Science.gov

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. PMID:22569432

  3. [The benefits of L-carnitine therapy in essential arterial hypertension with diabetes mellitus type II].

    PubMed

    Digiesi, V; Palchetti, R; Cantini, F

    1989-03-01

    Carnitine is a natural substance essential for the mitochondrial oxidation of long-chain fatty acids and therefore regulates the energy metabolism of the cells. Tissue carnitine levels are altered under diabetes mellitus or hypertension. The aim of this study was to evaluate the efficacy and tolerability of L-carnitine therapy in essential hypertension with diabetes mellitus type II. A clinical trial was performed in two homogeneous groups with essential hypertension and diabetes mellitus type II. L-carnitine was given orally, 2 g twice daily, for 45 weeks. In the group of patients treated with L-carnitine in comparison with control group cardiac arrhythmias, chiefly extrasystoles, some disorders of A-V conduction and some electrocardiographic signs of ischaemia stopped or diminished and symptoms, chiefly asthenia, significantly improved. No side effects were observed during the treatment. These results show that treatment with L-carnitine is useful and well tolerated in patients with essential hypertension and diabetes mellitus type II.

  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. Glycine and L-carnitine therapy in 3-methylcrotonyl-CoA carboxylase deficiency.

    PubMed

    Rutledge, S L; Berry, G T; Stanley, C A; van Hove, J L; Millington, D

    1995-01-01

    Genetic deficiency of 3-methylcrotonyl-CoA carboxylase (3-MCC) is a rare inborn error of leucine metabolism producing an organic acidaemia. With accumulation of 3-methylcrotonyl-CoA, there is increased production of 3-hydroxyisovaleric acid, the glycine conjugate (3-methylcrotonylglycine), and the carnitine conjugate (3-hydroxyisovalerylcarnitine). The conjugates represent endogenous detoxification products. We studied excretion rates of these conjugates at baseline and with glycine and carnitine therapy in an 8-year-old girl with 3-MCC deficiency. Her preadmission diet was continued. Plasma and urine samples were obtained after 24 h of each of the following: L-carnitine 100 mg/kg per day and glycine 100, 175 and 250 mg/kg per day. Plasma and urinary carnitine levels were reduced by 80% and 50%, respectively with abnormal urinary excretion patterns. These normalized with carnitine therapy. Acylcarnitine excretion increased with carnitine therapy. The glycine conjugate, 3-methylcrotonylglycine (3-MCG), was the major metabolite excreted at all times and its excretion increased with glycine therapy. Clearly, in 3-MCC deficiency the available glycine and carnitine pools are not sufficient to meet the potential for conjugation of accumulated metabolites, suggesting a possible therapeutic role for glycine and carnitine therapy in this disorder.

  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

    2014-12-01

    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. Effects of Oral L-Carnitine on Liver Functions after Transarterial Chemoembolization in Intermediate-Stage HCC Patients

    PubMed Central

    Hassan, Abeer; Tsuda, Yasuhiro; Asai, Akira; Yokohama, Keisuke; Nakamura, Ken; Sujishi, Tetsuya; Ohama, Hideko; Tsuchimoto, Yusuke; Fukunishi, Shinya; Abdelaal, Usama M.; Arafa, Usama A.; Hassan, Ali T.; Kassem, Ali M.; Higuchi, Kazuhide

    2015-01-01

    Transarterial chemoembolization (TACE) is usually followed by hepatic dysfunction. We evaluated the effects of L-carnitine on post-TACE impaired liver functions. Methods. 53 cirrhotic hepatocellular carcinoma patients at Osaka Medical College were enrolled in this study and assigned into either L-carnitine group receiving 600 mg oral L-carnitine daily or control group. Liver functions were evaluated at pre-TACE and 1, 4, and 12 weeks after TACE. Results. The L-carnitine group maintained Child-Pugh (CP) score at 1 week after TACE and exhibited significant improvement at 4 weeks after TACE (P < 0.01). Conversely, the control group reported a significant CP score deterioration at 1 week (P < 0.05) and 12 weeks after TACE (P < 0.05). L-carnitine suppressed serum albumin deterioration at 1 week after TACE. There were significant differences between L-carnitine and control groups regarding mean serum albumin changes from baseline to 1 week (P < 0.05) and 4 weeks after TACE (P < 0.05). L-carnitine caused prothrombin time improvement from baseline to 1, 4 (P < 0.05), and 12 weeks after TACE. Total bilirubin mean changes from baseline to 1 week after TACE exhibited significant differences between L-carnitine and control groups (P < 0.05). The hepatoprotective effects of L-carnitine were enhanced by branched chain amino acids combination. Conclusion. L-carnitine maintained and improved liver functions after TACE. PMID:26664151

  9. 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. PMID:23138103

  10. 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

  11. Does L-carnitine improve endothelial function in hemodialysis patients?

    PubMed Central

    Sabri, Mohammad Reza; Fahimi, Farnaz; Hajialiasgar, Soheila; Etminan, Abbas; Nazemi, Sarir; Salehi, Farzaneh

    2012-01-01

    Background: Atherosclerosis is the leading cause of death in hemodialysis patients. These patients are also very prone to L-carnitine deficiency due to kidney disease. In this clinical trial, we investigated the effect of oral L-carnitine on endothelial function of these patients. Materials ans Methods: We studied 31 adult chronic hemodialysis patients in our center and divided them into two groups. The first group (n = 20) received 1500 mg/dialysis interval (every other day) oral L-carnitine. The control group (n = 11) received placebo for one month. Ultrasonographic measurements of flow mediated dilation and carotid intima-media thickness were performed before and after one month of L-carnitine and placebo therapy. Results: This study showed that after one month of L-carnitine or placebo therapy there was no significant improvement in flow mediated dilation (p = 0.80 and p = 0.59, respectively) or decrease in carotid intima-media thickness (p = 0.12 and p = 0.50, respectively). Conclusions: Our study revealed that one month of oral L-carnitine therapy did not improve endothelial function in hemodialysis patients. Long-term studies with large sample size using intravenous form and higher doses of the drug are required to clarify the questionable role of L-carnitine in hemodialysis patients. PMID:23626603

  12. New Oral Therapies for Psoriasis

    PubMed Central

    Lanoue, Julien; Dong, Joanna

    2016-01-01

    Conventional oral therapies for psoriasis, including methotrexate, cyclosporine, and acitretin, have generally unfavorable safety profiles and are not ideal for long-standing use. Thus, new oral therapies are necessary for patients with more moderate disease, patients who prefer oral treatments to injectable biologies, and patients who failed conventional therapies. The authors review here the clinical and safety evidence of phosphodiesterase 4 inhibitor, apremilast, janus kinase inhibitors, including tofacitinib, and fumarie acid esters as additional options in oral psoriasis therapy.

  13. New Oral Therapies for Psoriasis

    PubMed Central

    Lanoue, Julien; Dong, Joanna

    2016-01-01

    Conventional oral therapies for psoriasis, including methotrexate, cyclosporine, and acitretin, have generally unfavorable safety profiles and are not ideal for long-standing use. Thus, new oral therapies are necessary for patients with more moderate disease, patients who prefer oral treatments to injectable biologies, and patients who failed conventional therapies. The authors review here the clinical and safety evidence of phosphodiesterase 4 inhibitor, apremilast, janus kinase inhibitors, including tofacitinib, and fumarie acid esters as additional options in oral psoriasis therapy. PMID:27672415

  14. 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

  15. 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

  16. 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.

  17. Chronic oral ingestion of l-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans

    PubMed Central

    Wall, Benjamin T; Stephens, Francis B; Constantin-Teodosiu, Dumitru; Marimuthu, Kanagaraj; Macdonald, Ian A; Greenhaff, Paul L

    2011-01-01

    We have previously shown that insulin increases muscle total carnitine (TC) content during acute i.v. l-carnitine infusion. Here we determined the effects of chronic l-carnitine and carbohydrate (CHO; to elevate serum insulin) ingestion on muscle TC content and exercise metabolism and performance in humans. On three visits, each separated by 12 weeks, 14 healthy male volunteers (age 25.9 ± 2.1 years, BMI 23.0 ± 0.8 kg m−2) performed an exercise test comprising 30 min cycling at 50%, 30 min at 80%, then a 30 min work output performance trial. Muscle biopsies were obtained at rest and after exercise at 50% and 80% on each occasion. Following visit one, volunteers ingested either 80 g of CHO (Control) or 2 g of l-carnitine-l-tartrate and 80 g of CHO (Carnitine) twice daily for 24 weeks in a randomised, double blind manner. All significant effects reported occurred after 24 weeks. Muscle TC increased from basal by 21% in Carnitine (P < 0.05), and was unchanged in Control. At 50%, the Carnitine group utilised 55% less muscle glycogen compared to Control (P < 0.05) and 31% less pyruvate dehydrogenase complex (PDC) activation compared to before supplementation (P < 0.05). Conversely, at 80%, muscle PDC activation was 38% higher (P < 0.05), acetylcarnitine content showed a trend to be 16% greater (P < 0.10), muscle lactate content was 44% lower (P < 0.05) and the muscle PCr/ATP ratio was better maintained (P < 0.05) in Carnitine compared to Control. The Carnitine group increased work output 11% from baseline in the performance trial, while Control showed no change. This is the first demonstration that human muscle TC can be increased by dietary means and results in muscle glycogen sparing during low intensity exercise (consistent with an increase in lipid utilisation) and a better matching of glycolytic, PDC and mitochondrial flux during high intensity exercise, thereby reducing muscle anaerobic ATP production. Furthermore, these changes were associated with an

  18. 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

  19. Immunological responses in patients with tuberculosis and in vivo effects of acetyl-L-carnitine oral administration

    PubMed Central

    Altamura, Maria; Marcuccio, Carlo; Tortorella, Cosimo; De Simone, Claudio; Antonaci, Salvatore

    1993-01-01

    Tuberculosis (TBC) is characterized by a complex immune response which parallels the clinical course of the disease. In this respect, acquired resistance, delayed hypersensitivity reaction and anergy are the main types of immune reactivity to mycobacterial antigens. In view of the presence of nonspecific and specific immune deficits in TBC patients, a clinical trial was carried out in a group of 20 individuals with active pulmonary TBC by oral administration of acetyl-L-carnitine (ALC). This drug, which has been shown to possess immunomodulating activities, was able to upregulate the T-dependent antibacterial activity in TBC patients after 30 days' treatment, while the same activity decreased in patients receiving placebo only. On the other hand, ALC did not modify serum levels of tumour necrosis factor-α, in the same individuals. This cytokine plays a detrimental rather than beneficial role in TBC pathogenesis. In the light of these data, ALC seems to be a powerful immunomodulator in the course of Mycobacterium tuberculosis infection and other mycobacteriosis. PMID:18475563

  20. [Oral therapy of interstitial cystitis].

    PubMed

    Sievert, K D; Edenfeld, K D; Oberpenning, F; Piechota, H J

    2000-11-01

    Up to now there is no specific treatment targeting the ultimate cause of interstitial cystitis (IC), since its pathogenesis and etiology are still unknown. Most studies focussing on oral medication have not been randomized, double-blinded or placebo-controlled. Numerous case reports and intent-to-treat trials are lacking a systematic approach and do not meet evidence-based medicine criteria. Consequently there is as yet no standard oral therapy available for the treatment of IC. However, only a few oral substances have shown a potential to improve symptoms such as frequency and pain. The best results were obtained from monotherapeutic use of pentosanpolysulfate, amitriptylin and hydroxycin. The true benefit of these substances alone should be compared to analgesics and anticholinergics in the course of controlled clinical trials.

  1. 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…

  2. The neurotoxic effect of clindamycin - induced gut bacterial imbalance and orally administered propionic acid on DNA damage assessed by the comet assay: protective potency of carnosine and carnitine

    PubMed Central

    2013-01-01

    Background Comet assay is a quick method for assessing DNA damage in individual cells. It allows the detection of single and double DNA strand breaks, which represent the direct effect of some damaging agents. This study uses standard comet quantification models to compare the neurotoxic effect of orally administered propionic acid (PA) to that produced as a metabolite of bacterial overgrowth induced by clindamycin. Additionally, the protective effect of carnosine and carnitine as natural dietary supplements is assessed. Methods Single cell gel electrophoresis (comet assays) were performed on brain cortex and medulla samples after removal from nine groups of hamsters including: a control (untreated) group; PA-intoxicated group; clindamycin treated group; clindamycin-carnosine group and; clindamycin-carnitine group. Results There were significant double strand breaks recorded as tail length, tail moment and % DNA damage in PA and clindamycin-treated groups for the cortex and medulla compared to the control group. Neuroprotective effects of carnosine and carnitine were observed. Receiver Operating Characteristics curve (ROC) analysis showed satisfactory values of sensitivity and specificity of the comet assay parameters. Conclusion Percentage DNA damage, tail length, and tail moment are adequate biomarkers of PA neurotoxicity due to oral administration or as a metabolite of induced enteric bacterial overgrowth. Establishing biomarkers of these two exposures is important for protecting children’s health by documenting the role of the imbalance in gut microbiota in the etiology of autism through the gut-brain axis. These outcomes will help efforts directed at controlling the prevalence of autism, a disorder recently related to PA neurotoxicity. PMID:23587115

  3. 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

  4. Anticancer oral therapy: emerging related issues.

    PubMed

    Banna, Giuseppe Luigi; Collovà, Elena; Gebbia, Vittorio; Lipari, Helga; Giuffrida, Pietro; Cavallaro, Sebastiano; Condorelli, Rosaria; Buscarino, Calogero; Tralongo, Paolo; Ferraù, Francesco

    2010-12-01

    The use of oral anticancer drugs has shown a steady increase. Most patients prefer anticancer oral therapy to intravenous treatment primarily for the convenience of a home-based therapy, although they require that the efficacy of oral therapy must be equivalent and toxicity not superior than those expected with the intravenous treatment. A better patient compliance, drug tolerability, convenience and possible better efficacy for oral therapy as compared to intravenous emerge as the major reasons to use oral anticancer agents among oncologists. Inter- and intra-individual pharmacokinetic variations in the bioavailability of oral anticancer drugs may be more relevant than for intravenous agents. Compliance is particularly important for oral therapy because it determines the dose-intensity of the treatment and ultimately treatment efficacy and toxicity. Patient stands as the most important determinant of compliance. Possible measures for an active and safe administration of oral therapy include a careful preliminary medical evaluation and selection of patients based on possible barriers to an adequate compliance, pharmacologic issues, patient-focused education, an improvement of the accessibility to healthcare service, as well as the development of home-care nursing symptom-focused interventions. Current evidences show similar quality of life profile between oral and intravenous treatments, although anticancer oral therapy seems to be more convenient in terms of administration and reduced time lost for work or other activities. Regarding cost-effectiveness, current evidences are in favor of oral therapy, mainly due to reduced need of visits and/or day in hospital for the administration of the drug and/or the management of adverse events. PMID:20570443

  5. Oral surgery in patients undergoing chemoradiation therapy.

    PubMed

    Demian, Nagi M; Shum, Jonathan W; Kessel, Ivan L; Eid, Ahmed

    2014-05-01

    Oral health care in patients undergoing chemotherapy and/or radiation therapy can be complex. Care delivered by a multidisciplinary approach is timely and streamlines the allocation of resources to provide prompt care and to attain favorable outcomes. A hospital dentist, oral and maxillofacial surgeon, and a maxillofacial prosthodontist must be involved early to prevent avoidable oral complications. Prevention and thorough preparation are vital before the start of chemotherapy and radiation therapy. Oral complications must be addressed immediately and, even with the best management, can cause delays and interruption in treatment, with serious consequences for the outcome and prognosis.

  6. Oral surgery in patients undergoing chemoradiation therapy.

    PubMed

    Demian, Nagi M; Shum, Jonathan W; Kessel, Ivan L; Eid, Ahmed

    2014-05-01

    Oral health care in patients undergoing chemotherapy and/or radiation therapy can be complex. Care delivered by a multidisciplinary approach is timely and streamlines the allocation of resources to provide prompt care and to attain favorable outcomes. A hospital dentist, oral and maxillofacial surgeon, and a maxillofacial prosthodontist must be involved early to prevent avoidable oral complications. Prevention and thorough preparation are vital before the start of chemotherapy and radiation therapy. Oral complications must be addressed immediately and, even with the best management, can cause delays and interruption in treatment, with serious consequences for the outcome and prognosis. PMID:24794266

  7. 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. PMID:79826

  8. Carnitine in parenteral nutrition.

    PubMed

    Borum, Peggy R

    2009-11-01

    Several new functions or metabolic uses of carnitine and improvements in assessment of carnitine status impact carnitine dosing recommendations. Carnitine dosing will likely be customized for patients at different stages of the life cycle and for patients with dysfunction of different organs. Nutrition supplementation of carnitine should be 2-5 mg x kg(-1) x day(-1) and be administrated via the route used for administration of macronutrients. Pharmacologic supplementation of carnitine should be 50-100 mg x kg(-1) x day(-1) and be reserved for the removal of toxic compounds from the body.

  9. 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

  10. [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.

  11. 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

  12. New Oral Therapies for Psoriasis: A Comprehensive Review.

    PubMed

    Goldenberg, Gary; Lanoue, Julien; Dong, Joanna

    2016-08-01

    Conventional oral therapies for psoriasis, including methotrexate, cyclosporine, and acitretin, have generally unfavorable safety profiles and are not ideal for long-standing use. Thus, new oral therapies are necessary for patients with more moderate disease, patients who prefer oral treatments to injectable biologies, and patients who failed conventional therapies. The authors review here the clinical and safety evidence of phosphodiesterase 4 inhibitor, apremilast, janus kinase inhibitors, including tofacitinib, and fumarie acid esters as additional options in oral psoriasis therapy. PMID:27672415

  13. The effect of homozygous deletion of the BBOX1 and Fibin genes on carnitine level and acyl carnitine profile

    PubMed Central

    2014-01-01

    Background Carnitine is a key molecule in energy metabolism that helps transport activated fatty acids into the mitochondria. Its homeostasis is achieved through oral intake, renal reabsorption and de novo biosynthesis. Unlike dietary intake and renal reabsorption, the importance of de novo biosynthesis pathway in carnitine homeostasis remains unclear, due to lack of animal models and description of a single patient defective in this pathway. Case presentation We identified by array comparative genomic hybridization a 42 months-old girl homozygote for a 221 Kb interstitial deletions at 11p14.2, that overlaps the genes encoding Fibin and butyrobetaine-gamma 2-oxoglutarate dioxygenase 1 (BBOX1), an enzyme essential for the biosynthesis of carnitine de novo. She presented microcephaly, speech delay, growth retardation and minor facial anomalies. The levels of almost all evaluated metabolites were normal. Her serum level of free carnitine was at the lower limit of the reference range, while her acylcarnitine to free carnitine ratio was normal. Conclusions We present an individual with a completely defective carnitine de novo biosynthesis. This condition results in mildly decreased free carnitine level, but not in clinical manifestations characteristic of carnitine deficiency disorders, suggesting that dietary carnitine intake and renal reabsorption are sufficient to carnitine homeostasis. Our results also demonstrate that haploinsufficiency of BBOX1 and/or Fibin is not associated with Primrose syndrome as previously suggested. PMID:24986124

  14. Effect of oral acetyl L-carnitine arginate on resting and postprandial blood biomarkers in pre-diabetics

    PubMed Central

    Bloomer, Richard J; Fisher-Wellman, Kelsey H; Tucker, Patrick S

    2009-01-01

    Background Resting and postprandial oxidative stress is elevated in those with metabolic disorders such as diabetes. Antioxidant supplementation may attenuate the rise in oxidative stress following feeding. Therefore we sought to determine the effects of acetyl L-carnitine arginate (ALCA) on resting and postprandial biomarkers of glucose and lipid metabolism, as well as oxidative stress. Methods Twenty-nine pre-diabetic men and women were randomly assigned to either 3 g·day-1 of ALCA (n = 14; 31 ± 3 yrs) or placebo (n = 15; 35 ± 3 yrs) in a double-blind design, to consume for eight weeks. Fasting blood samples were taken from subjects both pre and post intervention. After each fasting sample was obtained, subjects consumed a high fat, high carbohydrate meal and additional blood samples were taken at 1, 2, 4, and 6 hours post meal. Samples were analyzed for a variety of metabolic variables (e.g., glucose, HbA1c, lipid panel, C-reactive protein, nitrate/nitrite, and several markers of oxidative stress). Area under the curve (AUC) was calculated for each variable measured post meal, both pre and post intervention. Results ALCA, but not placebo, resulted in an increase in nitrate/nitrite (25.4 ± 1.9 to 30.1 ± 2.8 μmol·L-1) from pre to post intervention, with post intervention values greater compared to placebo (p = 0.01). No other changes of statistical significance were noted (p > 0.05), although ALCA resulted in slight improvements in glucose (109 ± 5 to 103 ± 5 mg·dL-1), HbA1c (6.6 ± 1.1 to 6.2 ± 1.2%), and HOMA-IR (3.3 ± 1.3 to 2.9 ± 1.2). AUC postprandial data were not statistically different between ALCA and placebo for any variable (p > 0.05). However, nitrate/nitrite demonstrated a moderate effect size (r = 0.35) for increase from pre (139.50 ± 18.35 μmol·L-1·6 hr-1) to post (172.40 ± 21.75 μmol·L-1·6 hr-1) intervention with ALCA, and the magnitude of decrease following feeding was not as pronounced as with placebo. Conclusion

  15. 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

  16. 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.

  17. 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

  18. Teriflunomide for oral therapy in multiple sclerosis.

    PubMed

    Papadopoulou, Athina; Kappos, Ludwig; Sprenger, Till

    2012-11-01

    Teriflunomide, the active metabolite of an approved antirheumatic drug, is an emerging oral therapy for multiple sclerosis (MS). Next to the inhibition of pyrimidine biosynthesis and proliferation of activated lymphocytes, it seems to have multiple anti-inflammatory and immunomodulating effects. Phase II and III clinical trials in relapsing MS demonstrated favorable safety and tolerability of the drug, as well as clinical efficacy, with a significant reduction of relapse rate, comparable with those of the available injectable immunomodulatory agents. While multiple other studies with teriflunomide are currently ongoing, its exact place in future treatment algorithms for MS is difficult to predict. It may be a good alternative for patients wishing to have an oral treatment with relatively large data regarding long-term safety. PMID:23234322

  19. Cereal-based oral rehydration therapy.

    PubMed

    1987-01-01

    A symposium reviewing and updating experience with oral rehydration therapy for childhood diarrhea, held in Washington, D.C., February 17, 1987, harkened back to traditional methods of treating this condition by examining cereal-based oral rehydration therapy. The formula recommended by WHO currently is a specific mixture of water, salt and sugar. Glucose in sugar facilitates absorption of sodium in salt, and water. Recent research has addressed the superior ability of carbohydrates present in certain cereal grains to facilitate water absorption. Folk remedies have employed such mixtures to treat diarrhea for millennia. The Centre for Diarrheal Disease Research, Bangladesh, has done significant research using rice water. Others have looked at solutions containing maize, sorghum or millet. Some advantages of cereal-based solutions are: better nutrition, readily available ingredients, low cost, familiarity of preparation as gruels, little chance of error. The solution is prepared as thick as possible while still fluid. Only salt has to be measured. Further research is necessary because some studies are inconclusive on the efficacy of cereal solutions for malnourished children or on stability of such solutions. Some broader implications of the topic were use of amino acids with the cereal solutions, and use of such mixtures in industrial countries. PMID:12281245

  20. 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

  1. Acetyl-L-carnitine as an adjunctive therapy in the treatment of attention-deficit/hyperactivity disorder in children and adolescents: a placebo-controlled trial.

    PubMed

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

    2011-06-01

    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 clinic. Subjects included 40 outpatients (28 boys and 12 girls) between the ages of 7-13 who met the DSM-IV-TR diagnostic criteria for ADHD. All study subjects were randomly assigned to receive treatment using capsules of ALC doses ranging from 500 to 1,500 mg/day depending on the weight of the child plus methylphenidate at a dose of 20-30 mg/day depending on weight or Placebo plus methylphenidate at a dose of 20-30 mg/day depending on weight. The principal measure of outcome was the Teacher and Parent attention deficit/hyperactivity disorder Rating Scale- IV. No difference was observed between the two groups on the Parent and Teacher Rating Scale scores (df = 1; F = 0.10; P = 0.74 and df = 1; F = 0.22; P = 0.63 respectively). Side effects consisting of headache and irritability were observed more frequently in the methylphenidate plus placebo group. The results of this study do not support the application of ALC as an adjunctive therapy to methylphenidate in children and adolescents with ADHD. PMID:21336630

  2. Combined oral corticosteroid-methotrexate therapy in Eales' disease.

    PubMed

    Saxena, Sandeep

    2009-01-01

    The efficacy of combined oral corticosteroid and low-dose oral methotrexate pulsed therapy in Eales' disease was evaluated prospectively, based on weighted visual morbidity scale for disease activity and visual acuity grading in 36 consecutive cases. Oral corticosteroids in a weekly tapering dose for 4 weeks and 12.5 mg methotrexate as a single oral dose, once per week for 12 weeks, were administered simultaneously. We concluded that this combined oral therapy is clinically effective with an acceptable safety profile. PMID:19845224

  3. Oral complications of cancer therapies. Oral complications in the pediatric population

    SciTech Connect

    Leggott, P.J. )

    1990-01-01

    A number of acute oral complications may be associated with cancer therapy in children, but the extent and duration of these complications, and the most effective management techniques. have not been well described. The few studies differ in design, making comparisons difficult. Well-controlled, prospective clinical studies are needed to define the most effective strategies for the management of acute oral complications in children. However, it is clear that dental intervention prior to cancer therapy is an important factor in the optimal preparation of the patient. During cancer therapy, intensive supervised oral preventive protocols appear to be of benefit to the child's oral health, overall comfort, and well-being. Furthermore, the prevention of oral infection may significantly reduce the morbidity associated with cancer therapy. Long-term preventive oral care may help prevent dental disease and infection in medically compromised children and contribute to improving the quality of life. 41 references.

  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. Analytical approaches to determination of carnitine in biological materials, foods and dietary supplements.

    PubMed

    Dąbrowska, Monika; Starek, Małgorzata

    2014-01-01

    l-Carnitine is a vitamin-like amino acid derivative, which is an essential factor in fatty acid metabolism as acyltransferase cofactor and in energy production processes, such as interconversion in the mechanisms of regulation of cetogenesis and termogenesis, and it is also used in the therapy of primary and secondary deficiency, and in other diseases. The determination of carnitine and acyl-carnitines can provide important information about inherited or acquired metabolic disorders, and for monitoring the biochemical effect of carnitine therapy. The endogenous carnitine pool in humans is maintained by biosynthesis and absorption of carnitine from the diet. Carnitine has one asymmetric carbon giving two stereoisomers d and l, but only the l form has a biological positive effect, thus chiral recognition of l-carnitine enantiomers is extremely important in biological, chemical and pharmaceutical sciences. In order to get more insight into carnitine metabolism and synthesis, a sensitive analysis for the determination of the concentration of free carnitine, carnitine esters and the carnitine precursors is required. Carnitine has been investigated in many biochemical, pharmacokinetic, metabolic and toxicokinetic studies and thus many analytical methods have been developed and published for the determination of carnitine in foods, dietary supplements, pharmaceutical formulations, biological tissues and body fluid. The analytical procedures presented in this review have been validated in terms of basic parameters (linearity, limit of detection, limit of quantitation, sensitivity, accuracy, and precision). This article presented the impact of different analytical techniques, and provides an overview of applications that address a diverse array of pharmaceutical and biological questions and samples.

