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Sample records for oral carnitine therapy

  1. Oral carnitine therapy in children with cystinosis and renal Fanconi syndrome

    SciTech Connect

    Gahl, W.A.; Bernardini, I.; Dalakas, M.; Rizzo, W.B.; Harper, G.S.; Hoeg, J.M.; Hurko, O.; Bernar, J.

    1988-02-01

    11 children with either cystinosis or Lowe's syndrome had a reduced content of plasma and muscle carnitine due to renal Fanconi syndrome. After treatment with oral L-carnitine, 100 mg/kg per d divided every 6 h, plasma carnitine concentrations became normal in all subjects within 2 d. Initial plasma free fatty acid concentrations, inversely related to free carnitine concentrations, were reduced after 7-20 mo of carnitine therapy. Muscle lipid accumulation, which varied directly with duration of carnitine deficiency (r = 0.73), improved significantly in three of seven rebiopsied patients after carnitine therapy. One Lowe's syndrome patient achieved a normal muscle carnitine level after therapy. Muscle carnitine levels remained low in all cystinosis patients, even though cystinotic muscle cells in culture took up L-(/sup 3/H)carnitine normally. The half-life of plasma carnitine for cystinotic children given a single oral dose approximated 6.3 h; 14% of ingested L-carnitine was excreted within 24 h. Studies in a uremic patient with cystinosis showed that her plasma carnitine was in equilibrium with some larger compartment and may have been maintained by release of carnitine from the muscle during dialysis. Because oral L-carnitine corrects plasma carnitine deficiency, lowers plasma free fatty acid concentrations, and reverses muscle lipid accumulation in some patients, its use as therapy in renal Fanconi syndrome should be considered. However, its efficacy in restoring muscle carnitine to normal, and the optimal dosage regimen, have yet to be determined.

  2. Oral carnitine supplementation for dyslipidemia in chronic hemodialysis patients.

    PubMed

    Naini, Afsoon Emami; Sadeghi, Masoumeh; Mortazavi, Mojgan; Moghadasi, Mojdeh; Harandi, Asghar Amini

    2012-05-01

    Carnitine deficiency is a commonly observed problem in maintenance hemodialysis (MHD) patients, which results in altered metabolism of fatty acids and subsequently development of dyslipidemia. To evaluate the effect of oral L-carnitine (LC) supplementation on lipid profile of adult MHD patients, we studied 30 of them (19 males, 11 females) who received LC supplementation of 250 mg tablets three times a day for eight weeks. They were compared with 30 matched patients as a control group. Serum lipid profiles were compared before and after the intervention between the two groups. There was a significant decrease of the values of the lipid profile in the intervention group before and after carnitine supplementation including the mean values of total cholesterol (190 ± 36.8 vs. 177 ± 31.2 mg/dL), triglyceride (210 ± 64.7 vs. 190 ± 54.1 mg/dL) and LDL-cholesterol (117 ± 30.1 vs. 106 ± 26.3 mg/dL), while the values did not change siginificantly from base line in the control group. However, the difference for HDL-cholesterol in intervention group was not statistically significant. None of the patients dropped out of the study due to drug side effects. Oral LC supplementation (750 mg/day) is able to improve lipid profile in patients on MHD. Further long-term studies with adequate sample size are needed to define the population of patients who would benefit more from carnitine therapy and the optimal dose and the most efficient route for administration of the drug.

  3. Chronic Oral L-Carnitine Supplementation Drives Marked Plasma TMAO Elevations in Patients with Organic Acidemias Despite Dietary Meat Restrictions.

    PubMed

    Miller, Marcus J; Bostwick, Bret L; Kennedy, Adam D; Donti, Taraka R; Sun, Qin; Sutton, V Reid; Elsea, Sarah H

    2016-01-01

    Recent studies have implicated trimethylamine N-oxide (TMAO) in atherosclerosis, raising concern about L-carnitine, a common supplement for patients with inborn errors of metabolism (IEMs) and a TMAO precursor metabolized, in part, by intestinal microbes. Dietary meat restriction attenuates carnitine-to-TMAO conversion, suggesting that TMAO production may not occur in meat-restricted individuals taking supplemental L-carnitine, but this has not been tested. Here, we mine a metabolomic dataset to assess TMAO levels in patients with diverse IEMs, including organic acidemias. These data were correlated with clinical information and confirmed using a quantitative TMAO assay. Marked plasma TMAO elevations were detected in patients treated with supplemental L-carnitine, including those on a meat-free diet. On average, patients with an organic acidemia had ~45-fold elevated [TMAO], as compared to the reference population. This effect was mitigated by metronidazole therapy lasting 7 days each month. Collectively, our data show that TMAO production occurs at high levels in patients with IEMs receiving oral L-carnitine. Further studies are needed to determine the long-term safety and efficacy of chronic oral L-carnitine supplementation and whether suppression or circumvention of intestinal bacteria may improve L-carnitine therapy.

  4. Carnitine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Carnitine (L-g-trimethylamino-ß-hydroxybutyrate) functions metabolically as a covalent molecular chaperone of acyl compounds esterified to its hydroxyl moiety (1,2). The quintessentialmetabolic function of L-carnitine is to shuttle long-chain FAs (LCFAs)2 across the inner mitochondrial membrane to t...

  5. Inflammation and L-carnitine therapy in hemodialysis patients: a review.

    PubMed

    Khalatbari-Soltani, Saman; Tabibi, Hadi

    2015-06-01

    Inflammation is a common complication in hemodialysis (HD) patients with no valid treatment strategy. In addition, carnitine deficiency occurs frequently in HD patients because of intradialytic loss of carnitine, impaired de novo carnitine renal synthesis, and reduced dietary intake. It appears that carnitine deficiency is related to inflammation in HD patients. A few clinical trials have investigated the effect of L-carnitine supplement on inflammatory markers in HD patients. All studies in this field, except one, showed that L-carnitine could significantly reduce C-reactive protein and serum amyloid A, as two systemic inflammation markers, in HD patients. Therefore, considering high prevalence of inflammation and carnitine deficiency in HD patients, L-carnitine therapy is a reasonable approach for reducing systemic inflammation and its complications in these patients.

  6. Carnitine deficiency in children receiving continuous renal replacement therapy.

    PubMed

    Sgambat, Kristen; Moudgil, Asha

    2016-01-01

    Carnitine deficiency is known to occur in chronic hemodialysis; however, the effect of continuous renal replacement therapy (CRRT) on carnitine homeostasis has not been studied. We hypothesized that children receiving CRRT are at risk for deficiency because of continuous removal, absent intake, decreased production, and comorbidities related to critical illness. Records of patients with acute kidney injury receiving CRRT at Children's National Health System between 2011 and 2014 were reviewed for total carnitine (TC), free carnitine (FC), feeding modality, severity of illness, and survival outcome. The proportion of carnitine-deficient patients at baseline, 1, 2, and ≥3 weeks on CRRT were compared by chi-square, and relationships with other variables assessed by Pearson's correlation and logistic regression. The study group included 42 CRRT patients, age 7.9 + 1.1 years. At baseline, 30.7% and 35.7% of patients were TC and FC deficient. Within 1 week, 64.5% (P = 0.03) and 70% (P = 0.03) were TC and FC deficient, and prevalence of deficiency increased to 80% (P = 0.01) and 90% (P = 0.008) by 2 weeks; 100% of patients were TC and FC deficient after being on CRRT for ≥3 weeks (P = 0.005 and P = 0.01, respectively, vs. baseline). TC and FC levels negatively correlated with days on CRRT (r = -0.39, P = 0.001 and r = -0.35, P = 0.005). Patients with TC and FC deficiency had 5.9 and 4.9 greater odds of death than those with normal levels (P = 0.02 and P = 0.03). Carnitine is significantly and rapidly depleted with longer time on CRRT, and carnitine deficiency is associated with increased mortality. Consequences of deficiency and benefits of supplementation in the pediatric CRRT population should be investigated.

  7. Combination therapy with losartan and L-carnitine protects against endothelial dysfunction of streptozotocin-induced diabetic rats.

    PubMed

    Sleem, Mostafa; Taye, Ashraf; El-Moselhy, Mohamed A; Mangoura, Safwat A

    2014-12-05

    Endothelial dysfunction is a critical factor during the initiation of diabetic cardiovascular complications and angiotensin II appears to play a pivotal role in this setting. The present study aimed to investigate whether the combination therapy with losartan and the nutritional supplement, L-carnitine can provide an additional protection against diabetes-associated endothelial dysfunction and elucidate the possible mechanism(s) underlying this effect. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg) in rat. Effects of losartan (20 mg/kg, orally, 3 months) and L-carnitine (200 mg/kg, orally, 3 months) on tumor necrosis factor (TNF)-α, oxidative stress parameters, endothelial nitric oxide synthase expression (eNOS), and vascular function were evaluated. Our results showed a marked increase in aortic superoxide anion (O2(-)) production and serum malondialdehyde (MDA) level alongside attenuating antioxidant enzyme capacities in diabetic rats. This was associated with a significant increase in anigiotensin II type 1 receptor gene expression and TNF-α serum level of diabetic rats alongside reducing aortic eNOS gene expression and nitric oxide (NO) bioavailability. The single or combined administration of losartan and L-carnitine significantly inhibited these changes. Additionally, the vascular endothelium-dependent relaxation with acetylcholine (ACh) in aortic diabetic rat was significantly ameliorated by the single and combined administration of losartan or L-carnitine. Noteworthy, the combination therapy exhibited a more profound response over the monotherapy. Collectively, our results demonstrate that the combined therapy of losartan and L-carnitine affords additive beneficial effects against diabetes-associated endothelial dysfunction, possibly via normalizing the dysregulated eNOS and reducing the inflammation and oxidative stress in diabetic rats.

  8. [Therapy of arrhythmia induced by myocardial ischemia. Association of L-carnitine, propafenone and mexiletine].

    PubMed

    Mondillo, S; Faglia, S; D'Aprile, N; Mangiacotti, L; Campolo, M A; Agricola, E; Palazzuoli, V

    1995-12-01

    To assess the anti-arrythmic effect of L-carnitina, propafenone and mexiletine, we tested the drugs in 50 patients with effort angina and ventricular ectopic beats (VEB). The patients were randomized in 5 groups: Group A: was treated with oral L-carnitine at the dose of 2 g x 3 for two weeks. Group B: oral propafenone at the dose of 300 mg x 3 for two weeks. Group C: as group B+L-carnitine+g x 3 at the second weeks. Group D: oral mexiletine at the dose of 200 mg x 3 for two weeks. Group E: as group D+L-carnitine 2 gr x 3 at the second week. After 7 and 14 days of treatment, in all patients an Holter examination was performed. Our results show that L-carnitine exerts a significant reduction of the VEB and its administration potentiates the anti-arrythmic effect of propafenone and mexiletine.

  9. Carnitine levels and cardiac functions in children with solid malignancies receiving doxorubicin therapy

    PubMed Central

    Khositseth, Anant; Jirasakpisarn, Suwadee; Pakakasama, Samart; Choubtuym, Lulin; Wattanasirichaigoon, Duangrurdee

    2011-01-01

    Aim: Previous studies demonstrated l-carnitine decreasing doxorubicin-induced cardiotoxicity. Our objectives were to study carnitine levels and cardiac functions in children treated with doxorubicin and the effect of short-term l-carnitine supplements. Materials and Methods: Serial carnitine levels and cardiac functions were obtained in children with newly diagnosed solid malignancies before doxorubicin, after cumulative doses of ≥150 mg/m2 and ≥300 mg/m2, respectively. Oral l-carnitine 100 mg/kg/day for 3 days were given to the children treated with doxorubicin at cumulative doses of ≥150 mg/m2 and ≥300 mg/m2. Carnitine levels and cardiac functions were also obtained in those children before and after short-term oral l-carnitine at each cumulative dose of doxorubicin. Results: Five children (3 females), median age of 9.1 years (range 1.5–13 years) with newly diagnosed solid malignancies were enrolled in the study. Free carnitine (FC) tended to decrease while acyl-carnitine (AC) increased making AC/FC ratio increased after cumulative dose of ≥150 and ≥300 mg/m2 but the statistics was not significant. Left ventricular (LV) systolic function was not significantly changed. Interestingly, LV global function (LV myocardial performance index) was significantly increased after 150 mg/m2 (median 0.39, 0.27–0.51) and 300 mg/2 (median 0.46, 0.27–0.50) when compared to baseline (median 0.28, 0.14–0.48) (P=0.05). Carnitine levels and cardiac functions were not significantly changed after oral l-carnitine supplement at cumulative dose of ≥150 mg/m2 (n=6) and ≥300 mg/m2 (n=9). Conclusions: Carnitine levels tended to decrease after doxorubicin treatment. LV global dysfunction was documented early after doxorubicin. However, short-term l-carnitine supplement did not improve cardiac function. PMID:21731215

  10. Translating the basic knowledge of mitochondrial functions to metabolic therapy: role of L-carnitine.

    PubMed

    Marcovina, Santica M; Sirtori, Cesare; Peracino, Andrea; Gheorghiade, Mihai; Borum, Peggy; Remuzzi, Giuseppe; Ardehali, Hossein

    2013-02-01

    Mitochondria play important roles in human physiological processes, and therefore, their dysfunction can lead to a constellation of metabolic and nonmetabolic abnormalities such as a defect in mitochondrial gene expression, imbalance in fuel and energy homeostasis, impairment in oxidative phosphorylation, enhancement of insulin resistance, and abnormalities in fatty acid metabolism. As a consequence, mitochondrial dysfunction contributes to the pathophysiology of insulin resistance, obesity, diabetes, vascular disease, and chronic heart failure. The increased knowledge on mitochondria and their role in cellular metabolism is providing new evidence that these disorders may benefit from mitochondrial-targeted therapies. We review the current knowledge of the contribution of mitochondrial dysfunction to chronic diseases, the outcomes of experimental studies on mitochondrial-targeted therapies, and explore the potential of metabolic modulators in the treatment of selected chronic conditions. As an example of such modulators, we evaluate the efficacy of the administration of L-carnitine and its analogues acetyl and propionyl L-carnitine in several chronic diseases. L-carnitine is intrinsically involved in mitochondrial metabolism and function as it plays a key role in fatty acid oxidation and energy metabolism. In addition to the transportation of free fatty acids across the inner mitochondrial membrane, L-carnitine modulates their oxidation rate and is involved in the regulation of vital cellular functions such as apoptosis. Thus, L-carnitine and its derivatives show promise in the treatment of chronic conditions and diseases associated with mitochondrial dysfunction but further translational studies are needed to fully explore their potential.

  11. L-carnitine in cardiogenic shock therapy: pharmacodynamic aspects and clinical data.

    PubMed

    Corbucci, G G; Loche, F

    1993-01-01

    Following our previous work on biochemical and clinical aspects of cardiogenic shock, we carried out an open study on 27 patients hospitalized in shock condition and investigated for the entire period of permanence in intensive care units (ICU). The subjects were treated with high doses of L-carnitine following previous results on the use of this molecule in conditions of oxidative damage due to acute cellular hypoxia. When compared with the data reported in the literature, the results obtained in this study show a surprisingly positive trend for the carnitine-treated patients in terms of survival rate to the cardiogenic shock. This finding and statistical analysis of the clinical parameters confirm the suggestion that L-carnitine could be credited with a new and interesting role in the therapy of cardiogenic shock.

  12. Effects of oral L-carnitine supplementation in low-birth-weight premature infants maintained on human milk.

    PubMed

    Melegh, B; Kerner, J; Sándor, A; Vincellér, M; Kispál, G

    1987-01-01

    Effects of oral L-carnitine supplementation on fat and protein metabolism have been studied in 20 low-birth-weight premature infants (mean weight at birth 1.519 g, range 1,200-1,880 g) fed with pooled pasteurized human milk. Throughout 7 consecutive days, started at various postnatal ages (range 10-33 days) infants were fed exclusively with milk containing 300 nmol/ml L-carnitine as added supplement. The amount of extra carnitine intake ranged from 42.6 to 72.0 mumol/kg/day. Until day 5 of supplementation there was a continuous increase in the daily urinary excretion of total carnitine, which levelled off thereafter, corresponding approximately to 50% of the extra L-carnitine intake, indicating that a part of the supplement was retained by the body. Total, free and esterified carnitine levels were significantly elevated in the plasma at the end of the study period. The increased levels of acylcarnitines in plasma and urine indicate that the carnitine supplement was taken up by tissues and entered the intermediary metabolism. Plasma triglyceride level was decreased, whereas 3-hydroxybutyrate level was increased at the end of supplementation, indicating an enhanced fat utilization. Plasma and urine analysis also revealed an altered nitrogen handling. There was a marked decrease in plasma urea level as well as a significant fall in the urea and total N excretion, with a trend of decrease in excretion of 3-methylhistidine, suggesting a reduced amino acid and protein catabolism during L-carnitine supplementation.

  13. Oral Anticoagulant Therapy

    PubMed Central

    Gallus, Alexander S.; Wittkowsky, Ann; Crowther, Mark; Hylek, Elaine M.; Palareti, Gualtiero

    2012-01-01

    Background: The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management. Methods: We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban Results: The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal. Conclusions: There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban. PMID:22315269

  14. Carnitine and physical exercise.

    PubMed

    Heinonen, O J

    1996-08-01

    Carnitine plays a central role in fatty acid (FA) metabolism. It transports long-chain fatty acids into mitochondria for beta-oxidation. Carnitine also modulates the metabolism of coenzyme-A (CoA). It is not surprising that the use of supplementary carnitine to improve physical performance has become widespread in recent years, although there is no unequivocal support to this practice. However, critical reflections and current scientific-based knowledge are important because the implications of reduced or increased carnitine concentrations in vivo are not thoroughly understood. Several rationales have been forwarded in support of the potential ergogenic effects of oral carnitine supplementation. However, the following arguments derived from established scientific observations may be forwarded: (i) carnitine supplementation neither enhances FA oxidation in vivo or spares glycogen or postpones fatigue during exercise. Carnitine supplementation does not unequivocally improve performance of athletes; (ii) carnitine supplementation does not reduce body fat or help to lose weight; (iii) in vivo pyruvate dehydrogenase complex (PDC) is fully active already after a few seconds of intense exercise. Carnitine supplementation induces no further activation of PDC in vivo; (iv) despite an increased acetyl-CoA/free CoA ratio, PDC is not depressed during exercise in vivo and therefore supplementary carnitine has no effect on lactate accumulation; (v) carnitine supplementation per se does not affect the maximal oxygen uptake (VO2max); (vi) during exercise there is a redistribution of free carnitine and acylcarnitines in the muscle but there is no loss of total carnitine. Athletes are not at risk for carnitine deficiency and do not have an increased need for carnitine. Although there are some theoretical points favouring potential ergogenic effects of carnitine supplementation, there is currently no scientific basis for healthy individuals or athletes to use carnitine

  15. Comparison of the Effects of Varicocelectomy and Oral L-carnitine on Sperm Parameters in Infertile Men with Varicocele

    PubMed Central

    Ghaderi, Ebrahim; Ganji, Omid

    2016-01-01

    Background Varicocele is defined as dilated and twisted veins of the pampiniform plexus in the spermatic cord. It is the most common cause of male infertility. There are various medical and surgical procedures for the treatment of this disease. Aim This study was aimed to compare the effects of oral administration of L-Carnitine and varicocelectomy on spermogram parameters. Materials and Methods This study was conducted as a double blind clinical trial without randomization. Inclusion criteria were, all married infertile men with varicocele. Patients chose their treatment personally and spermogram was carried out for all patients before and after the third and sixth months of treatment. Then, the sperm parameters of the two groups were compared using repeated measures ANOVA. Results In our study, trend of sperm count in the surgery group changed from 22 to 28.61 million (vs 34.6 to 45.37 in L-Carnitine group), motility changed from 21.74 to 35.38 percent (vs 33.9 to 47.48 in L-Carnitine group), normal sperm morphology changed from 46.25 to 60 percent (vs 56.61 to 69.7 in L-Carnitine group) and volume of semen changed from 3.5 to 4.17 cc (vs 2.95 to 4.33 in L-Carnitine group). These values were not statistically different between the two groups. Conclusion Based on the results of this study, we can say that medicinal treatment by administration of oral L-Carnitine is as effective as varicocelectomy in improving semen parameters and can be used as an alternative to surgery for varicocele grade II. PMID:27190879

  16. Ameliorating hypertension and insulin resistance in subjects at increased cardiovascular risk: effects of acetyl-L-carnitine therapy.

    PubMed

    Ruggenenti, Piero; Cattaneo, Dario; Loriga, Giacomina; Ledda, Franca; Motterlini, Nicola; Gherardi, Giulia; Orisio, Silvia; Remuzzi, Giuseppe

    2009-09-01

    Insulin resistance, a key component of the metabolic syndrome, is a risk factor for diabetes mellitus and cardiovascular disease. Acetyl-L-carnitine infusion acutely ameliorated insulin sensitivity in type 2 diabetics with insulin resistance. In this sequential off-on-off pilot study, we prospectively evaluated the effects of 24-week oral acetyl-L-carnitine (1 g twice daily) therapy on the glucose disposal rate (GDR), assessed by hyperinsulinemic euglycemic clamps, and components of the metabolic syndrome in nondiabetic subjects at increased cardiovascular risk a priori segregated into 2 groups with GDR < or =7.9 (n=16) or >7.9 (n=16) mg/kg per minute, respectively. Baseline GDR and systolic blood pressure were negatively correlated (n=32; P=0.001; r=-0.545), and patients with GDR < or =7.9 mg/kg per minute had higher systolic/diastolic blood pressure than those with higher GDR. Acetyl-L-carnitine increased GDR from 4.89+/-1.47 to 6.72+/-3.12 mg/kg per minute (P=0.003, Bonferroni-adjusted) and improved glucose tolerance in patients with GDR < or =7.9 mg/kg per minute, whereas it had no effects in those with higher GDRs. Changes in GDR were significantly different between groups (P=0.017, ANCOVA). Systolic blood pressure decreased from 144.0+/-13.6 to 135.1+/-8.4 mm Hg and from 130.8+/-12.4 to 123.8+/-10.8 mm Hg in the lower and higher GDR groups, respectively (P<0.05 for both; P<0.001 overall) and progressively recovered toward baseline over 8 weeks posttreatment. Total and high molecular weight adiponectin levels followed specular trends. Diastolic blood pressure significantly decreased only in those with higher GDRs. Treatment was well tolerated in all of the patients. Acetyl-L-carnitine safely ameliorated arterial hypertension, insulin resistance, impaired glucose tolerance, and hypoadiponectinemia in subjects at increased cardiovascular risk. Whether these effects may translate into long-term cardioprotection is worth investigating.

  17. Reversible weakness and encephalopathy while on long-term valproate treatment due to carnitine deficiency.

    PubMed

    Al-sharefi, Ahmed; Bilous, Rudy

    2015-09-02

    We describe a case of a 35-year-old woman who presented with bilateral leg weakness and encephalopathy while on long-term valproate therapy. She was diagnosed with valproate-induced encephalopathy due to carnitine deficiency. Clinical improvement occurred with oral carnitine supplementation. Our case report highlights the importance of considering carnitine deficiency in patients presenting with unexplained neurological signs while on long-term valproate treatment.

  18. L-Carnitine Preserves Endothelial Function in a Lamb Model of Increased Pulmonary Blood Flow

    PubMed Central

    Sharma, Shruti; Aramburo, Angela; Rafikov, Ruslan; Sun, Xutong; Kumar, Sanjiv; Oishi, Peter E.; Datar, Sanjeev A.; Raff, Gary; Xoinis, Kon; Kalkan, Gohkan; Fratz, Sohrab; Fineman, Jeffrey R.; Black, Stephen M.

    2013-01-01

    Background In our model of congenital heart disease (CHD) with increased pulmonary blood flow (Shunt), we have recently shown a disruption in carnitine homeostasis, associated with mitochondrial dysfunction and decreased eNOS/Hsp90 interactions that contribute to eNOS uncoupling, increased superoxide levels, and decreased bioavailable NO. Thus, we undertook this study to test the hypothesis that L-carnitine therapy would maintain mitochondrial function, and NO signaling. Methods Thirteen fetal lambs underwent in utero placement of an aortopulmonary graft. Immediately following delivery, lambs received daily treatment with oral L-carnitine or its vehicle. Results L-carnitine-treated lambs had decreased levels of acyl carnitine, and a reduced acyl carnitine: free carnitine ratio compared to vehicle treated Shunt lambs. These changes correlated with increased carnitine acetyl transferase (CrAT) protein and enzyme activity and decreased levels of nitrated CrAT. The lactate: pyruvate ratio was also decreased in L-carnitine-treated lambs. Hsp70 protein levels were significantly decreased and this correlated with increases in eNOS/Hsp90 interactions, NOS activity, NOx levels, and a significant decrease in eNOS-derived superoxide. Further, acetylcholine significantly decreased left pulmonary vascular resistance (PVR) only in L-carnitine-treated lambs. Conclusion L-carnitine therapy may improve the endothelial dysfunction noted in children with CHD, and has important clinical implications that warrant further investigation. PMID:23628882

  19. Carbohydrate, protein, and fat metabolism during exercise after oral carnitine supplementation in humans.

    PubMed

    Broad, Elizabeth M; Maughan, Ronald J; Galloway, Stuart D

    2008-12-01

    Twenty nonvegetarian active males were pair-matched and randomly assigned to receive 2 g of L-carnitine L-tartrate (LC) or placebo per day for 2 wk. Participants exercised for 90 min at 70% VO2max after 2 days of a prescribed diet (M +/- SD: 13.6 +/- 1.6 MJ, 57% carbohydrate, 15% protein, 26% fat, 2% alcohol) before and after supplementation. Results indicated no change in carbohydrate oxidation, nitrogen excretion, branched-chain amino acid oxidation, or plasma urea during exercise between the beginning and end of supplementation in either group. After 2 wk of LC supplementation the plasma ammonia response to exercise tended to be suppressed (0 vs. 2 wk at 60 min exercise, 97 +/- 26 vs. 80 +/- 9, and 90 min exercise, 116 +/- 47 vs. 87 +/- 25 micromol/L), with no change in the placebo group. The data indicate that 2 wk of LC supplementation does not affect fat, carbohydrate, and protein contribution to metabolism during prolonged moderate-intensity cycling exercise. The tendency toward suppressed ammonia accumulation, however, indicates that oral LC supplementation might have the potential to reduce the metabolic stress of exercise or alter ammonia production or removal, which warrants further investigation.

  20. Serum carnitine as an independent biomarker of malnutrition in patients with impaired oral intake

    PubMed Central

    Iwamoto, Junichi; Honda, Akira; Miyamoto, Yasunori; Miyazaki, Teruo; Murakami, Masashi; Saito, Yoshifumi; Ikegami, Tadashi; Miyamoto, Jiro; Matsuzaki, Yasushi

    2014-01-01

    Carnitine is a vitamin-like compound that plays important roles in fatty acid β-oxidation and the control of the mitochondrial coenzyme A/acetyl-CoA ratio. However, carnitine is not added to ordinary enteral nutrition or total parenteral nutrition. In this study, we determined the serum carnitine concentrations in subjects receiving ordinary enteral nutrition (EN) or total parenteral nutrition (TPN) and in patients with inflammatory bowel diseases to compare its levels with those of other nutritional markers. Serum samples obtained from 11 EN and 11 TPN patients and 82 healthy controls were examined. In addition, 10 Crohn’s disease and 10 ulcerative colitis patients with malnutrition who were barely able to ingest an ordinary diet were also evaluated. Carnitine and its derivatives were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The carnitine concentrations in EN and TPN subjects were significantly lower compared with those of the control subjects. Neither the serum albumin nor the total cholesterol level was correlated with the carnitine concentration, although a significant positive correlation was found between the serum albumin and total cholesterol levels. Indeed, patients with CD and UC showed significantly reduced serum albumin and/or total cholesterol levels, but their carnitine concentrations remained normal. In conclusion, only a complete blockade of an ordinary diet, such as EN or TPN, caused a reduction in the serum carnitine concentration. Serum carnitine may be an independent biomarker of malnutrition, and its supplementation is needed in EN and TPN subjects even if their serum albumin and total cholesterol levels are normal. PMID:25411530

  1. Serum carnitine as an independent biomarker of malnutrition in patients with impaired oral intake.

    PubMed

    Iwamoto, Junichi; Honda, Akira; Miyamoto, Yasunori; Miyazaki, Teruo; Murakami, Masashi; Saito, Yoshifumi; Ikegami, Tadashi; Miyamoto, Jiro; Matsuzaki, Yasushi

    2014-11-01

    Carnitine is a vitamin-like compound that plays important roles in fatty acid β-oxidation and the control of the mitochondrial coenzyme A/acetyl-CoA ratio. However, carnitine is not added to ordinary enteral nutrition or total parenteral nutrition. In this study, we determined the serum carnitine concentrations in subjects receiving ordinary enteral nutrition (EN) or total parenteral nutrition (TPN) and in patients with inflammatory bowel diseases to compare its levels with those of other nutritional markers. Serum samples obtained from 11 EN and 11 TPN patients and 82 healthy controls were examined. In addition, 10 Crohn's disease and 10 ulcerative colitis patients with malnutrition who were barely able to ingest an ordinary diet were also evaluated. Carnitine and its derivatives were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The carnitine concentrations in EN and TPN subjects were significantly lower compared with those of the control subjects. Neither the serum albumin nor the total cholesterol level was correlated with the carnitine concentration, although a significant positive correlation was found between the serum albumin and total cholesterol levels. Indeed, patients with CD and UC showed significantly reduced serum albumin and/or total cholesterol levels, but their carnitine concentrations remained normal. In conclusion, only a complete blockade of an ordinary diet, such as EN or TPN, caused a reduction in the serum carnitine concentration. Serum carnitine may be an independent biomarker of malnutrition, and its supplementation is needed in EN and TPN subjects even if their serum albumin and total cholesterol levels are normal.

  2. Oral targeted therapy for cancer

    PubMed Central

    Carrington, Christine

    2015-01-01

    SUMMARY Oral targeted therapies are increasingly being used to treat cancer. They work by interfering with specific molecules or pathways involved in tumour growth. It is essential that health professionals managing patients taking these drugs have appropriate training and skills. They should be aware of potential adverse effects and drug interactions, and be able to manage toxicities when they occur. Despite the selectivity of these targeted therapies, they still have serious adverse effects including skin reactions, diarrhoea and altered organ function. PMID:26648656

  3. The clinical and metabolic effects of rapid weight loss in obese pet cats and the influence of supplemental oral L-carnitine.

    PubMed

    Center, S A; Harte, J; Watrous, D; Reynolds, A; Watson, T D; Markwell, P J; Millington, D S; Wood, P A; Yeager, A E; Erb, H N

    2000-01-01

    The efficacy, safety, and metabolic consequences of rapid weight loss in privately owned obese cats by means of a canned weight-reduction diet and the influence of orally administered L-carnitine on rate of weight loss, routine clinical evaluations, hepatic ultrasonography, plasma amino acid profiles, and carnitine analytes were evaluated. A double-blinded placebo-controlled design was used with cats randomly divided into 2 groups: Group 1 (n = 14) received L-carnitine (250 mg PO q24h) in aqueous solution and group 2 (n = 10) received an identical-appearing water placebo. Median obesity (body condition scores and percentage ideal body weight) in each group was 25%. Caloric intake was restricted to 60% of maintenance energy requirements (60 kcal/kg) for targeted ideal weight. The reducing formula was readily accepted by all cats. Significant weight loss was achieved by week 18 in each group without adverse effects (group 1 = 23.7%, group 2 = 19.6%). Cats receiving carnitine lost weight at a significantly faster rate (P < .05). Significant increases in carnitine values developed in each group (P < .02). However, significantly higher concentrations of all carnitine moieties and a greater percentage of acetylcarnitine developed in cats of group 1 (P < .01). The dietary formula and described reducing strategy can safely achieve a 20% weight reduction within 18 weeks in obese cats. An aqueous solution of L-carnitine (250 mg PO q12h) was at least partially absorbed, was nontoxic, and significantly increased plasma carnitine analyte concentrations as well as rate of weight loss.

  4. Partial muscle carnitine palmitoyltransferase-A deficiency

    SciTech Connect

    Ross, N.S.; Hoppel, C.L.

    1987-01-02

    After initiation of ibuprofen therapy, a 45-year-old woman developed muscle weakness and tenderness with rhabdomyolysis, culminating in respiratory failure. A muscle biopsy specimen showed a vacuolar myopathy, and markedly decreased muscle carnitine content and carnitine palmitoyltransferase activity. Following recovery, muscle carnitine content was normal but carnitine palmitoyltransferase activity was still abnormally low. The ratio of palmitoyl-coenzyme A plus carnitine to palmitoylcarnitine oxidation by muscle mitochondria isolated from the patient was markedly decreased. The authors conclude that transiently decreased muscle carnitine content interacted with partial deficiency of carnitine palmitoyltransferase-A to produce rhabdomyolysis and respiratory failure and that ibuprofen may have precipitated the clinical event.

  5. L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders.

    PubMed

    Ribas, Graziela S; Vargas, Carmen R; Wajner, Moacir

    2014-01-10

    In recent years increasing evidence has emerged suggesting that oxidative stress is involved in the pathophysiology of a number of inherited metabolic disorders. However the clinical use of classical antioxidants in these diseases has been poorly evaluated and so far no benefit has been demonstrated. l-Carnitine is an endogenous substance that acts as a carrier for fatty acids across the inner mitochondrial membrane necessary for subsequent beta-oxidation and ATP production. Besides its important role in the metabolism of lipids, l-carnitine is also a potent antioxidant (free radical scavenger) and thus may protect tissues from oxidative damage. This review addresses recent findings obtained from patients with some inherited neurometabolic diseases showing that l-carnitine may be involved in the reduction of oxidative damage observed in these disorders. For some of these diseases, reduced concentrations of l-carnitine may occur due to the combination of this compound to the accumulating toxic metabolites, especially organic acids, or as a result of protein restricted diets. Thus, l-carnitine supplementation may be useful not only to prevent tissue deficiency of this element, but also to avoid oxidative damage secondary to increased production of reactive species in these diseases. Considering the ability of l-carnitine to easily cross the blood-brain barrier, l-carnitine supplementation may also be beneficial in preventing neurological damage derived from oxidative injury. However further studies are required to better explore this potential.

  6. Carnitine in maintenance hemodialysis patients.

    PubMed

    Guarnieri, Gianfranco

    2015-03-01

    Carnitine is a conditionally essential metabolite that plays a critical role in cell physiology. Carnitine is necessary for fatty acid transport to sites of beta-oxidation in the mitochondria, where it also helps to prevent organic acid accumulation. Because of these key regulatory functions, carnitine represents a crucial determinant of mitochondrial energy metabolism, whose deficiency may lead to metabolic and clinical disturbances. Loss of carnitine through dialytic membranes occurs in maintenance hemodialysis, resulting in potential carnitine depletion and relative increments of esterified carnitine forms. Carnitine supplementation has been reported to counteract some of these alterations and has been associated with some clinical benefits, such as enhanced response to erythropoietin as well as improvement in exercise tolerance, intradialytic symptom, hyperparathyroidism, insulin resistance, inflammatory and oxidant status, protein balance, lipid profile, cardiac function, and quality of life. Carnitine supplementation has an attractive theoretical rationale; however, there are no definitive supportive studies and conclusive evidence that L-carnitine supplementation in maintenance hemodialysis patients could improve these conditions. A trial of carnitine administration could be attempted for 6 to 12 months only in selected patients on dialysis who do not adequately respond to standard therapies, in the presence of symptomatology, and in conjunction with patient dialysis age and documented L-carnitine deficiency.

  7. Hypocalcaemia following thyroidectomy unresponsive to oral therapy.

    PubMed

    Etheridge, Zac C; Schofield, Christopher; Prinsloo, Peter J J; Sturrock, Nigel D C

    2014-01-01

    Hypocalcaemia due to hypoparathyroidism following thyroidectomy is a relatively common occurrence. Standard treatment is with oral calcium and vitamin D replacement therapy; lack of response to oral therapy is rare. Herein we describe a case of hypoparathyroidism following thyroidectomy unresponsive to oral therapy in a patient with a complex medical history. We consider the potential causes in the context of calcium metabolism including: poor adherence, hungry bone syndrome, malabsorption, vitamin D resistance, bisphosphonate use and functional hypoparathyroidism secondary to magnesium deficiency. Malabsorption due to intestinal hurry was likely to be a contributory factor in this case and very large doses of oral therapy were required to avoid symptomatic hypocalcaemia.

  8. [Oral ciprofloxacin therapy in salpingitis].

    PubMed

    De Wilde, R

    1988-01-01

    Thirty patients with clinical pelvic inflammatory disease were studied. Diagnosis was confirmed by laparoscopy. To determine the microbiological etiology, swab specimen for detection of aerobic, anaerobic and chlamydial infections were obtained from the endocervix, fimbriae and cul-de-sac. In 22 of 30 patients, microorganisms were detected. The patients received ciprofloxacin 2 X 750 mg p.o. daily at 12 hours interval for 10 days. During and after therapy, bacteriological examinations of the endocervix were performed. Based on the microbiological evaluation and clinical aspects, the bacteriological response and clinical efficacy were 86%. Laboratory analysis showed no alterations of blood values. As side effects we noticed gastrointestinal complaints (6/30), candidiasis vulvovaginalis (6/30), allergic exanthema (5/30) and non-bacterial cystitis (2/30). Oral ciprofloxacin-monotherapy proved to be safe and effective in pelvic inflammatory disease.

  9. Multiple acyl-CoA dehydrogenation deficiency as decreased acyl-carnitine profile in serum.

    PubMed

    Wen, Bing; Li, Duoling; Li, Wei; Zhao, Yuying; Yan, Chuanzhu

    2015-06-01

    We report a case with late onset riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency (MADD) characterized by decreased acyl-carnitine profile in serum which is consistent with primary systemic carnitine deficiency (CDSP) while just the contrary to a typical MADD. This patient complained with muscle weakness, muscle pain and intermittent vomiting, and was diagnosed as polymyositis, received prednisone therapy before consulted with us. Muscle biopsy revealed mild lipid storage. The findings of serum acyl-carnitines were consistent with CDSP manifesting as decreased free and total carnitines in serum. But oral L-carnitine supplementation was not very effective to this patient and mutation analysis of the SLC22A5 gene for CDSP was normal. Later, another acyl-carnitine analysis revealed a typical MADD profile in serum, which was characterized by increased multiple acyl-carnitines. Compound heterozygous mutations were identified in electron transferring-flavoprotein dehydrogenase (ETFDH) gene which confirmed the diagnosis of MADD. After administration of riboflavin, he improved dramatically, both clinically and biochemically. Thus, late onset riboflavin-responsive MADD should be included in the differential diagnosis for adult carnitine deficiency.

  10. Regression of oral hairy leukoplakia after orally administered acyclovir therapy.

    PubMed

    Resnick, L; Herbst, J S; Ablashi, D V; Atherton, S; Frank, B; Rosen, L; Horwitz, S N

    1988-01-15

    To define the role of Epstein-Barr virus (EBV) in the pathogenesis of oral hairy leukoplakia, 13 human immunodeficiency virus-seropositive men with clinical and histologic evidence of oral hairy leukoplakia were enrolled in an open-label trial of orally administered acyclovir therapy (3.2 g/d for 20 days). Of six patients who received therapy, five exhibited clinical regression. Once therapy was discontinued, recurrences occurred in all responders. Among seven patients who refused therapy, no spontaneous remissions occurred. Before therapy, EBV replication within the leukoplakia was demonstrated by immunofluorescence tissue staining or electron microscopy in five patients who were studied. Human papillomavirus was not detected by immunocytochemistry or electron microscopy from tissue specimens of six patients. After therapy, biopsy specimens from two patients with complete responses revealed a normalization of histologic abnormalities and an inability to detect EBV in previously involved mucosa by immunofluorescence or in situ DNA hybridization assays. It was concluded that EBV replication within the epithelial cells of the tongue is necessary for the development of oral hairy leukoplakia.

  11. Oral therapy of infant diarrhoea.

    PubMed

    Ransome-Kuti, O; Bamisaiye, A

    1978-08-26

    Immediate oral therapy at home by the mother using a sugar-salt solution offers a real prospect of reducing mortality from gastroenteritis among preschool children in the developing world. The sugar-salt solution enables the mother to take action against a disease which is the most frequent cause of death among young children. In Lagos, Nigeria, knowledge of the treatment has diffused rapidly in a low-income community served by a clinic run by the Institute of Child Health. In a recent study, women expecting their 1st child and others who had never used the service were able to describe the sugar-salt solution treatment taught to all who attend the clinic. However, of the 217 women who described the method, less than 1/2 (34%) could give the correct proportions of sugar and salt to be used (4 teaspoons and 1/4 teaspoon respectively in a standard local beer bottle filled with water). Most errors involved the use of too much salt. In nearly 1/2 these cases, 4 times too much salt was described, and in 3 cases, 16 times too much salt. Under these circumstances, we can expect a possible increase in children admitted with hypernatremia, a situation which would bring the method into disrepute. Any attempt to transfer health skills to mothers in developing countries must recognize, as in this example, the problems posed by lack of education and unfamiliarity with measurement terms such as "1/4" or even "a teaspoon." What is required is a simple measuring spoon giving the actual quantity to be used. Manufactured on a large scale in plastic, this would be inexpensive. Ideally, every mother of a preschool child should have 1, but where this is not possible, all health workers should have such spoons so that they can measure into a mother's hand the correct amounts. In this way the mother can make correct use of a treatment which has such potential for saving lives.

  12. Acetyl-L-Carnitine as an Adjunctive Therapy in the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Placebo-Controlled Trial

    ERIC Educational Resources Information Center

    Abbasi, Seyed-Hesameddin; Heidari, Shahram; Mohammadi, Mohammad-Reza; Tabrizi, Mina; Ghaleiha, Ali; Akhondzadeh, Shahin

    2011-01-01

    The objective of this study was to test whether a previous observed Acetyl-L-carnitine (ALC) treatment effect could be repeated in an ALC adjunctive therapy treatment trial of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This was a six-week, randomized clinical trial undertaken in an outpatient child and adolescent…

  13. Plasma carnitine concentrations in patients undergoing open heart surgery.

    PubMed

    Nemoto, Shintaro; Yasuhara, Kiyomitsu; Nakamura, Katsutoshi; Miyoshi, Yutaka; Sakai, Akira

    2004-02-01

    Carnitine is an essential cofactor for fatty acid (FA) metabolism, the predominant source of ATP in the normal aerobic heart. During myocardial ischemia, FA metabolism is impaired and tissue carnitine levels are depleted. Since the heart cannot synthesize carnitine, plasma carnitine could play an important role in maintaining myocardial carnitine levels during reperfusion. The purpose of this study was to determine the incidence of abnormal plasma carnitine concentrations in open heart surgery. Blood samples were obtained from eleven patients before, immediately after, and two hours after cardiopulmonary bypass (CPB). Total and free carnitine levels were significantly reduced immediately after CPB (p<0.01) and remained depressed until two hours after CPB (p<0.01 vs. pre CPB), while acyl carnitine levels were unchanged over the course of this study. These depressed free carnitine levels might affect cardiac metabolism in the heart after open heart surgery. Carnitine supplement might be a useful adjunct in the therapy after open heart surgery.

  14. Erythema nodosum and oral contraceptive therapy.

    PubMed

    Winkelman, R K

    1978-04-03

    A generalized erythema nodosum developed in a 17 year old girl receiving oral contraceptive therapy, which was immediately discontinued. The erythema failed to respond to tetracycline, potassium iodide or prednisone therapy (partially successful), and recurred 6 times, usually just before menstruation. The recommended therapy is bed rest, salicylates and 10 cm roller elastic bandages. No medication can help in the face of unrestricted physical activity.

  15. [Adherence to oral antineoplastic therapy].

    PubMed

    Olivera-Fernandez, R; Fernandez-Ribeiro, F; Piñeiro-Corrales, G; Crespo-Diz, C

    2014-11-03

    Introducción: Los tratamientos antineoplasicos orales presentan ventajas en cuanto a coste, comodidad y mejora potencial en la calidad de vida respecto al tratamiento endovenoso, pero es mas dificil controlar la adherencia y monitorizar los efectos adversos. El objetivo de este estudio fue conocer la adherencia real en pacientes con antineoplasicos orales en nuestro centro, analizar la influencia de las caracteristicas del paciente y del tratamiento, identificar motivos de no adherencia, oportunidades de mejora en la atencion farmaceutica y evaluar la posible relacion adherencia y respuesta al tratamiento. Método: estudio prospectivo observacional de cuatro meses de duracion, en los pacientes con tratamiento antineoplasico oral dispensado desde la consulta de farmacia oncologica. Para la recogida de datos se utilizaron: orden medica, historia clinica y visita con entrevistas al paciente. Resultados: Se evaluaron un total de 141 pacientes. Un 72% se considero totalmente adherente, mientras que en un 28% se detecto algun tipo de no adherencia. El tiempo desde el diagnostico y la presencia de efectos adversos fueron las variables que afectaron a la adherencia. No se pudo demostrar relacion entre adherencia y respuesta al tratamiento. Conclusiones: La adherencia al tratamiento antineoplasico oral en nuestro centro fue del 72%, identificando oportunidades de mejora en la atencion farmaceutica dirigidas a prevenir los efectos adversos y a potenciar la adherencia de nuestros pacientes.

  16. Science review: Carnitine in the treatment of valproic acid-induced toxicity – what is the evidence?

    PubMed Central

    Lheureux, Philippe ER; Penaloza, Andrea; Zahir, Soheil; Gris, Mireille

    2005-01-01

    Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well tolerated, but rare serious complications may occur in some patients receiving VPA chronically, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity (VHT) and VPA-induced hyperammonaemic encephalopathy (VHE). Some data suggest that VHT and VHE may be promoted by carnitine deficiency. Acute VPA intoxication also occurs as a consequence of intentional or accidental overdose and its incidence is increasing, because of use of VPA in psychiatric disorders. Although it usually results in mild central nervous system depression, serious toxicity and even fatal cases have been reported. Several studies or isolated clinical observations have suggested the potential value of oral L-carnitine in reversing carnitine deficiency or preventing its development as well as some adverse effects due to VPA. Carnitine supplementation during VPA therapy in high-risk patients is now recommended by some scientific committees and textbooks, especially paediatricians. L-carnitine therapy could also be valuable in those patients who develop VHT or VHE. A few isolated observations also suggest that L-carnitine may be useful in patients with coma or in preventing hepatic dysfunction after acute VPA overdose. However, these issues deserve further investigation in controlled, randomized and probably multicentre trials to evaluate the clinical value and the appropriate dosage of L-carnitine in each of these conditions. PMID:16277730

  17. Effects of Oral L-Carnitine Supplementation on Lipid Profile, Anemia, and Quality of Life in Chronic Renal Disease Patients under Hemodialysis: A Randomized, Double-Blinded, Placebo-Controlled Trial

    PubMed Central

    Emami Naini, Afsoon; Moradi, Mahnaz; Mortazavi, Mojgan; Amini Harandi, Asghar; Hadizadeh, Mehdi; Shirani, Farhad; Basir Ghafoori, Hamed; Emami Naini, Pardis

    2012-01-01

    In patients on maintenance hemodialysis several factors reduce the body stored carnitine which could lead to dyslipidemia, anemia, and general health in these patients. We evaluated the effect of oral L-carnitine supplementation on lipid profiles, anemia, and quality of life (QOL) in hemodialysis patients. In a randomized, double-blinded, placebo-controlled trial, end-stage renal disease (ESRD) patients on hemodialysis received either L-carnitine 1 g/d (n = 24) or placebo (27 patients) for 16 weeks. At the end of the study, there was a significant decrease in triglyceride (−31.1 ± 38.7 mg/dL, P = 0.001) and a significant increase in HDL (3.7 ± 2.8 mg/dL, P < 0.001) levels in the carnitine group. Decrease in total cholesterol (−6.6 ± 16.0 mg/dL, P = 0.075) and increase in hemoglobin (0.7 ± 1.7 g/dL, P = 0.081) concentrations in the carnitine group were not significant. There was no statistically significant changes in LDL in any group (P > 0.05). Erythropoietin dose was significantly decreased in both the carnitine (−4750 ± 5772 mg, P = 0.001) and the placebo group (−2000 ± 4296 mg, P < 0.05). No improvement was observed in QOL scores of two groups. In ESRD patients under maintenance hemodialysis, oral L-carnitine supplementation may reduce triglyceride and cholesterol and increase HDL and hemoglobin and subsequently reduce needed erythropoietin dose without effect on QOL. PMID:22720143

  18. Carnitine palmitoyltransferase 2 deficiency: the time-course of blood and urinary acylcarnitine levels during initial L-carnitine supplementation.

    PubMed

    Hori, Tomohiro; Fukao, Toshiyuki; Kobayashi, Hironori; Teramoto, Takahide; Takayanagi, Masaki; Hasegawa, Yuki; Yasuno, Tetsuhiko; Yamaguchi, Seiji; Kondo, Naomi

    2010-07-01

    Carnitine palmitoyltransferase 2 (CPT2) deficiency is one of the most common mitochondrial beta-oxidation defects. A female patient with an infantile form of CPT2 deficiency first presented as having a Reye-like syndrome with hypoglycemic convulsions. Oral L-carnitine supplementation was administered since serum free carnitine level was very low (less than 10 micromol/L), indicating secondary carnitine deficiency. Her serum and urinary acylcarnitine profiles were analyzed successively to evaluate time-course effects of L-carnitine supplementation. After the first two days of L-carnitine supplementation, the serum level of free carnitine was elevated; however, the serum levels of acylcarnitines and the urinary excretion of both free carnitine and acylcarnitines remained low. A peak of the serum free carnitine level was detected on day 5, followed by a peak of acetylcarnitine on day 7, and peaks of long-chain acylcarnitines, such as C16, C18, C18:1 and C18:2 carnitines, on day 9. Thereafter free carnitine became predominant again. These peaks of the serum levels corresponded to urinary excretion peaks of free carnitine, acetylcarnitine, and medium-chain dicarboxylic carnitines, respectively. It took several days for oral L-carnitine administration to increase the serum carnitine levels, probably because the intracellular stores were depleted. Thereafter, the administration increased the excretion of abnormal acylcarnitines, some of which had accumulated within the tissues. The excretion of medium-chain dicarboxylic carnitines dramatically decreased on day 13, suggesting improvement of tissue acylcarnitine accumulation. These time-course changes in blood and urinary acylcarnitine levels after L-carnitine supplementation support the effectiveness of L-carnitine supplementation to CPT2-deficient patients.

  19. Oral ixazomib maintenance therapy in multiple myeloma.

    PubMed

    Offidani, Massimo; Corvatta, Laura; Gentili, Silvia; Maracci, Laura; Leoni, Pietro

    2016-01-01

    Continuous therapy has proven to be an effective therapeutic strategy to improve the outcome of both young and elderly multiple myeloma patients. Remarkably, lenalidomide and bortezomib showed to play a crucial role in this setting due to their safety profile allowing long-term exposure. Ixazomib, the first oral proteasome inhibitor to be evaluated in multiple myeloma, exerts substantial anti-myeloma activity as a single agent and particularly in combination with immunomodulatory drugs and it may be an attractive option for maintenance therapy. Here we address the issue of maintenance therapy as part of a therapeutic approach of multiple myeloma patients focusing on the potential role of ixazomib.

  20. State of the art: Oral antiplatelet therapy

    PubMed Central

    Myat, Aung; Kubica, Jacek; Tantry, Udaya S

    2016-01-01

    Platelet adhesion, activation, and aggregation are central to the propagation of coronary thrombosis following rupture, fissure, or erosion of an atherosclerotic plaque. This chain of deleterious events underlies the pathophysiological process leading to an acute coronary syndrome. Therefore, oral antiplatelet therapy has become the cornerstone of therapy for the management of acute coronary syndrome and the prevention of ischemic complications associated with percutaneous coronary intervention. Landmark trials have established aspirin, and the addition of clopidogrel to aspirin, as key therapeutic agents in the context of acute coronary syndrome and percutaneous coronary intervention. Dual antiplatelet therapy has been the guideline-mandated standard of care in acute coronary syndrome and percutaneous coronary intervention. Despite the proven efficacy of dual antiplatelet therapy, adverse ischemic events continue to occur and this has stimulated the development of novel, more potent antiplatelet agents. We focus this state-of-the-art review on the most recent advances in oral antiplatelet therapy, treading the tightrope of potency versus bleeding risk, the quest to determine the optimal duration of dual antiplatelet therapy and future of personalized antiplatelet therapy. PMID:27298725

  1. Oral enzyme therapy for celiac sprue

    PubMed Central

    Bethune, Michael T; Khosla, Chaitan

    2012-01-01

    Celiac sprue is an inflammatory disease of the small intestine caused by dietary gluten and treated by adherence to a lifelong gluten-free diet. The recent identification of immunodominant gluten peptides, the discovery of their cogent properties, and the elucidation of the mechanisms by which they engender immunopathology in genetically-susceptible individuals have advanced our understanding of the molecular pathogenesis of this complex disease, enabling the rational design of new therapeutic strategies. The most clinically advanced of these is oral enzyme therapy, in which enzymes capable of proteolyzing gluten (i.e. glutenases) are delivered to the alimentary tract of a celiac sprue patient to detoxify ingested gluten in situ. In this chapter, we discuss the key challenges for discovery and preclinical development of oral enzyme therapies for celiac sprue. Methods for lead identification, assay development, gram-scale production and formulation, and lead optimization for next-generation proteases are described and critically assessed. PMID:22208988

  2. Primary carnitine deficiency in a male adult.

    PubMed

    Karmaniolas, Konstantinos; Ioannidis, Panagiotis; Liatis, Stavros; Dalamanga, Maria; Papalambros, Theoharis; Migdalis, Ilias

    2002-01-01

    The case is described of a 36 year-old man who presented with progressive proximal muscle weakness and weight loss. His serum creatine phosphokinase (CPK) levels were markedly elevated. The muscle biopsy showed lipid storage myopathy. The muscle carnitine concentration was extremely low (5.6% of normal levels), establishing the diagnosis of myopathic carnitine deficiency. The disorder was considered as primary because there were no indications of any other identifiable condition which could result in a secondary carnitine deficiency. The patient was treated with oral L-carnitine (2 g per day) and showed rapid improvement. Primary myopathic carnitine deficiency is a curable disorder and therefore it should always be considered as a potential diagnosis in cases of myopathy in young adults.

  3. Refractory overactive bladder: Beyond oral anticholinergic therapy

    PubMed Central

    Glinski, Ronald W.; Siegel, Steven

    2007-01-01

    Objectives: In this review, we discuss the treatment of refractory overactive bladder (OAB) that has not adequately responded to medication therapy and we propose an appropriate care pathway to the treatment of OAB. We also attempt to address the cost of OAB treatments. Materials and Methods: A selective expert review of the current literature on the subject of refractory OAB using MEDLINE was performed and the data is summarized. We also review our experience in treating refractory OAB. The role and outcomes of various treatment options for refractory OAB are discussed and combined therapy with oral anticholinergics is explored. Emerging remedies including intravesical botulinum toxin injection and pudendal neuromodulation are also reviewed, along with conventional surgical options. Results: In general behavioral therapy, pelvic floor electrical stimulation, magnetic therapy and posterior tibial nerve stimulation (PTNS), have shown symptom decreases in 50-80% of patients with OAB. Depending on the study, combination therapy with oral anticholinergics seems to improve efficacy of behavioral therapy and PTNS in approximately 10-30%. In multicenter, long-term randomized controlled trials, sacral neuromodulation has been shown to improve symptoms of OAB and OAB incontinence in up to 80% of the patients treated. Studies involving emerging therapies such as pudendal serve stimulation suggest that there may be a 15-20% increase in efficacy over sacral neuromodulation, but long-term studies are not yet available. Another emerging therapy, botulinum toxin, is also showing similar success in reducing OAB symptoms in 80-90% of patients. Surgical approaches, such as bladder augmentation, are a last resort in the treatment of OAB and are rarely used at this point unless upper tract damage is a concern and all other treatment options have been exhausted. Conclusion: The vast majority of OAB patients can be managed successfully by behavioral options with or without

  4. Effects of oral L-carnitine supplementation on insulin sensitivity indices in response to glucose feeding in lean and overweight/obese males.

    PubMed

    Galloway, Stuart D R; Craig, Thomas P; Cleland, Stephen J

    2011-07-01

    Infusion of carnitine has been observed to increase non-oxidative glucose disposal in several studies, but the effect of oral carnitine on glucose disposal in non-diabetic lean versus overweight/obese humans has not been examined. This study examined the effects of 14 days of L-carnitine L-tartrate oral supplementation (LC) on blood glucose, insulin, NEFA and GLP-1 responses to an oral glucose tolerance test (OGTT). Sixteen male participants were recruited [lean (n = 8) and overweight/obese (n = 8)]. After completing a submaximal predictive exercise test, participants were asked to attend three experimental sessions. These three visits were conducted in the morning to obtain fasting blood samples and to conduct 2 h OGTTs. The first visit was a familiarisation trial and the final two visits were conducted 2 weeks apart following 14 days of ingestion of placebo (PL, 3 g glucose/day) and then LC (3 g LC/day) ingested as two capsules 3×/day with meals. On each visit, blood was drawn at rest, at intervals during the OGTT for analysis of glucose, insulin, non-esterified fatty acids (NEFA) and total glucagon-like peptide-1 (GLP-1). Data obtained were used for determination of usual insulin sensitivity indices (HOMA-IR, AUC glucose, AUC insulin, 1st phase and 2nd phase β-cell function, estimated insulin sensitivity index and estimated metabolic clearance rate). Data were analysed using RMANOVA and post hoc comparisons where appropriate. There was a significant difference between groups for body mass, % fat and BMI with no significant difference in age and height. Mean (SEM) plasma glucose concentration at 30 min was significantly lower (p < 0.05) in the lean group on the LC trial compared with PL [8.71(0.70) PL; 7.32(0.36) LC; mmol/L]. Conversely, plasma glucose concentration was not different at 30 min, but was significantly higher at 90 min (p < 0.05) in the overweight/obese group on the LC trial [5.09(0.41) PL; 7.11(0.59) LC; mmol/L]. Estimated first phase and second

  5. Oral Complications and Management Strategies for Patients Undergoing Cancer Therapy

    PubMed Central

    2014-01-01

    With cancer survival rate climbing up over the past three decades, quality of life for cancer patients has become an issue of major concern. Oral health plays an important part in one's overall quality of life. However, oral health status can be severely hampered by side effects of cancer therapies including surgery, chemotherapy, radiotherapy, and hematopoietic stem cell transplantation. Moreover, prevention and treatment of these complications are often overlooked in clinical practice. The present paper aims at drawing health care professionals' attention to oral complications associated with cancer therapy by giving a comprehensive review. Brief comments on contemporary cancer therapies will be given first, followed by detailed description of oral complications associated with cancer therapy. Finally, a summary of preventive strategies and treatment options for common oral complications including oral mucositis, oral infections, xerostomia, and dysgeusia will be given. PMID:24511293

  6. Carnitine palmitoyltransferase II deficiency

    PubMed Central

    Roe, C R.; Yang, B-Z; Brunengraber, H; Roe, D S.; Wallace, M; Garritson, B K.

    2008-01-01

    Background: Carnitine palmitoyltransferase II (CPT II) deficiency is an important cause of recurrent rhabdomyolysis in children and adults. Current treatment includes dietary fat restriction, with increased carbohydrate intake and exercise restriction to avoid muscle pain and rhabdomyolysis. Methods: CPT II enzyme assay, DNA mutation analysis, quantitative analysis of acylcarnitines in blood and cultured fibroblasts, urinary organic acids, the standardized 36-item Short-Form Health Status survey (SF-36) version 2, and bioelectric impedance for body fat composition. Diet treatment with triheptanoin at 30% to 35% of total daily caloric intake was used for all patients. Results: Seven patients with CPT II deficiency were studied from 7 to 61 months on the triheptanoin (anaplerotic) diet. Five had previous episodes of rhabdomyolysis requiring hospitalizations and muscle pain on exertion prior to the diet (two younger patients had not had rhabdomyolysis). While on the diet, only two patients experienced mild muscle pain with exercise. During short periods of noncompliance, two patients experienced rhabdomyolysis with exercise. None experienced rhabdomyolysis or hospitalizations while on the diet. All patients returned to normal physical activities including strenuous sports. Exercise restriction was eliminated. Previously abnormal SF-36 physical composite scores returned to normal levels that persisted for the duration of the therapy in all five symptomatic patients. Conclusions: The triheptanoin diet seems to be an effective therapy for adult-onset carnitine palmitoyltransferase II deficiency. GLOSSARY ALT = alanine aminotransferase; AST = aspartate aminotransferase; ATP = adenosine triphosphate; BHP = β-hydroxypentanoate; BKP = β-ketopentanoate; BKP-CoA = β-ketopentanoyl–coenzyme A; BUN = blood urea nitrogen; CAC = citric acid cycle; CoA = coenzyme A; CPK = creatine phosphokinase; CPT II = carnitine palmitoyltransferase II; LDL = low-density lipoprotein; MCT

  7. L-carnitine--metabolic functions and meaning in humans life.

    PubMed

    Pekala, Jolanta; Patkowska-Sokoła, Bozena; Bodkowski, Robert; Jamroz, Dorota; Nowakowski, Piotr; Lochyński, Stanisław; Librowski, Tadeusz

    2011-09-01

    L-Carnitine is an endogenous molecule involved in fatty acid metabolism, biosynthesized within the human body using amino acids: L-lysine and L-methionine, as substrates. L-Carnitine can also be found in many foods, but red meats, such as beef and lamb, are the best choices for adding carnitine into the diet. Good carnitine sources also include fish, poultry and milk. Essentially, L-carnitine transports the chains of fatty acids into the mitochondrial matrix, thus allowing the cells to break down fat and get energy from the stored fat reserves. Recent studies have started to shed light on the beneficial effects of L-carnitine when used in various clinical therapies. Because L-carnitine and its esters help reduce oxidative stress, they have been proposed as a treatment for many conditions, i.e. heart failure, angina and weight loss. For other conditions, such as fatigue or improving exercise performance, L-carnitine appears safe but does not seem to have a significant effect. The presented review of the literature suggests that continued studies are required before L-carnitine administration could be recommended as a routine procedure in the noted disorders. Further research is warranted in order to evaluate the biochemical, pharmacological, and physiological determinants of the response to carnitine supplementation, as well as to determine the potential benefits of carnitine supplements in selected categories of individuals who do not have fatty acid oxidation defects.

  8. A prospective study to evaluate the efficacy and safety of oral acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy.

    PubMed

    Sun, Yuanjue; Shu, Yongqian; Liu, Baorui; Liu, Ping; Wu, Changping; Zheng, Rongsheng; Zhang, Xiaohua; Zhuang, Zhixiang; Deng, Yongchuan; Zheng, Leizhen; Xu, Qing; Jiang, Bin; Ouyang, Xuenong; Gao, Jianfei; Xu, Nong; Li, Xiaoyi; Jiang, Su; Liang, Chaofan; Yao, Yang

    2016-12-01

    The present study aimed to evaluate the efficacy and safety of acetyl-L-carnitine (ALC) for the treatment of chemotherapy-induced peripheral neuropathy (CIPN). The study was carried out as a prospective, randomized, double-blind, placebo-controlled and paralleled clinical study. A total of 239 patients with CIPN were selected as the study subjects. Of the 239 subjects, 118 subjects received 3 g/day ALC orally for 8 weeks and 121 received a placebo. The primary endpoint was improvement of peripheral neuropathy by at least one grade. Patient status was assessed at week 4, 8 and 12 after enrollment into the study. In both the full analysis set (FAS) and the per-protocol set (PPS), peripheral sensory neuropathy was significantly ameliorated in the ALC group with 50.5 and 51.6% patients meeting the primary endpoint at week 8, compared with 24.1 and 23.1% of patients in the placebo group (P<0.001 in both sets). Secondary endpoints, such as the nerve electrophysiological examination and the Karnofsky physical score were also significantly improved in patients receiving ALC treatment, as compared with the placebo group (FAS, P=0.0463 and P=0.022; PPS, P=0.0076 and P=0.0064, respectively). Cancer-associated fatigue was significantly alleviated following ALC treatment in the PPS (P=0.0135). In the safety analysis set, the difference in adverse events incidence between the two groups was not statistically significant (P=0.3903). There were only two severe adverse events in the ALC group, which were not associated with the effect of ALC. In conclusion, the results of the present study demonstrated that in Chinese patients with cancer, oral administration of ALC is effective at ameliorating peripheral sensory neuropathy induced by chemotherapy, as well as reducing of cancer-associated fatigue and improving physical conditions.

  9. A prospective study to evaluate the efficacy and safety of oral acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy

    PubMed Central

    Sun, Yuanjue; Shu, Yongqian; Liu, Baorui; Liu, Ping; Wu, Changping; Zheng, Rongsheng; Zhang, Xiaohua; Zhuang, Zhixiang; Deng, Yongchuan; Zheng, Leizhen; Xu, Qing; Jiang, Bin; Ouyang, Xuenong; Gao, Jianfei; Xu, Nong; Li, Xiaoyi; Jiang, Su; Liang, Chaofan; Yao, Yang

    2016-01-01

    The present study aimed to evaluate the efficacy and safety of acetyl-L-carnitine (ALC) for the treatment of chemotherapy-induced peripheral neuropathy (CIPN). The study was carried out as a prospective, randomized, double-blind, placebo-controlled and paralleled clinical study. A total of 239 patients with CIPN were selected as the study subjects. Of the 239 subjects, 118 subjects received 3 g/day ALC orally for 8 weeks and 121 received a placebo. The primary endpoint was improvement of peripheral neuropathy by at least one grade. Patient status was assessed at week 4, 8 and 12 after enrollment into the study. In both the full analysis set (FAS) and the per-protocol set (PPS), peripheral sensory neuropathy was significantly ameliorated in the ALC group with 50.5 and 51.6% patients meeting the primary endpoint at week 8, compared with 24.1 and 23.1% of patients in the placebo group (P<0.001 in both sets). Secondary endpoints, such as the nerve electrophysiological examination and the Karnofsky physical score were also significantly improved in patients receiving ALC treatment, as compared with the placebo group (FAS, P=0.0463 and P=0.022; PPS, P=0.0076 and P=0.0064, respectively). Cancer-associated fatigue was significantly alleviated following ALC treatment in the PPS (P=0.0135). In the safety analysis set, the difference in adverse events incidence between the two groups was not statistically significant (P=0.3903). There were only two severe adverse events in the ALC group, which were not associated with the effect of ALC. In conclusion, the results of the present study demonstrated that in Chinese patients with cancer, oral administration of ALC is effective at ameliorating peripheral sensory neuropathy induced by chemotherapy, as well as reducing of cancer-associated fatigue and improving physical conditions. PMID:28105133

  10. Impact of L-carnitine on plasma lipoprotein(a) concentrations: A systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Serban, Maria-Corina; Sahebkar, Amirhossein; Mikhailidis, Dimitri P; Toth, Peter P; Jones, Steven R; Muntner, Paul; Blaha, Michael J; Andrica, Florina; Martin, Seth S; Borza, Claudia; Lip, Gregory Y H; Ray, Kausik K; Rysz, Jacek; Hazen, Stanley L; Banach, Maciej

    2016-01-12

    We aimed to assess the impact of L-carnitine on plasma Lp(a) concentrations through systematic review and meta-analysis of available RCTs. The literature search included selected databases up to 31(st) January 2015. Meta-analysis was performed using fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The meta-analysis showed a significant reduction of Lp(a) levels following L-carnitine supplementation (WMD: -8.82 mg/dL, 95% CI: -10.09, -7.55, p < 0.001). When the studies were categorized according to the route of administration, a significant reduction in plasma Lp(a) concentration was observed with oral (WMD: -9.00 mg/dL, 95% CI: -10.29, -7.72, p < 0.001) but not intravenous L-carnitine (WMD: -2.91 mg/dL, 95% CI: -10.22, 4.41, p = 0.436). The results of the meta-regression analysis showed that the pooled estimate is independent of L-carnitine dose (slope: -0.30; 95% CI: -4.19, 3.59; p = 0.878) and duration of therapy (slope: 0.18; 95% CI: -0.22, 0.59; p = 0.374). In conclusion, the meta-analysis suggests a significant Lp(a) lowering by oral L-carnitine supplementation. Taking into account the limited number of available Lp(a)-targeted drugs, L-carnitine might be an effective alternative to effectively reduce Lp(a). Prospective outcome trials will be required to fully elucidate the clinical value and safety of oral L-carnitine supplementation.

  11. Carnitine in human nutrition.

    PubMed

    Bach, A C

    1982-12-01

    The oxidation of long-chain fatty acids is carnitine-dependent. Indeed, only when they are bound to carnitine, in the form of acyl-carnitines, do fatty acids penetrate into the mitochondria to be oxidized. To meet the need for carnitine, animals depend on both endogenous synthesis and an exogenous supply. A diet rich in meat supplies a lot of carnitine, while vegetables, fruits, and grains furnish relatively little. Although it has a low molecular weight and acts at low doses in a vital metabolic pathway, carnitine should not be considered a vitamin, but rather a nutritive substance. Indeed, it seems that the diet of the adult human need not necessarily furnish carnitine: the healthy organism, given a balanced nutrition (sufficiently rich in lysine and methionine), may well be able to meet all its needs. Furthermore, it seems that a reduction of the exogenous supply of carnitine results in a lowering of its elimination in the urine. However, dietary carnitine is more important during the neonatal period. The transition from fetal to extrauterine life is accompanied by an increased role of lipids in meeting energy needs. This change is accompanied by a rise in the body of the levels of carnitine, which is mainly supplied in the maternal milk. Finally, this review briefly surveys the illnesses in which a dietary carnitine supplement proves useful.

  12. epsilon-N-trimethyllysine availability regulates the rate of carnitine biosynthesis in the growing rat

    SciTech Connect

    Rebouche, C.J.; Lehman, L.J.; Olson, L.

    1986-05-01

    Rates of carnitine biosynthesis in mammals depend on the availability of substrates and the activity of enzymes subserving the pathway. This study was undertaken to test the hypothesis that the availability of epsilon-N-trimethyllysine is rate-limiting for synthesis of carnitine in the growing rat and to evaluate diet as a source of this precursor for carnitine biosynthesis. Rats apparently absorbed greater than 90% of a tracer dose of (methyl-/sup 3/H)epsilon-N-trimethyllysine, and approximately 30% of that was incorporated into tissues as (/sup 3/H)carnitine. Rats given oral supplements of epsilon-N-trimethyllysine (0.5-20 mg/d), but no dietary carnitine, excreted more carnitine than control animals receiving no dietary epsilon-N-trimethyllysine or carnitine. Rates of carnitine excretion increased in a dose-dependent manner. Tissue and serum levels of carnitine also increased with dietary epsilon-N-trimethyllysine supplementation. There was no evidence that the capacity for carnitine biosynthesis was saturated even at the highest level of oral epsilon-N-trimethyllysine supplementation. Common dietary proteins (casein, soy protein and wheat gluten) were found to be poor sources of epsilon-N-trimethyllysine for carnitine biosynthesis. The results of this study indicate that the availability of epsilon-N-trimethyllysine limits the rate of carnitine biosynthesis in the growing rat.

  13. Metabolic fate of dietary carnitine in human adults: Identification and quantification of urinary and fecal metabolites

    SciTech Connect

    Rebouche, C.J.; Chenard, C.A. )

    1991-04-01

    Results of kinetic and pharmacokinetic studies have suggested that dietary carnitine is not totally absorbed and is in part degraded in the gastrointestinal tract of humans. To determine the metabolic fate of dietary carnitine in humans, we administered orally a tracer dose of methyl-{sup 3}H L-carnitine with a meal to subjects who had been adapted to a low-carnitine diet or a high-carnitine diet. Urinary and fecal excretion of radiolabeled carnitine and metabolites was monitored for 5 to 11 d following administration of the test dose. Total radioactive metabolites excreted ranged from 13 to 34% (low carnitine diet) and 27 to 46% (high carnitine diet) of the ingested tracer. Major metabolites found were ({sup 3}H)trimethylamine N-oxide (8 to 39% of the administered dose; excreted primarily in urine) and ({sup 3}H)gamma-butyrobetaine (0.09 to 8% of the administered dose; excreted primarily in feces). Urinary excretion of total carnitine was 42 to 95% (high carnitine diet) and 190 to 364% (low carnitine diet) of intake. These results indicate that oral carnitine is 54 to 87% bioavailable from normal Western diets; the percentage of intake absorbed is related to the quantity ingested.

  14. Oral reconstructive and corrective considerations in periodontal therapy.

    PubMed

    Greenwell, Henry; Fiorellini, Joseph; Giannobile, William; Offenbacher, Steven; Salkin, Leslie; Townsend, Cheryl; Sheridan, Phillip; Genco, Robert

    2005-09-01

    This paper was prepared by the Research, Science and Therapy Committee of the American Academy of Periodontology. It is intended to provide information for the dental profession and other interested parties. The purpose of this paper is to provide a general overview of oral reconstructive and corrective procedures used in periodontal therapy. It is not intended to be a comprehensive review of this subject.

  15. A Systematic Review of Adherence to Oral Antineoplastic Therapies

    PubMed Central

    Amoyal, Nicole; Nisotel, Lauren; Fishbein, Joel N.; MacDonald, James; Stagl, Jamie; Lennes, Inga; Temel, Jennifer S.; Safren, Steven A.; Pirl, William F.

