and vitamin E treated group (positive control) were included. A 0.2 g/kg BW/day of ALE decreased oxidative stress: malondialdehyde and 8-hydroxydeoxyguanosine levels significantly diminished, whereas erythrocyte glutathione levels significantly increased. A 1.0 g/kg BW/day ALE did not show higher antioxidant activity. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Right heart mechanics in untreated normotensive patients with prediabetes and type 2 diabetes mellitus: a two- and three-dimensional echocardiographic study.

PubMed

Tadic, Marijana; Celic, Vera; Cuspidi, Cesare; Ilic, Sanja; Pencic, Biljana; Radojkovic, Jana; Ivanovic, Branislava; Stanisavljevic, Dejana; Kocabay, Gonenc; Marjanovic, Tamara

2015-03-01

The aim of this study was to determine right ventricular (RV) and right atrial (RA) deformation assessed by two-dimensional echocardiographic and three-dimensional echocardiographic (3DE) imaging in patients with prediabetes and type 2 diabetes mellitus. This cross-sectional study included 47 untreated normotensive subjects with prediabetes, 57 recently diagnosed normotensive patients with diabetes, and 54 healthy controls of similar sex and age distributions. All subjects underwent laboratory analyses and complete two-dimensional echocardiographic and 3DE examinations. Three-dimensional echocardiographic RV end-diastolic volume index gradually decreased from controls across patients with diabetes to those with diabetes (69 ± 10 vs 63 ± 8 vs 58 ± 8 mL/m(2), P < .001), whereas 3DE RV end-systolic volume index was higher in controls compared with patients with diabetes and those with diabetes (25 ± 4 vs 23 ± 4 vs 22 ± 4 mL/m(2), P < .001). However, there was no difference in 3DE RV ejection fraction among the three groups (63 ± 4% vs 62 ± 4% vs 61 ± 5%, P = .063). RV and RA global strain and systolic and early diastolic strain rates were decreased in patients with prediabetes and in those with diabetes compared with controls, whereas RV and RA late diastolic strain rates were increased in these patients. Multivariate regression analysis showed that RV global strain was associated with glycated hemoglobin, independent of left ventricular parameters. RV and RA myocardial deformation and function obtained by 3DE and two-dimensional echocardiographic strain, even in normal ranges, were decreased in patients with prediabetes and in those with diabetes compared with controls. The long-term parameter of glucose control was correlated with the right heart mechanics. Copyright © 2015 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Aspartame Administration and Insulin Treatment Altered Brain Levels of CYP2E1 and CYP3A2 in Streptozotocin-Induced Diabetic Rats.

PubMed

Nosti-Palacios, Rosario; Gómez-Garduño, Josefina; Molina-Ortiz, Dora; Calzada-León, Raúl; Dorado-González, Víctor Manuel; Vences-Mejía, Araceli

2014-07-01

This study demonstrates that aspartame consumption and insulin treatment in a juvenile diabetic rat model leads to increase in cytochrome P450 (CYP) 2E1 and CYP3A2 isozymes in brain. Diabetes mellitus was induced in postweaned 21-day-old Wistar male rat by streptozotocin. Animals were randomly assigned to one of the following groups: untreated control, diabetic (D), D-insulin, D-aspartame, or the D-insulin + aspartame-treated group. Brain and liver tissue samples were used to analyze the activity of CYP2E1 and CYP3A2 and protein levels. Our results indicate that combined treatment with insulin and aspartame in juvenile diabetic rats significantly induced CYP2E1 in the cerebrum and cerebellum without modifying it in the liver, while CYP3A2 protein activity increased both in the brain and in the liver. The induction of CYP2E1 in the brain could have important in situ toxicological effects, given that this CYP isoform is capable of bioactivating various toxic substances. Additionally, CYP3A2 induction in the liver and brain could be considered a decisive factor in the variation of drug response and toxicity. © The Author(s) 2014.

Endothelin-1 and big endothelin-1 in NIDDM patients with and without microangiopathy.

PubMed

Kamoi, K; Ishibashi, M; Yamaji, T

1994-07-01

To examine a possible role for endothelin-1 in the pathophysiology of diabetic microangiopathy, we measured plasma levels of endothelin-1 and big endothelin-1, a precursor peptide of endothelin-1, in 33 untreated patients with non-insulin-dependent diabetes mellitus. There was no significant difference among the mean plasma endothelin-1 concentrations in 18 patients with microangiopathy, in 15 patients without microangiopathy and in 33 age-matched normal subjects. In contrast, the mean plasma big endothelin-1 concentration in patients with microangiopathy was significantly higher than in those without microangiopathy or in normal subjects. As a consequence, the mean big endothelin-1 to endothelin-1 ratio in patients with microangiopathy was significantly higher than in the other two groups. There was no significant correlation between plasma levels of endothelin-1 or big endothelin-1 and fasting blood glucose, HbA1c, mean blood pressure, or period of duration of diabetes mellitus in the patient groups. The results indicate that elevation of plasma big endothelin-1 levels with diminished conversion of big endothelin-1 to endothelin-1 is associated with diabetic microangiopathy, which may be the effect rather than the cause of endothelial dysfunction.

Effect of the Direct Renin Inhibitor Aliskiren on Urinary Albumin Excretion in Spontaneous Type 2 Diabetic KK-A y Mouse

PubMed Central

Furukawa, Masako; Horikoshi, Satoshi; Funabiki, Kazuhiko; Tomino, Yasuhiko

2013-01-01

Objective. Although angiotensin II-mediated inflammation and extracellular matrix accumulation are considered to be associated with the progression of diabetic nephropathy, these processes have not yet been sufficiently clarified. The objective of this study was to determine whether the correction of the abnormal renal expression of MMPs and its inhibitors (MMPs/TIMPs) and cytokines following the administration of aliskiren to KK-A y mice results in a renoprotective effect. Methods. KK-A y mice were divided into two groups, that is, untreated (saline) and treated (aliskiren) groups. Systolic BP, HbA1c levels, and the albumin-creatinine ratio (ACR) were measured. The renal expression of MMPs/TIMPs, fibronectin, type IV collagen, MCP-1, and (pro)renin receptor ((P)RR) was examined using real-time PCR and/or immunohistochemical staining. Renal MAPK and NF-κB activity were also examined by Western blot analyses and ELISA, respectively. Results. Significant decreases in systolic BP and ACR levels were observed in treated KK-A y mice compared with the findings in untreated KK-A y mice. Furthermore, increases in MMPs/TIMPs, fibronectin, type IV collagen, MCP-1, and (P)RR expression, in addition to MAPK and NF-κB activity, were significantly attenuated by aliskiren administration. Conclusions. It appears that aliskiren improves albuminuria and renal fibrosis by regulating inflammation and the alteration of collagen synthesis and degradation. PMID:23819050

Microperimetry and fundus autofluorescence in diabetic macular edema: subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation.

PubMed

Vujosevic, Stela; Bottega, Elisa; Casciano, Margherita; Pilotto, Elisabetta; Convento, Enrica; Midena, Edoardo

2010-06-01

The purpose of this study was to evaluate and compare microperimetry and fundus autofluorescence (FAF) after subthreshold micropulse diode laser versus modified Early Treatment Diabetic Retinopathy Study photocoagulation for clinically significant diabetic macular edema. A prospective randomized clinical trial including 62 eyes (50 patients) with untreated, center-involving, clinically significant diabetic macular edema was performed. All patients underwent best-corrected visual acuity determination (logarithm of the minimum angle of resolution), slit-lamp biomicroscopy, FAF, optical coherence tomography, microperimetry (macular sensitivity), and fluorescein angiography before and after treatment. Best-corrected visual acuity, optical coherence tomography, microperimetry, and FAF were repeated at 1-, 3-, 6-, 9-, and 12-month follow-up examinations. Fluorescein angiography was performed at baseline and at 6 and 12 months. Before treatment, demographic and macular parameters were not different between the two treatment groups. At 12 months, best-corrected visual acuity remained stable in both groups (P = 0.41 and P = 0.82), mean central retinal thickness decreased in both groups (P = 0.0002 and P < 0.0001), and mean central 4 degrees and 12 degrees retinal sensitivity increased in the micropulse diode laser group (P = 0.02 and P = 0.0075) and decreased in the Early Treatment Diabetic Retinopathy Study group (P = 0.2 and P = 0.0026). There was no significant difference in either best-corrected visual acuity or central retinal thickness between the 2 treatment groups (P = 0.48 and P = 0.29), whereas there was a significant difference in 4 degrees and 12 degrees retinal sensitivity (P = 0.04 and P < 0.0001). Fundus autofluorescence never changed in the micropulse diode laser group even after retreatment. In the Early Treatment Diabetic Retinopathy Study group, FAF increased up to 9 months and decreased in 6 eyes (20%) at 12 months. Micropulse diode laser seems to be as effective as modified Early Treatment Diabetic Retinopathy Study laser photocoagulation in the treatment of clinically significant diabetic macular edema. Micropulse diode laser treatment does not determine any change on FAF showing (at least) nonclinically visible damage of the retinal pigment epithelium. Microperimetry data encourage the use of a new, less aggressive laser therapeutic approach in the treatment of clinically significant diabetic macular edema.

Lubiprostone improves intestinal permeability in humans, a novel therapy for the leaky gut: A prospective randomized pilot study in healthy volunteers

PubMed Central

Honda, Yasushi; Kurita, Yusuke; Iwasaki, Akito; Sato, Takamitsu; Kessoku, Takaomi; Uchiyama, Shiori; Ogawa, Yuji; Ohkubo, Hidenori; Higurashi, Takuma; Yamanaka, Takeharu; Usuda, Haruki; Wada, Koichiro; Nakajima, Atsushi

2017-01-01

Background and aims The barrier function of the small intestinal mucosa prevents the introduction of undesired pathogens into the body. Breakdown of this barrier function increases intestinal permeability. This has been proposed to induce not only gastrointestinal diseases, including inflammatory bowel disease and irritable bowel syndrome, but also various other diseases, including allergies, diabetes mellitus, liver diseases, and collagen diseases, which are associated with this so called “leaky gut syndrome.” As such, a method to prevent leaky gut syndrome would have substantial clinical value. However, no drugs have been demonstrated to improve disturbed intestinal permeability in humans to date. Therefore, we investigated whether a drug used to treat chronic constipation, lubiprostone, was effective for this purpose. Methods Healthy male volunteers were treated with lubiprostone (24 μg/day) for 28 days. Intestinal permeability was evaluated by measuring the lactulose-mannitol ratio (LMR) after administration of diclofenac and compared with an untreated group. The examination was conducted three times in total, i.e., at baseline before diclofenac administration and after 14 and 28 days of lubiprostone treatment. Blood endotoxin activity was also evaluated at the same time points. Results The final analysis was conducted on 28 subjects (14 in the lubiprostone group and 14 in the untreated group). The LMR after 28 days of treatment was significantly lower in the lubiprostone group than that in the untreated group (0.017 vs. 0.028, respectively; 95% confidence interval, −0.022–−0.0001; p = 0.049). Blood endotoxin activity exhibited almost no change over time in the lubiprostone and untreated groups and displayed no significant differences at any time point of examination. Conclusions This study is the first to report an improvement in leaky gut using an available drug in humans. The result suggests that lubiprostone may prevent and ameliorate “leaky gut syndrome”. However, a pivotal trial is needed to confirm our finding. PMID:28410406

Lubiprostone improves intestinal permeability in humans, a novel therapy for the leaky gut: A prospective randomized pilot study in healthy volunteers.

PubMed

Kato, Takayuki; Honda, Yasushi; Kurita, Yusuke; Iwasaki, Akito; Sato, Takamitsu; Kessoku, Takaomi; Uchiyama, Shiori; Ogawa, Yuji; Ohkubo, Hidenori; Higurashi, Takuma; Yamanaka, Takeharu; Usuda, Haruki; Wada, Koichiro; Nakajima, Atsushi

2017-01-01

The barrier function of the small intestinal mucosa prevents the introduction of undesired pathogens into the body. Breakdown of this barrier function increases intestinal permeability. This has been proposed to induce not only gastrointestinal diseases, including inflammatory bowel disease and irritable bowel syndrome, but also various other diseases, including allergies, diabetes mellitus, liver diseases, and collagen diseases, which are associated with this so called "leaky gut syndrome." As such, a method to prevent leaky gut syndrome would have substantial clinical value. However, no drugs have been demonstrated to improve disturbed intestinal permeability in humans to date. Therefore, we investigated whether a drug used to treat chronic constipation, lubiprostone, was effective for this purpose. Healthy male volunteers were treated with lubiprostone (24 μg/day) for 28 days. Intestinal permeability was evaluated by measuring the lactulose-mannitol ratio (LMR) after administration of diclofenac and compared with an untreated group. The examination was conducted three times in total, i.e., at baseline before diclofenac administration and after 14 and 28 days of lubiprostone treatment. Blood endotoxin activity was also evaluated at the same time points. The final analysis was conducted on 28 subjects (14 in the lubiprostone group and 14 in the untreated group). The LMR after 28 days of treatment was significantly lower in the lubiprostone group than that in the untreated group (0.017 vs. 0.028, respectively; 95% confidence interval, -0.022--0.0001; p = 0.049). Blood endotoxin activity exhibited almost no change over time in the lubiprostone and untreated groups and displayed no significant differences at any time point of examination. This study is the first to report an improvement in leaky gut using an available drug in humans. The result suggests that lubiprostone may prevent and ameliorate "leaky gut syndrome". However, a pivotal trial is needed to confirm our finding.

Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type 1 diabetic mice.

PubMed

Ezquer, Fernando E; Ezquer, Marcelo E; Parrau, Daniela B; Carpio, Daniel; Yañez, Alejandro J; Conget, Paulette A

2008-06-01

Multipotent mesenchymal stromal cells (MSCs), often labeled mesenchymal stem cells, contribute to tissue regeneration in injured bone and cartilage, as well as in the infarcted heart, brain, and kidney. We hypothesize that MSCs might also contribute to pancreas and kidney regeneration in diabetic individuals. Therefore, in streptozotocin (STZ)-induced type 1 diabetes C57BL/6 mice, we tested whether a single intravenous dose of MSCs led to recovery of pancreatic and renal function and structure. When hyperglycemia, glycosuria, massive beta-pancreatic islets destruction, and mild albuminuria were evident (but still without renal histopathologic changes), mice were randomly separated in 2 groups: 1 received 0.5 x 10(6) MSCs that have been ex vivo expanded (and characterized according to their mesenchymal differentiation potential), and the other group received the vehicle. Within a week, only MSC-treated diabetic mice exhibited significant reduction in their blood glucose levels, reaching nearly euglycemic values a month later. Reversion of hyperglycemia and glycosuria remained for 2 months at least. An increase in morphologically normal beta-pancreatic islets was observed only in MSC-treated diabetic mice. Furthermore, in those animals albuminuria was reduced and glomeruli were histologically normal. On the other side, untreated diabetic mice presented glomerular hyalinosis and mesangial expansion. Thus, MSC administration resulted in beta-pancreatic islets regeneration and prevented renal damage in diabetic animals. Our preclinical results suggest bone marrow-derived MSC transplantation as a cell therapy strategy to treat type 1 diabetes and prevent diabetic nephropathy, its main complication.

Evaluation of toxicity after one-months treatment with Bauhinia forficata decoction in streptozotocin-induced diabetic rats

PubMed Central

Pepato, Maria Teresa; Baviera, Amanda Martins; Vendramini, Regina Célia; Brunetti, Iguatemy Lourenço

2004-01-01

Background Previous experiments have shown that a decoction of Bauhinia forficata leaves reduces the changes in carbohydrate and protein metabolism that occur in rats with streptozotocin-induced diabetes. In the present investigation, the serum activities of enzymes known to be reliable toxicity markers were monitored in normal and streptozotocin-diabetic rats to discover whether the use of B. forficata decoction has toxic effects on liver, muscle or pancreas tissue or on renal microcirculation. Methods An experimental group of normal and streptozotocin-diabetic rats received an aqueous decoction of fresh B. forficata leaves (150 g/L) by mouth for 33 days while a control group of normal and diabetic rats received water for the same length of time. The serum activity of the toxicity markers lactate dehydrogenase, creatine kinase, amylase, angiotensin-converting enzyme and bilirubin were assayed before receiving B. forficata decoction and on day 19 and 33 of treatment. Results The toxicity markers in normal and diabetic rats were not altered by the diabetes itself nor by treatment with decoction. Whether or not they received B. forficata decoction the normal rats showed a significant increase in serum amylase activity during the experimental period while there was a tendency for the diabetic rats, both treated and untreated with decoction, to have lower serum amylase activities than the normal rats. Conclusions Administration of an aqueous decoction of B. forficata is a potential treatment for diabetes and does not produce toxic effects measurable with the enzyme markers used in our study. PMID:15186500

Poly ADP-Ribose Polymerase Inhibition Ameliorates Hind Limb Ischemia Reperfusion Injury in a Murine Model of Type 2 Diabetes

PubMed Central

Long, Chandler A.; Boloum, Valy; Albadawi, Hassan; Tsai, Shirling; Yoo, Hyung-Jin; Oklu, Rahmi; Goldman, Mitchell H.; Watkins, Michael T.

2013-01-01

Introduction Diabetes is known to increase poly-ADP-ribose-polymerase (PARP) activity and posttranslational poly-ADP-ribosylation of several regulatory proteins involved in inflammation and energy metabolism. These experiments test the hypothesis that PARP inhibition will modulate hind limb ischemia reperfusion (IR) in a mouse model of type-II diabetes; ameliorate the ribosylation and the activity/transnuclear localization of the key glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Methods db/db mice underwent 1.5hrs of hind limb ischemia followed by 1, 7, or 24hrs reperfusion. The treatment group received the PARP inhibitor PJ34 (PJ34) over a 24hrs period; the untreated group received Lactated ringer’s (LR) at the same time points. IR muscles were analyzed for indices of PARP activity, fiber injury, metabolic activity, inflammation, GAPDH activity /intracellular localization and poly-ADP-ribosylation of GAPDH. Results PARP activity was significantly lower in the PJ34 treated groups compared to the LR group at 7 and 24 hours reperfusion. There was significantly less muscle fiber injury in the PJ34 treated group compared to LR treated mice at 24 hrs reperfusion. PJ34 lowered levels of select proinflammatory molecules at 7hrs and 24hrs IR. There were significant increases in metabolic activity only at 24 hours IR in the PJ34 group, which temporally correlated with increase in GAPDH activity, decreased GAPDH poly ADP-ribosylation and nuclear translocation of GAPDH. Conclusions PJ34 reduced PARP activity, GAPDH ribosylation, GAPDH translocation, ameliorated muscle fiber injury, and increased metabolic activity following hind limb IR injury in a murine model of type-II diabetes. PARP inhibition might be a therapeutic strategy following IR in diabetic humans. PMID:23549425

Red onion scales ameliorated streptozotocin-induced diabetes and diabetic nephropathy in Wistar rats in relation to their metabolite fingerprint.

PubMed

Abouzed, Tarek Kamal; Contreras, María Del Mar; Sadek, Kadry Mohamed; Shukry, Moustafa; H Abdelhady, Doaa; Gouda, Wael Mohamed; Abdo, Walied; Nasr, Nasr Elsayed; Mekky, Reham Hassan; Segura-Carretero, Antonio; Kahilo, Khaled Abdel-Aleim; Abdel-Sattar, Essam

2018-06-01

The present study was designed to investigate the effect of red onion scales extract (ROS) against diabetic nephropathy, in relation to its metabolic profiling. Four groups of male Wistar rats were assigned as follows; 1st untreated group, 2nd group (animals with diabetes) treated with streptozotocin (STZ, 50 mg/kg) IP, 3rd group co-treated with ROS (150 mg/kg + STZ, 50 mg/kg) and 4th group co-treated with ROS by a dose (300 mg/kg + STZ, 50 mg/kg) daily. After four weeks, random and fasting blood glucose (FBG) levels, serum insulin, advanced glycation end products (AGEs), urea, uric acid and inflammatory and fibrotic gene expression were evaluated. Moreover, histopathological examination of the renal tissues was performed. In addition, the metabolic profiling of ROS was performed via RP-HPLC-DAD-QTOF-MS and -MS/MS. The metabolic profiling of ROS revealed that protocatechuic acid and cyanidin-3-O-glucoside were the predominant compounds among 32 metabolites identified in the extract. ROS treated groups showed improvement of FBG and AGEs levels, whereas serum insulin level showed significant elevation. In addition, down-regulation of inflammatory mRNA expression associated with the hyperglycemic condition and amelioration in histopathological alterations in kidney tissues were observed. This study displayed the presence of 32 phenolic compounds in the ethanolic extract of ROS, a common by-product of the industrial production of onion in Egypt. This study proved the therapeutic potential of ROS as antidiabetic agent and its preventive effect against diabetic nephropathy. Therefore, this study represents a perspective of the utilization of food waste products. Copyright © 2018 Elsevier B.V. All rights reserved.

Interleukin-6 (IL-6) mediated the increased contraction of distal colon in streptozotocin-induced diabetes in rats via IL-6 receptor pathway

PubMed Central

Chang, Xin-Wen; Qin, Ying; Jin, Zhi; Xi, Tao-Fang; Yang, Xiao; Lu, Ze-Hao; Tang, Yu-Ping; Cai, Wen-Ting; Chen, Shao-Jun; Xie, Dong-Ping

2015-01-01

Colonic dysmotility occurs in diabetes and blood plasma interleukin (IL)-6 levels are significantly elevated in type 1 diabetes mellitus. The aim of this study was to investigate whether IL-6 and the IL-6 receptor pathway mediates colonic dysfunction in type 1 diabetes mellitus. Male SD rats were treated with a single intraperitoneally injected dose of streptozotocin (STZ), and those displaying sustained high blood glucose were selected as diabetes mellitus models. Longitudinal muscle strips of colon were prepared to monitor colonic contraction in vitro. Contractile responses of strips of colon were recorded following treatment with IL-6 in control animals, and following anti IL-6 antibody treatment in STZ-induced diabetes in rats. Concentration of IL-6 in plasma and colon were determined by ELISA. Expressions of IL-6 α-receptor and IL-6 β-receptor in colon tissues were determined by immunohistochemistry or Western blot analysis. The non-diabetes rats treated with IL-6 and the untreated diabetes rats showed increased contraction of distal colon, whereas the diabetes rats treated with anti-IL-6 antibody showed decreased contraction of distal colon compared with the untreated diabetes rats. The IL-6 levels of plasma but not colon increased in diabetes rats. The expression of IL-6 α-receptor increased in diabetes rats. These results indicate that diabetes rats show an increase in the contractions of distal colon partly via the IL-6-IL-6 receptor pathway. PMID:26191141

Gestational diabetes insipidus. Case Report.

PubMed

Ejmocka-Ambroziak, Anna; Grzechocińska, Barbara; Jastrzebska, Helena; Kochman, Magdalena; Cyganek, Anna; Wielgoś, Mirosław; Zgliczyński, Wojciech

2015-01-01

Gestational diabetes insipidus is a very rare complication. However, undiagnosed and untreated may lead to serious complications in both mother and fetus. In this study, a case of 34-year-old female patient with diabetes insipidus associated with pregnancy was reported. We discussed process of diagnosis and treatment with particular emphasis on the monitoring of water-electrolyte imbalance during labor.

Targets of vascular protection in acute ischemic stroke differ in type 2 diabetes

PubMed Central

Kelly-Cobbs, Aisha I.; Prakash, Roshini; Li, Weiguo; Pillai, Bindu; Hafez, Sherif; Coucha, Maha; Johnson, Maribeth H.; Ogbi, Safia N.; Fagan, Susan C.

2013-01-01

Hemorrhagic transformation is an important complication of acute ischemic stroke, particularly in diabetic patients receiving thrombolytic treatment with tissue plasminogen activator, the only approved drug for the treatment of acute ischemic stroke. The objective of the present study was to determine the effects of acute manipulation of potential targets for vascular protection [i.e., NF-κB, peroxynitrite, and matrix metalloproteinases (MMPs)] on vascular injury and functional outcome in a diabetic model of cerebral ischemia. Ischemia was induced by middle cerebral artery occlusion in control and type 2 diabetic Goto-Kakizaki rats. Treatment groups received a single dose of the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), the nonspecific NF-κB inhibitor curcumin, or the broad-spectrum MMP inhibitor minocycline at reperfusion. Poststroke infarct volume, edema, hemorrhage, neurological deficits, and MMP-9 activity were evaluated. All acute treatments reduced MMP-9 and hemorrhagic transformation in diabetic groups. In addition, acute curcumin and minocycline therapy reduced edema in these animals. Improved neurological function was observed in varying degrees with treatment, as indicated by beam-walk performance, modified Bederson scores, and grip strength; however, infarct size was similar to untreated diabetic animals. In control animals, all treatments reduced MMP-9 activity, yet bleeding was not improved. Neuroprotection was only conferred by curcumin and minocycline. Uncovering the underlying mechanisms contributing to the success of acute therapy in diabetes will advance tailored stroke therapies. PMID:23335797

Medical consequences and associations with untreated sleep-related breathing disorders and outcomes of treatments.

PubMed

Norman, Daniel; Haberman, Paul B; Valladares, Edwin M

2012-02-01

Sleep-related breathing disorders are a broad group of disorders that include obstructive sleep apnea, central sleep apnea, and periodic breathing disorders. This article reviews the scientific literature that links SRBD to various medical conditions including hypertension, coronary artery disease, cardiac arrhythmias, stroke, diabetes mellitus, obesity, and depression. Pathophysiologic mechanisms by which SRBD may contribute to these disorders will be discussed, as will data on the degree to which treatment of SRBD may improve these conditions.

Vascularized tissue-engineered chambers promote survival and function of transplanted islets and improve glycemic control.

PubMed

Knight, K R; Uda, Y; Findlay, M W; Brown, D L; Cronin, K J; Jamieson, E; Tai, T; Keramidaris, E; Penington, A J; Rophael, J; Harrison, L C; Morrison, W A

2006-03-01

We have developed a chamber model of islet engraftment that optimizes islet survival by rapidly restoring islet-extracellular matrix relationships and vascularization. Our aim was to assess the ability of syngeneic adult islets seeded into blood vessel-containing chambers to correct streptozotocin-induced diabetes in mice. Approximately 350 syngeneic islets suspended in Matrigel extracellular matrix were inserted into chambers based on either the splenic or groin (epigastric) vascular beds, or, in the standard approach, injected under the renal capsule. Blood glucose was monitored weekly for 7 weeks, and an intraperitoneal glucose tolerance test performed at 6 weeks in the presence of the islet grafts. Relative to untreated diabetic animals, glycemic control significantly improved in all islet transplant groups, strongly correlating with islet counts in the graft (P<0.01), and with best results in the splenic chamber group. Glycemic control deteriorated after chambers were surgically removed at week 8. Immunohistochemistry revealed islets with abundant insulin content in grafts from all groups, but with significantly more islets in splenic chamber grafts than the other treatment groups (P<0.05). It is concluded that hyperglycemia in experimental type 1 diabetes can be effectively treated by islets seeded into a vascularized chamber functioning as a "pancreatic organoid."

Carrot juice fermented with Lactobacillus plantarum NCU116 ameliorates type 2 diabetes in rats.

PubMed

Li, Chuan; Ding, Qiao; Nie, Shao-Ping; Zhang, Yan-Song; Xiong, Tao; Xie, Ming-Yong

2014-12-10

The effect of carrot juice fermented with Lactobacillus plantarum NCU116 on high-fat and low-dose streptozotocin (STZ)-induced type 2 diabetes in rats was studied. Rats were randomly divided into five groups: non-diabetes mellitus (NDM), untreated diabetes mellitus (DM), DM plus L. plantarum NCU116 (NCU), DM plus fermented carrot juice with L. plantarum NCU116 (FCJ), and DM plus non-fermented carrot juice (NFCJ). Treatments of NCU and FCJ for 5 weeks were found to favorably regulate blood glucose, hormones, and lipid metabolism in the diabetic rats, accompanied by an increase in short-chain fatty acid (SCFA) in the colon. In addition, NCU and FCJ had restored the antioxidant capacity and morphology of the pancreas and kidney and upregulated mRNA of low-density lipoprotein (LDL) receptor, cholesterol 7α-hydroxylase (CYP7A1), glucose transporter-4 (GLUT-4), peroxisome proliferator-activated receptor-α (PPAR-α), and peroxisome proliferator-activated receptor-γ (PPAR-γ). These results have for the first time demonstrated that L. plantarum NCU116 and the fermented carrot juice had the potential ability to ameliorate type 2 diabetes in rats.

International Association of Diabetes and Pregnancy Study Group criteria is suitable for gestational diabetes mellitus diagnosis: further evidence from China.

PubMed

Wei, Yumei; Yang, Huixia; Zhu, Weiwei; Yang, Hongyun; Li, Haixia; Yan, Jie; Zhang, Cuilin

2014-01-01

The International Association of Diabetes and Pregnancy Study Group (IADPSG) recommended new diagnostic criteria for gestational diabetes mellitus (GDM) after extensive analyses of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. Unfortunately, there was no data from mainland of China in this study. We evaluated the feasibility of IADPSG criteria for GDM diagnosis in China. A large prospective study was conducted. We reviewed medical records of a total of 25 674 pregnant women who underwent GDM screening and diagnosis between January 1, 2005 and December 31, 2012 in the Peking University First Hospital. The prevalence of gestational glucose metabolism abnormalities was calculated according to different cut off values defined by the National Diabetes Data Group (NDDG) or the IADPSG, and the incidence of adverse pregnancy outcomes related to GDM was analyzed. According to the cut off values of NDDG and IADPSG criteria, the prevalence of gestational glucose metabolism abnormalities was 8.4% and 18.9% (P < 0.01) respectively, and the prevalence of cesarean section (52.5% vs. 46.0%, P < 0.01), macrosomia (7.5% vs. 6.3%, P < 0.05), neonatal hypoglycemia (1.6% vs. 1.0%, P < 0.01), and perinatal death (0.5% vs. 0.2%, P < 0.01); the prevalence was significantly lower when IADPSG criteria were applied. The prevalence of macrosomia, cesarean section, neonatal hypoglycemia, pregnancy induced hypertension, etc. was also higher in the GDM group than in the normal group. The prevalence of cesarean section (62.3%) and macrosomia (14.8%) was the highest in untreated mild GDM patients. Our results indicated that treatment/intervention of women with GDM identified by IADPSG criteria was related to significantly lower risk of multiple adverse pregnancy outcomes. Such findings provide support for applying IADPSG criteria in China.

Niceritrol prevents the decrease in red blood cell 2,3-diphosphoglycerate and neuropathy in streptozotocin-induced diabetic rats.

PubMed

Hotta, N; Nakamura, J; Kakuta, H; Fukasawa, H; Koh, N; Sakakibara, F; Mori, K; Sakamoto, N

1995-01-01

Nerve ischemia/hypoxia has been linked to the pathogenesis of diabetic complications. Red blood cell 2,3-diphosphoglycerate is an important regulator of peripheral tissue oxygenation; however, the relationship between 2,3-diphosphoglycerate concentration and diabetic complications has not been studied in detail. This investigation focused on the relationship between red blood cell 2,3-diphosphoglycerate and diabetic neuropathy, by measuring motor nerve conduction velocity and sciatic nerve blood flow in streptozotocin-induced diabetic rats. The effect of treatment with niceritrol, a nicotinic acid derivative that acts as a vasodilator and reduces serum lipid concentrations, on 2,3-diphosphoglycerate concentration and diabetic neuropathy was also examined. Untreated diabetic rats had significantly lower concentrations of red blood cell 2,3-diphosphoglycerate, higher concentrations of serum total cholesterol and triglyceride, as well as reduced motor nerve conduction velocity and sciatic nerve blood flow, compared to untreated normal rats. Niceritrol prevented these abnormalities without correcting hyperglycemia in diabetic rats, but had no effect on these parameters in normal rats. Red blood cell 2,3-diphosphoglycerate concentration and motor nerve conduction velocity showed a positive correlation with sciatic nerve blood flow and 2,3-diphosphoglycerate, respectively. These observations suggest that ischemia/hypoxia plays an important role in the development of diabetic neuropathy, and that niceritrol has a therapeutic effect on this condition by improving endoneurial ischemia/hypoxia.

Effects of separate and concurrent supplementation of Nano-sized clinoptilolite and Nigella sativa on oxidative stress, anti-oxidative parameters and body weight in rats with type 2 diabetes.

PubMed

Omidi, Hossein; Khorram, Sirus; Mesgari, Mehran; Asghari-Jafarabadi, Mohammad; Tarighat-Esfanjani, Ali

2017-12-01

The objective of this study was to investigate the effects of separate and concurrent supplementation of natural nano-sized clinoptilolite (NCLN) and Nigella sativa (NS) on oxidative stress (OS), anti-oxidative parameters and body weight (BW) in high-fat-diet (HFD)/streptozotocin (STZ)-induced diabetic rats. In this experimental study, 42 male Wistar rats were divided into diabetic (n=36) and non-diabetic (n=6) groups. The diabetic group (DG) was fed with a HFD for one month, then injected with intra-peritoneal single dose STZ (35 mg/kg BW). The DG was divided into 4 subgroups: [1] control (DC), [2] NS 1%/food, [3] NCLN 2%/food, [4] NS 1%/food + NCLN 2%/food. At the end of the 7th week, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX) levels and total antioxidant capacity (TAC) were measured. The MDA level was decreased in the NCLN (p = 0.011) and NCLN+NS (p = 0.007) groups compared to the DC group. The GPX level increased in the NS and NCLN groups compared to the DC group (p = 0.014 and p = 0.034). In addition, the level of TAC demonstrated increase in the untreated DG and NS groups, as compared to the normal control (NC) group (p DC  = 0.031 and p NS  = 0.024). Moreover, in the NS+NCLN group, the level of SOD decreased in comparison to the NS and NCLN groups (p < 0.01). At the end of the 7th week, BW decreased in the diabetic subgroups in comparison to the NC group. Treatment with NS and/or NS+NCLN insignificantly prevented severe weight loss in the fifth week of the treatment. According to results, separate supplementation of NS and NCLN was more beneficent on anti-oxidative parameters than concurrent supplementation of NS and NCLN. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Silymarin: A Novel Natural Agent to Restore Defective Pancreatic β Cells in Streptozotocin (STZ)-induced Diabetic Rats

PubMed Central

Amniattalab, Amir; Malekinejad, Hassan; Rezabakhsh, Aysa; Rokhsartalab-Azar, Shirin; Alizade-Fanalou, Shahin

2016-01-01

This study aimed to investigate the potency of silymarin (SMN) and melatonin (MEL) on restoring the pancreatic   cells in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were divided into five groups, including: control (C), untreated diabetic (D), SMN-treated diabetic (50 mg/Kg, orally), MEL-treated diabetic (10 mg/Kg, i.p.), and SMN plus MEL-treated diabetic rats. Diabetes was induced by injection of STZ (50 mg/Kg, i.p.). The blood glucose and insulin levels were measured. After the 28 days treatment period, antioxidant status was analyzed by determination of total antioxidant capacity (TAC) in the liver and serum. The histopathological changes in the pancreatic islets were examined by histochemical staining and enumeration of   cells. Although none of the test compounds reduced the blood glucose level to normal concentration, however SMN alone and in combination with MEL was able to decline it significantly (P<0.05) after 28 days administration. Both SMN and MEL could recover the diabetes-reduced TAC values. Moreover, the diabetes-induced cellular vacuolation and   cells depletion were improved by the SMN treatment. Our data suggest that the SMN and MEL treatment was able to normalize the antioxidant status, while only SMN administration could restore the  cells of Langerhans islets in diabetic rats. PMID:27980584

Glomerular hemodynamic alterations during acute hyperinsulinemia in normal and diabetic rats

NASA Technical Reports Server (NTRS)

Tucker, B. J.; Anderson, C. M.; Thies, R. S.; Collins, R. C.; Blantz, R. C.

1992-01-01

Treatment of insulin dependent diabetes invariably requires exogenous insulin to control blood glucose. Insulin treatment, independent of other factors associated with insulin dependent diabetes, may induce changes that affect glomerular function. Due to exogenous delivery of insulin in insulin dependent diabetes entering systemic circulation prior to the portal vein, plasma levels of insulin are often in excess of that observed in non-diabetics. The specific effects of hyperinsulinemia on glomerular hemodynamics have not been previously examined. Micropuncture studies were performed in control (non-diabetic), untreated diabetic and insulin-treated diabetic rats 7 to 10 days after administration of 65 mg/kg body weight streptozotocin. After the first period micropuncture measurements were obtained, 5 U of regular insulin (Humulin-R) was infused i.v., and glucose clamped at euglycemic values (80 to 120 mg/dl). Blood glucose concentration in non-diabetic controls was 99 +/- 6 mg/dl. In control rats, insulin infusion and glucose clamp increased nephron filtration rate due to decreases in both afferent and efferent arteriolar resistance (afferent greater than efferent) resulting in increased plasma flow and increased glomerular hydrostatic pressure gradient. However, insulin infusion and glucose clamp produced the opposite effect in both untreated and insulin-treated diabetic rats with afferent arteriolar vasoconstriction resulting in decreases in plasma flow, glomerular hydrostatic pressure gradient and nephron filtration rate. Thromboxane A2 (TX) synthetase inhibition partially decreased the vasoconstrictive response due to acute insulin infusion in diabetic rats preventing the decrease in nephron filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS).

Intracavernous Delivery of a Designed Angiopoietin-1 Variant Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse

PubMed Central

Jin, Hai-Rong; Kim, Woo Jean; Song, Jae Sook; Piao, Shuguang; Choi, Min Ji; Tumurbaatar, Munkhbayar; Shin, Sun Hwa; Yin, Guo Nan; Koh, Gou Young; Ryu, Ji-Kan; Suh, Jun-Kyu

2011-01-01

OBJECTIVE Patients with diabetic erectile dysfunction often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. We examined the effectiveness of the potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous endothelial regeneration and restoring erectile function in diabetic animals. RESEARCH DESIGN AND METHODS Four groups of mice were used: controls; streptozotocin (STZ)-induced diabetic mice; STZ-induced diabetic mice treated with repeated intracavernous injections of PBS; and STZ-induced diabetic mice treated with COMP-Ang1 protein (days −3 and 0). Two and 4 weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations, Western blot analysis, and cGMP quantification. We also performed a vascular permeability test. RESULTS Local delivery of the COMP-Ang1 protein significantly increased cavernous endothelial proliferation, endothelial nitric oxide (NO) synthase (NOS) phosphorylation, and cGMP expression compared with that in the untreated or PBS-treated STZ-induced diabetic group. The changes in the group that received COMP-Ang1 restored erectile function up to 4 weeks after treatment. Endothelial protective effects, such as marked decreases in the expression of p47phox and inducible NOS, in the generation of superoxide anion and nitrotyrosine, and in the number of apoptotic cells in the corpus cavernosum tissue, were noted in COMP-Ang1–treated STZ-induced diabetic mice. An intracavernous injection of COMP-Ang1 completely restored endothelial cell-cell junction proteins and decreased cavernous endothelial permeability. COMP-Ang1–induced promotion of cavernous angiogenesis and erectile function was abolished by the NOS inhibitor, N-nitro-L-arginine methyl ester, but not by the NADPH oxidase inhibitor, apocynin. CONCLUSIONS These findings support the concept of cavernous endothelial regeneration by use of the recombinant Ang1 protein as a curative therapy for diabetic erectile dysfunction. PMID:21270241

HealthLines The Pain Before the Fall | NIH MedlinePlus the Magazine

MedlinePlus

... the condition than those who drank less than one serving a month. Left untreated, gestational diabetes can cause complications during pregnancy. It also raises the risk of the mother and the baby developing type 2 diabetes later in life. The Eunice Kennedy ...

Pancreatic response to gold nanoparticles includes decrease of oxidative stress and inflammation in autistic diabetic model.

PubMed

Selim, Manar E; Abd-Elhakim, Yasmina M; Al-Ayadhi, Laila Y

2015-01-01

Gold nanoparticles (AuNPs) have a wide range of applications in various fields. This study provides an understanding of the modulatory effects of AuNPs on an antioxidant system in male Wistar diabetic rats with autism spectrum disorder (ASD). Normal littermates fed by control mothers were injected with citrate buffer alone and served as normal, untreated controls controlin this study. Diabetes mellitus (DM) was induced by administering a single intraperitoneal injection of streptozotocin (STZ) (100 mg/kg) to the pups of (ND) diabetic group, which had been fasted overnight. Autistic pups from mothers that had received a single intraperitoneal injection of 600 mg/kg sodium valproate on day 12.5 after conception were randomly divided into 2 groups (n 2 7/group) as follow; administering single intraperitoneal injection of streptozotocin (STZ) ( (100 mg/kg) to the overnight fasted autistic pups of (AD) autistic diabetic group. The treatment was started on the 5th day after STZ injection with the same dose as in group II and it was considered as 1st day of treatment with gold nanoparticles for 7 days to each rat of (group IV) treated autistic diabetic group(TAD) at a dosage of 2.5 mg/kg. b. wt. At this dose of administration AuNPs, the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase were greater in group TAD compared with the control group (P < 0.05). Oxidised glutathione levels were lower (P > 0.05) in the liver of autistic diabetic AuNPs -supplemented rats, whereas reduced glutathione was markedly higher than in control rats, especially after administration of AuNPs. Moreover, the kidney functions in addition to the fat profile scoring supported the protective potential of that dose of AuNPs. The beta cells revealed euchromatic nuclei with no evidence of separation of nuclear membrane. Our results showed that AuNPs improved many of the oxidative stress parameters (SOD, GPx and, CAT), plasma antioxidant capacity (ORAC) and lipid profile relative to the other parameters. In addition to the apparent reversibility of the pancreatic B cell in group IV which may reflect the regenerative capacity of AuNPs. © 2015 S. Karger AG, Basel.

Chromium-picolinate therapy in diabetes care: molecular and subcellular profiling revealed a necessity for individual outcome prediction, personalised treatment algorithms & new guidelines

PubMed Central

Yeghiazaryan, Kristina; Peeva, Viktoriya; Shenoy, Aparna; Schild, Hans H.; Golubnitschaja, Olga

2013-01-01

Aims Global figures clearly demonstrate inadequacy of current diabetes care: every 10 seconds one patient dies of diabetes-related pathologies. Nephropathy is the leading secondary complication of the disease. Nutritional supplement by chromium-picolinate is assumed to have beneficial therapeutic effects. However, potential toxic effects reported increase concerns about safety of chromium-picolinate. The experimental design aimed at determining, whether the treatment with clinically relevant doses of chromium-picolinate can harm through DNA damage and extensive alterations in central detoxification / cell-cycle regulating pathways in treatment of diabetes. Methods Well-acknowledged animal model of db/db-mice and clinically relevant doses of chromium-picolinate were used. As an index of DNA-damage, measurement of DNA-breaks was performed using “Comet Assay”-analysis. Individual and group-specific expression patterns of SOD-1 and P53 were evaluated to give a clue about central detoxification and cell-cycle regulating pathways under treatment conditions. The study was performed in a double-blind manner. Results Experimental data revealed highly individual reaction under treatment conditions. However, group-specific patterns were monitored: highest amount of damaged DNA - under the longest treatment with high doses, in contrast to groups with low doses of chromium-picolinate. Comet patterns were intermediate between untreated diabetized and control animals. Expression patterns demonstrated a correlation with subcellular imaging and dosage-dependent suppression under chromium-picolinate treatment. Conclusions This article highlights possible risks for individual long-term effects, when chromium-picolinate is used freely as a therapeutic nutritional modality agent without application of advanced diagnostic tools to predict risks and individual outcomes. Targeted measures require a creation of new guidelines for advanced Diabetes care. PMID:21470100

The possible antidiabetic effects of vitamin D receptors agonist in rat model of type 2 diabetes.

PubMed

Abdel-Rehim, Wafaa M; El-Tahan, Rasha A; El-Tarawy, Mennatullah A; Shehata, Rowaida R; Kamel, Maher A

2018-06-16

Vitamin D 3 deficiency was found to be tightly linked to many health problems including metabolic syndrome, cancer, cardiovascular diseases, and type 2 diabetes mellitus. In our study, we tested the possible antidiabetic effects of one of vitamin D 3 analogs, alfacalcidol, solely or in a combination with metformin on type 2 diabetic rats. Type 2 diabetic model rats were induced by feeding high-fat diet for 4 weeks followed by intraperitoneal injection of streptozotocin. In addition to the control group, the diabetic rats were divided into four groups: untreated, metformin-treated, alfacalcidol-treated, and combination-treated group (metformin + alfacalcidol) for 4 weeks. The level of fasting blood glucose, fasting serum insulin, homeostatic model of insulin resistance, serum lipid profile, liver enzymes, calcium, phosphorus, and 25-hydroxyvitamin D 3 were also determined. Besides, sterol regulatory element binding protein-1c (SREBP-1c) and vitamin D receptors (VDR) gene expression at mRNA and protein levels were evaluated. The level of significance was fixed at P ≤ 0.05 for all statistical tests. Alfacalcidol, solely or combined with metformin, significantly ameliorated glucose homeostasis and lipid profile parameters (P < 0.001) with a neutral effect on calcium and phosphorus levels. Significant downregulation of mRNA expression of SREBP-1c in the liver, white as well as brown adipose tissues (P < 0.001) and different patterns of mRNA expression of VDR gene in pancreas and white adipose tissue were observed in rats treated with alfacalcidol solely or in combination with metformin. Vitamin D 3 analogs can modulate glucose parameters and lipid metabolism in a diabetic rat model and it provides additional protective effects when combined with metformin.

The impact of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) fasting glucose diagnostic criterion on the prevalence and outcomes of gestational diabetes mellitus in Han Chinese women.

PubMed

Liao, S; Mei, J; Song, W; Liu, Y; Tan, Y-D; Chi, S; Li, P; Chen, X; Deng, S

2014-03-01

The International Association of Diabetes and Pregnancy Study Groups (IADPSG) proposed that a one-time value of fasting plasma glucose of 5.1 mmol/l or over at any time of the pregnancy is sufficient to diagnose gestational diabetes. We evaluated the repercussions of the application of this threshold in pregnant Han Chinese women. This is a retrospective study of 5360 (72.3% of total) consecutively recruited pregnant Han Chinese women in one centre from 2008 to 2011. These women underwent a two-step gestational diabetes diagnostic protocol according to the previous American Diabetes Association criteria. The IADPSG fasting plasma glucose criterion was used to reclassify these 5360 women. The prevalence, clinical characteristics and obstetric outcomes were compared among the women classified as having gestational diabetes by the previous American Diabetes Association criteria (approximately 90% were treated), those reclassified as having gestational diabetes by the single IADPSG fasting plasma glucose criterion (untreated), but not as having gestational diabetes by the previous American Diabetes Association criteria, and those with normal glucose tolerance. There were 626 cases of gestational diabetes defined by the previous American Diabetes Association criteria (11.7%) and these cases were associated with increased risks of maternal and neonatal outcomes when compared with the women with normal glucose tolerance. With the IADPSG fasting plasma glucose criterion, another 1314 (24.5%) women were reclassified as having gestational diabetes. Gestational diabetes classified by the IADPSG fasting plasma glucose criterion was associated with gestational hypertension (P = 0.0094) and neonatal admission to nursery (P = 0.035) prior to adjustment for maternal age and BMI, but was no longer a predictor for adverse pregnancy outcomes after adjustment. The simple IADPSG fasting plasma glucose criterion increased the Chinese population with gestational diabetes by 200%. The increased population with gestational diabetes was not significantly associated with excess obstetric and neonatal morbidity. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Effects of exendin-4 and selenium on the expression of GLP-1R, IRS-1, and preproinsulin in the pancreas of diabetic rats.

PubMed

Barakat, Ghinwa; Moustafa, Mohamed E; Khalifeh, Ibrahim; Hodroj, Mohammad H; Bikhazi, Anwar; Rizk, Sandra

2016-08-01

The mechanisms by which exendin-4 and selenium exert their antidiabetic actions are still unclear. Here, we investigated the effects of exendin-4 or selenium administration on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and preproinsulin in the pancreas of diabetic rats. Diabetes was induced by streptozotocin administration. Diabetic rats were injected intraperitoneally with 0.03 μg exendin-4/kg body weight/daily or treated with 5 ppm selenium in drinking water for a period of 4 weeks. GLP-1R and IRS-1 levels were decreased while the level of preproinsulin messenger RNA (mRNA) was increased in the pancreas of diabetic untreated rats, as compared to that in control rats. Treatment of diabetic rats with exendin-4 increased protein and mRNA levels of GLP-1R, and IRS-1, and the mRNA level of preproinsulin in the pancreas, as compared to their levels in diabetic untreated rats. Selenium treatment of diabetic rats increased the pancreatic mRNA levels of GLP-1R, IRS-1, and preproinsulin. Exendin-4 or selenium treatment of diabetic rats also increased the numbers of pancreatic islets and GLP-1R molecules in the pancreas. Therefore, exendin-4 and selenium may exert their antidiabetic effects by increasing GLP-1R, IRS-1, and preproinsulin expression in the pancreas and by increasing the number of pancreatic islets.

Treatment of diabetic rats with encapsulated islets.

PubMed

Sweet, Ian R; Yanay, Ofer; Waldron, Lanaya; Gilbert, Merle; Fuller, Jessica M; Tupling, Terry; Lernmark, Ake; Osborne, William R A

2008-12-01

Immunoprotection of islets using bioisolator systems permits introduction of allogeneic cells to diabetic patients without the need for immunosuppression. Using TheraCyte immunoisolation devices, we investigated two rat models of type 1 diabetes mellitus (T1DM), BB rats and rats made diabetic by streptozotocin (STZ) treatment. We chose to implant islets after the onset of diabetes to mimic the probable treatment of children with T1DM as they are usually diagnosed after disease onset. We encapsulated 1000 rat islets and implanted them subcutaneously (SQ) into diabetic biobreeding (BB) rats and STZ-induced diabetic rats, defined as two or more consecutive days of blood glucose>350 mg/dl. Rats were monitored for weight and blood glucose. Untreated BB rats rapidly lost weight and were euthanized at >20% weight loss that occurred between 4 and 10 days from implantation. For period of 30-40 days following islet implantation weights of treated rats remained steady or increased. Rapid weight loss occurred after surgical removal of devices that contained insulin positive islets. STZ-treated rats that received encapsulated islets showed steady weight gain for up to 130 days, whereas untreated control rats showed steady weight loss that achieved >20% at around 55 days. Although islet implants did not normalize blood glucose, treated rats were apparently healthy and groomed normally. Autologous or allogeneic islets were equally effective in providing treatment. TheraCyte devices can sustain islets, protect allogeneic cells from immune attack and provide treatment for diabetic-mediated weight loss in both BB rats and STZ-induced diabetic rats.

Determining the amounts of urea and glucose in urine of patients with renal complications from diabetes mellitus and hypertension by near-infrared Raman spectroscopy

NASA Astrophysics Data System (ADS)

Bispo, Jeyse A. M.; Silveira, Landulfo; Vieira, Elzo E. d. S.; Fernandes, Adriana B.

2013-02-01

Diabetes mellitus and hypertension diseases are frequently found in the same patient, which if untreated predispose to atherosclerotic and kidney diseases. The objective of this study was to identify potential biomarkers in the urine of diabetic and hypertensive patients through dispersive near-infrared Raman spectroscopy. Urine samples were collected from patients with diabetes and hypertension but no complications (LG), high degree of complications (HG), and control ones: one fraction was submitted to biochemical tests and another one was stored frozen (-20°C) until spectral analysis. Samples were warmed up and placed in an aluminum sample holder for Raman spectra collection using a dispersive spectrometer (830 nm wavelength, 300 mW laser power and 20 s exposure time). Spectra were then submitted to Principal Components Analysis. The PCA loading vectors 1 and 3 revealed spectral features of urea/creatinine and glucose, respectively; the PCA scores showed that patients with diabetes/hypertension (LG and HG) had higher amount of glucose in the urine compared to the normal group (p < 0.05), which can bring serious consequences to patients. Also, the PCA scores showed that the amount of urea decreased in the groups with diabetes/hypertension (p < 0.05), which generates the same concern as it is a marker that has a strong importance in the metabolic changes induced by such diseases. These results, applied to the analysis of urine of patients with diabetes/hypertension, can lead to early diagnostic information of complications and a possible disease prognosis in the patients where no complications from diabetes and hypertension were found.

The effect of metformin on the hypothalamic-pituitary-thyroid axis in patients with type 2 diabetes and subclinical hyperthyroidism.

PubMed

Krysiak, R; Szkrobka, W; Okopien, B

2015-04-01

In hypothyroid patients, metformin was found to reduce serum levels of TSH. No previous study investigated metformin action on hypothalamic-pituitary-thyroid axis in patients with hyperthyroidism. The aim of our study was to assess the effect of metformin treatment on thyroid function tests in patients with untreated subclinical hyperthyroidism. We studied 15 patients with low but detectable TSH levels (0.1-0.4 mIU/L) (group 1), 12 patients with suppressed TSH levels (less than 0.1 mIU/L) (group 2) and 15 euthyroid patients with a history of hyperthyroidism, who because of coexisting 2 diabetes were treated with metformin (2.55-3 g daily). Glucose homeostasis markers, as well as serum levels of TSH and total and free thyroxine and triiodothyronine levels were assessed at baseline and after 3 and 6 months of therapy. As expected, metformin reduced plasma glucose, insulin resistance and glycated hemoglobin. However, with the exception of an insignificant decrease in TSH levels after 3-month therapy in group 2, metformin therapy did not affect thyroid function tests. Our results indicate that metformin has a negligible effect on hypothalamic-pituitary-thyroid axis activity in type 2 diabetic patients with subclinical hyperthyroidism. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of antioxidant extract from cherries on diabetes.

PubMed

Lachin, Tahsini

2014-01-01

Diabetes is a chronic metabolic disorder in humans constituting a major health concern today whose prevalence has continuously increased worldwide over the past few decades. Production of reactive oxygen species (ROS) and disturbed capacity of antioxidant defense in diabetic subjects have been reported. It has been suggested that enhanced production of free radicals and oxidative stress is the central event for the development of diabetic complications. Antioxidants can play an important role in the improvement of diabetes. There are many reports on the effects of antioxidants in the management of diabetes. This study aimed at evaluating the effect of antioxidant extract and purified sweet and sour Cherries on hyperglycemia, microalbumin and creatinine level in alloxan-induced diabetic rats. Thirty six adult Male Wistar rats were divided equally into six groups. Diabetes was induced in the rats by an intraperitoneal injection with 120 mg/kg body weight of alloxan. Oral administration of cherry extract at a concentration of 200 mg/kg body weight for 30 days significantly reduced the levels of blood glucose, and urinary microalbumin. Also an increase in the creatinine secretion level in urine was observed in the diabetic rats treated with the cherry extract as compared to untreated diabetic rats. In this paper, the most recent patent on the identification and treatment of diabetes is used. In conclusion, cherry antioxidant extract proved to have a beneficial effect on the diabetic rats in this study. In light of these advantageous results, it is advisable to broaden the scale of use of sweet and sour cherries extract in a trial to alleviate the adverse effects of diabetes.

The impact of SGLT2 inhibitors, compared with insulin, on diabetic bone disease in a mouse model of type 1 diabetes.

PubMed

Thrailkill, Kathryn M; Nyman, Jeffry S; Bunn, R Clay; Uppuganti, Sasidhar; Thompson, Katherine L; Lumpkin, Charles K; Kalaitzoglou, Evangelia; Fowlkes, John L

2017-01-01

Skeletal co-morbidities in type 1 diabetes include an increased risk for fracture and delayed fracture healing, which are intertwined with disease duration and the presence of other diabetic complications. As such, chronic hyperglycemia is undoubtedly a major contributor to these outcomes, despite standard insulin-replacement therapy. Therefore, using the streptozotocin (STZ)-induced model of hypoinsulinemic hyperglycemia in DBA/2J male mice, we compared the effects of two glucose lowering therapies on the fracture resistance of bone and markers of bone turnover. Twelve week-old diabetic (DM) mice were treated for 9weeks with: 1) oral canagliflozin (CANA, dose range ~10-16mg/kg/day), an inhibitor of the renal sodium-dependent glucose co-transporter type 2 (SGLT2); 2) subcutaneous insulin, via minipump (INS, 0.125units/day); 3) co-therapy (CANA+INS); or 4) no treatment (STZ, without therapy). These groups were also compared to non-diabetic control groups. Untreated diabetic mice experienced increased bone resorption and significant deficits in cortical and trabecular bone that contributed to structural weakness of the femur mid-shaft and the lumbar vertebra, as determined by three-point bending and compression tests, respectively. Treatment with either canagliflozin or insulin alone only partially rectified hyperglycemia and the diabetic bone phenotype. However, when used in combination, normalization of glycemic control was achieved, and a prevention of the DM-related deterioration in bone microarchitecture and bone strength occurred, due to additive effects of canagliflozin and insulin. Nevertheless, CANA-treated mice, whether diabetic or non-diabetic, demonstrated an increase in urinary calcium loss; FGF23 was also increased in CANA-treated DM mice. These findings could herald ongoing bone mineral losses following CANA exposure, suggesting that certain CANA-induced skeletal consequences might detract from therapeutic improvements in glycemic control, as they relate to diabetic bone disease. Copyright © 2016 Elsevier Inc. All rights reserved.

The impact of SGLT2 Inhibitors, compared with Insulin, on Diabetic Bone Disease in a mouse model of Type 1 Diabetes

PubMed Central

Thrailkill, Kathryn M.; Nyman, Jeffry S.; Bunn, R. Clay; Uppuganti, Sasidhar; Thompson, Katherine L.; Lumpkin, Charles K.; Kalaitzoglou, Evangelia; Fowlkes, John L.

2016-01-01

Skeletal co-morbidities in type 1 diabetes include an increased risk for fracture and delayed fracture healing, which are intertwined with disease duration and the presence of other diabetic complications. As such, chronic hyperglycemia is undoubtedly a major contributor to these outcomes, despite standard insulin-replacement therapy. Therefore, using the streptozotocin (STZ)-induced model of hypoinsulinemic hyperglycemia in DBA/2J male mice, we compared the effects of two glucose lowering therapies on the fracture resistance of bone and markers of bone turnover. Twelve week-old diabetic (DM) mice were treated for 9 weeks with: 1) oral canagliflozin (CANA, dose range ~10-16 mg/kg/day), an inhibitor of the renal sodium-dependent glucose co-transporter type 2 (SGLT2); 2) subcutaneous insulin, via minipump (INS, 0.125 units/day); 3) co-therapy (CANA + INS); or 4) no treatment (STZ, without therapy). These groups were also compared to non-diabetic control groups. Untreated diabetic mice experienced increased bone resorption and significant deficits in cortical and trabecular bone that contributed to structural weakness of the femur mid-shaft and the lumbar vertebra, as determined by three-point bending and compression tests, respectively. Treatment with either canagliflozin or insulin alone only partially rectified hyperglycemia and the diabetic bone phenotype. However, when used in combination, normalization of glycemic control was achieved, and a prevention of the DM-related deterioration in bone microarchitecture and bone strength occurred, due to additive effects of canagliflozin and insulin. Nevertheless, CANA-treated mice, whether diabetic or non-diabetic, demonstrated an increase in urinary calcium loss; FGF23 was also increased in CANA-treated DM mice. These findings could herald ongoing bone mineral losses following CANA exposure, suggesting that certain CANA-induced skeletal consequences might detract from therapeutic improvements in glycemic control, as they relate to diabetic bone disease. PMID:27989651

Angiotensin II receptor blocker inhibits abnormal accumulation of advanced glycation end products and retinal damage in a rat model of type 2 diabetes.

PubMed

Sugiyama, Tetsuya; Okuno, Takashi; Fukuhara, Masayuki; Oku, Hidehiro; Ikeda, Tsunehiko; Obayashi, Hiroshi; Ohta, Mitsuhiro; Fukui, Michiaki; Hasegawa, Goji; Nakamura, Naoto

2007-09-01

The effects of an angiotensin II receptor blocker (ARB) on the accumulation of one of advanced glycation end products (AGEs), pentosidine, expression of vascular endothelial growth factor (VEGF) and retinal function were investigated in Spontaneously Diabetic Torii (SDT) rats. Candesartan, an ARB, was administered to SDT rats from 10 to 44 weeks of age and the results compared with untreated SDT rats and SD rats. Electroretinograms (ERGs) were recorded to evaluate retinal function. At 44 weeks of age, pentosidine was quantified in the vitreous, lens and plasma using high-performance liquid chromatography (HPLC). Real-time reverse transcription-PCR (RT-PCR) analysis was also performed in order to measure VEGF mRNA expression in the retina. Histological changes were examined and immunohistochemistry for pentosidine performed on the retina and retinal microvasculature. In untreated SDT rats, the amplitudes of a- and b-waves, oscillatory potentials were reduced significantly at 44 weeks of age compared with the 10-week levels, whereas they remained unchanged in SDT rats treated with candesartan. The concentration of pentosidine in the vitreous and lens did not change in treated SDT rats but increased in untreated SDT rats. Retinal VEGF mRNA expression was inhibited in treated SDT rats. Histologically, proliferative tissue was detected around the optic disc, with pentosidine being detected only in untreated SDT rats. Our findings indicate the ARB may inhibit the development of diabetic retinopathy by reducing the accumulation of pentosidine, one of AGEs and expression of VEGF in the retina.

Effects of motivational enhancement therapy plus cognitive behaviour therapy on depressive symptoms and health-related quality of life in adults with type II diabetes mellitus: a randomised controlled trial.

PubMed

Huang, Chiung-Yu; Lai, Hui-Ling; Chen, Chun-I; Lu, Yung-Chuan; Li, Su-Chen; Wang, Long-Whou; Su, Yi

2016-05-01

This paper evaluates the effectiveness of motivational enhancement therapy plus cognitive behavioural therapy on depressive symptoms, glycosylated haemoglobin, fasting glucose, body mass index (BMI), and health-related quality of life in type II diabetes patients. A controlled trial was conducted to compare patients who received the behavioural intervention with untreated controls on measures of health outcomes. A total of 31 intervention group participants and 30 controls were selected from patients that met the inclusion criteria from a hospital-based endocrinology outpatient department. The outcome measures including depressive symptoms, glycosylated haemoglobin, fasting glucose, BMI, and both physical and mental quality of life were collected before (T1), after (T2), and after 90 days (T3) following the intervention. The experimental group showed a significant reduction in glycosylated haemoglobin, fasting glucose, and depressive symptoms and a significant increase in physical quality of life and mental quality of life at T2 and T3, while patients in the control group with usual care showed no changes over time. The behavioural intervention facilitated a significant improvement in psychological adjustment and glycemic control, thus strengthening diabetes control skills and leading to healthy outcomes. It is feasible that nurses and psychiatrists can deliver the behavioural intervention for diabetes patients to decrease their depressive symptoms. Sharing discussion and problem-solving experiences is particularly helpful method for self-control, and these will be beneficially influential on further research.

Orally Active Multi-Functional Antioxidants Delay Cataract Formation in Streptozotocin (Type 1) Diabetic and Gamma-Irradiated Rats

PubMed Central

Randazzo, James; Zhang, Peng; Makita, Jun; Blessing, Karen; Kador, Peter F.

2011-01-01

Background Age-related cataract is a worldwide health care problem whose progression has been linked to oxidative stress and the accumulation of redox-active metals. Since there is no specific animal model for human age-related cataract, multiple animal models must be used to evaluate potential therapies that may delay and/or prevent cataract formation. Methods/Principal Findings Proof of concept studies were conducted to evaluate 4-(5-hydroxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 4) and 4-(5-hydroxy-4,6-dimethoxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 8), multi-functional antioxidants that can independently chelate redox metals and quench free radicals, on their ability to delay the progression of diabetic “sugar” cataracts and gamma radiation-induced cataracts. Prior to 15 Gy of whole head irradiation, select groups of Long Evans rats received either diet containing compound 4 or 8, or a single i.p. injection of panthethine, a radioprotective agent. Compared to untreated, irradiated rats, treatment with pantethine, 4 and 8 delayed initial lens changes by 4, 47, and 38 days, respectively, and the average formation of posterior subcapsular opacities by 23, 53 and 58 days, respectively. In the second study, select groups of diabetic Sprague Dawley rats were administered chow containing compounds 4, 8 or the aldose reductase inhibitor AL1576. As anticipated, treatment with AL1576 prevented cataract by inhibiting sorbitol formation in the lens. However, compared to untreated rats, compounds 4 and 8 delayed vacuole formation by 20 days and 12 days, respectively, and cortical cataract formation by 8 and 3 days, respectively, without reducing lenticular sorbitol. Using in vitro lens culture in 30 mM xylose to model diabetic “sugar” cataract formation, western blots confirmed that multi-functional antioxidants reduced endoplasmic reticulum stress. Conclusions/Significance Multi-functional antioxidants delayed cataract formation in two diverse rat models. These studies provide a proof of concept that a general cataract treatment focused on reducing oxidative stress instead of a specific mechanism of cataractogenesis can be developed. PMID:21541328

N-Acetylcysteine Restores Sevoflurane Postconditioning Cardioprotection against Myocardial Ischemia-Reperfusion Injury in Diabetic Rats.

PubMed

Lin, Jiefu; Wang, Tingting; Li, Yalan; Wang, Mengxia; Li, Haobo; Irwin, Michael G; Xia, Zhengyuan

2016-01-01

The effect of sevoflurane postconditioning (sevo-postC) cardioprotection is compromised in diabetes which is associated with increased oxidative stress. We hypothesized that antioxidant N-Acetylcysteine may enhance or restore sevo-postC cardioprotection in diabetes. Control or streptozotocin-induced Type 1 diabetic rats were either untreated or treated with N-Acetylcysteine for four weeks starting at five weeks after streptozotocin injection and were subjected to myocardial ischemia-reperfusion injury (IRI), in the absence or presence of sevo-postC. Diabetes showed reduction of cardiac STAT3 activation (p-STAT3) and adiponectin with concomitantly increase of FoxO1 and CD36, which associated with reduced sevo-postC cardioprotection. N-Acetylcysteine and sevo-postC synergistically reduced the infarct size in diabetic groups. N-Acetylcysteine remarkably increased cardiac p-STAT3 which was further enhanced by sevo-postC. N-Acetylcysteine but not sevo-postC decreased myocardial FoxO1 while sevo-postC but not N-Acetylcysteine significantly increased myocardiac adiponectin in diabetic rats. It is concluded that late stage diabetic rats displayed reduction of cardiac p-STAT3, adiponectin deficiency, and increase of FoxO1 and CD36 expression, which may be responsible for the loss of myocardial responsiveness to sevo-postC cardioprotection. N-Acetylcysteine restored Sevo-postC cardioprotection in diabetes possibly through enhancing cardiac p-STAT3 and adiponectin and reducing Fox1 and CD36.

The effect of nonsurgical periodontal therapy on hemoglobin A1c levels in persons with type 2 diabetes and chronic periodontitis: a randomized clinical trial.

PubMed

Engebretson, Steven P; Hyman, Leslie G; Michalowicz, Bryan S; Schoenfeld, Elinor R; Gelato, Marie C; Hou, Wei; Seaquist, Elizabeth R; Reddy, Michael S; Lewis, Cora E; Oates, Thomas W; Tripathy, Devjit; Katancik, James A; Orlander, Philip R; Paquette, David W; Hanson, Naomi Q; Tsai, Michael Y

2013-12-18

Chronic periodontitis, a destructive inflammatory disorder of the supporting structures of the teeth, is prevalent in patients with diabetes. Limited evidence suggests that periodontal therapy may improve glycemic control. To determine if nonsurgical periodontal treatment reduces levels of glycated hemoglobin (HbA1c) in persons with type 2 diabetes and moderate to advanced chronic periodontitis. The Diabetes and Periodontal Therapy Trial (DPTT), a 6-month, single-masked, multicenter, randomized clinical trial. Participants had type 2 diabetes, were taking stable doses of medications, had HbA1c levels between 7% and less than 9%, and untreated chronic periodontitis. Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with 5 academic medical centers. The treatment group (n = 257) received scaling and root planing plus chlorhexidine oral rinse at baseline and supportive periodontal therapy at 3 and 6 months. The control group (n = 257) received no treatment for 6 months. Difference in change in HbA1c level from baseline between groups at 6 months. Secondary outcomes included changes in probing pocket depths, clinical attachment loss, bleeding on probing, gingival index, fasting glucose level, and Homeostasis Model Assessment (HOMA2) score. Enrollment was stopped early because of futility. At 6 months, mean HbA1c levels in the periodontal therapy group increased 0.17% (SD, 1.0), compared with 0.11% (SD, 1.0) in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference, -0.05% [95% CI, -0.23% to 0.12%]; P = .55). Periodontal measures improved in the treatment group compared with the control group at 6 months, with adjusted between-group differences of 0.28 mm (95% CI, 0.18 to 0.37) for probing depth, 0.25 mm (95% CI, 0.14 to 0.36) for clinical attachment loss, 13.1% (95% CI, 8.1% to 18.1%) for bleeding on probing, and 0.27 (95% CI, 0.17 to 0.37) for gingival index (P < .001 for all). Nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes and moderate to advanced chronic periodontitis. These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering levels of HbA1c. clinicaltrials.gov Identifier: NCT00997178.

Anti-diabetic activity of methanol/methylene chloride stem bark extracts of Terminalia superba and Canarium schweinfurthii on streptozotocin-induced diabetic rats.

PubMed

Kamtchouing, P; Kahpui, S M; Dzeufiet, P-D Djomeni; Tédong, L; Asongalem, E A; Dimo, T

2006-04-06

Stem bark extracts of Terminalia superba Engl. and Diels and Canarium schweinfurthii Engl. are used in Africa for the treatment of various ailments, including diabetes mellitus. The anti-diabetic effects of the methanol/methylene chloride extracts of the stem barks on streptozotocin (STZ)-induced diabetes were evaluated on male rats. Through the subcutaneous route, diabetes was induced using 60 mg/mL of streptozotocin. After 2 days, the rats received, by gavage, 150 mg/kg and 300 mg/kg of extract daily for 14 days. At 300 mg/kg, the two extracts (Terminalia superba and Canarium schweinfurthii), significantly showed at least 67.1% and 69.9% reduction in blood glucose level, respectively, while insulin (three units) given subcutaneously and once daily, had 76.8% reduction compared to diabetic untreated control rats. Similarly, the weight gains were 6.6% and 4.9%, respectively, and were comparable to the normal rats, whereas, diabetic untreated rats lost 14.1% body weight. Still with the same dose, there was 68.5% and 58.5% (p < 0.001) significant decrease in food consumption and 79.7% and 64.0% (p < 0.001) in fluid intake by diabetic rats treated with the respective plant extracts. The insulin-treated rats showed 56.4% and 75.8% decrease in food and fluid intake compared to an augmentation for diabetic control rats, 43.0% and 383.8%, respectively, at the end of the second week of experimentation. These results showed that the plant extracts can reverse hyperglycemia, polyphagia and polydipsia provoked by streptozotocin, and thus, they have anti-diabetic properties.

The combined effect of metformin and L-cysteine on inflammation, oxidative stress and insulin resistance in streptozotocin-induced type 2 diabetes in rats.

PubMed

Salman, Zenat K; Refaat, Rowaida; Selima, Eman; El Sarha, Ashgan; Ismail, Menna A

2013-08-15

Increasing evidence has established causative links between obesity, chronic inflammation and insulin resistance; the core pathophysiological feature in type 2 diabetes mellitus. This study was designed to examine whether the combination of L-cysteine and metformin would provide additional benefits in reducing oxidative stress, inflammation and insulin resistance in streptozotocin-induced type 2 diabetes in rats. Male Wistar rats were fed a high-fat diet (HFD) for 8 weeks to induce insulin resistance after which they were rendered diabetic with low-dose streptozotocin. Diabetic rats were treated with metformin (300 mg/kg/day), L-cysteine (300 mg/kg/day) and their combination along with HFD for another 2 weeks. Control rats were fed normal rat chow throughout the experiment. At the end of treatment, fasting blood glucose, fasting serum insulin, homeostasis model assessment-insulin resistance index (HOMA-IR) and serum free fatty acids (FFAs) were measured. Serum levels of the inflammatory markers; monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) and nitrite/nitrate were also determined. The liver was isolated and used for determination of malondialdehyde (MDA), reduced glutathione (GSH), caspase-3 and cytochrome c levels. The hypoglycemic effect of the combination therapy exceeded that of metformin and L-cysteine monotherapies with more improvement in insulin resistance. All treated groups exhibited significant reductions in serum FFAs, oxidative stress and inflammatory parameters, caspase-3 and cytochrome c levels compared to untreated diabetic rats with the highest improvement observed in the combination group. In conclusion, the present results clearly suggest that L-cysteine can be strongly considered as an adjunct to metformin in management of type 2 diabetes. © 2013 Elsevier B.V. All rights reserved.

Treatment of diabetic rats with encapsulated islets

PubMed Central

Sweet, Ian R; Yanay, Ofer; Waldron, Lanaya; Gilbert, Merle; Fuller, Jessica M; Tupling, Terry; Lernmark, Ake; Osborne, William R A

2008-01-01

Immunoprotection of islets using bioisolator systems permits introduction of allogeneic cells to diabetic patients without the need for immunosuppression. Using TheraCyte™ immunoisolation devices, we investigated two rat models of type 1 diabetes mellitus (T1DM), BB rats and rats made diabetic by streptozotocin (STZ) treatment. We chose to implant islets after the onset of diabetes to mimic the probable treatment of children with T1DM as they are usually diagnosed after disease onset. We encapsulated 1000 rat islets and implanted them subcutaneously (SQ) into diabetic biobreeding (BB) rats and STZ-induced diabetic rats, defined as two or more consecutive days of blood glucose >350 mg/dl. Rats were monitored for weight and blood glucose. Untreated BB rats rapidly lost weight and were euthanized at >20% weight loss that occurred between 4 and 10 days from implantation. For period of 30–40 days following islet implantation weights of treated rats remained steady or increased. Rapid weight loss occurred after surgical removal of devices that contained insulin positive islets. STZ-treated rats that received encapsulated islets showed steady weight gain for up to 130 days, whereas untreated control rats showed steady weight loss that achieved >20% at around 55 days. Although islet implants did not normalize blood glucose, treated rats were apparently healthy and groomed normally. Autologous or allogeneic islets were equally effective in providing treatment. TheraCyte™ devices can sustain islets, protect allogeneic cells from immune attack and provide treatment for diabetic-mediated weight loss in both BB rats and STZ-induced diabetic rats. PMID:18373735

Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment.

PubMed

Maraka, Spyridoula; Mwangi, Raphael; McCoy, Rozalina G; Yao, Xiaoxi; Sangaralingham, Lindsey R; Singh Ospina, Naykky M; O'Keeffe, Derek T; De Ycaza, Ana E Espinosa; Rodriguez-Gutierrez, Rene; Coddington, Charles C; Stan, Marius N; Brito, Juan P; Montori, Victor M

2017-01-25

 To estimate the effectiveness and safety of thyroid hormone treatment among pregnant women with subclinical hypothyroidism.  Retrospective cohort study.  Large US administrative database between 1 January 2010 and 31 December 2014.  5405 pregnant women with subclinical hypothyroidism, defined as untreated thyroid stimulating hormone (TSH) concentration 2.5-10 mIU/L.  Thyroid hormone therapy.  Pregnancy loss and other pre-specified maternal and fetal pregnancy related adverse outcomes.  Among 5405 pregnant women with subclinical hypothyroidism, 843 with a mean pre-treatment TSH concentration of 4.8 (SD 1.7) mIU/L were treated with thyroid hormone and 4562 with a mean baseline TSH concentration of 3.3 (SD 0.9) mIU/L were not treated (P<0.01). Pregnancy loss was significantly less common among treated women (n=89; 10.6%) than among untreated women (n=614; 13.5%) (P<0.01). Compared with the untreated group, treated women had lower adjusted odds of pregnancy loss (odds ratio 0.62, 95% confidence interval 0.48 to 0.82) but higher odds of preterm delivery (1.60, 1.14 to 2.24), gestational diabetes (1.37, 1.05 to 1.79), and pre-eclampsia (1.61, 1.10 to 2.37); other pregnancy related adverse outcomes were similar between the two groups. The adjusted odds of pregnancy loss were lower in treated women than in untreated women if their pre-treatment TSH concentration was 4.1-10 mIU/L (odds ratio 0.45, 0.30 to 0.65) but not if it was 2.5-4.0 mIU/L (0.91, 0.65 to 1.23) (P<0.01).  Thyroid hormone treatment was associated with decreased risk of pregnancy loss among women with subclinical hypothyroidism, especially those with pre-treatment TSH concentrations of 4.1-10 mIU/L. However, the increased risk of other pregnancy related adverse outcomes calls for additional studies evaluating the safety of thyroid hormone treatment in this patient population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chromium-picolinate therapy in diabetes care: molecular and subcellular profiling revealed a necessity for individual outcome prediction, personalised treatment algorithms and new guidelines.

PubMed

Yeghiazaryan, Kristina; Peeva, Viktoriya; Shenoy, Aparna; Schild, Hans H; Golubnitschaja, Olga

2011-04-01

Global figures clearly demonstrate inadequacy of current diabetes care: every 10 seconds one patient dies of diabetes-related pathologies. Nephropathy is the leading secondary complication of the disease. Nutritional supplement by chromium-picolinate is assumed to have beneficial therapeutic effects. However, potential toxic effects reported increase concerns about safety of chromium-picolinate. The experimental design aimed at determining, whether the treatment with clinically relevant doses of chromium-picolinate can harm through DNA damage and extensive alterations in central detoxification / cell-cycle regulating pathways in treatment of diabetes. Well-acknowledged animal model of db/db-mice and clinically relevant doses of chromium-picolinate were used. As an index of DNA-damage, measurement of DNA-breaks was performed using "Comet Assay"-analysis. Individual and group-specific expression patterns of SOD-1 and P53 were evaluated to give a clue about central detoxification and cell-cycle regulating pathways under treatment conditions. The study was performed in a double-blind manner. Experimental data revealed highly individual reaction under treatment conditions. However, group-specific patterns were monitored: highest amount of damaged DNA--under the longest treatment with high doses, in contrast to groups with low doses of chromium-picolinate. Comet patterns were intermediate between untreated diabetised and control animals. Expression patterns demonstrated a correlation with subcellular imaging and dosage-dependent suppression under chromium-picolinate treatment. This article highlights possible risks for individual long-term effects, when chromium-picolinate is used freely as a therapeutic nutritional modality agent without application of advanced diagnostic tools to predict risks and individual outcomes. Targeted measures require a creation of new guidelines for advanced Diabetes care.

Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart following hypoxia/reoxygenation

PubMed Central

Mansor, Latt S.; Sousa Fialho, Maria da Luz; Yea, Georgina; Coumans, Will A.; West, James A.; Kerr, Matthew; Carr, Carolyn A.; Luiken, Joost J.F.P.; Glatz, Jan F.C.; Evans, Rhys D.; Griffin, Julian L.; Tyler, Damian J.; Clarke, Kieran

2017-01-01

Aims The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress. Methods and results Hearts from type 2 diabetic and control male Wistar rats were perfused in normoxia, hypoxia and reoxygenation, with the FAT/CD36 inhibitor sulfo-N-succinimidyl oleate (SSO) infused 4 min before hypoxia. SSO infusion into diabetic hearts decreased the fatty acid oxidation rate by 29% and myocardial triglyceride concentration by 48% compared with untreated diabetic hearts, restoring fatty acid metabolism to control levels following hypoxia-reoxygenation. SSO infusion increased the glycolytic rate by 46% in diabetic hearts during hypoxia, increased pyruvate dehydrogenase activity by 53% and decreased lactate efflux rate by 56% compared with untreated diabetic hearts during reoxygenation. In addition, SSO treatment of diabetic hearts increased intermediates within the second span of the Krebs cycle, namely fumarate, oxaloacetate, and the FAD total pool. The cardiac dysfunction in diabetic hearts following decreased oxygen availability was prevented by SSO-infusion prior to the hypoxic stress. Infusing SSO into diabetic hearts increased rate pressure product by 60% during hypoxia and by 32% following reoxygenation, restoring function to control levels. Conclusions Diabetic hearts have limited metabolic flexibility and cardiac dysfunction when stressed, which can be rapidly rectified by reducing fatty acid uptake with the FAT/CD36 inhibitor, SSO. This novel therapeutic approach not only reduces fat oxidation but also lipotoxicity, by targeting the primary step in the fatty acid metabolism pathway. PMID:28419197

The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes.

PubMed

Rubino, Francesco; Forgione, Antonello; Cummings, David E; Vix, Michel; Gnuli, Donatella; Mingrone, Geltrude; Castagneto, Marco; Marescaux, Jacques

2006-11-01

Most patients who undergo Roux-en-Y gastric bypass (RYGB) experience rapid resolution of type 2 diabetes. Prior studies indicate that this results from more than gastric restriction and weight loss, implicating the rearranged intestine as a primary mediator. It is unclear, however, if diabetes improves because of enhanced delivery of nutrients to the distal intestine and increased secretion of hindgut signals that improve glucose homeostasis, or because of altered signals from the excluded segment of proximal intestine. We sought to distinguish between these two mechanisms. Goto-Kakizaki (GK) type 2 diabetic rats underwent duodenal-jejunal bypass (DJB), a stomach-preserving RYGB that excludes the proximal intestine, or a gastrojejunostomy (GJ), which creates a shortcut for ingested nutrients without bypassing any intestine. Controls were pair-fed (PF) sham-operated and untreated GK rats. Rats that had undergone GJ were then reoperated to exclude the proximal intestine; and conversely, duodenal passage was restored in rats that had undergone DJB. Oral glucose tolerance (OGTT), food intake, body weight, and intestinal nutrient absorption were measured. There were no differences in food intake, body weight, or nutrient absorption among surgical groups. DJB-treated rats had markedly better oral glucose tolerance compared with all control groups as shown by lower peak and area-under-the-curve glucose values (P < 0.001 for both). GJ did not affect glucose homeostasis, but exclusion of duodenal nutrient passage in reoperated GJ rats significantly improved glucose tolerance. Conversely, restoration of duodenal passage in DJB rats reestablished impaired glucose tolerance. This study shows that bypassing a short segment of proximal intestine directly ameliorates type 2 diabetes, independently of effects on food intake, body weight, malabsorption, or nutrient delivery to the hindgut. These findings suggest that a proximal intestinal bypass could be considered for diabetes treatment and that potentially undiscovered factors from the proximal bowel might contribute to the pathophysiology of type 2 diabetes.