  6. 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. PMID:27159507

  7. Sudden sensorineural hearing loss during oral anticoagulant therapy.

    PubMed

    Mierzwa, Kathleen; Schneider, Gerlind; Müller, Andreas

    2004-11-01

    This study investigated the role of sudden sensorineural hearing loss (SSNHL) as a symptom in oral anticoagulant therapy with vitamin K antagonists (Phenprocoumon; Marcumar, Falithrom). Vascular compromise of the cochlea due to thrombosis, embolus, reduced blood flow or vasospasm is one of the four possible pathways that can lead to SSNHL. Oral anticoagulant therapy should prevent thrombosis; if it does not the question arises as to whether the anticoagulation is working, or the wrong hypothesis of vascular compromise has been made. Patients with SSNHL during oral anticoagulant therapy who were admitted to the ENT Department of the University Hospital in Jena from 1998 to 2001 were included. The pure-tone audiograms and the prothrombin time (PT) values before and after the event of the SSNHL were evaluated. The study found 10 patients with SSNHL during oral anticoagulant therapy. Although the audiograms showed some improvement in the majority of cases, three cases showed almost no improvement in hearing. On admission, half of the patients showed a PT-value higher than 30 per cent and in nine cases a PT-value >30 per cent could be demonstrated at least once during testing. It was not possible to demonstrate a relationship between the SSNHL and oral anticoagulation. Vascular compromise cannot be excluded as a cause for sudden hearing loss in patients undergoing oral anticoagulant therapy. It is possible that oral anticoagulants influence the viscosity of the plasma leading to interference with the microcirculation in the inner ear. Further research into this area is currently being conducted.

  8. Understanding instructions for oral rehydration therapy.

    PubMed

    Eisemon, T O; Patel, V L

    1989-01-01

    Oral rehydration mixtures are readily available in rural Kenya, but the instructions that accompany them are not always clear. Mothers will understand such instructions more readily if they explain the principles of oral rehydration and describe in a logical way the sequence of procedures to be followed. PMID:2637708

  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. Optimizing Outcomes of Oral Therapy for Patients With Erectile Dysfunction

    PubMed Central

    Barada, James H

    2003-01-01

    The evaluation and treatment of erectile dysfunction (ED) differs from that of many medical conditions. An intimate dialogue between the patient and physician must be established for accurate assessment of ED severity and successful therapy. Patient and partner education on the nuances of oral phosphodiesterase inhibitor therapy is important to maximize treatment success with this currently first-line therapy. Realistic expectations for the erectile response and patience are necessary to resume satisfactory sexual functioning. Relationship issues or partner resistance can contribute to a suboptimal erectile response to therapy, in which case the patient may benefit from sexual therapy referral. PMID:16985980

  11. Oral capsaicin provides temporary relief for oral mucositis pain secondary to chemotherapy/radiation therapy.

    PubMed

    Berger, A; Henderson, M; Nadoolman, W; Duffy, V; Cooper, D; Saberski, L; Bartoshuk, L

    1995-04-01

    Pain from oral mucositis afflicts from 40% to 70% of patients receiving chemotherapy or radiation therapy. Current methods of clinical pain management (for example, topical anesthetics, systemic analgesics) have limited success. In a pilot study, we examined the ability of oral capsaicin to provide temporary relief of oral mucositis pain. Capsaicin, the active ingredient in chili peppers, desensitizes some neurons and has provided moderate pain relief when applied to the skin surface. Oral capsaicin in a candy (taffy) vehicle produced substantial pain reduction in 11 patients with oral mucositis pain from cancer therapy. However, this pain relief was not complete for most patients and was only temporary. Additional research is needed to fully utilize the properties of capsaicin desensitization and thus optimize analgesia. PMID:7629418

  12. 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 ...

  13. 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.

  14. Conventional and alternative antifungal therapies to oral candidiasis.

    PubMed

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

    2010-10-01

    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.

  15. Oral therapy for Peyronie’s disease, does it work?

    PubMed Central

    Barrett-Harlow, Brittani

    2016-01-01

    Peyronie’s disease (PD) is a localized, wound-healing, connective tissue disorder of the penis characterized by scarring of the tunica albuginea. This fibrous inelastic scar leads to penile pain, penile deformity and erectile dysfunction (ED), and a difficulty performing coitus. Over the past several decades, a myriad of oral agents for the treatment of PD have been studied and suggested. While the gold standard of care remains surgical therapy, many physicians continue to prescribe oral and intralesional injections for treatment during the acute phase of the disease. This article seeks to summarize the different oral therapy agents for PD and the research associated with each medication. While the American Urological Association has not recommended most of the mentioned medications for the treatment of PD, two newer therapies have shown success and have the potential of becoming baseline treatments for the acute phase of PD. PMID:27298776

  16. 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

  17. 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

  18. Photodynamic Therapy: The Imminent Milieu For Treating Oral Lesions

    PubMed Central

    Mohanty, Neeta; Jalaluddin, MD; Kotina, Sreekanth; Routray, Samapika; Ingale, Yashwant

    2013-01-01

    Photodynamic therapy (PDT) is used in curative and palliative treatment of head and neck squamous cell carcinoma (HNSCC) and other oral lesions. Oral infections (such as mucosal and endodontic infections, periodontal diseases, caries, and peri-implantitis) are among the specific targets where PDT can be applied Photodynamic therapy (PDT) efficacy depends on the local dose deposited in the lesion as well as oxygen availability in the lesion. Further long-term clinical studies are necessary in establishing a more specific place of the technique in the field of dentistry. PMID:23905154

  19. Monitoring anticoagulant therapy with new oral agents.

    PubMed

    Ramos-Esquivel, Allan

    2015-12-26

    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

  20. 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…

  1. 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…

  2. 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

  3. Acetyl-L-Carnitine Supplementation During HCV Therapy With Pegylated Interferon-α 2b Plus Ribavirin: Effect on Work Performance; A Randomized Clinical Trial

    PubMed Central

    Malaguarnera, Giulia; Pennisi, Manuela; Gagliano, Caterina; Vacante, Marco; Malaguarnera, Michele; Salomone, Salvatore; Drago, Filippo; Bertino, Gaetano; Caraci, Filippo; Nunnari, Giuseppe; Malaguarnera, Mariano

    2014-01-01

    Background: The health status of employees with chronic hepatitis C has major implications for organizations and labour market. Objectives: To assess the effects of Acetyl-L-Carnitine administration on work productivity, daily activity, and fatigue in subjects with chronic hepatitis C treated with Pegylated-Interferon-α2b and Ribavirin. Patients and Methods: In this prospective, randomized, placebo controlled, double blind clinical trial, 30 subjects (Group A) with chronic hepatitis, received Pegylated-Interferon-α2b (1.5 mg/kg per week) plus Ribavirin and placebo, while 32 subjects (Group B) received the same dosage of Pegylated-Interferon-α2b plus Ribavirin plus 2g Acetyl-L-Carnitine twice per day, for 12 months. Work productivity loss, impairment in daily activities, presenteeism, absenteeism, have been assessed using the Work Productivity and Activity Impairment questionnaire. We also evaluated severity of fatigue, mental fatigue and physical fatigue. Results: Significant difference were observed in physical fatigue, mental fatigue and severity of fatigue, aspartate aminotransferase, alanine aminotransferase, and viremia after 12 months treatment. In Group B we observed a significant decrease of presenteeism and daily activity impairment after 6 months, 12 months and at follow up. A significant increase of work productivity was observed after 12 months and at follow up. Conclusions: Office workers with chronic hepatitis C, treated with Pegylated-Interferon-α2b plus Ribavirin, had work performance loss. In subjects treated with Acetyl-L-Carnitine supplementation we observed increased daily activity and reduced presenteeism and fatigue. Acetyl-L-Carnitinegroup had a smaller reduction of productivity comparing to placebo group. PMID:24910702

  4. The limits of oral therapy in pulmonary arterial hypertension management

    PubMed Central

    Liu, Qian-Qian; Jing, Zhi-Cheng

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease in which remodeling of the small pulmonary arteries leads to a progressive increase in pulmonary vascular resistance and right-sided heart failure. Over the past decade, new treatments for PAH, such as the use of ERAs, PDE-5 inhibitors and prostacyclin analogs, have brought about dramatic improvements in clinical outcomes. Epoprostenol infusion therapy has been shown to improve hemodynamics, functional status, and survival, and it remains the gold standard for treatment of patients with severe PAH. Many agents, approved for PAH are always delivered in pill form. Although oral therapy occupies an important position, it has some drawbacks and limitations in PAH management. For patients in World Health Organization functional class IV and with severe right heart failure, there are few data on the long-term survival of patients treated with oral medications. Further research, exploration, and clinical experience with oral therapy in severe PAH and combination therapy will redefine its position in PAH management. PMID:26648729

  5. The limits of oral therapy in pulmonary arterial hypertension management.

    PubMed

    Liu, Qian-Qian; Jing, Zhi-Cheng

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease in which remodeling of the small pulmonary arteries leads to a progressive increase in pulmonary vascular resistance and right-sided heart failure. Over the past decade, new treatments for PAH, such as the use of ERAs, PDE-5 inhibitors and prostacyclin analogs, have brought about dramatic improvements in clinical outcomes. Epoprostenol infusion therapy has been shown to improve hemodynamics, functional status, and survival, and it remains the gold standard for treatment of patients with severe PAH. Many agents, approved for PAH are always delivered in pill form. Although oral therapy occupies an important position, it has some drawbacks and limitations in PAH management. For patients in World Health Organization functional class IV and with severe right heart failure, there are few data on the long-term survival of patients treated with oral medications. Further research, exploration, and clinical experience with oral therapy in severe PAH and combination therapy will redefine its position in PAH management. PMID:26648729

  6. Oral tolerance: mechanisms and therapy of autoimmune diseases.

    PubMed

    Koh, D R

    1998-01-01

    Oral tolerance is a state of immune hyporesponsiveness induced by the oral or mucosal exposure to antigens. This state is dependent on the dose of the oral antigen administered, with a low dose stimulating regulatory T cell development leading to an active immune suppression that is transferable via T cells. The active mechanism appears to be a cytokine mediated immune deviation with a predominant Th2 and Th3 response (TGF-beta). In contrast, high dose oral antigens lead to clonal deletion and anergy. The active suppression of low dose oral tolerance can also suppress an unrelated immune response (bystander suppression) paving the way for therapy of autoimmune diseases like rheumatoid arthritis. Oral tolerance has been effective in the treatment of autoimmune diseases like experimental autoimmune encephalomyelitis (EAE), collagen-induced arthritis (CIA) and insulin-dependent diabetes in animals. However, recent studies in human autoimmune diseases have not been as effective but the results are encouraging and more work is required to understand the mechanisms involved and other factors that may modulate the response. PMID:9588275

  7. Oral atenolol therapy for proliferating infantile hemangioma

    PubMed Central

    Ji, Yi; Wang, Qi; Chen, Siyuan; Xiang, Bo; Xu, Zhicheng; Li, Yuan; Zhong, Lin; Jiang, Xiaoping; Yang, Xiaodong

    2016-01-01

    Abstract Propranolol, a lipophilic nonselective β-blocker, has recently been reported to be the treatment of choice for select types of infantile hemangiomas (IHs). Atenolol is a hydrophilic, selective β1-blocker and therefore may be not associated with side effects attributable to β2-adrenergic receptor blockade and lipophilicity. However, the efficacy and safety of atenolol in the treatment of IH are poorly understood. The aim of this study was to evaluate the efficacy and safety of atenolol in the treatment of proliferating IHs. A study of 76 infants between the ages of 5 to 20 weeks with superficial or mixed IH was conducted between August 2013 and March 2015. Oral atenolol was administered in a progressive schedule to 1 mg/kg per day in a single dose. Efficacy was assessed using the Hemangioma Activity Score (HAS) at weeks 0, 1, 4, 12, and 24. Safety was evaluated at weeks 0, 1, 4, 8, 12, 16, 20, and 24. In total, 70 patients completed 24 weeks of treatment. IH growth abruptly stopped for 93.4% of patients within the fourth week of treatment with atenolol. In ulcerated IHs, complete healing of the ulcerations occurred in an average treatment time of 5.5 weeks. Atenolol treatment promoted dramatic decreases in HAS scores after week 1. An “excellent” treatment response (compete or nearly complete resolution of the IH) was observed in 56.5% of patients at week 24. No significant hypoglycemia, bronchospasm, bradycardia, or hypotension occurred. The most common adverse event was diarrhea, followed by agitation and sleep disturbance. This study demonstrated that atenolol was effective and safe at a dose of 1 mg/kg per day for 24 weeks in the treatment of proliferating IHs. PMID:27310994

  8. 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

  9. Oral disease-modifying therapies for multiple sclerosis.

    PubMed

    Kim, Woojun; Zandoná, Manuella Edler; Kim, Su-Hyun; Kim, Ho Jin

    2015-01-01

    Classical multiple sclerosis (MS) treatments using first-line injectable drugs, although widely applied, remain a major concern in terms of therapeutic adherence and efficacy. New oral drugs recently approved for MS treatment represent significant advances in therapy. The oral route of administration clearly promotes patient satisfaction and increases therapeutic compliance. However, these drugs may also have safety and tolerability issues, and a thorough analysis of the risks and benefits is required. Three oral drugs have been approved by regulatory agencies for MS treatment: fingolimod, teriflunomide, and dimethyl fumarate. This article reviews the mechanisms of action, safety, and efficacy of these drugs and two other drugs that have yielded positive results in phase III trials: cladribine and laquinimod. PMID:25628732

  10. Stem cell therapy in oral and maxillofacial region: An overview

    PubMed Central

    Sunil, PM; Manikandhan, R; Muthu, MS; Abraham, S

    2012-01-01

    Cells with unique capacity for self-renewal and potency are called stem cells. With appropriate biochemical signals stem cells can be transformed into desirable cells. The idea behind this article is to shortly review the obtained literature on stem cell with respect to their properties, types and advantages of dental stem cells. Emphasis has been given to the possibilities of stem cell therapy in the oral and maxillofacial region including regeneration of tooth and craniofacial defects. PMID:22434942

  11. Oral fungi in HIV: challenges in antifungal therapies.

    PubMed

    Nittayananta, W

    2016-04-01

    Oral candidiasis (OC) caused by Candida species is a common fungal infection among HIV-infected individuals. Despite the wide use of antiretroviral therapy (ART) resulting in a declined prevalence, OC remains the most common oral lesions seen in those living with HIV/AIDS. Various topical and systemic antifungal drugs are available to treat OC. However, due to the patients' immunodeficiency and the nature of OC as biofilm-associated infection, relapse is frequently observed after cessation of antifungal therapy. In addition, long-term antifungal therapy may lead to drug resistance. This review article addressed three major challenges in the treatment of OC in HIV infection including antifungal drug resistance, biofilm-associated infection of OC, and the host underlying immunodeficiency. To reduce the risks of antifungal drug resistance, the author recommends that future studies should focus on herbal plant-derived compounds with antifungal activity that may be used in combination with the drugs. Also, it is recommended that more research should be carried out to explore how to enhance the host innate immunity against oral Candida. PMID:27109279

  12. Initial dual oral combination therapy in pulmonary arterial hypertension.

    PubMed

    Sitbon, Olivier; Sattler, Caroline; Bertoletti, Laurent; Savale, Laurent; Cottin, Vincent; Jaïs, Xavier; De Groote, Pascal; Chaouat, Ari; Chabannes, Céline; Bergot, Emmanuel; Bouvaist, Hélène; Dauphin, Claire; Bourdin, Arnaud; Bauer, Fabrice; Montani, David; Humbert, Marc; Simonneau, Gérald

    2016-06-01

    Treatment for pulmonary arterial hypertension (PAH) has been underpinned by single-agent therapy to which concomitant drugs are added sequentially when pre-defined treatment goals are not met.This retrospective analysis of real-world clinical data in 97 patients with newly diagnosed PAH (86% in New York Heart Association functional class III-IV) explored initial dual oral combination treatment with bosentan plus sildenafil (n=61), bosentan plus tadalafil (n=17), ambrisentan plus tadalafil (n=11) or ambrisentan plus sildenafil (n=8).All regimens were associated with significant improvements in functional class, exercise capacity, dyspnoea and haemodynamic indices after 4 months of therapy. Over a median follow-up period of 30 months, 75 (82%) patients were still alive, 53 (71%) of whom received only dual oral combination therapy. Overall survival rates were 97%, 94% and 83% at 1, 2 and 3 years, respectively, and 96%, 94% and 84%, respectively, for the patients with idiopathic PAH, heritable PAH and anorexigen-induced PAH. Expected survival rates calculated from the French equation for the latter were 86%, 75% and 66% at 1, 2 and 3 years, respectively.Initial combination of oral PAH-targeted medications may offer clinical benefits, especially in PAH patients with severe haemodynamic impairment. PMID:26989105

  13. 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

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

    PubMed Central

    Rebouche, C J; Engel, A G

    1984-01-01

    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. PMID:6707204

  15. 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.

  16. Illumination devices for photodynamic therapy of the oral cavity.

    PubMed

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

    2010-11-23

    Three compact and efficient designs are proposed to deliver an average irradiance of 50 mW/cm(2) with spatial uniformity well above 90% over a 25 mm(2) target area for photodynamic therapy of the oral cavity. The main goal is to produce uniform illumination on the target while limiting irradiation of healthy tissue, thus overcoming the need of shielding the whole oral cavity and greatly simplifying the treatment protocol. The first design proposed consists of a cylindrical diffusing fiber placed in a tailored reflector derived from the edge-ray theorem with dimensions 5.5 × 7.2 × 10 mm(3); the second device combines a fiber illuminator and a lightpipe with dimensions 6.8 × 6.8 × 50 mm(3); the third design, inspired by the tailored reflector, is based on a cylindrical diffusing fiber and a cylinder reflector with dimensions 5 × 10 × 11 mm(3). A prototype for the cylinder reflector was built that provided the required illumination for photodynamic therapy of the oral cavity, producing a spatial uniformity on the target above 94% and an average irradiance of 51 mW/cm(2) for an input power of 70 mW.

  17. Illumination devices for photodynamic therapy of the oral cavity

    PubMed Central

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

    2010-01-01

    Three compact and efficient designs are proposed to deliver an average irradiance of 50 mW/cm2 with spatial uniformity well above 90% over a 25 mm2 target area for photodynamic therapy of the oral cavity. The main goal is to produce uniform illumination on the target while limiting irradiation of healthy tissue, thus overcoming the need of shielding the whole oral cavity and greatly simplifying the treatment protocol. The first design proposed consists of a cylindrical diffusing fiber placed in a tailored reflector derived from the edge-ray theorem with dimensions 5.5 × 7.2 × 10 mm3; the second device combines a fiber illuminator and a lightpipe with dimensions 6.8 × 6.8 × 50 mm3; the third design, inspired by the tailored reflector, is based on a cylindrical diffusing fiber and a cylinder reflector with dimensions 5 × 10 × 11 mm3. A prototype for the cylinder reflector was built that provided the required illumination for photodynamic therapy of the oral cavity, producing a spatial uniformity on the target above 94% and an average irradiance of 51 mW/cm2 for an input power of 70 mW. PMID:21157577

  18. HBO: a possible supplementary therapy for oral potentially malignant disorders.

    PubMed

    Ye, Xiaojing; Zhang, Jing; Lu, Rui; Zhou, Gang

    2014-08-01

    Oral potentially malignant disorders (OPMDs) are chronic inflammatory diseases in which cells suffer hypoxia referring to deprivation of adequate oxygen supply. Hyperbaric oxygen treatment (HBO), which can increase oxygen tension and delivery to oxygen-deficient tissue, is a supplementary therapy to improve or cure disorders involving hypoxia. Although the applications of HBO in wound healings, acute ischemic stroke, radiation-induced soft tissue injury and cancers are extensively reported, there are only few studies on their effect in OPMDs. Not only does HBO furnish oxygen-it also possesses potent anti-inflammatory properties. At the cellular level, HBO can decrease lymphocyte proliferation and promote apoptosis of fibroblasts. At the molecular level, it can decrease expression of HIF, ICAM-1, TNF-α, TGF-β, and IFN-γ, as well as increase vascular VEGF expression and angiogenesis. Thus, we hypothesize that HBO may contribute to treat OPMDs, including oral lichen planus, oral leukoplakia, and oral submucous fibrosis both at the cellular level and the molecular level, and that it would be a safe and inexpensive therapeutic strategy. PMID:24908359

  19. 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.

  20. 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.

  1. Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage.

    PubMed

    Dalakas, M C; Leon-Monzon, M E; Bernardini, I; Gahl, W A; Jay, C A

    1994-04-01

    The use of zidovudine (AZT) for the treatment of acquired immunodeficiency syndrome (AIDS) induces a DNA-depleting mitochondrial myopathy, which is histologically characterized by the presence of muscle fibers with "ragged-red"-like features, red-rimmed or empty cracks, granular degeneration, and rods (AZT fibers). Because dysfunctioning muscle mitochondria may lead to defects of beta-oxidation of fatty acids, we examined the degree of neutral fat accumulation and muscle carnitine levels in the muscle biopsy specimens from 21 patients with AZT-induced myopathic symptoms of varying severity. Six patients with no AZT fibers had normal endomyofibrillar lipid deposits and muscle carnitine levels; 7 patients with fewer than 5 AZT fibers per field had a mild (+) to moderate (++) increase in lipid droplets, and reduced muscle carnitine levels (3 patients); and 8 patients with more than 5 AZT fibers had severe muscle changes, a ++ to marked ( ) increase in lipid droplets, and reduced muscle carnitine levels (6 patients). Serial sections showed lipid globules often within "cracks" or vacuoles of the abnormal muscle fibers. We conclude that the muscle mitochondrial impairment caused by AZT results in (1) accumulation of lipid within the muscle fibers owing to poor utilization of long-chain fatty acids, (2) reduction of muscle carnitine levels probably due to decreased carnitine uptake by the muscle, and (3) depletion of energy stores within the muscle fibers. The findings may have potential therapeutic implications in the treatment of AZT-induced myopathic symptoms using oral carnitine supplementation.

  2. The efficacy of sucralfate suspension in the prevention of oral mucositis due to radiation therapy

    SciTech Connect

    Epstein, J.B.; Wong, F.L.W. )

    1994-02-01

    The purpose of this study was to assess the value of sucralfate suspension in prevention of oral mucositis and for reduction of oral pain in patients who develop mucositis during radiation therapy. The study was a double-blind, placebo-controlled, randomized prospective trial of a sucralfate suspension in the prevention and management of oral mucositis during radiation therapy. Oral mucositis was assessed using a quantitative scale and symptoms were assessed using visual analogue scales. The statistical model was developed to detect a 40% reduction in mucositis. No statistically significant reduction in mucositis was seen. Early during radiation therapy less oral pain was reported in the sucralfate group, but as treatment progressed all patients experienced pain. Patients in the sucralfate group were prescribed topical and systemic analgesics later in the course of radiation therapy. Prophylactic oral rinsing with sucralfate did not prevent oral ulcerative mucositis. Sucralfate may reduce the experience of pain during radiation therapy. 32 refs., 3 tabs.

  3. [Primary combined oral antidiabetic therapy in type-2 diabetes mellitus].

    PubMed

    Winkler, Gábor; Baranyi, Eva

    2002-10-27

    New target values of the metabolic control and recent directions in the therapeutic strategies of type 2 diabetes mellitus are overviewed. Attention is called to the atherogenic effect of blood glucose elevations exceeding physiological level, even when only post-prandial and with short duration. The significance of early phase prandial insulin secretion in the metabolic state is underlined, and the related new therapeutic possibilities are discussed. Practical guidelines are given to the introduction of oral antidiabetic therapy, and the importance of the early, aggressive, combined treatment with a complex mechanism of action is emphasized.

  4. [Oral disease modifying therapy of multiple sclerosis: the current view].

    PubMed

    Kappos, L; Boĭko, A N

    2014-01-01

    The review includes data on experimental and clinical studies of new oral methods of multiple sclerosis (MS) disease modifying therapy (DMT). The mechanisms of action, results of clinical trials of stages II and III with the data on their clinical and MRI-efficacy, tolerability and safety of fingolimod, dimethylfumarate (BG-12), teriflunomide and laquinimod are included. The risk management plans for possible side-effects of every product and the peculiarities of their use in individually selected MS treatment are discussed. PMID:24662359

  5. Oral silicon supplementation: an effective therapy for preventing oral aluminum absorption and retention in mammals.

    PubMed

    Domingo, José L; Gómez, Mercedes; Colomina, M Teresa

    2011-01-01

    Silicon is an essential element for some lower forms of life. However, it is not generally considered an essential nutrient for mammals and the mechanisms underlying its potential essentiality remain partially unknown. In recent years, a possible association between the aluminum and silicon levels in drinking water and Alzheimer's disease (AD) has been suggested. It has been reported that silicon might have a protective effect for limiting oral aluminum absorption. This review is focused primarily on the potential role of silicon in preventing oral aluminum absorption and retention in mammals. The results of a number of studies suggest that dietary silicon supplementation could be of therapeutic value for preventing chronic aluminum accumulation in the brain, and hence, be a potential therapy for AD. However, it must be noted that controversy remains about whether aluminum accumulation in the brain is a cause or a consequence of AD. It is suggested that further investigation of this issue is warranted.