    2016-01-01

    Background. Oral antineoplastic therapies not only improve survival but also reduce the burden of care for patients. Yet patients and clinicians face new challenges in managing adherence to these oral therapies. We conducted a systematic literature review to assess rates and correlates of adherence to oral antineoplastic therapies and interventions aimed at improving adherence. Methods. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive literature search of the Ovid MEDLINE database from January 1, 2003 to June 30, 2015, using relevant terminology for oral antineoplastic agents. We included observational, database, and intervention studies. At least two researchers evaluated each paper to ensure accuracy of results and determine risk of bias. Results. We identified 927 records from the search and screened 214 abstracts. After conducting a full-text review of 167 papers, we included in the final sample 51 papers on rates/correlates of adherence to oral antineoplastic therapy and 12 papers on intervention studies to improve adherence. Rates of adherence varied widely, from 46% to 100%, depending on patient sample, medication type, follow-up period, assessment measure, and calculation of adherence. Of the intervention studies, only 1 of the randomized trials and 2 of the cohort studies showed benefit regarding adherence, with the majority suffering high risk of bias. Conclusions. Although no reliable estimate of adherence to oral antineoplastic therapies can be gleaned from the literature, a substantial proportion of patients struggle to adhere to these medications as prescribed. The few intervention studies for adherence have notable methodological concerns, thereby limiting the evidence to guide practice in promoting medication adherence among patients with cancer. Implications for Practice: Given the tremendous growth and development of oral antineoplastic therapies in the last decade, significant

  16. L-carnitine supplementation in childhood epilepsy: current perspectives.

    PubMed

    De Vivo, D C; Bohan, T P; Coulter, D L; Dreifuss, F E; Greenwood, R S; Nordli, D R; Shields, W D; Stafstrom, C E; Tein, I

    1998-11-01

    In November 1996, a panel of pediatric neurologists met to update the consensus statement issued in 1989 by a panel of neurologists and metabolic experts on L-carnitine supplementation in childhood epilepsy. The panelists agreed that intravenous L-carnitine supplementation is clearly indicated for valproate (VPA)-induced hepatotoxicity, overdose, and other acute metabolic crises associated with carnitine deficiency. Oral supplementation is clearly indicated for the primary plasmalemmal carnitine transporter defect. The panelists concurred that oral L-carnitine supplementation is strongly suggested for the following groups as well: patients with certain secondary carnitine-deficiency syndromes, symptomatic VPA-associated hyperammonemia, multiple risk factors for VPA hepatotoxicity, or renal-associated syndromes; infants and young children taking VPA; patients with epilepsy using the ketogenic diet who have hypocarnitinemia; patients receiving dialysis; and premature infants who are receiving total parenteral nutrition. The panel recommended an oral L-carnitine dosage of 100 mg/kg/day, up to a maximum of 2 g/day. Intravenous supplementation for medical emergency situations usually exceeds this recommended dosage.

  17. Oral complications of cancer therapies. Management of mucositis during therapy

    SciTech Connect

    Miaskowski, C. )

    1990-01-01

    This paper reviews the purposes of an oral care protocol, the major components of an oral care regimen, and oral care protocols and studies done to date. Many questions remain in the area of optimal oral care for the patient experiencing mucositis as a sequela of cancer treatment. Research is needed on types and use of mouth rinses, effective, harmless, and pleasant lip lubricants, appropriate analgesic and anti-inflammatory combinations, and the effectiveness of a variety of devices for oral cleansing, to name a few areas. As outpatient oncology services grow, oral care protocols must be developed to meet the needs of ambulatory patient populations. Oral care regimens must be safe, easy to use, and economical as well as effective to ensure patient and staff compliance. Research on the management of mucositis must be conducted in both inpatient and outpatient settings. Finally, in order to obtain sufficient sample sizes and optimize data collection, these studies will need to be conducted by multidisciplinary teams (including dentists, oncologists, radiation therapists, and nurses) across multiple sites. Not until large-scale clinical trials are done on the treatment of mucositis will we be able to optimize the therapeutic regimen for the patient. 43 references.

  18. Carnitine prolongs the half-life of ethanol in broilers.

    PubMed

    Smith, M O; Cha, Y S; Sachan, D S

    1994-09-01

    The object was to determine if carnitine attenuated ethanol metabolism in broilers similar to that reported in the rats. Two groups (n = 5) of 5-week-old broilers were given for 10 days the feed with or without 0.5% L-carnitine supplement. A single oral dose of ethanol on day 8 was followed by serial blood samples which were analysed for ethanol. Another dose of ethanol was given on day 10 and 2 hr later, plasma and liver were collected and analysed for ethanol, total lipid, triglycerides and carnitine. The carnitine supplemented diet prolonged the half-life of ethanol due to attenuation of ethanol metabolism which is similar to that reported earlier in rodents. The increases in plasma and hepatic acylcarnitines indicate that supplementary carnitine lessens the load of free acyl groups in the liver by eventual oxidation or excretion.

  19. Low Level Laser Therapy: A Panacea for oral maladies

    PubMed Central

    Kathuria, Vartika; Kalra, Gauri

    2015-01-01

    Aim: To review the applications of low level laser therapy on various soft and hard oral tissues. A variety of therapeutic effects of Low Level Laser Therapy have been reported on a broad range of disorders. It has been found amenably practical in dental applications including soft as well as hard tissues of the oral cavity. LLLT has been found to be efficient in acceleration of wound healing, enhanced remodelling and bone repair, regeneration of neural cells following injury, pain attenuation, endorphin release stimulation and modulation of immune system. The aforementioned biological processes induced by Low level lasers have been effectively applied in treating various pathological conditions in the oral cavity. With is article, we attempt to review the possible application of Low Laser Therapy in the field of dentistry. PMID:26557737

  20. Conventional and alternative antifungal therapies to oral candidiasis

    PubMed Central

    Anibal, Paula Cristina; de Cássia Orlandi Sardi, Janaina; Peixoto, Iza Teixeira Alves; de Carvalho Moraes, Julianna Joanna; Höfling, José Francisco

    2010-01-01

    Candida-associated denture stomatitis is the most common form of oral candidal infection, with Candida albicans being the principal etiological agent. Candida adheres directly or via an intermediary layer of plaque-forming bacteria to denture acrylic. Despite antifungal therapy to treat denture stomatitis, infection is reestablished soon after the treatment ceases. In addition, many predisposing factors have been identified as important in the development of oral candidiasis, including malnourishment, common endocrine disorders, such as diabetis mellitus, antibacterial drug therapy, corticosteroids, radiotherapy and other immunocompromised conditions, such as acquired immunodeficiency syndrome (AIDS). These often results in increased tolerance to the most commonly used antifungals. So this review suggests new therapies to oral candidiasis. PMID:24031562

  1. Design of amphotericin B oral formulation for antifungal therapy.

    PubMed

    Liu, Min; Chen, Meiwan; Yang, Zhiwen

    2017-11-01

    Amphotericin B (AmB) remains the "gold standard" for systemic antifungal therapy, even though new drugs are emerging as the attractive antifungal agents. Since AmB has negligible oral absorption as a consequence of its unfavorable physicochemical characterizations, its use is restricted to parenteral administration which is accompanied by severe side effects. As greater understanding of the gastrointestinal tract has developed, the advanced drug delivery systems are emerging with the potential to overcome the barriers of AmB oral delivery. Much research has demonstrated that oral AmB formulations such as lipid formulations may have beneficial therapeutic efficacy with reduced adverse effects and suitable for clinical application. Here we reviewed the different formulation strategies to enhance oral drug efficacy, and discussed the current trends and future perspectives for AmB oral administration in the treatment of antifungal infections.

  2. [Carnitine - mitochondria and beyond].

    PubMed

    Nałęcz, Katarzyna A; Nałęcz, Maciej J

    2016-01-01

    Carnitine [(3R)-3-hydroxy-4-(trimethylazaniumyl)butanoate] in mammals is mainly delivered with diet. It enters the cell due to the activity of organic cation/carnitine transporter OCTN2 (SLC22A5), it can be as well transported by CT2 (SLC22A16) and a transporter of neutral and basic amino acids ATB(0, +) (SLC6A14). The hydroxyl group of carnitine is able to form esters with organic acids (xenobiotics, fatty acids) due to the activity of acylcarnitine transferases. Carnitine is necessary for transfer of fatty acids to mitochondria: in functioning of the so-called carnitine shuttle an essential role is fulfilled by palmitoylcarnitine transferase 1, carnitine carrier (SLC25A20) in the inner mitochondrial membrane and palmitoylcarnitine transferase 2. Oxidation of fatty acids takes also place in peroxisomes. The produced medium-chain acyl derivatives are exported as acylcarnitines, most probably by OCTN3 (Slc22a21). It has been postulated that acylcarnitines can cross the outer mitochondrial membrane through the voltage-dependent anion channel (VDAC) and/or through the palmitoycarnitine transferase 1 oligomer. Mutations of genes coding carnitine plasma membrane transporters result in the primary carnitine deficiency, with symptoms affecting normal functioning of muscles (including heart) and brain. Mechanisms regulating functioning of these transporters have been presented with emphasis on their role as potential therapeutic targets.

  3. Monitoring anticoagulant therapy with new oral agents

    PubMed Central

    Ramos-Esquivel, Allan

    2015-01-01

    Thromboembolic disease is a major leading cause of mortality and morbidity in industrialized countries. Currently, the management of these patients is challenging due to the availability of new drugs with proven efficacy and security compared to traditional oral vitamin K antagonists. These compounds are characterized by a predictable pharmacokinetic profile for which blood monitoring is not routinely needed. Nevertheless, some data have suggested inter-patient variability in the anticoagulant effect of these drugs, raising concerns about their effectiveness and safety. Although mass-spectrometry is the gold standard to determine drug plasma concentrations, this method is not widely available in every-day practice and some coagulation assays are commonly used to determine the anticoagulant effect of these drugs. The present review aims to summarize the current knowledge regarding the clinical question of how and when to monitor patients with new anticoagulant oral agents. PMID:26713281

  4. The Efficacy of Medical Treatment of Peyronie's Disease: Potassium Para-Aminobenzoate Monotherapy vs. Combination Therapy with Tamoxifen, L-Carnitine, and Phosphodiesterase Type 5 Inhibitor

    PubMed Central

    Park, Tae Yong; Jeong, Hyeong Guk; Park, Jong Jin; Chae, Ji Yun; Kim, Jong Wook; Oh, Mi Mi; Park, Hong Seok; Kim, Je Jong

    2016-01-01

    Purpose This study was designed to evaluate the efficacy of medical treatment of Peyronie's disease. Materials and Methods A total of 109 patients with Peyronie's disease who had been treated from January 2011 to December 2014 were retrospectively reviewed in this study. Forty-four patients (Group 1) were treated with 12 mg of potassium para-aminobenzoate daily. Sixty-five patients (Group 2) were treated with combination therapy: tamoxifen (20 mg) and acetyl-L-carnitine (300 mg) twice daily in addition to a phosphodiesterase type 5 inhibitor. Ability to perform sexual intercourse, pain during erection, size of plaque, and penile curvature angle were assessed. Results In Group 1, 30 of 44 patients (68.2%) discontinued treatment within 12 weeks, while 5 patients (7.7%) in Group 2 discontinued treatment. Pain during erection and plaque size were improved in both groups but showed no statistical difference due to the high dropout rate in Group 1. In both groups, penile curvature was improved, but demonstrated no statistical difference between the treatment groups. However, combination therapy demonstrated a better response rate in patients whose penile curvature angle was less than 30° (44.4% vs. 79.1%, p=0.048). The rate of successful sexual intercourse was significantly higher in Group 2 (42.8% vs. 78.3%, p=0.034). The number of patients who underwent surgical correction despite medical treatment was significantly higher in Group 1 (35.7% vs. 13.3%, p=0.048). Conclusions Early medical combination therapy in Peyronie's disease may present better results in patients whose curvature angle is less than 30°. PMID:27169128

  5. Effects of oral motor therapy in children with cerebral palsy

    PubMed Central

    Sığan, Seray Nural; Uzunhan, Tuğçe Aksu; Aydınlı, Nur; Eraslan, Emine; Ekici, Barış; Çalışkan, Mine

    2013-01-01

    Aim: Oral motor dysfunction is a common issue in children with cerebral palsy (CP). Drooling, difficulties with sucking, swallowing, and chewing are some of the problems often seen. In this study, we aimed to research the effect of oral motor therapy on pediatric CP patients with feeding problems. Materials and Methods: Included in this single centered, randomized, prospective study were 81 children aged 12-42 months who had been diagnosed with CP, had oral motor dysfunction and were observed at the Pediatric Neurology outpatient clinic of the Children's Health and Diseases Department, Istanbul Medical Faculty, Istanbul University. Patients were randomized into two groups: The training group and the control group. One patient from the training group dropped out of the study because of not participating regularly. Following initial evaluation of all patients by a blinded physiotherapist and pedagogue, patients in the training group participated in 1 h oral motor training sessions with a different physiotherapist once a week for 6 months. All patients kept on routine physiotherapy by their own physiotherapists. Oral motor assessment form, functional feeding assessment (FFA) subscale of the multidisciplinary feeding profile (MFP) and the Bayley scales of infant development (BSID-II) were used to evaluate oral motor function, swallowing, chewing, the gag reflex, the asymmetrical tonic neck reflex, tongue, jaw, and mouth function, severity of drooling, aspiration, choking, independent feeding and tolerated food texture during the initial examination and 6 months later. Results: When the initial and post-therapy FFA and BSID-II scores received by patients in the training and the study group were compared, the training group showed a statistically significant improvement (P < 0.05). Conclusion: Oral motor therapy has a beneficial effect on feeding problems in children with CP. PMID:24101813

  6. Quantitative estimation of absorption and degradation of a carnitine supplement by human adults.

    PubMed

    Rebouche, C J

    1991-12-01

    Results of kinetic and pharmacokinetic studies have suggested that dietary carnitine supplements are not totally absorbed, and are in part degraded in the gastrointestinal tract of humans. To determine the metabolic fate of dietary carnitine supplements in humans, we administered orally a tracer dose of [methyl-3H]L-carnitine with a meal to five normal adult males, who had been adapted to a high-carnitine diet plus carnitine supplement (2 g/d) for 14 days. Appearance of [methyl-3H]L-carnitine and metabolites in serum, and urinary and fecal excretion of radiolabeled carnitine and metabolites was monitored for 5 to 11 days following administration of the test dose. Maximum concentration of [methyl-3H]L-carnitine in serum occurred at 2.0 to 4.5 hours after administration of the tracer, indicating relatively slow absorption from the intestinal lumen. Total radioactive metabolites excreted in urine and feces ranged from 47% to 55% of the ingested tracer. Major metabolites found were [3H]trimethylamine N-oxide (8% to 49% of the administered dose; excreted primarily in urine) and [3H]gamma-butyrobetaine (0.44% to 45% of the administered dose; excreted primarily in feces). Urinary excretion of total carnitine was 16% to 23% of intake. Fecal excretion of total carnitine was negligible (less than 2% of total carnitine excretion).

  7. [Antibiotic therapy of bacterial infections of the oral cavity].

    PubMed

    Scaglione, F; Castorina, A

    1989-09-30

    More than 300 commencial bacterial species may be found in the oral cavity. Other microorganisms, such as mycoplasms, mycetes, protozoa and viruses are present as well. The virulency of the saprofites and additional contamination by outside microorganisms are factors determining the development of infectious process in the oral tissues. Moreover, streptococci and anaerobes are the most frequent aetiology agents. The antibiotic therapy should comply with the general treatment criteria, on the one hand, and should be specific for these microorganism, on the other. The penicillines (ampicillin, bacampicillin and especially amoxycillin) process pharmacokinetic properties which make them a favorable choice for treatment. These drugs are effective in case of streptococcal infections, with cariogenic processes involvement and dissemination (endocarditis, glomerulonephritis). Other, frequently used drugs are spiramycin, erythromycin, josamycin and myocamycin that are selectively taken up by the oral tissues and present in large quantities in the saliva. The macrolides have a large spectrum of action on microorganisms normally found in the oral cavity. Lincosamides (lincomycin and clindamycin) are active on anaerobes and are drugs of choice for treatment of staphylococcal osteomyelitis. Tetracycline therapy is restricted usually to parodontite cases caused by Actinobacillus actinomycetemcomitans and Capnocytophaga. In conclusion, the choice of antibacterial therapy should be based on the bacterial aetiology, as well as on the intrinsic drug characteristics (pharmacokinetic, side effects, toxicity etc.).

  8. The effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation in migraine prophylaxis.

    PubMed

    Tarighat Esfanjani, Ali; Mahdavi, Reza; Ebrahimi Mameghani, Mehrangiz; Talebi, Mahnaz; Nikniaz, Zeinab; Safaiyan, Abdolrasool

    2012-12-01

    Given the conflicting results about the positive effects of magnesium and L-carnitine and as there is no report concerning concurrent supplementation of magnesium and L-carnitine on migraine prophylaxis, the effects of magnesium, L-carnitine, and concurrent magnesium-L-carnitine supplementation on migraine indicators were assessed. In this clinical trial, 133 migrainous patients were randomly assigned into three intervention groups: magnesium oxide (500 mg/day), L-carnitine (500 mg/day), and Mg-L-carnitine (500 mg/day magnesium and 500 mg/day L-carnitine), and a control group. After 12 weeks of supplementation, the checklist of migraine indicators including migraine attacks/month, migraine days/month, and headache severity was completed, and serum concentrations of magnesium and L-carnitine were measured by atomic absorption spectrophotometry and enzymatic UV test, respectively. The results showed a significant reduction in all migraine indicators in all studied groups (p < 0.05). The ANOVA results showed a significant reduction in migraine frequency across various supplemented and control groups (p = 0.008). By separating the effects of magnesium supplementation from other confounding factors such as routine treatments using the repeated measures and nested model, it was clarified that magnesium supplementation had a significant effect on all migraine indicators. Oral supplementation with magnesium oxide and L-carnitine and concurrent supplementation of Mg-L-carnitine besides routine treatments could be effective in migraine prophylaxis; however, larger trials are needed to confirm these preliminary findings.

  9. [Slow replenishment of carnitine level after long-term treatment with pivampicillin/pivmecillinam].

    PubMed

    Diep, Q N; Bøhmer, T; Storrøsten, O T; Holme, J I; Torvik, A; Loennecken, C W; Monstad, P; Jellum, E

    1994-05-30

    Long-term treatment with pivampicillin and pivmecillinam for 6-24 months in five adults and one child reduced the total serum carnitine concentrations to 3.7-14.0 mumol/l (reference value 25-66 mumol/l). The muscle carnitine was reduced to 0.3-0.7 mumol/g wet weight (reference value 3-5 mumol/g) in two cases. All patients had asthenia and muscle symptoms with weakness and pain. One showed signs of carnitine depletion in the liver, with increased secretion of dicarboxylic acids (C6, C8, C10) in urine and limited ketone body formation during prolonged fasting (32 hours). The serum carnitine increased slowly after cessation of therapy and reached normal concentrations after 6-12 months. All symptoms caused by carnitine depletion disappeared after the serum carnitine reached 20 mumol/l. This was achieved on a normal diet without carnitine supplement.

  10. Supplemental oxygen therapy: Important considerations in oral and maxillofacial surgery

    PubMed Central

    Singh, Virendra; Gupta, Pranav; Khatana, Shruti; Bhagol, Amrish

    2011-01-01

    The administration of supplemental oxygen is an essential element of appropriate management for a wide range of clinical conditions; crossing different medical and surgical specialities. The present review summarizes the role of supportive oxygen therapy in various clinical conditions encountered in our day-to-day practice in the speciality of oral and maxillofacial surgery; including major trauma, shock, sepsis; perioperative and postoperative considerations and in patients with various other medical comorbidities. Regular and judicious use of oxygen as a drug is thus recommended in our day-to-day practice in oral and maxillofacial surgery to reduce the morbidity and improve the prognosis of patients. PMID:22442602

  11. Targeted therapy of oral hairy leukoplakia with gentian violet.

    PubMed

    Bhandarkar, Sulochana S; MacKelfresh, Jamie; Fried, Levi; Arbiser, Jack L

    2008-04-01

    Oral hairy leukoplakia (OHL) is a common oral manifestation of HIV infection. Clinically, these lesions appear as white plaques on the edges of the tongue. Pathophysiologically, these lesions occur because of infection of oral epithelium with Epstein-Barr virus (EBV). No universally effective therapy exists for OHL. We have previously shown that EBV infection and EBV viral products induce the generation of reactive oxygen. We have also demonstrated that the Food and Drug Administration-approved over-the-counter medication gentian violet is a potent inhibitor of reactive oxygen species. We thus chose to treat a patient with biopsy-proven OHL with topical gentian violet. Gentian violet solution was applied topically to the tongue of a patient with OHL. Complete clinical resolution was noted after three treatments. Treatment with topical gentian violet resulted in resolution of the lesions. Further studies with larger numbers of patients are required. The application of gentian violet can be used as a method to OHL treatment. Gentian violet is an inexpensive and safe therapy and, given that it inhibits reactive oxygen, this old therapy is now a targeted novel therapy.

  12. Oral herbal therapies for treating osteoarthritis

    PubMed Central

    Cameron, Melainie; Chrubasik, Sigrun

    2015-01-01

    Background Medicinal plant products are used orally for treating osteoarthritis. Although their mechanisms of action have not yet been elucidated in full detail, interactions with common inflammatory mediators provide a rationale for using them to treat osteoarthritic complaints. Objectives To update a previous Cochrane review to assess the benefits and harms of oral medicinal plant products in treating osteoarthritis. Search methods We searched electronic databases (CENTRAL, MEDLINE, EMBASE, AMED, CINAHL, ISI Web of Science, World Health Organization Clinical Trials Registry Platform) to 29 August 2013, unrestricted by language, and the reference lists from retrieved trials. Selection criteria Randomised controlled trials of orally consumed herbal interventions compared with placebo or active controls in people with osteoarthritis were included. Herbal interventions included any plant preparation but excluded homeopathy or aromatherapy products, or any preparation of synthetic origin. Data collection and analysis Two authors used standard methods for trial selection and data extraction, and assessed the quality of the body of evidence using the GRADE approach for major outcomes (pain, function, radiographic joint changes, quality of life, withdrawals due to adverse events, total adverse events, and serious adverse events). Main results Forty-nine randomised controlled studies (33 interventions, 5980 participants) were included. Seventeen studies of confirmatory design (sample and effect sizes pre-specified) were mostly at moderate risk of bias. The remaining 32 studies of exploratory design were at higher risk of bias. Due to differing interventions, meta-analyses were restricted to Boswellia serrata (monoherbal) and avocado-soyabean unsaponifiables (ASU) (two herb combination) products. Five studies of three different extracts from Boswellia serrata were included. High-quality evidence from two studies (85 participants) indicated that 90 days treatment with 100

  13. Acetyl-L-carnitine and α-lipoic acid affect rotenone-induced damage in nigral dopaminergic neurons of rat brain, implication for Parkinson's disease therapy.

    PubMed

    Zaitone, Sawsan A; Abo-Elmatty, Dina M; Shaalan, Aly A

    2012-01-01

    Although the mechanisms of neurodegeneration in Parkinson's disease are not fully understood, mitochondrial dysfunction, oxidative stress and environmental toxins may be involved. The current research was directed to investigate the protective role of two bioenergetic antioxidants, acetyl-L-carnitine and α-lipoic acid, in rotenone-parkinsonian rats. Ninety six male rats were divided into five groups. Group I is the vehicle-injected group, group II is the disease control group and was injected with six doses of rotenone (1.5 mg/kg/48 h, s.c.). Groups III, IV and V received rotenone in addition to acetyl-L-carnitine (100 mg/kg/day, p.o.), α-lipoic acid (50 mg/kg/day, p.o.) or their combination, respectively. Results showed that rotenone-treated rats exhibited bradykinesia and motor impairment in the open-field and square bridge tests. In addition, ATP level was decreased whereas lipid peroxides and protein carbonyls increased in the striata of rotenone-treated rats as compared to vehicle-treated rats. Treatment with acetyl-L-carnitine or α-lipoic acid improved the motor performance and reduced the level of lipid peroxides in rat brains as compared to rotenone group. Further, ATP production was enhanced along with acetyl-L-carnitine treatments (p≤0.05). Taken together, our study reinforces the view that acetyl-L-carnitine and α-lipoic acid are promising candidates for neuroprotection in Parkinson's disease.

  14. Oral anticoagulant therapy in patients undergoing dental surgery.

    PubMed

    Weibert, R T

    1992-10-01

    The literature on dental surgery in patients receiving oral anticoagulants is reviewed, and methods of managing anticoagulant therapy to minimize the risk of complications are discussed. Although blood loss during and after oral surgery in patients receiving oral anticoagulant drugs can be substantial, research indicates that most bleeding incidents are not serious and can be controlled by local measures. Studies of 241 anticoagulant-treated patients undergoing more than 500 dental extractions during the 1950s and 1960s showed that only 9 had postoperative bleeding. More recent studies indicate that continued anticoagulation can increase the frequency of prolonged bleeding and delay wound healing. An antifibrinolytic mouthwash containing tranexamic acid can effectively suppress postoperative bleeding. Gelatin sponges, oxidized cellulose, and microcrystalline collagen are other useful hemostatic agents. A reduction in the intensity of anticoagulation therapy has been recommended; the prothrombin time should be measured shortly before the procedure in such patients. In many patients the duration of subtherapeutic anticoagulation must be minimized to reduce the possibility of thromboembolism. An option for high-risk patients is to switch them to heparin. Each patient must be evaluated individually, and the level of risk of the dental procedure and the risk of thromboembolism should be taken into account. In patients taking oral anticoagulants who must undergo dental surgery, careful control of the intensity of anticoagulation and improved methods of local hemostasis can minimize the risk of hemorrhagic complications and thromboembolism.

  15. L-carnitine administration and withdrawal affect plasma and hepatic carnitine concentrations, plasma lipid and lipoprotein composition, and in vitro hepatic lipogenesis from labeled mevalonate and oleate in normal rabbits.

    PubMed

    Bell, F P; Vidmar, T J; Raymond, T L

    1992-04-01

    Carnitine was administered to normal rabbits to investigate the possible effects of pharmacologic doses on various aspects of normal lipid and lipoprotein metabolism. Carnitine concentrations were measured in the plasma and liver of normal rabbits that received L-carnitine orally [40 mg/(kg.d)] for 21 d and after withdrawal from the carnitine supplement for 21 d. Plasma lipids, plasma lipoprotein composition and in vitro hepatic lipid biosynthesis from [2-14C]mevalonate and [1-14C]oleate were also measured. Threefold elevations in plasma carnitine with carnitine treatment were essentially reversed after 48 h of carnitine withdrawal, but elevated hepatic carnitine accumulation (twofold) persisted for 21 d, suggesting that the accumulated carnitine constituted a pool that is only slowly miscible with plasma. The rabbits withdrawn from L-carnitine for 21 d experienced a 35% decrease in plasma cholesterol, a 50% decrease in VLDL cholesterol, and an increase in the protein content of HDL and of intermediate density lipoprotein + LDL. Additionally, the proportion of [14C]oleate incorporated into hepatic phospholipids increased 35% at the expense of triglyceride and the ratio of hepatic [14C]cholesterol to [14C]squalene derived from [14C]mevalonate increased over twofold following carnitine withdrawal. These studies provide evidence that normal lipid homeostasis can be altered by supplemental carnitine and that the perturbations are reflected by changes in plasma lipids and lipoproteins and in the proportions of the hepatic lipids synthesized.

  16. Patient with Eating Disorder, Carnitine Deficiency and Dilated Cardiomyopathy.

    PubMed

    Fotino, A Domnica; Sherma, A

    2015-01-01

    Dilated cardiomyopathy is characterized by a dilated and poorly functioning left ventricle and can result from several different etiologies including ischemic, infectious, metabolic, toxins, autoimmune processes or nutritional deficiencies. Carnitine deficiency-induced cardiomyopathy (CDIM) is an uncommon cause of dilated cardiomyopathy that can go untreated if not considered. Here, we describe a 30-year-old woman with an eating disorder and recent percutaneous endoscopic gastrotomy (PEG) tube placement for weight loss admitted to the hospital for possible PEG tube infection. Carnitine level was found to be low. Transthoracic echocardiogram (TTE) revealed ejection fraction 15%. Her hospital course was complicated by sepsis from a peripherally inserted central catheter (PICC). She was discharged on a beta-blocker and carnitine supplementation. One month later her cardiac function had normalized. Carnitine deficiency-induced myopathy is an unusual cause of cardiomyopathy and should be considered in adults with decreased oral intake or malabsorption who present with cardiomyopathy.

  17. Transient carnitine transport defect with cholestatic jaundice: report of one case in a premature baby

    PubMed Central

    Cho, Hyun-Seok; Choo, Young Kwang; Lee, Hong Jin

    2012-01-01

    Carnitine (β-hydroxy-γ-trimethylaminobutyric acid) is involved in the transport of long-chain fatty acids into the mitochondrial matrix and the removal of potentially toxic acylcarnitine esters. Transient carnitine transport defect is a rare condition in newborns reported in 1/90,000 live births. In this paper, we describe a case of transient carnitine transport defect found in a premature baby who had prolonged cholestatic jaundice and poor weight gain, and who responded dramatically to oral carnitine supplementation. PMID:22375151

  18. L-carnitine ameliorates cancer cachexia in mice by regulating the expression and activity of carnitine palmityl transferase.

    PubMed

    Liu, Su; Wu, Han-Jun; Zhang, Zong-Qi; Chen, Qing; Liu, Bin; Wu, Jian-Ping; Zhu, Liang

    2011-07-15

    Cancer cachexia is characterized by progressive weight loss with the depletion of adipose tissue and skeletal muscle. Impaired fatty acid oxidation mainly resulting from the decrease of carnitine palmitoyltransferase I and II activities in the liver is an important factor that contributes to cancer cachexia . Although recent studies suggest a potential application of L-carnitine in treatment of cancer cachexia, the underlying mechanisms are unknown. In the present study, we aim to assess the effects of L-carnitine on the activity and expression of CPT I and II in the liver of cachectic cancer mice. Our results show that the inoculation of colon-26 adenocarcinoma cells into mice led to cancer cachexia characterized by notable decreases in food intake, gastrocnemius muscle and epididymus fat weight. In addition, the mRNA level and activity of liver carnitine palmitoyltransferase (CPT) I and II, and serum levels of free carnitine and acetylcarnitine were markedly decreased in cachectic mice, accompanied by marked increases in serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). A continuous oral treatment with L-carnitine at 18 mg/kg per day increased dietary uptake, gastrocnemius muscle weight and epididymus fat weight, increased blood glucose and serum albumin levels, and decreased total cholesterol level in cancer cachectic mice, but did not affect tumor growth. These effects of L-carnitine on cancer cachexia mice were accompanied by the upregulation of mRNA level of CPT I and II and increased enzyme activity of CPT I in the liver, as well as the downregulation of serum TNF-α and IL-6 levels. Moreover, free carnitine levels were negatively correlated with serum TNF-α or IL-6 level. These results indicate that L-carnitine ameliorates cancer cachexia by regulating serum TNF-α and IL-6 levels and modulating the expression and activity of CPT in the liver.

  19. Revisiting the Cutaneous Impact of Oral Hormone Replacement Therapy

    PubMed Central

    Piérard, Gérald E.; Humbert, Philippe; Berardesca, Enzo; Gaspard, Ulysse; Hermanns-Lê, Trinh; Piérard-Franchimont, Claudine

    2013-01-01

    Menopause is a key point moment in the specific aging process of women. It represents a universal evolution in life. Its initiation is defined by a 12-month amenorrhea following the ultimate menstrual period. It encompasses a series of different biologic and physiologic characteristics. This period of life appears to spot a decline in a series of skin functional performances initiating tissue atrophy, withering, and slackness. Any part of the skin is possibly altered, including the epidermis, dermis, hypodermis, and hair follicles. Hormone replacement therapy (oral and nonoral) and transdermal estrogen therapy represent possible specific managements for women engaged in the climacteric phase. All the current reports indicate that chronologic aging, climacteric estrogen deficiency, and adequate hormone therapy exert profound effects on various parts of the skin. PMID:24455744

  20. Oral iron therapy and chronic idiopathic urticaria: sideropenic urticaria?

    PubMed

    Guarneri, Fabrizio; Guarneri, Claudio; Cannavò, Serafinella Patrizia

    2014-01-01

    Chronic urticaria (CU) is frequent, remains often idiopathic despite diagnostic efforts, and sometimes poorly responds to oral antihistamines and/or corticosteroids. We noticed that hyposideremia is often found in patients with chronic idiopathic urticaria poorly responsive to usual treatments (prCIU), and oral iron therapy is frequently associated to improvement or resolution of urticaria. Between 2003 and 2012, we observed 122 patients with prCIU, of which 81 had moderate hyposideremia at our first visit. They continued the antihistamines already practiced and received oral iron therapy for 30 or 45 days. Two months after our first visit, all had normal serum iron levels; 64 reported complete remission of urticaria and 17 reported improvement superior to 80%. No adverse reactions to treatment were observed. Follow-up visits confirmed stability of results over 6 months. Our preliminary data show that hyposideremia is the only abnormality in many patients with prCIU, and restoration of normal iron serum levels is associated to remission or remarkable clinical improvement of urticaria. In consideration of low cost and potential benefits for some patients, determination of serum levels of iron could be introduced in the diagnostic workup of chronic urticaria, maybe as a second-level exam in patients without other relevant clinical or laboratory abnormalities.

  1. Disorders of carnitine biosynthesis and transport.

    PubMed

    El-Hattab, Ayman W; Scaglia, Fernando

    2015-11-01

    Carnitine is a hydrophilic quaternary amine that plays a number of essential roles in metabolism with the main function being the transport of long-chain fatty acids from the cytosol to the mitochondrial matrix for β-oxidation. Carnitine can be endogenously synthesized. However, only a small fraction of carnitine is obtained endogenously while the majority is obtained from diet, mainly animal products. Carnitine is not metabolized and is excreted in urine. Carnitine homeostasis is regulated by efficient renal reabsorption that maintains carnitine levels within the normal range despite variabilities in dietary intake. Diseases occurring due to primary defects in carnitine metabolism and homeostasis are comprised in two groups: disorders of carnitine biosynthesis and carnitine transport defect. While the hallmark of carnitine transport defect is profound carnitine depletion, disorders of carnitine biosynthesis do not cause carnitine deficiency due to the fact that both carnitine obtained from diet and efficient renal carnitine reabsorption can maintain normal carnitine levels with the absence of endogenously synthesized carnitine. Carnitine transport defect phenotype encompasses a broad clinical spectrum including metabolic decompensation in infancy, cardiomyopathy in childhood, fatigability in adulthood, or absence of symptoms. The phenotypes associated with the carnitine transport defect result from the unavailability of enough carnitine to perform its functions particularly in fatty acid β-oxidation. Carnitine biosynthetic defects have been recently described and the phenotypic consequences of these defects are still emerging. Although these defects do not result in carnitine deficiency, they still could be associated with pathological phenotypes due to excess or deficiency of intermediate metabolites in the carnitine biosynthetic pathway and potential carnitine deficiency in early stages of life when brain and other organs develop. In addition to these two

  2. Nonsurgical Management of Oral Mucocele by Intralesional Corticosteroid Therapy

    PubMed Central

    Sinha, Rupam; Sarkar, Soumyabrata; Kabiraj, Arpita; Maji, Anirban

    2016-01-01

    Background. Oral mucocele is a common lesion resulting from an alteration of minor salivary glands due to mucus accumulation. Rapid appearance, specific location, history of trauma, bluish colour, and consistency help in the diagnosis. Conventional surgical removal is the treatment of choice but has several disadvantages like damage to adjacent ducts with further development of satellite lesions. Therefore, the present study was undertaken to evaluate the efficacy of intralesional corticosteroid injection (betamethasone) as a nonsurgical treatment procedure in oral mucoceles. Material and Method. A total of 20 cases (males and females, 10–30 years of age) with clinically diagnosed oral mucoceles were given 1 mL of betamethasone intralesionally. All the patients were examined after a period of 7, 14, and 21 days to evaluate the response of the lesion towards treatment and consequently given the 2nd, 3rd, 4th injections. If the lesion resolved after one or two injections, the treatment was discontinued. Results. Out of the 20 cases, 18 of them showed complete regression of the lesion whereas the remaining 2 cases showed decrease in size. All the patients received maximum of 4 consecutive shots in weekly interval. Conclusion. Intralesional corticosteroid therapy can be considered as the first choice in the treatment of oral mucoceles. PMID:27822227

  3. Photodynamic therapy of oral Candida infection in a mouse model.

    PubMed

    Freire, Fernanda; Ferraresi, Cleber; Jorge, Antonio Olavo C; Hamblin, Michael R

    2016-06-01

    Species of the fungal genus Candida, can cause oral candidiasis especially in immunosuppressed patients. Many studies have investigated the use of photodynamic therapy (PDT) to kill fungi in vitro, but this approach has seldom been reported in animal models of infection. This study investigated the effects of PDT on Candida albicans as biofilms grown in vitro and also in an immunosuppressed mouse model of oral candidiasis infection. We used a luciferase-expressing strain that allowed non-invasive monitoring of the infection by bioluminescence imaging. The phenothiazinium salts, methylene blue (MB) and new methylene blue (NMB) were used as photosensitizers (PS), combined or not with potassium iodide (KI), and red laser (660nm) at four different light doses (10J, 20J, 40J and 60J). The best in vitro log reduction of CFU/ml on biofilm grown cells was: MB plus KI with 40J (2.31 log; p<0.001); and NMB without KI with 60J (1.77 log; p<0.001). These conditions were chosen for treating the in vivo model of oral Candida infection. After 5days of treatment the disease was practically eradicated, especially using MB plus KI with 40J. This study suggests that KI can potentiate PDT of fungal infection using MB (but not NMB) and could be a promising new approach for the treatment of oral candidiasis.

  4. New oral anticoagulants and dual antiplatelet therapy: Focus on apixaban.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J; Rosano, Giuseppe

    2016-12-15

    The combination of AF and coronary artery disease not only is a common clinical setting, it is also a complex setting to deal with anticoagulation and antiplatelet therapy, and it is associated with significantly higher mortality rates. Unfortunately, there are no sufficient data available to optimally guide clinical practice in such settings. This review focuses specifically on newer oral anticoagulants (NOACs) associated with dual antiplatelet therapy (DAPT) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). There are no randomized studies comparing vitamin K antagonists and NOACs in patients with AF undergoing PCI either for acute coronary syndromes or for stable patients, i.e. those patients who have an indication to receive DAPT. Moreover, new antiplatelet agents such as ticagrelor and prasugrel have entered the market for acute coronary syndromes. So far, there are no large-scale randomized studies published evaluating these newer antiplatelet agents in patients with AF receiving either vitamin K antagonists or NOACs, adding to the uncertainty on how to use these antithrombotics in combination when both coronary artery disease (unstable or stable patients) and AF converge in a given patient. The lack of large outcome trials and the large number of possible combinations are reflected in the wide variety of practices in the real world. To date, given the lack of data, watchfulness when using NOACs as component of DAPT or triple oral antithrombotic therapy is warranted.

  5. Oral anatomy laboratory examinations in a physical therapy program.

    PubMed

    Fabrizio, Philip A

    2013-01-01

    The process of creating and administering traditional tagged anatomy laboratory examinations is time consuming for instructors and limits laboratory access for students. Depending on class size and the number of class, sections, creating, administering, and breaking down a tagged laboratory examination may involve one to two eight-hour days. During the time that a tagged examination is being created, student productivity may be reduced as the anatomy laboratory is inaccessible to students. Further, the type of questions that can be asked in a tagged laboratory examination may limit student assessment to lower level cognitive abilities and may limit the instructors' ability to assess the students' understanding of anatomical and clinical concepts. Anatomy is a foundational science in the Physical Therapy curriculum and a thorough understanding of anatomy is necessary to progress through the subsequent clinical courses. Physical therapy curricula have evolved to reflect the changing role of physical therapists to primary caregivers by introducing a greater scope of clinical courses earlier in the curriculum. Physical therapy students must have a thorough understanding of clinical anatomy early in the education process. However, traditional anatomy examination methods may not be reflective of the clinical thought processes required of physical therapy students. Traditional laboratory examination methods also reduce student productivity by limiting access during examination set-up and breakdown. To provide a greater complexity of questions and reduced overall laboratory time required for examinations, the Physical Therapy Program at Mercer University has introduced oral laboratory examinations for the gross anatomy course series.

  6. Risk assessment for carnitine.

    PubMed

    Hathcock, John N; Shao, Andrew

    2006-10-01

    Carnitine is a conditionally essential amino acid-like compound involved in the transport of long-chain fatty acids into the mitochondria during the beta-oxidation process. Carnitine has become an increasingly popular ingredient in dietary supplements, especially weight loss and some sports nutrition products. A number of clinical trials have been conducted examining the effect of carnitine supplementation on weight loss and energy balance. Regarding safety, systematic evaluation of the research designs and data do not provide a basis for risk assessment and the usual safe upper level of intake (UL) derived from it unless the newer methods described as the observed safe level (OSL) or highest observed intake (HOI) are utilized. The OSL risk assessment method indicates that the evidence of safety is strong at intakes up to 2000mg/day l-carnitine equivalents for chronic supplementation, and this level is identified as the OSL. Although much higher levels have been tested without adverse effects and may be safe, the data for intakes above 2000mg/day are not sufficient for a confident conclusion of long-term safety.

  7. L-carnitine.

    PubMed

    2004-11-22

    Although advertised on the Internet for weight loss, prevention of aging and enhancement of athletic and sexual performance, levocarnitine has only one well-established indication, and that is for treatment of carnitine deficiency. In clinical trials, the drug also seems to have had modest effects in some other conditions, particularly intermittent claudication and recovery after myocardial infarction, but more studies are needed.

  8. Bridging of oral anticoagulation therapy for invasive procedures.

    PubMed

    Spyropoulos, Alex C

    2005-09-01

    The management of patients who need temporary interruption of chronic oral anticoagulant (OAC) therapy for an elective surgical or invasive procedure is problematic and complex. Patient and procedural risk factors for thrombosis and bleeding, anticoagulant-related risks of bleeding, and clinical consequences of a thrombotic or bleeding event need to be assessed and properly risk-stratified in the perioperative period. Certain procedures, such as dental, endoscopic, and cutaneous procedures, can be completed without discontinuing OAC, but most procedures with a high bleeding risk (including major surgeries) will necessitate temporary discontinuation of OAC. Bridging therapy with shorter-acting anticoagulants, such as heparin, for patients at intermediate to high risk of thromboembolism represents one strategy to maintain functional anticoagulation during this period. Large, prospective cohort studies and registries of patients on chronic OAC who underwent bridging therapy mostly with low-molecular-weight heparin have been completed recently. This paper reviews these clinical data on bridging therapy and provides an evidence-based perioperative management strategy for the at-risk patient on chronic OAC.

  9. Role of carnitine in disease

    PubMed Central

    2010-01-01

    Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure. PMID:20398344

  10. Dental procedures in patients receiving oral anticoagulation therapy.

    PubMed

    Saour, J N; Ali, H A; Mammo, L A; Sieck, J O

    1994-05-01

    Over a 10-year period a uniform management plan for patients receiving long term oral anticoagulation therapy for prosthetic heart valves and needing dental procedures was instituted. Those undergoing dental extraction or gum hygiene in the presence of gross gum pathology (Group A) had their oral anticoagulation discontinued two days prior to the procedure which was carried out only if the INR was 1.5 or less on the day of the procedure. Patients who needed dental fillings or gum hygiene in the absence of gross gum pathology (Group B) continued their anticoagulation therapy and had these procedures completed provided the INR was 3.0 or less. The main outcome measured were valve thrombosis, thromboembolism and excessive bleeding requiring hospitalization and/or blood transfusion. In Group A, 240 procedures were carried out; 212 dental extractions and 28 dental hygiene in the presence of gross gum pathology. They had a brief period of under-anticoagulation (3-7 days) to an INR of 1.5 or less. In Group B, 156 procedures were performed. No patient developed valve thrombosis or thromboembolism. Two patients, both in Group A needed hospitalization for observation but no blood transfusion. This management plan was easy to implement. Patients needed one extra visit to the anticoagulation clinic within one week of the procedure. It was both safe and effective.

  11. Genetics Home Reference: carnitine palmitoyltransferase I deficiency

    MedlinePlus

    ... in cells. A group of fats called long-chain fatty acids cannot enter mitochondria unless they are ... carnitine. Carnitine palmitoyltransferase 1A connects carnitine to long-chain fatty acids so they can enter mitochondria and ...

  12. The Effect of Acetyl-L-Carnitine Administration on Persons with Down Syndrome

    ERIC Educational Resources Information Center

    Pueschel, Siegfried M.

    2006-01-01

    Since previous investigations reported improvements in cognition of patients with dementia after acetyl-L-carnitine therapy and since there is an increased risk for persons with Down syndrome to develop Alzheimer disease, this study was designed to investigate the effect of acetyl-L-carnitine administration on neurological, intellectual, and…

  13. Carnitine deficiency and oxidative stress provoke cardiotoxicity in an ifosfamide-induced Fanconi Syndrome rat model

    PubMed Central

    Darweesh, Amal Q; Fatani, Amal J

    2010-01-01

    In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO) therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC) could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day) combined with mildronate (MD, 200 mg/kg/day) and PLC (250 mg/kg/day), respectively, for 10 successive days. The 4th, 5th and 6th groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day). IFO significantly increased serum creatinine, blood urea nitrogen (BUN), urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS) in cardiac tissues and significantly decreased adenosine triphosphate (ATP) and total carnitine and reduced glutathione (GSH) content in cardiac tissues. In carnitine

  14. Anti-adipogenic and antiviral effects of l-carnitine on hepatitis C virus infection.

    PubMed

    Tsukuda, Yoko; Suda, Goki; Tsunematsu, Seiji; Ito, Jun; Sato, Fumiyuki; Terashita, Katsumi; Nakai, Masato; Sho, Takuya; Maehara, Osamu; Shimazaki, Tomoe; Kimura, Megumi; Morikawa, Kenichi; Natsuizaka, Mitsuteru; Ogawa, Koji; Ohnishi, Shunsuke; Chuma, Makoto; Sakamoto, Naoya

    2017-05-01

    Hepatitis C virus (HCV) has been reported to hijack fatty acid metabolism in infected hepatocytes, taking advantage of lipid droplets for virus assembly. In this study, we analyzed the anti-HCV activity of l-carnitine, a substance involved in the transport of fatty acids into mitochondria. JFH-1 or HCV replicon-transfected Huh7.5.1 cells were treated with or without l-carnitine to examine its anti-HCV effects. The effects of l-carnitine on HCV entry, HCV-induced adipogenesis and lipid droplet formation, and HCV-induced oxidative stress were examined. Treatment of JFH-1-infected cells with l-carnitine inhibited HCV propagation in a concentration-dependent manner. In contrast, l-carnitine had no anti-HCV activity in the HCV replicon system, which is lacking viral assembly. In addition, l-carnitine did not affect HCV entry. However, l-carnitine treatment decreased intracellular lipid droplets, which are crucial for HCV assembly in JFH-1-infected cells. The expression level of CPT-1 was decreased in JFH-1-infected cells, and l-carnitine treatment restored this expression. HCV-infected cells exhibited increased production of reactive oxygen species and glutathione oxidation. l-carnitine decreased oxidative stress induced by JFH-1-infection, as shown by glutathione/glutathione disulfide assays and MitoSOX staining. l-carnitine exhibited anti-HCV activity, possibly by inhibiting HCV assembly and through its anti-adipogenic activity in HCV-infected cells. Moreover, l-carnitine has antioxidant properties in HCV-infected hepatocytes. Overall, these results indicated that l-carnitine may be an effective adjunctive agent in antiviral therapies to treat chronic hepatitis C. J. Med. Virol. 89:857-866, 2017. © 2016 Wiley Periodicals, Inc.

  15. [Orthodontic and oral surgery therapy in cleidocranial dysplasia].

    PubMed

    Balaton, Gergely; Tarján, Ildikó; Balaton, Péter; Barabási, Zoltán; Gyulai Gál, Szabolcs; Nagy, Katalin; Vajó, Zoltán

    2007-02-01

    A cleidocranial dysplasia is an autosomal dominant inherited condition consisting of generalized skeletal disorder. Associated dental signs are present in 93,5%; failure of tooth eruption with multiple supernumerary teeth, dilaceration of roots, crown germination, microdontia, high arched palate, midface hypoplasia, high gonion angle. The molecular- genetic analysis revealed a missense mutation in the CBFA1 gene located on chromosome 6p21, which is considered to be etiological factor for CCD. Orthodontic and oral surgery therapy of a 13 year-old child with CCD was performed due to aesthetic and functional problems. The supernumerary germs were removed and the teeth were aligned with orthodontic appliances. Temporary functional rehabilitation was solved with partial denture. The presented case and the literature data support the importance of early diagnosis of CCD. The good collaboration of the orthodontic and maxillo-facial surgery specialists help achieve the correct rehabilitation of the patient.

  16. [New therapies for diabetes: beyond injectable insulin and oral antidiabetics].

    PubMed

    Alfonso, John Edwin Feliciano; Ariza, Iván Darío Sierra

    2008-01-01

    New medicines for the therapy of the type 1 and type 2 diabetes have been incorporated in the list of traditional drugs: oral agents and injectable insulin. These treatment alternatives have a new mechanism of action that takes advantage of the antidiabetic properties of certain peptides such as amylin and glucagon like peptide-1 (GLP-1), whose levels are wanting or insufficient in diabetes. This is attained through amylin and GLP-1 analogues, although it can also be achieved by inhibiting the enzyme that degrades the latter. Furthermore, a new system to administer insulin in a noninvasive way through inhalation has become available in the market. This paper summarizes the most important and updated findings on the action mechanism, efficacy, adverse effects and indications of these innovative drugs.

  17. Evaluation of social marketing of oral rehydration therapy.

    PubMed

    Koul, P B; Murali, M V; Gupta, P; Sharma, P P

    1991-09-01

    Attempts, at social marketing of oral rehydration therapy (ORT) through television, in changing the knowledge and practice of mothers with regard to its use was assessed. One hundred and eighty seven consecutive mothers (38 excluded due to non use of ORT) were administered a preplanned questionnaire to assess their socio-economic profile, educational status, concept of diarrhea and correct use of ORT. Fifty nine mothers who watched these programmes on TV regularly formed the study group. These were compared with 90 mothers who had gained such knowledge from non-television sources. The correct application of knowledge of ORT was significantly better in study group compared with control group. The educational status of mothers had a positive impact on motivation to use ORT at home in the study group. Mass media campaigns through "TV spots" is an effective way of improving knowledge of mothers on ORT in a developing country.

  18. Stroke in women - oral contraception, pregnancy, and hormone replacement therapy.

    PubMed

    Rantanen, Kirsi; Tatlisumak, Turgut

    2013-01-01

    Stroke is a devastating disease affecting millions of people worldwide every year. Female stroke victims have higher mortality rates and they do not re-cover as well as men. Women's longevity and different vascular risk factor burden like a larger prevalence of atrial fibrillation play a role. Women also have unique risk factors such as oral contraception, pregnancy, estrogen decrease after the menopause and hormone replacement therapy, which should all be evaluated and taken into consideration in treatment decisions both in the acute phase of stroke and in secondary prevention. In this review, the evidence regarding these hormonal aspects and the risk of stroke in women are evaluated. The relevant guidelines are studied and research gaps identified. Future topics for research are recommended and current treatment possibilities and their risks discussed.

  19. Safety assessment of oral photodynamic therapy in rats.

    PubMed

    Fontana, Carla R; Lerman, Mark A; Patel, Niraj; Grecco, Clovis; Costa, Carlos A de Souza; Amiji, Mansoor M; Bagnato, Vanderlei S; Soukos, Nikolaos S

    2013-02-01

    Photodynamic therapy (PDT) is based on the synergism of a photosensitive drug (a photosensitizer) and visible light to destroy target cells (e.g., malignant, premalignant, or bacterial cells). The aim of this study was to investigate the response of normal rat tongue mucosa to PDT following the topical application of hematoporphyrin derivative (Photogem®), Photodithazine®, methylene blue (MB), and poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with MB. One hundred and thirty three rats were randomly divided in various groups: the PDT groups were treated with the photosensitizers for 10 min followed by exposure to red light. Those in control groups received neither photosensitizer nor light, and they were subjected to light exposure alone or to photosensitizer alone. Fluorescent signals were obtained from tongue tissue immediately after the topical application of photosensitizers and 24 h following PDT. Histological changes were evaluated at baseline and at 1, 3, 7, and 15 days post-PDT treatment. Fluorescence was detected immediately after the application of the photosensitizers, but not 24 h following PDT. Histology revealed intact mucosa in all experimental groups at all evaluation time points. The results suggest that there is a therapeutic window where PDT with Photogem®, Photodithazine®, MB, and MB-loaded PLGA nanoparticles could safely target oral pathogenic bacteria without damaging normal oral tissue.

  20. Abbreviated oral itraconazole therapy for tinea corporis and tinea cruris.

    PubMed

    Sanmano, B; Hiruma, M; Mizoguchi, M; Ogawa, H

    2003-09-01

    The present study was designed to determine the lowest dose of orally administered itraconazole and the shortest duration of therapy necessary for treatment of tinea corporis and tinea cruris. For all patients, the itraconazole dose was 100 mg twice a day immediately after meals. Twenty-eight patients received itraconazole on days 1 and 8, 12 patients received itraconazole on days 1 and 2, and five patients received itraconazole only on day 1. Clinical and mycological evaluations were performed at baseline and on day 14. Based on the clinical and mycological responses, treatment efficacy was classified as excellent, good, fair, or poor. "Excellent" and "good" responses made up 86% of the first group, 100% of the second group, and 20% of the third group. A comparison of efficacy ratings of the three regimens showed that the patients who received a single 200-mg dose had a significantly inferior outcome compared with the other two groups. We conclude that an abbreviated oral regimen of itraconazole for treatment of tinea corporis and tinea cruris requires a total dose of at least 400 mg to induce a favorable outcome.

  1. Hypofractionated radiation therapy of oral melanoma in five cats.

    PubMed

    Farrelly, John; Denman, David L; Hohenhaus, Ann E; Patnaik, Amiya K; Bergman, Philip J

    2004-01-01

    Five cats with melanoma involving the oral cavity were treated with hypofractionated radiation therapy (RT). Cobalt photons were used to administer three fractions of 8.0 Gray (Gy) for a total dose of 24 Gy. Four cats received radiation on days 0, 7, and 21 and one cat received radiation on days 0, 7, and 13. One of the cats received additional irradiation following the initial treatment course. Two cats received chemotherapy. Their age ranged from 11 to 15 years with a median age of 12 years. Three cats had a response to radiation, including one complete response and two partial responses. All five cats were euthanized due to progression of disease, with one cat having evidence of metastatic disease at the time of euthanasia. The median survival time for the five cats was 146 days (range 66-224 days) from the start of RT. The results of this study suggest that oral melanoma in cats may be responsive to hypofractionated RT, but response does not seem to be durable.

  2. Influence of radiation therapy on oral Candida albicans colonization: a quantitative assessment

    SciTech Connect

    Rossie, K.M.; Taylor, J.; Beck, F.M.; Hodgson, S.E.; Blozis, G.G.

    1987-12-01

    An increase in quantity of oral Candida albicans was documented in patients receiving head and neck radiation therapy during and after therapy, as assessed by an oral-rinse culturing technique. The amount of the increase was greater in denture wearers and directly related to increasing radiation dose and increasing volume of parotid gland included in the radiation portal. A significant number of patients who did not carry C. albicans prior to radiation therapy developed positive cultures by 1 month after radiation therapy. The percentage of patients receiving head and neck radiation therapy who carried C. albicans prior to radiation therapy did not differ significantly from matched dental patient controls.

  3. Relative Carnitine Deficiency in Autism

    ERIC Educational Resources Information Center

    Filipek, Pauline A.; Juranek, Jenifer; Nguyen, Minh T.; Cummings, Christa; Gargus, J. Jay

    2004-01-01

    A random retrospective chart review was conducted to document serum carnitine levels on 100 children with autism. Concurrently drawn serum pyruvate, lactate, ammonia, and alanine levels were also available in many of these children. Values of free and total carnitine ([rho] less than 0.001), and pyruvate ([rho]=0.006) were significantly reduced…

  4. Carnitines slow down tumor development of colon cancer in the DMH-chemical carcinogenesis mouse model.

    PubMed

    Roscilli, Giuseppe; Marra, Emanuele; Mori, Federica; Di Napoli, Arianna; Mancini, Rita; Serlupi-Crescenzi, Ottaviano; Virmani, Ashraf; Aurisicchio, Luigi; Ciliberto, Gennaro

    2013-07-01

    Dietary agents are receiving much attention for the chemoprevention of cancer. While curcumin is known to influence several pathways and affect tumor growth in vivo, carnitin and its congeners play a variety of important metabolic functions: are involved in the oxydation of long-chain fatty acids, regulate acyl-CoA levels and influence protein activity and stability by modifying the extent of protein acetylation. In this study we evaluated the efficacy of carnitines in the prevention of cancer development using the 1,2,-dimethylhydrazine (DMH)-induced colon carcinogenesis model. We also assessed whether their combination was able to give rise to increased protection from cancer development. Mice treated with DMH were dosed orally with curcumin and/or carnitine and acylcarnitines for 20 weeks. At the end of the treatment colon samples were collected, and scored for multiple ACF and adenomas. We observed that carnitine and acyl-carnitines had same, if not higher, efficacy than curcumin alone in inhibiting the formation of neoplastic lesions induced by DMH treatment. Interestingly, the combination of curcumin and acetyl-L-carnitine was able to fully inhibit the development of advanced adenoma lesions. Our data unveil the antitumor effects of carnitines and warrant additional studies to further support the adoption of carnitines as cancer chemopreventative agents.

  5. L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study.

    PubMed

    Cruciani, Ricardo A; Dvorkin, Ella; Homel, Peter; Culliney, Bruce; Malamud, Stephen; Lapin, Jeanne; Portenoy, Russell K; Esteban-Cruciani, Nora

    2009-04-01

    Carnitine deficiency is prevalent in populations with chronic illness, including cancer. In a recent open-label study, L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients. To further evaluate this finding, adult patients with advanced cancer, carnitine deficiency (free carnitine more than 35 micromol/L for males or less than 25 micromol/L for females, or acyl/free carnitine ratio of more than 0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score of 50 or more, were randomly assigned to receive either L-carnitine (0.5 g/day for two days, followed by 1g/day for two days, and then 2g/day for 10 days) or placebo. This double-blind phase was followed by an open-label phase, during which all patients received L-carnitine supplementation for two weeks. Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Linear Analog Scale Assessments (LASA), the Mini-Mental State Exam (MMSE), and the KPS. Twenty-nine patients (12 placebo, 17 L-carnitine) were included in the intent-to-treat (ITT) analysis. From baseline to the end of the double-blind phase, serum total and free L-carnitine increased from 32.9+/-3.8 to 56.6+/-20.5 (P=0.004), and from 22.9+/-19.4 to 45.3+/-17.2 (P=0.004), respectively, in the L-carnitine-treated group, and from 28.2+/-10.2 to 36.2+/-8.7 (P=ns), and from 22.6+/-7.9 to 28.7+/-8.6 (P=ns) in the placebo group, respectively. The planned ITT analysis revealed no significant improvement in any of the study's endpoints, and these negative findings were not different when data from two patients who did not adhere to the protocol were eliminated. However, an exploratory covariate analysis that excluded these two protocol violators and included outcome data from both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale (P<0.03), and significantly improved FACT

  6. Enzymology of the carnitine biosynthesis pathway.

    PubMed

    Strijbis, Karin; Vaz, Frédéric M; Distel, Ben

    2010-05-01

    The water-soluble zwitterion carnitine is an essential metabolite in eukaryotes required for fatty acid oxidation as it functions as a carrier during transfer of activated acyl and acetyl groups across intracellular membranes. Most eukaryotes are able to synthesize carnitine endogenously, besides their capacity to take up carnitine from the diet or extracellular medium through plasma membrane transporters. This review discusses the current knowledge on carnitine homeostasis with special emphasis on the enzymology of the four steps of the carnitine biosynthesis pathway.

  7. L-carnitine and propionyl-L-carnitine improve endothelial dysfunction in spontaneously hypertensive rats: different participation of NO and COX-products.

    PubMed

    Bueno, Rosario; Alvarez de Sotomayor, Maria; Perez-Guerrero, Concepción; Gomez-Amores, Lucia; Vazquez, Carmen M; Herrera, M Dolores

    2005-09-09

    L-carnitine and propionyl-L-carnitine are supplements to therapy in cardiovascular pathologies. Their effect on endothelial dysfunction in hypertension was studied after treatment with either 200 mg/kg of L-carnitine or propionyl-L-carnitine during 8 weeks of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Endothelial function was assessed in aortic rings by carbachol-induced relaxation (CCh 10(-8) to 10(-4) M) and factors involved were characterized in the presence of the inhibitors: L-NAME, indomethacin, the TXA2/PGH2 Tp receptor antagonist ICI-192,605 and the thromboxane synthetase inhibitor-Tp receptor antagonist, Ro-68,070. The effect on phenylephrine-induced contractions was also observed. To identify the nature of vasoactive COX-derived products, enzyme-immunoassay of incubation media was assessed. Involvement of reactive oxygen species was evaluated by incubating with superoxide dismutase and catalase. Nitric oxide production was evaluated by serum concentration of NO2+NO3.Treatment with both compounds improved endothelial function of rings from SHR without blood pressure change. Propionyl-L-carnitine increased NO participation in WKY and SHR. L-carnitine reduced endothelium-dependent responses to CCh in WKY due to an increase of TXA2 production. In both SHR and WKY, L-carnitine enhanced concentration of PGI2 and increased participation of NO. Results in the presence of SOD plus catalase show that it might be related to antioxidant properties of L-carnitine and propionyl-L-carnitine. Comparison between the effect of both compounds shows that both may reduce reactive oxygen species and increase NO participation in endothelium-dependent relaxations in SHR. However, only L-carnitine was able to increase the release of the vasodilator PGI2 and even enhanced TXA2 production in normotensive rats.

  8. Inhibition of Gene Expression of Organic Cation/Carnitine Transporter and Antioxidant Enzymes in Oxazaphosphorines-Induced Acute Cardiomyopathic Rat Models

    PubMed Central

    Sayed-Ahmed, Mohamed M.; Aldelemy, Meshan Lafi; Hafez, Mohamed M.; Al-Shabanah, Othman A.

    2012-01-01

    It is well documented that high therapeutic doses of oxazaphosphorines, cyclophosphamide (CP) and ifosfamide (IFO), are associated with cardiomyopathy. This study investigated whether oxazaphosphorines alter the expression of organic cation/carnitine transporter (OCTN2) and antioxidant genes and if so, whether these alterations contribute to CP and IFO-induced cardiotoxicity. Adult male Wistar albino rats were assigned to one of six treatment groups namely, control, L carnitine, CP, IFO, CP plus L carnitine and IFO plus L carnitine. In cardiac and kidney tissues, CP and IFO significantly decreased mRNA and protein expression of OCTN2. Oxazaphosphorines significantly increased serum acyl-carnitine/free carnitine ratio and urinary carnitine excretion and significantly decreased total carnitine in cardiac tissues. Interestingly, carnitine supplementation completely reversed the biochemical and gene expression changes-induced by oxazaphosphorines to the control values, except OCTN2 expression remained inhibited by IFO. Data from this study suggest that: (1) Oxazaphosphorines decreased myocardial carnitine content following the inhibition of OCTN2 mRNA and protein expression in cardiac tissues. (2) Oxazaphosphorine therapy increased urinary loss of carnitine secondary to the inhibition of OCTN2 mRNA and protein expression in proximal tubules of the kidney. (3) Carnitine supplementation attenuates CP but not IFO-induced inhibition of OCTN2 mRNA and protein expression in heart and kidney tissues. PMID:22701146

  9. Bullous Lichen Planus treated with Oral Minipulse Therapy: A Rare Case Report

    PubMed Central

    Sunitha, K; Boyapati, Ramanaryana; Kumar D.R., Shravan

    2014-01-01

    Oral Lichen planus (OLP) is a common mucocutaneous disorder with a multifactorial aetiology, affecting the women more commonly than men. Most OLP are asymptomatic, except the atrophic and erosive forms.Till date many treatment modalities are implicated to treat this disorder, but no therapy is considered as the single most effective, without side-effects and remission of the lesion. As the treatment of OLP is challenging to the oral practitioners, here we report a case of successful management of extensive, symptomatic bullous and erosive oral lichen planus with a novel treatment protocol- oral minipulse therapy with betamethasone. PMID:25654047

  10. The reduction of heat production in exercising pigeons after L-carnitine supplementation.

    PubMed

    Janssens, G P; Buyse, J; Seynaeve, M; Decuypere, E; De Wilde, R

    1998-04-01

    Four groups (CS,CR,PS,PR) of nine trained male racing pigeons were deprived of feed for 1 d and then subjected to a respiration chamber test in order to study the effect of oral 1-carnitine supplementation on the energy metabolism during flight. One week before, groups CS and CR were orally supplemented with 90 mg of 1-carnitine daily, whereas PS and PR were given a placebo. Groups CS and PS underwent flight simulation by electrostimulation of the breast muscles. Flight simulation increased heat production, kept respiratory quotient from decreasing, decreased thyroxine levels, and increased weight loss. L-Carnitine decreased the rise in heat production during electrostimulation but did not influence respiratory quotient, weight loss, or thyroid hormones. L-Carnitine supplementation in pigeons improves fatty acid combustion efficiency during heavy exercise.

  11. Oral complications of cancer and cancer therapy: from cancer treatment to survivorship.

    PubMed

    Epstein, Joel B; Thariat, Juliette; Bensadoun, Rene-Jean; Barasch, Andrei; Murphy, Barbara A; Kolnick, Leanne; Popplewell, Leslie; Maghami, Ellie

    2012-01-01

    Answer questions and earn CME/CNE Oral complications resulting from cancer and cancer therapies cause acute and late toxicities that may be underreported, underrecognized, and undertreated. Recent advances in cancer treatment have led to changes in the incidence, nature, and severity of oral complications. As the number of survivors increases, it is becoming increasingly recognized that the aggressive management of oral toxicities is needed to ensure optimal long-term oral health and general well-being. Advances in care have had an impact on previously recognized oral complications and are leading to newly recognized adverse effects. Here, the authors briefly review advances in cancer therapy, including recent advances in surgery, oral care, radiation therapy, hematopoietic cell transplantation, and medical oncology; describe how these advances affect oral health; and discuss the frequent and/or severe oral health complications associated with cancer and cancer treatment and their effect upon long-term health. Although some of the acute oral toxicities of cancer therapies may be reduced, they remain essentially unavoidable. The significant impact of long-term complications requires increased awareness and recognition to promote prevention and appropriate intervention. It is therefore important for the primary oncologist to be aware of these complications so that appropriate measures can be implemented in a timely manner. Prevention and management is best provided via multidisciplinary health care teams, which must be integrated and communicate effectively in order to provide the best patient care in a coordinated manner at the appropriate time.

  12. Plasma L-carnitine levels of obese and non-obese polycystic ovary syndrome patients.

    PubMed

    Celik, Fatih; Kose, Mesut; Yilmazer, Mehmet; Köken, Gülengül N; Arioz, Dagistan Tolga; Kanat Pektas, Mine

    2017-01-31

    It is well-known that plasma L-carnitine concentrations are significantly decreased in obese individuals. A study showed that L-carnitine concentrations are significantly lower in lean PCOS patients than in lean healthy women. Thus, it has been suggested that lowered L-carnitine is associated with PCOS. This study also showed that the women with PCOS had significantly lower L-carnitine levels than those of the healthy controls. In addition, this study hypothesised that low L-carnitine levels in PCOS patients were associated with obesity and/or insulin resistance. Moreover, plasma L-carnitine concentrations were found to be statistically similar in PCOS patients and healthy controls, when controlled for obesity. This study implied that L-carnitine could be used as an adjunctive therapy in the management of insulin resistance or obesity in women who have PCOS. Further research might be planned to clarify the clinical effects of L-carnitine administration in PCOS patients with insulin resistance and/or obesity.

  13. Effect of L-carnitine Supplementation on Nutritional Status and Physical Performance Under Calorie Restriction.

    PubMed

    Jain, Swati; Singh, Som Nath

    2015-04-01

    L-carnitine is popular as a potential ergogenic aid because of its role in the conversion of fat into energy. The present study was undertaken to investigate the effect of short term supplementation of L-carnitine on metabolic markers and physical efficiency tests under short term calorie restriction. Male albino rats were divided into four groups (n = 12 in each)-control, calorie restricted (CR for 5 days, 25 % of basal food intake), L-carnitine supplemented (CAR, given orally for 5 days at a dose of 100 mg/kg), CR with L-carnitine supplementation (CR + CAR). Food intake and body weight of the rats were measured along with biochemical variables like blood glucose, tissue glycogen, plasma and muscle protein and enzymatic activities of CPT-1 (carnitine palmitoyl transferase-1) and AMP kinase. Results demonstrated that L-carnitine caused marked increase in muscle glycogen, plasma protein, CPT-1 activity and swim time of rats (P < 0.05) on short term supplementation. In addition to the substantive effects caused by CR alone, L-carnitine under CR significantly affected muscle glycogen, plasma protein, CPT-1 activity and AMP kinase (P < 0.05). Short term CR along with L-carnitine also resulted in increased swim time of rats than control, CR and L-carnitine treated rats (P < 0.05). The present study was an attempt towards developing an approach for better adherence to dietary restriction regimen, with the use of L-carnitine.

  14. Primary systemic carnitine deficiency: a Turkish case with a novel homozygous SLC22A5 mutation and 14 years follow-up.

    PubMed

    Yilmaz, Berna Seker; Kor, Deniz; Mungan, Neslihan Onenli; Erdem, Sevcan; Ceylaner, Serdar

    2015-09-01

    Systemic primary carnitine deficiency is an autosomal recessive disorder caused by the deficiency of carnitine transporter. Main features are cardiomyopathy, myopathy and hypoglycemic encephalopathy. We report a Turkish case with a novel SLC22A5 gene mutation presented with a pure cardiac phenotype. During the 14-year follow-up study, cardiac functions were remained within a normal range with oral L-carnitine supplementation.

  15. The adverse effects of long-term l-carnitine supplementation on liver and kidney function in rats.

    PubMed

    Liu, L; Zhang, D-M; Wang, M-X; Fan, C-Y; Zhou, F; Wang, S-J; Kong, L-D

    2015-11-01

    Levo-Carnitine (l-carnitine) is widely used in health and food. This study was to focus on the adverse effects of 8-week oral supplementation of l-carnitine (0.3 and 0.6 g/kg) in female and male Sprague Dawley rats. l-carnitine reduced body and fat weights, as well as serum, liver, and kidney lipid levels in rats. Simultaneously, hepatic fatty acid β-oxidation and lipid synthesis were disturbed in l-carnitine-fed rats. Moreover, l-carnitine accelerated reactive oxygen species production in serum and liver, thereby triggering hepatic NOD-like receptor 3 (NLRP3) inflammasome activation to elevate serum interleukin (IL)-1β and IL-18 levels in rats. Alteration of serum alkaline phosphatase levels further confirmed liver dysfunction in l-carnitine-fed rats. Additionally, l-carnitine may potentially disturb kidney function by altering renal protein levels of rat organic ion transporters. These observations may provide the caution information for the safety of long-term l-carnitine supplementation.

  16. Use of Low Level Laser Therapy for Oral Lichen Planus: Report of Two Cases

    PubMed Central

    Mahdavi, O; Boostani, N; Jajarm, HH; Falaki, F; Tabesh, A

    2013-01-01

    Oral Lichen Planus is a chronic inflammatory disease of unknown etiology. Erosive/ ulcerative oral lichen planus is often a painful condition that tends to become malignant, urging appropriate therapy. Laser therapy has recently been suggested as a new treatment option without significant side effects. This article presents two cases of erosive/ ulcerative oral lichen planus, who had not received any treatment before, treated with 630 nm low level laser. Lesion type and pain was recorded before and after treatment. Severity of lesions and pain were reduced after treatment. Low Level Laser Therapy was an effective treatment with no side effects and it may be considered as an alternative therapy for erosive/ulcerative oral lichen planus. PMID:24724146

  17. The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

    PubMed

    Afdhal, N H; Zeuzem, S; Schooley, R T; Thomas, D L; Ward, J W; Litwin, A H; Razavi, H; Castera, L; Poynard, T; Muir, A; Mehta, S H; Dee, L; Graham, C; Church, D R; Talal, A H; Sulkowski, M S; Jacobson, I M

    2013-11-01

    Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels.

  18. Stem cell therapy: A novel treatment approach for oral mucosal lesions

    PubMed Central

    Suma, G. N.; Arora, Madhu Pruthi; Lakhanpal, Manisha

    2015-01-01

    Stem cells have enormous potential to alleviate sufferings of many diseases that currently have no effective therapy. The research in this field is growing at an exponential rate. Stem cells are master cells that have specialized capability for self-renewal, potency and capability to differentiate to many cell types. At present, the adult mesenchymal stem cells are being used in the head and neck region for orofacial regeneration (including enamel, dentin, pulp and alveolar bone) in lieu of their proliferative and regenerative properties, their use in the treatment of oral mucosal lesions is still in budding stages. Moreover, there is scanty literature available regarding role of stem cell therapy in the treatment of commonly seen oral mucosal lesions like oral submucous fibrosis, oral lichen planus, oral ulcers and oral mucositis. The present review will focus on the current knowledge about the role of stem cell therapies in oral mucosal lesions and could facilitate new advancements in this area (articles were obtained from electronic media like PubMed, EBSCO, Cochrane and Medline etc., from year 2000 to 2014 to review the role of stem cell therapy in oral mucosal lesions). PMID:25709329

  19. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport

    SciTech Connect

    Rebouche, C.J.; Engel, A.G.