Effects of Short-Term Very Low Calorie Diet on Intramyocellular Lipid and Insulin Sensitivity in Non-diabetics and Type 2 Diabetic Patients

PubMed Central

Lara-Castro, Cristina; Newcomer, Bradley R; Rowell, Jennifer; Wallace, Penny; Shaughnessy, Sara M; Munoz, A Julian; Shiflett, Alanna M; Rigsby, Dana Y; Lawrence, Jeannine C; Bohning, Daryl E; Buchthal, Steven; Garvey, W Timothy

2008-01-01

Objective To study the effects of a short-term very-low calorie diet (VLCD) on intramyocellular lipid (IMCL), total body fat, and insulin sensitivity in a group of obese non-diabetic and Type 2 Diabetic (T2DM) patients. Research Methods and Procedures Seven untreated T2DM and 5 obese non-diabetic individuals were studied before and after a 6-day VLCD using proton-magnetic resonance spectroscopy to quantify IMCL, DXA to assess body fat, and hyperinsulinemic-euglycemic clamps to measure peripheral insulin sensitivity. Results In both groups, decrements in total body fat mass and BMI were small but statistically significant. In contrast, the diet resulted in a pronounced reduction in IMCL compared to baseline values in non-diabetics (56% decrease) and T2DM (40% decrease), P<0.05, and this was accompanied by an overall 9.3% increase in maximally-stimulated glucose disposal rate (P<0.01). IMCL was significantly correlated with insulin sensitivity, (r=−0.69; P<0.01) and waist circumference (r = 0.72 and 0.83, baseline and post-diet respectively, both P < 0.01), but neither IMCL nor insulin sensitivity was related to measures of general adiposity such as BMI, % body fat, or total body fat (P=NS). Conclusions Short-term VLCD is accompanied by small decrements in general adiposity, marked decrease in IMCL, and an increase in insulin sensitivity in non-diabetic and T2DM subjects. Therefore, rapid amelioration of insulin resistance by VLCD can be partially explained by loss of IMCL in both non-diabetics and in T2DM in the absence of substantial changes in total body fat. These observations are consistent with the idea that insulin resistance is more directly related to IMCL rather than body fat per se. PMID:18078853

Hypoglycemic and hypolipidemic effects of Bersama engleriana leaves in nicotinamide/streptozotocin-induced type 2 diabetic rats

PubMed Central

2012-01-01

Background The present investigation was aimed at evaluating the hypoglycemic and hypolipidemic properties of the aqueous and methanolic extracts from Bersama engleriana leaves in streptozotocin/nicotinamide (STZ-NA)-induced type 2 diabetic rats. Methods Animals were orally treated for 4 consecutive weeks with Bersama engleriana extracts at doses of 300 or 600 mg/kg. The anti-diabetic effect was examined by measuring blood glucose (BG) at 0, 1, 14 and 28 days after STZ-NA treatment and, total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) levels at sacrifice (day 29). Glibenclamide (0.25 mg/kg) was used for comparison. Results STZ-NA-induced diabetic rats showed moderate to significant increases in the levels of BG, TG, TC, LDL-C while body weight, HDL-C levels and relative weights of liver and pancreas were decreased compared to controls (non diabetic rats). Administration of the plant extracts to STZ-NA diabetic rats resulted in a significant decrease in BG, TG, TC and LDL-C and the dose 600 mg/kg of the methanolic extract was the most effective; HDL-C level was markedly increased after four weeks compared to untreated diabetic rats. A dose-dependent increase in the relative weights of the diabetogenic organs was observed in the Bersama engleriana groups. It can be also noticed that the methanolic extract, especially the dose 600 mg/kg (p<0.001), produced more effects than glibenclamide and aqueous extract. Rats treated with glibenclamide (0.25 mg/kg) generally gave lower results compared to groups treated with plant extracts. Conclusion Results of the present study showed that Bersama engleriana extracts and especially its methanolic extract possess antidiabetogenic properties and beneficial effects on diabetic hyperlipidemia. All these effects could be due to the bioactive components revealed in the Bersama engleriana extracts such as triterpenes and phenols and which could justify its ethnomedical use. PMID:23267560

Prevalence and clinical characteristics of white-coat hypertension based on different definition criteria in untreated and treated patients.

PubMed

de la Sierra, Alejandro; Vinyoles, Ernest; Banegas, José R; Segura, Julián; Gorostidi, Manuel; de la Cruz, Juan J; Ruilope, Luis M

2017-12-01

The prevalence and associated risks of white-coat hypertension (WCH) are still a matter of debate. We aimed to assess differences in prevalence and associated conditions of WCH defined on the basis of the normality of all daytime, night-time, and 24-h blood pressure (BP), only daytime, or only 24-h BP. We selected 115 708 patients (45 020 untreated and 70 688 treated) from the Spanish Ambulatory BP Monitoring Registry. WCH was estimated in patients with elevated office BP (≥140 and/or 90 mmHg) by using normal daytime (<135/85) BP, normal 24-h BP (<130/80), or normal daytime, night-time (<120/70) and 24-h BP. Demographic and clinical data (associated risk factors and organ damage) were compared among groups. Prevalence of WCH was 41.3, 35.2, and 26.1% in untreated, and 45.8, 38.9, and 27.2% in treated patients with elevated office BP, by using the criteria of daytime, 24-h, or all ambulatory periods. Compared with the normotensive group, WCH defined by normal daytime, night-time, and 24-h BP did not significantly differ in terms of other cardiovascular risk factors or organ damage. In contrast, patients from other groups (either only normal daytime BP or 24-h BP) had significantly more prevalence of diabetes, dyslipidaemia, microalbuminuria, left ventricular hypertrophy, reduced renal function, and previous history of cardiovascular disease. Prevalence of WCH is dependent on definition criteria. Only diagnostic criteria which considers the normality of all ambulatory periods identifies patients with cardiovascular risk similar to normotensive patients. These results support using such criteria for a more accurate definition of WCH.

Antidiabetic and antihyperlipidemic activity of Piper longum root aqueous extract in STZ induced diabetic rats

PubMed Central

2013-01-01

Background The available drugs for diabetes, Insulin or Oral hypoglycemic agents have one or more side effects. Search for new antidiabetic drugs with minimal or no side effects from medicinal plants is a challenge according to WHO recommendations. In this aspect, the present study was undertaken to evaluate the antihyperglycemic and antihyperlipidemic effects of Piper longum root aqueous extract (PlrAqe) in streptozotocin (STZ) induced diabetic rats. Methods Diabetes was induced in male Wister albino rats by intraperitoneal administration of STZ (50 mg/kg.b.w). Fasting blood glucose (FBG) levels were measured by glucose-oxidase & peroxidase reactive strips. Serum biochemical parameters such as glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol were estimated. The activities of liver and kidney functional markers were measured. The statistical analysis of results was carried out using Student t-test and one-way analysis (ANOVA) followed by DMRT. Results During the short term study the aqueous extract at a dosage of 200 mg/kg.b.w was found to possess significant antidiabetic activity after 6 h of the treatment. The administration of aqueous extract at the same dose for 30 days in STZ induced diabetic rats resulted in a significant decrease in FBG levels with the corrections of diabetic dyslipidemia compared to untreated diabetic rats. There was a significant decrease in the activities of liver and renal functional markers in diabetic treated rats compared to untreated diabetic rats indicating the protective role of the aqueous extract against liver and kidney damage and its non-toxic property. Conclusions From the above results it is concluded that the plant extract is capable of managing hyperglycemia and complications of diabetes in STZ induced diabetic rats. Hence this plant may be considered as one of the potential sources for the isolation of new oral anti hypoglycemic agent(s). PMID:23414307

Renal accumulation of pentosidine in non-diabetic proteinuria-induced renal damage in rats.

PubMed

Waanders, Femke; Greven, Wendela L; Baynes, John W; Thorpe, Suzanne R; Kramer, Andrea B; Nagai, Ryoji; Sakata, Noriyuki; van Goor, Harry; Navis, Gerjan

2005-10-01

Advanced glycation end-products (AGEs) contribute to the pathogenesis of diabetic glomerulopathy. The role of AGEs in non-diabetic renal damage is not well characterized. First, we studied whether renal AGE accumulation occurs in non-diabetic proteinuria-induced renal damage and whether this is ameliorated by renoprotective treatment. Secondly, we investigated whether renal AGE accumulation was due to intrarenal effects of local protein trafficking. Pentosidine was measured (by high-performance liquid chromatography) in rats with chronic bilateral adriamycin nephropathy (AN), untreated and treated with lisinopril. Age-matched healthy rats served as negative controls. Secondly, we compared renal pentosidine in mild proteinuric and non-proteinuric kidneys of unilateral AN and in age-matched controls at 12 and 30 weeks. Intrarenal localization of pentosidine was studied by immunohistochemistry. Renal pentosidine was elevated in untreated AN (0.14+/-0.04 micromol/mol valine) vs healthy controls (0.04+/-0.01 micromol/mol valine, P<0.01). In lisinopril-treated AN, pentosidine was lower (0.09+/-0.02 micromol/mol valine) than in untreated AN (P<0.05). In unilateral proteinuria, pentosidine was similar in non-proteinuric and proteinuric kidneys. After 30 weeks of unilateral proteinuria, pentosidine was increased in both kidneys (0.26+/-0.10 micromol/mol valine) compared with controls (0.18+/-0.06 micromol/mol valine, P<0.05). Pentosidine (AN, week 30) was also increased compared with AN at week 12 (0.16+/-0.06 micromol/mol valine, P<0.01). In control and diseased kidneys, pentosidine was present in the collecting ducts. In proteinuric kidneys, in addition, pentosidine was present in the brush border and cytoplasm of dilated tubular structures, i.e. at sites of proteinuria-induced tubular damage. Pentosidine accumulates in non-diabetic proteinuric kidneys in damaged tubules, and renoprotective treatment by angiotensin-converting enzyme (ACE) inhibitors inhibits AGE accumulation, supporting a relationship between abnormal renal protein trafficking, proteinuria-induced tubular damage and tubular pentosidine accumulation. Future studies, applying specific AGE inhibitors, should be conducted to provide insight into the pathophysiological significance of renal AGEs in non-diabetic renal disease.

Effect of diabetes and elevated glucose on nitric oxide-mediated neurotransmission in rat anococcygeus muscle.

PubMed Central

Way, K. J.; Reid, J. J.

1995-01-01

1. Nitric oxide (NO)-mediated neurotransmission is impaired in anococcygeus muscle from 8-week streptozotocin-induced diabetic rats. This study investigated the effects of insulin treatment, and the duration of diabetes on this impairment. In addition, the effect of in vitro exposure to elevated glucose has been investigated on NO-mediated relaxations, in muscles from untreated rats. 2. Relaxant responses to field stimulation (0.5-5 Hz, 10s train), sodium nitroprusside (SNP; 5 and 10 nM) and NO (1 and 3 microM) were significantly impaired in anococcygeus muscles from 8-week diabetic rats, compared to responses from control rats. Insulin treatment (5 u Lente day-1, s.c.) of diabetic rats prevented the development of this impairment. 3. Consistent with findings in 8-week diabetic rats, relaxation induced by field stimulation, SNP and NO were attenuated in tissues from 2-week and 4-week diabetic rats compared to corresponding control responses, whereas relaxations to papaverine (3 and 10 microM) were not reduced. In contrast, diabetes of 3-days duration did not affect relaxations to field stimulation, SNP or NO. 4. Incubation of anococcygeus muscles from untreated rats in medium containing elevated glucose (44.1 mM) for 6 h, significantly impaired relaxations to field stimulation compared to responses obtained after normal glucose (11.1 mM) incubation. Relaxations to SNP and to NO were not affected by 6 h exposure to elevated glucose. Similarly, incubation in hyperosmolar solutions containing mannose or sucrose for 6 h, impaired relaxations to field stimulation, but not to SNP or NO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7582450

HbA1c in the diagnosis of diabetes and abnormal glucose tolerance in patients with Graves' hyperthyroidism.

PubMed

Yang, Liyong; Shen, Ximei; Yan, Sunjie; Yuan, Xin; Lu, Juanjuan; Wei, Wenfeng

2013-07-01

To assess the suitability of HbA1c as a criterion for the diagnosis of diabetes in patients with Graves' disease. This study enrolled 310 patients with untreated newly diagnosed Graves' disease, 208 patients with euthyroid goiter and 329 age-matched (control) subjects without thyroid disease from Fuzhou, China. The performance of HbA1c against the OGTT for diagnosing diabetes was determined. The Framingham risk score was used to assess general cardiovascular disease (CVD) risk. The percentage of patients with abnormal glucose metabolism as classified by HbA1c levels was lower than by OGTT criteria in patients with Graves' disease-33.2% vs. 41.3% for pre-diabetes and 4.5% vs. 11.3% for diabetes, respectively. The sensitivity of HbA1c for diagnosing diabetes in patients with Graves' disease was lower than in patients with euthyroid goiter and subjects without thyroid disease (34.9%, 63.2% and 60.6% respectively), while the specificity was similar (99.3%, 98.6%, 97.4%). Approximately 7.4% of patients with Graves' disease diagnosed with diabetes according to OGTT criteria were misdiagnosed as not having the disease by HbA1c, much higher than that for the other two groups. Patients with Graves' disease with diabetes not diagnosed with the disease by HbA1c showed a high risk for CVD. The low sensitivity of the HbA1c criterion underestimated the percentage of diabetes in patients with Graves' disease. Patients with diabetes who were misdiagnosed as not having the disease by HbA1c were at high risk for CVD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Sargassum polycystum reduces hyperglycaemia, dyslipidaemia and oxidative stress via increasing insulin sensitivity in a rat model of type 2 diabetes.

PubMed

Motshakeri, Mahsa; Ebrahimi, Mahdi; Goh, Yong Meng; Matanjun, Patricia; Mohamed, Suhaila

2013-05-01

Sargassum polycystum, a brown seaweed, contains various nutrients and bioactive compounds that have antioxidant and healing properties. The research hypothesises that antioxidants and pigments in dietary S. polycystum extracts can improve insulin sensitivity, blood sugar levels and blood lipid levels in a rat model of type 2 diabetes. The diabetes was induced by a high-sugar, high-fat diet for 16 weeks to enhance insulin resistance, followed by a low-dose intraperitoneal injection of streptozotocin (35 mg kg(-1) body weight). The doses of S. polycystum tested on diabetic rats were 150 and 300 mg kg(-1) body weight for the ethanolic extract or 150 and 300 mg kg(-1) for the water extract. Normal rats, untreated diabetic and metformin-treated diabetic rats (n = 6) were used as control. Both doses of the alcohol extract of S. polycystum and the 300 mg kg(-1) water extract, significantly reduced blood glucose and glycosylated haemoglobin (HbA1C ) levels. Serum total cholesterol, triglyceride levels and plasma atherogenic index were significantly decreased after 22 days treatment in all seaweed groups. Unlike metformin, S. polycystum did not significantly change plasma insulin in the rats, but increased the response to insulin. The consumption of either ethanolic or water extracts of S. polycystum dose dependently reduced dyslipidaemia in type 2 diabetic rats. S. polycystum is a potential insulin sensitiser, for a comestible complementary therapy in the management of type 2 diabetes which can help reduce atherogenic risk. © 2012 Society of Chemical Industry.

Comparison of exendin-4 on beta-cell replication in mouse and human islet grafts.

PubMed

Tian, Lei; Gao, Jie; Weng, Guangbin; Yi, Huimin; Tian, Bole; O'Brien, Timothy D; Guo, Zhiguang

2011-08-01

Exendin-4 can stimulate β-cell replication in mice. Whether it can stimulate β-cell replication in human islet grafts remains unknown. Therefore, we compared the effects of exendin-4 on β-cell replication in mouse and human islet grafts. Islets, isolated from mouse and human donors at different ages, were transplanted into diabetic mice and/or diabetic nude mice that were given bromodeoxyuridine (BrdU) with or without exendin-4. At 4 weeks post-transplantation, islet grafts were removed for insulin and BrdU staining and quantification of insulin(+)/BrdU(+) cells. Although diabetes was reversed in all mice transplanting syngeneic mouse islets from young or old donors, normoglycemia was achieved significantly faster in exendin-4 treated mice. Mouse islet grafts in exendin-4 treated mice had significantly more insulin(+)/BrdU(+) β cells than in untreated mice (P < 0.01). Human islet grafts from ≤22-year-old donors had more insulin(+)/BrdU(+) β cells in exendin-4 treated mice than that in untreated mice (P < 0.01). However, human islet grafts from ≥35-year-old donors contained few insulin(+)/BrdU(+) β cells in exendin-4 treated or untreated mice. Our data demonstrated that the capacity for β-cell replication in mouse and human islet grafts is different with and without exendin-4 treatment and indicated that GLP-1 agonists can stimulate β-cell replication in human islets from young donors. © 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.

Secoisolariciresinol diglucoside in high-fat diet and streptozotocin-induced diabetic nephropathy in rats: a possible renoprotective effect.

PubMed

Sherif, Iman O

2014-12-01

Due to substantial morbidity and high complication rate of diabetes mellitus, which is considered as the third killer in the world, a search for the effective blockade of the progression of diabetic nephropathy (DN) remains a therapeutic challenge. Alternative antidiabetic drugs from natural plants are highly demanded nowadays. The aim of this study was to investigate the renoprotective effect of secoisolariciresinol diglucoside (SDG) on DN induced in rats. Diabetes was induced in male Sprague-Dawley rats by a high-fat diet (HFD) and an intraperitoneal 35 mg/kg streptozotocin (STZ) injection. Rats were divided into four groups: normal control rats, diabetic control rats, diabetic rats treated with SDG at 10 mg/kg/day for 4 weeks, and diabetic rats treated with SDG at 20 mg/kg/day for 4 weeks. At the end of the treatment, blood and renal tissue samples were collected for biochemical examination. The results revealed that SDG treatment significantly increased insulin level and decreased blood glucose, fructosamine, creatinine, and blood urea nitrogen levels in diabetic rats. Also, SDG significantly increased renal reduced glutathione, superoxide dismutase and decreased malondialdehyde and nitric oxide levels. In addition, SDG downregulated the renal nuclear factor kappa-B (NF-κB), tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) and upregulated renal survivin and B-cell lymphoma-2 (Bcl-2) expressions when compared with untreated diabetic control rats. This study demonstrated, for the first time, the renoprotective effects of SDG in HFD/STZ-induced DN in rats through correction of hyperglycemia; attenuation of oxidative/nitrosative stress markers; downregulation of renal expressions of inflammatory markers NF-κB, TNF-α, and iNOS; along with upregulation of renal expressions of antiapoptotic markers survivin and Bcl-2.

The effect of alloxan diabetes on the activity of some mixed function oxidases in male rats.

PubMed

Nedjar, A; Stoytchev, T

1990-01-01

The effect of alloxan-induced diabetes on the duration of hexobarbital sleep (HB sleep) the activity of ethylmorphine-N-demethylase (EMND), aniline hydroxylase (AH), the content of microsomal cytochrome P-450 and b5, on the activity of ethoxycumarine-0-deethylase (ECOD) and ethoxyresorufine-0-deethylase (EROD) after induction with beta naphthoflavone (beta-NF), as well as the activity of benzphetamine-N-demethylase and pentoxyresorufine-O-dealkylase (PROD) after induction with phenobarbital (PB), was studied in experiments on male Wistar rats. In rats with alloxan diabetes there was a significant prolongation of HB sleep (by 106%) and inhibition of the liver EMND (by 54%), while the AH activity increased by 131%, with a parallel rise in the content of microsomal cytochromes P-450 (by 67%) and b5 (by 113%). In rats with alloxan diabetes the enzyme-inducing effect of beta-NF with respect to the activities of EROD and ECOD is reduced, although diabetes by itself causes a rise in the ECOD activity in untreated animals. When induced with PB, the PROD and benzphetamine-N-demethylase activity in diabetic rats is lower than in the healthy animals. However, if the enzyme activity after the application of inducers is referred to the respective starting enzyme activities of the two groups of animals, it is found that the enzyme-inducing effect of PB is preserved and even slightly potentiated in the diabetic rats compared with the healthy ones: the increases in the benzphetamine-N-demethylase activity is by 60% in the diabetic rats, compared with a rise of 28% in the healthy animals, of the PROD activity 19 times for the diabetic compared with 16 times increase for the healthy rats.

A search for malnutrition-related diabetes mellitus among Ethiopian patients.

PubMed

Lester, F T

1993-01-01

To search for evidence of MRDM among Ethiopian patients. We reviewed the records from March 1976 to January 1991 of 1835 Ethiopian diabetic patients registered consecutively in the Diabetic Clinic of Yekatit 12 Hospital in Addis Ababa, Ethiopia. Of those aged 15-30 at onset, 41.3% had a BMI < 19 kg/m2 at diagnosis, and 55% of the latter had a history of normal weight before the onset of symptoms. The frequency of KA was similar in the very thin patients and others of the same age-group, and only 1 patient required > 1.5 IU insulin in 24 h. Pancreatic calcification was observed in only 4 middle-aged men with histories of alcohol abuse, and the very thin patients did not have other stigmata of malnutrition. Of the 1604 patients > or = 18 yr of age at diagnosis, only 21 of 1116 who knew their previous weight had a BMI < 19 kg/m2 before the onset of diabetic symptoms, and most of the 178 patients with a BMI < 19 kg/m2 on treatment had been normal or even overweight. In regression analysis, the factors associated with weight loss before diagnosis were the duration of symptoms in type I diabetes patients and the need for insulin from diagnosis, poverty certification, and symptom duration in type II diabetes patients. Weight gain with treatment was related to female sex, the duration of symptoms, and the absence of tuberculosis in type I diabetes patients and related to an address/birthplace not in Addis Ababa in type II diabetes patients. The undernutrition at presentation is probably caused by the untreated diabetic state and is reversible with treatment, even if the patient is poor and/or lives in a rural area. No convincing cases of MRDM fulfilling the published definition could be found.

Balanites aegyptiaca ameliorates insulin secretion and decreases pancreatic apoptosis in diabetic rats: Role of SAPK/JNK pathway.

PubMed

Hassanin, Kamel M A; Mahmoud, Mohamed O; Hassan, Hossam M; Abdel-Razik, Abdel-Razik H; Aziz, Lourin N; Rateb, Mostafa E

2018-06-01

SAPK-JNK pathway performs a significant role in the pathogenesis of type 2 diabetes. Balanites aegyptiaca (BA) is used as an anti-diabetic agent in folk medicine however its hypoglycemic mechanism is not fully elucidated. The current study aimed to evaluate the effect of crude extract, butanol, and dichloromethane fractions from BA on the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK-JNK) pathway in experimental diabetic rats. Six groups of male Wistar rats were included: normal control, diabetic, diabetic rats treated with crude, butanol or dichloromethane fraction from BA (50 mg/kg BW) and diabetic rats treated with gliclazide as a reference drug for one month. Our results suggested a protective role of treatment of diabetic rats with BA against oxidative stress-induced SAPK-JNK pathway. Moreover, BA treatment produced a reduction in plasma glucose, HbA 1c , lactic acid, lipid profile, malondialdehyde levels and produced an increase in insulin, reduced glutathione levels, catalase and superoxide dismutase activities compared with untreated diabetic rats. Moreover, it decreased apoptosis signal-regulating kinase 1, c-Jun N-terminal kinase 1, protein 53 and increased insulin receptor substrate 1 in rat pancreas while it increased glucose transporter 4 in rat muscle. Analysis of BA extracts by LC-HRMS revealed the presence of different saponins with reported hypoglycemic effect. In conclusion, BA exerted hypoglycemic, hypolipidemic, insulinotropic and antioxidant effects. Additionally, it reduced apoptosis in pancreatic β-cells and increased glucose uptake in muscle. These results suggest that the hypoglycemic effect of BA is due to the inhibition of the SAPK-JNK pathway. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Extracellular Matrix Remodeling and Modulation of Inflammation and Oxidative Stress by Sulforaphane in Experimental Diabetic Peripheral Neuropathy.

PubMed

Moustafa, Passant E; Abdelkader, Noha F; El Awdan, Sally A; El-Shabrawy, Osama A; Zaki, Hala F

2018-04-27

The peripheral nervous system is one of many organ systems that can be profoundly impacted in diabetes mellitus. Diabetic peripheral neuropathy has a significant negative effect on patients' quality of life as it begins with loss of limbs' sensation and may result in lower limb amputation. This investigation aimed at exploring the effect of sulforaphane on peripheral neuropathy in diabetic rats. Experimental diabetes was induced through single intraperitoneal injections of nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Rats were divided into five groups. Two groups were treated with saline or sulforaphane (1 mg/kg, p.o.). Three diabetic groups were either untreated or given sulforaphane (1 mg/kg, p.o.) or pregabalin (10 mg/kg, i.p.). Two weeks after drugs' administration, biochemical, behavioral, histopathological, and immunohistochemical investigations were carried out. Treatment with sulforaphane restored animals' body weight, reduced blood glucose, glycated hemoglobin, and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test, and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, and matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents. These results reveal the neuroprotective effect of sulforaphane against peripheral neuropathy in diabetic rats possibly through modulating oxidative stress, inflammation, and extracellular matrix remodeling. Graphical Abstract Diagram that illustrates the effects of sulforaphane in treating experimental diabetic peripheral neuropathy. In NA-STZ model of diabetes mellitus, sulforaphane, restored animals' body weight, reduced blood glucose, glycated hemoglobin and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents.

Anti-diabetic activity of extract from Persea americana Mill. leaf via the activation of protein kinase B (PKB/Akt) in streptozotocin-induced diabetic rats.

PubMed

Lima, C R; Vasconcelos, C F B; Costa-Silva, J H; Maranhão, C A; Costa, J; Batista, T M; Carneiro, E M; Soares, L A L; Ferreira, F; Wanderley, A G

2012-05-07

The leaves of Persea americana Mill. (Lauraceae) have been popularly used in the treatment of diabetes in countries in Latin America and Africa. To investigate the hypoglycaemic properties and to determine the molecular mechanism by which the hydroalcoholic extract of the leaves of Persea americana reduce blood glucose levels in streptozotocin (STZ)-induced diabetes in rats via the enzymatic pathway of protein kinase B (PKB/Akt). The hydroalcoholic extract of the leaves of Persea americana (0.15 and 0.3g/kg/day), vehicle and metformin (0.5g/kg/day) were administered orally to STZ-diabetic rats (n=7/group) for 4 weeks. Changes in body weight, food and water intake, fasting glucose levels and oral glucose tolerance were evaluated. Phosphorylation and the expression of PKB in the liver and soleus muscle were determined by Western blot. The hydroalcoholic extract of the leaves of Persea americana reduced blood glucose levels and improved the metabolic state of the animals. Additionally, PKB activation was observed in the liver and skeletal muscle of treated rats when compared with untreated rats. The results indicate that the hydroalcoholic extract of the leaves of Persea americana has anti-diabetic properties and possibly acts to regulate glucose uptake in liver and muscles by way of PKB/Akt activation, restoring the intracellular energy balance. Copyright © 2012. Published by Elsevier Ireland Ltd.

Effect of Chronic Administration of Forskolin on Glycemia and Oxidative Stress in Rats with and without Experimental Diabetes

PubMed Central

Ríos-Silva, Mónica; Trujillo, Xóchitl; Trujillo-Hernández, Benjamín; Sánchez-Pastor, Enrique; Urzúa, Zorayda; Mancilla, Evelyn; Huerta, Miguel

2014-01-01

Forskolin is a diterpene derived from the plant Coleus forskohlii. Forskolin activates adenylate cyclase, which increases intracellular cAMP levels. The antioxidant and antiinflammatory action of forskolin is due to inhibition of macrophage activation with a subsequent reduction in thromboxane B2 and superoxide levels. These characteristics have made forskolin an effective medication for heart disease, hypertension, diabetes, and asthma. Here, we evaluated the effects of chronic forskolin administration on blood glucose and oxidative stress in 19 male Wistar rats with streptozotocin-induced diabetes compared to 8 healthy male Wistar rats. Rats were treated with forskolin, delivered daily for 8 weeks. Glucose was assessed by measuring fasting blood glucose in diabetic rats and with an oral glucose tolerance test (OGTT) in healthy rats. Oxidative stress was assessed by measuring 8-hydroxydeoxyguanosine (8‑OHdG) in 24-h urine samples. In diabetic rats, without forskolin, fasting blood glucose was significantly higher at the end than at the beginning of the experiment (8 weeks). In both healthy and diabetic rats, forskolin treatment lowered the fasting glucose at the end of the experiment but no effect was found on oral glucose tolerance. The 8-OHdG levels tended to be less elevated in forskolin-treated than in untreated group. Our results showed that chronic administration of forskolin decreased fasting blood glucose levels; however, the reductions of 8-OHdG were not statistically significant. PMID:24688307

Effect of chronic administration of forskolin on glycemia and oxidative stress in rats with and without experimental diabetes.

PubMed

Ríos-Silva, Mónica; Trujillo, Xóchitl; Trujillo-Hernández, Benjamín; Sánchez-Pastor, Enrique; Urzúa, Zorayda; Mancilla, Evelyn; Huerta, Miguel

2014-01-01

Forskolin is a diterpene derived from the plant Coleus forskohlii. Forskolin activates adenylate cyclase, which increases intracellular cAMP levels. The antioxidant and antiinflammatory action of forskolin is due to inhibition of macrophage activation with a subsequent reduction in thromboxane B2 and superoxide levels. These characteristics have made forskolin an effective medication for heart disease, hypertension, diabetes, and asthma. Here, we evaluated the effects of chronic forskolin administration on blood glucose and oxidative stress in 19 male Wistar rats with streptozotocin-induced diabetes compared to 8 healthy male Wistar rats. Rats were treated with forskolin, delivered daily for 8 weeks. Glucose was assessed by measuring fasting blood glucose in diabetic rats and with an oral glucose tolerance test (OGTT) in healthy rats. Oxidative stress was assessed by measuring 8-hydroxydeoxyguanosine (8‑OHdG) in 24-h urine samples. In diabetic rats, without forskolin, fasting blood glucose was significantly higher at the end than at the beginning of the experiment (8 weeks). In both healthy and diabetic rats, forskolin treatment lowered the fasting glucose at the end of the experiment but no effect was found on oral glucose tolerance. The 8-OHdG levels tended to be less elevated in forskolin-treated than in untreated group. Our results showed that chronic administration of forskolin decreased fasting blood glucose levels; however, the reductions of 8-OHdG were not statistically significant.

The Effectiveness of Various Salacca Vinegars as Therapeutic Agent for Management of Hyperglycemia and Dyslipidemia on Diabetic Rats

PubMed Central

Rukmi Putri, Widya Dwi; Puspitasari, Tiara; Kalsum, Umi; Dianawati, Dianawati

2017-01-01

The aim of this study was to explore the potency of salacca vinegar made from various Indonesian salacca fruit extracts as therapeutic agent for hyperglycemia and dyslipidemia for STZ-induced diabetic rats. The rats were grouped into untreated rats, STZ-induced diabetic rats without treatment, and STZ-induced diabetic rats treated with Pondoh salacca vinegar, Swaru salacca vinegar, Gula Pasir salacca vinegar, Madu salacca vinegar, or Madura salacca vinegar. Parameter observed included blood glucose, total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglyceride (TG), malondialdehyde (MDA), superoxide dismutase (SOD), and pancreas histopathology of the samples. The results demonstrated that all salacca vinegars were capable of reducing blood sugar (from 25.1 to 62%) and reducing LDL (from 9.5 to 14.8 mg/dL), TG (from 58.3 to 69.5 mg/dL), MDA (from 1.1 to 2.2 mg/dL), and TC (from 56.3 to 70.5 mg/dL) as well as increasing HDL blood sugar of STZ-induced diabetic Wistar rats (from 52.3 to 60 mg/dL). Various salacca vinegars were also capable of regenerating pancreatic cells. Nevertheless, the ability of Swaru salacca vinegar to manage hyperglycemia and dyslipidemia appeared to be superior to other salacca vinegars. Swaru salacca vinegar is a potential therapeutic agent to manage hyperglycemia and dyslipidemia of STZ-induced diabetic rats. PMID:28424779

Suramin-restricted blood volume in the placenta of normal and diabetic rats is normalized by vitamin E treatment.

PubMed

Nash, P; Eriksson, U J

2007-01-01

Previously maternal and fetal alterations resembling human pre-eclampsia were induced in pregnant rats by injections of the angiogenesis inhibitor Suramin. These alterations were aggravated by maternal diabetes and partly rectified by vitamin E supplementation. In the present study we evaluated the morphology of placentae and kidneys in this model. Non-diabetic and streptozotocin-induced diabetic pregnant rats of two rat strains (U and H) were treated with Suramin or saline, and given standard or vitamin E-enriched food. On gestational day 20 one placenta and the left kidney of the mother were collected for morphological and stereological analysis. In the placental trophospongium Suramin treatment caused cysts, which were further enhanced by maternal diabetes. Vitamin E treatment had no effect on the vacuolization. In the placental labyrinth of the non-diabetic rats Suramin treatment restricted maternal placental blood volume and increased the interface between maternal and fetal circulation. These changes were reversed by vitamin E treatment. Diabetes increased slightly the interface between the circulations in both rat strains. Suramin treatment decreased the interface, and vitamin E further decreased the interface in the diabetic U rats, whereas neither treatment affected the maternal-fetal interface in the diabetic H rats. The kidneys of Suramin-treated and diabetic rats were heavier compared to controls. Suramin treatment and maternal diabetes damaged renal glomeruli to a similar extent. Vitamin E treatment diminished the Suramin- and diabetes-induced glomerular damage in U rats, but not in H rats. The average cell count per glomerulus was decreased by Suramin in the U rats. Vitamin E treatment did not affect cell number per glomerulus in any group. We conclude that Suramin-injected pregnant rats constitute a valid animal model for placental dysfunction and pre-eclampsia, also from the histological perspective. The present work supports the notion that one important effect of untreated maternal diabetes may be impaired placentation, leading to oxidative stress, morphological damage, and compromised placental function.

Dietary Treatment Options for Depression among Diabetic Patient, Focusing on Macronutrients

PubMed Central

Azadbakht, Leila

2013-01-01

There is a bidirectional adverse association between diabetes and depression. The odds for experiencing depressive symptoms in diabetic patients are two times more than nondiabetic persons, and depression is an independent predictor for the onset of diabetes. However, depression has been approximately unrecognized and untreated in two-thirds of diabetic patients, which may lead to worsened diabetes complications. A cornerstone strategy for managing depression among diabetic patients is the use of diet to improve both health problems. Because of similar pathophysiology for chronic diseases and depression, it seems that similar dietary recommendations could be useful. However, few studies have been conducted among diabetic patients. Regarding the complications of diabetes such as renal diseases and coronary heart diseases, the proper range of various macronutrients should be clarified in depressed diabetic patients as well as the proper type of each macronutrient. In this paper, we reviewed the available data on the treatment of depression in diabetic patients. PMID:24199205

Investigation of aquaporins and apparent diffusion coefficient from ultra-high b-values in a rat model of diabetic nephropathy.

PubMed

Wang, Yu; Zhang, Heng; Zhang, Ruzhi; Zhao, Zhoushe; Xu, Ziqian; Wang, Lei; Liu, Rongbo; Gao, Fabao

2017-01-01

To assess kidney damage in a rat model of type-2 diabetic nephropathy based on apparent diffusion coefficient (ADC) data obtained from ultra-high b-values and discuss its relationship to the expression of aquaporins (AQPs). This study was approved by the institutional Animal Care and Use Committee. Thirty male Sprague-Dawley rats were randomised into two groups: (1) untreated controls and (2) diabetes mellitus (DM). All rats underwent diffusion-weighted imaging (DWI) with 18 b-values (0-4500 s/mm 2 ). Maps of low ADC (ADC low ), standard ADC (ADC st ) and ultra-high ADC (ADC uh ) were calculated from low b-values (0-200 s/mm 2 ), standard b-values (300-1500 s/mm 2 ) and ultra-high b-values (1700-4500 s/mm 2 ), respectively. The expression of AQPs in the kidneys was studied using immunohistochemistry. Laboratory parameters of diabetic and kidney functions, ADC low , ADC st , ADC uh , and the optical density (OD) of AQP expression in the two groups were compared using an independent t test. Correlations between ADCs and the OD of AQP expression were evaluated by Pearson's correlation analysis. ADC uh were significantly higher in the cortex (CO), outer stripe of the outer medulla (OS) and inner stripe of the outer medulla (IS), and the OD values of AQ-2 were significantly higher in the OS, IS and inner medulla (IM) in DM animals compared with control animals. ADC uh and OD values of AQP-2 expression were positively correlated in the OS, IS and IM of the kidney. ADC uh may work as useful metrics for early detection of kidney damage in diabetic nephropathy and may be associated with AQP-2 expression.

Endothelin Receptor-A Antagonist Attenuates Retinal Vascular and Neuroretinal Pathology in Diabetic Mice

PubMed Central

Chou, Jonathan C.; Rollins, Stuart D.; Ye, Minghao; Batlle, Daniel; Fawzi, Amani A.

2014-01-01

Purpose. We sought to determine the effects of atrasentan, a selective endothelin-A receptor antagonist, on the retinal vascular and structural integrity in a db/db mouse, an animal model of type 2 diabetes and diabetic retinopathy. Methods. Diabetic mice, 23 weeks old, were given either atrasentan or vehicle treatment in drinking water for 8 weeks. At the end of the treatment period, eyes underwent trypsin digest to assess the retinal vascular pathology focusing on capillary degeneration, endothelial cell, and pericyte loss. Paraffin-embedded retinal cross sections were used to evaluate retinal sublayer thickness both near the optic nerve and in the retinal periphery. Immunohistochemistry and TUNEL assay were done to evaluate retinal cellular and vascular apoptosis. Results. Compared with untreated db/db mice, atrasentan treatment was able to ameliorate the retinal vascular pathology by reducing pericyte loss (29.2% ± 0.4% vs. 44.4% ± 2.0%, respectively, P < 0.05) and capillary degeneration as determined by the percentage of acellular capillaries (8.6% ± 0.3% vs. 3.3% ± 0.41%, respectively, P < 0.05). A reduction in inner retinal thinning both at the optic nerve and at the periphery in treated diabetic mice was also observed in db/db mice treated with atrasentan as compared with untreated db/db mice (P < 0.05). TUNEL assay suggested that atrasentan may decrease enhanced apoptosis in neuroretinal layers and vascular pericytes in the db/db mice. Conclusions. Endothelin-A receptor blockade using atrasentan significantly reduces the vascular and neuroretinal complications in diabetic mice. Endothelin-A receptor blockade is a promising therapeutic target in diabetic retinopathy. PMID:24644048

Role of Purified Anthocyanins in Improving Cardiometabolic Risk Factors in Chinese Men and Women with Prediabetes or Early Untreated Diabetes-A Randomized Controlled Trial.

PubMed

Yang, Liping; Ling, Wenhua; Yang, Yan; Chen, Yuming; Tian, Zezhong; Du, Zhicheng; Chen, Jianying; Xie, Yuanling; Liu, Zhaomin; Yang, Lili

2017-10-10

Objective: In vitro and animal studies suggest that purified anthocyanins have favorable effects on metabolic profiles, but clinical trials have reported inconsistent findings. Furthermore, no study has been specifically conducted among individuals with prediabetes. The aim of this study was to investigate whether purified anthocyanins could improve cardiometabolic risk factors in Chinese adults with early untreated hyperglycemia. Research Design and Methods: This was a 12-week randomized, double-blind, placebo-controlled trial. A total of 160 participants aged 40-75 years with prediabetes or early untreated diabetes were randomly allocated to receive either purified anthocyanins (320 mg/day, n = 80) or placebo ( n = 80) of identical appearance. A three-hour oral glucose tolerance test (OGTT) was performed, and cardiometabolic biomarkers (glycated hemoglobin A1c (HbA1c), fasting and postprandial glucose, insulin, C-peptide, and lipids) were measured at baseline and at the end of the trial. Results: A total of 138 subjects completed the protocol. Compared with placebo, purified anthocyanins moderately reduced HbA1c (-0.14%, 95% CI: -0.23~-0.04%; p = 0.005), low-density lipoprotein-c (LDL-c) (-0.2 mmol/L, 95% CI: -0.38~-0.01, p = 0.04), apolipoprotein A-1 (apo A1) (0.09 g/L, 95% CI: 0.02~0.17; p = 0.02), and apolipoprotein B (apo B) (-0.07 g/L, 95% CI: -0.13~-0.01; p = 0.01) according to intention-to-treat analysis. Subgroup analyses suggested that purified anthocyanins were more effective at improving glycemic control, insulin sensitivity, and lipids among patients with elevated metabolic markers. Conclusions: The 12-week randomized controlled trials (RCT) in Chinese adults with prediabetes or early untreated diabetes indicated that purified anthocyanins favorably affected glycemic control and lipid profile. Future studies of a longer duration that explore the dose-response relationship among patients with cardiometabolic disorders are needed to confirm our findings.

QUALITY ASSURANCE FOR METHODS TO DETECT HUMAN ENTERIC VIRUSES IN DRINKING WATER

EPA Science Inventory

Surface or groundwaters impacted by untreated or inadequately treated domestic wastes may contain human pathogenic viruses that cause hepatitis, gastroenteritis, meningitis, encephalitis, myocarditis, diabetes, conjunctivitis and temporary or permanent paralysis. These viruses c...

Autologous circulating angiogenic cells treated with osteopontin and delivered via a collagen scaffold enhance wound healing in the alloxan-induced diabetic rabbit ear ulcer model.

PubMed

O'Loughlin, Aonghus; Kulkarni, Mangesh; Vaughan, Erin E; Creane, Michael; Liew, Aaron; Dockery, Peter; Pandit, Abhay; O'Brien, Timothy

2013-01-01

Diabetic foot ulceration is the leading cause of amputation in people with diabetes mellitus. Peripheral vascular disease is present in the majority of patients with diabetic foot ulcers. Despite standard treatments there exists a high amputation rate. Circulating angiogenic cells previously known as early endothelial progenitor cells are derived from peripheral blood and support angiogenesis and vasculogenesis, providing a potential topical treatment for non-healing diabetic foot ulcers. A scaffold fabricated from Type 1 collagen facilitates topical cell delivery to a diabetic wound. Osteopontin is a matricellular protein involved in wound healing and increases the angiogenic potential of circulating angiogenic cells. A collagen scaffold seeded with circulating angiogenic cells was developed. Subsequently the effect of autologous circulating angiogenic cells that were seeded in a collagen scaffold and topically delivered to a hyperglycemic cutaneous wound was assessed. The alloxan-induced diabetic rabbit ear ulcer model was used to determine healing in response to the following treatments: collagen seeded with autologous circulating angiogenic cells exposed to osteopontin, collagen seeded with autologous circulating angiogenic cells, collagen alone and untreated wound. Stereology was used to assess angiogenesis in wounds. The cells exposed to osteopontin and seeded on collagen increased percentage wound closure as compared to other groups. Increased angiogenesis was observed with the treatment of collagen and collagen seeded with circulating angiogenic cells. These results demonstrate that topical treatment of full thickness cutaneous ulcers with autologous circulating angiogenic cells increases wound healing. Cells exposed to the matricellular protein osteopontin result in superior wound healing. The wound healing benefit is associated with a more efficient vascular network. This topical therapy provides a potential novel therapy for the treatment of non-healing diabetic foot ulcers in humans.

Gene Therapy for the Treatment of Diabetic Neuropathy

PubMed Central

Mata, Marina; Chattopadhyay, Munmun; Fink, David J

2009-01-01

Neuropathy is a common, untreatable complication of both type 1 and type 2 diabetes. In animal models peptide neurotrophic factors can be used to protect against the development of neuropathy, but the combination of short half-life and off-target effects of these potent pleiotropic peptides has limited translation to human therapy. Gene transfer is a promising strategy that might circumvent these limitations. In this essay we review the basic methods of gene transfer and the preclinical data in rodent models that support the utility of this approach in the treatment of diabetic neuropathy. The path to a clinical applications and potential pitfalls in developing gene therapy for the treatment of diabetic neuropathy are considered. PMID:18990298

Is cardiovascular risk reduction therapy effective in South Asian, Chinese and other patients with diabetes? A population-based cohort study from Canada.

PubMed

Ke, Calvin H; Morgan, Steve; Smolina, Kate; Gasevic, Danijela; Qian, Hong; Khan, Nadia A

2017-08-31

Guidelines recommend ACE inhibitors (ACEi), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics in all patients with diabetes mellitus. However, the effectiveness of these agents in South Asian and Chinese populations is unknown. We sought to determine whether ACEi, ARB, CCB and diuretics are associated with reduced mortality in South Asian, Chinese and other patients with diabetes. Population-based cohort study using administrative health databases. Province of British Columbia, Canada (2006-2013). Patients aged ≥35 years with incident diabetes. Primary outcome was all-cause mortality for each medication class compared with untreated patients within each ethnicity. Treatment effect was assessed using inverse probability of treatment weighted Cox proportional hazards models. Medication adherence effect on mortality was also evaluated. 208 870 patients (13 755 South Asian, 22 871 Chinese, 172 244 other Canadian) were included. ACEi reduced mortality in other patients (HR=0.88, 0.84-0.91), but power was insufficient to evaluate for benefit in Chinese and South Asian patients. ARB and diuretics reduced mortality in Chinese (ARB HR=0.64, 0.50-0.82; diuretics HR=0.77, 0.62-0.96) and other patients (ARB HR=0.69, 0.64-0.74; diuretics HR=0.66, 0.63-0.69) compared with untreated patients. No mortality benefit was observed among South Asians for any drug class or for CCB among all ethnicities. Higher medication adherence was associated with lower mortality for other patients only (HR=0.79, 0.72-0.86). Effectiveness of cardiovascular risk reduction therapy on mortality varies considerably by ethnicity. Further study is needed to evaluate the mortality benefit of antihypertensive agents in South Asians. Inclusion of these ethnic groups in future clinical trials is essential to examine for differential responses. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Sub-antimicrobial Doxycycline for Periodontitis Reduces Hemoglobin A1c in Subjects with Type 2 Diabetes: a Pilot Study

PubMed Central

Engebretson, Steven P.; Hey-Hadavi, Judith

2011-01-01

In vitro and animal studies suggest a possible role for the tetracycline class of drugs in the inhibition of non-enzymatic protein glycation. We conducted a 3-month, randomized placebo-controlled pilot clinical trial of conventional sub-gingival debridement, (periodontal therapy) combined with either a three month regimen of sub-antimicrobial-dose doxycycline (SDD), a two week regimen of antimicrobial-dose doxycycline (ADD), or placebo in 45 patients with long-standing type 2 diabetes (mean duration 9 years) and untreated chronic periodontitis. Subjects were taking stable doses of oral hypoglycemic medications and/or insulin. Treatment response was assessed by measuring hemoglobin A1c (HbA1c),plasma glucose, and clinical periodontal disease measures. At one-month and three-month follow-up, clinical measures of periodontitis were decreased in all groups(data to be presented elsewhere). At three months, mean HbA1c levels in the SDD group were reduced 0.9% unitsfrom 7.2% units ± 2.2(±SD), to 6.3% units ±1.1, which represents a 12.5% improvement. In contrast, there was no significant change in HbA1c in the ADD (7.5%± 2.0 to 7.8%± 2.1) or placebo (8.5%± 2.0 to 8.5%± 2.6) groups. Mean HbA1c change from baseline was significantly greater in the SDD group compared with the ADD group (p=0.04) but not placebo (p=0.22). Moreover, a larger proportion of subjects in the SDD group experienced improvement (p<0.05) compared to the ADD or placebo groups. Mean plasma glucose levels were not significantly different between or within the groups. The results of this pilot study suggest that the treatment of periodontitis with sub-gingival debridement and 3-months of daily sub-antimicrobial-dose doxycycline may decrease HbA1c in patients with type 2 diabetes taking normally prescribed hypoglycemic agents. PMID:21782948

Diabetes abolishes the cardioprotection induced by sevoflurane postconditioning in the rat heart in vivo: roles of glycogen synthase kinase-3β and its upstream pathways.

PubMed

Tai, Wenjun; Shi, Enyi; Yan, Lihui; Jiang, Xiaojing; Ma, Hong; Ai, Chunyu

2012-11-01

We measured the cardioprotection afforded by sevoflurane postconditioning in streptozotocin-induced diabetic rats (DRs) and determined the roles of glycogen synthase kinase (GSK), phosphatidylinositol-3-kinase/Akt, and extracellular signal-regulated kinase (ERK1/2) in such a procedure. DRs and nondiabetic rats (NDRs) were subjected to a 30-min coronary artery occlusion followed by a 120-min reperfusion. Postconditioning was achieved by inhalation of 1 minimum alveolar concentration sevoflurane at the first 5 min of reperfusion. The infarct size was determined by triphenyltetrazolium chloride staining. Expressions of GSK-3β, Akt, and ERK1/2 were measured using Western blotting. In NDRs, the infarct size was significantly decreased from 53.4% ± 7.6% to 34.9% ± 5.6% by sevoflurane postconditioning (P < 0.01). Such an anti-infarct effect was abolished completely in the DRs, as evidenced by a similar infarct size observed between the sevoflurane-treated and untreated DRs (49.3% ± 8.6% and 49.6% ± 9.3%, respectively, P > 0.05). Direct inhibition of GSK-3β by injection of SB216763 just before the start of reperfusion induced equivalent infarct-sparing effects in both NDRs (37.8% ± 3.9% and 53.4% ± 7.6% in SB216763-treated and untreated NDRs, respectively; P < 0.01) and DRs (38.8% ± 3.2% and 49.3% ± 8.6% in SB216763-treated and untreated DRs, respectively; P < 0.05). Sevoflurane postconditioning remarkably enhanced the phosphorylation of GSK-3β Ser(9), Akt Ser(473), and ERK1/2 in NDRs, which were blocked in DRs. The cardioprotection induced by sevoflurane postconditioning is abolished by diabetes. This might be due to the impairment of phosphorylation of GSK-3β and its upstream signaling pathways of phosphatidylinositol-3-kinase/Akt and ERK1/2 in the presence of diabetes. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of short-term very low-calorie diet on intramyocellular lipid and insulin sensitivity in nondiabetic and type 2 diabetic subjects.

PubMed

Lara-Castro, Cristina; Newcomer, Bradley R; Rowell, Jennifer; Wallace, Penny; Shaughnessy, Sara M; Munoz, A Julian; Shiflett, Alanna M; Rigsby, Dana Y; Lawrence, Jeannine C; Bohning, Daryl E; Buchthal, Steven; Garvey, W Timothy

2008-01-01

The study aimed to analyze the effects of a short-term very low-calorie diet (VLCD) on intramyocellular lipid (IMCL), total body fat, and insulin sensitivity in a group of obese nondiabetic and type 2 diabetic subjects. Seven untreated type 2 diabetic and 5 obese nondiabetic individuals were studied before and after a 6-day VLCD using proton magnetic resonance spectroscopy to quantify IMCL, dual-energy x-ray absorptiometry to assess body fat, and hyperinsulinemic-euglycemic clamps to measure peripheral insulin sensitivity. In both groups, decrements in total body fat mass and body mass index were small but statistically significant. In contrast, the diet resulted in a pronounced reduction in IMCL compared with baseline values in nondiabetic subjects (56% decrease) and type 2 diabetic subjects (40% decrease) (P < .05), and this was accompanied by an overall 9.3% increase in maximally stimulated glucose disposal rate (P < .01). Intramyocellular lipid was significantly correlated with insulin sensitivity (r = -0.69, P < .01) and waist circumference (r = 0.72 and 0.83, baseline and postdiet, respectively; both P < .01), but neither IMCL nor insulin sensitivity was related to measures of general adiposity such as body mass index, percentage of body fat, or total body fat (P = not significant). In conclusion, short-term VLCD is accompanied by small decrements in general adiposity, marked decrease in IMCL, and an increase in insulin sensitivity in nondiabetic and type 2 diabetic subjects. Therefore, rapid amelioration of insulin resistance by VLCD can be partially explained by loss of IMCL both in nondiabetic and type 2 diabetic subjects in the absence of substantial changes in total body fat. These observations are consistent with the idea that insulin resistance is more directly related to IMCL rather than to body fat per se.

Obstructive sleep apnea.

PubMed

Ho, Matthew L; Brass, Steven D

2011-11-29

Obstructive sleep apnea (OSA) affects millions of Americans and is estimated to be as prevalent as asthma and diabetes. Given the fact that obesity is a major risk factor for OSA, and given the current global rise in obesity, the prevalence of OSA will increase in the future. Individuals with sleep apnea are often unaware of their sleep disorder. It is usually first recognized as a problem by family members who witness the apneic episodes or is suspected by their primary care doctor because of the individual's risk factors and symptoms. The vast majority remain undiagnosed and untreated, despite the fact that this serious disorder can have significant consequences. Individuals with untreated OSA can stop breathing hundreds of times a night during their sleep. These apneic events can lead to fragmented sleep that is of poor quality, as the brain arouses briefly in order for the body to resume breathing. Untreated, sleep apnea can have dire health consequences and can increase the risk of hypertension, diabetes, heart disease, and heart failure. OSA management has also become important in a number of comorbid neurological conditions, including epilepsy, stroke, multiple sclerosis, and headache. Diagnosis typically involves use of screening questionnaires, physical exam, and an overnight polysomnography or a portable home study. Treatment options include changes in lifestyle, positive airway pressure, surgery, and dental appliances.

Saffron with resistance exercise improves diabetic parameters through the GLUT4/AMPK pathway in-vitro and in-vivo

PubMed Central

Dehghan, Firouzeh; Hajiaghaalipour, Fatemeh; Yusof, Ashril; Muniandy, Sekaran; Hosseini, Seyed Ali; Heydari, Sedigheh; Salim, Landa Zeenelabdin Ali; Azarbayjani, Mohammad Ali

2016-01-01

Saffron is consumed as food and medicine to treat several illnesses. This study elucidates the saffron effectiveness on diabetic parameters in-vitro and combined with resistance exercise in-vivo. The antioxidant properties of saffron was examined. Insulin secretion and glucose uptake were examined by cultured RIN-5F and L6 myotubes cells. The expressions of GLUT2, GLUT4, and AMPKα were determined by Western blot. Diabetic and non-diabetic male rats were divided into: control, training, extract treatment, training + extract treatment and metformin. The exercise and 40 mg/kg/day saffron treatments were carried out for six weeks. The antioxidant capacity of saffron was higher compare to positive control (P < 0.01). High dose of saffron stimulated insulin release in RIN-5F cells and improved glucose uptake in L6 myotubes. GLUT4 and AMPKα expressions increased in both doses of saffron (P < 0.01), whereas GLUT2 not changed (p > 0.05). Serum glucose, cholesterol, triglyceride, low-density lipoprotein, very low-density lipoprotein, insulin resistance, and glycated hemoglobin levels decreased in treated rats compared to untreated (p < 0.01). However, no significant differences were observed in the high-density lipoprotein, insulin, adiponectin, and leptin concentration levels in all groups (p > 0.05). The findings suggest that saffron consuming alongside exercise could improve diabetic parameters through redox-mediated mechanisms and GLUT4/AMPK pathway to entrap glucose uptake. PMID:27122001

Lycium chinense leaves extract ameliorates diabetic nephropathy by suppressing hyperglycemia mediated renal oxidative stress and inflammation.

PubMed

Olatunji, Opeyemi Joshua; Chen, Hongxia; Zhou, Yifeng

2018-06-01

Diabetic nephropathy is one of the most serious and most frequently encountered diabetic complication, accounting for the highest cause of end-stage renal disease. This present study was aimed at exploring the protective/attenuative effect of Lycium chinense leaf extract (MELC) on streptozotocin induced diabetic nephropathy in experimental Sprague Dawley rats. The oral administration of diabetic rats with MELC markedly ameliorated renal dysfunction as observed in the significant reduction in the serum levels of creatinine, blood urea nitrogen (BUN), albumin and TGF-β1 as compared to the untreated diabetic control rats. In addition, the elevated levels of renal oxidative stress markers and pro-inflammatory parameters (GSH, SOD, CAT, MDA, TNF-α, IL-6 and IL-1β) were significantly reduced in MELC treated diabetic rats. The results obtained in this study suggests that L. chinense leaf might have the potential as possible pharmacological agent against diabetic nephropathy by suppressing renal oxidative stress and inflammation. Copyright © 2018. Published by Elsevier Masson SAS.

Piperine, a Natural Bioenhancer, Nullifies the Antidiabetic and Antioxidant Activities of Curcumin in Streptozotocin-Diabetic Rats

PubMed Central

Arcaro, Carlos Alberto; Gutierres, Vânia Ortega; Assis, Renata Pires; Moreira, Thais Fernanda; Costa, Paulo Inácio; Baviera, Amanda Martins; Brunetti, Iguatemy Lourenço

2014-01-01

Knowing that curcumin has low bioavailability when administered orally, and that piperine has bioenhancer activity by inhibition of hepatic and intestinal biotransformation processes, the aim of this study was to investigate the antidiabetic and antioxidant activities of curcumin (90 mg/kg) and piperine (20 or 40 mg/kg), alone or co-administered, incorporated in yoghurt, in streptozotocin (STZ)-diabetic rats. The treatment for 45 days of STZ-diabetic rats with curcumin-enriched yoghurt improved all parameters altered in this experimental model of diabetes: the body weight was increased in association with the weight of skeletal muscles and white adipose tissues; the progressive increase in the glycemia levels was avoided, as well as in the glycosuria, urinary urea, dyslipidemia, and markers of liver (alanine and aspartate aminotransferases and alkaline phosphatase) and kidney (urinary protein) dysfunction; the hepatic oxidative stress was decreased, since the activities of the antioxidant enzymes superoxide dismutase, catalase and gluthatione peroxidase were increased, and the levels of malondialdehyde and protein carbonyl groups were reduced. The dose of 20 mg/kg piperine also showed antidiabetic and antioxidant activities. The treatment of STZ-diabetic rats with both curcumin and 20 mg/kg piperine in yoghurt did not change the antidiabetic and antioxidant activities of curcumin; notably, the treatment with both curcumin and 40 mg/kg piperine abrogated the beneficial effects of curcumin. In addition, the alanine aminotransferase levels were further increased in diabetic rats treated with curcumin and 40 mg/kg piperine in comparison with untreated diabetic rats. These findings support that the co-administration of curcumin with a bioenhancer did not bring any advantage to the curcumin effects, at least about the antidiabetic and antioxidant activities, which could be related to changes on its biotransformation. PMID:25469699

The antidiabetic action of camel milk in experimental type 2 diabetes mellitus: an overview on the changes in incretin hormones, insulin resistance, and inflammatory cytokines.

PubMed

Korish, A A

2014-06-01

Folk medicine stories accredited the aptitude of camel milk (CMK) as a hypoglycemic agent and recent studies have confirmed this in the diabetic patients and experimental animals. However, the mechanism(s) by which CMK influences glucose homeostasis is yet unclear. The current study investigated the changes in the glucose homeostatic parameters, the incretin hormones, and the inflammatory cytokines in the CMK-treated diabetic animals. A model of type 2 diabetes mellitus was induced in rats by intraperitoneal injection of streptozotocin 40 mg/kg/day for 4 repeated doses. Camel milk treatment was administered for 8 weeks. The changes in glucagon like peptide-1 (GLP-1), glucose dependent insulinotropic peptide (GIP), glucose tolerance, fasting and glucose-stimulated insulin secretion, insulin resistance (IR), TNF-α, TGF-β1, lipid profile, atherogenic index (AI), and body weight were investigated. The untreated diabetic animals showed hyperglycemia, increased HOMA-IR, hyperlipidemia, elevated AI, high serum incretins [GLP-1 and GIP], TNF-α, and TGF-β1 levels and weight loss as compared with the control group. Camel milk treatment to the diabetic animals resulted in significant lowered fasting glucose level, hypolipidemia, decreased HOMA-IR, recovery of insulin secretion, weight gain, and no mortality during the study. Additionally, CMK inhibits the diabetes-induced elevation in incretin hormones, TNF-α and TGF-β1 levels. The increase in glucose-stimulated insulin secretion, decreased HOMA-IR, modulation of the secretion and/or the action of incretins, and the anti-inflammatory effect are anticipated mechanisms to the antidiabetic effect of CMK and suggest it as a valuable adjuvant antidiabetic therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Neurophysiological role of sildenafil citrate (Viagra) on seminal parameters in diabetic males with and without neuropathy.

PubMed

Ali, Syed Tabrez; Rakkah, Nabeeh I

2007-01-01

Sildenafil citrate is a specific inhibitor of phosphodiesterase (PDE) type-5 and represents a powerful therapy for male erectile and fertility dysfunctions of different etiologies. Present study demonstrates whether sildenafil administration modifies seminal parameters in diabetic neuropathic patients. In this investigation 50 insulin dependent (IDDM) and 50 non insulin dependent (NIDDM) diabetic male patients with and without an objective evidence of neuropathy and 50 age matched non diabetic male controls were selected. Every male had age between 20 to 65 years with duration of diabetes distributed over 1 to 20 years. Treatment with 100 mg of oral sildenafil citrate on seminal parameters was evaluated by semen analysis in these patients. In both IDDM and NIDDM diabetic neuropathic patients, chronic sildenafil treatment exhibited a significant decrease in total sperm output and sperm concentration (p<0.001). On the other hand, sperm motility and semen volume were found to be increased by about 40% and 48% respectively in these patients, where as sperm morphology and quality of sperm motility remained unaffected. However both types of non neuropathic diabetics showed a non significant difference in all the above mentioned parameters when compared with the untreated groups and their respective control subjects. A comparison between IDDM and NIDDM neuropathic and non neuropathic diabetic groups further indicated a non significant difference in all the parameters of semen analysis. These findings suggest a chronic neuro physiological effect of sildenafil treatment on male fertility profile exclusively in diabetic neuropathic condition with an improvement in testicular function which was probably arrested due to some kind of testicular hyperplasia resulted by testicular necrosis and promoted spermatogenesis. Sildenafil seems to be associated with an improvement in the entire smooth musculature of reproductive tract and testicular morphology which was altered due to neuropathy like a reduction in excess accumulation of interstitial collagen and calcification in the smooth muscles of seminiferous tubules which made them rigid leading to atonia of bladder and urethra which resulted in partial or retrograde ejaculation associated with a decreased sperm motility. Sildenafil treatment returned back the spermatogenesis to normal with a positive influence on sperm motility and ejaculate volume in these neuropathic patients irrespective of the type of diabetes.

[Effects of Chinese herbal medicine Yiqi Huayu Recipe on apoptosis of dorsal root ganglion neurons and expression of caspase-3 in rats with lumbar nerve root compression].

PubMed

Xu, Le-qin; Li, Xiao-feng; Zhang, You-wei; Shu, Bing; Shi, Qi; Wang, Yong-jun; Zhou, Chong-jian

2010-12-01

To observe the effects of Yiqi Huayu Recipe, a Chinese compound herbal medicine, on apoptosis of dorsal root ganglion (DRG) neurons and expression of caspase-3 in rats after lumbar nerve root compression injury. A total of 40 male Sprague-Dawley rats were randomly allocated into 4 groups: control group, untreated group, Methylcobal group and Yiqi Huayu Recipe group. Surgery was performed on rats of untreated group, Methylcobal group and Yiqi Huayu Recipe group to place a micro-silica gel on right L₄ DRG, while control group received skin and paravertebral muscle incision only. Rats in Methylcobal group and Yiqi Huayu Recipe group were given Methylcobal by intramuscular injection and Yiqi Huayu Recipe intragastrically respectively. Rats in control group and untreated group received saline intragastrically as equal amount as Yiqi Huayu Recipe group. The compressed nerve roots were harvested at the 10th day after treatment. Apoptosis of DRG neurons was detected by terminal deoxynucleotidyl transferase-mediated nick-end labeling. Caspase-3 activity and mRNA expression in compressed nerve roots were detected with spectrophotography and real-time polymerase chain reaction respectively. Apoptosis of DRG neurons was significantly increased in the rat model. The apoptosis index of untreated group was higher than that of control group (P<0.01). Yiqi Huayu Recipe and Methylcobal could reduce the apoptosis of DRG neurons, and both groups showed a lower apoptosis index than untreated group (P<0.01). Caspase-3 activity and its gene expression were significantly increased in untreated group. The levels of caspase-3 activity and its gene expression in untreated group were higher than those in control group (P<0.05 or P<0.01). Yiqi Huayu Recipe and Methylcobal could reduce the overexpression of caspase-3 mRNA, and statistically significant differences were found between the untreated group and Yiqi Huayu Recipe group or Methylcobal group (P<0.01). Lumbar nerve root compression results in overexpression of caspase-3 in nerve root tissue and increase of DRG neuron apoptosis. Yiqi Huayu Recipe can inhibit the overexpression of caspase-3 and alleviate the apoptosis of DRG neurons after nerve injury.

Glyoxalase I is critical for human retinal capillary pericyte survival under hyperglycemic conditions.

PubMed

Miller, Antonia G; Smith, Dawn G; Bhat, Manjunatha; Nagaraj, Ram H

2006-04-28

Retinal capillary pericytes undergo premature death, possibly by apoptosis, during the early stages of diabetic retinopathy. The alpha-oxoaldehyde, methylglyoxal (MGO), has been implicated as a cause of cell damage in diabetes. We have investigated the role of MGO and its metabolizing enzyme, glyoxalase I, in high glucose-induced apoptosis (annexin V binding) of human retinal pericyte (HRP). HRP incubated with high glucose (30 mm d-glucose) for 7 days did not undergo apoptosis despite accumulation of MGO. However, treatment with a combination of high glucose and S-p-bromobenzylglutathione cyclopentyl diester, a competitive inhibitor of glyoxalase I, resulted in apoptosis along with a dramatic increase in MGO. Overexpression of glyoxalase I in HRP protected against S-p-bromobenzylglutathione cyclopentyl diester-induced apoptosis under high glucose conditions. Incubation of HRP with high concentrations of MGO resulted in an increase of apoptosis relative to untreated controls. We found an elevation of nitric oxide (NO.) in HRP that was incubated with high glucose when compared with those incubated with either the l-glucose or untreated controls. When HRP were incubated with an NO. donor, DETANONOATE ((Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate), we observed both decreased glyoxalase I expression and activity relative to untreated control cells. Further studies showed that HRP underwent apoptosis when incubated with DETANONOATE and that apoptosis increased further on co-incubation with high glucose. Our findings indicate that glyoxalase I is critical for pericyte survival under hyperglycemic conditions, and its inactivation and/or down-regulation by NO. may contribute to pericyte death by apoptosis during the early stages of diabetic retinopathy.

Distribution pattern of urine albumin creatinine ratio and the prevalence of high-normal levels in untreated asymptomatic non-diabetic hypertensive patients.

PubMed

Ohmaru, Natsuki; Nakatsu, Takaaki; Izumi, Reishi; Mashima, Keiichi; Toki, Misako; Kobayashi, Asako; Ogawa, Hiroko; Hirohata, Satoshi; Ikeda, Satoru; Kusachi, Shozo

2011-01-01

Even high-normal albuminuria is reportedly associated with cardiovascular events. We determined the urine albumin creatinine ratio (UACR) in spot urine samples and analyzed the UACR distribution and the prevalence of high-normal levels. The UACR was determined using immunoturbidimetry in 332 untreated asymptomatic non-diabetic Japanese patients with hypertension and in 69 control subjects. The microalbuminuria and macroalbuminuria levels were defined as a UCAR ≥30 and <300 µg/mg·creatinine and a UCAR ≥300 µg/mg·creatinine, respectively. The distribution patterns showed a highly skewed distribution for the lower levels, and a common logarithmic transformation produced a close fit to a Gaussian distribution with median, 25th and 75th percentile values of 22.6, 13.5 and 48.2 µg/mg·creatinine, respectively. When a high-normal UACR was set at >20 to <30 µg/mg·creatinine, 19.9% (66/332) of the hypertensive patients exhibited a high-normal UACR. Microalbuminuria and macroalbuminuria were observed in 36.1% (120/336) and 2.1% (7/332) of the patients, respectively. UACR was significantly correlated with the systolic and diastolic blood pressures and the pulse pressure. A stepwise multivariate analysis revealed that these pressures as well as age were independent factors that increased UACR. The UACR distribution exhibited a highly skewed pattern, with approximately 60% of untreated, non-diabetic hypertensive patients exhibiting a high-normal or larger UACR. Both hypertension and age are independent risk factors that increase the UACR. The present study indicated that a considerable percentage of patients require anti-hypertensive drugs with antiproteinuric effects at the start of treatment.

Influence of dyslipidemia in control of arterial hypertension among type-2 diabetics in the western region of the Republic of Macedonia.

PubMed

Jani, Ylber; Kamberi, Amet; Ferati, Fatmir; Rexhepi, Atila; Pocesta, Bekim; Orovcanec, Nikola; Lala, Dali; Polisi, Gafur; Iseni, Mair; Mirto, Arben; Zeqiri, Agim

2014-01-01

To determine the influence of dyslipidemia in control of blood pressure in patients with type 2 Diabetes. To test the hypothesis that, blood pressure and lipid levels are not sufficiently controlled in patients with type 2 Diabetes, in the western region of the Republic of Macedonia. Abnormalities of lipid and lipoprotein levels in the serum (dyslipidemia) are recognized as major modifiable cardiovascular disease risk factors and have been identified as independent risk factors for essential hypertension, giving rise to the term dyslipidemic hypertension. While patient-related data from primary care that demonstrate an under-treatment of blood pressure and dyslipidemia in type 2 Diabetics are vastly available in clinical practice, results from population-based studies are scarce. The study was conducted on outpatients in Primary Health Care Clinics in 8 cities on the western region of the Republic of Macedonia. Prospectively the tests were performed on 600 (45.6% women and 54.4% men) participants with a mean age of 62 ± 5.8. Study participants were selected among primary care patients, who were actively on therapy for diabetes mellitus and hypertension during the period of March 2013 - March 2014. Patients' demographic characteristics, clinical laboratory and drug usage data were obtained. The patients were classified according to the BP control, into 2 groups. A total of 600 patients, of which 45.6% female and 54.3% male, completed the survey and had data for a 1-year medical record review. It was observed that a high percentage, 65.3% of patients, did not have controlled blood pressure despite the ongoing medical treatment, according to evidence and current guidelines in a cohort of hypertensive diabetics. (Chi-square: 19.85, p<0.001). Among participants with controled BP, untreated or insufficiently treated dyslipidemia was recorded in 23% of them, whereas among participants with uncontrolled BP, untreated or insufficiently treated dyslipidemia was recorded in 67% of the participants. (Chi-square: 15.01, p=0.0001). A significant influence of dyslipidemia on the control of blood pressure in patients with type 2 Diabetes, was observed in our study. In a small country as Republic of Macedonia (with a population of around 2.000.000, especially the western region with approximately 1/2 of the overall population), this study highlights the considerable lack of awareness and insufficient management of the most important preventable and treatable cardiovascular risk factors (hypertension and dyslipidemia). These findings provide a possible explanation of the steadily high cardiovascular mortality rate despite the clinical and therapeutic progress and accessibility. Besides current hospital-based prevention and pharmaceutical control measures, mass education campaigns, lifestyle interventions etc., emphasis should be given to the role of family doctor as a primary-care health provider.

Improved brachial artery shear patterns and increased flow-mediated dilation after low-volume high-intensity interval training in type 2 diabetes.

PubMed

Ghardashi Afousi, Alireza; Izadi, Mohammad Reza; Rakhshan, Kamran; Mafi, Farnoosh; Biglari, Soheil; Gandomkar Bagheri, Habibalah

2018-06-22

What is the central question of this study? Endothelial function is impaired because of increased oscillatory and retrograde shear in patients with type 2 diabetes. It is unclear whether low-volume high-intensity interval training and continuous moderate intensity exercise can modulate oscillatory and retrograde shear, blood flow and flow-mediated arterial dilation in these patients. What is the main finding and its importance? We found that low-volume high-intensity interval training, by increasing anterograde shear and decreasing retrograde shear and oscillatory index, can increase nitric oxide production and consequently result in increased flow-mediated dilation and outward arterial remodelling in patients with type 2 diabetes. Atherosclerosis in patients with type 2 diabetes is characterized by endothelial dysfunction associated with impaired flow-mediated dilation (FMD) and increases retrograde and oscillatory shear. The present study investigated endothelium-dependent vasodilation and shear rate in patients with type 2 diabetes at baseline and follow-up after 12 weeks of low-volume high-intensity interval training (LV-HIIT) or continuous moderate intensity training (CMIT). Seventy five sedentary patients with type 2 diabetes and untreated pre- or stage I hypertension were randomly divided into LV-HIIT, CMIT and control groups. The LV-HIIT group intervention was 12 intervals of 1.5 min at 85%-90% HR max and 2 min at 55%-60% HR max . The CMIT group intervention was 42 min of exercise at 70% HR max for 3 sessions per week during 12 weeks. High-resolution Doppler ultrasound was used to measure FMD, arterial diameter, anterograde and retrograde blood flow and shear rate patterns. Brachial artery FMD increased significantly in the LV-HIIT group (3.83 ± 1.13 baseline, 7.39 ± 3.6% follow-up), whereas there were no significant increase in the CMIT group (3.45 ± 0.97 baseline, 4.81 ± 2.36% follow-up) compared to the control group (3.16 ± 0.78 baseline, 4.04 ± 1.28% follow-up) (P < 0.05). Retrograde shear in the LV-HIIT group decreased significantly (P < 0.05), and no significant decrease in retrograde shear was seen in the CMIT group. Anterograde shear after LV-HIIT increased significantly (P < 0.05) but was unchanged in the CMIT group. However, oscillatory shear index in both exercise groups decreased significantly (P = 0.029). Nitrite/nitrate (NOx) level increased in both exercise groups, but the increase was greater in the LV-HIIT group (P < 0.001). Our results indicate that by increasing NOx, HIIT decreases the oscillatory shear-induced improvement in FMD and outward artery remodelling in patients with T2D. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evaluation of glycated albumin (GA) and GA/HbA1c ratio for diagnosis of diabetes and glycemic control: A comprehensive review.

PubMed

Yazdanpanah, Sara; Rabiee, Mohammad; Tahriri, Mohammadreza; Abdolrahim, Mojgan; Rajab, Asadollah; Jazayeri, Hossein E; Tayebi, Lobat

2017-06-01

Diabetes Mellitus (DM) is a group of metabolic diseases characterized by chronic high blood glucose concentrations (hyperglycemia). When it is left untreated or improperly managed, it can lead to acute complications including diabetic ketoacidosis and non-ketotic hyperosmolar coma. In addition, possible long-term complications include impotence, nerve damage, stroke, chronic kidney failure, cardiovascular disease, foot ulcers, and retinopathy. Historically, universal methods to measure glycemic control for the diagnosis of diabetes included fasting plasma glucose level (FPG), 2-h plasma glucose (2HP), and random plasma glucose. However, these measurements did not provide information about glycemic control over a long period of time. To address this problem, there has been a switch in the past decade to diagnosing diabetes and its severity through measurement of blood glycated proteins such as Hemoglobin A1c (HbA1c) and glycated albumin (GA). Diagnosis and evaluation of diabetes using glycated proteins has many advantages including high accuracy of glycemic control over a period of time. Currently, common laboratory methods used to measure glycated proteins are high-performance liquid chromatography (HPLC), immunoassay, and electrophoresis. HbA1c is one of the most important diagnostic factors for diabetes. However, some reports indicate that HbA1c is not a suitable marker to determine glycemic control in all diabetic patients. GA, which is not influenced by changes in the lifespan of erythrocytes, is thought to be a good alternative indicator of glycemic control in diabetic patients. Here, we review the literature that has investigated the suitability of HbA1c, GA and GA:HbA1c as indicators of long-term glycemic control and demonstrate the importance of selecting the appropriate glycated protein based on the patient's health status in order to provide useful and modern point-of-care monitoring and treatment.

Untreated head and neck cancer in Korea: a national cohort study.

PubMed

Choi, Hyo Geun; Park, Bumjung; Ahn, Soon-Hyun

2017-03-01

Few studies have analyzed the survival of patients with untreated head and neck cancer. The objective of this study is to assess the survival rates of untreated head and neck cancer patients and to determine why the patients were not treated. Using data from a national patient sample cohort (1,025,340 cases) from the Korean Health Insurance Review and Assessment Service, 605 patients with diagnoses of head and neck cancer (lip and oral cavity, oropharynx, hypopharynx, and laryngeal cancer) between 2003 and 2013 were evaluated. Cox proportional hazards modeling and multiple logistic regression analysis were performed. Of the considered cases of head and neck cancer, 32.2% were untreated. The median survival rate of untreated groups was 9 months. The untreated group showed poorer survival than the treatment groups. Old age [adjusted odds ratio (AOR) = 1.37, 95% confidence internal (CI) 1.25-1.49, P < 0.001] and low income (AOR = 0.94, 95% CI 0.89-1.00, P = 0.028) were related to not receiving treatment. Many head and neck cancers go untreated. Clinicians should focus on untreated patients and seek to understand the reasons for their lack of treatment.

Daily Physical Activity Assessed by a Triaxial Accelerometer Is Beneficially Associated with Waist Circumference, Serum Triglycerides, and Insulin Resistance in Japanese Patients with Prediabetes or Untreated Early Type 2 Diabetes.

PubMed

Hamasaki, Hidetaka; Noda, Mitsuhiko; Moriyama, Sumie; Yoshikawa, Reo; Katsuyama, Hisayuki; Sako, Akahito; Mishima, Shuichi; Kakei, Masafumi; Ezaki, Osamu; Yanai, Hidekatsu

2015-01-01

To investigate the association between daily physical activity and metabolic risk factors in Japanese adults with prediabetes or untreated early type 2 diabetes (T2D). Daily physical activity level was measured using a triaxial accelerometer. We assessed correlations between physical activity level and waist circumference, blood pressure, fasting levels of plasma glucose, serum triglycerides, and insulin and homeostasis model assessment-insulin resistance (HOMA-IR). A total of 80 patients were studied. After adjustment for age and body mass index, in all subjects, physical activity level was negatively associated with waist circumference (β = -0.124, P = 0.018) and fasting serum triglycerides (β = -0.239, P = 0.035), insulin (β = -0.224, P = 0.022). In men, physical activity level was negatively associated with systolic blood pressure (β = -0.351, P = 0.044), fasting plasma glucose (β = -0.369, P = 0.025) and insulin (β = -0.362, P = 0.012), and HOMA-IR (β = -0.371, P = 0.011). No significant associations were found between physical activity level and metabolic risk factors in women. Objectively measured daily physical activity is beneficially associated with waist circumference, serum triglycerides, and insulin resistance in individuals with prediabetes or untreated early T2D. (This trial is registered with UMIN000015774.).

Effects of N-[Imino(1-Piperidinyl)Methyl] Guanidine on the Intensity of Free Radical Processes, Aconitase Activity, and Citrate Level in the Tissues of Rats with Experimental Type 2 Diabetes Mellitus.

PubMed

Skliarova, E I; Popova, T N; Shulgin, K K

2016-06-01

Effects of a synthetic biguanide derivative N-[imino(1-piperidinyl)methyl] guanidine (NIPMG) on free radical homeostasis, aconitase activity, and citrate concentration were studied in the liver and blood serum of rats with type 2 diabetes mellitus. Analysis of biochemiluminescence parameters showed that administration of this agent (10 mg/kg body weight) to animals with diabetes reduced the intensity of free radical processes in study tissues relative to the increased values in untreated diabetic animals. Under these conditions, aconitase activity, a principal target of ROS effects, and citrate level in the liver and blood serum of rats approached the control levels. The results show that NIPMG can positively regulate free radical homeostasis and reduce the intensity of oxidative stress in type 2 diabetes mellitus, which was accompanied by normalization of the studied parameters.

Subacute diabetic proximal neuropathy

NASA Technical Reports Server (NTRS)

Pascoe, M. K.; Low, P. A.; Windebank, A. J.; Litchy, W. J.

1997-01-01

OBJECTIVE: To evaluate the clinical, electrophysiologic, autonomic, and neuropathologic characteristics and the natural history of subacute diabetic proximal neuropathy and its response to immunotherapy. MATERIAL AND METHODS: For the 12-year period from 1983 to 1995, we conducted a retrospective review of medical records of Mayo Clinic patients with diabetes who had subacute onset and progression of proximal weakness. The responses of treated versus untreated patients were compared statistically. RESULTS: During the designated study period, 44 patients with subacute diabetic proximal neuropathy were encountered. Most patients were middle-aged or elderly, and no sex preponderance was noted. The proximal muscle weakness often was associated with reduced or absent lower extremity reflexes. Associated weight loss was a common finding. Frequently, patients had some evidence of demyelination on nerve conduction studies, but it invariably was accompanied by concomitant axonal degeneration. The cerebrospinal fluid protein concentration was usually increased. Diffuse and substantial autonomic failure was generally present. In most cases, a sural nerve biopsy specimen suggested demyelination, although evidence of an inflammatory infiltrate was less common. Of 12 patients who received treatment (with prednisone, intravenous immune globulin, or plasma exchange), 9 had improvement of their conditions, but 17 of 29 untreated patients (59%) with follow-up also eventually had improvement, albeit at a much slower rate. Improvement was usually incomplete. CONCLUSION: We suggest that the entity of subacute diabetic proximal neuropathy is an extensive and severe variant of bilateral lumbosacral radiculoplexopathy, with some features suggestive of an immune-mediated cause. It differs from chronic inflammatory demyelinating polyradiculoneuropathy in that most cases have a more restricted distribution and seem to be monophasic and self-limiting. The efficacy of immunotherapy is unproved, but such intervention may be considered in the severe and progressive cases or ones associated with severe neuropathic pain.

Topically applied connective tissue growth factor/CCN2 improves diabetic preclinical cutaneous wound healing: potential role for CTGF in human diabetic foot ulcer healing.

PubMed

Henshaw, F R; Boughton, P; Lo, L; McLennan, S V; Twigg, S M

2015-01-01

Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Wound α-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r = 0.406; P < 0.001). These data collectively increasingly substantiate a functional role for CTGF in human diabetic foot ulcers.