  6. [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. PMID:8526737

  7. Application of the theory of planned behavior to oral anticoagulant therapy.

    PubMed

    Burns, Sharita

    2009-03-01

    Anticoagulation control is imperative for individuals who are prescribed long-term oral anticoagulation therapy. Therapeutic international normalized ratios decrease the risk of the thromboembolic complications that are associated with oral anticoagulation therapy. Individuals on oral anticoagulation therapy are often asked to make lifestyle modifications that can become barriers to medication adherence. The application of the theory of planned behavior to oral anticoagulation therapy can be used to assist advanced practice nurses in assessing individuals for the perceived barriers or obstacles that might interfere with the behavioral changes necessary to successfully comply with the recommended treatment plan. PMID:19298315

  8. 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

  9. Role of carnitine in cancer chemotherapy-induced multiple organ toxicity.

    PubMed

    Sayed-Ahmed, Mohamed M

    2010-10-01

    In the last few years, cancer chemotherapy has been successfully employed in the treatment of different types of human tumours. Unfortunately, the optimal clinical usefulness of this important treatment modality is usually limited secondary to the development of life-threatening multiple organ toxicity. Cancer chemotherapy may cause these toxic effects by mechanisms not involved in their anticancer activity that can severely affect the life of patients and represent a direct cause of death. Several experimental and clinical studies have demonstrated that some important anticancer drugs interfere with the absorption, synthesis, and excretion of carnitine in non-tumour tissues, resulting in a secondary carnitine deficiency which is reversed by carnitine treatment without affecting anticancer therapeutic efficacy. Prototypes of anticancer drugs that alter carnitine system are doxorubicin, cisplatin, carboplatin, oxaliplatin, cyclophosphamide and ifosfamide. Furthermore, cachectic cancer patients are especially at risk for carnitine deficiency due to decreased oral intake and/or increased renal losses. Altered serum and urine carnitine levels have been reported in cancer patients with various forms of malignant diseases. Recent studies in our laboratory have demonstrated that carnitine deficiency constitute a risk factor and should be viewed as a mechanism during development of oxazaphosphorines-induced cardiotoxicity in rats. Similarly, inhibition of gene expression of heart fatty acid-binding protein and organic cation/carnitine transporter in doxorubicin cardiomyopathic rat model has been reported. In view of these facts and in view of irreplaceability of these important anticancer drugs, this review aimed to highlight the role of carnitine depletion and supplementation during development of chemotherapy-induced multiple organ toxicity. PMID:23960728

  10. The risks of oral contraceptives and estrogen replacement therapy.

    PubMed

    Coe, F L; Parks, J H

    1989-01-01

    The benefits and risks of both oral contraceptives and estrogen replacement therapy (ERT) are evaluated by summarizing briefly the results of the most evidential studies on breast, ovarian, endometrial, and hepatobiliary cancer, heart attack, stroke and venous thromboembolism. The methods used to estimate risk ratios, prospective random-allocation, double-blind trials, and retrospective case- controlled studies, are explained briefly. The ERT used today resemble sequential oral contraceptives, except that only 10-20 mcg ethinyl estradiol is taken for 25 days, and progestins are used on the last 10 days. Breast cancer risk is not different in pill users from nonusers, based on the U.K. General PRactitioner, Oxford Family Planning, Harvard nurses or U.S. SEER National Cancer Institute studies. Studies on ERT and breast cancer are mixed, but only injected estrogens raised the risks. Ovarian cancer is prevented by pill use in proportion to length of use. No studies were reported for ERT. The risk of hepatic cancer is 3.8 to 7.8 higher in pill users, but the number of cases is so rare that this should not affect prescriptions. Neither pill nor ERT raise the risk of myocardial infarction, and after premature surgical menopause, ERT lowers the risk. Based on studies done in the 1970s, oral contraceptives raise the risk of thrombotic stroke while women are taking them, from 10-13/100,000 to 41/100,000. ERT has no clear association with stroke. Similarly, orals increase the risk of venous thromboembolism, 8-fold in the Oxford Family Planning study published in 1986, although the absolute numbers are very small. ERT had no effects no risk of thromboembolism according to the lipid Research, Framingham and Nachtigall studies.

  11. 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.

  12. 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. PMID:1802837

  13. Improving adherence to oral cancer therapy in clinical practice.

    PubMed

    McCue, Debbie A; Lohr, Lisa K; Pick, Amy M

    2014-05-01

    Adherence to oral chemotherapy regimens maximizes their effectiveness and minimizes any potential toxicities. Factors specifically related to the treatment, patient, and health care provider may influence medication adherence. Treatment-related factors include the complexity of the regimen, the cost of therapy, the possibility of side effects, and the delay in treatment benefits. Meanwhile, patients may not have an adequate support system or an understanding of the need for the medication, and providers may not fully succeed in communicating the importance of adherence and the types of side effects that may occur. Nonadherence may lead to an increased risk of toxicity, decreased effectiveness, and increased utilization of health care resources. Although various methods for measuring adherence are available, self-reporting is the most widely used. Studies describing adherence in a broad range of cancers are reviewed. Treatment of chronic myeloid leukemia has been revolutionized by the development of oral tyrosine kinase inhibitors that are highly effective in managing the disease when taken consistently. However, nonadherence is relatively common and can lead to reduced rates of response and increased medical costs. Similar effects of nonadherence on outcome and cost have also been observed in patients with various other hematologic malignancies and solid tumors. Interventions to improve adherence to oral chemotherapy regimens include communication about the importance of adherence and the potential consequences of nonadherence, simplification of the patient's medication schedule (if possible), and inclusion of a caregiver or family member in the conversation. Written materials should always be provided to accompany verbal instructions. This review summarizes factors influencing medication adherence, impact of nonadherence on patient outcomes, methods for measuring adherence, previous studies of nonadherence in patients with cancer, common barriers to access, and

  14. The effects of "BAR" therapy on oral malignant tumors.

    PubMed

    Nagai, T; Sakaizumi, K; Asanami, S; Lian, S L; Tomita, O; Hirayama, T

    1978-05-01

    "BAR" therapy is a combined therapy with BUdR (Radiosensitizer), Antimetabolites (5-FU, FT-207 etc.) and Radiation for malignant tumours. How radiation can be reduced as far as possible and how the effects of treatment can be increased as much as possible are the objectives of this study of combining radiation and BUdR therapy. The authors attempted to irradiate 3-5 days after the BUdR and antimetabolite had been infused via the superficial temporal artery, in 12 malignant oral tumours (11 squamous cell carcinomas and 1 reticulum-cell sarcoma). BUdR 50-250 mg/day, antimetabolites (5-FU) 10-250 mg/day and a total irradiation dose of 6000 rads by 6 MeV Linac X-ray or Co-60 gamma ray, 200 rads/day were given. 9 marked responses, 2 moderate responses and 1 no response (2 cases were operated on by local resection) were obtained by the authors. Side effects of treatment were observed during the course of "BAR" therapy. Stomatitis was found in all patients and it occurred on the mucosa of the tumour-affected site especially. Dermatitis of the skin of the face was noted in 6 cases, resembling irradiation dermatitis. Fever was observed in 4 cases and it always occurred after irradiation. Diarrhoea was noted in 3 cases and occurred before irradiation, 2 out of 3 were given BUdR 0.1 g and the remaining one was given BUdR 1 g, and 5-FU lg. In addition, there were: 1 loss of appetite, 1 nausea and 1 exfoliation of nails. PMID:353211

  15. Photodynamic Therapy in Treatment of Oral Lichen Planus

    PubMed Central

    Mostafa, Diana; Tarakji, Bassel

    2015-01-01

    Oral lichen planus (OLP) is a relatively common chronic immunologic mucocutaneous disorder. Although there are many presenting treatments, some of them proved its failure. Recently, the use of photodynamic therapy (PDT) has been expanding due to its numerous advantages, as it is safe, convenient, and non-invasive and has toxic effect towards selective tissues. This article provides comprehensive review on OLP, its etiology, clinical features and recent non-pharmacological treatments. We also describe the topical PDT and its mechanisms. Our purpose was to evaluate the efficacy of PDT in treatment of OLP through collecting the data of the related clinical studies. We searched in PubMed website for the clinical studies that were reported from 2000 to 2014 using specific keywords: “photodynamic therapy” and “treatment of oral lichen planus”. Inclusion criteria were English publications only were concerned. In the selected studies of photodynamic treatment, adult patients (more than 20 years) were conducted and the OLP lesions were clinically and histologically confirmed. Exclusion criteria were classical and pharmacological treatments of OLP were excluded and also the using of PDT on skin lesions of lichen planus. We established five clinical studies in this review where all of them reported improvement and effectiveness of PDT in treatment of OLP lesions. The main outcome of comparing the related clinical studies is that the photodynamic is considered as a safe, effective and promising treatment modality for OLP. PMID:25883701

  16. Active Targeted Nanoparticles for Oral Administration of Gastric Cancer Therapy.

    PubMed

    Lin, Yu-Hsin; Chen, Zih-Rou; Lai, Chih-Ho; Hsieh, Chia-Hung; Feng, Chun-Lung

    2015-09-14

    Gastric carcinogenesis is a commonly diagnosed type of cancer and has a dismal prognosis because of the rate at which it aggressively spreads and because of the lack of effective therapies to stop its progression. This study evaluated a type of oral drug delivery system of a potential target-activated nanosizer comprising a fucose-conjugated chitosan and polyethylene glycol-conjugated chitosan complex with gelatin containing encapsulated green tea polyphenol extract epigallocatechin-3-gallate, allowing oral administration of the drug through a site-specific release in gastric cancer cells. The results demonstrated that the nanoparticles effectively reduced drug release within gastric acids and that a controlled epigallocatechin-3-gallate release inhibited gastric cancer cell growth, induced cell apoptosis, and reduced vascular endothelial growth factor protein expression. Furthermore, in vivo assay results indicated that the prepared epigallocatechin-3-gallate-loaded fucose-chitosan/polyethylene glycol-chitosan/gelatin nanoparticles significantly affected gastric tumor activity and reduced gastric and liver tissue inflammatory reaction in an orthotopic gastric tumor mouse model.

  17. Oral small molecule therapy for lysosomal storage diseases.

    PubMed

    Weinreb, Neal J

    2013-11-01

    For more than 20 years, "enzyme replacement therapy" (ERT) has been the prevalent treatment approach for lysosomal storage disorders (LSDs). Unfortunately, ERT, as currently administered, is ineffective for primary neuronopathic LSDs. For LSDs whose major disease burden is non-neurological, ERT efficacy is limited by uneven tissue distribution and penetration, immunological intolerance, and disturbed intracellular homeostasis associated with persistent mutant enzymes that are not "replaced" by ERT. Many of these limitations might be circumvented by oral, low molecular weight pharmaceuticals that address relevant LSD pathophysiology and distribute widely in steady state concentrations in all cells and body tissues including the CNS. Two oral small molecule drugs (miglustat and cysteamine) are currently approved for clinical use and two (eliglustat and migalastat) are in advanced stage clinical trials. Several others are in early stages of clinical or pre-clinical investigation. This article reviews current knowledge of small molecule treatment for LSDs including approaches such as substrate synthesis inhibition, pharmacological chaperones, and proteostasis modification. PMID:24380126

  18. Possible alternative therapies for oral lichen planus cases refractory to steroid therapies.

    PubMed

    Yang, Huamei; Wu, Yuanqin; Ma, Hui; Jiang, Lu; Zeng, Xin; Dan, Hongxia; Zhou, Yu; Chen, Qianming

    2016-05-01

    Oral lichen planus (OLP) is a chronic inflammatory disorder with a multifactorial etiopathogenesis. Immune dysregulation plays a critical role in the development and progression of this disease. Patients' lives may be affected by pain caused by atrophic-erosive lesions. Given the obscure etiology, treatment is usually symptomatic. Topical steroids remain the mainstay of management. However, their therapeutic benefits are not always evident. There are substantial data on the possible therapeutic strategies that are effective in OLP cases refractory to steroids. This review provides an overview of the current approaches for the management of steroid-refractory OLP. The miscellaneous treatment regimens include tacrolimus, pimecrolimus, thalidomide, low-level laser therapy, photodynamic therapy, and surgical excision. Some results obtained from these studies were promising. However, further studies, especially randomized controlled trials with strict inclusion and exclusion criteria and larger sample sizes, are required for the evaluation of the long-term safety and efficacy of these therapies. PMID:27068310

  19. 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

  20. 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

  1. Tissue carnitine reserves of newborn infants.

    PubMed

    Shenai, J P; Borum, P R

    1984-07-01

    This study assessed the tissue reserves of carnitine at birth in a group of neonates (n = 22) of varying gestational age dying within 24 h of birth, prior to possible changes in carnitine status induced by postnatal intervention. Tissue carnitine concentration was highest in the muscle in each infant. The mean (+/- SD) muscle carnitine concentration of 8.4 +/- 3.6 nmol/mg noncollagen protein (NCP) in very immature infants (less than or equal to 1000 g birth weight) was significantly lower than the corresponding mean (+/- SD) values of 14.0 +/- 3.2 nmol/mg NCP in larger preterm infants (1001-2500 g; P less than 0.01) and 19.4 +/- 2.6 nmol/mg NCP in term infants (greater than or equal to 2501 g; P less than 0.001). Muscle carnitine concentration correlated positively with gestational age (r = 0.832; P less than 0.001) and with body dimensions. Liver and heart carnitine concentrations did not correlate significantly with gestation or body dimensions. The mean (+/- SD) liver carnitine concentration for all the neonates as a group was 4.1 +/- 1.5 nmol/mg NCP. The mean (+/- SD) heart carnitine concentration was 4.7 +/- 1.3 nmol/mg NCP. In comparison to adult controls, tissue carnitine concentrations were markedly lower in neonates, particularly in immature newborns. These data suggest that newborn infants, especially premature babies, are born with limited tissue reserves of carnitine and are therefore at an increased risk for developing carnitine deficiency and its adverse effects in the postnatal period, particularly if maintained on carnitine-free intravenous nutrition for prolonged periods of time.

  2. Combination of Cilostazol and L-Carnitine Improves Walking Performance in Peripheral Arterial Disease Model Rats.

    PubMed

    Shiga, Toshinori; Sahara, Hiroeki; Orito, Kensuke

    2015-01-01

    Cilostazol and L-carnitine have been used as a first-line drug and supplement, respectively, in patients with peripheral arterial disease with intermittent claudication. In this study, the effect of the combination of cilostazol and L-carnitine has been investigated in rats with unilateral hindlimb ischemia. For 28 days, cilostazol and L-carnitine were administrated separately or as a combination. The distance walked before gait disturbance developed was measured using a treadmill for 5 days a week. The capillary density of the ischemic hindlimb was evaluated by immunohistochemical staining at days 7, 14, 21, and 28. Angiogenic gene expression was measured by real-time RT-PCR at days 7 and 28. The greatest increase in the distance was observed in the combination therapy group when compared to the other groups. The capillary density in the adductor muscles of rats treated with cilostazol alone and combination therapy increased at day 28. Angiopoietin-2/Angiopoietin-1 expression ratios were higher, suggesting the promotion of angiogenesis, with cilostazol alone and combination therapy at day 7. This is the first study to show functional improvement of the hind limb following combination therapy with cilostazol and L-carnitine in experimental animals. This study also revealed that cilostazol promotes angiogenesis, and L-carnitine additively contributes to functional improvement via a non-angiogenic mechanism.

  3. Oral nitrite therapy improves vascular function in diabetic mice

    PubMed Central

    Sindler, Amy L; Cox-York, Kimberly; Reese, Lauren; Bryan, Nathan S; Seals, Douglas R; Gentile, Christopher L

    2016-01-01

    Aim We tested the hypothesis that short-term oral sodium nitrite supplementation would improve vascular dysfunction in obese, diabetic mice. Methods and results Vascular function was determined in control mice and in db/db mice receiving drinking water with or without sodium nitrite (50 mg/L) for 5 weeks. Nitrite supplementation increased plasma nitrite concentrations in db/db mice (0.19±0.02 μM vs 0.80±0.26μM; p < 0.05). Db/db mice had lower endothelium-dependent dilation (EDD) in response to increasing doses of acetylcholine versus heterozygous control mice (71.2% ± 14.3% vs 93% ± 7.0%; p < 0.05), and sodium nitrite supplementation restored endothelium-dependent dilation to control levels (92.9% ± 2.3% vs 93% ± 7.0%; p < 0.05). The improvement in endothelial function was accompanied by a reduction in intrinsic stiffness, but not by alterations in plasma or vascular markers of inflammation. Conclusion These data suggest that sodium nitrite may be a novel therapy for treating diabetes-related vascular dysfunction; however, the mechanisms of improvement are unknown. PMID:25696116

  4. 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

  5. Implant therapy for a patient with Down syndrome and oral habits: A clinical report.

    PubMed

    Saponaro, Paola C; Deguchi, Toru; Lee, Damian J

    2016-09-01

    This clinical report describes prosthodontic therapy with an implant-supported partial fixed dental prosthesis for a patient with Down syndrome and concomitant oral habits, including tongue thrusting and thumb sucking.

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

    PubMed Central

    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 for the New Paradigm of HCV Therapy Meeting Participants

    2013-01-01

    SUMMARY. 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. PMID:24168254

  7. 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.

  8. Oral antibiotic therapy for the treatment of infective endocarditis: a systematic review

    PubMed Central

    2014-01-01

    Background The role of oral antibiotic therapy in treating infective endocarditis (IE) is not well established. Methods We searched MEDLINE, EMBASE and Scopus for studies in which oral antibiotic therapy was used for the treatment of IE. Results Seven observational studies evaluating the use oral beta-lactams (five), oral ciprofloxacin in combination with rifampin (one), and linezolid (one) for the treatment of IE caused by susceptible bacteria reported cure rates between 77% and 100%. Two other observational studies using aureomycin or sulfonamide, however, had failure rates >75%. One clinical trial comparing oral amoxicillin versus intravenous ceftriaxone for streptococcal IE reported 100% cure in both arms but its reporting had serious methodological limitations. One small clinical trial (n = 85) comparing oral ciprofloxacin and rifampin versus conventional intravenous antibiotic therapy for uncomplicated right-sided S. aureus IE in intravenous drug users (IVDUs) reported cure rates of 89% and 90% in each arm, respectively (P =0.9); however, drug toxicities were more common in the latter group (62% versus 3%; P <0.01). Major limitations of this trial were lack of allocation concealment and blinding at the delivery of the study drug(s) and assessment of outcomes. Conclusion Reported cure rates for IE treated with oral antibiotic regimens vary widely. The use of oral ciprofloxacin in combination with rifampin for uncomplicated right-sided S. aureus IE in IVDUs is supported by one small clinical trial of relatively good quality and could be considered when conventional IV antibiotic therapy is not possible. PMID:24624933

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

    PubMed

    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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. Efficacy of a dentifrice and oral rinse containing sanguinaria extract in conjunction with initial periodontal therapy.

    PubMed

    Cullinan, M P; Powell, R N; Faddy, M J; Seymour, G J

    1997-02-01

    In the treatment of periodontal disease initial therapy aims at reducing marginal inflammation so allowing assessment of residual disease and further treatment options. The aim of the present study was to determine whether the use of a dentifrice and oral rinse containing sanguinaria extract led to a more rapid resolution of gingival inflammation following initial therapy. Thirty-four subjects, randomly assigned to one of two treatment groups, took part in this randomized double-blind parallel study. All subjects received initial therapy including oral hygiene instruction and scaling and root planing as required. One group also received an active dentifrice and oral rinse containing sanguinaria extract (an antiplaque agent) and zinc chloride. The other group received a placebo dentifrice and oral rinse. The gingival index (GI), plaque index (PLI) and probing pocket depths (PD) were recorded at six sites per tooth at baseline, two weeks after initial therapy and six weeks after initial therapy. There was no significant difference between the groups for any of the parameters at the baseline examination. Two weeks following initial therapy both groups showed a statistically significant increase in the number of sites with PLI of 0 or 1 (p < 0.0001) and a statistically significant increase in the number of sites with a GI of 0 or 1 (that is, no bleeding on probing), (p < 0.0001). Also there was a statistically significant increase in the number of sites with probing depths < or = 3 mm (p < 0.0001) compared with baseline. These changes were maintained through to six weeks post therapy. There was no significant advantage to the sanguinaria group. Results demonstrate that initial therapy in the form of oral hygiene instruction, scaling and root planing leads to a significant improvement in periodontal status which is maintained at least in the short term. Further, use of a dentifrice and oral rinse containing sanguinaria did not improve the efficacy of initial therapy.

  15. 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.

  16. 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

  17. 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 ...

  18. 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.

  19. Plasma carnitine alterations in premature infants receiving various nutritional regimes.

    PubMed

    Smith, R B; Sachan, D S; Plattsmier, J; Feld, N; Lorch, V

    1988-01-01

    Plasma carnitine, carnitine esters, and triglyceride concentrations were determined in 36 appropriate-forgestational-age (AGA) infants at various stages of prematurity throughout hospitalization to determine the effect of a carnitine-free and carnitine-containing diet on plasma carnitine and triglyceride concentrations. The infants were entered into one of three experimental groups based on birth weight: group I less than 1.0 kg; group II 1.0-1.51 kg; and group III 1.52-2.5 kg. Throughout the study subjects were placed on appropriate nutritional regimes which included hyperalimentation (HA), intravenous (iv) fat emulsion (Intralipid), Portagen, Enfamil-24 Premature Formula, Enfamil-20, and breastmilk. Blood samples were drawn from each infant at birth, days 1-5,7 then weekly, also before and after each nutritional intervention to determine carnitine and triglyceride concentrations. Results showed that plasma total carnitine and nonesterified carnitine decreased in all groups when the infants were maintained on a carnitine-free diet (HA, Intralipid, Portagen). In general, the carnitine levels continued to decrease until a carnitine-containing diet was initiated. Once a carnitine-containing diet was begun, plasma total carnitine (TC) and nonesterified carnitine (NEC) levels increased at fairly similar rates in all groups. However, an inverse relationship between carnitine and triglyceride (TG) concentrations were not seen in these infants. This would indicate that most premature infants require exogenous carnitine to maintain the plasma concentration of carnitine. However, a decreased concentration of plasma carnitine was not correlated with an elevated TG level under the conditions of this study.

  20. 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

  1. Medical management of neurogenic bladder with oral therapy.

    PubMed

    Cameron, Anne P

    2016-02-01

    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.

  2. 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.

  3. Ocular changes with oral and transepidermal diethylcarbamazine therapy of onchocerciasis.

    PubMed

    Taylor, H R; Greene, B M

    1981-07-01

    Twenty men with moderate infection of Onchocerca volvulus were studied in a double-masked, controlled clinical trial to compare the safety and efficacy of oral diethylcarbamazine (DEC) with topical DEC lotion. Visual acuity and colour vision did not alter during the 6 months of observation, although 2 patients receiving DEC lotion and 3 patients receiving oral DEC developed either visual field constriction or optic atrophy. Fluffy corneal opacities were common in both groups. Intraocular microfilariae also appeared in both groups but to a greater extent in those receiving DEC lotion. New chorioretinal changes developed in 4 men receiving lotion and in only 1 receiving tablets. It is concluded that DEC lotion offers no advantage over tablets in the treatment of ocular onchocerciasis and in fact may be associated with more ocular complications than the conventional oral treatment.

  4. 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

  5. Photodynamic Therapy As a Promising Method Used in the Treatment of Oral Diseases.

    PubMed

    Prażmo, Ewa J; Kwaśny, Mirosław; Łapiński, Mariusz; Mielczarek, Agnieszka

    2016-01-01

    Photodynamic therapy (PDT) consists of three elements: photosensitizer, light and oxygen. The photosensitizer has the property of selective accumulation in abnormal or infected tissues without causing any damage to the healthy cells. This innovative therapeutic method has already been successfully adapted in many fields of medicine, e.g. dermatology, gynecology, urology and cancer therapy. Dentistry is also beginning to incorporate photodisinfection for treatment of the oral cavity. The antibacterial and fungicidal properties of the photosensitizer have been used to achieve better results in root canal treatment, periodontal therapy and the eradication of candidiasis in prosthodontics. The aim of this article is to discuss the effectiveness of photodynamic methods in the diagnosis and therapy of selected oral diseases. Scientific data and published papers regarding the antibacterial properties of PDT will be subjected to analysis. Photodynamic therapy will be discussed as an alternative treatment protocol in oncology, endodontics, periodontology and other fields of dentistry.

  6. Photodynamic Therapy As a Promising Method Used in the Treatment of Oral Diseases.

    PubMed

    Prażmo, Ewa J; Kwaśny, Mirosław; Łapiński, Mariusz; Mielczarek, Agnieszka

    2016-01-01

    Photodynamic therapy (PDT) consists of three elements: photosensitizer, light and oxygen. The photosensitizer has the property of selective accumulation in abnormal or infected tissues without causing any damage to the healthy cells. This innovative therapeutic method has already been successfully adapted in many fields of medicine, e.g. dermatology, gynecology, urology and cancer therapy. Dentistry is also beginning to incorporate photodisinfection for treatment of the oral cavity. The antibacterial and fungicidal properties of the photosensitizer have been used to achieve better results in root canal treatment, periodontal therapy and the eradication of candidiasis in prosthodontics. The aim of this article is to discuss the effectiveness of photodynamic methods in the diagnosis and therapy of selected oral diseases. Scientific data and published papers regarding the antibacterial properties of PDT will be subjected to analysis. Photodynamic therapy will be discussed as an alternative treatment protocol in oncology, endodontics, periodontology and other fields of dentistry. PMID:27629857

  7. 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.

  8. [Physiological functions of carnitine and carnitine transporters in the central nervous system].

    PubMed

    Inazu, Masato; Matsumiya, Teruhiko

    2008-06-01

    L-Carnitine is an essential co-factor in the metabolism of lipids and consequently in the production of cellular energy. This molecule has important physiological roles, including its involvement in the beta-oxidation of fatty acids by facilitating the transport of long-chain fatty acids across the mitochondrial inner membrane as acylcarnitine esters. In the brain, L-carnitine and acetyl-L-carnitine have important roles in cerebral bioenergetics and in neuroprotection through a variety of mechanisms including their antioxidant properties and in the modulation and promotion of synaptic neurotransmission, most notably cholinergic neurotransmission. Acetyl-L-carnitine was successfully applied as pharmacological agents for treatment of chronic degenerative diseases of the senile brain and for slowing down the progression of mental deterioration in Alzheimer's disease, and they may involve both the cholinergic neuronal transmission activity of acetyl-L-carnitine and its ability to enhance neuronal metabolism in mitochondria. Astrocytes are able to produce large amounts of ketone bodies, which are thought to supply adjacent neurons with easily transferable substrates for generation of energy. Thus, the L-carnitine uptake mechanism becomes the rate-limiting step for astrocyte ketogenesis. Several carnitine transporters have been known to be present in peripheral tissues. In this review, the functional expression and physiological role of carnitine transporters in central nervous system is further discussed. PMID:18646596

  9. Nd:YAG laser therapy of an oral verrucous leukoplakia.

    PubMed

    Landthaler, M; Brunner, R; Haina, D

    1989-01-01

    A 75-year-old female patient afflicted with an extensive verrucous oral leukoplakia is reported. With treatment by the Nd:YAG laser under local anesthesia on an outpatient basis, the disease could be kept under control for 4 years.

  10. 'Ins' and 'outs' of triple therapy: Optimal antiplatelet therapy in patients on chronic oral anticoagulation who need coronary stenting.

    PubMed

    Dewilde, W; Verheugt, F W A; Breet, N; Koolen, J J; Ten Berg, J M

    2010-09-01

    Chronic oral anticoagulant treatment is obligatory in patients (class I) with mechanical heart valves and in patients with atrial fibrillation with CHADS2 score >1. When these patients undergo percutaneous coronary intervention with placement of a stent, there is also an indication for treatment with aspirin and clopidogrel. Unfortunately, triple therapy is known to increase the bleeding risk. For this group of patients, the bottom line is to find the ideal therapy in patients with indications for both chronic anticoagulation therapy and percutaneous intervention to prevent thromboembolic complications such as stent thrombosis without increasing the risk of bleeding. (Neth Heart J 2010;18:444-50.).