    1984-03-01

    The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-(methyl-3H)carnitine was administered intravenously to six normal subjects, one patient with primary muscle carnitine deficiency (MCD), and four patients with primary systemic carnitine deficiency (SCD). Specific radioactivity was followed in plasma for 28 d. A three-compartment model (extracellular fluid, muscle, and ''other tissues'') was adopted. Rate constants, fluxes, pool sizes, and turnover times were calculated. Results of these calculations indicated reduced transport of carnitine into muscle in both forms of primary carnitine deficiency. However, in SCD, the reduced rate of carnitine transport was attributed to reduced plasma carnitine concentration. In MCD, the results are consistent with an intrinsic defect in the transport process. Abnormal fluctuations of the plasma carnitine, but of a different form, occurred in MCD and SCD. The significance of these are unclear, but in SCD they suggest abnormal regulation of the muscle/plasma carnitine concentration gradient. In 8 of 11 subjects, carnitine excretion was less than dietary carnitine intake. Carnitine excretion rates calculated by kinetic compartmental analysis were higher than corresponding rates measured directly, indicating degradation of carnitine. However, we found no radioactive metabolites of L-(methyl-3H)carnitine in urine. These observations suggest that dietary carnitine was metabolized in the gastrointestinal tract.

  20. Evaluation of Serum Carnitine Levels for Pediatric Patients Receiving Carnitine-Free and Carnitine-Supplemented Parenteral Nutrition

    PubMed Central

    Jackson, Daniel; Mulroy, Cecilia; MacKay, Mark

    2014-01-01

    Purpose: Carnitine is a carrier molecule transporting long-chain fatty acids (LCFAs) into the mitochondria for fatty acid β-oxidation. The purpose of this study is to evaluate the role of carnitine supplementation in parenteral nutrition (PN) within the pediatric population. Our goal was to determine a weight range for which empiric carnitine supplementation is justified and to determine a weight range at which a carnitine level should first be drawn to confirm a deficiency prior to supplementation. Secondarily, we tried to determine a relationship among carnitine deficiency, hypoglycemia, and hypertriglyceridemia. Methods: This was a retrospective observational study to evaluate 2 groups of pediatric patients (weighing 0.68 kg to 60 kg) who were NPO and receiving PN. The first group of patients (n = 454) received carnitine supplementation (15 mg/kg/day) upon initiation of PN. The second group (n = 299) did not receive carnitine supplementation until they were determined to have a carnitine deficiency. Results: The data indicated that 82% of the patients weighing less than 5 kg were deficient. Patients weighing more than 5 kg had serum carnitine levels within the normal range. Therefore, patients receiving PN and weighing less than 5 kg should be supplemented with carnitine. Comparison of triglyceride, glucose, and carnitine showed no statistically significant difference (P = .1936). Conclusion: Patients weighing more than 5 kg should have serum carnitine levels drawn within 7 days to determine whether supplementation is needed. There is no statistical correlation among carnitine deficiency, hypoglycemia, and hypertriglyceridemia. PMID:24958973

  1. Design of quality indicators for oral nutritional therapy.

    PubMed

    Gimenez Verotti, Cristiane Comeron; de Miranda Torrinhas, Raquel Susana Matos; Pires Corona, Ligiana; Waitzberg, Dan Linetzky

    2015-06-01

    Objetivo: los indicadores de calidad en la terapia nutricional han sido propuestos como herramientas útiles para mejorar la terapia nutricional (TN). Este estudio pretende diseñar indicadores de calidad de terapia nutricional oral (ICTNO) factibles en el control de calidad de TN oral. Métodos: el diseño de ICTNO fue realizado por una comisión de nutrición clínica compuesta por brasileños expertos en TN del International Life Science Institute (ILSI). Más tarde, la aprobación de estos ICTNO fue valorada con análisis psicométricos recogiendo las opiniones de otros brasileños dedicados independientemente a la TN (n = 40) vía SurveyMonkey (encuesta por internet). Esta consistió en cuatro atributos valorando cada ICTNO (simplicidad, utilidad, objetividad y bajo precio) seguida de una escala Likert con cinco puntos. Resultados: los expertos en TN de ILSI proporcionaron el diseño de 12 QIONT, que fueron todos consistentemente (Alfa de Cronbach = 0,84) clasificados como válidos por expertos independientes en NT. Por orden de relevancia, los nuevos ICTNO valoraron: la frecuencia de screening nutricional, la prescripción de suplementos de nutrición oral para pacientes desnutridos que ya reciben dieta oral, la prescripción de suplementos de nutrición oral para pacientes con bajo riesgo nutricional que ya reciben dieta oral, el consejo nutricional, la adhesión al suplemento nutricional oral, los pacientes hospitalizados con dieta oral insuficiente y prescripción de suplementos nutricionales orales, los pacientes de UCI con dieta oral insuficiente y prescripción de suplementos nutricionales orales, el consejo de nutrición oral en pacientes de UCI, el consejo de nutrición oral en pacientes en planta, la intolerancia al volumen de suplemento oral debido a dosificación inadecuada, la intolerancia al sabor del suplemento oral y la intolerancia al volumen de suplemento oral. Conclusión: según la opinión experta, 12 potenciales y factibles nuevos ICTNO

  2. Potential implications of adjuvant endocrine therapy for the oral health of postmenopausal women with breast cancer

    PubMed Central

    Taichman, L. Susan; Havens, Aaron M.

    2012-01-01

    Current adjuvant treatment modalities for breast cancer that express the estrogen receptor or progesterone receptor include adjuvant anti-estrogen therapies, and tamoxifen and aromatase inhibitors. Bone, including the jaw, is an endocrine-sensitive organ, as are other oral structures. This review examines the potential links between adjuvant anti-estrogen treatments in postmenopausal women with hormone receptor positive breast cancer and oral health. A search of PubMed, EMBASE, CENTRAL, and the Web of Knowledge was conducted using combinations of key terms “breast,” “cancer,” “neoplasm,” “Tamoxifen,” “Aromatase Inhibitor,” “chemotherapy,” “hormone therapy,” “alveolar bone loss,” “postmenopausal bone loss,” “estrogen,” “SERM,” “hormone replacement therapy,” and “quality of life.” We selected articles published in peer-reviewed journals in the English. The authors found no studies reporting on periodontal diseases, alveolar bone loss, oral health, or oral health-related quality of life in association with anti-estrogen breast cancer treatments in postmenopausal women. Periodontal diseases, alveolar bone density, tooth loss, and conditions of the soft tissues of the mouth have all been associated with menopausal status supporting the hypothesis that the soft tissues and bone of the oral cavity could be negatively affected by anti-estrogen therapy. As a conclusion, the impact of adjuvant endocrine breast cancer therapy on the oral health of postmenopausal women is undefined. The structures of the oral cavity are influenced by estrogen; therefore, anti-estrogen therapies may carry the risk of oral toxicities. Oral health care for breast cancer patients is an important but understudied aspect of cancer survivorship. PMID:22986813

  3. Administration of Coagulation-Altering Therapy in the Patient Presenting for Oral Health and Maxillofacial Surgery.

    PubMed

    Halaszynski, Thomas M

    2016-11-01

    Oral health care providers are concerned with how to manage patients prescribed coagulation-altering therapy during the perioperative/periprocedural period for dental and oral surgery interventions. Management and recommendation can be based on medication pharmacology and the clinical relevance of coagulation factor levels/deficiencies. Caution should be used with concurrent use of medications that affect other components of the clotting mechanisms; prompt diagnosis and any necessary intervention to optimize outcome is warranted. However, evidence-based data on management of anticoagulation therapy during oral and maxillofacial surgery/interventions is lacking. Therefore, clinical understanding and judgment are needed along with appropriate guidelines matching patient- and intervention-specific recommendations.

  4. CPEO and carnitine deficiency overlapping in MELAS syndrome.

    PubMed

    Hsu, C C; Chuang, Y H; Tsai, J L; Jong, H J; Shen, Y Y; Huang, H L; Chen, H L; Lee, H C; Pang, C Y; Wei, Y H

    1995-09-01

    Mitochondrial myopathy, encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is one of the mitochondrial encephalomyopathies that has distinct clinical features including stroke-like episodes with migraine-like headache, nausea, vomiting, encephalopathy and lactic acidosis. We report a 27-year-old woman who presented with partial seizure, stroke-like episodes including hemiparesis, hemianopia and hemihypethesia, sensorineural hearing loss, migraine-like headache, and lactic acidosis. Brain computed tomographic scan showed encephalomalacia in the right parieto-occipital area and recent hypodensity in the left temporoparieto-occipital area with cortical atrophy. Muscle biopsy revealed ragged-red fibers and paracrystaline inclusions in the mitochondria. Genetic study revealed an A to G point mutation at nucleotide position (np) 3243 of mitochondrial DNA. External ophthalmoplegia and ptosis were also found during two exaggerated episodes in this patient. Therefore, the overlapping syndrome of chronic progressive external ophthalmoplegia in the MELAS syndrome is considered in this case. Furthermore, we also found carnitine deficiency in this patient and she was responsive well to steroid therapy. Muscle biopsy also revealed excessive lipid droplets deposits. Therefore, the carnitine deficiency may occur in MELAS syndrome with the A to G point mutation at np 3243. We recommend the steroid or carnitine supplement therapy be applied to the MELAS syndrome with carnitine deficiency.

  5. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN) - a randomized multicentre trial

    PubMed Central

    2012-01-01

    Background Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia. Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g) or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM) kg. During treatment body-mass-index increased by 3,4 ± 1,4% under L-Carnitine and decreased (−1,5 ± 1,4%) in controls (p < 0,05). Moreover, nutritional status (body cell mass, body fat) and quality-of-life parameters improved under L-Carnitine. There was a trend towards an increased overall survival in the L-Carnitine group (median 519 ± 50 d versus 399 ± 43 d, not significant) and towards a reduced hospital-stay (36 ± 4d versus 41 ± 9d,n.s.). Conclusion While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinically relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine. PMID:22824168

  6. Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy era. A literature analysis.

    PubMed

    Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia

    2015-08-01

    SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy.

  7. Genetics Home Reference: carnitine palmitoyltransferase II deficiency

    MedlinePlus

    ... into energy. Fatty acid oxidation takes place within mitochondria , which are the energy-producing centers in cells. ... to a substance known as carnitine to enter mitochondria. Once these fatty acids are inside mitochondria, carnitine ...

  8. Reducing deaths from diarrhoea through oral rehydration therapy.

    PubMed Central

    Victora, C. G.; Bryce, J.; Fontaine, O.; Monasch, R.

    2000-01-01

    In 1980, diarrhoea was the leading cause of child mortality, accounting for 4.6 million deaths annually. Efforts to control diarrhoea over the past decade have been based on multiple, potentially powerful interventions implemented more or less simultaneously. Oral rehydration therapy (ORT) was introduced in 1979 and rapidly became the cornerstone of programmes for the control of diarrhoeal diseases. We report on the strategy for controlling diarrhoea through case management, with special reference to ORT, and on the relationship between its implementation and reduced mortality. Population-based data on the coverage and quality of facility-based use of ORT are scarce, despite its potential importance in reducing mortality, especially for severe cases. ORT use rates during the 1980s are available for only a few countries. An improvement in the availability of data occurred in the mid-1990s. The study of time trends is hampered by the use of several different definitions of ORT. Nevertheless, the data show positive trends in diarrhoea management in most parts of the world. ORT is now given to the majority of children with diarrhoea. The annual number of deaths attributable to diarrhoea among children aged under 5 years fell from the estimated 4.6 million in 1980 to about 1.5 million today. Case studies in Brazil, Egypt, Mexico, and the Philippines confirm increases in the use of ORT which are concomitant with marked falls in mortality. In some countries, possible alternative explanations for the observed decline in mortality have been fairly confidently ruled out. Experience with ORT can provide useful guidance for child survival programmes. With adequate political will and financial support, cost-effective interventions other than that of immunization can be successfully delivered by national programmes. Furthermore, there are important lessons for evaluators. The population-based data needed to establish trends in health service delivery, outcomes and impact are not

  9. Protective role of L-carnitine supplementation against exhaustive exercise induced oxidative stress in rats.

    PubMed

    Síktar, Elif; Ekinci, Deniz; Síktar, Erdinç; Beydemir, Sükrü; Gülçin, Ilhami; Günay, Mehmet

    2011-10-15

    The objective of this study was to investigate temperature dependent effects of oral l-carnitine supplementation on exhaustive exercise induced oxidative damage in rats. 42 male Spraque Dawley rats were randomly divided into seven experimental groups. These groups were formed as three non-carnitine exercise groups, three carnitine-exercise groups and a sedentary group. l-carnitine was given intraperitoneally to the carnitine-exercise groups 1h before the exercise in 100mg/kg. Blood was collected to measure paraoxonase-1 (PON1) activity, plasma malondialdehyde (MDA), low-density lipoprotein (LDL) and cholesterol concentrations. These biomarkers were measured in venous blood samples collected before and after the rats swam in pools at different water temperatures (18°C, 28°C and 38°C). In the non-carnitine group, exercise caused a significant decrease in PON1 activity and a significant elevation in MDA concentration at 28°C compared to the sedentary group. No significant alterations were evidenced in LDL and cholesterol concentrations upon exercise. The decrease in PON1 activity became higher with increasing temperature whereas the elevation in MDA levels increased at 18°C. In the l-carnitine supplementation group, recovery in PON1 activity was observed significant at 28°C and very significant at 38°C. MDA concentration was almost the same with that of the non-carnitine group at 18 and 38°C, but it significantly decreased at 28°C. Considering the recovery in PON1 and MDA levels at 28°C, which is the temperature of the sedentary group; our results suggest that l-carnitine supplementation has a protective role on exhaustive exercise-induced oxidative stress. Findings of this study also demonstrate influences of thermal stress on these parameters during exhaustive exercise.

  10. The use of acrylic resin oral prosthesis in radiation therapy of oral cavity and paranasal sinus cancer

    SciTech Connect

    Cheng, V.S.T.; Oral, K.; Aramamy, M.A.

    1982-07-01

    In radiation therapy of cancer of the oral cavity and the paranasal sinuses, the extent to which the tissues of the oral cavity are included in the radiation treatment portals will determine the severity of the oral discomfort during treatment. This will affect the nutritional status of the patients, and may eventually affect the total dose of radiation which the patients can receive for treatment of their cancers. In cooperation with the Maxillofacial Prosthetic Department, an acrylic resin oral prosthesis was developed. This prosthesis is easy to use and can be made for each individual patient within 24 hours. It allows for maximum sparing of the normal tissues in the oral cavity and can be modified for shielding of backscattered electrons from heavy metals in the teeth. We have also found that acrylic resin extensions can be built onto the posterior edge of post-maxillectomy obturators; this extension can be used as a carrier for radioactive sources to deliver radiation to deep seated tumor modules in the paranasal sinuses.

  11. Medical management of neurogenic bladder with oral therapy

    PubMed Central

    2016-01-01

    This is a review of the most current literature on medical management of the neurogenic bladder (NGB) to treat detrusor overactivity (DO), improve bladder compliance and treat urinary incontinence. The use of antimuscarinics, alpha blockers, tricyclic antidepressants, desmopressin and mirabegron will be discussed along with combination therapy to improve efficacy. These medical therapies will be the focus of this review with surgical therapy and botulinum toxin injections being the subject of other articles in this series. PMID:26904412

  12. [Effects of L-carnitine in poultry].

    PubMed

    Leibetseder, J

    1995-01-01

    Because of the well established function of carnitine possible effects of carnitine were studied in poultry. In trial I it was investigated if carnitine and its precursors (lysine, methionine) reduce the formation of abdominal fat in broilers. Chickens (10 groups of 10 chickens each) were fed different diets (control, lysine and methionine in excess and deficient, respectively, with or without 5% fat supplement, L-carnitine and DL-carnitine supplement, respectively). Performance (body weight gain, feed conversion), amount of abdominal fat and carnitine concentration in blood, muscles (M. sartorius, M. pectoralis superficialis, cardiac), liver and kidney were determined. Performance and abdominal fat were influenced by dietary fat, lysine and methionine as expected and were not altered by carnitine. Excess and deficiency of lysine and methionine did not influence, fat supplement reduced and carnitine supplementation significantly increased tissue concentration of carnitine. In trial II it was studied if supplementation of a commercial layers' ration with either 500 mg L-carnitine or 500 mg nicotinic acid or both per kg reduces the cholesterol concentration in yolk. Influence on body weight, feed intake, laying performance, serum and yolk cholesterol concentration could not be observed, but yolk concentration of carnitine was significantly increased in supplemented groups. Trial III should clarify if the L-carnitine content in broiler parent stock ration influences hatchability. Four groups of 1350 hens each were fed a commercial all-mash supplemented with 0, 20, 50 and 100 mg L-carnitine, respectively. Hatching rate was increased from 83% to 87% and from 82.4% to 85.3% in groups supplemented with 50 and 100 mg L-carnitine, respectively, and in randomly sampled eggs of these groups carnitine concentration in yolk was higher.

  13. Oral complications of cancer therapies. Description and incidence of oral complications

    SciTech Connect

    Dreizen, S. )

    1990-01-01

    No part of the body reflects the complications of cancer chemotherapy as visibly and as vividly as the mouth. The infectious, hemorrhagic, cytotoxic, nutritional, and neurologic signs of drug toxicity are reflected in the mouth by changes in the color, character, comfort, and continuity of the mucosa. The stomatologic complications of radiotherapy for oral cancer are physical and physiological in nature, transient or lasting in duration, and reversible or irreversible in type. Some linger as permanent mementos long after the cancer has been destroyed. They stem from radiation injury to the salivary glands, oral mucosa, oral musculature, alveolar bone, and developing teeth. They are expressed clinically by xerostomia, trismus, radiation dermatitis, nutritional stomatitis, and dentofacial malformation. In both cancer chemotherapy and cancer radiotherapy, the oral complications vary in pattern, duration, intensity, and number, with not every patient developing every complication. 21 references.

  14. Tutorial in oral antithrombotic therapy: Biology and dental implications

    PubMed Central

    Fakhri, Hamid R.; Janket, Sok J.; Baird, Alison E.; Dinnocenzo, Richard; Meurman, Jukka H.

    2013-01-01

    Objectives: Recent developments of new direct oral anticoagulants that target specific clotting factors necessitate understanding of coagulation biology. The objective of this tutorial is to offer dental professionals a review of coagulation mechanisms and the pharmacodynamics of the conventional and new oral anticoagulants. Also, we summarized the dental implications of the conventional and new anticoagulants. Method: We searched Medline using search terms “antithrombotic”, “antihemostasis” or “anticoagulation” and combined them with the search results of “dental”, “oral surgery” or “periodontal”. We restricted the results to “human” and “English”. Results: The early coagulation cascade, the new cell-based coagulation model, the pharmacokinetics and pharmacodynamics of conventional antithrombotics, and new oral anticoagulants were reviewed. The new direct factor Xa inhibitors and the direct thrombin inhibitor (s), called direct oral anticoagulants (DOAs) have rapid onset of action, fast elimination on cessation, and fewer drug-drug or drug-food interactions than warfarin. However, the lack of antidotes raises concerns that some dental procedures may trigger serious hemorrhagic events. Additionally, careful perioperative withdrawal and resumption protocols for the DOAs are reviewed, because DOAs’ blood levels are dependent on renal function. Also, various reversal strategies in the event of excessive bleedings are summarized. Perioperative management of dental patients taking new DOAs and conventional oral anticoagulants are also discussed. However, the perioperative strategies for DOAs are yet to be validated in randomized trials. Key words:Coagulation cascade, cell-based coagulation model, factor Xa inhibitors, direct thrombin inhibitors, prothrombin complex concentrates. PMID:23524440

  15. Carnitine and type 2 diabetes.

    PubMed

    Mynatt, Randall L

    2009-09-01

    Studies in humans and animals demonstrate that "lipid over supply" causes or worsens insulin resistance via multiple mechanisms involving the accumulation of intracellular lipids in multiple tissues. In particular, the accumulation of fatty acyl CoA derivatives/metabolites in muscle inhibits both insulin signaling and glucose oxidation. Therefore agents that ameliorate the accumulation of fatty acyl CoA derivatives and/or their metabolites would be beneficial in the treatment or prevention of insulin resistance and T2D. Hyperinsulemic/euglycemic clamp studies in humans and carnitine supplementation studies in rodents provide "proof-of-concept" that carnitine is effective at improving insulin-stimulated glucose utilization and in reversing abnormalities of fuel metabolism associated with T2D. Carefully controlled clinical trials are warranted to determine the efficacy dietary carnitine supplementation as an adjunctive treatment for type 2 diabetes.

  16. Boron neutron capture therapy for oral precancer: proof of principle in an experimental animal model

    SciTech Connect

    A. Monti Hughes; ECC Pozzi; S. Thorp; M. A. Garabalino; R. O. Farias; S. J. Gonzalez; E. M. Heber; M. E. Itoiz; R. F. Aromando; A. J. Molinari; M. Miller; D. W. Nigg; P. Curotto; V. A. Trivillin; A. E. Schwint

    2013-11-01

    Field-cancerized tissue can give rise to second primary tumours, causing therapeutic failure. Boron neutron capture therapy (BNCT) is based on biological targeting and would serve to treat undetectable foci of malignant transformation. The aim of this study was to optimize BNCT for the integral treatment for oral cancer, with particular emphasis on the inhibitory effect on tumour development originating in precancerous conditions, and radiotoxicity of different BNCT protocols in a hamster cheek pouch oral precancer model.

  17. Topical and systemic therapies for oral and perioral herpes simplex virus infections.

    PubMed

    Stoopler, Eric T; Balasubramaniam, Ramesh

    2013-04-01

    Oral and perioral herpes simplex virus (HSV) infections in healthy individuals often present with signs and symptoms that are clearly recognized by oral health care providers (OHCPs). Management of these infections is dependent upon a variety of factors and several agents may be used for treatment to accelerate healing and decrease symptoms associated with lesions. This article will review the pertinent aspects of topical and systemic therapies of HSV infections for the OHCP.

  18. Novel oral taxane therapies: recent Phase I results

    PubMed Central

    Flores, John Paul; Saif, M Wasif

    2015-01-01

    The oral taxanes are analogues of existing taxanes with a possible broad range of antitumor activity. They also have the potential advantages of ease of administration, better efficacy and lesser toxicity than currently available taxanes. These drugs have been used in several Phase I clinical trials, the methodology and results of which will be reviewed here. PMID:26146540

  19. Oral targeted therapies: managing drug interactions, enhancing adherence and optimizing medication safety in lymphoma patients.

    PubMed

    Liewer, Susanne; Huddleston, Ashley N

    2015-04-01

    The advent of newer, targeted oral chemotherapy medications such as small molecule kinase inhibitors, ibrutinib and idelalisib, has created additional options for the treatment of lymphoma. The targeted nature of these agents offers many patient-identified advantages over older, intravenously administered chemotherapy regimens such as ease of self-administration and an increased sense of independence. However, newer oral agents also present unique challenges not previously experienced with older therapies that may affect safety, efficacy and patient adherence. In this article, we review oral agents for the treatment of lymphoma, how to evaluate and manage drug-drug and drug-food interactions with concomitant oral medications, and issues with patient adherence as well as methods to determine adherence for oral chemotherapy.

  20. Oral Nanostructured Lipid Carriers Loaded with Near-Infrared Dye for Image-Guided Photothermal Therapy.

    PubMed

    Chen, Gang; Wang, Kaikai; Zhou, Yiwen; Ding, Ling; Ullah, Aftab; Hu, Qi; Sun, Minjie; Oupický, David

    2016-09-28

    Photothermal therapy exerts its anticancer effect by converting laser radiation energy into hyperthermia using a suitable photosensitizer. This study reports development of nanostructured lipid carriers (NLCs) suitable for noninvasive oral delivery of a near-infrared photosensitizer dye IR780. The carrier encapsulating the dye (IR780@NLCs) was stable in simulated gastric and intestinal conditions and showed greatly enhanced oral absorption of IR780 when compared with the free dye. As a result of increased oral bioavailability, enhanced accumulation of the dye in subcutaneous mouse colon tumors (CT-26 cells) was observed following oral gavage of IR780@NLCs. Photothermal antitumor activity of orally administered IR780@NLCs was evaluated following local laser irradiation of the CT-26 tumors. We observed significant effect of the photothermal IR780@NLCs treatment on the rate of the tumor growth and no toxicity associated with the oral administration of IR780@NLCs. Overall, orally administered IR780@NLCs represents a safe and noninvasive method to achieve systemic tumor delivery of a photosensitizing dye for applications in photothermal anticancer therapies.

  1. Deficiency of Carnitine in Cachectic Cirrhotic Patients

    PubMed Central

    Rudman, Daniel; Sewell, Charles W.; Ansley, Joseph D.

    1977-01-01

    Carnitine is synthesized from lysine and methionine. In the rat, inadequate intake of either of these essential amino acids causes carnitine depletion. Inasmuch as protein deficiency is common in the hospital population, we have investigated the possible occurrence of nosocomial carnitine deficiency. Fasting serum carnitine concentration was measured in 16 normal and 247 patients in 16 disease groups. Normal range of carnitine was 55-103 μM. Only the cirrhotic group showed significant (P < 0.05) hypocarnitinemia. 14 of 36 hospitalized cirrhotics had subnormal values for serum carnitine. The creatinine/height index, midarm muscle circumference, and triceps skin-fold thickness indicated protein-calorie starvation in the 14 hypocarnitinemic liver patients. In six of the hypocarnitinemic cirrhotics (average serum level 50% of normal), spontaneous dietary intakes of carnitine, lysine, and methionine were measured and found to be only 5-15% as great as in six normocarnitinemic, healthy controls. When these six cirrhotic and six normal subjects were given the same lysine-rich, methionine-rich, and carnitine-free nutritional intake, the normals maintained normal serum carnitine levels and excreted 100 μmol/day, whereas the cirrhotics' serum level fell to 25% of normal, and urinary excretion declined to 15 μmol/day. Seven hypocarnitinemic cirrhotics died. Postmortem concentrations of carnitine in liver, muscle, heart, kidney, and brain averaged only one-fourth to one-third those in corresponding tissues of eight normally nourished nonhepatic patients who died after an acute illness of a 1-3-day duration. These data show that carnitine depletion is common in patients hospitalized for advanced cirrhosis, and that it results from three factors: substandard intake of dietary carnitine; substandard intake of lysine and methionine, the precursors for endogenous carnitine synthesis; and loss of capacity to synthesize carnitine from lysine and methionine. PMID:893675

  2. Bilateral nasal bone osteophytosis associated with short-term oral isotretinoin therapy for cystic acne vulgaris.

    PubMed

    Novick, N L; Lawson, W; Schwartz, I S

    1984-10-01

    Bilateral 2.5 and 3.0 mm nasal bone osteophytes developed five weeks following the initiation of oral isotretinoin therapy (50 mg daily) for severe cystic acne vulgaris in a healthy 30-year-old white woman who had undergone uneventful rhinoplasty 12 years earlier. Histologically mature bone fragments were removed at surgery. Vitamin A and its analogs have been reported to cause hyperostosis of the vertebrae and long bones, but no known reports link them to nasal bone changes. Clinically significant nasal bone osteophytosis may be another adverse reaction to oral isotretinoin therapy.

  3. Acute Demyelinating Disease after Oral Therapy with Herbal Extracts

    PubMed Central

    Kostianovsky, Alex; Maskin, Patricio; Noriega, María M.; Soler, Cristina; Bonelli, Ignacio; Riley, Claire S.; O'Connor, Kevin C.; Saubidet, Cristi´n López; Alvarez, Paulino A.

    2011-01-01

    Central nervous system demyelinating processes such as multiple sclerosis and acute disseminated encephalomyelitis constitute a group of diseases not completely understood in their physiopathology. Environmental and toxic insults are thought to play a role in priming autoimmunity. The aim of the present report is to describe a case of acute demyelinating disease with fatal outcome occurring 15 days after oral exposure to herbal extracts. PMID:21738505

  4. Impaired Exercise Performance and Skeletal Muscle Mitochondrial Function in Rats with Secondary Carnitine Deficiency

    PubMed Central

    Bouitbir, Jamal; Haegler, Patrizia; Singh, François; Joerin, Lorenz; Felser, Andrea; Duthaler, Urs; Krähenbühl, Stephan

    2016-01-01

    Purpose: The effects of carnitine depletion upon exercise performance and skeletal muscle mitochondrial function remain largely unexplored. We therefore investigated the effect of N-trimethyl-hydrazine-3-propionate (THP), a carnitine analog inhibiting carnitine biosynthesis and renal carnitine reabsorption, on physical performance and skeletal muscle mitochondrial function in rats. Methods: Male Sprague Dawley rats were treated daily with water (control rats; n = 12) or with 20 mg/100 g body weight THP (n = 12) via oral gavage for 3 weeks. Following treatment, half of the animals of each group performed an exercise test until exhaustion. Results: Distance covered and exercise performance were lower in THP-treated compared to control rats. In the oxidative soleus muscle, carnitine depletion caused atrophy (–24%) and impaired function of complex II and IV of the mitochondrial electron transport chain. The free radical leak (ROS production relative to oxygen consumption) was increased and the cellular glutathione pool decreased. Moreover, mRNA expression of markers of mitochondrial biogenesis and mitochondrial DNA were decreased in THP-treated compared to control rats. In comparison, in the glycolytic gastrocnemius muscle, carnitine depletion was associated with impaired function of complex IV and increased free radical leak, whilst muscle weight and cellular glutathione pool were maintained. Markers of mitochondrial proliferation and mitochondrial DNA were unaffected. Conclusions: Carnitine deficiency is associated with impaired exercise capacity in rats treated with THP. THP-induced carnitine deficiency is associated with impaired function of the electron transport chain in oxidative and glycolytic muscle as well as with atrophy and decreased mitochondrial DNA in oxidative muscle. PMID:27559315

  5. Examining the use of oral rehydration salts and other oral rehydration therapy for childhood diarrhea in Kenya.

    PubMed

    Blum, Lauren S; Oria, Prisca A; Olson, Christine K; Breiman, Robert F; Ram, Pavani K

    2011-12-01

    Reductions in the use of oral rehydration therapy (ORT) in sub-Saharan Africa highlight the need to examine caregiver perceptions of ORT during diarrheal episodes. Qualitative research involving group discussions with childcare providers and in-depth interviews with 45 caregivers of children < 5 years of age who had experienced diarrhea was conducted in one rural and urban site in Kenya during July-December 2007. Diarrhea was considered a dangerous condition that can kill young children. Caregivers preferred to treat diarrhea with Western drugs believed to be more effective in stopping diarrhea than ORT. Inconsistent recommendations from health workers regarding use of oral rehydration solution (ORS) caused confusion about when ORS is appropriate and whether it requires a medical prescription. In the rural community, causal explanations about diarrhea, beliefs in herbal remedies, cost, and distance to health facilities presented additional barriers to ORS use. Health communication is needed to clarify the function of ORT in preventing dehydration.

  6. Examining the Use of Oral Rehydration Salts and Other Oral Rehydration Therapy for Childhood Diarrhea in Kenya

    PubMed Central

    Blum, Lauren S.; Oria, Prisca A.; Olson, Christine K.; Breiman, Robert F.; Ram, Pavani K.

    2011-01-01

    Reductions in the use of oral rehydration therapy (ORT) in sub-Saharan Africa highlight the need to examine caregiver perceptions of ORT during diarrheal episodes. Qualitative research involving group discussions with childcare providers and in-depth interviews with 45 caregivers of children < 5 years of age who had experienced diarrhea was conducted in one rural and urban site in Kenya during July–December 2007. Diarrhea was considered a dangerous condition that can kill young children. Caregivers preferred to treat diarrhea with Western drugs believed to be more effective in stopping diarrhea than ORT. Inconsistent recommendations from health workers regarding use of oral rehydration solution (ORS) caused confusion about when ORS is appropriate and whether it requires a medical prescription. In the rural community, causal explanations about diarrhea, beliefs in herbal remedies, cost, and distance to health facilities presented additional barriers to ORS use. Health communication is needed to clarify the function of ORT in preventing dehydration. PMID:22144457

  7. Effectiveness of oral antibiotics for definitive therapy of Gram-negative bloodstream infections.

    PubMed

    Kutob, Leila F; Justo, Julie Ann; Bookstaver, P Brandon; Kohn, Joseph; Albrecht, Helmut; Al-Hasan, Majdi N

    2016-11-01

    There is paucity of data evaluating intravenous-to-oral antibiotic switch options for Gram-negative bloodstream infections (BSIs). This retrospective cohort study examined the effectiveness of oral antibiotics for definitive treatment of Gram-negative BSI. Patients with Gram-negative BSI hospitalised for <14 days at Palmetto Health Hospitals in Columbia, SC, from 1 January 2010 through 31 December 2013 and discharged on oral antibiotics were included in this study. The cohort was stratified into three groups based on bioavailability of oral antibiotics prescribed (high, ≥95%; moderate, 75-94%; and low, <75%). Kaplan-Meier analysis and multivariate Cox proportional hazards regression were used to examine treatment failure. Among the 362 patients, high, moderate and low bioavailability oral antibiotics were prescribed to 106, 179 and 77 patients, respectively, for definitive therapy of Gram-negative BSI. Mean patient age was 63 years, 217 (59.9%) were women and 254 (70.2%) had a urinary source of infection. Treatment failure rates were 2%, 12% and 14% in patients receiving oral antibiotics with high, moderate and low bioavailability, respectively (P = 0.02). Risk of treatment failure in the multivariate Cox model was higher in patients receiving antibiotics with moderate [adjusted hazard ratio (aHR) = 5.9, 95% CI 1.6-38.5; P = 0.005] and low bioavailability (aHR = 7.7, 95% CI 1.9-51.5; P = 0.003) compared with those receiving oral antimicrobial agents with high bioavailability. These data demonstrate the effectiveness of oral antibiotics with high bioavailability for definitive therapy of Gram-negative BSI. Risk of treatment failure increases as bioavailability of the oral regimen declines.

  8. Gene therapy in the management of oral cancer: review of the literature.

    PubMed

    Ayllón Barbellido, Sonia; Campo Trapero, Julián; Cano Sánchez, Jorge; Perea García, Miguel A; Escudero Castaño, Nayra; Bascones Martínez, Antonio

    2008-01-01

    Gene therapy essentially consists of introducing specific genetic material into target cells without producing toxic effects on surrounding tissue. Advances over recent decades in the surgical, radiotherapeutic and chemotherapeutic treatment of oral cancer patients have not produced a significant improvement in patient survival. Increasing interest is being shown in developing novel therapies to reverse oral epithelial dysplastic lesions. This review provides an update on transfer techniques, therapeutic strategies, and the clinical applications and limitations of gene therapy in the management of oral cancer and precancer. We highlight the combination of gene therapy with chemotherapy (e.g., 5-Fluoracil) and immunotherapy, given the promising results obtained in the use of adenovirus to act at altered gene level (e.g., p53). Other techniques such as suicide gene therapy, use of oncolytic viruses or the use of antisense RNA have shown positive although very preliminary results. Therefore, further research into these promising gene therapy techniques is required to assess their true efficacy and safety in the management of these lesions.

  9. Treatment of oral fungal infections using antimicrobial photodynamic therapy: a systematic review of currently available evidence.

    PubMed

    Javed, Fawad; Samaranayake, Lakshman P; Romanos, Georgios E

    2014-05-01

    The aim was to review the efficacy of antimicrobial photodynamic therapy (PDT) in the treatment of oral fungal infections. To address the focused question "Should PDT be considered a possible treatment regimen for oral fungal infections?" PubMed/Medline and Google-Scholar databases were searched from 1997 up to March 2014 using various combinations of the following key words: "Candida albicans"; "Candidiasis"; "Candidosis"; "denture stomatitis"; "oral" and "photodynamic therapy". Original studies, experimental studies and articles published solely in English language were sought. Letters to the editor, historic reviews and unpublished data were excluded. Pattern of the present literature review was customized to mainly summarize the pertinent information. Fifteen studies (3 clinical and 12 experimental) were included. All studies reported antimicrobial PDT to be an effective antifungal treatment strategy. One study reported PDT and azole therapy to be equally effective in the treatment of oral fungal infections. Methylene blue, toluidine blue and porphyrin derivative were the most commonly used photosensitizers. The laser wavelengths and power output ranged between ∼455 nm-660 nm and 30 mW-400 mW. The energy fluence ranged between 26-245 J cm(-2) and the duration or irradiation ranged between 10 seconds and 26 minutes. Clinical effectiveness of antimicrobial PDT as a potent therapeutic strategy for oral fungal infections requires further investigations.

  10. Oral ofloxacin therapy of Pseudomonas aeruginosa sepsis in mice after irradiation.

    PubMed Central

    Brook, I; Ledney, G D

    1990-01-01

    Death subsequent to whole-body irradiation is associated with gram-negative bacterial sepsis. The effect of oral therapy with the new quinolone ofloxacin for orally acquired Pseudomonas aeruginosa infection was tested in B6D2F1 mice exposed to 7.0 Gy of bilateral radiation from 60Co. A dose of 10(7) organisms was given orally 2 days after irradiation, and therapy was started 1 day later. Only 4 of 20 untreated mice (20%) survived for at least 30 days compared with 19 of 20 mice (95%) treated with ofloxacin (P less than 0.005). P. aeruginosa was isolated from the livers of 21 to 28 untreated mice (75%), compared with only 2 of 30 treated mice (P less than 0.005). Ofloxacin reduced colonization of the ileum by P. aeruginosa; 24 of 28 untreated mice (86%) harbored the organisms, compared with only 5 of 30 (17%) with ofloxacin (P less than 0.005). This experiment was replicated twice, and similar results were obtained. These data illustrate the efficacy of the quinolone ofloxacin for oral therapy of orally acquired P. aeruginosa infection in irradiated hosts. PMID:2117418

  11. Status report from the American Acne & Rosacea Society on medical management of acne in adult women, part 3: oral therapies.

    PubMed

    Del Rosso, James Q; Harper, Julie C; Graber, Emmy M; Thiboutot, Diane; Silverberg, Nanette B; Eichenfield, Lawrence F

    2015-12-01

    Parts 1 and 2 of this 3-part series provided an overview of the epidemiology, visible patterns, and important considerations for clinical and laboratory evaluation of acne vulgaris (AV) in adult women and reviewed the role of proper skin care and topical therapies in this patient population. In Part 3, oral therapies including combination oral contraceptives, spironolactone, antibiotics, and isotretinoin are discussed along with important considerations that clinicians should keep in mind when selecting oral agents for management of AV in adult women.

  12. Postoperative Bleeding Risk for Oral Surgery under Continued Clopidogrel Antiplatelet Therapy

    PubMed Central

    Zeuch, Jürgen; Haase, Martina; Semmusch, Jan; Eichhorn, Wolfgang

    2015-01-01

    Object. To determine the incidence of postoperative bleeding for oral osteotomy carried out under continued monoantiplatelet therapy with clopidogrel and dual therapy with clopidogrel/aspirin. Design. Retrospective single center observatory study of two study groups and a control group. Methods. A total of 64 and 60 oral osteotomy procedures carried out under continued monoclopidogrel therapy and dual clopidogrel/aspirin therapy, respectively, were followed for two weeks for postoperative bleeding. Another 281 similar procedures were also followed as a control group. All oral osteotomy procedures were carried out on an outpatient basis. Results. We observed postoperative bleeding in 2/281 (0.7%) cases in the control group, in 1/64 (1.6%) cases in the clopidogrel group, and in 2/60 (3.3%) cases in the dual clopidogrel/aspirin group. The corresponding 95% confidence intervals are 0–1.7%, 0–4.7%, and 0–7.8%, respectively, and the incidences did not differ significantly among the three groups (P > 0.09). Postoperative hemorrhage was treated successfully in all cases with local measures. No changes of antiplatelet medication, transfusion, nor hospitalisation were necessary. No major cardiovascular events were recorded. Conclusions. Our results indicate that minor oral surgery can be performed safely under continued monoantiplatelet medication with clopidogrel or dual antiplatelet medication with clopidogrel/aspirin. PMID:25632402

  13. Effects of oral tacrolimus as a rapid induction therapy in ulcerative colitis

    PubMed Central

    Kawakami, Ken; Inoue, Takuya; Murano, Mitsuyuki; Narabayashi, Ken; Nouda, Sadaharu; Ishida, Kumi; Abe, Yosuke; Nogami, Koji; Hida, Nobuyuki; Yamagami, Hirokazu; Watanabe, Kenji; Umegaki, Eiji; Nakamura, Shiro; Arakawa, Tetsuo; Higuchi, Kazuhide

    2015-01-01

    AIM: To determine the efficacy and safety of rapid induction therapy with oral tacrolimus without a meal in steroid-refractory ulcerative colitis (UC) patients. METHODS: This was a prospective, multicenter, observational study. Between May 2010 and August 2012, 49 steroid-refractory UC patients (55 flare-ups) were consecutively enrolled. All patients were treated with oral tacrolimus without a meal at an initial dose of 0.1 mg/kg per day. The dose was adjusted to maintain trough whole-blood levels of 10-15 ng/mL for the first 2 wk. Induction of remission at 2 and 4 wk after tacrolimus treatment initiation was evaluated using Lichtiger’s clinical activity index (CAI). RESULTS: The mean CAI was 12.6 ± 3.6 at onset. Within the first 7 d, 93.5% of patients maintained high trough levels (10-15 ng/mL). The CAI significantly decreased beginning 2 d after treatment initiation. At 2 wk, 73.1% of patients experienced clinical responses. After tacrolimus initiation, 31.4% and 75.6% of patients achieved clinical remission at 2 and 4 wk, respectively. Treatment was well tolerated. CONCLUSION: Rapid induction therapy with oral tacrolimus shortened the time to achievement of appropriate trough levels and demonstrated a high remission rate 28 d after treatment initiation. Rapid induction therapy with oral tacrolimus appears to be a useful therapy for the treatment of refractory UC. PMID:25684955

  14. Antimicrobial Photodynamic Therapy to treat chemotherapy-induced oral lesions: Report of three cases.

    PubMed

    Rocha, Breno Amaral; Melo Filho, Mário Rodrigues; Simões, Alyne

    2016-03-01

    The development of Angular Cheilitis and the reactivation of Herpes Simplex Virus, could be related to a decrease in the resistance of the immune system in the infected host, being common in cancer patients receiving antineoplastic chemotherapy. The objective of the present manuscript is to report Antimicrobial Photodynamic Therapy as a treatment of infected oral lesions of patients submitted to chemotherapy.

  15. Oral Vancomycin Therapy in a Child with Primary Sclerosing Cholangitis and Severe Ulcerative Colitis

    PubMed Central

    Buness, Cynthia; Miloh, Tamir

    2016-01-01

    Primary sclerosing cholangitis (PSC), a rare progressive liver disease characterized by cholestasis and bile duct fibrosis, has no accepted, effective therapy known to delay or arrest its progression. We report a 15 year old female patient diagnosed with PSC and moderate chronic active ulcerative colitis (UC) who achieved normalization of her liver enzymes and bile ducts, and resolution of her UC symptoms with colonic mucosal healing, after treatment with a single drug therapy of the antibiotic oral vancomycin. We postulate that the oral vancomycin may be acting both as an antibiotic by altering the intestinal microbiome and as an immunomodulator. Oral vancomycin may be a promising treatment for PSC that needs to be further studied in randomized trials. PMID:27738604

  16. [Dentistry oral hygiene and endocarditis. Pathophysiology and prophylactic therapy].

    PubMed

    Santacroce, Luigi; Cagiano, Raffaele; Carlaio, Roberto G; Del Prete, Raffaele; Bottalico, Lucrezia

    2008-10-01

    Infectious endocarditis is a cardiac pathology of bacterial, viral or more rarely mycotic origin developing on the surfaces of the endocardium or heart valves. Predisposing conditions are congenital malformations of the heart or valvular acquired alterations, as well as the presence of a valvular prosthesis. The microorganisms involved in the etiology and pathogenesis of the damage of such infection (bacterias, viruses or yeasts) determine the formation of the endocardic vegetations typical of this condition. Such lesions can be located on the valvular or the parietal endocardium and sometimes on the endothelium of a great artery. In despite of the elevated standards of instrumental investigations and therapeutic protocols, the bacterial endocarditis represents a pathology of wide interest, scientific and social, due to its high rate of incidence, morbility and mortality. Still now infectious endocarditis causes death in 20-30% of the patients. Although the significant progress on prevention of the infectious diseases and of the cross infections in dentistry practice, from the tartar ablation up to the oncologic oral surgery, still now the skills of oral hygiene and dentistry represent a potential threat for the development of an infectious endocarditis in predisposed patients. The authors, on the base of the revision of the literature and of their own clinical experience, show the etiology, pathophysiology and the clinical pictures related to such complex disease.

  17. Relapse after Oral Terbinafine Therapy in Dermatophytosis: A Clinical and Mycological Study

    PubMed Central

    Majid, Imran; Sheikh, Gousia; Kanth, Farhath; Hakak, Rubeena

    2016-01-01

    Background: The incidence of recurrent tinea infections after oral terbinafine therapy is on the rise. Aim: This study aims to identify the appearance of incomplete cure and relapse after 2-week oral terbinafine therapy in tinea corporis and/or tinea cruris. Materials and Methods: A total of 100 consecutive patients clinically and mycologically diagnosed to have tinea corporis and/or tinea cruris were included in the study. The enrolled patients were administered oral terbinafine 250 mg once daily for 2 weeks. All clinically cured patients were then followed up for 12 weeks to look for any relapse/cure. Results: The common dermatophytes grown on culture were Trichophyton rubrum and Trichophyton tonsurans in 55% and 20% patients, respectively. At the end of 2-week oral terbinafine therapy, 30% patients showed a persistent disease on clinical examination while 35% patients showed a persistent positive fungal culture (persisters) at this time. These culture positive patients included all the clinically positive cases. Rest of the patients (65/100) demonstrated both clinical and mycological cure at this time (cured). Over the 12-week follow-up, clinical relapse was seen in 22 more patients (relapse) among those who had shown clinical and mycological cure at the end of terbinafine therapy. Thus, only 43% patients could achieve a long-term clinical and mycological cure after 2 weeks of oral terbinafine treatment. Majority of the relapses (16/22) were seen after 8 weeks of completion of treatment. There was no statistically significant difference in the body surface area involvement or the causative organism involved between the cured, persister, or relapse groups. Conclusions: Incomplete mycological cure as well as relapse is very common after standard (2-week) terbinafine therapy in our patients of tinea cruris/corporis. PMID:27688443

  18. Long-term oral antiarrhythmic therapy with mexiletine.

    PubMed Central

    Campbell, N P; Pantridge, J F; Adgey, A A

    1978-01-01

    Forty-eight patients with ischaemic heart disease received oral mexiletine for the control or prevention of ventricular arrhythmias. The most frequently used doses were 200, 250, and 300 mg 8-hourly. The treatment period varied from 2 days to more than 1 year (median 3 months). No ventricular arrhythmias were detected in more than one-half of the patients. Severe side effects occurred in 15 (31%) of the 48 patients. Major ventricular arrhythmias were observed in 14 (29%) of the 48 patients at a time when the majority had plasma concentrations within the therapeutic range. The value of mexiletine in the management of patients at risk of sudden death is likely to be limited. PMID:687477

  19. [Improvements in oral anticoagulant therapy for atrial fibrillation].

    PubMed

    Briongos Figuero, Sem; García Santos-Gallego, Carlos; Badimón, Juan José

    2013-12-07

    For the last decades vitamin K antagonists have been the most effective anticoagulant treatment of atrial fibrillation. New molecules are being designed, mainly due to the great amount of disadvantages in the management of conventional anticoagulation. Dabigatran, rivaroxaban and apixaban will soon be available as an alternative to warfarin/acenocumarol. All of them have demonstrated to be non-inferior to warfarin in preventing stroke and systemic embolism, with even dabigatran 150 mg bid and apixaban being superior. They have also a lower risk of bleeding, especially regarding severe/fatal and intracranial hemorrhages. This is a real revolution. The advance of these new anticoagulants will be limited only by the higher cost, and will progressively become the protagonists of oral anticoagulation in patients with nonvalvular atrial fibrillation.

  20. Adverse effects of oral antiviral therapy in chronic hepatitis B

    PubMed Central

    Kayaaslan, Bircan; Guner, Rahmet

    2017-01-01

    Oral nucleoside/nucleotide analogues (NAs) are currently the backbone of chronic hepatitis B (CHB) infection treatment. They are generally well-tolerated by patients and safe to use. To date, a significant number of patients have been treated with NAs. Safety data has accumulated over the years. The aim of this article is to review and update the adverse effects of oral NAs. NAs can cause class adverse effects (i.e., myopathy, neuropathy, lactic acidosis) and dissimilar adverse effects. All NAs carry a “Black Box” warning because of the potential risk for mitochondrial dysfunction. However, these adverse effects are rarely reported. The majority of cases are associated with lamivudine and telbivudine. Adefovir can lead to dose- and time-dependent nephrotoxicity, even at low doses. Tenofovir has significant renal and bone toxicity in patients with human immunodeficiency virus (HIV) infection. However, bone and renal toxicity in patients with CHB are not as prominent as in HIV infection. Entecavir and lamivudine are not generally associated with renal adverse events. Entecavir has been claimed to increase the risk of lactic acidosis in decompensated liver disease and high Model for End-Stage Liver Disease scores. However, current studies reported that entecavir could be safely used in decompensated cirrhosis. An increase in fetal adverse events has not been reported with lamivudine, telbivudine and tenofovir use in pregnant women, while there is no adequate data regarding entecavir and adefovir. Further long-term experience is required to highlight the adverse effects of NAs, especially in special patient populations, including pregnant women, elderly and patients with renal impairment. PMID:28261380

  1. Nutritional support and cardioprotection with L-carnitine: prescription appropriateness and safety concerns in Mexican neonates.

    PubMed

    Gómez-Oliván, Leobardo Manuel; Valdés-Alanis, Analleli; Castro-Pastrana, Lucila I; Galar-Martinez, Marcela; Romero-Castillo, Carolina Angélica

    2011-01-01

    Medication errors are probably more common in neonates than is generally appreciated. In Mexican pediatric hospitals, L-carnitine is mainly used for nutritional support and to treat cardiomyopathy secondary to neonatal asphyxia. Using a longitudinal-retrospective approach we assessed the appropriateness of all L-carnitine prescriptions written during a 12-month period at a NICU of a second-level hospital located in Toluca, Mexico. Reports of adverse reactions possibly related to L-carnitine therapy were collected and characterized. Overall, administration of L-carnitine was considered justified and appropriate only in 18% of patients. 60.7% of L-carnitine prescriptions were rated as inappropriate because the prescribed doses fell outside the recommendations. The overall rate of ADRs calculated from the patient population was 18.03%. All of them were of gastrointestinal type: abdominal cramps (8 cases, 61.54%) and vomiting (5 cases, 38.46%). Our results supported the establishment of an L-carnitine rational use policy at the NICU of the hospital under study.

  2. Suppression of aflatoxin B1-induced lipid abnormalities and macromolecule-adduct formation by L-carnitine.

    PubMed

    Sachan, D S; Yatim, A M

    1992-01-01

    The fatty liver and hypolipidemia caused by aflatoxin B1 (AFB1) were studied in male Sprague-Dawley rats fed Purina Rat Chow with or without L-carnitine supplement for 6 weeks. In Experiment 1, the rats (n = 20) were divided into four groups, i.e., nonsupplemented control (NSC), nonsupplemented AFB1 (NSA), carnitine supplemented control (CSC), and carnitine supplemented AFB1 (CSA). The NSA and CSA groups were given an oral dose of [3H]AFB1 (1 mg/kg) 6 hr before kill. In Experiment 2 (n = 10) there were only NSA and CSA groups and they were killed 24 hr post-AFB1 administration. Hepatic and plasma concentrations of total lipid, triglycerides, AFB1-macromolecules adducts and urinary excretion of AFB1 were determined. Carnitine supplementation ameliorated AFB1-induced hepatic steatosis and hypolipidemia. Supplementary carnitine reduced covalent binding of AFB1 to hepatic DNA, RNA, and protein. The carnitine effect was more pronounced after 24 hr than after 6 hr of AFB1 treatment. We conclude that supplementary carnitine suppressed AFB1-induced fatty liver and AFB1-macromolecule adduct formation in the rat.

  3. Tumor-targeting bacterial therapy: A potential treatment for oral cancer (Review)

    PubMed Central

    LIU, SAI; XU, XIAOPING; ZENG, XIN; LI, LONGJIANG; CHEN, QIANMING; LI, JING

    2014-01-01

    Certain obligate or facultative anaerobic bacteria, which exhibit an inherent ability to colonize solid tumors in vivo, may be used in tumor targeting. As genetically manipulated bacteria may actively and specifically penetrate into the tumor tissue, bacterial therapy is becoming a promising approach in the treatment of tumors. However, to the best of our knowledge, no reports have been published thus far regarding the bacterial treatment of oral cancer, one of the most common types of cancer worldwide. In this review, the progress in the understanding of bacterial strategies used in tumor-targeted therapy is discussed and particular bacterial strains that may have great therapeutic potential in oral squamous cell carcinoma (OSCC) tumor-targeted therapy are predicted as determined by previous studies. PMID:25364397

  4. CARNITINE HOMEOSTASIS, MITOCHONDRIAL FUNCTION, AND CARDIOVASCULAR DISEASE

    PubMed Central

    Sharma, Shruti; Black, Stephen M.

    2009-01-01

    Carnitines are involved in mitochondrial transport of fatty acids and are of critical importance for maintaining normal mitochondrial function. This review summarizes recent experimental and clinical studies showing that mitochondrial dysfunction secondary to a disruption of carnitine homeostasis may play a role in decreased NO signaling and the development of endothelial dysfunction. Future challenges include development of agents that can positively modulate L-carnitine homeostasis which may have high therapeutic potential. PMID:20648231

  5. Cancer incidence attributable to the use of oral contraceptives and hormone therapy in Alberta in 2012

    PubMed Central

    Grevers, Xin; Grundy, Anne; Poirier, Abbey E.; Khandwala, Farah; Feldman, Matthew; Friedenreich, Christine M.; Brenner, Darren R.

    2016-01-01

    Background: Hormonal contraceptives and hormone replacement therapies are classified as carcinogenic to humans (group 1) by the International Agency for Research on Cancer. We sought to estimate the proportion and total number of cancers attributable to the use of oral contraceptives and hormone therapy in Alberta in 2012. Methods: Population attributable risks were used to estimate the proportion of attributable cases for each associated cancer site. Relative risk estimates were obtained from the most relevant and recent epidemiologic literature. Prevalences of the use of oral contraceptives and hormone therapy in Alberta were collected from Alberta's Tomorrow Project. Specific cancer incidence data were obtained from the Alberta Cancer Registry for the year 2012. Results: Overall, 6.3% of breast cancers (n = 135) diagnosed in Alberta in 2012 were estimated to be attributable to the use of oral contraceptives, and the exposure potentially prevented about 57.3% of endometrial cancers (n = 276) and 29.1% of ovarian cancers (n = 52). About 15.5% of breast cancers (n = 258) and 8.9% of ovarian cancers (n = 13) were estimated to be attributable to the use of hormone therapy, whereas 11.3% of endometrial cancers (n = 48) were possibly prevented by the exposure. Interpretation: Based on our estimates, oral contraceptive use resulted in a net protective effect among the cancer sites studied, thus reducing the cancer burden in Alberta in 2012. The use of hormone therapy was estimated to increase the cancer burden in the province, therefore the risk and benefit of hormone therapy should be carefully considered before use. PMID:28018891

  6. Effects of Long Term Antibiotic Therapy on Human Oral and Fecal Viromes

    PubMed Central

    Abeles, Shira R.; Ly, Melissa; Santiago-Rodriguez, Tasha M.; Pride, David T.

    2015-01-01

    Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances. PMID:26309137

  7. Inflammation and Oral Cancer: An Update Review on Targeted Therapies.

    PubMed

    Sarode, Gargi S; Sarode, Sachin C; Patil, Anuprita; Anand, Rahul; Patil, Shankar Gouda; Rao, Roopa S; Augustine, Dominic

    2015-07-01

    In the recent past, numerous inflammation-mediated molecular pathways have been explored and studied as important events in carcinogenesis with respect to oral squamous cell carcinoma (OSCC). These pathways are engaged in numerous stages during tumorigenesis; which includes processes, like initiation, promotion, malignant conversion, invasion and metastasis. The inflammation-mediated/related carcinogenesis pathways reported in OSCC involves COX-2, epidermal growth factor receptor (EGFR), p38a MAP kinase, NF-kB, STAT, RhoC, PPARy, etc. Many researchers are trying to target these pathways to explore more effective therapeutic interventions in OSCC. The aim of the present paper is to briefly discuss these pathways, with special emphasis on the therapeutic utilities. The therapeutic targets for the aforementioned pathways were searched in databases pubmed and scopus with no restriction to date of publication. Articles published in English medical literature on OSCC were selected for discussion. The recent combinations, modifications in dosage and frequency, or the use of new anti-inflammatory compounds, may exemplify the next generation care for OSCC.

  8. Suppressive therapy versus episodic therapy with oral valacyclovir for recurrent herpes labialis: efficacy and tolerability in an open-label, crossover study.

    PubMed

    Gilbert, Stanley C

    2007-04-01

    Oral valacyclovir's efficacy and tolerability as suppressive therapy versus episodic therapy were compared for recurrent herpes labialis (RHL). Subjects with a history of at least 3 RHL episodes in the past year were randomized to receive 6 months of oral valacyclovir episodic therapy at the first sign of prodrome (two 2-g doses separated by 12 hours) and 6 months of oral valacyclovir suppressive therapy (1 g once daily) for 6 months in open-label, crossover fashion. The mean +/- SE number of recurrences per 120 days of follow-up (primary endpoint) was lower with suppressive therapy (0.30 +/- 0.41) than episodic therapy (0.71 +/- 0.79) (P < .005). The probability of remaining recurrence free over 6 months was significantly higher with suppressive therapy than episodic therapy. The median time to first recurrence was 81 days with episodic therapy and was not calculable (> 180 days) for suppressive therapy (P = 0.021). Data for secondary efficacy endpoints (pain severity score, mean duration of recurrences, maximal total lesion area) showed approximately a 30% to 50% reduction in mean values with suppressive therapy compared with episodic therapy, but results were statistically significantly different between the regimens for pain severity only. The percentage of subjects with at least one adverse event over 6 months of treatment that was considered to be drug related was 3% with suppressive therapy and 6% with episodic therapy. Suppressive therapy with oral valacyclovir was more effective than episodic therapy with oral valacyclovir in reducing the frequency of recurrences of herpes labialis and prolonging the time to first recurrence and was also similarly well-tolerated.

  9. Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction

    PubMed Central

    Scioli, Maria Giovanna; Lo Giudice, Pietro; Bielli, Alessandra; Tarallo, Valeria; De Rosa, Alfonso; De Falco, Sandro; Orlandi, Augusto

    2015-01-01

    Background Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO) production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC) is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery. Methods and Results We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and reduction of NADPH-oxidase 4 (Nox4) expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM) expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction. Conclusion PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction

  10. Prostacyclin and Oral Vasodilator Therapy in Sarcoidosis-Associated Pulmonary Hypertension

    PubMed Central

    Oldham, Justin M.; Gomberg-Maitland, Mardi; Vij, Rekha

    2015-01-01

    BACKGROUND: It is unclear whether recent advances in pulmonary arterial hypertension therapy can be safely applied to sarcoidosis-associated pulmonary hypertension (SAPH). Evidence for prostacyclin (PG) therapy in SAPH is limited. METHODS: We conducted a single-center, retrospective review of 46 patients with sarcoidosis, 26 of whom had SAPH. Thirteen received PG as monotherapy or in combination with oral vasodilators. RESULTS: Follow-up right-sided heart catheterization at a mean of 12.7 months revealed improved cardiac output, cardiac index, and pulmonary vascular resistance. Functional class and N-terminal pro-brain natriuretic peptide levels also improved in patients treated with PG. No significant change in oxygen requirement was seen with vasodilator therapy initiation. At 2 years, 15 patients with SAPH survived, including eight on PG, and at 5 years, seven survived, including five on PG. Survival was significantly reduced in patients with SAPH compared with patients who had sarcoidosis without pulmonary hypertension. Multivariate analysis demonstrated that the use of PG therapy in SAPH is not associated with increased mortality. CONCLUSIONS: Many patients with severe SAPH showed significant hemodynamic and clinical improvement on long-term IV or subcutaneous PG therapy and had survival outcomes similar to patients with moderate SAPH on oral vasodilator therapy. PMID:26437815

  11. TransOral Robotic Photodynamic Therapy for the Oropharynx

    PubMed Central

    Quon, Harry; Finlay, Jarod; Cengel, Keith; Zhu, Timothy; O’Malley, Bert; Weinstein, Gregory

    2015-01-01

    Photodynamic therapy (PDT) has been used for head and neck carcinomas with little experience in the oropharynx due to technical challenges in achieving adequate exposure. We present the case of a patient with a second right tonsil carcinoma following previous treatment with transoral robotic surgery (TORS) and postoperative chemoradiation for a left tonsil carcinoma. Repeat TORS for the right tonsil carcinoma reviewed multiple positive surgical margins. The power output from the robotic camera was modified to facilitate safe intraoperative three dimensional visualization of the tumor bed. The robotic arms facilitated clear exposure of the tonsil and tongue base with stable administration of the fluence. Real-time measurements confirmed stable photobleaching with augmentation of the prescribed light fluence secondary to light scatter in the oropharynx. We report a potential new role using TORS for exposure and accurate PDT in the oropharynx. PMID:21333937

  12. Prospects in the Application of Photodynamic Therapy in Oral Cancer and Premalignant Lesions

    PubMed Central

    Saini, Rajan; Lee, Nathan V.; Liu, Kelly Y. P.; Poh, Catherine F.

    2016-01-01

    Oral cancer is a global health burden with significantly poor survival, especially when the diagnosis is at its late stage. Despite advances in current treatment modalities, there has been minimal improvement in survival rates over the last five decades. The development of local recurrence, regional failure, and the formation of second primary tumors accounts for this poor outcome. For survivors, cosmetic and functional compromises resulting from treatment are often devastating. These statistics underscore the need for novel approaches in the management of this deadly disease. Photodynamic therapy (PDT) is a treatment modality that involves administration of a light-sensitive drug, known as a photosensitizer, followed by light irradiation of an appropriate wavelength that corresponds to an absorbance band of the sensitizer. In the presence of tissue oxygen, cytotoxic free radicals that are produced cause direct tumor cell death, damage to the microvasculature, and induction of inflammatory reactions at the target sites. PDT offers a prospective new approach in controlling this disease at its various stages either as a stand-alone therapy for early lesions or as an adjuvant therapy for advanced cases. In this review, we aim to explore the applications of PDT in oral cancer therapy and to present an overview of the recent advances in PDT that can potentially reposition its utility for oral cancer treatment. PMID:27598202

  13. Laser therapy and sclerotherapy in the treatment of oral and maxillofacial hemangioma and vascular malformations

    NASA Astrophysics Data System (ADS)

    Crişan, Bogdan; BǎciuÅ£, Mihaela; BǎciuÅ£, Grigore; Crişan, Liana; Bran, Simion; Rotar, Horatiu; Moldovan, Iuliu; Vǎcǎraş, Sergiu; Mitre, Ileana; Barbur, Ioan; Magdaş, Andreea; Dinu, Cristian

    2016-03-01

    Hemangioma and vascular malformations in the field of oral and maxillofacial surgery is a pathology more often found in recent years in patients. The aim of this study was to evaluate the efficacy of the laser photocoagulation performed with a diode laser (Ga-Al-As) 980 nm wavelength in the treatment of vascular lesions which are located on the oral and maxillofacial areas, using color Doppler ultrasonography for evaluation of the results. We also made a comparison between laser therapy and sclerotherapy in order to establish treatment protocols and recommendations associated with this pathology. We conducted a controlled study on a group of 92 patients (38 male and 54 female patients, with an average age of 36 years) having low flow hemangioma and vascular malformations. Patients in this trial received one of the methods of treatment for vascular lesions such as hemangioma and vascular malformations: laser therapy or sclerotherapy. After laser therapy we have achieved a reduction in size of hemangioma and vascular malformations treated with such a procedure, and the aesthetic results were favorable. No reperfusion or recanalization of laser treated vascular lesions was observed after an average follow-up of 6 to 12 months. In case of sclerotherapy a reduction in the size of vascular lesions was also obtained. The 980 nm diode laser has been proved to be an effective tool in the treatment of hemangioma and vascular malformations in oral and maxillofacial area. Laser therapy in the treatment of vascular lesions was more effective than the sclerotherapy procedure.

  14. Specific alkylation of a histidine residue in carnitine acetyltransferase by bromoacetyl-l-carnitine

    PubMed Central

    Chase, J. F. A.; Tubbs, P. K.

    1970-01-01

    Incubation of carnitine acetyltransferase with low concentrations of bromoacetyl-l-carnitine causes a rapid and irreversible loss of enzyme activity; one mol of inhibitor can inactivate one mol of enzyme. Bromoacetyl-d-carnitine, iodoacetate or iodoacetamide are ineffective. l-Carnitine protects the transferase from bromoacetyl-l-carnitine. Investigation shows that the enzyme first reversibly binds bromoacetyl-l-carnitine with an affinity similar to that shown for the normal substrate acetyl-l-carnitine; this binding is followed by an alkylation reaction, forming the carnitine ester of a monocarboxymethyl-protein, which is catalytically inactive. The carnitine is released at an appreciable rate by spontaneous hydrolysis, and the resulting carboxymethyl-enzyme is also inactive. Total acid hydrolysis of enzyme after treatment with 2-[14C]bromoacetyl-l-carnitine yields N-3-carboxy[14C]methylhistidine as the only labelled amino acid. These findings, taken in conjunction with previous work, suggest that the single active centre of carnitine acetyltransferase contains a histidine residue. PMID:5461620

  15. Pregnancy increases urinary loss of carnitine and reduces plasma carnitine in Korean women.

    PubMed

    Cho, Sang-Woon; Cha, Youn-Soo

    2005-05-01

    This study compared plasma and urinary carnitine concentrations in pregnant and non-pregnant Korean women. The subjects were fifty pregnant women and thirty non-pregnant women aged 24-28 years. During the first trimester, dietary carnitine intakes in the pregnant women were much lower than in non-pregnant women (70.00 (SD 29.22) micromol/d), but over the course of pregnancy carnitine intake increased from 44.64 (SD 24.84) micromol/d during the first trimester to 96.11 (SD 36.56) micromol/d during the third trimester. Pregnant women had a significantly lower plasma carnitine concentration than non-pregnant women. Plasma concentrations of non-esterified carnitine, acid-soluble acylcarnitine and total carnitine were significantly lower during the second and third trimesters than the first. Plasma acid-insoluble acylcarnitine levels, which tended to be higher in the non-pregnant women compared with the pregnant women, increased significantly as gestation proceeded. The urinary excretion of non-esterified carnitine, acid-soluble acylcarnitine and total carnitine was significantly higher in the pregnant women during the first and second trimesters than in non-pregnant women and decreased significantly as gestation proceeded. We found that there was a significant decrease in plasma carnitine level even though dietary carnitine intake increased as gestation proceeded. The low urinary excretion of carnitine in late pregnancy may be caused by an increased demand during pregnancy.

  16. Myocardial infarction and left ventricular remodeling: results of the CEDIM trial. Carnitine Ecocardiografia Digitalizzata Infarto Miocardico.

    PubMed

    Colonna, P; Iliceto, S

    2000-02-01

    Left ventricular dilatation after acute myocardial infarction (MI) is a powerful predictor of progressive functional deterioration, culminating in heart failure and death. The most important determinants of post-MI left ventricular remodeling are the size of the infarct, the degree of residual stenosis in the infarct-related artery, and the viability of the infarct zone. In addition to reperfusion therapy and angiotensin-converting enzyme inhibition, metabolic intervention with L-carnitine may represent a therapeutic approach for preventing left ventricular dilatation and preserving cardiac function. Ongoing studies with early metabolic intervention with carnitine in the acute phase of infarction may prove successful in protecting the microcirculation against ischemic damage and enhancing its ability to respond to blood flow resumption. The results of the multicenter, randomized, double-blind Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial suggest that the early and long-term administration of L-carnitine attenuates progressive left ventricular dilatation after acute anterior MI. Results show significant, consistent reductions in end-diastolic volume and end-systolic volume in patients who received L-carnitine compared with placebo. The ongoing CEDIM-2 trial (projected 4000 patients with acute MI) will assess the efficacy of L-carnitine in reducing the combined incidence of death and heart failure at 6 months. In addition to standard reperfusion therapy and angiotensin-converting enzyme inhibition, metabolic intervention with L-carnitine may be a therapeutic approach for preventing left ventricular dilatation and preserving cardiac function by limiting infarct size, decreasing residual stenosis in the infarct-related artery, and increasing viability of the infarct zone.

  17. Studies concerning the ergogenic value of protein supply and 1-carnitine in elite junior cyclists.

    PubMed

    Drăgan, G I; Wagner, W; Ploeşteanu, E

    1988-01-01

    The effects of protein supply and 1-carnitine were recorded in a group of junior elite cyclists by a prospective double blind placebo controlled trial for six weeks (Refit milk powder containing about 90% proteins and 5% mineral salts-Ca, P, K, Na and 1-carnitine tablets). Seven top junior cyclists received orally 1 g protein/kg.d as supplement of food for six weeks and 2 g 1-carnitine, also orally, per day, 10 days before an important competition; other 7 cyclists received the same regimen as placebo. Significant and favourable changes were recorded in the treated group for the strength index, lean body mass, fat mass, TWP (total work-kgm, performed on cycloergometer 1', serum proteins, serum Hb, serum calcium) changes which did not appear in the control group. Serum cholesterol, creatinine, thymol test and serum GPT did not change significantly in either group. All athletes were under medical supervision, had a controlled training programme and food and received daily only vitamins and mineral salts. The treated group supported better the stress-induced efforts and obtained higher performances in the international competition which took place at the end of the experiment. Based on these data the authors recommend a supply of protein ratio up to 3.2 g/kg.d, six weeks before competition and 2 g 1-carnitine daily, also orally, 10 to 14 days before competition, including the day of competition, for cyclists, in order to improve the biological potential of the body.

  18. Oral but not transdermal estrogen replacement therapy changes the composition of plasma lipoproteins.

    PubMed

    Vrablik, Michal; Fait, Tomas; Kovar, Jan; Poledne, Rudolf; Ceska, Richard

    2008-08-01

    The role of hormone replacement therapy and estrogen replacement therapy (ERT) in cardiovascular disease prevention has not been unambiguously defined yet. The metabolic effects of estrogens may vary depending upon the route of administration. Therefore, we compared the impact of unopposed oral or transdermal ERT on plasma lipids and lipoproteins in 41 hysterectomized women. This was an open-label, randomized, crossover study (with 2 treatments and 2 periods). The 41 hysterectomized women were randomized to receive oral or transdermal 17beta-estradiol in the first or second of two 12-week study periods. Plasma lipid and lipoprotein levels were assayed before and after each treatment using standard automated methods. Lipid content of lipoprotein subclasses was assessed by sequential ultracentrifugation. The atherogenic index of plasma (AIP) was calculated as log(triglyceride [TG]/high-density lipoprotein [HDL] cholesterol). The difference between the 2 forms of administration was tested using a linear mixed model. The change from baseline for each of the forms was tested using paired t test. Oral ERT resulted in a significant increase in HDL cholesterol and apolipoprotein A-I levels, whereas it significantly decreased total and low-density lipoprotein (LDL) cholesterol and increased TG concentrations. Transdermal ERT had no such effect. Oral ERT led to a significant TG enrichment of HDL (0.19 +/- 0.06 vs 0.27 +/- 0.07 mmol/L, P < .001) and LDL particles (0.23 +/- 0.08 vs 0.26 +/- 0.10 mmol/L, P < .001) compared with baseline, whereas transdermal therapy did not have any effect on lipoprotein subclasses composition. The difference between the 2 treatments was statistically significant for HDL-TG and LDL-TG (0.27 +/- 0.07 vs 0.19 +/- 0.05 mmol/L, P < .001 and 0.26 +/- 0.10 vs 0.22 +/- 0.07 mmol/L, P< .001, respectively). The transdermal but not oral ERT significantly reduced the AIP compared with baseline (-0.17 +/- 0.26 vs -0.23 +/- 0.25, P = .023), making the

  19. Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial

    PubMed Central

    Pfrunder, Arabelle; Schiesser, Monika; Gerber, Simone; Haschke, Manuel; Bitzer, Johannes; Drewe, Juergen

    2003-01-01

    Aims Breakthrough bleeding or even unwanted pregnancies have been reported in women during concomitant therapy with oral contraceptives and St John's wort extract. The aim of the present study was to investigate the effects of St John's wort extract on oral contraceptive therapy with respect to ovarian activity, breakthrough bleeding episodes and the pharmacokinetics of ethinyloestradiol and 3-ketodesogestrel. Methods Eighteen healthy females were treated with a low-dose oral contraceptive (0.02 mg ethinyloestradiol, 0.150 mg desogestrel) alone (control cycle) or combined with 300 mg St John's wort extract given twice daily (cycle A) or three times daily (cycle B). Ovarian activity was assessed by measuring follicle maturation and serum oestradiol and progesterone concentrations. The number of breakthrough bleeding episodes and the pharmacokinetics of ethinyloestradiol and 3-ketodesogestrel were assessed under steady-state conditions. Results During concomitant administration of low-dose oral contraceptive and St John's wort, there was no significant change in follicle maturation, serum oestradiol or progesterone concentrations when compared with oral contraceptive treatment alone. However, significantly more subjects reported intracyclic bleeding during cycles A (13/17 (77%), P < 0.015) and cycle B (15/17 (88%), P < 0.001) than with oral contraceptives alone (6/17 (35%)). The AUC(0,24 h) and Cmax of ethinyloestradiol remained unchanged during all study cycles, whereas the AUC(0,24 h) and Cmax of 3-ketodesogestrel decreased significantly from 31.2 ng ml−1 h to 17.7 ng ml−1 h (43.9%; 95% confidence interval (CI) −49.3, −38.5, P = 0.001) and from 3.6 ng ml −1 to 3.0 ng ml −1(17.8%; CI −29.9, −5.7, P = 0.005), respectively, during cycle A and by 41.7% (CI −47.9, −35.6; P = 0.001) and by 22.8% (CI −31.2, −13.3; P < 0.001) during cycle B respectively, compared with the control cycle. Conclusions There was no evidence of ovulation during low

  20. Uptake of carnitine by red blood cells

    SciTech Connect

    Campa, M.; Borum, P.