Rebamipide improves chronic inflammation in the lesser curvature of the corpus after Helicobacter pylori eradication: a multicenter study.

PubMed

Kamada, Tomoari; Sato, Motonori; Tokutomi, Tadashi; Watanabe, Tetsuo; Murao, Takahisa; Matsumoto, Hiroshi; Manabe, Noriaki; Ito, Masanori; Tanaka, Shinji; Inoue, Kazuhiko; Shiotani, Akiko; Akiyama, Takashi; Hata, Jiro; Haruma, Ken

2015-01-01

Background and Aim. Although many epidemiologic studies have shown that Helicobacter pylori eradication has prophylactic effects on gastric cancer, it does not completely eliminate the risk of gastric cancer. We aimed to investigate the changes in histological gastritis in patients receiving rebamipide treatment after H. pylori eradication. Methods. 206 patients who had undergone H. pylori eradication were evaluated. Of these, 169 patients who achieved successful eradication were randomly allocated to 2 groups: the rebamipide group (n = 82) and the untreated group (n = 87). The primary endpoints were histopathological findings according to the updated Sydney system at the start of the study and after 1 year. Results. Final assessment for histological gastritis was possible in 50 cases from the rebamipide group and 53 cases from the untreated group. The activity and atrophy improved in both the rebamipide and untreated groups, and no significant intergroup differences were observed. Chronic inflammation affecting the lesser curvature of the corpus was significantly improved in the rebamipide group compared to in the untreated group (1.12 ± 0.08 versus 1.35 ± 0.08; P = 0.043). Conclusions. Rebamipide treatment after H. pylori eradication alleviated chronic inflammation in the lesser curvature of the corpus compared to that in the untreated group. This trial is registered with UMIN000002369.

Bilateral Ramsay Hunt syndrome in a diabetic patient

PubMed Central

Syal, Rajan; Tyagi, Isha; Goyal, Amit

2004-01-01

Background Herpes zoster oticus accounts for about 10% cases of facial palsy, which is usually unilateral and complete and full recovery occurs in only about 20% of untreated patients. Bilateral herpes zoster oticus can sometime occur in immunocompromised patients, though incidence is very rare. Case presentation Diabetic male, 57 year old presented to us with bilateral facial palsy due to herpes zoster oticus. Patient was having bilateral mild to moderate sensorineural hearing loss. Patient was treated with appropriate metabolic control, anti-inflammatory drugs and intravenous acyclovir. Due to uncontrolled diabetes, glucocorticoids were not used in this patient. Significant improvement in hearing status and facial nerve functions were seen in this patient. Conclusions Herpes zoster causes severe infections in diabetic patients and can be a cause of bilateral facial palsy and bilateral Ramsay Hunt syndrome. Herpes zoster in diabetic patients should be treated with appropriate metabolic control, NSAIDS and intravenous acyclovir, which we feel should be started at the earliest. Glucocorticoids should be avoided in diabetic patients. PMID:15575957

Bilateral Ramsay Hunt syndrome in a diabetic patient.

PubMed

Syal, Rajan; Tyagi, Isha; Goyal, Amit

2004-12-02

BACKGROUND: Herpes zoster oticus accounts for about 10% cases of facial palsy, which is usually unilateral and complete and full recovery occurs in only about 20% of untreated patients. Bilateral herpes zoster oticus can sometime occur in immunocompromised patients, though incidence is very rare. CASE PRESENTATION: Diabetic male, 57 year old presented to us with bilateral facial palsy due to herpes zoster oticus. Patient was having bilateral mild to moderate sensorineural hearing loss. Patient was treated with appropriate metabolic control, anti-inflammatory drugs and intravenous acyclovir. Due to uncontrolled diabetes, glucocorticoids were not used in this patient. Significant improvement in hearing status and facial nerve functions were seen in this patient. CONCLUSIONS: Herpes zoster causes severe infections in diabetic patients and can be a cause of bilateral facial palsy and bilateral Ramsay Hunt syndrome. Herpes zoster in diabetic patients should be treated with appropriate metabolic control, NSAIDS and intravenous acyclovir, which we feel should be started at the earliest. Glucocorticoids should be avoided in diabetic patients.

Heijiangdan ointment relieves oxidative stress from radiation dermatitis induced by (60)Co γ-ray in mice.

PubMed

Yang, Lin; Yu, Ming-wei; Wang, Xiao-min; Zhang, Yi; Yang, Guo-wang; Luo, Xiao-qin; Peng, Rui-yun; Gao, Ya-bing; Zhao, Li; Wang, Li-feng

2016-02-01

To investigate the effects of Heijiangdan Ointment ( HJD) on oxidative stress in (60)Co γ-ray radiation-induced dermatitis in mice. Female Wistar mice with grade 4 radiation dermatitis induced by (60)Co γ-rays were randomly divided into four groups (n=12 per group); the HJD-treated, recombinant human epidermal growth factor (rhEGF)-treated, Trolox-treated, and untreated groups, along with a negative control group. On the 11th and 21st days after treatment, 6 mice in each group were chosen for evaluation. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and lactate dehydrogenase (LDH) were detected using spectrophotometric methods. The fibroblast mitochondria were observed by transmission electron microscopy (TEM). The expressions of fibroblast growth factor 2 (FGF-2) and transforming growth factor β1 (TGF-β1) were analyzed by western blot. Compared with the untreated group, the levels of SOD, MDA and LDH, on the 11th and 21st days after treatment showed significant difference (P<0.05). TEM analysis indicated that fibroblast mitochondria in the untreated group exhibited swelling and the cristae appeared fractured, while in the HJD group, the swelling of mitochondria was limited and the rough endoplasmic reticulum appeared more relaxed. The expressions of FGF-2 and TGF-β1 increased in the untreated group compared with the negative control group (P<0.05). After treatment, the expression of FGF-2, rhEGF and Trolox in the HJD group were significantly increased compared with the untreated group (P<0.05), or compared with the negative control group (P<0.05). The expression of TGF-β1 showed significant difference between untreated and negative control groups (P<0.05). HJD and Trolox increased the level of TGF-β1 and the difference was marked as compared with the untreated and negative control groups (P<0.05). HJD relieves oxidative stress-induced injury, increases the antioxidant activity, mitigates the fibroblast mitochondrial damage, up-regulates the expression of growth factor, and promotes mitochondrial repair in mice.

[Postmarketing study of efficacy and safety of losartan during the treatment of patients with mild and moderate hypertension: LOTAR (corrected) study].

PubMed

Vasilijević, Zorana; Dimković, Nada; Lazarević, Katarina; Burmazović, Snežana; Krstić, Nebojša; Milanović, Sladjan; Zorić, Svetlana; Micić, Dragan

2013-01-01

Losartan, the angiotensin type 1 receptor blocker (ARB) exercises its main antihypertensive effect by vasodilatation of peripheral arteries. The aim of this study was to evaluate the antihypertensive effect and safety of losartan in patients with mild and moderate arterial hypertension (AH). This was an open post-marketing study with losartan as monotherapy in previously treated or untreated patients with AH. Primary efficacy parameter was the percentage of patients that achieved target blood pressure after 8-week treatment with a single daily dose of losartan of 50-100 mg. Safety parameters were assessed according to the percentage of adverse events and metabolic effects of therapy. The study included 550 patients with AH (59% female and 41% male), mean age 56.8 +/-11.4 years, BMI = 27 +/- 4 kg/m2. Losartan was applied in 31% of untreated and 69% of previously treatment-resistant patients After 8 weeks target blood pressure was achieved in 67.8% (SBP) and in 81.1% (DBP) of patients, respectively. The mean decrease was 21.8% for SBP and 21.1% for DBP (p < 0.001). Out of all, 65% of patients achieved both target SBP and DBP values. Hydrochlorothiazide was added to the therapy in 11.6% of patients. There were no significant differences in drug efficacy between the entire group and subgroups of patients with diabetes mellitus and impaired renal function (p = ns). Adverse events were rare and metabolic effect was favorable. Monotherapy with losartan in a dosage of 50-100 mg applied during 8 weeks resulted in achieving target values of blood pressure in 65% of patient with mild and moderate hypertension, also including the patients with diabetes mellitus and impaired renal function. Losartan is a safe and metabolically neutral medication.

One year of sitagliptin treatment protects against islet amyloid-associated β-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice

PubMed Central

Aston-Mourney, Kathryn; Subramanian, Shoba L.; Zraika, Sakeneh; Samarasekera, Thanya; Meier, Daniel T.; Goldstein, Lynn C.

2013-01-01

The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve β-cell mass. However, sitagliptin also increases β-cell release of human islet amyloid polypeptide (hIAPP), the peptide component of islet amyloid, which is cosecreted with insulin. Thus, sitagliptin treatment may promote islet amyloid formation and its associated β-cell toxicity. Conversely, metformin treatment decreases islet amyloid formation by decreasing β-cell secretory demand and could therefore offset sitagliptin's potential proamyloidogenic effects. Sitagliptin treatment has also been reported to be detrimental to the exocrine pancreas. We investigated whether long-term sitagliptin treatment, alone or with metformin, increased islet amyloid deposition and β-cell toxicity and induced pancreatic ductal proliferation, pancreatitis, and/or pancreatic metaplasia/neoplasia. hIAPP transgenic and nontransgenic littermates were followed for 1 yr on no treatment, sitagliptin, metformin, or the combination. Islet amyloid deposition, β-cell mass, insulin release, and measures of exocrine pancreas pathology were determined. Relative to untreated mice, sitagliptin treatment did not increase amyloid deposition, despite increasing hIAPP release, and prevented amyloid-induced β-cell loss. Metformin treatment alone or with sitagliptin decreased islet amyloid deposition to a similar extent vs untreated mice. Ductal proliferation was not altered among treatment groups, and no evidence of pancreatitis, ductal metaplasia, or neoplasia were observed. Therefore, long-term sitagliptin treatment stimulates β-cell secretion without increasing amyloid formation and protects against amyloid-induced β-cell loss. This suggests a novel effect of sitagliptin to protect the β-cell in type 2 diabetes that appears to occur without adverse effects on the exocrine pancreas. PMID:23736544

Diabetes management in an Australian primary care population.

PubMed

Krass, I; Hebing, R; Mitchell, B; Hughes, J; Peterson, G; Song, Y J C; Stewart, K; Armour, C L

2011-12-01

Worldwide studies have shown that significant proportions of patients with type 2 diabetes (T2DM) do not meet targets for glycaemic control, blood pressure (BP) and lipids, putting them at higher risk of developing complications. However, little is known about medicines management in Australian primary care populations with T2DM. The aim of this study was to (i) describe the management of a large group of patients in primary care, (ii) identify areas for improvement in management and (iii) determine any relationship between adherence and glycaemic, BP and lipid control. This was a retrospective, epidemiological study of primary care patients with T2DM diabetes, with HbA(1c) of >7%, recruited in 90 Australian community pharmacies. Data collected included demographic details, diabetes history, current medication regimen, height, weight, BP, physical activity and smoking status. Of the 430 patients, 98% used antidiabetics, 80% antihypertensives, 73% lipid lowering drugs and 38% aspirin. BP and all lipid targets were met by only 21% and 14% of the treated patients and 21% and 12% of the untreated patients respectively. Medication adherence was related to better glycaemic control (P = 0.04). An evidence-base prescribing practice gap was seen in this Australian primary care population of T2DM patients. Patients were undertreated with antihypertensive and lipid lowering medication, and several subgroups with co-morbidities were not receiving the recommended pharmacotherapy. Interventions are required to redress the current evidence-base prescribing practice gap in disease management in primary care. © 2011 Blackwell Publishing Ltd.

Bradykinin-forming components in Kuwaiti patients with type 2 diabetes.

PubMed

Sharma, J N; Al-Shoumer, K A S; Matar, K M; Al-Gharee, H Y; Madathil, N V

2013-01-01

Diabetes is the most common risk factor in inducing hypertension, nephropathy and retinopathy. The bradykinin (BK)-forming system has been proposed to protect cardiovascular and renal functions. We therefore evaluated urinary active and proactive kallikrein, total kininogen, plasma tissue kallikrein, plasma creatinine, plasma glucose and plasma HbA1c in newly diagnosed untreated type 2 diabetic patients and healthy subjects. In diabetic patients, urinary and plasma tissue kallikrein concentrations were significantly increased. In addition, plasma prekallikrein levels were also significantly higher. However, urinary kininogen values were significantly reduced in diabetic patients when compared with healthy subjects. This is the first investigation among Kuwaiti Arab patients with type 2 diabetes showing abnormal activities in the BK-forming system. High levels of plasma prekallikrein may be a risk factor for developing high blood pressure as well as nephropathy. The urinary and plasma tissue kallikrein concentrations were higher in diabetic patients, which could indicate the hyperactivities of these components, and may result in increased levels of plasma glucose to induce diabetes. Furthermore, the urinary kininogen levels were reduced in diabetic patients. These alterations might reflect the utilization of urinary kininogen to form BK, a potent inflammatory agent. However, this hypothesis needs further investigation.

Saxagliptin reduces renal tubulointerstitial inflammation, hypertrophy and fibrosis in diabetes.

PubMed

Gangadharan Komala, Muralikrishna; Gross, Simon; Zaky, Amgad; Pollock, Carol; Panchapakesan, Usha

2016-05-01

In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4) inhibitors have been shown to be antifibrotic and anti-inflammatory. We have previously shown that DPP4 inhibition in human kidney proximal tubular cells exposed to high glucose reduced fibrotic and inflammatory markers. Hence, we wanted to demonstrate renoprotection in an in vivo model. We used a type 1 diabetic animal model to explore the renoprotective potential of saxagliptin independent of glucose lowering. We induced diabetes in enos -/- mice using streptozotocin and matched glucose levels using insulin. Diabetic mice were treated with saxagliptin and outcomes compared with untreated diabetic mice. We provide novel data that saxagliptin limits renal hypertrophy, transforming growth factor beta-related fibrosis and NF-κBp65-mediated macrophage infiltration. Overall, there was a reduction in histological markers of tubulointerstitial fibrosis. There was no reduction in albuminuria or glomerulosclerosis. Our findings highlight the potential of DPP4 inhibition as additional therapy in addressing the multiple pathways to achieve renoprotection in diabetic nephropathy. © 2015 Asian Pacific Society of Nephrology.

Effects of diabetes and gender on mechanical properties of the arterial system in rats: aortic impedance analysis.

PubMed

Chang, Kuo-Chu; Hsu, Kwan-Lih; Tseng, Yung-Zu

2003-01-01

We determined the effects of diabetes and gender on the physical properties of the vasculature in streptozotocin (STZ)-treated rats based on the aortic input impedance analysis. Rats given STZ 65 mg/kg i.v. were compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured and were then subjected to Fourier transformation for the analysis of aortic input impedance. Wave transit time was determined using the impulse response function of the filtered aortic input impedance spectra. Male but not female diabetic rats exhibited an increase in cardiac output in the absence of any significant changes in arterial blood pressure, resulting in a decline in total peripheral resistance. However, in each gender group, diabetes contributed to an increase in wave reflection factor, from 0.47 +/- 0.04 to 0.84 +/- 0.03 in males and from 0.46 +/- 0.03 to 0.81 +/- 0.03 in females. Diabetic rats had reduced wave transit time, at 18.82 +/- 0.60 vs 21.34 +/- 0.51 msec in males and at 19.63 +/- 0.37 vs 22.74 +/- 0.57 msec in females. Changes in wave transit time and reflection factor indicate that diabetes can modify the timing and magnitude of the wave reflection in the rat arterial system. Meanwhile, diabetes produced a fall in aortic characteristic impedance from 0.023 +/- 0.002 to 0.009 +/- 0.001 mmHg/min/kg/ml in males and from 0.028 +/- 0.002 to 0.014 +/- 0.001 mmHg/min/kg/ml in females. With unaltered aortic pressure, both the diminished aortic characteristic impedance and wave transit time suggest that the muscle inactivation in diabetes may occur in aortas and large arteries and may cause a detriment to the aortic distensibility in rats with either sex. We conclude that only rats with male gender diabetes produce a detriment to the physical properties of the resistance arterioles. In spite of male or female gender, diabetes decreases the aortic distensibility and impairs the wave reflection phenomenon in the rat arterial system.

Influence of dyslipidemia in control of arterial hypertension among type-2 diabetics in the western region of the Republic of Macedonia

PubMed Central

Jani, Ylber; Kamberi, Amet; Ferati, Fatmir; Rexhepi, Atila; Pocesta, Bekim; Orovcanec, Nikola; Lala, Dali; Polisi, Gafur; Iseni, Mair; Mirto, Arben; Zeqiri, Agim

2014-01-01

Objective: To determine the influence of dyslipidemia in control of blood pressure in patients with type 2 Diabetes. To test the hypothesis that, blood pressure and lipid levels are not sufficiently controlled in patients with type 2 Diabetes, in the western region of the Republic of Macedonia. Background: Abnormalities of lipid and lipoprotein levels in the serum (dyslipidemia) are recognized as major modifiable cardiovascular disease risk factors and have been identified as independent risk factors for essential hypertension, giving rise to the term dyslipidemic hypertension. While patient-related data from primary care that demonstrate an under-treatment of blood pressure and dyslipidemia in type 2 Diabetics are vastly available in clinical practice, results from population-based studies are scarce. Material and methods: The study was conducted on outpatients in Primary Health Care Clinics in 8 cities on the western region of the Republic of Macedonia. Prospectively the tests were performed on 600 (45.6% women and 54.4% men) participants with a mean age of 62 ± 5.8. Study participants were selected among primary care patients, who were actively on therapy for diabetes mellitus and hypertension during the period of March 2013 - March 2014. Patients’ demographic characteristics, clinical laboratory and drug usage data were obtained. The patients were classified according to the BP control, into 2 groups. Results: A total of 600 patients, of which 45.6% female and 54.3% male, completed the survey and had data for a 1-year medical record review. It was observed that a high percentage, 65.3% of patients, did not have controlled blood pressure despite the ongoing medical treatment, according to evidence and current guidelines in a cohort of hypertensive diabetics. (Chi-square: 19.85, p<0.001). Among participants with controled BP, untreated or insufficiently treated dyslipidemia was recorded in 23% of them, whereas among participants with uncontrolled BP, untreated or insufficiently treated dyslipidemia was recorded in 67% of the participants. (Chi-square: 15.01, p=0.0001). Conclusion: A significant influence of dyslipidemia on the control of blood pressure in patients with type 2 Diabetes, was observed in our study. In a small country as Republic of Macedonia (with a population of around 2.000.000, especially the western region with approximately 1/2 of the overall population), this study highlights the considerable lack of awareness and insufficient management of the most important preventable and treatable cardiovascular risk factors (hypertension and dyslipidemia). These findings provide a possible explanation of the steadily high cardiovascular mortality rate despite the clinical and therapeutic progress and accessibility. Besides current hospital-based prevention and pharmaceutical control measures, mass education campaigns, lifestyle interventions etc., emphasis should be given to the role of family doctor as a primary-care health provider. PMID:25006533

Rebamipide Improves Chronic Inflammation in the Lesser Curvature of the Corpus after Helicobacter pylori Eradication: A Multicenter Study

PubMed Central

Kamada, Tomoari; Sato, Motonori; Tokutomi, Tadashi; Watanabe, Tetsuo; Murao, Takahisa; Matsumoto, Hiroshi; Manabe, Noriaki; Ito, Masanori; Tanaka, Shinji; Inoue, Kazuhiko; Shiotani, Akiko; Akiyama, Takashi; Hata, Jiro; Haruma, Ken

2015-01-01

Background and Aim. Although many epidemiologic studies have shown that Helicobacter pylori eradication has prophylactic effects on gastric cancer, it does not completely eliminate the risk of gastric cancer. We aimed to investigate the changes in histological gastritis in patients receiving rebamipide treatment after H. pylori eradication. Methods. 206 patients who had undergone H. pylori eradication were evaluated. Of these, 169 patients who achieved successful eradication were randomly allocated to 2 groups: the rebamipide group (n = 82) and the untreated group (n = 87). The primary endpoints were histopathological findings according to the updated Sydney system at the start of the study and after 1 year. Results. Final assessment for histological gastritis was possible in 50 cases from the rebamipide group and 53 cases from the untreated group. The activity and atrophy improved in both the rebamipide and untreated groups, and no significant intergroup differences were observed. Chronic inflammation affecting the lesser curvature of the corpus was significantly improved in the rebamipide group compared to in the untreated group (1.12 ± 0.08 versus 1.35 ± 0.08; P = 0.043). Conclusions. Rebamipide treatment after H. pylori eradication alleviated chronic inflammation in the lesser curvature of the corpus compared to that in the untreated group. This trial is registered with UMIN000002369. PMID:26060821

A case of herpes zoster ophthalmicus preceded one week by diplopia and ophthalmalgia.

PubMed

Ota, Tomohiro; Yamazaki, Mineo; Toda, Yusuke; Ozawa, Akiko; Kimura, Kazumi

2017-04-28

A 66-year-old man presented with headache and ophthalmalgia. Diplopia developed, and he was hospitalized. The left eye had abducent paralysis and proptosis. We diagnosed him with Tolosa-Hunt syndrome and administered methylprednisolone at 1 g/day for 3 days. However, the patient did not respond to treatment. No abnormality was found on his MRI or cerebrospinal fluid examination. Tests showed his serum immunoglobulin G4 and antineutrophil cytoplasmic antibody titers were within normal limits. He also had untreated diabetes mellitus (HbA1c 9.2). One week after first presenting with symptoms, herpes zoster appeared on the patient's dorsum nasi, followed by keratitis and a corneal ulcer. Herpes zoster ophthalmicus with ophthalmoplegia was diagnosed. We began treatment with acyclovir (15 mg/kg) and prednisolone (1 mg/kg, decreased gradually). Ophthalmalgia and the eruption improved immediately. The eye movement disorder improved gradually over several months. It is rare that diplopia appears prior to cingulate eruption of herpes zoster ophthalmicus. We speculated that onset of the eruption was inhibited by strong steroid therapy and untreated diabetes mellitus.

Novel synergic antidiabetic effects of Astragalus polysaccharides combined with Crataegus flavonoids via improvement of islet function and liver metabolism.

PubMed

Cui, Kai; Zhang, Shaobo; Jiang, Xin; Xie, Weidong

2016-06-01

The present study investigated the synergic effects and potential mechanisms of action of Astragalus polysaccharides (APS) combined with Crataegus flavonoids (CF) in the treatment of type 1 diabetes. Diabetes was induced by intraperitoneal injection of 100 mg/kg streptozotocin in mice. Normal and untreated diabetic control mice were used, and CF‑treated (200 mg/kg/day), APS‑treated (200 mg/kg/day), APS + CF (AC)‑treated (200 mg/kg/day of each) and metformin‑treated (200 mg/kg/day) diabetic mice were orally administrated the appropriate therapeutic agent for 4 weeks. The results demonstrated that AC treatment significantly reduced the fasting blood glucose, food and water intake in the diabetic mice. The AC group demonstrated increased serum insulin levels and islet cell function was restored. Furthermore, the AC‑treated mice demonstrated significant increases in the protein expression levels of pancreatic and duodenal homeobox‑1 and phosphorylated adenosine 5'‑monophosphate‑activated protein kinase in the pancreatic and liver tissue samples, respectively. In addition, AC significantly increased the mRNA expression levels of neurogenin 3, v‑maf musculoaponeurotic fibrosarcoma oncogene family, protein A and insulin, and simultaneously decreased the expressions of interleukin 6, tumor necrosis factor‑α and chemokine (C‑C motif) ligand 2 in the pancreatic islet cells of diabetic mice. The anti‑inflammatory activity of APS and the islet‑restoring effect of CF may contribute to the improvement of islet function. AC exerted greater antidiabetic effects compared with APS or CF treatments alone. These results indicated that AC treatment had a synergic antidiabetic effect, which may involve improvements in islet function and liver metabolism. These effects of AC may facilitate the treatment of type 1 or 2 diabetes, as these patients frequently experience impaired islet function and disordered extrapancreatic metabolism.

Does footprint preparation influence tendon-to-bone healing after rotator cuff repair in an animal model?

PubMed

Ficklscherer, Andreas; Loitsch, Thomas; Serr, Michaela; Gülecyüz, Mehmet F; Niethammer, Thomas R; Müller, Hans-Helge; Milz, Stefan; Pietschmann, Matthias F; Müller, Peter E

2014-02-01

The aim of this study was to investigate the influence of footprint spongialization and radiofrequency ablation on rotator cuff repair outcomes compared with an untreated group in a rat model. We randomly assigned 189 Sprague-Dawley rats to either a spongialization, radiofrequency ablation, or untreated group. After separation of the supraspinatus tendon from the greater tubercle, the footprint was prepared by removing the cortical bone with a burr (spongialization), was prepared by ablating soft tissue with a radiofrequency ablation device, or was left unaltered (untreated). Biomechanical testing (after 7 weeks, n = 165) and histologic analysis after 1 and 7 weeks (n = 24) followed reinsertion. The mean load to failure was 17.51 ± 4.46 N/mm(2) in the spongialization group, 15.56 ± 4.85 N/mm(2) in the radiofrequency ablation group, and 19.21 ± 5.19 N/mm(2) in the untreated group. A significant difference was found between the spongialization and radiofrequency ablation groups (P = .0409), as well as between the untreated and radiofrequency ablation groups (P = .0014). There was no significant difference between the spongialization and untreated groups (P = .2456). The mean area of fibrocartilage transition, characterized by the presence of type II collagen, was larger after 1 and 7 weeks in the spongialization group (0.57 ± 0.1 mm(2) and 0.58 ± 0.1 mm(2), respectively) and untreated group (0.51 ± 0.1 mm(2) and 0.51 ± 0.2 mm(2), respectively) than in the radiofrequency ablation group (0.11 ± 0.1 mm(2) and 0.4 ± 0.1 mm(2), respectively) with P < .05 and P < .01. The results of this study show that radiofrequency ablation of the footprint results in a poor biomechanical and histologic outcome in an animal model. No preparation of the footprint has the same effect as spongialization. Different techniques of footprint preparation in rotator cuff repair may influence tendon-to-bone healing. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Psychological distress of patients suffering from restless legs syndrome: a cross-sectional study

PubMed Central

2011-01-01

Background Restless legs syndrome (RLS) is a chronic disorder with substantial impact on quality of life similar to that seen in diabetes mellitus or osteoarthritis. Little is known about the psychological characteristics of RLS patients although psychological factors may contribute to unfavourable treatment outcome. Methods In an observational cross-sectional design, we evaluated the psychological features of 166 consecutive RLS patients from three outpatient clinics, by means of the Symptom Checklist 90-R (SCL-90-R) questionnaire. Additionally, the Beck Depression Inventory-II (BDI-II) and the International RLS Severity Scale (IRLS) were measured. Both treated and untreated patients were included, all patients sought treatment. Results Untreated patients (n = 69) had elevated but normal scores on the SCL-90-R Global Severity Index (GSI; p = 0.002) and on the sub-scales somatisation (p < 0.001), compulsivity (p = 0.003), depression (p = 0.02), and anxiety (p = 0.004) compared with a German representative sample. In the treated group, particularly in those patients who were dissatisfied with their actual treatment (n = 62), psychological distress was higher than in the untreated group with elevated scores for the GSI (p = 0.03) and the sub-scales compulsivity (p = 0.006), depression (p = 0.012), anxiety (p = 0.031), hostility (p = 0.013), phobic anxiety (p = 0.024), and paranoid ideation (p = 0.012). Augmentation, the most serious side effect of dopaminergic, i.e. first-line treatment of RLS, and loss of efficacy were accompanied with the highest psychological distress, as seen particularly in the normative values of the sub-scales compulsivity and anxiety. Generally, higher RLS severity was correlated with higher psychological impairment (p < 0.001). Conclusion Severely affected RLS patients show psychological impairment in multiple psychological domains which has to be taken into account in the treatment regimen. PMID:21933380

Bone morphogenetic protein-7 (BMP-7) augments insulin sensitivity in mice with type II diabetes mellitus by potentiating PI3K/AKT pathway.

PubMed

Chattopadhyay, Tandrika; Singh, Rajiv Ranjan; Gupta, Sarika; Surolia, Avadhesha

2017-03-01

A direct link between development of insulin resistance and the presence of chronic inflammation, in case of obesity exists, with cytokines playing an important role in glucose metabolism. Members of TGF-β superfamily, including bone morphogenetic proteins (BMPs), have been shown to be involved in islet morphogenesis, establishment of β-cell mass and adipose cell fate determination. Here, we demonstrate a novel and direct role of BMP-4 and -7 in the regulation of glucose homeostasis and insulin resistance. An age-dependent increase in serum BMP-4 and decrease in serum BMP-7 levels was observed in animal models of type II diabetes. In this study, BMP-7 and -4 have been demonstrated to have antagonistic effects on insulin signaling and thereby on glucose homeostasis. BMP-7 augmented glucose uptake in the insulin sensitive tissues such as the adipose and muscle by increasing Glut4 translocation to the plasma membrane through phosphorylation and activation of PDK1 and Akt, and phosphorylation and translocation of FoxO1 to the cytoplasm in liver/HepG2 cells. Restoration of BMP-7 levels in serum of diabetic animals resulted in decreased blood glucose levels in contrast to age matched untreated control groups, opening up a new therapeutic avenue for diabetes. On the contrary, BMP-4 inhibited insulin signaling through activation of PKC-θ isoform, and resulted in insulin resistance through the attenuation of insulin signaling. BMP-7 therefore is an attractive candidate for tackling a multifaceted disease such as diabetes, since it not only reduces body fat, but also strengthens insulin signaling, causing improved glucose uptake and ameliorating peripheral insulin resistance. © 2017 BioFactors, 43(2):195-209, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Glucose and Insulin Secretory Response Patterns Following Diet and Tolazamide Therapy in Diabetes

PubMed Central

Turtle, J. R.

1970-01-01

Glucose and insulin secretory response patterns during glucose tolerance tests were determined in 28 maturity-onset diabetics, and the sequential effects of diet and a sulphonylurea, tolazamide, were assessed. Untreated diabetics showed hyperglycaemia, increased serum immunoreactive insulin response patterns, delayed insulin release, and relative insulin deficiency. Diet alone partially corrected the hyperglycaemia and serum immunoreactive insulin response but had no effect on the delayed insulin release or relative insulin deficiency. Tolazamide plus diet restored all values towards normal. The net effect of maintenance tolazamide therapy was to (1) restore the insulin secretory response pattern to normal, (2) reduce total pancreatic insulin output, and (3) improve the efficiency of insulin secretion. The results suggest that there is a rational basis for the use of sulphonylurea in all maturity-onset diabetics, including patients with mild carbohydrate intolerance and those who are apparently controlled by diet alone. PMID:5470087

Increased gluconeogenesis in youth with newly diagnosed type 2 diabetes

PubMed Central

Chung, Stephanie T.; Hsia, Daniel S.; Chacko, Shaji K.; Rodriguez, Luisa M.; Haymond, Morey W.

2014-01-01

Aims/hypothesis The role of increased gluconeogenesis as an important contributor to fasting hyperglycaemia at diabetes onset is not known. We evaluated the contribution of gluconeogenesis and glycogenolysis to fasting hyperglycaemia in newly diagnosed youths with type 2 diabetes following an overnight fast. Methods Basal rates (μmol kgFFM−1 min−1) of gluconeogenesis (2H20), glycogenolysis and glycerol production ([2H5] glycerol) were measured in 18 adolescents (nine treatment naive diabetic and nine normal-glucose-tolerant obese adolescents). Results Type 2 diabetes was associated with higher gluconeogenesis (9.2±0.6 vs 7.0±0.3 μmol kgFFM−1 min−1, p < 0.01), plasma fasting glucose (7.0±0.6 vs 5.0±0.2 mmol/l, p = 0.004) and insulin (300±30 vs 126±31 pmol/l, p = 0.001). Glucose production and glycogenolysis were similar between the groups (15.4±0.3 vs 12.4±1.4 μmol kgFFM−1 min−1, p = 0.06; and 6.2±0.8 vs 5.3±0.7 μmol kgFFM−1 min−1, p = 0.5, respectively). After controlling for differences in adiposity, gluconeogenesis, glycogenolysis and glucose production were higher in diabetic youth (p ≤ 0.02). Glycerol concentration (84±6 vs 57±6 μmol/l, p = 0.01) and glycerol production (5.0±0.3 vs 3.6±0.5 μmol kgFFM−1 min−1, p =0.03) were 40% higher in youth with diabetes. The increased glycerol production could account for only ~1/3 of substrate needed for the increased gluconeogenesis in diabetic youth. Conclusion/interpretations Increased gluconeogenesis was a major contributor to fasting hyperglycaemia and hepatic insulin resistance in newly diagnosed untreated adolescents and was an early pathological feature of type 2 diabetes. Increased glycerol availability may represent a significant source of new carbon substrates for increased gluconeogenesis but would not account for all the carbons required to sustain the increased rates. PMID:25447079

Diffuse reflectance spectroscopy for monitoring diabetic foot ulcer - A pilot study

NASA Astrophysics Data System (ADS)

Anand, Suresh; Sujatha, N.; Narayanamurthy, V. B.; Seshadri, V.; Poddar, Richa

2014-02-01

Foot ulceration due to diabetes mellitus is a major problem affecting 12-25% of diabetic subjects in their lifetime. An untreated ulcer further gets infected which causes necrosis leading to amputation of lower extremities. Early identification of risk factors and treatment for these chronic wounds would reduce health care costs and improve the quality of life for people with diabetes. Recent clinical investigations have shown that a series of factors including reduced oxygen delivery and disturbed metabolism have been observed on patients with foot ulceration due to diabetes. Also, these factors can impair the wound healing process. Optical techniques based on diffuse reflectance spectroscopy provide characteristic spectral finger prints shed light on tissue oxygenation levels and morphological composition of a tissue. This study deals with the application of diffuse reflectance intensity ratios based on oxyhemoglobin bands (R542/R580), ratios of oxy- and deoxy-hemoglobin bands (R580/R555), total hemoglobin concentration and hemoglobin oxygen saturation between normal and diabetic foot ulcer sites. Preliminary results obtained are found to be promising indicating the application of reflectance spectroscopy in the assessment of foot ulcer healing.

Untreated asymptomatic group B streptococcal bacteriuria early in pregnancy and chorioamnionitis at delivery.

PubMed

Anderson, Brenna L; Simhan, Hyagriv N; Simons, Kathryn M; Wiesenfeld, Harold C

2007-06-01

The objective of the study was to determine the frequency of adverse pregnancy outcomes in women with untreated asymptomatic group B beta-hemolytic streptococcal (GBS) bacteriuria during pregnancy. In this retrospective cohort, all women with antepartum GBS bacteriuria in a research registry were included. Controls were women with negative urine cultures. The frequency of chorioamnionitis was compared between groups. Chorioamnionitis was defined as intrapartum fever, fetal tachycardia, and histologic inflammation of the membranes. One hundred twenty-two women with bacteriuria (study group) and 183 women with negative antepartum cultures (controls) were included. There were no differences in demographic characteristics between the groups. Thirty-one women (10.2%) had chorioamnionitis. Untreated GBS bacteriuria was associated with chorioamnionitis after controlling for confounding variables, adjusted odds ratio 7.2 (95% confidence interval 2.4 to 21.2). There was also a significant positive rank correlation between increasing colony count of GBS bacteriuria and increasing grade of chorioamnionitis (P = .02). Untreated antepartum GBS bacteriuria is associated with chorioamnionitis.

Treatment of Diabetic Autonomic Neuropathy in Older Adults with Diabetes Mellitus.

PubMed

Scheinberg, Nataliya; Salbu, Rebecca L; Goswami, Gayotri; Cohen, Kenneth

2016-11-01

To review the epidemiology, pathophysiology, screening and diagnosis, and optimal treatment of diabetic autonomic neuropathy (DAN) and its implications in older adults. A search of PubMed using the Mesh terms "diabetes," "type 1," "insulin-dependent," "T1DM," and "diabetic autonomic neuropathy" was performed to find relevant primary literature. Additional search terms "epidemiology," "geriatric," and "risk" were employed. All English-language articles from 2005 to 2015 appearing in these searches were reviewed for relevance. Related articles suggested in the PubMed search and clinical guidelines from the American Diabetes Association and the American Association of Clinical Endocrinologists were reviewed. These uncovered further resources for risk stratification, pathophysiology, diagnosis, and treatment of DAN. DAN is highly prevalent in the diabetes population and increases the risk of morbidity and mortality in older adults, yet, often goes undiagnosed and untreated. Treatment of DAN is complex in the older adult because of poor tolerability of many pharmacologic treatment options; therefore, great care must be taken when selecting therapy as to avoid unwanted adverse effects. With increasing life-expectancy of patients with diabetes mellitus, awareness of DAN and its implications to older adults is needed in primary care. Consistent screening and appropriate treatment of DAN in older adults with diabetes mellitus is essential in helping to maintain functional status and avoid adverse events.

Relationship Between Excessive Gestational Weight Gain and Neonatal Adiposity in Women With Mild Gestational Diabetes Mellitus.

PubMed

Blackwell, Sean C; Landon, Mark B; Mele, Lisa; Reddy, Uma M; Casey, Brian M; Wapner, Ronald J; Varner, Michael W; Rouse, Dwight J; Thorp, John M; Sciscione, Anthony; Catalano, Patrick; Saade, George; Caritis, Steve N; Sorokin, Yoram; Grobman, William A

2016-12-01

To evaluate the relationships among excessive gestational weight gain, neonatal adiposity, and adverse obstetric outcomes in women with mild gestational diabetes mellitus. This is a secondary analysis of a multicenter randomized clinical trial of women with mild gestational diabetes mellitus. Based on self-reported prepregnancy body weight, gestational weight gain was categorized as excessive if it was greater than 2009 Institute of Medicine guidelines. Maternal outcomes and neonatal anthropomorphic characteristics were compared between women with excessive weight gain and those without excessive weight gain. Multiple linear and logistic regression analyses were performed to adjust for confounding factors. We studied 841 women who participated in the main trial and had prepregnancy body mass index (BMI) and delivery information available (n=431 treatment group, n=410 no treatment). After adjustment for factors including treatment and prepregnancy BMI, excessive weight gain remained associated with large for gestational age (adjusted odds ratio [OR] 2.94, 95% confidence interval [CI] 1.81-4.93), birth weight greater than 4,000 g (adjusted OR 2.56, 95% CI 1.54-4.40), preeclampsia (adjusted OR 2.96, 95% CI 1.35-7.03), and cesarean delivery for labor arrest (adjusted OR 2.37, 95% CI 1.30-4.44). In addition, excessive weight gain was independently associated with increased total neonatal fat (P<.001) and birth weight (P<.001). In women with both treated and untreated mild gestational diabetes mellitus, excessive gestational weight gain was independently associated with both greater birth weight and adiposity.

Type 2 diabetes mellitus treatment patterns in U.S. nursing home residents.

PubMed

Zarowitz, Barbara; Allen, Carrie; O'Shea, Terrence; Dalal, Mehul R; Haumschild, Mark; DiGenio, Andres

2015-06-01

The prevalence of type 2 diabetes mellitus (diabetes) in nursing home residents (NHRs) is increasing, concurrently with obesity and other comorbid conditions. NHR would benefit greatly from antidiabetic medications that would improve glycemic control and give a lower risk of hypoglycemia but that do not contribute to weight gain in obese individuals. To examine the prescription patterns to NHRs with diabetes, including the use of newer injectable therapies such as glucagon-like peptide-1 (GLP-1) receptor agonists. Treatment patterns of diabetes in NHR were analyzed using Minimum Data Set records and prescription claims from the Omnicare Senior Health Outcomes data repository (May 2011-September 2012). The prevalence of diabetes in this population of 229,283 NHRs was 35.4%. Among the 44,665 NHRs with diabetes and prescription claims data, the prevalence of obesity (40.3%) and multiple comorbidities (100%) was high. Approximately 20% of the NHRs with diabetes were aged <65 years. Overall, 20% of NHRs had diabetes that was untreated with medications during the study period. Insulin was the mainstay of treatment (>80%), followed by oral agents (54%). GLP-1 receptor agonist use was low (0.5%) and associated with poor treatment persistence. Considerations other than glycemic control may drive prescribing decisions, contrary to recommendations from the American Diabetes Association, American Medical Directors Association, and European Association for the Study of Diabetes.

The glycated albumin to HbA1c ratio is elevated in patients with fulminant type 1 diabetes mellitus with onset during pregnancy.

PubMed

Koga, Masafumi; Shimizu, Ikki; Murai, Jun; Saito, Hiroshi; Kasayama, Soji; Kobayashi, Tetsuro; Imagawa, Akihisa; Hanafusa, Toshiaki

2013-01-01

Fulminant type 1 diabetes mellitus (FT1DM) develops as a result of very rapid and almost complete destruction of pancreatic β cell. The most common form of type 1 diabetes mellitus with onset during pregnancy has been shown to be FT1DM at least in Japan. We previously reported that the ratio of glycated albumin (GA) to HbA1c (GA/HbA1c ratio) is elevated in FT1DM patients at the diagnosis. In the present study, we investigated whether the GA/HbA1c ratio is also elevated in FT1DM with onset during pregnancy (P-FT1DM). The study subjects consisted of 7 patients with P-FT1DM. Ten patients with untreated type 2 diabetes mellitus (T2DM) discovered during pregnancy (P-T2DM) and 9 non-pregnant women with untreated T2DM (NP-T2DM) were used as controls. All study patients satisfied HbA1c < 8.7%, the diagnostic criteria for FT1DM. The GA/HbA1c ratio in the P-FT1DM patients at the diagnosis was significantly higher than that in the P-T2DM patients and the NP-T2DM patients. The GA/HbA1c ratio was ≥ 3.0 in all P-FT1DM patients, whereas it was < 3.0 in 8 of 10 P-T2DM patients and all NP-T2DM patients. The GA/HbA1c ratio was also elevated in P-FT1DM patients at the diagnosis compared with T2DM with or without pregnancy.

Interferon-free therapy of chronic hepatitis C with direct-acting antivirals does not change the short-term risk for de novo hepatocellular carcinoma in patients with liver cirrhosis.

PubMed

Mettke, F; Schlevogt, B; Deterding, K; Wranke, A; Smith, A; Port, K; Manns, M P; Vogel, A; Cornberg, M; Wedemeyer, H

2018-02-01

Hepatitis C virus (HCV) clearance with IFN-based therapies reduces the incidence of hepatocellular carcinoma (HCC). There has been some debate if IFN-free therapy with direct-acting antivirals alters the risk for HCC. To investigate the HCC incidence in cirrhotic HCV patients who cleared HCV with direct-acting antivirals vs untreated controls. We prospectively monitored 373 patients with chronic hepatitis C who received IFN-free therapies with direct-acting antiviral after January 2014. A retrospective control cohort of untreated cirrhotic patients was recruited out of 3715 HCV patients who were followed at our centre between 2007 and 2013, with similar HCC screening protocols. 158 direct-acting antiviral-treated and 184 control patients with liver cirrhosis were included in this analysis. The groups did not differ in gender and genotype distribution, severity of liver disease and prevalence of diabetes mellitus. Patients were followed up for a median of 440 (range 91-908) and 592 (range 90-1000) days. HCCs developed in 6 and 14 patients during follow-up, resulting in an incidence of 2.90 vs 4.48 HCCs per 100 person-years. In the direct-acting antiviral-treated group, there was no new case of HCC later than 450 days after treatment initiation. In multivariate analysis, higher MELD-Scores and AFP-levels were independently associated with HCC development. Transplant-free patient survival was similar in both groups. IFN-free direct-acting antiviral therapy of chronic hepatitis C does not alter the short-term risk for HCC in patients with liver cirrhosis. A reduced HCC incidence may become evident after more than 1.5 years of follow-up. © 2017 John Wiley & Sons Ltd.

Repaglinide-loaded long-circulating biodegradable nanoparticles: rational approach for the management of type 2 diabetes mellitus.

PubMed

Jain, Shelesh; Saraf, Swarnlata

2009-03-01

Repaglinide (RPG) is an oral hypoglycemic agent with excellent bioavailability (90-98%) and a short plasma half-life (2-6 h). A full dose of RPG is required before each meal; hence, therapy may become inconvenient. Thus, the aim of the present study was to design a novel delivery system to maintain peak plasma levels of RPG for the long-term management of diabetes mellitus. Two nanoparticle formulations were prepared by combining RPG with poly (lactic-co-glycolic) acid alone or as a copolymer with methoxypolyethylene glycol (RPGNP1 and RPGNP2, respectively); both formulations were subjected to in vitro and in vivo characterization. In vivo characterization was performed in a streptozotocin (STZ)-induced diabetic male albino rats. The mean particle size of the RPGNP1 and RPGNP2 formulations was 387.8 ± 11.9 and 310.2 ± 12.4 nm, respectively, with a zeta potential of -27.4 ± 0.7 and -15.7 ± 0.5 mV, respectively. The entrapment efficiency and drug content of RPGNP1 (58.7 ± 1.3% and 27.4 ± 2.3%, respectively) was better than that of RPGNP2 (45.8 ± 1.2% and 24.3 ± 1.1%, respectively). Blood glucose levels of RPGNP1- and RPGNP2-treated STZ-diabetic rats were reduced significantly (to normal levels) compared with untreated STZ-diabetic rats (P < 0.05), but there was no difference between the two treatment groups (P > 0.05). However, whereas RPGNP1 was effective for a period of only 24 h, RPGNP2 was effective for up to 1 week. The results of the present study show that RPGNP2 effectively manages type 2 diabetes mellitus for up to 1 week. Surface-modified NPs could be used to improve patient compliance with drug treatment as a result of decreased dosing frequency. © 2009 Ruijin Hospital and Blackwell Publishing Asia Pty Ltd.

Effect of insulin sensitizer therapy on amino acids and their metabolites.

PubMed

Irving, Brian A; Carter, Rickey E; Soop, Mattias; Weymiller, Audrey; Syed, Husnain; Karakelides, Helen; Bhagra, Sumit; Short, Kevin R; Tatpati, Laura; Barazzoni, Rocco; Nair, K Sreekumaran

2015-06-01

Prior studies have reported that elevated concentrations of several plasma amino acids (AA), particularly branched chain (BCAA) and aromatic AA predict the onset of type 2 diabetes. We sought to test the hypothesis that circulating BCAA, aromatic AA and related AA metabolites decline in response to the use of insulin sensitizing agents in overweight/obese adults with impaired fasting glucose or untreated diabetes. We performed a secondary analysis of a randomized, double-blind, placebo, controlled study conducted in twenty five overweight/obese (BMI ~30kg/m(2)) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45mg per day) plus metformin (1000mg twice per day, N=12 participants) or placebo (N=13). We measured insulin sensitivity by the euglycemic-hyperinsulinemic clamp and fasting concentrations of AA and AA metabolites using ultra-pressure liquid chromatography tandem mass spectrometry before and after the three-month intervention. Insulin sensitizer therapy that significantly enhanced insulin sensitivity reduced 9 out of 33 AA and AA metabolites measured compared to placebo treatment. Moreover, insulin sensitizer therapy significantly reduced three functionally clustered AA and metabolite pairs: i) phenylalanine/tyrosine, ii) citrulline/arginine, and iii) lysine/α-aminoadipic acid. Reductions in plasma concentrations of several AA and AA metabolites in response to three months of insulin sensitizer therapy support the concept that reduced insulin sensitivity alters AA and AA metabolites. Copyright © 2015 Elsevier Inc. All rights reserved.

Investigation on the effects of the atmospheric pressure plasma on wound healing in diabetic rats

NASA Astrophysics Data System (ADS)

Fathollah, Sara; Mirpour, Shahriar; Mansouri, Parvin; Dehpour, Ahmad Reza; Ghoranneviss, Mahmood; Rahimi, Nastaran; Safaie Naraghi, Zahra; Chalangari, Reza; Chalangari, Katalin Martits

2016-02-01

It is estimated that 15 percent of individuals with diabetes mellitus suffer from diabetic ulcers worldwide. The aim of this study is to present a non-thermal atmospheric plasma treatment as a novel therapy for diabetic wounds. The plasma consists of ionized helium gas that is produced by a high-voltage (8 kV) and high-frequency (6 kHz) power supply. Diabetes was induced in rats via an intravascular injection of streptozotocin. The plasma was then introduced to artificial xerograph wounds in the rats for 10 minutes. Immunohistochemistry assays was performed to determine the level of transforming growth factor (TGF-β1) cytokine. The results showed a low healing rate in the diabetic wounds compared with the wound-healing rate in non-diabetic animals (P < 0.05). Moreover, the results noted that plasma enhanced the wound-healing rate in the non-diabetic rats (P < 0.05), and significant wound contraction occurred after the plasma treatment compared with untreated diabetic wounds (P < 0.05). Histological analyses revealed the formation of an epidermis layer, neovascularization and cell proliferation. The plasma treatment also resulted in the release of TGF-β1 cytokine from cells in the tissue medium. The findings of this study demonstrate the effect of plasma treatment for wound healing in diabetic rats.

Low molecular weight fucoidan alleviates cardiac dysfunction in diabetic Goto-Kakizaki rats by reducing oxidative stress and cardiomyocyte apoptosis.

PubMed

Yu, Xinfeng; Zhang, Quanbin; Cui, Wentong; Zeng, Zheng; Yang, Wenzhe; Zhang, Chao; Zhao, Hongwei; Gao, Weidong; Wang, Xiaomin; Luo, Dali

2014-01-01

Diabetic cardiomyopathy (DCM) is characterized by cardiac dysfunction and cardiomyocyte apoptosis. Oxidative stress is suggested to be the major contributor to the development of DCM. This study was intended to evaluate the protective effect of low molecular weight fucoidan (LMWF) against cardiac dysfunction in diabetic rats. Type 2 diabetic goto-kakizaki rats were untreated or treated with LMWF (50 and 100 mg/kg/day) for three months. The establishment of DCM model and the effects of LMWF on cardiac function were evaluated by echocardiography and isolated heart perfusion. Ventricle staining with H-E or Sirius Red was performed to investigate the structural changes in myocardium. Functional evaluation demonstrated that LMWF has a beneficial effect on DCM by enhancing myocardial contractility and mitigating cardiac fibrosis. Additionally, LMWF exerted significant inhibitory effects on the reactive oxygen species production and myocyte apoptosis in diabetic hearts. The depressed activity of superoxide dismutase in diabetic heart was also improved by intervention with LMWF. Moreover, LMWF robustly inhibited the enhanced expression of protein kinase C β, an important contributor to oxidative stress, in diabetic heart and high glucose-treated cardiomyocytes. In conclusion, LMWF possesses a protective effect against DCM through ameliorations of PKCβ-mediated oxidative stress and subsequent cardiomyocyte apoptosis in diabetes.

Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide.

PubMed

Nurliyani; Harmayani, Eni; Sunarti

2015-01-01

The study aimed to evaluate the effect of kefir combination from goat milk and soy milk on lipid profile, plasma glucose, glutathione peroxidase (GPx) activity and the improvement of pancreatic β-cell in diabetic rats. Male rats were divided into five treatments: normal control, diabetic control, goat milk kefir, combination of goat milk-soy milk kefir and soy milk kefir. All rats were induced by streptooztocin-nicotinamide (STZ-NA), except for normal control. After 35 d experiment, the rats were sampled for blood, sacrificed and sampled for pancreatic tissues. Results showed that diabetic rats fed kefir combination had higher (p<0.05) triglyceride than the rats fed goat milk or soy milk kefir. Decreasing of plasma glucose in diabetic rats fed kefir combination was higher (p<0.05) than rats fed goat millk kefir. The activity of GPx in diabetic rats fed three kinds of kefir were higher (p<0.01) than untreated diabetic rats. The average number of Langerhans and β-cells in diabetic rats fed kefir combination was the same as the normal control, but it was higher than diabetic control. It was concluded that kefir combination can be used as antidiabetic through maintaining in serum triglyceride, decreasing in plasma glucose, increasing in GPx activity and improving in pancreatic β-cells.

Hyperspectral Imaging in Diabetic Foot Wound Care

PubMed Central

Yudovsky, Dmitry; Nouvong, Aksone; Pilon, Laurent

2010-01-01

Diabetic foot ulceration is a major complication of diabetes and afflicts as many as 15 to 25% of type 1 and 2 diabetes patients during their lifetime. If untreated, diabetic foot ulcers may become infected and require total or partial amputation of the affected limb. Early identification of tissue at risk of ulcerating could enable proper preventive care, thereby reducing the incidence of foot ulceration. Furthermore, noninvasive assessment of tissue viability around already formed ulcers could inform the diabetes caregiver about the severity of the wound and help assess the need for amputation. This article reviews how hyperspectral imaging between 450 and 700 nm can be used to assess the risk of diabetic foot ulcer development and to predict the likelihood of healing noninvasively. Two methods are described to analyze the in vivo hyperspectral measurements. The first method is based on the modified Beer-Lambert law and produces a map of oxyhemoglobin and deoxyhemoglobin concentrations in the dermis of the foot. The second is based on a two-layer optical model of skin and can retrieve not only oxyhemoglobin and deoxyhemoglobin concentrations but also epidermal thickness and melanin concentration along with skin scattering properties. It can detect changes in the diabetic foot and help predict and understand ulceration mechanisms. PMID:20920429

Elevated serum IGF-1 level enhances retinal and choroidal thickness in untreated acromegaly patients.

PubMed

Zhang, Xia; Ma, Jin; Wang, Yuhan; Li, Lüe; Gao, Lu; Guo, Xiaopeng; Xing, Bing; Zhong, Yong

2018-03-01

1) To compare the retinal, choroidal, Haller's layer, and Sattler's/choriocapillaris thicknesses of untreated acromegaly patients without chiasm compression or diabetes mellitus and healthy controls. 2) To evaluate the correlations of retinal and choroidal thicknesses with serum growth hormone (GH) and insulin-like growth factor 1 (IGF) burden. This prospective, case-control study included 27 untreated acromegaly patients and 27 sex-matched and age-matched controls. Subfoveal choroidal, Haller's layer and Sattler's/choriocapillaris thicknesses were determined by enhanced-depth imaging optical coherence tomography (EDI-OCT). Foveal and macular retinal thicknesses were determined with SD-OCT. GH and IGF-1 burdens were defined as the product of disease duration and treatment-naïve serum GH and IGF-1 levels. Compared with healthy controls, patients with acromegaly exhibited significantly increased foveal retinal (p = 0.003), subfoveal choroidal (p < 0.001), and Haller's layer (p < 0.001) thicknesses, with no differences in Sattler's/choriocapillaris layer thickness. Multiple point measurements in the posterior pole area showed equally increased nasal and temporal parts of the choroid. The retinal thickness maps of the two groups did not significantly differ. Correlation analysis indicated that choroidal thickness was significantly correlated with disease duration (p = 0.01), serum IGF-1 level (p = 0.03) and IGF-1 burden (p = 0.009). No significant correlations were detected between choroidal thickness and GH burden (p = 0.44). Retinal thickness was not significantly correlated with any factor. The choroidal thickness of acromegaly patients was greater than that of healthy controls and was significantly correlated with disease duration, IGF-1 level and IGF-1 burden, indicating that excessive serum IGF-1 and its exposure time have a combined effect on choroidal thickness.

Depression among older adults with diabetes mellitus.

PubMed

Park, Mijung; Reynolds, Charles F

2015-02-01

Older adults with Diabetes Mellitus (DM) experience greater risk for comorbid depression compared to those who do not have DM. Undetected, untreated or under-treated depression impinges an individual's ability to manage their DM successfully, hinders their adherence to treatment regime, and undermines provider-patient relationships. Thus, in the context of caring for older adults with DM, comorbid depression presents special challenges and opportunities for clinicians. In this article, we summarize the clinical presentation of late-life depression, potential mechanisms of comorbidity of depression and DM, importance of depression in the successful management of DM, and available best practice models for depression treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Pre- Versus Posttransplant Treatment of Hepatitis C Virus With Direct-Acting Antivirals in Liver Transplant Recipients: More Issues to be Solved.

PubMed

Abdelqader, Abdelhai; Kabacam, Gokhan; Woreta, Tinsay A; Hamilton, James P; Luu, Harry; Al Khalloufi, Kawtar; Saberi, Behnam; Philosophe, Benjamin; Cameron, Andrew M; Gurakar, Ahmet

2017-02-01

Our goal was to investigate wait times related to hepatitis C virus treatment with direct acting antivirals before versus after liver transplant at a single center as well as wait times for insurance approval for preemptive treatment with these agents after liver transplant. We retrospectively evaluated hepatitis C virus infections in transplant recipients of deceased liver donations in 2014 and 2015. Demographics, hepatocellular carcinoma incidence, Model for End-Stage Liver Disease scores, and transplant wait times were compared between patients treated before or after liver transplant. Wait times to approval of direct-acting antiviral treatment were evaluated in those untreated before transplant. During our study period, of 67 deceased-donor liver transplants, 21 patients received hepatitis C virus treatment pretransplant (treated group) and 46 patients were not treated pretransplant (untreated group). Twenty-five patients in the untreated group received hepatitis C virus-positive donations, with all in this group treated with direct-acting antivirals. We found no statistically significant differences regarding age, sex, race, donation after cardiac death, or incidence of hepatocellular carcinoma between groups. The treated group had a longer median wait time (287 vs 172 days; P = .02). Twelve of the 46 untreated patients (26.1%) developed biopsy-proven hepatitis C virus-related relapse (median 87 days; range, 55-383 days). Preemptive direct-acting antiviral therapy was initiated at a median of 81 days in the untreated group. Although treatment of hepatitis C virus before liver transplant is an attractive option to eliminate the risk of complications, it can limit the donor pool for recipients to uninfected donors, significantly increasing wait times in regions with large hepatitis C virus-positive donor pools. Allocation of Model for End-Stage Liver Disease score was not different between the treated and untreated groups. Insurance companies should revise their policies for rapid approval of preemptive direct-acting antiviral treatment after liver transplant.

Effect of preoperative regional artery chemotherapy on proliferation and apoptosis of gastric carcinoma cells

PubMed Central

Tao, Hou-Quan; Zou, Shou-Chun

2002-01-01

AIM: To study the effects of preoperative regional artery chemotherapy (PRACT) in inducing growth inhibition and apoptosis of gastric carcinoma (GC) cells. METHODS: TUNEL (terminal-deoxynucleotidyl-transferase TdT-mediated dUTP-fluorescein and labeling) method and immunohistochemical techniques were used to detect the state of apoptosis and proliferation of GC cells in histopathologic sections. A total of 110 cases of GC and 68 cases of metastatic lymph node with or without PRACT were adopted. Correlations between apoptosis index (AI), proliferation index (PI) and PRACT and prognosis were analysed. RESULTS: The apoptosis index (AI) was significantly higher in the PRACT group (12.5‰ ± 4.33‰) than in the untreated group (7.1‰ ± 3.43‰, P < 0.001), whereas the proliferation index (PI) in the PRACT group (33.8% ± 8.8%) was significantly lower than that in untreated group (43.6% ± 12.8%, P < 0.01). Both AI and PI were correlated to the differentiation degree of GC in PRACT group, the AI in the differentiated group was higher than that in undifferentiated group (P < 0.001), but the PI was lower in the differentiated group than that of the undifferentiated group (P < 0.01). The AI of GC cells in metastatic lymph node was also significantly higher in the PRACT group (7.9‰ ± 3.41‰) than in the untreated group (3.6‰ ± 2.93‰, P < 0.01), though the PI of GC cells in metastatic lymph nodes in the PRACT group (17.2% ± 6.8%) was significantly lower than that in the untreated group (26.7% ± 9.3%, P < 0.01). The severity of histopathologic changes was significantly higher in the PRACT group than in the untreated group (P < 0.05). In addition, postoperative surveys demonstrated that the 5-year survival rate of GC patients in the PRACT group was significantly higher than that of patients in the untreated group (P < 0.01). CONCLUSION: Preoperative regional artery chemotherapy (PRACT) showed inhibitory action on the growth of GC cells mainly through inhibiting proliferation and inducing the apoptosis of tumor cells. PRACT can improve the prognosis of GC patients also. PMID:12046068

Cortisol Levels in Children With Diabetic Ketoacidosis Associated With New-Onset Type 1 Diabetes Mellitus.

PubMed

Williams, Kristen M; Fazzio, Pamela; Oberfield, Sharon E; Gallagher, Mary P; Aranoff, Gaya S

2017-02-01

There is little data documenting cortisol levels in children with diabetic ketoacidosis (DKA), despite the fact that untreated adrenal insufficiency (AI) could worsen the outcome of DKA. In this cross-sectional study, we assessed serum cortisol levels in 28 children with DKA and new onset type 1 diabetes mellitus evaluated at our center over a 5-year period. Average duration of diabetes-related symptoms was positively associated with age ( P = .002), and significantly lower hemoglobin A1c levels were observed in the youngest children. The mean cortisol level was 40.9 µg/dL, with a range of 7.8 to 119 µg/dL. Cortisol levels were found to be inversely associated with serum pH ( P = .007). There was no difference in the clinical outcome of the 4 patients who had cortisol levels less than 18 µg/dL. Overall, we did not find clinical or laboratory evidence of diminished cortisol reserve; however, the possibility of AI must be kept in mind when treating children with DKA.

Effects of Orthosiphon grandiflorus, Hibiscus sabdariffa and Phyllanthus amarus extracts on risk factors for urinary calcium oxalate stones in rats.

PubMed

Woottisin, Surachet; Hossain, Rayhan Zubair; Yachantha, Chatchai; Sriboonlue, Pote; Ogawa, Yoshihide; Saito, Seiichi

2011-01-01

We evaluated the antilithic effect of Orthosiphon grandiflorus, Hibiscus sabdariffa and Phyllanthus amarus extracts on known risk factors for calcium oxalate stones in rats. We divided 30 male Wistar rats into 5 equal groups. Controls were fed a standard diet and the remaining groups received a 3% glycolate diet for 4 weeks to induce hyperoxaluria. One glycolate fed group served as the untreated group and the others were given oral extracts of Orthosiphon grandiflorus, Hibiscus sabdariffa or Phyllanthus amarus at a dose of 3.5 mg daily. We collected 24-hour urine and blood samples. Kidneys were harvested for histological examination. We measured the renal tissue content of calcium and oxalate. The Hibiscus sabdariffa group showed significantly decreased serum oxalate and glycolate, and higher oxalate urinary excretion. The Phyllanthus amarus group showed significantly increased urinary citrate vs the untreated group. Histological examination revealed less CaOx crystal deposition in the kidneys of Hibiscus sabdariffa and Phyllanthus amarus treated rats than in untreated rats. Those rats also had significantly lower renal tissue calcium content than untreated rats. All parameters in the Orthosiphon grandiflorus treated group were comparable to those in the untreated group. Hibiscus sabdariffa and Phyllanthus amarus decreased calcium crystal deposition in the kidneys. The antilithic effect of Hibiscus sabdariffa may be related to decreased oxalate retention in the kidney and more excretion into urine while that of Phyllanthus amarus may depend on increased urinary citrate. In contrast, administering Orthosiphon grandiflorus had no antilithic effect. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prediabetes and Lifestyle Modification: Time to Prevent a Preventable Disease

PubMed Central

Tuso, Phillip

2014-01-01

More than 100 million Americans have prediabetes or diabetes. Prediabetes is a condition in which individuals have blood glucose levels higher than normal but not high enough to be classified as diabetes. People with prediabetes have an increased risk of Type 2 diabetes. An estimated 34% of adults have prediabetes. Prediabetes is now recognized as a reversible condition that increases an individual’s risk for development of diabetes. Lifestyle risk factors for prediabetes include overweight and physical inactivity. Increasing awareness and risk stratification of individuals with prediabetes may help physicians understand potential interventions that may help decrease the percentage of patients in their panels in whom diabetes develops. If untreated, 37% of the individuals with prediabetes may have diabetes in 4 years. Lifestyle intervention may decrease the percentage of prediabetic patients in whom diabetes develops to 20%. Long-term data also suggest that lifestyle intervention may decrease the risk of prediabetes progressing to diabetes for as long as 10 years. To prevent 1 case of diabetes during a 3-year period, 6.9 persons would have to participate in the lifestyle intervention program. In addition, recent data suggest that the difference in direct and indirect costs to care for a patient with prediabetes vs a patient with diabetes may be as much as $7000 per year. Investment in a diabetes prevention program now may have a substantial return on investment in the future and help prevent a preventable disease. PMID:25102521

Diabetes mellitus, part 1: physiology and complications.

PubMed

Nair, Muralitharan

In part 1 of this 2-part article the author discusses the physiology and complications of diabetes mellitus (DM), a chronic and progressive disorder which affects all ages of the population. The number of people diagnosed with diabetes is approximately 1.8 million and an estimated further 1 million are undiagnosed (Department of Health, 2005). In the UK, 1-2% of the population have diabetes and among school children this is approximately 2 in 1000 (Watkins, 1996). There are two main types of diabetes--type 1 and type 2 (Porth, 2005). The aetiology of DM is unknown; however, genetic and environmental factors have been linked to its development. Type 1 results from the loss of insulin production in the beta cells of the pancreas, and type 2 from a lack of serum insulin or poor uptake of glucose into the cells. Diabetes causes disease in many organs in the body, which may be life-threatening if untreated. Complications such as heart disease, vascular disease, renal failure and blindness (Roberts, 2005) have all been reported. The increased prevalence may be caused by factors such as environmental aspects, diet, an ageing population and low levels of physical exercise.

From menarche to menopause: the fertile life span of celiac women.

PubMed

Santonicola, Antonella; Iovino, Paola; Cappello, Carmelina; Capone, Pietro; Andreozzi, Paolo; Ciacci, Carolina

2011-10-01

We evaluated menopause-associated disorders and fertile life span in women with celiac disease (CD) under untreated conditions and after long-term treatment with a gluten-free diet. The participants were 33 women with CD after menopause (untreated CD group), 25 celiac women consuming a gluten-free diet at least 10 years before menopause (treated CD group), and 45 healthy volunteers (control group). The Menopause Rating Scale questionnaire was used to gather information on menopause-associated disorders. The International Physical Activity Questionnaire was used to acquire information on physical activity. Untreated celiac women had a shorter duration of fertile life span than did the control women because of an older age of menarche and a younger age of menopause (P < 0.01). The scores for hot flushes, muscle/joint problems, and irritability were higher in untreated celiac women than in the control women (higher by 49.4%, 121.4%, and 58.6%, respectively; P < 0.05). In comparison with untreated CD, long-lasting treatment of CD was not associated with a significant difference in the duration of fertile life span, but was only associated with a significant reduction in muscle/joint problems (a reduction of 47.1%; P < 0.05). Late menarche and early menopause causes a shorter fertile period in untreated celiac women compared with control women. A gluten-free diet that started at least 10 years before menopause prolongs the fertile life span of celiac women. The perception of intensity of hot flushes and irritability is more severe in untreated celiac women than in controls. Low physical exercise and/or poorer quality of life frequently reported by untreated celiac women might be the cause of reduced discomfort tolerance, thus increasing the subjective perception of menopausal symptoms.

Effective prevention of cardiovascular disease and diabetes-related events with atorvastatin in Japanese elderly patients with type 2 diabetes mellitus: adjusting for treatment changes using a marginal structural proportional hazards model and a rank-preserving structural failure time model.

PubMed

Shinozaki, Tomohiro; Matsuyama, Yutaka; Iimuro, Satoshi; Umegaki, Hiroyuki; Sakurai, Takashi; Araki, Atsushi; Ohashi, Yasuo; Ito, Hideki

2012-04-01

To assess the preventive effect of atorvastatin on cardiovascular disease and on diabetes-related events in elderly type 2 diabetic patients enrolled in the Japanese Elderly Diabetes Intervention Trial (J-EDIT). Data were obtained from 1173 patients aged 65-84 years who were enrolled in the J-EDIT. Patients were followed prospectively for 6 years to determine the effects of atorvastatin on serum cholesterol levels, and cardiovascular and diabetes-related events. Because the study protocol allowed atorvastatin to be prescribed according to the clinical needs of each patient, we regarded the J-EDIT data as if they came from a cohort study. We adjusted for clinical characteristics during the study as time-dependent confounders using two methods, inverse-probability-of-treatment (IPT) weighting and g-estimation method. The total follow-up period was 5310.8 person-years (5.7 years of median follow up), during which 202 patients received atorvastatin treatment. Atorvastatin was associated with moderate reductions in cholesterol levels: 24.2 mg/dL for total cholesterol, 22.9 mg/dL for low-density lipoprotein (LDL) cholesterol and 24.3 mg/dL for non-high-density lipoprotein cholesterol at the first post-treatment year. As a result, the proportion of patients who achieved targeted levels of LDL cholesterol clearly increased after atorvastatin treatment. Eight patients in 476.6 person-years among atorvastatin-treated and 113 untreated patients in 4721.4 person-years had cardiovascular events (the composite end-point of fatal/non-fatal myocardial infarction, angina pectoris, coronary intervention, and fatal/non-fatal cerebrovascular disease); hazard ratio (HR) = 0.48, 95% confidence interval (CI) = 0.19-1.16, P = 0.10, and HR = 0.32, 95% CI = 0.05-1.87, P = 0.21 from IPT weighting and g-estimation method, respectively. Furthermore, seven in 475.0 person-years among atorvastatin-treated and 149 untreated patients in 4682.4 person-years had diabetes-related events (the composite end-point of sudden death, renal failure death, death as a result of hyperglycemia or hypoglycemia, diabetic gangrene and congestive heart failure in addition to cardiovascular event); HR = 0.30, 95% CI = 0.12-0.77, P = 0.01, and HR = 0.40, 95% CI = 0.09-0.89, P = 0.03 from IPT weighting and g-estimation method, respectively. When cardiovascular events were further differentiated into coronary vascular and cerebrovascular events, atorvastatin especially decreased the cerebrovascular risk. The use of atorvastatin to lower cholesterol levels in elderly Japanese patients with type 2 diabetes mellitus appears to reduce the risk of cardiovascular and diabetes-related events. © 2012 Japan Geriatrics Society.

Social Resources That Preserve Functional Independence After Memory Loss

DTIC Science & Technology

2013-05-01

RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE May 2013 2 . REPORT TYPE Annual 3. DATES COVERED 20 April 2012 – 19 April 2013 4. TITLE...Even traditional vascular risk factors like high blood pressure, dyslipidemia, diabetes mellitus , smoking and atherosclerotic disease may be untreated...May 2013 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel Command Fort

Mangiferin induces islet regeneration in aged mice through regulating p16INK4a

PubMed Central

Liu, Yilong; Huai, Guoli; Sun, Minghan; Deng, Shaoping; Yang, Hongji; Tong, Rongsheng; Wang, Yi

2018-01-01

Previous studies by our group on mangiferin demonstrated that it exerts an antihyperglycemic effect through the regulation of cell cycle proteins in 3-month-old, partially pancreatectomized (PPx) mice. However, β-cell proliferation is known to become severely restricted with advanced age. Therefore, it is unknown whether mangiferin is able to reverse the diabetic condition and retain β-cell regeneration capability in aged mice. In the present study, 12-month-old C57BL/6J mice that had undergone PPx were subjected to mangiferin treatment (90 mg/kg) for 28 days. Mangiferin-treated aged mice exhibited decreased blood glucose levels and increased glucose tolerance, which was accompanied with higher serum insulin levels when compared with those in untreated PPx control mice. In addition, islet hyperplasia, elevated β-cell proliferation and reduced β-cell apoptosis were also identified in the mice that received mangiferin treatment. Further studies on the mRNA transcript and protein expression levels indicated comparatively increased levels of cyclins D1 and D2 and cyclin-dependent kinase 4 in mangiferin-treated mice, while the levels of p27Kip1 and p16INK4a were decreased relative to those in the untreated PPx controls. Of note, mangiferin treatment improved the proliferation rate of islet β-cells in adult mice overexpressing p16INK4a, suggesting that mangiferin induced β-cell proliferation via the regulation of p16INK4a. In addition, the mRNA transcription levels of critical genes associated with insulin secretion, including pancreatic and duodenal homeobox 1, glucose transporter 2 and glucokinase, were observed to be upregulated after mangiferin treatment. Taken together, it was indicated that mangiferin treatment significantly induced β-cell proliferation and inhibited β-cell apoptosis by regulating cell cycle checkpoint proteins. Furthermore, mangiferin was also demonstrated to regulate genes associated with insulin secretion. Collectively these, results suggest the therapeutic potential of mangiferin in the treatment of diabetes in aged individuals. PMID:29512742

Longitudinal studies of time-dependent changes in both bladder and erectile function after streptozotocin-induced diabetes in Fischer 344 male rats.

PubMed

Melman, Arnold; Zotova, Elena; Kim, Mimi; Arezzo, Joseph; Davies, Kelvin; DiSanto, Michael; Tar, Moses

2009-11-01

To provide sensitive physiological endpoints for the onset and long-term progression of deficits induced by diabetes mellitus (DM) in bladder and erectile function in male rats, and to evaluate parallel changes in urogenital and nerve function induced by hyperglycaemia over a protracted period as a model for chronic deficits in patients with diabetes. The study comprised in 877 male, 3-month-old, Fischer 344 rats; 666 were injected intraperitoneally with 35 mg/kg streptozotocin (STZ) and divided into insulin-treated and untreated diabetic groups. The rats were studied over 8 months and measurements made of both erectile and bladder function, as well as nerve conduction studies over the duration of the study. There was an early (first month) abnormality of both erectile and bladder function that persisted through the 8 months of the study. The erectile dysfunction was manifest as reduced intracavernous pressure/blood pressure ratio, and the bladder dysfunction as a persistent increase in detrusor overactivity with no detrusor decompensation. Insulin treatment prevented or modified the abnormality in each organ. Hyperglycaemia caused a progressive decrease in caudal nerve conduction velocity. The mean digital sensory and tibial motor nerve conduction velocity did not deteriorate over time. Correlation measurements of nerve and organ function were not consistent. The results of this extensive long-term study show early and profound effects of hyperglycaemia on the smooth muscle of the penis and bladder, that were persistent and stable in surviving rats over the 8 months. The physiological changes did not correlate well with neurological measurements of those organs. Significantly, diverse smooth-muscle cellular and subcellular events antedated the measured neurological manifestations of the hyperglycaemia by several months. Although autonomic diabetic neuropathy is a primary life-threatening complication of long-term diabetes in humans, this rat model of STZ-induced diabetes showed that the rapid onset of physiological manifestations was based on many molecular changes in the smooth muscle cells in this model of type 1 DM.

Cardiovascular risk factors and TIA characteristics in 19,872 Swedish TIA patients.

PubMed

Ström, J O; Tavosian, A; Appelros, P

2016-12-01

Transient ischemic attack (TIA) constitutes a major risk factor for stroke, making TIA patients an important group for secondary intervention. The aim of this study was to account for risk factor prevalence in TIA patients and analyze the association between TIA characteristics and risk factors. We included 20,871 TIA events in 19,872 patients who were registered in the Swedish Riksstroke registry during the years 2010 through 2012. Data from other Swedish registers were used for comparison. The following variables were analyzed: age, sex, diabetes mellitus, atrial fibrillation (AF), cigarette smoking, and antihypertensive treatment. Compared to the general population (based on data retrieved from Sweden's national public health survey 'Health on equal terms'), TIA patients more often had diabetes mellitus (prevalence ratio, PR = 2.3), AF without oral anticoagulants (OAC) (PR = 2.8), and AF on OAC (PR = 1.6). Blood pressure medication was less prevalent among TIA patients than in the general population (PR = 0.57). Increasing age was associated with longer attacks. The fact that diabetes mellitus, atrial fibrillation, and smoking are more common in TIA patients than in the general population suggests that these factors are risk factors for TIA, even if causal relations cannot be proven. The relation between increasing age and longer attacks possibly reflects an increased proportion of embolic TIAs, or impaired recovery ability. Our results also suggest a significant proportion of untreated hypertension cases in the population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of 1-Methylnicotinamide (MNA) on Exercise Capacity and Endothelial Response in Diabetic Mice.

PubMed

Przyborowski, Kamil; Wojewoda, Marta; Sitek, Barbara; Zakrzewska, Agnieszka; Kij, Agnieszka; Wandzel, Krystyna; Zoladz, Jerzy Andrzej; Chlopicki, Stefan

2015-01-01

1-Methylnicotinamide (MNA), which was initially considered to be a biologically inactive endogenous metabolite of nicotinamide, has emerged as an anti-thrombotic and anti-inflammatory agent with the capacity to release prostacyclin (PGI2). In the present study, we characterized the effects of MNA on exercise capacity and the endothelial response to exercise in diabetic mice. Eight-week-old db/db mice were untreated or treated with MNA for 4 weeks (100 mg·kg-1), and their exercise capacity as well as NO- and PGI2-dependent response to endurance running were subsequently assessed. MNA treatment of db/db mice resulted in four-fold and three-fold elevation of urine concentrations of MNA and its metabolites (Met-2PY + Met-4PY), respectively (P<0.01), but did not affect HbA1c concentration, fasting glucose concentration or lipid profile. However, insulin sensitivity was improved (P<0.01). In MNA-treated db/db mice, the time to fatigue for endurance exercise was significantly prolonged (P<0.05). Post-exercise Δ6-keto-PGF1α (difference between mean concentration in the sedentary and exercised groups) tended to increase, and post-exercise leukocytosis was substantially reduced in MNA-treated animals. In turn, the post-exercise fall in plasma concentration of nitrate was not affected by MNA. In conclusion, we demonstrated for the first time that MNA improves endurance exercise capacity in mice with diabetes, and may also decrease the cardiovascular risk of exercise.

Hypoglycaemic and Antioxidant Effects of Propolis of Chihuahua in a Model of Experimental Diabetes.

PubMed

Rivera-Yañez, Nelly; Rodriguez-Canales, Mario; Nieto-Yañez, Oscar; Jimenez-Estrada, Manuel; Ibarra-Barajas, Maximiliano; Canales-Martinez, M M; Rodriguez-Monroy, M A

2018-01-01

Propolis is a bee-collected natural product that has been proven to have various bioactivities. This study tested the effects of a Mexican propolis on streptozotocin-induced diabetes mellitus in a murine model. The results showed that an ethanolic extract of propolis of Chihuahua (EEPCh) significantly inhibited increases in blood glucose and the loss of body weight in diabetic mice. EEPCh increased plasma insulin levels in STZ-diabetic mice, whereas, in untreated diabetic mice, there was no detection of insulin. EEPCh had a high antioxidant capacity (SA 50 = 15.75  μ g/mL), which was directly related to the concentrations of total phenols (314 mg GAE/g of extract) and flavonoids (6.25 mg QE/g of extract). In addition, increased activities of the enzymes superoxide dismutase, catalase, and glutathione peroxidase were observed in diabetic mice treated with EEPCh. Compounds such as pinocembrin, quercetin, naringin, naringenin, kaempferol, acacetin, luteolin, and chrysin were identified by HPLC-MS analysis. This investigation demonstrated that propolis of Chihuahua possesses hypoglycaemic and antioxidant activities and can alleviate symptoms of diabetes mellitus in mice. These effects may be directly related to the chemical composition of propolis, as most of the compounds identified in propolis are reportedly active in terms of the different parameters evaluated in this work.

Hypoglycaemic and Antioxidant Effects of Propolis of Chihuahua in a Model of Experimental Diabetes

PubMed Central

Jimenez-Estrada, Manuel; Ibarra-Barajas, Maximiliano

2018-01-01

Propolis is a bee-collected natural product that has been proven to have various bioactivities. This study tested the effects of a Mexican propolis on streptozotocin-induced diabetes mellitus in a murine model. The results showed that an ethanolic extract of propolis of Chihuahua (EEPCh) significantly inhibited increases in blood glucose and the loss of body weight in diabetic mice. EEPCh increased plasma insulin levels in STZ-diabetic mice, whereas, in untreated diabetic mice, there was no detection of insulin. EEPCh had a high antioxidant capacity (SA50 = 15.75 μg/mL), which was directly related to the concentrations of total phenols (314 mg GAE/g of extract) and flavonoids (6.25 mg QE/g of extract). In addition, increased activities of the enzymes superoxide dismutase, catalase, and glutathione peroxidase were observed in diabetic mice treated with EEPCh. Compounds such as pinocembrin, quercetin, naringin, naringenin, kaempferol, acacetin, luteolin, and chrysin were identified by HPLC-MS analysis. This investigation demonstrated that propolis of Chihuahua possesses hypoglycaemic and antioxidant activities and can alleviate symptoms of diabetes mellitus in mice. These effects may be directly related to the chemical composition of propolis, as most of the compounds identified in propolis are reportedly active in terms of the different parameters evaluated in this work. PMID:29713363

The Role of Teleophthalmology in the Management of Diabetic Retinopathy.

PubMed

Salongcay, Recivall P; Silva, Paolo S

2018-01-01

The emergence of diabetes as a global epidemic is accompanied by the rise in diabetes‑related retinal complications. Diabetic retinopathy, if left undetected and untreated, can lead to severe visual impairment and affect an individual's productivity and quality of life. Globally, diabetic retinopathy remains one of the leading causes of visual loss in the working‑age population. Teleophthalmology for diabetic retinopathy is an innovative means of retinal evaluation that allows identification of eyes at risk for visual loss, thereby preserving vision and decreasing the overall burden to the health care system. Numerous studies worldwide have found teleophthalmology to be a reliable and cost‑efficient alternative to traditional clinical examinations. It has reduced barriers to access to specialized eye care in both rural and urban communities. In teleophthalmology applications for diabetic retinopathy, it is critical that standardized protocols in image acquisition and evaluation are used to ensure low image ungradable rates and maintain the quality of images taken. Innovative imaging technology such as ultrawide field imaging has the potential to provide significant benefit with integration into teleophthalmology programs. Teleophthalmology programs for diabetic retinopathy rely on a comprehensive and multidisciplinary approach with partnerships across specialties and health care professionals to attain wider acceptability and allow evidence‑based eye care to reach a much broader population. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

A novel chemically modified curcumin reduces inflammation-mediated connective tissue breakdown in a rat model of diabetes: periodontal and systemic effects.