  11. Patterned orocutaneous therapy improves sucking and oral feeding in preterm infants

    PubMed Central

    Poore, M; Zimmerman, E; Barlow, SM; Wang, J; Gu, F

    2008-01-01

    Aim To determine whether NTrainer patterned orocutaneous therapy affects preterm infants' non-nutritive suck and/or oral feeding success. Subjects Thirty-one preterm infants (mean gestational age 29.3 weeks) who demonstrated minimal non-nutritive suck output and delayed transition to oral feeds at 34 weeks post-menstrual age. Intervention NTrainer treatment was provided to 21 infants. The NTrainer promotes non-nutritive suck output by providing patterned orocutaneous stimulation through a silicone pacifier that mimics the temporal organization of suck. Method Infants' non-nutritive suck pressure signals were digitized in the NICU before and after NTrainer therapy and compared to matched controls. Non-nutritive suck motor pattern stability was calculated based on infants' time- and amplitude-normalized digital suck pressure signals, producing a single value termed the Non-Nutritive Suck Spatiotemporal Index. Percent oral feeding was the other outcome of interest, and revealed the NTrainer's ability to advance the infant from gavage to oral feeding. Results Multilevel regression analyses revealed that treated infants manifest a disproportionate increase in suck pattern stability and percent oral feeding, beyond that attributed to maturational effects alone. Conclusion The NTrainer patterned orocutaneous therapy effectively accelerates non-nutritive suck development and oral feeding success in preterm infants who are at risk for oromotor dysfunction. PMID:18462468

  12. 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

  13. Safety, tolerability, and efficacy of oral therapies for relapsing-remitting multiple sclerosis.

    PubMed

    Oh, Jiwon; O'Connor, Paul W

    2013-08-01

    Treatment options for relapsing-remitting multiple sclerosis (RRMS) have been continuously expanding in recent years, and the emergence of a number of oral disease-modifying agents (DMAs) has significantly changed the landscape of therapeutic options for MS patients. Many of these oral DMAs have demonstrated satisfactory safety and tolerability profiles in clinical trial settings, but the long-term safety of these agents is an important concern. This review discusses salient points on the safety and clinical efficacy of the approved and emerging novel oral therapies in RRMS, including fingolimod, teriflunomide, dimethyl fumarate, laquinimod, and cladribine. PMID:23801528

  14. 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

  15. 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

  16. 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. PMID:24686309

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

    SciTech Connect

    Brook, I.; Ledney, G.D. )

    1990-07-01

    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.

  18. Modulation of cytokine production by carnitine

    PubMed Central

    De Simone, Claudio

    1993-01-01

    The ability of carnitine congeners to modulate cytokine production by human peripheral blood mononuclear cells (PBMC) was investigated. Modulation of cytokine production by PBMC of young (30 years of age or younger) and old (70 years of age or older) normal donors was first compared. The PBMC were collected over Ficoll–Hypaque and incubated in the presence of various concentrations of acetyl L-carnitine for 24 h. Subsequently the supernatants were collected and examined for cytokine production. The presence of cytokines in tissue culture supernatants was examined by ELISA. The cytokines measured included IL-1α, IL-1β, IL-2, IL-4, IL-6, TNFα, GM–CSF, and IFNγ. The results showed that at 50 μg/ml of acetyl L-carnitine the most significant response was obtained for TNFα. In this regard four of five young donors responded, but only one of five old donors responded. More recently these studies were expanded to examine the ability of L-carnitine to modulate cytokine production at higher doses, 200 and 400 μg/ml, in young donors. The results of these studies showed that in addition to TNFα, significant production of IL-1β and IL-6 was observed. These preliminary studies provide evidence that carnitine may modulate immune functions through the production of selected cytokines. PMID:18475565

  19. 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.

  20. 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.

  1. Development of a device for photodynamic therapy of oral cavity mucous

    NASA Astrophysics Data System (ADS)

    Ovchinnikov, Ilya S.; Tuchin, Valery V.; Ulyanov, Sergey S.

    1999-03-01

    The device, offered for reviewing, was designed and developed for photodynamic therapy of oral cavity mucous diseases and for laboratory experiments on the red light influence on the bacterial colonies in presence of a dye. The device has rather simple construction, it is cheap but convenience in use.

  2. Response and Tolerance to Oral Vasodilator Uptitration after Intravenous Vasodilator Therapy in Advanced Decompensated Heart Failure

    PubMed Central

    Verbrugge, Frederik H.; Dupont, Matthias; Finucan, Michael; Gabi, Alaa; Hawwa, Nael; Mullens, Wilfried; Taylor, David O.; Young, James B.; Starling, Randall C.; Wilson Tang, W.H.

    2015-01-01

    Aims To assess the hemodynamic response and tolerance to aggressive oral hydralazine/isosorbide dinitrate (HYD/ISDN) uptitration after intravenous vasodilator therapy in advanced decompensated heart failure (ADHF). Methods and Results Medical records of 147 consecutive ADHF patients who underwent placement of a pulmonary artery catheter and received intravenous vasodilator therapy were reviewed. Intravenous sodium nitroprusside and sodium nitroglycerin as first-line agent for those with preserved blood pressures were utilized in 143 and 32 patients, respectively. Sixty-one percent of patients were converted to oral HYD/ISDN combination therapy through a standardized conversion protocol. These patients had a significantly higher admission mean pulmonary arterial wedge pressure compared to patients not converted (28 ± 7 versus 25 ± 8 mmHg, respectively; P-value=0.024). Beneficial hemodynamic response to decongestive therapy, defined as low cardiac filling pressures and cardiac index ≥2.20 L/min/m² without emergent hypotension, was achieved in 32% and 29% of patients who did or did not receive oral HYD/ISDN, respectively (P-value=0.762). HYD/ISDN dosing was progressively and consistently decreased up to the moment of hospital discharge and during outpatient follow-up primarily due to incident hypotension. Conclusion The use of a standardized hemodynamically-guided uptitration protocol for conversion from intravenous to oral vasodilators may warrant subsequent dose reductions upon stabilization. PMID:26213182

  3. 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

  4. Regression of both oral mucocele and parotid swellings, following antiretroviral therapy.

    PubMed

    Syebele, Kabunda

    2010-01-01

    HIV-salivary gland associated disease is a well accepted concept in the HIV-related literature. Parotid swellings, especially in its cystic benign lymphoepithelial form, have been largely reported. Oral mucoceles (ranulas) were also associated with HIV in some publications. The exact nature of this link between mucoceles and HIV is still to be clarified. The mainstream treatment of most of parotid pathologies and oral mucoceles remains surgical approach. Strong evidences do, however, exist about lymphopithelial lesions of parotid glands that have been successfully treated with antiretroviral drugs. We present a case of intraoral mucocele, coexisting with bilateral parotid gland lymphoepithelial lesions, on a 2-year-old HIV-positive patient. Both parotid gland swellings and the sublingual mucocele have completely regressed following antiretroviral therapy. No surgical intervention was required. Conversely to benign lymphoepithelial lesions of parotid glands, the regression of oral mucocele on HIV-positive patient, following antiretroviral drugs therapy appears to be a rare phenomenon.

  5. Antipyretic therapy. Comparison of rectal and oral paracetamol.

    PubMed

    Keinänen, S; Hietula, M; Similä, S; Kouvalainen, K

    1977-08-17

    The absorption of paracetamol from syrup, tablet and two different suppository bases was compared in six adult volunteers using urinary excretion measurements. The total amount of paracetamol and its metabolites excreted and the peak excretion rates were lower from the suppository bases than from the oral dosage forms. Absorption was a little better from a polyethylene glycol suppository base than from a triglyceride base. The antipyretic efficacy of a paracetamol syrup and suppository at a dose of 10 mg/kg was compared in 30 children between the age of 4 months and 12 years, who had infections and a rectal temperature above 38.5 degrees C. Both dosage forms produced a significant decrease in temperature, the greatest fall being about 2 hours earlier with the oral dosage form. The syrup also seemed to be significantly (p less than 0.05) more effective (maximum fall of temperature 1.58 degrees C) in reducing fever than the suppository, which produced its greatest fall of temperature (1.24 degrees C) six hours after insertion of the suppository. From the practical point of view both forms can be regarded as safe and effective antipyretics. PMID:332506

  6. 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.

  7. 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

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

    PubMed

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

    2013-12-01

    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.

  9. Clinical and radiological assessment of effects of long-term corticosteroid therapy on oral health

    PubMed Central

    Beeraka, Swapna Sridevi; Natarajan, Kannan; Patil, Rajendra; Manne, Rakesh Kumar; Prathi, Venkata Sarath; Kolaparthi, Venkata Suneel Kumar

    2013-01-01

    Background: Corticosteroids (Cs) are used widely for their anti-inflammatory and immunosuppressive properties. They have the potential to cause dramatic improvement as well as produce equally dramatic adverse effects. The clinical misuse like over prescription of the drug should be avoided. Long-term administration may cause many adverse effects leading to impaired oral health. Oral health is usually not considered during management of patients on long-term corticosteroid therapy. The aim of this study was to assess the oral health status and radiological changes in the jaw bones of the patients under long-term corticosteroid therapy. Materials and Methods: Oral health of 100 patients under long-term corticosteroid therapy with a minimum of 3 months duration was compared with sex- and age-matched 100 healthy controls. The clinical examination included complete examination of the mouth and periodontal status. Radiographic evaluation of bone with the help of intra oral periapical radiograph and digital orthopantomograph and levels of serum calcium, alkaline phosphatase, and random blood sugar were assessed. ‘Chi-square test’, ‘Kolmogorov-Smirnov test’ and ‘Mann-Whitney U test’ were used for statistical analysis. P > 0.05 was considered significant. Results: Patients on steroids exhibited significantly higher levels of candidiasis and clinical attachment loss of the periodontal ligament, probing pocket depth. Bone density was significantly lower in the study group than that in the control group. Random blood glucose was significantly higher and significant lower levels of calcium were observed in patients on steroids. Conclusion: Long-term use of Cs may affect oral health adversely leading to candidiasis as well as impair bone metabolism leading to a considerable decrease in the mandibular bone mineral density. PMID:24348627

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

    PubMed

    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

  11. Plasma fibrinogen in women: relationships with oral contraception, the menopause and hormone replacement therapy.

    PubMed

    Lee, A J; Lowe, G D; Smith, W C; Tunstall-Pedoe, H

    1993-04-01

    Plasma fibrinogen was measured in 4837 women aged 25-64 years as part of the Scottish Heart Health Study and Scottish MONICA population surveys. The relationships of oral contraceptive use, the menopause and hormone replacement therapy were examined. Univariate analyses found that women with a history of oral contraceptive use, premenopausal women and those on hormone replacement therapy all had significantly lower fibrinogen levels than women who had never used oral contraceptives, postmenopausal women and non-hormone replacement users respectively. These differences persisted after age standardization. On multivariate analysis, menopausal status and hormone replacement therapy had independent effects on fibrinogen levels. Together with the common risk factors, 9.9% of the total variation in plasma fibrinogen levels was explained. However, less than 1% of this was from the combined menopausal and hormonal factors. These results confirm a postmenopausal rise in fibrinogen level which may be relevant to an increased risk of coronary heart disease. In addition, a protective effect with hormone replacement therapy is noted, although this was probably due to selection bias.

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

    PubMed

    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

  14. 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.

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

    PubMed

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

    2016-09-02

    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.

  16. Clinical, MRI, and histological results after photodynamic therapy of oral cancer

    NASA Astrophysics Data System (ADS)

    Herzog, Michael; Fellbaum, Ch.; Wagner-Manslau, C.; Horch, Hans-Henning

    1992-06-01

    Twenty-one carcinomas of the oral cavity in 18 patients were treated by photodynamic therapy (PDT). Patients were sensitized with Photosan III (2 mg/kg body weight), a modified HPD. Forty-eight hours after application of Photosan III, the tumor and surrounding tissues were irradiated with red laser light (200 mW/cm2, 120 J/cm2). MRI controls were carried out 24 hours after irradiation. Three to five days after irradiation, tumors were removed by conventional surgery. All specimens underwent histological examination. Histologically, hemorrhagic necroses of the irradiated tumors was found in all cases. The depth of necrosis varied from 2 to 8 mm. By MRI controls it was possible to detect edemas as change of signal resonance. PDT is a reliable therapy to reduce oral cancer selectively. Cancer destruction is limited by penetration depth of the laser light.

  17. Oral complications of cancer therapies. Pretherapy interventions to modify salivary dysfunction

    SciTech Connect

    Wolff, A.; Atkinson, J.C.; Macynski, A.A.; Fox, P.C. )

    1990-01-01

    Salivary gland dysfunction is a common side effect of cancer therapies. Salivary secretions are reduced rapidly after starting head and neck radiotherapy. Salivary gland dysfunction has also been linked to bone marrow transplantation and to cytotoxic chemotherapy. Salivary gland stimulation during radiation has been suggested as a means of reducing radiation damage. Results of an ongoing study investigating the effects of pilocarpine on radiation-induced salivary gland dysfunction suggest that parotid function was preserved, but not submandibular/sublingual function. Also, patients receiving pilocarpine had less frequent oral complaints. Further research is necessary to develop means of preventing or alleviating the salivary side effects of cancer therapies. 37 references.

  18. Assessment of bleeding during minor oral surgical procedures and extraction in patients on anticoagulant therapy

    PubMed Central

    Jimson, S.; Amaldhas, Julius; Jimson, Sudha; Kannan, I.; Parthiban, J.

    2015-01-01

    Introduction: The risk of postoperative hemorrhage from oral surgical procedures has been a concern in the treatment of patients who are receiving long-term anticoagulation therapy. A study undertaken in our institution to address questions about the amount and severity of bleeding associated with minor outpatient oral surgery procedures by assessing bleeding in patients who did not alter their anticoagulant regimen. Subjects and Methods: Eighty-three patients receiving long-term anticoagulant therapy visited Department of Oral and Maxillofacial Surgery from May 2010 to October 2011 for extractions and minor oral surgical procedures. Each patient was required to undergo preoperative assessment of prothrombin time (PT) and measurement of the international normalized ratio. Fifty-six patients with preoperative PT values within the therapeutic range 3–4 were included in the study. The patients’ age ranged between 30 and 75 years. Application of surgispon was done following the procedure. Extraction of teeth performed with minimal trauma to the surrounding tissues, the socket margins sutured, and sutures removed after 5 days. Results: There was no significant incidence of prolonged or excessive hemorrhage and wound infection and the healing process was normal. PMID:26015691

  19. Development of pulmonary arterial hypertension during oral dasatinib therapy for chronic myelogenous leukemia.

    PubMed

    Morishita, Sakura; Hagihara, Maki; Itabashi, Megumi; Ishii, Yoshimi; Yamamoto, Wataru; Numata, Ayumi; Motohashi, Kenji; Matsumoto, Kenji; Fujisawa, Shin; Nakajima, Hideaki

    2016-08-01

    We present a 36-year-old woman who had been taking oral dasatinib for 3 years for the treatment of chronic myelogenous leukemia (CML). Although adverse events such as thrombocytopenia and pleural effusion developed, she showed a major molecular response (MMR) 22 months after the initiation of oral dasatinib administration, and the therapy was thus continued. Approximately 34 months after oral dasatinib initiation, she developed severe exertional dyspnea and had to be urgently hospitalized. There was no apparent pleural effusion increase, and neither imaging nor blood test results suggested pneumonia or other infections. Pulmonary arterial hypertension (PAH) was suspected on the basis of transthoracic echocardiography. PAH was then confirmed by right heart catheterization. Though dasatinib was discontinued on the day of hospitalization, pulmonary hypertension and heart failure progressed, and she did not respond to catecholamines or PDE5 (phosphodiesterase type 5) inhibitors. On the 4(th) hospital day, she experienced cardiopulmonary arrest and died 1 week later. Cases with PAH due to oral administration of dasatinib have been reported previously. However, cases showing the rapid progression documented in our patient are rare and we advocate that PAH be considered a potential adverse event associated with dasatinib therapy. PMID:27599415

  20. Illumination devices for uniform delivery of light to the oral cavity for photodynamic therapy

    NASA Astrophysics Data System (ADS)

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

    2011-10-01

    To date, the lack of light delivery mechanisms to the oral cavity remains a barrier to the treatment of oral cancer with photodynamic therapy (PDT). The greatest impediment to medical practitioners is the current need to shield the normal tissues of the oral cavity, a costly and time-consuming procedure. In this research, we present the design of illumination devices to deliver light to the oral cavity for PDT, which will facilitate administration of PDT in the clinic. The goal for such an illumination device, as indicated by our clinical collaborators at Roswell Park Cancer Institute in Buffalo, NY, is to limit exposure of healthy tissue and produce an average irradiance of 100 mW/cm2 over the treatment field, with spatial non-uniformities below 10%. Furthermore, the size of the device must be compact to allow use in the oral cavity. Our research led to the design and fabrication of two devices producing spatial non-uniformities below 6% over a treatment area of 0.25 cm2 by design. One device consisted of an appropriately-sized reflector, inspired by solar concentrators, illuminated by a cylindrical diffusing fiber optimally located within the reflector; another was a solid lightpipe with a combination of optimized tapered and straight components.

  1. Prevention of Nausea and Vomiting in Patients Undergoing Oral Anticancer Therapies for Solid Tumors

    PubMed Central

    Costa, Ana Lúcia; Abreu, Catarina; Pacheco, Teresa Raquel; Macedo, Daniela; Sousa, Ana Rita; Pulido, Catarina; Quintela, António; Costa, Luís

    2015-01-01

    Chemotherapy-induced nausea and vomiting (CINV) is still a common and debilitating side effect despite recent advances in its prevention and treatment. The intrinsic emetogenicity of chemotherapy agents allowed grouping into four risk groups (high, moderate, low, and minimal risk of emetogenicity). The prevention of acute and delayed CINV for intravenous agents and one day regimens is well studied, although, there are few data about management of CINV induced by oral cytotoxic agents and targeted therapies, usually administered in extended regimens of daily oral use. Until now treatment of nausea and vomiting caused by oral antineoplastic agents remains largely empirical. The level of evidence of prophylactic antiemetics recommended for these agents is low. There are differences in the classification of emetogenic potential of oral antineoplastic agents between the international guidelines and different recommendations for prophylactic antiemetic regimens. Herein we review the evidence for antiemetic regimens for the most used oral antineoplastic agents for solid tumors and propose antiemetic regimens for high to moderate risk and low to minimal risk of emetogenicity. PMID:26421283

  2. 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

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

    PubMed

    Carmello, Juliana Cabrini; Alves, Fernanda; 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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. PMID:26703886

  11. 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.

  12. 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.

  13. Autogenous bone grafting in a patient on long-term oral bisphosphonate therapy: case report.

    PubMed

    El-Halaby, Ahmed; Becker, Jeffery; Bissada, Nabil F

    2009-12-01

    A 66-year-old patient was referred to the Periodontal Clinic at Case Western Reserve University for implant placement in the mandibular left first molar area. The patient reported a history of oral bisphosphonate intake for the last 7 years for the treatment of osteoporosis. Autogenous bone block grafting was planned to augment the ridge before implant placement. The surgery was performed under local anesthesia, and the implant was successfully placed 8 months after ridge augmentation. Healing was uneventful postoperatively, and the buccolingual width of the ridge increased significantly, allowing placement of a 5-mm-diameter dental implant. The patient showed proper healing of both the donor site and the recipient site, in spite of the long-term oral bisphosphonate therapy, with no resulting osteonecrosis of the jawbone.

  14. Indigenously developed close delivery system for oral iodine-131 therapy: Nominal cost but phenomenal protection

    PubMed Central

    Fatima, Nosheen; uz Zaman, Maseeh; Shah, Imran A; Ul Haq, Imtiaz; Javed, Ali

    2013-01-01

    Background: Administration of radiopharmaceuticals through intravenous and oral routes is the major source of radiation exposure to nuclear medicine (NM) technologists. Adopting new strategies to minimize radiation exposure is an important step toward safe practice in nuclear pharmacy. Materials and Methods: We have indigenously developed a relatively close delivery system for oral administration of radioiodine-131 (131I) to minimize radiation exposure to the technologists. Results: The efficacy of this indigenously developed close system was assessed upon 23 patients who were given 131I therapies for benign (13 patients) and malignant thyroid disorders (10 patients). There was 64 ± 6% (P < 0.05) reduction in exposure rate using indigenously developed delivery system. Conclusion: The cost involved in developing this system was very nominal, but efficacy in terms of radiation safety and confidence of our technologists were phenomenal. PMID:24379529

  15. Mandibular advancement oral appliance therapy for obstructive sleep apnoea: effect on awake calibre of the velopharynx

    PubMed Central

    Ryan, C; Love, L; Peat, D; Fleetham, J; Lowe, A

    1999-01-01

    BACKGROUND—The mechanisms of action of oral appliance therapy in obstructive sleep apnoea are poorly understood. Videoendoscopy of the upper airway was used during wakefulness to examine whether the changes in pharyngeal dimensions produced by a mandibular advancement oral appliance are related to the improvement in the severity of obstructive sleep apnoea.
METHODS—Fifteen patients with mild to moderate obstructive sleep apnoea (median (range) apnoea index (AI) 4(0-38)/h, apnoea-hypopnoea index (AHI) 28(9-45)/h) underwent overnight polysomnography and imaging of the upper airway before and after insertion of the oral appliance. Images were obtained in the hypopharynx, oropharynx, and velopharynx at end tidal expiration during quiet nasal breathing in the supine position. The cross sectional area and diameters of the upper airway were measured using image processing software with an intraluminal catheter as a linear calibration.
RESULTS—AI decreased to a median (range) value of 0 (0-6)/h (p<0.01) and AHI to 8 (1-28)/h (p<0.001) following insertion of the oral appliance. The median (95% confidence interval) cross sectional area of the upper airway increased by 18% (3 to 35) (p<0.02) in the hypopharynx and by 25% (11 to 69) (p<0.005) in the velopharynx, but not significantly in the oropharynx. Although in general the shape of the pharynx did not change following insertion of the oral appliance, the lateral diameter of the velopharynx increased to a greater extent than the anteroposterior diameter. Following insertion of the oral appliance the reduction in AHI was related to the increase in cross sectional area of the velopharynx (p= 0.01).
CONCLUSIONS—A mandibular advancement oral appliance increases the cross sectional area of the upper airway during wakefulness, particularly in the velopharynx. Assuming this effect on upper airway calibre is not eliminated by sleep, mandibular advancement oral appliances may reduce the severity of obstructive sleep

  16. 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

  17. Surviving with lung cancer: medication-taking and oral targeted therapy.

    PubMed

    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.

  18. 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

  19. Reported Rates of Diarrhea Following Oral Penicillin Therapy in Pediatric Clinical Trials

    PubMed Central

    Kuehn, Jemima; Ismael, Zareen; Long, Paul F.; Barker, Charlotte I.S.

    2015-01-01

    OBJECTIVES: Antibiotic-associated diarrhea (AAD) is a well-recognized adverse reaction to oral penicillins. This review analyzed the literature to determine the incidence of AAD following amoxicillin, amoxicillin/clavulanate, and penicillin V oral therapy in pediatric clinical trials. METHODS: An advanced search was conducted in MEDLINE and Embase databases for articles in any language reporting the incidence of AAD following oral penicillin therapy for any indicated infection in children (0–17 years). The search was limited to clinical trials. Articles were excluded if treatment was related to chronic conditions, involved concomitant antimicrobials, or if the dose or number of patients was not specified. RESULTS: Four hundred thirty-five articles relating to clinical trials were identified (307 from Embase; 128 from MEDLINE). Thirty-five articles reporting on 42 studies were included for analysis. The indications included acute otitis media, sinusitis, pharyngitis, and pneumonia. Thirty-three trials reported on amoxicillin/clavulanate, 6 on amoxicillin, and 3 on penicillin V. In total, the 42 trials included 7729 children who were treated with an oral penicillin. On average, 17.2% had AAD. Data were pooled for each penicillin. The AAD incidence was 19.8% for amoxicillin/clavulanate, 8.1% for amoxicillin, and 1.2% for penicillin V. The amoxicillin/clavulanate data were analyzed according to formulation: pooled-average. The incidence of ADD was 24.6% for the 4:1 formulation, 12.8% for the 7:1 formulation, 19.0% for the 8:1 formulation, and 20.2% for the 14:1 formulation. CONCLUSIONS: These results demonstrate substantially increased incidence of AAD following use of amoxicillin/clavulanate, compared to use of amoxicillin and penicillin V, as well as varying AAD rates with diffierent amoxicillin/clavulanate formulations. These findings warrant consideration when prescribing. The underlying mechanisms of AAD in children remain unclear. PMID:25964726

  20. Correlation of carnitine levels to methionine and lysine intake.

    PubMed

    Krajcovicová-Kudlácková, M; Simoncic, R; Béderová, A; Babinská, K; Béder, I

    2000-01-01

    Plasma carnitine levels were measured in two alternative nutrition groups--strict vegetarians (vegans) and lactoovovegetarians (vegetarians consuming limited amounts of animal products such as milk products and eggs). The results were compared to an average sample of probands on mixed nutrition (omnivores). Carnitine levels were correlated with the intake of essential amino acids, methionine and lysine (as substrates of its endogenous synthesis), since the intake of carnitine in food is negligible in the alternative nutrition groups (the highest carnitine content is in meat, lower is in milk products, while fruit, cereals and vegetables contain low or no carnitine at all). An average carnitine level in vegans was significantly reduced with hypocarnitinemia present in 52.9% of probands. Similarly, the intake of methionine and lysine was significantly lower in this group due to the exclusive consumption of plant proteins with reduced content of these amino acids. Carnitine level in lactoovovegetarians was also significantly reduced, but the incidence of values below 30 micromol/l was lower than in vegans representing 17.8% vs. 3.3% in omnivores. Intake of methionine and lysine was also significantly reduced in this group, but still higher compared to vegans (73% of protein intake covered by plant proteins). Significant positive correlation of carnitine levels with methionine and lysine intake in alternative nutrition groups indicates that a significant portion of carnitine requirement is covered by endogenous synthesis. Approximately two thirds of carnitine requirement in omnivores comes from exogenous sources. The results demonstrate the risks of alternative nutrition with respect to the intake of essential amino acids, methionine and lysine, and with respect to the intake and biosynthesis of carnitine. PMID:11043928

  1. Correlation of carnitine levels to methionine and lysine intake.

    PubMed

    Krajcovicová-Kudlácková, M; Simoncic, R; Béderová, A; Babinská, K; Béder, I

    2000-01-01

    Plasma carnitine levels were measured in two alternative nutrition groups--strict vegetarians (vegans) and lactoovovegetarians (vegetarians consuming limited amounts of animal products such as milk products and eggs). The results were compared to an average sample of probands on mixed nutrition (omnivores). Carnitine levels were correlated with the intake of essential amino acids, methionine and lysine (as substrates of its endogenous synthesis), since the intake of carnitine in food is negligible in the alternative nutrition groups (the highest carnitine content is in meat, lower is in milk products, while fruit, cereals and vegetables contain low or no carnitine at all). An average carnitine level in vegans was significantly reduced with hypocarnitinemia present in 52.9% of probands. Similarly, the intake of methionine and lysine was significantly lower in this group due to the exclusive consumption of plant proteins with reduced content of these amino acids. Carnitine level in lactoovovegetarians was also significantly reduced, but the incidence of values below 30 micromol/l was lower than in vegans representing 17.8% vs. 3.3% in omnivores. Intake of methionine and lysine was also significantly reduced in this group, but still higher compared to vegans (73% of protein intake covered by plant proteins). Significant positive correlation of carnitine levels with methionine and lysine intake in alternative nutrition groups indicates that a significant portion of carnitine requirement is covered by endogenous synthesis. Approximately two thirds of carnitine requirement in omnivores comes from exogenous sources. The results demonstrate the risks of alternative nutrition with respect to the intake of essential amino acids, methionine and lysine, and with respect to the intake and biosynthesis of carnitine.