    1986-05-01

    A significant amount of blood carnitine (70% of cord blood and 40% of blood from healthy adults) is partitioned into the red blood cell compartment of whole blood. Data indicate that the plasma compartment and the red blood cell compartment of whole blood represent different metabolic pools of carnitine. There are no data to indicate that red blood cells synthesize carnitine, but our understanding of the uptake of carnitine by red blood cells is negligible. Red blood cells were obtained from healthy adults, washed twice with normal saline, and used for uptake experiments. When the cells were incubated at 37/sup 0/C in the presence of /sup 14/C-carnitine, radioactivity was found both in the soluble cytosolic and membrane fractions of the cells following lysis. The uptake was dependent upon the time of incubation, temperature of incubation, and carnitine concentration in the incubation medium. Washed red blood cell membranes incubated with /sup 14/C-carnitine showed specific binding of radioactivity. These data are consistent with the hypothesis that red blood cells have an uptake mechanism for L-carnitine.

  1. Initial antibiotic therapy for alligator bites: characterization of the oral flora of Alligator mississippiensis.

    PubMed

    Flandry, F; Lisecki, E J; Domingue, G J; Nichols, R L; Greer, D L; Haddad, R J

    1989-02-01

    An open thumb fracture resulting from an alligator bite became infected with Aeromonas hydrophila, Enterobacter agglomerans, and Citrobacter diversus. The patient was treated by surgical debridement and antibiotic therapy. We obtained cultures from the mouth of ten alligators to characterize their oral flora. Initial empiric therapy after alligator bites should be directed at gram-negative species, in particular, Aeromonas hydrophila and anaerobic species including Clostridium. Of the numerous fungi that were isolated, none has been reported to result in wound infection after alligator bites.

  2. [A case of possible retroperitoneal metastasis of breast cancer successfully treated with oral S-1 and cyclophosphamide therapy after TC therapy].

    PubMed

    Yoneyama, Kimiyasu; Takeshita, Toshio; Suzuki, Hiroshi; Morise, Masaki; Suzuki, Tetsutarou; Kishi, Shinya; Tsutsui, Atsuko; Matsumoto, Akiko

    2011-03-01

    We report a case of possible retroperitoneal metastasis of breast cancer successfully treated with oral S-1 and cyclophosphamide therapy after docetaxel and cyclophosphamide (TC) therapy. A 57-year-old woman with a history of bilateral breast cancer showed an increase in tumor markers during treatment with oral anastrozole as postoperative adjuvant therapy 4 years after her second cancer surgery. After careful examination, the patient was diagnosed as having multiple bone metastases and her medication was changed to oral letrozole. After 3 months, the patient developed left back pain and was referred to our hospital. CT scanning showed an enhanced mass in the region from the left perirenal and posterior pararenal spaces to the left psoas major muscle and the anterior aspect of the left iliacus muscle, suggesting retroperitoneal metastasis. TC therapy was performed and, as a result, tumor markers decreased and the mass disappeared on CT imaging. After discontinuation of TC therapy, the tumor markers increased again, following which oral S-1 and cyclophosphamide therapy were administered, and the tumor markers decreased. At the time of this writing, the patient is still undergoing therapy, and no recurrence has been observed. We concluded that oral S-1 and cyclophosphamide therapy were useful in the present case and were associated with few adverse effects.

  3. The effect of L-carnitine on T-maze learning ability in aged rats.

    PubMed

    Lohninger, S; Strasser, A; Bubna-Littitz, H

    2001-06-01

    L-carnitine is of considerable interest because of its capacity to counteract several physiological and pathological phenomena typical of brain aging processes. We examined the effects of L-carnitine on the learning ability of old rats. 100 mg/kg per body weight per day L-carnitine was administered orally to old (21 months) male Sprague-Dawley rats (OLD-CAR) for a period of 2 months. Old (21 months, OLD-CO) and young (7 months, YG-CO) control animals received tap water exclusively. Performance of the OLD-CAR and OLD-CO was compared with that of YG-CO in a multiple T-maze. The mean run time values showed a significant (P=0.01) difference of the OLD-CAR rats to the OLD-CO but no significant differences between OLD-CAR and YG-CO. For the T-maze parameter mean correct responses we were able to demonstrate that L-carnitine treated old rats made significantly (P=0.03) less errors and significantly (P=0.01) more animals reached the T-maze goal compared with OLD-CO but no significant differences were observed between OLD-CAR and YG-CO. The results of the present study clearly demonstrate that carnitine treatment improves the learning ability of old rats and seems to be able to reduce the loss of cognitive functions that occur with aging.

  4. Positive influence of L-carnitine on the different muscle fibres types of racing pigeons.

    PubMed

    Chang, M H; Tsai, F H; Chou, S J; Wang, J H; Lo, D Y; Zheng, Z Z; Chan, K W; Lai, J M

    2014-08-01

    Succinate dehydrogenase (SDH), Ca(2+) ATPase, Lactate dehydrogenase (LDH), are involved in energy metabolism. These enzymes can be used as indicators of the energy capacity of aerobic cells. The study investigated the effects of L-carnitine supplementation on M. pectoralis superficialis, M. pectoralis profundus, M. extensor carpi radialis muscle and M. flexor carpi ulnaris. Twenty-eight racing pigeons hatched at the same time were divided randomly into three groups. Eight pigeons, which were used as the control group, were sacrificed at 92-day old. The remaining twenty pigeons continued training until they reached 157-day old, with half the pigeons getting 25 mg/head/day of L-carnitine, while the other half given the same amount of water. The pigeons were assessed by histochemical methods and reverse transcription polymerase chain reaction (RT-PCR). To assess influence of L-carnitine on muscle fibre composition and the performance of three genes' mRNA, this study applied SDH localization, SDH, Ca(2+) ATPase and LDH mRNA expression to examine the results after oral administration of L-carnitine in vivo in racing pigeons. The results showed that L-carnitine significantly elevated the amount of white muscle fibre type IIa (p < 0.05). The mRNA expression quantities of SDH and LDH gene was higher via RT-PCR method. However, the expression of Ca(2+) ATPase remains similar. In conclusion, appropriate oral administration of L-carnitine of 25 mg/pigeon/day will result in an improvement of muscles related to flying.

  5. Carnitine in bacterial physiology and metabolism

    PubMed Central

    Meadows, Jamie A.

    2015-01-01

    Carnitine is a quaternary amine compound found at high concentration in animal tissues, particularly muscle, and is most well studied for its contribution to fatty acid transport into mitochondria. In bacteria, carnitine is an important osmoprotectant, and can also enhance thermotolerance, cryotolerance and barotolerance. Carnitine can be transported into the cell or acquired from metabolic precursors, where it can serve directly as a compatible solute for stress protection or be metabolized through one of a few distinct pathways as a nutrient source. In this review, we summarize what is known about carnitine physiology and metabolism in bacteria. In particular, recent advances in the aerobic and anaerobic metabolic pathways as well as the use of carnitine as an electron acceptor have addressed some long-standing questions in the field. PMID:25787873

  6. Effect of L-Carnitine in Patients With Liver Cirrhosis on Energy Metabolism Using Indirect Calorimetry: A Pilot Study

    PubMed Central

    Sakai, Yoshiyuki; Nishikawa, Hiroki; Enomoto, Hirayuki; Yoh, Kazunori; Iwata, Yoshinori; Hasegawa, Kunihiro; Nakano, Chikage; Kishino, Kyohei; Shimono, Yoshihiro; Takata, Ryo; Nishimura, Takashi; Aizawa, Nobuhiro; Ikeda, Naoto; Takashima, Tomoyuki; Ishii, Akio; Iijima, Hiroko; Nishiguchi, Shuhei

    2016-01-01

    Background L-carnitine supplementation has been suggested to show several favorable effects on patients with liver cirrhosis (LC). However, there have been no reports regarding the effect of L-carnitine on energy metabolism in patients with LC using indirect calorimetry which is a well-established method for assessing the degree of liver malnutrition. We examined the effect of L-carnitine in patients with LC on energy metabolism using indirect calorimetry. Methods A total of 13 LC patients who are scheduled to be treated with L-carnitine (1,800 mg/day) were analyzed in this study. None of the patients previously received L-carnitine. An evaluation of the nutritional status was performed at the initiation of L-carnitine therapy and after 4 weeks of L-carnitine therapy. We evaluated the effect of L-carnitine on the nutritional status and energy metabolism by comparing various clinical variables at these two time points. In addition, the changes in the nutritional status of the patients were also evaluated using indirect calorimetry. Results After 4 weeks of L-carnitine treatment, for all cases, the mean substrate oxidation rates of carbohydrate (%C) increased from 37.6% to 48.2%, the mean substrate oxidation rates of fat (%F) decreased from 40.2% to 31.9% and the mean substrate oxidation rates of protein (%P) decreased from 22.2% to 19.9%. In a subgroup analysis of patients with baseline non-protein respiratory quotient (npRQ) < 0.85, the mean %C increased from 15.3% to 34.2%, the mean %F decreased from 59.9% to 45.1%, and the mean %P decreased from 24.8% to 20.6%. After 4 weeks of L-carnitine treatment, for all cases (n = 13), the mean value of npRQ increased in comparison with the baseline levels, although the difference was not significant (0.868 ± 0.060 vs. 0.838 ± 0.097, P = 0.19). Conversely, in patients with baseline npRQ < 0.85, the npRQ value significantly increased after 4 weeks treatment of L-carnitine compared with the baseline levels (0.827 ± 0.030 vs

  7. Treatment of Oral Candidiasis Using Photodithazine®- Mediated Photodynamic Therapy In Vivo

    PubMed Central

    G. Basso, Fernanda; de Souza Costa, Carlos Alberto; Bagnato, Vanderlei Salvador; Mima, Ewerton Garcia de Oliveira; Pavarina, Ana Cláudia

    2016-01-01

    This study evaluated the effectiveness of antimicrobial photodynamic therapy (aPDT) in the treatment of oral candidiasis in a murine model using Photodithazine® (PDZ). This model of oral candidiasis was developed to allow the monitoring of the infection and the establishment of the aPDT treatment. Six-week-old female mice were immunosuppressed and inoculated with C. albicans to induce oral candidiasis. PDZ-mediated aPDT and nystatin treatment were carried out for 5 consecutive days with one application per day. The macroscopic evaluation of oral lesions was performed. After each treatment, the tongue was swabbed to recover C. albicans cells. Viable colonies were quantified and the number of CFU/ml determined. The animals were sacrificed 24 hours and 7 days after treatment and the tongues were surgically removed for histological analysis and analysis of inflammatory cytokines expression (IL-1, TNF-α and IL-6) by RT-qPCR. Data were analyzed by two-way ANOVA. PDZ-mediated aPDT was as effective as Nystatin (NYS group) in the inactivation of C. albicans, reducing 3 and 3.2 logs10 respectively, 24 h after treatment (p<0.05). Animals underwent PDZ-mediated aPDT showed complete remission of oral lesions, while animals treated with NYS presented partial remission of oral lesions in both periods assessed. Histological evaluation revealed mild inflammatory infiltrate in the groups treated with aPDT and NYS in both periods assessed. The aPDT induced the TNF-α expression when compared with the control (P-L-) (p<0.05), 24 h and 7 days after treatment. In summary, the murine model developed here was able to mimic the infection and PDZ-mediated aPDT was effective to treat mice with oral candidiasis. PMID:27253525

  8. The effect of low level laser therapy in different wavelengths in the treatment of oral mucositis—proposal for extra-oral implementation

    NASA Astrophysics Data System (ADS)

    Moraes, J. J. C.; Queiroga, A. S.; de Biase, R. C. C. G.; Leite, E. P.; Cabral Júnior, C. R.; Limeira Júnior, F. A.

    2009-09-01

    The oral mucositis is the most frequent acute oral complication resulting from antineoplastic treatment and may worsen the clinical condition of the patient and interfere with his/her quality of life. This study aimed to comparatively evaluate, from a clinical point of view, the effect of Laser Therapy λ660 nm (wavelength of the red Laser) and λ830 nm (wavelength of the infrared Laser), at extra-oral points, in remission of severity of oral mucositis and pain associated with it in pediatric oncological patients undergoing chemotherapy with the anticancer drug methotrexate, noting which of the two wavelength is the most appropriate to this new technique. The sample consisted of 13 patients placed at random in each group and subjected to sessions of Low Level Laser Therapy, at pre-determined extra-oral points for five consecutive days, starting at the beginning of the observation of mucositis injuries. It became possible to note that from the group of patients in the group of Laser λ830 nm ( n = 6; 46.15%), four ( n = 4; 66.67%) of these patients had remission of injuries to grade 0 (WHO), and as for pain, five patients ( n = 5; 83.33%) showed no painful symptoms for mucositis injuries. In the Laser λ660 nm group ( n = 7; 53.85%), only two patients ( n = 2; 28.57%) achieved a regression of lesions to grade 0 (WHO), while four patients ( n = 4; 57.14%) had no pain. So, the extra-oral application of Laser Therapy was effective in treating injuries of oral mucositis in the patients treated; and Laser Therapy in the infrared spectrum (λ830 nm) was more effective in the treatment of oral mucositis injuries compared to the red spectrum (λ660 nm), which can be explained by the greater power of penetration of infrared rays, acting in a more expressive way in deeper places.

  9. Preliminary study on radio-chemo-induced oral mucositis and low level laser therapy

    NASA Astrophysics Data System (ADS)

    Merigo, Elisabetta; Fontana, Matteo; Fornaini, Carlo; Clini, Fabio; Cella, Luigi; Vescovi, Paolo; Oppici, Aldo

    2012-09-01

    Background: Oral mucositis remains one of the most common and troubling side effects of antineoplastic radiation and drug therapy: its incidence in onco-hematological radio-chemotreated patients is variable between 50 and 100% and its impact on this populations is directly linked with the experience of intense pain causing reduction and modification of therapy regimens, decreased survival rates and increased cost of care. Purpose: Aim of this study is the preliminary evaluation of a Low Level Laser therapy (LLLT) protocol on healing process of oral mucositis and on pain and quality of life of patients experiencing this dramatic side-effect. Materials and methods: Patients were evaluated and treated at the Unita` Operativa Semplice Dipartimentale di Odontostomatologia e Chirurgia Maxillo-Facciale of the Hospital of Piacenza were they were treated for primary disease with protocols of chemotherapy and/or radiotherapy. LLLT protocol was performed with a diode laser (808 nm -XD Smile - Fotona -Slovenia) on a two weeks-6 treatments schedule with power of 0.5 W and application of 30 seconds. Mucositis grading was scored on the basis of WHO classification by two blind operators at each treatment and at 1 and 2 weeks after treatment. Pain and capability of deglutition were described by patients by means questionnaires based on Visual Analogue Scale, Numerical Rating Scale and Quality of Life. Results: A relevant improvement of healing of oral mucositis, in terms of reduction of grading score, and of pain, swallowing discomfort and quality of life was recorded. Discussion and conclusion: Results of this preliminary study are encouraging for the realization of larger studies focused on the application of LLLT protocols in management of radio-chemotreated patients with oral mucositis.

  10. Experimental study of antiangiogenic gene therapy targeting VEGF in oral cancer.

    PubMed

    Okada, Yasuo; Ueno, Hikaru; Katagiri, Masataka; Oneyama, Takahiro; Shimomura, Kana; Sakurai, Satoshi; Mataga, Izumi; Moride, Michiko; Hasegawa, Hitoshi

    2010-02-01

    It is well known that tumor angiogenesis plays an important role in local growth and metastasis of oral cancer; therefore, inhibiting angiogenesis is considered to be effective for treating oral cancer. This study aimed to investigate the effectiveness of systemically available antiangiogenic gene therapy targeting vascular endothelial growth factor (VEGF), which is one of the most important angiogenesis accelerators. We administered a soluble form of VEGF receptor-expressing gene incorporated into adenovirus (AdVEGF-ExR) intraperitoneally to nude mice to which oral cancer cell lines (SAS, HSC-3, and Ca9-22) had been transplanted subcutaneously in vivo to inhibit angiogenesis and tumor proliferation. Then, we measured tumor volumes over time, and tumors were enucleated and examined histopathologically and immunohistologically at 28 days after AdVEGF-ExR administration. Compared to the controls to which we administered AdLacZ or saline, significant antiproliferative effects were observed (P < 0.05) in the AdVEGF-ExR administration group, and extensive tumor necrosis was found histopathologically. Immunohistochemical analysis with CD34 (NU-4A1) revealed tumor angiogenesis was suppressed significantly (P < 0.05), and that with ssDNA revealed apoptosis induction was significantly high (P < 0.05) in the AdVEGF-ExR group. However, analysis with Ki-67 (MIB-1) revealed tumor proliferative capacity was not significantly different between the groups. Consequently, we consider that AdVEGF-ExR administration achieved tumor growth suppression by inhibiting angiogenesis and inducing apoptosis, but not by inhibiting the proliferative capacity of tumor cells. Neither topical administration of a soluble form of VEGF receptor (sVEGFR) to the tumor nor a megadose was needed to achieve this inhibition effect. These results suggest gene therapy via sVEGFR would be an effective oral cancer therapy and benefit future clinical applications.

  11. Influence of acetyl-L-carnitine infusion on haemodynamic parameters and survival of circulatory-shock patients.

    PubMed

    Gasparetto, A; Corbucci, G G; De Blasi, R A; Antonelli, M; Bagiella, E; D'Iddio, S; Trevisani, C

    1991-01-01

    The clinical use of acetyl carnitine in circulatory shock has its theoretical basis in the ability of this molecule to restore enzyme activity inhibited by hypoxia, acting as an acetyl donor. Moreover the action of carnitine on an injured myocardium encouraged us to examine the clinical effect of this drug during heart failure. A double-blind clinical study was performed in ten Italian intensive care units on 115 patients with septic, cardiac of traumatic shock, by using acetyl-L-carnitine infusion for 12 hours, with a previous single bolus intravenously. The results showed a good response to the drug in terms of blood oxygenation during the course of sepsis and heart failure. The heart rate as well as right atrial pressure decreased significantly in patients with cardiogenic shock. In septic patients systolic and mean arterial pressures increased also. The present data suggests the use of acetyl-L-carnitine as an adjuvant to the commonly used therapy in hypoxic conditions.

  12. Medication adherence to oral iron therapy in patients with iron deficiency anemia

    PubMed Central

    Gereklioglu, Cigdem; Asma, Suheyl; Korur, Asli; Erdogan, Ferit; Kut, Altug

    2016-01-01

    Objective: This study aimed at investigating the factors affecting medication adherence in patients who use oral iron therapy due to iron deficiency anemia. Methods: A total of 96 female patients in fertile age with mean age of 30±10.1 years (range 18-53) who were admitted to Family Medicine Clinic between 01 January and 31 March 2015 and who had received iron therapy within the recent three years were enrolled in the study. Data were collected through a questionnaire form. Results: Of the patients, 39 (40,6%) were detected not to use the medication regularly or during the recommended period. A statistically significant relationship was found between non-adherence to therapy and gastrointestinal side effects and weight gain (p<0.05). Conclusion: Medication adherence is deficient in patients with iron deficiency anemia. The most important reason for this seems gastrointestinal side effects, in addition to weight gain under treatment. PMID:27375698

  13. Efficacy and tolerability of oral versus injectable disease-modifying therapies for multiple sclerosis in clinical practice

    PubMed Central

    Longbrake, Erin E; Cross, Anne H; Salter, Amber

    2016-01-01

    Background The advent of oral disease-modifying therapies fundamentally changed the treatment of multiple sclerosis. Nevertheless, impressions of their relative efficacy and tolerability are primarily founded on expert opinion. Objective The purpose of this study was to determine whether oral disease-modifying therapies were better tolerated and/or more effective for controlling multiple sclerosis compared to injectable therapies in clinical practice. Methods Single-center, retrospective cohort study. 480 patients initiated oral (fingolimod, teriflunomide, or dimethyl fumarate) or injectable therapy between March 2013–March 2015 and follow-up data was collected for 5–31 months. Outcomes included on-drug multiple sclerosis activity and drug discontinuation. Cox proportional hazards models were used to control for baseline differences and sensitivity analyses using propensity-weighted matching were performed. Results A higher proportion of teriflunomide-treated patients experienced multiple sclerosis activity compared to those treated with injectable therapies (p = 0.0053) in the adjusted model. Breakthrough multiple sclerosis was equally prevalent among fingolimod and dimethyl fumarate-treated compared to injectable therapy-treated patients. Of patients initiating a disease-modifying therapy, 32–46% discontinued or switched treatments during the study. After controlling for baseline differences, discontinuation rates were comparable across treatment groups. Conclusions In this cohort, oral and injectable disease-modifying therapies were equally well tolerated, but teriflunomide appeared less effective for controlling multiple sclerosis activity than injectable therapies. Further study is needed.

  14. Long-term oral appliance therapy in obstructive sleep apnea syndrome: a controlled study on temporomandibular side effects.

    PubMed

    Doff, Michiel H J; Veldhuis, Steffanie K B; Hoekema, Aarnoud; Slater, James J R Huddleston; Wijkstra, P J; de Bont, Lambert G M; Stegenga, Boudewijn

    2012-06-01

    The objective of this study was to assess variations in the occurrence of temporomandibular disorders (TMDs) and the risk of developing pain and function impairment of the temporomandibular complex in obstructive sleep apnea syndrome (OSAS) patients treated with either an oral appliance (mandibular advancement device) or continuous positive airway pressure (CPAP) in a 2-year follow-up study. In addition, we assessed the relationship between the mean mandibular protrusion and the frequency of wearing the appliance during follow-up with the occurrence of pain and function impairment of the temporomandibular complex. Fifty-one patients were randomized to oral appliance therapy and 52 patients to CPAP therapy. TMDs (diagnosed according to the Axis I Research Diagnostic Criteria for TMD), pain intensity and disability and mandibular function impairment were recorded at baseline, after 2 months, 1 year and 2 years of therapy. Only in the initial period of treatment the occurrence of pain-related TMDs was considerably higher (24%) in the oral appliance group compared to CPAP (6%). Oral appliance therapy furthermore resulted in more temporomandibular pain compared to CPAP (odds ratio 2.33, 95% confidence interval (1.22-4.43)). However, there were no limitations in mandibular function in both groups during the (entire) follow-up period. Although generally not serious and of transient nature, oral appliance therapy results in more pain-related TMDs in the initial period of use compared with CPAP therapy. Oral appliance therapy is associated with increased pain in the temporomandibular complex in the initial period of use. Because of the transient nature, this pain is not a reason to contra-indicate an oral appliance in OSAS patients. Moreover, TMDs and the risk of developing pain and function impairment of the temporomandibular complex appear limited with long-term oral appliance use.

  15. Endometrial Hyperplasia Risk in Relation to Recent Use of Oral Contraceptives and Hormone Therapy

    PubMed Central

    Epplein, Meira; Reed, Susan D.; Voigt, Lynda F.; Newton, Katherine M.; Holt, Victoria L.; Weiss, Noel S.

    2008-01-01

    Purpose Examine the relationship between recent use of oral contraceptives and hormone therapy and endometrial hyperplasia (EH) risk. Methods Cases comprised women diagnosed with complex EH (n=289) or atypical EH (n=173) between 1985-2003. One age-matched control was selected for each case; excluded were women with a prior hysterectomy or diagnosis of EH or endometrial cancer. Hormone use in the six months prior to the date of the case’s first symptoms was ascertained using a pharmacy database and medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results Three (1.1%) cases had used oral contraceptives, compared to sixteen (6.0%) controls (OR = 0.2, 95% CI: 0.0–0.6). Fifty-one (16.8%) cases had taken estrogen-only hormone therapy, in contrast to two (0.7%) controls (OR = 37.6, 95% CI: 8.8–160.0). The risk of EH among estrogen plus progestin hormone users did not differ from that of non-users (OR = 0.7, 95% CI: 0.4–1.1). Conclusions This study suggests that previous findings of the association of estrogen-only hormone therapy with increased risk of EH and the lack of an association between estrogen plus progestin hormone therapy and EH risk are likely to apply to both complex EH and atypical EH. Further examination of the association between oral contraceptives and EH, with greater numbers of OC users, is warranted. PMID:19064186

  16. New directions in type 2 diabetes mellitus: an update of current oral antidiabetic therapy.

    PubMed Central

    Brown, D. L.; Brillon, D.

    1999-01-01

    This article reviewed the relevant literature including published clinical trials and reviews on currently available oral hypoglycemic agents. Results showed that the benefits of glycemic control have been established through multiple clinical trials. Long-term control of blood glucose levels in type 1 and type 2 diabetic patients will decrease the incidence and prolong the time until progression of diabetic retinopathy, nephropathy, and neuropathy. Our increased understanding of the pathophysiology behind type 2 diabetes has led to the development of many new agents that are aimed at treating the underlying insulin resistance and relative insulinopenia. The sulfonylureas as a group have been used for many years and act by stimulating insulin secretion. They are useful alone or as combination therapy with insulin or another oral hypoglycemic agent. The biguanides act by decreasing hepatic glucose production and by increasing peripheral insulin sensitivity. The alpha-glucosidase inhibitors act nonsystemically by blocking the metabolism of digested polysaccharides and therefore lowering the amount of carbohydrate absorbed in a meal. Benzoic acid derivatives act in a manner similar to that of sulfonylureas by enhancing pancreatic insulin production. They offer a shorter duration of action, lowering the risk of hypoglycemia. The thiazolidinediones increase peripheral insulin sensitivity and are effective as both monotherapy and combination therapy. Oral hypoglycemic agents, when properly administered, are very effective in controlling type 2 diabetes and preventing long-term complications. PMID:10643211

  17. Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus.

    PubMed

    Beckman, Joshua A; Goldfine, Allison B; Gordon, Mary Beth; Garrett, Leslie A; Keaney, John F; Creager, Mark A

    2003-12-01

    Oxidative stress decreases the bioavailability of endothelium-derived nitric oxide in diabetic patients. We investigated whether impaired endothelium-dependent vasodilation (EDV) in diabetes can be improved by long-term administration of oral antioxidants. Forty-nine diabetic subjects [26 Type 1 (T1) and 23 Type 2 (T2)] and 45 matched healthy control subjects were randomized to receive oral vitamin C (1,000 mg) and vitamin E (800 IU) daily or matching placebo for 6 mo. Vascular ultrasonography was used to determine brachial artery EDV and endothelium-independent vasodilation (EIV). EDV was decreased in both T1 (4.9 +/- 0.9%, P = 0.015) and T2 (4.1 +/- 1.0%, P < 0.01) subjects compared with control subjects (7.7 +/- 0.7%). EIV was decreased in T2 (15.0 +/- 1.2%, P < 0.01) but not T1 subjects (18.5 +/- 2.3%, P = 0.3) compared with controls (21.8 +/- 1.8%). Administration of antioxidant vitamins increased EDV in T1 (by 3.4 +/- 1.4%, P = 0.023) but not T2 subjects (by 0.5. +/- 0.4%, P = 0.3). Antioxidant therapy had no significant affect on EIV. Oral antioxidant therapy improves EDV in T1 but not T2 diabetes. These results are consistent with the lack of clinical benefit in studies that have included primarily T2 diabetic patients.

  18. Intravenous Iron Sucrose for Children with Iron Deficiency Failing to Respond to Oral Iron Therapy

    PubMed Central

    Crary, Shelley E.; Hall, Katherine; Buchanan, George R.

    2010-01-01

    Background For decades parenteral iron has been used in patients with iron deficiency unresponsive to oral iron therapy and in hemodialysis-dependent patients receiving erythropoietin. Newer intravenous (IV) iron formulations such as iron sucrose have replaced high molecular weight iron dextran in dialysis patients; however, the use of parenteral iron in children without renal disease has not been well defined. Procedure Pharmacy records were reviewed on children (≤ 18 yrs of age) who received IV iron sucrose at Children's Medical Center Dallas between January 1, 2004 and June 30, 2009. Patients who received iron sucrose for chronic renal disease were excluded from analysis. Results Thirty-eight children received iron sucrose for non-renal indications, 13 with iron deficiency refractory to oral iron therapy, 13 with iron malabsorption or dependence on parenteral nutrition, 7 for chronic gastrointestinal blood loss, and 5 for miscellaneous indications. Among these 38 children, who received a total of 510 doses of IV iron sucrose, there were only 6 adverse reactions. Patients in all categories had a good response to the iron sucrose, with a median hemoglobin rise of 1.9 – 3.1 g/dl depending on the indication. Conclusions Parenteral iron is a safe and effective means to treat iron deficiency in children who cannot receive or do not respond to oral iron due to intolerance, poor adherence or iron malabsorption. PMID:21298748

  19. Effects of L-carnitine supplement on serum inflammatory cytokines, C-reactive protein, lipoprotein (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia.

    PubMed

    Shakeri, Azam; Tabibi, Hadi; Hedayati, Mehdi

    2010-10-01

    Inflammation, oxidative stress, and high concentration of serum lipoprotein (a) [Lp (a)] are common complications in hemodialysis patients. The present study was designed to investigate the effects of L-carnitine supplement on serum inflammatory cytokines, C-reactive protein (CRP), Lp (a), and oxidative stress in hemodialysis patients with Lp (a) hyperlipoproteinemia [hyper Lp (a)]. This was an unblinded, randomized clinical trial. Thirty-six hyper Lp (a) hemodialysis patients (23 men and 13 women) were randomly assigned to either a carnitine or control group. Patients in the carnitine group received 1000 mg/d oral L-carnitine for 12 weeks, whereas patients in the control group did not receive any L-carnitine supplement. At baseline and the end of week 12, 5 mL of blood were collected after a 12- to 14-hours fast and serum free carnitine, CRP, interleukin-1β, interleukin-6 (IL-6), tumor necrosis factor-α, Lp (a), and oxidized low-density lipoprotein were measured. Serum free carnitine concentration increased significantly by 86% in the carnitine group at the end of week 12 compared with baseline (P<0.001), while serum CRP and IL-6 showed a significant decrease of 29% (P<0.05) and 61% (P<0.001), respectively. No significant changes were observed in serum free carnitine, CRP, and IL-6 in the control group. There were no significant differences between the two groups in mean changes of serum interleukin-1β, tumor necrosis factor-α, Lp (a), and oxidized low-density lipoprotein concentrations. L-carnitine supplement reduces inflammation in hemodialysis patients, but has no effect on hyper Lp (a) and oxidative stress.

  20. Iron deficiency anaemia in pregnancy and postpartum: pathophysiology and effect of oral versus intravenous iron therapy.

    PubMed

    Khalafallah, Alhossain A; Dennis, Amanda E

    2012-01-01

    Nutritional iron-deficiency anaemia (IDA) is the most common disorder in the world, affecting more than two billion people. The World Health Organization's global database on anaemia has estimated a prevalence of 14% based on a regression-based analysis. Recent data show that the prevalence of IDA in pregnant women in industrialized countries is 17.4% while the incidence of IDA in developing countries increases significantly up to 56%. Although oral iron supplementation is widely used for the treatment of IDA, not all patients respond adequately to oral iron therapy. This is due to several factors including the side effects of oral iron which lead to poor compliance and lack of efficacy. The side effects, predominantly gastrointestinal discomfort, occur in a large cohort of patients taking oral iron preparations. Previously, the use of intravenous iron had been associated with undesirable and sometimes serious side effects and therefore was underutilised. However, in recent years, new type II and III iron complexes have been developed, which offer better compliance and toleration as well as high efficacy with a good safety profile. In summary, intravenous iron can be used safely for a rapid repletion of iron stores and correction of anaemia during and after pregnancy.

  1. Combination oral antiangiogenic therapy with thalidomide and sulindac inhibits tumour growth in rabbits

    PubMed Central

    Verheul, H M W; Panigrahy, D; Yuan, J; D'Amato, R J

    1999-01-01

    Neovascularization facilitates tumour growth and metastasis formation. In our laboratory, we attempt to identify clinically available oral efficacious drugs for antiangiogenic activity. Here, we report which non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit corneal neovascularization, induced by basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF). This antiangiogenic activity may contribute to the known effects of NSAIDs on gastric ulcers, polyps and tumours. We found that sulindac was one of the most potent antiangiogenic NSAIDs, inhibiting bFGF-induced neovascularization by 50% and VEGF-induced neovascularization by 55%. Previously, we reported that thalidomide inhibited growth factor-induced corneal neovascularization. When we combined sulindac with thalidomide, we found a significantly increased inhibition of bFGF- or VEGF-induced corneal neovascularization (by 63% or 74% respectively) compared with either agent alone (P< 0.01). Because of this strong antiangiogenic effect, we tested the oral combination of thalidomide and sulindac for its ability to inhibit the growth of V2 carcinoma in rabbits. Oral treatment of thalidomide or sulindac alone inhibited tumour growth by 55% and 35% respectively. When given together, the growth of the V2 carcinoma was inhibited by 75%. Our results indicated that oral antiangiogenic combination therapy with thalidomide and sulindac may be a useful non-toxic treatment for cancer. © 1999 Cancer Research Campaign PMID:10408702

  2. Currently approved and emerging oral therapies in multiple sclerosis: An update for the ophthalmologist.

    PubMed

    Eckstein, Christopher; Bhatti, M Tariq

    2016-01-01

    Although our understanding of multiple sclerosis (MS) has grown substantially, its cause remains unknown. Nonetheless, in the past 3 decades, there have been tremendous advancements in the development of disease-modifying drugs (DMDs). In July 1993, the United States Food and Drug Administration approved the first disease-modifying drug-interferon β- and there are currently 13 medications approved for use in relapsing MS. All the early medications are administered either as a subcutaneous or intramuscular injection, and despite the clinical efficacy and safety of these medications, many patients were hampered by the inconvenience of injections and injection-related side effects. In September 2010, the first oral DMD-fingolimod-was approved. Since then, 2 additional oral DMDs (teriflunomide and dimethyl fumarate) have been approved, and several other oral medications are being evaluated in extensive MS development programs. Because of frequent ocular involvement, ophthalmologists are often involved in the care of MS patients and therefore need to be aware of the current treatment regimens prescribed by neurologists, some of which can have significant ophthalmic adverse events. We update the current advancements in the treatment of MS and discuss the published clinical data on the efficacy and safety of the currently approved and emerging oral therapies in MS.

  3. Low level laser therapy in the treatment of oral mucositis in cancer patients: systematic review of literature

    NASA Astrophysics Data System (ADS)

    El-Sabbagh, Rula Fawzi; Selting, Wayne J.

    2016-03-01

    Oral mucositis is a debilitating and dose limiting side effect of oncotherapy in cancer patients. Low Level Laser Therapy (LLLT) is a promising new intervention for the treatment of oral mucositis. Aims and objectives: 1. Perform a systematic review of available literature on the therapeutic effect of LLLT on established oral mucositis. 2. Formulate recommendations for future studies based on results of review. Methods: Electronic search oflow level laser therapy in the treatment of oral mucositis was conducted and eligible studies reviewed. Results: Four studies met the inclusion criteria and were analyzed. A total of 109 patients were included, 59 of which received LLLT as a therapeutic measure. An overall success rate of 81.4% success rate was reported in regard to OM. Conclusion: The review demonstrated the positive therapeutic effect of LLLT on oral mucositis. However, the need for future studies with standardized reporting of parameters and methods is needed to increase the level of evidence of this intervention.

  4. Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

    SciTech Connect

    Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

    2012-07-01

    Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

  5. Odontostomatologic management of patients receiving oral anticoagulant therapy: a retrospective multicentric study

    PubMed Central

    2011-01-01

    Introduction Today, we frequently find patients taking oral anticoagulant therapy (OAT), a prophylaxis against the occurrence of thromboembolic events. An oral surgeon needs to know how to better manage such patients, in order to avoid hemorrhagic and thromboembolic complications. Materials and methods A group of 193 patients (119 men aged between 46 and 82 and 74 women aged between 54 and 76) undergoing OAT for more than 5 years were managed with a standardized management protocol and a 2-months follow-up. The aim of the present study was to apply a protocol, which could provide a safe intra- and postoperative management of patients on OAT. Results Among the 193 patients, only 2 had postoperative complications. Conclusions We think that the protocol used in the present study can be used for complete safety in the treatment of this type of patients. PMID:21771331

  6. Oral anticoagulation to reduce risk of stroke in patients with atrial fibrillation: current and future therapies.

    PubMed

    Amin, Alpesh

    2013-01-01

    Atrial fibrillation (AF) is associated with an increased incidence and severity of strokes. The burden of AF-related stroke is expected to increase in parallel with the aging of the population. Oral anticoagulation with warfarin has been the pharmacologic standard for stroke risk reduction in patients with AF. When used with close attention to dosing and monitoring, warfarin is effective prophylactic therapy against thromboembolic stroke. However, it is underused by physicians, in part because of the known risks of adverse events with warfarin. Consequently, many patients with AF live with an avoidably elevated risk of stroke. New options, ie, oral anticoagulants with novel mechanisms of action, have recently been approved to reduce the risk of stroke in AF, and others are in development. These newer agents may address some of the complexities of warfarin use while providing similar or better efficacy and safety.

  7. A Comparative Study of Oral Cyclosporine and Betamethasone Minipulse Therapy in the Treatment of Alopecia Areata

    PubMed Central

    Jang, Yong Hyun; Kim, Sang Lim; Lee, Kyou Chae; Kim, Min Ji; Park, Kyung Hea; Lee, Weon Ju; Lee, Seok-Jong

    2016-01-01

    Background Various systemic agents have been assessed for the treatment of alopecia areata (AA); however, there is a paucity of comparative studies. Objective To assess and compare cyclosporine and betamethasone minipulse therapy as treatments for AA with regard to effectiveness and safety. Methods Data were collected from 88 patients who received at least 3 months of oral cyclosporine (n=51) or betamethasone minipulse therapy (n=37) for AA. Patients with ≥50% of terminal hair regrowth in the alopecic area were considered responders. Results The responder of the cyclosporine group was 54.9% and that of the betamethasone minipulse group was 37.8%. In the cyclosporine group, patients with mild AA were found to respond better to the treatment. Based on the patient self-assessments, 70.6% of patients in the cyclosporine group and 43.2% of patients in the betamethasone minipulse group rated their hair regrowth as excellent or good. Side effects were less frequent in the cyclosporine group. Conclusion Oral cyclosporine appeared to be superior to betamethasone minipulse therapy in terms of treatment effectiveness and safety. PMID:27746635

  8. Surviving with Lung Cancer: Medication-Taking and Oral Targeted Therapy

    PubMed Central

    WICKERSHAM, Karen E.; HAPP, Mary Beth; BENDER, Catherine M.; ENGBERG, Sandra J.; TARHINI, Ahmad; ERLEN, Judith A.

    2014-01-01

    Oral epidermal growth factor receptor inhibitors (EGFRIs) improve survival for non-small cell lung cancer (NSCLC) patients; however, medication-taking implications are unknown. We used grounded theory to explore the process of medication-taking for NSCLC patients receiving oral EGFRIs. Thirty-two interviews were conducted for 13 participants purposively selected for gender, race/ethnicity, age, time in therapy, dose reductions, and therapy discontinuation and theoretically sampled for age and health insurance carrier. The study produced a grounded theory, Surviving with Lung Cancer, in which participants framed EGFRI therapy within recognition of NSCLC as a life-limiting illness without cure. Medication-taking was a “window” into participants’ process of surviving with metastatic cancer that included deciding and preparing to take EGFRIs and treating lung cancer as a chronic condition. Our results contribute to understanding how NSCLC patients view themselves in the context of a life-limiting illness and support development of a theoretically-based intervention to improve medication-taking with EGFRIs. PMID:24702721

  9. Carnitine Deficiency as the Possible Etiology of Idiopathic Mitral Valve Prolapse

    PubMed Central

    Trivellato, Mario; De Palo, Elio; Gatti, Rosalba; Parenti, Anna; Piazza, Mario

    1984-01-01

    Idiopathic mitral valve prolapse (IMVP) is a very common cardiac abnormality that may be linked to carnitine deficit (inadequate nutritional intake or absorption). One patient with IMVP and related symptoms that were resistant to drug therapy was fully studied. Free plasma carnitine and 24-hour free urine carnitine were measured twice, 10 days apart, after an overnight fast. Findings: Free plasma carnitine 23 and 28 μM/L (our laboratory N=38±2 μM/L); free urine C 25 and 44 μM/24 hr (N=255±66 μM/24 hr); FFA 0.88 mEq/L, Duncombe method (N=0.09-0.60); LDL 42% (N = 44-65); cholesterol 161 mg/dl (N = 180-280); triglycerides 84 mg/dl (N = 50-172); SGOT 79 MU/ml (N = up to 40); SGPT 147 MU/ml (N = up to 40); OCT 11.2 MU/ml (N = up to 10.0); aldolase 11.5 MU/ml (N = up to 3.1, Bruns method). Deltoid biopsy: light microscopy showed the presence of optically empty vacuoles; electron microscopy showed lipid droplets near the subsarcolemma area and intermyofibrillar spaces. The mitochondria contained electron dense granules. The electromyogram was also abnormal. In a random sample of four patients with IMVP and related classic symptoms, we have found low levels of plasma and/or urinary carnitine in each case. This study may be the first step towards L-carnitine therapy for what has previously appeared to be idiopathic cardiomyopathy. Images PMID:15226877

  10. Effects of L-carnitine supplementation to suckling piglets on carcass and meat quality at market age.

    PubMed

    Lösel, D; Rehfeldt, C

    2013-07-01

    In a previous study, carnitine supplementation to piglets during the suckling period resulted in an increased total muscle fibre number at weaning in piglets of low birth weight. The objective of the present study was to investigate whether this effect is maintained until market age and whether this would attenuate the negative consequences of low birth weight on carcass and meat quality. Using a split-plot design with litter as block, sex as whole plot and treatment as subplot, the effects of early-postnatal l-carnitine supplementation on female and castrated male piglets of low birth weight were investigated on a total of 56 German Landrace piglets from 14 litters. From days 7 to 27 of age piglets were orally supplemented once daily with 400 mg of l-carnitine dissolved in 1 ml of water or received an equal volume of water without carnitine. From weaning (day 28) until slaughter (day 166 of age) all pigs were fed standard diets. At weaning, carnitine-supplemented piglets had a twofold increased concentration of free carnitine (P < 0.001) and a lower concentration of non-esterified fatty acids (P < 0.05) in blood plasma indicating that carnitine became bioavailable and increased fatty acid utilization during the period of supplementation. Growth performance was not influenced by treatment in any growth period. Dual-energy X-ray absorptiometry revealed no differences in body composition between groups in weeks 12, 16 and 20 of age. LW at slaughter, carcass weight, measures of meat yield and fat accretion, as well as body composition by chemical analyses and dissection of primal cuts did not differ between treatments. No differences between control and carnitine-treated pigs in total fibre number (P = 0.85) and fibre cross-sectional area (P = 0.68) in m. semitendinosus (ST) measured at slaughter could be observed. The carnitine group tended to exhibit a smaller proportion of slow-twitch oxidative fibres (P = 0.08), a greater proportion of fast-twitch glycolytic

  11. Comparison of Low-Level Laser Therapy versus Ozone Therapy in the Treatment of Oral Lichen Planus

    PubMed Central

    Erisen, Merve

    2015-01-01

    Background The treatment options for oral lichen planus (OLP) are numerous and include topical and systemic agents. Intralesional and systemic corticosteroids are used; however, the therapeutic results are often disappointing. Objective To compare the influence of ozone, laser, and topical corticosteroid therapies in the treatment of OLP. Methods One hundred twenty adult patients with ≤3 cm atrophic-erosive biopsy-proven OLPs in the tongue or buccal mucosa were recruited into the study. They were randomly assigned, by preoperative envelope drawing, to be treated with low-level laser therapy (LLLT group), ozone therapy (ozonated group), and topical corticosteroid therapy (positive control group). A placebo treatment containing base ointment without the active corticosteroid component was administered to patients in the negative control group. Response rate scores were determined on the basis of changes in the appearance score and pain score of the lesions between baseline and after each treatment. Results The study subjects consisted of 56 male and 64 female OLP patients with a combined mean age of 42.6±8.3 years (range, 28~55 years). No statistically significant difference was detected in clinical severity among the groups. The sign scores decreased in almost all scoring groups; however, statistically significant improvement was found in the ozonated and corticosteroid-treated groups. Symptom improvement was achieved after treatment with LLLT, ozone, and corticosteroid (p<0.05). The efficacy indices were significantly higher in the ozonated and corticosteroid-treated groups. Conclusion Ozone and corticosteroid therapies were more effective than 808-nm LLLT in the treatment of OLP. PMID:26512161

  12. L-Carnitine improves gastrointestinal disorders and altered the intestinal microbiota in hemodialysis patients

    PubMed Central

    IRIE, Junichiro; KANNO, Yoshihiko; KIKUCHI, Rieko; YOSHIDA, Tadashi; MURAI, Seizo; WATANABE, Miwako; ITOH, Hiroshi; HAYASHI, Matsuhiko

    2016-01-01

    Patients receiving hemodialysis also manifest gastrointestinal symptoms, such as constipation, caused by restriction of water intake and the loss of body water balance. Because dietary carnitine deficiency is considered to cause smooth muscle dysmotility of the gastrointestinal tract similarly to that in skeletal muscles, carnitine deficiency in hemodialysis patients may be one cause of gastrointestinal discomfort and dysfunctions. We performed a multicenter nonrandomized single-arm prospective clinical trial. Fifteen Japanese patients receiving hemodialysis were administered L-carnitine tablets (900 mg) for 3 months, and clinical and biochemical analyses were performed before and after treatment. The serum total carnitine level was increased significantly by supplementation with L-carnitine for 3 months (from 40.9 ± 2.6 μmol/l to 172.3 ± 19.0 μmol/l, p<0.05). The myasthenia score was decreased significantly by the supplementation (from 1.3 ± 0.3 to 0.8 ± 0.2, p<0.05). The frequency of passing stool tended to increase with the treatment for 3 months (from 4.2 ± 0.5 times/week to 4.8 ± 0.5 times/week). A phyla-level analysis of the microbiota showed that the composition of the individual microbiota was not different between before and after supplementation. A genus-level analysis, however, revealed that the relative abundance of genus Clostridium subcluster 4 was significantly decreased by the supplementation (from 7.7 ± 1.9% to 4.7 ± 1.3%, p<0.05). Oral supplementation of L-carnitine to the patients receiving hemodialysis improved not only their muscle discomfort but also their gastrointestinal disorders and microbiota, although its effect on the prognosis of hemodialysis patients should be further investigated. PMID:28243546

  13. L-Carnitine improves gastrointestinal disorders and altered the intestinal microbiota in hemodialysis patients.

    PubMed

    Irie, Junichiro; Kanno, Yoshihiko; Kikuchi, Rieko; Yoshida, Tadashi; Murai, Seizo; Watanabe, Miwako; Itoh, Hiroshi; Hayashi, Matsuhiko

    2017-01-01

    Patients receiving hemodialysis also manifest gastrointestinal symptoms, such as constipation, caused by restriction of water intake and the loss of body water balance. Because dietary carnitine deficiency is considered to cause smooth muscle dysmotility of the gastrointestinal tract similarly to that in skeletal muscles, carnitine deficiency in hemodialysis patients may be one cause of gastrointestinal discomfort and dysfunctions. We performed a multicenter nonrandomized single-arm prospective clinical trial. Fifteen Japanese patients receiving hemodialysis were administered L-carnitine tablets (900 mg) for 3 months, and clinical and biochemical analyses were performed before and after treatment. The serum total carnitine level was increased significantly by supplementation with L-carnitine for 3 months (from 40.9 ± 2.6 μmol/l to 172.3 ± 19.0 μmol/l, p<0.05). The myasthenia score was decreased significantly by the supplementation (from 1.3 ± 0.3 to 0.8 ± 0.2, p<0.05). The frequency of passing stool tended to increase with the treatment for 3 months (from 4.2 ± 0.5 times/week to 4.8 ± 0.5 times/week). A phyla-level analysis of the microbiota showed that the composition of the individual microbiota was not different between before and after supplementation. A genus-level analysis, however, revealed that the relative abundance of genus Clostridium subcluster 4 was significantly decreased by the supplementation (from 7.7 ± 1.9% to 4.7 ± 1.3%, p<0.05). Oral supplementation of L-carnitine to the patients receiving hemodialysis improved not only their muscle discomfort but also their gastrointestinal disorders and microbiota, although its effect on the prognosis of hemodialysis patients should be further investigated.

  14. Safety and efficacy of bone wax in patients on oral anticoagulant therapy.

    PubMed

    Krasny, Marta; Krasny, Kornel; Fiedor, Piotr

    2014-01-01

    Cardiovascular conditions, apart from neoplastic diseases, remain the major cause of death in developed countries; therefore, the number of patients receiving oral anticoagulants is constantly increasing. Anticoagulant therapy considerably reduced mortality in patients with history of myocardial infarction among others. Although many interventions may be performed without withdrawal of the anticoagulant and tooth extraction was qualified as a procedure of low hemorrhage risk, a majority of dentists refer the patient to a cardiologist several days before the elective tooth extraction to withdraw anticoagulants. The aim of the study was to evaluate the efficacy and safety of bone wax used to stop bleeding after dental procedures in a group of patients on chronic anticoagulant therapy and find an answer to a question, whether it is justified to temporarily withdraw anticoagulants for this type of procedures. The study involved 176 patients on chronic anticoagulant therapy undergoing tooth extraction (154 subjects) or surgical extraction of a retained tooth (48 subjects). After the procedure, in each case the alveolus was filled with bone wax to stop bleeding. In all patients involved in the study bleeding from the alveolus was successfully stopped during the procedure. None of the subjects reported increased bleeding from the operational site after coming back home. Bone wax is a good, efficient, and safe material to block bleeding from the alveolus following tooth extractions, also in patients on chronic anticoagulant therapy. The study demonstrated that withdrawal or adjustment of anticoagulant therapy is not necessary before an elective tooth extraction.

  15. Iron therapy for the treatment of iron deficiency in chronic heart failure: intravenous or oral?

    PubMed Central

    McDonagh, Theresa; Macdougall, Iain C

    2015-01-01

    This article considers the use and modality of iron therapy to treat iron deficiency in patients with heart failure, an aspect of care which has received relatively little attention compared with the wider topic of anaemia management. Iron deficiency affects up to 50% of heart failure patients, and is associated with poor quality of life, impaired exercise tolerance, and mortality independent of haematopoietic effects in this patient population. The European Society of Cardiology Guidelines for heart failure 2012 recommend a diagnostic work-up for iron deficiency in patients with suspected heart failure. Iron absorption from oral iron preparations is generally poor, with slow and often inefficient iron repletion; moreover, up to 60% of patients experience gastrointestinal side effects. These problems may be exacerbated in heart failure due to decreased gastrointestinal absorption and poor compliance due to pill burden. Evidence for clinical benefits using oral iron is lacking. I.v. iron sucrose has consistently been shown to improve exercise capacity, cardiac function, symptom severity, and quality of life. Similar findings were observed recently for i.v. ferric carboxymaltose in patients with systolic heart failure and impaired LVEF in the double-blind, placebo-controlled FAIR-HF and CONFIRM-HF trials. I.v. iron therapy may be better tolerated than oral iron, although confirmation in longer clinical trials is awaited. Routine diagnosis and management of iron deficiency in patients with symptomatic heart failure regardless of anaemia status is advisable, and, based on current evidence, prompt intervention using i.v. iron therapy should now be considered. PMID:25639592

  16. Prophylaxis and antibiotic therapy in management protocols of patients treated with oral and intravenous bisphosphonates

    PubMed Central

    Bermúdez-Bejarano, Elena-Beatriz; Serrera-Figallo, María-Ángeles; Gutiérrez-Corrales, Aida; Romero-Ruiz, Manuel-María; Castillo-de-Oyagüe, Raquel; Gutiérrez-Pérez, José-Luis

    2017-01-01

    Introduction Osteonecrosis of the jaw (MRONJ) linked to bisphosphonate treatment has specific characteristics that render its therapeutic management challenging for clinicians. Poor response to standard treatment makes it essential to take special precautions when treating this type of disease; therefore, antibiotic prophylaxis and/or antibiotic therapy have been proposed as effective and helpful tools in these situations. Objectives This article seeks to assess published evidence in order to evaluate the different protocols used for antibiotic prophylaxis and/or antibiotic therapy in the general context of patients treated with bisphosphonates. Material and Methods A literature review of the last 10 years was carried out in PubMed using the following keywords: “antibiotic prophylaxis and osteonecrosis,” “bisphosphonates AND osteonecrosis AND dental management,” “bisphosphonate AND osteonecrosis AND antibiotic prophylaxis AND oral surgery.” A total of 188 articles were obtained, of which 18 were ultimately selected. Results and Discussion In patients treated with oral and intravenous bisphosphonates without chemotherapy-associated osteonecrosis of the jaw, antibiotic prophylaxis prior to oral surgery is an important tool to avoid osteonecrosis and promote healing of the affected area. If the patient previously exhibited chemotherapy-associated osteonecrosis after tooth extraction, antibiotic prophylaxis is indicated to prevent recurrent osteonecrosis and promote healing of the extraction site. If chemotherapy-associated osteonecrosis is already present, antibiotic therapy is a vital part of conservative management to reduce the symptomatology of MRONJ and keep it from worsening. Finally, a lack of clinical data and randomized controlled trials makes it difficult to choose the most appropriate protocol for the various clinical situations studied. Key words:Bisphosphonates, antibiotic prophylaxis, maxillary osteonecrosis, antibiotic treatment. PMID

  17. Iron therapy for the treatment of iron deficiency in chronic heart failure: intravenous or oral?

    PubMed

    McDonagh, Theresa; Macdougall, Iain C

    2015-03-01

    This article considers the use and modality of iron therapy to treat iron deficiency in patients with heart failure, an aspect of care which has received relatively little attention compared with the wider topic of anaemia management. Iron deficiency affects up to 50% of heart failure patients, and is associated with poor quality of life, impaired exercise tolerance, and mortality independent of haematopoietic effects in this patient population. The European Society of Cardiology Guidelines for heart failure 2012 recommend a diagnostic work-up for iron deficiency in patients with suspected heart failure. Iron absorption from oral iron preparations is generally poor, with slow and often inefficient iron repletion; moreover, up to 60% of patients experience gastrointestinal side effects. These problems may be exacerbated in heart failure due to decreased gastrointestinal absorption and poor compliance due to pill burden. Evidence for clinical benefits using oral iron is lacking. I.v. iron sucrose has consistently been shown to improve exercise capacity, cardiac function, symptom severity, and quality of life. Similar findings were observed recently for i.v. ferric carboxymaltose in patients with systolic heart failure and impaired LVEF in the double-blind, placebo-controlled FAIR-HF and CONFIRM-HF trials. I.v. iron therapy may be better tolerated than oral iron, although confirmation in longer clinical trials is awaited. Routine diagnosis and management of iron deficiency in patients with symptomatic heart failure regardless of anaemia status is advisable, and, based on current evidence, prompt intervention using i.v. iron therapy should now be considered.

  18. Utility of metformin as an adjunct to hydroxycitrate/carnitine for reducing body fat in diabetics.

    PubMed

    McCarty, M F

    1998-11-01

    Excessive exposure of tissues to fatty acids is likely to be the chief cause of the various dysfunctions that lead to sustained hyperglycemia in type II diabetes. These dysfunctions are likely to be substantially reversible if body fat and dietary fat can be greatly reduced. Disinhibition of hepatic fatty acid oxidation with hydroxycitrate (HCA) and carnitine has considerable potential as a new weight-loss strategy, but in diabetics runs the risk of further enhancing excessive hepatic gluconeogenesis. Since the clinical utility of metformin in diabetes is probably traceable to inhibition of gluconeogenesis, its use as an adjunct to HCA/carnitine treatment of obesity in diabetics deserves evaluation, particularly as metformin therapy itself tends to reduce body weight. A consideration of relevant evidence suggests that metformin therapy will not impede the activation of fatty acid oxidation by HCA/carnitine, and is likely to potentiate the appetite-suppressant and thermogenic benefits of this strategy. Indeed, since metformin has been reported to lower body weight and improve cardiovascular risk factors in obese non-diabetics, a broader application of a metformin/HCA/carnitine therapy for obesity can be contemplated.

  19. Topical tacrolimus and periodontal therapy in the management of a case of oral chronic GVHD characterized by specific gingival localization.

    PubMed

    Conrotto, Davide; Broccoletti, Roberto; Carcieri, Paola; Giaccone, Luisa; Arduino, Paolo G

    2014-01-01

    Background. Chronic graft versus host disease (cGVHD) is a complication following bone marrow transplantation. The oral lesions are difficult to control with a systemic pharmacological therapy. Case Description. A 63-year-old female patient, who underwent an allogeniec transplantation for acute myeloid leukemia, developed a chronic oral and cutaneous GVHD. The patient was treated with topical tacrolimus 0.1%, twice daily for two months, and underwent a protocol of oral hygiene characterized by 3 appointments of scaling, root planning, and daily oral hygiene instructions. The patient showed marked resolution of gingival lesions and a significant improvement of related pain and gingival inflammatory indexes. Clinical Implications. This case report suggests that treatment with topical tacrolimus and professional oral hygiene may be helpful in the management of chronic oral GVHD with severe gingival involvement.

  20. Oral and subcutaneous therapy of canine atopic dermatitis with recombinant feline interferon omega.

    PubMed

    Litzlbauer, Petra; Weber, Karin; Mueller, Ralf S

    2014-03-01

    Canine atopic dermatitis (CAD) is a common allergic skin disease that has been treated with subcutaneously administered interferons (IFN). Recombinant feline IFN-ω (rFeIFN-ω) was reported to be efficacious for CAD. Whether dogs develop neutralizing antibodies against rFeIFN-ω during long-term treatment and whether orally administered IFNs are efficacious in CAD is unknown. The aim of this study was to evaluate the potential development of antibodies against rFeIFN-ω in atopic dogs and to compare subcutaneous and oral IFN therapy. Twenty-six atopic dogs were randomly assigned to two groups. The first group (n=15) received eight subcutaneous injections of rFeIFN-ω (Virbagen® omega, Virbac, Carros, France) over four months, the second group (n=11) received rFeIFN-ω daily orally. Concurrent medication was permitted, except systemically acting glucocorticoids and cyclosporin, which had to be withdrawn at least two weeks prior to the study. Serum samples for antibody detection were collected before and after the study. On days 0, 60 and 120 skin lesions and pruritus were evaluated using a validated lesion score (Canine Atopic Dermatitis Extent and Severity Index=CADESI) and a validated pruritus score. Concurrent medications were recorded. For every visit a total score, consisting of CADESI, pruritus score and medication score was created. For antibody detection an indirect ELISA, using Virbagen® omega as antigen, was performed. Comparison of pruritus scores, CADESI and total scores between days 0 and 120 showed improvement in both groups, however, significant improvement could only be detected in the oral group with CADESI and total scores (61%, P=0.04 and 36%, P=0.02 respectively). Serum antibodies against rFeIFN-ω could not be detected in any of the dogs. In this study antibody production could not be demonstrated. It suggests better efficacy with oral IFN administration, which should be further verified in larger, randomized, controlled studies.

  1. Oral surgery for patients on anticoagulant therapy: current thoughts on patient management.

    PubMed

    Doonquah, Ladi; Mitchell, Anika D

    2012-01-01

    Minor oral surgical procedures make up a significant part of the daily practice of dentistry. With the increased sophistication of medical technology and medications there is increased likelihood of performing surgery on patients who are being treated for conditions that require some type of anticoagulant therapy. These patients are at an increased risk for perioperative bleeding or thrombotic complications if anticoagulation is discontinued or the dosage is adjusted. Therefore, a fine balance needs to be obtained and adequate preparation of these patients is the key to establishing this balance. This article reviews suggested approaches to the management of such patients.

  2. Mineral derivatives in alleviating oral mucositis during cancer therapy: a systematic review

    PubMed Central

    2015-01-01

    Objectives. Oral mucositis (mouth ulcers) is a cancer therapy side effect. Costly treatment interventions are often neglected in favor of cost-effective agents. This review assessed the general efficacy of mineral derivatives (a cost-effective agent) in alleviating oral mucositis (OM) during cancer therapy compared to the standard care, or placebo—including a decision tree to aide healthcare workers. Data Sources. Electronic searches of MEDLINE via OVID, EMBASE, CENTRAL, CANCERLIT via PubMed, and CINAHL via EBSCO (year 2000 to 11 September 2014) were undertaken for randomised controlled trials. A meta-search strategy extracted content from aggregate online databases. Review Methods. Randomized controlled trials were assessed (participants, intervention, outcome, results, and risk of bias) for inclusion. The author abstracted binary and continuous data synthesised to Hedges’ g in a random effects model. The primary outcome measures were severity (incidence of peak oral mucositis, duration of oral mucositis, and time to onset); secondary outcome measures were the incidence of pain, and analgesic use. Serum mineral levels, total parenteral nutrition, and adverse events were discussed. The decision tree was mapped using sensitivity, specificity, pre-test and post-test Bayesian probability. Results. 1027 citations were identified and 16 studies were included (n = 1120; mean age 49 years). Cancer therapies consisted of chemotherapy, radiotherapy, chemo-radiotherapy, or hematopoietic stem cell transplantation. Outcome mineral derivatives were zinc (n = 549), calcium phosphate (n = 227), povidone-iodine (n = 228), or selenium (n = 116). Severity was measured across variable OM grading systems: In 13 studies, individuals in treatment groups (n = 958) experienced peak OM less than controls (g = −0.47, 95% CI −0.7 to −0.2, p = 0.0006); time to OM onset was significantly delayed in treatment than controls (g = −0.51, 95% CI−0.8 to −0.2, p = 0.0002; five studies

  3. The effect of magnesium oral therapy on spasticity in a patient with multiple sclerosis.

    PubMed

    Rossier, P; van Erven, S; Wade, D T

    2000-11-01

    The effects of magnesium glycerophosphate oral therapy on spasticity was studied in a 35-year-old woman with severe spastic paraplegia resulting from multiple sclerosis (MS). We found a significant improvement in the spasticity after only 1 week from the onset of the treatment on the modified Ashworth scale, an improvement in the range of motion and in the measures of angles at resting position in lower limbs. No side-effects were reported and there was no weakness in the arms during the treatment.

  4. Lightpipe device for delivery of uniform illumination for photodynamic therapy of the oral cavity

    PubMed Central

    Canavesi, Cristina; Cassarly, William J.; Foster, Thomas H.; Rolland, Jannick P.

    2011-01-01

    A compact and efficient lightpipe device to deliver light to the human oral cavity for photodynamic therapy was designed and fabricated, having dimensions 6.8 mm × 6.8 mm × 46 mm. An average irradiance of 76 mW/cm2 with an average deviation of 5% was measured on a square 25 mm2 treatment field for an input power of 100 mW. The device limits irradiation of healthy tissue and offers potential for improvement over the current treatment procedure, which requires shielding of the whole cavity to avoid damage to healthy tissue. PMID:21629308

  5. Genetics Home Reference: primary carnitine deficiency

    MedlinePlus

    ... bring certain types of fats (fatty acids) into mitochondria , which are the energy-producing centers within cells. ... within cells. Without carnitine, fatty acids cannot enter mitochondria and be used to make energy. Reduced energy ...

  6. [Changes in myocardium, skeletal muscle and liver of rats fed carnitine-deficient diet and treated with carnitine optical isomers].

    PubMed

    Spasov, A A; Iezhitsa, I N; Pisarev, V B; Snigur, G L; Kravchenko, M S

    2006-01-01

    The aim of the present study was a comparative assessment of L-, D-and DL-carnitine effect on morphometric and histological parameters of myocardium, skeletal muscles (m. gastrocnemius) and liver in 60 rats fed carnitine-deficient diet. Carnitine-deficient diet fed 2 months resulted in a substantial reduction of carnitine concentration in blood plasma of rats. In carnitine-deficient animals, lipid vacuoles were found to accumulate within the hepatocytes in all the zones of hepatic lobules, which mainly had the character of micro- and macrovesicular steatosis. This was accompanied by a reduction of skeletal muscle fiber and cardiomyocyte average thickness. L-carnitine administration resulted in the compensation of carnitine deficiency in animals with alimentary carnitine deficient state, while the racemate and D-stereoisomere did not affect its content in blood. Pharmacological correction of carnitine deficiency with L-carnitine prevented the development of liver fatty dystrophy to a greater degree, than the administration of other carnitine stereoisomeres and promoted the restoration of muscular fiber thickness of skeletal muscles. DL-carnitine administration was accompanied by a moderate correction of fatty dystrophy and did not prevent the development of skeletal muscles atrophy. D-carnitine stereoisomere did not prevent liver fatty dystrophy, but it reduced its severity. Correction of carnitine deficiency with D- stereoisomere was not accompanied by essential morphological and morphometric differences in degree of skeletal muscle atrophy.

  7. Oral propranolol therapy for infantile hemangiomas beyond the proliferation phase: a multicenter retrospective study.

    PubMed

    Zvulunov, Alex; McCuaig, Catherine; Frieden, Ilona J; Mancini, Anthony J; Puttgen, Kate B; Dohil, Magdalene; Fischer, Gayle; Powell, Julie; Cohen, Bernard; Ben Amitai, Dan

    2011-01-01

    Pharmacological therapies for infantile hemangiomas were considered effective only during the proliferative phases. Recently reported beneficial effects of propranolol may extend beyond the proliferative phase of infantile hemangiomas. The purpose of the study was to assess the effect of oral propranolol therapy for infantile hemangiomas beyond the proliferative phase of these lesions. Members of the Society for Pediatric Dermatology were invited to participate in a multicenter retrospective study. Only children with infantile hemangiomas with documented cessation of lesions' growth or those older than 12 months of age were eligible for the study. Clinical and demographic information and digital photographs before, at the start, and following the treatment were collected. Scaled panels of photographs were distributed among preselected experienced pediatric dermatologists. Visual analog scale was used to assess photographs for each case. Paired t-test was used for statistical analyses. Data on 49 eligible patients from eight pediatric dermatology centers was collected. Seven cases were excluded because of insufficient photographic documentation. The age of the patients at the start of propranolol therapy ranged 7 to 120 months (mean 28 mos, median 22 mos). The duration of propranolol therapy ranged 1 to 8 months (mean 3.6 mos). The mean visual analog scale score before the treatment was 6.8 ± 2.15, and mean reduction in the visual analog scale score at the assessment was 2.6 ± 1.74 (p < 0.001). The rate of visual analog scale reduction was 0.4 per month before the start of the therapy, while this rate was accelerated to 0.9 per months following the therapy (p < 0.001). No significant side effects were reported. We conclude that propranolol is effective in infantile hemangiomas, including post-proliferative phase, and should be considered as the first-line therapy in that setting.

  8. Systemic primary carnitine deficiency with hypoglycemic encephalopathy

    PubMed Central

    Jun, Jae Sung; Lee, Eun Joo; Park, Hyung Doo

    2016-01-01

    Acute hypoglycemia in children is not an uncommon disease that can be encountered in the Emergency Department. Most cases of childhood hypoglycemia are caused by ketotic hypoglycemia due to missed meals. Often, hypoketotic hypoglycemia can also occur, which suggests hyperinsulinemia or a defect in fatty acid oxidation. Carnitine is essential for long chain fatty acids transfer into mitochondria for oxidation. We present a case of systemic primary carnitine deficiency who presented with seizures due to hypoketotic hypoglycemia. PMID:28164076

  9. L-carnitine supplementation in hemodialysis patients.

    PubMed

    Mitwalli, Ahmed Hassan; Al-Wakeel, Jamal S; Alam, Awatif; Tarif, Nauman; Abu-Aisha, Hassan; Rashed, Mohamed; Al Nahed, Nora

    2005-01-01

    L-Carnitine supplementation has shown beneficial effects in patients on hemodialysis. We studied 36 ESRD adult patients with a mean age of 47.5 +/- 15 years to evaluate the effect of L-Carnitine supplementation on hemoglobin, lipid levels and physical performance in patients on hemodialysis. The study group consisted of 18 randomly selected patients who received L-Carnitine 15 mg/kg and the control group consisted of 18 randomly selected patients who received equal volume of normal saline as a placebo three times a week for six months. Laboratory tests were performed at baseline, then monthly until the end of the study. A significant increase in the hemoglobin (Hb) and hematocrit (HCT) in the presence of unchanged doses of erythropoietin hormonal supplementation was observed (pre 79 +/- 7.5 gm/l, post 103 +/- 10.6 gm/l) P< 0.001 (pre 24+/- 2 %, post 33 +/- 4%) P< 0.001 respectively) in the L-Carnitine treated group. Similarly total serum cholesterol (TCL) and serum triglyceride (TG) levels showed a statistically significant decrease in the study group, TCL (pre 4.6 +/- 1.2, post 3.7 +/- 1.1 mmol/L), P < 0.03 and TG (pre 3.1 +/- 1.7, post 1.8 +/- 0.6 mmol/L) P < 0.004. The physical performance as assessed by mild and moderate exercise showed a trend towards improvement. There was a significant increase in free carnitine and total carnitine levels in the L-Carnitine treated group. In conclusion, these results demostrate positive effect of L-Carnitine supplementation in the hemodialysis patients marked by an increase in Hb, HCT, a decrease in TCL and TG and improved physical performance in comparison to the control group.

  10. Management of antiplatelet and anticoagulant therapy for endoscopic procedures: Introduction to novel oral anticoagulants.

    PubMed

    González Bárcenas, Martha L; Pérez Aisa, Ángeles

    2016-02-01

    The development of novel antithrombotic therapy in the past few years and its prescription in patients with cardiovascular and circulatory disease has widened the spectrum of drugs that need to be considered when performing an endoscopic procedure. The balance between the thrombotic risk patients carry due to their medical history and the bleeding risk involved in endoscopic procedures should be thoroughly analyzed by Gastroenterologists. New oral anticoagulants (NOACs) impose an additional task. These agents, that specifically target factor IIa or Xa, do not dispose of an anticoagulation monitoring method nor have an antidote to revert their effect, just as with antiplatelet agents. Understanding the fundamental aspects of these drugs provides the necessary knowledge to determine the ideal period the antithrombotic therapy should be interrupted in order to perform the endoscopic procedure, offering maximum safety for patients and optimal results.

  11. L-Carnitine, but not coenzyme Q10, enhances the anti-osteoporotic effect of atorvastatin in ovariectomized rats

    PubMed Central

    Murad, Hussam A. S.

    2016-01-01

    Objective: Statins’ therapy in osteoporosis can aggravate muscle damage. This study was designed to assess which agent, L-carnitine or coenzyme Q10, could enhance the anti-osteoporotic effect of atorvastatin while antagonizing myopathy in ovariectomized rats. Methods: Forty-eight female Sprague Dawley rats were used; forty rats were ovariectomized while eight were sham-operated. Eight weeks post-ovariectomy, rats were divided into ovariectomized-untreated group and four ovariectomized-treated groups (n=8) which received by gavage (mg/(kg∙d), for 8 weeks) 17β-estradiol (0.1), atorvastatin (50), atorvastatin (50)+L-carnitine (100), or atorvastatin (50)+coenzyme Q10 (20). At the end of therapy, bone mineral density (BMD), bone mineral content (BMC), and serum levels of bone metabolic markers (BMMs) and creatine kinase (CK) were measured. Femurs were used for studying the breaking strength and histopathological changes. Results: Treatment with atorvastatin+L-carnitine restored BMD, BMC, and bone strength to near normal levels. Estrogen therapy restored BMD and BMC to near normal levels, but failed to increase bone strength. Although atorvastatin and atorvastatin+coenzyme Q10 improved BMD, BMC, and bone strength, they failed to restore levels to normal. All treatments decreased BMMs and improved histopathological changes maximally with atorvastatin+L-carnitine which restored levels to near normal. Atorvastatin aggravated the ovariectomy-induced increase in CK level while estrogen, atorvastatin+L-carnitine, and atorvastatin+coenzyme Q10 decreased its level mainly with atorvastatin+L-carnitine which restored the level to near normal. Conclusions: Co-administration of L-carnitine, but not coenzyme Q10, enhances the anti-osteoporotic effect of atorvastatin while antagonizing myopathy in ovariectomized rats. This could be valuable in treatment of osteoporotic patients. However, further confirmatory studies are needed. PMID:26739525

  12. Mechanisms for altered carnitine content in hypertrophied rat hearts

    SciTech Connect

    Reibel, D.K.; O'Rourke, B.; Foster, K.A.

    1987-03-01

    Carnitine levels are reduced in hypertrophied hearts of rats subjected to aortic constriction (banding) and evaluated in hypertrophied hearts of spontaneously hypertensive rats (SHR). In an attempt to determine the mechanisms for these alterations, L-(/sup 14/C)carnitine transport was examined in isolated perfused hearts. Total carnitine uptake was significantly reduced by approx.20% in hypertrophied hearts of banded rats at all perfusate carnitine concentrations employed. The reduction in total uptake was due to a 40% reduction in carrier-mediated carnitine uptake with no difference in uptake by diffusion. In contrast, carnitine uptake was not altered in isolated hypertrophied hearts of SHR. However, serum carnitine levels were elevated in SHR, which could result in increased myocardial carnitine uptake in vivo. The data suggest that altered carnitine content in hypertrophied hearts of aortic-banded rats is due to an alteration in the carrier-mediated carnitine transport system in the myocardium. However, altered carnitine content in hypertrophied hearts of SHR is not due to a change in the carnitine transport system per se but may rather be due to a change in serum carnitine levels.