PubMed

Elburki, M S; Moore, D D; Terezakis, N G; Zhang, Y; Lee, H-M; Johnson, F; Golub, L M

2017-04-01

Periodontal disease is the most common chronic inflammatory disease known to mankind (and the major cause of tooth loss in the adult population) and has also been linked to various systemic diseases, particularly diabetes mellitus. Based on the literature linking periodontal disease with diabetes in a "bidirectional manner", the objectives of the current study were to determine: (i) the effect of a model of periodontitis, complicated by diabetes, on mechanisms of tissue breakdown including bone loss; and (ii) the response of the combination of this local and systemic phenotype to a novel pleiotropic matrix metalloproteinase inhibitor, chemically modified curcumin (CMC) 2.24. Diabetes was induced in adult male rats by intravenous injection of streptozotocin (nondiabetic rats served as controls), and Escherichia coli endotoxin (lipopolysaccharide) was repeatedly injected into the gingiva to induce periodontitis. CMC 2.24 was administered by oral gavage (30 mg/kg) daily; untreated diabetic rats received vehicle alone. After 3 wk of treatment, the rats were killed, and gingiva, jaws, tibia and skin were collected. The maxillary jaws and tibia were dissected and radiographed. The gingival tissues of each experimental group (n = 6 rats/group) were pooled, extracted, partially purified and, together with individual skin samples, analyzed for matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography; MMP-8 was analyzed in gingival and skin tissue extracts, and in serum, by western blotting. The levels of three bone-resorptive cytokines [interleukin (IL)-1β, IL-6 and tumor necrosis factor-α], were measured in gingival tissue extracts and serum by ELISA. Systemic administration of CMC 2.24 to diabetic rats with endotoxin-induced periodontitis significantly inhibited alveolar bone loss and attenuated the severity of local and systemic inflammation. Moreover, this novel tri-ketonic phenylaminocarbonyl curcumin (CMC 2.24) appeared to reduce the pathologically excessive levels of inducible MMPs to near-normal levels, but appeared to have no significant effect on the constitutive MMPs required for physiologic connective tissue turnover. In addition to the beneficial effects on periodontal disease, induced both locally and systemically, CMC 2.24 also favorably affected extra-oral connective tissues, skin and skeletal bone. This study supports our hypothesis that CMC 2.24 is a potential therapeutic pleiotropic MMP inhibitor, with both intracellular and extracellular effects, which reduces local and systemic inflammation and prevents hyperglycemia- and bacteria-induced connective tissue destruction. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of the effects of glimepiride (Amaryl) and repaglinide (novoNorm) on atherosclerosis progression in high cholesterol-fed male rabbits.

PubMed

Hadi, Najah R; Al-Amran, Fadhil; Hussein, Mohammad A A; Rezeg, Fadhil A

2012-01-01

Atherosclerosis is an inflammatory disease of the blood vessel wall, characterized in early stages by endothelial dysfunction, recruitment and activation of monocyte/macrophages. Glimepiride is one of the third generation sulphonylurea drugs, useful for control of diabetes mellitus type two and it may exert anti inflammatory activity, by induction of nitric oxide production or through selective suppression of the cyclooxygenase pathway. Repaglinide is a new hypoglycemic agent, and a member of the carbamoylmethyl benzoic acid family. Some results from the literature demonstrate that repaglinide has favorable effects on the parameters of antioxidative balance. The objective of the present study was to assess the effect of glimepiride and repaglinide on atherosclerosis via interfering with the inflammatory and oxidative pathways. Twenty four local domestic male rabbits were involved in this study. The animals were randomly divided into four groups; Group I rabbits fed normal chow (oxiod) diet for 10 weeks. Group II rabbits were fed with 1% cholesterol enriched diet. Group III rabbits were fed with 1% cholesterol enriched diet together with Glimepiride (0.1 mg/kg once daily before morning feed). Group IV rabbits were fed with 1% cholesterol enriched diet together with Repaglinide (0.3 mg/kg once daily before morning feed). Blood samples were collected before (0 time) and every two weeks of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), high sensitive C - reactive protein (hsCRP), Interleukin - 6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α) levels. At the end of 10 weeks, the aorta was removed for measurement of aortic Malondialdehyde (MDA), reduced glutathione (GSH) and aortic intimal thickness. Glimepiride and repaglinide treatment did show significant effect on lipid parameters compared with induced untreated group (P < 0.05). Also, they significantly reduced the elevation in hsCRP, IL-6, TNF-α, aortic MDA and aortic intimal thickness compared with induced untreated group (P < 0.05), and they helped to restore the aortic GSH levels (P < 0.05). Glimepiride and repaglinide may reduce atherosclerosis progression in hypercholesterolemic rabbits by interfering with the inflammatory and oxidative pathways without affecting lipid parameters.

Sleep-disordered Breathing in Hispanic/Latino Individuals of Diverse Backgrounds. The Hispanic Community Health Study/Study of Latinos

PubMed Central

Sotres-Alvarez, Daniela; Loredo, Jose; Hall, Martica; Patel, Sanjay R.; Ramos, Alberto; Shah, Neomi; Ries, Andrew; Arens, Raanan; Barnhart, Janice; Youngblood, Marston; Zee, Phyllis; Daviglus, Martha L.

2014-01-01

Rationale: Hispanic/Latino populations have a high prevalence of cardiovascular risk factors and may be at risk for sleep-disordered breathing (SDB). An understanding of SDB among these populations is needed given evidence that SDB increases cardiovascular risk. Objectives: To quantify SDB prevalence in the U.S. Hispanic/Latino population and its association with symptoms, risk factors, diabetes, and hypertension; and to explore variation by sex and Hispanic/Latino background. Methods: Cross-sectional analysis from the baseline examination of the Hispanic Community Health Study/Study of Latinos. Measurements and Main Results: The apnea–hypopnea index (AHI) was derived from standardized sleep tests; diabetes and hypertension were based on measurement and history. The sample of 14,440 individuals had an age-adjusted prevalence of minimal SDB (AHI ≥ 5), moderate SDB (AHI ≥ 15), and severe SDB (AHI ≥ 30) of 25.8, 9.8, and 3.9%, respectively. Only 1.3% of participants reported a sleep apnea diagnosis. Moderate SDB was associated with being male (adjusted odds ratio, 2.7; 95% confidence interval, 2.3–3.1), obese (16.8; 11.6–24.4), and older. SDB was associated with an increased adjusted odds of impaired glucose tolerance (1.7; 1.3–2.1), diabetes (2.3; 1.8–2.9), and hypertension. The association with hypertension varied across background groups with the strongest associations among individuals of Puerto Rican and Central American background. Conclusions: SDB is prevalent in U.S. Latinos but rarely associated with a clinical diagnosis. Associations with diabetes and hypertension suggest a large burden of disease may be attributed to untreated SDB, supporting the development and evaluation of culturally relevant detection and treatment approaches. PMID:24392863

Modest Salt Reduction Lowers Blood Pressure and Albumin Excretion in Impaired Glucose Tolerance and Type 2 Diabetes Mellitus: A Randomized Double-Blind Trial.

PubMed

Suckling, Rebecca J; He, Feng J; Markandu, Nirmala D; MacGregor, Graham A

2016-06-01

The role of salt restriction in patients with impaired glucose tolerance and diabetes mellitus is controversial, with a lack of well controlled, longer term, modest salt reduction trials in this group of patients, in spite of the marked increase in cardiovascular risk. We carried out a 12-week randomized double-blind, crossover trial of salt restriction with salt or placebo tablets, each for 6 weeks, in 46 individuals with diet-controlled type 2 diabetes mellitus or impaired glucose tolerance and untreated normal or high normal blood pressure (BP). From salt to placebo, 24-hour urinary sodium was reduced by 49±9 mmol (2.9 g salt). This reduction in salt intake led to fall in clinic BP from 136/81±2/1 mm Hg to 131/80±2/1 mm Hg, (systolic BP; P<0.01). Mean ambulatory 24-hour BP was reduced by 3/2±1/1 mm Hg (systolic BP, P<0.01 and diastolic BP, P<0.05), and albumin/creatinine ratio was reduced from 0.73 mg/mmol (0.5-1.5) to 0.64 mg/mmol (0.3-1.1; P<0.05). There was no significant change in fasting glucose, hemoglobin A1c, or insulin sensitivity. These results demonstrate that a modest reduction in salt intake, to approximately the amount recommended in public health guidelines, leads to significant and clinically relevant falls in BP in individuals who are early on in the progression of diabetes mellitus with normal or mildly raised BP. The reduction in urinary albumin excretion may carry additional benefits in reducing cardiovascular disease above the effects on BP. © 2016 American Heart Association, Inc.

Tension cost correlates with mechanical and biochemical parameters in different myocardial contractility conditions

PubMed Central

Moreira, Cleci M.; Meira, Eduardo F.; Vestena, Luis; Stefanon, Ivanita; Vassallo, Dalton V.; Padilha, Alessandra S.

2012-01-01

OBJECTIVES: Tension cost, the ratio of myosin ATPase activity to tension, reflects the economy of tension development in the myocardium. To evaluate the mechanical advantage represented by the tension cost, we studied papillary muscle contractility and the activity of myosin ATPase in the left ventricles in normal and pathophysiological conditions. METHODS: Experimental protocols were performed using rat left ventricles from: (1) streptozotocin-induced diabetic and control Wistar rats; (2) N-nitro-L-arginine methyl ester (L-NAME) hypertensive and untreated Wistar rats; (3) deoxycorticosterone acetate (DOCA) salt-treated, nephrectomized and salt- and DOCA-treated rats; (4) spontaneous hypertensive rats (SHR) and Wistar Kyoto (WKY) rats; (5) rats with myocardial infarction and sham-operated rats. The isometric force, tetanic tension, and the activity of myosin ATPase were measured. RESULTS: The results obtained from infarcted, diabetic, and deoxycorticosterone acetate-salt-treated rats showed reductions in twitch and tetanic tension compared to the control and sham-operated groups. Twitch and tetanic tension increased in the N-nitro-L-arginine methyl ester-treated rats compared with the Wistar rats. Myosin ATPase activity was depressed in the infarcted, diabetic, and deoxycorticosterone acetate salt-treated rats compared with control and sham-operated rats and was increased in N-nitro-L-arginine methyl ester-treated rats. These parameters did not differ between SHR and WKY rats. In the studied conditions (e.g., post-myocardial infarction, deoxycorticosterone acetate salt-induced hypertension, chronic N-nitro-L-arginine methyl ester treatment, and streptozotocin-induced diabetes), a positive correlation between force or plateau tetanic tension and myosin ATPase activity was observed. CONCLUSION: Our results suggest that the myocardium adapts to force generation by increasing or reducing the tension cost to maintain myocardial contractility with a better mechanical advantage. PMID:22666794

Follow-up study of children whose mothers were treated with transcranial magnetic stimulation during pregnancy: preliminary results.

PubMed

Eryılmaz, Gul; Sayar, Gökben Hızlı; Özten, Eylem; Gül, Işıl Göğcegöz; Yorbik, Özgür; Işiten, Nuket; Bağcı, Eda

2015-06-01

The purpose of this study is to determine the impact of repetitive transcranial stimulation (rTMS) treatment during pregnancy on neurodevelopment of children. Women who were treated with rTMS during pregnancy and delivered liveborn children between 2008 and 2013 were selected. A control group consisted of children whose mothers had a history of untreated depression during their pregnancy (N = 26). Early developmental characteristics of all the children in the study were evaluated, and their developmental levels were determined using the Ankara Developmental Screening Inventory. The mean age of the children in the rTMS treatment group was 32.4 months (range 16-64 months), and that of the untreated group was 29.04 (range 14-63 months). Jaundice (N = 2) and febrile convulsion (N = 1) were the reported medical conditions in the children of the rTMS-treated group; jaundice (N = 3) and low birth weight (N = 1) were reported in the untreated group. In the rTMS group, mothers' perception of delay in language development was observed, but there were not any statistically significant differences in the prevalence rate compared with the untreated group (OR = 0.38; 95% CI 0.0860-1.6580). Our results suggest that rTMS exposure during pregnancy is not associated with poorer cognitive or motor development outcomes in children aged 18-62 months. Although language development as reported by the mothers was found to be poorer than expected in the rTMS-treated group, the delay was found to be similar to the language delay observed in offspring of untreated mothers, as reported in previous studies of prenatal depression treated with selective serotonin reuptake inhibitors. © 2014 International Neuromodulation Society.

Increased gluconeogenesis in youth with newly diagnosed type 2 diabetes.

PubMed

Chung, Stephanie T; Hsia, Daniel S; Chacko, Shaji K; Rodriguez, Luisa M; Haymond, Morey W

2015-03-01

The role of increased gluconeogenesis as an important contributor to fasting hyperglycaemia at diabetes onset is not known. We evaluated the contribution of gluconeogenesis and glycogenolysis to fasting hyperglycaemia in newly diagnosed youths with type 2 diabetes following an overnight fast. Basal rates (μmol kg(FFM) (-1) min(-1)) of gluconeogenesis ((2)H2O), glycogenolysis and glycerol production ([(2)H5] glycerol) were measured in 18 adolescents (nine treatment naive diabetic and nine normal-glucose-tolerant obese adolescents). Type 2 diabetes was associated with higher gluconeogenesis (9.2 ± 0.6 vs 7.0 ± 0.3 μmol kg(FFM) (-1) min(-1), p < 0.01), plasma fasting glucose (7.0 ± 0.6 vs 5.0 ± 0.2 mmol/l, p = 0.004) and insulin (300 ± 30 vs 126 ± 31 pmol/l, p = 0.001). Glucose production and glycogenolysis were similar between the groups (15.4 ± 0.3 vs 12.4 ± 1.4 μmol kg(FFM) (-1) min(-1), p = 0.06; and 6.2 ± 0.8 vs 5.3 ± 0.7 μmol kg(FFM) (-1) min(-1), p = 0.5, respectively). After controlling for differences in adiposity, gluconeogenesis, glycogenolysis and glucose production were higher in diabetic youth (p ≤ 0.02). Glycerol concentration (84 ± 6 vs 57 ± 6 μmol/l, p = 0.01) and glycerol production (5.0 ± 0.3 vs 3.6 ± 0.5 μmol kg(FFM) (-1) min(-1), p = 0.03) were 40% higher in youth with diabetes. The increased glycerol production could account for only ~1/3 of substrate needed for the increased gluconeogenesis in diabetic youth. Increased gluconeogenesis was a major contributor to fasting hyperglycaemia and hepatic insulin resistance in newly diagnosed untreated adolescents and was an early pathological feature of type 2 diabetes. Increased glycerol availability may represent a significant source of new carbon substrates for increased gluconeogenesis but would not account for all the carbons required to sustain the increased rates.

Prevention of Arterial Stiffening by Using Low-Dose Atorvastatin in Diabetes Is Associated with Decreased Malondialdehyde

PubMed Central

Wang, Chih-Hsien; Chang, Ru-Wen; Ko, Ya-Hui; Tsai, Pi-Ru; Wang, Shoei-Shen; Chen, Yih-Sharng; Ko, Wen-Je; Chang, Chun-Yi; Young, Tai-Horng; Chang, Kuo-Chu

2014-01-01

Introduction Without affecting the lipid profile, a low-dose treatment with atorvastatin contributes to the reduction of oxidative stress, inflammation, and adverse cardiovascular events in diabetes. In this study, we investigated whether low-dose atorvastatin exerts any beneficial effect on vascular dynamics in streptozotocin (STZ)-induced diabetes in male Wistar rats. Methods Diabetes was induced using a single tail-vein injection of STZ at 55 mg kg−1. The diabetic rats were treated daily with atorvastatin (10 mg kg−1 by oral gavage) for 6 weeks. They were also compared with untreated age-matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. A thiobarbituric acid reactive substances measurement was used to estimate the malondialdehyde content. Results The high plasma level of total cholesterol in the diabetic rats did not change in response to this low-dose treatment with atorvastatin. Atorvastatin resulted in a significant increase of 15.4% in wave transit time and a decrease of 33.5% in wave reflection factor, suggesting that atorvastatin may attenuate the diabetes-induced deterioration in systolic loads imposed on the heart. This was in parallel with its lowering of malondialdehyde content in plasma and aortic walls in diabetes. Atorvastatin therapy also prevented the diabetes-related cardiac hypertrophy, as evidenced by the diminished ratio of left ventricular weight to body weight. Conclusion These findings indicate that low-dose atorvastatin might protect diabetic vasculature against diabetes-associated deterioration in aorta stiffness and cardiac hypertrophy, possibly through its decrease of lipid oxidation-derived malondialdehyde. PMID:24595201

Conventional fascial technique versus mesh repair for advanced pelvic organ prolapse: Analysis of recurrences in treated and untreated compartments.

PubMed

Damiani, G R; Riva, D; Pellegrino, A; Gaetani, M; Tafuri, S; Turoli, D; Croce, P; Loverro, G

2016-01-01

117 women with severe pelvic organ prolapse (POP; stage > 2) were enrolled to elucidate a 24-month outcome of POP surgery, using conventional or mesh repair with 3 techniques. 59 patients underwent conventional repair and 58 underwent mesh repair. Two types of mesh were used: a trocar-guided transobturator polypropylene (Avaulta, Bard Inc.) and a porcine dermis mesh (Pelvisoft, Bard Inc.). Women with recurrences, who underwent previous unsuccessful conventional repair, were randomised. Primary outcome was the evaluation of anatomic failures (prolapse stage > 1) in treated and untreated compartments. Anatomic failure was observed in 11 of 58 patients (19%; CI 8.9-29) in the mesh group and in 16 of 59 patients (27.1%; p value = 0.3) in the conventional group. 9 of 11 failures in the mesh group (15.5%; CI 6.2-24.8) were observed in the untreated compartment (de novo recurrences), 14.3% in Pelvisoft and 16.7% in Avaulta arm, while only 1 recurrence in the untreated compartment (1.7%) was observed in the conventional group (odds ratio 10.6, p = 0.03).

[Effects of Huoxue Bushen Mixture on skin blood vessel neogenesis and vascular endothelial growth factor expression in hair follicle of C57BL/6 mice].

PubMed

Gao, Shang-pu; Huang, Lan; Yang, Xin-wei

2007-03-01

To investigate the possible stimulating mechanism of Huoxue Bushen Mixture (HXBSM), a traditional Chinese compound medicine, on hair growth of mice via measuring the variance of skin blood vessel neogenesis and vascular endothelial growth factor (VEGF) expression in the hair follicle. Hot rosin and paraffin mixture depilation were used to induce C57BL/6 mice hair follicle to enter from telogen into anagen. Ninety C57BL/6 mice were divided into 3 groups randomly: HXBSM group, Yangxue Shengfa Capsule (YXSFC, another traditional Chinese compound medicine) group and untreated group. The mice were fed with corresponding drugs after modeling. The hair growth of the mice was observed every day. Every ten mice out of each group were executed respectively at day 4, 11 and day 17. Skin blood vessel neogenesis was counted through pathological section and VEGF expression in the hair follicle was measured via immunohistochemical method. The number of local blood vessel neogenisis in the HXBSM group observed was larger than that in the untreated group at day 4 (P<0.05); and evidently larger than that in the YXSFC group and the untreated group at day 11 (P<0.05). The expression of VEGF in the hair follicle was distinctively higher than that in the YXSFC group and the untreated group at day 11 and day 17 (P<0.05). HXBSM up-regulates VEGF expression to accelerate blood vessel neogenesis and hair growth.

Incidence and prevalence of type 2 diabetes mellitus with HIV infection in Africa: a systematic review and meta-analysis.

PubMed

Prioreschi, A; Munthali, R J; Soepnel, L; Goldstein, J A; Micklesfield, L K; Aronoff, D M; Norris, S A

2017-03-29

This systematic review aims to investigate the incidence and prevalence of type 2 diabetes mellitus (T2DM) in patients with HIV infection in African populations. Only studies reporting data from Africa were included. A systematic search was conducted using four databases for articles referring to HIV infection and antiretroviral therapy, and T2DM in Africa. Articles were excluded if they reported data on children, animals or type 1 diabetes exclusively. Incidence of T2DM and prevalence of T2DM. Risk ratios were generated for pooled data using random effects models. Bias was assessed using an adapted Cochrane Collaboration bias assessment tool. Of 1056 references that were screened, only 20 were selected for inclusion. Seven reported the incidence of T2DM in patients with HIV infection, eight reported the prevalence of T2DM in HIV-infected versus uninfected individuals and five reported prevalence of T2DM in HIV-treated versus untreated patients. Incidence rates ranged from 4 to 59 per 1000 person years. Meta-analysis showed no significant differences between T2DM prevalence in HIV-infected individuals versus uninfected individuals (risk ratio (RR) =1.61, 95% CI 0.62 to 4.21, p=0.33), or between HIV-treated patients versus untreated patients (RR=1.38, 95% CI 0.66 to 2.87, p=0.39), and heterogeneity was high in both meta-analyses (I 2 =87% and 52%, respectively). Meta-analysis showed no association between T2DM prevalence and HIV infection or antiretroviral therapy; however, these results are limited by the high heterogeneity of the included studies and moderate-to-high risk of bias, as well as, the small number of studies included. There is a need for well-designed prospective longitudinal studies with larger population sizes to better assess incidence and prevalence of T2DM in African patients with HIV. Furthermore, screening for T2DM using gold standard methods in this population is necessary. PROSPERO42016038689. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Antioxidant N-acetylcysteine restores systemic nitric oxide availability and corrects depressions in arterial blood pressure and heart rate in diabetic rats.

PubMed

Xia, Zhengyuan; Nagareddy, Prabhakara R; Guo, Zhixin; Zhang, Wei; McNeill, John H

2006-02-01

Increased oxidative stress and reduced nitric oxide (NO) bioactivity are key features of diabetes mellitus that eventually result in cardiovascular abnormalities. We assessed whether N-acetylcysteine (NAC), an antioxidant and glutathione precursor, could prevent the hyperglycaemia induced increase in oxidative stress, restore NO availability and prevent depression of arterial blood pressure and heart rate in vivo in experimental diabetes. Control (C) and streptozotocin-induced diabetic (D) rats were treated or not treated with NAC in drinking water for 8 weeks, initiated 1 week after induction of diabetes. At termination, plasma levels of free 15-F2t-isoprostane, a specific marker of oxygen free radical induced lipid peroxidation, was increased while the plasma total antioxidant concentration was decreased in untreated diabetic rats as compared to control rats (P<0.05). This was accompanied by a significant reduction of plasma levels of nitrate and nitrite, stable metabolites of NO, (P<0.05, D vs. C) and a reduced endothelial NO synthase protein expression in the heart and in aortic and mesenteric artery tissues. Systolic, diastolic and mean arterial blood pressures (SBP, DBP and MAP) and heart rate (HR) were reduced in diabetic rats (P<0.05 vs. C) and NAC normalised the changes that occurred in the diabetic rats. The protective effects may be attributable to restoration of NO bioavailability in the circulation.

Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide

PubMed Central

Harmayani, Eni; Sunarti

2015-01-01

The study aimed to evaluate the effect of kefir combination from goat milk and soy milk on lipid profile, plasma glucose, glutathione peroxidase (GPx) activity and the improvement of pancreatic β-cell in diabetic rats. Male rats were divided into five treatments: normal control, diabetic control, goat milk kefir, combination of goat milk-soy milk kefir and soy milk kefir. All rats were induced by streptooztocin-nicotinamide (STZ-NA), except for normal control. After 35 d experiment, the rats were sampled for blood, sacrificed and sampled for pancreatic tissues. Results showed that diabetic rats fed kefir combination had higher (p<0.05) triglyceride than the rats fed goat milk or soy milk kefir. Decreasing of plasma glucose in diabetic rats fed kefir combination was higher (p<0.05) than rats fed goat millk kefir. The activity of GPx in diabetic rats fed three kinds of kefir were higher (p<0.01) than untreated diabetic rats. The average number of Langerhans and β-cells in diabetic rats fed kefir combination was the same as the normal control, but it was higher than diabetic control. It was concluded that kefir combination can be used as antidiabetic through maintaining in serum triglyceride, decreasing in plasma glucose, increasing in GPx activity and improving in pancreatic β-cells. PMID:26877646

Bone Mineral Density in Adolescent Females Using Injectable or Oral Contraceptives: A 24 Month Prospective Study

PubMed Central

Cromer, Barbara A.; Bonny, Andrea E.; Stager, Margaret; Lazebnik, Rina; Rome, Ellen; Ziegler, Julie; Camlin-Shingler, Kelly; Secic, Michelle

2008-01-01

Study Objective To determine whether bone mineral density (BMD) is lower in hormonal contraceptive users than that in an untreated, comparison group. Design Observational, prospective cohort; duration: 24 months. Setting Adolescent clinics in a midwestern, metropolitan setting. Patients 433 postmenarcheal girls, aged 12–18 years, on depot medroxyprogesterone acetate (DMPA) [n=58], oral contraceptives (OC) [n=187], or untreated (n=188). Intervention DMPA and OC containing 100 mcg levonorgestrel and 20 mcg ethinyl estradiol. Main Outcome Measure BMD measurements at spine and femoral neck were obtained with dual x-ray absorptiometry (DXA) at baseline and 6-month intervals. Results Over 24 months, mean percent change in spine BMD was: DMPA −1.5%, OC +4.2%, and untreated +6.3%. Mean percent change in femoral neck BMD was: DMPA −5.2%, OC +3.0%, untreated +3.8%. Statistical significance was found between the DMPA group and other two groups (p<.001). In the DMPA group, mean percent change in spine BMD over the first 12 months was −1.4%; the rate of change slowed to −0.1% over the second 12 months. No bone density loss reached the level of osteopenia. Conclusions Adolescent girls receiving DMPA had significant loss in BMD compared with bone gain in the OC and untreated group. However, its clinical significance is mitigated by slowed loss after the first year of DMPA use and general maintenance of bone density values within the normal range. PMID:18222431

Evaluation of the Curative Effect of Umbilical Cord Mesenchymal Stem Cell Therapy for Knee Arthritis in Dogs Using Imaging Technology.

PubMed

Zhang, Bei-Ying; Wang, Bing-Yun; Li, Shao-Chuan; Luo, Dong-Zhang; Zhan, Xiaoshu; Chen, Sheng-Feng; Chen, Zhi-Sheng; Liu, Can-Ying; Ji, Hui-Qin; Bai, Yin-Shan; Li, Dong-Sheng; He, Yang

2018-01-01

The aim of this study was to assess the efficacy of canine umbilical cord mesenchymal stem cells (UC-MSCs) on the treatment of knee osteoarthritis in dogs. Eight dogs were evenly assigned to two groups. The canine model of knee osteoarthritis was established by surgical manipulation of knee articular cartilage on these eight dogs. UC-MSCs were isolated from umbilical cord Wharton's jelly by 0.1% type collagenase I and identified by immunofluorescence staining and adipogenic and osteogenic differentiation in vitro . A suspension of allogeneic UC-MSCs (1 × 10 6 ) and an equal amount of physiological saline was injected into the cavitas articularis in the treated and untreated control groups, respectively, on days 1 and 3 posttreatment. The structure of the canine knee joint was observed by magnetic resonance imaging (MRI), B-mode ultrasonography, and X-ray imaging at the 3rd, 7th, 14th, and 28th days after treatment. Concurrently, the levels of IL-6, IL-7, and TNF- α in the blood of the examined dogs were measured. Moreover, the recovery of cartilage and patella surface in the treated group and untreated group was compared using a scanning electron microscope (SEM) after a 35-day treatment. Results revealed that the isolated cells were UC-MSCs, because they were positive for CD44 and negative for CD34 surface markers, and the cells were differentiated into adipocytes and osteoblasts. Imaging technology showed that as treatment time increased, the high signal in the MRI T2-weighted images decreased, the echo-free space in B ultrasonography images disappeared basically, and the continuous linear hypoechoic region at the trochlear sulcus thickened. On X-ray images, the serrate defect at the ventral cortex of the patella improved, and the low-density gap of the ventral patella and trochlear crest gradually increased in the treated group. On the contrary, the high signal in the MRI T2-weighted images and the echo-free space in B ultrasonography images still increased after a 14-day treatment in the untreated control group, and the linear hypoechoic region was discontinuous. On the X-ray images, there was no improvement in the serrate defect of the ventral cortex of the patella. Results for inflammatory factors showed that the blood levels of IL-6, IL-7, and TNF- α of the untreated control group were significantly higher than those of the treated group ( P < 0.05) 7-14 days posttreatment. The result of SEM showed that the cartilage neogenesis in the treated group had visible neonatal tissue and more irregular arrangement of new tissue fibers than that of the untreated control group. Furthermore, more vacuoles but without collagen fibers were observed in the cartilage of the untreated control group, and the thickness of the neogenetic cartilage in the treated group (65.13 ± 5.29, 65.30 ± 5.83) and the untreated control group (34.27 ± 5.42) showed a significant difference ( P < 0.01). Significantly higher improvement in cartilage neogenesis and recovery was observed in the treated group compared to the untreated control group. The joint fluid and the inflammatory response in the treated group decreased. Moreover, improved recovery in the neogenetic cartilage, damaged skin fascia, and muscle tissue around the joints was more significant in the treated group than in the untreated control group. In conclusion, canine UC-MSCs promote the repair of cartilage and patella injury in osteoarthritis, improve the healing of the surrounding tissues, and reduce the inflammatory response.

Evaluation of the Curative Effect of Umbilical Cord Mesenchymal Stem Cell Therapy for Knee Arthritis in Dogs Using Imaging Technology

PubMed Central

Zhang, Bei-ying; Li, Shao-chuan; Luo, Dong-zhang; Zhan, Xiaoshu; Chen, Sheng-feng; Chen, Zhi-sheng; Liu, Can-ying; Ji, Hui-qin; Bai, Yin-shan; Li, Dong-sheng; He, Yang

2018-01-01

Objective The aim of this study was to assess the efficacy of canine umbilical cord mesenchymal stem cells (UC-MSCs) on the treatment of knee osteoarthritis in dogs. Methods Eight dogs were evenly assigned to two groups. The canine model of knee osteoarthritis was established by surgical manipulation of knee articular cartilage on these eight dogs. UC-MSCs were isolated from umbilical cord Wharton's jelly by 0.1% type collagenase I and identified by immunofluorescence staining and adipogenic and osteogenic differentiation in vitro. A suspension of allogeneic UC-MSCs (1 × 106) and an equal amount of physiological saline was injected into the cavitas articularis in the treated and untreated control groups, respectively, on days 1 and 3 posttreatment. The structure of the canine knee joint was observed by magnetic resonance imaging (MRI), B-mode ultrasonography, and X-ray imaging at the 3rd, 7th, 14th, and 28th days after treatment. Concurrently, the levels of IL-6, IL-7, and TNF-α in the blood of the examined dogs were measured. Moreover, the recovery of cartilage and patella surface in the treated group and untreated group was compared using a scanning electron microscope (SEM) after a 35-day treatment. Results Results revealed that the isolated cells were UC-MSCs, because they were positive for CD44 and negative for CD34 surface markers, and the cells were differentiated into adipocytes and osteoblasts. Imaging technology showed that as treatment time increased, the high signal in the MRI T2-weighted images decreased, the echo-free space in B ultrasonography images disappeared basically, and the continuous linear hypoechoic region at the trochlear sulcus thickened. On X-ray images, the serrate defect at the ventral cortex of the patella improved, and the low-density gap of the ventral patella and trochlear crest gradually increased in the treated group. On the contrary, the high signal in the MRI T2-weighted images and the echo-free space in B ultrasonography images still increased after a 14-day treatment in the untreated control group, and the linear hypoechoic region was discontinuous. On the X-ray images, there was no improvement in the serrate defect of the ventral cortex of the patella. Results for inflammatory factors showed that the blood levels of IL-6, IL-7, and TNF-α of the untreated control group were significantly higher than those of the treated group (P < 0.05) 7–14 days posttreatment. The result of SEM showed that the cartilage neogenesis in the treated group had visible neonatal tissue and more irregular arrangement of new tissue fibers than that of the untreated control group. Furthermore, more vacuoles but without collagen fibers were observed in the cartilage of the untreated control group, and the thickness of the neogenetic cartilage in the treated group (65.13 ± 5.29, 65.30 ± 5.83) and the untreated control group (34.27 ± 5.42) showed a significant difference (P < 0.01). Conclusion Significantly higher improvement in cartilage neogenesis and recovery was observed in the treated group compared to the untreated control group. The joint fluid and the inflammatory response in the treated group decreased. Moreover, improved recovery in the neogenetic cartilage, damaged skin fascia, and muscle tissue around the joints was more significant in the treated group than in the untreated control group. In conclusion, canine UC-MSCs promote the repair of cartilage and patella injury in osteoarthritis, improve the healing of the surrounding tissues, and reduce the inflammatory response. PMID:29861739

Sulfasalazine Blocks the Development of Tactile Allodynia in Diabetic Rats

PubMed Central

Berti-Mattera, Liliana N.; Kern, Timothy S.; Siegel, Ruth E.; Nemet, Ina; Mitchell, Rochanda

2008-01-01

OBJECTIVE—Diabetic neuropathy is manifested either by loss of nociception (painless syndrome) or by mechanical hyperalgesia and tactile allodynia (pain in response to nonpainful stimuli). While therapies with vasodilators or neurotrophins reverse some functional and metabolic abnormalities in diabetic nerves, they only partially ameliorate neuropathic pain. The reported link between nociception and targets of the anti-inflammatory drug sulfasalazine prompted us to investigate its effect on neuropathic pain in diabetes. RESEARCH DESIGN AND METHODS—We examined the effects of sulfasalazine, salicylates, and the poly(ADP-ribose) polymerase-1 inhibitor PJ34 on altered nociception in streptozotocin-induced diabetic rats. We also evaluated the levels of sulfasalazine targets in sciatic nerves and dorsal root ganglia (DRG) of treated animals. Finally, we analyzed the development of tactile allodynia in diabetic mice lacking expression of the sulfasalazine target nuclear factor-κB (NF-κB) p50. RESULTS—Sulfasalazine completely blocked the development of tactile allodynia in diabetic rats, whereas relatively minor effects were observed with other salicylates and PJ34. Along with the behavioral findings, sciatic nerves and DRG from sulfasalazine-treated diabetic rats displayed a decrease in NF-κB p50 expression compared with untreated diabetic animals. Importantly, the absence of tactile allodynia in diabetic NF-κB p50−/− mice supported a role for NF-κB in diabetic neuropathy. Sulfasalazine treatment also increased inosine levels in sciatic nerves of diabetic rats. CONCLUSIONS—The complete inhibition of tactile allodynia in experimental diabetes by sulfasalazine may stem from its ability to regulate both NF-κB and inosine. Sulfasalazine might be useful in the treatment of nociceptive alterations in diabetic patients. PMID:18633115

Suppression of Type-II Diabetes with Dyslipidemia and Nephropathy by Peels of Musa cavendish Fruit.

PubMed

Navghare, Vijay; Dhawale, Shashikant

2016-10-01

Musa cavendish, peels has local and traditional use to promote wound healing, hyperglycemia, ulceration etc. The present work investigated the lipid lowering; nephroprotective and glucose lowering properties of ethanolic extract of peels of Musa cavendish (EMC) in alloxan-induced diabetic rats. The EMC 250, 500 and 1000 mg/kg/day and the vehicle were administered orally to alloxan-induced diabetic rats (n = 6) for 3 weeks. Changes in plasma glucose, lipid profile along with kidney function before and after treatment with EMC were recorded. The ethanolic extract of peels of Musa cavendish reduced blood glucose, serum triglyceride, cholesterol, LDL cholesterol and creatinine levels and improvement in body weight, liver glycogen, serum HDL cholesterol, serum albumin and total protein level when compared with untreated rats. Musa cavendish has lipid lowering, nephroprotective and antidiabetic property by regulating glucose uptake in the liver and muscles by restoring the intracellular energy balance.

Enhanced activity of the purine nucleotide cycle of the exercising muscle in patients with hyperthyroidism.

PubMed

Fukui, H; Taniguchi , S; Ueta, Y; Yoshida, A; Ohtahara, A; Hisatome, I; Shigemasa, C

2001-05-01

Myopathy frequently develops in patients with hyperthyroidism, but its precise mechanism is not clearly understood. In this study we focused on the purine nucleotide cycle, which contributes to ATP balance in skeletal muscles. To investigate purine metabolism in muscles, we measured metabolites related to the purine nucleotide cycle using the semiischemic forearm test. We examined the following four groups: patients with untreated thyrotoxic Graves' disease (untreated group), patients with Graves' disease treated with methimazole (treated group), patients in remission (remission group), and healthy volunteers (control group). To trace the glycolytic process, we measured glycolytic metabolites (lactate and pyruvate) as well as purine metabolites (ammonia and hypoxanthine). In the untreated group, the levels of lactate, pyruvate, and ammonia released were remarkably higher than those in the control group. Hypoxanthine release also increased in the untreated group, but the difference among the patient groups was not statistically significant. The accelerated purine catabolism did not improve after 3 months of treatment with methimazole, but it was completely normalized in the remission group. This indicated that long-term maintenance of thyroid function was necessary for purine catabolism to recover. We presume that an unbalanced ATP supply or conversion of muscle fiber type may account for the acceleration of the purine nucleotide cycle under thyrotoxicosis. Such acceleration of the purine nucleotide cycle is thought to be in part a protective mechanism against a rapid collapse of the ATP energy balance in exercising muscles of patients with hyperthyroidism.

Monosodium Glutamate Dietary Consumption Decreases Pancreatic β-Cell Mass in Adult Wistar Rats

PubMed Central

Boonnate, Piyanard; Waraasawapati, Sakda; Hipkaeo, Wiphawi; Pethlert, Supattra; Sharma, Amod; Selmi, Carlo; Prasongwattana, Vitoon; Cha’on, Ubon

2015-01-01

Background The amount of dietary monosodium glutamate (MSG) is increasing worldwide, in parallel with the epidemics of metabolic syndrome. Parenteral administration of MSG to rodents induces obesity, hyperglycemia, hyperlipidemia, insulin resistance, and type 2 diabetes. However, the impact of dietary MSG is still being debated. We investigated the morphological and functional effects of prolonged MSG consumption on rat glucose metabolism and on pancreatic islet histology. Methods Eighty adult male Wistar rats were randomly subdivided into 4 groups, and test rats in each group were supplemented with MSG for a different duration (1, 3, 6, or 9 months, n=20 for each group). All rats were fed ad libitum with a standard rat chow and water. Ten test rats in each group were provided MSG 2 mg/g body weight/day in drinking water and the 10 remaining rats in each group served as non-MSG treated controls. Oral glucose tolerance tests (OGTT) were performed and serum insulin measured at 9 months. Animals were sacrificed at 1, 3, 6, or 9 months to examine the histopathology of pancreatic islets. Results MSG-treated rats had significantly lower pancreatic β-cell mass at 1, 6 and 9 months of study. Islet hemorrhages increased with age in all groups and fibrosis was significantly more frequent in MSG-treated rats at 1 and 3 months. Serum insulin levels and glucose tolerance in MSG-treated and untreated rats were similar at all time points we investigated. Conclusion Daily MSG dietary consumption was associated with reduced pancreatic β-cell mass and enhanced hemorrhages and fibrosis, but did not affect glucose homeostasis. We speculate that high dietary MSG intake may exert a negative effect on the pancreas and such effect might become functionally significant in the presence or susceptibility to diabetes or NaCl; future experiments will take these crucial cofactors into account. PMID:26121281

Monosodium Glutamate Dietary Consumption Decreases Pancreatic β-Cell Mass in Adult Wistar Rats.

PubMed

Boonnate, Piyanard; Waraasawapati, Sakda; Hipkaeo, Wiphawi; Pethlert, Supattra; Sharma, Amod; Selmi, Carlo; Prasongwattana, Vitoon; Cha'on, Ubon

2015-01-01

The amount of dietary monosodium glutamate (MSG) is increasing worldwide, in parallel with the epidemics of metabolic syndrome. Parenteral administration of MSG to rodents induces obesity, hyperglycemia, hyperlipidemia, insulin resistance, and type 2 diabetes. However, the impact of dietary MSG is still being debated. We investigated the morphological and functional effects of prolonged MSG consumption on rat glucose metabolism and on pancreatic islet histology. Eighty adult male Wistar rats were randomly subdivided into 4 groups, and test rats in each group were supplemented with MSG for a different duration (1, 3, 6, or 9 months, n=20 for each group). All rats were fed ad libitum with a standard rat chow and water. Ten test rats in each group were provided MSG 2 mg/g body weight/day in drinking water and the 10 remaining rats in each group served as non-MSG treated controls. Oral glucose tolerance tests (OGTT) were performed and serum insulin measured at 9 months. Animals were sacrificed at 1, 3, 6, or 9 months to examine the histopathology of pancreatic islets. MSG-treated rats had significantly lower pancreatic β-cell mass at 1, 6 and 9 months of study. Islet hemorrhages increased with age in all groups and fibrosis was significantly more frequent in MSG-treated rats at 1 and 3 months. Serum insulin levels and glucose tolerance in MSG-treated and untreated rats were similar at all time points we investigated. Daily MSG dietary consumption was associated with reduced pancreatic β-cell mass and enhanced hemorrhages and fibrosis, but did not affect glucose homeostasis. We speculate that high dietary MSG intake may exert a negative effect on the pancreas and such effect might become functionally significant in the presence or susceptibility to diabetes or NaCl; future experiments will take these crucial cofactors into account.

Trypanocide Treatment of Women Infected with Trypanosoma cruzi and Its Effect on Preventing Congenital Chagas

PubMed Central

Fabbro, Diana L.; Danesi, Emmaria; Olivera, Veronica; Codebó, Maria Olenka; Denner, Susana; Heredia, Cecilia; Streiger, Mirtha; Sosa-Estani, Sergio

2014-01-01

With the control of the vectorial and transfusional routes of infection with Trypanosoma cruzi, congenital transmission has become an important source of new cases. This study evaluated the efficacy of trypanocidal therapy to prevent congenital Chagas disease and compared the clinical and serological evolution between treated and untreated infected mothers. We conducted a multicenter, observational study on a cohort of mothers infected with T. cruzi, with and without trypanocidal treatment before pregnancy. Their children were studied to detect congenital infection. Among 354 “chronically infected mother-biological child” pairs, 132 were treated women and 222 were untreated women. Among the children born to untreated women, we detected 34 infected with T. cruzi (15.3%), whose only antecedent was maternal infection. Among the 132 children of previously treated women, no infection with T. cruzi was found (0.0%) (p<0.05). Among 117 mothers with clinical and serological follow up, 71 had been treated and 46 were untreated. The women were grouped into three groups. Group A: 25 treated before 15 years of age; Group B: 46 treated at 15 or more years of age; Group C: untreated, average age of 29.2±6.2 years at study entry. Follow-up for Groups A, B and C was 16.3±5.8, 17.5±9.2 and 18.6±8.6 years respectively. Negative seroconversion: Group A, 64.0% (16/25); Group B, 32.6% (15/46); Group C, no seronegativity was observed. Clinical electrocardiographic alterations compatible with chagasic cardiomyopathy: Group A 0.0% (0/25); B 2.2% (1/46) and C 15.2% (7/46). The trypanocidal treatment of women with chronic Chagas infection was effective in preventing the congenital transmission of Trypanosoma cruzi to their children; it had also a protective effect on the women's clinical evolution and deparasitation could be demonstrated in many treated women after over 10 years of follow up. PMID:25411847

Trypanocide treatment of women infected with Trypanosoma cruzi and its effect on preventing congenital Chagas.

PubMed

Fabbro, Diana L; Danesi, Emmaria; Olivera, Veronica; Codebó, Maria Olenka; Denner, Susana; Heredia, Cecilia; Streiger, Mirtha; Sosa-Estani, Sergio

2014-11-01

With the control of the vectorial and transfusional routes of infection with Trypanosoma cruzi, congenital transmission has become an important source of new cases. This study evaluated the efficacy of trypanocidal therapy to prevent congenital Chagas disease and compared the clinical and serological evolution between treated and untreated infected mothers. We conducted a multicenter, observational study on a cohort of mothers infected with T. cruzi, with and without trypanocidal treatment before pregnancy. Their children were studied to detect congenital infection. Among 354 "chronically infected mother-biological child" pairs, 132 were treated women and 222 were untreated women. Among the children born to untreated women, we detected 34 infected with T. cruzi (15.3%), whose only antecedent was maternal infection. Among the 132 children of previously treated women, no infection with T. cruzi was found (0.0%) (p<0.05). Among 117 mothers with clinical and serological follow up, 71 had been treated and 46 were untreated. The women were grouped into three groups. Group A: 25 treated before 15 years of age; Group B: 46 treated at 15 or more years of age; Group C: untreated, average age of 29.2 ± 6.2 years at study entry. Follow-up for Groups A, B and C was 16.3 ± 5.8, 17.5 ± 9.2 and 18.6 ± 8.6 years respectively. Negative seroconversion: Group A, 64.0% (16/25); Group B, 32.6% (15/46); Group C, no seronegativity was observed. Clinical electrocardiographic alterations compatible with chagasic cardiomyopathy: Group A 0.0% (0/25); B 2.2% (1/46) and C 15.2% (7/46). The trypanocidal treatment of women with chronic Chagas infection was effective in preventing the congenital transmission of Trypanosoma cruzi to their children; it had also a protective effect on the women's clinical evolution and deparasitation could be demonstrated in many treated women after over 10 years of follow up.

[An in vivo study of basic fibroblast growth factor on activation and proliferation of retinal progenitor cell in RCS rats].

PubMed

Xia, Xiaoping; Song, Guoxiang; Liu, Xiangfu; Tang, Xiangchen; Ye, Hui

2010-11-01

To investigate the effect of intravitreal basic fibroblast growth factor(bFGF) on activation and proliferation of endogenous retinal progenitor cells in the Royal College of Surgeons(RCS) rats. Twenty-four rats were studied after the 30th postnatal day(≥30). Eighteen affected rats were randomly divided into 3 groups: bFGF-treated, vehicle-treated and untreated group, and 6 unaffected rats were used as normal controls. Six μl of bFGF (5μg/10 μl) or vehicle was injected into the vitreous on days 31, 33 and 35 after birth (P31, P33, P35) in the bFGF group and vehicle group, and no injection was administered in the untreated and control groups. All the rats were euthanized, and their eyes were enucleated, hemisected and fixed at 50 d after birth for immunohistochemistry and measurement of outer nuclear layer thickness. Nestin and Chx10 were positively expressed in all retinal layers, intravitreous injection of bFGF in retina-dystrophic RCS(RCS-p+/Lav) rats induced intense labeling for the retinal progenitor cell markers Chx10 and Nestin, which were highly colocalized. Fluorescence intensity for both labels was slightly less in the control rats, and much less in the vehicle-injected rats as well as in the untreated RCS rats. The outer nuclear layer (ONL) was significantly thicker in bFGF group than that of vehicle-treated or untreated group(p<0.01), but thinner than that of the control group(p<0.01). No significant difference was observed in the ONL thicknesses between the vehicle group and untreated group(P>0.05). bFGF may contribute to the activation of retinal progenitor cells in RCS rats, thus counteract degeneration by promoting the proliferation of the progenitor cells.

NADPH oxidase-derived overproduction of reactive oxygen species impairs postischemic neovascularization in mice with type 1 diabetes.

PubMed

Ebrahimian, Téni G; Heymes, Christophe; You, Dong; Blanc-Brude, Olivier; Mees, Barend; Waeckel, Ludovic; Duriez, Micheline; Vilar, José; Brandes, Ralph P; Levy, Bernard I; Shah, Ajay M; Silvestre, Jean-Sébastien

2006-08-01

We hypothesized that diabetes-induced oxidative stress may affect postischemic neovascularization. The response to unilateral femoral artery ligation was studied in wild-type or gp91(phox)-deficient control or type 1 diabetic mice or in animals treated with the anti-oxidant N-acetyl-l-cysteine (NAC) or with in vivo electrotransfer of a plasmid encoding dominant-negative Rac1 (50 microg) for 21 days. Postischemic neovascularization was reduced in diabetic mice in association with down-regulated vascular endothelial growth factor-A protein levels. In diabetic animals vascular endothelial growth factor levels and postischemic neovascularization were restored to nondiabetic levels by the scavenging of reactive oxygen species (ROS) by NAC administration or the inhibition of ROS generation by gp91(phox) deficiency or by administration of dominant-negative Rac1. Finally, diabetes reduced the ability of adherent bone marrow-derived mononuclear cells (BM-MNCs) to differentiate into endothelial progenitor cells. Treatment with NAC (3 mmol/L), apocynin (200 micromol/L), or the p38MAPK inhibitor LY333351 (10 micromol/L) up-regulated the number of endothelial progenitor cell colonies derived from diabetic BM-MNCs by 1.5-, 1.6-, and 1.5-fold, respectively (P < 0.05). In the ischemic hindlimb model, injection of diabetic BM-MNCs isolated from NAC-treated or gp91(phox)-deficient diabetic mice increased neovascularization by approximately 1.5-fold greater than untreated diabetic BM-MNCs (P < 0.05). Thus, inhibition of NADPH oxidase-derived ROS overproduction improves the angiogenic and vasculogenic processes and restores postischemic neovascularization in type 1 diabetic mice.

Wireless nanosensor system for diagnosis of sleep disorders

NASA Astrophysics Data System (ADS)

Ramasamy, Mouli; Varadan, Vijay K.

2016-04-01

A good night's sleep plays a vital role in physical and mental wellbeing by performing the recuperative function for the brain and the body. Notwithstanding the fact that, good sleep is an essential part of a person's life, an increasing number of people are experiencing sleep disorders and loss of sleep. According to the research by the National Institutes of Health (NIH), 50 to 70 million Americans suffer from sleep disorders and sleep deprivation. Although sleep disorder is a highly prevalent condition like diabetes or asthma, 80 to 90 percent of the cases remain undiagnosed. The short-term effects of sleep disorder are morning headaches, excessive daytime sleepiness, shot-term memory loss and depression, but the cumulative long-term effects result in severe health consequences like heart attacks and strokes. In addition, people suffering from sleep disorders are 7.5 times more likely to have a higher body mass index and 2.5 times more likely to have diabetes. Further, undiagnosed and untreated sleep disorders have a significant direct and indirect economic impact. The costs associated with untreated sleep disorders are far higher than the costs for adequate treatment. According to the survey, approximately 16 billion of dollars are spent on medical expenses associated with repeated doctor visits, prescriptions and medications.

Microarray profile of human kidney from diabetes, renal cell carcinoma and renal cell carcinoma with diabetes

PubMed Central

Kosti, Adam; Harry Chen, Hung-I; Mohan, Sumathy; Liang, Sitai; Chen, Yidong; Habib, Samy L.

2015-01-01

Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have screened whole human DNA genome from healthy control, patients with diabetes or renal cell carcinoma (RCC) or RCC+diabetes. We found that 883 genes gain/163 genes loss of copy number in RCC+diabetes group, 669 genes gain/307 genes loss in RCC group and 458 genes gain/38 genes loss of copy number in diabetes group, after removing gain/loss genes obtained from healthy control group. Data analyzed for functional annotation enrichment pathways showed that control group had the highest number (280) of enriched pathways, 191 in diabetes+RCC group, 148 in RCC group, and 81 in diabetes group. The overlap GO pathways between RCC+diabetes and RCC groups showed that nine were enriched, between RCC+diabetes and diabetes groups was four and between diabetes and RCC groups was eight GO pathways. Overall, we observed majority of DNA alterations in patients from RCC+diabetes group. Interestingly, insulin receptor (INSR) is highly expressed and had gains in copy number in RCC+diabetes and diabetes groups. The changes in INSR copy number may use as a biomarker for predicting RCC development in diabetic patients. PMID:25821562

Diet quality and adherence to a healthy diet in Japanese male workers with untreated hypertension.

PubMed

Kanauchi, Masao; Kanauchi, Kimiko

2015-07-10

As Japanese societies rapidly undergo westernisation, the prevalence of hypertension is increasing. We investigated the association between dietary quality and the prevalence of untreated hypertension in Japanese male workers. We conducted a cross-sectional study of 433 male workers who completed a brief food frequency questionnaire. Adherence to the WHO-based Healthy Diet Indicator (HDI), the American Heart Association 2006 Diet and Lifestyle Recommendations, the Dietary Approaches to Stop Hypertension (DASH) diet, and Mediterranean-style diet was assessed using four adherence indexes (HDI score, AI-84 score, DASH score and MED score). Hypertension classes were classified into three categories: non-hypertension, untreated hypertension and treated hypertension (ie, taking antihypertensive medication). The prevalence of untreated hypertension and treated hypertension was 22.4% and 8.5%, respectively. Patients with untreated hypertension had significantly lower HDI and AI-84 scores compared with non-hypertension. DASH and MED scores across the three hypertension classes were comparable. After adjusting for age, energy intake, smoking habit, alcohol drinking, physical activity and salt intake, a low adherence to HDI and a lowest quartile of AI-84 score were associated with a significantly higher prevalence of untreated hypertension, with an OR of 3.33 (95% CI 1.39 to 7.94, p=0.007) and 2.23 (1.09 to 4.53, p=0.027), respectively. A lower dietary quality was associated with increased prevalence of untreated hypertension in Japanese male workers. Our findings support a potential beneficial impact of nutritional assessment using diet qualities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Biomarker evidence of axonal injury in neuroasymptomatic HIV-1 patients.

PubMed

Jessen Krut, Jan; Mellberg, Tomas; Price, Richard W; Hagberg, Lars; Fuchs, Dietmar; Rosengren, Lars; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

2014-01-01

Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method. With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use.

Obstructive sleep apnea and stroke: links to health disparities☆, ☆☆

PubMed Central

Ramos, Alberto R.; Seixas, Azizi; Dib, Salim I.

2018-01-01

Obstructive sleep apnea (OSA) is a novel cardiovascular and cerebrovascular risk factor that presents unique opportunities to understand and reduce seemingly intractable stroke disparity among non-Hispanic blacks and Hispanic/Latinos. Individuals from these 2 groups have up to a 2-fold risk of stroke and greater burden of OSA. Obstructive sleep apnea directly and indirectly increases risk of stroke through a variety of autonomic, chemical, and inflammatory mechanisms and vascular risk factors such as hypertension, obesity, and diabetes mellitus. Untreated OSA exacerbates poststroke prognosis, as it may also influence rehabilitation efforts and functional outcomes such as cognitive function after a stroke. Conversely, treatment of OSA may reduce the risk of stroke and may yield better poststroke prognosis. Unfortunately, in racial/ethnic minority groups, there are limited awareness, knowledge, and screening opportunities for OSA. Increasing awareness and improving screening strategies for OSA in minorities may alleviate stroke risk burden and improve stroke outcomes in these populations. This review article is intended to highlight the epidemiology, clinical characteristics, pathophysiology, diagnosis, and treatment of OSA in relation to stroke risk, with an emphasis on race-ethnic disparities. PMID:29073399

Healthy Lifestyle through Young Adulthood and Presence of Low Cardiovascular Disease Risk Profile in Middle Age: The Coronary Artery Risk Development in (Young) Adults (CARDIA) Study

PubMed Central

Liu, Kiang; Daviglus, Martha L.; Loria, Catherine M.; Colangelo, Laura A.; Spring, Bonnie; Moller, Arlen C.; Lloyd-Jones, Donald M.

2012-01-01

Background A low cardiovascular disease (CVD) risk profile (untreated cholesterol < 200 mg/dl, untreated blood pressure < 120/<80 mmHg, never smoking, and no history of diabetes and myocardial infarction) in middle age is associated with markedly better health outcomes in older age, but few middle aged adults have this low risk profile. We examined whether adopting a healthy lifestyle throughout young adulthood is associated with presence of the low CVD risk profile in middle age. Methods and Results The CARDIA study sample consisted of 3,154 black and white participants aged 18 to 30 years at Year 0 (Y0, 1985-86) who attended the Year 0, 7 and 20 (Y0, Y7 and Y20) examinations. Healthy lifestyle factors (HLFs) defined at Y0, Y7 and Y20 included: 1) Average BMI < 25 kg/m2; 2) No or moderate alcohol intake; 3) higher healthy diet score; 4) higher physical activity score; and 5) Never smoking. Mean age (25 years) and percentage of women (56%) were comparable across groups defined by number of HLFs. The age-, sex- and race-adjusted prevalences of low CVD risk profile at Y20 were 3.0%, 14.6%, 29.5%, 39.2% and 60.7% for people with 0 or 1, 2, 3, 4, and 5 HLFs, respectively (p-trend <0.0001). Similar graded relationships were observed for each sex-race group (all p-trend<0.0001). Conclusions Maintaining a healthy lifestyle throughout young adulthood is strongly associated with low CVD risk profile in middle age. Public health and individual efforts are needed to improve adoption and maintenance of healthy lifestyles in young adults. PMID:22291127

Healthy lifestyle through young adulthood and the presence of low cardiovascular disease risk profile in middle age: the Coronary Artery Risk Development in (Young) Adults (CARDIA) study.

PubMed

Liu, Kiang; Daviglus, Martha L; Loria, Catherine M; Colangelo, Laura A; Spring, Bonnie; Moller, Arlen C; Lloyd-Jones, Donald M

2012-02-28

A low cardiovascular disease risk profile (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80 mm Hg, never smoking, and no history of diabetes mellitus or myocardial infarction) in middle age is associated with markedly better health outcomes in older age, but few middle-aged adults have this low risk profile. We examined whether adopting a healthy lifestyle throughout young adulthood is associated with the presence of the low cardiovascular disease risk profile in middle age. The Coronary Artery Risk Development in (Young) Adults (CARDIA) study sample consisted of 3154 black and white participants 18 to 30 years of age at year 0 (1985-1986) who attended the year 0, 7, and 20 examinations. Healthy lifestyle factors defined at years 0, 7, and 20 included average body mass index <25 kg/m(2), no or moderate alcohol intake, higher healthy diet score, higher physical activity score, and never smoking. Mean age (25 years) and percentage of women (56%) were comparable across groups defined by number of healthy lifestyle factors. The age-, sex-, and race-adjusted prevalences of low cardiovascular disease risk profile at year 20 were 3.0%, 14.6%, 29.5%, 39.2%, and 60.7% for people with 0 or 1, 2, 3, 4, and 5 healthy lifestyle factors, respectively (P for trend <0.0001). Similar graded relationships were observed for each sex-race group (all P for trend <0.0001). Maintaining a healthy lifestyle throughout young adulthood is strongly associated with a low cardiovascular disease risk profile in middle age. Public health and individual efforts are needed to improve the adoption and maintenance of healthy lifestyles in young adults.

The effect of intralesional steroid injections on the volume and blood flow in periocular capillary haemangiomas.

PubMed

Verity, David H; Rose, Geoffrey E; Restori, M

2008-01-01

To examine the effect of steroid therapy on the volume estimates and blood flow characteristics of childhood periorbital capillary haemangiomas. Children at risk of amblyopia due to periorbital haemangiomas were treated with intralesional steroid injections (between 1 and 4 courses) and serial assessment of the volume and blood-flow characteristics of the lesions measured using colour Doppler ultrasonography. The characteristics of the haemangiomas in these children were compared with a cohort of untreated cases. Eight of nine treated children were female, this proportion being significantly different from the equal sex distribution of an untreated cohort (p < 0.05). All children in the steroid-treated group presented within 1 month of birth, compared to the untreated children, who presented at an average of 2.1 months of age (range 0-14, median 2.9 months) (p = 0.04) and they required significantly longer follow-up in the Orbital service (mean 65 months, range 26-105), compared with an average of 35 months (range 4-92, median 23) in the untreated group (p = 0.002). The maximum estimated volume of the lesions were significantly larger in the treated group (treated group mean 8.9 ml, untreated group mean 4.1 ml; p = 0.016), with a trend towards higher maximum measured blood velocities in the treated group (treated mean 64 cm compared with untreated mean 52 cm; p = 0.1). Steroid injections appear to reduce the volume and blood flow of haemangiomas, this suppression persisting for several months (between 5 and 20) before the lesion later displays the cyclic fluctuations in volume and flow seen with untreated lesions. All treated haemangiomas had some residual vascular anomaly, detectable on ultrasonography, at last follow-up--this being despite absence of clinical signs in most cases. Periorbital capillary haemangiomas requiring steroid therapy for risk of amblyopia were significantly commoner in females, were larger lesions and presented at an earlier age. Intralesional steroids appear to cause a reduction of blood flow, with a transient reduction in volume and a suppression of the natural cyclic variation seen without treatment. The changes after a course of steroid therapy appear to last for between 5 and 20 months, this period of suppression of the lesion probably being particularly useful during infancy and early childhood when the child is at greatest risk of amblyopia.

Sinomenine prevents the development of cardiomyopathy in diabetic rats by inhibiting inflammatory responses and blocking activation of NF-κB.

PubMed

Jiang, Cheng; Tong, Yun-Long; Zhang, Dan; Liu, Li-Zhi; Wang, Ju-Fei

2017-01-01

Diabetic cardiomyopathy is a severe complication of diabetes mellitus (DM). The goal of current work was to study the effects of sinomenine on streptozotocin-induced cardiomyopathy in rats. DM in rats was induced by intraperitoneal injection of streptozotocin. Cardiac function was evaluated by measuring left ventricle end-diastolic diameter, left ventricle end-systolic diameter and ejection fraction. Cardiac inflammation was evaluated by the degree of infiltration of T lymphocytes and the levels of pro-inflammatory cytokines. Sinomenine attenuated diabetic symptoms without affecting plasma glucose. Cardiac dysfunction in the sinomenine-treated diabetic rats was significantly improved, as reflected by decreased levels of left ventricle end-diastolic diameter, left ventricle end systolic diameter and an increased level of ejection fraction. Sinomenine observably reduced cardiomyocyte hypertrophy in DM rats. Moreover, sinomenine reduced infiltration of CD3+ and CD68+ positive cells and decreased the levels of tumor necrosis factor-α, interlukin-1 and interlukin-6. Finally, sinomenine-treated rats showed a reduced expression of NF-κB and an increased expression of IκB in the myocardium compared with the myocardium of untreated diabetic rats. Our results indicate sinomenine significantly improves cardiac function in diabetic rats, which may be attributed to the deactivation of NF-κB and the blockade of inflammatory cytokine-mediated immune reactions.

Biomarkers of chronic kidney disease in the urine of diabetic/hypertensive patients by means of Raman spectroscopy

NASA Astrophysics Data System (ADS)

Vieira, Elzo Everton de Sousa; Bispo, Jeyse Aliana Martis; Fernandes, Adriana Barrinha; Silveira, Landulfo

2016-03-01

Diabetes mellitus (DM) and arterial hypertension (AH) are common diseases that, if untreated, predispose the patient to renal failure. This study aimed to evaluate possible biomarkers in the urine of patients with DM and AH capable to predict the chronic renal disease, by means of Raman spectroscopy. Urines were obtained from patients with DM and AH, and separated into four groups: no symptoms of diseases related to DM and AH (G1), with low clinical complications (G2), with severe clinical complications (G3), and with chronic kidney disease (G4) arised from DM and AH. It has been used a dispersive Raman spectrometer (830nm, 250mW, 20s accumulation). In the spectra of urine it was identified Raman peaks at 680cm-1 (creatinine), 1004cm-1 (urea) and 1128cm-1 (glucose). The results revealed that G2, G3 and G4 presented the creatinine peak with lower intensity than G1 (p < 0.05). It was observed that G2, G3 and G4 showed lower intensity of the urea peak compared to G1 (p < 0.05) and G4 showed lower intensity compared to G2 and G3 (p < 0.05). Despite not significant, the glucose peak showed lower intensity in G1 when compared to the other groups. A model for classification of groups according to clinical criteria, using Sparse Multinomial Logistic Regression, taking as inputs the intensities of creatine, urea and glucose peaks allowed correct classification of 88.9% for G1, 36.8% for G2, 43.8% for G3 and 84.2% for G4. These results demonstrated the possibility of obtaining diagnostic information for complications of kidney disease associated to DM and AH, particularly the renal failure.

Protective effect of treatment with black cumin oil on spatial cognitive functions of rats that suffered global cerebrovascular hypoperfusion.

PubMed

Azzubaidi, Marwan Saad; Saxena, Anil Kumar; Talib, Norlelawati Abi; Ahmed, Qamar Uddin; Dogarai, Bashar Bello

2012-01-01

The fixed oil of black cumin seeds, Nigella sativa L. (NSO), has shown considerable antioxidant and anti-inflammatory activities. Chronic cerebral hypoperfusion has been linked to neurodegenerative disorders including Alzheimer's disease (AD) and its subsequent cognitive impairment in which oxidative stress and neuroinflammation are the principal culprits. Cerebrovascular hypoperfusion was experimentally achieved by bilateral common carotid arteries occlusion (2VO) in rats. Morris water maze (MWM) test was employed to assess the effects of NSO on spatial cognitive function before and after 2VO intervention. Rats were divided into long-term memory (LTM) and short-term memory (STM) groups, each was further subdivided into 3 subgroups: sham control, untreated 2VO and NSO treated 2VO group. All subgroups were tested with MWM at the tenth postoperative week. Working memory test results for both sham control and NSO treated groups showed significantly lower escape latency time and total distance travelled than untreated 2VO group. Similarly, LTM and STM MWM tests for sham control and NSO treated groups revealed significantly better maze test performance as compared to untreated 2VO group. Sham control and NSO treated 2VO groups demonstrated superior probe memory test performance as compared to untreated 2VO group. The fixed oil of Nigella sativa seeds has demonstrated noticeable spatial cognitive preservation in rats challenged with chronic cerebral hypoperfusion which indicates a promising prospective neuroprotective effect.

Antibacterial and residual antimicrobial activities against Enterococcus faecalis biofilm: A comparison between EDTA, chlorhexidine, cetrimide, MTAD and QMix.

PubMed

Zhang, Rui; Chen, Min; Lu, Yan; Guo, Xiangjun; Qiao, Feng; Wu, Ligeng

2015-08-06

We compared the antibacterial and residual antimicrobial activities of five root canal irrigants (17% EDTA,2% chlorhexidine,0.2% cetrimide, MTAD, and QMix) in a model of Enterococcus faecalis biofilm formation. Sixty dentin blocks with 3-week E. faecalis biofilm were divided into six equal groups and flushed with irrigant for 2 min or left untreated. A blank control group was also established. Antibacterial activities of the irrigants were evaluated by counting colony forming units. To test residual antimicrobial activities, 280 dentin blocks were divided into seven equal groups and flushed with irrigant for 2 min or left untreated and then incubated with E. faecalis suspension for 48 h, or used as a blank. No bacteria were observed in the blank control group. The number of viable E. faecalis was significantly fewer in the irrigant-treated groups compared with the untreated control (P < 0.05). Among the five irrigants, QMix had the strongest antibacterial activity. Residual antimicrobial activities of CHX were significantly higher at 12 h, 24 h and 36 h compared to untreated control (P < 0.05). All five root canal irrigants were effective to some extent against E. faecalis, but QMix and CHX had the strongest, and CHX the longest (up to 36 h), antimicrobial activity.

Estimation of prediagnostic duration of type 2 diabetes mellitus by lens autofluorometry

NASA Astrophysics Data System (ADS)

Kessel, Line; Glumer, Charlotte; Larsen, Michael

2003-10-01

Type 2 diabetes mellitus is a global epidemic with the number of affected subjects exceeding 4% of the adult population world-wide. Undiagnosed and untreated, the disease results in long-term complications such as myocardial infarction, stroke, and blindness. Treatment reduces the number and severity of long-term complications but treatment is often delayed by a time-lag of 10 years or more from the onset of disease to diagnosis. Earlier diagnosis can be achieved by systematic screening programs but the potential time won is unknown. The aim of the present study was to develop a mathematical model estimating the prediagnostic duration of type 2 diabetes mellitus using lens autofluorescence as an indicator of lifetime glycemic load. Fluorometry of the human is lens a quantitative measurement which is attractive because of the ease by which it can be performed. It is our hope that lens fluorometry will prove useful in estimating the prediagnostic duration of type 2 diabetes mellitus in population studies, a property of profound clinical relevance that is difficult to estimate by any other currently available method.

Dorzagliatin monotherapy in Chinese patients with type 2 diabetes: a dose-ranging, randomised, double-blind, placebo-controlled, phase 2 study.

PubMed

Zhu, Dalong; Gan, Shenglian; Liu, Yu; Ma, Jianhua; Dong, Xiaolin; Song, Weihong; Zeng, Jiao'e; Wang, Guixia; Zhao, Wenjuan; Zhang, Qiu; Li, Yukun; Fang, Hui; Lv, Xiaofeng; Shi, Yongquan; Tian, Haoming; Ji, Linong; Gao, Xin; Zhang, Lihui; Bao, Yuqian; Lei, Minxiang; Li, Ling; Zeng, Longyi; Li, Xiaoying; Hou, Xinghua; Zhao, Yu; Hu, Tianxin; Ge, Xiaoyun; Zhao, Guiyu; Li, Yongguo; Zhang, Yi; Chen, Li

2018-05-04

Glucokinase acts as a glucose sensor in the pancreas and a glucose processor in the liver, and has a central role in glucose homoeostasis. Dorzagliatin is a new, dual-acting, allosteric glucokinase activator that targets both pancreatic and hepatic glucokinases. Dorzagliatin has good pharmacokinetic and pharmacodynamic properties in humans, and provides effective 24-h glycaemic control and improves glucose sensitivity in patients with type 2 diabetes. We aimed to assess the efficacy and safety of dorzagliatin monotherapy at different doses in Chinese patients with type 2 diabetes. In this multicentre, randomised, double-blind, placebo-controlled, phase 2 study, we randomly assigned (1:1:1:1:1) patients to receive oral placebo or one of four doses of oral dorzagliatin (75 mg once a day, 100 mg once a day, 50 mg twice a day, or 75 mg twice a day) using permuted-block randomisation, with a block size of ten and without stratification. Eligible patients were men or non-fertile women (aged 40-75 years) with type 2 diabetes who had a BMI of 19·0-30·0 kg/m 2 , were on a diet and exercise regimen, and were previously untreated or treated with metformin or α-glucosidase inhibitor monotherapy. The study started with a 4-week placebo run-in period followed by a 12-week treatment period. The primary endpoint was the change in HbA 1c from baseline to week 12, which was assessed in all patients who received at least one dose of study drug and had both baseline and at least one post-baseline HbA 1c value. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02561338. Between Sept 29, 2015, and Aug 17, 2016, we randomly assigned 258 patients to one of the five study groups. At the end of 12 weeks, the least squares mean change in HbA 1c from baseline was -0·35% (95% CI -0·60 to -0·10) in the placebo group, -0·39% (-0·64 to -0·14) in the 75 mg once daily group, -0·65% (-0·92 to -0·38) in the 100 mg once daily group, -0·79% (-1·06 to -0·52) in the 50 mg twice daily group, and -1·12% (-1·39 to -0·86) in the 75 mg twice daily group. Compared with the placebo group, the change in HbA 1c between baseline and 12 weeks was significant in the 50 mg twice daily (p=0·0104) and the 75 mg twice daily (p<0·0001) groups. The number of adverse events was similar between the treatment groups and the placebo group. There were no reports of drug-related serious adverse events or severe hypoglycaemia. Dorzagliatin had a beneficial effect on glycaemic control and was safe and well tolerated over 12 weeks in Chinese patients with type 2 diabetes. Hua Medicine, National Major Scientific and Technological Special Project for Significant New Drugs Development, Shanghai Science and Technology Innovation Action Project, Shanghai Pudong District Science and Technology Innovation Action Project, and Shanghai Municipal Commission of Economy and Informatisation Innovation Action Project. Copyright © 2018 Elsevier Ltd. All rights reserved.

Presence of chronic diabetic foot ulcers is associated with more frequent and more advanced retinopathy.

PubMed

Sellman, A; Katzman, P; Andreasson, S; Löndahl, M

2018-05-23

To clarify the frequency and severity of diabetic retinopathy in a group of people with Type 2 diabetes and chronic diabetic foot ulcers, and to compare visual acuity, levels of retinopathy and clinical significant macular oedema with a matched control group of people with Type 2 diabetes without a history of chronic diabetic foot ulcers. Visual acuity and fundus imaging were evaluated in 90 white people with at least 3 months' duration of full-thickness diabetic foot ulcers below the ankle and the results compared with those in 180 white people with Type 2 diabetes without a history of chronic diabetic foot ulcers (control group). Controls were matched for age, sex and duration of diabetes. Despite similar age and diabetes duration, severe non-proliferative or proliferative diabetic retinopathy was present in 41% of the people in the diabetic foot ulcer group as compared to 15% in the control group (P<0.001). Only 6% in the diabetic foot ulcer group was without any diabetic retinopathy as compared to 34% among controls. Proliferative diabetic retinopathy was more common in the diabetic foot ulcer group (31% vs 8%; P<0.001), but time-to-proliferative diabetic retinopathy did not differ between groups. Clinically significant macular oedema was more frequently present, and the diabetic foot ulcer group exhibited significantly worse results in best and worst eye visual acuity testing. In this northern European setting almost all people with Type 2 diabetes and chronic diabetic foot ulcers had diabetic retinopathy. Almost one-third had proliferative diabetic retinopathy as compared to <10% in our matched control group. More advanced diabetic retinopathy was linked to worse visual acuity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Impact of experimental type 1 diabetes mellitus on systemic and coagulation vulnerability in mice acutely exposed to diesel exhaust particles.

PubMed

Nemmar, Abderrahim; Subramaniyan, Deepa; Yasin, Javed; Ali, Badreldin H

2013-04-15

Epidemiological evidence indicates that diabetic patients have increased susceptibility to adverse cardiovascular outcomes related to acute increases in exposures to particulate air pollution. However, mechanisms underlying these effects remain unclear. To evaluate the possible mechanisms underlying these actions, we assessed the systemic effects of diesel exhaust particles (DEP) in control mice, and mice with streptozotocin-induced type 1 diabetes. Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4 mg/kg) or saline, and several cardiovascular endpoints were measured 24 h thereafter. DEP caused leukocytosis and a significant increase in plasma C-reactive protein and 8-isoprostane concentrations in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. The arterial PO2 as well as the number of platelets and the thrombotic occlusion time in pial arterioles assessed in vivo were significantly decreased following the i.t. instillation of DEP in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. Both alanine aminotransferase and aspartate transaminase activities, as well as the plasma concentrations of plasminogen activator inhibitor and von Willebrand factor were significantly increased in DEP-exposed diabetic mice compared to diabetic mice exposed to saline or DEP-exposed non-diabetic mice. The in vitro addition of DEP (0.25-1 μg/ml) to untreated mouse blood significantly and dose-dependently induced in vitro platelet aggregation, and these effects were exacerbated in blood of diabetic mice. This study has shown that systemic and coagulation events are aggravated by type 1 diabetes in mice, acutely exposed to DEP and has described the possible mechanisms for these actions that may also be relevant to the exacerbation of cardiovascular morbidity accompanying particulate air pollution in diabetic patients.

Impact of experimental type 1 diabetes mellitus on systemic and coagulation vulnerability in mice acutely exposed to diesel exhaust particles

PubMed Central

2013-01-01

Background Epidemiological evidence indicates that diabetic patients have increased susceptibility to adverse cardiovascular outcomes related to acute increases in exposures to particulate air pollution. However, mechanisms underlying these effects remain unclear. Methods To evaluate the possible mechanisms underlying these actions, we assessed the systemic effects of diesel exhaust particles (DEP) in control mice, and mice with streptozotocin–induced type 1 diabetes. Four weeks following induction of diabetes, the animals were intratracheally instilled (i.t.) with DEP (0.4 mg/kg) or saline, and several cardiovascular endpoints were measured 24 h thereafter. Results DEP caused leukocytosis and a significant increase in plasma C-reactive protein and 8-isoprostane concentrations in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. The arterial PO2 as well as the number of platelets and the thrombotic occlusion time in pial arterioles assessed in vivo were significantly decreased following the i.t. instillation of DEP in diabetic mice compared to diabetic mice exposed to saline or non-diabetic mice exposed to DEP. Both alanine aminotransferase and aspartate transaminase activities, as well as the plasma concentrations of plasminogen activator inhibitor and von Willebrand factor were significantly increased in DEP-exposed diabetic mice compared to diabetic mice exposed to saline or DEP-exposed non-diabetic mice. The in vitro addition of DEP (0.25-1 μg/ml) to untreated mouse blood significantly and dose-dependently induced in vitro platelet aggregation, and these effects were exacerbated in blood of diabetic mice. Conclusion This study has shown that systemic and coagulation events are aggravated by type 1 diabetes in mice, acutely exposed to DEP and has described the possible mechanisms for these actions that may also be relevant to the exacerbation of cardiovascular morbidity accompanying particulate air pollution in diabetic patients. PMID:23587270

Effects of triple antioxidant combination (vitamin E, vitamin C and alpha-lipoic acid) with insulin on lipid and cholesterol levels and fatty acid composition of brain tissue in experimental diabetic and non-diabetic rats.

PubMed

Ozkan, Yusuf; Yilmaz, Okkeş; Oztürk, Ali Ihsan; Erşan, Yasemin

2005-09-01

The aim of this research was to examine the effects of a triple antioxidant combination (vitamins E (VE) and C (VC) plus alpha-lipoic acid (LA)) on the total lipid and cholesterol levels and the fatty acid composition of brain tissues in experimental diabetic and non-diabetic rats. VE and LA were injected intraperitoneally (50 mg/kg) four times per week and VC was provided as a supplement dissolved in the drinking water (50 mg/kg). In addition, rats in the diabetes 1 and D+VELAVC groups were given daily by subcutaneous insulin injections (8 IU/kg), but no insulin was given to rats in the diabetes 2 group. The results indicate that the brain lipid levels in the D+VELAVC, diabetes 1 and diabetes 2 groups were higher than in the control group (P<0.01). Total lipid was also higher in the non-diabetic rats treated with LA and VC. Total cholesterol was higher in the diabetes 1 and diabetes 2 groups (P<0.05) than in controls. Cholesterol levels were similar in the D+VELAVC and LA groups but lower in the VC, VE and VELAVC groups of non-diabetic rats (P<0.05 and P<0.01). In respect of fatty acid composition, palmitic acid levels were lower in the diabetes 2 and non-diabetic VE groups than the control group (P<0.05), but higher in the non-diabetic LA group (P<0.05). Oleic acid (18:1 n-9) levels were lower in the diabetic and non-diabetic groups than the control group (P<0.01), but higher in the non-diabetic LA group. Arachidonic acid (20:4 n-6) levels were similar in the diabetes 1, D+VELAVC and control groups (P>0.05) but higher in the non-diabetic VE, VC, LA and VEVCLA groups (P<0.05) and lower in the diabetes 2 group (P<0.05). Docosahexaenoic acid (22:6 n-3) was elevated in the diabetes 2 and VEVCLA groups (P<0.01, P<0.05). In conclusion, the current study confirmed that treatment with a triple combination of VE, VC and LA protects the arachidonic acid level in the brains of diabetic and non-diabetic rats.

Effect of antihypertensive therapy on renal artery structure in type 2 diabetic rats with hypertension.

PubMed

Reddi, A S; Nimmagadda, V R; Arora, R

2001-05-01

We have previously demonstrated that antihypertensive treatment with doxazosin (DZN), an alpha-adrenergic blocker, and lisinopril (LIS), an ACE inhibitor, reverse glomerular sclerosis in corpulent spontaneously hypertensive rats with type 2 diabetes. In this study, we examined the effects of the above-mentioned antihypertensive drugs alone and in combination on the structure of interlobular and arcuate arteries in these rats. Both male and female rats aged 6 months were treated with antihypertensive drugs for 16 weeks. Various structural parameters were evaluated by light microscopy, with the use of digital image analysis, in kidney sections stained with periodic acid-SCHIFF: Systolic blood pressure was significantly lower in treated than in untreated rats. Untreated diabetic rats had a significantly higher media/lumen ratio (smaller luminal diameter) of both arteries compared with the ratio in treated rats (for interlobular artery, 0.72+/-0.06 [no treatment], 0.49+/-0.03 [DZN treatment], 0.54+/-0.06 [LIS treatment], and 0.52+/-0.04 [combination therapy], P<0.05 to <0.001 for no treatment versus treatment; for arcuate artery, 0.66+/-0.11 [no treatment], 0.40+/-0.02 [DZN treatment], 0.39+/-0.04 [LIS treatment], and 0.40+/-0.03 [combination therapy], P<0.05 for no treatment versus treatment). Antihypertensive treatment caused significant increases in total arterial cross-sectional area, internal and external diameters, luminal and medial cross-sectional area, and medial thickness in both interlobular and arcuate arteries. The improvement in arterial structure after antihypertensive treatment was due to remodeling and growth of the vessels. Both DZN and LIS were equally efficacious, and combination therapy had no additive or synergistic effect.

Association of Hypothyroidism with Body Mass Index, Systolic Blood Pressure and Proteinuria in Diabetic Patients: Does treated Hypothyroidism with Thyroxine Replacement Therapy Prevent Nephropathy/Chronic Renal Disease?

PubMed

Aziz, Kamran M A

2016-01-01

Untreated or sub-clinical hypothyroidism is associated with insulin resistance, obesity, adverse effects on cardiovascular system, hypertension and in turn risk of nephropathy. However, these changes are reversible with thyroxine replacement therapy (TRT). Current research studied 4235 diabetic patients, divided into two groups, those with clinical hypothyroidism /on TRT, compared to those without thyroid disease or undiagnosed. BMI, blood pressure, creatinine, urine microalbumin and spot urine protein levels were compared between these two groups. Study finding demonstrated that for hypothyroid cases, BMI was higher (32.2 ± 7.44 versus 29.4 ± 5.7; p < 0.0001), serum creatinine was on lower levels (0.75 ± 0.27 versus 1.0 ± 0.74; p = 0.001), systolic BP was on lower side (123.7 ± 15.9 versus 128.13 ± 16.8; p= 0.015); spot urine microalbumin was on lower side (52.58 ± 71.65; versus 87.77 ± 140.86; p=0.010) and spot urine protein had lower levels (25.3 ± 38.3 versus 44.28 ± 123.58; p < 0.0001). Current research also demonstrated that Pearson`s x2 and odds/protective odds for hypothyroidism (on TRT) was strongly associated with obesity (p <0.0001; odds ratio 2.28, 95% CI 1.47 to 3.56). However, they were protected from HTN (p= 0.272; protective odds ratio 1.28, 95%CI 0.824 to 1.98), nephropathy (p=0.386; protective odds 1.36, 95% CI 0.861 to 2.14) and chronic renal disease (p= 0.112; protective odds 3.42, 95% CI 0.83 to 14.13). In conclusion, TRT itself has protective effects on cardiovascular and renal system. Hence, thyroid screening is essential among diabetics to detect sub clinical or clinical hypothyroidism.