  2. Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer

    PubMed Central

    Qu, Q; Zeng, F; Liu, X; Wang, Q J; Deng, F

    2016-01-01

    Tumor cells exhibit unique metabolic adaptations that are increasingly viewed as potential targets for novel and specific cancer therapies. Among these targets, the carnitine palmitoyltransferase system is responsible for delivering the long-chain fatty acid (FA) from cytoplasm into mitochondria for oxidation, where carnitine palmitoyltransferase I (CPTI) catalyzes the rate-limiting step of fatty acid oxidation (FAO). With increasing understanding of the crucial role had by fatty acid oxidation in cancer, CPTI has received renewed attention as a pivotal mediator in cancer metabolic mechanism. CPTI activates FAO and fuels cancer growth via ATP and NADPH production, constituting an essential part of cancer metabolism adaptation. Moreover, CPTI also functionally intertwines with other key pathways and factors to regulate gene expression and apoptosis of cancer cell. Here, we summarize recent findings and update the current understanding of FAO and CPTI in cancer and provide theoretical basis for this enzyme as an emerging potential molecular target in cancer therapeutic intervention. PMID:27195673

  3. Treatment of Wilson's disease with zinc. I. Oral zinc therapy regimens.

    PubMed

    Hill, G M; Brewer, G J; Prasad, A S; Hydrick, C R; Hartmann, D E

    1987-01-01

    The standard therapy for preventing copper accumulation in Wilson's disease, D-penicillamine, has been a life-saving drug, but it has many side effects and some patients are completely intolerant. We have been using oral zinc as another approach to the therapy for Wilson's disease, with copper balance studies as the key initial assessment of the adequacy of a given dose or regimen of zinc therapy. We earlier reported that an intensive regimen of zinc (zinc taken every 4 hr) was effective in controlling copper balance. We have now shown with balance studies that a simplified zinc therapy regimen of 50 mg zinc taken 3 times per day is effective in controlling copper balance. Preliminary work presented here with other simplified regimens also indicate their effectiveness. These studies increase the data base, in terms of copper balance, for zinc therapy of Wilson's disease, and expand the dose range and regimens of zinc which have been shown to control copper balance. PMID:3570163

  4. Topical Tacrolimus and Periodontal Therapy in the Management of a Case of Oral Chronic GVHD Characterized by Specific Gingival Localization

    PubMed Central

    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. PMID:24639902

  5. 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.

  6. Allergy to nickel: first results on patients administered with an oral hyposensitization therapy.

    PubMed

    Tammaro, A; De Marco, G; Persechino, S; Narcisi, A; Camplone, G

    2009-01-01

    Nickel sulphate allergy is the most common contact allergy. In fact, nickel sulphate is an ubiquitous element, contained in various objects and food; it occurs in igneous rocks, as a free metal and together with iron, but it is also a component of living organism, mainly vegetables. We carried out a clinical trial of oral hyposensitization therapy with low doses of nickel in a group of 67 patients affected by systemic allergy to this sensitizer element. We obtained good results on consequent tolerance to nickel in treated patients.

  7. 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

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

    PubMed

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

    2011-06-01

    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.

  9. 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

  10. Allergy to nickel: first results on patients administered with an oral hyposensitization therapy.

    PubMed

    Tammaro, A; De Marco, G; Persechino, S; Narcisi, A; Camplone, G

    2009-01-01

    Nickel sulphate allergy is the most common contact allergy. In fact, nickel sulphate is an ubiquitous element, contained in various objects and food; it occurs in igneous rocks, as a free metal and together with iron, but it is also a component of living organism, mainly vegetables. We carried out a clinical trial of oral hyposensitization therapy with low doses of nickel in a group of 67 patients affected by systemic allergy to this sensitizer element. We obtained good results on consequent tolerance to nickel in treated patients. PMID:19822100

  11. Comparison of High-Dose Corticosteroid Pulse Therapy and Combination Therapy Using Oral Cyclosporine with Low-Dose Corticosteroid in Severe Alopecia Areata

    PubMed Central

    Yeo, In Kwon; Ko, Eun Jung; No, Yeon A; Lim, Ee Seok; Park, Kui Young; Li, Kapsok; Kim, Beom Joon; Seo, Seong Jun; Kim, Myeung Nam

    2015-01-01

    Background Severe alopecia areata (AA) is resistant to conventional treatment. Although systemic oral corticosteroids are an effective treatment for patients with severe AA, those drugs have many adverse effects. Corticosteroid pulse therapy has been introduced to increase therapeutic effects and reduce adverse effects. However, the treatment modality in severe AA is still controversial. Objective To evaluate the effectiveness of corticosteroid pulse therapy in patients with severe AA compared with treatment with oral cyclosporine with corticosteroid. Methods A total of 82 patients with severe AA were treated with corticosteroid pulse therapy, and 60 patients were treated with oral cyclosporine with corticosteroid. Both groups were retrospectively evaluated for therapeutic efficacy according to AA type and disease duration. Results In 82 patients treated with corticosteroid pulse therapy, 53 (64.6%) were good responders (>50% hair regrowth). Patients with the plurifocal (PF) type of AA and those with a short disease duration (≤3 months) showed better responses. In 60 patients treated with oral cyclosporine with corticosteroid, 30 (50.0%) patients showed a good response. The AA type or disease duration, however, did not significantly affect the response to treatment. Conclusion Corticosteroid pulse therapy may be a better treatment option than combination therapy in severe AA patients with the PF type. PMID:26719635

  12. 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.

  13. Associations among the use of highly active antiretroviral therapy, oral candidiasis, oral Candida species and salivary immunoglobulin A in HIV-infected children

    PubMed Central

    Pomarico, Luciana; Ferraz Cerqueira, Daniella; de Araujo Soares, Rosangela Maria; Ribeiro de Souza, Ivete Pomarico; Barbosa de Araujo Castro, Gloria Fernanda; Socransky, Sigmund; Haffajee, Anne; Palmier Teles, Ricardo

    2009-01-01

    Objectives To examine the impact of antiretroviral therapy on the prevalence of oral candidiasis, recovery of oral Candida species (spp) and salivary levels of total secretory immunoglobulin A (SIgA) and Candida-specific SIgA in human immunodeficiency virus (HIV)-infected children. Methods Sixty six HIV-positive and 40 HIV-negative children were cross-sectionally examined for the presence of oral lesions. Whole stimulated saliva samples were collected for the identification of Candida spp using culture and measurement of total and specific SIgA using enzyme-linked immunosorbent assay (ELISA). Results HIV-positive children had a higher prevalence of oral candidiasis (p < 0.05); higher frequency of detection of Candida spp (p < 0.05) and higher levels of total (p < 0.05) and Candida-specific SIgA (p < 0.001) than did HIV-negative children. Among HIV-positive subjects, antiretroviral users had lower viral loads (p < 0.001), lower levels of Candida spp (p < 0.05) and total SIgA (p < 0.05) compared with antiretroviral non-users. Conclusions The use of antiretroviral therapy was associated with decreases in the prevalence of oral candidiasis. This diminished exposure to Candida spp was accompanied by decreases in levels of total and Candida-specific SIgA. PMID:19615660

  14. Triple Oral Antithrombotic Therapy in Atrial Fibrillation and Coronary Artery Stenting: Searching for the Best Combination.

    PubMed

    Elewa, Hazem; Ahmed, Dina; Barnes, Geoffrey D

    2016-09-01

    Patients with atrial fibrillation (AF) who are treated with oral anticoagulants often have concurrent coronary artery disease. Triple oral antithrombotic therapy (TOAT) is often necessity to prevent stent thrombosis or myocardial infarction associated with percutaneous coronary intervention or acute coronary syndrome in patients with comorbid coronary artery disease and AF. Although the use of TOAT (aspirin, clopidogrel, and warfarin) has excellent efficacy against thrombotic complications, this comes on the expense of increased bleeding risk. This review discusses potential strategies to improve TOAT benefit-risk ratio evidence from the literature. These strategies include: (1) dropping aspirin; (2) reducing the duration of TOAT; (3) switching warfarin to a direct oral anticoagulant (DOAC); (4) the use of DOAC in combination with a single antiplatelet agent; and (5) switching clopidogrel to a novel antiplatelet agent. Although dropping aspirin and reducing TOAT duration should be considered in selected AF patients at low risk of thrombosis, the role of DOACs and novel antiplatelets in TOAT has not been thoroughly studied, and there is limited evidence to support their use currently. Ongoing studies will provide safety and efficacy data to guide clinicians who frequently face the challenge of determining the best TOAT combination for their patients. PMID:27235831

  15. Rapid and sustained oral theophylline loading. An alternative to intravenous aminophylline therapy.

    PubMed

    Brown, D L; Maddux, M S; Organek, H W; Bauman, J L

    1983-04-01

    We evaluated an oral theophylline loading-dose procedure that was designed to rapidly achieve and sustain theophylline serum concentrations of approximately 10 to 12 micrograms/mL. Ten healthy adults were given an oral loading dose of approximately 6 mg/kg of aminophylline, (Aminophyllin) (ie, 4.8 mg/kg of theophylline). Two hours later, each subject was given approximately 6 mg/kg of a sustained-release theophylline tablet (Theo-Dur). Serum samples were collected at 1/2, 1, 2, 3, 6, 9, and 12 hours, then assayed for theophylline concentration. The mean theophylline concentration (+/- SD) one hour after the initial loading dose was 10.5 +/- 2.3 micrograms/mL. Subsequent theophylline concentrations demonstrated minimal fluctuation, with means ranging from 10.7 +/- 1.6 to 13.6 +/- 2.8 micrograms/mL. Four of the subjects reported headache; none vomited or experienced severe nausea. We conclude that this method of oral theophylline loading can be effective in achieving prompt and sustained therapeutic theophylline levels without significant side effects and that this may provide a valuable therapeutic alternative in those asthmatic patients who do not clearly require intravenous aminophylline therapy. PMID:6838301

  16. Antiplatelet therapy strategies after percutaneous coronary intervention in patients needing oral anticoagulation.

    PubMed

    Saint Etienne, Christophe; Angoulvant, Denis; Simeon, Edouard; Fauchier, Laurent

    2013-11-01

    Long-term oral anticoagulant (OAC) and dual-antiplatelet therapy are commonly needed in patients with atrial fibrillation and in patients undergoing percutaneous coronary intervention (PCI), respectively. The combination of atrial fibrillation and PCI is frequent, and leads to a dilemma for antithrombotic therapy, where risk of stroke or stent thrombosis must be balanced with bleeding risk. In the WOEST study, 573 patients on OAC undergoing PCI were randomly assigned to receive clopidogrel alone or clopidogrel plus aspirin. The primary end point was the occurrence of any bleeding episode during 1-year follow-up. Clopidogrel alone administered to patients taking OAC after PCI was associated with a significantly lower rate of bleeding complications than clopidogrel plus aspirin. Moreover, a composite secondary end point of death, myocardial infarction and stent thrombosis was significantly lower in the dual-therapy group compared with the triple-therapy group. In spite of its limitations, the WOEST study constitutes a major breakthrough, showing that long-term aspirin after PCI may be obsolete in certain circumstances. This needs to be confirmed in further studies.

  17. 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

  18. Hemolysis after Oral Artemisinin Combination Therapy for Uncomplicated Plasmodium falciparum Malaria

    PubMed Central

    Lingscheid, Tilman; Steiner, Florian; Stegemann, Miriam S.; Bélard, Sabine; Menner, Nikolai; Pongratz, Peter; Kim, Johanna; von Bernuth, Horst; Mayer, Beate; Damm, Georg; Seehofer, Daniel; Salama, Abdulgabar; Suttorp, Norbert; Zoller, Thomas

    2016-01-01

    Episodes of delayed hemolysis 2–6 weeks after treatment of severe malaria with intravenous artesunate have been described. We performed a prospective observational study of patients with uncomplicated malaria to investigate whether posttreatment hemolysis also occurs after oral artemisinin-based combination therapy. Eight of 20 patients with uncomplicated malaria who were given oral artemisinin-based combination therapy met the definition of posttreatment hemolysis (low haptoglobin level and increased lactate dehydrogenase level on day 14). Five patients had hemolysis persisting for 1 month. Patients with posttreatment hemolysis had a median decrease in hemoglobin level of 1.3 g/dL (interquartile range 0.3–2.0 g/dL) in the posttreatment period, and patients without posttreatment hemolysis had a median increase of 0.3 g/dL (IQR −0.1 to 0.7 g/dL; p = 0.002). These findings indicate a need for increased vigilance for hemolytic events in malaria patients, particularly those with predisposing factors for anemia. PMID:27434054

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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

  4. Effect of long-term therapy with oral steroids on respiratory muscle function and ventilatory drive.

    PubMed

    Zanotti, E; Corsico, R; Rampulla, C; Ambrosino, N; Fracchia, C; Crotti, P; Rubini, F; Nava, S

    1993-01-01

    It has been shown that chronic oral steroid therapy (ST) does not induce respiratory muscle dysfunction in normal and asthmatic subjects. As corticosteroids are sometimes chronically used in the treatment of the patients with chronic obstructive pulmonary disease (COPD), the aim of our study was to verify whether ST could cause respiratory muscle impairment and, since ST also affects the central nervous system, whether ST could influence the ventilatory pattern. We retrospectively studied 12 COPD patients (group A), on long-term therapy (for at least 4 consecutive months, range 4-18 months) with an oral steroid, deflazacort, 15 mg.d-1. The subjects were strictly matched, with regard to age, sex, height, weight, forced expiratory volume in one second (FEV1), residual volume (RV), arterial oxygen tension (PaCO2), arterial carbon dioxide tension (PaCO2) and pH, with 12 COPD patients (Group B) who had never taken oral steroids. To assess respiratory muscle strength, we measured maximal inspiratory (MIP) and expiratory (MEP) pressures, while mouth occlusion pressure (P0.1) was employed to assess neuromuscular drive; ventilatory pattern and airway impedence were also evaluated. Effectiveness of ST was confirmed by the plasmatic levels of endogenous cortisol. No significant differences were observed between the two groups with regard to MIP (A 72.2 +/- 9.7 vs B: 70 +/- 7.2 cmH2O) and MEP (A 91.6 +/- 10.5 vs B 94.4 +/- 7.6 cmH2O) whilst P0.1 was significantly higher in group A (2.6 +/- 0.3 cmH2O) than in group B (1.8 +/- 0.1 cmH2O). No significant differences were found among all the ventilatory parameters, but the impedence was significantly higher in group A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8472057

  5. Reduced inhibition of Candida albicans adhesion by saliva from patients receiving oral cancer therapy.

    PubMed Central

    Umazume, M; Ueta, E; Osaki, T

    1995-01-01

    The effect of saliva on the adhesion of Candida albicans to epithelial cells was examined in vitro by using saliva from healthy controls and patients with oral squamous cell carcinoma. The adhesion of C. albicans to established epithelial tumor cells was reduced by 40% by salivary treatment of the C. albicans or epithelial cells. The inhibitory activity of saliva was almost completely abolished by anti-secretory immunoglobulin A antibody, concanavalin A, and mannose. Compared with saliva from healthy individuals, that from patients who had received chemoradiotherapy for oral carcinoma showed reduced suppression of C. albicans adhesion, which accompanied decreased salivary secretory immunoglobulin A and lactoferrin concentrations. A greater number of C. albicans cells adhered to buccal cells obtained from patients who had received chemoradiotherapy than to those from healthy individuals. Treatment of either epithelial cells or C. albicans with anticancer drugs induced an increase in adherence of epithelial cells and yeast cells. In contrast, concanavalin A- and mannose-pretreated C. albicans exhibited reduced adhesion to epithelial cells. No further decrease of C. albicans adhesion was observed when both epithelial cells and yeast phase C. albicans were treated with mannose. In conclusion, the inhibition of C. albicans adhesion by saliva depends largely on mannose residues on salivary glycoproteins and mannose is one of the binding ligands on both C. albicans and epithelial cells. In addition, anticancer therapy may induce oral C. albicans overgrowth by decreasing salivation and the concentrations of glycoproteins in saliva inhibiting C. albicans adhesion and by increasing the adhesive properties of both C. albicans and oral epithelial cells. PMID:7714204

  6. The correlation between response to oral cyclosporin therapy and systemic inflammation, metabolic abnormality in patients with psoriasis.

    PubMed

    Ohtsuka, Tsutomu

    2008-11-01

    Psoriasis is a disease presenting cutaneous, immunological and vascular abnormalities. Oral cyclosporin therapy has been shown to be effective for the disease. Clinical and laboratory findings affecting the response of oral cyclosporin therapy in patients with psoriasis were studied. Forty-seven patients with psoriasis (male:female = 27:20, age 56.7 + 12.6 years) were studied. The response to oral cyclosporin therapy was categorized as excellent, good, fair and poor according to decrease of PASI score and decrease of cyclosporin dose. Clinical and laboratory findings including cyclosporin trough level and high sensitivity-CRP were statistically analyzed. Nine patients showed excellent response, 17 good response, 19 fair response and 2 poor response. High sensitivity-CRP (0.11 +/- 0.02 mg/dl) in fair response patients to oral cyclosporin therapy was significantly lower than those in excellent response patients (0.42 +/- 0.21 mg/dl) (P < or = 0.05). Body mass index (23.4 +/- 0.6 kg/m(2)), HDL-cholesterol (57.1 +/- 3.6 mg/dl) and fasting plasma glucose (105 +/- 5 mg/dl) in fair response patients to oral cyclosporin therapy was significantly lower, higher and lower than those in excellent response patients (25.7 +/- 0.9 kg/m(2); 43.0 +/- 2.8, 140 +/- 20 mg/dl) (P < 0.05, P < 0.05, P < 0.05), respectively. No other clinical and laboratory findings showed statistical significance among excellent, good and fair response patients. These results showed the correlation between response of oral cyclosporin therapy and systemic inflammation, metabolic abnormality in patients with psoriasis.

  7. Stabilization of the thermolabile variant S113L of carnitine palmitoyltransferase II

    PubMed Central

    Golbik, Ralph; Sippl, Wolfgang; Zierz, Stephan

    2016-01-01

    Objective: Muscle carnitine palmitoyltransferase (CPT) II deficiency, the most common defect of lipid metabolism in muscle, is characterized by attacks of myoglobinuria without persistent muscle weakness. Methods: His6-N-hCPT2 (wild-type) and His6-N-hCPT2/S113L (variant) were produced recombinantly in prokaryotic host and characterized according to their functional and regulatory properties. Results: The wild-type and the variant S113L showed the same enzymatic activity and thermostability at 30°C. The mutated enzyme, however, revealed an abnormal thermal destabilization at 40°C and 45°C. This was consistent with an increased flexibility (B-factor) of the variant at 40°C compared with that of the wild-type shown by molecular dynamics analysis. Preincubation of the enzymes with l-carnitine and acyl-l-carnitines containing more than 10 carbons in the acyl side-chain stabilized the mutated enzyme against thermal inactivation. In contrast, palmitoyl-CoA destabilized both enzymes. Conclusions: The problems in CPT II deficiency originating from the S113L mutation are not caused by the loss of catalytically active enzyme. They might be at least partially related to an impaired thermal stability of the protein. The lower thermodynamic stability of the variant might explain why fever and prolonged exertion provoke attacks of myoglobinuria in CPT II deficiency. The stabilization by acyl-l-carnitines might provide the basis for possible preventive therapy of CPT II deficiency. PMID:27123472

  8. 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.

  9. A common X-linked inborn error of carnitine biosynthesis may be a risk factor for nondysmorphic autism.

    PubMed

    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

    2012-05-22

    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.

  10. 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

  11. 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.

  12. 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

  13. From a pump handle to oral rehydration therapy: a model of translational research.

    PubMed

    Schultz, Stanley G

    2007-12-01

    Few afflictions have attracted as much attention and impacted on as many societal and biomedical areas as cholera. Dr. John Snow's studies launched the field of epidemiology, were early applications of medical cartography, and promoted the use of statistical methods in medicine. The finding that cholera was due to the ingestion of contaminated water lent to the demise of the prevalent "miasmatic theory of contagion," set the platform for the "germ theory of disease," and promoted the growth of public health concerns for water purification and sanitation. More recent attention to this disease led to the notion of "secretory diarrhea" and the translation of basic principles to the development of oral rehydration therapy and its "spin-offs" (Gatorade and Pedilyte).

  14. Current status of oral PUVA therapy for psoriasis. Eye protection revisions.

    PubMed

    1982-05-01

    Recommendations for the use of oral psoralens and long-wave ultraviolet light (PUVA) were published in 1979. Since that time advances in optics technology and new knowledge on eye toxicity associated with PUVA therapy have prompted the original compilers to revise the eye protection segments of the PUVA recommendations. It is recommended that during day 1 of PUVA treatment, UVA-blocking plastic wraparound glasses be worn while outdoors from time of ingestion of the drug until bedtime. While indoors or in dim light, either the wraparound glasses or clear UVA-blocking glasses should be worn. During day 2, either the plastic wraparounds or the clear UVA-blocking glasses should be worn the entire day. Shielding of the eyes during day 2 is an absolute requirement, and on day 2 it should be encouraged but is a relative requirement. The revisions were compiled with the view of urging patient compliance. PMID:7096648

  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. 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

  17. Oral administration of pH-sensitive curcumin-loaded microparticles for ulcerative colitis therapy.

    PubMed

    Xiao, Bo; Si, Xiaoying; Zhang, Mingzhen; Merlin, Didier

    2015-11-01

    Oral colon-specific drug delivery is of great interest for ulcerative colitis (UC) therapy. Here, an emulsion-solvent evaporation method was used to fabricate microparticles (MPs) with pH-sensitive Eudragit S100 (ERS100) and poly(lactide-co-glycolide) (PLGA), and the MPs were loaded with curcumin (an efficient anti-inflammatory agent). The resultant spherical MPs had a desirable particle size ranging from 1.52 to 1.91 μm. Their loading efficiency could be regulated by changing the weight ratios of ERS100 and PLGA, with some MPs exhibiting loading efficiencies over 80%. It was observed that the fast release of curcumin from MPs in buffers (pH 1.2 and 6.8) could be significantly decreased by increasing the PLGA content. ERS100/PLGA MPs with a weight ratio of 1:2 (MPs-4) were able to maintain sustained release of curcumin, releasing ∼ 48% of the initial drug load at pH 7.2-7.4 during a 20 h-incubation. Most importantly, in vivo experiments revealed that orally administered MPs-4 had a superior therapeutic efficiency in alleviating colitis in a UC mouse model, compared to curcumin. Collectively, our one-step-fabricated curcumin-loaded MPs have the properties of pH-sensitivity, controlled drug release and colon targeting, and thus, may hold promise as a readily scalable drug carrier for the efficient clinical treatment of UC.

  18. Comparative pharmacokinetics of oral and intravenous ifosfamide/mesna/methylene blue therapy.

    PubMed

    Aeschlimann, C; Küpfer, A; Schefer, H; Cerny, T

    1998-09-01

    Oral treatment with ifosfamide results in dose-limiting encephalopathy. Methylene blue is effective in reversal and prophylaxis of this side effect. In the present study, the pharmacokinetics of ifosfamide after iv and po therapy in combination with prophylactic administration of methylene blue were investigated. Nine patients with metastatic non-small cell lung cancer were treated by a combination of ifosfamide (3 days), sodium 2-mercaptoethane sulfonate (4 days), and etoposide (8 days). Cycles were repeated every 28 days. Ifosfamide was administered orally, with the exception of one of the first two cycles, when it was administered as a short infusion (randomly assigned). The patients received methylene blue in doses of 50 mg po 3 times daily; an initial dose of 50 mg was given the evening before chemotherapy. Urine samples were collected over the entire treatment period, and concentrations of ifosfamide and its major metabolite, 2-chloroethylamine, were measured by gas liquid chromatography. By the same technique, 2- and 3-dechloroethylifosfamide were determined in plasma and urine. Overall alkylating activity in urine was assayed by reaction of the alkylating metabolites with 4-(4'-nitrobenzyl)-pyridine. The chemotherapeutic regimen was well-tolerated by all of the patients studied. There was no evidence of a shift in the metabolic pattern dependent on the route of administration. From the data, we conclude that methylene blue has a neuroprotective effect and that the pharmacokinetics of ifosfamide are not influenced by its comedication.

  19. Design of illumination devices for delivery of photodynamic therapy in the oral cavity

    NASA Astrophysics Data System (ADS)

    Canavesi, Cristina; Fournier, Florian; Foster, Thomas H.; Rolland, Jannick P.

    2010-08-01

    We present three designs for delivery of light in the oral cavity for photodynamic therapy (PDT) under the requirements of average irradiance of 50 mW/cm2 and spatial non-uniformities well under 10% over a square area of 25 mm2. The main goal is to design a device that avoids having to shield the oral cavity prior to irradiation for PDT. Illumination theory is instrumental in identifying an effective geometry for the device. The designs proposed build upon the technology that is already available for PDT and use illumination theory concepts to maximize the efficiency of the light delivery. One design combines a cylindrical diffusing fiber with a reflector derived from the edge-ray theorem while a second consists of a fiber illuminator coupled to a lightpipe device. Both designs are successful in delivering the light reducing the need of shielding and in providing the desired irradiance and uniformity. The two approaches performed comparably and provided a higher irradiance than needed, thus inspiring the design of a third, simpler design based on an off-axis cylinder reflector.

  20. Oral testosterone undecanoate (Andriol) supplement therapy improves the quality of life for men with testosterone deficiency.

    PubMed

    Park, N C; Yan, B Q; Chung, J M; Lee, K M

    2003-06-01

    In a single-blind, placebo-controlled study, the effects of a 3-month oral administration of 160 mg/day testosterone undecanoate (Andriol) on the quality of life of men with testosterone deficiency were evaluated. The subjects included ten men with primary hypogonadism and 29 with andropause with sexual dysfunction as the most common problem. The changes in subjective symptoms were evaluated by the PNUH QoL scoring system and the St. Louis University Questionnaire for androgen deficiency in aging males (ADAM). Digital rectal examination (DRE) was performed and serum testosterone, prostate-specific antigen (PSA) and liver profile were monitored. Testosterone undecanoate treatment (n = 33) significantly improved sexual dysfunction and symptom scores of metabolic, cardiopulmonary, musculoskeletal and gastrointestinal functions compared to baseline and to placebo (n = 6). ADAM score also significantly improved after 3 months of treatment. Serum testosterone was significantly increased compared to pretreatment levels only in the testosterone undecanoate group. In the placebo group, no significant changes compared to baseline were found for testosterone levels and QoL questionnaires. No abnormal findings were detected on DRE or laboratory findings in either group. Adverse events, such as gastrointestinal problems and fatigue, were mild and self-limiting. It is concluded that androgen supplement therapy with oral testosterone undecanoate (Andriol) restores the quality of life through improvement of general body functions in men with testosterone deficiency. PMID:12898792

  1. Tumor dynamics in response to antiangiogenic therapy with oral metronomic topotecan and pazopanib in neuroblastoma xenografts.

    PubMed

    Kumar, Sushil; Mokhtari, Reza Bayat; Oliveira, Indhira Dias; Islam, Syed; Toledo, Silvia Regina Caminada; Yeger, Herman; Baruchel, Sylvain

    2013-08-01

    Metronomic chemotherapy, combined with targeted antiangiogenic drugs, has demonstrated significant anticancer efficacy in various studies. Though, tumors do acquire resistance. Here, we have investigated the effect of prolonged therapy with oral metronomic topotecan and pazopanib on tumor behavior in a neuroblastoma mouse xenograft model. SK-N-BE(2) xenograft-bearing mice were treated with either of the following regimens (daily, orally): vehicle (control), 150 mg/kg pazopanib, 1.0 mg/kg topotecan, and combination of topotecan and pazopanib. Planned durations of treatment for each regimen were 28, 56, and 80 days or until the end point, after which animals were sacrificed. We found that only combination-treated animals survived until 80 days. Combination halted tumor growth for up to 50 days, after which gradual growth was observed. Unlike single agents, all three durations of combination significantly lowered microvessel densities compared to the control. However, the tumors treated with the combination for 56 and 80 days had higher pericyte coverage compared to control and those treated for 28 days. The proliferative and mitotic indices of combination-treated tumors were higher after 28 days of treatment and comparable after 56 days and 80 days of treatment compared to control. Immunohistochemistry, Western blot, and real-time polymerase chain reaction revealed that combination treatment increased the hypoxia and angiogenic expression. Immunohistochemistry for Glut-1 and hexokinase II expression revealed a metabolic switch toward elevated glycolysis in the combination-treated tumors. We conclude that prolonged combination therapy with metronomic topotecan and pazopanib demonstrates sustained antiangiogenic activity but also incurs resistance potentially mediated by elevated glycolysis.