  13. Altered carnitine transport in pressure-overload hypertrophied rat hearts

    SciTech Connect

    O'Rourke, B.; Foster, K.; Reibel, D.K.

    1986-03-01

    The authors have previously observed reduced carnitine levels in hypertrophied hearts of rats subjected to aortic constriction. In an attempt to determine the mechanism for reduced myocardial carnitine content, carnitine transport was examined in isolated perfused hearts. Hearts were excised from sham-operated and aortic-constricted rats 3 weeks following surgery and perfused at 60 mm Hg aortic pressure with buffer containing various concentrations of L-/sup 14/C-carnitine. Carnitine uptake by control and hypertrophied hearts was linear throughout 30 minutes of perfusion with 40 ..mu..M carnitine. Total carnitine uptake was significantly reduced by 25% in hypertrophied hearts at each time point examined. The reduction in uptake by hypertrophied hearts was also evident when hearts were perfused with 100 or 200 ..mu..M carnitine. When 0.05 mM mersalyl acid was included in the buffer to inhibit the carrier-mediated component of transport, no difference in carnitine uptake was observed indicating that the transport of carnitine by diffusion was unaltered in the hypertrophied myocardium. Carrier-mediated carnitine uptake (total uptake - uptake by diffusion) was significantly reduced by approximately 40% in hypertrophied hearts at all concentrations examined. Thus, the reduction in carnitine content in the pressure-overload hypertrophied rat heart appears to be due to a reduction in carrier-mediated carnitine uptake by the heart.

  14. Carnitine deficiency in premature infants receiving total parenteral nutrition: effect of L-carnitine supplementation.

    PubMed

    Schmidt-Sommerfeld, E; Penn, D; Wolf, H

    1983-06-01

    To investigate whether L-carnitine supplementation may correct nutritional carnitine deficiency and associated metabolic disturbances in premature infants receiving total parenteral nutrition, an intravenous fat tolerance test (1 gm/kg Intralipid over four hours) was performed in 29 premature infants 6 to 10 days of age (15 receiving carnitine supplement 10 mg/kg . day L-carnitine IV, and 14 receiving no supplement). Total carnitine plasma values were normal or slightly elevated in supplemented but decreased in nonsupplemented infants. In both groups, fat infusion resulted in an increase in plasma concentrations of triglycerides, free fatty acids, D-beta-hydroxybutyrate, and short-chain and long-chain acylcarnitine, but total carnitine values did not change. After fat infusion, the free fatty acids/D-beta-hydroxybutyrate ratios were lower and the increase of acylcarnitine greater in supplemented infants of 29 to 33 weeks' gestation than in nonsupplemented infants of the same gestational age. This study provides evidence that premature infants of less than 34 weeks' gestation requiring total parenteral nutrition develop nutritional carnitine deficiency with impaired fatty acid oxidation and ketogenesis. Carnitine supplementation improves this metabolic disturbance.

  15. Oral mucositis in pediatric patients undergoing hematopoietic stem cell transplantation: clinical outcomes in a context of specialized oral care using low-level laser therapy.

    PubMed

    Eduardo, Fernanda de Paula; Bezinelli, Leticia Mello; de Carvalho, Danielle Lima Corrêa; Lopes, Roberta Marques da Graça; Fernandes, Juliana Folloni; Brumatti, Melina; Vince, Carolina Sgaroni Camargo; de Azambuja, Alessandra Milani Prandini; Vogel, Cristina; Hamerschlak, Nelson; Correa, Luciana

    2015-05-01

    OM is a painful inflammatory condition of the oral mucosa, derived from the toxic effects of chemotherapy and radiotherapy. High OM severity is frequently present in HSCT pediatric patients, who exhibit multiple painful ulcers that limit their mastication and swallowing, leading to poor nutritional status. Few studies have demonstrated OM clinical outcomes in young patients undergoing HSCT. Feasibility of oral care and LLLT on OM prophylaxis and treatment is also poorly discussed. The aim of this study was to describe a specialized oral care protocol that included LLLT for pediatric patients undergoing transplantation and to demonstrate the clinical outcomes after OM prevention and treatment. Data from OM-related morbidity were collected from 51 HSCT pediatric patients treated daily with LLLT, followed by standard oral care protocols. All the patients, even infants and young children, accepted the daily oral care and LLLT well. The majority (80.0%) only exhibited erythema in the oral mucosa, and the maximum OM degree was WHO II. Patients who had undergone autologous and HLA-haploidentical transplants showed OM with the lowest severity. The frequency of total body irradiation and methotrexate prescriptions was higher in adolescents when compared with infants (p = 0.044), and adolescents also exhibited OM more severely than infants and young children. We found that good clinical outcomes were obtained using this therapy, mainly in regard to the control of OM severity and pain reduction in the oral cavity. Specialized oral care, including LLLT, is feasible and affordable for HSCT pediatric patients, although some adaptation in the patient's oral hygiene routine must be adopted with help from parents/companions and clinical staff.

  16. Antimicrobial photodynamic therapy with two photosensitizers on two oral streptococci: an in vitro study

    NASA Astrophysics Data System (ADS)

    Vahabi, S.; Fekrazad, R.; Ayremlou, S.; Taheri, S.; Lizarelli, R. F. Z.; Kalhori, K. A. M.

    2011-12-01

    Periodontal diseases are caused by infection of tissues supporting the teeth due to complex aggregate of bacteria known as biofilm and firstly colonized by streptococci. The aim of this in vitro study was to evaluate the effect of Radachlorin® and Toluidine Blue O (TBO)-mediated photodynamic therapy (PDT) on the viability of two oral streptococci. Bacterial suspensions of Streptococcus mutans and Streptococcus sanguis were subjected to either TBO or Radachlorin®, Then exposed to two different diode laser light at energy densities of 3, 6 J/cm2 at 633 nm and 6, 12 J/cm2 at 662 nm, respectively. The control groups were subjected to laser light alone, photosensitizer alone or received neither photosensitizer nor light exposure. The suspensions were then spread over specific agar mediums and viable microorganisms were counted after overnight incubation aerobically at 37°C, 5% CO2 and then reported as colony forming unit. The results indicated that photosensitization by the energy density of 6 J/cm2 with Radachlorin® and both 3 and 6 J/cm2 with TBO caused significant reduction in bacterial colony formation ( p < 0.05). Radachlorin® and TBO-mediated photodynamic therapy seem to show excellent potential in significantly killing of two oral streptococci in vitro.

  17. Oral tegafur-uracil as metronomic therapy following intravenous FOLFOX for stage III colon cancer

    PubMed Central

    Huang, Wen-Yen; Ho, Ching-Liang; Lee, Chia-Cheng; Hsiao, Cheng-Wen; Wu, Chang-Chieh; Jao, Shu-Wen; Yang, Jen-Fu; Lo, Cheng-Hsiang; Chen, Jia-Hong

    2017-01-01

    The purpose of this study was to estimate the impact of metronomic therapy with oral tegafur-uracil (UFUR) following an intravenous FOLFOX regimen as surgical adjuvant chemotherapy on the overall survival (OS) and disease-free survival (DFS) of stage III colon cancer patients. From the retrospective database of patients who underwent a surgical resection for colorectal cancer at the Tri-Service General Hospital from October 2008 through December 2014, stage III colon carcinomas treated with radical R0 resection were reviewed. One hundred thirty two patients were treated with a FOLFOX regimen (comparison group), and 113 patients were treated with the same regimen followed by additional oral UFUR (UFUR group). The clinical characteristics and mean age of the comparison and UFUR groups were similar. Furthermore, for all study patients, DFS was not significantly different between the two groups. However, 5-year OS rates were 86.8% and 68.5% in the UFUR and comparison groups, respectively (p = 0.0107). Adding UFUR to a FOLFOX regimen was found to significantly improve the OS in patients with stage III colon cancer. UFUR as a maintenance therapy following FOLFOX regimen as an alternative therapeutic option for the treatment of stage III colon cancer patients. PMID:28328969

  18. Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection

    PubMed Central

    Tokuhara, Daisuke; ρlvarez, Beatriz; Mejima, Mio; Hiroiwa, Tomoko; Takahashi, Yuko; Kurokawa, Shiho; Kuroda, Masaharu; Oyama, Masaaki; Kozuka-Hata, Hiroko; Nochi, Tomonori; Sagara, Hiroshi; Aladin, Farah; Marcotte, Harold; Frenken, Leon G.J.; Iturriza-Gómara, Miren; Kiyono, Hiroshi; Hammarström, Lennart; Yuki, Yoshikazu

    2013-01-01

    Rotavirus-induced diarrhea is a life-threatening disease in immunocompromised individuals and in children in developing countries. We have developed a system for prophylaxis and therapy against rotavirus disease using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (MucoRice-ARP1). MucoRice-ARP1 was produced at high levels in rice seeds using an overexpression system and RNAi technology to suppress the production of major rice endogenous storage proteins. Orally administered MucoRice-ARP1 markedly decreased the viral load in immunocompetent and immunodeficient mice. The antibody retained in vitro neutralizing activity after long-term storage (>1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. High-yield, water-soluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections. PMID:23925294

  19. Exogenous Hormone Use: Oral Contraceptives, Postmenopausal Hormone Therapy, and Health Outcomes in the Nurses’ Health Study

    PubMed Central

    Grodstein, Francine; Stampfer, Meir J.; Willett, Walter C.; Hu, Frank B.; Manson, JoAnn E.

    2016-01-01

    Objectives. To review the contribution of the Nurses’ Health Study (NHS) to our understanding of the complex relationship between exogenous hormones and health outcomes in women. Methods. We performed a narrative review of the publications of the NHS and NHS II from 1976 to 2016. Results. Oral contraceptive and postmenopausal hormone use were studied in relation to major health outcomes, including cardiovascular disease and cancer. Current or recent oral contraceptive use is associated with a higher risk of cardiovascular disease (mainly among smokers), melanoma, and breast cancer, and a lower risk of colorectal and ovarian cancer. Although hormone therapy is not indicated primarily for chronic disease prevention, findings from the NHS and a recent analysis of the Women’s Health Initiative indicate that younger women who are closer to menopause onset have a more favorable risk–benefit profile than do older women from use of hormone therapy for relief of vasomotor symptoms. Conclusions. With updated information on hormone use, lifestyle factors, and other variables, the NHS and NHS II continue to contribute to our understanding of the complex relationship between exogenous hormones and health outcomes in women. PMID:27459451

  20. Human papillomavirus infection in the oral cavity of HIV patients is not reduced by initiating antiretroviral therapy

    PubMed Central

    Shiboski, Caroline H.; Lee, Anthony; Chen, Huichao; Webster-Cyriaque, Jennifer; Seaman, Todd; Landovitz, Raphael J.; John, Malcolm; Reilly, Nancy; Naini, Linda; Palefsky, Joel; Jacobson, Mark A.

    2016-01-01

    Objective: The incidence of human papillomavirus (HPV)-related oral malignancies is increasing among HIV-infected populations, and the prevalence of oral warts has reportedly increased among HIV patients receiving antiretroviral therapy (ART). We explored whether ART initiation among treatment-naive HIV-positive adults is followed by a change in oral HPV infection or the occurrence of oral warts. Design: Prospective, observational study. Methods: HIV-1 infected, ART-naive adults initiating ART in a clinical trial were enrolled. End points included detection of HPV DNA in throat-washes, changes in CD4+ T-cell count and HIV RNA, and oral wart diagnosis. Results: Among 388 participants, 18% had at least one HPV genotype present before initiating ART, and 24% had at least one genotype present after 12–24 weeks of ART. Among those with undetectable oral HPV DNA before ART, median change in CD4+ count from study entry to 4 weeks after ART initiation was larger for those with detectable HPV DNA during follow-up than those without (P =  0.003). Both prevalence and incidence of oral warts were low (3% of participants having oral warts at study entry; 2.5% acquiring oral warts during 48 weeks of follow-up). Conclusion: These results suggest: effective immune control of HPV in the oral cavity of HIV-infected patients is not reconstituted by 24 weeks of ART; whereas ART initiation was not followed by an increase in oral warts, we observed an increase in oral HPV DNA detection after 12–24 weeks. The prevalence of HPV-associated oral malignancies may continue to increase in the modern ART era. PMID:26919735

  1. Endovascular Therapy for Management of Oral Hemorrhage in Malignant Head and Neck Tumors

    SciTech Connect

    Kakizawa, Hideaki Toyota, Naoyuki; Naito, Akira; Ito, Katsuhide

    2005-12-15

    Purpose. To evaluate the efficacy and safety of endovascular therapy in oral hemorrhage from malignant head and neck tumors. Methods. Ten patients (mean age 56 years) with oral hemorrhage caused by malignant head and neck tumors underwent a total of 13 emergency embolization procedures using gelatin sponge particles, steel and/or platinum coils, or a combination of these embolic materials. Angiographic abnormalities, technical success rate, clinical success rate, recurrence rate, complications, hemostatic period, hospital days, survival days, and patient outcome were all analyzed. Results. Angiographic abnormalities were identified during 85% of procedures (11/13). The technical success rate was 100% (13/13 procedures). The primary and secondary clinical success rates were 77% (10/13 procedures) and 67% (2/3 procedures), respectively. The overall clinical success rate was 92%, and the recurrence rate was 22% (2/9 procedures) in patients whom we were able to observe during the 1-month period after embolization. No major complications occurred. Several patients in whom gelatin sponge particles had been used complained of transient local pain after the procedure. The median hemostatic period was 71 days (range 0-518 days). Median hospital and survival days were 59 days (range 3-209 days) and 141 days (range 4-518 days), respectively. Three patients survived and 7 patients died during the observation period. Only 1 of these 7 patients died from hemorrhage. Conclusion. In conclusion, our findings suggest that endovascular therapy is an effective, safe, and repeatable treatment for oral hemorrhage caused by malignant head and neck tumors.

  2. Role of serum interleukin-6 in deciding therapy for multidrug resistant oral lichen planus

    PubMed Central

    Marwah, Akanksha; Kaushik, Smita; Garg, Vijay K.; Gupta, Sunita

    2015-01-01

    Background Oral lichen planus (OLP) is a T cell mediated immune response. T cells locally present in the involved tissues release cytokines like interleukin-6 (IL-6), which contributes to pathogenesis of OLP. Also IL-6 has been associated with multidrug resistance protein (MRP) expression by keratinocytes. Correspondingly, upregulation of MRP was found in OLP. We conducted this study to evaluate the effects of various drugs on serum IL-6 in OLP; and correlation of these effects with the nature of clinical response and resistance pattern seen in OLP lesions with various therapeutic modalities. Thus we evaluated the role of serum IL-6 in deciding therapy for multidrug resistant OLP. Material and Methods Serum IL-6 was evaluated in 42 erosive OLP (EOLP) patients and 10 normal mucosa and 10 oral squamous cell carcinoma cases using ELISA technique. OLP patients were randomly divided into 3 groups of 14 patients each and were subjected to Pimecrolimus local application, oral Mycophenolate Mofetil (MMF) and Methotrexate (MTX) alongwith Pimecrolimus local application. IL-6 levels were evaluated before and after treatment. Results Serum IL-6 levels were raised above 3pg/ml in 26.19% erosive OLP (EOLP) cases (mean- 3.72±8.14). EOLP (5%) cases with IL-6 levels above 5pg/ml were resistant in MTX group. However significant decrease in serum IL-6 corresponding with the clinical resolution was seen in MMF group. Conclusions Significantly raised IL-6 levels in EOLP reflect the chronic inflammatory nature of the disease. As serum IL-6 levels significantly decreased in MMF group, correspondingly no resistance to treatment was noted. However with MTX there was no significant decrease in IL-6 and resistance to treatment was noted in some, especially plaque type lesions. Thus IL-6 can be a possible biomarker in deciding the best possible therapy for treatment resistant OLP. Key words:Lichen planus, biological markers, cytokines, enzyme-linked immunosorbent assay, immunosuppressive

  3. Inhibition of carnitine biosynthesis by valproic acid in rats--the biochemical mechanism of inhibition.

    PubMed

    Farkas, V; Bock, I; Cseko, J; Sandor, A

    1996-11-08

    The anticonvulsive drug, valproic acid (VPA), inhibits the biosynthesis of carnitine, and may contribute in this way to carnitine deficiency associated with VPA therapy. The conversion of [3H]-butyrobetaine into [3H]-carnitine was determined 60 min following a single intraperitoneal (i.p.) dose of 1.2 mmol/kg VPA in rats. The fraction of radioactivity found in [3H]-carnitine in the liver decreased from 63.2 +/- 1.50% to 39.2 +/- 1.11% (mean +/- SEM). Total carnitine in the liver also decreased, whereas the precursor butyrobetaine increased from 5.01 +/- 0.71 nmol/g to 8.22 +/- 0.82 nmol/g (mean +/- SEM). VPA also exhibited a dramatic effect on the conversion of an unlabeled loading amount of butyrobetaine. The increment in total carnitine caused by butyrobetaine in liver was reduced from 161 +/- 15.4 nmol/g to 53.2 +/- 5.11 nmol/g (mean +/- SEM). These data prove that VPA reduces the flux through butyrobetaine hydroxylase (EC 1.14.11.1.). The drug in vitro, however, did not inhibit the enzyme directly. Searching for the mechanism of action, we found that VPA decreased the level of alpha-ketoglutarate (alpha-KG; a cofactor of butyrobetaine hydroxylase) from 73.5 +/- 2.90 nmol/g to 52.9 +/- 2.2 nmol/g (mean +/- SEM) in the liver. The level of 1-glutamate showed a rather dramatic decrease in the liver. Moreover, alpha-KG proved to have a protective role against VPA in the [3H]-butyrobetaine conversion experiment.

  4. Designing and Dosimetry of a Shield for Photon Fields of Radiation Therapy in Oral Cavity Cancer.

    PubMed

    Jabbari, Keyvan; Senobari, Somayeh; Roayaei, Mahnaz; Rostampour, Masoumeh

    2015-01-01

    The cancer of oral cavity is related to lesions of mucous membrane of tongue and gum that can be treated with radiation therapy. A lateral photon field can be used to treat this kind of tumor, which has a side-effect on normal tissue in the opposite side of the oral cavity. In this study the dosimetric effect of the various shields in oral cavity is evaluated. In this study, a special phantom similar to the structure of oral cavity with capability of film dosimetry was designed and constructed. The various shield slabs were made of five materials: Lead, Plexiglas, Acrylic resin, Silicon and Plaster. For irradiation, Cobalt 60 (60Co) and 6 MV photon beams were used. The film dosimetry before and after the shield was performed using GAFCHROMIC EBT2 films. The film before the shield measures the magnitude of backscattering radiation from the shield. The prescribed dose was 150 cGy. Results showed that 3 cm of the lead in both energies had the maximum absorption of radiation. The absorbed dose to opposite side of shield for 6 MV photon beams and 60Co were 21 and 32 cGy, respectively. The minimum attenuation on radiation was observed in silicon shield for which the dose of opposite side were 116 and 147 cGy for 6 MV and 60Co respectively. The maximum backscattered dose was measured 177 cGy and 219 cGy using 3 cm thickness of lead, which was quite considerable. The minimum backscattering where for acrylic resin 101 and 118 cGy for 6 MV and cobalt. In this study, it was concluded that the amount of backscattering for 3 cm Lead shield is quite considerable and increases the dose significantly. A composite layer of shield with 1-2 cm lead and 1 cm acrylic resin can have the protective effect and low backscattering radiation at the same time.

  5. Designing and Dosimetry of a Shield for Photon Fields of Radiation Therapy in Oral Cavity Cancer

    PubMed Central

    Jabbari, Keyvan; Senobari, Somayeh; Roayaei, Mahnaz; Rostampour, Masoumeh

    2015-01-01

    The cancer of oral cavity is related to lesions of mucous membrane of tongue and gum that can be treated with radiation therapy. A lateral photon field can be used to treat this kind of tumor, which has a side-effect on normal tissue in the opposite side of the oral cavity. In this study the dosimetric effect of the various shields in oral cavity is evaluated. In this study, a special phantom similar to the structure of oral cavity with capability of film dosimetry was designed and constructed. The various shield slabs were made of five materials: Lead, Plexiglas, Acrylic resin, Silicon and Plaster. For irradiation, Cobalt 60 (60Co) and 6 MV photon beams were used. The film dosimetry before and after the shield was performed using GAFCHROMIC EBT2 films. The film before the shield measures the magnitude of backscattering radiation from the shield. The prescribed dose was 150 cGy. Results showed that 3 cm of the lead in both energies had the maximum absorption of radiation. The absorbed dose to opposite side of shield for 6 MV photon beams and 60Co were 21 and 32 cGy, respectively. The minimum attenuation on radiation was observed in silicon shield for which the dose of opposite side were 116 and 147 cGy for 6 MV and 60Co respectively. The maximum backscattered dose was measured 177 cGy and 219 cGy using 3 cm thickness of lead, which was quite considerable. The minimum backscattering where for acrylic resin 101 and 118 cGy for 6 MV and cobalt. In this study, it was concluded that the amount of backscattering for 3 cm Lead shield is quite considerable and increases the dose significantly. A composite layer of shield with 1–2 cm lead and 1 cm acrylic resin can have the protective effect and low backscattering radiation at the same time. PMID:26120570

  6. Effects of Citric Acid and l-Carnitine on Physical Fatigue.

    PubMed

    Sugino, Tomohiro; Aoyagi, Sayaka; Shirai, Tomoko; Kajimoto, Yoshitaka; Kajimoto, Osami

    2007-11-01

    We examined the effects of citric acid and l-carnitine administration on physical fatigue. In a double-blind, placebo-controlled, 3-way crossover study, 18 healthy volunteers were randomized to oral citric acid (2,700 mg/day), l-carnitine (1,000 mg/day), or placebo for 8 days. The fatigue-inducing physical task consisted of workload trials on a cycle ergometer at fixed workloads for 2 h on 2 occasions. Before the physical load, salivary chromogranin A, measured as a physiological stress marker, was lower in the group given citric acid than in the group given placebo. Also, after the physical load, the subjective feeling of fatigue assessed with a visual analogue scale was lower in the citric acid group than in the placebo group. In contrast, l-carnitine had no effect on chromogranin A or subjective fatigue. These results suggest that citric acid reduces physiological stress and attenuates physical fatigue, whereas l-carnitine does not.

  7. Insulin versus an oral antidiabetic agent as add-on therapy in type 2 diabetes after failure of an oral antidiabetic regimen: a meta-analysis

    PubMed Central

    Gamble, JM; Brown, Lauren C; Johnson, Jeffrey A

    2008-01-01

    Background Although evidence-based guidelines for the treatment of type 2 diabetes mellitus provide clear recommendations for initial therapy, evidence on an optimal treatment strategy after secondary failure is unclear. Purpose To compare the efficacy of add-on therapy using basal insulin versus an additional oral antidiabetic agent in patients with type 2 diabetes and secondary failure. Data sources We searched the following electronic databases from inception until June 2007: MEDLINE; EMBASE; Cochrane Central Register of Controlled Trials; Web of Science; Scopus; CINAHL; International Pharmaceutical Abstracts; Academic OneFile; PASCAL; Global Health Database; LILACS; HealthSTAR; PubMed. Reference lists of potentially relevant articles and clinical trial databases were searched, pharmaceutical manufacturers were contacted, and grey literature sources were sought. Study selection Randomized controlled trials (RCTs) involving subjects with type 2 diabetes with secondary failure who were randomly assigned to receive additional basal insulin therapy (insulin glargine, detemir, or NPH [neutral protamine Hagedorn]) versus another oral antidiabetic agent from any class. Data extraction Two reviewers independently screened articles, extracted data and assessed methodological quality. Our primary outcome was glycemic control measured by change in glycosylated hemoglobin (HbA1C) and the proportion of subjects achieving a HbA1C value of ≤ 7%. Data synthesis To compare overall efficacy between the 2 treatment strategies, change in HbA1C was pooled across studies using a random-effects model and weighted mean difference (WMD). Eleven RCTs, involving 757 participants with a median age of 56 and a median known duration of diabetes of 11 years, were included in our analysis. Insulin treatment demonstrated a small but statistically significant improvement in HbA1C compared with the use of an additional oral agent as add-on therapy (WMD -0.17; 95% CI [confidence interval] -0

  8. Radioiodinated carnitine and acylcarnitine analogs as potential myocardial imaging agents

    SciTech Connect

    McConnell, D.S.

    1991-01-01

    R-carnitine is extremely important in mammalian energy metabolism. Gamma-butyrobetaine, the immediate biosynthetic precursor to R-carnitine, is synthesized in many organs. However, only liver can hydroxylate gamma-butyrobetaine to carnitine. Thus the transport of carnitine from its site of synthesis to the site of utilization is of utmost importance. Carnitine is found in highest concentration in cardiac and skeletal muscle, where it is required for the transport of fatty acids into the mitochondria. Before fatty acids are utilized as fuel for the myocyte by beta-oxidation, they are bound to carnitine as an acylcarnitine ester at the 3-hydroxyl, and transported across the micochondrial membranes. R,S-Carnitine has been shown to be taken up by myocytes. The author has begun a study on the use of carnitine derivatives as potential carriers for the site-specific delivery of radioiodine to bidning sites in the myocardium. Such agents labeled with a gamma-emitting nuclide such as iodine-123 would be useful for the noninvasive imaging of these tissues. The aim was to synthesize a variety of radiolabeled analogs of carnitine and acylcarnitine to address questions of transport, binding and availability for myocardial metabolism. These analogs consist of N-alkylated derivatives of carnitine, acylcarnitine esters as well as carnitine amides and ethers. One C-alkylated derivative showed interesting biodistribution, elevated myocardial uptake and competition with carnitine for binding in the myocardium.

  9. Topical therapies for oral lichen planus management and their efficacy: a narrative review.

    PubMed

    Bagan, José; Compilato, Domenico; Paderni, Carlo; Campisi, Giuseppina; Panzarella, Vera; Picciotti, Maria; Lorenzini, Guido; Di Fede, Olga

    2012-01-01

    Oral Lichen Planus (OLP) is a chronic inflammatory condition implicating T cell-mediated cytotoxicity, and involving oral mucosal surfaces. Several therapeutic regimens have been evaluated to treat OLP and pain related, but often without high level of evidence. Topical formulations are the favourite for the majority of cases; bioadhesive formulations have been considered very useful and practical for local drug delivery in oral mucosa, due to the increased residence time on the oral mucosa of the dosage forms and better therapeutic efficacy. In this narrative review, authors try to illustrate the current topical managements for OLP from the accessible literature on this topic. Steroids are very helpful in discomfort and making better quality of life: they are considered the first-line treatment even if they could cause secondary candidosis, and sometimes bad taste, nausea, dry mouth, sore throat or swollen mouth. Other substances or devices by topical administration are adopted especially when the first line approach is refractory. This is the case when retinol with its synthetic and natural analogues (retinoids), hyaluronic acid, or Aloe Vera are chosen. Recent topical applications for OLP therapy include phototherapy and low/high energy pulsing light; the treatment with extracorporeal photochemotherapy is also reasonable and promising. Finally, calcineurin inhibitors (i.e. cyclosporine, tacrolimus and pimecrolimus), antioxidant and biologics (i.e alefacept, efalizumab, basiliximab, TNF-α inhibitors - infliximab, rituximab) may be alternative approaches when OLP does not respond to the standard protocols. In this scenario, there are several studies on molecules different from glucocorticosteroids, but not sufficient or statistically adequate to justify their evidence-based use in OLP; large randomized placebo controlled trials are required to evaluate the safety and effectiveness of these non conventional therapies. In conclusion, since OLP is a chronic disease

  10. Hemostasis and Post-operative Care of Oral Surgical Wounds by Hemcon Dental Dressing in Patients on Oral Anticoagulant Therapy: A Split Mouth Randomized Controlled Clinical Trial

    PubMed Central

    Kumar, K.R. Ashok; Sarvagna, Jagadesh; Gadde, Praveen; Chikkaboriah, Shwetha

    2016-01-01

    Introduction Hemostasis is a fundamental management issue post-operatively in minor oral surgical procedures. To ensure safety and therapeutic efficacy in patients, under oral anti coagulant therapy, is complicated by necessity for frequent determination of prothrombin time or international normalised ratio. Aim The aim of the study was to determine whether early hemostasis achieved by using Hemcon Dental Dressing (HDD) will affect post-operative care and surgical healing outcome in minor oral surgical procedures. Materials and Methods A total of 30 patients, aged 18 years to 90 years, except those allergic to seafood, who consented to participate, were enrolled into this study. Patients were required to have two or more surgical sites so that they would have both surgical and control sites. All patients taking Oral Anticoagulation Therapy (OAT) were included for treatment in the study without altering the anticoagulant regimens. Institutional Review Board approval was obtained for the same. The collected data was subjected to statistical analysis using unpaired t-test. Results All HDD surgically treated sites achieved hemostasis in 1.49 minutes and control wounds in 4.06 minutes (p < 0.001). Post-operative pain at HDD treated sites (1.87,1.27 on 1st and 3rd day respectively) was significantly lower than the control sites (4.0,1.87 on 1st and 3rd day respectively) p-value (0.001, 0.001 respectively). HDD treated oral surgery wounds achieved statistically significant improved healing both at 1st and 3rd post-operative days (p <0.0001). Conclusion The HDD has been proven to be a clinically effective hemostatic dressing material that significantly shortens bleeding time following minor oral surgical procedures under local anaesthesia, including those patients taking OAT. Patients receiving the HDD had improved surgical wound healing as compared to controls. PMID:27790577

  11. Effect of (L-Carnitine) on acetyl-L-carnitine production by heart mitochondria

    SciTech Connect

    Bieber, L.L.; Lilly, K.; Lysiak, W.

    1986-05-01

    The authors recently reported a large efflux of acetyl-L-carnitine from rat heart mitochondria during state 3 respiration with pyruvate as substrate both in the presence and absence of malate. In this series of experiments, the effect of the concentration of L-carnitine on the efflux of acetyl-L-carnitine and on the production of /sup 14/CO/sub 2/ from 2-/sup 14/C-pyruvate was determined. Maximum acetylcarnitine production (approximately 25 n moles/min/mg protein) was obtained at 3-5 mM L-carnitine in the absence of added malate. /sup 14/CO/sub 2/ production decreased as the concentration of L-carnitine increased; it plateaued at 3-5 mM L-carnitine. These data indicate carnitine can stimulate flux of pyruvate through pyruvate dehydrogenase and can reduce flux of acetyl CoA through the Krebs cycle by acting as an acceptor of the acetyl moieties of acetyl CoA generated by pyruvate dehydrogenase.

  12. Effects of carnitine coingested caffeine on carnitine metabolism and endurance capacity in athletes.

    PubMed

    Cha, Y S; Choi, S K; Suh, H; Lee, S N; Cho, D; Li, K

    2001-12-01

    The purpose of this study was to examine whether caffeine (CAF), carnitine (CAR), or CAF+CAR mixture administration affects exercise endurance time via carnitine metabolism. Water (CON), CAF, CAR, or CAF+CAR mixture was administered to five male rugby athletes participating in this study by a randomized double-blind fashion who were made to ride a cycle ergometer for exercise. The CAF effect on exercise endurance time was small, but the CAR trial significantly increased the exercise endurance time compared with CON trial; a further CAF+CAR mixture trial had greater effects on the exercise endurance time than those of a CON, CAF, or CAR trial. A CAR or CAF+CAR mixed trial increased urinary nonesterified carnitine (NEC) and total carnitine (TCAR), but no changes were observed in acid-soluble acylcarnitine (ASAC) and acid-insoluble acylcarnitine (AIAC) excretion. A CAR or CAF+CAR mixed trial resulted in higher levels of plasma NEC, ASAC, and TCAR fractions than the CON and CAF trials did on exhaustion time. Total cholesterol, triglyceride, and free fatty acid in blood were significantly increased at exhaustion time, but they were not affected in the CAF or the CAR trial. These results suggest that carnitine ingestion could promote fat oxidation, resulting in higher endurance performance in athletes, and especially these ergogenic effects of carnitine coingested with caffeine may be greater than those of carnitine alone.

  13. Acetyl-L-carnitine in hepatic encephalopathy.

    PubMed

    Malaguarnera, Michele

    2013-06-01

    Hepatic encephalopathy is a common complication of hepatic cirrhosis. The clinical diagnosis is based on two concurrent types of symptoms: impaired mental status and impaired neuromotor function. Impaired mental status is characterized by deterioration in mental status with psychomotor dysfunction, impaired memory, and increased reaction time, sensory abnormalities, poor concentration, disorientation and coma. Impaired neuromotor function include hyperreflexia, rigidity, myoclonus and asterixis. The pathogenesis of hepatic encephalopathy has not been clearly defined. The general consensus is that elevated levels of ammonia and an inflammatory response work in synergy to cause astrocyte to swell and fluid to accumulate in the brain which is thought to explain the symptoms of hepatic encephalopathy. Acetyl-L-carnitine, the short-chain ester of carnitine is endogenously produced within mitochondria and peroxisomes and is involved in the transport of acetyl-moieties across the membranes of these organelles. Acetyl-L-carnitine administration has shown the recovery of neuropsychological activities related to attention/concentration, visual scanning and tracking, psychomotor speed and mental flexibility, language short-term memory, attention, and computing ability. In fact, Acetyl-L-carnitine induces ureagenesis leading to decreased blood and brain ammonia levels. Acetyl-L-carnitine treatment decreases the severity of mental and physical fatigue, depression cognitive impairment and improves health-related quality of life. The aim of this review was to provide an explanation on the possible toxic effects of ammonia in HE and evaluate the potential clinical benefits of ALC.

  14. Carnitine metabolism in patients with chronic liver disease.

    PubMed

    Krähenbühl, S; Reichen, J

    1997-01-01

    Carnitine metabolism was studied in 79 patients with chronic liver disease, including 22 patients with noncirrhotic liver disease and 57 patients with different types of cirrhosis (22 patients with hepatitis B- or C-associated cirrhosis, 15 patients with alcohol-induced cirrhosis, 15 patients with primary biliary cirrhosis [PBC], and 5 patients with cryptogenic cirrhosis), and compared with 28 control subjects. In comparison with control subjects, patients with noncirrhotic liver disease showed no change in the plasma carnitine pool, whereas patients with cirrhosis had a 29% increase in the long-chain acylcarnitine concentration. Analysis of subgroups of patients with cirrhosis showed that patients with alcohol-induced cirrhosis had an increase in the total plasma carnitine concentration (67.8 +/- 29.5 vs. 55.2 +/- 9.9 micromol/L in control subjects), resulting from increases in both the short-chain and long-chain acylcarnitine concentration. In this group of patients, the acylcarnitine concentrations showed a close correlation with the total carnitine concentration, and the total carnitine concentration with the serum bilirubin concentration. Urinary excretion of carnitine was not different between patients with noncirrhotic or cirrhotic liver disease and control patients. However, patients with PBC showed an increased urinary excretion of total carnitine (52.5 +/- 40.0 vs. 28.0 +/- 16.7 micromol carnitine/mmol creatinine), resulting from an increase in the fractional excretion of both free carnitine and short-chain acylcarnitine. The current studies show that patients with cirrhosis are normally not carnitine deficient. Patients with alcohol-induced cirrhosis have increased plasma carnitine concentrations, which may result from increased carnitine biosynthesis because of increased skeletal muscle protein turnover. The increase in the fractional carnitine excretion in patients with primary biliary cirrhosis may result from competition of bile acids and

  15. Photodynamic Therapy Using Temoporfin Before Surgery in Treating Patients With Recurrent Oral Cavity or Oropharyngeal Cancer

    ClinicalTrials.gov

    2014-09-02

    Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  16. Clinical evaluation of near-continuous oral micronized progesterone therapy in estrogenized postmenopausal women.

    PubMed

    Bolaji, I I; Mortimer, G; Grimes, H; Tallon, D F; O'Dwyer, E; Fottrell, P F

    1996-02-01

    In an open non-comparative prospective trial of 12 months' duration, we investigated the role of a novel hormone replacement therapy regimen in 40 post-menopausal women who sought hormone replacement therapy. The regimen consisted of continuous administration of 0.625 mg of conjugated equine estrogen coupled with a fixed low-dose of micronized oral progesterone administered for 23 days every calendar month. The regimen was well-tolerated, producing no major side-effects and was effective in relieving menopausal symptoms. The study showed that 40% of the women experienced side-effects and 20% withdrew from the study. Half of the 20% of the women who dropped out did so for reasons not related to treatment. All symptomatic women experienced improvement after the 1st month, and virtually all were asymptomatic by the 3rd month of treatment, persisting until the end of the trial with the average number of hot flushes per day declining from the pretreatment levels by 96%. Amenorrhea was observed in 47% of patients, amenorrhea and minimal vaginal bleeding in 78% but acyclic bleeding was present in 28% of those in whom bleeding was re-established. Endometrial atrophy was induced in the majority of patients and no atypical endometrial hyperplasia was encountered. No significant changes were observed in blood glucose or liver enzymes. The mean percentage changes from baseline for serum cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoproteins (LDL) and LDL/HDL ratio were -6%, +32% (p < 0.001), -16% (p < 0.05), +15% (p < 0.05) and -23% (p < 0.05), respectively. The regimen was clinically effective and its apparent lack of major side-effects, the protective effect on the endometrium, the added advantage of minimal vaginal bleeding and the beneficial effect on lipid/lipoprotein levels, offer an attractive therapy and improved compliance with postmenopausal hormone replacement therapy.

  17. Characteristics of Symptomatic Intracranial Hemorrhage in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulant Therapy

    PubMed Central

    2015-01-01

    Objectives The first non-vitamin K antagonist oral anticoagulant (NOAC) introduced to the market in Japan was dabigatran in March 2011, and three more NOACs, rivaroxaban, apixaban, and edoxaban, have since become available. Randomized controlled trials of NOACs have revealed that intracranial hemorrhage (ICH) occurs less frequently with NOACs compared with warfarin. However, the absolute incidence of ICH associated with NOACs has increased with greater use of these anticoagulants, and we wanted to explore the incidence, clinical characteristics, and treatment course of patients with NOACs-associated ICH. Methods We retrospectively analyzed the characteristics of symptomatic ICH patients receiving NOACs between March 2011 and September 2014. Results ICH occurred in 6 patients (5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years). Mean time to onset was 146.2 ± 111.5 days after starting NOACs. Five patients received rivaroxaban and 1 patient received apixaban. None received dabigatran or edoxaban. Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis. When NOAC therapy was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively. Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset. Conclusion Six symptomatic ICHs occurred early in NOAC therapy but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis. The occurrence of ICH during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control (137.8 ± 15.9 mmHg) and HAS-BLED score ≤ 2. Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent ICH during NOAC therapy. PMID:26171862

  18. Computer-aided dosage in oral anticoagulation therapy using phenprocoumon. Problems and approaches.

    PubMed

    Cromme, L; Völler, H; Gäbler, F; Salzwedel, A; Taborski, U

    2010-11-01

    Oral anticoagulation using vitamin K antagonists has been established for over 50 years. Although it is highly effective in preventing thromboembolic incidents, its therapeutic control still remains problematic. Therefore, a computer-aided approach is recommended for deriving dosages. Up to now, the dosage is often based on the visual inspection of previous INR measurements, average weekly doses, and the INR target range. Statistical variations of measurement results and time-delayed effects of dosages, however, frequently result in the misinterpretation of data and suggest pseudo-trends. Treating physicians are not only responsible for determining the patient-specific maintenance dose, but must also respond to deviating INR values, overdosage or underdosage, initiate the oral anticoagulation therapy, and control the INR level in case of a new target range (bridging). Instructive examples are provided to illustrate the described difficulties. A computer-aided expert system is currently developed to ensure the therapeutic safety under the specified conditions. We present preliminary results from a study designed to validate mathematical models underlying such expert systems.

  19. Bioidentical menopausal hormone therapy: registered hormones (non-oral estradiol ± progesterone) are optimal.

    PubMed

    L'Hermite, M

    2017-03-16

    The many advantages of registered bioidentical sex hormones over registered, conventional, non-bioidentical menopausal hormone therapy (MHT) are considered. The transdermal route of estrogen administration avoids excess venous thromboembolic and ischemic stroke events. There is some indication that conjugated equine estrogens are more thrombogenic and most likely induce some hypertensive responses; estradiol might also be superior to conjugated equine estrogens (CEE) in terms of global cardiovascular health. The most valid evidence presently suggests that CEE-only treatment does not increase the risk of breast cancer and even may reduce it. But its combination with a synthetic progestogen (mainly medroxyprogesterone acetate) is a critical issue since it seems to be primarily associated with an increased incidence of breast cancer, however similar to or lower than that associated with some common lifestyle factors. Though not yet proven in a randomized, controlled trial, MHT continuously combining oral micronized progesterone with transdermal estradiol can presently be considered as the optimal MHT. It is not only safer than custom-compounded bioidentical hormones but also than oral conventional MHT and has the best breast profile; registered products for such optimal MHT are available around the world and must be preferred.

  20. Should transdermal rather than oral estrogens be used in menopausal hormone therapy? A review.

    PubMed

    Fournier, Agnès

    2010-03-01

    The current evaluation of the benefit/risk ratio associated with menopausal hormone therapy (MHT) use is largely based on clinical trials which investigated the effects of oral treatments. Would MHT with transdermal estrogens be associated with a more favourable benefit/risk ratio? We reviewed the available epidemiologic evidence on that question. Epidemiologic studies were considered if they provided risk estimates of conditions which carry an important weight among menopausal women, and for which epidemiologic evidence of a possible link with MHT use is convincing: cardiovascular diseases, breast cancer, diabetes, colorectal cancer and hip fracture. We did not include studies with only surrogate measures. We found that the available information on the potential impact of the route of administration of MHT on the risk of our selected outcomes is limited. To date, epidemiologic data suggest that it has no impact on the risk of breast cancer and hip fracture. Results on the risk of coronary heart disease and colorectal cancer are inconsistent. Studies on stroke and diabetes risk are too few to allow meaningful conclusions. There is a suggestion that transdermal MHT may be less deleterious than oral MHT regarding venous thromboembolism which needs to be confirmed. The issue of the route of administration of MHT should remain an active area of research as part of an attempt to identify treatment modalities that would have the least potential for exerting adverse effects.

  1. Predictors of Oral Rehydration Therapy use among under-five children with diarrhea in Eastern Ethiopia: a community based case control study

    PubMed Central

    2012-01-01

    Background Rehydration therapy is a critical intervention to save the lives of children during the episodes of diarrhea. However, millions of children die every year due to failure to replace fluid effectively. The objective of this study was to identify the predictors of Oral Rehydration Therapy use among under-five children with diarrhea. Method A community based unmatched case control study was conducted in Kersa district, Eastern Ethiopia, in February, 2011. The cases were 241 under-five children with diarrhea in the preceding two weeks before the survey and who had received Oral Rehydration Therapy while the controls were 253 under-five children with diarrhea in the preceding two weeks before the survey and who had not received Oral Rehydration Therapy. The cases and the controls were compared to find out the factors that were associated with the utilization of Oral Rehydration Therapy. Result The study revealed that caregivers’ previous experience of Oral Rehydration Therapy use (AOR = 4.05, 95% CI = 2.63–6.22), seeking advice or treatment from health facilities, (AOR = 3.25, 95% CI = 2.06–5.11) and knowledge of Oral Rehydration Therapy (AOR = 3.09, 95% CI = 1.97–4.85) were found to be the positive determinants of Oral Rehydration Therapy use. Perception of teething as a cause of diarrhea was negatively associated with the utilization of Oral rehydration Therapy (AOR = 0.61, 95% CI = 0.37–0.98). Conclusion Health education should be strengthened on the benefit, preparation, early initiation of Oral Rehydration Therapy and the causes of diarrhea. Attention should be given to those who do not have previous experience of Oral Rehydration Therapy use and have less frequent contacts with the health facilities. PMID:23176055

  2. Effect of oil gum massage therapy on common pathogenic oral microorganisms - A randomized controlled trial

    PubMed Central

    Singla, Nishu; Acharya, Shashidhar; Martena, Suganthi; Singla, Ritesh

    2014-01-01

    Objectives: (i) To assess reduction in Streptococcus mutans and Lactobacillus species count in saliva sample after ten minutes of oil gum massage therapy (massage of gingival tissues) per day for three weeks with sesame oil, olive oil, and coconut oil in three different groups of subjects. (ii) To compare the efficacy between three different oils and the “gold standard” chlorhexidine gel. (iii) To assess reduction in gingival scores and plaque scores of study subjects. Materials and Methods: Study design – Single center, parallel design, and triple blind randomized clinical study with four treatment groups. Participants: 32 of the 40 study subjects working as housekeeping personnel at Kasturba Hospital, Manipal; aged 18-55 years completed the three-week study period. Interventions: Subjects were randomly assigned to massage their gingiva everyday for three weeks with sesame oil, olive oil, coconut oil (tests), and Chlorhexidine gel (control). Oral health status and paraffin stimulated saliva samples were obtained at baseline and after three weeks of oil gum massage therapy. Outcome measures: Microbial culture, plaque index, and gingival index. Statistical analysis: Paired t test and Kruskal Wallis test. Results: There was a significant reduction in mean Streptococcus mutans count, Lactobacillus count, plaque scores, and gingival scores in all four groups after the study. However, there was no significant difference found in percentage reduction of these variables between the four groups. Conclusion: These oils can be used as valuable preventive agents in maintaining and improving oral health in low socioeconomic status population. However, it is recommended that further research should be conducted in other populations with a larger sample and longer duration of follow-up period. PMID:25210256

  3. Novel Oral Therapies for Opioid-induced Bowel Dysfunction in Patients with Chronic Noncancer Pain.

    PubMed

    Holder, Renee M; Rhee, Diane

    2016-03-01

    Opioid analgesics are frequently prescribed and play an important role in chronic pain management. Opioid-induced bowel dysfunction, which includes constipation, hardened stool, incomplete evacuation, gas, and nausea and vomiting, is the most common adverse event associated with opioid use. Mu-opioid receptors are specifically responsible for opioid-induced bowel dysfunction, resulting in reduced peristaltic and secretory actions. Agents that reverse these actions in the bowel without reversing pain control in the central nervous system may be preferred over traditional laxatives. The efficacy and safety of these agents in chronic noncancer pain were assessed from publications identified through Ovid and PubMed database searches. Trials that evaluated the safety and efficacy of oral agents for opioid-induced constipation or opioid-induced bowel dysfunction, excluding laxatives, were reviewed. Lubiprostone and naloxegol are approved in the United States by the Food and Drug Administration for use in opioid-induced constipation. Axelopran (TD-1211) and sustained-release naloxone have undergone phase 2 and phase 1 studies, respectively, for the same indication. Naloxegol and axelopran are peripherally acting μ-opioid receptor antagonists. Naloxone essentially functions as a peripherally acting μ-opioid receptor antagonist when administered orally in a sustained-release formulation. Lubiprostone is a locally acting chloride channel (CIC-2) activator that increases secretions and peristalsis. All agents increase spontaneous bowel movements and reduce other bowel symptoms compared with placebo in patients with noncancer pain who are chronic opioid users. The most common adverse events were gastrointestinal in nature, and none of the drugs were associated with severe adverse or cardiovascular events. Investigations comparing these agents to regimens using standard laxative and combination therapy and trials in special populations and patients with active cancer are

  4. ANALYSIS OF FLOW THROUGH A HUMAN ORAL MODEL FOR USE IN INHALATION TOXICOLOGY AND AEROSOL THERAPY PROTOCOLS

    EPA Science Inventory


    RATIONALE
    Understanding the transport and deposition of inhaled aerosols is of fundamental importance to inhalation toxicology and aerosol therapy. Herein, we focus on the development of a computer based oral morphology and related computational fluid dynamics (CFD) studi...

  5. Cost-effectiveness of combined oral bisphosphonate therapy and falls prevention exercise for fracture prevention in the USA.

    PubMed

    Mori, T; Crandall, C J; Ganz, D A

    2017-02-01

    We developed a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women without prior major osteoporotic fractures over a lifetime horizon. At ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a conventionally accepted threshold compared with bisphosphonates alone.

  6. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease

    PubMed Central

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD. PMID:26900473

  7. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease.

    PubMed

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD.

  8. Evaluating the Primary Prevention of Ischemic Stroke of Oral Antithrombotic Therapy in Head and Neck Cancer Patients with Radiation Therapy

    PubMed Central

    Hsu, Chin-Wei

    2016-01-01

    Although previous studies demonstrated the risk of ischemic stroke (IS) in patients with head and neck cancer (HNC), the impact of oral antithrombotic therapy (OAT) on this risk has not yet been assessed. We aimed to evaluate the effectiveness and safety of OAT in patients with HNC treated with RT. This retrospective cohort study was performed using the National Health Insurance Research Database of Taiwan. A total of 37,638 patients diagnosed with HNC included in the study were classified as users and nonusers of OAT. Primary outcome was IS or transient ischemic attack (TIA), and secondary outcomes were death and major bleeding. The Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). There was no significant difference in the risk of IS or TIA between patients on continuous OAT and nonusers (adjusted HR, 0.812; 95% CI, 0.199–3.309). The risk of major bleeding was not significantly different between the groups. From a national population database, we did not find an association between OAT and decreasing risk of ischemic stroke/TIA or increasing hazard of major bleeding. PMID:27990433

  9. Inflammation and carnitine in hemodialysis patients.

    PubMed

    Pertosa, Giovanni; Grandaliano, Giuseppe; Simone, Simona; Soccio, Michela; Schena, Francesco Paolo

    2005-01-01

    The bioincompatibility of dialytic systems along with the loss of antioxidant substances via the dialysis may contribute to peripheral blood mononuclear cell (PBMC) activation and the production of inflammatory mediators, such as cytokines, oxygen radicals, and complement fragments, that may sustain a state of chronic microinflammation responsible for the pathogenesis of a variety of diseases, including atherosclerosis, anemia, and malnutrition. Moreover, during hemodialysis (HD), oxidative stress may influence several intracellular signaling enzymes, including some stress-activated kinases, such as jun-N-terminal kinase (JNK), potentially leading to PBMC activation and proinflammatory cytokine production. Recent reports suggest that L-carnitine may play an important role in balancing antioxidative systems. Therefore, we sought to evaluate the effect of L-carnitine supplementation on the PBMC responses to oxidative stress induced by different HD membranes. We observed in PBMC from cellulosic (C)-treated patients an increase in the amount of intracellular tyrosine-phosphorylated proteins and a striking activation of JNK, as compared with synthetic (S)-treated patients. On the contrary, 3 months of L-carnitine supplementation significantly lowered intracellular levels of phosphorylated proteins and JNK activity in PBMC from C-treated patients. In addition, after 180 minutes of HD, a significant decrease in global plasma antioxidant capacity was found, particularly in C-treated patients, whereas L-carnitine supplementation improved plasma antioxidant capacity levels in these patients. These observations were also confirmed by in vitro experiments, showing the ability of L-carnitine to reduce the JNK activation in normal PBMC exposed to different amounts of hydrogen peroxide. In conclusion, the uremic milieu is characterized by an enhanced inflammatory response and an increased oxidant load, affecting lipids, carbohydrates, and proteins. Regular L-carnitine

  10. Does carnitine have a role in fat absorption

    SciTech Connect

    Leichter, J.; Ottem, A.; Hahn, P.

    1987-08-24

    The effect of D-carnitine and tetradecylglycidic acid (TDGA), an inhibitor of carnitine palmitoyltransferase, on intestinal absorption of palmitic acid was determined. The proximal intestinal segment was ligated in adult male rats and filled with 0.5 ..mu..Ci of /sup 14/C-palmitic acid alone or with either D-carnitine or TDGA. Thirty minutes alter the radioactivity was determined in the intestinal lumen, intestinal wall and plasma. The absorption of palmitic acid was decreased in the presence of D-carnitine (10 mg/ml) as evidenced by significantly lower levels of radioactivity in the gut wall and the plasma and by significantly greater residual radioactivity in the lumenal contents. L-carnitine had no effect on plasma radioactivity but if D- and L-carnitine were given together the effect of D-carnitine was still in evidence. TDGA also inhibited intestinal absorption of palmitic acid. 8 references, 2 tables.

  11. Oxidative stress parameters in urine from patients with disorders of propionate metabolism: a beneficial effect of L:-carnitine supplementation.

    PubMed

    Ribas, Graziela S; Biancini, Giovana B; Mescka, Caroline; Wayhs, Carlos Y; Sitta, Angela; Wajner, Moacir; Vargas, Carmen R

    2012-01-01

    Propionic (PA) and methylmalonic (MMA) acidurias are inherited disorders caused by deficiency of propionyl-CoA carboxylase and methylmalonyl-CoA mutase, respectively. Affected patients present acute metabolic crises in the neonatal period and long-term neurological deficits. Treatments of these diseases include a protein restricted diet and L: -carnitine supplementation. L: -Carnitine is widely used in the therapy of these diseases to prevent secondary L: -carnitine deficiency and promote detoxification, and several recent in vitro and in vivo studies have reported antioxidant and antiperoxidative effects of this compound. In this study, we evaluated the oxidative stress parameters, isoprostane and di-tyrosine levels, and the antioxidant capacity, in urine from patients with PA and MMA at the diagnosis, and during treatment with L: -carnitine and protein-restricted diet. We verified a significant increase of isoprostanes and di-tyrosine, as well as a significant reduction of the antioxidant capacity in urine from these patients at diagnosis, as compared to controls. Furthermore, treated patients presented a marked reduction of isoprostanes and di-tyrosine levels in relation to untreated patients. In addition, patients with higher levels of protein and lipid oxidative damage, determined by di-tyrosine and isoprostanes levels, also presented lower urinary concentrations of total and free L: -carnitine. In conclusion, the present results indicate that treatment with low protein diet and L: -carnitine significantly reduces urinary biomarkers of protein and lipid oxidative damage in patients with disorders of propionate metabolism and that L: -carnitine supplementation may be specially involved in this protection.

  12. L-carnitine supplementation and adipokines in patients with end-stage renal disease on regular hemodialysis.

    PubMed

    Csiky, B; Nyul, Z; Tóth, G; Wittmann, I; Melegh, B; Rauh, M; Rascher, W; Sulyok, E

    2010-11-01

    Chronic hemodialysis (HD) patients frequently encounter carnitine depletion, elevated adipose tissue-derived hormones/cytokines, that may contribute to accelerated arteriosclerosis. 10 non-diabetic HD patients were studied over 28 weeks. In the 12 weeks treatment period 1 g L-carnitine was given iv after each HD session. Measurements of plasma free- and acylcarnitines, insulin, leptin, adiponectin, resistin and ghrelin were performed at baseline, at weeks 2, 4, 8, 12 (treatment period) and at weeks 24-28 (post-treatment period). L-carnitine supplementation resulted in progressive increase of free- and acylcarnitine levels. Plasma levels of insulin, resistin, leptin and ghrelin remained at the already elevated baseline values. L-carnitine therapy induced a significant increase in plasma adiponectin from 20.2 ± 12.7 μg/ml (baseline) to 32.7 ± 20.2 μg/ml in week 2 (p<0.05) and 35.4 ± 19.6 μg/ml in week 12 (p < 0.03), which remained unchanged in the post-carnitine period. Plasma insulin levels correlated positively with leptin (r = 0.525, p<0.0001) and resistin (r = 0.284, p<0.005); adiponectin levels correlated inversely with leptin (r = -0.255, p<0.02) and resistin (r = -0.213, p<0.04) irrespective of carnitine status. Plasma levels of adipokines and related hormones are greatly elevated in patients on regular HD. L-carnitine administration further augmented the plasma levels of protective adiponectin, therefore it may have a role in preventing cardiovascular complications of uremia.

  13. Effect of class IV laser therapy on chemotherapy-induced oral mucositis: a clinical and experimental study.

    PubMed

    Ottaviani, Giulia; Gobbo, Margherita; Sturnega, Mauro; Martinelli, Valentina; Mano, Miguel; Zanconati, Fabrizio; Bussani, Rossana; Perinetti, Giuseppe; Long, Carlin S; Di Lenarda, Roberto; Giacca, Mauro; Biasotto, Matteo; Zacchigna, Serena

    2013-12-01

    Oral mucositis (OM) is a serious and acute side effect in patients with cancer who receive chemotherapy or radiotherapy, often leading to the suspension of therapy and a need for opioid analgesic and enteral/parenteral nutrition, with an effect on patient survival. Among the various interventions proposed in OM management, laser therapy is becoming a recommended treatment option but has limitations due to its heterogeneous laser parameters. Here, we report on our successful clinical experience on the use of class IV laser therapy to treat OM induced by different chemotherapy regimens. To shed light on the mechanisms of action of laser therapy in improving OM resolution, we have developed an animal model of chemotherapy-induced OM, in which we compare the efficacy of the standard low-power laser therapy protocol with an innovative protocol, defined as high-power laser therapy. We show that high-power laser therapy is more effective than low-power laser therapy in improving OM lesion healing, reducing the inflammatory burden, and preserving tissue integrity. In addition, high-power laser therapy has been particularly effective in promoting the formation of new arterioles within the granulation tissue. Our results provide important insights into the mechanism of action of biostimulating laser therapy on OM in vivo and pave a way for clinical experimentation with the use of high-power laser therapy.

  14. [Correlation between serum L-carnitine concentration and neutrophil engraftment in patients treated with cord blood transplantation].

    PubMed

    Sano, Fuminori; Kondo, Toshinori; Matsuhashi, Yoshiko; Hyo, Rui; Koresawa, Risa; Susuki, Seiko; Hayashi, Kiyoto; Tasaka, Taizo; Wada, Hideho; Sugihara, Takashi

    2016-02-01

    In cord blood transplantation (CBT), the amount of time elapsing until hematological engraftment has effects on the transplantation results. Carnitine deficiency has been reported to cause erythropoietin refractory anemia in chronic hemodialysis patients and thrombocytopenia or leukopenia of cirrhosis, and carnitine supplementation can improve hematopoiesis in patients with hepatic or renal failure. Patients who receive CBT may suffer from carnitine deficiency, but no studies have investigated the carnitine status of such patients. Herein, we determined the concentration of free carnitine (FC) and investigated the correlation between FC and engraftment in patients who received CBT. Twenty-three patients who received CBT at our hospital during the period from April 2013 to January 2015 were enrolled in this study. One patient was excluded because of graft failure, such that 22 patients were ultimately evaluable. FC concentrations of the patients were sequentially monitored at 4 time points (before conditioning therapy, day 0, day 7, and day 14), basic laboratory data were collected, and their correlations with engraftment were analyzed. FC concentrations of the patients were generally low (before conditioning therapy: 33.1, day 0: 43.2, day 7: 38.3, and day 14: 37.8 μmol/l). Significant inverse correlations were observed between FC concentrations and the number of days required for neutrophil engraftment on day 0 and day 14 (before conditioning therapy: P=0.15, r=-0.33, day 0: P=0.04, r=-0.43, day 7: P=0.30, r=-0.23, and day 14: P=0.01, r=-0.55). These results suggest carnitine to be an important nutrient that promotes hematopoietic recovery after CBT.

  15. Acute Disseminated Encephalomyelitis after Oral Therapy with Herbal Extracts: A Case Report

    PubMed Central

    Kaymakamzade, Bahar; Karabudak, Rana; Kurne, Aslı Tuncer; Nurlu, Gülay

    2016-01-01

    Background: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating disease of the central nervous system, commonly attributed to infections or vaccinations. Toxic or allergenic compounds can also trigger a response in the immune system and may cause demyelination. We present a case with ADEM after using oral herbal medications. Case Report: A 25 year-old male developed bilateral central facial palsy and severe quadriparesis after taking herbal drugs (containing echinacea and many other herbal ingredients) for two weeks. He had used the extract to increase his potency and reproductivity. He had no past history of recent immunization or viral infection. The clinical findings, cerebrospinal fluid (CSF) analysis and brain magnetic resonance imaging (MRI) were compatible with ADEM. The neurological findings were improved after seven doses of pulse methylprednisolone treatment. To our knowledge, this is the third report in the literature that links herbal therapy and demyelinating disease. Conclusion: Most of the ADEM cases related to herbal therapy in the literature similarly used echinacea. It is our opinion that other ingredients of the herbal extract used by our case, besides echinacea, could have the potential to cause a trigger in the immune system. Further studies are needed to clarify the immunological effects of different kinds of herbal compounds, as well as the effects of different parts of the plants and the results of various dosages. Moreover, ingredients should also be tested for toxicity, adverse effects and drug interactions. PMID:27308086

  16. Cupreous Complex-Loaded Chitosan Nanoparticles for Photothermal Therapy and Chemotherapy of Oral Epithelial Carcinoma.

    PubMed

    Lin, Min; Wang, Dandan; Liu, Shuwei; Huang, Tingting; Sun, Bin; Cui, Yan; Zhang, Daqi; Sun, Hongchen; Zhang, Hao; Sun, Hui; Yang, Bai

    2015-09-23

    Electron transition materials on the basis of transition metal ions usually possess higher photothermal transduction efficiency but lower extinction ability, which have not been considered as efficient photothermal agents for therapeutic applications. In this work, we demonstrate a facile and feasible approach for enhancing 808 nm photothermal conversion effect of d orbits transition Cu(II) ions by forming Cu-carboxylate complexes. The coordination with carboxylate groups greatly enlarges the splitting energy gap of Cu(II) and the capability of electron transition, thus enhancing the extinction ability in near-infrared region. The cupreous complexes are further loaded in biocompatible and biodegradable polymer nanoparticles (NPs) of chitosan to temporarily lower the toxicity, which allows the photothermal therapy of human oral epithelial carcinoma (KB) cells in vitro and KB tumors in vivo. Animal experiments indicate the photothermal tumor inhibition rate of 100%. In addition, the gradual degradation of chitosan NPs leads to the release of cupreous complexes, thus exhibiting additional chemotherapeutic behavior in KB tumor treatment. Onefold chemotherapy experiments indicate the tumor inhibition rate of 93.1%. The combination of photothermal therapy and chemotherapy of cupreous complex-loaded chitosan NPs indicates the possibility of inhibiting tumor recurrence.

  17. Combination therapy of orally administered glycyrrhizin and UVB improved active-stage generalized vitiligo

    PubMed Central

    Mou, K.H.; Han, D.; Liu, W.L.; Li, P.

    2016-01-01

    Glycyrrhizin has been used clinically for several years due to its beneficial effect on immunoglobulin E (IgE)-induced allergic diseases, alopecia areata and psoriasis. In this study, glycyrrhizin, ultraviolet B light (UVB) or a combination of both were used to treat active-stage generalized vitiligo. One hundred and forty-four patients between the ages of 3 and 48 years were divided into three groups: group A received oral compound glycyrrhizin (OCG); group B received UVB applications twice weekly, and group C received OCG+UVB. Follow-ups were performed at 2, 4, and 6 months after the treatment was initiated. The Vitiligo Area Scoring Index (VASI) and the Vitiligo Disease Activity (VIDA) instrument were used to assess the affected body surface, at each follow-up. Results showed that 77.1, 75.0 and 87.5% in groups A, B and C, respectively, presented repigmentation of lesions. Responsiveness to therapy seemed to be associated with lesion location and patient compliance. Adverse events were limited and transient. This study showed that, although the three treatment protocols had positive results, OCG and UVB combination therapy was the most effective and led to improvement in disease stage from active to stable. PMID:27464024

  18. Use of oral combination therapy for type 2 diabetes in primary care: Meeting individualized patient goals.

    PubMed

    Lavernia, Frank; Adkins, Sarah E; Shubrook, Jay H

    2015-01-01

    The management of type 2 diabetes mellitus (T2DM) by primary care physicians (PCPs) has become increasingly complex due to limitations on consultation time, an increasing array of drug treatment options, and issues of comorbidities and polypharmacy. Diabetes is a progressive condition and treatment with a single glucose-lowering agent can only address limited pathophysiologic targets and does not provide adequate glycemic control in many cases. Consequently, most patients with T2DM will eventually require treatment with multiple glucose-lowering medications. Oral combination therapy in T2DM may be given as multiple-pills, or as single-pill, fixed-dose combinations (FDCs), the latter of which offer convenience, ease of administration, and a reduction in the medication burden. Therefore, FDCs can potentially improve patients' treatment adherence and optimize achievement and maintenance of glycemic targets. However, cost factors also need to be considered. An understanding of the issues associated with the use of combination therapy in T2DM will help PCPs to guide patient-centered decision making and promote the effective management of T2DM.

  19. [Protein catabolism and malnutrition in liver cirrhosis - impact of oral nutritional therapy].

    PubMed

    Norman, K; Valentini, L; Lochs, H; Pirlich, M

    2010-07-01

    Malnutrition with loss of muscle is common in patients with liver cirrhosis and has negative impact on morbidity and mortality. The aetiology of malnutrition is multifactorial and includes inflammation, early onset of gluconeogenesis due to impaired glycogen storage and sometimes hypermetabolism. Reduced nutritional intake, however, plays the most important role in the pathogenesis of malnutrition. There is, however, ample evidence that nutritional intake and therapy are inadequate in liver cirrhosis although studies have clearly shown that dietary counselling and nutritional therapy with oral supplements improve intake in these patients. Protein requirement is considered to be increased in liver cirrhosis and high protein intake has been shown to be well tolerated and associated with an improvement of liver function and nutritional status. Protein intolerance on the other hand is uncommon and hepatic encephalopathy can thus rarely be attributed to high protein consumption. Recommendations for general protein restriction must therefore be considered obsolete and rather a risk factor for an impaired clinical outcome. Furthermore, the administration of late evening meals is highly beneficial in patients with liver disease since the rapid onset of the overnight catabolic state is counteracted. The serum concentration of branched-chain amino acids (BCAA) is decreased in patients with liver cirrhosis and long-term supplementation of BCAA has been shown to improve nutritional status and prolong event-free survival and quality of life.

  20. Effects of L-carnitine supplementation on respiratory distress syndrome development and prognosis in premature infants: A single blind randomized controlled trial.

    PubMed

    Ozturk, Mehmet Adnan; Kardas, Zehra; Kardas, Fatih; Gunes, Tamer; Kurtoglu, Selim

    2016-03-01

    The aim of the present study was to investigate the efficacy of L-carnitine therapy on the occurrence and prognosis of respiratory distress syndrome (RDS). A single blind, randomized controlled trial study was conducted on 130 infants with gestational ages of 28-36 weeks. Infants were assigned to experimental groups (groups 1 and 2) and control groups (groups 3 and 4). Groups 1 and 3 consisted of infants with RDS, and groups 2 and 4 groups were composed of infants without RDS. The experimental groups were treated with carnitine. No statistically significant differences in serum carnitine levels were detected between the study and the control groups on day 1 of treatment (P=0.06). However, on day 7 of treatment, serum carnitine levels in the experimental groups were significantly increased (P=0.02), as compared with the control groups. The surfactant requirement value, which is how many rounds of surfactant therapy were required, was 1.56±0.97 in group 1, and 2.12±0.99 in group 3 (P<0.001). The mean duration of mechanical ventilation required was 3.04±3.60 days in group 1, and 4.73±5.63 days in group 3 (P<0.001). The present results indicate that carnitine supplementation in premature infants with RDS may help to increase carnitine levels, thus decreasing the duration of mechanical ventilation and surfactant requirement.

  1. Effective dosing of L-carnitine in the secondary prevention of cardiovascular disease: a systematic review and meta-analysis

    PubMed Central

    2014-01-01

    Background L-carnitine supplementation has been associated with a significant reduction in all-cause mortality, ventricular arrhythmia, and angina in the setting of acute myocardial infarction (MI). However, on account of strict homeostatic regulation of plasma L-carnitine concentrations, higher doses of L-carnitine supplementation may not provide additional therapeutic benefits. This study aims to evaluate the effects of various oral maintenance dosages of L-carnitine on all-cause mortality and cardiovascular morbidities in the setting of acute MI. Methods After a systematic review of several major electronic databases (PubMed, EMBASE, and the Cochrane Library) up to November 2013, a meta-analysis of five controlled trials (n = 3108) was conducted to determine the effects of L-carnitine on all-cause mortality and cardiovascular morbidities in the setting of acute MI. Results The interaction test yielded no significant differences between the effects of the four daily oral maintenance dosages of L-carnitine (i.e., 2 g, 3 g, 4 g, and 6 g) on all-cause mortality (risk ratio [RR] = 0.77, 95% CI [0.57-1.03], P = 0.08) with a statistically insignificant trend favoring the 3 g dose (RR = 0.48) over the lower 2 g dose (RR = 0.62), which was favored over the higher 4 g and 6 g doses (RR = 0.78, 0.78). There was no significant differences between the effects of the daily oral maintenance dosages of 2 g and 6 g on heart failure (RR = 0.53, 95% CI [0.25-1.13], P = 0.10), unstable angina (RR = 0.90, 95% CI [0.51-1.58], P = 0.71), or myocardial reinfarction (RR = 0.74, 95% CI [0.30-1.80], P = 0.50). Conclusions There appears to be no significant marginal benefit in terms of all-cause mortality, heart failure, unstable angina, or myocardial reinfarction in the setting of acute MI for oral L-carnitine maintenance doses of greater or less than 3 g per day. PMID:25044037

  2. Oral antioxidant therapy for juvenile rats with kaolin-induced hydrocephalus

    PubMed Central

    2014-01-01

    Background Oxidative and nitrosylative changes have been shown to occur in conjunction with the hypoxic changes and cellular/axonal damage in hydrocephalic rodent brains. We hypothesized that antioxidant therapy would improve behavioral, neurophysiological, and/or neurobiochemical outcomes in juvenile rats following induction of hydrocephalus. Methods Three-week old rats received an injection of kaolin (aluminum silicate) into the cisterna magna. Magnetic resonance (MR) imaging was performed two weeks later to assess ventricle size and stratify rats to four treatment conditions. Rats were treated for two weeks daily with sham therapy of either oral canola oil or dextrose or experimental therapy of a low or high dose of an antioxidant mixture containing α-tocopherol, L-ascorbic acid, coenzyme Q10 (CoQ10), reduced glutathione, and reduced lipoic acid. Behavior was examined thrice weekly. Results All hydrocephalic groups lagged in weight gain in comparison to non-hydrocephalic controls, all developed significant ventriculomegaly, and all exhibited white matter destruction. Canola oil with or without the antioxidant mixture normalized antioxidant capacity in brain tissue, and the dextrose-treated rats had the greatest ventricular enlargement during the treatment period. However, there were no significant differences between the four treatment groups of hydrocephalic rats for the various behavioral tasks. Glial fibrillary acidic protein and myelin basic protein quantitation showed no differences between the treatment groups or with control rats. There was increased lipid peroxidation in the hydrocephalic rats compared to controls but no differences between treatment groups. Conclusion The antioxidant cocktail showed no therapeutic benefits for juvenile rats with kaolin-induced hydrocephalus although canola oil might have mild benefit. PMID:25324960

  3. Combination Therapy for Ulcerative Colitis: Orally Targeted Nanoparticles Prevent Mucosal Damage and Relieve Inflammation

    PubMed Central

    Xiao, Bo; Zhang, Zhan; Viennois, Emilie; Kang, Yuejun; Zhang, Mingzhen; Han, Moon Kwon; Chen, Jiucun; Merlin, Didier

    2016-01-01

    Combination therapy is an emerging strategy that is under intensive preclinical investigation for the treatment of various diseases. CD98 is highly overexpressed on the surfaces of epithelial cells and macrophages in the colon tissue with ulcerative colitis (UC), which is usually associated with mucosal damage and inflammation. We previously proved that CD98 siRNA (siCD98)-induced down-regulation of CD98 in colitis tissue decreased the severity of UC to a certain extent. In an effort to further improve the therapeutic efficacy, we aim to simultaneously deliver siCD98 in combination with a potent anti-inflammatory agent, curcumin (CUR), using hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant spherical HA-siCD98/CUR-NPs are featured by a desirable particle size (∼246 nm) and slightly negative zeta potential (∼-14 mV). The NPs functionalized with HA are able to guide the co-delivery of drugs to the targeted cells related to UC therapy (colonic epithelial cells and macrophages). Compared to either siCD98- or CUR-based monotherapy, co-delivery of siCD98 and CUR by HA-functionalized NPs can exert combinational effects against UC by protecting the mucosal layer and alleviating inflammation both in vitro and in vivo. This study shows the promising capability of the co-delivered siCD98 and CUR for boosting the conventional monotherapy via this novel nanotherapeutic agent, which offers a structurally simple platform for orally administered delivery of drugs to target cells in UC therapy. PMID:27924161

  4. Comparison of Vitamin E and L-Carnitine, Separately or in Combination in Patients With Intradialytic Complications

    PubMed Central

    Tayebi Khosroshahi, Hamid; Habibi Asl, Bohlul; Habibzadeh, Afshin; Chaichi, Parastoo; Ghanbarpour, Amin; Hossein Badie, Amir

    2013-01-01

    Background The most common complications during dialysis are hypotension and muscle cramps. There are many strategies to prevent and treat these complications. Objectives The aim of this study is to evaluate effects of vitamin E and L-carnitine supplementation alone and in combination on intradialytic complications. Patients and Methods In a prospective study, 20 patients with end stage renal disease on chronic hemodialysis that had intradialytic complications such as hypotension, muscle cramp, nausea, vomiting and headache were studied. These patients were studied in four 45 day periods, beginning with no treatment (step 1), receiving vitamin E (200 IU/d) (step 2), receiving L-carnitine (500 mg/d) (step 3) and their combination (step 4). Intradialytic complications were recorded in each step and compared between treatments. Results All three treatments significantly reduced frequency of muscle cramps in comparison to baseline values. Vitamin E alone and in combination with L-carnitine reduced the frequency of muscle cramps more effectively. Hypotension was significantly lower in combination therapy in comparison to baseline values and vitamin E treatment. Conclusions Vitamin E and L-carnitine both have comparative effects on intradialytic complications. As the combination use of vitamin E and L-carnitine could more effectively reduce the intradialytic complications, it is recommended for daily use in hemodialysis patients. PMID:24350082

  5. Downregulation of Oxidative and Nitrosative Apoptotic Signaling by L-Carnitine in Ifosfamide-Induced Fanconi Syndrome Rat Model

    PubMed Central

    Sayed-Ahmed, Mohamed M.; Hafez, Mohamed M.; Aldelemy, Meshan Lafi; Aleisa, Abdulaziz M.; Al-Rejaie, Salem S.; Al-Hosaini, Khaled A.; Al-Harbi, Naif O.; Al-Harbi, Mohamed M.; Al-Shabanah, Othman A.