Effects of estradiol, estrogen receptor subtype-selective agonists and genistein on glucose metabolism in leptin resistant female Zucker diabetic fatty (ZDF) rats.

PubMed

Weigt, Carmen; Hertrampf, Torsten; Flenker, Ulrich; Hülsemann, Frank; Kurnaz, Pinar; Fritzemeier, Karl Heinrich; Diel, Patrick

2015-11-01

The leptin resistant Zucker diabetic fatty (ZDF) rats are hyperphagic and become obese, but whereas the males develop type 2 diabetes mellitus (T2DM), the females remain euglycaemic. As estrogen deficiency is known to increase the risk of developing T2DM, we evaluated the role of ER subtypes alpha and beta in the development of glucose tolerance in leptin resistant ovariectomized (OVX) ZDF rats. At least six rats per group were treated with either vehicle (OVX), 17β-estradiol (E2), ER subtype-selective agonists (Alpha and Beta), or genistein (Gen) for 17 weeks. At the end of the treatment period a glucose tolerance assay was performed and the metabolic flux of (13)C-glucose for the E2 group was investigated. OVX ZDF rats treated with E2, Alpha, Beta, and Gen tolerated the glucose significantly better than untreated controls. E2 treatment increased absorbance/flux of (13)C-glucose to metabolic relevant tissues such liver, adipose tissue, gastrocnemius, and soleus muscle. Moreover, whereas Alpha treatment markedly increased mRNA expression of GLUT4 in gastrocnemius muscle, Beta treatment resulted in the largest fiber sizes of the soleus muscle. Treatment with Gen increased both the mRNA expression of GLUT 4 and the fiber sizes in the skeletal muscle. In addition, E2 and Alpha treatment decreased food intake and body weight gain. In summary, estrogen-improved glucose absorption is mediated via different molecular mechanisms: while activation of ER alpha seems to stimulate muscular GLUT4 functionality, activation of ER beta results in a hypertrophy of muscle fibers. In addition, selective activation of ER alpha decreased food intake and body weight gain. Our data further indicate that ER subtype-selective agonists and genistein improve systemic glucose tolerance also in the absence of a functional leptin signaling pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phoenix dactylifera seeds ameliorate early diabetic complications in streptozotocin-induced diabetic rats.

PubMed

Abdelaziz, Dalia H A; Ali, Sahar A; Mostafa, Mahmoud M A

2015-06-01

In Arabic folk medicine, the seeds of Phoenix dactylifera L. (Arecaceae) have been used to manage diabetes for many years. Few studies have reported the antidiabetic effect of P. dactylifera seeds; however, their effect on diabetic complications is still unexplored. The present study investigates the protective effect of P. dactylifera seeds against diabetic complications in rats. The aqueous suspension of P. dactylifera seeds (aqPDS) (1 g/kg/d) was orally administered to streptozotocin-induced diabetic rats for 4 weeks. The serum biochemical parameters were assessed spectrophotometrically. Furthermore, oxidative stress was examined in both liver and kidney tissues by assessment of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), reduced glutathione, superoxide dismutase (SOD), glutathione S-transferase, and catalase. Oral administration of aqPDS significantly ameliorated the elevated levels of glucose (248 ± 42 versus 508 ± 60 mg/dl), urea (32 ± 3.3 versus 48.3 ± 5.6 mg/dl), creatinine (2.2 ± 0.35 versus 3.8 ± 0.37 mg/dl), ALT (29.6 ± 3.9 versus 46.4 ± 5.9 IU/l), and AST (73.3 ± 13 versus 127.8 ± 18.7 IU/l) compared with the untreated diabetic rats. In addition to significant augmentation in the activities of antioxidant enzymes, there was reduction in TBARS and NO levels and improvement of histopathological architecture of the liver and kidney of diabetic rats. The aqPDS showed potential protective effects against early diabetic complications of both liver and kidney. This effect may be explained by the antioxidant and free radical scavenging capabilities of P. dactylifera seeds.

Bias from historical control groups used in orthodontic research: a meta-epidemiological study.

PubMed

Papageorgiou, Spyridon N; Koretsi, Vasiliki; Jäger, Andreas

2017-02-01

The validity of meta-analysis is dependent upon the quality of included studies. Here, we investigated whether the design of untreated control groups (i.e. source and timing of data collection) influences the results of clinical trials in orthodontic research. This meta-epidemiological study used unrestricted literature searching for meta-analyses in orthodontics including clinical trials with untreated control groups. Differences in standardized mean differences (ΔSMD) and their 95% confidence intervals (CIs) were calculated according to the untreated control group through multivariable random-effects meta-regression controlling for nature of the interventional group and study sample size. Effects were pooled with random-effects synthesis, followed by mixed-effect subgroup and sensitivity analyses. Studies with historical control groups reported deflated treatment effects compared to studies with concurrent control groups (13 meta-analyses; ΔSMD = -0.31; 95% CI = -0.53, -0.10; P = 0.004). Significant differences were found according to the type of historical control group (based either on growth study or clinical archive; 11 meta-analyses; ΔSMD = 0.40; 95% CI = 0.21, 0.59; P < 0.001). The use of historical control groups in orthodontic clinical research was associated with deflation of treatment effects, which was independent from whether the interventional group was prospective or retrospective and from the study's sample size. Caution is warranted when interpreting clinical studies with historical untreated control groups or when interpreting systematic reviews that include such studies. PROSPERO (CRD42015024179). None. © The Author 2016. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Grape seed extract has superior beneficial effects than vitamin E on oxidative stress and apoptosis in the hippocampus of streptozotocin induced diabetic rats.

PubMed

Yonguc, Goksin Nilufer; Dodurga, Yavuz; Adiguzel, Esat; Gundogdu, Gulsah; Kucukatay, Vural; Ozbal, Seda; Yilmaz, Ismail; Cankurt, Ulker; Yilmaz, Yusuf; Akdogan, Ilgaz

2015-01-25

We aimed to investigate the effects of grape seed extract (GSE) and vitamin E (Vit E) on oxidative stress and apoptosis in the hippocampus of streptozotocin-induced diabetic rats. In Control, Diabetic, and Diabetic treated with GSE (Diabetic+GSE) and vitamin E (Diabetic+Vit E) groups, oxidative stress index (OSI), TUNEL staining and Bcl-2, Bcl-XL, Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB gene expressions were evaluated. OSI was significantly increased in the plasma and hippocampus of the Diabetic compared to Control group and decreased in Diabetic+GSE and Diabetic+Vit E groups compared to Diabetic. TUNEL positive neurons significantly increased in the hippocampus of the Diabetic group compared to Control and decreased in Diabetic+GSE (more prominently) and Diabetic+Vit E groups compared to Diabetic. In the hippocampus of the Diabetic group, Bcl-2 and Bcl-XL gene expressions were significantly decreased; Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB gene expressions were significantly increased compared to Control. In Diabetic+GSE and Diabetic+Vit E groups, Bcl-2 gene expressions were significantly increased; Bcl-XL gene expressions did not differ compared to the Diabetic group. The expression of Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB genes in the Diabetic+GSE group and the expression of caspase-3 and -9, TNF-α, and NF-κB genes in the Diabetic+Vit E group were significantly decreased compared to Diabetic. In conclusion, GSE (more prominently) and vitamin E decreased oxidative stress and neuronal apoptosis occurring in the hippocampus of diabetic rats. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of tick infestation and tick-borne disease infections (heartwater, anaplasmosis and babesiosis) on the lactation and weight gain of Mashona cattle in south-eastern Zimbabwe.

PubMed

Meltzer, M I; Norval, R A; Donachie, P L

1995-08-01

The effects of ticks and tick-borne disease infections on the lactation and weight gain of Mashona cattle were studied at Mbizi Quarantine Station in the south-eastern lowveld of Zimbabwe. Twenty-nine Mashona cows were allocated to 2 balanced groups and kept in separate paddocks at a stocking rate of one animal per 8 ha. One group received regular acaricide treatment to control bont (Amblyomma hebraeum) and other ticks. The other group was left untreated. The cows were artificially inseminated. The acaricide-treated cows and calves were essentially tick free throughout the experiment, while the untreated cows and calves were continuously tick infested. There was a drought-related decline in tick infestations in the second year of the experiment. Antibodies to Cowdria ruminantium, Babesia bigemina and Anaplasma marginale were detected in cows and calves from both groups, though the untreated group had significantly higher titres to C. ruminantium (P < 0.001). The total, measured amount of milk suckled by untreated calves was significantly more than treated calves (273 kg vs. 241 kg, P < or = 0.05). By interpolating between the twice weekly measurements, it was calculated that over the entire lactation untreated calves suckled an average of 935 kg/hd vs. 837 kg/hd for the treated group. There were no statistical differences in the weights of the 2 groups of calves at birth, weaning, 180 and 210 days post partum (P < 0.05). For cows, there were no statistically significant differences in gestation periods (288 vs. 279 days), reconception rates or weight patterns over time (P < 0.05). The results show that intensive acaricide treatment in areas of Zimbabwe where heartwater is enzootically stable is uneconomical. The maintenance of enzootic stability for tick-borne diseases through minimal tick control is clearly a more economic and practical control option.

Frequency of ABO/Rhesus Blood Groups in Patients with Diabetes Mellitus.

PubMed

Oner, Can; Dogan, Burcu; Telatar, Berrin; Celik Yagan, Canan Fidan; Oguz, Aytekin

2016-01-01

The correlation between ABO/Rh blood groups and diabetes mellitus is still controversial. The aim of this study was to determine the relationship between ABO/Rhesus blood groups and diabetes in Turkish population. This cross-sectional study was conducted in Istanbul Medeniyet University Göztepe Education and Training Hospital's Diabetes Units. The study group was composed of 421 patients with type-1 diabetes, 484 patients with type-2 diabetes and 432 controls. Blood samples were collected and tested for ABO/Rhesus blood groups. Data was analyzed by SPSS version 17.0. A significant association was found between blood groups and diabetes mellitus. The frequency of AB blood group was significantly higher in type-1 diabetics; and A blood group was significantly higher in type-2 diabetics. Furthermore, Rh negativity were significantly more frequent in type-2 diabetics.

Depression, anxiety and self-care behaviours of young adults with Type 2 diabetes: results from the International Diabetes Management and Impact for Long-term Empowerment and Success (MILES) Study.

PubMed

Browne, J L; Nefs, G; Pouwer, F; Speight, J

2015-01-01

Young adults with Type 2 diabetes have higher physical morbidity and mortality than other diabetes sub-groups, but differences in psychosocial outcomes have not yet been investigated. We sought to compare depression and anxiety symptoms and self-care behaviours of young adults with Type 2 diabetes with two matched control groups. Using cross-sectional survey data from the Australian and Dutch Diabetes Management and Impact for Long-term Empowerment and Success (MILES) studies, we matched 93 young adults (aged 18-39 years) with Type 2 diabetes (case group) with: (i) 93 older adults ( ≥ 40 years) with Type 2 diabetes (Type 2 diabetes control group; matched on country, gender, education, diabetes duration and insulin use) and (ii) 93 young adults with Type 1 diabetes (Type 1 diabetes control group; matched on country, gender, age and education). Groups were compared with regard to depression symptoms (nine-item Patient Health Questionnaire), anxiety symptoms (seven-item Generalised Anxiety Disorder questionnaire) and frequency of selected self-care behaviours (single item per behaviour). Participants in the case group had higher depression scores (Cohen's d = 0.40) and were more likely to have clinically meaningful depressive symptoms (Cramer's V = 0.23) than those in the Type 2 diabetes control group. Participants in the case group had statistically equivalent depression scores to the Type 1 diabetes control group. The groups did not differ in anxiety scores. Those in the case group were less likely than both control groups to take insulin as recommended (Cramer's V = 0.24-0.34), but there were no significant differences between the groups in oral medication-taking. The case group were less likely than the Type 2 diabetes control group to eat healthily (Cramer's V = 0.16), and less likely than the Type 1 diabetes control group to be physically active (Cramer's V = 0.15). Our results suggest that Type 2 diabetes is as challenging as Type 1 diabetes for young adults and more so than for older adults. Young adults with Type 2 diabetes may require more intensive psychological and self-care support than their older counterparts. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Antibacterial and residual antimicrobial activities against Enterococcus faecalis biofilm: A comparison between EDTA, chlorhexidine, cetrimide, MTAD and QMix

NASA Astrophysics Data System (ADS)

Zhang, Rui; Chen, Min; Lu, Yan; Guo, Xiangjun; Qiao, Feng; Wu, Ligeng

2015-08-01

We compared the antibacterial and residual antimicrobial activities of five root canal irrigants (17% EDTA,2% chlorhexidine,0.2% cetrimide, MTAD, and QMix) in a model of Enterococcus faecalis biofilm formation. Sixty dentin blocks with 3-week E. faecalis biofilm were divided into six equal groups and flushed with irrigant for 2 min or left untreated. A blank control group was also established. Antibacterial activities of the irrigants were evaluated by counting colony forming units. To test residual antimicrobial activities, 280 dentin blocks were divided into seven equal groups and flushed with irrigant for 2 min or left untreated and then incubated with E. faecalis suspension for 48 h, or used as a blank. No bacteria were observed in the blank control group. The number of viable E. faecalis was significantly fewer in the irrigant-treated groups compared with the untreated control (P < 0.05). Among the five irrigants, QMix had the strongest antibacterial activity. Residual antimicrobial activities of CHX were significantly higher at 12 h, 24 h and 36 h compared to untreated control (P < 0.05). All five root canal irrigants were effective to some extent against E. faecalis, but QMix and CHX had the strongest, and CHX the longest (up to 36 h), antimicrobial activity.

The prevalence of hypertension in the Indian population of Durban.

PubMed

Seedat, Y K; Seedat, M A; Reddy, K

1978-07-01

In a random house-to-house study of 1 000 Indians the prevalence of essential hypertension according to the World Health Organization (WHO) criteria was 19% (females 22%; males 15%). The study revealed that the prevalence of hypertension was higher than in published data from India. Ethnicity in our study caused a significant variation in prevalence. Prevalence was lower than in our urban Zulu study. Blood pressure rose with age, but there was a greater rise in systolic than in diastolic blood pressure. Prevalence in males and females under 40 years were equal. There was an association between hypertension and diabetes mellitus. More effective screening and therapeutic programmes should be initiated in the Indian population because of the high prevalence of hypertension which may lead to complications if untreated, and because 58% of the hypertensive subjects were untreated or had discontinued therapy.

The properties of red seaweed (Kappaphycus alvarezii) and its effect on mammary carcinogenesis.

PubMed

Chang, Vi-Sion; Okechukwu, Patrick N; Teo, Swee-Sen

2017-03-01

The edible red seaweed (Kappaphycus alvarezii) is one of the algae species which was found to be rich in nutrients and nutraceutical. Hence, K. alvarezii may have the ability to suppress cancer through its antiproliferative properties. The aim of this study was to investigate the potential compounds of K. alvarezii, cytotoxicity properties of K. alvarezii extract on breast cancer cell line (MCF-7), investigated toxicity effect of high dosage K. alvarezii extract in rats and determined the effect of K. alvarezii on 7, 12-dimethylbenz[a]anthracene (DMBA) mammary carcinogenesis in rats. The method of LCMS/MS and MTT assay were used. For animal study, sub-chronic toxicity method was used, the rats were supplemented with 2000mg/kg body weight daily of K. alvarezii crude extracts by oral gavage. For the anticancer effect of K. alvarezii crude extracts, this study consisted of three groups of the experimental, untreated and normal group of rats. The experimental and untreated groups of rats were induced with mammary tumour with DMBA. The experimental group of rats was given with K. alvarezii crude extracts orally. The results were being used to compare with the untreated group of rats and normal group of rats. All the rats were fed with standard diet and water ad libitum. Mortality, behavior changes and tumour sizes were observed specifically. The differences between the three groups of rats were evaluated by using the ANOVA test. By using LCMS/MS method, six unknown compounds were analysed. K. alvarezii crude extract reduced the cell viability of MCF-7 from 84.91% to 0.81% and the IC 50 value is 4.1±0.69mg/mL. For sub-chronic and heavy metal toxicity studies, no significant difference was found in haematological and biochemical values of the control group and experimental group. The growth rate of tumours in the untreated group of rats was found significantly higher than the experimental group of rats. Besides that, the white blood cells level in untreated group was found significantly higher than the experimental group and the normal group. In conclusion, K. alvarezii extract might able to slow down the growth rate of the tumour cells, therefore, identification of an active compound of inhibition growth rate of the tumour cells can be positively carried out in the future. Copyright © 2016. Published by Elsevier Masson SAS.

Tempol prevents altered K(+) channel regulation of afferent arteriolar tone in diabetic rat kidney.

PubMed

Troncoso Brindeiro, Carmen M; Lane, Pascale H; Carmines, Pamela K

2012-03-01

Experiments were performed to test the hypothesis that oxidative stress underlies the enhanced tonic dilator impact of inward-rectifier K(+) channels on renal afferent arterioles of rats with streptozotocin-induced diabetes mellitus. Sham and diabetic rats were left untreated or provided Tempol in their drinking water for 26±1 days, after which afferent arteriolar lumen diameter and its responsiveness to K(+) channel blockade were measured using the in vitro blood-perfused juxtamedullary nephron technique. Afferent diameter averaged 19.4±0.8 μm in sham rats and 24.4±0.8 μm in diabetic rats (P<0.05). The decrease in diameter evoked by Ba(2+) (inward-rectifier K(+) channel blocker) was 3 times greater in diabetic rats than in sham rats. Glibenclamide (K(ATP) channel blocker) and tertiapin-Q (Kir1.1/Kir3.x channel blocker) decreased afferent diameter in diabetic rats but had no effect on arterioles from sham rats. Chronic Tempol treatment prevented diabetes mellitus-induced increases in both renal vascular dihydroethidium staining and baseline afferent arteriolar diameter. Moreover, Tempol prevented the exaggeration of afferent arteriolar responses to Ba(2+), tertiapin-Q, and glibenclamide otherwise evident in diabetic rats. Preglomerular microvascular smooth muscle cells expressed mRNA encoding Kir1.1, Kir2.1, and Kir6.1. Neither diabetes mellitus nor Tempol altered Kir1.1, Kir2.1, Kir6.1, or SUR2B protein levels in renal cortical microvessels. To the extent that the effects of Tempol reflect its antioxidant actions, our observations indicate that oxidative stress contributes to the exaggerated impact of Kir1.1, Kir2.1, and K(ATP) channels on afferent arteriolar tone during diabetes mellitus and that this phenomenon involves posttranslational modulation of channel function.

Effects of streptozotocin-induced diabetes on bladder and erectile (dys)function in the same rat in vivo.

PubMed

Christ, George J; Hsieh, Yi; Zhao, Weixin; Schenk, Gregory; Venkateswarlu, Karicheti; Wang, Hong-Zhan; Tar, Moses T; Melman, Arnold

2006-05-01

To establish the methods, feasibility and utility of evaluating the impact of diabetes on bladder and erectile function in the same rat, as more than half of diabetic patients have bladder dysfunction, and half of diabetic men have erectile dysfunction, but the severity of coincident disease has not been rigorously assessed. In all, 16 F-344 rats had diabetes induced by streptozotocin (STZ), and were divided into insulin-treated (five) and untreated (11), and compared with age-matched controls (10), all assessed in parallel. All STZ rats were diabetic for 8-11 weeks. Cystometric studies were conducted on all rats, with cavernosometric studies conducted on a subset of rats. There were insulin-reversible increases in the following cystometric variables; bladder weight, bladder capacity, micturition volume, residual volume, micturition pressure and spontaneous activity (P < 0.05, in all, one-way analysis of variance, anova). Cavernosometry showed a diabetes-related, insulin-reversible decline in the cavernosal nerve-stimulated intracavernosal pressure (ICP) response at all levels of current stimulation (P < 0.05, in all one-way anova). Plotting erectile capacity (i.e. ICP) against bladder capacity showed no correlation between the extent of the decline in erectile capacity and the magnitude of the increase in bladder capacity. These studies extend previous work to indicate that the extent of diabetes-related bladder and erectile dysfunction can vary in the same rat. As such, these findings highlight the importance of evaluating the impact of diabetes on multiple organ systems in the lower urinary tract. Future studies using this model system should lead to a better understanding of the initiation, development, progression and coincidence of these common diabetic complications.

DNA-protective effects of quercetin or naringenin in alloxan-induced diabetic mice.

PubMed

Oršolić, Nada; Gajski, Goran; Garaj-Vrhovac, Vera; Dikić, Domagoj; Prskalo, Zvjezdana Špacir; Sirovina, Damir

2011-04-10

Diabetes mellitus is associated with a high production of reactive oxygen species, which may cause oxidative DNA damage. High levels of genomic damage have been associated with liver and renal failure as well as immune-system decline. Flavonoids are effective antioxidants and may protect against several chronic diseases including diabetes. This study used the comet assay to assess the levels of DNA damage in the blood, liver and kidney cells in untreated and quercetin (QU) or naringenin treated diabetic mice. In addition, the study was designed to establish whether QU or naringenin might have a biological effect in protecting diabetic mice against oxidative stress by using survival studies to observe total body injury at the level of the organism. QU or naringenin were injected to mice intraperitoneally (i.p.) at a dose of 50mg/kg for 7days starting 2days after a single dose (75mg/kg, i.v.) alloxan injection. These findings suggest that QU or naringenin treatment resulted in a significant increase in the body weight, the haematological and immunological parameters of blood, as well as leading to 100% survival of diabetic mice. The tested flavonoids have protective effects against alloxan-induced DNA-damage in peripheral lymphocytes but not in the liver and kidney cells of diabetic mice. It might be hypothesised that diabetic mice with a high intake of flavonoid-rich foods, and specifically foods rich in quercetin or naringenin, might be relatively protected against long-term complications of diabetes due to decreased oxidative stress. Various co-operative and synergistic action mechanisms of the tested flavonoids may lead to the protection of the whole organism against diabetes. Copyright © 2011 Elsevier B.V. All rights reserved.

Glyoxal administration induces formation of high molecular weight aggregates of hemoglobin exhibiting amyloidal nature in experimental rats: An in vivo study.

PubMed

Banerjee, Sauradipta; Chakraborti, Abhay Sankar

2016-12-01

Glyoxal, a highly reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs). In the present study, we have investigated the effect of glyoxal on experimental rat hemoglobin in vivo after external administration of the α-dicarbonyl compound in animals. Gel electrophoretic profile of hemolysate collected from glyoxal-treated rats (32mg/kg body wt. dose) after one week exhibited the presence of some high molecular weight protein bands that were found to be absent for control, untreated rats. Mass spectrometric and absorption studies indicated that the bands represented hemoglobin. Further studies revealed that the fraction exhibited the presence of intermolecular cross β-sheet structure. Thus glyoxal administration induces formation of high molecular weight aggregates of hemoglobin with amyloid characteristics in rats. Aggregated hemoglobin fraction was found to exhibit higher stability compared to glyoxal-untreated hemoglobin. As evident from mass spectrometric studies, glyoxal was found to modify Arg-30β and Arg-31α of rat hemoglobin to hydroimidazolone adducts. The modifications thus appear to induce amyloid-like aggregation of hemoglobin in rats. Considering the increased level of glyoxal in diabetes mellitus as well as its high reactivity, the above findings may be physiologically significant. Copyright © 2016 Elsevier B.V. All rights reserved.

Treatment with specific soluble factors promotes the functional maturation of transcription factor-mediated, pancreatic transdifferentiated cells.

PubMed

Motoyama, Hiroaki; Kobayashi, Akira; Yokoyama, Takahide; Shimizu, Akira; Sakai, Hiroshi; Notake, Tsuyoshi; Fukushima, Kentaro; Miyagawa, Shin-Ichi

2018-01-01

Pancreatic lineage-specific transcription factors (TFs) display instructive roles in converting adult cells to endocrine pancreatic cells through a process known as transdifferentiation. However, little is known about potential factors capable of accelerating transdifferentiation following transduction to achieve the functional maturation of transdifferentiated cells. In this study, we demonstrated, using adult liver-derived progenitor cells, that soluble factors utilized in pancreatic differentiation protocols of pluripotent stem cells promote functional maturation of TFs-mediated transdifferentiated cells. Treatment with an N2 supplement in combination with three soluble factors (glucagon-like peptide-1 [GLP-1] receptor agonist, notch inhibitor, and transforming growth factor-β [TGF-β] inhibitor) enhanced liver-to-pancreas transdifferentiation based on the following findings: i) the incidence of c-peptide-positive cells increased by approximately 1.2-fold after the aforementioned treatment; ii) the c-peptide expression level in the treated cells increased by approximately 12-fold as compared with the level in the untreated cells; iii) the treated cells secreted insulin in a glucose-dependent manner, whereas the untreated cells did not; and iv) transplantation of treated-transdifferentiated cells into streptozotocin-induced immunodeficient diabetic mice led to the amelioration of hyperglycemia. These results suggest that treatment with specific soluble factors promotes the functional maturation of transdifferentiated cells. Our findings could facilitate the development of new modalities for cell-replacement therapy for patients with diabetes.

Effect of positive airway pressure therapy on seizure control in patients with epilepsy and obstructive sleep apnea.

PubMed

Pornsriniyom, Darakul; Kim, Hu won; Bena, James; Andrews, Noah D; Moul, Douglas; Foldvary-Schaefer, Nancy

2014-08-01

Previous studies suggest that treatment for obstructive sleep apnea (OSA) in patients with epilepsy can improve seizure control. We investigated the effect of positive airway pressure (PAP) therapy on seizures in adults with epilepsy referred to the Cleveland Clinic for polysomnography (PSG) from 1997 to 2010. Seizure outcome at baseline and 1 year later was compared in patients with no OSA (apnea-hypopnea index [AHI] <5), patients with PAP-treated OSA, and patients with untreated OSA. One hundred thirty-two subjects (age: 40.2±13 (18-76) years, 65.4% female) were included. Seventy-six (57.6%) subjects had OSA; of these, 43 (56.6%) were on PAP therapy, and 33 (43.4%) were not on PAP therapy (either PAP-intolerant or refused therapy). Of the group with PAP-treated OSA, 83.7% were adherent (use ≥4 h/night at least 5 nights/week). The percentage of subjects with ≥50% seizure reduction and the mean percentage of seizure reduction were significantly greater in the group with PAP-treated OSA (73.9%; 58.5%) than in subjects with untreated OSA (14.3%; 17.0%). There were significantly more subjects with successful outcomes (with ≥50% seizure reduction or seizure-free at both baseline and follow-up) in the group with PAP-treated OSA (83.7%) than in the groups with no OSA (53.6%) and untreated OSA (39.4%). After adjusting for age, gender, body mass index, AHI, and epilepsy duration, we found that the odds of successful outcomes in subjects in the group with PAP-treated OSA were 9.9 and 3.91 times those of the groups with untreated OSA and no OSA, respectively. The group with PAP-treated OSA had 32.3 times the odds of having a ≥50% seizure reduction compared with the group with untreated OSA and 6.13 times compared with the group with no OSA. Positive airway pressure therapy appears to produce beneficial effects on seizures in adult patients with epilepsy and OSA. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of the effects of glimepiride (Amaryl) and repaglinide (novoNorm) on atherosclerosis progression in high cholesterol-fed male rabbits

PubMed Central

Hadi, Najah R.; Al-Amran, Fadhil; Hussein, Mohammad A. A.; Rezeg, Fadhil A.

2012-01-01

Background: Atherosclerosis is an inflammatory disease of the blood vessel wall, characterized in early stages by endothelial dysfunction, recruitment and activation of monocyte/macrophages. Glimepiride is one of the third generation sulphonylurea drugs, useful for control of diabetes mellitus type two and it may exert anti inflammatory activity, by induction of nitric oxide production or through selective suppression of the cyclooxygenase pathway. Repaglinide is a new hypoglycemic agent, and a member of the carbamoylmethyl benzoic acid family. Some results from the literature demonstrate that repaglinide has favorable effects on the parameters of antioxidative balance. Objectives: The objective of the present study was to assess the effect of glimepiride and repaglinide on atherosclerosis via interfering with the inflammatory and oxidative pathways. Materials and Methods: Twenty four local domestic male rabbits were involved in this study. The animals were randomly divided into four groups; Group I rabbits fed normal chow (oxiod) diet for 10 weeks. Group II rabbits were fed with 1% cholesterol enriched diet. Group III rabbits were fed with 1% cholesterol enriched diet together with Glimepiride (0.1 mg/kg once daily before morning feed). Group IV rabbits were fed with 1% cholesterol enriched diet together with Repaglinide (0.3 mg/kg once daily before morning feed). Blood samples were collected before (0 time) and every two weeks of experimental diets for measurement of serum triglycerides (TG), total cholesterol (TC), High-density lipoprotein cholesterol (HDL-C), high sensitive C - reactive protein (hsCRP), Interleukin – 6 (IL-6) and Tumor Necrosis Factor alpha (TNF-α) levels. At the end of 10 weeks, the aorta was removed for measurement of aortic Malondialdehyde (MDA), reduced glutathione (GSH) and aortic intimal thickness. Results: Glimepiride and repaglinide treatment did show significant effect on lipid parameters compared with induced untreated group (P < 0.05). Also, they significantly reduced the elevation in hsCRP, IL-6, TNF-α, aortic MDA and aortic intimal thickness compared with induced untreated group (P < 0.05), and they helped to restore the aortic GSH levels (P < 0.05). Conclusions: Glimepiride and repaglinide may reduce atherosclerosis progression in hypercholesterolemic rabbits by interfering with the inflammatory and oxidative pathways without affecting lipid parameters. PMID:22346138

Meglumine exerts protective effects against features of metabolic syndrome and type II diabetes.

PubMed

Bravo-Nuevo, Arturo; Marcy, Alice; Huang, Minzhou; Kappler, Frank; Mulgrew, Jennifer; Laury-Kleintop, Lisa; Reichman, Melvin; Tobia, Annette; Prendergast, George C

2014-01-01

Metabolic syndrome, diabetes and diabetes complications pose a growing medical challenge worldwide, accentuating the need of safe and effective strategies for their clinical management. Here we present preclinical evidence that the sorbitol derivative meglumine (N-methyl-D-glucamine) can safely protect against several features of metabolic syndrome and diabetes, as well as elicit enhancement in muscle stamina. Meglumine is a compound routinely used as an approved excipient to improve drug absorption that has not been ascribed any direct biological effects in vivo. Normal mice (SV129) administered 18 mM meglumine orally for six weeks did not display any gastrointestinal or other observable adverse effects, but had a marked effect on enhancing muscle stamina and at longer times in limiting weight gain. In the established KK.Cg-Ay/J model of non-insulin dependent diabetes, oral administration of meglumine significantly improved glycemic control and significantly lowered levels of plasma and liver triglycerides. Compared to untreated control animals, meglumine reduced apparent diabetic nephropathy. Sorbitol can improve blood glucose uptake by liver and muscle in a manner associated with upregulation of the AMPK-related enzyme SNARK, but with undesirable gastrointestinal side effects not seen with meglumine. In murine myoblasts, we found that meglumine increased steady-state SNARK levels in a dose-dependent manner more potently than sorbitol. Taken together, these findings provide support for the clinical evaluation of meglumine as a low-cost, safe supplement offering the potential to improve muscle function, limit metabolic syndrome and reduce diabetic complications.

Meglumine Exerts Protective Effects against Features of Metabolic Syndrome and Type II Diabetes

PubMed Central

Bravo-Nuevo, Arturo; Marcy, Alice; Huang, Minzhou; Kappler, Frank; Mulgrew, Jennifer; Laury-Kleintop, Lisa; Reichman, Melvin; Tobia, Annette; Prendergast, George C.

2014-01-01

Metabolic syndrome, diabetes and diabetes complications pose a growing medical challenge worldwide, accentuating the need of safe and effective strategies for their clinical management. Here we present preclinical evidence that the sorbitol derivative meglumine (N-methyl-D-glucamine) can safely protect against several features of metabolic syndrome and diabetes, as well as elicit enhancement in muscle stamina. Meglumine is a compound routinely used as an approved excipient to improve drug absorption that has not been ascribed any direct biological effects in vivo. Normal mice (SV129) administered 18 mM meglumine orally for six weeks did not display any gastrointestinal or other observable adverse effects, but had a marked effect on enhancing muscle stamina and at longer times in limiting weight gain. In the established KK.Cg-Ay/J model of non-insulin dependent diabetes, oral administration of meglumine significantly improved glycemic control and significantly lowered levels of plasma and liver triglycerides. Compared to untreated control animals, meglumine reduced apparent diabetic nephropathy. Sorbitol can improve blood glucose uptake by liver and muscle in a manner associated with upregulation of the AMPK-related enzyme SNARK, but with undesirable gastrointestinal side effects not seen with meglumine. In murine myoblasts, we found that meglumine increased steady-state SNARK levels in a dose-dependent manner more potently than sorbitol. Taken together, these findings provide support for the clinical evaluation of meglumine as a low-cost, safe supplement offering the potential to improve muscle function, limit metabolic syndrome and reduce diabetic complications. PMID:24587200

Prognosis and treatment of diabetic nephropathy: Recent advances and perspectives.

PubMed

Rossing, Peter; Persson, Frederik; Frimodt-Møller, Marie

2018-04-01

Approximately 20 to 40% of patients with type 1 or type 2 diabetes develop diabetic kidney disease. It is a clinical syndrome characterized by persistent albuminuria (>300mg/24h, or 300mg/g creatinine), a relentless decline in glomerular filtration rate, raised arterial blood pressure and enhanced cardiovascular morbidity and mortality. The natural course of classical diabetic nephropathy is initially microalbuminuria or moderately increased urine albumin excretion (30-300mg/g creatinine). Untreated microalbuminuria may then rise gradually, reaching severely increased albuminuric (macroalbuminuria) over 5 to 15 years. Glomerular filtration rate then begins to decline and end-stage renal failure is reached without treatment in 5 to 7 years. Regular, systematic screening for diabetic kidney disease is needed to identify patients at risk for, or with presymptomatic stages of diabetic kidney disease. Multifactorial intervention targeting glucose, lipids and blood pressure including blockade of renin angiotensin system and lifestyle, has improved renal and cardiovascular prognosis and reduced mortality with 50%. Recent data suggest beneficial pleiotropic effects on renal endpoint with new glucose lowering agents. It is also being investigated if blocking aldosterone could be an option as a potential new treatment. Thus, although diabetic nephropathy remains a major burden, prognosis has improved and new options for further improvements are currently tested in phase 3 clinical renal outcome studies. Copyright © 2018 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

Adipose-derived stem cells seeded in Pluronic F-127 hydrogel promotes diabetic wound healing.

PubMed

Kaisang, Lin; Siyu, Wang; Lijun, Fan; Daoyan, Pan; Xian, Cory J; Jie, Shen

2017-09-01

Chronic nonhealing wound is a multifactorial complication of diabetes that results specifically as a consequence of impaired angiogenesis and currently lacks in effective treatments. Although a stem cell-based therapy may provide a novel treatment to augment diabetic wound healing, inferior cell survival at the diabetic skin wound is one of the key causes that are responsible for the low efficacy of the stem cell therapy. In this work, we used an injectable, biocompatible, and thermosensitive hydrogel Pluronic F-127 to encapsulate allogeneic nondiabetic adipose-derived stem cells (ADSCs) and topically applied the cells to a full-thickness cutaneous wound in the streptozotocin-induced diabetic model in rats. The cells seeded in the hydrogel enhanced angiogenesis (CD31 marker) and promoted the cell proliferation (Ki67 marker) at the wound site and significantly accelerated wound closure, which was accompanied by facilitated regeneration of granulation tissue. Consistently, levels of the messenger RNA expression of key angiogenesis growth factor, vascular endothelial growth factor, and key wound healing growth factor, transforming growth factor beta 1, were also upregulated in the cell-treated wounds when compared with untreated wounds. The results indicated that the transplantation of allogeneic ADSCs via the hydrogel improves the efficiency of cell delivery and optimizes the performance of ADSCs for augmenting diabetic wound healing. In conclusion, this ADSC-based therapy may provide a novel therapeutic strategy for the treatment of nonhealing diabetic foot ulcers. Copyright © 2017 Elsevier Inc. All rights reserved.

Biomarker Evidence of Axonal Injury in Neuroasymptomatic HIV-1 Patients

PubMed Central

Price, Richard W.; Hagberg, Lars; Fuchs, Dietmar; Rosengren, Lars; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

2014-01-01

Background Prevalence of neurocognitive impairment in HIV-1 infected patients is reported to be high. Whether this is a result of active HIV-related neurodegeneration is unclear. We examined axonal injury in HIV-1 patients by measuring the light subunit of neurofilament protein (NFL) in CSF with a novel, sensitive method. Methods With a cross-sectional design, CSF concentrations of neurofilament protein light (NFL) (marker of neuronal injury), neopterin (intrathecal immunoactivation) and CSF/Plasma albumin ratio (blood-brain barrier integrity) were analyzed on CSF from 252 HIV-infected patients, subdivided into untreated neuroasymptomatics (n = 200), HIV-associated dementia (HAD) (n = 14) and on combinations antiretroviral treatment (cART) (n = 85), and healthy controls (n = 204). 46 HIV-infected patients were included in both treated and untreated groups, but sampled at different timepoints. Furthermore, 78 neuroasymptomatic patients were analyzed before and after treatment initiation. Results While HAD patients had the highest NFL concentrations, elevated CSF NFL was also found in 33% of untreated neuroasymptomatic patients, mainly in those with blood CD4+ cell counts below 250 cells/μL. CSF NFL concentrations in the untreated neuroasymptomatics and treated groups were equivalent to controls 18.5 and 3.9 years older, respectively. Neopterin correlated with NFL levels in untreated groups while the albumin ratio correlated with NFL in both untreated and treated groups. Conclusions Increased CSF NFL indicates ongoing axonal injury in many neuroasymptomatic patients. Treatment decreases NFL, but treated patients retain higher levels than controls, indicating either continued virus-related injury or an aging-like effect of HIV infection. NFL correlates with neopterin and albumin ratio, suggesting an association between axonal injury, neuroinflammation and blood-brain barrier permeability. NFL appears to be a sensitive biomarker of subclinical and clinical brain injury in HIV and warrants further assessment for broader clinical use. PMID:24523921

Antihyperglycemic activity of Piper betle leaf on streptozotocin-induced diabetic rats.

PubMed

Santhakumari, P; Prakasam, A; Pugalendi, K V

2006-01-01

Piper betle, an indigenous medicinal plant, has a folk (Siddha and Ayurvedha) reputation in the rural southern India. The present study was carried out to evaluate the effect of P. betle on glucose metabolism since it is consumed as betel-quid after meals. Plasma levels of glucose and glycosylated hemoglobin and activities of liver hexokinase and gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase in control and streptozotocin (STZ) diabetic rats were assayed. Oral administration of leaf suspension of P. betle (75 and 150 mg/kg of body weight) for 30 days resulted in significant reduction in blood glucose (from 205.00 +/- 10.80 mg/dL to 151.30 +/- 6.53 mg/dL) and glycosylated hemoglobin and decreased activities of liver glucose-6-phosphatase and fructose-1,6-bisphosphatase, while liver hexokinase increased (P < .05), in STZ diabetic rats when compared with untreated diabetic rats. P. betle at a dose of 75 mg/kg of body weight exhibited better sugar reduction than 150 mg/kg of body weight. In addition, protection against body weight loss of diabetic animals was also observed. The effects produced by P. betle were compared with the standard drug glibenclamide. Thus, the present study clearly shows that P. betle intake influences glucose metabolism beneficially.

Roles of polyuria and hyperglycemia in bladder dysfunction in diabetes.

PubMed

Xiao, Nan; Wang, Zhiping; Huang, Yexiang; Daneshgari, Firouz; Liu, Guiming

2013-03-01

Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats. A total of 72 female Sprague-Dawley® rats were divided into 6 groups, including age matched controls, and rats with sham urinary diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham urinary diversion, streptozotocin induced diabetes mellitus after urinary diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary diversion was performed by ureterovaginostomy 10 days before diabetes mellitus induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis induction. We measured 24-hour drinking and voiding volumes, and cystometry. Bladders were harvested to quantify smooth muscle, urothelium and collagen. We measured nitrotyrosine and Mn superoxide dismutase in the bladder. Diabetes and diuresis caused increases in drinking and voiding volume, and bladder weight. Bladder weight decreased in the urinary diversion group and the urinary diversion plus diabetes group. The intercontractile interval, voided volume and compliance increased in the diuresis and diabetes groups, decreased in the urinary diversion group and further decreased in the urinary diversion plus diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas increased in the diuresis and diabetes groups, and decreased in the urinary diversion and urinary diversion plus diabetes groups. As a percent of total tissue area, collagen decreased in the diuresis and diabetes groups, and increased in the urinary diversion and urinary diversion plus diabetes groups. Smooth muscle and urothelium decreased in the urinary diversion and urinary diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase increased in rats with diabetes and urinary diversion plus diabetes. Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may have a pathogenic role in late stage diabetic bladder dysfunction. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Successful treatment of refractory demodicosis and transient papules with a single dose of fluralaner in a dog with uncontrolled severe endocrine disease.

PubMed

Morita, Tatsushi; Momota, Yutaka; Mori, Akihiro; Oda, Hitomi; Ike, Kazunori; Sako, Toshinori

2018-04-27

A 12-year-old female Shih-Tzu with hyperadrenocorticism and hypothyroidism developed concurrent refractory generalized demodicosis that did not respond to doramectin treatment. Although amitraz treatment was effective, the dog developed severe diabetes, which resulted in the cessation of amitraz and trilostane. Attempts to control the diabetes were unsuccessful, and its hyperadrenocorticism was left untreated, leading to the recurrence of demodicosis. However, demodicosis went into complete remission with a single dose of fluralaner. Transient erythematous papules appeared on the trunk three days after the administration of fluralaner, but no other adverse reactions were noted. We demonstrated that fluralaner is a potent treatment for demodicosis, and skin eruptions are possible after the first dose of the drug.

Type 1 Diabetes in Young Rats Leads to Progressive Trabecular Bone Loss, Cessation of Cortical Bone Growth, and Diminished Whole Bone Strength and Fatigue Life

PubMed Central

Silva, Matthew J.; Brodt, Michael D.; Lynch, Michelle A.; McKenzie, Jennifer A.; Tanouye, Kristi M.; Nyman, Jeffry S.; Wang, Xiaodu

2009-01-01

People with diabetes have increased risk of fracture disproportionate to BMD, suggesting reduced material strength (quality). We quantified the skeletal effects of type 1 diabetes in the rat. Fischer 344 and Sprague-Dawley rats (12 wk of age) were injected with either vehicle (Control) or streptozotocin (Diabetic). Forelimbs were scanned at 0, 4, 8, and 12 wk using pQCT. Rats were killed after 12 wk. We observed progressive osteopenia in diabetic rats. Trabecular osteopenia was caused by bone loss: volumetric BMD decreased progressively with time in diabetic rats but was constant in controls. Cortical osteopenia was caused by premature arrest of cortical expansion: cortical area did not increase after 4–8 wk in diabetic rats but continued to increase in controls. Postmortem μCT showed a 60% reduction in proximal tibial trabecular BV/TV in diabetic versus control rats, whereas moments of inertia of the ulnar and femoral diaphysis were reduced ∼30%. Monotonic bending tests indicated that ulna and femora from diabetic animals were ∼25% less stiff and strong versus controls. Estimates of material properties indicated no changes in elastic modulus or ultimate stress but modest (∼10%) declines in yield stress for diabetic bone. These changes were associated with a ∼50% increase in the nonenzymatic collagen cross-link pentosidine. Last, cyclic testing showed diminished fatigue life in diabetic bones at the structural (force) level but not at the material (stress) level. In summary, type 1 diabetes, left untreated, causes trabecular bone loss and a reduction in diaphyseal growth. Diabetic bone has greatly increased nonenzymatic collagen cross-links but only modestly reduced material properties. The loss of whole bone strength under both monotonic and fatigue loading is attributed mainly to reduced bone size. PMID:19338453

Remodeling of the rat distal colon in diabetes: function and ultrastructure.

PubMed

Siegman, Marion J; Eto, Masumi; Butler, Thomas M

2016-01-15

This study seeks to define and explain remodeling of the distal colon in the streptozotocin (STZ)-treated rat model of diabetes through analysis of resting and active length dependence of force production, chemical composition, and ultrastructure. Compared with untreated controls, the passive stiffness on extension of the diabetic muscle is high, and active force produced at short muscle lengths is amplified but is limited by an internal resistance to shortening. The latter are accounted for by a significant increase in collagen type 1, with no changes in types 3 and 4. In the diabetic colon, ultrastructural studies show unique, conspicuous pockets of collagen among muscle cells, in addition to a thickened basement membrane and an extracellular space filled with collagen fibers and various fibrils. Measurements of DNA and total protein content revealed that the diabetic colon underwent hypertrophy, along with a proportional increase in actin and myosin contents, with no change in the actin-to-myosin ratio. Active force production per cross-sectional area was not different in the diabetic and normal muscles, consistent with the proportionality of changes in contractile proteins. The stiffness and the limit to shortening of the diabetic colon were significantly reduced by treatment with the glycation breaker alagebrium chloride (ALT-711), with no change in collagen contents. Functionally, this study shows that, in diabetes, the production of collagen type 1 and glycation increase stiffness, which limits distensibility on filling and limits shortening and expulsion of contents, both of which can be alleviated by treatment with ALT-711. Copyright © 2016 the American Physiological Society.

Topical Naltrexone Is a Safe and Effective Alternative to Standard Treatment of Diabetic Wounds.

PubMed

McLaughlin, Patricia J; Cain, Jarrett D; Titunick, Michelle B; Sassani, Joseph W; Zagon, Ian S

2017-09-01

Objective: Diabetes affects more than 29 million individuals in the United States, resulting in healthcare costs approaching $245 billion. Approximately 15% of these individuals will develop a chronic, non-healing foot ulcer (diabetic foot ulcer [DFU]) that, if untreated, may lead to amputation. The current treatments for DFU are expensive, have significant side-effects, and often result in non-compliance. A new topical treatment is described that accelerates cutaneous wound repair and is disease modifying by targeting underlying aberrant diabetic pathways. Approach: The efficacy of naltrexone (NTX), an opioid receptor antagonist, and Regranex ® was compared in preclinical studies using type 1 diabetic rats. Dorsal cutaneous wounds were treated topically with 0.03% NTX, Regranex, or moisturizing cream alone. Wound closure, DNA synthesis, and cytokine production were monitored. Results: Wound closure rates with topical NTX in type 1 diabetic rats were comparable to Regranex. Topical NTX accelerated DNA synthesis, as measured by BrdU incorporation, increased mast cells, and enhanced expression of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), a marker for angiogenesis. Regranex had little effect on DNA synthesis, mast cells, and VEGF expression relative to vehicle-treated wounds, and it only temporarily increased PDGF expression. Fibroblast growth factor expression was not altered by either treatment. Innovation: Topical application of 0.03% NTX cream accelerates diabetic wound closure. Conclusion: Blockade of the opioid growth factor (OGF)-OGF receptor (OGFr) axis utilizing 0.03% NTX cream is comparable to standard care in preclinical studies, and it provides a safe, inexpensive, and effective alternative for treatment of diabetic wounds.

Prevalence of mental disorders and related functioning and treatment engagement among people with diabetes.

PubMed

Boden, Matthew Tyler

2018-03-01

To examine prevalence, functioning and treatment associated with all DSM-5 12-month mood, anxiety, eating and substance use disorders among people with diabetes in data obtained from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Through multistage stratified randomized sampling a sample representative of the United States civilian population was obtained. Prevalence of diabetes (Type 1 and 2), DSM-5 disorders, physical and mental functioning, and treatment utilization were assessed via telephone interview. Analyses of weighted data (N=36,138) included calculation of descriptive statistics, and chi-square, logistic and linear regression analyses. Participants with (vs. without) diabetes (9.3% of weighted sample) had a significantly: (a) higher prevalence of any anxiety disorder and posttraumatic stress disorder (with and without adjustment for sociodemographic characteristics), and any mood disorder, major depressive disorder and specific phobia (with adjustment), (b) lower prevalence of any substance use disorder and alcohol and tobacco use disorders (with and without adjustment), and cannabis use disorder (without adjustment). Among participants with diabetes, mental disorder prevalence was consistently associated with sex and age, and to a lesser frequency, race/ethnicity. Lower levels of physical and mental functioning were found among participants with diabetes and a comorbid mental disorder. A minority of participants with diabetes and a comorbid mental disorder received treatment for mood and anxiety disorders, and few received treatment for eating and substance use disorders. Multiple types of mood, anxiety, eating and substance use disorders are prevalent, problematic, and often untreated among people with diabetes. Published by Elsevier Inc.

Repressible Transgenic Sterilization in Channel Catfish, Ictalurus punctatus, by Knockdown of Primordial Germ Cell Genes with Copper-Sensitive Constructs.

PubMed

Li, Hanbo; Su, Baofeng; Qin, Guyu; Ye, Zhi; Elaswad, Ahmed; Alsaqufi, Ahmed; Perera, Dayan A; Qin, Zhenkui; Odin, Ramji; Vo, Khoi; Drescher, David; Robinson, Dalton; Dong, Sheng; Zhang, Dan; Shang, Mei; Abass, Nermeen; Das, Sanjay K; Bangs, Max; Dunham, Rex A

2018-06-01

Repressible knockdown approaches were investigated to manipulate for transgenic sterilization in channel catfish, Ictalurus punctatus. Two primordial germ cell (PGC) marker genes, nanos and dead end, were targeted for knockdown and an off-target gene, vasa, was monitored. Two potentially copper-sensitive repressible promoters, yeast ctr3 (M) and ctr3-reduced (Mctr), were coupled with four knockdown strategies separately including: ds-sh RNA targeting the 5' end (N1) or 3' end (N2) of channel catfish nanos, full-length cDNA sequence of channel catfish nanos for overexpression (cDNA), and ds-sh RNA-targeting channel catfish dead end (DND). Each construct had an untreated group and treated group with copper sulfate as the repressor compound. Spawning rates of full-sibling P 1 fish exposed or not exposed to the constructs as treated and untreated embryos were 85 and 54%, respectively, indicating potential sterilization of fish and repression of the constructs. In F 1 fish, mRNA expressions of PGC marker genes for most constructs were downregulated in the untreated group and the knockdown was repressed in the treated group. Gonad development in transgenic, untreated F 1 channel catfish was reduced compared to non-transgenic fish for MctrN2, MN1, MN2, and MDND. For 3-year-old adults, gonad size in the transgenic untreated group was 93.4% smaller than the non-transgenic group for females and 92.3% for males. However, mean body weight of transgenic females (781.8 g) and males (883.8 g) was smaller than of non-transgenic counterparts (984.2 and 1254.3 g) at 3 years of age, a 25.8 and 41.9% difference for females and males, respectively. The results indicate that repressible transgenic sterilization is feasible for reproductive control of fish, but negative pleiotropic effects can result.

Recognition and treatment of sleep-disordered breathing: an important component of chronic disease management.

PubMed

Farrell, Peter C; Richards, Glenn

2017-05-25

Sleep-disordered breathing (SDB) is a highly prevalent condition, and is associated with many debilitating chronic diseases. The role of untreated obstructive sleep apnea (OSA) in arterial hypertension has been recognized in international guidelines. Treatment with continuous positive airway pressure (CPAP) is associated with clinically-relevant reductions in blood pressure. In heart failure (HF), SDB is associated with worse prognosis and increased mortality. Major HF guidelines recommend that patients should be treated for sleep apnea to improve their HF status. Severe OSA increases the risk of arrhythmias, including atrial fibrillation, influences risk management in stroke, and is highly prevalent in patients with type 2 diabetes. Effective treatment with CPAP improves the success of antiarrhythmic interventions, improves outcomes in stroke and reduces hyperglycemia in diabetes. Patients with coronary artery disease also have a high prevalence of SDB, which is independently associated with worse outcomes. The role of CPAP for secondary cardiovascular prevention remains to be determined. Data from large, well-conducted clinical trials have shown that noninvasive ventilation, targeted to markedly reduce hypercapnia, significantly improves survival and reduces readmission in stable hypercapnic chronic obstructive pulmonary disease. The association of SDB with chronic diseases contributes to the high healthcare costs incurred by SDB patients. SDB also has an important negative impact on quality of life, which is reversed by CPAP treatment. The high prevalence of SDB, and its association with diseases that cause significant morbidity and mortality, suggest that the diagnosis and management of SDB is an important therapeutic goal. First, adherent CPAP treatment significantly improves the quality of life of all patients with SDB; second, it eliminates the negative impact of untreated SDB on any associated chronic diseases; and third, it significantly reduces the increased costs of all hospital and medical services directly associated with untreated SDB. In short, the recognition and treatment of SDB is vital for the continued health and wellbeing of individual patients with SDB.

Comparison of Modified-ETDRS and Mild Macular Grid Laser Photocoagulation Strategies for Diabetic Macular Edema

PubMed Central

2008-01-01

Purpose To compare two laser photocoagulation techniques for treatment of diabetic macular edema (DME): modified-ETDRS direct/grid photocoagulation (mETDRS) and a, potentially milder, but potentially more extensive, mild macular grid (MMG) laser technique in which small mild burns are placed throughout the macula, whether or not edema is present, and microaneurysms are not treated directly. Methods 263 subjects (mean age 59 years) with previously untreated DME were randomly assigned to receive laser photocoagulation by mETDRS (N=162 eyes) or MMG (N=161 eyes) technique. Visual acuity, fundus photographs and OCT measurements were obtained at baseline and after 3.5, 8, and 12 months. Treatment was repeated if DME persisted. Main Outcome Measure Change in OCT measures at 12-months follow up. Results From baseline to 12 months, among eyes with baseline central subfield thickness ≥ 250 microns, central subfield thickening decreased by an average of 88 microns in the mETDRS group and decreased by 49 microns in the MMG group (adjusted mean difference: 33 microns, 95% confidence interval 5 to 61 microns, P=0.02). Weighted inner zone thickening by OCT decreased by 42 and 28 microns, respectively (adjusted mean difference: 14 microns, 95% confidence interval 1 to 27 microns, P=0.04), maximum retinal thickening (maximum of the central and four inner subfields) decreased by 66 and 39 microns, respectively (adjusted mean difference: 27 microns, 95% confidence interval 6 to 47 microns, P=0.01), and retinal volume decreased by 0.8 and 0.4 mm3, respectively (adjusted mean difference: 0.3 mm3, 95% confidence interval 0.02 to 0.53 mm3, P=0.03). At 12 months, the mean change in visual acuity was 0 letters in the mETDRS group and 2 letters worse in the MMG group (adjusted mean difference: 2 letters, 95% confidence interval −0.5 to 5 letters, P=0.10). Conclusions At 12 months after treatment, the MMG technique is less effective at reducing OCT measured retinal thickening than the more extensively evaluated current mETDRS laser photocoagulation approach. However, the visual acuity outcome with both approaches is not substantially different. Given these findings a larger long-term trial of the MMG technique is not justified. Application to Clinical Practice Modified ETDRS focal photocoagulation should continue as a standard approach for treating diabetic macular edema. PMID:17420366

Mangiferin induces islet regeneration in aged mice through regulating p16INK4a.

PubMed

Wang, Hailian; He, Xia; Lei, Tiantian; Liu, Yilong; Huai, Guoli; Sun, Minghan; Deng, Shaoping; Yang, Hongji; Tong, Rongsheng; Wang, Yi

2018-06-01

Previous studies by our group on mangiferin demonstrated that it exerts an anti‑hyperglycemic effect through the regulation of cell cycle proteins in 3‑month‑old, partially pancreatectomized (PPx) mice. However, β‑cell proliferation is known to become severely restricted with advanced age. Therefore, it is unknown whether mangiferin is able to reverse the diabetic condition and retain β‑cell regeneration capability in aged mice. In the present study, 12‑month‑old C57BL/6J mice that had undergone PPx were subjected to mangiferin treatment (90 mg/kg) for 28 days. Mangiferin‑treated aged mice exhibited decreased blood glucose levels and increased glucose tolerance, which was accompanied with higher serum insulin levels when compared with those in untreated PPx control mice. In addition, islet hyperplasia, elevated β‑cell proliferation and reduced β‑cell apoptosis were also identified in the mice that received mangiferin treatment. Further studies on the mRNA transcript and protein expression levels indicated comparatively increased levels of cyclins D1 and D2 and cyclin‑dependent kinase 4 in mangiferin‑treated mice, while the levels of p27Kip1 and p16INK4a were decreased relative to those in the untreated PPx controls. Of note, mangiferin treatment improved the proliferation rate of islet β‑cells in adult mice overexpressing p16INK4a, suggesting that mangiferin induced β‑cell proliferation via the regulation of p16INK4a. In addition, the mRNA transcription levels of critical genes associated with insulin secretion, including pancreatic and duodenal homeobox 1, glucose transporter 2 and glucokinase, were observed to be upregulated after mangiferin treatment. Taken together, it was indicated that mangiferin treatment significantly induced β‑cell proliferation and inhibited β‑cell apoptosis by regulating cell cycle checkpoint proteins. Furthermore, mangiferin was also demonstrated to regulate genes associated with insulin secretion. Collectively these, results suggest the therapeutic potential of mangiferin in the treatment of diabetes in aged individuals.

Red krypton and blue-green argon panretinal laser photocoagulation for proliferative diabetic retinopathy: a laboratory and clinical comparison.

PubMed

Blankenship, G W

1986-01-01

The effects of PRP with red krypton laser are essentially identical to those produced with blue-green argon laser. Burns of the rabbit retina produced with these two different lasers are almost the same. In a prospective and randomized clinical trial of proliferative diabetic retinopathy treatment there was no significant difference between PRP using these two different lasers. The characteristic changes of rabbit fundi 3, 7, and 30 days after PRP with red krypton laser were almost the same as those following blue-green argon laser. Both types of treatment frequently produced small vitreous hemorrhages and exudative retinal detachments, but choroidal thickening occurred more frequently with argon treatment. These changes were transient and had resolved within 30 days of treatment. The microscopic changes consisted of pigment epithelial disruption with pigment migration into the retina, heat coagulation of the photoreceptors, disruption of the outer and inner nuclear layers with atrophy of the nuclei, and temporary swelling of the nerve fiber layer. The untreated retina and choroid between burns was not involved and appeared normal at each period. Thirty days after treatment, the scarring produced by these two types of burns was identical. Seventy-one eyes with proliferative diabetic retinopathy having three or four retinopathy risk factors were treated with panretinal laser photocoagulation, and followed in a prospective study for 6 months. Thirty-six eyes were randomly selected for blue-green argon treatment, and 35 were randomly selected for red krypton treatment. The incidence of undesired side effects during the first 2 weeks following treatment was almost identical between the two groups. However, by 1 month the majority of eyes in both groups had visual acuities equal to or better than the pretreatment acuities and complete regression of NVD. Six months after treatment, the majority of eyes in both groups continued to have visual acuities equal to or better than the pretreatment acuities with fewer cases having larger losses of vision in the krypton treated group. Loss of peripheral visual field was equal with the two types of treatment having a minimal decrease with the IV-4e isopter, but substantial loss with the I-4e isopter. Additional vitreous hemorrhage rarely occurred in either group, but was slightly more frequent in those treated with krypton. Complete regression was accomplished in most eyes with pretreatment disc and/or NVE in both groups, but persistence of neovascularization was more frequent in those treated with krypton. Overall, the wavelength used seemingly had little effect on the result.(ABSTRACT TRUNCATED AT 400 WORDS)

Mechanical modifications to human pericardium after a brief immersion in 0.625% glutaraldehyde.

PubMed

Vincentelli, A; Zegdi, R; Prat, A; Lajos, P; Latrémouille, C; LeBret, E; De Boisbaudry, G; Carpentier, A; Fabiani, J N

1998-01-01

The use of human pericardium pretreated for 10 min with 0.625% glutaraldehyde (GLUT) in valvular repair or intracardiac reconstruction has produced good results. However, to date, no investigations have been made to determine the mechanical changes that occur in the tissue following such pretreatment. Human pericardial samples were harvested from 25 patients and immersed in GLUT for increasing times (5, 10, 30, 60 min and 6 months). Either untreated human pericardium or bovine pericardium treated for six months with GLUT served as controls. Tensile tests were performed with a uniaxial load machine and a pulsative bench. Fatigue testing was for 14 days; each sample was tested at 1,200 cycles/min at a controlled pressure of 90-120 mmHg. Untreated tissue thickness was 0.44+/-0.16 mm, but after six months GLUT treatment it was 0.53+/-0.15 mm (p<0.001). There was a 13.7% shrinkage of tissue after six months immersion. Strain was significantly greater in treated tissue than in untreated tissue, while stiffness decreased with the duration of GLUT immersion. Young's modulus was significantly lower after six months GLUT treatment (0.26+/-0.06 MPa) compared with untreated, and 5-, 10- and 30-min GLUT treatment (0.32+/-0.15, 0.35+/-0.09, 0.32+/-0.09 and 0.36+/-0.10 MPa (p<0.05)), respectively. Creep was greater after six months GLUT treatment (0.5+/-0.03%) than in untreated and 10-, 30- and 60-min treatments (0.3+/-0.50, 0.27+/-0.01, 0.27+/-0.02, 0.3+/-0.01% (p<0.05)), respectively. Ultimate tensile stress (UTS) was greater in 10-min treated pericardium than in untreated tissue: 38.46+/-11.75 versus 22.17+/-8.30 MPa (p<0.05) respectively. Strain at rupture was greater in the 6-month group (30.62+/-2.54%) than for untreated and 10-, 30- and 60-min GLUT immersion 16.3+/-0.73, 21.85+/-0.75, 20.12+/-1.04 and 18.87+/-0.86% (p<0.05), respectively. Fatigue testing showed an increased length after five and 10 min, and six months, with a lengthening of 14.66, 12.53, 7.66%, respectively compared with 3.5% for untreated tissue (p<0.05). There were three failures in the untreated group (n = 5), none in the 5- and 10-min groups, and one in the 6-month group (p<0.05). Brief immersion of human pericardial tissue in 0.625% glutaraldehyde reduces the tissue's stiffness and improves its durability for use in cardiac surgery.

Use of tylvalosin-medicated feed to control porcine proliferative enteropathy.

PubMed

Guedes, R M C; França, S A; Machado, G S; Blumer, M A; da Costa Cruz, E C

2009-09-19

The effect of an oral treatment with the tartrate salt of tylvalosin on the development of proliferative enteropathy in 60 experimentally challenged pigs was studied. Thirty of the pigs were fed a diet medicated with 50 ppm tylvalosin and 30 were fed the unmedicated diet. The treated animals started to receive the medicated feed the day before they were inoculated, and continued to receive it for 14 days. The pigs' bodyweight, feed consumption and clinical signs were evaluated, and they were examined postmortem 20 days after inoculation, and samples of ileum were collected for immunohistochemistry (IHC) for Lawsonia intracellularis. Clinical signs of the disease were more evident in the untreated group than in the treated group. The average daily weight gain, average daily feed consumption and feed conversion efficiency were better in the treated group. The combined length of intestine with lesions was 2847 cm in the untreated group and 183 cm in the treated group. The tylvalosin treatment significantly reduced the level of L intracellularis infection; almost half of the treated pigs were IHC-negative compared with 3.3 per cent of the untreated pigs.

Imaging of vascular dynamics within the foot using dynamic diffuse optical tomography to diagnose peripheral arterial disease

NASA Astrophysics Data System (ADS)

Khalil, M. A.; Kim, H. K.; Hoi, J. W.; Kim, I.; Dayal, R.; Shrikande, G.; Hielscher, A. H.

2013-03-01

Peripheral Arterial Disease (PAD) is the narrowing of the functional area of the artery generally due to atherosclerosis. It affects between 8-12 million people in the United States and if untreated this can lead to ulceration, gangrene and ultimately amputation. The current diagnostic method for PAD is the ankle-brachial index (ABI). The ABI is a ratio of the patient's systolic blood pressure in the foot to that of the brachial artery in the arm, a ratio below 0.9 is indicative of affected vasculature. However, this method is ineffective in patients with calcified arteries (diabetic and end-stage renal failure patients), which falsely elevates the ABI recording resulting in a false negative reading. In this paper we present our results in a pilot study to deduce optical tomography's ability to detect poor blood perfusion in the foot. We performed an IRB approved 30 patient study, where we imaged the feet of the enrolled patients during a five stage dynamic imaging sequence. The patients were split up into three groups: 10 healthy subjects, 10 PAD patients and 10 PAD patients with diabetes and they were imaged while applying a pressure cuff to their thigh. Differences in the magnitude of blood pooling in the foot and rate at which the blood pools in the foot are all indicative of arterial disease.

Chronic diabetes alters function and expression of ryanodine receptor calcium-release channels in rat hearts.

PubMed

Bidasee, Keshore R; Nallani, Karuna; Henry, Bruce; Dincer, U Deniz; Besch, Henry R

2003-07-01

Alteration in cardiac function is one of the hallmarks of diabetes and in late stage is manifested as a decrease in contractility. While it is established that the release of calcium ions from internal sarcoplasmic reticulum via type 2 ryanodine receptor calcium-release channels (RyR2) is vital for efficient contraction, the relationship between diabetes-induced decrease in cardiac performance and alterations in expression and/or function of RyR2 is not well delineated. The present study was designed to address this question and to determine whether changes to RyR2 induced by chronic diabetes could be minimized with insulin-treatment. When paced at 3.3 Hz (200 beats per minute), hearts from 8-week streptozotocin-induced diabetic rats showed decreased responsiveness to isoproterenol stimulation; +dT/dt and -dT/dt were 56.5 +/- 11.4% and 42.1 +/- 12.1% that of control, respectively. Hearts from 8-week diabetic rats expressed 51.2% less RyR2 than controls, In addition, RyR2 from diabetic rats also showed decreased ability to bind the specific ligand [3H]ryanodine (22.4 +/- 1.8% less [3H]ryanodine per microg of RyR2 protein), suggesting dysfunction. Two-weeks of insulin treatment, initiated after 6 weeks of untreated diabetes was able to minimize loss in function and expression of RyR2. Taken collectively, these data suggest that the decrease in cardiac contractility induced by chronic diabetes results in part from decreases in expression and alteration in function of RyR2 and these changes could be attenuated with insulin treatment.

Assessing evidence of inequalities in access to medication for diabetic populations in low- and middle-income countries: a systematic review

PubMed Central

Christiani, Yodi; Dhippayom, Teerapon; Chaiyakunapruk, Nathorn

2016-01-01

Background Inequalities in access to medications among people diagnosed with diabetes inlow- and middle-income countries (LMICs) is a public health concern since untreated diabetes can lead to severe complications and premature death. Objective To assess evidence of inequalities in access to medication for diabetes in adult populations of people with diagnosed diabetes in LMICs. Design We conducted a systematic review of the literature using the PRISMA-Equity guidelines. A search of five databases – PubMed, Cochrane, CINAHL, PsycINFO, and EMBASE – was conducted from inception to November 2015. Using deductive content analysis, information extracted from the selected articles was analysed according to the PRISMA-Equity guidelines, based on exposure variables (place of residence, race/ethnicity, occupation, gender, religion, education, socio-economic status, social capital, and others). Results Fifteen articles (seven quantitative and eight qualitative studies) are included in this review. There were inconsistent findings between studies conducted in different countries and regions although financial and geographic barriers generally contributed to inequalities in access to diabetes medications. The poor, those with relatively low education, and people living in remote areas had less access to diabetes medications. Furthermore, we found that the level of government political commitment through primary health care and in the provision of essential medicines was an important factor in promoting access to medications. Conclusions The review indicates that inequalities exist in accessing medication among diabetic populations, although this was not evident in all LMICs. Further research is needed to assess the social determinants of health and medication access for people with diabetes in LMICs. PMID:27938647

INTERPLAY OF SORBITOL PATHWAY OF GLUCOSE METABOLISM, 12/15-LIPOXYGENASE, AND MITOGEN-ACTIVATED PROTEIN KINASES IN THE PATHOGENESIS OF DIABETIC PERIPHERAL NEUROPATHY

PubMed Central

Stavniichuk, Roman; Shevalye, Hanna; Hirooka, Hiroko; Nadler, Jerry L.; Obrosova, Irina G.

2012-01-01

The interactions among multiple pathogenetic mechanisms of diabetic peripheral neuropathy largely remain unexplored. Increased activity of aldose reductase, the first enzyme of the sorbitol pathway, leads to accumulation of cytosolic Ca++, essentially required for 12/15-lipoxygenase activation. The latter, in turn, causes oxidative-nitrosative stress, an important trigger of MAPK phosphorylation. This study therefore evaluated the interplay of aldose reductase, 12/15-lipoxygenase, and MAPKs in diabetic peripheral neuropathy. In experiment 1, male control and streptozotocin-diabetic mice were maintained with or without the aldose reductase inhibitor fidarestat, 16 mg kg−1 d−1, for 12 weeks. In experiment 2, male control and streptozotocin-diabetic wild-type (C57Bl6/J) and 12/15-lipoxygenase-deficient mice were used. Fidarestat treatment did not affect diabetes-induced increase in glucose concentrations, but normalized sorbitol and fructose concentrations (enzymatic spectrofluorometric assays) as well as 12(S) hydroxyeicosatetraenoic concentration (ELISA), a measure of 12/15-lipoxygenase activity, in the sciatic nerve and spinal cord. 12/15-lipoxygenase expression in these two tissues (Western blot analysis) as well as dorsal root ganglia (immunohistochemistry) was similarly elevated in untreated and fidarestat-treated diabetic mice. 12/15-lipoxygenase gene deficiency prevented diabetesassociated p38 MAPK and ERK, but not SAPK/JNK, activation in the sciatic nerve (Western blot analysis) and all three MAPK activation in the dorsal root ganglia (immunohistochemistry). In contrast, spinal cord p38 MAPK, ERK, and SAPK/JNK were similarly activated in diabetic wild-type and 12/15-lipoxygenase−/− mice. These findings identify the nature and tissue specificity of interactions among three major mechanisms of diabetic peripheral neuropathy, and suggest that combination treatments, rather than monotherapies, can sometimes be an optimal choice for its management. PMID:22285226

[Effect of dust aerosol exposure on lung function and lung histopathology in rats].

PubMed

Lei, Fengfeng; Wang, Xuebin; Liu, Hua; Chen, Qizhang; Ma, Hui; Dong, Zhibao; Sang, Yingzhu

2015-08-25

To investigate the effect of dust aerosol exposure on lung function and lung histopathology in rats. According to random number table method, 120 Wistar male rats were divided into untreated control group, treated control group and experimental group, with 40 rats in each group. Experimental group were exposed to the wind tunnel simulation of sandstorm for 5 hours in every day; the untreated control group were put in the standard living environment next to the wind tunnel; the treated control group were exposed to the same wind tunnel simulation of sandstorm for 5 hours in every day, and the speed of wind was the same as the experimental group, but excluding dust. At different time points, the lung function and electron microscopy were performed in all rats. The level of Dynamic Compliance (Cdyn) ((0.227 ± 0.023), (0.198 ± 0.022) ml/cmH₂O, 1 cmH₂O=0.098 kPa) and forced vital capacity (FVC) ((6.24 ± 0.29), (5.59 ± 0.19) ml) were lower in the experimental group at 90 and 120 days, as compared to the untreated control group (Cdyn: (0.266 ± 0.014), (0.265 ± 0.018) ml/cmH2O; FVC: (7.15 ± 0.23), (7.17 ± 0.20) ml) and treated control group (Cdyn: (0.269 ± 0.015), (0.264 ± 0.019) ml/cmH2O; FVC: (7.14 ± 0.19), (7.15 ± 0.21) ml) (all P<0.05). At 120 days, The level of the forced expiratory flow after 50% of the FVC ((12.3 ± 2.2) ml/s) and peak expiratory flow ((25.79 ± 0.42) ml/s) were lower in the experimental group, as compared to the untreated control group ((15.9 ± 2.5), (27.99 ± 0.36) ml/s) and treated control group ((15.8 ± 2.1), (27.90 ± 0.38) ml/s) (all P<0.01). The FVC rate of 0.2 second in the experimental group was higher than that in the untreated control group and treated control group ( (85 ± 5)%, (73 ± 4)%, (73 ± 4)%, all P<0.05). The electron microscopy showed that the lung tissues had no obvious abnormalities at 30, 60, 90 and 120 days in untreated control group and treated control group. But in the experimental group, at 30 days, the endothelial cells of alveolar type I cells were swelled and the number of alveolar type II cells were increased; at 60 days, alveolar type II cells hyperplastic, basement membrane thinned and destructed; at 90 days, the number of alveolar type II cells decreased, Lamellar body evacuation; at 120 days, a lot of collagen fiber was formed in the alveolar septa. The strong sandstorm environmental exposure to a certain period of time can cause the decline of lung function and the damage of lung histopathology in rats. Exposure time was positively correlated with the damage of lung tissue.

The Therapeutic Effect of Zuogui Wan in Gestational Diabetes Mellitus Rats

PubMed Central

Feng, Qianjin; Niu, Xin; Liu, Xinshe; Xu, Kaixia; Yang, Xiangzhu; Wang, Huifeng

2014-01-01

In this experiment, we established an animal model of gestational diabetes mellitus rats using streptozotocin. Using the rat model of GDM, the pregnant rats in 1-19d were divided into three groups: (1) Zuogui Wan gestational diabetes mellitus group (group I, n = 12), (2) gestational diabetes mellitus rats as the control group (group II, n = 11), and (3) rats of normal pregnancy group (group III, n = 11). Compared with gestational diabetes mellitus rats as the control group, Zuogui Wan can change the indexes of fasting blood glucose, body weight, total cholesterol, insulin, and metabolism cage index significantly in Zuogui Wan gestational diabetes mellitus group. We can conclude that Zuogui Wan has the therapeutic effect on gestational diabetes mellitus. PMID:25136475

Causes of anorexia in untreated hyperthyroidism: a prospective study

PubMed Central

Dai, W.; Meng, X.

2000-01-01

Seventeen consecutive patients (mean (SD) 46 (11) years) with untreated hyperthyroidism and anorexia and 29 patients (35 (9) years) with untreated hyperthyroidism without anorexia were studied. The study was conducted at the thyroid clinic of the PUMC Hospital, Beijing, China from March to August 1997. The patients' ages, serum free calcium, liver function and emotional state, specifically the level of anxiety (using the self anxiety scale, Chinese version), were compared before and/or after antithyroid drug treatment in the two groups. This prospective study suggested that the causes of anorexia in untreated hyperthyroidism are complicated. Older age, abnormal liver function, and the level of anxiety are significantly related to anorexia in untreated hyperthyroidism, but hypercalcaemia was not confirmed to be related to anorexia in the study.


Keywords: hypercalcaemia; hyperthyroidism; anorexia; anxiety PMID:10775283

Ambulatory blood pressure and arterial stiffness in individuals with type 1 diabetes.

PubMed

Lithovius, Raija; Gordin, Daniel; Forsblom, Carol; Saraheimo, Markku; Harjutsalo, Valma; Groop, Per-Henrik

2018-05-24

This study aimed to assess the use of ambulatory BP monitoring (ABPM) to identify the presence of masked, nocturnal and white-coat hypertension in individuals with type 1 diabetes, patterns that could not be detected by regular office-based BP monitoring alone. We also analysed associations between BP patterns and arterial stiffness in order to identify individuals at cardiovascular risk. This substudy included 140 individuals with type 1 diabetes from the Helsinki metropolitan area, who attended the Finnish Diabetic Nephropathy Study (FinnDiane) Centre in Helsinki between January 2013 and August 2017. Twenty-four hour ABPM and pulse wave analysis were performed simultaneously using a validated non-invasive brachial oscillometric device (Mobil-O-Graph). Definitions of hypertension were based on the European Society of Hypertension guidelines. Masked hypertension was defined as normal office BP (BP obtained using a standardised automated BP device) but elevated 24 h ABPM, and white-coat hypertension as elevated office BP but normal 24 h ABPM. A total of 38% of individuals were normotensive and 33% had sustained hypertension, while 23% had masked and 6% had white-coat hypertension. About half of the cohort had increased absolute levels of night-time BP, half of whom were untreated. In the ambulatory setting, central BP and pulse wave velocity (PWV) were higher in participants with masked hypertension than in those with normotension (p ≤ 0.001). In a multivariable linear regression model adjusted for age, sex, BMI, antihypertensive treatment and eGFR, masked hypertension was independently associated with higher 24 h PWV (β 0.50 [95% CI 0.34, 0.66]), but not with PWV obtained during resting conditions (adjusted β 0.28 [95% CI -0.53, 1.10]), using normotension as the reference group. ABPM analysis revealed that one-quarter of the participants with type 1 diabetes had masked hypertension; these individuals would not have been detected by office BP alone. Moreover, arterial stiffness was increased in individuals with masked hypertension. These findings support the use of ABPM to identify individuals at risk of cardiovascular disease.

Sample Size Requirements for Studies of Treatment Effects on Beta-Cell Function in Newly Diagnosed Type 1 Diabetes

PubMed Central

Lachin, John M.; McGee, Paula L.; Greenbaum, Carla J.; Palmer, Jerry; Gottlieb, Peter; Skyler, Jay

2011-01-01

Preservation of -cell function as measured by stimulated C-peptide has recently been accepted as a therapeutic target for subjects with newly diagnosed type 1 diabetes. In recently completed studies conducted by the Type 1 Diabetes Trial Network (TrialNet), repeated 2-hour Mixed Meal Tolerance Tests (MMTT) were obtained for up to 24 months from 156 subjects with up to 3 months duration of type 1 diabetes at the time of study enrollment. These data provide the information needed to more accurately determine the sample size needed for future studies of the effects of new agents on the 2-hour area under the curve (AUC) of the C-peptide values. The natural log(), log(+1) and square-root transformations of the AUC were assessed. In general, a transformation of the data is needed to better satisfy the normality assumptions for commonly used statistical tests. Statistical analysis of the raw and transformed data are provided to estimate the mean levels over time and the residual variation in untreated subjects that allow sample size calculations for future studies at either 12 or 24 months of follow-up and among children 8–12 years of age, adolescents (13–17 years) and adults (18+ years). The sample size needed to detect a given relative (percentage) difference with treatment versus control is greater at 24 months than at 12 months of follow-up, and differs among age categories. Owing to greater residual variation among those 13–17 years of age, a larger sample size is required for this age group. Methods are also described for assessment of sample size for mixtures of subjects among the age categories. Statistical expressions are presented for the presentation of analyses of log(+1) and transformed values in terms of the original units of measurement (pmol/ml). Analyses using different transformations are described for the TrialNet study of masked anti-CD20 (rituximab) versus masked placebo. These results provide the information needed to accurately evaluate the sample size for studies of new agents to preserve C-peptide levels in newly diagnosed type 1 diabetes. PMID:22102862

Sample size requirements for studies of treatment effects on beta-cell function in newly diagnosed type 1 diabetes.

PubMed

Lachin, John M; McGee, Paula L; Greenbaum, Carla J; Palmer, Jerry; Pescovitz, Mark D; Gottlieb, Peter; Skyler, Jay

2011-01-01

Preservation of β-cell function as measured by stimulated C-peptide has recently been accepted as a therapeutic target for subjects with newly diagnosed type 1 diabetes. In recently completed studies conducted by the Type 1 Diabetes Trial Network (TrialNet), repeated 2-hour Mixed Meal Tolerance Tests (MMTT) were obtained for up to 24 months from 156 subjects with up to 3 months duration of type 1 diabetes at the time of study enrollment. These data provide the information needed to more accurately determine the sample size needed for future studies of the effects of new agents on the 2-hour area under the curve (AUC) of the C-peptide values. The natural log(x), log(x+1) and square-root (√x) transformations of the AUC were assessed. In general, a transformation of the data is needed to better satisfy the normality assumptions for commonly used statistical tests. Statistical analysis of the raw and transformed data are provided to estimate the mean levels over time and the residual variation in untreated subjects that allow sample size calculations for future studies at either 12 or 24 months of follow-up and among children 8-12 years of age, adolescents (13-17 years) and adults (18+ years). The sample size needed to detect a given relative (percentage) difference with treatment versus control is greater at 24 months than at 12 months of follow-up, and differs among age categories. Owing to greater residual variation among those 13-17 years of age, a larger sample size is required for this age group. Methods are also described for assessment of sample size for mixtures of subjects among the age categories. Statistical expressions are presented for the presentation of analyses of log(x+1) and √x transformed values in terms of the original units of measurement (pmol/ml). Analyses using different transformations are described for the TrialNet study of masked anti-CD20 (rituximab) versus masked placebo. These results provide the information needed to accurately evaluate the sample size for studies of new agents to preserve C-peptide levels in newly diagnosed type 1 diabetes.

Furan-induced hepatotoxic and hematologic changes in diabetic rats: the protective role of lycopene.

PubMed

Baş, Hatice; Pandır, Dilek; Kalender, Suna

2016-09-01

Furan forms as a result of thermal treatment of food and induces harmful effects on organisms. In our work, lycopene, furan, and a combination of the two were given to diabetic male rats for 28 days. Hematological changes, total protein and cholesterol, triglyceride, and albumin levels, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase activities of the serum, malondialdehyde levels, glutathione peroxidase, catalase, glutathione-S-transferase, superoxide dismutase activities, DNA damage in liver tissues and hepatic histopathological alterations were compared to a control group. There were significant changes in the liver function tests, DNA damage, activities of antioxidant enzymes, and malondialdehyde levels between diabetic control and non-diabetic control groups, between diabetic control and diabetic lycopene groups, and also between diabetic furan and diabetic control groups. In diabetic lycopene and diabetic furan + lycopene treated groups we designated the preventive effects of lycopene against diabetes and furan, however, on the analysed parameters only. In spite of some pathological alterations designated in diabetic furan treated group's liver, fewer pathological alterations were observed in furan+lycopene treated groups at the end of week 4. Consequently, lycopene significantly reduced furan- and diabetes-induced toxicity in rat liver.

Classification of Forefoot Plantar Pressure Distribution in Persons with Diabetes: A Novel Perspective for the Mechanical Management of Diabetic Foot?