  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. 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...

  4. 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.

  5. 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

  6. A randomized trial of transdermal and oral estrogen therapy in adolescent girls with hypogonadism

    PubMed Central

    2014-01-01

    Background Adolescent females with ovarian failure require estrogen therapy for induction of puberty and other important physiologic effects. Currently, health care providers have varying practices without evidence-based standards, thus investigating potential differences between oral and transdermal preparations is essential. The purpose of this study was to compare the differential effects of treatment with oral conjugated equine estrogen (OCEE), oral 17β estradiol (OBE), or transdermal 17β estradiol (TBE) on biochemical profiles and feminization in girls with ovarian failure. Study design 20 prepubertal adolescent females with ovarian failure, ages 12–18 years, were randomized to OCEE (n = 8), OBE (n = 7), or TBE (n = 5) for 24 months. Estrogen replacement was initiated at a low dose (0.15 mg OCEE, 0.25 mg OBE, or 0.0125 mg TBE) and doubled every 6 months to a maximum dose of 0.625 mg/d OCEE, 1 mg/d OBE, or 0.05 mg/d TBE. At 18 months, micronized progesterone was added to induce menstrual cycles. Biochemical markers including sex hormones, inflammatory markers, liver enzymes, coagulation factors, and lipids were obtained at baseline and 6 month intervals. Differences in levels of treatment parameters between the groups were evaluated with one-way analysis of variance (ANOVA). The effect of progesterone on biochemical markers was evaluated with the paired t-test. Results Mean (±SE) estradiol levels at maximum estrogen dose (18 months) were higher in the TBE group (53 ± 19 pg/mL) compared to OCEE (14 ± 5 pg/mL) and OBE (12 ± 5 pg/mL) (p ≤ 0.01). The TBE and OBE groups had more effective feminization (100% Tanner 3 breast stage at 18 months). There were no statistical differences in other biochemical markers between treatment groups at 18 months or after the introduction of progesterone. Conclusions Treatment with transdermal 17β estradiol resulted in higher estradiol levels and more effective feminization

  7. Oral fluid cannabinoids in chronic cannabis smokers during oral Δ9-tetrahydrocannabinol therapy and smoked cannabis challenge

    PubMed Central

    Lee, Dayong; Vandrey, Ryan; Mendu, Damodara R.; Anizan, Sebastien; Milman, Garry; Murray, Jeannie A.; Barnes, Allan J.; Huestis, Marilyn A.

    2014-01-01

    BACKGROUND Oral Δ9-tetrahydrocannabinol (THC) is effective for attenuating cannabis withdrawal and may benefit treatment of cannabis use disorders. Oral fluid (OF) cannabinoid testing, increasing in forensic and workplace settings, could be valuable for monitoring during cannabis treatment. METHODS Eleven cannabis smokers resided on a closed research unit for 51 days, and received daily 0, 30, 60, and 120 mg oral THC in divided doses for 5 days. There was a 5-puff smoked cannabis challenge on the 5th day. Each medication session was separated by 9 days of ad libitum cannabis smoking. OF was collected the evening prior to and throughout oral THC sessions and analyzed by 2-dimensional GC-MS for THC, cannabidiol (CBD), cannabinol (CBN), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). RESULTS During all oral THC administrations, THC OF concentrations decreased to ≤78.2, 33.2, and 1.4 μg/L by 24, 48, and 72h, respectively. CBN also decreased over time with concentrations 10-fold lower than THC, with none detected beyond 69h. CBD and 11-OH-THC were rarely detected, only within 19 and 1.6h post smoking, respectively. THCCOOH OF concentrations were dose-dependent and increased over time during 120 mg THC dosing. After cannabis smoking, THC, CBN, and THCCOOH concentrations showed a significant dose-effect and decreased significantly over time. CONCLUSIONS Oral THC dosing significantly affected OF THCCOOH but minimally contributed to THC OF concentrations; prior ad libitum smoking was the primary source of THC, CBD and CBN. Higher cannabinoid concentrations following active oral THC administrations versus placebo suggest a compensatory effect of THC tolerance on smoking topography. PMID:23938457

  8. 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.

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

    PubMed

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

    2016-07-25

    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

  10. 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

  11. 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. PMID:26339804

  12. 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.

  13. 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

  14. Cancer stem cells - new and potentially important targets for the therapy of oral squamous cell carcinoma.

    PubMed

    Costea, D E; Tsinkalovsky, O; Vintermyr, O K; Johannessen, A C; Mackenzie, I C

    2006-09-01

    There is increasing evidence that the growth and spread of cancers is driven by a small subpopulation of cancer stem cells (CSCs) - the only cells that are capable of long-term self-renewal and generation of the phenotypically diverse tumour cell population. Current failure of cancer therapies may be due to their lesser effect on potentially quiescent CSCs which remain vital and retain their full capacity to repopulate the tumour. Treatment strategies for the elimination of cancer therefore need to consider the consequences of the presence of CSCs. However, the development of new CSC-targeted strategies is currently hindered by the lack of reliable markers for the identification of CSCs and the poor understanding of their behaviour and fate determinants. Recent studies of cell lines derived from oral squamous cell carcinoma (OSCC) indicate the presence of subpopulations of cells with phenotypic and behavioural characteristics corresponding to both normal epithelial stem cells and to cells capable of initiating tumours in vivo. The present review discusses the relevance to OSCC of current CSC concepts, the state of various methods for CSC identification, characterization and isolation (clonal functional assay, cell sorting based on surface markers or uptake of Hoechst dye), and possible new approaches to therapy.

  15. 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

  16. Basal-Supported Oral Therapy with Sitagliptin Counteracts Rebound Hyperglycemia Caused by GLP-1 Tachyphylaxis.

    PubMed

    Meguro, Shu; Kawai, Toshihide; Matsuhashi, Tomohiro; Sano, Motoaki; Fukuda, Keiichi; Itoh, Hiroshi; Suzuki, Yoshihiko

    2014-01-01

    Introduction. Treatment with a glucagon-like peptide 1 (GLP-1) analog fails in some patients due to rebound hyperglycemia caused by tachyphylaxis (GLP-1 tachyphylaxis). We investigated the efficacy of basal-supported oral therapy (BOT) with insulin glargine and sitagliptin for counteracting GLP-1 tachyphylaxis. Materials and Methods. The subjects were 12 men and 3 women aged 59.9 ± 10.0 years who had been treated with GLP-1 analogs. All of them had developed rebound hyperglycemia caused by GLP-1 tachyphylaxis. Their GLP-1 analog-based therapy was switched to BOT with insulin glargine plus sitagliptin and other medications. The primary outcomes were whether switching of therapy was associated with a change of hemoglobin A1c (HbA1c) and whether weight gain occurred. Results. Baseline HbA1c was 8.0 ± 0.9%. It decreased to 7.3 ± 0.9% at 3 months after switching (P < 0.01) and to 7.2 ± 0.9% at 4 months (P < 0.05). Weight gain was 1.1 kg after 1 month (P < 0.01) and 2.3 kg after 5 months (P < 0.01). Conclusion. Switching to BOT with insulin glargine and sitagliptin improved glycemic control. The significant decrease of HbA1c demonstrated that this combination can counteract deterioration of glycemic control due to rebound hyperglycemia secondary to GLP-1 tachyphylaxis. However, weight gain remains a problem.

  17. 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

  18. Monitoring of ketogenic diet for carnitine metabolites by subcutaneous microdialysis.

    PubMed

    Hack, Alexandra; Busch, Verena; Pascher, Bettina; Busch, Raymonde; Bieger, Iris; Gempel, Klaus; Baumeister, Friedrich A M

    2006-07-01

    The ketogenic diet (KD) provides ketones from the degradation of free fatty acids for energy metabolism. It is a therapeutic option for pharmacoresistant epilepsies. Carnitine is the carrier molecule that transports fatty acids across the mitochondrial membrane for degradation into ketones. The integrity of this transport system is a prerequisite for an adequate ketogenic response. For monitoring of tissue metabolism with KD, we used the sampling method of s.c. microdialysis (MD), which permits minimally invasive, frequent, and extensive metabolic monitoring independent of blood tests. By using this new method, we monitored changes in carnitine metabolism induced by KD, particularly in free carnitine (C0), acetylcarnitine (C2), and hydroxybutyrylcarnitine (C4OH). Correlation of microdialysate and tissue concentrations for carnitines in vitro was about 85%. Carnitine metabolism was monitored in seven children started on a KD for pharmacoresistant epilepsy after a conventional initial fasting period. Detected metabolic changes consisted of a slight decrease in s.c. C0 and a marked increase in C2/CO and C4OH/CO levels. The levels of s.c. C4OH strongly correlate with beta-hydroxybutyrate (beta-OHB) levels in plasma providing an additional parameter for the carnitine reserve of the body and reflect an optimal ketogenic energy supply. Subcutaneous MD allows close and extensive monitoring of metabolism with a KD.

  19. Survey of carnitine content of human semen using a semiquantitative auxanographic method: decreased semen total carnitine concentration in patients with azoospermia or severe oligozoospermia.

    PubMed

    Soffer, Y; Shalev, D P; Weissenberg, R; Orenstein, H; Nebel, L; Lewin, L M

    1981-01-01

    A microbiological method, using the carnitine-requiring yeast, Torulopsis bovina ATCC 26014, was developed to identify samples of human semen which contained low levels (less than 250 micron M) of total carnitine. Of 399 semen samples from a male infertility clinic which were tested, 30 (7.5%) were low in carnitine. Of these, 14 were azoospermic and 16 were severely oligozoospermic. Some azoospermic samples (19 = 58%) and severely oligozoospermic samples (51 = 79%) did not give evidence of low carnitine concentrations. These results indicate that decreased total carnitine concentration in semen occurs in certain classes of azoospermic and severely oligozoospermic patients.

  20. [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.

  1. 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

  2. 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. PMID:21830351

  3. Melatonin and L-carnitin improves endothelial disfunction and oxidative stress in Type 2 diabetic rats

    PubMed Central

    Salmanoglu, Derya Selcen; Gurpinar, Tugba; Vural, Kamil; Ekerbicer, Nuran; Darıverenli, Ertan; Var, Ahmet

    2016-01-01

    Vascular dysfunction is thought to play a major role in the development of diabetic cardiovascular disease. The roles of endothelial dysfunction, oxidative stress, and dyslipidemia will be considered. Melatonin as well as L-carnitine were shown to possess strong antioxidant properties. Diabetes induced with high fat diet (for 8 weeks) and multipl low doses intraperitoneal injection of STZ (twice, 30 mg/kg/d i.p). The diabetic animals were randomly assigned to one of the experimental groups as follows: Control group (C), high fat diet (HFD), STZ-induced diabetic group (HFD+STZ) , HFD+STZ diabetic group received melatonin (10 mg/kg/d i.p), HFD+STZ diabetic group received L-carnitine (0.6 g/kg/d i.p), and HFD+STZ diabetic group received glibenclamide (5 mg/kg/d, oral). The serum fasting blood glucose, insulin, total cholesterol, HDL- cholesterol, LDL-cholesterol, triglyceride and malondialdehyde (MDA) levels were tested. Acetylcholine induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. Also, glutathione peroxidase (GPx), superoxide dismutase (SOD) and nitric oxide (NO) levels activities were determined in rat liver. According to our results melatonin and L-carnitine treatment decreased fasting blood glucose, total cholesterol, and LDL levels. MDA levels significantly decreased with the melatonin treatment whereas SOD levels were not significantly changed between the groups. The results suggest that especially melatonin restores the vascular responses and endothelial dysfunction in diabetes. PMID:26803481

  4. Oral administration of lactulose: a novel therapy for acute carbon monoxide poisoning via increasing intestinal hydrogen production.

    PubMed

    Fan, Dan-Feng; Hu, Hui-Jun; Sun, Xue-Jun; Meng, Xiang-En; Zhang, Yu; Pan, Shu-Yi

    2016-01-01

    It has been known that the pathophysiology of carbon monoxide (CO) poisoning is related to hypoxia, the increased production of reactive oxygen species (ROS) and oxidative stress. Studies have shown that the novel, safe and effective free radical scavenger, hydrogen, has neuroprotective effects in both acute CO poisoning and delayed neuropsychological sequelae in CO poisoning. Orally administered lactulose, which may be used by some intestinal bacteria as a food source to produce endogenous hydrogen, can ameliorate oxidative stress. Based on the available findings, we hypothesize that oral administration of lactulose may be a novel therapy for acute CO poisoning via increasing intestinal hydrogen production.

  5. 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.

  6. Implementation of a Training Program for Low Literacy Promotoras in Oral Rehydration Therapy

    PubMed Central

    Amerson, Roxanne; Hall-Clifford, Rachel; Thompson, Beti; Comninellas, Nicholas

    2015-01-01

    Objective The purpose of this study was to ascertain the effectiveness of a culturally appropriate promotora training program related to oral rehydration therapy and diarrheal management. Factors that influenced the development, implementation, and evaluation of the program provided to low-literacy women in Guatemala are explored. Design and Sample Promotora training was conducted with 15 Mayan women from a rural community in the highlands of Guatemala. Women were selected by leaders of the community to participate in the program. Measures Quantitative data were collected and analyzed to determine descriptive statistics and reliability coefficients for the pretests and posttests. A non-parametric Wilcoxon test for paired-samples was conducted. The qualitative data from the program evaluations were analyzed for themes. Results Mean scores increased from 41.73 (sd = 9.65) to 70.33 (sd = 21.29) on the pretest and posttest. The Cronbach’s alpha was 0.54 on the pretest with 0.65 on the posttest. The Wilcoxon test demonstrated a significant difference between the pretest and posttest scores (Z = 3.040, p < .05). Conclusions Extremely low literacy levels played a major role in the ability of the women to successfully complete the requirements of the training program. The curriculum demonstrated effectiveness, but will benefit from replication with a larger sample. PMID:25154975

  7. 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. PMID:26892241

  8. 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

  9. A Behavior Analysis of the Promotion of Oral Rehydration Therapy (ORT) in Guatemala.

    PubMed

    Elder, J P; Pradesaba, M E; Pineda, O P; Enge, K I; Graeff, J A; Urban, D; Romero, J

    1988-01-01

    The present report presents the results and preliminary recommendations of a behavior analysis study of an oral rehydration therapy (ORT) promotion in four localities in San Marcos, Guatemala. In this study, we used behavioral observation techniques to look at one-to-one communication and health education efforts in health clinics as well as to evaluate the effectiveness of these health education efforts by observing mothers' behavioral skills in their own homes. Subsequently, we also observed canalizatión (outreach) strategies to see whether we could learn more from these health workers' activities, and conducted "behavioral focus group" research with teams of health workers to determine how best to promote effective health education activities to other health workers. Results of our study indicate that health workers already spent a substantial amount of time doing health education and primary prevention, and were fairly effective at doing so. Their communication, however, tended to be relatively unilateral and failed to involve some of the more progressive aspects of behavioral skills training.

  10. [The role of bleomycin combination in radiation therapy of squamous cell carcinoma of the oral cavity].

    PubMed

    Masaki, N

    1986-04-01

    In an effort to improve tumor control by radiation therapy, a treatment regimen consisting of concurrent combination of bleomycin (90 mg/3 weeks) and radiation (30 Gy/3 weeks) was applied. Between 1972 and 1981, 287 patients with squamous cell carcinoma in the oral cavity were subjected to this bleomycin-radiation combination regimen. All except 4 patients experienced marked response after treatment using the bleomycin-radiation combination alone. One hundred thirty-four patients (47%) obtained CR and 149 (53%) PR. Higher CR rates were obtained in patients with carcinoma of the lower gum (62%), of the upper gum (68%), and of the cheek mucosa (43%), compared to patients with carcinoma of the floor of the mouth (21%), and of the tongue (15%). In each of the tumor sites, small lesions (T1, T2) obtained higher CR rates, compared with large lesions (T3, T4). Of the 134 patients who experienced CR, 83 were observed without any further treatment after bleomycin-radiation combination alone. Local recurrence-free rates of these patients were 72% for T1, T2 lesions and 48% for T3, T4 lesions. Local control rates were increased to 85% and 78%, respectively, with successful salvage treatment involving surgery or interstitial radiotherapy for post-irradiation failures. PMID:2425746

  11. 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.

  12. 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.

  13. Private Sector Provision of Oral Rehydration Therapy for Child Diarrhea in Sub-Saharan Africa

    PubMed Central

    Sood, Neeraj; Wagner, Zachary

    2014-01-01

    Although diarrheal mortality is cheaply preventable with oral rehydration therapy (ORT), over 700,000 children die of diarrhea annually and many health providers fail to treat diarrheal cases with ORT. Provision of ORT may differ between for-profit and public providers. This study used Demographic and Health Survey data from 19,059 children across 29 countries in sub-Saharan Africa from 2003 to 2011 to measure differences in child diarrhea treatment between private for-profit and public health providers. Differences in treatment provision were estimated using probit regression models controlling for key confounders. For-profit providers were 15% points less likely to provide ORT (95% confidence interval [CI] 13–17) than public providers and 12% points more likely to provide other treatments (95% CI 10–15). These disparities in ORT provision were more pronounced for poorer children in rural areas. As private healthcare in sub-Saharan Africa continues to expand, interventions to increase private sector provision of ORT should be explored. PMID:24732456

  14. 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.

  15. Examining the Mechanism of Action of a New Device Using Oral Pressure Therapy for the Treatment of Obstructive Sleep Apnea

    PubMed Central

    Schwab, Richard J.; Kim, C.; Siegel, Lawrence; Keenan, B.T.; Black, Jed; Farid-Moayer, Mehran; Podmore, Jonathan; Vaska, Matt

    2014-01-01

    Study Objectives: The objective of this study was to explore the mechanism of action of the oral pressure therapy (OPT) device, a new treatment for sleep apnea. Design: Case series. Setting: Academic medical center. Patients: Fifteen subjects with sleep apnea who had been successfully treated (responders) with the OPT device and 4 subjects who were not successfully treated (non-responders) with the OPT device. Interventions: All subjects underwent a MRI (without the device, with the device in place without vacuum and with the device in place with vacuum) to examine the biomechanical changes associated with the OPT device. Measurements and Results: Oral pressure therapy significantly (P = 0.002) increased the size of the retropalatal airway in both the lateral and anterior-posterior dimensions by moving the soft palate anteriorly and superiorly and the anterior-superior segment of the tongue forward, toward the teeth. The percentage and absolute increase in the cross-sectional area of the retropalatal region, the superior movement of the soft palate, and the anterior displacement of the tongue were significantly greater in the responders than in the non-responders. In responders, there were significant increases in the mean (P = 0.002), maximum (P = 0.0002), and minimum (P = 0.04) cross-sectional areas of the retropalatal region with the OPT device. However, in the retroglossal region, airway caliber decreased with the OPT device. Conclusions: In those who responded to oral pressure therapy, it increased airway caliber in the retropalatal region by moving the soft palate anteriorly and superiorly and the anterior-superior segment of the tongue forward. Citation: Schwab RJ, Kim C, Siegel L, Keenan BT, Black J, Farid-Moayer M, Podmore J, Vaska M. Examining the mechanism of action of a new device using oral pressure therapy for the treatment of obstructive sleep apnea. SLEEP 2014;37(7):1237-1247. PMID:25061252

  16. Development of oral agent in the treatment of multiple sclerosis: how the first available oral therapy, fingolimod will change therapeutic paradigm approach

    PubMed Central

    Gasperini, Claudio; Ruggieri, Serena

    2012-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. At present, there are five licensed first-line disease-modifying drugs and two second-line treatments in MS. Currently available MS therapies have shown significant efficacy throughout many trials, but they produce different side-effect profiles in patients. Since they are well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Thus, there is an important need for the development of new therapeutic strategies. Several oral compounds are in late-stage development for treating MS. Fingolimod (FTY720; Novartis, Basel, Switzerland) is an oral sphingosine-1-phosphase receptor modulator which has demonstrated superior efficacy compared with placebo and interferon β-1a in Phase III studies and has been approved in the treatment of MS. We summarily review the oral compounds in study, focusing on the recent development, approval and the clinical experience with FTY720. PMID:22888218

  17. Effects of humic acid-metal complexes on hepatic carnitine palmitoyltransferase, carnitine acetyltransferase and catalase activities

    SciTech Connect

    Fungjou Lu; Youngshin Chen . Dept. of Biochemistry); Tienshang Huang . Dept. of Medicine)

    1994-03-01

    A significant increase in activities of hepatic carnitine palmitoyltransferase and carnitine acetyltransferase was observed in male Balb/c mice intraperitoneally injected for 40 d with 0.125 mg/0.1 ml/d humic acid-metal complexes. Among these complexes, the humic acid-As complex was relatively effective, whereas humic acid-25 metal complex was more effective, and humic acid-26 metal complex was most effective. However, humic acid or metal mixtures, or metal such as As alone, was not effective. Humic acid-metal complexes also significantly decreased hepatic catalase activity. A marked decrease of 60-kDa polypeptide in liver cytoplasm was also observed on SDS-polyacrylamide gel electrophoresis after the mice had been injected with the complexes. Morphological analysis of a histopathological biopsy of such treated mice revealed several changes in hepatocytes, including focal necrosis and cell infiltration, mild fatty changes, reactive nuclei, and hypertrophy. Humic acid-metal complexes affect activities of metabolic enzymes of fatty acids, and this results in accumulation of hydrogen peroxide and increase of the lipid peroxidation. The products of lipid peroxidation may be responsible for liver damage and possible carcinogenesis. Previous studies in this laboratory had shown that humic acid-metal complex altered the coagulation system and that humic acid, per se, caused vasculopathy. Therefore, humic acid-metal complexes may be main causal factors of not only so-called blackfoot disease, but also the liver cancer prevailing on the southwestern coast of Taiwan.

  18. Doxazosin oral intake therapy to relieve stent - related urinary symptoms and pain: a prospective, randomized, controlled study

    PubMed Central

    Zhang, Long; Li, Junping; Pan, Minjie; Han, Weiwei; Liu, Shucheng; Xiao, Yajun

    2016-01-01

    ABSTRACT Objective: To assess the impact of Doxazosin Oral Intake Therapy on urinary symptoms and pain in patients with indwelling ureteral stents Patients and Methods: A total of 239 patients with ureteral stone-related hydronephrosis who underwent a double-J stent insertion after ureteroscopic lithotripsy were enrolled. Patients were randomized to receive doxazosin cotrolled release 4 mg once daily for 4 weeks or matching placebo. Patients completed the brief-form Chinese version Ureteric Stent Symptom Questionnaire (USSQ) and quality of life (QoL) score 2 weeks and 4 weeks after stent placement and 4 weeks after stent withdrawal. The analgesic use was also recorded during the stenting period. Results: Patients in Doxazosin Oral Intake Therapy group, in the first 2 weeks and second 2 weeks with the stent in situ, expressed significant lower daytime frequency (p=0.028 and p=0.038), nocturia (p=0.021 and p=0.008) and urgency (p=0.012 and p=0.014), respectively. Similarly, flank pain score, QoL score and analgesic use were also significant less in the stenting period. There was no significant difference in scores of urinary symptoms, pain and QoL during the post-stent period between two cohorts. Conclusions: Doxazosin Oral Intake Therapy reduced stent-related urinary symptoms, pain and the negative impact on QoL. PMID:27564283

  19. 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

  20. 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

  1. [Efficacy of oral drug Thrombovasim® in therapy of lower extremity deep vein thromboses].

    PubMed

    Mishenina, S V; Madonov, P G; Kinsht, D N; Émedova, T A; Zotov, S P; Ufimtsev, M S; Leont'ev, S G

    2016-01-01

    Within the framework of the multicenter randomized placebo-controlled double-blind clinical trial "VETTER-1" the authors carried out assessment of therapeutic efficacy and safety of oral drug Thrombovasim® possessing a thrombolytic effect in comprehensive treatment of lower-extremity deep vein thrombosis (LEDVT). The clinical study comprised a total of 154 patients. All patients received standard therapy accepted in LEDVT. The patients were subdivided into 4 groups. Patients from the three study groups received Thrombovasim® at a daily dose of 1,600, 3,200, and 4,800 IU. The control group patients were given placebo. Efficacy was assessed by the results of ultrasound duplex scanning first performed before treatment commenced and then after it terminated. The relative frequency of positive dynamics according to the findings of instrumental methods of study in patients taking Thrombovasim® amounted to 0.728 and in the group of patients receiving placebo to 0.585, p=0.0031. Comparing the degree of blood flow normalization in the zone of the compromised blood flow revealed a pronounced dose-dependent effect: in patients taking the drug at a daily dose of 1,600 IU, the relative frequency of positive dynamics amounted to 0.707 corresponding to an increase in therapeutic efficacy by 21%, for a dose of 3,200 IU these parameters amounted to 0.0257 and 24% and for 4,800 IU - 0.747 and 28%, respectively. In patients taking Thrombovasim® there were no cases of negative dynamics observed. Of the patients taking Thrombovasim®, none developed undesirable or severe adverse events. Inclusion of Thrombovasim® into the composition of comprehensive therapy for LEDVT increases efficacy of treatment at the expense of a spontaneous thrombolytic effect. The most effective dose amounted to 4,800 IU daily. Thrombovasim® turned out to be an efficient and safe agent in treatment of venous thromboses. PMID:27626255

  2. 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

  3. 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. PMID:12285815

  4. Prevalence of carnitine depletion in critically ill patients with undernutrition.

    PubMed

    Wennberg, A; Hyltander, A; Sjöberg, A; Arfvidsson, B; Sandström, R; Wickström, I; Lundholm, K

    1992-02-01

    The aim of this study was to evaluate to what extent secondary carnitine deficiency may exist based on the prevalence of subnormal carnitine status in patients with critical illness and abnormal nutritional state. Healthy control patients (n = 12) were investigated and compared with patients with possible secondary carnitine deficiency, ie, patients with overt severe protein-energy malnutrition (PEM, n = 28), postoperative long-term (greater than 14 days) parenteral glucose feeding (250 g glucose/d, n = 7), severe liver disease (n = 10), renal insufficiency (n = 7), and sustained septicemia with increased metabolic rate (n = 8). Nutritional status, energy expenditure, creatinine excretion, and blood biochemical tests were measured in relationship to free and total carnitine concentrations in plasma and skeletal muscle tissue, as well as urinary excretion of free and total carnitine. The overall mortality rate was 48% within 30 days of the investigation in study patients with the highest mortality in liver disease (90%). The hospitalization range was 14 to 129 days in study patients. Most study patients had lost weight (4% to 19%) and had abnormal body composition. Patients with liver disease, septicemia, renal insufficiency, and those on long-term glucose feeding had significantly higher than predicted metabolic rate (+25% +/- 3%), while patients with severe malnutrition had decreased metabolic rate compared with controls. Patients with liver disease had increased plasma concentrations of free (96 +/- 16 mumol/L) and total (144 +/- 27 mumol/L) carnitine compared with controls (45 +/- 3, 58 +/- 7 mumol/L, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1736038

  5. Delivery of (10)boron to oral squamous cell carcinoma using boronophenylalanine and borocaptate sodium for boron neutron capture therapy.