    2012-01-01

    It is well documented that ifosfamide (IFO) therapy is associated with sever nephropathy in the form of Fanconi syndrome. Although oxidative stress has been reported as a major player in IFO-induced Fanconi syndrome, no mechanism for this effect has been ascertained. Therefore, this study has been initiated to investigate, on gene expression level, the mechanism of IFO-induce nephrotoxicity and those whereby carnitine supplementation attenuates this serious side effect of IFO. To achieve the ultimate goals of this study, adult male rats were assigned to one of four treatment groups, namely, control, L-carnitine, IFO, and IFO plus L-carnitine. Administration of IFO for 5 days significantly increased serum creatinine, blood urea nitrogen (BUN), and total nitrate/nitrite (NOx) production in kidney tissues. In addition, IFO significantly increased mRNA expression of inducible nitric oxide synthase (iNOS), caspase-9, and caspase-3 and significantly decreased expression of glutathione peroxides (GPx), catalase (CAT), and Bcl2 in kidney tissues. Administration of L-carnitine to IFO-treated rats resulted in a complete reversal of the all biochemical and gene expression changes, induced by IFO, to the control values. Data from this study suggest that L-carnitine prevents the development of IFO-induced nephrotoxicity via downregulation of oxidative and nitrosative apoptotic signaling in kidney tissues. PMID:23213347

  6. [Oral rehydration therapy: an analysis of its results and impact on the hospitalization and mortality of children with diarrhea].

    PubMed

    Dohi-Fujii, B; Godoy-Olvera, L M; Durazo-Ortíz, J

    1993-11-01

    We present results of four years in oral rehydration therapy (ORT) in the Hospital Infantil del Estado de Sonora. There was 10.2 consults by diarrhoea for day. Children lower of one year old received oral rehydration therapy in 86.8%, were included 11% of prolonged diarrhoea and 32.3% of children with malnutrition. During the procedure diarrhoea there was complicated in 3% with paralytic ileus sepsis and pneumonia. Effectivity of ORT was in 90.9%; 92.8% in light dehydration and 78.7% moderate. Failure in 8.6% was due to vomitus, no acceptation of the oral solution, abundant evacuations and other complication presented. Were observed reduction in hospitalization, rate of 19.2% in 1986 to 38.4% in 1989. The diarrheal mortality decreased in the Urgence Department in 42% and in the Infectology Department in 54%. We considered these results as satisfactory, but are susceptible to better when we diffuse more the oral rehydration therapy in own region.

  7. Oral Recombinant Feline Interferon-Omega as an alternative immune modulation therapy in FIV positive cats: clinical and laboratory evaluation.

    PubMed

    Gil, S; Leal, R O; McGahie, D; Sepúlveda, N; Duarte, A; Niza, M M R E; Tavares, L

    2014-02-01

    Recombinant-Feline Interferon-Omega (rFeIFN-ω) is an immune-modulator licensed for use subcutaneously in Feline Immunodeficiency virus (FIV) therapy. Despite oral protocols have been suggested, little is known about such use in FIV-infected cats. This study aimed to evaluate the clinical improvement, laboratory findings, concurrent viral excretion and acute phase proteins (APPs) in naturally FIV-infected cats under oral rFeIFN-ω therapy (0.1 MU/cat rFeIFN-ω PO, SID, 90 days). 11 FIV-positive cats were treated with oral rFeIFN-ω (PO Group). Results were compared to previous data from 7 FIV-positive cats treated with the subcutaneous licensed protocol (SC Group). Initial clinical scores were similar in both groups. Independently of the protocol, rFeIFN-ω induced a significant clinical improvement of treated cats. Concurrent viral excretion and APP's variation were not significant in the PO Group. Oral rFeIFN-ω can be an effective alternative therapy for FIV-infected cats, being also an option for treatment follow-up in cats submitted to the licensed protocol.

  8. Photodynamic Therapy With HPPH in Treating Patients With Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2016-04-19

    Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Oral Cavity

  9. Phenytoin (Dilantin) and acupuncture therapy in the treatment of intractable oral and facial pain.

    PubMed

    Lu, Dominic P; Lu, Winston I; Lu, Gabriel P

    2011-01-01

    Phenytoin is an anti-convulsant and anti-arrhythmic medication. Manufactured by various pharmaceutical companies with various brand names, phenytoin (PHT) is also known as Dilantain, Hydantoin or Phenytek in the United States; Dilantain or Remytoine in Canada; Epamin, Hidantoina in Mexico; and Fenidatoin or Fenitron or other names elsewhere in the world. Phenytoin (PHT) is especially useful for patients suffering from intractable oral and facial pain especially those who exhibit anger, stress, depression and irrational emotions commonly seen in the patients with oral and facial pain. When used properly, Phenytoin is also an effective anxiolysis drug in addition to its theraputic effects on pain and can be used alone or, even better, if combined with other compatible sedatives. Phenytoin is particularly valuable when combined with acupuncture for patients with trigeminal neuralgia, glossopharyneal neuralgia, Bell's palsy, and some other facial paralysis and pain. It also has an advantage of keeping the patient relatively lucid after treatment. Either PHT or acupuncture alone can benefit patients but the success of treatment outcome may be limited. We found by combining both acupuncture and PHT with Selective Drug Uptake Enhancement by stimulating middle finger at the first segment of ventral (palmar) and lateral surfaces, as well as prescribing PHT with the dosage predetermined for each patient by Bi-Digital O-Ring Test (BDORT), the treatment outcome was much better resulted with less recurrence and intensity of pain during episodes of attack. Patients with Bell's palsy were most benefited by acupuncture therapy that could completely get rid of the illness.

  10. Biodistribution of sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) in an oral cancer model.

    PubMed

    Garabalino, Marcela A; Heber, Elisa M; Monti Hughes, Andrea; González, Sara J; Molinari, Ana J; Pozzi, Emiliano C C; Nievas, Susana; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Bauer, William; Trivillin, Verónica A; Schwint, Amanda E

    2013-08-01

    Boron neutron capture therapy (BNCT) is based on selective accumulation of ¹⁰B carriers in tumor followed by neutron irradiation. We previously proved the therapeutic success of BNCT mediated by the boron compounds boronophenylalanine and sodium decahydrodecaborate (GB-10) in the hamster cheek pouch oral cancer model. Based on the clinical relevance of the boron carrier sodium borocaptate (BSH) and the knowledge that the most effective way to optimize BNCT is to improve tumor boron targeting, the specific aim of this study was to perform biodistribution studies of BSH in the hamster cheek pouch oral cancer model and evaluate the feasibility of BNCT mediated by BSH at nuclear reactor RA-3. The general aim of these studies is to contribute to the knowledge of BNCT radiobiology and optimize BNCT for head and neck cancer. Sodium borocaptate (50 mg ¹⁰B/kg) was administered to tumor-bearing hamsters. Groups of 3-5 animals were killed humanely at nine time-points, 3-12 h post-administration. Samples of blood, tumor, precancerous pouch tissue, normal pouch tissue and other clinically relevant normal tissues were processed for boron measurement by optic emission spectroscopy. Tumor boron concentration peaked to therapeutically useful boron concentration values of 24-35 ppm. The boron concentration ratio tumor/normal pouch tissue ranged from 1.1 to 1.8. Pharmacokinetic curves showed that the optimum interval between BSH administration and neutron irradiation was 7-11 h. It is concluded that BNCT mediated by BSH at nuclear reactor RA-3 would be feasible.

  11. Metronomic therapy with oral 6-mercaptopurine in elderly acute myeloid leukemia: A prospective pilot study

    PubMed Central

    Kapoor, Akhil; Beniwal, Surender Kumar; Kalwar, Ashok; Singhal, Mukesh Kumar; Nirban, Raj Kumar; Kumar, Harvindra Singh

    2016-01-01

    Introduction: Acute myeloid leukemia (AML) in elderly patients differs biologically from that in younger patients and is known to have unfavorable chromosomal rearrangements, higher resistance, and lower tolerance to chemotherapy. In such circumstances, instead of giving full-blown chemotherapy, palliative metronomic chemotherapy (MCT) could be a treatment option. Patients and Methods: We performed a prospective pilot study of old AML patients (age >60 years) not amenable to curative treatment. Thirty-two patients were enrolled into the study and were treated with daily oral 6-mercaptopurine 75 mg/m2. The following inclusion criteria were used: age >60 years, nonpromyelocytic AML, the absence of uncontrolled comorbidities, and patient not amenable to curative treatment. Overall survival (OS) was calculated using Kaplan–Meier method and Cox regression analysis were used to calculate the hazards ratio of significant factors. Results: The median age of the patients was 69 years (range: 61–86 years) with male: female ratio of 2.5:1. About 59.4% of patients had Eastern Cooperative Oncology Group performance status of 2 while rest had the status of 3. The median OS was 6 months (95% confidence interval [CI]: 4.4–7.6). Males had median OS of 7 months (95% CI: 5.4–8.6) versus females with OS of 3 months (95% CI: 1.5–4.4; P = 0.008). There was no survival difference on the basis of baseline hemoglobin or French-American-British class. There were no Grade 4 toxicities and no episode of febrile neutropenia. Conclusions: MCT with oral 6-mercaptopurine is an attractive treatment option in elderly AML patients who are not amenable to curative therapy with minimal toxicities. PMID:27275453

  12. Carnitine supplementation effects on nonenzymatic antioxidants in young rats submitted to exhaustive exercise stress.

    PubMed

    Bucioli, Sérvio A; De Abreu, Luiz C; Valenti, Vitor E; Vannucchi, Helio

    2012-06-01

    Previous studies have demonstrated that exercise stress increases oxidative stress in rats. However, antioxidant supplement therapy effects on reactive oxygen substances are conflicting. We evaluated the effects of carnitine on renal nonenzymatic antioxidants in young rats submitted to exhaustive exercise stress. Wistar rats were divided into 3 groups: (a) control group (not submitted to exercise stress), (b) exercise stress group, and (c) exercise stress and carnitine group. The rats from group 3 were treated with gavage administration of 1 ml of carnitine (5 mg·kg⁻¹) for 7 consecutive days. The animals from groups 2 and 3 were submitted to a bout of swimming exhaustive exercise stress. Kidney samples were analyzed for reactive substances to thiobarbituric acid by malondialdehyde (MDA), reduced glutathione (GSH), and vitamin-E levels. Carnitine treatment attenuated MDA increase caused by exercise stress (1: 0.16 ± 0.02 vs. 2: 0.34 ± 0.07 vs. 3: 0.1 ± 0.01 mmmol per milligram of protein; p < 0.0001). It also increased the renal levels of GSH (1: 23 ± 4 vs. 2: 23 ± 2 vs. 3: 58 ± 9 μmol per gram of protein; p < 0.0001); however, it did not change renal vitamin E (1: 24 ± 5 vs. 2: 27 ± 1 vs. 3: 28 ± 5 μM per gram of tissue; p < 0.001). In conclusion, carnitine improved oxidative stress and partially improved the nonenzymatic antioxidant activity in young rats submitted to exhaustive exercise stress.

  13. Comparison between once weekly, twice weekly, and daily oral iron therapy in Jordanian children suffering from iron deficiency anemia.

    PubMed

    Hawamdeh, Hasan M; Rawashdeh, Mohammad; Aughsteen, Adib Abdulahad

    2013-02-01

    The efficacy of daily versus twice weekly and once weekly oral iron therapy was analyzed to optimize a protocol for treatment of IDM among Jordanian children. One hundred and forty-eight children aged between 6 and 60 months with Hb estimate less than 11 gm/dl were screened. They were randomly divided into three regimens of oral iron therapy for a period of 12 weeks; a group was supplemented with a single weekly dose of iron; a second group received two doses weekly; and a third group had a daily dose of iron. Hb was assayed 3 and 12 weeks after therapy, while ferritin was assayed after 12 weeks of treatment. A significant rise in Hb concentration was observed which was most significant 12 weeks after treatment. Iron supplementation after 3 weeks was similar in all treated groups, and no significant difference in Hb concentration among the three groups was noticed. By the end of the third week, the anemia had respectively resolved by 18, 11.8 and 23.4% in the daily, twice weekly, and once weekly groups. On the other hand, the percentage of recovery of anemia respectively was 78, 90.2 and 74.5% at the end of 12 weeks of iron therapy. Hb recovery percentage was comparable in the three treated groups, and no significant difference was reported between them either at 3 or at 12 weeks of therapy. Ferritin levels in the daily and twice weekly treated groups were similar after 12 weeks of iron therapy and were significantly higher than the ferritin levels of weekly treated group. Although the anemia in the three treated groups was resolved after 3 and 12 weeks of oral iron therapy, we conclude that the regimen of two doses per week is the most effective in resolving anemia with less cost and fewer side effects.

  14. The effectiveness of oral resonance therapy on the perception of femininity of voice in male-to-female transsexuals.

    PubMed

    Carew, Lisa; Dacakis, Georgia; Oates, Jennifer

    2007-09-01

    Ten male-to-female transsexuals participated in five sessions of oral resonance voice therapy targeting lip spreading and forward tongue carriage. Acoustic analysis of recordings made pre- and posttherapy found that participant formant frequency values (F1, F2, and F3, from the vowels /a/, /i/, and /mho/), as well as fundamental frequency (F0), underwent a general increase posttherapy. F3 values, in particular, increased significantly posttreatment. Trends in listener ratings of these recordings showed that the majority of participants were perceived to sound more feminine following treatment. Participants' self-ratings of their voices pre- and posttreatment also indicated that participants perceived their voices as sounding more feminine and that they were more satisfied with their voices following treatment. The present study supports the findings of previous studies that have demonstrated that resonance characteristics in male-to-female transsexuals can be changed to more closely approximate those of females through oral resonance therapy. This intervention study also demonstrates that a spontaneous increase in F0 is achieved during the course of therapy. Further, this study provides preliminary evidence to suggest that oral resonance therapy may be effective in increasing femininity of voice in male-to-female transsexual clients.

  15. Protective effect of R. glutinosa oligosaccharides against high L-carnitine diet-induced endothelial dysfunction and hepatic injury in mice.

    PubMed

    Li, Wenfeng; Zhang, Ruijun; Guo, Jianjun; Shao, Hongjun; Yang, Xingbin

    2016-04-01

    Current research for the first time demonstrated that endothelial dysfunction and hepatic injury in mice were induced by ingestion of 3% l-carnitine water for consecutive 10 weeks. Interestingly, oral administration of dietary raffinose family oligosaccharides (RFOs) at 400 and 800 mg/kg bw significantly reduced the impact of l-carnitine on the serum total cholesterol, triglycerides, high- and low-density lipoproteins, alanine aminotransferase, aspartate amino-transferase, NO, endothelin-1 and C-reactive protein. Furthermore, l-carnitine-induced elevation of hepatic lipid contents and malonaldehyde formation, and the inhibition of SOD and GSH-Px activities in mice were markedly ameliorated by oral administration of RFOs. Moreover, histopathology of H&E and Oil Red O staining of the liver also confirmed the protective effect of RFOs against hepatic steatosis and oxidative injury induced by high l-carnitine diet in mice. These findings for the first time suggest that RFOs may alleviate endothelial dysfunction and liver injury from ingestion of high l-carnitine diet.

  16. "Zeus" a new oral anticoagulant therapy dosing algorithm: a cohort study.

    PubMed

    Cafolla, A; Melizzi, R; Baldacci, E; Pignoloni, P; Dragoni, F; Campanelli, M; Caraccini, R; Foà, R

    2011-10-01

    The demand for oral anticoagulant therapy (OAT) has constantly increased during the last ten years with an extended use of computer assistance. Many mathematical algorithms have been projected to suggest doses and time to next visit for patients on OAT. We designed a new algorithm: "Zeus". A "before-after" study was planned to compare the efficacy and safety of this algorithm dosing OAT with manual dosage decided by the same expert physicians according to the target of International Normalized Ratio (INR). The study analysed data of 1876 patients managed with each of the two modalities for eight months, with an interval of two years between them. The aim was to verify the increased quality of therapy by time spent in INR target and efficiency and safety of Zeus algorithm. Time in therapeutic range (TTR) was significantly (p < 0.0001) higher during the algorithm dosing period in comparison with the TTR during manual management period (62.3% vs 50.3%). The number of PT/INR tests above 5 was significantly (p < 0.001) reduced by algorithm suggested prescriptions in comparison with manual those (254 vs 537 times). The anticoagulant drug amount prescribed according to the algorithm suggestions was significantly (p < 0.0001) lower than that of the manual method. The number of clinical events observed in patients during the algorithm management time was significantly (p < 0.05) lower than that in those managed with the manual dosage. This study confirms the clinical utility of the computer-assisted OAT and shows the efficacy and safety of the Zeus algorithm.

  17. Precise optical dosimetry in low-level laser therapy of soft tissues in oral cavity

    NASA Astrophysics Data System (ADS)

    Stoykova, Elena V.; Sabotinov, O.

    2004-06-01

    The new low level laser therapy (LLLT) is widely applied for treatment of diseases of the oral mucosa and parodont. Depending on indication, different optical tips and light-guides are used to create beams with a required shape. However, to the best of our knowledge, the developed irradiation geometries are usually proposed assuming validity of Bouger-Lambert law. This hardly corresponds to the real situation because of the dominating multiple scattering within 600-1200 nm range that destroys correlation between the emitted laser beam and the spatial distribution of the absorbed dose inside the tissue. The aim of this work is to base the dosimetry of the LLLT procedures of periodontal tissues on radiation transfer theory using a flexible Monte-Carlo code. We studied quantitatively the influence of tissue optical parameters (absorption and scattering coefficients, tissue refraction index, anisotropy factor) on decreasing of correlation between the emitted beam and the energy deposition for converging or diverging beams. We evaluated energy deposition for the developed by us LLLT system in a 3-D model of periodontal tissues created using a cross-sectional image of this region with internal structural information on the gingival and the tooth. The laser source is a CW diode laser emitting elliptical beam within 650-675 nm at output power 5-30 mW. To determine the geometry of the irradiating beam we used CCD camera Spiricon LBA 300.

  18. Efficacy of gasiform ozone and photodynamic therapy on a multispecies oral biofilm in vitro.

    PubMed

    Müller, Philipp; Guggenheim, Bernhard; Schmidlin, Patrick R

    2007-02-01

    Ozone gas and photodynamic therapy (PDT) have been claimed to be antimicrobially effective. This study assessed their antimicrobial potential in vitro. Mature six-species oral biofilms were treated as follows (n = 9 per group): (i) a 60-s application of gasiform vacuum-ozone or vacuum alone (on wet or air-dried biofilm samples); (ii) PDT (i.e. methylene blue in combination with or without a diode soft laser, and a soft laser alone); or (iii) antimicrobial solutions: immersion of biofilms for 60 s in 0.2 and 2% chlorhexidine or in 0.5 and 5% hypochlorite solution. Treatment with chlorhexidine or hypochlorite served as a positive control, whereas untreated samples served as negative controls. Colony-forming units on blood agar were counted. Only the 5% hypochlorite solution was able to totally eliminate the microorganisms in the biofilm. The observed reduction of viable counts by vacuum-ozone application and PDT was less than one log(10) step. Under the conditions of the current study, gasiform ozone and PDT had a minimal effect on the viability of microorganisms organized in a cariogenic biofilm.

  19. Amelioration of lipid abnormalities by vitamin therapy in women using oral contraceptives

    PubMed Central

    Torkzahrani, Shahnaz; Heidari, Afrooz; Mostafavi-pour, Zohreh; Ahmadi, Majid

    2014-01-01

    Objective Combined oral contraceptives (COCs) have some adverse effects on the serum lipid profile. Because hyperlipidemia is one of the risk factors in cardiovascular diseases, lipid abnormalities should be evaluated in women consuming COCs. Vitamins E and C are known to have beneficial effects on serum lipid profiles. Therefore, in this study, we evaluated the effects of vitamins E and C on serum lipids in women using COCs. Methods The study compared changes in lipid parameters with and without vitamin therapy in women consuming COCs compared to those of a control group (40 non-contraceptive users or NCU) for 4 weeks. Total cholesterol and triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels along with HDL/LDL ratios were measured for all participants. Results COC users experienced significantly higher increases in the levels of triglycerides and LDL than non-users (p<0.05). However, no significant differences were noted in the total cholesterol and HDL levels. In the treated COC group receiving vitamins E and C, the HDL level and the HDL/LDL ratio increased and the LDL and triglycerides levels decreased significantly compared with those of the other groups. Conclusion The results of our study indicate that supplementation with antioxidant vitamins E and C restores a normal lipid profile in COC users. PMID:24693493

  20. Oral hormone replacement therapy: factors that influence the estradiol concentrations achieved in a multiracial study population.

    PubMed

    Gavaler, Judith S

    2002-02-01

    The assumption that estradiol (E2) concentrations are reliably increased to therapeutic levels in postmenopausal women receiving hormone replacement therapy (HRT) has not been explicitly tested. Nor have factors that may modulate the E2 levels achieved been evaluated. The author examined E2 concentrations in a multiracial study population of 309 postmenopausal women treated with oral HRT and observed that 51.1% had achieved estradiol levels of at least 45 pg/ml (achievers). The odds of being an achiever were significantly elevated among non-Caucasian women by a HRT dose greater than 0.625 mg, current moderate drinking, and increasing duration of HRT use. The odds were significantly decreased by having a high school education or less and increasing time since last HRT dose. White postmenopausal women had significantly reduced odds of being an achiever, and both a dose of less than 0.625 mg and a dose equal to 0.625 mg significantly reduced the odds of being an achiever. Increasing body mass index and menopause duration were both associated with lower odds. This report demonstrates not only that women treated with HRTdo not all achieve therapeutic levels of estradiol but also that factors can be identified that modulate the E2 concentration achieved in response to HRT administration.

  1. Dosimetric study of photobiomodulation therapy in 5-FU-induced oral mucositis in hamsters

    NASA Astrophysics Data System (ADS)

    Cotomacio, Claudia Carrara; Campos, Luana; Nesadal de Souza, Douglas; Arana-Chavez, Victor Elias; Simões, Alyne

    2017-01-01

    Oral mucositis (OM) is a debilitating consequence of cancer treatment that could be treated with photobiomodulation therapy (PBMT); however, there is no consensus about its dosimetric parameters for OM healing. The aim of this study was to compare different PBMT protocols on OM treatment, through clinical and histological analysis. Thirty hamsters were used, in an induced model of OM by 5-fluorouracil (5-FU) and superficial scratching, in seven days of follow-up. The animals were divided into five groups: control (C), which received only anesthesia and chemotherapeutic vehicle; chemotherapy (Ch), which received anesthesia, 5-FU, and scratches; laser 1 (L1), the same as Ch group, PBMT 6 J/cm2 and 0.24 J (one point); laser 2 (L2), the same as Ch group, PBMT 25 J/cm2 and 1 J (one point); and laser 3 (L3), the same as Ch group, PBMT 4 points of 0.24 J and 6 J/cm2 each. The laser used has λ=660 nm, 0.04 cm2 of spot area, and 40 mW. The best PBMT protocol to maintain lowest OM levels compared to Ch group was L1, followed by L2 and L3. Our results suggest that the application mode of PBMT and the energy delivered per area could interfere with the OM healing.

  2. Antimicrobial photodynamic therapy for inactivation of biofilms formed by oral key pathogens

    PubMed Central

    Cieplik, Fabian; Tabenski, Laura; Buchalla, Wolfgang; Maisch, Tim

    2014-01-01

    With increasing numbers of antibiotic-resistant pathogens all over the world there is a pressing need for strategies that are capable of inactivating biofilm-state pathogens with less potential of developing resistances in pathogens. Antimicrobial strategies of that kind are especially needed in dentistry in order to avoid the usage of antibiotics for treatment of periodontal, endodontic or mucosal topical infections caused by bacterial or yeast biofilms. One possible option could be the antimicrobial photodynamic therapy (aPDT), whereby the lethal effect of aPDT is based on the principle that visible light activates a photosensitizer (PS), leading to the formation of reactive oxygen species, e.g., singlet oxygen, which induce phototoxicity immediately during illumination. Many compounds have been described as potential PS for aPDT against bacterial and yeast biofilms so far, but conflicting results have been reported. Therefore, the aim of the present review is to outline the actual state of the art regarding the potential of aPDT for inactivation of biofilms formed in vitro with a main focus on those formed by oral key pathogens and structured regarding the distinct types of PS. PMID:25161649

  3. Anti-angiogenic therapy (bevacizumab) in the management of oral lichen planus.

    PubMed

    Mahmoud, Maha M; Afifi, Marwa M

    2016-04-01

    Oral lichen planus (OLP), a mucocutaneous chronic inflammatory disease, is conventionally managed using topical corticosteroid therapy. Given the fact that OLP is strongly linked to angiogenesis, anti-angiogenic drugs, such as bevacizumab, might be introduced as an alternative treatment for contraindicated, non-responsive patients. The aim of the present study was to report the short-term effectiveness and safety of intralesional bevacizumab injection in the management of atrophic/erosive OLP. A case series study was conducted in patients with atrophic/erosive OLP in the buccal mucosa, assigned to receive either 2.5 mg of bevacizumab, by intralesional injection (n = 20, test), or topical 0.1% triamcinolone acetonide ointment (n = 20, control). The size, score, and pain intensity of the lesions were assessed pre- and post-treatment. Tissue biopsies were collected for histopathologic, immunohistochemical, and ultrastructural examination. After 1 wk, the test group had significant reductions both in lesion seize and in pain scores compared with controls. A marked decrease in vascular endothelial growth factor (VEGF) and interleukin-8 immunoexpression was noted in tissue biopsies from bevacizumab-treated lesions compared with control lesions. Furthermore, ultrastructural examination of OLP tissue specimens revealed significant healing signs associated with bevacizumab treatment. Short-term data suggest that intralesional bevacizumab injection effectively and safely achieved resolution of atrophic/erosive OLP lesions without disease exacerbations during a 3-month follow-up period.

  4. Continuation rates for oral contraceptives and hormone replacement therapy. The ESHRE Capri Workshop Group.

    PubMed

    2000-08-01

    Despite the safety and effectiveness of low oestrogen-dose oral contraceptives (OC) and postmenopausal hormone replacement there is poor continuity of use of these agents by women. Patterns of use and the reasons affecting different frequencies of use in different countries are presented. Continuity and discontinuation rates are difficult to assess accurately but it is believed that the main reasons why women discontinue use of these agents are concerns about their perceived health risks and the presence of, or fear of, adverse clinical effects, particularly unscheduled uterine bleeding and weight gain. More information is needed about OC continuation rates in order to improve the acceptability of these safe, effective agents. Most women discontinue use of postmenopausal hormonal replacement within 2 years of initiating the therapy. Reasons include disappearance of symptoms of oestrogen deficiency, lack of awareness of health benefits of oestrogen, presence of side-effects (such as breast tenderness and weight gain), presence of uterine bleeding and increasing age. Suggestions to increase continuation of OC include extensive individual pretreatment counselling with a different emphasis in different age groups, education at the time of follow-up visits and telephone calls, and extensive use of educational aids such as brochures, pamphlets and audio tapes, and improvement of pharmaceutical packaging information. In conclusion there is an urgent need to assess the value of these strategies by long-term large controlled studies.

  5. Carnitine is associated with fatty acid metabolism in plants.

    PubMed

    Bourdin, Benoîte; Adenier, Hervé; Perrin, Yolande

    2007-12-01

    The finding of acylcarnitines alongside free carnitine in Arabidopsis thaliana and other plant species, using tandem mass spectrometry coupled to liquid chromatography shows a link between carnitine and plant fatty acid metabolism. Moreover the occurrence of both medium- and long-chain acylcarnitines suggests that carnitine is connected to diverse fatty acid metabolic pathways in plant tissues. The carnitine and acylcarnitine contents in plant tissues are respectively a hundred and a thousand times lower than in animal tissues, and acylcarnitines represent less than 2% of the total carnitine pool whereas this percentage reaches 30% in animal tissues. These results suggest that carnitine plays a lesser role in lipid metabolism in plants than it does in animals.

  6. [Contributions by integrative community therapy to users of Psychosocial Care Centers (CAPS) and family members: thematic oral history].

    PubMed

    Carvalho, Mariana Albernaz Pinheiro de; Dias, Maria Djair; Miranda, Francisco Arnoldo Nunes de; Ferreira Filha, Maria de Oliveira

    2013-10-01

    The aim of this study was to analyze contributions by integrative community therapy to behavior changes in users of Psychosocial Care Centers (CAPS). This was a comprehensive-interpretative study with a qualitative approach, based on thematic oral history. The study site was the Caminhar Center in João Pessoa, Paraíba State, Brazil. The study material was produced with interviews conducted with six subjects and was discussed using thematic analysis as proposed by Minayo, providing the basis for two major thematic lines: integrative community therapy as a liberating praxis and changes that make the difference. The subjects' stories revealed significant changes in the personal, professional, and community fields, based on their inclusion in the integrative community therapy circles, a strategy that promoted the recovery of processes of natural socialization that constitute human life. The use of integrative community therapy was clearly related to proposals for the participants' psychosocial integration and rehabilitation.

  7. Kinetic compartmental analysis of carnitine metabolism in the dog

    SciTech Connect

    Rebouche, C.J.; Engel, A.G.

    1983-01-01

    This study was undertaken to quantitate the dynamic parameters of carnitine metabolism in the dog. Six mongrel dogs were given intravenous injections of L-(methyl-3H)carnitine and the specific radioactivity of carnitine was followed in plasma and urine for 19-28 days. The data were analyzed by kinetic compartmental analysis. A three-compartment, open-system model ((a) extracellular fluid, (b) cardiac and skeletal muscle, (c) other tissues, particularly liver and kidney) was adopted and kinetic parameters (carnitine flux, pool sizes, kinetic constants) were derived. In four of six dogs the size of the muscle carnitine pool obtained by kinetic compartmental analysis agreed (+/- 5%) with estimates based on measurement of carnitine concentrations in different muscles. In three of six dogs carnitine excretion rates derived from kinetic compartmental analysis agreed (+/- 9%) with experimentally measured values, but in three dogs the rates by kinetic compartmental analysis were significantly higher than the corresponding rates measured directly. Appropriate chromatographic analyses revealed no radioactive metabolites in muscle or urine of any of the dogs. Turnover times for carnitine were (mean +/- SEM): 0.44 +/- 0.05 h for extracellular fluid, 232 +/- 22 h for muscle, and 7.9 +/- 1.1 h for other tissues. The estimated flux of carnitine in muscle was 210 pmol/min/g of tissue. Whole-body turnover time for carnitine was 62.9 +/- 5.6 days (mean +/- SEM). Estimated carnitine biosynthesis ranged from 2.9 to 28 mumol/kg body wt/day. Results of this study indicate that kinetic compartmental analysis may be applicable to study of human carnitine metabolism.

  8. Cardiac conduction improvement in two heterozygotes for primary carnitine deficiency on L-carnitine supplementation.

    PubMed

    Sarafoglou, K; Tridgell, A H C; Bentler, K; Redlinger-Grosse, K; Berry, S A; Schimmenti, L A

    2010-08-01

    Expanded newborn screening (NBS) for free carnitine levels has led to the identification of a larger number of heterozygous infants of undiagnosed mothers affected with systemic primary carnitine deficiency (PCD), which in turn leads to the identification of other undiagnosed heterozygous family members. There is an increasing recognition that individuals heterozygous for mutations of genes involved in fatty acid oxidation (FAO) may become symptomatic under environmental stress (fasting, prolonged exercise and illness). Considering the importance of carnitine in FAO, its role in heart and bowel function and in lipid metabolism, what is still little known is the phenotypic variability, biochemical parameters and clinical course of PCD heterozygotes with consistently low-to-normal levels to low levels of carnitine over a lifetime. We report on three generations of a family--an asymptomatic PCD heterozygous infant identified through NBS that led to the diagnosis of her asymptomatic PCD-affected mother and the heterozygous status of the maternal grandparents who report some cardiac symptoms that overlap with PCD that improved with L-carnitine supplementation.

  9. Structural model of carnitine palmitoyltransferase I based on the carnitine acetyltransferase crystal.

    PubMed Central

    Morillas, Montserrat; López-VViñas, Eduardo; Valencia, Alfonso; Serra, Dolors; Gómez-Puertas, Paulino; Hegardt, Fausto G; Asins, Guillermina

    2004-01-01

    CPT I (carnitine palmitoyltransferase I) catalyses the conversion of palmitoyl-CoA into palmitoylcarnitine in the presence of L-carnitine, facilitating the entry of fatty acids into mitochondria. We propose a 3-D (three-dimensional) structural model for L-CPT I (liver CPT I), based on the similarity of this enzyme to the recently crystallized mouse carnitine acetyltransferase. The model includes 607 of the 773 amino acids of L-CPT I, and the positions of carnitine, CoA and the palmitoyl group were assigned by superposition and docking analysis. Functional analysis of this 3-D model included the mutagenesis of several amino acids in order to identify putative catalytic residues. Mutants D477A, D567A and E590D showed reduced L-CPT I activity. In addition, individual mutation of amino acids forming the conserved Ser685-Thr686-Ser687 motif abolished enzyme activity in mutants T686A and S687A and altered K(m) and the catalytic efficiency for carnitine in mutant S685A. We conclude that the catalytic residues are His473 and Asp477, while Ser687 probably stabilizes the transition state. Several conserved lysines, i.e. Lys455, Lys505, Lys560 and Lys561, were also mutated. Only mutants K455A and K560A showed decreases in activity of 50%. The model rationalizes the finding of nine natural mutations in patients with hereditary L-CPT I deficiencies. PMID:14711372

  10. Clinical Assessment of the Efficiency of Low Level Laser Therapy in the Treatment of Oral Lichen Planus

    PubMed Central

    Elshenawy, Hanaa M.; Eldin, Amany Mohy; Abdelmonem, Mohamed Adel

    2015-01-01

    BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa of uncertain etiology. AIM: To evaluate the effect of using low level laser therapy (LLLT (970 nm Siro laser Advance) for the treatment of symptomatic (OLP). SUBJECTS AND METHODS: The present study was conducted on ten patients suffering from persistent oral lichen planus (OLP). Patients were treated with diode laser (970nm) for the symptomatic relief of pain and burning sensation. The patients were assessed before, during and after the completion of the laser treatment which was done twice weekly for two successive months with maximum of ten sessions. The assessment was performed using visual analogue scale (VAS) and clinical investigation for each patient. RESULTS: Detailed significant reduction in lesion size and showed complete remission of burning sensation and pain. No reported complications or therapy side effects were observed in any of the treated patients. CONCLUSION: Diode laser therapy seems to be an effective adjunctive treatment modality for relieving pain and clinical symptoms of OLP. PMID:27275315

  11. Clinical Practice Guideline for the Treatment of Obstructive Sleep Apnea and Snoring with Oral Appliance Therapy: An Update for 2015

    PubMed Central

    Ramar, Kannan; Dort, Leslie C.; Katz, Sheri G.; Lettieri, Christopher J.; Harrod, Christopher G.; Thomas, Sherene M.; Chervin, Ronald D.

    2015-01-01

    Introduction: Since the previous parameter and review paper publication on oral appliances (OAs) in 2006, the relevant scientific literature has grown considerably, particularly in relation to clinical outcomes. The purpose of this new guideline is to replace the previous and update recommendations for the use of OAs in the treatment of obstructive sleep apnea (OSA) and snoring. Methods: The American Academy of Sleep Medicine (AASM) and American Academy of Dental Sleep Medicine (AADSM) commissioned a seven-member task force. A systematic review of the literature was performed and a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the quality of evidence. The task force developed recommendations and assigned strengths based on the quality of the evidence counterbalanced by an assessment of the relative benefit of the treatment versus the potential harms. The AASM and AADSM Board of Directors approved the final guideline recommendations. Recommendations: We recommend that sleep physicians prescribe oral appliances, rather than no therapy, for adult patients who request treatment of primary snoring (without obstructive sleep apnea). (STANDARD) When oral appliance therapy is prescribed by a sleep physician for an adult patient with obstructive sleep apnea, we suggest that a qualified dentist use a custom, titratable appliance over non-custom oral devices. (GUIDELINE) We recommend that sleep physicians consider prescription of oral appliances, rather than no treatment, for adult patients with obstructive sleep apnea who are intolerant of CPAP therapy or prefer alternate therapy. (STANDARD) We suggest that qualified dentists provide oversight— rather than no follow-up—of oral appliance therapy in adult patients with obstructive sleep apnea, to survey for dental-related side effects or occlusal changes and reduce their incidence. (GUIDELINE) We suggest that sleep physicians conduct follow-up sleep testing

  12. Aspects of carnitine ester metabolism in sheep liver

    PubMed Central

    Snoswell, A. M.; Henderson, G. D.

    1970-01-01

    1. Carnitine acetyltransferase (EC 2.3.1.7) activity in sheep liver mitochondria was 76nmol/min per mg of protein, in contrast with 1.7 for rat liver mitochondria. The activity in bovine liver mitochondria was comparable with that of sheep liver mitochondria. Carnitine palmitoyltransferase activity was the same in both sheep and rat liver mitochondria. 2. The [free carnitine]/[acetylcarnitine] ratio in sheep liver ranged from 6:1 for animals fed ad libitum on lucerne to approx. 1:1 for animals grazed on open pastures. This change in ratio appeared to reflect the ratio of propionic acid to acetic acid produced in the rumen of the sheep under the two dietary conditions. 3. In sheep starved for 7 days the [free carnitine]/[acetylcarnitine] ratio in the liver was 0.46:1. The increase in acetylcarnitine on starvation was not at the expense of free carnitine, as the amounts of free carnitine and total acid-soluble carnitine rose approximately fivefold on starvation. An even more dramatic increase in total acid-soluble carnitine of the liver was seen in an alloxan-diabetic sheep. 4. The [free CoA]/[acetyl-CoA] ratio in the liver ranged from 1:1 in the sheep fed on lucerne to 0.34:1 for animals starved for 7 days. 5. The importance of carnitine acetyltransferase in sheep liver and its role in relieving `acetyl pressure' on the CoA system is discussed. PMID:5485754

  13. Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

    SciTech Connect

    Sher, David J.; Thotakura, Vijaya; Balboni, Tracy A.; Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Lorch, Jochen; Goguen, Laura A.; Annino, Donald J.; Tishler, Roy B.

    2011-11-15

    Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distribution of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with promising LRC

  14. Low-level Laser Therapy: A Review of Its Applications in the Management of Oral Mucosal Disorders.

    PubMed

    Spanemberg, Juliana Cassol; Figueiredo, Maria Antonia Zancanaro; Cherubini, Karen; Salum, Fernanda Gonçalves

    2016-11-01

    Due to its analgesic, anti-inflammatory, and biostimulating effects, low-level laser therapy (LLLT) has been widely used for oral disorders, such as oral lichen planus (OLP), xerostomia, recurrent aphthous stomatitis (RAS), herpes labialis, burning mouth syndrome (BMS), and oral mucositis (OM). The research team for the present study has reviewed the literature on the subject, with an emphasis on the applicability of LLLT in general and of its various clinical protocols for the management of those oral disorders. In lesions such as the ones occurring in OM, RAS, herpes labialis, and OLP, the course of wound healing and the pain have been shown to decrease, with a few, or most often, no adverse side effects. The literature shows that LLLT can also be effective in reducing symptoms in patients with BMS. For the treatment of hyposalivation and xerostomia, the use of LLLT has been described in the literature, but no consensus has resulted. Very few controlled clinical studies with well-established therapeutic protocols have occurred, except for OM, for which LLLT has been widely researched. Although information on the use of the laser for some lesions has already been consolidated, further research is needed, especially randomized, controlled clinical trials with long-term follow-up. Those studies will allow the safe use of LLLT, permitting the creation of care protocols for the management of oral disorders.

  15. Dietary L-carnitine supplementation in obese cats alters carnitine metabolism and decreases ketosis during fasting and induced hepatic lipidosis.

    PubMed

    Blanchard, Géraldine; Paragon, Bernard M; Milliat, Fabien; Lutton, Claude

    2002-02-01

    This study was designed to determine whether dietary carnitine supplement could protect cats from ketosis and improve carnitine and lipid metabolism in experimental feline hepatic lipidosis (FHL). Lean spayed queens received a diet containing 40 (CL group, n = 7) or 1000 (CH group, n = 4) mg/kg of L-carnitine during obesity development. Plasma fatty acid, beta-hydroxybutyrate and carnitine, and liver and muscle carnitine concentrations were measured during experimental induction of FHL and after treatment. In control cats (CL group), fasting and FHL increased the plasma concentrations of fatty acids two- to threefold (P < 0.0001) and beta-hydroxybutyrate > 10-fold (from a basal 0.22 +/- 0.03 to 1.70 +/- 0.73 after 3 wk fasting and 3.13 +/- 0.49 mmol/L during FHL). In carnitine-supplemented cats, these variables increased significantly (P < 0.0001) only during FHL (beta-hydroxybutyrate, 1.42 +/- 0.17 mmol/L). L-Carnitine supplementation significantly increased plasma, muscle and liver carnitine concentrations. Liver carnitine concentration increased dramatically from the obese state to FHL in nonsupplemented cats, but not in supplemented cats, which suggests de novo synthesis of carnitine from endogenous amino acids in control cats and reversible storage in supplemented cats. These results demonstrate the protective effect of a dietary L-carnitine supplement against fasting ketosis during obesity induction. Increasing the L-carnitine level of diets in cats with low energy requirements, such as after neutering, and a high risk of obesity could therefore be recommended.

  16. A matched cohort comparison of mTHPC-mediated photodynamic therapy and trans-oral surgery of early stage oral cavity squamous cell cancer.

    PubMed

    Karakullukcu, Baris; Stoker, Sharon D; Wildeman, Anne P E; Copper, Marcel P; Wildeman, Maarten A; Tan, I Bing

    2013-03-01

    Photodynamic therapy (PDT) of early stage oral cavity tumors have been thoroughly reported. However, statistical comparison of PDT to the surgical treatment is not available in published literature. We have identified and matched cohorts of patients with early stage oral cavity cancers undergoing surgery (n = 43) and PDT (n = 55) from a single institute experience. The groups are matched demographically and had the same pre-treatment screening and follow-up schedule. Both groups consisted only of tumors thinner than 5 mm to ensure comparability. The endpoints were local disease free survival, disease free survival, overall survival and response to initial treatment. Local disease free survival at 5 years were 67 and 74 % for PDT and surgery groups, respectively [univariate HR = 1.9 (p = 0.26), multivariable HR = 2.7 (p = 0.13)]. Disease free survival at 5 years are 47 and 53 % for PDT and surgery groups, respectively [univariate HR = 0.8 (p = 0.52), multivariable HR = 0.75 (p = 0.45)]. Overall survival was 83 and 75 % for PDT and surgery groups, respectively [(univariate HR = 0.5 (p = 0.19), multivariable HR = 0.5 (p = 0.17)]. In the PDT group, six patients (11 %) and in the surgery group 11 patients (26 %) had to receive additional treatments after the initial. All of the tested parameters did not have statistical significant difference. Although there is probably a selection bias due to the non-randomized design, this study shows that PDT of early stage oral cavity cancer is comparable in terms of disease control and survival to trans-oral resection and can be offered as an alternative to surgical treatment.

  17. Effect of L-carnitine Supplementation on Circulating C-reactive Protein Levels: A Systematic Review and Meta-Analysis

    PubMed Central

    Sahebkar, Amirhossein

    2015-01-01

    Summary Background C-reactive protein (CRP) has been proposed as a risk marker and risk factor of cardiovascular disease. There have been a number of clinical reports suggesting that supplementation with L-carnitine can modulate systemic inflammation and lower circulating CRP concentrations, but the results have not been consistent. Methods A comprehensive literature search in Medline, Scopus and Cochrane Central Register of Controlled Trials was performed in December 2012 to identify clinical trials investigating the impact of oral L-carnitine supplementation on serum/plasma CRP concentration. A random effect method was used to calculate the combined effect size. Results Six studies comprising 541 cases and 546 controls met the inclusion criteria. Meta-analysis of included trials revealed a significant reduction of circulating CRP concentrations in subjects under L-carnitine intervention compared to the control treatment. The calculated combined weighted mean reduction in CRP concentrations was −0.39 mg/L [95% CI (−0.62 – −0.16)]. This effect size estimate was found to be robust and remained unaffected by the removal of each single study. Conclusions The overall findings of the present meta-analysis support the clinically relevant benefit of L-carnitine supplementation in lowering the circulating levels of CRP. PMID:28356827

  18. Single-agent therapy with oral mercaptopurine for nonlymphoid blast crisis of chronic myeloid leukemia.

    PubMed

    Hernández-Boluda, J C; Cervantes, F; Alvarez, A; Costa, D; Montserrat, E

    2001-09-01

    Currently, no effective treatment is available for the nonlymphoid blast crisis (BC) of chronic myeloid leukemia (CML) and because of this the prognosis for such patients remains invariably poor. In an attempt to determine the results provided by palliative treatment with oral 6-mercaptopurine (6-MP) in the above hematological condition, 30 such patients were analyzed for hospital stay, days of intravenous (i.v.) antibiotics, transfusion requirements, response rate, and survival. Thirty patients with nonlymphoid BC matched for their initial characteristics and treated with different i.v. regimens were used for comparison purposes. Patients managed with 6-MP spent less days in hospital (median: 9, range: 0-46 vs median: 42, range: 5-140; P<0.0001), needed antibiotics for less days (median: 0. range: 0-46 vs median: 20, range: 0-57; P<0.0001), and received less platelet transfusions (median: 0, range: 0-20 vs median: 6, range: 0-63; P=0.004) than those treated with i.v. chemotherapy. Although no complete or partial remission was achieved by patients receiving 6-MP vs six in the i.v. chemotherapy group, no significant difference was observed when the survival of both groups was compared (median: 4.7 months, range: 0.1-22.7 vs median: 3.8 months, range: 0.2-12, respectively). These results indicate that 6-MP therapy constitutes a good palliative treatment for patients with nonlymphoid BC of CML. However, new treatment strategies for this hematological condition are required.

  19. Patients' perspectives on self-testing of oral anticoagulation therapy: Content analysis of patients' internet blogs

    PubMed Central

    2011-01-01

    Background Patients on oral anticoagulant therapy (OAT) require regular testing of the prothrombin time (PT) and the international normalised ratio (INR) to monitor their blood coagulation level to avoid complications of either over or under coagulation. PT/INR can be tested by a healthcare professional or by the patient. The latter mode of the testing is known as patient self-testing or home testing. The objective of this study was to elicit patients' perspectives and experiences regarding PT/INR self-testing using portable coagulometer devices. Methods Internet blog text mining was used to collect 246 blog postings by 108 patients, mainly from the USA and the UK. The content of these qualitative data were analysed using XSight and NVivo software packages. Results The key themes in relation to self-testing of OAT identified were as follows: Patient benefits reported were time saved, personal control, choice, travel reduction, cheaper testing, and peace of mind. Equipment issues included high costs, reliability, quality, and learning how to use the device. PT/INR issues focused on the frequency of testing, INR fluctuations and individual target (therapeutic) INR level. Other themes noted were INR testing at laboratories, the interactions with healthcare professionals in managing and testing OAT and insurance companies' involvement in acquiring the self-testing equipment. Social issues included the pain and stress of taking and testing for OAT. Conclusions Patients' blogs on PT/INR testing provide insightful information that can help in understanding the nature of the experiences and perspectives of patients on self-testing of OAT. The themes identified in this paper highlight the substantial complexities involved in self-testing programmes in the healthcare system. Thus, the issues elicited in this study are very valuable for all stakeholders involved in developing effective self-testing strategies in healthcare that are gaining considerable current momentum

  20. Child survival in the Third World: a functional analysis of oral rehydration therapy dissemination campaigns.

    PubMed

    Suarez De Balcazar, Y; Balcazar, F E

    1991-01-01

    Behavior analysts conducted a functional analysis of different intervention strategies employed in 14 oral rehydration therapy (ORT) campaigns in 10 developing countries. The intervention researchers manipulated antecedents, behaviors, and/or consequences to improve diarrhea management. The strategies used radio announcements, posters, and pamphlets to promote behavior change. Only 2 campaigns (Thailand and Egypt) limited their intervention to these antecedents. Only 3 programs manipulated antecedents, behaviors, and consequences. The 1983 campaign in Bangladesh incorporated school instruction to siblings and home visits as part of skill training and provided incentives to trainers (US$30) as its consequences. The 1985 project in the Gambia used health workers to teach mothers at home about ORT and awarded happy baby lottery prizes (rice, sugar, and soap). The skills training component of the 1984 campaign in Honduras involved 1-on-1 instruction. A radio course on breast feeding, school instruction of siblings, and an illustrated health care manual. Its consequences were games and prizes on radio program call in, free calendars, key rings, t-shirts and a trip to Tegucigalpa. The only program limited to a skills training component was the campaign in South India in 1976. The training involved training nurses to instruct mothers about diarrhea management. An obstacle in all the campaigns was that ORT does not outwardly improve diarrhea and vomiting immediately. Those campaigns that had a skills training component were more effective than those that did not. Behavior analysts could contribute to ORT campaigns by developing simple and effective training programs and developing economical and effective mechanisms to evaluate the effectiveness of such campaigns.

  1. Prevalence and Clinical Significance of Supine-Dependent Obstructive Sleep Apnea in Patients Using Oral Appliance Therapy

    PubMed Central

    Dieltjens, Marijke; Braem, Marc J.; Van de Heyning, Paul H.; Wouters, Kristien; Vanderveken, Olivier M.

    2014-01-01

    Study Objective: The prevalence of supine-dependent obstructive sleep apnea (sdOSA) in a general population ranges from 20% to 60%, depending on the criteria used. Currently, the prevalence and evolution of sdOSA once oral appliance therapy with a mandibular advancement device (OAm) has started is unknown. In addition, literature on the correlation between sdOSA and treatment success with OAm is not unequivocal. The first purpose of this study was to assess the prevalence of sdOSA before and under OAm therapy. Second, the conversion rate from non-sdOSA to sdOSA during OAm therapy was evaluated. The third and final goal was to analyze the correlation between sdOSA and treatment success with OAm therapy in the patient population. Methods: Two hundred thirty-seven consecutive patients (age 48 ± 9 years; male/female ratio 173/64; AHI 20.1 ± 14.7 events/h; BMI 27.2 ± 4.3 kg/m2) starting OAm therapy were included. Results: The prevalence of sdOSA before the start of OAm therapy, ranged from 27.0% to 67.5%. The prevalence of residual sdOSA under OAm therapy in this study ranged from 17.5% to 33.9%. Second, the conversion rate from non-sdOSA to sdOSA ranged from 23.0% to 37.5%. Third, the presence of sdOSA at baseline was not a significant factor for treatment success with OAm therapy. Conclusions: The results of this study indicate that the prevalence of sdOSA before and under OAm therapy is relatively high. One-third of patients shift from non-sdOSA to sdOSA. Finally, treatment success for OAm therapy was not significantly correlated with the presence of sdOSA at baseline. Citation: Dieltjens M, Braem MJ, Van de Heyning PH, Wouters K, Vanderveken OM. Prevalence and clinical significance of supine-dependent obstructive sleep apnea in patients using oral appliance therapy. J Clin Sleep Med 2014;10(9):959-964. PMID:25142766

  2. Adjuvant antifungal therapy using tissue tolerable plasma on oral mucosa and removable dentures in oral candidiasis patients: a randomised double-blinded split-mouth pilot study.

    PubMed

    Preissner, Saskia; Kastner, Isabell; Schütte, Eyke; Hartwig, Stefan; Schmidt-Westhausen, Andrea Maria; Paris, Sebastian; Preissner, Robert; Hertel, Moritz

    2016-07-01

    Extended use of antimycotics in oral candidiasis therapy gives rise to problems related to fungal drug resistance. The aim of this pilot study was to investigate the efficacy of tissue tolerable plasma (TTP) in denture stomatitis patients. It was hypothesised that (I): erythema and (IIa): complaint remission would be accelerated and (IIb): colony forming unit (CFU) reduction would be improved. The halves of the upper jaws of eight patients were randomly assigned to control (nystatin, chlorhexidine and placebo treatment) and test sides (nystatin, chlorhexidine and TTP administered six times each 7 days). The patients and the investigators, who were different from the therapists, were both blinded. Compared to the control sides, the erythema surface was reduced significantly more extensively on the test sides between 2 and 6 weeks of antifungal therapy (P ≤ 0.05). Visual analogue scale values and the frequency of moderate or heavy growth of Candida post-treatment did not differ significantly between both sides (P > 0.05). The primary hypothesis was confirmed, which may be interpreted as an accelerated remission. As drug therapy is usually limited to the time in which signs of infection are present, TTP might help reducing antifungal use. Even though the secondary hypotheses were not confirmed, persistence of Candida might be only colonisation.

  3. Phase II Study of Preoperative Concurrent Chemoradiation Therapy With S-1 in Patients With T4 Oral Squamous Cell Carcinoma

    SciTech Connect

    Nomura, Tomoko; Murakami, Ryuji; Toya, Ryo; Teshima, Keiko; Nakahara, Aya; Hirai, Toshinori; Hiraki, Akimitsu; Nakayama, Hideki; Yoshitake, Yoshihiro; Ota, Kazutoshi; Obayashi, Takehisa; Yamashita, Yasuyuki; Oya, Natsuo; Shinohara, Masanori

    2010-04-15

    Purpose: To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC). Methods and Materials: Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks. Concurrently, S-1 (80 mg/m{sup 2}/day) was administered orally twice daily for 14 consecutive days. Results: We enrolled 46 patients. All underwent radiotherapy as planned; however, oral S-1 was discontinued in 3 patients who manifested acute toxicity. Grade 3 toxicities were mucositis (20%), anorexia (9%), and neutropenia (4%). We encountered no Grade 4 adverse events or serious postoperative morbidity requiring surgical intervention. After CCRT, 32 of the 46 patients underwent radical resection; in 17 (53%) of the operated patients, the pathologic response was complete. During follow-up ranging from 7 to 58 months (median, 22 months), tumor control failed in 5 (16%) of the 32 operated patients; there were 3 local and 2 regional failures. Of the 14 non-operated patients, 8 (57%) manifested local (n = 7) or regional failure (n = 1). The 3-year overall survival rate for all 46 patients was 69%; it was significantly higher for operated than for non-operated patients (82% vs. 48%; p = 0.0288). Conclusion: Preoperative CCRT with S-1 is feasible and effective in patients with T4 oral SCC. Even in inoperable cases, CCRT with S-1 provides adequate tumor control.

  4. The role of carnitine in the perinatal period.

    PubMed

    Kępka, Alina; Chojnowska, Sylwia; Okungbowa, Osazee E; Zwierz, Krzysztof

    2014-01-01

    Carnitine (2-hydroxy-4-trimethylammonium butyrate, vitamin BT) is a small hydrophilic molecule derived from protein-bound lysine, not degraded in the body but excreted via urine, bile and breast milk. Carnitine stimulates the catabolism of long-chain fatty acids (FAs), by transporting them to mitochondria for oxidation, and the intracellular decomposition of branched-chain ketoacids. It also helps to excrete toxic exogenous and nontoxic endogenous organic acids via urine. It further participates in the production of pulmonary surfactant, inhibits free radicals production and demonstrates other antioxidant properties. After delivery, infants dramatically increase energy demands for movement, growth, differentiation and maintenance of the body temperature that strongly depend on FAs oxidation which is facilitated by carnitine. At early stages of life, carnitine biosynthesis is less efficient than in adults and immature infants have less carnitine tissue reserves than term infants. Carnitine supplementation is recommended in newborns with aciduria, childhood epilepsy associated with valproate-induced hepatotoxicity, in kidney-associated syndromes, and premature infants receiving total parenteral nutrition. Concentrations of carnitine and acylcarnitines in neonatal blood have been postulated a useful tool for the diagnosis of type 1 diabetes, as well as the detection and monitoring of many inherited and acquired metabolic disorders. Taking into account the complex metabolic role of cellular FAs transporters, further studies are needed on indications and contraindications for carnitine supplementation in different clinical settings during early developmental period.

  5. Transport of L-carnitine in isolated cerebral cortex neurons.

    PubMed

    Wawrzeńczyk, A; Sacher, A; Mac, M; Nałecz, M J; Nałecz, K A

    2001-04-01

    The accumulation of carnitine was measured in cerebral cortex neurons isolated from adult rat brain. This process was found to be lowered by 40% after preincubation with ouabain and with SH-group reagents (N-ethylmaleimide and mersalyl). The initial velocity of carnitine transport was found to be inhibited by 4-aminobutyrate (GABA) in a competitive way (Ki = 20.9 +/- 2.4 mM). However, of various inhibitors of GABA transporters, only nipecotic acid and very high concentrations of 1-[2-([(diphenylmethylene)amino]oxy)ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride (NO-711) acid decreased carnitine accumulation while betaine, taurine and beta-alanine had no effect. The GABA transporters expressed in Xenopus laevis oocytes did not transport carnitine. Moreover, carnitine was not observed to diminish the accumulation of GABA in cerebral cortex neurons, which further excluded a possible involvement of the GABA transporter GAT1 in the process of carnitine accumulation, despite the expression of this protein in the cells under study. The absence of carnitine transporter OCTN2 in rat cerebral cortex neurons (K. A. Nałecz, D. Dymna, J. E. Mroczkowska, A. Broër, S. Broër, M. J. Nałecz and R. Cecchelli, unpublished results), together with the insensitivity of carnitine accumulation towards betaines, implies that a novel transporting protein is present in these cells.

  6. The influence of chronic L-carnitine supplementation on the formation of preneoplastic and atherosclerotic lesions in the colon and aorta of male F344 rats.

    PubMed

    Empl, Michael T; Kammeyer, Patricia; Ulrich, Reiner; Joseph, Jan F; Parr, Maria K; Willenberg, Ina; Schebb, Nils H; Baumgärtner, Wolfgang; Röhrdanz, Elke; Steffen, Christian; Steinberg, Pablo

    2015-11-01

    L-Carnitine, a key component of fatty acid oxidation, is nowadays being extensively used as a nutritional supplement with allegedly "fat burning" and performance-enhancing properties, although to date there are no conclusive data supporting these claims. Furthermore, there is an inverse relationship between exogenous supplementation and bioavailability, i.e., fairly high oral doses are not fully absorbed and thus a significant amount of carnitine remains in the gut. Human and rat enterobacteria can degrade unabsorbed L-carnitine to trimethylamine or trimethylamine-N-oxide, which, under certain conditions, may be transformed to the known carcinogen N-nitrosodimethylamine. Recent findings indicate that trimethylamine-N-oxide might also be involved in the development of atherosclerotic lesions. We therefore investigated whether a 1-year administration of different L-carnitine concentrations (0, 1, 2 and 5 g/l) via drinking water leads to an increased incidence of preneoplastic lesions (so-called aberrant crypt foci) in the colon of Fischer 344 rats as well as to the appearance of atherosclerotic lesions in the aorta of these animals. No significant difference between the test groups regarding the formation of lesions in the colon and aorta of the rats was observed, suggesting that, under the given experimental conditions, L-carnitine up to a concentration of 5 g/l in the drinking water does not have adverse effects on the gastrointestinal and vascular system of Fischer 344 rats.

  7. Plant-based oral delivery of β-glucocerebrosidase as an enzyme replacement therapy for Gaucher's disease.

    PubMed

    Shaaltiel, Yoseph; Gingis-Velitski, Svetlana; Tzaban, Salit; Fiks, Nadia; Tekoah, Yoram; Aviezer, David

    2015-10-01

    Gaucher's disease (GD), a lysosomal storage disorder caused by mutations in the gene encoding glucocerebrosidase (GCD), is currently treated by enzyme replacement therapy (ERT) using recombinant GCD that is administered intravenously every 2 weeks. However, intravenous administration includes discomfort or pain and might cause local and systemic infections that may lead to low patient compliance. An orally administered drug has the potential to alleviate these problems. In this study, we describe the potential use of plant cells as a vehicle for the oral delivery of recombinant human GCD (prGCD) expressed in carrot cells. The in vitro results demonstrate that the plant cells protect the recombinant protein in the gastric fluids and may enable absorption into the blood. Feeding experiments, with rat and pig as model animals, using carrot cells containing prGCD, show that active recombinant prGCD was found in the digestive tract and blood system and reached both, liver and spleen, the target organs in GD. These results demonstrate that the oral administration of proteins encapsulated in plant cells is feasible. Specifically, carrot cells containing recombinant human prGCD can be used as an oral delivery system and are a feasible alternative to intravenous administration of ERT for GD.

  8. Recent advances in host defense mechanisms/therapies against oral infectious diseases and consequences for systemic disease.

    PubMed

    Gaffen, S L; Herzberg, M C; Taubman, M A; Van Dyke, T E

    2014-05-01

    The innate and adaptive immune systems are both crucial to oral disease mechanisms and their impact on systemic health status. Greater understanding of these interrelationships will yield opportunities to identify new therapeutic targets to modulate disease processes and/or increase host resistance to infectious or inflammatory insult. The topics addressed reflect the latest advances in our knowledge of the role of innate and adaptive immune systems and inflammatory mechanisms in infectious diseases affecting the oral cavity, including periodontitis and candidiasis. In addition, several potential links with systemic inflammatory conditions, such as cardiovascular disease, are explored. The findings elucidate some of the defense mechanisms utilized by host tissues, including the role of IL-17 in providing immunity to oral candidiasis, the antimicrobial defense of mucosal epithelial cells, and the pro-resolution effects of the natural inflammatory regulators, proresolvins and lipoxins. They also describe the role of immune cells in mediating pathologic bone resorption in periodontal disease. These insights highlight the potential for therapeutic benefit of immunomodulatory interventions that bolster or modulate host defense mechanisms in both oral and systemic disease. Among the promising new therapeutic approaches discussed here are epithelial cell gene therapy, passive immunization against immune cell targets, and the use of proresolvin agents.

  9. Brazilian popular healers as effective promoters of oral rehydration therapy (ORT) and related child survival strategies.

    PubMed

    Nations, M K; de Sousa, M A; Correia, L L; da Silva, D M

    1988-01-01

    In Ceara State in northeastern Brazil in 1986 infant mortality reached 110-139 per 1000 live births, and 50% of those deaths were due to diarrhea and dehydration. Diarrheal deaths can be prevented by oral rehydration therapy (ORT), which replaces lost fluids and electrolytes with oral rehydration salts (ORS) and water. ORT was known in the 1830s, but only in the 1960s was the importance of sugar, which increases the body's ability to absorb fluid some 25 times, realized. In northeastern Brazil access to ORT has been severely limited by poverty, official incompetence, and bureaucratic restrictions. In 1984 a 2-year research project was initiated in the village of Pacatuba to test the theory that mobilizing and training popular healers in ORT would 1) increase awareness and use of ORS, 2) promote continued feeding during diarrhea, 3) increase breast feeding, and 4) reduce the use of costly and nonindicated drugs. 46 popular healers, including rezadeiras and oradores (prayers), Umbandistas (priests), espiritas (mediums), an herbalist, and a lay doctor, were recruited and trained. Most of these people practiced a mixture of folk medicine and religion and were highly respected in the community. For purposes of survey, Pacatuba was divided into 3 groups, each containing houses at 4 different income levels. The mothers in 204 Group 1 homes were interviewed concerning ORT and diarrhea-related knowledge before intervention, and 226 households in Group 2 were interviewed after intervention. The healers were taught the basic biomedical concept of rehydration and how to mix the ORS -- 7 bottle cap-fulls of sugar and 1 of salt in a liter of unsweetened traditional tea. The healers were also taught how to use the World Health Organization's (WHO) ORS packets (2% glucose, 90 mmol/1 of sodium chloride, 1.5 gm potassium chloride, and 2.9 gm sodium bicarbonate) for cases of moderate to severe dehydration. In addition, the healers were taught the 5 basic health messages: give ORS

  10. Effects of dehydroepiandrosterone and carnitine treatment on rat liver.

    PubMed

    Battelli, D; Bellei, M; Kneer, N; Contri, M B; Ronchetti, I P; Bobyleva, V; Lardy, H A

    1994-08-01

    It is well established that DHEA treatment is associated in the rat to an increase in fatty acids metabolism. This condition would require levels of L-carnitine much higher than those physiologically present in the liver. The possibility thus exist that during DHEA treatment the concentration of L-carnitine may become a limiting factor for fatty acids oxidation and therefore responsible of some of the effects observed after administration of the hormone. The present experiments were designed to test this hypothesis. The results show that the increase in the levels of peroxisomal enzymes induced in hepatocytes by DHEA, is greatly reduced by parallel administration of L-carnitine. Furthermore, L-carnitine administration counteracts the effect of DHEA on mitochondrial structure. On the contrary, carnitine has no significant effect on the reduction in weight gain observed upon short- or long-term treatment with DHEA.

  11. Carnitine acts as a compatible solute in Brevibacterium linens.

    PubMed

    Jebbar, M; Champion, C; Blanco, C; Bonnassie, S

    1998-03-01

    Carnitine is a trimethyl amino acid found at relatively high concentrations in materials of animal origin. Exogenously provided L-carnitine was found to stimulate growth of Brevibacterium linens ATCC 19391 in media with inhibitory osmotic strength. Its osmoprotective ability was as potent as that of glycine betaine. Electrophoretic and spectroscopic (NMR) analysis showed that this compound is only transiently accumulated, but in significant amounts, by B. linens under hyperosmotic stress and is converted into glycine betaine. The L-carnitine/glycine betaine pathway is inducible by L-carnitine in B. linens. The D-enantiomer did not improve growth of B. linens, even though this solute is accumulated by B. linens at the same level as glycine betaine. The two isomeric forms of carnitine repress the build-up of ectoine, the main endogenous osmolyte in B. linens.

  12. Transport of carnitine in neuroblastoma NB-2a cells.

    PubMed

    Nałecz, K A; Korzon, D; Wawrzeńczyk, A; Nałecz, M J

    1995-09-10

    Carnitine accumulation was measured in cultured neuroblastoma NB-2a cells. This process was found partially sodium dependent and its kinetics to be a sum of a saturable transport (Km = 123 +/- 13 microM) and diffusion (D = 63 +/- 7 pmol/mg protein/min/mM). On the contrary to previous reports on neural cells, the accumulation of carnitine was found insensitive to gamma-aminobutyric acid (GABA). Measurements of carnitine accumulation in the presence of different compounds resulted in the conclusion that carnitine transport does not occur through the known systems specific toward choline and/or amino acids. For instance, an observed inhibition of carnitine transport by serine and cysteine, without any effect of alanine, excluded a possible role of ASC amino acid transport system. An involvement of a new transporter is thus postulated, specific toward compounds with a polar group in the beta position with respect to the carboxylic group.

  13. Risks and benefits of carnitine supplementation in diabetes.

    PubMed

    Dambrova, M; Liepinsh, E

    2015-02-01

    L-carnitine is a very popular food supplement due to its safety profile, antioxidant-type activity and suggested effects on energy metabolism pathways. L-carnitine participates in both fatty acid transport pathways and the export of acetyl groups out of the mitochondria. However, contradictory data exist concerning the pharmacological outcomes of L-carnitine treatment in diabetes mellitus, which is a highly prevalent metabolic disease characterised by hyperglycemia and associated with severe complications, including cardiovascular disease and dyslipidemia. Recently, the L-carnitine-derived metabolites, acylcarnitines and trimethylamine-N-oxide, have been associated with increased cardio-metabolic risks. This review aims to highlight the possible risks and benefits of L-carnitine supplementation.

  14. Effect of carnitine supplement to the dam on plasma carnitine concentration in the sucking foal.

    PubMed

    Benamou, A E; Harris, R C

    1993-01-01

    The changes in carnitine in plasma and milk during the first 3 months of lactation were studied in 14 broodmares and their foals. Six of the mares (Group S) were given a supplement of 10 g carnitine split between the morning and evening feeds, starting 2 weeks before birth. At birth the plasma carnitine concentration in Group S mares was about twice that in Group NS mares (no supplement). In both groups the concentration initially declined in the days after birth. Whilst this trend was reversed in Group S mares, the concentration in Group NS mares remained at a reduced level for the remainder of the study. Milk concentrations declined continuously over the monitoring period in both groups. There was no apparent relationship between milk and plasma concentrations. Despite this the milk concentration tended to be higher in Group S than in Group NS mares although differences were not significant. There was an immediate drop in the plasma concentration in foals after birth which was reversed in foals of Group S mares but not in those of Group NS mares. There were no apparent side effects of carnitine supplementation.

  15. Dietary l-carnitine supplementation improves bone mineral density by suppressing bone turnover in aged ovariectomized rats.

    PubMed

    Hooshmand, Shirin; Balakrishnan, Anju; Clark, Richard M; Owen, Kevin Q; Koo, Sung I; Arjmandi, Bahram H

    2008-08-01

    Postmenopausal bone loss is a major public health concern. Although drug therapies are available, women are interested in alternative/adjunct therapies to slow down the bone loss associated with ovarian hormone deficiency. The purpose of this study was to determine whether dietary supplementation of l-carnitine can influence bone density and slow the rate of bone turnover in an aging ovariectomized rat model. Eighteen-month-old Fisher-344 female rats were ovariectomized and assigned to two groups: (1) a control group in which rats were fed ad libitum a carnitine-free (-CN) diet (AIN-93M) and (2) another fed the same diet but supplemented with l-carnitine (+CN). At the end of 8 weeks of feeding, animals were sacrificed and bone specimens were collected for measuring bone mineral content (BMC) and density (BMD) using dual energy X-ray absorptiometry. Femoral microarchitectural properties were assessed by microcomputed tomography. Femoral mRNA levels of selected bone matrix proteins were determined by northern blot analysis. Data showed that tibial BMD was significantly higher in the rat fed the +CN diet than those fed the -CN (control) diet. Dietary carnitine significantly decreased the mRNA level of tartrate-resistant acid phosphatase (TRAP), an indicator of bone resorption by 72.8%, and decreased the mRNA abundance of alkaline phosphatase (ALP) and collagen type-1 (COL), measures of bone formation by 63.6% and 61.2%, respectively. The findings suggest that carnitine supplementation slows bone loss and improves bone microstructural properties by decreasing bone turnover.

  16. Combination therapy of potential gene to enhance oral cancer therapeutic effect

    NASA Astrophysics Data System (ADS)

    Yeh, Chia-Hsien; Hsu, Yih-Chih

    2015-03-01

    The epidermal growth factor receptor (EGFR) over-regulation related to uncontrolled cell division and promotes progression in tumor. Over-expression of human epidermal growth factor receptor (EGFR) has been detected in oral cancer cells. EGFR-targeting agents are potential therapeutic modalities for treating oral cancer based on our in vitro study. Liposome nanotechnology is used to encapsulate siRNA and were modified with target ligand to receptors on the surface of tumor cells. We used EGFR siRNA to treat oral cancer in vitro.

  17. Effect of dosage and application mode of L-carnitine on plasma lipid and egg-yolk cholesterol of turkeys, hatchability of eggs and post-hatch growth of their offsprings.

    PubMed

    Oso, A O; Fafiolu, A O; Adeleke, M A; Ladokun, O A; Sobayo, R A; Jegede, A V; Peters, S O; Oyebamiji, O A; Akinsola, J

    2014-08-01

    The effect of dosage and application mode of L-carnitine on plasma lipid and egg-yolk cholesterol of breeder turkeys, hatchability of eggs and post-hatch growth response was investigated using 180 breeder hens. The hens were assigned to six dietary treatments in a 2 × 3 factorial arrangements of two application modes of L-carnitine (diet and drinking water) supplemented at 0, 50 and 100 ppm (mg/kg or mg/l) levels, respectively. Each treatment was replicated five times with six hens per replicate. Dietary inclusion of 50 ppm L-carnitine showed the lowest (p < 0.01) plasma total cholesterol (TC) and low-density lipoprotein concentration (LDL). Breeder hens offered 50 ppm L-carnitine with no regard to application mode recorded the highest (p < 0.01) plasma high-density lipoprotein (HDL). Hens offered 50 and 100 ppm L-carnitine irrespective of application mode also showed reduced (p < 0.01) egg-yolk TC concentration at 32 weeks of age. Dietary supplementation of 50 ppm L-carnitine for breeder turkeys recorded the lowest (p < 0.01) egg-yolk triglyceride (TG) at 40 weeks of age. Hens offered 50 ppm L-carnitine irrespective of application mode recorded the highest (p < 0.05) hen-day egg production. Incidence of dead-in-shell also reduced (p < 0.05) with increasing dosage of L-carnitine. Dietary supplementation of 50 ppm and oral application in drinking water of 100 ppm L-carnitine for breeder turkeys resulted in highest (p < 0.05) egg fertility. Offsprings from breeder hens fed diets supplemented with L-carnitine recorded no post-hatch mortality. Highest (p < 0.05) post-hatch final live weight and weight gain was obtained with poults obtained from hens fed diet supplemented with 50 ppm L-carnitine. In conclusion, dietary supplementation of 50 ppm L-carnitine for turkey hens showed improved serum lipid profile, egg fertility, reduced dead-in-shell, egg-yolk cholesterol and resulted in improved post-hatch growth performance.