PubMed Central

Deschamps, Kevin; Matricali, Giovanni Arnoldo; Roosen, Philip; Desloovere, Kaat; Bruyninckx, Herman; Spaepen, Pieter; Nobels, Frank; Tits, Jos; Flour, Mieke; Staes, Filip

2013-01-01

Background The aim of this study was to identify groups of subjects with similar patterns of forefoot loading and verify if specific groups of patients with diabetes could be isolated from non-diabetics. Methodology/Principal Findings Ninety-seven patients with diabetes and 33 control participants between 45 and 70 years were prospectively recruited in two Belgian Diabetic Foot Clinics. Barefoot plantar pressure measurements were recorded and subsequently analysed using a semi-automatic total mapping technique. Kmeans cluster analysis was applied on relative regional impulses of six forefoot segments in order to pursue a classification for the control group separately, the diabetic group separately and both groups together. Cluster analysis led to identification of three distinct groups when considering only the control group. For the diabetic group, and the computation considering both groups together, four distinct groups were isolated. Compared to the cluster analysis of the control group an additional forefoot loading pattern was identified. This group comprised diabetic feet only. The relevance of the reported clusters was supported by ANOVA statistics indicating significant differences between different regions of interest and different clusters. Conclusion/s Significance There seems to emerge a new era in diabetic foot medicine which embraces the classification of diabetic patients according to their biomechanical profile. Classification of the plantar pressure distribution has the potential to provide a means to determine mechanical interventions for the prevention and/or treatment of the diabetic foot. PMID:24278219

Association of ABO and Rh blood groups with type 2 diabetes mellitus.

PubMed

Meo, S A; Rouq, F A; Suraya, F; Zaidi, S Z

2016-01-01

The phenotypic "ABO" blood groups are inherited antigenic substances which are found on the surface of red blood cells in addition to other tissues. Certain hypothesis advocates that genetic predisposition like "ABO" blood group would be associated with occurrence of diseases including type 2 diabetes. This study aimed to investigate the potential association between "ABO" and "Rhesus" blood groups with type 2 diabetes. We identified 47 research documents in a data based search including ISI-Web of Science, EMBASE and PubMed. Literature was explored using the key terms including "ABO blood groups" "type 2 diabetes". Studies in which "ABO" blood types and diabetes mellitus were discussed included without restrictions of research documents, types, status and language of the publications. Finally, 15 publications which matched our criteria were included, and remaining studies were excluded. Blood group "B" was associated with high incidence of type 2 diabetes and blood group "O" has a minimum association with type 2 diabetes. Blood group "A" and "AB" were almost equally distributed in both diabetic and non-diabetic population. However, we were unable to find an association between "Rh+ve" and "Rh-ve" blood groups with type 2 diabetes. Subjects with blood group "B" are at high risk while individuals with blood group "O" are at low peril of evolving type 2 diabetes. It is suggested that subjects with blood group "B" should be closely monitored by physicians as these subjects have an increased risk of type 2 diabetes.

Protective effects of sodium selenite on lead nitrate-induced hepatotoxicity in diabetic and non-diabetic rats.

PubMed

Kalender, Suna; Apaydin, Fatma Gökçe; Baş, Hatice; Kalender, Yusuf

2015-09-01

In the present study, the effect of sodium selenite on lead induced toxicity was studied in Wistar rats. Sodium selenite and lead nitrate were administered orally for 28 days to streptozotocin induced diabetic and non-diabetic rats. Eight groups of rats were used in the study: control, sodium selenite, lead nitrate, lead nitrate+sodium selenite, streptozotocin-induced diabetic-control, diabetic-sodium selenite, diabetic-lead nitrate, diabetic-lead nitrate+sodium selenite groups. Serum biochemical parameters, lipid peroxidation, antioxidant enzymes and histopathological changes in liver tissues were investigated in all groups. There were statistically significant changes in liver function tests, antioxidant enzyme activities and lipid peroxidation levels in lead nitrate and sodium selenite+lead nitrate treated groups, also in diabetic and non-diabetic groups. Furthermore, histopathological alterations were demonstrated in same groups. In the present study we found that sodium selenite treatment did not show completely protective effect on diabetes mellitus caused damages, but diabetic rats are more susceptible to lead toxicity than non-diabetic rats. Copyright © 2015 Elsevier B.V. All rights reserved.

Adopting the new World Health Organization diagnostic criteria for gestational diabetes: How the prevalence changes in a high-risk region in Australia.

PubMed

Wong, Vincent W; Lin, Andrew; Russell, Hamish

2017-07-01

In this study, we assessed changes in prevalence of gestational diabetes mellitus (GDM) in a region with diverse cultural backgrounds in Australia under the new World Health Organization (WHO) diagnostic criteria, with reference to the woman's ethnicity, age and pre-pregnant body mass index (BMI). We recorded results of all 75-gram oral glucose tolerance tests (OGTTs) performed on pregnant women between February and December 2015 together with their demographic details, and determined the prevalence of GDM based on the old Australian Diabetes in Pregnancy Society (ADIPS) and the new WHO criteria respectively. Over that period, 2140 OGTTs were performed in 1725 pregnant women. The prevalence of GDM was 14.8% (255/1725 women) under old ADIPS criteria, but went up to 29.6% (510/1725) when using WHO criteria. An increase in prevalence was observed in all ethnic groups. Women from East/South-East Asia had the lowest increment (from 19.2 to 22.3%) while those from South Asia had the highest (from 22.0 to 44.4%). Prevalence of GDM was 45.9% amongst women with BMI>30kg/m 2 . For women from South Asia with BMI>30kg/m 2 , 70.0% would have GDM. Birth outcomes were similar between women who would have GDM under WHO but not the old ADIPS criteria (untreated), and those who were treated for GDM under old criteria. In parts of Australia, adoption of WHO diagnostic criteria could result in doubling of the prevalence of GDM, depending on the women's demographic characteristics. Women from South Asia or those with obesity should be targeted for pre-pregnant lifestyle intervention. Copyright © 2017 Elsevier B.V. All rights reserved.

Quality of life in the patients with central diabetes insipidus assessed by Nagasaki Diabetes Insipidus Questionnaire.

PubMed

Nozaki, Aya; Ando, Takao; Akazawa, Satoru; Satoh, Tsuyoshi; Sagara, Ikuko; Horie, Ichiro; Imaizumi, Misa; Usa, Toshiro; Yanagisawa, Robert T; Kawakami, Atsushi

2016-01-01

Central diabetes insipidus (CDI) is characterized by polyuria and polydipsia due to a deficiency of vasopressin. Currently, the treatment goal for CDI is improvement of quality of life (QOL) by desmopressin (DDAVP) without developing hyponatremia. However, there is no reliable measure for QOL in CDI patients. We evaluate our original questionnaire for QOL, consisting of 12 questions focusing on polyuria, polydipsia, and DDAVP treatment, in CDI patients who underwent a switch from nasal spray to oral disintegrating tablets of DDAVP. Twenty-five CDI patients under nasal DDAVP treatment, six with newly developed CDI, and 18 healthy individuals without known polyuric/polydipsic disorders as control subjects were enrolled. QOL scores were determined by our questionnaire at the enrollment and 3 months after the start of oral DDAVP treatment and were examined by the Wilcoxon signed-rank test. Eleven questions detected improvement in QOL. The sum of the QOL scores of the eleven questions increased from 29.2 ± 5.6 under nasal to 36.8 ± 4.5 under oral DDAVP (p < 0.001). There were no clinically relevant changes in serum levels of Na. After eliminating two questions about DDAVP treatment, the sum of QOL scores was 15.3 ± 6.5 in untreated CDI patients, 24.4 ± 5.2 in those with nasal treatment, 28.9 ± 4.9 in those with oral DDAVP, and 29.5 ± 3.6 in healthy controls. The difference among groups was significant (p < 0.05 in Steel-Dwass test) except between patients treated with oral DDAVP and healthy controls. Our questionnaire can be used to accurately assess QOL in CDI patients.

Amitriptyline and phenytoin prevents memory deficit in sciatic nerve ligation model of neuropathic pain.

PubMed

Abdulmajeed, Wahab Imam; Ibrahim, Ridwan Babatunde; Ishola, Azeez Olakunle; Balogun, Wasiu Gbolahan; Cobham, Ansa Emmanuel; Amin, Abdulbasit

2016-03-01

Phenytoin and amitriptyline are often reported to attenuate pain in chronic conditions. Information on their ability to ameliorate cognitive impairment associated with neuropathic pain remains unclear due to mixed results from studies. This study investigated the effects of phenytoin and amitriptyline on memory deficit associated with neuropathic pain. Twenty-eight adult male Wistar rats were randomly divided into four groups: A, B, C, and D (n=7). Groups A, B, C, and D served as sham control, sciatic nerve ligated untreated, sciatic nerve ligated receiving amitriptyline (5 mg/kg), and sciatic nerve ligated receiving phenytoin (10 mg/kg) respectively. Treatments lasted for 14 days, after which both 'Y' maze and novel object recognition test (NOR) were performed. On the last day of treatment, the animals were anesthetized and their brain excised, and the prefrontal cortices and sciatic nerve were processed histologically using hematoxylin and eosin. There was memory impairment in the sciatic nerve ligated untreated group which was statistically significant (p<0.05) when compared to the phenytoin-treated, amitriptyline-treated, and sham control groups using the 'Y' maze and NOR tests. Histological quantification showed that the prefrontal cortices of the ligated animals showed increased neural population in comparison to normal control. These increases were significantly marked in the untreated ligated group. Sciatic nerve of untreated ligated group showed high demyelination and axonal degeneration which was ameliorated in the treated animals. The administration of amitriptyline and phenytoin can ameliorate neuronal injury, demyelination, and memory impairment associated with neuropathic pain in Wistar rats.

A comparative research on obesity hypertension by the comparisons and associations between waist circumference, body mass index with systolic and diastolic blood pressure, and the clinical laboratory data between four special Chinese adult groups.

PubMed

Wu, Ou; Leng, Jian-Hang; Yang, Fen-Fang; Yang, Hai-Ming; Zhang, Hu; Li, Zeng-Fang; Zhang, Xing-Yu; Yuan, Cheng-Da; Li, Jia-Jia; Pan, Qi; Liu, Wei; Ren, Yan-Jun; Liu, Bing; Liu, Qing-Min; Cao, Cheng-Jian

2018-01-01

The obesity-hypertension pathogenesis is complex. From the phenotype to molecular mechanism, there is a long way to clarify the mechanism. To explore the association between obesity and hypertension, we correlate the phenotypes such as the waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), and diastolic blood pressure (DB) with the clinical laboratory data between four specific Chinese adult physical examination groups (newly diagnosed untreated just-obesity group, newly diagnosed untreated obesity-hypertension group, newly diagnosed untreated just-hypertension group, and normal healthy group), and the results may show something. To explore the mechanisms from obesity to hypertension by analyzing the correlations and differences between WC, BMI, SB, DB, and other clinical laboratory data indices in four specific Chinese adult physical examination groups. This cross-sectional study was conducted from September 2012 to July 2014, and 153 adult subjects, 34 women and 119 men, from 21 to 69 years, were taken from four characteristic Chinese adult physical examination groups (newly diagnosed untreated just-obesity group, newly diagnosed untreated obesity-hypertension group, newly diagnosed untreated just-hypertension group, and normal healthy group). The study was approved by the ethics committee of Hangzhou Center for Disease Control and Prevention. WC, BMI, SB, DB, and other clinical laboratory data were collected and analyzed by SPSS. Serum levels of albumin (ALB)，alanine aminotransferase (ALT), low density lipoprotein cholesterol (LDLC), triglyceride (TG), high density lipoprotein cholesterol (HDLC), alkaline phosphatase (ALP), uric acid (Ua), and TC/HDLC (odds ratio) were statistically significantly different between the four groups. WC statistically significantly positively correlated with BMI, ALT, Ua, and serum levels of glucose (GLU), and TC/HDLC, and negatively with ALB, HDLC, and serum levels of conjugated bilirubin (CB). BMI was statistically significantly positively related to ALT, Ua, LDLC, WC, and TC/HDLC, and negatively to ALB, HDLC, and CB. DB statistically significantly positively correlated with ALP, BMI, and WC. SB was statistically significantly positively related to LDLC, GLU, serum levels of fructosamine (FA), serum levels of the total protein (TC), BMI, and WC. The negative body effects of obesity are comprehensive. Obesity may lead to hypertension through multiple ways by different percents. GGT, serum levels of gamma glutamyltransferase; ALB, serum levels of albumin; ALT, serum levels of alanine aminotransferase; LDLC, serum levels of low density lipoprotein cholesterol; TG, serum levels of triglyceride; HDLC, serum levels of high density lipoprotein cholesterol; FA, serum levels of fructosamine; S.C.R, serum levels of creatinine; IB, serum levels of indirect bilirubin; ALP, serum levels of alkaline phosphatase; CB, serum levels of conjugated bilirubin; UREA, Urea; Ua, serum levels of uric acid; GLU, serum levels of glucose; TC, serum levels of the total cholesterol; TB, serum levels of the total bilirubin; TP, serum levels of the total protein; TC/HDLC, TC/HDLC ratio.

Comparative analysis of diabetic nephropathy and non-diabetic nephropathy disease.

PubMed

Chen, Qiuxiang; Zhu, Aimin; Wang, Junsheng; Huan, Xuelai

2017-12-01

Clinical symptoms of diabetic nephropathy patients and non-diabetic nephropathy are compared and analyzed, hemodialysis effect and quality of life of two kinds of nephrotic patients are analyzed. Respectively extract 1300 cases of diabetic nephropathy and non-diabetic nephropathy patients admitted to different hospitals during December 2011-December 2014. Based on whether the patient suffers from diabetes, they were divided into diabetic group and control group. Hemodialysis of two groups of patients were followed up to observe effectiveness of blood treatment, and complications were observed after one year of follow-up. Hematodialysis effectiveness of diabetic nephropathy patients is significantly lower than that of non-diabetic nephropathy group. After 1 year's follow-up, it can be found that survival rate of diabetic nephropathy patients is much lower than that of control group. In statistical comparison of data involved in the two groups of patients, P < 0.05, the difference is statistically significant. Treatment effect of diabetic nephropathy patients is relatively poor compared to that of non-diabetic patients. In clinics, management and prevention of diabetic patients should be strengthened to avoid complication of nephropathy which brings serious injury to patients.

Extract of Bauhinia vahlii Shows Antihyperglycemic Activity, Reverses Oxidative Stress, and Protects against Liver Damage in Streptozotocin-induced Diabetic Rats

PubMed Central

Elbanna, Ahmed H.; Nooh, Mohammed M.; Mahrous, Engy A.; Khaleel, Amal E.; Elalfy, Taha S.

2017-01-01

Background: Several studies have affirmed the effectiveness of some Bauhinia plants as antihyperglycemic agents. Objective: We investigated the possible effect of Bauhinia vahlii leaves extract in reducing hyperglycemia and reversing signs of organ damage associated with diabetes in streptozotocin (STZ) rat model. Materials and Methods: Both polar fraction of the B. vahlii leaves (defatted ethanolic extract [DEE]) and nonpolar fraction (n-hexane extract) were evaluated in vitro for α-glucosidase inhibition and 2,2-diphenyl-1-picrylhydrazyl radical scavenging potential. DEE was selected for further in vivo studies and was administered at two doses, i.e., 150 or 300 mg/kg to STZ-diabetic rats for 4 weeks. Results: Only DEE exhibited in vitro antioxidant and antihyperglycemic activities and its oral administration at both dose levels resulted in significant reduction in fasting blood glucose and glycated hemoglobin. Furthermore, signs of oxidative stress as indicated by hepatic reduced glutathione, nitric oxide, and malondialdehyde levels were completely reversed. In addition, histopathological examination and measurement of serum aspartate transaminase and alanine transaminase levels showed that DEE protected the liver from signs of liver pathogenesis when compared to diabetic untreated animals and those treated with metformin. Phytochemical analysis of DEE showed high flavonoids content with quercitrin as the major constituent along with other quercetin glycosides. Conclusion: This study strongly highlights the possible beneficial effect of B. vahlii leaves extract in relieving hyperglycemia and liver damage in STZ-diabetic rats and recommends further investigation of the value of quercetin derivatives in controlling diabetes and ameliorating liver damage associated with it. SUMMARY The polar fraction of the Bauhinia vahlii leaves (defatted ethanolic extract [DEE]) exhibited both in vitro antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl scavenging assay and strong α-glucosidase inhibition while the nonpolar fraction (n-hexane extract) failed to show any activity in both assays. DEE was further investigated in streptozotocin-induced diabetic rat model where oral administration of DEE at 2 doses (150 and 300 mg/kg) for 4 weeks resulted in significant reduction in fasting blood glucose and glycated hemoglobin and reversal of oxidative stress signs as indicated by measurement of hepatic reduced glutathione, nitric oxide, and malondialdehyde levels. In addition, histopathological examination and measurement of serum aspartate transaminase and alanine transaminase levels showed that DEE protected the liver from signs of pathogenesis observed in diabetic untreated rats. Phytochemical analysis of DEE showed high flavonoid content with quercitrin as the major constituent (62.9 ± 0.18 mg/mg). Abbreviations used: ALT: Alanine transaminase, AST: Aspartate transaminase, DEE: Defatted ethanol extract, DPPH: 2,2-diphenyl-1-picrylhydrazyl, FBG: Fasting blood glucose, GAE: Gallic acid equivalent, GSH: Reduced glutathione, Hb1Ac: Glycated hemoglobin, HE: Hexane extract MDA: Malondialdehyde, QE: Quercetin equivalent, STZ: Streptozotocin, TAC: Total antioxidant capacity. PMID:29142421

Study of the propensity for hemorrhage in Hispanic Americans with stroke.

PubMed

Frey, James L; Jahnke, Heidi K; Goslar, Pamela W

2008-01-01

Multiple sources document a higher proportion of intraparenchymal hemorrhage (HEM) in Hispanic (HIS) than white (WHI) patients with stroke. We sought an explanation for this phenomenon through analysis of multiple variables in our hospital-based stroke population. We performed univariate and multivariate analysis of risk factors in our HIS and WHI patients with stroke to identify differences that might account for a greater propensity for HEM in HIS patients. Multivariate analysis disclosed that the risk of HEM correlated significantly with untreated hypertension (HTN), HIS ethnicity, and heavy alcohol intake. A negative correlation was found for hyperlipidemia and diabetes. Our HIS patients with stroke had a greater prevalence of untreated HTN and heavy alcohol intake, with HIS men being at greatest risk. HIS patients with stroke in our hospital-based population appear relatively more prone to HEM than do WHI patients. This risk correlates with a greater likelihood of having untreated HTN and heavy alcohol intake, more so for HIS men. The explanation appears to be a relative lack of health awareness and involvement in our health care system. The possibility that HIS ethnicity itself constitutes a biological risk factor for HEM remains a matter of speculation. Validation of this work with community data should lead to remediation through a community-based effort.

Diagnosis of co-morbid axis-I psychiatric disorders among women with newly diagnosed, untreated endocrine disorders.

PubMed

Fornaro, Michele; Iovieno, Nadia; Clementi, Nicoletta; Boscaro, Marco; Paggi, Francesca; Balercia, Giancarlo; Fava, Maurizio; Papakostas, George I

2010-12-01

To determine the prevalence of major depressive disorder (MDD) and other selected axis-I disorders among women with newly diagnosed, untreated endocrine disorders. Two hundred and eighteen consecutive women, aged 18-65, with newly diagnosed, untreated endocrine disorders were referred for potential diagnosis of co-morbid axis-I disorders with the use of the Structured Clinical Interview for Axis I-Patient Edition (SCID-P). The SCID-P was re-administered after 12 weeks. At baseline, 64 (29.3%) women met criteria for at least one axis-I disorder. Women who were diagnosed with hyperthyroidism were more likely to meet criteria for generalized anxiety disorder and panic disorder than women without hyperthyroidism. Nine of 154 (5.8 %) women who did not meet criteria for an axis-I disorder at baseline met criteria for at least one axis-I disorder during follow-up. Among them, the presence of diabetes mellitus was statistically correlated with a higher probability of developing major depressive disorder at follow-up. Although preliminary, our findings are consistent with previous studies and suggest an increased prevalence of MDD and other axis-I disorders among women with newly diagnosed endocrine disorders, providing further evidence suggesting that women with endocrine abnormalities may be at increased risk of depression and/or anxiety disorders.

Effects of recombinant human growth hormone and nandrolone phenylpropionate on the healing of ischemic colon anastomosis in rats.

PubMed

Yarimkaya, Ali; Apaydin, Berat; Unal, Ethem; Karabicak, Ilhan; Aydogan, Fatih; Uslu, Ezel; Erginoz, Ethem; Artis, Tarik; Eyuboglu, Erhun

2003-12-01

Recombinant human growth hormone and nandrolone phenylpropionate are two different anabolic agents. This study was designed to investigate the effects of these anabolic agents on the healing of ischemic colon anastomosis in rats. Seventy adult male Wistar rats were divided into five groups (n = 14). Group I was the sham laparotomy group. In the other groups, surgical procedures consisting of transsection and anastomosis were made at a distance 3 cm from the peritoneal reflection. Group II was the nonischemic control group. Ischemic colon model was produced in the remaining groups. Group III was the untreated control group. Groups IV and V received recombinant human growth hormone and nandrolone phenylpropionate, respectively. Bursting pressure and hydroxyproline levels were measured on the third and seventh postoperative days to evaluate anastomotic healing. Recombinant human growth hormone increased both collagen deposition and bursting pressure significantly at postoperative Days 3 and 7 compared with the sham and untreated control groups (P < 0.005). When compared with the untreated control, nandrolone phenylpropionate significantly increased collagen deposition at postoperative Days 3 and 7 (P < 0.005) and bursting pressure only at postoperative Day 3 (P < 0.005). Recombinant human growth hormone has more favorable therapeutic effects on the healing of ischemic colonic anastomoses than nandrolone phenylpropionate. Recombinant human growth hormone also improves healing of nonischemic colonic anastomosis.

Changes in color vision and contrast sensitivity after descemet membrane endothelial keratoplasty for fuchs endothelial dystrophy.

PubMed

Cabrerizo, Javier; Livny, Eitan; Musa, Fayyaz U; Leeuwenburgh, Paulien; van Dijk, Korine; Melles, Gerrit R J

2014-10-01

The aim of this study is to evaluate contrast sensitivity, color vision, and subjective patient satisfaction after Descemet membrane endothelial keratoplasty (DMEK) in patients with bilateral Fuchs endothelial dystrophy (FED). From a group of 500 DMEK surgeries performed in our center, patients with a history of bilateral FED and unilateral DMEK were identified. A total of 29 patients were included in the study and divided into 2 groups: phakic (n = 12) and pseudophakic unilateral DMEK (n = 17) and their contralateral, untreated FED-affected eye. In addition, a control group of 10 healthy eyes of 10 patients was included. Pelli-Robson contrast sensitivity and Farnsworth-Munsell 100 hue color vision tests were performed. Subjective optical quality was graded with a questionnaire. Compared with untreated FED-affected eyes, best spectacle-corrected visual acuity was higher after DMEK in phakic and pseudophakic eyes (P = 0.030 and P < 0.001, respectively); a similar result was obtained for contrast sensitivity (P < 0.001 and P < 0.001, respectively). Color vision did not differ between untreated FED-affected and DMEK-operated eyes in the phakic group (P = 0.802) and the pseudophakic group (P = 0.227). Subjective optical quality was better in DMEK-operated eyes than in untreated FED-affected eyes in the phakic group (P < 0.001) and in the pseudophakic group (P < 0.001). In FED, DMEK may not only be effective for obtaining a higher visual acuity but particularly improving the contrast sensitivity may also lead to better subjective optical performance. Although frequently mentioned spontaneously by patients, an objective change in color vision could not be substantiated. Hence, quantifying contrast sensitivity before surgery may aid in the decision for surgery, and in the evaluation of surgical outcome.

Glucocorticoid receptors in bronchial epithelial cells in asthma.

PubMed

Vachier, I; Chiappara, G; Vignola, A M; Gagliardo, R; Altieri, E; Térouanne, B; Vic, P; Bousquet, J; Godard, P; Chanez, P

1998-09-01

The expression of the glucocorticoid receptor (GR) in untreated or in steroid-dependent asthmatic patients is poorly understood. We therefore studied GR mRNA and protein levels in bronchial biopsies obtained from seven untreated asthmatic patients, seven control volunteers, and seven patients with chronic bronchitis. We also studied in bronchial epithelial cells obtained by brushing from 13 untreated asthmatics, 18 steroid-dependent asthmatics, 11 control volunteers, and 12 patients with chronic bronchitis, GR and heat shock protein 90 kD (hsp90) mRNA as well as the immunoreactivity of GR, intercellular adhesion molecule (ICAM-1), and granulocyte macrophage-colony-stimulating factor (GM-CSF). GR mRNA and protein level was similar in all subject groups in both biopsies and bronchial epithelial cells. Hsp90 mRNA level was also similar in all subject groups. ICAM-1 expression was significantly increased in bronchial epithelial cells from untreated asthmatics, but ICAM-1 was not expressed in those from steroid-dependent asthmatic patients. GM-CSF expression was significantly increased in bronchial epithelial cells from untreated and steroid-dependent asthmatic patients. GR expression within the airways is unaltered by oral long-term steroid treatment in asthma, but the expression of some but not all specific markers for asthma is modified by oral steroid.

Dental caries among children visiting a mobile dental clinic in South Central Kentucky: a pooled cross-sectional study.

PubMed

Dawkins, Erika; Michimi, Akihiko; Ellis-Griffith, Gregory; Peterson, Tina; Carter, Daniel; English, Gary

2013-05-02

Dental caries is one of the most common chronic childhood diseases affecting a large portion of children in the United States. The prevalence of childhood dental caries in Kentucky is among the highest in the nation. The purposes of this study are to (1) compare sociodemographic differences between caries and no caries groups and (2) investigate factors associated with untreated dental caries among children who visited a mobile dental clinic in South Central Kentucky. Study subjects were children aged 6 to 15 years who participated in the school-based dental sealant program through the mobile dental clinic operated by the Institute for Rural Health at Western Kentucky University between September 2006 and May 2011 (n = 2,453). Descriptive statistics were calculated for sociodemographic factors (age, gender, race/ethnicity, insurance status, and urban versus rural residential location) and caries status. We used chi-square tests to compare sociodemographic differences of children stratified by caries and no caries status as well as three levels of caries severity. We developed a logistic regression model to investigate factors associated with untreated dental caries while controlling for sociodemographic characteristics. The proportion of children having untreated dental caries was 49.7% and the mean number of untreated dental caries was 2.0. The proportion of untreated dental caries was higher in older children, children with no insurance and living in rural residential locations, and caries severity was also higher in these groups. Odds ratio indicated that older ages, not having private insurance (having only public, government-sponsored insurance or no insurance at all) and rural residential location were associated with having untreated dental caries after controlling for sociodemographic characteristics of children. Untreated dental caries was more likely to be present in older children living in rural areas without insurance. Health interventionists may use this information and target rural children without having proper insurance in order to reduce geographic disparities in untreated dental caries in South Central Kentucky.

Comparison of maternal morbidity and medical costs during pregnancy and delivery between patients with gestational diabetes and patients with pre-existing diabetes

PubMed Central

Son, K H; Lim, N-K; Lee, J-W; Cho, M-C; Park, H-Y

2015-01-01

Aims To evaluate the effects of gestational diabetes and pre-existing diabetes on maternal morbidity and medical costs, using data from the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service. Methods Delivery cases in 2010, 2011 and 2012 (459 842, 442 225 and 380 431 deliveries) were extracted from the Health Insurance Review and Assessment Service database. The complications and medical costs were compared among the following three pregnancy groups: normal, gestational diabetes and pre-existing diabetes. Results Although, the rates of pre-existing diabetes did not fluctuate (2.5, 2.4 and 2.7%) throughout the study, the rate of gestational diabetes steadily increased (4.6, 6.2 and 8.0%). Furthermore, the rates of pre-existing diabetes and gestational diabetes increased in conjunction with maternal age, pre-existing hypertension and cases of multiple pregnancy. The risk of pregnancy-induced hypertension, urinary tract infections, premature delivery, liver disease and chronic renal disease were greater in the gestational diabetes and pre-existing diabetes groups than in the normal group. The risk of venous thromboembolism, antepartum haemorrhage, shoulder dystocia and placenta disorder were greater in the pre-existing diabetes group, but not the gestational diabetes group, compared with the normal group. The medical costs associated with delivery, the costs during pregnancy and the number of in-hospital days for the subjects in the pre-existing diabetes group were the highest among the three groups. Conclusions The study showed that the rates of pre-existing diabetes and gestational diabetes increased with maternal age at pregnancy and were associated with increases in medical costs and pregnancy-related complications. PMID:25472691

Short term resistance training enhanced plasma apoA-I and FABP4 levels in Streptozotocin-induced diabetic rats.

PubMed

Safarzade, Alireza; Talebi-Garakani, Elahe

2014-03-04

Type 1 diabetes mellitus is associated with a high risk for early atherosclerotic complications. Altered lipids and lipoprotein metabolism in chronic diabetes mellitus is associated with pathogenesis of atherosclerosis and other cardiovascular diseases. The aim of this study was to investigate the effects of 4 weeks resistance training on plasma lipid profile, fatty acid binding protein (FABP) 4 and apolipoprotein (apo) A-I levels in type 1 diabetic rats. Thirty two male Wister rats (12-14 weeks old) were randomly divided into four groups: non-diabetic control; non-diabetic trained; diabetic control; diabetic trained. The rats in training groups were subjected to a resistance training program (3 days/wk, for 4 wk) consisted of climbing a ladder carrying a load suspended from the tail. Diabetic inducing increased plasma apoA-I and decreased FABP4 levels compared with non-diabetic control group (respectively, P = 0.001 & P = 0.041). After 4 weeks' resistance training, plasma levels of apoA-I and FABP4 in the diabetic trained rats were significantly higher compared with the diabetic control group (respectively, P = 0.003 & P = 0.017). Plasma HDL-C level in diabetic trained group was higher than diabetic control group (P = 0.048). Liver triglycerides concentrations were significantly lower in both trained (non-diabetic and diabetic) groups compared with their control groups (respectively, P = 0.041 and P = 0.002). These data indicated that resistance training may be an efficient intervention strategy to increase plasma apoA-I, HDL-C and FABP4 concentrations, along with decreases liver triglycerides in streptozotocin induced diabetic rats. Further research is needed to elucidate physiological significance of circulating FABP4 levels.

Acceleration of diabetic wound healing with adipose-derived stem cells, endothelial-differentiated stem cells, and topical conditioned medium therapy in a swine model.

PubMed

Irons, Robin F; Cahill, Kevin W; Rattigan, Deviney A; Marcotte, Joseph H; Fromer, Marc W; Chang, Shaohua; Zhang, Ping; Behling, Eric M; Behling, Kathryn C; Caputo, Francis J

2018-05-09

The purpose of our study was to investigate the effect of adipose-derived stem cells (ASCs), endothelial-differentiated ASCs (EC/ASCs), and various conditioned media (CM) on wound healing in a diabetic swine model. We hypothesized that ASC-based therapies would accelerate wound healing. Diabetes was induced in four Yorkshire swine through intravenous injection of streptozotocin. ASCs were harvested from flank fat and cultured in either M199 or EGM-2 medium. A duplicate series of seven full-thickness dorsal wounds were surgically created on each swine. The wounds in the cellular treatment group underwent injection of low-dose or high-dose ASCs or EC/ASCs on day 0, with a repeat injection of one half of the initial dose on day 15. Wounds assigned to the topical CM therapy were covered with 2 mL of either serum-free M199 primed by ASCs or human umbilical vein endothelial cells every 3 days. Wounds were assessed at day 0, 10, 15, 20, and 28. The swine were sacrificed on day 28. ImageJ software was used to evaluate the percentage of wound healing. The wounded skin underwent histologic, reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay examinations to evaluate markers of angiogenesis and inflammation. We found an increase in the percentage of wound closure rates in cell-based treatments and topical therapies at various points compared with the untreated control wounds (P < .05). The results from the histologic, messenger RNA, and protein analyses suggested the treated wounds displayed increased angiogenesis and a diminished inflammatory response. Cellular therapy with ASCs, EC/ASCs, and topical CM accelerated diabetic wound healing in the swine model. Enhanced angiogenesis and immunomodulation might be key contributors to this process. The purpose of the present study was to translate the known beneficial effects of adipose-derived stem cells and associated conditioned medium therapy on diabetic wound healing to a large animal model. We demonstrated that stem cell and conditioned medium therapy significantly accelerate gross wound healing in diabetic swine, with data suggesting this might result from a decreased inflammatory response and increased angiogenesis. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Prevalence of blindness and diabetic retinopathy in northern Jordan.

PubMed

Rabiu, Mansur M; Al Bdour, Muawyah D; Abu Ameerh, Mohammed A; Jadoon, Muhammed Z

2015-01-01

To estimate the prevalence of blindness, visual impairment, diabetes, and diabetic retinopathy in north Jordan (Irbid) using the rapid assessment of avoidable blindness and diabetic retinopathy methodology. A multistage cluster random sampling technique was used to select participants for this survey. A total of 108 clusters were selected using probability proportional to size method while subjects within the clusters were selected using compact segment method. Survey teams moved from house to house in selected segments examining residents 50 years and older until 35 participants were recruited. All eligible people underwent a standardized examination protocol, which included ophthalmic examination and random blood sugar test using digital glucometers (Accu-Chek) in their homes. Diabetic retinopathy among diabetic patients was assessed through dilated fundus examination. A total of 3638 out of the 3780 eligible participants were examined. Age- and sex-adjusted prevalence of blindness, severe visual impairment, and visual impairment with available correction were 1.33% (95% confidence interval [CI] 0.87-1.73), 1.82% (95% CI 1.35-2.25), and 9.49% (95% CI 8.26-10.74), respectively, all higher in women. Untreated cataract and diabetic retinopathy were the major causes of blindness, accounting for 46.7% and 33.2% of total blindness cases, respectively. Glaucoma was the third major cause, accounting for 8.9% of cases. The prevalence of diabetes mellitus was 28.6% (95% CI 26.9-30.3) among the study population and higher in women. The prevalence of any retinopathy among diabetic patients was 48.4%. Cataract and diabetic retinopathy are the 2 major causes of blindness and visual impairment in northern Jordan. For both conditions, women are primarily affected, suggesting possible limitations to access to services. A diabetic retinopathy screening program needs to proactively create sex-sensitive awareness and provide easily accessible screening services with prompt treatment.

[Diabetes and pregnancy].

PubMed

Somville, T

1990-01-01

In recent years, new findings in the pathophysiology and treatment of diabetes mellitus during pregnancy and the development of improved fetal monitoring methods have considerably reduced the risk for mother and child. Given good metabolism the fertility of diabetics is comparable to that of nondiabetics. Perinatal mortality in centers is below 2%, and in 40% of the cases it is caused by congenital malformations. The incidence of malformations is 4-8%. Regulation of metabolism to near-normal values is vital for further improvement of mortality and morbidity rates, and should be aimed for prior to conception. In many cases insufficient attention is given to gestational diabetes. The risks accompanying untreated gestational diabetes are underestimated. In approx. 15% of such patients insulin therapy during pregnancy is necessary in addition to dietary measures. The goal of near normal metabolism (60-120 mg/dl, with mean daily values around 85-90 mg/dl) can usually be achieved during training, either prior to conception or at the latest during early pregnancy, by improved substitutional insulin therapy or insulin pump therapy. Short-term combined internalistic-obstetric follow-up at 14-day intervals ensures early prevention and detection of complications. The pregnancy can be continued to term in over 80% of cases, and spontaneous birth aimed for as the primary goal in the majority. With careful monitoring of metabolism, diabetics with no vascular complications may take low-dosage ovulation inhibitors to prevent conception. In isolated cases termination may be indicated in patients with severe vascular complications (proliferative retinopathy, severe nephropathy).

Community Evaluation of the National Diabetes Education Program's Diabetes HealthSense Website.

PubMed

Sadler, Michele DeBarthe; Saperstein, Sandra L; Carpenter, Carrie; Devchand, Roshni; Tuncer, Diane; O'Brian, Catherine; Nicols, Christina; Gallivan, Joanne

2017-10-01

Purpose The purpose of this study was to assess the impact of Diabetes HealthSense on knowledge, attitudes, and behavior changes that prevent, delay, or manage diabetes among people at risk (PAR) for diabetes and people with diabetes (PWD). Methods Using a 2-group pretest-posttest design, 15 community sites were randomly assigned to either an intervention or comparison group. Intervention participants attended a group education session with a diabetes educator, followed by 4 weeks of independent use of the Diabetes HealthSense website. The comparison group received no intervention. A total of 311 adults (n = 135 intervention, n = 176 comparison) completed both a pretest and posttest. Outcome measures examined changes in self-reported knowledge, self-efficacy, and behaviors that support diabetes prevention or management. Results Statistically significant within-group pretest to posttest changes were found for almost all outcome measures in the intervention group, with no significant changes in the comparison group. Significant between-group differences were also found for almost all outcome measures at posttest, with the intervention group having more positive outcomes than the comparison group. Conclusions Patient referral to online tools is considered one key component of initial and ongoing diabetes self-management education and support (DSME/S) and is recommended as a way to enhance and extend the reach of in-person diabetes education. Positive outcomes were found for PWD/PAR who used Diabetes HealthSense following a guided education session. Study results suggested that with guided exploration, Diabetes HealthSense provided a valuable tool for educators to use with patients to support and extend the reach of DSME/S.

Influence of hyperbaric oxygen on biomechanics and structural bone matrix in type 1 diabetes mellitus rats.

PubMed

Limirio, Pedro Henrique Justino Oliveira; da Rocha Junior, Huberth Alexandre; Morais, Richarlisson Borges de; Hiraki, Karen Renata Nakamura; Balbi, Ana Paula Coelho; Soares, Priscilla Barbosa Ferreira; Dechichi, Paula

2018-01-01

The aim of this study was to evaluate the biomechanics and structural bone matrix in diabetic rats subjected to hyperbaric oxygen therapy (HBO). Twenty-four male rats were divided into the following groups: Control; Control + HBO; Diabetic, and Diabetic + HBO. Diabetes was induced with streptozotocin (STZ) in the diabetic Groups. After 30 days, HBO was performed every 48h in HBO groups and all animals were euthanized 60 days after diabetic induction. The femur was submitted to a biomechanical (maximum strength, energy-to-failure and stiffness) and Attenuated Total Reflectance Fourier transform infrared (ATR-FTIR) analyses (crosslink ratio, crystallinity index, matrix-to-mineral ratio: Amide I + II/Hydroxyapatite (M:MI) and Amide III + Collagen/HA (M:MIII)). In biomechanical analysis, diabetic animals showed lower values of maximum strength, energy and stiffness than non-diabetic animals. However, structural strength and stiffness were increased in groups with HBO compared with non-HBO. ATR-FTIR analysis showed decreased collagen maturity in the ratio of crosslink peaks in diabetic compared with the other groups. The bone from the diabetic groups showed decreased crystallinity compared with non-diabetic groups. M:MI showed no statistical difference between groups. However, M:MIII showed an increased matrix mineral ratio in diabetic+HBO and control+HBO compared with control and diabetic groups. Correlations between mechanical and ATR-FTIR analyses showed significant positive correlation between collagen maturity and stiffness. Diabetes decreased collagen maturation and the mineral deposition process, thus reducing biomechanical properties. Moreover, the study showed that HBO improved crosslink maturation and increased maximum strength and stiffness in the femur of T1DM animals.

Integrating Oral and General Health Screening at Senior Centers for Minority Elders

PubMed Central

Cheng, Bin; Northridge, Mary E.; Kunzel, Carol; Huang, Catherine; Lamster, Ira B.

2013-01-01

Racial/ethnic and socioeconomic disparities regarding untreated oral disease exist for older adults, and poor oral health diminishes quality of life. The ElderSmile program integrated screening for diabetes and hypertension into its community-based oral health activities at senior centers in northern Manhattan. The program found a willingness among minority seniors (aged ≥ 50 years) to be screened for primary care sensitive conditions by dental professionals and a high level of unrecognized disease (7.8% and 24.6% of ElderSmile participants had positive screening results for previously undiagnosed diabetes and hypertension, respectively). Dental professionals may screen for primary care–sensitive conditions and refer patients to health care providers for definitive diagnosis and treatment. The ElderSmile program is a replicable model for community-based oral and general health screening. PMID:23597378

Streptozotocin diabetes attenuates the effects of nondepolarizing neuromuscular relaxants on rat muscles.

PubMed

Huang, Lina; Chen, Dan; Li, Shitong

2014-12-01

The hypothesis of this study was that diabetes-induced desensitization of rat soleus (SOL) and extensor digitorum longus (EDL) to non-depolarizing muscle relaxants (NDMRs) depends on the stage of diabetes and on the kind of NDMRs. We tested the different magnitude of resistance to vecuronium, cisatracurium, and rocuronium at different stages of streptozotocin (STZ)-induced diabetes by the EDL sciatic nerve-muscle preparations, and the SOL sciatic nerve-muscle preparations from rats after 4 and 16 weeks of STZ treatment. The concentration-twitch tension curves were significantly shifted from those of the control group to the right in the diabetic groups. Concentration giving 50% of maximal inhibition (IC50) was larger in the diabetic groups for all the NDMRs. For rocuronium and cisatracurium in both SOL and EDL, IC50 was significantly larger in diabetic 16 weeks group than those in the diabetic 4 weeks group. For SOL/EDL, the IC50 ratios were significantly largest in the diabetic 16 weeks group, second largest in the diabetic 4 weeks group, and smallest for the control group. Diabetes-induced desensitization to NDMRs depended on the stage of diabetes and on the different kind of muscles observed while was independent on different kind of NDMRs. The resistance to NDMRs was stronger in the later stage of diabetes (16 versus 4 weeks after STZ treatment). Additionally, when monitoring in SOL, diabetes attenuated the actions of neuromuscular blockade more intensely than that in EDL. Nonetheless, the hyposensitivity to NDMRs in diabetes was not relevant for the kind of NDMRs.

The Effects of Diabetic Retinopathy and Pan-Retinal Photocoagulation on Photoreceptor Cell Function as Assessed by Dark Adaptometry

PubMed Central

Bavinger, J. Clay; Dunbar, Grace E.; Stem, Maxwell S.; Blachley, Taylor S.; Kwark, Leon; Farsiu, Sina; Jackson, Gregory R.; Gardner, Thomas W.

2016-01-01

Purpose The pathophysiology of vision loss in persons with diabetic retinopathy (DR) is complex and incompletely defined. We hypothesized that retinal pigment epithelium (RPE) and rod and cone photoreceptor dysfunction, as measured by dark adaptometry, would increase with severity of DR, and that pan-retinal photocoagulation (PRP) would exacerbate this dysfunction. Methods Dark adaptation (DA) was measured in subjects with diabetes mellitus and healthy controls. Dark adaptation was measured at 5° superior to the fovea following a flash bleach, and the data were analyzed to yield cone and rod sensitivity curves. Retinal layer thicknesses were quantified using spectral-domain optical coherence tomography (OCT). Results The sample consisted of 23 controls and 73 diabetic subjects. Subjects with moderate nonproliferative diabetic retinopathy (NPDR) exhibited significant impairment of rod recovery rate compared with control subjects (P = 0.04). Cone sensitivity was impaired in subjects with proliferative diabetic retinopathy (PDR) (type 1 diabetes mellitus [T1DM]: P = 0.0047; type 2 diabetes mellitus [T2DM]: P < 0.001). Subjects with untreated PDR compared with subjects treated with PRP exhibited similar rod recovery rates and cone sensitivities. Thinner RPE as assessed by OCT was associated with slower rod recovery and lower cone sensitivity, and thinner photoreceptor inner segment/outer segment layer was associated with lower cone sensitivity. Conclusions The results suggest that RPE and photoreceptor cell dysfunction, as assessed by cone sensitivity level and rod- and RPE-mediated dark adaptation, progresses with worsening DR, and rod recovery dysfunction occurs earlier than cone dysfunction. Function was preserved following PRP. The findings suggest multiple defects in retinoid function and provide potential points to improve visual function in persons with PDR. PMID:26803796

Evaluation of the anti-diabetic properties of Mucuna pruriens seed extract.

PubMed

Majekodunmi, Stephen O; Oyagbemi, Ademola A; Umukoro, Solomon; Odeku, Oluwatoyin A

2011-08-01

To explore the antidiabetic properties of Mucuna pruriens(M. pruriens). Diabetes was induced in Wistar rats by single intravenous injection of 120 mg/kg of alloxan monohydrate and different doses of the extract were administered to diabetic rats. The blood glucose level was determined using a glucometer and results were compared with normal and untreated diabetic rats. The acute toxicity was also determined in albino mice. Results showed that the administration of 5, 10, 20, 30, 40, 50, and 100 mg/kg of the crude ethanolic extract of M. pruriens seeds to alloxan-induced diabetic rats (plasma glucose > 450 mg/dL) resulted in 18.6%, 24.9%, 30.8%, 41.4%, 49.7%, 53.1% and 55.4% reduction, respectively in blood glucose level of the diabetic rats after 8h of treatment while the administration of glibenclamide (5 mg/kg/day) resulted in 59.7% reduction. Chronic administration of the extract resulted in a significant dose dependent reduction in the blood glucose level (P<0.001). It also showed that the antidiabetic activity of M. pruriens seeds resides in the methanolic and ethanolic fractions of the extract. Acute toxicity studies indicated that the extract was relatively safe at low doses, although some adverse reactions were observed at higher doses (8-32 mg/kg body weight), no death was recorded. Furthermore, oral administration of M. pruriens seed extract also significantly reduced the weight loss associated with diabetes. The study clearly supports the traditional use of M. pruriens for the treatment of diabetes and indicates that the plant could be a good source of potent antidiabetic drug. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Management of diabetes and associated cardiovascular risk factors in seven countries: a comparison of data from national health examination surveys

PubMed Central

Mallinger, Leslie; Abbott-Klafter, Jesse; Guerrero, Ramiro; Villalpando, Salvador; Ridaura, Ruy Lopez; Aekplakorn, Wichai; Naghavi, Mohsen; Lim, Stephen; Lozano, Rafael; Murray, Christopher JL

2011-01-01

Abstract Objective To examine the effectiveness of the health system response to the challenge of diabetes across different settings and explore the inequalities in diabetes care that are attributable to socioeconomic factors. Methods We used nationally representative health examination surveys from Colombia, England, the Islamic Republic of Iran, Mexico, Scotland, Thailand and the United States of America to obtain data on diagnosis, treatment and control of hyperglycaemia, arterial hypertension and hypercholesterolaemia among individuals with diabetes. Using logistic regression, we explored the socioeconomic determinants of diagnosis and effective case management. Findings A substantial proportion of individuals with diabetes remain undiagnosed and untreated, both in developed and developing countries. The figures range from 24% of the women in Scotland and the USA to 62% of the men in Thailand. The proportion of individuals with diabetes reaching treatment targets for blood glucose, arterial blood pressure and serum cholesterol was very low, ranging from 1% of male patients in Mexico to about 12% in the United States. Income and education were not found to be significantly related to the rates of diagnosis and treatment anywhere except in Thailand, but in the three countries with available data insurance status was a strong predictor of diagnosis and effective management, especially in the United States. Conclusion There are many missed opportunities to reduce the burden of diabetes through improved control of blood glucose levels and improved diagnosis and treatment of arterial hypertension and hypercholesterolaemia. While no large socioeconomic inequalities were noted in the management of individuals with diabetes, financial access to care was a strong predictor of diagnosis and management. PMID:21379413

Insulin-secretagogue, antihyperlipidemic and other protective effects of gallic acid isolated from Terminalia bellerica Roxb. in streptozotocin-induced diabetic rats.

PubMed

Latha, R Cecily Rosemary; Daisy, P

2011-01-15

Diabetes mellitus causes derangement of carbohydrate, protein and lipid metabolism which eventually leads to a number of secondary complications. Terminalia bellerica is widely used in Indian medicine to treat various diseases including diabetes. The present study was carried out to isolate and identify the putative antidiabetic compound from the fruit rind of T. bellerica and assess its chemico-biological interaction in experimental diabetic rat models. Bioassay guided fractionation was followed to isolate the active compound, structure was elucidated using (1)H and (13)C NMR, IR, UV and mass spectrometry and the compound was identified as gallic acid (GA). GA isolated from T. bellerica and synthetic GA was administered to streptozotocin (STZ)-induced diabetic male Wistar rats at different doses for 28 days. Plasma glucose level was significantly (p<0.05) reduced in a dose-dependent manner when compared to the control.Histopathological examination of the pancreatic sections showed regeneration of β-cells of islets of GA-treated rats when compared to untreated diabetic rats. In addition, oral administration of GA (20mg/kg bw) significantly decreased serum total cholesterol, triglyceride, LDL-cholesterol, urea, uric acid, creatinine and at the same time markedly increased plasma insulin, C-peptide and glucose tolerance level. Also GA restored the total protein, albumin and body weight of diabetic rats to near normal. Thus our findings indicate that gallic acid present in fruit rind of T. bellerica is the active principle responsible for the regeneration of β-cells and normalizing all the biochemical parameters related to the patho-biochemistry of diabetes mellitus and hence it could be used as a potent antidiabetic agent. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Economic impact of multiple sclerosis disease-modifying drugs in an employed population: direct and indirect costs.

PubMed

Birnbaum, Howard G; Ivanova, Jasmina I; Samuels, Seth; Davis, Matthew; Cremieux, Pierre Y; Phillips, Amy L; Meletiche, Dennis

2009-04-01

The study objective is to compare the annual total medical and indirect costs of newly treated and untreated employees with multiple sclerosis (MS). A retrospective database analysis of employer medical, drug, and disability claims database (Ingenix Employer database, 1999-2005; 17 large US companies) was conducted for employees 18-64 years of age with > or =1 MS diagnosis after January 1, 2002. Employees with > or =1 MS disease-modifying drug (DMD) claim comprised the newly treated group; employees with MS but no DMD at any time comprised the untreated, comparison group. Index date was the day after the most recent claim (treated, DMD claim; untreated, MS claim) meeting the following requirements: continuous health coverage for 3 months before (baseline period) and 12 months after the index date (study period) and actively employed during baseline. Total medical costs and indirect (work loss) costs over the 1-year study period (2006 $US) were compared for DMD-treated and untreated MS employees, adjusting for baseline characteristics, including comorbidities. During the baseline, MS employees who became treated (n = 258) were younger (40.9 vs. 44.4 years, p < 0.0001) and had a higher proportion of women (72 vs. 62%, p = 0.007) than the untreated group of MS employees who never received DMD treatment (n = 322). The 3-month baseline MS-related medical costs were higher among treated MS employees ($2520 vs. $1012, p < 0.0001). There was a nonsignificant trend toward higher baseline non-MS-related medical costs in untreated versus treated MS employees. Risk-adjusted total annual medical costs ($4393 vs. $6187, p < 0.0001) and indirect costs ($2252 vs. $3053, p < 0.0001) were significantly lower for treated MS employees than for untreated MS employees. Initiation of MS disease-modifying drugs was associated with substantial significant medical and indirect savings for employees with MS. Study findings should be considered in the context of the study limitations (e.g., analytic focus on employees with at least 12-month follow-up; lack of clinical detail on MS severity).

Ursodeoxycholic acid after bile duct stone removal and risk factors for recurrence: a randomized trial.

PubMed

Yamamoto, Ryuichi; Tazuma, Susumu; Kanno, Keishi; Igarashi, Yoshinori; Inui, Kazuo; Ohara, Hirotaka; Tsuyuguchi, Toshio; Ryozawa, Shomei

2016-02-01

Currently, no established pharmacologic treatment exists for the prevention of recurrent common bile duct (CBD) stones. Here, we present a multi-center randomized trial that compared the CBD recurrence rate after bile duct stone removal between patients given ursodeoxycholic acid (UDCA) and the untreated group. A total of 36 patients were randomly assigned to either the UDCA (n = 15) or the untreated group (n = 21). The primary end-point was the recurrence rate of CBD stones. The recurrence rate of CBD stones was 6.6% in the UDCA group and 18.6% in the untreated group (P = 0.171). A multivariate analysis found that not receiving UDCA was an independent risk factor for stone recurrence. The recurrence rates of CBD stones did not differ by sex, past history of cholecystectomy, or the presence of gallstones. Our findings indicate that UDCA may be a novel treatment strategy to prevent the recurrence of CBD stones. However, further evaluation of UDCA in a larger number of subjects will be required to confirm the applicability of these results. © 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

[The role of diabetes mellitus as a risk factor of acute myocardial infarction].

PubMed

Peng, Xiao-ren; Zhao, Yan-fang; Zou, Da-jin; Gu, Ping

2011-06-01

To determine the impact of elevated in-hospital glucose level on outcome of patients with acute myocardial infarction (AMI), and evaluate the role of diabetes mellitus as a risk factor of AMI. The study included a retrospective analysis of AMI patients who were admitted to No. 81 Hospital of PLA from January 2000 to May 2010. In patients without a history of diabetes, and those with fasting blood glucose (FBG)≥7.0 mmol/L at admission but returned to normal range soon after admission were defined as stress hyperglycemia of non-diabetic AMI patients. Both diabetic patients and non-diabetic patients were stratified into four mutually exclusive groups according to FBG levels: <7.0, 7.0-7.9, 8.0-11.0 and ≥11.1 mmol/L. The in-hospital mortality, incidence of complications, and treatment to lower glucose level were analyzed. Logistic regression analysis was conducted on risk factors of outcome of AMI patients. One hundred and fifty-two AMI patients were enrolled with 45 diabetic patients and 107 patients without previous diabetes. In diabetic group patients with FBG≥8.0 mmol/L and those with FBG≥11.1 mmol/L accounted for 73.3% (33 cases) and 46.7% (21 cases), respectively. In non-diabetic group patients with stress hyperglycemia accounted for 43.9% (47 cases), among which patients with FBG levels of 7.011.0 mmol/L accounted for 91.5% (43 cases). Compared with the non-diabetic group, the in-hospital mortality was significantly higher in diabetic group (35.6% vs. 15.9%, P=0.007). In both groups, the in-hospital mortality presented an elevating tendency with an increasing FBG level. Multivariate Logistic regression analysis demonstrated that in diabetic group patients with FBG≥8.0 mmol/L had 12.28-fold higher risk of death than patients with FBG<8.0 mmol/L, and that in non-diabetic group patients with FBG≥7.0 mmol/L had 4.81-fold higher risk of death than patients with FBG<7.0 mmol/L. FBG was an independent risk factor of death with relative odds ratio (OR) 1.03, with 95% confidence interval (95%CI) 1.01-1.16, P=0.012, and OR 1.56, 95%CI 1.09-2.23, P=0.015 in diabetic group and non-diabetic group, respectively. The incidence of congestive heart failure in diabetic group was significantly higher than that in non-diabetic group (40.0% vs. 22.4%, P=0.027). In non-diabetic group, the incidence of lung infection, congestive heart failure, serious arrhythmias and acute cerebrovascular events (51.1%, 34.0%, 27.7%, 14.9%, respectively) was increased significantly in patients with FBG≥7.0 mmol/L than that in patients with FBG<7.0 mmol/L (18.3%, 13.3%, 10.0%, 0, respectively, P<0.05 or P<0.01). This association was not seen in diabetic group. 80.0% of patients (36 cases) in diabetic group received anti-hyperglycemia treatments in which insulin therapy accounted for 63.9% (23 cases), while there was not even 1 patient who needed insulin therapy in non-diabetic patients with stress hyperglycemia. In-hospital mortality and complications were significantly increased in diabetic AMI patients and in non-diabetic AMI patients with stress hyperglycemia. Both a history of diabetes mellitus and stress hyperglycemia have strong influence on AMI prognosis. It seems to be more plausible to collaborate blood glucose level with history of diabetes in considering risk factors in AMI patients.

Far red/near infrared light-induced cardioprotection under normal and diabetic conditions

NASA Astrophysics Data System (ADS)

Keszler, Agnes; Baumgardt, Shelley; Hwe, Christopher; Bienengraeber, Martin

2015-03-01

Far red/near infrared light (NIR) is beneficial against cardiac ischemia and reperfusion injury (I/R), although the exact underlying mechanism is unknown. Previously we established that NIR enhanced the cardioprotective effect of nitrite in the rabbit heart. Furthermore, we observed that the nitrosyl myoglobin (MbNO) level in ischemic tissue decreased upon irradiation of the heart. Our hypothesis was that protection against I/R is dependent on nitric oxide (NO)-release from heme-proteins, and remains present during diabetes. When mice were subjected to I/R NIR (660 nm) applied during the beginning of reperfusion reduced infarct size dose dependently compared to untreated animals. Similarly, the isolated (Langendorff) heart model resulted in sustained left ventricular diastolic pressure after I/R in NIR-treated hearts. NIRinduced protection was preserved in a diabetic mouse model (db/db) and during acute hyperglycemia. NIR liberated NO from nitrosyl hemoglobin (HbNO) and MbNO as well as from HbNO isolated from the blood of diabetic animals. In the Langendorff model, after application of the nitrosylated form of a hemoglobin-based oxygen carrier as an NO donor NIR induced an increase in NADH level, suggesting a mild inhibition of mitochondrial respiration by NO during reperfusion. Taken together, NIR applied during reperfusion protects the myocardium against I/R in a NO-dependent and mitochondrion-targeted manner. This unique mechanism is conserved under diabetic conditions where other protective strategies fail.

Additive enhancement of wound healing in diabetic mice by low level light and topical CoQ10.

PubMed

Mao, Zhigang; Wu, Jeffrey H; Dong, Tingting; Wu, Mei X

2016-02-02

Diabetes, a highly prevalent disease that affects 9.3% of Americans, often leads to severe complications and slow wound healing. Preclinical studies have suggested that low level light therapy (LLLT) can accelerate wound healing in diabetic subjects, but significant improvements must be made to overcome the absence of persuasive evidence for its clinical use. We demonstrate here that LLLT can be combined with topical Coenzyme Q10 (CoQ10) to heal wounds in diabetic mice significantly faster than LLLT alone, CoQ10 alone, or controls. LLLT followed by topical CoQ10 enhanced wound healing by 68~103% in diabetic mice in the first week and more than 24% in the second week compared with untreated controls. All wounds were fully healed in two weeks following the dual treatment, in contrast to only 50% wounds or a fewer being fully healed for single or sham treatment. The accelerated healing was corroborated by at least 50% higher hydroxyproline levels, and tripling cell proliferation rates in LLLT and CoQ10 treated wounds over controls. The beneficial effects on wound healing were probably attributed to additive enhancement of ATP production by LLLT and CoQ10 treatment. The combination of LLLT and topical CoQ10 is safe and convenient, and merits further clinical study.

Reducing Amputations in People with Diabetes (RAPID): Evaluation of a New Care Pathway

PubMed Central

MacRury, Sandra; Main, Fiona; Gorman, Jane; Jones, Sandra; Macfarlane, David

2018-01-01

People with diabetes are at increased risk of foot ulcers, which, if left untreated, can lead to infection, gangrene, and subsequent amputation. Management by a multidisciplinary diabetes foot team has been shown to reduce amputation rates; however, accessing specialist treatment is made particularly difficult when living in remote and rural locations, such as many individuals cared for within NHS Highland. The RAPID project was made up of two phases: firstly, to evaluate the technical feasibility of a new integrated care pathway using innovative technology, and secondly, to establish process enhancement of the pathway to justify a larger-scale study. Omni-HubTM enabled a face-to-face consultation by the community podiatrist to be enhanced by virtual consultation with members of the multidisciplinary foot team, including specialist diabetes podiatrists and a diabetes consultant. The technical feasibility study provided recommended changes focused around adaptations to the equipment used and the best means to gain successful connectivity. The process enhancement study demonstrated positive outcomes in the process with positive effects both in the service received by patients and experiences of healthcare professionals involved. The RAPID project provides evidence and justification for a larger-scale empirical study to test an embedded pathway and technology solution, which will inform policy change and a paradigm shift in the management of foot ulceration in the community. PMID:29772673

Additive enhancement of wound healing in diabetic mice by low level light and topical CoQ10

NASA Astrophysics Data System (ADS)

Mao, Zhigang; Wu, Jeffrey H.; Dong, Tingting; Wu, Mei X.

2016-02-01

Diabetes, a highly prevalent disease that affects 9.3% of Americans, often leads to severe complications and slow wound healing. Preclinical studies have suggested that low level light therapy (LLLT) can accelerate wound healing in diabetic subjects, but significant improvements must be made to overcome the absence of persuasive evidence for its clinical use. We demonstrate here that LLLT can be combined with topical Coenzyme Q10 (CoQ10) to heal wounds in diabetic mice significantly faster than LLLT alone, CoQ10 alone, or controls. LLLT followed by topical CoQ10 enhanced wound healing by 68~103% in diabetic mice in the first week and more than 24% in the second week compared with untreated controls. All wounds were fully healed in two weeks following the dual treatment, in contrast to only 50% wounds or a fewer being fully healed for single or sham treatment. The accelerated healing was corroborated by at least 50% higher hydroxyproline levels, and tripling cell proliferation rates in LLLT and CoQ10 treated wounds over controls. The beneficial effects on wound healing were probably attributed to additive enhancement of ATP production by LLLT and CoQ10 treatment. The combination of LLLT and topical CoQ10 is safe and convenient, and merits further clinical study.

Reducing Amputations in People with Diabetes (RAPID): Evaluation of a New Care Pathway.

PubMed

MacRury, Sandra; Stephen, Kate; Main, Fiona; Gorman, Jane; Jones, Sandra; Macfarlane, David

2018-05-16

People with diabetes are at increased risk of foot ulcers, which, if left untreated, can lead to infection, gangrene, and subsequent amputation. Management by a multidisciplinary diabetes foot team has been shown to reduce amputation rates; however, accessing specialist treatment is made particularly difficult when living in remote and rural locations, such as many individuals cared for within NHS Highland. The RAPID project was made up of two phases: firstly, to evaluate the technical feasibility of a new integrated care pathway using innovative technology, and secondly, to establish process enhancement of the pathway to justify a larger-scale study. Omni-Hub TM enabled a face-to-face consultation by the community podiatrist to be enhanced by virtual consultation with members of the multidisciplinary foot team, including specialist diabetes podiatrists and a diabetes consultant. The technical feasibility study provided recommended changes focused around adaptations to the equipment used and the best means to gain successful connectivity. The process enhancement study demonstrated positive outcomes in the process with positive effects both in the service received by patients and experiences of healthcare professionals involved. The RAPID project provides evidence and justification for a larger-scale empirical study to test an embedded pathway and technology solution, which will inform policy change and a paradigm shift in the management of foot ulceration in the community.

Additive enhancement of wound healing in diabetic mice by low level light and topical CoQ10

PubMed Central

Mao, Zhigang; Wu, Jeffrey H.; Dong, Tingting; Wu, Mei X.

2016-01-01

Diabetes, a highly prevalent disease that affects 9.3% of Americans, often leads to severe complications and slow wound healing. Preclinical studies have suggested that low level light therapy (LLLT) can accelerate wound healing in diabetic subjects, but significant improvements must be made to overcome the absence of persuasive evidence for its clinical use. We demonstrate here that LLLT can be combined with topical Coenzyme Q10 (CoQ10) to heal wounds in diabetic mice significantly faster than LLLT alone, CoQ10 alone, or controls. LLLT followed by topical CoQ10 enhanced wound healing by 68~103% in diabetic mice in the first week and more than 24% in the second week compared with untreated controls. All wounds were fully healed in two weeks following the dual treatment, in contrast to only 50% wounds or a fewer being fully healed for single or sham treatment. The accelerated healing was corroborated by at least 50% higher hydroxyproline levels, and tripling cell proliferation rates in LLLT and CoQ10 treated wounds over controls. The beneficial effects on wound healing were probably attributed to additive enhancement of ATP production by LLLT and CoQ10 treatment. The combination of LLLT and topical CoQ10 is safe and convenient, and merits further clinical study. PMID:26830658

Life experiences in active addiction and in recovery among treated and untreated persons: a national study.

PubMed

Laudet, Alexandre; Hill, Thomas

2015-01-01

Addiction treatment can be effective but fewer than 50% of addiction affected persons are ever treated. Little is known about the addiction and recovery experience of this large subgroup. A national sample of persons in recovery (N = 3,176, 29.5% untreated) was used to begin addressing these questions to inform strategies to encourage help-seeking and to contribute to the small knowledge base on untreated individuals. Study domains were finances, family, social and civic functioning, health, criminal justice involvement, and employment. Treated persons reported significantly greater levels of negative-and fewer positive-experiences in all areas during active addiction than did the untreated group. This gap was significantly narrowed in recovery.

Effects of alpha lipoic acid, ascorbic acid-6-palmitate, and fish oil on the glutathione, malonaldehyde, and fatty acids levels in erythrocytes of streptozotocin induced diabetic male rats.

PubMed

Yilmaz, Okkeş; Ozkan, Yusuf; Yildirim, Mehmet; Oztürk, A Ihsan; Erşan, Yasemin

2002-01-01

In this research, it has been aimed to evaluate the improvement effects of alpha lipoic acid (ALA), ascorbic acid-6-palmitate (AA6P), fish oil (FO), and their combination (COM) on some biochemical properties in erythrocytes of streptozotocin (STZ)-induced diabetic male rats. According to experimental results, glutathione (GSH) level in erythrocytes decreased in diabetes (P < 0.01), D + ALA, and D + AA6P groups (P < 0.001). Malonaldehyde (MA) level increased in diabetes (P < 0.05), D + FO, and D + COM groups (P < 0.001), but its level in D + AA6P and D + ALA groups was lower in diabetes group (P < 0.01). Total lipid level in diabetes and diabetes plus antioxidant administered groups were higher than control. Total cholesterol level was high in diabetes and D + ALA groups (P < 0.05), but its level reduced in D + FO compared to control and diabetes groups, P < 0.05, < 0.001, respectively. Total triglyceride (TTG) level was high in the D + ALA (P < 0.05) and D + COM (P < 0.001) groups. In contrast, TTG level in blood of diabetes group was higher than diabetes plus antioxidant and FO administered groups (P < 0.001). According to gas chromatography analysis results, while the palmitic acid raised in diabetes group (P < 0.05), stearic acid in D + FO, D + ALA, and diabetes groups was lower than control (P < 0.05), oleic acid reduced in D + COM and D + FO groups, but its level raised in D + AA6P and D + ALA groups (P < 0.01). As the linoleic acid (LA) elevated in ALA + D, D + AA6P, and diabetes groups, linolenic acid level in diabetes, D + AA6P, and D + FO groups was lower than control (P < 0.001). Arachidonic acid (AA) decreased in D + ALA, D+ AA6P, and diabetes groups (P < 0.01), but its level in D + COM and D + FO was higher than control (P < 0.05). Docosahexaenoic acid (DHA) increased in D + AA6P and D + COM (P < 0.05). While the total saturated fatty acid level raised in diabetes group, its level reduced in D + ALA and D + FO groups (P < 0.05). In contrast, total unsaturated fatty acid level in D + ALA and D + FO groups was higher than control (P < 0.05). In conclusion, present data have confirmed that the combination of the ALA, AA6P, and FO have improvement effects on the recycling of GSSG to reduced GSH in erythrocytes of diabetic rats, and in addition to this, oxidative stress was suppressed by ALA and AA6P, and unsaturated fatty acid degree was raised by the effects of ALA and FO. Copyright 2002 Wiley-Liss, Inc.

The Different Dynamic Changes of Nerve Growth Factor in the Dorsal Horn and Dorsal Root Ganglion Leads to Hyperalgesia and Allodynia in Diabetic Neuropathic Pain.

PubMed

Gao, Zhifeng; Feng, Yi; Ju, Hui

2017-05-01

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes and more than half of the patients with DPN have self-reported symptoms referring to painful diabetic neuropathy (PDN). Nerve growth factor (NGF) is a key factor for the nervous system, but the role of it in the neuropathic pain of diabetic patients is unclear. This study aimed to investigate the relationship between the dynamic expression of NGF in dorsal horn and dorsal root ganglion (DRG) of diabetic rats and hyperalgesia and allodynia in diabetic neuropathic pain. It also aimed to explore the effects of exogenous mouse NGF (mNGF) on NGF expression in dorsal horn, DRG, and mechanical pain threshold. Animal research study. Experimental research laboratory. The model of diabetes was established by a single intraperitoneal injection of streptozocin (STZ 55 mg/kg). Firstly, the rats were randomly divided into 2 groups: control group (n = 10) and diabetes group (n = 40). The diabetes group contained 4 subgroups: diabetes week 1 group (DM1, n = 10), diabetes week 2 group (DM2, n = 10), diabetes week 4 group (DM4, n = 10), and diabetes week 8 group (DM8, n = 10). Then, the other rats were randomly divided into 2 groups: control group (n = 10) and treatment group (n = 30). The treatment group contained 3 subgroups: saline group (n = 10), low dose mNGF group (mNGF1, n = 10), and high dose mNGF group (mNGF2, n = 10). Mechanical pain threshold was assessed using Von Frey hairs, before the establishment of the diabetes model and 1, 2, 4, and 8 weeks after the establishment. The NGF expression in dorsal horn and DRG was measured by western blot. The mechanical pain threshold decreased one week after the establishment of the diabetes model, which continued for 8 weeks. The NGF expression in the dorsal horn was reduced 2 weeks after diabetes induction and the decreased NGF expression continued for 4 weeks. However, the NGF expression in DRG was reduced one week after diabetes induction and remained at a low level for 8 weeks. Hyperalgesia occurred when the NGF expression in the DRG decreased and further reduction in the NGF expression in the dorsal horn caused concomitant allodynia. The mechanical pain threshold was significantly elevated 2 weeks after mNGF treatment. The course of diabetes should be much longer and there is not a precise analysis of the quantitative relation between the NGF expression in the dorsal horn/DRG and hyperalgesia/allodynia. In diabetic neuropathic pain, the dynamic changes of the NGF expression in dorsal horn and DRG is involved in the development of hyperalgesia and allodynia respectively. Exogenous mNGF may relieve diabetic neuropathic pain by increasing the NGF expression in dorsal horn and DRG.

The DISC (Diabetes in Social Context) Study-evaluation of a culturally sensitive social network intervention for diabetic patients in lower socioeconomic groups: a study protocol

PubMed Central

2012-01-01

Background Compared to those in higher socioeconomic groups, diabetic patients in lower socioeconomic groups have less favourable metabolic control and experience more diabetes-related complications. They encounter specific barriers that hinder optimal diabetes self-management, including a lack of social support and other psychosocial mechanisms in their immediate social environments. Powerful Together with Diabetes is a culturally sensitive social network intervention specifically targeted to ethnic Dutch, Moroccan, Turkish, and Surinamese diabetic patients in lower socioeconomic groups. For ten months, patients will participate in peer support groups in which they will share experiences, support each other in maintaining healthy lifestyles, and learn skills to resist social pressure. At the same time, their significant others will also receive an intervention, aimed at maximizing support for and minimizing the negative social influences on diabetes self-management. This study aims to test the effectiveness of Powerful Together with Diabetes. Methods/Design We will use a quasi-experimental design with an intervention group (Group 1) and two comparison groups (Groups 2 and 3), N = 128 in each group. Group 1 will receive Powerful Together with Diabetes. Group 2 will receive Know your Sugar, a six-week group intervention that does not focus on the participants' social environments. Group 3 receives standard care only. Participants in Groups 1 and 2 will be interviewed and physically examined at baseline, 3, 10, and 16 months. We will compare their haemoglobin A1C levels with the haemoglobin A1C levels of Group 3. Main outcome measures are haemoglobin A1C, diabetes-related quality of life, diabetes self-management, health-related, and intermediate outcome measures. We will conduct a process evaluation and a qualitative study to gain more insights into the intervention fidelity, feasibility, and changes in the psychosocial mechanism in the participants' immediate social environments. Discussion With this study, we will assess the feasibility and effectiveness of a culturally sensitive social network intervention for lower socioeconomic groups. Furthermore, we will study how to enable these patients to optimally manage their diabetes. This trial is registered in the Dutch Trial Register: NTR1886 PMID:22429263

The DISC (Diabetes in Social Context) Study-evaluation of a culturally sensitive social network intervention for diabetic patients in lower socioeconomic groups: a study protocol.

PubMed

Vissenberg, Charlotte; Nierkens, Vera; Uitewaal, Paul J M; Geraci, Diana; Middelkoop, Barend J C; Nijpels, Giel; Stronks, Karien

2012-03-19

Compared to those in higher socioeconomic groups, diabetic patients in lower socioeconomic groups have less favourable metabolic control and experience more diabetes-related complications. They encounter specific barriers that hinder optimal diabetes self-management, including a lack of social support and other psychosocial mechanisms in their immediate social environments. Powerful Together with Diabetes is a culturally sensitive social network intervention specifically targeted to ethnic Dutch, Moroccan, Turkish, and Surinamese diabetic patients in lower socioeconomic groups. For ten months, patients will participate in peer support groups in which they will share experiences, support each other in maintaining healthy lifestyles, and learn skills to resist social pressure. At the same time, their significant others will also receive an intervention, aimed at maximizing support for and minimizing the negative social influences on diabetes self-management. This study aims to test the effectiveness of Powerful Together with Diabetes. We will use a quasi-experimental design with an intervention group (Group 1) and two comparison groups (Groups 2 and 3), N = 128 in each group. Group 1 will receive Powerful Together with Diabetes. Group 2 will receive Know your Sugar, a six-week group intervention that does not focus on the participants' social environments. Group 3 receives standard care only. Participants in Groups 1 and 2 will be interviewed and physically examined at baseline, 3, 10, and 16 months. We will compare their haemoglobin A1C levels with the haemoglobin A1C levels of Group 3. Main outcome measures are haemoglobin A1C, diabetes-related quality of life, diabetes self-management, health-related, and intermediate outcome measures. We will conduct a process evaluation and a qualitative study to gain more insights into the intervention fidelity, feasibility, and changes in the psychosocial mechanism in the participants' immediate social environments. With this study, we will assess the feasibility and effectiveness of a culturally sensitive social network intervention for lower socioeconomic groups. Furthermore, we will study how to enable these patients to optimally manage their diabetes.

Prevalence and impact of gastrointestinal helminths on body weight gain in backyard chickens in subtropical and humid zone of Jammu, India.

PubMed

Katoch, R; Yadav, Anish; Godara, R; Khajuria, J K; Borkataki, S; Sodhi, S S

2012-04-01

Necropsy of gastrointestinal tract of 125 free-range chickens from a subtropical and humid zone of northwestern India revealed four nematode spp. (Ascaridia galli, Heterakis gallinarum, Capillaria spp. and Cheilospirura hamulosa) and four cestode spp. (Raillietina cesticillus, Raillietina echinobothrida, Raillietina tetragona and Amoebotaenia cuneata) The overall prevalence of the helminth parasites was 72.0%. Amongst various helminth species encountered in the region, A. galli emerged out as the most prevalent, followed by H. gallinarum, R. cesticillus and R. echinobothrida. The impact of helminthic infections on body weight gain in growing chickens was investigated. One hundred growing chickens, aged 40 days were randomly assigned to two groups (treated and untreated controls) of 50 birds each. The birds in treated group were given fenbendazole at 7.5 mg per kg body weight in drinking water, while the birds in other group served as untreated controls. At the end of the 90 days of the field trial, the mean body weight gain of untreated controls was 1232.2 ± 7.28 g (13.7 g/day) compared with 1617.6 ± 5.43 g (18.0 g/day) in the treated group. It was associated with a significantly (P < 0.05) higher mean worm burden (32.92 ± 6.12) in untreated controls than the treated group (2.46 ± 1.14). The prevalences of helminthic species and their impact on body weight gain in growing backyard chickens have been discussed.

Benzodiazepine sensitivity in panic disorder: effects of chronic alprazolam treatment.

PubMed

Cowley, D S; Roy-Byrne, P P; Radant, A; Ritchie, J C; Greenblatt, D J; Nemeroff, C B; Hommer, D W

1995-04-01

The aim of the current study was to determine the degree to which patients with panic disorder develop tolerance to subjective and physiological effects of benzodiazepine after chronic treatment with alprazolam. Response to acute administration of diazepam was assessed in 19 panic disorder patients receiving chronic treatment with alprazolam and 23 untreated panic disorder patients. At baseline in the laboratory, the two groups did not differ in peak saccadic eye movement velocity, saccade latency, short-term memory, plasma cortisol and growth hormone concentrations, heart rate, and self-rated levels of sedation and anxiety. Compared with untreated patients, alprazolam-treated patients displayed significantly less diazepam-induced change in peak saccadic velocity, saccade latency, growth hormone secretion, memory, and self-rated levels of sedation. There was no difference between groups in diazepam effects on plasma cortisol concentrations or self-rated anxiety. Within alprazolam-treated patients, diazepam-induced slowing of peak saccade velocity was significantly inversely correlated with illness severity, as measured by reported panic attacks per week and severity of phobic avoidance, but not with alprazolam dose, blood level, or duration of treatment. Because the alprazolam-treated group reported more panic attacks per week than the untreated panic patients, treated patients were divided into those who were asymptomatic versus those with continuing panic attacks. The subgroup of nine alprazolam-treated subjects who were asymptomatic also showed significantly less diazepam effects than the group of untreated panic disorder patients, suggesting that overall group differences were at least partially attributable to the development of tolerance to selected benzodiazepine effects with chronic alprazolam treatment.

Assessment of the relationship between non-alcoholic fatty liver disease and diabetic complications.

PubMed

Yan, Li-Hui; Mu, Biao; Guan, Yue; Liu, Xinyu; Zhao, Nan; Pan, Da; Wang, Shao-Zhen

2016-11-01

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder of the liver. The relationship between NAFLD and type 2 diabetes remains largely unknown. The aim of the present study was to determine the incidence of complications arising from the interaction between NAFLD and type 2 diabetes. A total of 212 individuals with type 2 diabetes were included in the study. The presence of NAFLD was determined in individuals using abdominal ultrasonography for the diagnosis of fatty liver disease. Patients were divided into three groups based on the duration of diabetes and NAFLD diagnosis. Type 2 diabetes patients were placed in group A; patients with type 2 diabetes longer than NAFLD were placed in group B; and patients with NAFLD longer than type 2 diabetes were placed in group C. All individuals had undergone electrocardiogram, blood pressure measurements, and thorough medical history and physical examinations (Doppler ultrasound, electrophysiology, fundoscopy, cardiac computed tomography). Laboratory measurements included fasting blood glucose, glycated hemoglobin, oral glucose tolerance test, liver and renal function, lipid profile, and urinary albumin excretion. Compared with groups A and B, the patients of group C showed a higher prevalence of significant coronary artery disease and hypertension (P < 0.05). Compared with groups A and B, the patients of group C showed a lower prevalence of diabetic retinopathy and diabetic peripheral neuropathy (P < 0.05). There was no significant difference in the prevalence of diabetic nephropathy among the three groups (P > 0.05). NAFLD combined with type 2 diabetes is associated with the presence of significant coronary artery disease and hypertension. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

[Morbidity and mortality cardiovascular risk in dependence of type 2 diabetes duration].

PubMed

Gimeno Orna, José Antonio; Blasco Lamarca, Yolanda; Campos Gutierrez, Belén; Molinero Herguedas, Edmundo; Lou Arnal, Luis Miguel

2014-01-01

This study was aimed to assess the prognostic importance of diabetes duration to predict cardiovascular risk in type 2 diabetic patients. Prospective cohort study with inclusion of type 2 diabetic patients. Follow-up lasted until the appearance of a cardiovascular event, until death or until 2012. Patients were classified into 5 groups in accordance to diabetes duration and baseline cardiovascular disease (CVD): group 1: ≤ 5 years without CVD; group 2: 6-10 years without CVD; group 3: 11-15 years without CVD; group 4: >15 years without CVD; group 5: baseline CVD independently of diabetes duration. CVD rates were expressed per 1000 patients-year and compared by Kaplan-Meier analysis and Log Rank Test. The predictive power of diabetes duration was evaluated by Cox regression. 457 patients, aged 64.9 (DE 9.3) years (38.9% males), were included. Diabetes duration was 10.5 (DE 7.6) years. 125 cardiovascular events occurred during 12.3 years follow-up. Cardiovascular event rates were progressively increased from groups 1 to 5 (group 1: 14.1; group 2: 18.3; group 3: 19.6; group 4: 32.9; group 5: 53.5; p<0.0001, linear tendency). Diabetes duration superior to 15 years significantly increased cardiovascular risk of the patients (HR=1.97; 95%CI: 1.23-3.15; P=.004). It could be useful to consider diabetes duration in order to stratify cardiovascular risk of type 2 diabetic patients. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Diabetes in adolescence: effects of multifamily group intervention and parent simulation of diabetes.

PubMed

Satin, W; La Greca, A M; Zigo, M A; Skyler, J S

1989-06-01

Insulin-dependent diabetes mellitus (IDDM) is a complex, chronic disease that is difficult to control during adolescence. This study evaluated the effects of a 6-week, family-oriented, group intervention on adolescents' metabolic control and psychosocial and family functioning. Thirty-two families were randomly assigned to one of three groups: multifamily (MF), multifamily plus parent simulation of diabetes (MF + S), and control (C). Outcome measures included glycosylated hemoglobin (Hb Al); perceptions of diabetes; estimates of youngsters' self-care; and family functioning. Adolescents in the MF + S group displayed significant decrements in Hb Al, and adolescents in both intervention groups reported more positive perceptions of a "teen-ager with diabetes" at posttreatment, relative to controls. Adolescents participating in smaller family groups demonstrated clinically significant improvements in Hb Al that were maintained at 6-month follow-up. Parent reports suggested that adolescents in the intervention groups improved their diabetes care. Findings support the use of multifamily groups plus parent simulation of diabetes as an intervention strategy for adolescents with IDDM.

Correlation between Cystatin C and retinopathy of type-two diabetes mellitus patients.