    PubMed

    Obayashi, Shigeki; Kato, Itsuro; Ono, Koji; Masunaga, Shin-Ichiro; Suzuki, Minoru; Nagata, Kenji; Sakurai, Yoshinori; Yura, Yoshiaki

    2004-05-01

    Boron neutron capture therapy (BNCT) is a unique radiation therapy in which boron compounds are trapped into tumor cells. To determine the biodistribution of boronophenylalanine (BPA) in nude mice carrying oral squamous cell carcinoma (SCC), BPA was administered at a dose of 250 mg/kg body weight intraperitoneally. Two hours later, (10)B concentration in the tumor was 15.96 ppm and tumor/blood, tumor/tongue, tumor/skin and tumor/bone (10)B concentration ratios were 6.44, 4.19, 4.68 and 4.56, respectively. Two hours after the administration of borocaptate sodium (BSH) at a dose of 75 mg/kg body weight, (10)B concentration in the tumor was 3.61 ppm, and tumor/blood, tumor/tongue, tumor/skin and tumor/bone (10)B concentration ratios were 0.77, 1.05, 0.60 and 0.59, respectively. When cultured oral SCC cells were incubated with BPA or BSH for 2 h and then exposed to thermal neutrons, the proportion of survival cells that were capable of forming cell colonies decreased exponentially, depending on (10)B concentration. BPA-mediated BNCT was more efficient than BSH-mediated BNCT. Addition of boron compounds in the cell suspension during neutron irradiation enhanced the cell-killing effect of the neutrons. These results indicate that BPA is more selectively incorporated into human oral SCC as compared with normal oral tissues, and that both extra- and intra-cellular BPA contribute to the cell-killing effect of BNCT. BPA may be a useful boron carrier for BNCT in the treatment of advanced oral SCC.

  6. Topical Tacrolimus with Custom Trays in the Treatment of Severe Oral cGVHD Refractory to a Potent Topical Steroid Therapy: A Case Report

    PubMed Central

    Brown, Ronald S.; Edwards, Dean; Walsh-Chocolaad, Tracey; Childs, Richard W.

    2012-01-01

    Background The authors present a case demonstrating the success of topical tacrolimus (TAC) therapy with custom trays in the treatment of oral chronic graft versus host disease (cGVHD). The 41 year-old male patient initially responded to topical steroid therapy (clobetasol propionate 0.05% ointment) applied both topically and with flexible carrier trays, but later became refractory to this potent topical agent. Topical TAC therapy with flexible carrier trays and systemic prednisone therapy was initiated. Results The patient responded favorably with the change to topical TAC therapy with custom trays (and oral prednisone). His oral cGVHD lesions resolved within a period of four weeks. The improvement has remained stable at 14 month follow-up. Clinical Implications This is the first case reported with regard to the successful resolution of steroid recalcitrant cGVHD successfully treated with topical TAC with custom trays. PMID:23102802

  7. 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.

  8. Direct effects of Facio-Oral Tract Therapy® on swallowing frequency of non-tracheotomised patients with acute neurogenic dysphagia

    PubMed Central

    Lerch, Annekatrin; Cataldo, Marilena; Kerz, Thomas

    2015-01-01

    Objectives: The aim of this study was to investigate the direct effect of Facio-Oral Tract Therapy® on swallowing frequency of non-tracheotomised patients with acute neurogenic dysphagia. Methods: Within a pre-, post-/during and follow-up study design, 19 non-tracheotomised dysphagic patients were included consecutively and treated according to three specific preselected Facio-Oral Tract Therapy stimulation techniques. Results: The primary outcome was the direct effect of the three different Facio-Oral Tract Therapy stimulation techniques on the number of swallows. We found a significant effect of Facio-Oral Tract Therapy on swallowing frequency as compared to baseline with an increase by 65.63% and medium effect size of D = 0.62. No significant difference could be demonstrated when comparing baseline to follow-up. Conclusion: For the first time, this positive therapy effect could be demonstrated on a population of non-tracheotomised patients. Facio-Oral Tract Therapy seems to be an appropriate means for improving effectiveness and safety of swallowing. Since improvement was not long lasting, it appears to be reasonable to apply therapy frequently during the day with the plausible result of minimising the amount of aspirated saliva and thereby reducing the risk of aspiration pneumonia. Further studies may consider choosing a randomised controlled trial design to demonstrate that change in swallow frequency is related to the target intervention only. PMID:26770778

  9. 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.

  10. Characterization of the endogenous carnitine transport and expression of a rat renal Na(+)-dependent carnitine transport system in Xenopus laevis oocytes.

    PubMed Central

    Berardi, S; Hagenbuch, B; Carafoli, E; Krähenbühl, S

    1995-01-01

    L-Carnitine transport was characterized in Xenopus laevis oocytes before and after injection of mRNA isolated from rat renal cortex. Non-injected oocytes revealed endogenous Na(+)-dependent transport of L-carnitine. After injection of 15 ng of rat kidney mRNA, the Na(+)-dependent L-carnitine transport increased 2-3-fold, reaching maximal activity after 5-6 days. The expressed carnitine transport was maximal at pH 7.5, whereas the endogenous transport showed no clear maximum between pH 6.0 and 8.5. Kinetic analysis revealed apparent Km values for L-carnitine of 66 microM for the endogenous and 149 microM for the expressed transport. Trimethyl-lysine and D-carnitine inhibited both the endogenous and the expressed transport. In contrast, L-acetylcarnitine, L-isovalerylcarnitine, L-palmitoylcarnitine and butyrobetaine inhibited predominantly the expressed transport, whereas glycinebetaine had no inhibitory effect on either transport system. Size-fractionated rat renal-cortex mRNA (median size 2 kb) induced a 3-fold higher L-carnitine transport than did unfractionated mRNA. These studies demonstrate that Xenopus laevis oocytes exhibit Na(+)-dependent L-carnitine transport and provide the basis for expression-cloning of a rat renal Na(+)-dependent L-carnitine transport system. PMID:7626001

  11. 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.

  12. 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.

  13. Crystal Structure of Rat Carnitine Palmitoyltransferase II (CPT-II)

    SciTech Connect

    Hsiao,Y.; Jogl, G.; Esser, V.; Tong, L.

    2006-01-01

    Carnitine palmitoyltransferase II (CPT-II) has a crucial role in the {beta}-oxidation of long-chain fatty acids in mitochondria. We report here the crystal structure of rat CPT-II at 1.9 Angstroms resolution. The overall structure shares strong similarity to those of short- and medium-chain carnitine acyltransferases, although detailed structural differences in the active site region have a significant impact on the substrate selectivity of CPT-II. Three aliphatic chains, possibly from a detergent that is used for the crystallization, were found in the structure. Two of them are located in the carnitine and CoA binding sites, respectively. The third aliphatic chain may mimic the long-chain acyl group in the substrate of CPT-II. The binding site for this aliphatic chain does not exist in the short- and medium-chain carnitine acyltransferases, due to conformational differences among the enzymes. A unique insert in CPT-II is positioned on the surface of the enzyme, with a highly hydrophobic surface. It is likely that this surface patch mediates the association of CPT-II with the inner membrane of the mitochondria.

  14. 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.

  15. Point-of-care testing for assessment of adequacy of oral antiplatelet therapy in patients with cardiovascular disease.

    PubMed

    Sobieraj-Teague, Magdalena; Eikelboom, John W

    2010-05-01

    Studies with recently introduced point-of-care (POC) platelet function tests have shown that individuals are variably responsive to aspirin and clopidogrel therapy, and that hyporesponsiveness to antiplatelet therapy is associated with an increased risk of cardiovascular events. However, the currently available POC tests have undergone only limited clinical evaluation and clinicians are uncertain about the best POC test, the optimal cut-off point to define hyporesponsiveness in different patient populations and clinical settings, the appropriate management of patients demonstrating hyporesponsiveness and the cost effectiveness of adjusting treatment on the basis of the results of POC platelet function testing. Several large randomized controlled trials currently underway are examining whether adjusting antiplatelet therapy on the basis of a POC test result can improve patient-important outcomes. Until these issues are resolved, POC testing to monitor antiplatelet therapy will largely remain a research tool and patients should continue to receive oral antiplatelet therapy without routine monitoring at doses that have been demonstrated to be effective in randomized controlled trials.

  16. The numerous microbial species in oral biofilms: how could antibacterial therapy be effective?

    PubMed

    ten Cate, J M; Zaura, E

    2012-09-01

    Hundreds of bacterial species inhabit the oral cavity. Many of these have never been cultivated and can be assessed only with DNA-based techniques. This new understanding has changed the paradigm of the etiology of oral disease from that associated with 'traditional pathogens' as being primarily responsible for all diseases. Increasingly, associations between oral bacteria and systemic diseases are being reported. The emergence of antibiotic resistance is alarming and calls for in-depth studies of biofilms, bacterial physiology, and a body-wide approach to infectious diseases. We propose that the borderline between commensal bacteria and pathogens is no longer discrete. In a field of science where so many of the established paradigms are being undermined, a thorough analysis of threats and opportunities is required. This article addresses some of the questions that can be raised and serves to identify research opportunities and needs to leverage the prevention of oral diseases through novel antimicrobial strategies.

  17. Oral Chronic Graft-versus-Host Disease: Current Pathogenesis, Therapy, and Research

    PubMed Central

    Mays, JW; Fassil, H; Edwards, DA; Pavletic, SZ; Bassim, CW

    2012-01-01

    Optimal management of complex autoimmune diseases requires a multidisciplinary medical team including dentists to care for lesions of the oral cavity. In this review, we discuss the presentation, prevalence, diagnosis and treatment of oral manifestations in chronic Graft-versus-Host Disease (cGVHD) which is a major late complication in patients treated by allogeneic hematopoietic stem cell transplantation. We assess current general knowledge of systemic and oral cGVHD, and present general treatment recommendations based on literature review and our clinical experience. Additionally, we review areas where the understanding of oral cGVHD could be improved by further research, and address tools with which to accomplish the long-term goal of providing better health and quality-of-life to patients with cGVHD. PMID:23107104

  18. Phase II Trial of Simple Oral Therapy with Capecitabine and Cyclophosphamide in Patients with Metastatic Breast Cancer: SWOG S0430

    PubMed Central

    Barlow, William E.; Albain, Kathy S.; Chew, Helen K.; Wade, James L.; Lanier, Keith S.; Lew, Danika L.; Hayes, Daniel F.; Gralow, Julie R.; Livingston, Robert B.; Hortobagyi, Gabriel N.

    2012-01-01

    Background. Interest in oral agents for the treatment of metastatic breast cancer (MBC) has increased because many patients prefer oral to i.v. regimens. We evaluated a simple oral combination of capecitabine with cyclophosphamide (CPA) for MBC. Methods. The trial was designed to determine whether or not combination therapy would achieve a 42% response rate (RR) using the Response Evaluation Criteria in Solid Tumors (RECIST) in MBC. Patients with two or fewer prior chemotherapy regimens for MBC were eligible. Those with estrogen receptor–positive MBC had to have progressed on endocrine therapy. Patients had measurable disease or elevated mucin (MUC)-1 antigen and received CPA, 100 mg daily on days 1–14, and capecitabine, 1,500 mg twice daily on days 8–21, in 21-day cycles. Results. In 96 eligible patients, the median progression-free survival (PFS) interval was 5.9 months (95% confidence interval [CI], 3.7–8.0 months) and median overall survival (OS) time was 18.8 months (95% CI, 13.1–22.0 months). The RR was 36% (95% CI, 26%–48%) in 80 patients with measurable disease. The MUC-1 antigen RR was 33% (95% CI, 20%–48%), occurring in 15 of 46 patients with elevated MUC-1 antigen. Toxicity was mild, with no treatment-related deaths. Conclusions. PFS, OS, and RR outcomes with capecitabine plus CPA compare favorably with those of capecitabine monotherapy and combination therapy with bevacizumab, sorafenib, or ixabepilone. The addition of these other agents to capecitabine does not improve OS time in MBC patients, and this single-arm study does not suggest that the addition of CPA to capecitabine has this potential in an unselected MBC population. When OS prolongation is the goal, clinicians should choose single-agent capecitabine. PMID:22267853

  19. Requirements for Carnitine Shuttle-Mediated Translocation of Mitochondrial Acetyl Moieties to the Yeast Cytosol

    PubMed Central

    van Rossum, Harmen M.; Kozak, Barbara U.; Niemeijer, Matthijs S.; Dykstra, James C.; Luttik, Marijke A. H.; van Maris, Antonius J. A.

    2016-01-01

    ABSTRACT In many eukaryotes, the carnitine shuttle plays a key role in intracellular transport of acyl moieties. Fatty acid-grown Saccharomyces cerevisiae cells employ this shuttle to translocate acetyl units into their mitochondria. Mechanistically, the carnitine shuttle should be reversible, but previous studies indicate that carnitine shuttle-mediated export of mitochondrial acetyl units to the yeast cytosol does not occur in vivo. This apparent unidirectionality was investigated by constitutively expressing genes encoding carnitine shuttle-related proteins in an engineered S. cerevisiae strain, in which cytosolic acetyl coenzyme A (acetyl-CoA) synthesis could be switched off by omitting lipoic acid from growth media. Laboratory evolution of this strain yielded mutants whose growth on glucose, in the absence of lipoic acid, was l-carnitine dependent, indicating that in vivo export of mitochondrial acetyl units to the cytosol occurred via the carnitine shuttle. The mitochondrial pyruvate dehydrogenase complex was identified as the predominant source of acetyl-CoA in the evolved strains. Whole-genome sequencing revealed mutations in genes involved in mitochondrial fatty acid synthesis (MCT1), nuclear-mitochondrial communication (RTG2), and encoding a carnitine acetyltransferase (YAT2). Introduction of these mutations into the nonevolved parental strain enabled l-carnitine-dependent growth on glucose. This study indicates intramitochondrial acetyl-CoA concentration and constitutive expression of carnitine shuttle genes as key factors in enabling in vivo export of mitochondrial acetyl units via the carnitine shuttle. PMID:27143389

  20. Oral Cancer

    MedlinePlus

    ... swallowing A lump in your neck An earache Oral cancer treatments may include surgery, radiation therapy or chemotherapy. Some patients have a combination of treatments. NIH: National Cancer Institute

  1. Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route

    PubMed Central

    Sharabi, Amir; Cohen, Eytan; Sulkes, Jaqueline; Garty, Moshe

    2003-01-01

    Aims To compare the efficacy of sublingual and oral administration of 500 µg of cobalamin in subjects with cobalamin deficiency. Materials and results Thirty subjects with low serum concentrations of cobalamin participated in the study. Subjects were randomly allocated to receive one tablet daily of 500 µg cobalamin sublingually or orally, or two tablets daily of a vitamin B complex. Serum cobalamin concentrations before treatment were 94 ± 30 pmol l−1, 108 ± 17 pmol l−1 and 98 ± 14 pmol l−1 in the sublingual B12, oral B12 and oral B-complex groups, respectively. After 4 weeks, concentrations rose to 288 ± 74 pmol l−1, 286 ± 87 pmol l−1 and 293 ± 78 pmol l−1, respectively. The increase in each group across time was statistically significant (P = 0.0001, differences [95% confidence intervals] 194.2 (114.5, 273.9), 178.3 (104.2, 252.4), and 195.1 (135.0, 255.2) pmol l−1, respectively). There was no significant difference in concentrations between the treatment groups. Conclusion A dose of 500 µg of cobalamin given either sublingually or orally is effective in correcting cobalamin deficiency. PMID:14616423

  2. Expression of oral cytokines in HIV-infected subjects with long-term use of antiretroviral therapy

    PubMed Central

    Nittayananta, Wipawee; Amornthatree, Korntip; Kemapunmanus, Marisa; Talungchit, Sineepat; Sriplung, Hutcha

    2013-01-01

    Objectives The objectives of this study were to determine 1) the expression of oral pro-inflammatory cytokines in HIV-infected subjects compared with non-HIV individuals, 2) the cytokine expression in the subjects with antiretroviral therapy (ART) compared with those without ART, and 3) factors associated with the expression of the cytokines. Materials and methods Oral examination was performed and saliva samples were collected and analyzed for the expression of pro-inflammatory cytokines using ELISA. Logistic regression analysis was performed to determine the association between HIV/ART status and the cytokine expression. Results One hundred and fifty-seven HIV-infected subjects with and without ART, and 50 non-HIV individuals were enrolled. TNF-α and IL-6 in saliva were significantly decreased, while IL-8 was significantly increased in HIV infection (p< 0.05). Changes in the expression of IL-8 was also observed between HIV-infected subjects who were and were not on ART (p< 0.05). Duration of HIV infection and smoking were significantly associated with the expression of pro-inflammatory cytokines in saliva (p< 0.05). Conclusion Oral innate immunity is affected by HIV infection and use of ART. IL-8 may be the useful biomarker to identify subjects at risk of infection and malignant transformation due to HIV infection and long-term use of ART. PMID:23718561

  3. 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

  4. 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.

  5. Artemether-lumefantrine nanostructured lipid carriers for oral malaria therapy: Enhanced efficacy at reduced dose and dosing frequency.

    PubMed

    Prabhu, Priyanka; Suryavanshi, Shital; Pathak, Sulabha; Sharma, Shobhona; Patravale, Vandana

    2016-09-10

    Artemether-lumefantrine (ARM-LFN) is a World Health Organization (WHO) approved fixed-dose combination having low solubility and poor oral bioavailability. Nanostructured lipid carriers (NLC) were developed to enhance the oral efficacy of this combination using the microemulsion template technique. They were characterized for drug content, entrapment efficiency, size distribution, in vitro release, antimalarial efficacy, and toxicity. The NLC showed sustained drug release. The recommended adult therapeutic dose is 80mg ARM and 480mg LFN (4 tablets) twice a day, which amounts to 160mg ARM and 960mg LFN daily. ARM-LFN NLC given once a day at 1/5 of therapeutic dose (16mg ARM and 96mg LFN) showed complete parasite clearance and 100% survival in Plasmodium berghei-infected mice. 33% of the mice treated with marketed tablets twice a day at the therapeutic dose showed late-stage recrudescence. Thus, NLC showed enhanced efficacy at 1/10 of the daily dose of ARM-LFN. The 10-fold reduced daily dose was formulated in two soft gelatin capsules thus reducing the number of units to be taken at a time by the patient. The capsules showed good stability at room temperature for a year. The NLC were found to be safe in rats. The biocompatible NLC developed using an industrially feasible technique offer a promising solution for oral malaria therapy. PMID:27421912

  6. Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2016-10-12

    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

  7. 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

  8. 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

  9. 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

  10. Gonadotropin and estradiol secretion during the week of placebo therapy in oral contraceptive pill users.

    PubMed

    van der Spuy, Z M; Sohnius, U; Pienaar, C A; Schall, R

    1990-12-01

    The changes in the hypothalamic-pituitary-ovarian axis during the placebo week in oral contraceptive pill users were assessed. Fifteen women using the combined oral contraceptive pill were studied for eight hours at the start and at the end of the placebo week and gonadotropin secretion and estradiol concentrations were compared with those in control women in the follicular phase of an unmedicated menstrual cycle. Both gonadotropin and estradiol concentrations were suppressed at the start of the placebo week. By day 7 of placebo, gonadotropin concentrations and pulse patterns were indistinguishable from those of the control subjects although estradiol concentrations were still significantly lower.

  11. A comparative evaluation of oral ofloxacin versus intravenous cefotaxime therapy for serious skin and skin structure infections.

    PubMed

    Gentry, L O; Rodriguez-Gomez, G; Zeluff, B J; Khoshdel, A; Price, M

    1989-12-29

    In a single-blind, placebo-controlled randomized trial, 100 successive patients were enrolled with serious skin and soft-tissue infections, whose illnesses had precipitated an initial hospital admission or an extension of inpatient care. There were 93 evaluable patients who received either ofloxacin, 400 mg orally every 12 hours plus an intravenously administered placebo every eight hours, or cefotaxime, 2.0 g intravenously every eight hours plus an orally administered placebo every 12 hours. The average length of therapy was 12 days. Both patient groups had similar demographics and underlying conditions. Wound infection was the most common diagnosis, followed by abscess, cellulitis, and trophic ulcer. Multiple pathogens were commonly isolated from infected sites (1.4 pathogens/patient). The most common pathogen was Staphylococcus aureus, followed by Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, Proteus/Providencia spp., and Enterobacter spp. Persistence of the initial pathogen at the end of therapy was observed in 22.5 percent of the cefotaxime-treated group, but in only 10 percent of the ofloxacin-treated group. There was one clinical failure in the cefotaxime group, caused by a susceptible strain of Enterobacter cloacae, and there was one clinical failure in the ofloxacin group, in which the patient had an Acinetobacter calcoaceticus var. anitratus wound infection and subsequently developed a P. aeruginosa superinfection. Adverse experiences, including rash, insomnia, and nausea, occurred in 16 percent of the patients in each group. It was concluded that oral ofloxacin is as safe and efficacious as parenteral cefotaxime in the treatment of serious skin and skin structure infections.

  12. Protection of isolated perfused working rat heart from oxidative stress by exogenous L-propionyl carnitine.

    PubMed

    Ronca, G; Ronca, F; Yu, G; Zucchi, R; Bertelli, A

    1992-01-01

    The effect of exogenous L-propionyl carnitine on peroxidative injury was investigated on isolated working rat hearts. The addition of 190 microM hydrogen peroxide to the perfusion buffer caused a marked decrease in aortic flow, minute work and peak aortic pressure, and a release of intracellular enzymes. In the presence of L-propionyl carnitine the haemodynamic damage was significantly lower and enzyme leakage remarkably decreased. The protection was concentration-dependent and the whole structure of the molecule was required, since carnitine alone was found less effective and propionate had no effect. In the absence of hydrogen peroxide L-propionyl carnitine increased heart performance. The effect of L-propionyl carnitine on oxidative stress could account for the beneficial effect of this substance in different models of ischaemic injury. L-propionyl carnitine increases the cardiac performance and protects the rat heart from peroxidation through metabolic and antiperoxidative mechanisms. PMID:1308473

  13. Monotherapy with Intravenous Followed by Oral High-Dose Ciprofloxacin versus Combination Therapy with Ceftazidime plus Amikacin as Initial Empiric Therapy for Granulocytopenic Patients with Fever

    PubMed Central

    Giamarellou, Helen; Bassaris, Harry P.; Petrikkos, George; Busch, Wilhelm; Voulgarelis, Michel; Antoniadou, Anastasia; Grouzi, Elisabeth; Zoumbos, Nikolaos

    2000-01-01

    The aim of the present study was to obtain clinical experience with the use of high-dose ciprofloxacin as monotherapy for the treatment of febrile neutropenia episodes (granulocyte count, <500/mm3) compared to a standard regimen and to clarify whether ciprofloxacin administration may be switched to the oral route. In a prospective randomized study ciprofloxacin was given at 400 mg three times a day (t.i.d.) for at least 72 h followed by oral administration at 750 mg twice a day (b.i.d). That regimen was compared with ceftazidime given intravenously at 2 g t.i.d. plus amikacin given intravenously at 500 mg b.i.d. The frequency of successful clinical response without modification at the end of therapy was almost identical for ciprofloxacin (50% [62 of 124 patients]) compared with that for ceftazidime plus amikacin (50.8% [62 of 122 patients]) in an intent-to-treat analysis; the frequencies were 48.3% (57 of 118 patients) versus 49.6% (56 of 113 patients), respectively, in a per-protocol analysis (P values for one-sided equivalence, 0.0485 and 0.0516, respectively; δ = 10%), with no significant differences among patients with bacteremia and other microbiologically or clinically documented infections and fever of unknown origin. For 82 (66.1%) patients, it was possible to switch from parenteral ciprofloxacin to the oral ciprofloxacin, and the response was successful for 61 (74.4%) patients. The efficacies of the regimens against streptococcal bacteremias were 16.6% (one of six patients) for the ciprofloxacin group and 33.3% (one of three patients) for the combination group (it was not statistically significant), with one breakthrough streptococcal bacteremia observed among the ciprofloxacin-treated patients. Adverse events were mostly self-limited and were observed in 27 (20.6%) ciprofloxacin-treated patients and 26 (19.7%) patients who were receiving the combination. This study demonstrates that high-dose ciprofloxacin given intravenously for at least 3 days and then

  14. [The biological function of L-carnitine and its content in the particular food examples].

    PubMed

    Rospond, Bartłomiej; Chłopicka, Joanna

    2013-01-01

    The aim of this article is to provide information about L-carnitine, its physiological role in the human body and its content in some foods. This chemical compound is mainly synthesized in the liver, kidney and brain and is composed of two aminoacids, lyzine and metionine. L-carnitine regulates the level of acylo-CoA and CoA in the mitochondium and cytozolum, and it provides acetyl moieties for the biosythesis of acetocholine. L-carnitine plays a vital function in the metabolism of lipids and it carries long-chain fatty acids into mitochondria for beta-oxidation. An increase of the amount of L-carnitine in the human body may lead to reduction and inhibition of production of fatty tissue. Despite the fact that human body can synthesise L-carnitine, about 80% of this chemical compound is delivered by food. It is crucial, especially for people who are on a slimming diet, to choose products rich in L-carnitine because this compound may potentially reduce the body weight. Animal by-products contain the highest amount of L-carnitine, and these are, e.g , kangaroo meat (637 mg), horse meat (423mg), beef (139 mg per 100 g of dry weight). The amount of L-carnitine in milk products may range from 1,4 to 42,8 mg per 100 g of dry matter. Vegetables and fruits are products which contain less than 5 mg of L-carnitine per 100 g of dry matter. Lipids are also very low in L-carnitine, e.g sunflower oil is free from this compound. It is worth mentioning that mushrooms are richer in L-carnitine than plants. The amount of L-carnitine (53 mg/100 g dry matter) in pleureotus ostreatus equals approximately 100 g of minced pork.

  15. 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…

  16. Oral 5-Aminosalicylate, Mesalamine Suppository, and Mesalamine Enema as Initial Therapy for Ulcerative Proctitis in Clinical Practice with Quality of Care Implications

    PubMed Central

    Richter, James M.; Arshi, Nabeela K.; Oster, Gerry

    2016-01-01

    Background. Ulcerative proctitis (UP) is typically treated initially with oral 5-aminosalicylate (“5-ASA”), mesalamine suppository, or mesalamine enema (“UP Rx”). Little is known about their effectiveness in practice. Methods. Using a US health insurance database, we identified new-onset UP patients between January 1, 2005, and December 31, 2007, based on the following: (1) initiation of UP Rx; (2) endoscopy in prior 30 days resulting in diagnosis of UP; and (3) no prior encounters for ulcerative colitis or Crohn's disease. We examined the incidence of therapy escalation and total costs in relation to initial UP Rx. Results. We identified 548 patients: 327 received mesalamine suppository, 138 received oral 5-ASA, and 83 received mesalamine enema, as initial UP Rx. One-third receiving oral 5-ASA experienced therapy escalation over 12 months, 21% for both mesalamine suppository and enema. Mean cumulative total cost of UP Rx over 12 months was $1552, $996, and $986 for patients beginning therapy with oral 5-ASA, mesalamine enema, and mesalamine suppository, respectively. Contrary to expert recommendations the treatments were often not continued prophylactically. Conclusions. Treatment escalation was common, and total costs of therapy were higher, in patients who initiated treatment with oral 5-ASA. Further study is necessary to assess the significance of these observations. PMID:27446860

  17. l-Carnitine improves cognitive and renal functions in a rat model of chronic kidney disease.