  18. Downregulation of carnitine acyl-carnitine translocase by miRNAs 132 and 212 amplifies glucose-stimulated insulin secretion.

    PubMed

    Soni, Mufaddal S; Rabaglia, Mary E; Bhatnagar, Sushant; Shang, Jin; Ilkayeva, Olga; Mynatt, Randall; Zhou, Yun-Ping; Schadt, Eric E; Thornberry, Nancy A; Muoio, Deborah M; Keller, Mark P; Attie, Alan D

    2014-11-01

    We previously demonstrated that micro-RNAs (miRNAs) 132 and 212 are differentially upregulated in response to obesity in two mouse strains that differ in their susceptibility to obesity-induced diabetes. Here we show the overexpression of miRNAs 132 and 212 enhances insulin secretion (IS) in response to glucose and other secretagogues including nonfuel stimuli. We determined that carnitine acyl-carnitine translocase (CACT; Slc25a20) is a direct target of these miRNAs. CACT is responsible for transporting long-chain acyl-carnitines into the mitochondria for β-oxidation. Small interfering RNA-mediated knockdown of CACT in β-cells led to the accumulation of fatty acyl-carnitines and enhanced IS. The addition of long-chain fatty acyl-carnitines promoted IS from rat insulinoma β-cells (INS-1) as well as primary mouse islets. The effect on INS-1 cells was augmented in response to suppression of CACT. A nonhydrolyzable ether analog of palmitoyl-carnitine stimulated IS, showing that β-oxidation of palmitoyl-carnitine is not required for its stimulation of IS. These studies establish a link between miRNA-dependent regulation of CACT and fatty acyl-carnitine-mediated regulation of IS.

  19. Efficacy and toxicity of an accelerated hypofractionated radiation therapy protocol in cats with oral squamous cell carcinoma.

    PubMed

    Poirier, Valérie J; Kaser-Hotz, Barbara; Vail, David M; Straw, Rodney C

    2013-01-01

    Squamous cell carcinoma (SCC) is the most common feline oral tumor. Standard radiation protocols have been reported to achieve tumor control durations of 1.5-5.5 months (45-165 days). The purpose of this study was to describe the efficacy and toxicity of an accelerated hypofractionated radiation therapy protocol in cats with oral SCC. Twenty-one cats with histologically confirmed oral SCC and T1-3N0M0 were treated with 10 once-daily fractions (Monday-Friday) of 4.8 Gy. Seventeen cats had macroscopic disease and four were microscopic after incomplete excision. Acute toxicity consisted of grade 2 mucositis in all cats and this was effectively managed using esophageal or gastric tube feeding, pain medication, and antibiotics. Late toxicity effects for cats with available follow-up data included alopecia (4 cats), leukotricia (6), tongue ulceration (1), and oronasal fistula (1). Response could be assessed in 17 cats (seven complete response and five partial response). Four cats (19%) developed metastatic disease without evidence of local progression. The median progression-free survival (PFS) was 105 days (1 year PFS of 23%), median local progression-free survival (LPFS) was 219 days (1 year LPFS of 41%), and median overall survival (OS) was 174 days (1 year OS of 29%). Only tumor stage was prognostic, with T1 having a median PFS of 590 days. Findings indicated that this accelerated hypofractionated radiation therapy protocol was well tolerated in cats with oral SCC, with manageable adverse events. Tumor response was observed in most cats and long tumor control durations were achieved in some cats.

  20. Biologic Mechanisms of Oral Cancer Pain and Implications for Clinical Therapy

    PubMed Central

    Viet, C.T.; Schmidt, B.L.

    2012-01-01

    Cancer pain is an ever-present public health concern. With innovations in treatment, cancer patients are surviving longer, but uncontrollable pain creates a poor quality of life for these patients. Oral cancer is unique in that it causes intense pain at the primary site and significantly impairs speech, swallowing, and masticatory functions. We propose that oral cancer pain has underlying biologic mechanisms that are generated within the cancer microenvironment. A comprehensive understanding of key mediators that control cross-talk between the cancer and peripheral nervous system, and possible interventions, underlies effective cancer pain management. The purpose of this review is to explore the current studies on oral cancer pain and their implications in clinical management for cancer pain in general. Furthermore, we will explore the endogenous opioid systems and novel cancer pain therapeutics that target these systems, which could solve the issue of opiate tolerance and improve quality of life in oral cancer patients. PMID:21972258

  1. A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism

    PubMed Central

    Celestino-Soper, Patrícia B. S.; Violante, Sara; Crawford, Emily L.; Luo, Rui; Lionel, Anath C.; Delaby, Elsa; Cai, Guiqing; Sadikovic, Bekim; Lee, Kwanghyuk; Lo, Charlene; Gao, Kun; Person, Richard E.; Moss, Timothy J.; German, Jennifer R.; Huang, Ni; Shinawi, Marwan; Treadwell-Deering, Diane; Szatmari, Peter; Roberts, Wendy; Fernandez, Bridget; Schroer, Richard J.; Stevenson, Roger E.; Buxbaum, Joseph D.; Betancur, Catalina; Scherer, Stephen W.; Sanders, Stephan J.; Geschwind, Daniel H.; Sutcliffe, James S.; Hurles, Matthew E.; Wanders, Ronald J. A.; Shaw, Chad A.; Leal, Suzanne M.; Cook, Edwin H.; Goin-Kochel, Robin P.; Vaz, Frédéric M.; Beaudet, Arthur L.

    2012-01-01

    We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene in a proband with autism. TMLHE maps to the X chromosome and encodes the first enzyme in carnitine biosynthesis, 6-N-trimethyllysine dioxygenase. Deletion of exon 2 of TMLHE causes enzyme deficiency, resulting in increased substrate concentration (6-N-trimethyllysine) and decreased product levels (3-hydroxy-6-N-trimethyllysine and γ-butyrobetaine) in plasma and urine. TMLHE deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; P = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2–4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism. PMID:22566635

  2. A preterm infant with secondary carnitine deficiency due to MCT formula--effective treatment of L-carnitine.

    PubMed

    Ishida, A; Goto, A; Takahashi, Y; Nakajima, W; Arai, H; Tazawa, Y; Takada, G

    1994-01-01

    We report a preterm infant who was prescribed an MCT formula and subsequently developed carnitine deficiency with liver dysfunction and an elevation of serum CK level. A male infant who had been born at 24 weeks' gestation with birth weight 799 g, was fed with an MCT formula containing 76.8% of all kinds of lipids, because of his steatorrhea after the 30th day. On the 100th day, he was noted hepatomegaly and elevation of serum levels of AST, ALT and CK. The needle biopsy of the liver indicated the existence of the liver damage. He showed low serum carnitine with high urinary loss of acylcarnitine and dicarboxylic aciduria. Administration of L-carnitine was an effective treatment. The carnitine deficiency might be exaggerated by an increased urinary loss of acylcarnitine. We should be cautious of the risk of carnitine deficiency in preterm infants during prolonged use of MCT formula.

  3. Oral Gentamicin Gut Decontamination for Prevention of KPC-Producing Klebsiella pneumoniae Infections: Relevance of Concomitant Systemic Antibiotic Therapy

    PubMed Central

    Tascini, Carlo; Sbrana, Francesco; Flammini, Sarah; Tagliaferri, Enrico; Arena, Fabio; Leonildi, Alessandro; Ciullo, Ilaria; Amadori, Francesco; Di Paolo, Antonello; Ripoli, Andrea; Lewis, Russell; Rossolini, Gian Maria

    2014-01-01

    Gut colonization represents the main source for KPC-producing Klebsiella pneumoniae (KPC-Kp) epidemic dissemination. Oral gentamicin, 80 mg four times daily, was administered to 50 consecutive patients with gut colonization by gentamicin-susceptible KPC-Kp in cases of planned surgery, major medical intervention, or need for patient transfer. The overall decontamination rate was 68% (34/50). The median duration of gentamicin treatment was 9 days (interquartile range, 7 to 15 days) in decontaminated patients compared to 24 days (interquartile range, 20 to 30 days) in those with persistent colonization (P < 0.001). In the six-month period of follow-up, KPC-Kp infections were documented in 5/34 (15%) successfully decontaminated patients compared to 12/16 (73%) persistent carriers (P < 0.001). The decontamination rate was 96% (22/23) in patients receiving oral gentamicin only, compared to 44% (12/27) of those treated with oral gentamicin and concomitant systemic antibiotic therapy (CSAT) (P < 0.001). The multivariate analysis confirmed CSAT and KPC-Kp infection as the variables associated with gut decontamination. In the follow-up period, KPC-Kp infections were documented in 2/23 (9%) of patients treated with oral gentamicin only and in 15/27 (56%) of those also receiving CSAT (P = 0.003). No difference in overall death rate between different groups was documented. Gentamicin-resistant KPC-Kp strains were isolated from stools of 4/16 persistent carriers. Peak gentamicin blood levels were below 1 mg/liter in 12/14 tested patients. Oral gentamicin was shown to be potentially useful for gut decontamination and prevention of infection due to KPC-Kp, especially in patients not receiving CSAT. The risk of emergence of gentamicin-resistant KPC-Kp should be considered. PMID:24419337

  4. Factors Affecting Patients' Perception On, and Adherence To, Anticoagulant Therapy: Anticipating the Role of Direct Oral Anticoagulants.

    PubMed

    Pandya, Ekta Y; Bajorek, Beata

    2017-04-01

    The role of the direct oral anticoagulants (DOACs) in practice has been given extensive consideration recently, albeit largely from the clinician's perspective. However, the effectiveness and safety of using anticoagulants is highly dependent on the patient's ability to manage and take these complex, high-risk medicines. This structured narrative review explores the published literature to identify the factors underpinning patients' non-adherence to anticoagulants in atrial fibrillation (AF), and subsequently contemplates to what extent the DOACs might overcome the known challenges with traditional warfarin therapy. This review comprised a two-tier search of various databases and search platforms (CINAHL, Cochrane, Current Contents Connect, EMBASE, MEDLINE Ovid, EBSCO, PubMed, Google, Google Scholar) to yield 47 articles reporting patients perspectives on, and patients adherence to, anticoagulant therapy. The findings from the literature were synthesised under five interacting dimensions of adherence: therapy-related factors, patient-related factors, condition-related factors, social-economic factors and health system factors. Factors negatively affecting patients' day-to-day lives (especially regular therapeutic drug monitoring, dose adjustments, dietary considerations) predominantly underpin a patient's reluctance to take warfarin therapy, leading to non-adherence. Other patient-related factors underpinning non-adherence include patients' perceptions and knowledge about the purpose of anticoagulation; understanding of the risks and benefits of therapy; socioeconomic status; and expectations of care from health professionals. In considering these findings, it is apparent that the DOACs may overcome some of the barriers to traditional warfarin therapy at least to an extent, particularly the need for regular monitoring, frequent dose adjustment and dietary considerations. However, their high cost, twice-daily dosing and gastrointestinal adverse effects may present

  5. Positive action of propionyl-L-carnitine on mechanical performance of papillary muscle from Syrian hamsters with hereditary dilated cardiomyopathy.

    PubMed

    Maresca, P; Mancinelli, R; Corsico, N; Arrigoni-Martelli, E; Manni, E

    1995-12-20

    Propionyl-L-carnitine has been shown to exert a beneficial effect on cardiac function in different experimental models of cardiomyopathy in the rat, most likely by improving cardiac metabolism and energy production. We have previously shown that, in a strain of hamsters with hereditary dilated cardiomyopathy (BIO TO.2), the mechanical activity of papillary muscle (length-tension, velocity of shortening, shortening, work and power relationship) is significantly depressed when compared to the same parameter in normal hamsters (BIO F1.B). The repeated oral treatment with propionyl-L-carnitine (60 mg/kg per os for 7 weeks) to BIO TO.2 hamsters had a significant positive inotropic effect, as indicated by an increase in developed tension up to the levels observed in papillary muscles from normal hamsters. This action is most likely associated with metabolic effects similar to those observed in rats.

  6. Is the 810-nm diode laser the best choice in oral soft tissue therapy?

    PubMed Central

    Akbulut, Nihat; Kursun, E. Sebnem; Tumer, M. Kemal; Kamburoglu, Kivanc; Gulsen, Ugur

    2013-01-01

    Objective: To evaluate the safety and efficacy of an 810-nm diode laser for treatment of benign oral soft tissue lesions. Materials and Methods: Treatment with the 810-nm diode laser was applied to a group of eighteen patients with pathological frenulum and epulis fissuratum; five patients with oral lichen planus, oral leukoplakia, and mucous membrane pemphigoid; and four patients with pyogenic granuloma. Results: Although the conventional surgery wound heals in a fairly short time, in the present study, the simple oral soft tissue lesions healed within two weeks, the white and vesiculobullous lesions healed completely within six weeks, and the pyogenic granuloma lesions healed within four weeks. Any complication was treated by using the 810-nm diode laser. Conclusions: Patient acceptance and satisfaction, without compromising health and function, have been found to be of a high degree in this present study. Thus, we can say that the use of the 810-nm diode laser may indeed be the best choice in oral soft tissue surgery. PMID:24883028

  7. Cardiac effects of carnitine supplementation in experimental uraemia.

    PubMed

    Seymour, Anne-Marie; Reddy, Veena; Bhandari, Sunil

    2013-06-01

    Cardiovascular complications are the leading cause of death in patients with chronic kidney disease. The uraemic heart undergoes remodelling and changes in metabolic function. Experimental uraemia produces a reduction in the myocardial energy reserve phosphocreatine in parallel with left ventricular hypertrophy and depletion of serum carnitine. This study investigated the effects of chronic L-carnitine supplementation on myocardial substrate metabolism and function in the experimental uraemia. Experimental uraemia was induced surgically in male Sprague-Dawley rats via a subtotal nephrectomy. Carnitine was administered continuously via subcutaneous mini-osmotic pumps. Cardiac function and substrate oxidation were assessed in vitro by means of isovolumic perfusion using 13C NMR, at 3 and 6 weeks. Uraemic animals exhibited anaemia, kidney dysfunction and systemic carnitine deficiency but no myocardial tissue carnitine deficiency. Myocardial hypertrophy was abolished following carnitine supplementation. This was associated with a reduction in glucose utilisation. In summary carnitine supplementation prevents cardiac hypertrophy, and this effect is amplified with the duration of treatment. This is associated with a reduction in myocardial glucose utilisation but no significant modulation of myocardial function.

  8. Development of low-cost devices for image-guided photodynamic therapy treatment of oral cancer in global health settings

    NASA Astrophysics Data System (ADS)

    Liu, Hui; Rudd, Grant; Daly, Liam; Hempstead, Joshua; Liu, Yiran; Khan, Amjad P.; Mallidi, Srivalleesha; Thomas, Richard; Rizvi, Imran; Arnason, Stephen; Cuckov, Filip; Hasan, Tayyaba; Celli, Jonathan P.

    2016-03-01

    Photodynamic therapy (PDT) is a light-based modality that shows promise for adaptation and implementation as a cancer treatment technology in resource-limited settings. In this context PDT is particularly well suited for treatment of pre-cancer and early stage malignancy of the oral cavity, that present a major global health challenge, but for which light delivery can be achieved without major infrastructure requirements. In recent reports we demonstrated that a prototype low-cost batterypowered 635nm LED light source for ALA-PpIX PDT achieves tumoricidal efficacy in vitro and vivo, comparable to a commercial turn-key laser source. Here, building on these reports, we describe the further development of a prototype PDT device to enable intraoral light delivery, designed for ALA- PDT treatment of precancerous and cancerous lesions of the oral cavity. We evaluate light delivery via fiber bundles and customized 3D printed light applicators for flexible delivery to lesions of varying size and position within the oral cavity. We also briefly address performance requirements (output power, stability, and light delivery) and present validation of the device for ALA-PDT treatment in monolayer squamous carcinoma cell cultures.

  9. Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects

    PubMed Central

    Rajagopalan, Viswanathan; Zhang, Youhua; Ojamaa, Kaie; Chen, Yue-feng; Pingitore, Alessandro; Pol, Christine J.; Saunders, Debra; Balasubramanian, Krithika; Towner, Rheal A.; Gerdes, A. Martin

    2016-01-01

    Background A large body of evidence suggests that thyroid hormones (THs) are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3) treatment in myocardial infarction (MI) rats increased left ventricular (LV) contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI. Methods and Results Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day) was available in drinking water ad libitum immediately following MI and continuing for 2 month(s) (mo). Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy. Conclusions Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans. PMID:26981865

  10. Muscle contraction increases carnitine uptake via translocation of OCTN2.

    PubMed

    Furuichi, Yasuro; Sugiura, Tomoko; Kato, Yukio; Takakura, Hisashi; Hanai, Yoshiteru; Hashimoto, Takeshi; Masuda, Kazumi

    2012-02-24

    Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL(uptake)) of l-[(3)H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL(uptake) of [(14)C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL(uptake) of l-[(3)H]carnitine in the contracting muscles increased 1.4-1.7-fold as compared to that in the contralateral resting muscles (p<0.05). The CL(uptake) of [(14)C]IAP was much higher than that of l-[(3)H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p<0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly via the contraction-induced translocation of its specific transporter OCTN2 to the plasma membrane.

  11. Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2017-01-19

    Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  12. Epigenetic Modifications and Accumulation of DNA Double-Strand Breaks in Oral Lichen Planus Lesions Presenting Poor Response to Therapy

    PubMed Central

    Dillenburg, Caroline S.; Martins, Marco A.T.; Almeida, Luciana O.; Meurer, Luise; Squarize, Cristiane H.; Martins, Manoela D.; Castilho, Rogerio M.

    2015-01-01

    Abstract Epigenetics refers to changes in cell characteristics that occur independently of modifications to the deoxyribonucleic acid (DNA) sequence. Alterations mediated by epigenetic mechanisms are important factors in cancer progression. Although an exciting prospect, the identification of early epigenetic markers associated with clinical outcome in premalignant and malignant disorders remains elusive. We examined alterations in chromatin acetylation in oral lichen planus (OLP) with distinct clinical behavior and compared the alterations to the levels of DNA double-strand breaks (DSBs). We analyzed 42 OLP patients, who had different responses to therapy, for acetyl-histone H3 at lys9 (H3K9ac), which is associated with enhanced transcription and nuclear decondensation, and the presence of DSBs, as determined by accumulation of phosphorylated γH2AX foci. Patients with high levels of H3K9ac acetylation failed to respond to therapy or experienced disease recurrence shortly after therapy. Similar to H3K9ac, patients who responded poorly to therapy had increased accumulation of DNA DSB, indicating genomic instability. These findings suggest that histone modifications occur in OLP, and H3K9ac and γH2AX histones may serve as epigenetic markers for OLP recurrence. PMID:26222871

  13. ER maleate is a novel anticancer agent in oral cancer: implications for cancer therapy

    PubMed Central

    Fu, Guodong; Somasundaram, Raj Thani; Jessa, Fatima; Srivastava, Gunjan; MacMillan, Christina; Witterick, Ian; Walfish, Paul G.; Ralhan, Ranju

    2016-01-01

    ER maleate [10-(3-Aminopropyl)-3, 4-dimethyl-9(10H)-acridinone maleate] identified in a kinome screen was investigated as a novel anticancer agent for oral squamous cell carcinoma (OSCC). Our aim was to demonstrate its anticancer effects, identify putative molecular targets and determine their clinical relevance and investigate its chemosensitization potential for platinum drugs to aid in OSCC management. Biologic effects of ER maleate were determined using oral cancer cell lines in vitro and oral tumor xenografts in vivo. mRNA profiling, real time PCR and western blot revealed ER maleate modulated the expression of polo-like kinase 1 (PLK1) and spleen tyrosine kinase (Syk). Their clinical significance was determined in oral SCC patients by immunohistochemistry and correlated with prognosis by Kaplan-Meier survival and multivariate Cox regression analyses. ER maleate induced cell apoptosis, inhibited proliferation, colony formation, migration and invasion in oral cancer cells. Imagestream analysis revealed cell cycle arrest in G2/M phase and increased polyploidy, unravelling deregulation of cell division and cell death. Mechanistically, ER maleate decreased expression of PLK1 and Syk, induced cleavage of PARP, caspase9 and caspase3, and increased chemosensitivity to carboplatin; significantly suppressed tumor growth and increased antitumor activity of carboplatin in tumor xenografts. ER maleate treated tumor xenografts showed reduced PLK1 and Syk expression. Clinical investigations revealed overexpression of PLK1 and Syk in oral SCC patients that correlated with disease prognosis. Our in vitro and in vivo findings provide a strong rationale for pre-clinical efficacy of ER maleate as a novel anticancer agent and chemosensitizer of platinum drugs for OSCC. PMID:26934445

  14. Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review

    PubMed Central

    Firoz, T; Magee, LA; MacDonell, K; Payne, BA; Gordon, R; Vidler, M; von Dadelszen, P

    2014-01-01

    Background Pregnant and postpartum women with severe hypertension are at increased risk of stroke and require blood pressure (BP) reduction. Parenteral antihypertensives have been most commonly studied, but oral agents would be ideal for use in busy and resource-constrained settings. Objectives To review systematically, the effectiveness of oral antihypertensive agents for treatment of severe pregnancy/postpartum hypertension. Search strategy A systematic search of MEDLINE, EMBASE and the Cochrane Library was performed. Selection criteria Randomised controlled trials in pregnancy and postpartum with at least one arm consisting of a single oral antihypertensive agent to treat systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 110 mmHg. Data collection and analysis Cochrane RevMan 5.1 was used to calculate relative risk (RR) and weighted mean difference by random effects. Main results We identified 15 randomised controlled trials (915 women) in pregnancy and one postpartum trial. Most trials in pregnancy compared oral/sublingual nifedipine capsules (8–10 mg) with another agent, usually parenteral hydralazine or labetalol. Nifedipine achieved treatment success in most women, similar to hydralazine (84% with nifedipine; relative risk [RR] 1.07, 95% confidence interval [95% CI] 0.98–1.17) or labetalol (100% with nifedipine; RR 1.02, 95% CI 0.95–1.09). Less than 2% of women treated with nifedipine experienced hypotension. There were no differences in adverse maternal or fetal outcomes. Target BP was achieved ∼ 50% of the time with oral labetalol (100 mg) or methyldopa (250 mg) (47% labetelol versus 56% methyldopa; RR 0.85 95% CI 0.54–1.33). Conclusions Oral nifedipine, and possibly labetalol and methyldopa, are suitable options for treatment of severe hypertension in pregnancy/postpartum. PMID:24832366

  15. Comparison of laboratory and immediate diagnosis of coagulation for patients under oral anticoagulation therapy before dental surgery

    PubMed Central

    Kruse-Loesler, Birgit; Kelker, Matthias; Kleinheinz, Johannes

    2005-01-01

    Background Dental surgery can be carried out on patients under oral anticoagulation therapy by using haemostyptic measures. The aim of the study was a comparative analysis of coagulation by laboratory methods and immediate patient diagnosis on the day of the planned procedure. Methods On the planned day of treatment, diagnoses were carried out on 298 patients for Prothrombin Time (PT), the International Normalised Ratio (INR), and Partial Thromboplastin Time (PTT). The decision to proceed with treatment was made with an INR < 4.0 according to laboratory results. Results Planned treatment did not go ahead in 2.7% of cases. Postoperatively, 14.8% resulted in secondary bleeding, but were able to be treated as out-patients. 1.7% had to be treated as in-patients. The average error between the immediate diagnosis and the laboratory method: 95% confidence interval was -5.8 ± 15.2% for PT, -2.7 ± 17.9 s for PTT and 0.23 ± 0.80 for INR. The limits for concordance were 9.4 and -21.1% for PT, 15.2 and -20.5 s for PTT, and 1.03 and -0.57 for INR. Conclusion This study showed a clinically acceptable concordance between laboratory and immediate diagnosis for INR. Concordance for PT and PTT did not meet clinical requirements. For patients under oral anticoagulation therapy, patient INR diagnosis enabled optimisation of the treatment procedure when planning dental surgery. PMID:16316464

  16. Nanoparticle delivery of Wnt-1 siRNA enhances photodynamic therapy by inhibiting epithelial-mesenchymal transition for oral cancer.

    PubMed

    Ma, Chuan; Shi, Leilei; Huang, Yu; Shen, Lingyue; Peng, Hao; Zhu, Xinyuan; Zhou, Guoyu

    2017-02-28

    Activation of the epithelial to mesenchymal transition (EMT) in photodynamic therapy (PDT) can lead to the recurrence and progression of tumors. To enhance the effects of PDT, it is essential to inhibit the Wnt/β-catenin signaling pathway involved in EMT progression. Herein, we used polyethylene glycol-polyethyleneimine-chlorin e6 (PEG-PEI-Ce6) nanoparticles to efficiently deliver Wnt-1 small interfering RNA (siRNA) to the cytoplasm of KB cells (oral squamous cell carcinoma) that were subjected to PDT. Wnt-1 siRNA effectively inhibited the Wnt/β-catenin signaling pathway, reducing the expression of Wnt-1, β-catenin and vimentin that are crucial to the EMT. Combined with Wnt-1 siRNA, PEG-PEI-Ce6 nanoparticle mediated PDT inhibited cell growth and enhanced the cancer cell killing effect remarkably. Our results show the promise of combination therapy of PEG-PEI-Ce6 nanoparticles for delivery of Wnt-1 siRNA along with PDT in the treatment of oral cancer.

  17. Gene Therapy for Bone Defects in Oral and Maxillofacial Surgery: A Systematic Review and Meta-Analysis of Animal Studies.

    PubMed

    Fliefel, Riham; Kühnisch, Jan; Ehrenfeld, Michael; Otto, Sven

    2017-02-15

    Craniofacial bone defects are challenging problems for maxillofacial surgeons over the years. With the development of cell and molecular biology, gene therapy is a breaking new technology with the aim of regenerating tissues by acting as a delivery system for therapeutic genes in the craniofacial region rather than treating genetic disorders. A systematic review was conducted summarizing the articles reporting gene therapy in maxillofacial surgery to answer the question: Was gene therapy successfully applied to regenerate bone in the maxillofacial region? Electronic searching of online databases was performed in addition to hand searching of the references of included articles. No language or time restrictions were enforced. Meta-analysis was done to assess significant bone formation after delivery of gene material in the surgically induced maxillofacial defects. The search identified 2081 articles, of which 57 were included with 1726 animals. Bone morphogenetic proteins were commonly used proteins for gene therapy. Viral vectors were the universally used vectors. Sprague-Dawley rats were the frequently used animal model in experimental studies. The quality of the articles ranged from excellent to average. Meta-analysis results performed on 21 articles showed that defects favored bone formation by gene therapy. Funnel plot showed symmetry with the absence of publication bias. Gene therapy is on the top list of innovative strategies that developed in the last 10 years with the hope of developing a simple chair-side protocol in the near future, combining improvement of gene delivery as well as knowledge of the molecular basis of oral and maxillofacial structures.

  18. Acute Diarrhoea in Children: Determination of Duration Using a Combined Bismuth Hydroxide Gel and Oral Rehydration Solution Therapy vs. Oral Rehydration Solution

    PubMed Central

    Oviedo, Adriana; Díaz, Mirna; Valenzuela, María Laura; Vidal, Victoria; Racca, Liliana; Bottai, Hebe; Priore, Graciela; Peluffo, Graciela; Di Bartolomeo, Susana; Cabral, Graciela; Toca, María del Carmen

    2016-01-01

    Oral rehydration salt (ORS) treatment in young children with acute diarrhoea (AD) has contributed to decrease mortality associated with dehydration although effective strategies to reduce morbidity associated with this disease are required. The aim of this study was to evaluate the diarrhoea duration when using combined colloidal bismuth hydroxide gel (CBHG) and oral rehydration salt treatment compared with ORS therapy in children with AD. We designed a double-blind, randomised prospective study with treatment and control groups. Patients aged one to 12 years, with no prior pathology and with AD of less than 48 h were included. The Chi-squared and Mann-Whitney tests were used, as well as the Cox proportional hazards model and the Kaplan-Meier estimator. Patients were randomised into an ORS and CBHG treatment group and a control group for ORS plus placebo. (Average age: 3.2 years). The result of the post-treatment evaluation with respect to the average duration of AD was 25.5 h for the treated group vs. 41.5 h for the control group (p = 0.015). The average number of stools was 4.8 in the treated group and 8.2 in the control group (p = 0.032). We conclude that the use of CBHG plus ORS significantly reduced the duration of AD, the number of stools and the percentage of children with persistent AD after 24 h of treatment compared to the control group. AD remitted almost twice as fast in patients treated with CBHG and ORS compared to those who received ORS plus placebo. PMID:28009823

  19. Acute Diarrhoea in Children: Determination of Duration Using a Combined Bismuth Hydroxide Gel and Oral Rehydration Solution Therapy vs. Oral Rehydration Solution.

    PubMed

    Oviedo, Adriana; Díaz, Mirna; Valenzuela, María Laura; Vidal, Victoria; Racca, Liliana; Bottai, Hebe; Priore, Graciela; Peluffo, Graciela; Di Bartolomeo, Susana; Cabral, Graciela; Toca, María Del Carmen

    2016-12-21

    Oral rehydration salt (ORS) treatment in young children with acute diarrhoea (AD) has contributed to decrease mortality associated with dehydration although effective strategies to reduce morbidity associated with this disease are required. The aim of this study was to evaluate the diarrhoea duration when using combined colloidal bismuth hydroxide gel (CBHG) and oral rehydration salt treatment compared with ORS therapy in children with AD. We designed a double-blind, randomised prospective study with treatment and control groups. Patients aged one to 12 years, with no prior pathology and with AD of less than 48 h were included. The Chi-squared and Mann-Whitney tests were used, as well as the Cox proportional hazards model and the Kaplan-Meier estimator. Patients were randomised into an ORS and CBHG treatment group and a control group for ORS plus placebo. (Average age: 3.2 years). The result of the post-treatment evaluation with respect to the average duration of AD was 25.5 h for the treated group vs. 41.5 h for the control group (p = 0.015). The average number of stools was 4.8 in the treated group and 8.2 in the control group (p = 0.032). We conclude that the use of CBHG plus ORS significantly reduced the duration of AD, the number of stools and the percentage of children with persistent AD after 24 h of treatment compared to the control group. AD remitted almost twice as fast in patients treated with CBHG and ORS compared to those who received ORS plus placebo.

  20. The neurobiology of acetyl-L-carnitine.

    PubMed

    Traina, Giovanna

    2016-06-01

    A large body of evidence points to the positive effects of dietary supplementation of acetyl-L-carnitine (ALC). Its use has shown health benefits in neuroinflammation, which is a common denominator in a host of neurodegenerative diseases. ALC is the principal acetyl ester of L-Carnitine (LC), and it plays an essential role in intermediary metabolism, acting as a donor of acetyl groups and facilitating the transfer of fatty acids from cytosol to mitochondria during beta-oxidation. Dietary supplementation of ALC exerts neuroprotective, neurotrophic, antidepressive and analgesic effects in painful neuropathies. ALC also has antioxidant and anti-apoptotic activity. Moreover, ALC exhibits positive effects on mitochondrial metabolism, and shows promise in the treatment of aging and neurodegenerative pathologies by slowing the progression of mental deterioration. In addition, ALC plays neuromodulatory effects on both synaptic morphology and synaptic transmission. These effects are likely due to affects of ALC through modulation of gene expression on several targets in the central nervous system. Here, we review the current state of knowledge on effects of ALC in the nervous system.

  1. Effectiveness of oral health education versus nicotine replacement therapy for tobacco cessation- a parallel randomized clinical trial

    PubMed Central

    Saha, Sabyasachi; Krishna-Reddy, Vamsi; Mohd, Shafaat; Narang, Ridhi; Sood, Poonam

    2016-01-01

    Background India has millions of tobacco users. It is the leading cause of deaths due to oral cancer and hence needs effective strategies to curb it. Hence the aim of present study was to evaluate and compare the effectiveness of Oral Health Education (OHE) and Nicotine Replacement Therapy (NRT) in tobacco cessation. Material and Methods The clinical trial consisted of Manohar Lal Kapoor (MLK) factory workers (n= 40) giving history of tobacco consumption (smoking/smokeless) within past 30 days. They were randomized into OHE (n=20) and NRT (n=20) groups. Baseline evaluation (demographic, smoking/ smokeless behaviour) was done. Fagerstrom test was used for Nicotine Dependence (FTND) and to assess nicotine addiction level. Follow up was done at an interval of 1week, 2 weeks, 1 month, 2 months and 3 months to assess the reduction in the mean FTND score. “Nano-CheckTM Rapid Nicotine test” was used for the qualitative detection of cotinine in human urine. Appropriate statistical analysis was performed (Paired and Unpaired t test). Results In both OHE and NRT group there was a significant reduction (p< 0.00001) in mean Fagerstrom score at every follow up but when both the groups were compared mean Fagerstrom score reduction was more in NRT than OHE at all time interval though it was not statistically significant (p>0.05). Conclusions NRT is better than OHE when both the groups were compared. However, it was found that any intervention given to tobacco users either NRT or OHE is helpful for the patients in the process of quitting tobacco. Key words:Tobacco cessation, nicotine replacement therapy, oral health education, fagerstrom test, urine cotinine. PMID:26855709

  2. A study on the effect of cimetidine and L-carnitine on myoglobinuric acute kidney injury in male rats.

    PubMed

    Estaphan, Suzanne; Eissa, Hassan; Elattar, Samah; Rashed, Laila; Farouk, Mira

    2015-07-01

    Myoglobinuric acute renal failure is the most important life threatening complication of rhabdomyolysis. Iron, free radicals, nitric oxide and cytochrome p450 are involved in the pathogenesis of mARF. The aim of this study is to compare the effect of cimetidine, l-carnitine and both agents together on mARF in rats. Forty rats were divided into 5 groups; group I: control rats, group II: myoglobinuric ARF rats, group III: mARF rats received l-carnitine (200mg/kg, i.p.), group IV: mARF rats received cimetidine (150mg/kg i.p.) and group V: mARF rats received both agents together. 48h after glycerol injection, systolic blood pressure was measured. Urine and blood samples were collected to evaluate urine volume, GFR, BUN, creatinine, K, Na, serum creatine kinase, NO and glutathione levels. Kidney specimens were taken to investigate renal cytochrome p450 and for histological examinations. Cimetidine treatment significantly decreased creatinine, BUN, K, Na, SBP and creatine kinase and increased GFR and urine volume compared to group II. l-carnitine exerted similar changes except for the effect on K and GFR. NO was significantly decreased, while renal glutathione and cytochrome p450 were significantly increased in groups treated with l-carnitine or cimetidine as compared to group II. Combined treatment further improved renal functions, creatine kinase, oxidative stress parameters and SBP as compared to each therapy alone. The histological changes confirmed the biochemical findings. Cimetidine and l-carnitine have protective effects - almost equally - against mARF. Using both agents together, minimises the renal injury.

  3. Downregulation of Carnitine Acyl-Carnitine Translocase by miRNAs 132 and 212 Amplifies Glucose-Stimulated Insulin Secretion

    PubMed Central

    Soni, Mufaddal S.; Rabaglia, Mary E.; Bhatnagar, Sushant; Shang, Jin; Ilkayeva, Olga; Mynatt, Randall; Zhou, Yun-Ping; Schadt, Eric E.; Thornberry, Nancy A.; Muoio, Deborah M.; Keller, Mark P.

    2014-01-01

    We previously demonstrated that micro-RNAs (miRNAs) 132 and 212 are differentially upregulated in response to obesity in two mouse strains that differ in their susceptibility to obesity-induced diabetes. Here we show the overexpression of miRNAs 132 and 212 enhances insulin secretion (IS) in response to glucose and other secretagogues including nonfuel stimuli. We determined that carnitine acyl-carnitine translocase (CACT; Slc25a20) is a direct target of these miRNAs. CACT is responsible for transporting long-chain acyl-carnitines into the mitochondria for β-oxidation. Small interfering RNA–mediated knockdown of CACT in β-cells led to the accumulation of fatty acyl-carnitines and enhanced IS. The addition of long-chain fatty acyl-carnitines promoted IS from rat insulinoma β-cells (INS-1) as well as primary mouse islets. The effect on INS-1 cells was augmented in response to suppression of CACT. A nonhydrolyzable ether analog of palmitoyl-carnitine stimulated IS, showing that β-oxidation of palmitoyl-carnitine is not required for its stimulation of IS. These studies establish a link between miRNA-dependent regulation of CACT and fatty acyl-carnitine–mediated regulation of IS. PMID:24969106

  4. Decision-making about the use of non-vitamin K oral anticoagulant therapies for patients with atrial fibrillation.

    PubMed

    Eckman, Mark H

    2016-02-01

    Until recently, vitamin K antagonists, warfarin being the most commonly used agent in the United States, have been the only oral anticoagulant therapies available to prevent stroke in patients with atrial fibrillation (AF). In the last 5 years four new, non-vitamin K oral anticoagulants, the so-called NOACs or novel oral anticoagulants, have come to market and been approved by the Federal Drug Administration. Despite comparable if not superior efficacy in preventing AF-related stroke, and generally lower risks of major hemorrhage, particularly intracranial bleeding, the uptake of these agents has been slow. A number of barriers stand in the way of the more widespread use of these novel agents. Chief among them is concern about the lack of antidotes or reversal agents. Other concerns include the need for strict medication adherence, since missing even a single dose can lead to a non-anticoagulated state; out-of-pocket costs for patients; the lack of easily available laboratory tests to quantitatively assess the level of anticoagulant activity when these agents are being used; contraindications to use in patients with severe chronic kidney disease; and black-box warnings about the increased risk of thromboembolic events if these agents are discontinued prematurely. Fortunately, a number of reversal agents are in the pipeline. Three reversal agents, idarucizumab, andexanet alfa, and aripazine, have already progressed to human studies and show great promise as either antidotes for specific drugs or as universal reversal agents. The availability of these reversal agents will likely increase the clinical use of the non-vitamin K oral anticoagulants. In light of the many complex and nuanced issues surrounding the choice of an optimal anticoagulant for any AF patient, a patient-centered/shared decision-making approach will be useful.

  5. Chelation Therapy with Oral Solution of Deferiprone in Transfusional Iron-Overloaded Children with Hemoglobinopathies

    PubMed Central

    Makis, Alexandros; Chaliasos, Nikolaos; Alfantaki, Sapfo; Karagouni, Paraskevi; Siamopoulou, Antigone

    2013-01-01

    Iron overload in hemoglobinopathies is secondary to blood transfusions, chronic hemolysis, and increased iron absorption and leads to tissue injury requiring the early use of chelating agents. The available agents are parenteral deferoxamine and oral deferiprone and deferasirox. There are limited data on the safety and efficacy of deferiprone at a very young age. The aim of our study was the presentation of data regarding the use of oral solution of deferiprone in 9 children (mean age 6.5, range 2–10) with transfusion dependent hemoglobinopathies (6 beta thalassemia major, 1 thalassemia intermedia, and 2 sickle cell beta thalassemia). The mean duration of treatment was 21.5 months (range 15–31). All children received the oral solution without any problems of compliance. Adverse reactions were temporary abdominal discomfort and diarrhea (1 child), mild neutropenia (1 child) that resolved with no need of discontinuation of treatment, and transient arthralgia (1 child) that resolved spontaneously. The mean ferritin levels were significantly reduced at the end of 12 months (initial 2440 versus final 1420 μg/L, P < 0.001). This small study shows that oral solution of deferiprone was well tolerated by young children and its use was not associated with major safety concerns. Furthermore, it was effective in decreasing serum ferritin. PMID:24294523

  6. Efficacy of oral zinc therapy in epidermodysplasia verruciformis with squamous cell carcinoma.

    PubMed

    Sharma, Sudhanshu; Barman, Krishna Deb; Sarkar, Rashmi; Manjhi, Mukesh; Garg, Vijay Kumar

    2014-01-01

    Epidermodysplasia verruciformis (EV) is a rare, inherited disorder that predisposes patients to widespread human papillomavirus (HPV) infection and cutaneous squamous cell carcinomas. There is still no definitive therapeutic modality for EV. A 24 year old male patient with EV was treated with oral zinc sulphate, one of the cheapest and safe immuno-modulator available as therapeutic agent with satisfactory result.

  7. Multiple subcutaneous mycetomas caused by Pseudallescheria boydii: response to therapy with oral potassium iodide solution.

    PubMed

    Khan, Fida A; Hashmi, Shahrukh; Sarwari, Arif R

    2010-02-01

    We describe the case of a sixteen-year-old male who presented with multiple subcutaneous mycetomas proven on culture to be secondary to Pseudallescheria boydi., The lesions responded completely to oral potassium iodide solution. To our knowledge this has never been reported in humans.

  8. The effect of highly active antiretroviral therapy on the prevalence of oral manifestation in human immunodeficiency virus-infected patients in Karnataka, India

    PubMed Central

    Patil, Neelkant; Chaurasia, Vishwajit Rampratap; Babaji, Prashant; Ramesh, Dnsv; Jhamb, Kshitij; Sharma, Akanksha Manmohan

    2015-01-01

    Objectives: Acquired Immunodeficiency Syndrome (AIDS) is a highly lethal, progressively epidemic viral infection characterized by profound impairment of the immune system. Oral manifestations are common in Human Immunodeficiency Virus (HIV) infected AIDS patients, and are usually the first indicator of symptom and disease progression. The main objective of the current study was to compare the prevalence of oral manifestations in HIV patients on Highly Active Antiretroviral Therapy (HAART) with those, not on HAART therapies. Materials and Methods: A cross sectional study was conducted among 100 patients diagnosed as human immune virus sero-positive. These patients were divided equally into two groups (50 each); Group I patients on HAART and Group II patients who were not on HAART. Information regarding age, sex and cluster of differentiation 4 cell count was obtained from the medical records. Oral examination was done, and findings were recorded by using internationally accepted presumptive clinical criteria. Statistical analysis was performed using Chi-square statistical test. Results: The presence of oral manifestations was significantly decreased in subjects on HAART (32%) compared to those who are not on HAART (56%). The most common oral lesions detected in patients on HAART were increased oral hyper-pigmentation (14%), recurrent aphthous stomatitis (8%), non-specific ulcerations (4%), pseudo-membranous candidiasis (2%), periodontitis (2%) and xerostomia (2%), whereas in non HAART oral hyperpigmentation (10%), pseudo-membranous candidiasis (8%), angular cheilitis (4%), and erythematous candidiasis (4%) and Periodontitis (14%) were more prevalent. Conclusion: The number and severity of oral manifestation decreased, and even there was a change in the type of oral manifestations on HAART, which may be because of the improvement in immunity gained by the therapy. PMID:25713484

  9. Quality Assessment of Systematic Reviews on the Efficacy of Oral Appliance Therapy for Adult and Pediatric Sleep-Disordered Breathing

    PubMed Central

    Al-Jewair, Thikriat S.; Gaffar, Balgis O.; Flores-Mir, Carlos

    2016-01-01

    Study Objectives: To assess the methodological quality of published systematic reviews (SRs) and meta-analyses (MAs) about the efficacy of oral appliances (OA) in the management of adult and pediatric sleep-disordered breathing (SDB). Methods: SRs/MAs that evaluated the efficacy of OA therapy on the treatment of SDB in human subjects of all age groups were sought. Multiple electronic databases were searched for articles published in any language from the database's inception until January 2016. Two reviewers independently selected and then assessed the methodological quality of the studies using the Assessment of Multiple Systematic Reviews (AMSTAR) measurement tool. Results: Thirteen reviews on adult SDB were included (2 SRs and 11 SRs with MAs). Of those, seven were medium quality and six were high quality. Only four reviews were included on pediatric SDB (3 SRs and 1 SR with MA). Three of these were of high quality and one was medium quality. The identified limitations in the included reviews were failing to reference the excluded studies or describe reasons for exclusion, lack of applying valid criteria to assess the quality of included studies, lack of publication bias assessment, and absence of conflicts of interest reporting. Conclusions: Overall, SRs/MAs on OA therapy for adult and pediatric SDB were conducted with acceptable methodological quality. High AMSTAR scores should not be extrapolated as a proxy of the methodological quality of the included evidence. There is a need for more primary studies and then that information can be used to be synthesized through SRs on pediatric SDB. Citation: Al-Jewair TS, Gaffar BO, Flores-Mir C. Quality assessment of systematic reviews on the efficacy of oral appliance therapy for adult and pediatric sleep-disordered breathing. J Clin Sleep Med 2016;12(8):1175–1183. PMID:27397656

  10. Diagnosis and indications for low-intensity laser therapy of the pathology of the oral cavity mucosa of patients with hematologic and gastroenteric diseases

    NASA Astrophysics Data System (ADS)

    Kunin, Anatoly A.; Minakov, E. V.; Sutscenko, A. V.; Vornovsky, V. A.; Dunaeva, S. V.; Stepanov, Nicolay N.; Shumilovitch, Bogdan R.

    1996-11-01

    In the recent years low intensity laser irradiation is made use of in stomatology with the view of treating numerous diseases of the oral cavity mucosa and parodontium. The oral cavity mucosa lesions caused by the internal organs diseases, especially those of blood and the gastroenteric tract, constitute a particular group. Such diseases are usually manifested by an inflammation, erosions, ulcers, hemorrhages. An abundant microflora of the oral cavity and diminished immunity of the patients contribute to the possibility of septicaemia development. Laser therapy of the oral cavity mucosa lesions according to strictly defined indications promotes rapid healing of ulcers, arresting the oral cavity mucosa inflammation, providing a reduction in bleeding and presents a safe prophylactic means of stomatogenic sepsis.

  11. Metabolic effects induced by L-carnitine and propionyl-L-carnitine in human hypoxic muscle tissue during exercise.

    PubMed

    Corbucci, G G; Montanari, G; Mancinelli, G; D'Iddio, S

    1990-01-01

    An experimental model was developed to investigate some metabolic effects of strenuous exercise in hypoxic muscle tissue of human volunteers. The incidence of carnitine supplementation was studied, assuming as marker the thiobarbituric acid reaction products analysed in plasma samples collected during the course of the protocol programme. Propionyl-L-carnitine appears to antagonize in a significant degree the damaging effects of muscle fatigue combined with hypoxic status. Under these conditions the detoxifying role played by propionyl-L-carnitine, previously reported in various tissues and in other pathological conditions, appears to be relevant, although further studies are needed to elucidate the pharmacodynamics of this molecule.

  12. Chronic invasive sinus and intracerebral aspergillosis controlled by combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution.

    PubMed

    Ogawa, Taku; Matsumoto, Kana; Tsujimoto, Kazunori; Hishiya, Naokuni; Yamada, Yutaka; Uno, Kenji; Kasahara, Kei; Maeda, Koichi; Nario, Kazuhiko; Mikasa, Keiichi; Morita, Kunihiko

    2015-02-01

    Chronic invasive aspergillosis of the sinus is frequently fatal in the absence of early surgical and chemotherapeutic intervention because of its invasion of vascular tissue. We attempted to control a case of inoperable invasive aspergillosis of the sinus with micafungin and itraconazole oral solution. We prescribed a daily oral dose of 400 mg of itraconazole, which is twice the usual dose, and monitored the serum concentration of the drug. Finally, we were able to control the spread of the lesion. This case indicates that combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution is an alternative treatment strategy for inoperable invasive aspergillosis of the sinus.

  13. Manual de Adiestramiento sobre Terapia de Rehidratacion Oral y Control de las Enfermedades Diarreicas (Oral Rehydration Therapy and the Control of Diarrheal Diseases). Training for Development. Peace Corps Information Collection & Exchange Training Manual No. T-53.

    ERIC Educational Resources Information Center

    Clark, Mari; And Others

    This Spanish-language manual was developed to train Peace Corps volunteers and other community health workers in Spanish-speaking countries in oral rehydration therapy (ORT) and the control of diarrheal diseases. Using a competency-based format, the manual contains three training modules (organized in seven sessions) that focus on interrelated…

  14. Familial combined deficiency of muscle carnitine and carnitine palmityl transferase (CPT).

    PubMed

    Skard Heier, M; Dietrichson, P; Landaas, S

    1986-12-01

    Two patients, brother and sister, aged 19 and 16, with combined, partial deficiency of carnitine palmityltransferase (CPT) are reported. Both patients had recurrent exercise-related myoglobinuria. The brother had also experienced an episode of transient renal failure associated with myoglobinuria. Both had elevated CK and myoglobin in plasma between attacks. There was a normal production of lactate in ischaemic forearm exercise, but elevated levels of NH3, resulting in an increased NH3/lactate ratio; 48-h fasting caused no significant changes in cholesterol, triglycerides or glucose, no rise of CK, and a normal ketogenic response, indicating no hepatic enzyme deficiency. Muscle biopsy showed slight changes of myopathy in both patients, with scattered atrophic fibres, but no lipid accumulation or other specific changes. Biochemical analysis of muscle tissue revealed a reduction of carnitine to 48% and 40% and a reduction of CPT to 55% and 59% of normal values, which is similar to the findings in the only previous report of combined partial carnitine and CPT deficiency. The heterogeneity of the laboratory findings in CPT deficiencies and the value of the various diagnostic procedures in metabolic myopathies are discussed.

  15. Free carnitine and acylcarnitine levels in sera of alcoholics.

    PubMed

    Alonso de la Peña, C; Rozas, I; Alvarez-Prechous, A; Pardiñas, M C; Paz, J M; Rodriguez-Segade, S

    1990-08-01

    We report the free, acyl-, and total carnitine contents of 49 clinically healthy volunteers and 167 chronic alcoholics with various clinically and/or anatomopathologically identified degrees of hepatic affection. There was a gradual upward trend in carnitine levels as the degree of hepatic affection increased. In cirrhotic patients, both free and acylcarnitine levels were significantly higher than normal, but there was no systematic hypercarnitinemia in other stages of alcoholism; on the contrary, noncirrhotic alcoholic patients accounted for 82.6% of all hypocarnitinemia cases. Hypercarnitinemia among cirrhotic alcoholics was due chiefly to increased free carnitine concentrations. Acylcarnitine levels in patients with hepatic steatosis were significantly higher than those in normal subjects (P less than 0.001), but there were no other statistically significant differences in either acyl- or free carnitine levels between normals on the one hand and, on the other, patients with hepatic steatosis, alcoholic hepatitis, slight hepatopathy, or chronic hepatopathy without portal hypertension.

  16. Hepatotoxicity in rat following administration of valproic acid: effect of L-carnitine supplementation.

    PubMed

    Sugimoto, T; Araki, A; Nishida, N; Sakane, Y; Woo, M; Takeuchi, T; Kobayashi, Y

    1987-01-01

    The effect of prolonged administration (7 days) of valproate (VPA, 500 mg/kg/day), or VPA (500 mg/kg/day) with L-carnitine (200 mg/kg/day) on blood carnitine levels and the appearance of liver mitochondria were assessed in the rat. VPA-treated rats showed hypocarnitinemia and enlarged mitochondria when compared with saline-injected control rats. In rats treated with both VPA and L-carnitine, serum and liver carnitine levels were increased by the L-carnitine supplement and the liver mitochondria were not enlarged. L-Carnitine supplement in VPA-medicated patients seems to prevent hepatotoxicity, especially mitochondrial dysfunction.

  17. Muscle contraction increases carnitine uptake via translocation of OCTN2

    SciTech Connect

    Furuichi, Yasuro; Sugiura, Tomoko; Kato, Yukio; Takakura, Hisashi; Hanai, Yoshiteru; Hashimoto, Takeshi; Masuda, Kazumi

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer Muscle contraction augmented carnitine uptake into rat hindlimb muscles. Black-Right-Pointing-Pointer An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. Black-Right-Pointing-Pointer Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. Black-Right-Pointing-Pointer OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL{sub uptake}) of L-[{sup 3}H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL{sub uptake} of [{sup 14}C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL{sub uptake} of L-[{sup 3}H]carnitine in the contracting muscles increased 1.4-1.7-fold as compared to that in the contralateral resting muscles (p < 0.05). The CL{sub uptake} of [{sup 14}C]IAP was much higher than that of L-[{sup 3}H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly

  18. Boron neutron capture therapy for recurrent oral cancer and metastasis of cervical lymph node.

    PubMed

    Kimura, Y; Ariyoshi, Y; Shimahara, M; Miyatake, S; Kawabata, S; Ono, K; Suzuki, M; Maruhashi, A

    2009-07-01

    We treated 6 patients with recurrent oral cancer and metastasis to the cervical lymph nodes after conventional treatments in 5 and non-conventional in 1 using BNCT, and herein report our results. The clinical response in our patients ranged from CR to PD. In 5 cases, spontaneous pain decreased immediately after BNCT. Three of the 6 are alive at the time of writing and we found that BNCT contributed to QOL improvement in all.

  19. The Use of Oral Disease-Modifying Therapies in Multiple Sclerosis.

    PubMed

    Kretzschmar, Benedikt; Pellkofer, Hannah; Weber, Martin S

    2016-04-01

    Three oral disease-modifying drugs-fingolimod, teriflunomide, and dimethyl fumarate (DMF)-are available for treatment of relapsing forms of multiple sclerosis (MS). All three agents were approved in the last decade, primarily on the basis of a moderate to substantial reduction in the occurrence of MS relapses and central nervous system lesion formation detected by MRI. In the trials leading to approval, the first oral disease-modifying drug, fingolimod, reduced the annualized relapse rate (ARR) from 0.40 in placebo-treated patients to 0.18 (FREEDOMS) and from 0.33 in patients treated with interferon β1a intramuscularly to 0.16 (TRANSFORMS). Teriflunomide, approved on the basis of the two placebo-controlled trials TEMSO and TOWER, demonstrated a reduction in the ARR from 0.54 to 0.37 and from 0.50 to 0.32 respectively. The latest oral MS medication, approved in 2014, is DMF, which had been used in a different formulation for treatment of psoriasis for decades. In the 2-year DEFINE study, the proportion of patients with a relapse was reduced to 27 %, compared with 46 % in placebo arm, whereas in the CONFIRM trial, the ARR was reduced from 0.40 (placebo) to 0.22 in the DMF-treated group of patients. In this review, we will elucidate the mechanisms of action of these three medications and compare their efficacy, safety, and tolerability as a practical guideline for their use. We will further discuss effects other than relapse reduction these small molecules may exert, including potential activities within the central nervous system, and briefly summarize emerging data on new oral MS drugs in clinical development.

  20. Oral Solubilized Ursodeoxycholic Acid Therapy in Amyotrophic Lateral Sclerosis: A Randomized Cross-Over Trial

    PubMed Central

    Min, Ju-Hong; Hong, Yoon-Ho; Sung, Jung-Joon; Kim, Sung-Min; Lee, Jung Bok

    2012-01-01

    To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial. PMID:22323869

  1. Oral drug therapy in elderly with dysphagia: between a rock and a hard place!

    PubMed

    Logrippo, Serena; Ricci, Giovanna; Sestili, Matteo; Cespi, Marco; Ferrara, Letizia; Palmieri, Giovanni F; Ganzetti, Roberta; Bonacucina, Giulia; Blasi, Paolo

    2017-01-01

    Demographic indicators forecast that by 2050, the elderly will account for about one-third of the global population. Geriatric patients require a large number of medicines, and in most cases, these products are administered as solid oral solid dosage forms, as they are by far the most common formulations on the market. However, this population tends to suffer difficulties with swallowing. Caregivers in hospital geriatric units routinely compound in solid oral dosage forms for dysphagic patients by crushing the tablets or opening the capsules to facilitate administration. The manipulation of a tablet or a capsule, if not clearly indicated in the product labeling, is an off-label use of the medicine, and must be supported by documented scientific evidence and requires the patient's informed consent. Compounding of marketed products has been recognized as being responsible for an increased number of adverse events and medical errors. Since extemporaneous compounding is the rule and not the exception in geriatrics departments, the seriousness and scope of issues caused by this daily practice are probably underestimated. In this article, the potential problems associated with the manipulation of authorized solid oral dosage forms are discussed.

  2. Oral and parenteral therapy with saperconazole (R 66905) of invasive aspergillosis in normal and immunocompromised animals.

    PubMed Central

    Van Cutsem, J; Van Gerven, F; Janssen, P A

    1989-01-01

    Saperconazole (R 66905) is a broad-spectrum antifungal triazole with potent in vitro activity against Aspergillus spp. A total of 279 strains were tested in brain heart infusion broth. Development of the Aspergillus spp. was completely inhibited at 0.1 and 1 microgram of saperconazole per ml for 80.3 and 99.6% of the strains, respectively. Normal and immunocompromised guinea pigs were infected intravenously with Aspergillus fumigatus and treated orally, intravenously, or intraperitoneally with saperconazole or intraperitoneally with amphotericin B. Leukopenia, neutropenia, lymphocytosis, and monocytosis were obtained with mechlorethamine hydrochloride; leukopenia, neutrophilia, and lymphopenia were obtained with cyclophosphamide. Saperconazole was dissolved for oral treatment in polyethylene glycol and for parenteral treatment in cyclodextrins. Amphotericin B was given parenterally as Fungizone (E.R. Squibb & Sons). Treatment was given once daily for 14 days. An early starting treatment was efficacious, but the activity of saperconazole was maintained even when the onset of the treatment was delayed to the moribund state. The activity of saperconazole was not altered in immunocompromised animals. Saperconazole was clearly superior to amphotericin B and free of side effects. The oral and parenteral formulations of saperconazole were equipotent. The systemic activity of saperconazole in guinea pigs was confirmed in invasive aspergillosis in pigeons. PMID:2619273

  3. [Oral hygiene, prophylaxis and therapy in patients with inflammatory rheumatic diseases].

    PubMed

    Willershausen, B; Kasaj, A

    2010-03-01

    Inflammatory disorders of the periodontium are often associated with chronic systemic diseases, which can demonstrate a reciprocal influence. Within the adult population at present, 74% of younger adults and 88% of older individuals require periodontal treatment. Due to inflammatory processes, patients with rheumatoid arthritis or other chronic polyarthritides frequently suffer from pain in the temporomandibular joint and, since finger mobility is often limited, their ability to perform oral hygiene measures is impeded. However, diligent and constant oral hygiene is of crucial importance both for maintaining a healthy periodontium and to prevent the development of caries. For their daily dental care, these patients should favor the use of electric toothbrushes, products for interdental cleaning and mouth rinses. The dentist should be informed immediately about increased and constant gingival bleeding, gingival hyperplasia, loosening or migration of teeth associated with gingival recession or other irritations in the oral cavity. Professional dental cleaning should be routinely performed at 3- to 6-month intervals in order to prevent an increase in the risk for periodontal disease.

  4. Oral drug therapy in elderly with dysphagia: between a rock and a hard place!

    PubMed Central

    Logrippo, Serena; Ricci, Giovanna; Sestili, Matteo; Cespi, Marco; Ferrara, Letizia; Palmieri, Giovanni F; Ganzetti, Roberta; Bonacucina, Giulia; Blasi, Paolo

    2017-01-01

    Demographic indicators forecast that by 2050, the elderly will account for about one-third of the global population. Geriatric patients require a large number of medicines, and in most cases, these products are administered as solid oral solid dosage forms, as they are by far the most common formulations on the market. However, this population tends to suffer difficulties with swallowing. Caregivers in hospital geriatric units routinely compound in solid oral dosage forms for dysphagic patients by crushing the tablets or opening the capsules to facilitate administration. The manipulation of a tablet or a capsule, if not clearly indicated in the product labeling, is an off-label use of the medicine, and must be supported by documented scientific evidence and requires the patient’s informed consent. Compounding of marketed products has been recognized as being responsible for an increased number of adverse events and medical errors. Since extemporaneous compounding is the rule and not the exception in geriatrics departments, the seriousness and scope of issues caused by this daily practice are probably underestimated. In this article, the potential problems associated with the manipulation of authorized solid oral dosage forms are discussed. PMID:28203065

  5. Recommendations for improving adherence to type 2 diabetes mellitus therapy--focus on optimizing oral and non-insulin therapies.

    PubMed

    Nau, David P

    2012-04-01

    Adherence to therapy in patients with type 2 diabetes mellitus is contingent upon a number of variables, including variables specific to the patient, to the provider, and to the treatment. While treatment selection will involve consideration to maximize effectiveness and minimize side effects, the physician must also take into account the priorities and preferences of each individual patient. For some patients, the risk of weight gain may exert a significant influence on adherence, while for others the risk of hypoglycemia or the cost of medications may be more important factors. It is incumbent upon physicians to discuss these issues with patients and to develop a patient-centric treatment plan to achieve optimal adherence and therapeutic outcomes. The nature of the clinical setting can also influence the likelihood of patient adherence to treatment. A multidisciplinary team approach to diabetes management has been shown to improve outcomes and to have a neutral or beneficial effect on costs. The treatment plan itself plays an additional role in the likelihood of a patient adhering to treatment. Less complex treatment regimens with fewer pills are associated with higher rates of adherence, as are fixed-dose combinations for those patients requiring combination therapy. Frequency and timing of dosing are also important aspects of adherence, as once-daily dosing is associated with higher rates of adherence than twice-daily dosing for anti-hyperglycemic medications.

  6. Oral Phage Therapy of Acute Bacterial Diarrhea With Two Coliphage Preparations: A Randomized Trial in Children From Bangladesh

    PubMed Central

    Sarker, Shafiqul Alam; Sultana, Shamima; Reuteler, Gloria; Moine, Deborah; Descombes, Patrick; Charton, Florence; Bourdin, Gilles; McCallin, Shawna; Ngom-Bru, Catherine; Neville, Tara; Akter, Mahmuda; Huq, Sayeeda; Qadri, Firdausi; Talukdar, Kaisar; Kassam, Mohamed; Delley, Michèle; Loiseau, Chloe; Deng, Ying; El Aidy, Sahar; Berger, Bernard; Brüssow, Harald

    2016-01-01

    Background Antibiotic resistance is rising in important bacterial pathogens. Phage therapy (PT), the use of bacterial viruses infecting the pathogen in a species-specific way, is a potential alternative. Method T4-like coliphages or a commercial Russian coliphage product or placebo was orally given over 4 days to Bangladeshi children hospitalized with acute bacterial diarrhea. Safety of oral phage was assessed clinically and by functional tests; coliphage and Escherichia coli titers and enteropathogens were determined in stool and quantitative diarrhea parameters (stool output, stool frequency) were measured. Stool microbiota was studied by 16S rRNA gene sequencing; the genomes of four fecal Streptococcus isolates were sequenced. Findings No adverse events attributable to oral phage application were observed (primary safety outcome). Fecal coliphage was increased in treated over control children, but the titers did not show substantial intestinal phage replication (secondary microbiology outcome). 60% of the children suffered from a microbiologically proven E. coli diarrhea; the most frequent diagnosis was ETEC infections. Bacterial co-pathogens were also detected. Half of the patients contained phage-susceptible E. coli colonies in the stool. E. coli represented less than 5% of fecal bacteria. Stool ETEC titers showed only a short-lived peak and were otherwise close to the replication threshold determined for T4 phage in vitro. An interim analysis after the enrollment of 120 patients showed no amelioration in quantitative diarrhea parameter by PT over standard care (tertiary clinical outcome). Stool microbiota was characterized by an overgrowth with Streptococcus belonging to the Streptococcus gallolyticus and Streptococcus salivarius species groups, their abundance correlated with quantitative diarrhea outcome, but genome sequencing did not identify virulence genes. Interpretation Oral coliphages showed a safe gut transit in children, but failed to achieve

  7. Monitoring oral iron therapy with protoporphyrin/heme ratios in pregnant women.

    PubMed

    Madan, N; Prasannaraj, P; Rusia, U; Sundaram, K R; Nath, L M; Sood, S K

    1999-06-01

    Assessment of the efficacy of iron therapy has usually been done in populations/patients by monitoring changes in hemoglobin concentration, serum iron, percent transferrin saturation, and serum ferritin. In this study the protoporphyrin heme (P/H) ratio (a measure of free erythrocyte protoporphyrin) was measured before and after iron therapy in three groups of pregnant women, who received 60 mg (group A), 120 mg (group B), and 240 mg (group C) of elemental iron with folic acid (0.5 mg) per day for a period of 12 weeks, to evaluate its efficacy to monitor iron therapy. The three groups were comparable regarding the initial mean Hb concentration and serum ferritin levels. The initial mean P/H ratios were markedly elevated in all three groups and were different in the three groups, being highest in group A (113.2+/-92.6), intermediate in group B (87.5+/-62.5), and lowest in group C (69.8+/-43.3). The initial P/H ratio was significantly higher in group A than in group C (p<0.05). This probably affected the efficacy of iron therapy in the three groups. The P/H ratio decreased significantly in each of the three groups after iron therapy (A and B: p<0.001; C p<0.01). Mean Hb concentration and serum ferritin increased in all three groups post therapy; however, the magnitude of change in P/H ratio in all three groups was much greater. This indicated that the predominant contributory factor for anemia was iron deficiency in this group of pregnant women. Serum iron and percent transferrin saturation are difficult to interpret in our population, as iron is freely available over the counter and is prescribed as soon as anemia is detected in patients; therefore, the reduction in P/H ratio may be used to monitor response to iron therapy in population groups.

  8. [Prevalence of oral lesions by Candida sp.: Their varieties and serotypes in a population of patients with AIDS under a highly active antiretroviral therapy.].

    PubMed

    Ceballos Salobreña, A; Gaitán Cepeda, L A; Ruesga, M T; Ceballos García, L; Quindós, G

    1998-09-01

    The aim of this study has been to determine the prevalence of oral candidiasis and oral Candida carriers in an AIDS population under highly active antiretroviral therapy. Eighty-six AIDS patients treated with an antiretroviral combination (indinavir o ritonavir o saquinavir + zidovudine [AZT] + lamivudine [3TC]). Patients were grouped attending the predisposing factors for HIV infection in: intravenous drug users (IDU), heterosexuals, homosexuals, patients using hematological products or having unknown factors. Oral cavity was examined and an oral specimen was inoculated in a chromogenic culture medium (Albicans ID, bioMérieux, France). The prevalence of oral Candida lesions was 30.2% and Candida was isolated from 54.7% of patients. The predominant species was C. albicans serotype A in all the groups with the exception of homosexual patients, were C. albicans serotype B was the predominant. The IDU group showed the higher prevalence of Candida lesions and oral yeasts colonization, followed by the group of heterosexuals and homosexuals. An association was found between the presence of lesions and/or Candida spp. and the clinical stage or the viral concentration. The species Candida dubliniensis was isolated in the oral samples of two patients with candidosis and in two individuals without oral candidosis. The finding of this species in Spanish patients can be added to the data obtained in epidemiological studies in other countries.

  9. The effect of hyperbaric oxygen therapy on quality of life in oral and oropharyngeal cancer patients treated with radiotherapy.

    PubMed

    Gerlach, N L; Barkhuysen, R; Kaanders, J H A M; Janssens, G O R J; Sterk, W; Merkx, M A W

    2008-03-01

    Radiotherapy is used in the setting of curative treatment for head and neck cancer. Xerostomia and related problems occur when major salivary glands are included in the irradiation fields. This reduces quality of life (QOL). Hyperbaric oxygen therapy (HBOT) is a well accepted treatment or prevention modality for osteoradionecrosis of the jawbones and soft-tissue necrosis. It is unknown if and to what extent HBOT influences xerostomia and xerostomia-related QOL. To address this, a prospective study was conducted. Twenty-one patients who underwent radiotherapy for an oral or oropharyngeal carcinoma completed a European Organization for Research and Treatment of Cancer QOL questionnaire before HBOT, as part of the treatment/prevention of osteoradionecrosis, and 1 and 2 years after HBOT. Swallowing-related problems significantly decreased in time, and there was a reported subjective increase in saliva quantity and an improvement in sense of taste. The results suggest that HBOT may positively influence these long-term radiotherapy sequelae.

  10. Antibiotic Susceptibilities of Bacteria Isolated within the Oral Flora of Florida Blacktip Sharks: Guidance for Empiric Antibiotic Therapy

    PubMed Central

    Unger, Nathan R.; Ritter, Erich; Borrego, Robert; Goodman, Jay; Osiyemi, Olayemi O.

    2014-01-01

    Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (±11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (±1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline. PMID:25110948

  11. Antibiotic susceptibilities of bacteria isolated within the oral flora of Florida blacktip sharks: guidance for empiric antibiotic therapy.

    PubMed

    Unger, Nathan R; Ritter, Erich; Borrego, Robert; Goodman, Jay; Osiyemi, Olayemi O

    2014-01-01

    Sharks possess a variety of pathogenic bacteria in their oral cavity that may potentially be transferred into humans during a bite. The aim of the presented study focused on the identification of the bacteria present in the mouths of live blacktip sharks, Carcharhinus limbatus, and the extent that these bacteria possess multi-drug resistance. Swabs were taken from the oral cavity of nineteen live blacktip sharks, which were subsequently released. The average fork length was 146 cm (±11), suggesting the blacktip sharks were mature adults at least 8 years old. All swabs underwent standard microbiological work-up with identification of organisms and reporting of antibiotic susceptibilities using an automated microbiology system. The oral samples revealed an average of 2.72 (±1.4) bacterial isolates per shark. Gram-negative bacteria, making up 61% of all bacterial isolates, were significantly (p<0.001) more common than gram-positive bacteria (39%). The most common organisms were Vibrio spp. (28%), various coagulase-negative Staphylococcus spp. (16%), and Pasteurella spp. (12%). The overall resistance rate was 12% for all antibiotics tested with nearly 43% of bacteria resistant to at least one antibiotic. Multi-drug resistance was seen in 4% of bacteria. No association between shark gender or fork length with bacterial density or antibiotic resistance was observed. Antibiotics with the highest overall susceptibility rates included fluoroquinolones, 3rd generation cephalosporins and sulfamethoxazole/trimethoprim. Recommended empiric antimicrobial therapy for adult blacktip shark bites should encompass either a fluoroquinolone or combination of a 3rd generation cephalosporin plus doxycycline.

  12. A fusion protein derived from plants holds promising potential as a new oral therapy for type 2 diabetes.

    PubMed

    Choi, Jeehye; Diao, Hong; Feng, Zhi-Chao; Lau, Arthur; Wang, Rennian; Jevnikar, Anthony M; Ma, Shengwu

    2014-05-01

    The incretin hormone glucagon-like peptide-1 (GLP-1) is recognized as a promising candidate for the treatment of type 2 diabetes (T2D), with one of its mimetics, exenatide (synthetic exendin-4) having already been licensed for clinical use. We seek to further improve the therapeutic efficacy of exendin-4 (Ex-4) using innovative fusion protein technology. Here, we report the production in plants a fusion protein containing Ex-4 coupled with human transferrin (Ex-4-Tf) and its characterization. We demonstrated that plant-made Ex-4-Tf retained the activity of both proteins. In particular, the fusion protein stimulated insulin release from pancreatic β-cells, promoted β-cell proliferation, stimulated differentiation of pancreatic precursor cells into insulin-producing cells, retained the ability to internalize into human intestinal cells and resisted stomach acid and proteolytic enzymes. Importantly, oral administration of partially purified Ex-4-Tf significantly improved glucose tolerance, whereas commercial Ex-4 administered by the same oral route failed to show any significant improvement in glucose tolerance in mice. Furthermore, intraperitoneal (IP) injection of Ex-4-Tf showed a beneficial effect in mice similar to IP-injected Ex-4. We also showed that plants provide a robust system for the expression of Ex-4-Tf, producing up to 37 μg prEx-4-Tf/g fresh leaf weight in transgenic tobacco and 137 μg prEx-4-Tf/g freshweight in transiently transformed leaves of N. benthamiana. These results indicate that Ex-4-Tf holds substantial promise as a new oral therapy for type 2 diabetes. The production of prEx-4-Tf in plants may offer a convenient and cost-effective method to deliver the antidiabetic medicine in partially processed plant food products.

  13. Orally Administered P22 Phage Tailspike Protein Reduces Salmonella Colonization in Chickens: Prospects of a Novel Therapy against Bacterial Infections

    PubMed Central

    Waseh, Shakeeba; Hanifi-Moghaddam, Pejman; Coleman, Russell; Masotti, Michael; Ryan, Shannon; Foss, Mary; MacKenzie, Roger; Henry, Matthew; Szymanski, Christine M.; Tanha, Jamshid

    2010-01-01

    One of the major causes of morbidity and mortality in man and economically important animals is bacterial infections of the gastrointestinal (GI) tract. The emergence of difficult-to-treat infections, primarily caused by antibiotic resistant bacteria, demands for alternatives to antibiotic therapy. Currently, one of the emerging therapeutic alternatives is the use of lytic bacteriophages. In an effort to exploit the target specificity and therapeutic potential of bacteriophages, we examined the utility of bacteriophage tailspike proteins (Tsps). Among the best-characterized Tsps is that from the Podoviridae P22 bacteriophage, which recognizes the lipopolysaccharides of Salmonella enterica serovar Typhimurium. In this study, we utilized a truncated, functionally equivalent version of the P22 tailspike protein, P22sTsp, as a prototype to demonstrate the therapeutic potential of Tsps in the GI tract of chickens. Bacterial agglutination assays showed that P22sTsp was capable of agglutinating S. Typhimurium at levels similar to antibodies and incubating the Tsp with chicken GI fluids showed no proteolytic activity against the Tsp. Testing P22sTsp against the three major GI proteases showed that P22sTsp was resistant to trypsin and partially to chymotrypsin, but sensitive to pepsin. However, in formulated form for oral administration, P22sTsp was resistant to all three proteases. When administered orally to chickens, P22sTsp significantly reduced Salmonella colonization in the gut and its further penetration into internal organs. In in vitro assays, P22sTsp effectively retarded Salmonella motility, a factor implicated in bacterial colonization and invasion, suggesting that the in vivo decolonization ability of P22sTsp may, at least in part, be due to its ability to interfere with motility… Our findings show promise in terms of opening novel Tsp-based oral therapeutic approaches against bacterial infections in production animals and potentially in humans. PMID:21124920

  14. Optimizing the use of oral anticoagulant therapy for atrial fibrilation in primary care: a pharmacist-led intervention.