PubMed

Qian, C; Wan, G M; Yan, P S; Wang, W Z; Liang, S Z; Dong, Y

2017-01-01

Diabetic retinopathy is one of most common diabetic microvascular complications. In recent years the incidence of the disease has increased, hence early diagnosis and treatment are of great importance. In order to find reliable biological indexes to diagnose and treat type-two diabetes mellitus promptly, this study focused on the correlation between Cystatin C (Cys C) and retinopathy of type-two diabetes mellitus patients. One hundred and eighty type-two diabetes mellitus patients and one hundred healthy controls (the control group) were chosen in this study. Of the patients ninety-eight patients had typetwo diabetes mellitus without retinopathy (non-diabetic retinopathy group) and eighty-two had typetwo diabetes mellitus with retinopathy (diabetic retinopathy group). Correlation of Cys C and typetwo diabetic retinopathy was analyzed by examining the waist-hip ratio, fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glycosylated hemoglobin (HbA1c), and Cys C of both groups. The results showed that FBG, TC, TG, LDL-C, HbA1c, Cys C in the type-two diabetes mellitus patients group were higher than those of the control group (P less than 0.05). Age, course of diabetes, FBG, HbA1c, and Cys C levels were statistically significant in both the DR group and NDR group (P less than 0.05). The result of logistic regression analysis indicates that there was a positive correlation between type-two diabetic retinopathy development and age, course of diabetes, and Cys C level (P less than 0.05). Thus, it can be seen that changes of Cys C levels can assist early diagnosis and treatment of diabetic retinopathy to some extent. The patients with high Cys C level, long course of diabetes, and old age are more likely to have diabetic retinopathy.

EEG abnormalities and two year outcome in first episode psychosis.

PubMed

Manchanda, R; Norman, R; Malla, A; Harricharan, R; Takhar, J; Northcott, S

2005-03-01

This study examines the relationship of EEG to 2 year symptomatic outcome, duration of illness and untreated psychosis and gender. A total of 122 patients presenting for treatment of first episode psychosis had their baseline EEG classified by modified Mayo Clinic system criteria as normal, essentially normal or dysrhythmia. Positive and negative symptoms of psychoses were rated on entry and after 2 years of treatment. The socio-demographic variables and duration of illness and of untreated psychosis were also recorded. Patients with a normal EEG showed significantly more reduction in both positive and negative symptoms of psychoses over 2 years and were more likely to be in 'remission' as compared with the essentially normal or dysrhythmia group. The dysrhythmic group had significantly higher duration of illness than either the normal or essentially normal groups. There were no gender differences in the distribution of EEGs. An abnormal EEG in patients with first episode psychosis is associated with a poorer prognosis and a longer duration of untreated illness. Copyright (c) Blackwell Munksgaard 2005

The effect of the ginger on the apoptosis of hippochampal cells according to the expression of BAX and Cyclin D1 genes and histological characteristics of brain in streptozotocin male diabetic rats.

PubMed

Molahosseini, A; Taghavi, M M; Taghipour, Z; Shabanizadeh, A; Fatehi, F; Kazemi Arababadi, M; Eftekhar Vaghefe, S H

2016-10-31

Diabetes is the most common endocrine disorder in humans with multiple complications including nervous system damages. The aim of the present study was to determine the effect of ginger extract on apoptosis of the neurons of hippocampus, via evaluation of BAX and Cyclin D1 and also histological analysis, in male diabetic rats. In this experimental study, 60 Wistar rats (220 ± 30gr) were conducted in 5 groups as follow: diabetic group treated with saline (group 1), normal group treated with saline (group 2), diabetic group treated with ginger (group 3), diabetic group treated with ginger-insulin (group 4), diabetic group treated with insulin (group 5). STZ (60 mg/kg) was intraperitoneally used to induce the diabetes. Expression levels of BAX and Cyclin D1 were examined using Real-Time PCR technique and the normality of neurons was evaluated using H&E staining method. The results showed that blood glucose level significantly decreased in group 4 when compared to group 1. In molecular analysis, there was no significant difference between groups regarding the expression of BAX gens, while, the expression of Cyclin D1 were significantly decreased in group 4 compared with group 1. Histological analysis revealed that pathological symptoms were lower in group 4 than the other diabetic groups. The results of present study showed that the ginger in addition to lowering blood sugar level, changes the expression of Cyclin D1 gene and histological characteristics in a positive manner. This means that the ginger may protects neurons of the hippocampus from apoptosis in diabetic patients.

The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes.

PubMed

Mohamed, Jamaludin; Shing, Saw Wuan; Idris, Muhd Hanis Md; Budin, Siti Balkis; Zainalabidin, Satirah

2013-10-01

The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes. Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight) for 28 days. The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle-treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained. The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients.

The protective effect of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes

PubMed Central

Mohamed, Jamaludin; Shing, Saw Wuan; Md Idris, Muhd Hanis; Budin, Siti Balkis; Zainalabidin, Satirah

2013-01-01

OBJECTIVES: The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes. METHODS: Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight) for 28 days. RESULTS: The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle-treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained. CONCLUSION: The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients. PMID:24212844

Interactive effects of melatonin, exercise and diabetes on liver glycogen levels.

PubMed

Bicer, Mursel; Akil, Mustafa; Avunduk, Mustafa Cihat; Kilic, Mehmet; Mogulkoc, Rasim; Baltaci, Abdulkerim Kasim

2011-01-01

This study aimed to examine the effects of melatonin supplementation on liver glycogen levels in rats with streptozotocin- induced diabetes and subjected to acute swimming exercise. Eighty Sprague-Dawley type adult male rats were divided into eight groups: Group 1, general control; Group 2, melatonin-supplemented control; Group 3, melatonin-supplemented diabetes; Group 4, swimming control; Group 5, melatonin-supplemented swimming; Group 6, melatonin-supplemented diabetic swimming; Group 7, diabetic swimming; Group 8, diabetic control. Melatonin was supplemented at a dose of 3 mg/kg/day intraperitoneally for four weeks. Liver tissue samples were collected and evaluated using a Nikon Eclipse E400 light microscope. All images obtained from the light microscope were transferred to PC medium and evaluated using Clemex PE 3.5 image analysis software. The lowest liver glycogen levels in the study were found in group 4. Liver glycogen levels in groups 3, 6, 7 and 8 (the diabetic groups) were higher than group 4, but lower than those in groups 1 and 2. The lowest liver glycogen levels were obtained in groups 1 and 2. The study indicates that melatonin supplementation maintains the liver glycogen levels that decrease in acute swimming exercise, while induced diabetes prevents this maintenance effect in rats.

Hyperbaric Oxygen therapy effects on bone regeneration in Type 1 diabetes mellitus in rats.

PubMed

Dias, Pâmella Coelho; Limirio, Pedro Henrique Justino Oliveira; Linhares, Camila Rodrigues Borges; Bergamini, Mariana Lobo; Rocha, Flaviana Soares; Morais, Richarlisson Borges de; Balbi, Ana Paula Coelho; Hiraki, Karen Renata Nakamura; Dechichi, Paula

2018-01-29

The aim of this study was evaluate the effect of HBO on diabetic rats. Twenty rats were distributed into four groups (n = 5): Control (C); Control + HBO (CH); Diabetes (D) and Diabetes + HBO (DH). Diabetes was induced by streptozotocin, and bone defects were created in both femurs in all animals. HBO therapy began immediately after surgery and was performed daily in the CH and DH groups. After 7 days, the animals were euthanized. The femurs were removed, demineralized, embedded in paraffin, and histologic images were analyzed. Qualitative histologic analyses showed more advanced stage bone regeneration in control groups (C and CH) compared with diabetic groups (D and DH). Histomorphometric analysis showed significantly increased bone neoformation in CH compared with the other groups (p < 0.001). Diabetic Group (D) showed decreased bone neoformation compared with non-diabetic groups (C and CH) (p < 0.001); however DH did not differ from C Group (p > 0.05). The mast cell population increased in CH compared with the other groups (C, D, and DH) (p < 0.05). The mast cell population did not differ between D and DH Groups. This study showed that HBO therapy improved early bone regeneration in diabetic rats and increased the mast cell population only in non-diabetic animals. HBO was shown to be important treatment for minimizing deleterious effects of diabetes on bone regeneration.

Magnetic resonance imaging retinal oximetry: a quantitative physiological biomarker for early diabetic retinopathy?

PubMed

Yang, Y; Zhu, X R; Xu, Q G; Metcalfe, H; Wang, Z C; Yang, J K

2012-04-01

To assess the efficacy of using magnetic resonance imaging measurements of retinal oxygenation response to detect early diabetic retinopathy in patients with Type 2 diabetes. Magnetic resonance imaging was conducted during 100% oxygen inhalation in patients with Type 2 diabetes with either no diabetic retinopathy (n = 12) or mild to moderate background diabetic retinopathy (n = 12), as well as in healthy control subjects (n = 12). Meanwhile, changes in retinal oxygenation response were measured. In the healthy control group, levels of retinal oxygenation response increased slowly during 100% oxygen inhalation. In contrast, they increased more quickly and attained homeostasis much earlier in the groups with background diabetic retinopathy (at the 20-min time point) and with no diabetic retinopathy (at the 25-min time point) than in the healthy control group (at the 42-min time point). Furthermore, levels of retinal oxygenation response in the group with background diabetic retinopathy increased more than that of the group with no diabetic retinopathy, which in turn increased more than that of the healthy control group. There are statistically significant differences between the group with background diabetic retinopathy and the healthy control group at 6-, 8-, 10-, 15-, 20- and 25-min time points (P < 0.05). According to the normal range of the healthy control group by setting fundus photography results as 'gold standard' in our research, the sensitivity, specificity, positive predictive value, negative predictive value and receiver operating characteristic area for reporting the early indications of utility of diabetic retinopathy were 83.33%, 58.33%, 50%, 87.5% and 0.774, respectively. The results indicate that magnetic resonance imaging is a potential screening method and probably a quantitative physiological biomarker to find early diabetic retinopathy in patients with Type 2 diabetes. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Use of the scoliosis research society outcomes instrument to evaluate patient outcome in untreated idiopathic scoliosis patients in Japan: part I: comparison with nonscoliosis group: preliminary/limited review in a Japanese population.

PubMed

Watanabe, Kei; Hasegawa, Kazuhiro; Hirano, Toru; Uchiyama, Seiji; Endo, Naoto

2005-05-15

This preliminary study evaluates untreated Japanese patients with idiopathic scoliosis using the Scoliosis Research Society Outcomes Instrument (SRS-24). To determine the baseline patient outcome score using the SRS-24 for untreated Japanese scoliosis patients compared with a nonscoliosis group. The SRS instrument with 24 questions was developed to help evaluate patient-perceived outcomes of idiopathic scoliosis treatment. Evaluation of untreated Japanese idiopathic scoliosis patients using the SRS instrument has not been reported. Japanese idiopathic scoliosis patients (n = 141) (mean age, 13.6 years; range, 10-17 years) with a Cobb angle of more than 20 degrees who were not treated with a brace or surgery, were evaluated in comparison with a nonscoliosis group (healthy junior high school students; n = 72) using the SRS-24. The scoliosis group was categorized as mild deformity group with a major curve Cobb angle of less than 30 degrees, moderate deformity group with 30 degrees to 49 degrees, and severe deformity group with more than 50 degrees. The patients were evaluated using section 1 (15 questions) of the SRS-24, which was divided into four domains: total pain, general self-image, general function, and activity. Reliability, as determined by internal consistency, was validated using Cronbach's alpha for these domain scales. The severe deformity group had the lowest scores compared with the other deformity groups and the nonscoliosis group in pain (P < 0.0001) and self-image (P < 0.05) domains. The scores for questions 3 (P < 0.0001) and 5 (P < 0.0001), evaluation of self-image of back appearance, were significantly lower in the scoliosis group than those in the nonscoliosis group. This tendency was more significant in the patients with greater curve magnitude. Scores for questions 14 and 15, evaluation of general self-image, in the scoliosis group were, however, higher than those in the nonscoliosis group. Internal consistency using Cronbach's alpha was 0.57 (pain), 0.27 (general self-image), -0.08 (general function), and 0.15 (overall level of activity). Untreated scoliosis patients with severe deformity were inclined to complain of being self-conscious or distressed regarding their back appearance compared with age- and sex-matched control adolescents. The control group was inclined to have, however, a negative general self-image compared with the patients group. Internal consistency using Cronbach's alpha for all domains was considerably low. The baseline of the SRS-24 scores in the Japanese population might differ from that of the Western population because of differences in national culture. Therefore, further study is necessary to clarify the validity of the SRS-24 domains for Japanese patients.

Protective role of Urtica dioica L. (Urticaceae) extract on hepatocytes morphometric changes in STZ diabetic Wistar rats.

PubMed

Golalipour, Mohammad Jafar; Ghafari, Soraya; Afshar, Mohammad

2010-09-01

The present investigation was carried out to evaluate the protective effect of the hydroalcoholic extract of Urtica dioica leaves on the quantitative morphometric changes in the liver of streptozotocin-induced diabetic rats. Thirty male Wistar rats were divided into control (G1), diabetic (G2), diabetic + Urtica dioica (G3) groups. The control group received only sham injections of intraperitoneal saline; the diabetic group received intraperitoneal saline for 5 days followed by streptozotocin (80 mg/kg) on the 6th day; and the diabetic + Urtica dioica group received 100 mg/kg Urtica dioica intraperitoneal (7) injections for 5 days and streptozotocin injection on the 6th day. After five weeks, the animals were sacrificed and whole livers removed. Liver specimens were used for quantitative morphometric analysis after hematoxylin and eosin staining. All data were statistically analyzed by one-way ANOVA and expressed as the mean with standard error of means. In the G3 (diabetic + Urtica diocia) group, the mean surface area of hepatocytes in the periportal zone (Z1) was greater than in G2 (diabetic) and G1 (control) groups, but this difference was not significant. No alteration was observed in the surface area of hepatocytes in the perivenous zone (Z3) in the diabetic + Urtica dioica (G3) group compared to the diabetic (G2) group. The mean nuclear area of hepatocytes of the rats in the diabetic + Urtica dioica (G3) group was higher in Z1 and lower in Z3 than that of rats in the diabetic (G2) group. The mean diameter of hepatocyte nuclei in the diabetic + Urtica dioica (G3) group was lower than that of diabetic (G2) and control (G1) groups in both Z1 and Z3. This study revealed that the administration of extract of Urtica dioica leaves before induction of diabetic with streptozotocin has a protective effect on the morphometric alterations of hepatocytes in the periportal and perivenous zones of the liver lobule in rats.

Oral Administration of Apple Procyanidins Ameliorates Insulin Resistance via Suppression of Pro-Inflammatory Cytokine Expression in Liver of Diabetic ob/ob Mice.

PubMed

Ogura, Kasane; Ogura, Masahito; Shoji, Toshihiko; Sato, Yuichi; Tahara, Yumiko; Yamano, Gen; Sato, Hiroki; Sugizaki, Kazu; Fujita, Naotaka; Tatsuoka, Hisato; Usui, Ryota; Mukai, Eri; Fujimoto, Shimpei; Inagaki, Nobuya; Nagashima, Kazuaki

2016-11-23

Procyanidins, the main ingredient of apple polyphenols, are known to possess antioxidative and anti-inflammatory effects associated closely with the pathophysiology of insulin resistance and type 2 diabetes. We investigated the effects of orally administered apple procyanidins (APCs) on glucose metabolism using diabetic ob/ob mice. We found no difference in body weight or body composition between mice treated with APCs and untreated mice. A 4 week oral administration of APCs containing water [0.5% (w/v)] ameliorated glucose tolerance, insulin resistance, and hepatic gluconeogenesis in ob/ob mice. APCs also suppressed the increase in the level of the pancreatic β-cell. Insulin-stimulated Akt phosphorylation was significantly enhanced; pro-inflammatory cytokine expression levels were significantly decreased, and c-Jun N-terminal kinase phosphorylation was downregulated in the liver of those mice treated with APCs. In conclusion, APCs ameliorate insulin resistance by improving hepatic insulin signaling through suppression of hepatic inflammation in ob/ob mice, which may be a mechanism with possible beneficial health effects of APCs in disturbed glucose metabolism.

Neuroretinal hypoxic signaling in a new preclinical murine model for proliferative diabetic retinopathy

PubMed Central

Wert, Katherine J; Mahajan, Vinit B; Zhang, Lijuan; Yan, Yuanqing; Li, Yao; Tosi, Joaquin; Wei Hsu, Chun; Nagasaki, Takayuki; Janisch, Kerstin M; Grant, Maria B; Mahajan, MaryAnn; Bassuk, Alexander G; Tsang, Stephen H

2016-01-01

Diabetic retinopathy (DR) affects approximately one-third of diabetic patients and, if left untreated, progresses to proliferative DR (PDR) with associated vitreous hemorrhage, retinal detachment, iris neovascularization, glaucoma and irreversible blindness. In vitreous samples of human patients with PDR, we found elevated levels of hypoxia inducible factor 1 alpha (HIF1α). HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases. To recreate the human PDR phenotype for a preclinical animal model, we generated a mouse with neuroretinal-specific loss of the von Hippel Lindau tumor suppressor protein, a protein that targets HIF1α for ubiquitination. We found that the neuroretinal cells in these mice overexpressed HIF1α and developed severe, irreversible ischemic retinopathy that has features of human PDR. Rapid progression of retinopathy in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders. In addition, this model system can be used to manipulate the modulation of the hypoxia signaling pathways, for the treatment of non-ocular ischemic and inflammatory disorders. PMID:27195131

Value of EZSCAN parameters for diabetes screening in Chinese.

PubMed

Lin, Yanhui; Chen, Zhiheng; Guo, Xu; Deng, Yulin

2017-05-23

To study the parameters of EZSCAN as a screening tool for diabetes in Chinese. A total of 6,270 subjects participated in the study. All subjects underwent tests of EZSCAN, fasting plasma glucose (FPG), oral glucose tolerance test and HbA 1c . 1. All subjects were divided into 4 groups: the normal group, sugar metabolic abnormalities as low-risk group, middle-risk group and high-risk group. The difference of diabetes incidence among the 4 groups was statistically significant. With the increase of EZSCAN score, the prevalence of diabetes increased significantly. But there is no statistically difference between the low-risk group and the middle-risk group. 2. After adjustment for other variables, there is significantly positive relationship among EZSCAN risk score and the risk of diabetes. Meanwhile there is no statistically difference between the low-risk group and the middle-risk group. 3. The cut-off point of EZSCAN for diabetes was 44.5% with the sensitivity was 73.2% which was higher than of FPG and HbA 1c . As EZSCAN-diabetes risk score increases, the risk of diabetes increases. EZSCAN can be used as a tool for screening for diabetes. At the best screening diabetes cut-off point value 44.5%, the sensitivity is higher than traditional method of FPG and HbA 1c . Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Effect of experimental diabetes on cholinergic, purinergic and peptidergic motor responses of the isolated rat bladder to electrical field stimulation or capsaicin.

PubMed

Benkó, Rita; Lázár, Zsófia; Pórszász, Róbert; Somogyi, George T; Barthó, Loránd

2003-09-30

An attempt has been made to pharmacologically isolate cholinergic, P(2) purinoceptor-mediated and peptidergic (capsaicin-sensitive, tachykinin-mediated) contraction of the guanethidine-treated rat bladder detrusor preparation, in vitro. The effect of experimental diabetes was assessed on these types of contraction. Responses were evoked by electrical field stimulation (single shocks or 1 Hz for 30 s or 10 Hz for 40 s). Single shocks and 1-Hz stimulation were applied in the presence of (a). atropine (1 microM) or (b). P(2) purinoceptor antagonists (50 microM pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid) [PPADS] plus 100 microM suramin. Long-term electrical field stimulation (10 Hz for 40 s) (c). was applied with both atropine and the P(2) purinoceptor antagonists present in the organ bath. The effects of capsaicin (d). and ATP (e). were also studied. Three groups of experimental animals were used: streptozotocin-treated (50 mg.kg(-1) i.p., 8 weeks before the experiment), parallel solvent-treated and untreated rats. (a). Responses to electrical field stimulation in the presence of atropine were reduced by half by PPADS plus suramin, but were resistant to capsaicin tachyphylaxis. They were enhanced in preparations taken from diabetic rats. (b). Contractions to electrical field stimulation in the presence of PPADS plus suramin were reduced by 2/3 by atropine, but were left unchanged by capsaicin or diabetes. (c). Contractions to long-term stimulation had a quick and a sustained phase. Especially the latter was inhibited by capsaicin tachypyhlaxis; it was also strongly reduced in preparations taken from diabetic rats. (d). Contractions to capsaicin (30 nM and 1 microM) were resistant to tetrodotoxin, strongly reduced by a combination of tachykinin NK(1) and NK(2) receptor antagonists, and slightly reduced in preparations from diabetic animals. Capsaicin (1 microM) had no acute inhibitory action on cholinergic or purinergic responses, nor did it cause relaxation in precontracted preparations treated with tachykinin receptor antagonists. (e) ATP-induced contractions were strongly reduced by PPADS plus suramin (50 plus 100 microM) and to a similar degree by 100 plus 200 microM, respectively. It is concluded that experimental diabetes selectively impairs peptidergic, capsaicin-sensitive responses (especially those that involve impulse conduction) in the rat detrusor preparation. The contractile response to electrical field stimulation that remains after atropine plus the P(2) purinoceptor antagonists has a yet unknown transmitter background.

BMS 493 Modulates Retinoic Acid-Induced Differentiation During Expansion of Human Hematopoietic Progenitor Cells for Islet Regeneration.

PubMed

Elgamal, Ruth M; Bell, Gillian I; Krause, Sarah C T; Hess, David A

2018-06-06

Cellular therapies are emerging as a novel treatment strategy for diabetes. Thus, the induction of endogenous islet regeneration in situ represents a feasible goal for diabetes therapy. Umbilical cord blood-derived hematopoietic progenitor cells (HPCs), isolated by high aldehyde dehydrogenase activity (ALDH hi ), have previously been shown to reduce hyperglycemia after intrapancreatic (iPan) transplantation into streptozotocin (STZ)-treated nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. However, these cells are rare and require ex vivo expansion to reach clinically applicable numbers for human therapy. Therefore, we investigated whether BMS 493, an inverse retinoic acid receptor agonist, could prevent retinoic acid-induced differentiation and preserve islet regenerative functions during expansion. After 6-day expansion, BMS 493-treated cells showed a twofold increase in the number of ALDH hi cells available for transplantation compared with untreated controls. Newly expanded ALDH hi cells showed increased numbers of CD34 and CD133-positive cells, as well as a reduction in CD38 expression, a marker of hematopoietic cell differentiation. BMS 493-treated cells showed similar hematopoietic colony-forming capacity compared with untreated cells, with ALDH hi subpopulations producing more colonies than low aldehyde dehydrogenase activity subpopulations for expanded cells. To determine if the secreted proteins of these cells could augment the survival and/or proliferation of β-cells in vitro, conditioned media (CM) from cells expanded with or without BMS 493 was added to human islet cultures. The total number of proliferating β-cells was increased after 3- or 7-day culture with CM generated from BMS 493-treated cells. In contrast to freshly isolated ALDH hi cells, 6-day expansion with or without BMS 493 generated progeny that were unable to reduce hyperglycemia after iPan transplantation into STZ-treated NOD/SCID mice. Further strategies to reduce retinoic acid differentiation during HPC expansion is required to expand ALDH hi cells without the loss of islet regenerative functions.

Tolerance in Maturity Groups V-VIII Soybean Cultivars to Heterodera glycines

PubMed Central

Hussey, R. S.; Boerma, H. R.

1989-01-01

Twenty-six susceptible and resistant soybean, Glycine max, cultivars in Maturity Groups V, VI, VII, and VIII were compared with Coker 156, Wright, and PI97100 for tolerance to Heterodera glycines races 3 and 14. Seed yields were compared in nematicide-treated (EDB, fenamiphos) and untreated plots at two H. glycines-infested locations over 3 years. Coker 488, DP 417, and NK S72-60 had the highest average tolerance indices ([yield in untreated plot + yield in nematicide-treated plot] x 100) of the race 3-susceptible cultivars to races 3 and 14. Plant height and seed weight of untreated soybean plants were suppressed in race 3-infested soil, but only plant height was suppressed at the race 14-infested location. Several race 3-resistant and race 14-susceptible cultivars were moderately tolerant to race 14. PMID:19287673

Flaxseed oil reduces oxidative stress and enhances brain monoamines release in streptozotocin-induced diabetic rats.

PubMed

Badawy, E A; Rasheed, W I; Elias, T R; Hussein, J; Harvi, M; Morsy, S; Mahmoud, Ya El-Latif

2015-11-01

This study was performed to investigate the biochemical effect of flaxseed oil on oxidative stress and brain monoamines release in streptozotocin-induced diabetic rats. Sixty male albino rats were divided into following four groups (15 for each group): control group, flaxseed oil group, diabetic group, and flaxseed oil-treated diabetic group. Serum glucose, insulin, pentosidine, plasma advanced oxidation protein products (AOPPs), and plasma total antioxidant capacity were estimated. Brain neurotransmitters, malondialdehyde (MDA), and nitric oxide (NO) were also determined. The mean values of serum pentosidine and plasma AOPP showed a significant decrease in treated diabetic group as compared to their values in the diabetic group. Also, brain neurotransmitters levels were improved after treatment with flaxseed. Brain MDA and NO were increased significantly in the diabetic group, while they were significantly decreased after treatment. Brain NO and brain MDA had a significant positive correlation with pentosidine, AOPP, and neurotransmitters. We concluded that flaxseed oil supplementation may be useful in the treatment of brain dysfunction in diabetes. © The Author(s) 2015.

Outcomes of polytrauma patients with diabetes mellitus

PubMed Central

2014-01-01

Background The impact of diabetes mellitus in patients with multiple system injuries remains obscure. This study was designed to increase knowledge of outcomes of polytrauma in patients who have diabetes mellitus. Methods Data from the Trauma Audit and Research Network was used to identify patients who had suffered polytrauma during 2003 to 2011. These patients were filtered to those with known outcomes, then separated into those with diabetes, those known to have other co-morbidities but not diabetes and those known not to have any co-morbidities or diabetes. The data were analyzed to establish if patients with diabetes had differing outcomes associated with their diabetes versus the other groups. Results In total, 222 patients had diabetes, 2,558 had no past medical co-morbidities (PMC), 2,709 had PMC but no diabetes. The diabetic group of patients was found to be older than the other groups (P <0.05). A higher mortality rate was found in the diabetic group compared to the non-PMC group (32.4% versus 12.9%), P <0.05). Rates of many complications including renal failure, myocardial infarction, acute respiratory distress syndrome, pulmonary embolism and deep vein thrombosis were all found to be higher in the diabetic group. Conclusions Close monitoring of diabetic patients may result in improved outcomes. Tighter glycemic control and earlier intervention for complications may reduce mortality and morbidity. PMID:25026864

Effects of rehabilitation management on gastric emptying function in older adults with diabetes.

PubMed

Shao, Z M; Yao, J F; Chen, J; Yu, Z W; Yu, X F; Zheng, J J; Tang, X

2014-01-24

The relationship between gastric emptying dysfunction and blood glucose concentration in elderly with type 2 diabetes mellitus was investigated, and the effect of rehabilitation exercise prescription training on gastric emptying in the geriatric diabetic patients was evaluated. A total of 160 older type 2 diabetic adults and 30 cases of non-diabetic patients were studied with regard to the gastric half emptying time (GET1/2) of solid meals radiolabelled with 99mTc. Eighty delayed gastric emptying diabetic patients were randomly divided into 4 four groups: rehabilitation exercise + mosapride group (N = 20), rehabilitation exercise group (N = 20), mosapride group (N = 20), and control group (N = 20). The level of blood glucose was measured every six months in a two-year follow-up. The solid GET1/2 of regulated blood glycemic control patients showed no statistically significant differences from non-diabetic patients (P > 0.05). However, the value for poor blood glycemic control patients exhibited significant statistical differences compared with both non-diabetic (P < 0.01) and regulated blood glycemic control group patients (P < 0.01). It showed that the gastric emptying time improved in the rehabilitation exercise group, mosapride group and rehabilitation exercise group + mosapride group after two years of treatment (P < 0.05). Fasting blood glucose in both rehabilitation exercise group and rehabilitation exercise + mosapride group was significantly decreased. Postprandial blood glucose in the rehabilitation exercise group, mosapride group, rehabilitation exercise group + mosapride group was significantly decreased. High blood glucose level can delay gastric emptying in older type 2 diabetic patients. Gastric emptying and blood glucose control affect each other. It was shown that appropriate rehabilitation exercise combined with prokinetic agent may improve gastric emptying in some geriatric type 2 diabetic patients and help control their blood glucose.

[Effect of nerve growth factor on osteogenic potential of type 2 diabetic mice bone marrow stromal cell in vitro].

PubMed

Cui, G S; Zeng, J Y; Zhang, J; Lu, R

2018-02-09

Objective: To study the effects of nerve growth factor (NGF) on the proliferation, osteogenic differentiation and mineralization of type 2 diabetic mice bone marrow stromal cell (BMSC), providing basis for clinical application of NGF. Methods: Three 8-week-old male db/db mice and two 8-week-old male C57BL/6J mice were used in the study. BMSC derived from femur were cultured though adherence method. BMSC of C57BL/6J mice and db/db mice was divided into normal group and diabetic group to conduct the osteogenic potential experiment, named experiment one. In experiment two, diabetic BMSC was divided into 3 groups: diabetic control group, NGF group, and K252a+NGF group [K252a was the inhibitor of tyrosine kinase A (TrkA), which was the high affinity receptor of NGF], to investigate effect of NGF on osteogenic potential of diabetic mice BMSC. After seeding BMSC, K252a was added into K252a+NGF group, then NGF was added 30 min later. NGF was added into NGF group and K252a+NGF group, but not diabetic control group. The proliferation of BMSC at 1, 3, 5 and 7 d in experiment one and the proliferation of BMSC at 1, 2 and 3 d in experiment two were evaluated through methyl thiazolyl tetrazolium, and the level of alkaline phosphatase (ALP) at 3, 5 and 7 d in both experiments were measured. After being osteogenic induced for 14 d, mineralized nodules in both experiments were quantitated by alizarin red calcium stain. Five holes were set in every group, and all experiments were repeated 3 times. Results: The BMSC proliferation of diabetic group was significantly higher than that of the normal group at 3, 5 and 7 d ( P< 0.05). After being osteogenic inducted for 3, 5 and 7 d, ALP level of diabetic group were significantly lower than that of normal group ( P< 0.05). After being osteogenic inducted for 14 d, calcium nodule count of diabetic group [(23.1±6.4) nodule/field] were significantly lower than that of normal group [(36.9±7.9) nodule/field]( P< 0.05). At 1, 2 and 3 d, BMSC proliferations of diabetic control group, NGF group and K252a+NGF group were not statistically different ( P> 0.05). After being osteogenic inducted for 3 and 5 d, ALP level of NGF group was significantly higher than that of diabetic control group ( P< 0.05). After being osteogenic inducted for 3, 5, and 7 d, ALP level of K252a+NGF group was significantly lower than that of NGF group ( P< 0.05) and diabetic control group ( P< 0.05). After being osteogenic induced for 14 d, calcium nodule count of NGF group [(45.2±6.8) nodule/field] was significantly more than that of diabetic control group [(23.1±6.4) nodule/field]( P< 0.05); while calcium nodule count of K252a+NGF group [(18.0±4.5) nodule/field] was significantly less than that of NGF group ( P< 0.05) and diabetic control group ( P< 0.05). Conclusions: The differentiation and mineralization of type 2 diabetic mice BMSC was significantly reduced. NGF promoted the osteoblastic differentiation and mineralization of diabetic mice BMSC in viro though combining with TrkA.

In vitro and in vivo inhibition of aldose reductase and advanced glycation end products by phloretin, epigallocatechin 3-gallate and [6]-gingerol.

PubMed

Sampath, Chethan; Sang, Shengmin; Ahmedna, Mohamed

2016-12-01

Hyperglycemic stress activates polyol pathway and aldose reductase (AR) key enzyme responsible for generating secondary complications during diabetes. In this study the therapeutic potential of phloretin, epigallocatechin 3-gallate (EGCG) and [6]-gingerol were evaluated for anti-glycating and AR inhibitory activity in vitro and in vivo systems. Human retinal pigment epithelial (HRPE) cells were induced with high glucose supplemented with the phloretin, EGCG and [6]-gingerol. Aldose reductase activity, total advanced glycation end products (AGEs) and enzyme inhibitor kinetics were assessed. Male C57BL/6J mice were randomly assigned to one of the different treatments (bioactive compounds at 2 concentrations each) with either a low fat diet or high fat diet (HFD). After sixteen weeks, AGE accumulation and AR activity was determined in heart, eyes and kidney. High glucose induced toxicity decreased cell viability compared to the untreated cells and AR activity increased to 2-5 folds from 24 to 96h. Pre-treatment of cells with phloretin, EGCG and [6]-gingerol improved cell viability and inhibited AR activity. The enzyme inhibition kinetics followed a non-competitive mode of inhibition for phloretin and EGCG whereas [6]-gingerol indicated uncompetitive type of inhibition against AR. Data from the animal studies showed high plasma glucose levels in HFD group over time, compared to the low fat diet. HFD group developed cataract and AR activity increased to 4 folds compared to the group with low fat diet. Administration of EGCG, phloretin and [6]-gingerol significantly reduced blood sugar levels, AGEs accumulation, and AR activity. These findings could provide a basis to consider using the selected dietary components alone or in combination with other therapeutic approaches to prevent diabetes-related complications in humans. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The relationship of Interleukin-6 -174 G>C gene polymorphism in type 2 diabetic patients with and without diabetic foot ulcers in Turkish population.

PubMed

Erdogan, Mehmet; Kulaksizoglu, Mustafa; Solmaz, Soner; Berdeli, Afig

2017-03-01

We aims investigate Turkish type 2 diabetic patients with/without diabetic foot ulcers and healthy group and examined the contribution of Interleukin (IL)-6 -174 G>C gene polymorphism to the development of diabetic foot ulcers. The Interleukin (IL)-6 -174 G>C genotypes were determined prospectively in 50 patients with diabetic foot ulcers and 35 without diabetic foot ulcers and a control group of 119 healthy individuals. Genotyping of the Interleukin (IL)-6 -174 G>C gene polymorphisms for all individuals was performed by PCR-RFLP method. The genotype IL6 distribution did differ between the control group (CC 13.3%, GC 66.7%, GG 20%) and type 2 diabetic patients (CC 2.4%, GC 47.1%, GG 50.6%) (P<0.001). The genotype IL6 distribution did not differ between type 2 diabetic patients group (CC 0%, GC 45.7%, GG 54.3%) and diabetic foot ulcers (CC 4%, GC 48%, 48%) (P>0.05). The frequency of the polymorphic G allele in between the control group and type 2 diabetic patients was no similar for the groups (58.4% and 74.1%, respectively) (p<0.05). The frequency of the polymorphic G allele in between the type 2 diabetic patients and diabetic foot ulcers was similar for the groups (77.1% and 72%, respectively) (p>0.05). The gene polymorphism of Interleukin-6 -174 G>C and G allele are an risk factor for diabetes, but gene polymorphism of Interleukin-6 -174 G>C is not an independent risk factor for diabetic foot. Genetic factors in the pathogenesis of diabetic foot may also show any changes in different populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Level of selected antibacterial tear proteins in children with diabetes type 1].

PubMed

Moll, Agnieszka; Wyka, Krystyna; Młynarski, Wojciech; Niwald, Anna

2011-01-01

Antibacterial immunity in diabetes is impaired, which increases the risk of general and local infections. The aim of the study was to evaluate non-specific local antibacterial immunity based on lactoferrin and lysozyme concentration in tears in children with diabetes type 1. Children at the age of 10-18 years old were studied. Group 1. consisted of children without diabetes, group 2. included patients with new onset of diabetes and group 3. consisted of children with decade-long diabetes. Among all patients tears were collected from inferior coniunctival fornix with hematocrit glass capillaries in purpose to measure lactoferrin and lysozyme concentration. ELISA method was used in laboratory testing. Level of lactoferrin did not differ significantly among all groups. Concentration of lysozyme was statistically lower in group with decade-long diabetes (group 3.) compared to patients without diabetes. Mild correlation between lactoferrin and lysozyme levels was seen in individual patients in whole group of probands together. Diabetes type 1 in children is associated with significant changes in concentration of tear proteins, which contribute to antibacterial immunity.

Changes in Matrix Metalloproteinases in Diabetes Patients' Tears After Vitrectomy and the Relationship With Corneal Epithelial Disorder.

PubMed

Matsumura, Takehiro; Takamura, Yoshihiro; Tomomatsu, Takeshi; Arimura, Shogo; Gozawa, Makoto; Takihara, Yuji; Inatani, Masaru

2015-06-01

Previous studies indicate involvement of matrix metalloproteinases (MMPs) in the pathogenesis of diabetic keratopathy. To evaluate MMP levels in the tears of patients with diabetes, we investigated changes in MMP levels during perioperative periods and clarify the relationship with corneal epithelial disorders following vitrectomy. Matrix metalloproteinase levels in tears were measured by multiplex bead array in patients with or without diabetes who were scheduled for vitrectomy. Twenty-two patients with diabetes and proliferative diabetic retinopathy, and 20 patients with epiretinal membrane or macular hole (control group), were recruited. Changes in MMP levels during perioperative periods and the relationship with corneal epithelial disorders after vitrectomy were analyzed. The levels of MMP-2, -9, and -10 at 1 day after surgery in the diabetic group were significantly higher than in the control group. At 1 week after surgery, MMP-10 levels in the diabetic group were significantly higher than in the control group. After vitrectomy, corneal epithelial disorders occurred in six patients in the diabetic group but not in the control group. In the diabetic group, MMP-10 levels in tears of patients with corneal epithelial disorders were significantly higher than those in patients without corneal epithelial disorders. The MMP concentration in tears of patients with diabetes was higher than in nondiabetic patients after vitrectomy. High MMP-10 levels were observed in patients with diabetes and corneal epithelial disorders after vitrectomy. Aberrant levels of MMP-10 may cause corneal epithelial disorder after vitrectomy.

Social Media as a Platform for Information About Diabetes Foot Care: A Study of Facebook Groups.

PubMed

Abedin, Tasnima; Al Mamun, Mohammad; Lasker, Mohammad A A; Ahmed, Syed Walid; Shommu, Nusrat; Rumana, Nahid; Turin, Tanvir C

2017-02-01

Diabetes is one of the most challenging chronic health conditions in the current era. Diabetes-related foot problems need proper patient education, and social media could a play role to disseminate proper information. A systematic search was performed on Facebook groups using the key words "diabetes foot care", "diabetes foot", "diabetes foot management" and "podiatric care". The search resulted in 57 groups and detailed activity information was collected from those groups. Usefulness of each relevant post was determined. Regression analysis was performed to explore the factors associated with the level of usefulness of diabetes foot care-related Facebook groups. Our search resulted in a total of 16 eligible diabetes foot care-related Facebook groups with a total of 103 eligible posts. The average number of group members for the selected groups were 265.75 with an interquartile range of 3.5-107.75. Of the total 103 timeline posts, 45.6% posts were categorized as useful, while the remaining posts were not useful. Top mentioned diabetes foot care practice was "Checking feet daily". Multivariable logistic regression analysis showed that the level of usefulness of diabetes foot care-related Facebook groups were significantly associated with the type of posts and no association was found with presence of "likes" and presence of comment. Facebook being a widely used social networking system, patient welfare organizations, doctors, nurses and podiatrists could use this platform to provide support to educating diabetes patients and their caregivers by disseminating useful and authentic knowledge and information related to diabetes foot care. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Long-term impact of earthquake stress on fasting glucose control and diabetes prevalence among Chinese adults of Tangshan.

PubMed

An, Cuixia; Zhang, Yun; Yu, Lulu; Li, Na; Song, Mei; Wang, Lan; Zhao, Xiaochuan; Gao, Yuanyuan; Wang, Xueyi

2014-01-01

To investigate the long-term influence of stresses from the 1976 Tangshan earthquake on blood glucose control and the incidence of diabetes mellitus in Chinese people of Tangshan. 1,551 adults ≥ 37 years of age were recruited for this investigation in Tangshan city of China, where one of the deadliest earthquakes occurred in 1796. All subjects finished a questionnaire. 1,030 of them who experienced that earthquake were selected into the exposure group, while 521 were gathered as the control group who have not exposed to any earthquake. The numbers of subjects who were first identified with diabetes or had normal FBG but with diabetic history were added for the calculation of diabetes prevalence. Statistic-analysis was applied on the baseline data, and incidences of IFG as well as diabetes among all groups. Statistic comparisons indicate there is no significant difference on average fasting glucose levels between the control group and the exposure group. However, the prevalence of IFG and diabetes among the exposure group displays significant variance with the control group. The prevalence of diabetes among exposure groups is significantly higher than the control group. Women are more likely to have diabetes after experiencing earthquake stresses compared to men. The earthquake stress was linked to higher diabetes incidence as an independent factor. The earthquake stress has long-term impacts on diabetes incidence as an independent risk factor. Emerging and long-term managements regarding the care of IFG and diabetes in populations exposed to earthquake stress should be concerned.

Sarcopenia in diabetic nephropathy: a cross-sectional study.

PubMed

Çeliker, Meral; Selçuk, Mustafa Yavuz; Olt, Serdar

2018-06-01

To investigate the relationship between sarcopenia and diabetic nephropathy. 56 diabetic patients without complications, 50 diabetic patients with nephropathy, 53 healthy controls included in this present study. Demographic characteristics such as sex, age, anthropometric measurements such as weight, body mass index [BMI], hip circumference, waist circumference and upper arm circumference were measured. Sarcopenia diagnosis was based on European Working Group on Sarcopenia in Older People [EWGSOP] criteria which consist of hand grip strength, 6-meter walking test and muscle mass. The frequency of sarcopenia increased gradually from 15.1% in healthy control group to 21.4% in the diabetes group, and 34% in diabetic nephropathy group (X2 for trend, p = 0.029). The frequency of sarcopenia was similar in diabetes and diabetic nephropathy group. However, the frequency of sarcopenia was higher in diabetic nephropathy than healthy controls (OR = 2.89, CI [1.11-7.51] in logistic regression). In the present study, the prevalence of sarcopenia was higher in patients with diabetic nephropathy compared to healthy controls.

The Role of Rac1 on Carbachol-induced Contractile Activity in Detrusor Smooth Muscle from Streptozotocin-induced Diabetic Rats.

PubMed

Evcim, Atiye Sinem; Micili, Serap Cilaker; Karaman, Meral; Erbil, Guven; Guneli, Ensari; Gidener, Sedef; Gumustekin, Mukaddes

2015-06-01

This study was designed to determine the role of the small GTPase Rac1 on carbachol-induced contractile activity in detrusor smooth muscle using small inhibitor NSC 23766 in diabetic rats. Rac1 expression in bladder tissue was also evaluated. In the streptozotocin (STZ)-induced diabetic rat model, three study groups were composed of control, diabetic and insulin-treated diabetic subjects. The detrusor muscle strips were suspended in organ baths at the end of 8-12 weeks after STZ injection. Carbachol (CCh) (10(-9) -10(-4) M) concentration-response curves were obtained both in the absence and in the presence of Rac1 inhibitor NSC 23766 (0.1, 1 and 10 μM). Diabetes-related histopathological changes and Rac1 expressions were assessed by haematoxylin and eosin staining and immunohistochemical staining, respectively. CCh caused dose-dependent contractile responses in all the study groups. Rac1 inhibitor NSC 23766 inhibited CCh-induced contractile responses in all groups, but this inhibition seen in both diabetes groups was greater than in the control group. Histological examination revealed an increased bladder wall thickness both in the diabetes and in the insulin-treated diabetes groups compared to the control group. In immunohistochemical staining, expression of Rac1 was observed to be increased in all layers of bladder in both diabetic groups compared to the control group. In the diabetic bladders, increased expression of Rac1 and considerable inhibition of CCh-induced responses in the presence of NSC 23766 compared to those of the control group may indicate a specific role of Rac1 in diabetes-related bladder dysfunction, especially associated with cholinergic mediated detrusor overactivity. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Molecular mechanisms of nano-selenium in mitigating hepatocellular carcinoma induced by N-nitrosodiethylamine (NDEA) in rats.

PubMed

Ahmed, Hanaa H; Khalil, Wagdy K B; Hamza, Amal H

2014-12-01

The possible molecular mechanisms of Nano-selenium (nano-se) in attenuating hepatocellular carcinoma (HCC) was investigated in this study. To achieve this target, the apoptotic/necrotic rate in hepatic cells was investigated morphologically by double staining with acridine orange/ethidium bromide to address the type of cell death induced by nano-Se in HCC-bearing rats. To predict the oxidative stress and DNA damage, the generation of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 2-deoxyguanosine (2-dG) was examined. Moreover, the expression of some HCC-related genes was investigated such as aldo-keto reductase 1B10 (Akr1b10), ING3 and Foxp1 genes. As well as the histopathological study of liver tissue sections was performed. The results obtained from this study revealed that (HCC+Nano Se) group shows the highest number of damaged cancerous cells. Furthermore, the necrotic/apoptotic rate was significantly higher in (nano-Se+HCC), (HCC+Doxo) and (HCC+Doxo+nano-se) compared to that in the untreated HCC group. Treatment of HCC group with nano-se decreased the ratio of 8-OHdG/2-dG generation significantly with respect to the untreated HCC group. The opposite was observed regarding the gene expression of AKr1b10 and ING3. The treatment of HCC group with nano-se elicited significant increase in the expression of Akr1b10 and ING3 genes compared with untreated HCC group. On the other hand, the expression of Foxp1 gene was significantly decreased in HCC group treated with nano-se in comparison with the untreated HCC group. The histopathological study provided a supportive evidence for the molecular genetics study. Our data shed light on the molecular mechanisms of nano-se in attenuating HCC in the experimental model.

How EFL Students Can Use Google to Correct Their "Untreatable" Written Errors

ERIC Educational Resources Information Center

Geiller, Luc

2014-01-01

This paper presents the findings of an experiment in which a group of 17 French post-secondary EFL learners used Google to self-correct several "untreatable" written errors. Whether or not error correction leads to improved writing has been much debated, some researchers dismissing it is as useless and others arguing that error feedback…

Lactobacillus casei CCFM419 attenuates type 2 diabetes via a gut microbiota dependent mechanism.

PubMed

Wang, Gang; Li, Xiangfei; Zhao, Jianxin; Zhang, Hao; Chen, Wei

2017-09-20

Probiotics, as dietary supplements, transmit their major effects through the regulation of gut microbiota. According to a previous study, one possible mechanism of Lactobacillus casei CCFM419 protection against diabetes may involve gut flora. To test this hypothesis, high fat and streptozotocin-induced C57BL/6J mice were fed L. casei CCFM419 at 10 8 , 10 9 , and 10 10 colony forming units (CFU). Compared to untreated mice, 10 9 CFU of L. casei CCFM419 attenuated several symptoms of diabetes, including fasting blood glucose, postprandial blood glucose, glucose intolerance, and insulin resistance. In addition, this CFU level also decreased the levels of the inflammatory markers tumor necrosis factor-α and interleukin-6 and increased intestinal glucagon-like peptide-1 (GLP-1) levels, which are associated with the production of short chain fatty acids (SCFAs). The 16S rRNA gene sequencing of fecal samples demonstrated that 10 9 CFU of L. casei CCFM419 dramatically increased the abundance of Bacteroidetes and decreased the proportion of Firmicutes at the phylum level, and enriched Bifidobacterium, Lactobacillus, and SCFA-producing bacteria, including Allobaculum and Bacteroides. These findings suggested that L. casei CCFM419 modified the gut flora-SCFA-inflammation/GLP-1 mechanism to ameliorate type 2 diabetes.

Synergistic effects of acarbose and an Oroxylum indicum seed extract in streptozotocin and high-fat-diet induced prediabetic mice.

PubMed

Sun, Wenlong; Sang, Yuanbin; Zhang, Bowei; Yu, Xiaoxia; Xu, Qinmin; Xiu, Zhilong; Dong, Yuesheng

2017-03-01

Prediabetes is defined as blood glucose levels above normal but below diabetes thresholds, and up to 70% of individuals with prediabetes will eventually develop diabetes if left untreated. Acarbose, the first FDA approved anti-prediabetes agent, has some disadvantages, such as reducing the risk of diabetes by only 36%, side effects and limited effects on complications. The aim of this study is to develop a new agent to treat prediabetes and to investigate the anti-prediabetes effects and mechanisms of acarbose and an Oroxylum indicum seed extract (OISE) in prediabetic mice. The combined drugs can reduce the dose of acarbose by 80% and reduce the risk of diabetes by 75%, which is one fold higher than acarbose monotherapy. The combined drugs showed synergistic anti-prediabetes effects and could be effective in preventing the complications of prediabetes. The combined drugs could improve glucose tolerance, improve lipid metabolism and reduce oxidative stress and tissue damage. For the mechanisms, the combined drugs can reduce synergistically postprandial hyperglycaemia by inhibiting α-glucosidase. Furthermore, baicalein in OISE was demonstrated to be a major component in reducing oxidative stress and chrysin was the primary compound that activated PPARγ. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A Novel Clinically Relevant Strategy to Abrogate Autoimmunity and Regulate Alloimmunity in NOD Mice

PubMed Central

Vergani, Andrea; D'Addio, Francesca; Jurewicz, Mollie; Petrelli, Alessandra; Watanabe, Toshihiko; Liu, Kaifeng; Law, Kenneth; Schuetz, Christian; Carvello, Michele; Orsenigo, Elena; Deng, Shaoping; Rodig, Scott J.; Ansari, Javeed M.; Staudacher, Carlo; Abdi, Reza; Williams, John; Markmann, James; Atkinson, Mark; Sayegh, Mohamed H.; Fiorina, Paolo

2010-01-01

OBJECTIVE To investigate a new clinically relevant immunoregulatory strategy based on treatment with murine Thymoglobulin mATG Genzyme and CTLA4-Ig in NOD mice to prevent allo- and autoimmune activation using a stringent model of islet transplantation and diabetes reversal. RESEARCH DESIGN AND METHODS Using allogeneic islet transplantation models as well as NOD mice with recent onset type 1 diabetes, we addressed the therapeutic efficacy and immunomodulatory mechanisms associated with a new immunoregulatory protocol based on prolonged low-dose mATG plus CTLA4-Ig. RESULTS BALB/c islets transplanted into hyperglycemic NOD mice under prolonged mATG+CTLA4-Ig treatment showed a pronounced delay in allograft rejection compared with untreated mice (mean survival time: 54 vs. 8 days, P < 0.0001). Immunologic analysis of mice receiving transplants revealed a complete abrogation of autoimmune responses and severe downregulation of alloimmunity in response to treatment. The striking effect on autoimmunity was confirmed by 100% diabetes reversal in newly hyperglycemic NOD mice and 100% indefinite survival of syngeneic islet transplantation (NOD.SCID into NOD mice). CONCLUSIONS The capacity to regulate alloimmunity and to abrogate the autoimmune response in NOD mice in different settings confirmed that prolonged mATG+CTLA4-Ig treatment is a clinically relevant strategy to translate to humans with type 1 diabetes. PMID:20805386

Cannabidiol lowers incidence of diabetes in non-obese diabetic mice.

PubMed

Weiss, L; Zeira, M; Reich, S; Har-Noy, M; Mechoulam, R; Slavin, S; Gallily, R

2006-03-01

Cannabidinoids are components of the Cannabis sativa (marijuana) plant that have been shown capable of suppressing inflammation and various aspects of cell-mediated immunity. Cannabidiol (CBD), a non-psychoactive cannabidinoid has been previously shown by us to suppress cell-mediated autoimmune joint destruction in an animal model of rheumatoid arthritis. We now report that CBD treatment significantly reduces the incidence of diabetes in NOD mice from an incidence of 86% in non-treated control mice to an incidence of 30% in CBD-treated mice. CBD treatment also resulted in the significant reduction of plasma levels of the pro-inflammatory cytokines, IFN-gamma and TNF-alpha. Th1-associated cytokine production of in vitro activated T-cells and peritoneal macrophages was also significantly reduced in CBD-treated mice, whereas production of the Th2-associated cytokines, IL-4 and IL-10, was increased when compared to untreated control mice. Histological examination of the pancreatic islets of CBD-treated mice revealed significantly reduced insulitis. Our results indicate that CBD can inhibit and delay destructive insulitis and inflammatory Th1-associated cytokine production in NOD mice resulting in a decreased incidence of diabetes possibly through an immunomodulatory mechanism shifting the immune response from Th1 to Th2 dominance.

Prostate cancer decision-making, health services, and the family physician workforce.

PubMed

Bowman, Marjorie A; Neale, Anne Victoria

2012-01-01

Does untreated cancer equal death? Does having a registered nurse versus a licensed practical nurse versus a medical assistant affect diabetes quality outcomes? Do physicians caring for stressed patients experience vicarious traumatic stress? Oregon presents an operationalized definition of a patient-centered medical home for their state. Lots of important clinical topics in family medicine--adult attention deficit disorder office questionnaire; Bell palsy; cancer screening and treatment decisions; lubrication during Papanicolaou testing; changes in maternity care training by residencies; changing prescribing patterns for thiazide diuretics; and night sweats remain a mystery.

Early diagnosis of diabetic vascular complications: impairment of red blood cell deformability

NASA Astrophysics Data System (ADS)

Shin, Sehyun; Ku, Yunhee; Park, Cheol-Woo; Suh, Jang-Soo

2006-02-01

Reduced deformability of red blood cells (RBCs) may play an important role on the pathogenesis of chronic vascular complications of diabetes mellitus. However, available techniques for measuring RBC deformability often require washing process after each measurement, which is not optimal for day-to-day clinical use at point of care. The objectives of the present study are to develop a device and to delineate the correlation of impaired RBC deformability with diabetic nephropathy. We developed a disposable ektacytometry to measure RBC deformability, which adopted a laser diffraction technique and slit rheometry. The essential features of this design are its simplicity (ease of operation and no moving parts) and a disposable element which is in contact with the blood sample. We studied adult diabetic patients divided into three groups according to diabetic complications. Group I comprised 57 diabetic patients with normal renal function. Group II comprised 26 diabetic patients with chronic renal failure (CRF). Group III consisted of 30 diabetic subjects with end-stage renal disease (ESRD) on hemodialysis. According to the renal function for the diabetic groups, matched non-diabetic groups were served as control. We found substantially impaired red blood cell deformability in those with normal renal function (group I) compared to non-diabetic control (P = 0.0005). As renal function decreases, an increased impairment in RBC deformability was found. Diabetic patients with chronic renal failure (group II) when compared to non-diabetic controls (CRF) had an apparently greater impairment in RBC deformability (P = 0.07). The non-diabetic cohort (CRF), on the other hand, manifested significant impairment in red blood cell deformability compared to healthy control (P = 0.0001). The newly developed slit ektacytometer can measure the RBC deformability with ease and accuracy. In addition, progressive impairment in cell deformability is associated with renal function loss in all patients regardless of the presence or absence of diabetes. In diabetic patients, early impairment in RBC deformability appears in patients with normal renal function.

Periodontal tissue repair after sealing of the gap in vertical root fracture.

PubMed

Sugaya, Tsutomu; Tomita, Mahito; Motoki, Youji; Zaman, Khurshiduz; Miyaji, Hirofumi; Kawanami, Masamitsu

2017-04-01

The aim of this study was to determine whether sealing of fracture gap using adhesive resin through the root canal can prevent inflammation of periodontal tissue, and resealing the incompletely sealed fracture gap from outside can resolve such inflammation in experimentally created vertical root fractures. Vertical root fractures were created in incisor of beagles. In the experimental group, the fracture gap was sealed through the root canal with adhesive resin. After 5 weeks, sites with the clinical attachment level ≥4 mm were further divided randomly into the poor-replanting group and the poor-untreated group. In the poor-replanting group, the tooth was extracted and replanted after resealing the fracture gap with adhesive resin from the outer surface. Sites with clinical attachment level ≤3 mm after 5 weeks were considered as the satisfactory group. The poor-untreated group and the satisfactory group were subjected to no further treatment. The clinical attachment level was evaluated at baseline and after 2, 5, and 9 weeks. After 9 weeks, histological measurements were made to determine the length of the epithelial downgrowth and the area of alveolar bone resorption. The clinical attachment level and the area of bone resorption were significantly smaller in the poor-replanting group and the satisfactory group than in the poor-untreated group (p < 0.05). The results indicate the possibility that periodontal inflammation along the fracture line can be prevented and improved if the fracture gap is sealed.

Comparison of Systemic and Topical Hypericum Perforatum on Diabetic Surgical Wounds.

PubMed

Altıparmak, Mehmet; Eskitaşçıoğlu, Teoman

2018-02-01

Surgical wounds in diabetic patients still remain a problem till the present day. As a common plant found around the world, Hypericum perforatum L. (Hypericaceae) is traditionally prepared as an oily extract and used as a folk remedy for various diseases such as wounds, burns, cuts, etc. This study aims to evaluate the effect of St. John's wort (Hypericum perforatum) on problematic wounds while comparing oral and topical applications. Incisional and excisional wound models were made on the dorsal regions of 54 diabetic Spraque-Dawley rats. The rats were divided into the following six groups (n = 9): Group 1: control, Group 2: diabetic, Group 3: diabetic oral Hypericum perforatum, Group 4: diabetic topical Hypericum perforatum, Group 5: diabetic oral olive oil, and Group 6: diabetic topical olive oil. Groups 3 and 4 had significantly higher tensile strength, tissue hydroxyproline concentration, and collagen density compared with Group 2. Inflammatory cell density and collagen density on day 3 were significantly higher in Groups 3 and 6 compared with Group 2. On day 21, Groups 3 and 6 had significantly higher fibroblastic activity compared with Group 2. This study has proved that oral St. John's wort has more positive effects on problematic wounds compared with topical St. John's wort and olive oil, which is a vehicle. Hypericum perforatum results with faster inflammatory response and better healing. These results could be an addition to literature about the clinical usage of Hypericum perforatum on diabetic wounds.

Penile histomorphometrical evaluation in hypertensive rats treated with sildenafil or enalapril alone or in combination: a comparison with normotensive and untreated hypertensive rats.

PubMed

Felix-Patrício, Bruno; Medeiros, Jorge L; De Souza, Diogo B; Costa, Waldemar S; Sampaio, Francisco J B

2015-01-01

Erectile dysfunction (ED) is frequently associated to hypertension and antihypertensive drugs; however, the penile morphological aspects on these situations are poorly known. Evaluate the penile morphology of untreated hypertensive rats and rats treated with enalapril or sildenafil alone or in combination to verify the hypothesis that morphological alterations promoted by hypertension on corpus cavernosum could be ameliorated by the use of angiotensin-converting enzyme inhibitors and/or phosphodiesterase type 5 inhibitors. Fifty male rats were assigned into five groups: normotensive rats, untreated spontaneously hypertensive rats (SHRs), and SHR treated with enalapril or sildenafil alone or in combination. Blood pressure was measured weekly. At the conclusion of the study, the rats were euthanized, and their penises were collected for histomorphometrical analysis. The cross-sectional areas of the penis, tunica albuginea, and corpus cavernosum were measured. The density of the corpus cavernosum structures was quantified. Both groups of SHR rats treated with enalapril became normotensive. Untreated SHR showed no difference in penile and cavernosal cross-sectional area compared with normotensive rats; however, those rats treated with enalapril or sildenafil alone demonstrated an increase in these parameters. Rats receiving combination therapy showed no cross-sectional area differences compared with normotensive rats. Cavernosal connective tissue density was increased, while the sinusoidal spaces were diminished in untreated SHR. All treatments were effective in maintaining connective tissue density in comparison with normotensive animals. Cavernosal smooth muscle density was similar in all groups, with the exception of the combination therapy group, which demonstrated a reduction in smooth muscle. Hypertension promoted structural alterations in the corpus cavernosum that may be related to ED. Enalapril- and sildenafil-treated animals had preservation of normal corpus cavernosum structure and an increase in penile and cavernosal cross-sectional area. The combination of these drugs showed less benefit than individual use. © 2014 International Society for Sexual Medicine.

Controlled Antenatal Thyroid Screening II: effect of treating maternal sub-optimal thyroid function on child cognition.

PubMed

Hales, Charlotte; Taylor, Peter N; Channon, Sue; Paradice, Ruth; McEwan, Kirsten; Zhang, Lei; Gyedu, Michael; Bakhsh, Ameen; Okosieme, Onyebuchi; Muller, Ilaria; Draman, Mohd S; Gregory, John W; Dayan, Colin; Lazarus, John H; Rees, D Aled; Ludgate, Marian

2018-01-15

The Controlled Antenatal Thyroid Screening (CATS) study investigated treatment for suboptimal gestational thyroid function (SGTF) on childhood cognition and found no difference in IQ at 3 years between children of treated and untreated SGTF mothers. We have measured IQ in the same children at age 9.5-years and included children from normal-GTF mothers. One examiner, blinded to participant group, assessed children's IQ (WISC-IV), long-term memory and motor function (NEPSY-II) from children of 119 treated and 98 untreated SGTF mothers plus children of 232 mothers with normal-GTF. Logistic regression explored the odds and percentages of IQ<85 in the groups. There was no difference in IQ<85 between children of mothers with normal-GTF and combined SGTF i.e. treated and untreated (fully adjusted OR=1.15 (95% CI 0.52, 2.51) p=0.731). Furthermore, there was no significant effect of treatment (untreated OR=1.33 (95% CI 0.53, 3.34), treated OR=0.75 (95% CI 0.27, 2.06) p=0.576). IQ< 85 was 6.03% in normal-GTF, 7.56% in treated and 11.22% in untreated groups. Analyses accounting for treated-SGTF women with FT4 >97.5th centile of the entire CATS-I cohort revealed no significant effect on child's IQ<85 in CATS-II. IQ at age 3 predicted IQ at age 9.5 (p<0.0001) and accounted for 45% of the variation. Maternal thyroxine during pregnancy did not improve child cognition at age 9.5 years. Our findings confirmed CATS-I and suggest that the lack of treatment effect may be due to the similar proportion of IQ<85 in children of women with normal-GTF and SGTF. Copyright © 2018 Endocrine Society

Preventive efficacy of a topical combination of fipronil--(S)-methoprene--eprinomectin--praziquantel against ear mite (Otodectes cynotis) infestation of cats through a natural infestation model.

PubMed

Beugnet, Frédéric; Bouhsira, Emilie; Halos, Lénaïg; Franc, Michel

2014-01-01

A study based on naturally infested cats was designed to evaluate the effectiveness of a single treatment with a topical formulation containing fipronil, (S)-methoprene, eprinomectin and praziquantel, for the prevention of Otodectes cynotis infestation in cats. Six treated cats and six untreated cats were housed with three chronically Otodectes cynotis-infested cats, respectively. The cats of each group were kept together in a 20-m(2) room for 1 month. Both clinical examination and ear mite counts were conducted on Day 28. All donor cats were confirmed to be chronically infested with Otodectes cynotis on Day -1 and Day 28. From untreated control cats, 129 live mites were recovered on Day 28 and all cats were found to be infested. In the treated group, three cats were found to be infested, with a total of five live mites recovered, the difference between the two groups being significant (p = 0.003). One treatment corresponded to 96% preventive efficacy at Day 28 based on ear mite counts. With regard to cerumen, the clinical score increased significantly for untreated cats between Day -1 and Day 28 (p = 0.00026) and not for treated cats (p = 0.30). The difference in cerumen abundance was significant between untreated and treated cats on Day 28 (p = 0.0035). Concerning the pruritic reflex in at least one ear, all cats were negative at inclusion. All six untreated cats became positive and showed a reflex on Day 28, whereas no treated cat showed ear pruritus (p = 0.00026). © F. Beugnet et al., published by EDP Sciences, 2014.

Antihyperglycaemic potential of the water-ethanol extract of Kalanchoe crenata (Crassulaceae).

PubMed

Kamgang, René; Mboumi, Rostand Youmbi; Fondjo, Angèle Foyet; Tagne, Michel Archange Fokam; N'dillé, Gabriel Patrice Roland Mengue; Yonkeu, Jeanne Ngogang

2008-01-01

Kalanchoe crenata is a vegetable widely used in Cameroon and largely efficient in the treatment of diabetes mellitus. The effect of the water-ethanol extract of this plant (WEKC) on blood glucose levels was investigated in fasting normal and diet-induced diabetic rats (MACAPOS 1) after a short- and medium-term treatment. Diabetes was induced by submitting Wistar rats to a hypercaloric sucrose diet over 4 months. Six hours after a single oral administration of WEKC, 135 and 200 mg kg(-1) body weight extracts significantly (P < 0.01) reduced the blood glucose levels both in normal and diabetic rats without real dose-dependent effect. During the medium-term treatment, 200 mg kg(-1) WEKC administered daily for 4 weeks significantly reduced blood glucose levels within week 1 (P < 0.05), with a maximum effect at week 4 (-52%, P < 0.01), while maintaining glycaemia within the normal range. All the WEKC-treated diabetic rats exhibited significant (P < 0.01) increase in insulin sensitivity index (K (ITT)) compared with the initial time and to the untreated diabetic animals. Animals treated for 4 weeks exhibited a slight resistance in body-weight gain and decrease in food and water intake. The WEKC activities on all parameters assessed were comparable with the glibenclamide effects. Qualitative phytochemical screening revealed that K. crenata contains terpenoids, tannins, polysaccharids, saponins, flavonoids and alkaloids. The data suggest that K. crenata might contain important chemical components that could induce significant improvement in glucose clearance and/or uptake and resistance to body-weight gain and insulin sensitivity, and could be a potent alternative or complementary therapeutic substance in the control of type 2 diabetes and other insulin-resistant conditions.

Sustained glucagon-like peptide 1 expression from encapsulated transduced cells to treat obese diabetic rats.

PubMed

Moralejo, Daniel; Yanay, Ofer; Kernan, Kelly; Bailey, Adam; Lernmark, Ake; Osborne, William

2011-04-01

Obesity and type 2 diabetes (T2D) are two prevalent chronic diseases that have become a major public health concern in industrialized countries. T2D is characterized by hyperglycemia and islet beta cell dysfunction. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. Leptin receptor deficient male rats are obese and diabetic and provide a model of T2D. We hypothesized that their treatment by sustained expression of GLP-1 using encapsulated cells may prevent or delay diabetes onset. Vascular smooth muscle cells (VSMC) retrovirally transduced to secrete GLP-1 were seeded into TheraCyte(TM) encapsulation devices, implanted subcutaneously and rats were monitored for diabetes. Rats that received cell implants showed mean plasma GLP-1 level of 119.3 ± 10.2pM that was significantly elevated over control values of 32.4 ± 2.9pM (P<0.001). GLP-1 treated rats had mean insulin levels of 45.9 ± 2.3ng/ml that were significantly increased over control levels of 7.3±1.5ng/ml (P<0.001). In rats treated before diabetes onset elevations in blood glucose were delayed and rats treated after onset became normoglycemic and showed improved glucose tolerance tests. Untreated diabetic rats possess abnormal islet structures characterized by enlarged islets with α-cell infiltration and multifocal vacuolization. GLP-1 treatment induced normalization of islet structures including a mantle of α-cells and increased islet mass. These data suggest that encapsulated transduced cells may offer a potential long term treatment of patients. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Sustained glucagon-like peptide 1 expression from encapsulated transduced cells to treat obese diabetic rats

PubMed Central

Moralejo, Daniel; Yanay, Ofer; Kernan, Kelly; Bailey, Adam; Lernmark, Ake; Osborne, William

2011-01-01

Obesity and type 2 diabetes (T2D) are two prevalent chronic diseases that have become a major public health concern in industrialized countries. T2D is characterized by hyperglycemia and islet beta cell dysfunction. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. Leptin receptor deficient male rats are obese and diabetic and provide a model of T2D. We hypothesized that their treatment by sustained expression of GLP-1 using encapsulated cells may prevent or delay diabetes onset. Vascular smooth muscle cells (VSMC) retrovirally transduced to secrete GLP-1 were seeded into TheraCyteTM encapsulation devices, implanted subcutaneously and rats monitored for diabetes. Rats that received cell implants showed mean plasma GLP-1 level of 119.3±10.2 pM that was significantly elevated over control values of 32.4±2.9 pM (P<0.001). GLP-1 treated rats had mean insulin levels of 45.9±2.3 ng/ml that were significantly increased over control levels of 7.3±1.5 ng/ml (P<0.001). In rats treated before diabetes onset elevations in blood glucose were delayed and rats treated after onset became normoglycemic and showed improved glucose tolerance tests. Untreated diabetic rats possess abnormal islet structures characterized by enlarged islets with β-cell infiltration and multifocal vacuolization. GLP-1 treatment induced normalization of islet structures including a mantle of β-cells and increased islet mass. These data suggest encapsulated transduced cells may offer a potential long term treatment of patients. PMID:21216666

Protective function of pyridoxamine on retinal photoreceptor cells via activation of the p‑Erk1/2/Nrf2/Trx/ASK1 signalling pathway in diabetic mice.

PubMed

Ren, Xiang; Sun, Hong; Zhang, Chenghong; Li, Chen; Wang, Jinlei; Shen, Jie; Yu, Dong; Kong, Li

2016-07-01

The present study aimed to investigate the mechanisms that mediate the protective effects of pyridoxamine (PM) on light‑damaged retinal photoreceptor cells in diabetic mice. A high‑fat diet and streptozotocin were used to induce a mouse model of type II diabetes. During the experiment, mice were divided the mice into three types of group, as follows: Control groups (negative control and light‑damaged groups); experimental groups (diabetic and diabetic light‑damaged groups); and treatment groups (25, 50 and 100 mg/kg PM‑treated groups). Using hematoxylin‑eosin staining, the number of nuclear layer cells were counted. Western blotting and immunohistochemistry were performed to measure the levels of thioredoxin (Trx), phospho‑extracellular signal‑regulated kinase 1/2 (p‑Erk1/2), nuclear factor erythroid 2‑related factor 2 (Nrf2) and apoptosis signal‑regulating kinase 1 (ASK1). The photoreceptor cell count in the outer nuclear layer of the light‑damaged, diabetic control and diabetic light‑damaged groups were significantly reduced compared with the negative control group (P<0.001). The cell counts in the PM‑treated groups were significantly increased compared with the diabetic group (P<0.001). Compared with the negative control group, the light‑damaged, diabetic and diabetic light‑damaged groups exhibited significantly decreased Trx, p‑Erk1/2 and Nrf2 expression levels (P<0.001), and significantly increased ASK1 expression levels (P<0.001). However, in the PM‑treated groups, Trx, p‑Erk1/2 and Nrf2 expression levels were significantly increased (P<0.001), and ASK1 expression was significantly decreased (P<0.001). The results of the present study demonstrate that PM protects retinal photoreceptor cells against light damage in diabetic mice, and that its mechanism may be associated with the upregulation of Trx, p‑Erk1/2 and Nrf2 expression, and the downregulation of ASK1 expression.

Decreased health-related quality of life in patients with diabetic foot problems

PubMed Central

Sothornwit, Jin; Srisawasdi, Gulapar; Suwannakin, Atchara; Sriwijitkamol, Apiradee

2018-01-01

Purpose The aim of this study was to investigate health-related quality of life (HRQoL) in patients with diabetic foot problems and compare the HRQoL between diabetic patients with: 1) diabetic foot problems (DF), including diabetic foot ulcer (DFU) or amputation (AMPU); 2) other diabetic complications (COM), such as diabetic retinopathy (DR), end-stage renal disease (ESRD), or coronary artery disease (CAD); and 3) no diabetic complication (CON). Patients and methods A total of 254 diabetic patients were studied in a cross-sectional setting. HRQoL was evaluated using Thai version of the Euro Quality of Life Questionnaire (EuroQoL), with five dimensions and five-level scale (EQ-5D-5L). Utility scores were calculated using time trade-off methods. Results A total of 141 patients in the DF group (98 DFU and 43 AMPU groups), 82 in the COM group (27 DR, 28 ESRD, and 27 CAD groups), and 31 in the CON group were interviewed. The mean age was 63.2±12.1 years, body mass index was 24.9±4.7 kg/m2, mean hemoglobin A1c was 7.7±2.1%, duration of diabetes was 13.1±9.9 years, and the mean utility scores were 0.799±0.25. After having DF, 21% of patients had lost their jobs. The COM group had lower utility scores than the CON group. Among the diabetic complications, the DF group had the lowest mean utility scores as compared to the COM and CON groups (0.703±0.28 in the DF group, 0.903±0.15 in the COM group, and 0.961±0.06 in the CON group, P<0.01). There was no difference in the mean utility scores between DFU and AMPU groups. Patients in the DF group reported moderate-to-severe problem in all dimensions more than the other groups. Conclusion DF have the greatest negative impact on HRQoL. Therefore, diabetic foot care should be emphasized in clinical practice to prevent foot complications. PMID:29563821

Decreased health-related quality of life in patients with diabetic foot problems.

PubMed

Sothornwit, Jin; Srisawasdi, Gulapar; Suwannakin, Atchara; Sriwijitkamol, Apiradee

2018-01-01

The aim of this study was to investigate health-related quality of life (HRQoL) in patients with diabetic foot problems and compare the HRQoL between diabetic patients with: 1) diabetic foot problems (DF), including diabetic foot ulcer (DFU) or amputation (AMPU); 2) other diabetic complications (COM), such as diabetic retinopathy (DR), end-stage renal disease (ESRD), or coronary artery disease (CAD); and 3) no diabetic complication (CON). A total of 254 diabetic patients were studied in a cross-sectional setting. HRQoL was evaluated using Thai version of the Euro Quality of Life Questionnaire (EuroQoL), with five dimensions and five-level scale (EQ-5D-5L). Utility scores were calculated using time trade-off methods. A total of 141 patients in the DF group (98 DFU and 43 AMPU groups), 82 in the COM group (27 DR, 28 ESRD, and 27 CAD groups), and 31 in the CON group were interviewed. The mean age was 63.2±12.1 years, body mass index was 24.9±4.7 kg/m 2 , mean hemoglobin A1c was 7.7±2.1%, duration of diabetes was 13.1±9.9 years, and the mean utility scores were 0.799±0.25. After having DF, 21% of patients had lost their jobs. The COM group had lower utility scores than the CON group. Among the diabetic complications, the DF group had the lowest mean utility scores as compared to the COM and CON groups (0.703±0.28 in the DF group, 0.903±0.15 in the COM group, and 0.961±0.06 in the CON group, P <0.01). There was no difference in the mean utility scores between DFU and AMPU groups. Patients in the DF group reported moderate-to-severe problem in all dimensions more than the other groups. DF have the greatest negative impact on HRQoL. Therefore, diabetic foot care should be emphasized in clinical practice to prevent foot complications.

Emotion, working memory, and cognitive control in patients with first-onset and previously untreated minor depressive disorders.

PubMed

Li, Mi; Lu, Shengfu; Wang, Gang; Feng, Lei; Fu, Bingbing; Zhong, Ning

2016-06-01

To explore working memory and the ability to process different emotional stimuli in patients with first-onset and untreated minor (mild or moderate) depression. Patients with first-onset and previously untreated minor depression, and healthy controls, were enrolled. Using a modified Sternberg working memory paradigm to investigate the combined effects of emotional stimuli with working memory, participants were exposed to experimental stimuli comprising pictures that represented positive, neutral and negative emotions. Working memory ability was measured using reaction time and accuracy, and emotion-processing ability was measured using pupil diameter. Out of 36 participants (18 patients with minor depression and 18 controls), there were no statistically significant between-group differences in response time and accuracy. Positive stimuli evoked changes in pupil diameter that were significantly smaller in patients with minor depression versus controls, but changes in pupil diameter evoked by negative stimuli were not significantly different between the two groups. Healthy subjects showed a stronger emotional response to positive emotional stimuli than patients with first onset and previously untreated minor depression, but there were no differences in response to negative emotions. There were no statistically significant between-group differences in terms of speed of cognitive response, but this may have been due to the relatively small samples sizes assessed. Studies with larger sample populations are required to further investigate these results. © The Author(s) 2016.

Evaluation of electrocardiographic parameters in patients with diabetes insipidus.

PubMed

Deniz, Ferhat; Kepez, Alper; Ay, Seyit Ahmet; Ergogan, Okan; Baskoy, Kamil; Guncıkan, Mustafa Nuri; Dogan, Zekeriya; Yonem, Arif

2015-11-01

There is limited data regarding the effect of altered serum osmolality on cardiac electrical activity. The aim of the present study is to evaluate the electrocardiographic (ECG) effects of diabetes insipidus (DI) and any related hyperosmolality in a population of young patients with DI and without any known cardiovascular disease or risk factors. Twelve-lead ECG's of 44 consecutive untreated young male patients (age: 21.8 ± 2.9 years) who had been referred to endocrinology clinic and diagnosed as DI based on water deprivation test were retrospectively evaluated. A total of 30 age-matched (21.9 ± 2.4 years) healthy males were selected as control group and ECG's of these controls were obtained for comparison with ECG's of DI patients. All ECG parameters were measured and compared. Duration of QRS complex was significantly shorter in patients with DI compared with controls (85.2 ± 12.0 vs. 94.0 ± 10.6 ms, p: 0.001). P wave dispersion (PWD) of patients with DI was significantly higher compared with controls (31.9 ± 9.9 vs. 26.5 ± 10.6 ms, p: 0.03) and it was significantly correlated with serum osmolality and serum sodium level (r = - 0.36, p: 0.02 and r: - 0.35, p: 0.02, respectively). DI patients without any cardiovascular disease or risk factors displayed significantly shorter QRS duration and increased p wave dispersion compared with controls.

Acquired perforating dermatosis in a patient with Poland syndrome.

PubMed

Fistarol, Susanna K; Itin, Peter H

2003-01-01

Acquired perforating dermatosis (APD) is characterized by umbilicated 1- to 10-mm-measuring papulonodules with a central adherent oystershell-like keratotic plug, typically on the dorsa of the hands, forearms and over the knees. APD is associated with systemic diseases, especially diabetes mellitus and/or renal failure. Histologically the lesions show transepidermal elimination of altered dermal components into a cup-shaped epidermal depression. We present a 69-year-old man with coexisting APD and Poland syndrome (PS), an association not yet described. PS (OMIM 173800) is a rare congenital anomaly consisting of unilateral partial or total absence of the greater pectoralis muscle and ipsilateral symbrachydactyly. Most cases of PS are sporadic as it was in our case. Our patient had, in addition, an untreated diabetic condition, hyperuricaemia, dilated cardiomyopathy and a very recent pulmonary embolism. He responded to therapy with allopurinol. Copyright 2003 S. Karger AG, Basel

Decrease in toe pinch force in male type 2 diabetic patients with diabetic nephropathy.

PubMed

Kataoka, Hiroaki; Miyatake, Nobuyuki; Kitayama, Naomi; Murao, Satoshi; Tanaka, Satoshi

2018-06-01

The purpose of this cross-sectional study was to investigate the toe pinch force (TPF) of type 2 diabetic patients with diabetic nephropathy by disease stage, and to clarify the factors affecting the TPF. Seventy-four men with diabetic nephropathy (age: 62.7 ± 8.9 years, duration of diabetes: 14.2 ± 8.6 years) were enrolled. According to the staging of diabetic nephropathy, TPF and knee extension force (KEF) were compared among three groups: normoalbuminuria, microalbuminuria, and overt nephropathy. In addition, we investigated factors influencing TPF and KEF by performing multiple regression analysis. Normoalbuminuria group, microalbuminuria group, and overt nephropathy group included 26, 25, and 23 patients, respectively. The TPF of the overt nephropathy group (3.15 ± 0.75 kg) was significantly lower than that of the normoalbuminuria (4.2 ± 0.7 kg, p < 0.001) and microalbuminuria groups (3.65 ± 0.81 kg, p = 0.022). The KEF of the overt nephropathy group (37.1 ± 8.3 kgf) was significantly lower than that of the normoalbuminuria group (44.8 ± 8.3 kgf, p = 0.010). Multiple regression analysis revealed that diabetic polyneuropathy (DPN) and diabetic nephropathy were determinant factors of the TPF; and age, body mass index, and diabetic nephropathy were determinant factors of the KEF. We found in male patients with diabetic nephropathy, the TPF and KEF decreased with progression of diabetic nephropathy. Furthermore, our findings suggest diabetic nephropathy and DPN are critically involved in the reduction of TPF and KEF.

Diabetes disease management in Medicare Advantage reduces hospitalizations and costs.

PubMed

Rosenzweig, James L; Taitel, Michael S; Norman, Gordon K; Moore, Tim J; Turenne, Wendy; Tang, Pei

2010-07-01

To evaluate the effectiveness of a telephonic diabetes disease management intervention in a Medicare Advantage population with comorbid diabetes and coronary artery disease (CAD). Prospective unequal randomization design of 526 members from a Medicare Advantage segment of one region of a large national health plan from May 2005 through April 2007. High-risk and high-cost patients with diabetes and CAD who were enrolled in telephonic diabetes disease management were compared with a randomly selected comparison group receiving usual care. Wilcoxon signed-rank tests were used to compare the groups on all-cause hospital admissions, diabetes-related hospital admissions, all-cause and diabetes-related emergency department (ED) visits, and all-cause medical costs. Changes in self-reported clinical outcomes also were measured in the intervention group. Patients receiving telephonic diabetes disease management had significantly decreased all-cause hospital admissions and diabetes-related hospital admissions (P <.05). The intervention group had decreased all-cause and diabetes-related ED visits, although the difference was not statistically significant. The comparison group had increased ED utilization. The intervention group decreased their all-cause total medical costs by $984.87 per member per year (PMPY) compared with a $4547.06 PMPY increase in the comparison group (P <.05). All clinical measures significantly improved (P <.05) in the intervention group. A disease management program for high-risk patients with diabetes and CAD was effective in reducing hospital inpatient admission and total costs in a Medicare Advantage population.

Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model.

PubMed

Marques, T M; Patterson, E; Wall, R; O'Sullivan, O; Fitzgerald, G F; Cotter, P D; Dinan, T G; Cryan, J F; Ross, R P; Stanton, C

2016-06-01

The aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~10(9)microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~10(9) L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P<0.05), but did not alter other metabolic markers in healthy rats. Diabetes induced by STZ injection decreased body weight (P<0.05), increased intestinal length (P<0.05) and stimulated water and food intake. Insulin was decreased (P<0.05), whereas glucose was increased (P<0.001) in all diabetic groups, compared with non-diabetic controls. A decrease (P<0.01) in glucose levels was observed in diabetic rats receiving L. brevis DPC 6108, compared with diabetic-controls. Both the composition and diversity of the intestinal microbiota were affected by diabetes. Microbial diversity in diabetic rats supplemented with low GABA was not reduced (P>0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.

Vibration perception threshold for sight-threatening retinopathy screening in type 2 diabetic outpatients.