    PubMed

    Virdee, Mandeep S; Stewart, Derek

    2017-02-01

    Background Updated evidence-based guidelines for the management of atrial fibrillation (AF) necessitate patient review, particularly with respect to oral anticoagulants, to ensure maximum health gain around stroke prophylaxis. Objective To quantify the level of anticoagulation utilisation in patients with a CHA2DS2-VASc ≥1/≥2 (male/female) according to evidence-based guidelines and to assess the impact of a pharmacist-led intervention to optimise therapy. Setting Fifteen general medical practices in Liverpool, North-West England with a practice population of 99,129. Method GRASP-AF software was employed to interrogate patient electronic medical records to identify and risk stratify AF patients (using CHA2DS2-VASc). A pharmacist then reviewed the medical records of those of patients not anticoagulated and with a CHA2DS2-VASc ≥1/≥2 (male/female). Recommendations were discussed with a general practitioner (GP) and those patients in whom the need for anticoagulation was agreed were invited for a consultation with either the pharmacist or GP and therapy optimised where appropriate. The GPs were responsible for managing those patients referred for diagnosis confirmation or further specialist opinion. Main outcome measure Proportion of patients eligible/not eligible for anticoagulation; proportions in whom anticoagulants initiated, refused, antiplatelets discontinued. Results Five hundred and twenty-three patients (31% of patients identified with AF and a CHA2DS2-VASc ≥1/≥2 (male/female)) were not receiving an anticoagulant (26 subsequently died or left the practice leaving 497). Three hundred and eighty-two (77%) pharmacist recommendations to a GP were agreed without modification. Following outcomes of diagnostic investigations and specialist referrals, 202 (41%) patients were candidates for anticoagulation, 251 (51%) were not eligible for anticoagulation, 103 (21%) were anticoagulated (56 warfarin, 47 DOAC). Conclusion A pharmacist-led intervention re

  15. Oral antiplatelet therapy for atherothrombotic disease: overview of current and emerging treatment options

    PubMed Central

    Fintel, Dan J

    2012-01-01

    Clinical presentations of atherothrombotic vascular disease, such as acute coronary syndromes, ischemic stroke or transient ischemic attack, and symptomatic peripheral arterial disease, are major causes of morbidity and mortality worldwide. Platelet activation and aggregation play a seminal role in the arterial thrombus formation that precipitates acute manifestations of atherothrombotic disease. As a result, antiplatelet therapy has become the cornerstone of therapy for the prevention and treatment of atherothrombotic disease. Dual antiplatelet therapy with aspirin and a P2Y12 adenosine diphosphate (ADP) receptor inhibitor, such as clopidogrel or prasugrel, is the current standard-of-care antiplatelet therapy in patients with acute coronary syndromes managed with an early invasive strategy. However, these agents are associated with several important clinical limitations, including significant residual risk for ischemic events, bleeding risk, and variability in the degree of platelet inhibition. The residual risk can be attributed to the fact that aspirin and P2Y12 inhibitors block only the thromboxane A2 and ADP platelet activation pathways but do not affect the other pathways that lead to thrombosis, such as the protease-activated receptor-1 pathway stimulated by thrombin, the most potent platelet agonist. Bleeding risk associated with aspirin and P2Y12 inhibitors can be explained by their inhibitory effects on the thromboxane A2 and ADP pathways, which are critical for protective hemostasis. Interpatient variability in the degree of platelet inhibition in response to antiplatelet therapy may have a genetic component and contribute to poor clinical outcomes. These considerations underscore the clinical need for therapies with a novel mechanism of action that may reduce ischemic events without increasing the bleeding risk. PMID:22393298

  16. [Effect of long-term therapy with oral Beraprost on survival of patients with arterial and inoperable thromboembolic pulmonary hypertension].

    PubMed

    Kurzyna, Marcin; Florczyk, Michał; Fijałkowska, Anna; Kuca, Paweł; Szewczyk, Grzegorz; Burakowski, Janusz; Kober, Jarosław; Sikora, Jarosław; Wawrzyńska, Liliana; Szturmowicz, Monika; Tomkowskil, Witold; Torbicki, Adam

    2004-04-01

    Beraprost sodium (BPS)--an orally active prostacyclin analogue--improves haemodynamic parameters and quality of life in group of patients with pulmonary arterial hypertension. Effect of long-term therapy with BPS is not well defined. This study assesses influence of long-term therapy with BPS on the survival of patients with precapillary pulmonary hypertension. Studied group consisted of 25 patients with precapillary PH (18 F, 7M, aged 34 +/- 13,9 years). Sixteen patients were diagnosed with primary PH, 3 pts had PH associated with connective tissue disease, 5 pts developed PH in course of congenital systemic to pulmonary shunt, and 1 patient suffered from inoperable chronic thromboembolic PH. At time of diagnosis 15 pts presented exercise impairment of WHO class II and 10 pts were in functional class III. All studied subjects had complete hemodynamic assessment of right heart and obtained values were used for estimation of hypothetic survival using prognostic equation proposed by D'Alonzo et al. On follow-up period patients received BPS in the highest tolerated dose (80-480 mg daily). During a follow-up period (mean: 22 months) 7 patients died. Cumulative survival rate BPS group was significantly higher in BPS group comparing to hypothetical survival at 6 months (96% (95% CI: 88-104%) vs 73% (95% CI: 67-78%), p = 0.02) and 12 months (94% (95% CI: 84-104%) vs 65% (58-71%), p = 0.01), respectively. At 18 and 24 months differences between BPS virtual and hypothetical survival were not statistically significant. There was no correlation between survival and maximal achieved dose of BPS. These results suggest, that BPS improves prognosis of patients with precapillary PH during 12 months after initiation of therapy. Later effect of BPS seems to decrease, requiring changing or intensification of therapy.

  17. Impact of oral beta-blocker therapy on mortality after primary percutaneous coronary intervention for Killip class 1 myocardial infarction.

    PubMed

    Hioki, Hirofumi; Motoki, Hirohiko; Izawa, Atsushi; Kashima, Yuichirou; Miura, Takashi; Ebisawa, Souichirou; Tomita, Takeshi; Miyashita, Yusuke; Koyama, Jun; Ikeda, Uichi

    2016-05-01

    The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PCI), which has become the mainstay of treatment for AMI, is associated with a lower mortality than fibrinolysis. The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear. We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure. The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (ALPS-AMI) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infarction. We prospectively tracked cardiovascular events for 3 years in 444 ALPS-AMI patients (median age 66 years; 18.2 % women) who had Killip class 1 on admission and were discharged alive. The primary endpoint was all-cause mortality. The 3-year follow-up was completed in 413 patients (93.0 %). During this follow-up, 21 patients (4.7 %) died. In Kaplan-Meier analysis, patients on beta-blockers had a significantly lower incidence of all-cause mortality (2.7 vs. 7.3 %, log-rank p = 0.025). After adjusting for the calculated propensity score for using beta-blockers, their use remained an independent predictor of all-cause mortality (hazard ratio 0.309; 95 % confidence interval 0.116-0.824; p = 0.019). In the statin era, the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission.

  18. A randomized, double-blind, placebo-controlled study of oral antioxidant supplement therapy in patients with dry eye syndrome

    PubMed Central

    Huang, Jehn-Yu; Yeh, Po-Ting; Hou, Yu-Chih

    2016-01-01

    Purpose To evaluate the efficacy of oral antioxidant supplementation in the treatment of patients with dry eye syndrome (DES). Methods A prospective, randomized, double-blinded study compared the effects of an antioxidant supplement (containing anthocyanosides, astaxanthin, vitamins A, C, and E, and several herbal extracts, including Cassiae semen and Ophiopogonis japonicus) with placebo on patients with DES. We assessed dry eye symptoms, visual acuity, Schirmer’s test, tear film breakup time, cornea and conjunctiva fluorescein staining, serum anti-SSA/anti-SSB antibodies, and the level of reactive oxygen species (ROS) in tears. The supplementation period was 8 weeks and patients were followed up every 4 weeks for 16 weeks. A linear mixed model was used to compare the groups, while within-group differences were tested by repeated-measures analysis of variance. Results Forty-three patients, 20 and 23 in treatment and placebo groups, respectively, completed the study. Liver and renal functions were normal. Diastolic blood pressure decreased in the treatment group. There were no significant differences in systolic blood pressure, dry eye symptoms, serum anti-SSA and anti-SSB, visual acuity, intraocular pressure, or fluorescein corneal staining between the groups. Tear film breakup time scores and Schirmer’s test without topical anesthesia significantly improved in the treatment group. Tear ROS level differed between the groups and decreased after treatment. Overall subjective impression revealed a significant improvement with treatment compared with placebo. Conclusion Oral antioxidant supplementations may increase tear production and improve tear film stability by reducing tear ROS. The vegetable-based antioxidant supplement used in this study is safe and can be utilized as an adjuvant therapy to conventional artificial tear therapy for patients with DES. PMID:27274185

  19. Efficacy of a supersaturated calcium phosphate oral rinse for the prevention and treatment of oral mucositis in patients receiving high-dose cancer therapy: a review of current data.

    PubMed

    Quinn, B

    2013-09-01

    Oral mucositis (OM) is a painful and debilitating complication of cancer therapy that can adversely affect patients' treatment regimens and quality of life. It is also considered to be a substantial burden on the financial and human resources of health services. Despite progress in the understanding of the pathophysiology of OM and the number of new treatments that have been developed, there remains an unmet need for effective preventative measures in clinical practice. Literature on oral healthcare management in oncology patients suggests that a preventative approach consisting of a supersaturated Ca2+ / PO4(3-) oral rinse (Caphosol(®)) aimed at maintaining oral hygiene, moistening and lubricating the oral cavity, effectively reduces the incidence and severity of OM. This review looked at data from all known adult and paediatric studies investigating the use of Caphosol(®) in patients receiving high-dose cancer therapy in order to evaluate its efficacy for both the prevention and treatment of OM. Thirty studies were identified. The majority of these studies (n = 24) found Caphosol(®) to be efficacious at reducing the grade and/or duration, as well as pain associated with OM. Despite important limitations, these data warrant serious consideration for the inclusion of Caphosol(®) in regimens for preventing or reducing the debilitating effects of OM.

  20. Oral sildenafil as a rescue therapy in presumed acute pulmonary hypertensive crisis.

    PubMed

    Maxted, Andrew Peter; Hill, Abigail; Davies, Patrick

    2013-02-01

    A 23-week-old baby, born at 26(+2) weeks, presented to the hospital with critical respiratory failure, which was impossible to stabilize. She had unstable oxygen saturations between 35% and 95%. A presumptive diagnosis of bronchopulmonary dysplasia with associated pulmonary hypertensive crisis was made. In the absence of inhaled nitric oxide, 2 oral doses of 1 mg/kg sildenafil were given, with a dramatic improvement 30 to 45 minutes later. Her oxygenation index fell from 43 to 14. She made a full recovery and was discharged from the hospital 2 weeks later.

  1. Oral Rehydration Therapy and the Control of Diarrheal Diseases. Training for Development. Peace Corps Information Collection & Exchange Training Manual No. T-34.

    ERIC Educational Resources Information Center

    Clark, Mari; And Others

    This manual was developed to train Peace Corps volunteers and other community health workers in oral rehydration therapy (ORT) and the control of diarrheal diseases. Using a competency-based format, the manual contains six training modules (organized in 22 sessions) that focus on interrelated health education and technical content areas. Each…

  2. Inadequate response or intolerability to oral methotrexate: Is it optimal to switch to subcutaneous methotrexate prior to considering therapy with biologics?

    PubMed

    Yadlapati, Sujani; Efthimiou, Petros

    2016-05-01

    Methotrexate (MTX) is considered an anchor drug in the treatment of rheumatoid arthritis. It is also the first-line therapy in a multitude of rheumatologic conditions. Low-dose oral MTX is the preliminary modality of treatment for rheumatoid arthritis due to its affordability, favorable outcomes, and limited risks. However, patients refractory to low-dose MTX therapy may require larger doses of oral MTX. Several studies in the past have demonstrated variability in bioavailability of oral MTX at high doses. This warrants a subsequent switch to parenteral MTX. Widely used among the parenteral preparations of MTX is subcutaneous (SC) MTX. SC MTX provides dependable efficacy, predictable bioavailability, sustained clinical outcomes, and minimal GI adverse effects. It is useful either singularly or in combination therapy regimens. Although SC MTX and intramuscular MTX have similar pharmacokinetics, SC MTX may be preferred by most patients. Development of prefilled syringes and auto-injectors have enabled self-administration of the medication providing the patients with a sense of independence and improved general well-being. Hence, SC MTX can prove to be more efficacious in patients refractory to oral MTX therapy or in patients experiencing severe gastrointestinal adverse effects.

  3. A Community-based Survey of the Awareness and Acceptability of Oral Rehydration Therapy (ORT) as a Treatment for Acute Diarrhoea in Children.

    ERIC Educational Resources Information Center

    Ekanem, E. E.; Benebo, N. S.

    1988-01-01

    A total of 267 Nigerian mothers with children under the age of five years were investigated regarding the degree of their awareness and acceptance of oral rehydration therapy in the treatment of childhood diarrhea. Results indicate that only 39 percent of the mothers had heard of ORT in treating diarrhea. (RJC)

  4. Oral Ciprofloxacin Prophylaxis in Patients Undergoing High DoseTherapy and Autologous Hematopoietic Stem Cell Transplantation

    PubMed Central

    Tabarraee, Mahdi; Tavakoli-Ardakani, Maria; Mehdizadeh, Mahshid; Ghadiani, Mojtaba; Rezvani, Hamid; Hajifathali, Abbas; khamsi, Samiyeh

    2016-01-01

    Antibiotic prophylaxis is usually used in allogeneic stem cell transplantation, but its use in Autologous Stem Cell Transplantation (ASCT) is controversial. We evaluated the efficacy of ciprofloxacin prophylaxis in ASCT. To identify the efficacy of ciprofloxacin on the incidence of neutropenic fever and its complications, 72 patients that had been admitted to Taleghani Hospital for ASCT between 2010 and 2012 were evaluated in our study. Oral ciprofloxacin 500 mg every 12 h was administered to 30 patients on the same day of high dose chemotherapy until the first febrile episode or until the recovery of neutropenia and the results were analyzed and compared with the historical control group 42 other transplanted patients who had not previously received ciprofloxacin. The incidence of neutropenic fever was 80% with no difference between the two groups. But in ciprofloxacin group, duration of fever (1.7 days VS 3.5 days P=0.017), hospitalization due to stem cell transfusion (18.2 days VS 12.2 days p=0.03), incidence of bacteremia 3.3 % VS 33.3%, p=0.002) and platelet recovery (13.9 VS 17.7 days= 0.035) and platelet transfusions (P=0.04) were significantly lower than the control group no side effects and no delay in. Based on this study oral ciprofloxacin prophylaxis is rational, efficacious and economic in ASCT. PMID:28228813

  5. Oral Adherence Monitoring Using a Breath Test to Supplement Highly Active Antiretroviral Therapy

    PubMed Central

    Morey, Timothy E.; Booth, Matthew; Wasdo, Scott; Wishin, Judith; Quinn, Brian; Gonzalez, Daniel; Derendorf, Hartmut; McGorray, Susan P.; Simoni, Jane; Melker, Richard J.; Dennis, Donn M.

    2012-01-01

    A breath-based adherence system to document ingestion of oral medications (e.g., HAART) was investigated. Specifically, the food additive 2-butanol, which can be easily packaged with a drug, is converted via alcohol dehydrogenase to the volatile metabolite 2-butanone that rapidly appears in breath, indicating adherence. In healthy adults using a portable sensor and GC-MS, the following experiments were performed: yield of 2-butanone in breath following ingestion of 2-butanol, adherence system accuracy, and potential interference of the adherence system by food or misplacement of 2-butanol on the tongue. During feasibility testing, every subject exhaled 2-butanone with 6.6±1.5 min to peak concentrations of 548±235 ppb following ingestion of 2-butanol (40 mg). ROC areas at 5 and 10 min were 0.95 (0.86–1.00) and 3 1.00 (1.00–1.00). Food did not interfere. Tongue application resulted in large concentrations of 2-butanol, but not 2-butanone. A breath test to provide definitive evidence of oral medication adherence appears technically feasible. PMID:23001413

  6. Individual Oral Therapy with Immediate Release and Effervescent Formulations Delivered by the Solid Dosage Pen

    PubMed Central

    Wening, Klaus; Laukamp, Eva Julia; Thommes, Markus; Breitkreutz, Jörg

    2012-01-01

    New devices enabling freely selectable dosing of solid oral medications are urgently needed for personalized medicine. One approach is the use of the recently published Solid Dosage Pen, allowing flexible dosing of tablet-like sustained release slices from drug loaded extruded strands. Slices were suitable for oral single dosed application. The aim of the present study was the development of immediate release dosage forms for applications of the device, especially for young children. Using two model drugs, two different concepts were investigated and evaluated. Effervescent formulations were manufactured by an organic wet-extrusion process and immediate release formulations by a melt-extrusion process. Dissolution experiments were performed for both formulations to ensure the immediate release behavior. Extruded strands were individually dosed by the Solid Dosage Pen. Various doses of the two formulations were analyzed regarding uniformity of mass and content according to pharmacopoeial specifications. Proof of concept was demonstrated in both approaches as results comply with the regulatory requirements. Furthermore, storing stress tests were performed and drug formulations were characterized after storing. The results show that suitable packaging material has been selected and storage stability is probable. PMID:25562361

  7. Improvement of regressive autism symptoms in a child with TMLHE deficiency following carnitine supplementation.

    PubMed

    Ziats, Mark N; Comeaux, Mathew S; Yang, Yaping; Scaglia, Fernando; Elsea, Sarah H; Sun, Qin; Beaudet, Arthur L; Schaaf, Christian P

    2015-09-01

    Disorders of carnitine biosynthesis have recently been associated with neurodevelopmental syndromes such as autism spectrum disorder (ASD). A 4-year-old male with autism and two episodes of neurodevelopmental regression was identified to have a mutation in the TMLHE gene, which encodes the first enzyme in the carnitine biosynthesis pathway, and concurrent carnitine deficiency. Following carnitine supplementation, the patient's regression ended, and the boy started gaining developmental milestones. This case report suggests that deficits in carnitine biosynthesis may be responsible for some cases of regression in individuals with ASD, and that testing for the respective biochemical pathway should be considered. Furthermore, this case suggests that carnitine supplementation may be useful in treating (and potentially preventing) regressive episodes in patients with carnitine deficiency. Further work to better define the role of disorders of carnitine biosynthesis in autism spectrum disorder is warranted.

  8. Community Case Management of Childhood Diarrhea in a Setting with Declining Use of Oral Rehydration Therapy: Findings from Cross-Sectional Studies among Primary Household Caregivers, Kenya, 2007

    PubMed Central

    Olson, Christine K.; Blum, Lauren S.; Patel, Kinnery N.; Oria, Prisca A.; Feikin, Daniel R.; Laserson, Kayla F.; Wamae, Annah W.; Bartlett, Alfred V.; Breiman, Robert F.; Ram, Pavani K.

    2011-01-01

    We sought to determine factors associated with appropriate diarrhea case management in Kenya. We conducted a cross-sectional survey of caregivers of children < 5 years of age with diarrhea in rural Asembo and urban Kibera. In Asembo, 61% of respondents provided oral rehydration therapy (ORT), 45% oral rehydration solution (ORS), and 64% continued feeding. In Kibera, 75% provided ORT, 43% ORS, and 46% continued feeding. Seeking care at a health facility, risk perception regarding death from diarrhea, and treating a child with oral medications were associated with ORT and ORS use. Availability of oral medication was negatively associated. A minority of caregivers reported that ORS is available in nearby shops. In Kenya, household case management of diarrhea remains inadequate for a substantial proportion of children. Health workers have a critical role in empowering caregivers regarding early treatment with ORT and continued feeding. Increasing community ORS availability is essential to improving diarrhea management. PMID:22144458

  9. Photodynamic therapy and the treatment of neoplastic diseases of the larynx, oral cavity, pharynx, and tracheobronchial tree

    NASA Astrophysics Data System (ADS)

    Biel, Merrill A.

    1993-06-01

    Photodynamic therapy has the potential to treat and cure early carcinomas of the head and neck while preserving normal tissue. Thirty patients with neoplasia of the head and neck have been treated with PDT with follow-up to twenty nine months. Four patients with T3 and T4 carcinomas of the upper aerodigestive tract had a partial response. Eleven patients with T1 and T2 carcinomas of the larynx obtained a complete response and are disease free. Seven patients with T1 carcinomas of the tongue, floor of mouth, and nasal cavity obtained a complete response. Three patients with mucosal melanomas of the nasopharynx obtained a complete response and have remained disease free. Two patients with Kaposi's sarcoma of the oral cavity were treated. One obtained a complete response. Three patients with recurrent juvenile laryngotracheal papillomatosis obtained a complete response, but one recurred four months post-PDT. PDT is a promising therapy for treatment of early neoplasia of the head and neck. There are, however, limitations to this treatment based on tumor size and site. Methodology, clinical response, limitations, and complications will be discussed.

  10. Photodynamic therapy and the treatment of neoplastic diseases of the larynx, pharynx, oral cavity, and tracheobronchial tree

    NASA Astrophysics Data System (ADS)

    Biel, Merrill A.

    1994-09-01

    Photodynamic therapy (PDT) has the potential to treat and cure early carcinomas of the head and neck while preserving normal tissue. Fifty-three patients with neoplasia of the head and neck have been treated with PDT with follow-up to 40 months. Eight patients with T2-T4 carcinomas of the upper aerodigestive tract had a partial response. Eighteen patients with CIS and T1 carcinomas of the larynx obtained a complete response and are disease free. Eleven patients with T1 carcinomas of the tongue, floor of mouth, and nasal cavity obtained a complete response. Three patients with mucosal melanomas of the nasopharynx obtained a complete response and remain disease free. Two patients with Kaposi's sarcoma or the oral cavity were treated, one obtained a complete response. Five patients with juvenile laryngotracheobronchial papillomatosis obtained a complete response, but all recurred within six months of treatment. PDT is a promising therapy for treatment of early neoplasia of the head and neck. There are, however limitations to this treatment based on tumor size and site. Methodology, clinical response, limitations and complications are discussed.

  11. Crystal Structure of an L-Carnitine Complex with Pyrogallol[4]arene

    NASA Astrophysics Data System (ADS)

    Fujisawa, I.; Takeuchi, D.; Kitamura, Y.; Okamoto, R.; Aoki, K.

    2012-03-01

    L-Carnitine is essential for the transport of long-chain fatty acids from cytosol into mitochondria for generating metabolic energy. The survey of crystal structures of carnitine-containing proteins in the Protein Data Bank reveals that carnitine can take several conformations with the quarternary trimethylammonium terminal being always bound to aromatic residues through cation-π interactions in acyltransferases or carnitine-binding proteins. In order to demonstrate the importance of cation-π interaction as a carnitine recognition mechanism in the artificial receptor-ligand system that mimics the carnitine-binding sites, we have determined the crystal structure of a complex formed between L-carnitine and pyrogallol[4]arene (pyrogallol cyclic tetramer: PCT) as a carnitine receptor, 2PCT·2(L-carnitine)·4EtOH. There form two crystallographically independent monomeric [PCT·L-carnitine] substructures, which further form an obliquely arranged capsule-like dimeric [PCT·L-carnitine]2 structure through a pair of O-H (PCT)···O (L-carnitine) hydrogen bonds. This is the first report of PCT complex with chiral molecules. In each of the two monomeric [PCT·L-carnitine] substructures, the L-carnitine molecule takes the elongated form with an intramolecular hydrogen bond between the hydroxyl group and the carboxylate oxygen, and the cationic trimethylammonium moiety is incorporated into the cavity of the bowl-shaped PCT molecule through cation-π interactions. These features are similar to those at the D-carnitine-binding site in the crystal structure of the glycine betaine/carnitine/choline-binding protein complex.

  12. OCTN3 is a mammalian peroxisomal membrane carnitine transporter

    SciTech Connect

    Lamhonwah, Anne-Marie; Ackerley, Cameron A.; Tilups, Aina; Edwards, Vernon D.; Wanders, Ronald J.; Tein, Ingrid . E-mail: ingrid.tein@sickkids.ca

    2005-12-30

    Carnitine is a zwitterion essential for the {beta}-oxidation of fatty acids. The role of the carnitine system is to maintain homeostasis in the acyl-CoA pools of the cell, keeping the acyl-CoA/CoA pool constant even under conditions of very high acyl-CoA turnover, thereby providing cells with a critical source of free CoA. Carnitine derivatives can be moved across intracellular barriers providing a shuttle mechanism between mitochondria, peroxisomes, and microsomes. We now demonstrate expression and colocalization of mOctn3, the intermediate-affinity carnitine transporter (K {sub m} 20 {mu}M), and catalase in murine liver peroxisomes by TEM using immunogold labelled anti-mOctn3 and anti-catalase antibodies. We further demonstrate expression of hOCTN3 in control human cultured skin fibroblasts both by Western blotting and immunostaining analysis using our specific anti-mOctn3 antibody. In contrast with two peroxisomal biogenesis disorders, we show reduced expression of hOCTN3 in human PEX 1 deficient Zellweger fibroblasts in which the uptake of peroxisomal matrix enzymes is impaired but the biosynthesis of peroxisomal membrane proteins is normal, versus a complete absence of hOCTN3 in human PEX 19 deficient Zellweger fibroblasts in which both the uptake of peroxisomal matrix enzymes as well as peroxisomal membranes are deficient. This supports the localization of hOCTN3 to the peroxisomal membrane. Given the impermeability of the peroxisomal membrane and the key role of carnitine in the transport of different chain-shortened products out of peroxisomes, there appears to be a critical need for the intermediate-affinity carnitine/organic cation transporter, OCTN3, on peroxisomal membranes now shown to be expressed in both human and murine peroxisomes. This Octn3 localization is in keeping with the essential role of carnitine in peroxisomal lipid metabolism.

  13. L-lysine in Treating Oral Mucositis in Patients Undergoing Radiation Therapy With or Without Chemotherapy For Head and Neck Cancer

    ClinicalTrials.gov

    2013-05-15

    Mucositis; Oral Complications of Chemotherapy; Oral Complications of Radiation Therapy; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Adenoid Cystic Carcinoma of the Oral Cavity; Stage II Basal Cell Carcinoma of the Lip; Stage II Lymphoepithelioma of the Nasopharynx; Stage II Lymphoepithelioma of the Oropharynx; Stage II Mucoepidermoid Carcinoma of the Oral Cavity; Stage II Salivary Gland Cancer; Stage II Squamous Cell Carcinoma of the Hypopharynx; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage

  14. Diagnosis of HIV-Associated Oral Lesions in Relation to Early versus Delayed Antiretroviral Therapy: Results from the CIPRA HT001 Trial.

    PubMed

    Batavia, Ashita S; Secours, Rode; Espinosa, Patrice; Jean Juste, Marc Antoine; Severe, Patrice; Pape, Jean William; Fitzgerald, Daniel W

    2016-01-01

    Oral mucosal lesions that are associated with HIV infection can play an important role in guiding the decision to initiate antiretroviral therapy (ART). The incidence of these lesions relative to the timing of ART initiation has not been well characterized. A randomized controlled clinical trial was conducted at the GHESKIO Center in Port-au-Prince, Haiti between 2004 and 2009. 816 HIV-infected ART-naïve participants with CD4 T cell counts between 200 and 350 cells/mm3 were randomized to either immediate ART initiation (early group; N = 408), or initiation when CD4 T cell count was less than or equal 200 cells/mm3 or with the development of an AIDS-defining condition (delayed group; N = 408). Every 3 months, all participants underwent an oral examination. The incidence of oral lesions was 4.10 in the early group and 17.85 in the delayed group (p-value <0.01). In comparison to the early group, there was a significantly higher incidence of candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex in the delayed group. The incidence of oral warts in delayed group was 0.97 before therapy and 4.27 post-ART initiation (p-value <0.01). In the delayed group the incidence of oral warts post-ART initiation was significantly higher than that seen in the early group (4.27 versus 1.09; p-value <0.01). The incidence of oral warts increased after ART was initiated, and relative to the early group there was a four-fold increase in oral warts if ART was initiated following an AIDS diagnosis. Based upon our findings, candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex indicate immune suppression and the need to start ART. In contrast, oral warts are a sign of immune reconstitution following ART initiation.

  15. Diagnosis of HIV-Associated Oral Lesions in Relation to Early versus Delayed Antiretroviral Therapy: Results from the CIPRA HT001 Trial

    PubMed Central

    Batavia, Ashita S.; Secours, Rode; Espinosa, Patrice; Jean Juste, Marc Antoine; Severe, Patrice; Pape, Jean William; Fitzgerald, Daniel W.

    2016-01-01

    Oral mucosal lesions that are associated with HIV infection can play an important role in guiding the decision to initiate antiretroviral therapy (ART). The incidence of these lesions relative to the timing of ART initiation has not been well characterized. A randomized controlled clinical trial was conducted at the GHESKIO Center in Port-au-Prince, Haiti between 2004 and 2009. 816 HIV-infected ART-naïve participants with CD4 T cell counts between 200 and 350 cells/mm3 were randomized to either immediate ART initiation (early group; N = 408), or initiation when CD4 T cell count was less than or equal 200 cells/mm3 or with the development of an AIDS-defining condition (delayed group; N = 408). Every 3 months, all participants underwent an oral examination. The incidence of oral lesions was 4.10 in the early group and 17.85 in the delayed group (p-value <0.01). In comparison to the early group, there was a significantly higher incidence of candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex in the delayed group. The incidence of oral warts in delayed group was 0.97 before therapy and 4.27 post-ART initiation (p-value <0.01). In the delayed group the incidence of oral warts post-ART initiation was significantly higher than that seen in the early group (4.27 versus 1.09; p-value <0.01). The incidence of oral warts increased after ART was initiated, and relative to the early group there was a four-fold increase in oral warts if ART was initiated following an AIDS diagnosis. Based upon our findings, candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex indicate immune suppression and the need to start ART. In contrast, oral warts are a sign of immune reconstitution following ART initiation. PMID:26930571

  16. Perioperative management of oral antiplatelet therapy and clinical outcomes in coronary stent patients undergoing surgery. Results of a multicentre registry.

    PubMed

    Rossini, Roberta; Musumeci, Giuseppe; Capodanno, Davide; Lettieri, Corrado; Limbruno, Ugo; Tarantini, Giuseppe; Russo, Nicolina; Calabria, Paolo; Romano, Michele; Inashvili, Ana; Sirbu, Vasile; Guagliumi, Giulio; Valsecchi, Orazio; Senni, Michele; Gavazzi, Antonello; Angiolillo, Dominick J

    2015-02-01

    The aim was to investigate the perioperative risk of ischaemic and bleeding events in patients with coronary stents undergoing cardiac and non-cardiac surgery and how these outcomes are affected by the perioperative use of oral antiplatelet therapy. This was a multicentre, retrospective, observational study conducted in patients with coronary stent(s) undergoing cardiac or non-cardiac surgery. The primary efficacy endpoint was the 30-day incidence of major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction (MI) or stroke. The primary safety endpoint was the 30-day incidence of Bleeding Academic Research Consortium (BARC) bleeding ≥ 2. A total of 666 patients were included. Of these, 371 (55.7 %) discontinued their antiplatelet medication(s) (all or partly) before undergoing surgery. At 30 days, patients with perioperative discontinuation of antiplatelet therapy experienced a significantly higher incidence of MACE (7.5 % vs 0.3 %, p< 0.001), cardiac death (2.7 % vs 0.3 %, p=0.027), and MI (4.0 % vs 0 %, p< 0.001). After adjustment, peri-operative antiplatelet discontinuation was the strongest independent predictor of 30-day MACE (odds ratio [OR]=25.8, confidence interval [CI]=3.37-198, p=0.002). Perioperative aspirin (adjusted OR 0.27, 95 % CI 0.11-0.71, p=0.008) was significantly associated with a lower risk of MACE. The overall incidence of BARC ≥ 2 bleeding events at 30-days was significantly higher in patients who discontinued oral antiplatelet therapy (25.6 % vs 13.9 %, p< 0.001). However, after adjustment, antiplatelet discontinuation was not independently associated with BARC ≥ 2 bleeding. In conclusion antiplatelet discontinuation increases the 30-day risk of MACE, in patients with coronary stents undergoing cardiac and non-cardiac surgery, while not offering significant protection from BARC≥ 2 bleeding.

  17. Partial correction of neutrophil dysfunction by oral galactose therapy in glycogen storage disease type Ib.

    PubMed

    Letkemann, Rudolf; Wittkowski, Helmut; Antonopoulos, Aristotelis; Podskabi, Teodor; Haslam, Stuart M; Föll, Dirk; Dell, Anne; Marquardt, Thorsten

    2017-03-01

    Glycogen storage disease type Ib (GSD-Ib) is characterized by impaired glucose homeostasis, neutropenia and neutrophil dysfunction. Mass spectrometric glycomic profiling of GSD-Ib neutrophils showed severely truncated N-glycans, lacking galactose. Experiments indicated the hypoglycosylation of the electron transporting subunit of NADPH oxidase, which is crucial for the defense against bacterial infections. In phosphoglucomutase 1 (PGM1) deficiency, an inherited disorder with an enzymatic defect just one metabolic step ahead, hypogalactosylation can be successfully treated by dietary galactose. We hypothesized the same pathomechanism in GSD-Ib and started a therapeutic trial with oral galactose and uridine. The aim was to improve neutrophil dysfunction through the correction of hypoglycosylation in neutrophils. The GSD-Ib patient was treated for 29weeks. Monitoring included glycomics analysis of the patient's neutrophils and neutrophil function tests including respiratory burst activity, phagocytosis and migration. Although no substantial restoration of neutrophil glycosylation was found, there was partial improvement of respiratory burst activity.

  18. Biomodulation of Inflammatory Cytokines Related to Oral Mucositis by Low-Level Laser Therapy.

    PubMed

    Basso, Fernanda G; Pansani, Taisa N; Soares, Diana G; Scheffel, Débora L; Bagnato, Vanderlei S; de Souza Costa, Carlos Alberto; Hebling, Josimeri

    2015-01-01

    This study evaluated the effects of LLLT on the expression of inflammatory cytokines related to the development of oral mucositis by gingival fibroblasts. Primary gingival fibroblasts were seeded on 24-well plates (10(5) cells/well) for 24 h. Fresh serum-free culture medium (DMEM) was then added, and cells were placed in contact with LPS (Escherichia coli, 1 μg mL(-1)), followed by LLLT irradiation (LaserTABLE-InGaAsP diode prototype-780 nm, 25 mW) delivering 0, 0.5, 1.5 or 3 J cm(-2)². Cells without contact with LPS were also irradiated with the same energy densities. Gene expression of TNF-α, IL-1β, IL-6 and IL-8 was evaluated by Real-Time PCR, and protein synthesis of these cytokines was determined by enzyme-linked immunosorbent (ELISA) assay. Data were statistically analyzed by the Kruskal-Wallis test, complemented by the Mann-Whitney test (P < 0.05). LPS treatment increased the gene expression and protein synthesis of TNF-α, IL-6 and IL-8, while the expression of IL-1β was not affected. For LPS-treated groups, LLLT promoted significant decreases in the expression of TNF-α, IL-6, and IL-8 at 1.5 J cm(-2) and 3 J cm(-2). These results demonstrate that LLLT promoted a beneficial biomodulatory effect on the expression of inflammatory cytokines related to oral mucositis by human gingival fibroblasts.

  19. Fosfomycin: A First-Line Oral Therapy for Acute Uncomplicated Cystitis

    PubMed Central

    Zhanel, George G.; Walkty, Andrew J.; Karlowsky, James A.

    2016-01-01

    Fosfomycin is a new agent to Canada approved for the treatment of acute uncomplicated cystitis (AUC) in adult women infected with susceptible isolates of E. coli and Enterococcus faecalis. We reviewed the literature regarding the use of oral fosfomycin for the treatment of AUC. All English-language references from 1975 to October 2015 were reviewed. In Canada, fosfomycin tromethamine is manufactured as Monurol® and is available as a 3-gram single dose sachet. Fosfomycin has a unique chemical structure, inhibiting peptidoglycan synthesis at an earlier site compared to β-lactams with no cross-resistance with other agents. Fosfomycin displays broad-spectrum activity against ESBL-producing, AmpC-producing, carbapenem-non-susceptible, and multidrug-resistant (MDR) E. coli. Resistance to fosfomycin in E. coli is rare (<1%). Fosfomycin is excreted unchanged in the urine by glomerular filtration with peak urinary concentration ~4000 µg/mL and remains at concentrations >100 µg/mL for 48 hours after a single 3-gram oral dose. No dosage adjustments are required in elderly patients, in pregnant patients, or in either renal or hepatic impairment. Fosfomycin demonstrates a favorable safety profile, and clinical trials have demonstrated efficacy in AUC that is comparable to ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole. Fosfomycin's in vitro activity against common uropathogens, including MDR isolates, its favorable safety profile including pregnancy patients, drug interactions, and clinical trials data demonstrating efficacy in AUC, has resulted in Canadian, US, and European guidelines/authorities recommending fosfomycin as a first line agent for the treatment of AUC. PMID:27366158

  20. Study on Biopharmaceutics Classification and Oral Bioavailability of a Novel Multikinase Inhibitor NCE for Cancer Therapy

    PubMed Central

    Yang, Yang; Fan, Chun-Mei; He, Xuan; Ren, Ke; Zhang, Jin-Kun; He, Ying-Ju; Yu, Luo-Ting; Zhao, Ying-Lan; Gong, Chang-Yang; Zheng, Yu; Song, Xiang-Rong; Zeng, Jun

    2014-01-01

    Specific biopharmaceutics classification investigation and study on phamacokinetic profile of a novel drug candidate (2-methylcarbamoyl-4-{4-[3- (trifluoromethyl) benzamido] phenoxy} pyridinium 4-methylbenzenesulfonate monohydrate, NCE) were carried out. Equilibrium solubility and intrinsic dissolution rate (IDR) of NCE were estimated in different phosphate buffers. Effective intestinal permeability (Peff) of NCE was determined using single-pass intestinal perfusion technique in rat duodenum, jejunum and ileum at three concentrations. Theophylline (high permeability) and ranitidine (low permeability) were also applied to access the permeability of NCE as reference compounds. The bioavailability after intragastrical and intravenous administration was measured in beagle dogs. The solubility of NCE in tested phosphate buffers was quite low with the maximum solubility of 81.73 μg/mL at pH 1.0. The intrinsic dissolution ratio of NCE was 1 × 10−4 mg·min−1·cm−2. The Peff value of NCE in all intestinal segments was more proximate to the high-permeability reference theophylline. Therefore, NCE was classified as class II drug according to Biopharmaceutics Classification System due to its low solubility and high intestinal permeability. In addition, concentration-dependent permeability was not observed in all the segments, indicating that there might be passive transportation for NCE. The absolute oral bioavailability of NCE in beagle dogs was 26.75%. Therefore, dissolution promotion will be crucial for oral formulation development and intravenous administration route will also be suggested for further NCE formulation development. All the data would provide a reference for biopharmaceutics classification research of other novel drug candidates. PMID:24776763

  1. The evolving role of oral hormonal therapies and review of conjugated estrogens/bazedoxifene for the management of menopausal symptoms.

    PubMed

    Parish, Sharon J; Gillespie, John A

    2017-04-01

    This review describes the evolving role of oral hormone therapy (HT) for treating menopausal symptoms and preventing osteoporosis, focusing on conjugated estrogens/bazedoxifene (CE/BZA). Estrogens alleviate hot flushes and prevent bone loss associated with menopause. In nonhysterectomized women, a progestin should be added to estrogens to reduce the risk of endometrial cancer. Use of HT declined since the Women's Health Initiative (WHI) studies showed that HT does not prevent coronary heart disease (CHD) and that conjugated estrogens/medroxyprogesterone acetate increased the risk of invasive breast cancer after nearly 5 years of use. However, re-analyses of the WHI data suggest that some risks (eg, CHD, all-cause mortality) may be reduced when HT is initiated in women <60 years of age and <10 years since menopause, compared with later. CE/BZA is the first menopausal HT without a progestogen for nonhysterectomized women. Instead, BZA, a selective estrogen receptor modulator, in combination with CE, protects against estrogenic effects on uterine and breast tissue. Data from 5 large, randomized clinical trials show that CE/BZA reduces hot flush frequency/severity, prevents bone loss, reduces bone turnover, improves the vaginal maturation index and ease of lubrication, and improves some measures of sleep and menopause-specific quality of life. In studies of up to 2 years, there was no increase in endometrial hyperplasia, vaginal bleeding, breast density, or breast pain/tenderness compared with placebo. Venous thromboembolism and stroke are risks of all estrogen-based therapies. The choice of HT should be individualized, with consideration of the risk/benefit profile and tolerability of therapy, as well as patient preferences.

  2. Characteristics Predictive for a Successful Switch from Insulin Analogue Therapy to Oral Hypoglycemic Agents in Patients with Type 2 Diabetes

    PubMed Central

    Kim, Gyuri; Lee, Yong-ho; Kang, Eun Seok; Cha, Bong-Soo; Lee, Hyun Chul

    2016-01-01

    Purpose The objective of this study was to investigate clinical and laboratory parameters that could predict which patients could maintain adequate glycemic control after switching from initial insulin therapy to oral hypoglycemic agents (OHAs) among patients with type 2 diabetes (T2D). Materials and Methods We recruited 275 patients with T2D who had been registered in 3 cohorts of initiated insulin therapy and followed up for 33 months. The participants were divided into 2 groups according to whether they switched from insulin to OHAs (Group I) or not (Group II), and Group I was further classified into 2 sub-groups: maintenance on OHAs (Group IA) or resumption of insulin (Group IB). Results Of 275 patients with insulin initiation, 63% switched to OHAs (Group I) and 37% continued insulin (Group II). Of these, 44% were in Group IA and 19% in Group IB. The lowest tertile of baseline postprandial C-peptide-to-glucose ratio (PCGR), higher insulin dose at switching to OHAs, and higher HbA1c level at 6 months after switching to OHAs were all associated with OHA failure (Group IB; p=0.001, 0.046, and 0.014, respectively). The lowest tertile of PCGR was associated with ultimate use of insulin (Group IB and Group II; p=0.029). Conclusion Higher baseline level of PCGR and lower HbA1c levels at 6 months after switching to OHAs may be strong predictors for the successful maintenance of OHAs after switching from insulin therapy in Korean patients with T2D. PMID:27593867

  3. Systemic regulation of L-carnitine in nutritional metabolism in zebrafish, Danio rerio

    PubMed Central

    Li, Jia-Min; Li, Ling-Yu; Qin, Xun; Ning, Li-Jun; Lu, Dong-Liang; Li, Dong-Liang; Zhang, Mei-Ling; Wang, Xin; Du, Zhen-Yu

    2017-01-01

    Excess fat accumulation has been observed widely in farmed fish; therefore, efficient lipid-lowering factors have obtained high attention in the current fish nutrition studies. Dietary L-carnitine can increase fatty acid β-oxidation in mammals, but has produced contradictory results in different fish species. To date, the mechanisms of metabolic regulation of L-carnitine in fish have not been fully determined. The present study used zebrafish to investigate the systemic regulation of nutrient metabolism by dietary L-carnitine supplementation. L-carnitine significantly decreased the lipid content in liver and muscle, accompanied by increased concentrations of total and free carnitine in tissues. Meanwhile, L-carnitine enhanced mitochondrial β-oxidation activities and the expression of carnitine palmitoyltransferase 1 mRNA significantly, whereas it depressed the mRNA expression of adipogenesis-related genes. In addition, L-carnitine caused higher glycogen deposition in the fasting state, and increased and decreased the mRNA expressions of gluconeogenesis-related and glycolysis-related genes, respectively. L-carnitine also increased the hepatic expression of mTOR in the feeding state. Taken together, dietary L-carnitine supplementation decreased lipid deposition by increasing mitochondrial fatty acid β-oxidation, and is likely to promote protein synthesis. However, the L-carnitine-enhanced lipid catabolism would cause a decrease in glucose utilization. Therefore, L-carnitine has comprehensive effects on nutrient metabolism in fish. PMID:28102299

  4. Conditions for the self-catalysed inactivation of carnitine acetyltransferase. A novel form of enzyme inhibition

    PubMed Central

    Chase, J. F. A.; Tubbs, P. K.

    1969-01-01

    1. Carnitine acetyltransferase is very rapidly inhibited in the presence of bromoacetyl-(−)-carnitine plus CoA or of bromoacetyl-CoA plus (−)-carnitine. 2. Under appropriate conditions, the enzyme may be titrated with either bromoacetyl substrate analogue; in each case about 1mole of inhibitor is required to inactivate completely 1mole of enzyme of molecular weight 58000±3000. 3. Inhibition by bromoacetyl-CoA plus (−)-carnitine results in the formation of an inactive enzyme species, containing stoicheiometric amounts of bound adenine nucleotide and (−)-carnitine in a form that is not removed by gel filtration. This is shown to be S-carboxymethyl-CoA (−)-carnitine ester. 4. The inhibited enzyme recovers activity slowly on prolonged standing at 4°. 5. Incubation with S-carboxymethyl-CoA (−)-carnitine ester causes a slow inhibition of carnitine acetyltransferase. 6. The formation of bound S-carboxymethyl-CoA (−)-carnitine ester by the enzyme is discussed. Presumably the resulting inhibition reflects binding of the ester to both the CoA- and carnitine-binding sites on the enzyme and its consequent very slow dissociation. These observations confirm that carnitine acetyltransferase can form ternary enzyme–substrate complexes; this also appears to be the case with carnitine palmitoyltransferase and choline acetyltransferase. PMID:5763788

  5. Carnitine supplementation has protective and detrimental effects in Saccharomyces cerevisiae that are genetically mediated.

    PubMed

    Franken, Jaco; Bauer, Florian F

    2010-05-01

    l-Carnitine plays a well-documented role in eukaryotic energy homeostasis by acting as a shuttling molecule for activated acyl residues across intracellular membranes. This activity, supported by carnitine acyl-transferases and transporters, is referred to as the carnitine shuttle. However, several pleiotropic and often beneficial effects of carnitine in humans have been reported that appear to be unrelated to shuttling activity, but little conclusive evidence regarding molecular mechanisms exists. We have recently demonstrated a role of carnitine, independent of the carnitine shuttle, in yeast stress protection. Here, we show that carnitine specifically protects against oxidative stress caused by H(2)O(2) and the superoxide-generating agent menadione. Surprisingly, carnitine has a detrimental effect on survival when combined with thiol-modifying agents. Central elements of the oxidative stress response, specifically the transcription factors Yap1p and Skn7p, are shown to be required for carnitine's protective effect, but several downstream effectors are dispensable. A DNA microarray-based analysis identifies Cyc3p, a cytochrome c heme lyase, as being important for carnitine's impact during oxidative stress. These findings establish a direct genetic link to a carnitine-related phenotype that is independent of the shuttle system and suggests that Saccharomyces cerevisiae should provide a useful model for further elucidation of carnitine's physiological roles.

  6. Kinetics of carnitine palmitoyltransferase-I are altered by dietary variables and suggest a metabolic need for supplemental carnitine in young pigs.

    PubMed

    Heo, K; Lin, X; Odle, J; Han, I K

    2000-10-01

    To examine the kinetics of carnitine palmitoyltransferase-I (CPT-I) and the influence of dietary variables, young pigs (18 kg, n = 20) were fed corn-soybean meal diets supplemented with 40 g soy oil/kg and containing either 136 or 180 g crude protein/kg and either 0 or 500 mg/kg L-carnitine (2 x 2 factorial design). Diets were offered for 10 d (85% of ad libitum); CPT-I activities in liver and skeletal muscle mitochondria were determined, and enzyme kinetic constants (V:(max) and K:(m) for carnitine) were estimated. Kinetics of CPT-I in muscle were not affected by diet (P: > 0.1; carnitine K:(m) = 480 +/- 44 micromol/L). In contrast, the K:(m) for carnitine in liver was increased from 164 to 216 +/- 20 micromol/L by dietary L-carnitine supplementation (P: < 0.01) and from 169 to 211 +/- 20 micromol/L by high protein feeding (P: < 0.05). Dietary L-carnitine increased muscle and liver free carnitine concentrations by 72 and 158% over control concentrations (770 and 80 micro;mol/kg wet muscle and liver, respectively). Because tissue carnitine concentrations were within the range of the respective K:(m) for both liver and muscle tissue, it is inferred that alteration of tissue carnitine concentrations via dietary supplementation could modulate CPT-I activity in young pigs.

  7. Oral Mucositis Prevention By Low-Level Laser Therapy in Head-and-Neck Cancer Patients Undergoing Concurrent Chemoradiotherapy: A Phase III Randomized Study

    SciTech Connect

    Gouvea de Lima, Aline; Villar, Rosangela Correa; Castro, Gilberto de; Antequera, Reynaldo; Gil, Erlon; Rosalmeida, Mauro Cabral; Federico, Miriam Hatsue Honda; Snitcovsky, Igor Moises Longo

    2012-01-01

    Purpose: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. Methods and Materials: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm{sup 2} or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. Results: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. Conclusions: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might

  8. Effects of dietary supplemental L-carnitine and ascorbic acid on performance, carcass composition and plasma L-carnitine concentration of broiler chicks reared under different temperature.

    PubMed

    Celik, L; Oztürkcan, O

    2003-02-01

    The present study was initiated to determine whether dietary supplemental L-carnitine and ascorbic acid affect growth performance, carcass yield and composition, abdominal fat and plasma L-carnitine concentration of broiler chicks reared under normal and high temperature. During the experiment, two temperature regimes were employed in two experimental rooms, which were identical but different in environmental temperature. The regimes were thermoneutral (20-22 degrees C for 24 h) or recycling hot (34-36 degrees C for 8 h and 20-22 degrees C for 16 h). One-day-old broiler chicks (ROSS) were used in the experiment. A 2 x 2 x 2 factorial arrangement was employed with two levels (0 and 50 mg/kg) of supplemental L-carnitine and two levels (0 or 500 mg/kg) of supplemental ascorbic acid in drinking water under thermoneutral or high temperature regimes. Body weight gain was affected by high temperature. However, body weight gain was significantly improved in animals receiving supplemental L-carnitine, ascorbic acid or L-carnitine + ascorbic acid compared to animals receiving unsupplemented diet under high temperature. On the other hand, supplemental L-carnitine or L-carnitine + ascorbic acid reduced body weight gain under thermoneutral condition. Supplemental ascorbic acid significantly improved feed conversion efficiency, the improvement was relatively greater under high temperature. The L-carnitine content in the plasma was higher in the groups receiving supplemental L-carnitine and ascorbic acid under high temperature, while broilers fed supplemental L-carnitine and ascorbic acid had a decreased level of plasma L-carnitine concentration under normal temperature. It is concluded that dietary supplemental L-carnitine or L-carnitine + ascorbic acid may have positive effects on body weight gain, carcass weight under high temperature conditions.

  9. Challenges in Oral Lipid-lowering Therapy: Position Document of the Spanish Society of Cardiology.

    PubMed

    Anguita Sánchez, Manuel; Castro Conde, Almudena; Cordero Fort, Alberto; García-Moll Marimón, Xavier; Gómez Doblas, Juan José; González-Juanatey, José R; Lidón Corbi, Rosa María; López-Sendón, José Luis; Mostaza Prieto, José; Rodríguez Padial, Luis

    2016-11-01

    Lipid-lowering therapy is one of the cornerstones of cardiovascular prevention and is one of the most effective strategies in the secondary prevention of ischemic heart disease. Nevertheless, the current treatment of lipid disorders, together with lifestyle changes, fails to achieve the targets recommended in clinical guidelines in a substantial proportion of patients. PCSK9 inhibitors have demonstrated safety and efficacy in the treatment of dyslipidemia. Due to their ability to reduce low-density lipoprotein cholesterol levels, these drugs have recently been approved for clinical use by Spanish regulatory agencies, with the aim of reducing cardiovascular risk in selected patient groups.

  10. Long-Term Fosfomycin-Tromethamine Oral Therapy for Difficult-To-Treat Chronic Bacterial Prostatitis

    PubMed Central

    Pigrau, Carles; Rodríguez-Pardo, Dolors; Fernández-Hidalgo, Nuria; Andreu, Antonia; Larrosa, Nieves; Almirante, Benito

    2015-01-01

    This is a retrospective study of 15 difficult-to-treat (i.e., exhibiting previous failure, patient side effects, or resistance to ciprofloxacin and co-trimoxazole) chronic bacterial prostatitis infections (5 patients with multidrug-resistant Enterobacteriaceae [MDRE]) receiving fosfomycin-tromethamine at a dose of 3 g per 48 to 72 h for 6 weeks. After a median follow-up of 20 months, 7 patients (47%) had a clinical response, and 8 patients (53%) had persistent microbiological eradication; 4/5 patients with MDRE isolates achieved eradication. There were no side effects. Fosfomycin-tromethamine is a possible alternative therapy for chronic bacterial prostatitis. PMID:26666924

  11. Low Level Laser Therapy to Reduce Recurrent Oral Ulcers in Behçet's Disease

    PubMed Central

    Babu, D. B. Gandhi; Chavva, Sunanda; Waghray, Shefali

    2016-01-01

    Behçet's disease (BD) is a chronic, relapsing multisystemic vascular condition. Behçet's disease was described by Hulusi Behçet in 1937. This rare multisystem relapsing-remitting inflammatory disease is poorly understood but is thought to be an autoimmune inflammatory vasculitic process in a genetically predisposed population. Diagnosis of Behçet's disease is based on International Criteria of Behçet's Disease (ICBD). The present paper describes a case report of Behçet's syndrome where aphthous stomatitis was treated with low level laser therapy. PMID:27555969

  12. Production of L-carnitine by secondary metabolism of bacteria

    PubMed Central

    Bernal, Vicente; Sevilla, Ángel; Cánovas, Manuel; Iborra, José L

    2007-01-01

    The increasing commercial demand for L-carnitine has led to a multiplication of efforts to improve its production with bacteria. The use of different cell environments, such as growing, resting, permeabilized, dried, osmotically stressed, freely suspended and immobilized cells, to maintain enzymes sufficiently active for L-carnitine production is discussed in the text. The different cell states of enterobacteria, such as Escherichia coli and Proteus sp., which can be used to produce L-carnitine from crotonobetaine or D-carnitine as substrate, are analyzed. Moreover, the combined application of both bioprocess and metabolic engineering has allowed a deeper understanding of the main factors controlling the production process, such as energy depletion and the alteration of the acetyl-CoA/CoA ratio which are coupled to the end of the biotransformation. Furthermore, the profiles of key central metabolic activities such as the TCA cycle, the glyoxylate shunt and the acetate metabolism are seen to be closely interrelated and affect the biotransformation efficiency. Although genetically modified strains have been obtained, new strain improvement strategies are still needed, especially in Escherichia coli as a model organism for molecular biology studies. This review aims to summarize and update the state of the art in L-carnitine production using E. coli and Proteus sp, emphasizing the importance of proper reactor design and operation strategies, together with metabolic engineering aspects and the need for feed-back between wet and in silico work to optimize this biotransformation. PMID:17910757

  13. Effect of inhibiting carnitine biosynthesis on male rat sexual performance.

    PubMed

    Dambrova, Maija; Cirule, Helena; Svalbe, Baiba; Zvejniece, Liga; Pugovichs, Osvalds; Zorenko, Tatjana; Kalvinsh, Ivars; Liepinsh, Edgars; Belozertseva, Irina

    2008-10-20

    l-carnitine has a documented role as a cofactor in cellular energy metabolism and fatty acid beta-oxidation pathways and it has also been considered to function in reproductive biology. We investigated whether decreasing concentrations of L-carnitine using an inhibitor of its biosynthesis, mildronate (3-(2,2,2-trimethylhydrazinium)-propionate), would influence the sexual behavior or sperm quality in male rats. Mildronate treatment induced a significant decrease in carnitine concentration and an increase in gamma-butyrobetaine (GBB) concentration in both plasma and testes extracts. However, the expression of carnitine palmitoyltransferase I in testes and testosterone concentration in plasma was not changed in mildronate treated rat. Behavioral experiments demonstrated that mildronate treatment did not decrease the sexual motivation in both sexually naive and sexually experienced rats. The densities of spermatozoa in the cauda epididymis, as well as motility, were unchanged after mildronate treatment at a dose of 100 mg/kg. In conclusion, our study provides experimental evidence that mildronate induces decrease in the free carnitine concentration in rat testes, but does not decrease the sexual activity or sperm quality of male rats.

  14. Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells

    PubMed Central

    Wang, Xiaomei; Su, Jin; Sherman, Alexandra; Rogers, Geoffrey L.; Liao, Gongxian; Hoffman, Brad E.; Leong, Kam W.; Terhorst, Cox; Daniell, Henry

    2015-01-01

    Coagulation factor replacement therapy for the X-linked bleeding disorder hemophilia is severely complicated by antibody (“inhibitor”) formation. We previously found that oral delivery to hemophilic mice of cholera toxin B subunit-coagulation factor fusion proteins expressed in chloroplasts of transgenic plants suppressed inhibitor formation directed against factors VIII and IX and anaphylaxis against factor IX (FIX). This observation and the relatively high concentration of antigen in the chloroplasts prompted us to evaluate the underlying tolerance mechanisms. The combination of oral delivery of bioencapsulated FIX and intravenous replacement therapy induced a complex, interleukin-10 (IL-10)–dependent, antigen-specific systemic immune suppression of pathogenic antibody formation (immunoglobulin [Ig] 1/inhibitors, IgE) in hemophilia B mice. Tolerance induction was also successful in preimmune mice but required prolonged oral delivery once replacement therapy was resumed. Orally delivered antigen, initially targeted to epithelial cells, was taken up by dendritic cells throughout the small intestine and additionally by F4/80+ cells in the duodenum. Consistent with the immunomodulatory responses, frequencies of tolerogenic CD103+ and plasmacytoid dendritic cells were increased. Ultimately, latency-associated peptide expressing CD4+ regulatory T cells (CD4+CD25−LAP+ cells with upregulated IL-10 and transforming growth factor-β (TGF-β) expression) as well as conventional CD4+CD25+ regulatory T cells systemically suppressed anti-FIX responses. PMID:25700434

  15. Histological Evaluation of Wound Healing Process after Photodynamic Therapy of Rat Oral Mucosal Ulcer

    PubMed Central

    Deyhimi, Parviz; Khademi, Heidar; Birang, Reza; Akhoondzadeh, Mohammad

    2016-01-01

    Statement of the Problem When the body defense is compromised, wounds can act as a route for entrance and colonization of microorganisms in the body. Photodynamic therapy with methylene blue is known as a promising antimicrobial modality. Purpose The present study aimed to investigate the effects of this procedure on wound healing processes. Materials and Method In this experimental study, 48 male Wistar rats were recruited. Experimental wounds were surgically made on their buccal mucosa. Based on the treatment modality, they were divided into 3 groups (n=16) of control (CG), laser (LG), photosensitizer+ laser (PLG) by methylene blue (MB). The treatment procedure in the two latter groups was done in days 1-4 and 6-9. After sacrificing on 2, 4, 7 and 14-day follow-ups, the microscopic grade of healing of the wounds was assigned on each interval according to histological grading criteria. Results A qualitative result was obtained that showed a healing progression in PLG at day 2 of follow-up. At day 4 of follow-up, no difference was seen in healing stage among the groups. However on day 7 of follow-up, samples of the LG showed a lower degree of healing compared with the other two groups. Likewise, on day 14 of follow- up, both PLG and LG showed lower degree of healing than CG. Conclusion This study qualitatively showed that MB- mediated photodynamic therapy would have an inhibitory effect on healing process after 14 days of the wound creation. PMID:26966708

  16. Systemic oxygen therapy versus oral enalapril for treatment of diabetic macular ischemia: a randomized controlled trial.

    PubMed

    Sharifipour, Farideh; Razzaghi, Mohammadreza; Ramezani, Alireza; Azarmina, Mohsen; Yaseri, Mehdi; Soheilian, Roham; Soheilian, Masoud

    2016-04-01

    The purpose of this study was to evaluate the structural and functional effects of systemic oxygen therapy and enalapril in patients with diabetic macular ischemia (DMI). This randomized clinical trial consisted of 105 eyes with DMI divided into three groups. Group I received systemic oxygen by face mask at a flow rate of 10 L/min; Group II received 5 mg enalapril daily; and Group III received placebo tablets for 3 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT) measured by optical coherence tomography (OCT), extent of foveal avascular zone (FAZ) on fluorescein angiograms, and electroretinograms (ERG) were obtained at baseline and after 3 and 6 months. Overall, 102 patients completed the study. Baseline characteristics were not significantly different among groups. Significant improvement in BCVA and decrease in CMT and FAZ occurred at months 3 and 6 in oxygen group compared to deterioration in enalapril and control groups (All P values <0.001). ERG parameters were significantly better in oxygen group compared to enalapril group at months 3 and 6 and better than those in control group at month 3. Normobaric oxygen therapy for 3 months in DMI decreased CMT and FAZ and improved BCVA and ERG parameters. Enalapril did not show any favorable effect.

  17. A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1

    PubMed Central

    Lukina, Elena; Watman, Nora; Arreguin, Elsa Avila; Banikazemi, Maryam; Dragosky, Marta; Iastrebner, Marcelo; Rosenbaum, Hanna; Phillips, Mici; Pastores, Gregory M.; Rosenthal, Daniel I.; Kaper, Mathilde; Singh, Tejdip; Puga, Ana Cristina; Bonate, Peter L.

    2010-01-01

    Eliglustat tartrate (Genz-112638), a specific inhibitor of glucosylceramide synthase, is under development as an oral substrate reduction therapy for Gaucher disease type 1 (GD1). A multinational, open-label, single-arm phase 2 study of 26 GD1 patients (16 female, 10 male; mean age, 34 years) evaluated the efficacy, safety, and pharmacokinetics of eliglustat tartrate administered twice daily by mouth at 50- or 100-mg doses based on plasma drug concentrations. Entry criteria required splenomegaly with thrombocytopenia and/or anemia. The composite primary efficacy end point required improvement after 52 weeks in at least 2 of these 3 disease manifestations and was met by 77% (95% confidence interval [CI] = 58%-89%) of all patients and 91% (95% CI = 72%-98%) of the 22 patients completing 52 weeks. Statistically significant improvements occurred in mean hemoglobin level (1.62 g/dL; 95% CI =1.05-2.18 g/dL), platelet count (40.3%; 95% CI = 23.7-57.0 g/dL), spleen volume (−38.5%; 95% CI = −43.5%-−33.5%), liver volume (−17.0%; 95% CI = −21.6%-12.3%), and lumbar spine bone mineral density (0.31 Z-score; 95% CI = 0.09-0.53). Elevated biomarkers (chitotriosidase; chemokine CCL18; angiotensin-converting enzyme; tartrate-resistant acid phosphatase) decreased by 35% to 50%. Plasma glucosylceramide and ganglioside GM3 normalized. Eliglustat tartrate was well tolerated: 7 mild, transient adverse events in 6 patients were considered treatment-related. Individual pharmacokinetics varied; mean time to maximal observed concentration was 2.3 hours and mean half-life was 6.8 hours. Eliglustat tartrate appears to be a promising oral treatment for GD1. This study is registered at www.clinicaltrials.gov as #NCT00358150. PMID:20439622

  18. Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever

    PubMed Central

    Mendenhall, Michelle; Russell, Andrew; Smee, Donald F.; Hall, Jeffery O.; Skirpstunas, Ramona; Furuta, Yousuke; Gowen, Brian B.

    2011-01-01

    Background Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed. Methodology/Principal Findings Here, we used a model of acute arenaviral infection in outbred guinea pigs based on challenge with an adapted strain of Pichindé virus (PICV) to further preclinical development of T-705 (Favipiravir), a promising broad-spectrum inhibitor of RNA virus infections. The guinea pig-adapted passage 19 PICV was uniformly lethal with an LD50 of ∼5 plaque-forming units and disease was associated with fever, weight loss, thrombocytopenia, coagulation defects, increases in serum aspartate aminotransferase (AST) concentrations, and pantropic viral infection. Favipiravir (300 mg/kg/day, twice daily orally for 14 days) was highly effective, as all animals recovered fully from PICV-induced disease even when therapy was initiated one week after virus challenge when animals were already significantly ill with marked fevers and thrombocytopenia. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in peak serum virus titers and AST concentrations in favipiravir-treated animals. Moreover, a sharp decrease in body temperature was observed shortly after the start of treatment. Oral ribavirin was also evaluated, and although effective, the slower rate of recovery may be a sign of the drug's known toxicity. Conclusions/Significance Our findings support further development of favipiravir for the treatment of severe arenaviral infections. The optimization of the experimental favipiravir treatment regimen in the PICV guinea pig model will inform critical future studies in the same species based

  19. Comparison of a commercially available oral nutritional supplement and intravenous fluid therapy for dehydration in dairy calves.

    PubMed

    Taylor, Jared D; Rodenburg, Merel; Snider, Timothy A

    2017-04-05

    Calf scours is a primary cause of morbidity and mortality in the dairy industry. Effective treatments are needed to minimize death, maximize welfare, and maintain growth and productivity. The objective of this trial was to compare the efficacy of a commercially available nutritional supplement (Diaque, Boehringer-Ingelheim Vetmedica Inc., St. Joseph, MO) and i.v. lactated Ringer's solution (LRS) in rehydrating, preventing acidemia, and correcting electrolyte imbalances in an experimental model for calf scours. Twenty-four colostrum-fed suckling dairy calves were used in a modified crossover design. An osmotic diarrhea was induced by orally feeding commercial milk replacer modified with high level of sucrose to create a hypertonic milk solution, and administering oral hydrochlorothiazide and spironolactone for 48 h. The intention was to create a challenge sufficient to result in moderately dehydrated, standing calves without producing severe depression or loss of suckle. The efficacy of i.v. fluid therapy and a commercial nutritional supplement were subsequently compared for reversing the effects of the diarrheal disease. Treatment A consisted of administering the nutritional supplement according to label directions (100 g in 1.9 L of warm water, 3 times a day), and treatment B consisted of i.v. LRS (2 L, once a day). Clinical signs and laboratory results were obtained once daily by a blinded observer. The induction method was effective in creating the desired effect, as demonstrated by weight loss and subjective health and hydration scores. Both treatment groups experienced increases in body weight, base excess, and bicarbonate, and decreases in total protein and packed cell volume following treatment. Both i.v. LRS and Diaque are effective methods to correct hypovolemia and control derangements in acid-base status in calves with diarrhea and dehydration.

  20. Perspectives on oral pulmonary hypertension therapies recently approved by the U.S. Food and Drug Administration.

    PubMed

    Hill, Nicholas S; Badesch, David; Benza, Raymond L; D'Eletto, Thomas A; Farber, Harrison W; Gomberg-Maitland, Mardi; Hassoun, Paul M; Preston, Ioana

    2015-02-01

    In the past 18 months, the U.S. Food and Drug Administration approved macitentan, riociguat, and treprostinil as oral agents for the treatment of pulmonary arterial hypertension (PAH); riociguat also became the first agent approved for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). These new agents are welcome additional therapeutic options for PAH and CTEPH. However, their use can be complicated by potential drug interactions, adverse effects, dosing complexity, and cost. Macitentan, the newest endothelin receptor antagonist, showed significant benefits in a long-term event-driven trial of morbidity and mortality. Dosed once daily and with minimal liver toxicity, it has potential drug interactions with potent CYP 3A4 inhibitors and inducers, and can decrease hemoglobin levels. Riociguat is approved for PAH and clinically inoperable CTEPH to improve exercise capacity and functional status. Riociguat requires dose titration beginning with 1 mg up to 2.5 mg three times a day, as tolerated, and should be used with caution in patients with underlying risk factors for systemic hypotension. Oral treprostinil, approved to improve exercise capacity in PAH, is associated with gastrointestinal side effects and headaches that are often dose limiting. Doses can begin with 0.125 mg or 0.25 mg twice a day with gradual increases on up to a weekly basis, as tolerated. Thrice daily dosing and administration with a meal can improve tolerance. These newer agents represent advances, but their specific roles in relation to pre-existing therapies are undergoing further evaluation. Therefore, close collaboration with clinicians at centers with therapeutic expertise is highly recommended to optimize patient outcomes.

  1. Clinical Application of Mesenchymal Stem Cells and Novel Supportive Therapies for Oral Bone Regeneration

    PubMed Central

    O'Valle, Francisco; Lanis, Alejandro; Dohan Ehrenfest, David M.; Wang, Hom-Lay; Galindo-Moreno, Pablo

    2015-01-01

    Bone regeneration is often needed prior to dental implant treatment due to the lack of adequate quantity and quality of the bone after infectious diseases, trauma, tumor, or congenital conditions. In these situations, cell transplantation technologies may help to overcome the limitations of autografts, xenografts, allografts, and alloplastic materials. A database search was conducted to include human clinical trials (randomized or controlled) and case reports/series describing the clinical use of mesenchymal stem cells (MSCs) in the oral cavity for bone regeneration only specifically excluding periodontal regeneration. Additionally, novel advances in related technologies are also described. 190 records were identified. 51 articles were selected for full-text assessment, and only 28 met the inclusion criteria: 9 case series, 10 case reports, and 9 randomized controlled clinical trials. Collectively, they evaluate the use of MSCs in a total of 290 patients in 342 interventions. The current published literature is very diverse in methodology and measurement of outcomes. Moreover, the clinical significance is limited. Therefore, the use of these techniques should be further studied in more challenging clinical scenarios with well-designed and standardized RCTs, potentially in combination with new scaffolding techniques and bioactive molecules to improve the final outcomes. PMID:26064899

  2. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester

    PubMed Central

    Hashim, Sami A.; VanItallie, Theodore B.

    2014-01-01

    Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer’s disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson’s disease. PMID:24598140

  3. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.

    PubMed

    Hashim, Sami A; VanItallie, Theodore B

    2014-09-01

    Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer's disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson's disease.

  4. Acetyl-L-carnitine: from a biological curiosity to a drug for the peripheral nervous system and beyond.

    PubMed

    Onofrj, Marco; Ciccocioppo, Fausta; Varanese, Sara; di Muzio, Antonio; Calvani, Menotti; Chiechio, Santina; Osio, Maurizio; Thomas, Astrid

    2013-08-01

    Acetyl-L-carnitine (ALC) is a molecule derived from acetylation of carnitine in the mitochondria. Carnitine acetylation enables the function of CoA and facilitates elimination of oxidative products. Beyond this metabolic activity, ALC provides acetyl groups for acetylcholine synthesis, exerts a cholinergic effect and optimizes the balance of energy processes. Acetylcarnitine supplementation induces neuroprotective, neurotrophic and analgesic effects in the peripheral nervous system. In the recent studies, ALC, by acting as a donor of acetyl groups to NF-kb p65/RelA, enhanced the transcription of the GRM2 gene encoding the mGLU2 receptors, inducing long-term upregulation of the mGluR2, evidencing therefore that its long-term analgesic effects are dependent on epigenetic modifications. Several studies, including double-blind, placebo-controlled, parallel group studies and few open studies showed the effect of ALC in diseases characterized by neuropathies and neuropathic pain: the studies included diabetic neuropathy, HIV and antiretroviral therapy-induced neuropathies, neuropathies due to compression and chemotherapeutic agents. Double-blinded studies involved 1773 patients. Statistical evaluations evidenced reduction of pain, improvements of nerve function and trophism. In conclusion, ALC represents a consistent therapeutic option for peripheral neuropathies, and its complex effects, neurotrophic and analgesic, based on epigenetic mechanism, open new pathways in the study of peripheral nerve disease management.

  5. A relationship between CD4 count and oral manifestations of human immunodeficiency virus-infected patients on highly active antiretroviral therapy in urban population

    PubMed Central

    Satyakiran, Gadavalli Vera Venkata; Bavle, Radhika Manoj; Alexander, Glory; Rao, Saritha; Venugopal, Reshma; Hosthor, Sreelatha S

    2016-01-01

    Introduction: Human immunodeficiency virus (HIV) infection gradually destroys the body's immune system, which makes it harder for the body to fight infections. HIV infection causes a quantitative and qualitative depletion of CD4 lymphocyte count, which increases the risk of opportunistic infections. Thus, CD4 count is one of the key factors in determining both the urgency of highly active antiretroviral therapy (HAART) initiation and the need of prophylaxis for opportunistic infections. Aim: This study aims to evaluate the prevalence and variations in the oral manifestations of HIV/acquired immune deficiency syndrome patients on HAART therapy in urban population and their association with CD4 count. Materials and Methods: A study was conducted by screening eighty patients who were HIV positive in an urban location. Both adult and pediatric patients were screened for oral manifestations and simultaneously CD4 count was also evaluated. Patients with HIV infection for variable time period who are under HAART were considered. Statistical Analysis: Measures of central tendency were used to analyse the data. Results: HIV infection destroys the immune system of an individual, making the patient susceptible to various infections and malignancies. With the advent of antiretroviral therapy, the scenario has changed drastically. We have observed that patients with CD4 counts between 164 and 1286 show relatively few oral manifestations. Long-term HAART therapy causes pigmentation, xerostomia and angular cheilitis but is taken up quite well by the patients. Conclusion: In this study, eighty patients with HAART from urban population showed very minimal oral findings because of good accessibility for treatment and awareness about HIV infections. The patients who were on long-standing HAART treatment also showed minimal oral manifestatio