PubMed

Shen, Jing; Hu, Yanyun; Liu, Fang; Zeng, Hui; Li, Lianxi; Zhao, Jun; Zhao, Jungong; Zheng, Taishan; Lu, Huijuan; Lu, Fengdi; Bao, Yuqian; Jia, Weiping

2013-10-01

We investigated the relationship between vibration perception threshold and diabetic retinopathy and verified the screening value of vibration perception threshold for severe diabetic retinopathy. A total of 955 patients with type 2 diabetes were recruited and divided into three groups according to their fundus oculi photography results: no diabetic retinopathy (n = 654, 68.48%), non-sight-threatening diabetic retinopathy (n = 189, 19.79%) and sight-threatening diabetic retinopathy (n = 112, 11.73%). Their clinical and biochemical characteristics, vibration perception threshold and the diabetic retinopathy grades were detected and compared. There were significant differences in diabetes duration and blood glucose levels among three groups (all p < 0.05). The values of vibration perception threshold increased with the rising severity of retinopathy, and the vibration perception threshold level of sight-threatening diabetic retinopathy group was significantly higher than both non-sight-threatening diabetic retinopathy and no diabetic retinopathy groups (both p < 0.01). The prevalence of sight-threatening diabetic retinopathy in vibration perception threshold >25 V group was significantly higher than those in 16-24 V group (p < 0.01). The severity of diabetic retinopathy was positively associated with diabetes duration, blood glucose indexes and vibration perception threshold (all p < 0.01). Multiple stepwise regression analysis proved that glycosylated haemoglobin (β = 0.385, p = 0.000), diabetes duration (β = 0.275, p = 0.000) and vibration perception threshold (β = 0.180, p = 0.015) were independent risk factors for diabetic retinopathy. Receiver operating characteristic analysis further revealed that vibration perception threshold higher than 18 V was the optimal cut point for reflecting high risk of sight-threatening diabetic retinopathy (odds ratio = 4.20, 95% confidence interval = 2.67-6.59). There was a close association between vibration perception threshold and the severity of diabetic retinopathy. vibration perception threshold was a potential screening method for diabetic retinopathy, and its optimal cut-off for prompting high risk of sight-threatening retinopathy was 18 V. Copyright © 2013 John Wiley & Sons, Ltd.

Estimation of salivary glucose, salivary amylase, salivary total protein and salivary flow rate in diabetics in India.

PubMed

Panchbhai, Arati S; Degwekar, Shirish S; Bhowte, Rahul R

2010-09-01

Diabetes is known to influence salivary composition and function, eventually affecting the oral cavity. We thus evaluated saliva samples for levels of glucose, amylase and total protein, and assessed salivary flow rate in diabetics and healthy non-diabetics. We also analyzed these parameters with regard to duration and type of diabetes mellitus and gender, and aimed to assess the interrelationships among the variables included in the study. A total of 120 age- and sex-matched participants were divided into 3 groups of 40 each; the uncontrolled diabetic group, the controlled diabetic group and the healthy non-diabetic group. Salivary investigations were performed using unstimulated whole saliva. Mean salivary glucose levels were found to be significantly elevated in both uncontrolled and controlled diabetics, as compared to healthy non-diabetics. There were significant decreases in mean salivary amylase levels in controlled diabetics when compared to healthy non-diabetics. Other than salivary glucose, no other parameters were found to be markedly affected in diabetes mellitus. Further research is needed to explore the clinical implications of these study results.

Population-based cohort study investigating the correlation of diabetes mellitus with pleural empyema in adults in Taiwan.

PubMed

Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

2017-09-01

We assessed the association between diabetes mellitus and the risk of pleural empyema in Taiwan.A population-based retrospective cohort study was conducted using the database of the Taiwan National Health Insurance Program. There were 28,802 subjects aged 20 to 84 years who were newly diagnosed with diabetes mellitus from 2000 to 2010 as the diabetes group and 114,916 randomly selected subjects without diabetes mellitus as the non-diabetes group. The diabetes group and the non-diabetes group were matched by sex, age, comorbidities, and the year of index date. The incidence of pleural empyema at the end of 2011 was estimated. A multivariable Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for pleural empyema associated with diabetes mellitus.The overall incidence of pleural empyema was 1.65-fold higher in the diabetes group than that in the non-diabetes group (1.58 vs 0.96 per 10,000 person-years, 95% CI 1.57-1.72). After adjusting for confounders, a multivariable Cox proportional hazards regression model revealed that the adjusted HR of pleural empyema was 1.71 in subjects with diabetes mellitus (95% CI 1.16-2.51), compared with those without diabetes mellitus. In further analysis, even in the absence of any comorbidity, the adjusted HR was 1.99 for subjects with diabetes mellitus alone (95% CI 1.18-3.38).Diabetic patients confer a 1.71-fold increased hazard of developing pleural empyema. Even in the absence of any comorbidity, the risk remains existent.

No significant differences in short-term renal prognosis between living kidney donors with and without diabetes.

PubMed

Shinzato, Takahiro; Kurosawa, Akira; Kubo, Taro; Shimizu, Toshihiro; Kimura, Takaaki; Nanmoku, Koji; Yagisawa, Takashi

2018-06-01

Renal prognosis in living kidney donors with diabetes is currently not known. In this study, we sought to investigate renal prognosis in living kidney donors with diabetes. We retrospectively investigated 241 living kidney donors who underwent nephrectomy at Jichi Medical University Hospital between January 2000 and December 2015. Donors with a follow-up period of less than 1 year were excluded. The remaining donors were divided into a diabetic group and a non-diabetic group. Their clinical parameters before donation and renal prognosis after donation were compared. Of the 241 donors, 16 were excluded due to their follow-up period being less than 1 year. Of the remaining 225 donors, 14 were diabetic and 211 were non-diabetic. There were no significant differences in variables at pre-donation. The median follow-up period was 4.3 (1.5-10.7) and 4.6 (1.0-13.0) years in kidney donors with and without diabetes, respectively. At the end of follow-up, the estimated glomerular filtration rate was 51.7 ± 7.1 ml/min/1.73 m 2 in the diabetic group and 52.1 ± 12.2 ml/min/1.73 m 2 (p = 0.906) in the non-diabetic group; urine albumin excretion was 9.5 (2-251) mg/day (or mg/g creatinine) in the diabetic group and 6 (0-626) mg/day (or mg/g creatinine) in the non-diabetic group (p = 0.130); and urine protein excretion was 0.079 (0-0.41) g/day in the diabetic group and 0.051 (0-3.7) g/day in the non-diabetic group (p = 0.455). There were no significant differences in short-term renal prognosis between kidney donors with and without diabetes.

Effect of hyperlipidemia on the incidence of cardio-cerebrovascular events in patients with type 2 diabetes.

PubMed

Fan, Dabei; Li, Li; Li, Zhizhen; Zhang, Ying; Ma, Xiaojun; Wu, Lina; Qin, Guijun

2018-05-08

This study was to explore the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes. Three hundred ninety five patients with type 2 diabetes in our hospital from January 2012 to January 2016 were followed up with an average of 3.8 years. The incidence of cardio-cerebrovascular diseases between diabetes combined with hyperlipidemia group (195 patients) and diabetes group (200 patients) were made a comparison. Multivariable Cox's proportional hazards regression model was used to analyze the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes. Diastolic blood pressure, systolic blood pressure, high-density lipoprotein, low-density lipoprotein, body mass index and hyper-sensitive C-reactive protein were higher in diabetes combined with hyperlipidemia group than in diabetes group (P < 0.05). At the end of the follow-up period, all-cause mortality, cardio-cerebrovascular diseases mortality, and the incidence of myocardial infarction, cerebral infarction, cerebral hemorrhage and total cardiovascular events were significantly higher in diabetes combined with hyperlipidemia group than in diabetes group (P < 0.05). The analysis results of multivariable Cox's proportional hazards regression model showed that the risks of myocardial infarction and total cardiovascular events in diabetes combined with hyperlipidemia group were respectively 1.54 times (95%CI 1.13-2.07) and 1.68 times (95%CI 1.23-2.24) higher than those in diabetes group. Population attributable risk percent of all-cause mortality and total cardiovascular events in patients with type 2 diabetes combined with hyperlipidemia was 9.6% and 26.8%, respectively. Hyperlipidemia may promote vascular endothelial injury, increasing the risk of cardio-cerebrovascular diseases in patients with type 2 diabetes. Medical staffs should pay attention to the control of blood lipids in patients with type 2 diabetes to delay the occurrence of cardio-cerebrovascular diseases.

Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis.

PubMed

Lupi, Isabella; Cosottini, Mirco; Caturegli, Patrizio; Manetti, Luca; Urbani, Claudio; Cappellani, Daniele; Scattina, Ilaria; Martino, Enio; Marcocci, Claudio; Bogazzi, Fausto

2017-08-01

Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. To identify clinical and radiological findings associated with response to glucocorticoids. 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis ( n  = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis ( n  = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P  = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P  = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients ( P  = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced ( P  = 0.008) but diabetes insipidus persisted in all. Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids. © 2017 European Society of Endocrinology.

PSYCHOSOCIAL PROFILE OF JUVENILE DIABETES

PubMed Central

Dass, Jyoti; Dhavale, H.S.; Rathi, Anup

1999-01-01

A study of the complex relationships between the patient characteristics, family and environmental influences, physician's behaviour and the demands of the disease with its management in Juvenile Diabetics was taken up at a general hospital. 90 subjects were selected for the study and grouped into three. Group A consisted of 30 Juvenile Diabetics, Group B of 30 Adult Diabetics and Group C of 30 Normal healthy adolescents. The impact of the illness was measured on the Diabetes Impact Measurement Scale (DIMS), the behavioural deviations and the parental attitudes towards child rearing on the Fallstrom's Questionnaire (FQ) and the family environment on the Family Climate Scale (FCS). Psychiatric morbidity was assessed using DSM-IV criteria. Group A & B were compared on the DIMS and Group A & C on FQ & FCS. Adult diabetics had a greater impact of diabetes. Juvenile diabetics had significantly higher frequency of behavioural deviations as compared to controls. Also there was a higher number of responses on questions indicating an overprotecting attitude amongst parents of juvenile diabetics. There was an increased incidence of psychiatric morbidity in juvenile diabetics as compared to normal adolescents irrespective of the family environment. The results are discussed in relation to current literature. PMID:21430802

An exploration of knowledge and attitudes related to pre-pregnancy care in women with diabetes.

PubMed

Spence, M; Alderdice, F A; Harper, R; McCance, D R; Holmes, V A

2010-12-01

Pre-pregnancy care optimizes pregnancy outcome in women with pre-gestational diabetes, yet most women enter pregnancy unprepared. We sought to determine knowledge and attitudes of women with Type 1 and Type 2 diabetes of childbearing age towards pre-pregnancy care. Twenty-four women (18 with Type 1 diabetes and six with Type 2 diabetes) aged 17-40 years took part in one of four focus group sessions: young nulliparous women with Type 1 diabetes (Group A), older nulliparous women with Type 1 diabetes (Group B), parous women with Type 1 diabetes (Group C) and women with Type 2 diabetes of mixed parity (Group D). Content analysis of transcribed focus groups revealed that, while women were well informed about the need to plan pregnancy, awareness of the rationale for planning was only evident in parous women or those who had actively sought pre-pregnancy advice. Within each group, there was uncertainty about what pre-pregnancy advice entailed. Despite many women reporting positive healthcare experiences, frequently cited barriers to discussing issues around family planning included unsupportive staff, busy clinics and perceived social stereotypes held by health professionals. Knowledge and attitudes reported in this study highlight the need for women with diabetes, regardless of age, marital status or type of diabetes, to receive guidance about planning pregnancy in a motivating, positive and supportive manner. The important patient viewpoints expressed in this study may help health professionals determine how best to encourage women to avail of pre-pregnancy care. © 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.

Dental caries among children visiting a mobile dental clinic in South Central Kentucky: a pooled cross-sectional study

PubMed Central

2013-01-01

Background Dental caries is one of the most common chronic childhood diseases affecting a large portion of children in the United States. The prevalence of childhood dental caries in Kentucky is among the highest in the nation. The purposes of this study are to (1) compare sociodemographic differences between caries and no caries groups and (2) investigate factors associated with untreated dental caries among children who visited a mobile dental clinic in South Central Kentucky. Methods Study subjects were children aged 6 to 15 years who participated in the school-based dental sealant program through the mobile dental clinic operated by the Institute for Rural Health at Western Kentucky University between September 2006 and May 2011 (n = 2,453). Descriptive statistics were calculated for sociodemographic factors (age, gender, race/ethnicity, insurance status, and urban versus rural residential location) and caries status. We used chi-square tests to compare sociodemographic differences of children stratified by caries and no caries status as well as three levels of caries severity. We developed a logistic regression model to investigate factors associated with untreated dental caries while controlling for sociodemographic characteristics. Results The proportion of children having untreated dental caries was 49.7% and the mean number of untreated dental caries was 2.0. The proportion of untreated dental caries was higher in older children, children with no insurance and living in rural residential locations, and caries severity was also higher in these groups. Odds ratio indicated that older ages, not having private insurance (having only public, government-sponsored insurance or no insurance at all) and rural residential location were associated with having untreated dental caries after controlling for sociodemographic characteristics of children. Conclusions Untreated dental caries was more likely to be present in older children living in rural areas without insurance. Health interventionists may use this information and target rural children without having proper insurance in order to reduce geographic disparities in untreated dental caries in South Central Kentucky. PMID:23639250

Diabetes-Related Distress Assessment among Type 2 Diabetes Patients.

PubMed

Aljuaid, Majed O; Almutairi, Abdulmajeed M; Assiri, Mohammed A; Almalki, Dhifallah M; Alswat, Khaled

2018-01-01

Diabetes is one of the most common chronic diseases; it is a debilitating and hard to live with. Diabetes-related distress (DRD) refers to the emotional and behavioral changes caused by diabetes. Our study aims to assess the prevalence of DRD among type 2 diabetes (T2D) patients using Diabetes Distress Scale-17 items (DDS-17) and its relation to complications and treatment modalities. A cross-sectional study of adult T2D patients with follow-up visits at the Diabetes and Endocrinology Center in Taif, Saudi Arabia, between January and July 2017. We excluded patients with other forms of diabetes, untreated hypothyroidism, and psychiatric illness. The total score of DDS-17 was calculated by summing the 17 items' results and then dividing the total by 17. If the total score was >2, then it was considered as clinically significant results (moderate distress), but if it is ≥3, then it is classified as a high distress. A total of 509 T2D patients with a mean age of 58 ± 14 years were included. The majority of participants were male, married, not college educated, and reported a sedentary lifestyle. We found 25% of the screened T2D patients have moderate to high DRD. Regarding the DRD components, emotional distress was the most prevalent followed by physician-related distress. HabA1c was significantly higher in those with high combined distress and high emotional distress compared to those with mild/moderate distress ( p = 0.015 and 0.030, resp.). Our study shows that DRD is a medically relevant issue that clinicians need to address. Despite observing a low prevalence of DRD compared to other studies, we found significant correlations between DRD scores and HabA1c, triglyceride levels, BMI, T2D duration, and interval between visits.

Delivery of integrated diabetes care using logistics and information technology--the Joint Asia Diabetes Evaluation (JADE) program.

PubMed

Chan, Juliana C N; Ozaki, Risa; Luk, Andrea; Kong, Alice P S; Ma, Ronald C W; Chow, Francis C C; Wong, Patrick; Wong, Rebecca; Chung, Harriet; Chiu, Cherry; Wolthers, Troels; Tong, Peter C Y; Ko, Gary T C; So, Wing-Yee; Lyubomirsky, Greg

2014-12-01

Diabetes is a global epidemic, and many affected individuals are undiagnosed, untreated, or uncontrolled. The silent and multi-system nature of diabetes and its complications, with complex care protocols, are often associated with omission of periodic assessments, clinical inertia, poor treatment compliance, and care fragmentation. These barriers at the system, patient, and care-provider levels have resulted in poor control of risk factors and under-usage of potentially life-saving medications such as statins and renin-angiotensin system inhibitors. However, in the clinical trial setting, use of nurses and protocol with frequent contact and regular monitoring have resulted in marked differences in event rates compared to epidemiological data collected in the real-world setting. The phenotypic heterogeneity and cognitive-psychological-behavioral needs of people with diabetes call for regular risk stratification to personalize care. Quality improvement initiatives targeted at patient education, task delegation, case management, and self-care promotion had the largest effect size in improving cardio-metabolic risk factors. The Joint Asia Diabetes Evaluation (JADE) program is an innovative care prototype that advocates a change in clinic setting and workflow, coordinated by a doctor-nurse team and augmented by a web-based portal, which incorporates care protocols and a validated risk engine to provide decision support and regular feedback. By using logistics and information technology, supported by a network of health-care professionals to provide integrated, holistic, and evidence-based care, the JADE Program aims to establish a high-quality regional diabetes database to reflect the status of diabetes care in real-world practice, confirm efficacy data, and identify unmet needs. Through collaborative efforts, we shall evaluate the feasibility, acceptability, and cost-effectiveness of this "high tech, soft touch" model to make diabetes and chronic disease care more accessible, affordable, and sustainable. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Possible mechanism of protective effect of thalidomide in STZ-induced-neuropathic pain behavior in rats.

PubMed

Taliyan, Rajeev; Sharma, Pyare Lal

2012-04-01

Diabetes-induced neuropathic pain is recognized as one of the most difficult type of pain to treat and conventional analgesics are well known to be partially effective or associated with potential toxicity. Recently, it has been demonstrated that thalidomide, besides its teratogenic potential, reduced chronic pain in an SNL experimental pain model. The present study was designed to investigate the effect of thalidomide on streptozotocin (STZ)-induced neuropathic pain in rats. Streptozotocin (20 mg/kg, i.p, daily × 4 days) was administered to induce diabetes in the rats. Nociceptive latency was measured using tail-flick and paw-withdrawal test. Thermal hyperalgesia and mechanical allodynia were measured using planter test and dynamic aesthesiometer (Ugo-Basile, Italy), respectively. Urinary and serum nitrite concentration was estimated using Greiss reagent method. Spleen homogenate supernatant was prepared from spleen of 28th day diabetic rats and administered to normal rats (400 ul, i.v) daily for 28 days. Pain threshold progressively decreased in STZ-treated rats, as compared with control rats. 3 weeks after induction of diabetes, the rat exhibited thermal hyperalgesia and mechanical allodynia. The analgesic effect of morphine (8 mg/kg, s.c.) was significantly decreased in both diabetic and in SHS-treated non-diabetic rats. Administration of thalidomide (25 and 50 mg/kg, i.p), a TNF-α inhibitor, significantly prevented hyperglycemia-induced thermal hyperalgesia and mechanical allodynia and also attenuated the increase in serum and urinary nitrite concentration, as compared with untreated diabetic rats. Also, thalidomide (25 and 50 mg/kg, i.p) 1 h before or concurrently with morphine significantly restored the analgesic effect of morphine in diabetic rats. It may be concluded that thalidomide has a beneficial effect in neuropathic pain by decreasing cytokines (TNF-α) and nitric oxide level and may provide a novel promising therapeutic approach for managing painful diabetic neuropathy.

Gestational diabetes history may signal deprivation in women with type 2 diabetes.

PubMed

Lega, Iliana; Ross, Nancy Annette; Zhong, Lihong; Dasgupta, Kaberi

2011-04-01

There is a higher prevalence of type 2 diabetes in lower income groups, particularly in women. Gestational diabetes (diabetes during pregnancy) has also been associated with lower income levels. What has not been studied is whether a past history of gestational diabetes retains an inverse association with income among women with type 2 diabetes. Among women with type 2 diabetes, we assessed for an association between history of gestational diabetes and lower income/lower educational attainment (multiple waves of Canadian Community Health Survey [CCHS]) through logistic regression models adjusted for age, body mass index (BMI), immigrant and marital status, smoking history, and physical activity. Compared to women in the highest income group, a gestational diabetes history was 71% more likely in the lower middle income group (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.06-2.74) and nearly two times more likely in the lowest income group (OR 1.94, 95% CI 1.15-3.27). Associations with education were inconclusive. Compared to married women, single women (divorced/separated/never married) were nearly two times more likely to have a gestational diabetes history (OR 1.71, 95% CI 1.17-2.49). These findings indicate that women with diabetes and past history of gestational diabetes constitute a particularly deprived group. A gestational diabetes history in women with type 2 diabetes may signal a need to assess and address material resources and social support as part of the diabetes management plan.

Microvascular diabetes complications in Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness [DIDMOAD]): an age- and duration-matched comparison with common type 1 diabetes.

PubMed

Cano, Aline; Molines, Laurent; Valéro, René; Simonin, Gilbert; Paquis-Flucklinger, Véronique; Vialettes, Bernard

2007-09-01

Some previous studies suggested that patients suffering from Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) might be relatively preserved from diabetic retinopathy and nephropathy. However, these data were not conclusive because either observations were only anecdotic or did not match with control type 1 diabetic populations. A group of 26 French diabetic patients with DIDMOAD was compared with a population of 52 patients with common type 1 diabetes matched for age at diabetes diagnosis (8.62 +/- 1.84 vs. 8.27 +/- 1.30 years; P = NS) and diabetes duration (12.88 +/- 1.58 vs. 12.87 +/- 1.13 years; P = NS) to study the quality of glycemic control and the incidence of microvascular complications. Glycemic control was significantly better in the DIDMOAD group than in the type 1 diabetic group (A1C: 7.72 +/- 0.21 vs. 8.99 +/- 0.25%, respectively; P = 0.002), with significant lower daily insulin requirements (0.71 +/- 0.07 vs. 0.88 +/- 0.04 UI x kg(-1) x day(-1), respectively; P = 0.0325). The prevalence of microvascular complications in the DIDMOAD group was half that observed in the type 1 diabetic group, but the difference was not significant. Diabetes in DIDMOAD patients is more easily controlled despite the presence of other handicaps. This better glycemic control could explain the trend to decreased microvascular diabetes complications observed in previous studies.

Disparities in untreated caries among children and adults in the U.S., 2011-2014.

PubMed

Gupta, Niodita; Vujicic, Marko; Yarbrough, Cassandra; Harrison, Brittany

2018-03-06

The Affordable Care Act of 2010 increased dental coverage for children in the United States, (U.S.) but not for adults. Few studies in current scholarship make use of up-to-date, nationally representative data to examine oral health disparities in the U.S. The purpose of this study is to use nationally representative data to determine the prevalence of untreated caries among children and adults of different socioeconomic and racial/ethnic groups and to examine the factors associated with untreated caries among children and adults. This study used the 2011-2014 National Health and Nutrition Examination Survey (NHANES) demographic, oral health questionnaire, and oral health dentition examination data (n = 7008 for children; n = 9673 for adults). Participants that had a standardized oral health examination and at least one natural primary or permanent tooth considering 28 tooth spaces were included in this study. Our main outcome measure was untreated coronal caries defined as decay on the crown or enamel surface of a tooth that had not been treated or filled. Population estimates were calculated to determine the prevalence of untreated caries among children and adults in the United States. Frequencies and Pearson's chi-square tests were used to compare those with and without untreated caries. Multivariate logistic regression models were used to evaluate the factors associated with untreated caries. We conducted analyses among children and adults separately. From 2011 to 2014, 12.4 million children and 57.6 million adults in the United States had untreated caries. Age, family income level, recent dental visit, and financial and non-financial barriers were significantly associated with untreated caries in both children and adults. Race/ethnicity, gender and education level were also significantly associated with untreated caries among adults. The odds of untreated caries associated with financial barriers were 2.06 for children and 2.84 for adults while the odds of untreated caries associated with non-financial barriers were 2.86 for children and 1.67 for adults. Demographic and socio-economic disparities in untreated caries exist among children and adults.

Auditory Temporal Resolution in Individuals with Diabetes Mellitus Type 2.

PubMed

Mishra, Rajkishor; Sanju, Himanshu Kumar; Kumar, Prawin

2016-10-01

Introduction  "Diabetes mellitus is a group of metabolic disorders characterized by elevated blood sugar and abnormalities in insulin secretion and action" (American Diabetes Association). Previous literature has reported connection between diabetes mellitus and hearing impairment. There is a dearth of literature on auditory temporal resolution ability in individuals with diabetes mellitus type 2. Objective  The main objective of the present study was to assess auditory temporal resolution ability through GDT (Gap Detection Threshold) in individuals with diabetes mellitus type 2 with high frequency hearing loss. Methods  Fifteen subjects with diabetes mellitus type 2 with high frequency hearing loss in the age range of 30 to 40 years participated in the study as the experimental group. Fifteen age-matched non-diabetic individuals with normal hearing served as the control group. We administered the Gap Detection Threshold (GDT) test to all participants to assess their temporal resolution ability. Result  We used the independent t -test to compare between groups. Results showed that the diabetic group (experimental) performed significantly poorer compared with the non-diabetic group (control). Conclusion  It is possible to conclude that widening of auditory filters and changes in the central auditory nervous system contributed to poorer performance for temporal resolution task (Gap Detection Threshold) in individuals with diabetes mellitus type 2. Findings of the present study revealed the deteriorating effect of diabetes mellitus type 2 at the central auditory processing level.

The impact of magnesium on isometric twitch parameters and resting membrane potential of the skeletal muscle in diabetic rats.

PubMed

Pelit, Aykut; Emre, Mustafa; Dağli, Kenan; Tuli, Abdullah

2013-04-01

To present the relationship between oral magnesium supplementation, blood glucose, and changes in isometric twitch parameters, resting membrane potential (RMP), in the gastrocnemius muscle in diabetic rats. Sixty rats were used in this study. The rats were divided into four groups: control (drinking tap water, Group I, n = 15), control with treated with magnesium sulfate (10 g/L) (Group II, n = 15), diabetic (Group III, n = 15), and diabetic with treated with magnesium sulfate (10 g/L) (Group IV, n = 15). In Group II and IV, the level of plasma magnesium was increased comparing to those of the control group (p < 0.05). Isometric twitch tensions were decreased significantly in the Group III, but Group IV isometric twitch tensions were increased significantly. Group IV RMP values were close to the Group I. Hyperglycemia decreases gastrocnemius muscle isometric twitch tension and increases RMP in diabetic rats. Magnesium treatment can prevent these diabetic complications.

Furan induced ovarian damage in non-diabetic and diabetic rats and cellular protective role of lycopene.

PubMed

Uçar, Semra; Pandir, Dilek

2017-11-01

In our work, furan, lycopene, and furan + lycopene treatments were applied to non-diabetic and diabetic female rats via gavage. Ovarian tissue alterations with histopathology, immunohistochemistry, malondialdehyde levels, oxidative stress parameters such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and harmful effect on ovarian tissue DNA were evaluated in all groups for 28 days. Furan caused the changes histological, ovarian cell's DNA structure, malondialdehyde levels, antioxidant enzymes activities as in a statistically significant manner in each group. Useful effect of lycopene was determined both in non-diabetic and diabetic treatment groups against furan according to the used experimental parameters. Although some histopathological alterations were seen in diabetic and non-diabetic/diabetic plus furan-treated group's ovarians, lycopene restored these variations near to normal levels in furan + lycopene treated groups for in 28 days. Additionally, the results of our immunohistochemical analysis and alterations of the oxidative stress parameters results also supported these findings. Our result confirms that lycopene has protective effect and significantly altered diabetes and furan-induced toxicity in the rat ovarian tissue.

Effect of zinc supplementation on lipid peroxidation and lactate levels in rats with diabetes induced by streptozotocin and subjected to acute swimming exercise.

PubMed

Bicer, M; Gunay, M; Baltaci, A K; Uney, K; Mogulkoc, R; Akil, M

2012-01-01

The present study aims to explore the effect of zinc supplementation on lipid peroxidation and lactate levels in rats having diabetes induced by streptozotocin and subjected to acute swimming exercise. A total of 80 adult male rats of Sprague-Dawley type were equally allocated to 8 groups: Group 1, general control. Group 2, zinc-supplemented group. Group 3, zinc-supplemented, diabetic group. Group 4, swimming control group. Group 5, zinc-supplemented swimming group. Group 6, zinc-supplemented diabetic swimming group. Group 7, diabetic swimming group. Group 8, diabetic group. At the end of the 4-week study, blood samples were collected to determine MDA, GSH, GPx, SOD, lactate and zinc levels. The highest MDA values were found in group 7 and 8 (p<0.001). GSH values in groups 5 and 6 were higher (p<0.001). The highest GPx values were established in groups 2, 5 and 6 (p<0.001). SOD values were the highest in groups 5 and 6 (p<0.001) and lowest in groups 2, 3 and 8 (p<0.001). The highest plasma lactate levels were found in group 7 (p<0.001). The highest zinc levels were obtained in groups 1, 2 and 5 (p<0.001), and the lowest zinc levels were found in groups 7 and 8 (p<0.001). Results of the study reveal that zinc supplementation prevents the increase of free radical formation, suppression of antioxidant activity and muscle exhaustion, all of which result from diabetes and acute exercise. Zinc supplementation may contribute to health performance in diabetes and acute exercise (Tab. 2, Fig. 1 Ref. 47). Full Text in PDF www.elis.sk.

The protective effects of silibinin in the treatment of streptozotocin-induced diabetic osteoporosis in rats.

PubMed

Wang, Te; Cai, Leyi; Wang, Yangyang; Wang, Qingqing; Lu, Di; Chen, Hua; Ying, Xiaozhou

2017-05-01

Diabetic osteoporosis (DO) is a complication of diabetes mellitus. Our previous study showed that silibinin can attenuate high glucose mediated human bone marrow stem cells dysfunction through antioxidant effect. However, no study has yet investigated the effect of silibinin in diabetic rats. Therefore, we assessed the effects of silibinin on bone characteristics in streptozotocin-induced diabetic rats. The aim of our study was to determine whether providing silibinin in the different supplementation could prevent bone loss in diabetic rats or not. Rats were randomly divided into four groups: (1) control group (CG) (n=10); (2) diabetic group (DG) (n=10); (3) diabetic group with 50mgkg -1 day -1 of silibinin orally (DG-50) (n=10); and (4) diabetic group with 100mgkg -1 day -1 of silibinin orally (DG-100) (n=10). 12 weeks after streptozotocin (STZ) injection, the femora from all rats were assessed and oxidative stress was evaluated. Bone mineral density was significantly decreased in diabetic rats; these effects were prevented by treatment with silibinin (100mgkg -1 day -1 orally). Similarly, in the DG and DG-50 groups, changes in microarchitecture of femoral metaphysis assessed by microcomputed tomography demonstrated simultaneous existence of diabetic osteoporosis; these impairments were prevented by silibinin (100mgkg -1 day -1 orally). In conclusion, silibinin supplementation may have potential use as a possible therapy for maintaining skeletal health and these results can enhance the understanding of diabetic osteoporosis induced by diabetes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

An Investigation of the Neurological and Neuropsychiatric Disturbances in Adults with Undiagnosed and/or Untreated Phenylketonuria in Poland

ERIC Educational Resources Information Center

Mazur, Artur; Jarochowicz, Sabina; Oltarzewski, Mariusz; Sykut-Cegielska, Jolanta; Gradowska, Wanda; Januszek-Trzciakowska, Aleksandra; O'Malley, Grace; Kwolek, Andrzej

2011-01-01

Background: The aim of the study was to determine neurological and neuropsychiatric manifestations in a group of patients with previously undiagnosed or untreated phenylketonuria (PKU) in the south-eastern part of Poland. Methods: The study was conducted among 400 adults with severe intellectual disability who were born prior to neonatal screening…

Generalized Difference in Differences with Panel Data and Least Squares Estimator

ERIC Educational Resources Information Center

Lee, Myoung-jae

2016-01-01

With one treated and one untreated periods, difference in differences (DD) requires the untreated response changes to be the same across the treatment and control groups, if the treatment were withheld contrary to the fact. A natural way to check the condition is to backtrack one period and examine the response changes in two pretreatment periods.…

Effectiveness of a group psychoeducation program for the treatment of subclinical disordered eating in women with type 1 diabetes.

PubMed

Alloway, S C; Toth, E L; McCargar, L J

2001-01-01

The coexistence of type 1 diabetes mellitus and disordered eating is associated with poor metabolic control, poor adherence to diabetes treatment regimens, and increased risk of long-term diabetic complications. This study assessed whether a six-session group psychoeducation program would improve metabolic control, diabetes treatment adherence, eating disorder symptomatology, and general psychopathology in women with coexisting type 1 diabetes and subclinical disordered eating. Fourteen women were assigned to the treatment group (n=8) or wait-list control group (n=6). Measurements were taken at baseline, post-intervention, and one month post-intervention. There were no significant differences in how the treatment group and wait-list control group changed over time. Between the first and second measurements, both groups demonstrated significant improvements in depression and general emotional distress. The results suggest that a six-session group psychoeducation program is no more effective than a wait-list control group for treating subclinical disordered eating in women with type 1 diabetes. Further research is required to determine the most effective treatment for this population.

Effect of captopril treatment on total and central vascular capacitance in dogs with chronic heart failure.

PubMed

Ogilvie, R I; Zborowska-Sluis, D

1994-09-01

Chronic rapid right ventricular pacing (RRVP) at 250 beats/min produces low cardiac output (CO) heart failure, marked reduction in total vascular capacitance, and a shift in volume centrally. The effect of converting enzyme inhibition with captopril on cardiac preload was investigated in this model of heart failure. Eight splenectomized dogs were treated with captopril (6.4 mg/kg daily) for 3 days before and 35 +/- 3 days (mean +/- SEM) after continuous RRVP was initiated and the outcome was compared with that of 5 untreated dogs subjected to RRVP for 32 +/- 3 days. Similar reductions in systemic arterial pressure (Psa) and CO and increases in right atrial pressure (Pra) and total peripheral resistance (TPR) were noted in both groups, however, pulmonary capillary wedge pressure (Ppcw) was higher in the untreated group (18.4 +/- 1.6 vs. 12.1 +/- 2.0 mm Hg). Total vascular compliance and capacitance was estimated from mean circulatory filling pressures (Pmcf) at different blood volumes (TBV) during transitory cardiac arrests with acetylcholine (ACh). Pmcf after chronic RRVP was higher in untreated animals (12.6 +/- 1.9 vs. 8.4 +/- 0.7 mm Hg) and compliance was lower (1.9 +/- 0.2 vs. 2.6 +/- 0.2 ml/mm Hg/kg). Total vascular capacitance at a Pmcf of 6 mm Hg was lower in untreated animals (50 +/- 6 vs. 68 +/- 3 ml/kg). Central vascular capacitance was also lower in untreated animals because Ppcw was higher and central blood volume (CBV) as a proportion of TBV was higher (21 +/- 3 vs. 15 +/- 2%). Four of 5 untreated and 1 of 8 treated dogs had severe ascites.(ABSTRACT TRUNCATED AT 250 WORDS)

The Efficacy of Gelam Honey Dressing towards Excisional Wound Healing

PubMed Central

Tan, Mui Koon; Hasan Adli, Durriyyah Sharifah; Tumiran, Mohd Amzari; Abdulla, Mahmood Ameen; Yusoff, Kamaruddin Mohd

2012-01-01

Honey is one of the oldest substances used in wound management. Efficacy of Gelam honey in wound healing was evaluated in this paper. Sprague-Dawley rats were randomly divided into four groups of 24 rats each (untreated group, saline group, Intrasite Gel group, and Gelam honey group) with 2 cm by 2 cm full thickness, excisional wound created on neck area. Wounds were dressed topically according to groups. Rats were sacrificed on days 1, 5, 10, and 15 of treatments. Wounds were then processed for macroscopic and histological observations. Gelam-honey-dressed wounds healed earlier (day 13) than untreated and saline treated groups, as did wounds treated with Intrasite Gel. Honey-treated wounds exhibited less scab and only thin scar formations. Histological features demonstrated positive effects of Gelam honey on the wounds. This paper showed that Gelam honey dressing on excisional wound accelerated the process of wound healing. PMID:22536292

40 CFR 798.2650 - Oral toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If... vehicle control groups are required. (3) Satellite group. (Rodent) A satellite group of 20 animals (10...

40 CFR 798.2650 - Oral toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If... vehicle control groups are required. (3) Satellite group. (Rodent) A satellite group of 20 animals (10...

40 CFR 798.2650 - Oral toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If... vehicle control groups are required. (3) Satellite group. (Rodent) A satellite group of 20 animals (10...

40 CFR 798.2650 - Oral toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If... vehicle control groups are required. (3) Satellite group. (Rodent) A satellite group of 20 animals (10...

40 CFR 798.2650 - Oral toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group or, if a vehicle is used in administering the test substance, a vehicle control group. If... vehicle control groups are required. (3) Satellite group. (Rodent) A satellite group of 20 animals (10...

N-terminal pro-brain natriuretic peptide levels and abnormal geometric patterns of left ventricle in untreated hypertensive patients.

PubMed

Elbasan, Zafer; Gür, Mustafa; Sahin, Durmuş Yıldıray; Kırım, Sinan; Akyol, Selahattin; Kuloğlu, Osman; Koyunsever, Nermin Yıldız; Seker, Taner; Kıvrak, Ali; Caylı, Murat

2014-01-01

N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts cardiovascular events and mortality in hypertensive patients. Relationship between NT-proBNP level and left ventricular (LV) hypertrophy is well known in hypertensive patients. However, the studies investigating relationship between LV geometric patterns and serum NT-proBNP level have conflicting results and are in a limited number. The goal of the present study is to investigate relation between NT-proBNP and abnormal LV geometric patterns in untreated hypertensive patients. Measurements were obtained from 273 patients with untreated essential hypertension (mean age = 51.7 ± 5.8 years) and 44 healthy control subjects (mean age; 51.3 ± 4.7). Four different geometric patterns (NG: normal geometry; CR: concentric remodelling; EH: eccentric hypertrophy; CH: concentric hypertrophy) were determined according to LV mass index (LVMI) and relative wall thickness. NT-proBNP and other biochemical markers were measured in all subjects. The highest NT-proBNP levels were determined in the CH group compared with the control group and other geometric patterns (p < 0.05). NT-proBNP levels of all geometric patterns were higher than the control group (p < 0.05, for all). NT-proBNP levels were similar between CR and NG groups (p > 0.05). NT-proBNP was independently associated with LV geometry (β = 0.304, p = 0.003) and LVMI (β = 0.266, p = 0.007) in multiple linear regression analysis. Serum NT-proBNP level was independently associated with LVMI and LV geometry in untreated hypertensive patients with preserved ejection fraction.

The platelet activating factor acetyl hydrolase, oxidized low-density lipoprotein, paraoxonase 1 and arylesterase levels in treated and untreated patients with polycystic ovary syndrome.

PubMed

Carlioglu, Ayse; Kaygusuz, Ikbal; Karakurt, Feridun; Gumus, Ilknur Inegol; Uysal, Aysel; Kasapoglu, Benan; Armutcu, Ferah; Uysal, Sema; Keskin, Esra Aktepe; Koca, Cemile

2014-11-01

To evaluate the platelet activating factor acetyl hydrolyze (PAF-AH), oxidized low-density lipoprotein (ox-LDL), paraoxonase 1 (PON1), arylesterase (ARE) levels and the effects of metformin and Diane-35 (ethinyl oestradiol + cyproterone acetate) therapies on these parameters and to determine the PON1 polymorphisms among PCOS patients. Ninety patients with PCOS, age 30, and body mass index-matched healthy controls were included in the study. Patients were divided into three groups: metformin treatment, Diane-35 treatment and no medication groups. The treatment with metformin or Diane-35 was continued for 6 months and all subjects were evaluated with clinical and biochemical parameters 6 months later. One-way Anova test, t test and non-parametric Mann-Whitney U tests were used for statistical analysis. PAF-AH and ox-LDL levels were statistically significantly higher in untreated PCOS patients than controls, and they were statistically significantly lower in patients treated with metformin or Diane-35 than untreated PCOS patients. In contrast, there were lower PON1 (not statistically significant) and ARE (statistically significant) levels in untreated PCOS patients than the control group and they significantly increased after metformin and Diane-35 treatments. In PCOS patients serum PON1 levels for QQ, QR and RR phenotypes were statistically significantly lower than the control group. In patients with PCOS, proatherogenic markers increase. The treatment of PCOS with metformin or Diane-35 had positive effects on lipid profile, increased PON1 level, which is a protector from atherosclerosis and decreased the proatherogenic PAF-AH and ox-LDL levels.

Importance of latency and amplitude values of recurrent laryngeal nerve during thyroidectomy in diabetic patients.

PubMed

Ozemir, Ibrahim Ali; Ozyalvac, Ferman; Yildiz, Gorkem; Eren, Tunc; Aydin-Ozemir, Zeynep; Alimoglu, Orhan

2016-11-01

Diabetes mellitus may cause degeneration in the myelin and/or axonal structures of peripheral nerves. The aim of this study was to investigate the effects of diabetic neuropathy on intraoperative neuromonitoring findings such as latency and amplitude values of the recurrent laryngeal nerves during thyroidectomy. To our knowledge this is the first study to report comparison of the electrophysiologic features of diabetic and non-diabetic patients. One-hundred-and-eleven consecutive patients who received neuromonitoring during thyroidectomy between 2013 and 2015 were included to study. The patients were divided into two groups according to the presence of diabetes mellitus. Pre-thyroidectomy and post thyroidectomy motor response latency and amplitude values of recurrent laryngeal nerves were compared between groups. Neuromonitoring findings, demographic data and postoperative complications were evaluated. The diabetic group consisted of 29 (26.1%) patients while 82 (73.9%) patients were in non-diabetic group. The mean post-thyroidectomy amplitude values (millivolts-mV) of the recurrent laryngeal nerve were significantly lower in diabetic group (0.51 ± 0.26 mV vs. 0,70 ± 0,46 mV, p < 0.05), whereas the latency values were significantly higher (2.50 ± 0.86 ms vs. 1.85 ± 0.59 ms, p < 0.01) compared to non-diabetic group. Additionally, post-thyroidectomy latency values were significantly increased compared to the pre-thyroidectomy latency values (2.50 ± 0.86 ms vs. 2.02 ± 0.43 ms) in diabetic group patients (p < 0.05). Although postoperative complication rates were higher in diabetic group (10.3% vs. 5.9%), there were no statistical significance differences. Prolonged latency and decreased amplitude values in recurrent laryngeal nerves of diabetic patients show that diabetic neuropathy of the recurrent laryngeal nerves develop similarly to the peripheral nerves. Increased post-thyroidectomy latency values reveal that the recurrent laryngeal nerve is more susceptible to surgical trauma in diabetic patients. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Comparative study of the concentration of salivary and blood glucose in type 2 diabetic patients.

PubMed

Vasconcelos, Ana Carolina U; Soares, Maria Sueli M; Almeida, Paulo C; Soares, Teresa C

2010-06-01

The objective of the present study was to comparatively evaluate the concentrations of blood and salivary glucose as well as salivary flow and xerostomia in type 2 diabetic and non-diabetic patients. The mean salivary glucose level in diabetic patients was 14.03 +/-16.76 mg/dl and 6.35 +/- 6.02 mg/dl (P = 0.036) in the control group. The mean capillary blood glucose level in diabetic patients was 213 +/- 88 mg/dl, while that in non-diabetic patients was 99 +/- 14 mg/dl (P = 0.000). The mean value for resting salivary flow was 0.21 +/- 0.16 ml/min in diabetic patients and 0.33 +/- 0.20 ml/min in the control group (P = 0.002). The stimulated salivary flow was lower in the group of diabetic patients, with a mean of 0.63 +/- 0.43 ml/min, whereas the control group showed a mean of 1.20 +/- 0.70 ml/min (P = 0.000). Of the diabetic patients, 45% exhibited hyposalivation, in contrast to 2.5% of the non-diabetic patients (P = 0.000). Xerostomia was reported in 12.5% of diabetic patients and 5% of non-diabetic patients (P = 0.23). We can conclude that salivary glucose concentration was significantly higher in the experimental group and that there was no correlation between salivary and blood glucose concentrations in diabetic patients. The total salivary flow was significantly reduced in diabetic patients and there was no significant difference as to the presence of xerostomia in both groups.

Prevalence of xerostomia and the salivary flow rate in diabetic patients.

PubMed

Malicka, Barbara; Kaczmarek, Urszula; Skośkiewicz-Malinowska, Katarzyna

2014-01-01

Diabetes is a metabolic disease characterized by hyperglycemia, which results from relative or absolute insulin deficiency. One of the first oral symptoms of diabetes is xerostomia. The aim of the study was to determine the prevalence of the xerostomia symptoms and salivary flow rate in diabetic patients according to the type of diabetes, the level of metabolic control and the duration of the disease. The study involved 156 adult patients of both sexes including 34 patients with diabetes type 1 (group C1), 59 with diabetes type 2 (group C2), and 63 generally healthy individuals as two control groups, sex- and age-matched to the diabetic group. The patients suffering from both types of diabetes were additionally subdivided according to the level of metabolic control and the duration of the disease. Xerostomia was diagnosed with the use of a specially prepared questionnaire and Fox's test. Moreover, the salivary flow rate of resting mixed saliva was measured. In type 1 diabetics, a significantly lower salivary flow rate in comparison to the age-matched control group (0.38 ± 0.19 mL/min vs. 0.53 ± 0.20 mL/min, p < 0.01) was found. However in type 2 diabetics, a slight lower salivary flow rate was noticed (on average, 20% lower). Dry mouth was far more frequently diagnosed in type 1 diabetics than in the control group. In type 1 diabetics, in comparison to healthy subjects, a significantly lower resting flow rate of saliva and significantly higher prevalence of xerosomia were observed, but in type 2 diabetics, only a trend of such variability was observed.

Prevalence of Diabetes Mellitus in the Surgical Population of the University of Puerto Rico Affiliated Hospitals: A Study using the Surgery Database.

PubMed

Cruz, Norma I; Santiago, Elvis; Abdul-Hadi, Anwar

2016-09-01

To evaluate the prevalence of diabetes mellitus in the surgical population of the University of Puerto Rico (UPR)-affiliated hospitals. We examined all the surgical cases that were entered into the Surgical Database from April 1, 2014 through September 30, 2014. This database collects patient and procedural information from different surgical services of various UPR-affiliated hospitals (the University District Hospital, the University Pediatric Hospital, the UPR Carolina Hospital, the Dr. Isaac Gonzalez Oncologic Hospital, the PR Cardiovascular Center [thoracic service], the Pavia Hospital [colorectal service], and the Auxilio Mutuo Hospital [colorectal and oncological services]). The prevalence of diabetes mellitus (types 1 and 2 combined) was estimated, and the nondiabetic and diabetic groups were compared. The difference between groups was evaluated using a Chi2 test, Student's t-test, or ANOVA, whichever was appropriate, with a p-value of less than 0.05 being considered significant. Information from 2,603 surgical patients was available. The mean age of the group was 49 (±23) years. The gender distribution indicated that 56% were women and 44% were men. Diabetes was present in 21% of the surgical population, increasing to 40% in patients aged 65 and over. The surgical procedures most frequently required by diabetic patients were in the categories of general surgery (36%), colorectal surgery (22%), vascular surgery (16%) and oncologic surgery (14%). Complications (5%, diabetic group vs. 2%, nondiabetic group; p < 0.05) and postoperative mortality (2%, diabetic group vs. 0.2%, nondiabetic group; p < 0.05) were significantly higher in the diabetic group than in the nondiabetic group. Our surgical population has a high prevalence of diabetes, and these diabetic patients showed higher complication and mortality rates from surgery than did the non-diabetic patients. Surgeons must consider the specific needs of these diabetic patients in order to provide optimal care.

The Influence of Maternal Obesity on Pregnancy Complications and Neonatal Outcomes in Diabetic and Nondiabetic Women

PubMed Central

Timur, Burcu Budak; Timur, Hakan; Tokmak, Aytekin; Isik, Hatice; Eyi, Elif Gul Yapar

2018-01-01

Introduction This study aimed to investigate the influence of obesity on pregnancy complications and neonatal outcomes in diabetic and nondiabetic women. Materials and Methods This retrospective case control study was conducted on 1193 pregnant women and their neonates at a tertiary level maternity hospital between March 2007 and 2011. The pregnant women were classified into 2 groups according to the presence of diabetes mellitus. Six hundred and seven patients with gestational diabetes or pregestational diabetes formed the diabetic group (study group) and 586 patients were in the nondiabetic group (control group). Demographic characteristics, body mass index, gestational weight gain, obstetric history, smoking status, type of delivery, gestational ages, pregnancy complications, neonatal outcomes were recorded for each patient. Multivariable logistic regression analysis was performed to evaluate the effect of obesity and diabetes on the pregnancy complications and neonatal outcomes. Results The mean age and pre-pregnancy body mass indices of women with diabetes mellitus were significantly higher than the control groupʼs (p < 0.001). Gestational weight gain and number of smokers were similar among the groups. Multiparity and obesity were more prevalent in the diabetic group compared to controls (both p < 0.001). Although gestational age at birth was earlier in the diabetic group, birth weights were higher in this group than in the control group (both p < 0.001). Cesarean delivery rates, the incidence of macrosomia, and neonatal intensive care unit admission rates were significantly higher in the diabetes group both with normal and increased body mass index (all p < 0.001). However, adverse pregnancy outcomes were comparable between the groups (p = 0.279). Multivariable logistic regression analysis showed that obesity is a significant risk factor for pregnancy complications (OR = 1.772 [95% CI, 1.283 – 2.449], p = 0.001) but not for adverse neonatal outcomes (OR = 1.068 [95% CI, 0.683 – 1.669], p = 0.773). Conclusion While obesity increases risk of developing a pregnancy complication, diabetes worsens neonatal outcomes. PMID:29720745

Effect of a polyherbal formulation cream on diabetic neuropathic pain among patients with type 2 diabetes – A pilot study

PubMed Central

Viswanathan, Vijay; Rajsekar, Seena; Selvaraj, Bamila; Kumpatla, Satyavani

2016-01-01

Background & objectives: Painful diabetic neuropathy is a common complication of diabetes and can severely limit patients’ daily functions. The aim of this pilot study was to evaluate the safety and effect of using a polyherbal formulation in reducing the symptoms of diabetic neuropathic pain in comparison with placebo among patients with type 2 diabetes. Methods: A total of 50 (M:F = 33:17) consecutive type 2 diabetes patients with painful diabetic neuropathy were enrolled in this study. All these patients had either two or more symptoms of diabetic neuropathy such as pain, burning and pricking sensations and numbness in their feet. They were randomly assigned to two groups: group 1 (n = 26) patients were treated with polyherbal formulation cream and group 2 (n = 24) patients were administered placebo. The patients were followed up for six months. Changes in the symptoms of painful diabetic neuropathy of each patient were recorded at baseline, third and sixth month using the Diabetic Neuropathic Score. Results: The mean age of the patients, duration of diabetes and glycated haemoglobin (HbA1c) were similar in both groups at baseline. During follow up visits, there was a decrease in the HbA1c levels in the study and control groups. The symptoms of painful diabetic neuropathy were also similar in both groups at baseline. A significant decrease in symptoms of neuropathic pain was observed among the group of patients treated with polyherbal formulation cream (76.9 per cent) compared to the placebo-treated group (12.5 per cent) (P<0.001), at the end of the final follow up. Interpretation & conclusions: In this pilot study polyherbal formulation cream was found to be effective as well as safe to treat painful diabetic neuropathy. However, its long term use needs to be evaluated for any further effectiveness and side effects. PMID:27934800

Effects of Persea americana Mill (Lauraceae) ["Avocado"] ethanolic leaf extract on blood glucose and kidney function in streptozotocin-induced diabetic rats and on kidney cell lines of the proximal (LLCPK1) and distal tubules (MDBK).

PubMed

Gondwe, M; Kamadyaapa, D R; Tufts, M A; Chuturgoon, A A; Ojewole, J A O; Musabayane, C T

2008-01-01

Extracts of Persea americana Mill (Lauraceae) ("Avocado") have been traditionally used to treat hypertension and diabetes mellitus. Accordingly, we studied the hypoglycaemic and renal function effects of P. americana leaf ethanolic extracts (PAE) in STZ-induced diabetic rats. Oral glucose tolerance responses to various doses of PAE were monitored in fasted rats following a glucose load. Rats treated with deionized water or standard hypoglycaemic drugs acted as untreated and treated positive controls, respectively. Acute renal effects of PAE were investigated in anesthetized rats challenged with 0.077 M NaCl after a 3.5-h equilibration for 4 h comprising 1 h control, 1.5 h treatment and 1.5 h recovery periods. PAE was added to the infusate during the treatment period. Hepatic glycogen concentration was measured after 6 weeks of daily treatment with PAE. PAE induced dose-dependent hypoglycaemic responses in STZ-induced diabetic rats while subchronic PAE treatment additionally increased hepatic glycogen concentrations. Acute PAE infusion decreased urine flow and electrolyte excretion rates, whilst subchronic treatment reduced plasma creatinine and urea concentrations. These results indicate not only the basis of the ethnomedicinal use of P. americana leaf extract in diabetes management, but also of need for further studies to identify and evaluate the safety of PAE's bioactive compounds. (c) 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

Effects of dietary glutamine on adhesion molecule expression and oxidative stress in mice with streptozotocin-induced type 1 diabetes.

PubMed

Tsai, Pei-Hsuan; Liu, Jun-Jen; Chiu, Wan-Chun; Pai, Man-Hui; Yeh, Sung-Ling

2011-02-01

Glutamine (Gln) is known to have immunomodulatory effects. Previous studies reported that Gln promotes insulin secretion in type 2 diabetes. However, the effects of Gln on insulin-deficient type 1 diabetes are not clear. This study investigated the effects of dietary Gln supplementation on adhesion molecule expression and oxidative damage in type 1 diabetic mice. There were 1 normal control (NC) group and 2 diabetic groups in this study. Mice in the NC group were fed a regular chow diet. One diabetic group (DM) was fed a common semipurified diet while the other diabetic group received a diet in which part of the casein was replaced by Gln (DM-Gln), which provided 25% of the total amino acid nitrogen for 6 wk. Diabetes was induced by an intraperitoneal injection of streptozotocin at a dose of 150 mg/kg body weight. Blood samples and the liver and kidneys of the animals were collected at the end of the study for further analysis. Plasma glucose, fructosamine contents and adhesion molecule expressions were significantly higher in the diabetic groups than in the NC group. The DM group had higher leukocyte CD11a/CD18 expression. In diabetic mice, nitrotyrosine concentrations and myeloperoxidase activities were higher and the reduced to oxidized glutathione ratio was lower in liver and/or kidney. These alterations were not found in diabetic mice supplemented with Gln. These results suggest that supplemental dietary Gln increased the antioxidant potential and consequently decreased leukocyte adhesion molecule expression and oxidative stress in organs of mice with type 1 diabetes. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Adipocytokine Levels in Genetically High Risk for Type 2 Diabetes in the Indian Population: A Cross-Sectional Study

PubMed Central

Bose, K. Subhash Chandra; Gupta, Shachin K.; Vyas, Prerna

2012-01-01

Introduction. In view of the noteworthy role of adipocytokines in the onset of insulin resistance and diabetes in gene-knockout-rat-model-cell-line studies we aimed to study the influence of genetic predisposition for diabetes on adipocytokine levels and their role in building insulin-resistance-like environment well before the onset of diabetes; thus a hypothesis can be drawn on their role in developing diabetes in high risk population. Methods. Ages between 18 and 22 years were selected and divided into three groups. Group I (n = 81): control group with no family history of diabetes. Group II (n = 157): with one of their parents with history of type 2 diabetes. Group III (n = 47): with both parents having history of type 2 diabetes. In all the groups we estimated fasting plasma glucose, insulin and adipocytokines like adiponectin, leptin, TNF-α, and IL-6. Results. Of all adipocytokines we observed significantly lower levels of adiponectin (8.7 ± 1 μg/mL in group III and 9.5 ± 1.3 μg/mL group II) when compared to control (11.0 ± 1.2 μg/mL; P < 0.01) and it has strong correlation with family history of diabetes with Pearson's coefficient of −0.502. Linear regression analysis showed significant negative association with HOMA-IR (P < 0.01) and logistic regression analysis showed highest association with parental diabetes (P < 0.01; OR .260, 95% CI .260–.468). Conclusion. Genetic predisposition for diabetes may influence adiponectin gene expression leading to decrease in its plasma concentration, which might play a key role in developing diabetes in near future. PMID:23213322

Effects of the Diabetes Manual 1:1 structured education in primary care.

PubMed

Sturt, J A; Whitlock, S; Fox, C; Hearnshaw, H; Farmer, A J; Wakelin, M; Eldridge, S; Griffiths, F; Dale, J

2008-06-01

To determine the effects of the Diabetes Manual on glycaemic control, diabetes-related distress and confidence to self-care of patients with Type 2 diabetes. A cluster randomized, controlled trial of an intervention group vs. a 6-month delayed-intervention control group with a nested qualitative study. Participants were 48 urban general practices in the West Midlands, UK, with high population deprivation levels and 245 adults with Type 2 diabetes with a mean age of 62 years recruited pre-randomization. The Diabetes Manual is 1:1 structured education designed for delivery by practice nurses. Measured outcomes were HbA(1c), cardiovascular risk factors, diabetes-related distress measured by the Problem Areas in Diabetes Scale and confidence to self-care measured by the Diabetes Management Self-Efficacy Scale. Outcomes were assessed at baseline and 26 weeks. There was no significant difference in HbA(1c) between the intervention group and the control group [difference -0.08%, 95% confidence interval (CI) -0.28, 0.11]. Diabetes-related distress scores were lower in the intervention group compared with the control group (difference -4.5, 95% CI -8.1, -1.0). Confidence to self-care Scores were 11.2 points higher (95% CI 4.4, 18.0) in the intervention group compared with the control group. The patient response rate was 18.5%. In this population, the Diabetes Manual achieved a small improvement in patient diabetes-related distress and confidence to self-care over 26 weeks, without a change in glycaemic control. Further study is needed to optimize the intervention and characterize those for whom it is more clinically and psychologically effective to support its use in primary care.

Astaxanthin from shrimp by-products ameliorates nephropathy in diabetic rats.

PubMed

Sila, Assaâd; Ghlissi, Zohra; Kamoun, Zeineb; Makni, Mohamed; Nasri, Moncef; Bougatef, Ali; Sahnoun, Zouheir

2015-03-01

This study investigated the hypoglycemic and antioxidant effects of shrimp astaxanthin on the kidney of alloxan-induced diabetic rats. Animals were distributed into four groups of six rats each: a control group (C), a diabetic group (D), a diabetic group supplemented with Astaxanthin (D+As) dissolved in olive oil and a diabetic group supplemented with olive oil (D+OO). In vitro antidiabetic effect was tested in plasma and kidney tissue. The group D of rats showed significant (P < 0.05) increase of glycemia, creatinine, urea and uric acid levels compared to those of the control group (C). Moreover, plasma and kidney malondialdehyde (MDA) and protein carbonyl (PCO) levels for the rats of the group D were significantly increased compared to the control group. Contrariwise, antioxidant enzyme activities, such as catalase (EC 1.11.1.6), superoxide dismutase (EC 1.15.1.1) and non-enzymatic levels of reduced glutathione, were significantly (P < 0.05) decreased in the plasma and kidney of diabetic rats compared to the control ones. The astaxanthin supplementation in rats diet improved the antioxidant enzyme activities and significantly decreased the MDA and PCO levels compared to diabetic rats. Indeed, no significant (P ≥ 0.05) improvement was observed for the fourth group (D+OO) compared to the control group (C). Histological analysis of kidney showed glomerular hypertrophy and tubular dilatation for the diabetic rats. For D+As rats, these histopathological changes were less prominent. Our results suggest that shrimp astaxanthin may play an important role in reduction of oxidative damage and could prevent pathological changes in diabetic rats suggesting promising application of shrimp astaxanthin in diabet treatment.

Expression profiles of eNOS, iNOS and microRNA-27b in the corpus cavernosum of rats submitted to chronic alcoholism and Diabetes mellitus.

PubMed

Cunha, Joao Paulo da; Lizarte, Fermino Sanches; Novais, Paulo Cezar; Gattas, Daniela; Carvalho, Camila Albuquerque Mello de; Tirapelli, Daniela Pretti da Cunha; Molina, Carlos Augusto Fernandes; Tirapelli, Luis Fernando; Tucci, Silvio

2017-01-01

To evaluate the expression of endothelial and inducible NOS in addition to the miRNA-27b in the corpus cavernosum and peripheral blood of healthy rats, diabetic rats, alcoholic rats and rats with both pathologies. Forty eight Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D) and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study protein expressions of eNOS and iNOS by immunohistochemistry and expression of miRNA-27b in the corpus cavernosum and peripheral blood. Immunohistochemistry for eNOS and iNOS showed an increase in cavernosal smooth muscle cells in the alcoholic, diabetic and alcoholic-diabetic groups when compared with the control group. Similarly, the mRNA levels for eNOS were increased in cavernosal smooth muscle (CSM) in the alcoholic, diabetic and alcoholic-diabetic groups and miRNA-27b were decreased in CSM in the alcoholic, diabetic and alcoholic-diabetic groups. The major new finding of our study was an impairment of relaxation of cavernosal smooth muscle in alcoholic, diabetic, and alcoholic-diabetic rats that involved a decrease in the nitric oxide pathway by endothelium-dependent mechanisms accompanied by a change in the corpus cavernosum contractile sensitivity.

People with diabetic peripheral neuropathy display a decreased stepping accuracy during walking: potential implications for risk of tripping.

PubMed

Handsaker, J C; Brown, S J; Bowling, F L; Marple-Horvat, D E; Boulton, A J M; Reeves, N D

2016-05-01

To examine the stepping accuracy of people with diabetes and diabetic peripheral neuropathy. Fourteen patients with diabetic peripheral neuropathy (DPN), 12 patients with diabetes but no neuropathy (D) and 10 healthy non-diabetic control participants (C). Accuracy of stepping was measured whilst the participants walked along a walkway consisting of 18 stepping targets. Preliminary data on visual gaze characteristics were also captured in a subset of participants (diabetic peripheral neuropathy group: n = 4; diabetes-alone group: n = 4; and control group: n = 4) during the same task. Patients in the diabetic peripheral neuropathy group, and patients in the diabetes-alone group were significantly less accurate at stepping on targets than were control subjects (P < 0.05). Preliminary visual gaze analysis identified that patients diabetic peripheral neuropathy were slower to look between targets, resulting in less time being spent looking at a target before foot-target contact. Impaired motor control is theorized to be a major factor underlying the changes in stepping accuracy, and potentially altered visual gaze behaviour may also play a role. Reduced stepping accuracy may indicate a decreased ability to control the placement of the lower limbs, leading to patients with neuropathy potentially being less able to avoid observed obstacles during walking. © 2015 Diabetes UK.

HNO3 modified biochars for uranium (VI) removal from aqueous solution.

PubMed

Jin, Jie; Li, Shiwei; Peng, Xianqiang; Liu, Wei; Zhang, Chenlu; Yang, Yan; Han, Lanfang; Du, Ziwen; Sun, Ke; Wang, Xiangke

2018-05-01

The HNO 3 treatment was used to chemically modify the biochars produced from wheat straw (WH) and cow manure for U(VI) removal from aqueous solution. Macroscopic experiments proved that the enrichment of U(VI) on the biochars was regulated by surface complexation and electrostatic interactions. FTIR and XPS analyses confirmed that the highly efficient adsorption of U(VI) was due to the carboxyl groups on the biochar surfaces. The reducing agents of the R-CH 2 OH groups facilitated U(VI) adsorption on the untreated biochars. Owing to the higher contents of surface COO groups and more negative surface charge, the modified biochars showed enhanced U(VI) adsorption ability than the untreated ones. The maximum adsorption capacity of U(VI) by the oxidized WH was calculated to be 355.6 mg/g at pH 4.5 and 298 K, which was an improvement of 40 times relative to the untreated WH and was higher than that of most carbon-based adsorbents. Copyright © 2018 Elsevier Ltd. All rights reserved.

Psychological response to growth hormone treatment in short normal children.

PubMed Central

Downie, A B; Mulligan, J; McCaughey, E S; Stratford, R J; Betts, P R; Voss, L D

1996-01-01

This study provides a controlled assessment of the psychological (and physical) effects of growth hormone treatment. Fifteen short 'normal' children (height SD score < -2) have been treated with growth hormone since the age of 7/8 years. They, together with untreated short controls and average controls (10th-90th centiles), were assessed at recruitment, after three years, and after five years. Only the treated group showed a significant height increase (SD score -2.44 to -1.21 over five years). No significant differences were found at recruitment, three years, or five years in IQ, attainment, behaviour, or self esteem. Also at five years, there were no significant differences in locus of control, self perception, or parental perceptions of competence. Both short groups displayed less satisfaction with their height than the controls (p < 0.01), though all groups were optimistic of being tall adults. The treated children were no more unrealistic over final height than the untreated children. To date, no psychological benefits of treatment have been demonstrated; but nor have there been any discernible ill effects for either the treated or the untreated children. PMID:8813867

Sequential mesenteric arteriography in pony foals during repeated inoculations of Strongylus vulgaris and treatments with ivermectin.

PubMed

Holmes, R A; Klei, T R; McClure, J R; Turk, M A; Watters, J W; Chapman, M R

1990-04-01

Semiselective mesenteric arteriography was performed at regular intervals (inoculation weeks [IW] 0, 11, 18, and 24) in 9 of 10 pony foals raised to be free of parasites. Fifty infective larvae (L3) of Strongylus vulgaris were administered weekly for 4 weeks, then every 2 weeks through the 20th week. Three ponies were given ivermectin (oral paste, 0.2 mg/kg of body weight) treatment at IW 8, 16 and 24. Four ponies were inoculated, but did not receive ivermectin, and a third group of 2 ponies acted as uninoculated controls. Control ponies did not have gross or arteriographic lesions, whereas the inoculated untreated ponies had gross and progressive arteriographic lesions typical of verminous arteritis. Arteriographic lesions in the ivermectin-treated inoculated ponies were not as severe those in the untreated inoculated group, and there was either a partial resolution or a lack of progression of arteriographic lesions in all treated ponies. One untreated inoculated pony did not have progressive arterial lesions as did the 3 others in the group, and may develop resistance to the parasite.

Effects of short-term streptozotocin-induced diabetes and vitamin C on platelet non-enzymatic glycation.

PubMed

Batırel, Saime; Yarat, Ayşen; Emekli, Nesrin

2010-01-01

Diabetes mellitus is one of the most prevalent metabolic syndromes worldwide. Glycation, a chemical modification of proteins with reducing sugars, indicates a possible explanation for the association between hyperglycemia and the wide variety of tissue pathologies. Non-enzymatic glycation (NEG) of platelet proteins is one of the key mechanisms in the pathogenesis of diabetic complications and may be significant in diabetic atherothrombosis. The aim of this study was to investigate the effects of streptozotocin (STZ)-induced short-term experimental diabetes on the glycation of platelets and to find out if vitamin C affected this glycation. A total of 40 male Wistar albino rats, 200-250 g, were randomly divided into 4 groups (2 diabetic and 2 control groups). The diabetic groups were made diabetic by intraperitoneal injection of STZ (65 mg/kg, citrate buffer pH 4.5). By daily intraperitoneal injection, 80 mg/kg vitamin C (Roche, Turkey) was administered until the end of the experiment. Blood glucose levels of the diabetic groups were significantly higher than those at day 0 and also higher than those of the non-diabetic control groups. The changes in total protein, NEG and vitamin C levels were not statistically significant. Although the differences among the groups were not statistically significant, vitamin C administration increased NEG levels in the diabetic group. The results of this study demonstrate that 8 days of STZ-induced short-term diabetes did not cause a significant increase in NEG of platelets. However, the effect of vitamin C on platelet NEG needs to be further investigated. Copyright © 2011 S. Karger AG, Basel.

S100A8/A9 (Calprotectin), Interleukin-6, and C-Reactive Protein in Obesity and Diabetes before and after Roux-en-Y Gastric Bypass Surgery.

PubMed

Lylloff, Louise; Bathum, Lise; Madsbad, Sten; Grundtvig, Josefine Liv Gilling; Nordgaard-Lassen, Inge; Fenger, Mogens

2017-01-01

In obesity, which is a major contributor to insulin resistance and diabetes, the circulating level of S100A8/A9 (calprotectin) is elevated and declines after Roux-en-Y gastric bypass surgery (RYGB). However, studies on S100A8/A9 and the pathophysiological mechanisms in insulin resistance and diabetes are few and contradictory. We studied 48 subjects who underwent RYGB, comprising a non-diabetic control group and two diabetic groups in whom diabetes either regressed or persisted, 6-12 months post-surgically. S100A8/A9, interleukin 6 (IL-6) as well as other inflammatory and diabetes-related markers were measured pre- and post-surgically. Significant and similar decreases of BMI were found in all groups. S100A8/A9 and IL-6 decreased significantly in the group with diabetes remission and in the control group, but not in the group with persistent diabetes. The relative changes in S100A8/A9 and IL-6 correlated significantly (r = 0.905, p = 0.005) only in the group with persistent diabetes. In contrast, leukocyte count and C-reactive protein correlated significantly to S100A8/A9 only in the control group. Our study is suggestive of S100A8/A9 and IL-6 being related to a persistent diabetes status post-surgically and of different pathophysiological mechanisms being involved in the post-surgical changes in the three groups, despite similar decreases in BMI. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

Effects of Icariside II on Corpus Cavernosum and Major Pelvic Ganglion Neuropathy in Streptozotocin-Induced Diabetic Rats

PubMed Central

Bai, Guang-Yi; Zhou, Feng; Hui, Yu; Xu, Yong-De; Lei, Hong-En; Pu, Jin-Xian; Xin, Zhong-Cheng

2014-01-01

Diabetic erectile dysfunction is associated with penile dorsal nerve bundle neuropathy in the corpus cavernosum and the mechanism is not well understood. We investigated the neuropathy changes in the corpus cavernosum of rats with streptozotocin-induced diabetes and the effects of Icariside II (ICA II) on improving neuropathy. Thirty-six 8-week-old Sprague-Dawley rats were randomly distributed into normal control group, diabetic group and ICA-II treated group. Diabetes was induced by a one-time intraperitoneal injection of streptozotocin (60 mg/kg). Three days later, the diabetic rats were randomly divided into 2 groups including a saline treated placebo group and an ICA II-treated group (5 mg/kg/day, by intragastric administration daily). Twelve weeks later, erectile function was measured by cavernous nerve electrostimulation with real time intracorporal pressure assessment. The penis was harvested for the histological examination (immunofluorescence and immunohistochemical staining) and transmission electron microscopy detecting. Diabetic animals exhibited a decreased density of dorsal nerve bundle in penis. The neurofilament of the dorsal nerve bundle was fragmented in the diabetic rats. There was a decreased expression of nNOS and NGF in the diabetic group. The ICA II group had higher density of dorsal nerve bundle, higher expression of NGF and nNOS in the penis. The pathological change of major pelvic nerve ganglion (including the microstructure by transmission electron microscope and the neurite outgrowth length of major pelvic nerve ganglion tissue cultured in vitro) was greatly attenuated in the ICA II-treated group (p < 0.01). ICA II treatment attenuates the diabetes-related impairment of corpus cavernosum and major pelvic ganglion neuropathy in rats with Streptozotocin-Induced Diabetes. PMID:25517034

An integrated intervention program to control diabetes in overweight Chinese women and men with type 2 diabetes.

PubMed

Sun, Jianqin; Wang, Yanfang; Chen, Xiafei; Chen, Yanqiu; Feng, Ying; Zhang, Xinyi; Pan, Yiru; Hu, Ting; Xu, Jianhua; Du, Luyuan; Zhou, Wei; Zhao, Huiping; Riley, Rosemary E; Mustad, Vikkie A

2008-01-01

This study evaluated a structured and integrated intervention program on diabetes management in individuals with type 2 diabetes in Shanghai, China. Men and women with type 2 diabetes and body mass index > 23 kg/m2 were randomized into a 24-week, prospective, randomized clinical trial. The Reference Group (n=50) received diabetes education including diet and physical activity instruction only; the Intervention Group (n=100) received more intensive intervention, including diabetes education with frequent blood glucose monitoring, nutritional counseling, meal plans with diabetes-specific nutritional meal replacement, and weekly progress updates with study staff. Major study assessments were obtained at baseline, and after 12 and/or 24 weeks of intervention. The Intervention Group improved fasting blood glucose, insulin, systolic and diastolic blood pressures compared to Reference Group ( p <0.05). Importantly, HbA1c was lower ( p <0.001) in the Intervention Group at 12 weeks (-0.6 +/- 0.1%) and 24 weeks (-0.8 +/- 0.1%). Weight loss was modest, but significant differences were observed between groups ( p <0.05). Weight change from baseline after 12 and 24 weeks was -2.8 +/- 0.2% and -3.7 +/- 0.3%, respectively, in the Intervention Group vs -1.8 +/- 0.4% and -2.5 +/- 0.4% in the Reference Group. Additionally, waist and hip circumferences and waist:hip ratio decreased in the Intervention compared to the Reference Group ( p <0.05). In conclusion, this study demonstrates that Chinese men and women with type 2 diabetes following an integrated intervention program including diabetes education, frequent blood glucose monitoring and daily use of a diabetes-specific meal replacement, can achieve significant improvements in glycemic control and markers of cardiovascular health.

Evaluating the Impact of Diabetes Self-Management Education Methods on Knowledge, Attitudes and Behaviours of Adult Patients With Type 2 Diabetes Mellitus.

PubMed

Adam, Laura; O'Connor, Colleen; Garcia, Alicia C

2017-11-23

Diabetes self-management refers to all activities patients undertake to care for their illness, promote health and prevent the long- and short-term effects of diabetes. This study compared the effectiveness of 2 diabetes self-management education methods by examining changes in glycated hemoglobin (A1C) levels and knowledge, attitudes and behaviours (KABs) after traditional group education (TE) or with diabetes conversation maps (CMs). The CMs group was postulated to show greater decrease in A1C levels and improved KABs scores compared to the TE group. A sample of 21 eligible clients from Diabetes Care Guelph were randomly assigned into 2 groups, 10 receiving education through CMs and 11 through TE. Changes in knowledge and attitude were determined by using questionnaires and repeated-measures pretest and post-test design before and after the education sessions. Changes in A1C levels were determined by comparing values at baseline and at 3 months after receiving diabetes education. Two focus groups were conducted to obtain participants' perceptions of the education methods and self-reported KABs changes. Significant differences in knowledge and attitude score changes were observed from baseline/initial education and after 3 months. Both groups had significant decreases in A1C levels from baseline to 3 months afterward. Focus groups revealed themes common to both groups, such as benefits of early education, need for multiple lifestyle behaviour changes and feelings of social support. CMs had significant impact and are effective for group education. The changes observed may lead to improved diabetes self-management, thus reducing costly health complications related to poorly controlled diabetes. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Effects of Diabetes on Post-Menopausal Rat Submandibular Glands: A Histopathological and Stereological Examination

PubMed Central

Buyuk, Basak; Parlak, Secil Nazife; Keles, Osman Nuri; Can, Ismail; Yetim, Zeliha; Toktay, Erdem; Selli, Jale; Unal, Bunyami

2015-01-01

Objective: The menopause in elderly women is a physiological process where ovarian and uterine cycles end. Diabetes means higher blood glucose level that is a metabolic disease and has an increased incidence. The aim of the study was to examine the single or combined effects of menopause and diabetes that causes pathophysiological processes on submandibular gland on ovariectomy and diabetes induced rat models. Materials and Methods: Sprague Dawley twelve weeks old female (n=24) rats were divided randomly into four groups; Healthy control group (n=6), diabetic group (DM, n=6), ovariectomized group (OVX, n=6), post ovariectomy diabetes induced group (DM+OVX, n=6) individually. Histopathological, histochemical and stereological analyses were done in these groups. Results: Significant neutrophil cell infiltrations and myoepithelial cell proliferations, granular duct and seromucous acini damages and changes in the content of especially seromucous acini secretion in DM and/or OVX groups and distinctive interstitial and striated duct damages in post ovariectomy diabetes induced group were detected. Alterations ingranular ducts hypertrophic and in seromucous acini atrophic were determined in DM and/or OVX groups. Conclusion: The results revealed the pathophysiological processes that lead to morphological and functional alterations on the cellular level in submandibular glands. The molecular mechanisms related with pathogenesis of diabetes and menopause need further investigation. PMID:26644770

A low-fat vegan diet elicits greater macronutrient changes, but is comparable in adherence and acceptability, compared with a more conventional diabetes diet among individuals with type 2 diabetes.

PubMed

Barnard, Neal D; Gloede, Lise; Cohen, Joshua; Jenkins, David J A; Turner-McGrievy, Gabrielle; Green, Amber A; Ferdowsian, Hope

2009-02-01

Although therapeutic diets are critical to diabetes management, their acceptability to patients is largely unstudied. To quantify adherence and acceptability for two types of diets for diabetes. Controlled trial conducted between 2004 and 2006. Individuals with type 2 diabetes (n=99) at a community-based research facility. Participants were randomly assigned to a diet following 2003 American Diabetes Association guidelines or a low-fat, vegan diet for 74 weeks. Attrition, adherence, dietary behavior, diet acceptability, and cravings. For nutrient intake and questionnaire scores, t tests determined between-group differences. For diet-acceptability measures, the related samples Wilcoxon sum rank test assessed within-group changes; the independent samples Mann-Whitney U test compared the diet groups. Changes in reported symptoms among the groups was compared using chi(2) for independent samples. All participants completed the initial 22 weeks; 90% (45/50) of American Diabetes Association guidelines diet group and 86% (42/49) of the vegan diet group participants completed 74 weeks. Fat and cholesterol intake fell more and carbohydrate and fiber intake increased more in the vegan group. At 22 weeks, group-specific diet adherence criteria were met by 44% (22/50) of members of the American Diabetes Association diet group and 67% (33/49) of vegan-group participants (P=0.019); the American Diabetes Association guidelines diet group reported a greater increase in dietary restraint; this difference was not significant at 74 weeks. Both groups reported reduced hunger and reduced disinhibition. Questionnaire responses rated both diets as satisfactory, with no significant differences between groups, except for ease of preparation, for which the 22-week ratings marginally favored the American Diabetes Association guideline group. Cravings for fatty foods diminished more in the vegan group at 22 weeks, with no significant difference at 74 weeks. Despite its greater influence on macronutrient intake, a low-fat, vegan diet has an acceptability similar to that of a more conventional diabetes diet. Acceptability appears to be no barrier to its use in medical nutrition therapy.

Diurnal behaviour of some salivary parameters in patients with diabetes mellitus (flow rate, pH, thiocianat, LDH activity)--note II.

PubMed

Ionescu, S; Bădiţă, D; Artino, M; Dragomir, M; Huidovici, E; Niţă, V; Chiţoi, E

1998-01-01

The study was performed on 31 diabetic patients of both sexes, divided in 2 groups: group I--17 patients with insulin-dependent diabetes (IDDM) and group II--14 patients with noninsulin-dependent diabetes (NIDDM) and compared with a control group of 16 non-diabetic subjects. Mixed saliva was sampled without stimulation during 2 periods of the day: 07:30-08:00 before breakfast and 17:30-18:00 before dinner. We determined: salivary flow rate, pH with Merck indicator and, after homogenization, the thiocianat with the FeCl3 method and LDH activity (the Norbert method adapted in our laboratory for saliva). Our study showed the same diurnal changes in flow rate and salivary pH in both diabetic and control groups: minimal values in the morning and maximal ones in the afternoon. In non-smoking diabetic patients the salivary thiocianat had maximal values in the morning and minimal ones in the afternoon; similar behaviour, but less obvious was observed in smoking diabetic patients and in the control group regardless of the smoking habit. LDH activity showed unsignificant diurnal variations in the diabetic patients. In the control group we found a significant decrease of LDH activity in the afternoon. The discussion is about the implication of these salivary parameters in the pathology of oral cavity: gingivitis, periodontitis and caries in diabetic patients.

40 CFR 798.2450 - Inhalation toxicity.

Code of Federal Regulations, 2010 CFR

2010-07-01

... study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group. Except for treatment with the test substance, animals in the control group... generate an appropriate concentration of the substance in the atmosphere, a vehicle control group shall be...

40 CFR 798.2450 - Inhalation toxicity.

Code of Federal Regulations, 2011 CFR

2011-07-01

... study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group. Except for treatment with the test substance, animals in the control group... generate an appropriate concentration of the substance in the atmosphere, a vehicle control group shall be...

40 CFR 798.2450 - Inhalation toxicity.

Code of Federal Regulations, 2013 CFR

2013-07-01

... study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group. Except for treatment with the test substance, animals in the control group... generate an appropriate concentration of the substance in the atmosphere, a vehicle control group shall be...

40 CFR 798.2450 - Inhalation toxicity.

Code of Federal Regulations, 2014 CFR

2014-07-01

... study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group. Except for treatment with the test substance, animals in the control group... generate an appropriate concentration of the substance in the atmosphere, a vehicle control group shall be...

40 CFR 798.2450 - Inhalation toxicity.

Code of Federal Regulations, 2012 CFR

2012-07-01

... study. (2) Control groups. A concurrent control group is required. This group shall be an untreated or sham-treated control group. Except for treatment with the test substance, animals in the control group... generate an appropriate concentration of the substance in the atmosphere, a vehicle control group shall be...

Is a diagnosis of metabolic syndrome applicable to children?

PubMed

Pergher, Rafael Nardini Queiroz; Melo, Maria Edna de; Halpern, Alfredo; Mancini, Marcio Corrêa

2010-01-01

To present the components of the metabolic syndrome in children and adolescents and to discuss how they are assessed in the pediatric population in addition to presenting the major metabolic syndrome classifications for the age group. A review of literature published from 1986 to 2008 and found on MEDLINE databases. The prevalence of childhood obesity has been increasing globally over recent decades and as a result its complications, such as diabetes mellitus, arterial hypertension and dyslipidemia, have also increased. The concept of metabolic syndrome, already common with adults, is now beginning to be applied to children through classifications using the criteria for adults modified for the younger age group. Notwithstanding, these classifications differ in terms of the cutoff points used and whether they employ body mass index or waist circumference to define obesity. The review presents these classifications, highlighting the points on which they differ and the debate about them. If childhood obesity goes untreated, it will have severe consequences in the future. A number of models for classifying metabolic syndrome in children have been published, but there is considerable diversions between them. The criteria for classifying metabolic syndrome in children therefore need to be standardized in order to identify those people at greatest risk of future complications.