    PubMed

    Abu Ahmad, Nur; Armaly, Zaher; Berman, Sylvia; Jabour, Adel; Aga-Mizrachi, Shlomit; Mosenego-Ornan, Efrat; Avital, Avi

    2016-10-01

    Over the past decade, the prevalence of chronic kidney disease (CKD) has reached epidemic proportions. The search for novel pharmacological treatment for CKD has become an area of intensive clinical research. l-Carnitine, considered as the "gatekeeper" responsible for admitting long chain fatty acids into cell mitochondria. l-Carnitine synthesis and turnover are regulated mainly by the kidney and its levels inversely correlate with serum creatinine of normal subjects and CKD patients. Previous studies showed that l-carnitine administration to elderly people is improving and preserving cognitive function. As yet, there are no clinical intervention studies that investigated the effect of l-carnitine administration on cognitive impairment evidenced in CKD patients. Thus, we aimed to investigate the effects of l-carnitine treatment on renal function and on the cognitive performance in a rat model of progressive CKD. To assess the role of l-carnitine on CKD condition, we estimated the renal function and cognitive abilities in a CKD rat model. We found that all CKD animals exhibited renal function deterioration, as indicated by elevated serum creatinine, BUN, and ample histopathological abnormalities. l-Carnitine treatment of CKD rats significantly reduced serum creatinine and BUN, attenuated renal hypertrophy and decreased renal tissue damage. In addition, in the two way shuttle avoidance learning, CKD animals showed cognitive impairment which recovered by the administration of l-carnitine. We conclude that in a rat model of CKD, l-carnitine administration significantly improved cognitive and renal functions.

  18. Comparative analysis of therapeutic efficiency and costs (experience in Bulgaria) of oral antidiabetic therapies based on glitazones and gliptins.

    PubMed

    Filipova, Elena Pavlova; Uzunova, Katya Hristova; Vekov, Toni Yonkov

    2015-01-01

    Type 2 diabetes mellitus is a serious, chronic, progressive and widespread disease. Metformin is the most commonly prescribed initial therapy, but combination with other antidiabetic agents usually becomes necessary due to the progression of the disease. Pioglitazone is recommended as a second-line therapy because of its strong antihyperglycemic effect and its ability to reduce insulin resistance. Treatment with pioglitazone is associated with a significantly lower risk of cardiovascular complications and hypoglycemia, while simultaneously improving the lipid profile and the symptomatic and histological changes in the liver. Gliptins (sitagliptin and vildagliptin) are a new class of oral antidiabetic drugs which reduce glycated hemoglobin by a different mechanism. Although the efficacy of sitagliptin and vildagliptin is close to that of pioglitazone, the lack of long-term safety data and the higher price question their predominant use. The objective of this review is to highlight the advantages of mono- and combination therapy with pioglitazone in comparison with gliptins and to underline the inconsistencies in the medicinal and reimbursement policy in Bulgaria. PMID:26288659

  19. 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.

  20. 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. PMID:26944956

  1. 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

  2. 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

  3. Changing trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged?

    PubMed

    Fareed, J; Iqbal, O; Cunanan, J; Demir, M; Wahi, R; Clarke, M; Adiguzel, C; Bick, R

    2008-06-01

    The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants and aspirin. Despite progress in the sciences, these drugs still remain a challenge and mystery. The development of low molecular weight heparins (LMWHS) and the synthesis of heparinomimetics represent a refined use of heparin. Additional drugs will continue to develop. However, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, GPIIb/IIIa inhibitors and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains the approach of choice to manage thrombotic disorders. The new anticoagulant targets, such as tissue factor, individual clotting factors, recombinant forms of serpins (antithrombin, heparin co-factor II and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin and site specific serine proteases inhibitors complexes have also been developed. There is a major thrust on the development of orally bioavailable anti-Xa and IIa agents, which are slated to replace oral anticoagulants. Both the anti-factor Xa and anti-IIa agents have been developed for oral use and have provided impressive clinical results. However, safety concerns related to liver enzyme elevations and thrombosis rebound have been reported with their use. For these reasons, the US Food and Drug Administration did not approve the orally active antithrombin agent Ximelagatran for several indications. The synthetic pentasaccharide (Fondaparinux) has undergone clinical development. Unexpectedly, Fondaparinux also produced major

  4. Therapy with newer oral beta-lactam and quinolone agents for infections of the skin and skin structures: a review.

    PubMed

    Gentry, L O

    1992-01-01

    Amoxicillin/clavulanic acid, cefuroxime axetil, ciprofloxacin, and ofloxacin are each effective against many bacteria that cause infections in the skin and skin structures. Amoxicillin/clavulanic acid is potent against staphylococci, streptococci (including enterococci), and anaerobes, although adverse gastrointestinal reactions are common. Cefuroxime axetil is similarly effective yet is used only rarely because of its more common use in infections of the respiratory tract and the prevalent use of second-generation cephalosporins in surgical prophylaxis. The newer quinolones ciprofloxacin and ofloxacin are effective against staphylococci, Enterobacteriaceae, and Pseudomonas aeruginosa and exhibit only low toxicity; these agents have been used in many difficult tissue infections--notably, chronic infected ulcers in diabetic patients. Oral antimicrobial therapy, when chosen on the basis of culture and susceptibility results and combined with surgical debridement and local management, may be effective for many problematic infections of the skin and skin structures heretofore treated with parenteral antibiotics.

  5. Orally administered P22 phage tailspike protein reduces salmonella colonization in chickens: prospects of a novel therapy against bacterial infections.

    PubMed

    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

  6. 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.

  7. 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. PMID:25110948

  8. 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

  9. Influence of l-carnitine on metabolism and performance of sows.

    PubMed

    Eder, Klaus

    2009-09-01

    In recent years, l-carnitine has been used increasingly as a supplement in livestock animals. The present review gives an overview of the effects of dietary l-carnitine supplementation on the reproductive performance of sows. Results concerning the effect of l-carnitine supplementation during pregnancy on litter sizes are controversial. There are some studies reporting an increased number of piglets born alive per litter, while others could not find such an effect. In contrast, most studies performed show consistently that l-carnitine supplementation to a sow diet low in native carnitine during gestation increases piglet and litter weights at birth and enhances growth of litters during the suckling period. Biochemical mechanisms underlying the favourable effect of carnitine on intra-uterine growth have not been fully elucidated. There is, however, some evidence that carnitine influences the insulin-like growth factor-axis in sows and leads to greater placentae, which in turn improves intra-uterine nutrition, and stimulates oxidation of glucose in the fetuses. These effects may, at least in part, be responsible for higher birth weights of piglets. The stimulating effect of carnitine on growth of the litters might be due to an improved suckling behaviour of piglets born to l-carnitine-supplemented sows, causing the sows' milk production to rise. In conclusion, recent studies have clearly shown that dietary l-carnitine supplementation increases the reproductive performance of sows. These findings suggest that endogenous de novo synthesis of carnitine is insufficient to meet the metabolic requirement of sows during gestation.

  10. L-carnitine suppresses the onset of neuromuscular degeneration and increases the life span of mice with familial amyotrophic lateral sclerosis.

    PubMed

    Kira, Yukimi; Nishikawa, Manabu; Ochi, Akemi; Sato, Eisuke; Inoue, Masayasu

    2006-01-27

    Amyotrophic lateral sclerosis (ALS) is a fatal disease caused by progressive degeneration of motor neurons in the spinal cord and motor cortex. Although the etiology of ALS remains unknown, a mutation of the gene encoding Cu,Zn-superoxide dismutase (SOD1) has been reported in 20% of familial cases of ALS (FALS). Transgenic mice that overexpress a mutated human SOD1 exhibit a phenotype and pathology similar to those observed in patients with FALS. Mitochondrial abnormality has been reported in patients with ALS and in animal models of FALS. We recently reported that L-carnitine, an essential cofactor for the beta-oxidation of long-chain fatty acids, effectively inhibits various types of mitochondrial injury and apoptosis both in vitro and in vivo. The present study demonstrates that oral administration of L-carnitine prior to disease onset significantly delayed the onset of signs of disease (log-rank P=0.0008), delayed deterioration of motor activity, and extended life span (log-rank P=0.0001) in transgenic mice carrying a human SOD1 gene with a G93A mutation (Tg). More importantly, subcutaneous injection of L-carnitine increased the life span of Tg mice (46% increase in male, 60% increase in female) even when given after the appearance of signs of disease.

  11. Increased uptake of guideline-recommended oral antiplatelet therapy: insights from the Canadian acute coronary syndrome reflective.

    PubMed

    Gandhi, Sumeet; Zile, Brigita; Tan, Mary K; Saranu, Jhansi; Bucci, Claudia; Yan, Andrew T; Robertson, Patrick; Quantz, Mackenzie A; Letovsky, Eric; Tanguay, Jean-Francois; Dery, Jean-Pierre; Fitchett, David; Madan, Mina; Cantor, Warren J; Heffernan, Michael; Natarajan, Madhu K; Wong, Graham C; Welsh, Robert C; Goodman, Shaun G

    2014-12-01

    Current guideline-based recommendations for oral dual-antiplatelet therapy in an acute coronary syndrome (ACS) include the use of newer adenosine diphosphate receptor inhibitor (ADPri) regimens and agents. The Canadian ACS Reflective Program is a multicenter observational quality-enhancement project that compared the use of ADPri therapy in 2 phases (November 2011-March 2013 and April 2013-November 2013) and also compared ADPri use with previous national data from the Canadian Global Registry of Acute Coronary Events (2000-2008). Of 3099 patients with ACS, 30.6% had ST-segment elevation myocardial infarction (STEMI), 52.3% had non-STEMI, and 17% had unstable angina. There was high use of dual-antiplatelet therapy for ≤ 24 hours, with important increases noted when compared with previous national experience (P for trend, < 0.0001). Clopidogrel was the most commonly used ADPri (82.2%), with lower use of the newer agents ticagrelor (9.0%) and prasugrel (3.1%). Ticagrelor and prasugrel use was most frequent in patients with STEMI undergoing percutaneous coronary intervention PCI (34.3%). There was relatively lower use of ADPri therapy at discharge; it was given mainly to patients who did not undergo PCI (68.2%) and to those with non-ST-elevation ACS (82%). When comparing the 2 consecutive phases of data collection in the ACS Reflective, there was an approximate 3- and 2-fold increase in the early and discharge use of the newer ADPri agents, respectively. In conclusion, there has been a temporal increase in ADPri use compared with previous national experience and an increased uptake of newer ADPri agents. Additional work is needed to identify and address barriers limiting optimal implementation of these newer guideline-recommended agents into routine Canadian practice. PMID:25475475

  12. Three-dimensional evaluation of upper airway in patients with obstructive sleep apnea syndrome during oral appliance therapy.

    PubMed

    Cossellu, Gianguido; Biagi, Roberto; Sarcina, Michele; Mortellaro, Carmen; Farronato, Giampietro

    2015-05-01

    Obstructive sleep apnea syndrome (OSAS) represents a frequent and common respiratory disease characterized by repeated episodes of complete and/or partial obstruction of upper airways during sleep, normally associated with reduction of oxygen saturation in blood. The oral appliances (OAs) are considered to be an effective treatment modality thanks to the upper airway enlargement. Lateral cephalometry has been used for the 2-dimensional evaluation of upper airway form with several limits. We obtained an accurate 3-dimensional (3D) volume analyses with cone beam computed tomography (CBCT) scans to confirm the effects of OA on the upper airway in patients with OSAS. Ten Italian patients with moderate or severe OSA (3 males and 7 females, 53.4 ± 11.3 years of age, and BMI 24.5 ± 2.7), who cannot tolerate continuous positive air pressure therapy and rejected a surgical approach, were treated with non-adjustable customized OAs and evaluated with CBCT and polysomnography. Upper airway form was examined in the presence and absence of OA and the volume was measured and compared in 2 different areas. Specific planes have been considered to match the data and calculate the benefit obtained with therapy. Nine out of ten patients showed an improvement of total upper airway volume and an improvement in apnea-hypopnea index. Volume increased both in the posterior soft palate region and in the posterior tongue region. In the inferior area, we observed greater differences. 3D image reconstruction accurately confirmed morphological changes in the upper airway during OA therapy. The use of this 3D evaluation is expected to improve the results of OA therapy in the future. PMID:25974784

  13. 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

  14. 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.

  15. Resolution of oral non-Hodgkin's lymphoma by reduction of immunosuppressive therapy in a renal allograft recipient: a case report and review of the literature.

    PubMed

    Keogh, Paul V; Fisher, Veronica; Flint, Stephen R

    2002-12-01

    A case of oral non-Hodgkin's lymphoma arising in a patient with insulin-dependent diabetes who had undergone renal allograft transplantation is described. The resolution of the disease was achieved by a reduction in her immunosuppressive therapy. The differential diagnosis is discussed, and the management of posttransplantation lymphoproliferative disorders is reviewed.

  16. 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)

  17. 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…

  18. SMA CARNI-VAL TRIAL PART II: A Prospective, Single-Armed Trial of L-Carnitine and Valproic Acid in Ambulatory Children with Spinal Muscular Atrophy

    PubMed Central

    Kissel, John T.; Scott, Charles B.; Reyna, Sandra P.; Crawford, Thomas O.; Simard, Louise R.; Krosschell, Kristin J.; Acsadi, Gyula; Elsheik, Bakri; Schroth, Mary K.; D'Anjou, Guy; LaSalle, Bernard; Prior, Thomas W.; Sorenson, Susan; Maczulski, Jo Anne; Bromberg, Mark B.; Chan, Gary M.; Swoboda, Kathryn J.

    2011-01-01

    Background Multiple lines of evidence have suggested that valproic acid (VPA) might benefit patients with spinal muscular atrophy (SMA). The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and l-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2–8 in a 12 month cross over design. We report here Part 2, a twelve month prospective, open-label trial of VPA and L-carnitine in ambulatory SMA children. Methods This study involved 33 genetically proven type 3 SMA subjects ages 3–17 years. Subjects underwent two baseline assessments over 4–6 weeks and then were placed on VPA and L-carnitine for 12 months. Assessments were performed at baseline, 3, 6 and 12 months. Primary outcomes included safety, adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend (MHFMS-Extend), timed motor tests and fine motor modules. Secondary outcomes included changes in ulnar compound muscle action potential amplitudes (CMAP), handheld dynamometry, pulmonary function, and Pediatric Quality of Life Inventory scores. Results Twenty-eight subjects completed the study. VPA and carnitine were generally well tolerated. Although adverse events occurred in 85% of subjects, they were usually mild and transient. Weight gain of 20% above body weight occurred in 17% of subjects. There was no significant change in any primary outcome at six or 12 months. Some pulmonary function measures showed improvement at one year as expected with normal growth. CMAP significantly improved suggesting a modest biologic effect not clinically meaningful. Conclusions This study, coupled with the CARNIVAL Part 1 study, indicate that VPA is not effective in improving strength or function in SMA children. The outcomes used in this study are feasible and reliable, and can be employed in future trials in SMA. Trial Regsitration Clinicaltrials.gov NCT00227266 PMID:21754985

  19. 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

  20. Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice.

    PubMed

    Steffens, Sabine; Veillard, Niels R; Arnaud, Claire; Pelli, Graziano; Burger, Fabienne; Staub, Christian; Karsak, Meliha; Zimmer, Andreas; Frossard, Jean-Louis; Mach, François

    2005-04-01

    Atherosclerosis is a chronic inflammatory disease, and is the primary cause of heart disease and stroke in Western countries. Derivatives of cannabinoids such as delta-9-tetrahydrocannabinol (THC) modulate immune functions and therefore have potential for the treatment of inflammatory diseases. We investigated the effects of THC in a murine model of established atherosclerosis. Oral administration of THC (1 mg kg(-1) per day) resulted in significant inhibition of disease progression. This effective dose is lower than the dose usually associated with psychotropic effects of THC. Furthermore, we detected the CB2 receptor (the main cannabinoid receptor expressed on immune cells) in both human and mouse atherosclerotic plaques. Lymphoid cells isolated from THC-treated mice showed diminished proliferation capacity and decreased interferon-gamma secretion. Macrophage chemotaxis, which is a crucial step for the development of atherosclerosis, was also inhibited in vitro by THC. All these effects were completely blocked by a specific CB2 receptor antagonist. Our data demonstrate that oral treatment with a low dose of THC inhibits atherosclerosis progression in the apolipoprotein E knockout mouse model, through pleiotropic immunomodulatory effects on lymphoid and myeloid cells. Thus, THC or cannabinoids with activity at the CB2 receptor may be valuable targets for treating atherosclerosis.

  1. 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

  2. Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review. The Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study.

    PubMed

    Wu, Olivia; Robertson, Lindsay; Langhorne, Peter; Twaddle, Sara; Lowe, Gordon D O; Clark, Peter; Greaves, Mike; Walker, Isobel D; Brenkel, Ivan; Regan, Lesley; Greer, Ian A

    2005-07-01

    Combined oral contraceptives, oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women. The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47). Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users.

  3. L-Carnitine Supplementation Improves the Behavioral Symptoms in Autistic Children

    ERIC Educational Resources Information Center

    Fahmy, Sarah Farid; El-hamamsy, Manal H.; Zaki, Osama K.; Badary, Osama A.

    2013-01-01

    L-Carnitine was proposed as a potential treatment for patients diagnosed with autism to ameliorate the behavioral symptoms associated with the disease. Thirty children diagnosed with autism were randomly assigned to receive (100 mg/kg bodyweight/day) of liquid L-carnitine (n = 16) or placebo (n = 14) for 6 months. Measurements included changes in…

  4. 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

  5. Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A - Medical results

    PubMed Central

    Adams, James B; Baral, Matthew; Geis, Elizabeth; Mitchell, Jessica; Ingram, Julie; Hensley, Andrea; Zappia, Irene; Newmark, Sanford; Gehn, Eva; Rubin, Robert A; Mitchell, Ken; Bradstreet, Jeff; El-Dahr, Jane

    2009-01-01

    Background This study investigated the effect of oral dimercapto succinic acid (DMSA) therapy for children with autism spectrum disorders ages 3-8 years. Methods Phase 1 involved 65 children who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo. Results DMSA greatly increased the excretion of lead, substantially increased excretion of tin and bismuth, and somewhat increased the excretion of thallium, mercury, antimony, and tungsten. There was some increase in urinary excretion of essential minerals, especially potassium and chromium. The Phase 1 single round of DMSA led to a dramatic normalization of RBC glutathione in almost all cases, and greatly improved abnormal platelet counts, suggesting a significant decrease in inflammation. Conclusion Overall, DMSA therapy seems to be reasonably safe, effective in removing several toxic metals (especially lead), dramatically effective in normalizing RBC glutathione, and effective in normalizing platelet counts. Only 1 round (3 days) was sufficient to improve glutathione and platelets. Additional rounds increased excretion of toxic metals. PMID:19852789

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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. PMID:26930571

  11. Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia.

    PubMed

    Cristofano, Adriana; Sapere, Nadia; La Marca, Giancarlo; Angiolillo, Antonella; Vitale, Michela; Corbi, Graziamaria; Scapagnini, Giovanni; Intrieri, Mariano; Russo, Claudio; Corso, Gaetano; Di Costanzo, Alfonso

    2016-01-01

    This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer's disease. Twenty-nine patients with probable Alzheimer's disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L) to subjective memory complaint (4.3±0.9 μmol/L), mild cognitive impairment (4.0±0.53 μmol/L), up to Alzheimer's disease (3.5±0.6 μmol/L) group (p<0.001). The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer's disease group; and subjective memory complaint vs. Alzheimer's disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer's disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer's disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer's disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal study is needed

  12. Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia

    PubMed Central

    Sapere, Nadia; La Marca, Giancarlo; Angiolillo, Antonella; Vitale, Michela; Corbi, Graziamaria; Scapagnini, Giovanni; Intrieri, Mariano; Russo, Claudio

    2016-01-01

    This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer’s disease. Twenty-nine patients with probable Alzheimer’s disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L) to subjective memory complaint (4.3±0.9 μmol/L), mild cognitive impairment (4.0±0.53 μmol/L), up to Alzheimer’s disease (3.5±0.6 μmol/L) group (p<0.001). The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer’s disease group; and subjective memory complaint vs. Alzheimer’s disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer’s disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer’s disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer’s disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal

  13. [Carnitine as a marker of atherosclerosis and other risks of cardiovascular diseases].

    PubMed

    Dambrova, M; Makretskaia, M; Vilshkersts, R; Kuka, Ia; Liepin'sh, É

    2014-01-01

    L-carnitine was first isolated from the extracts of muscle tissue in 1905 by the employees of the department of medicinal chemistry at Moscow University. Later the role of L-carnitine in both the oxidation of long chain fatty acids and the metabolism of carbohydrates was discovered. Today L-carnitine is not just a drug for the treatment of pathologies associated with its deficiency, but also a widespread dietary supplement, believed to be able to reduce weight and improve the physical qualities of a person. However, in light of the recent findings about a possible link between L-carnitine and the development of atherosclerosis, a careful assessment of the use of L-carnitine as a safe dietary supplement is required, particularly when there is no sound medical indication. PMID:25464617

  14. Biotin and carnitine deficiency due to hypoallergenic formula nutrition in infants with milk allergy.

    PubMed

    Hayashi, Hisako; Tokuriki, Shuko; Okuno, Takashi; Shigematsu, Yosuke; Yasushi, Akiba; Matsuyama, Go; Sawada, Ken; Ohshima, Yusei

    2014-04-01

    Amino acid formulas and hydrolyzed formulas given to infants in Japan with milk allergies theoretically contain little, if any, biotin and carnitine. We assessed biotin and carnitine insufficiency in six infants with milk allergy who were fed amino acid formulas and/or hydrolyzed formulas, by measuring urine 3-hydroxyisovaleric acid (3-HIA) and serum free carnitine (C0), respectively. All patients presented with elevated urine 3-HIA and lowered serum C0 compared with post-menstrual age-matched infants who were fed breast milk or standard infant formulas. Supplementation with biotin and L-carnitine immediately improved the insufficiency. Care should be taken to avoid biotin and carnitine deficiency in allergic infants fed amino acid or hydrolyzed formulas.

  15. Degenerative events in retina and optic nerve induced by inhibition of carnitine transport.

    PubMed

    Pescosolido, N; Pascarella, A; Nebbioso, M; Scarsella, G

    2014-01-01

    Biochemical and pharmacological evidence supports the hypothesis that the mechanism of action of mildronate [3-(2,2,2-trimethylhydrazinium)propionate dihydrate] is based on its regulatory effect on carnitine concentration. The present study demonstrates that carnitine acts as a neuroprotective agent both in optic nerve head and in retinal ganglion cell (RGC) by means of antioxidant and antiradical activities. In fact, carnitine normalized the increase in caspase-3, cellular apoptosis susceptibility protein (CAS) and inducible nitric oxide synthase (iNOS) expression by stabilizing mitochondrial membranes, as assessed by quantitative and qualitative analysis. This research shows that the neuroprotective effects of carnitine result, at least partially, from anti-neurodegenerative (anti-apoptotic) and anti-inflammatory mechanisms. It is suggested that the molecular conformation of carnitine can facilitate its easy binding to mitochondria, and regulate the expression of different signal molecules, hence maintaining normal cellular signaling and survival by modulating caspase-3 activity.

  16. [Severe osteoporosis with vertebral crushes in juvenile dermatomyositis. Effect of oral alendronate therapy].

    PubMed

    Tau, Cristina; Russo, Ricardo

    2007-01-01

    Glucocorticoids are used for the treatment of inflammatory and autoimmune diseases, cancer, and in prevention of organ rejects. A frequent secondary effect of longterm treatment with corticoids is the loss of bone mass, caused by several mechanisms: decrease in the intestinal calcium absorption, increase of the renal calcium excretion at the distal renal tubule, suppressive effect on the osteoblast and also in apoptosis of osteoclasts, inhibition in local production of IGF I (Insulin-like growth factor) and IGFBPs (binding IGF I proteins necessary for bone metabolism), and decrease on osteocalcin production. Longterm treatment with corticoids is associated with osteoporosis and vertebral fractures. To improve this condition, treatment with bisphosphonates has been proposed. We present here a clinical case of a girl with dermatomyositis and severe osteoporosis with vertebral crushes, who responded well to oral bisphophonate treatment.

  17. Persistence to oral 5-aminosalicylate therapy for inflammatory bowel disease in Australia.

    PubMed

    Selinger, Christian P; Kemp, Andrew; Leong, Rupert Wl

    2014-03-01

    Aminosalicylate (5-ASA) is effective treatment for inflammatory bowel diseases (IBDs) but requires continuous maintenance therapy. This study determines persistence of 5-ASA in IBD using national population-based data for Australia from 2002 to 2011 with follow up for 36 months. Non-persistence was defined as failing to fill a prescription for 3 months. Of 12,592 patients those initiated on non-sulphasalazine 5-ASA (2917) had significantly higher persistence (P < 0.001) than those on sulphasalazine (9675). Persistence for sulphasalazine and non-sulphasalazine 5-ASA initiation was 22.3% and 28.5% at 12-months, and 11.9% and 16.2% at 24-months. Sulphasalazine poor persistence continued despite intra-class switch to another 5-ASA. Patients receiving immunomodulator co-therapy had higher persistence (P < 0.001). National population-based data identified persistence to 5-ASA to be low but significantly lower when sulphasalazine is the initial drug. Physicians should stress the importance of long-term 5-ASA therapy as overall drug efficacy especially the 5-ASA chemo-prophylactic benefits may be reduced by non-persistence.

  18. 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

  19. Study on biopharmaceutics classification and oral bioavailability of a novel multikinase inhibitor NCE for cancer therapy.

    PubMed

    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

    2014-04-25

    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 (P(eff)) 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 P(eff) 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.

  20. Fluorescent derivatization combined with aqueous solvent-based dispersive liquid-liquid microextraction for determination of butyrobetaine, l-carnitine and acetyl-l-carnitine in human plasma.

    PubMed

    Chen, Yi-Ching; Tsai, Chia-Ju; Feng, Chia-Hsien

    2016-09-16

    A novel aqueous solvent-based dispersive liquid-liquid microextraction (AS-DLLME) method was combined with narrow-bore liquid chromatography and fluorescence detection for the determination of hydrophilic compounds. A remover (non-polar solvent) and extractant (aqueous solution) were introduced into the derivatization system (acetonitrile) to obtain a water-in-oil emulsion state that increased the mass transfer of analytes. As a proof of concept, three quaternary ammonium substances, including butyrobetaine, l-carnitine and acetyl-l-carnitine, were also used as analytes and determined in pharmaceuticals, personal care products, food and human plasma. The analytes were derivatized with 4-bromomethylbiphenyl for fluorescence detection and improved retention in the column. The linear response was 10-2000nM for l-carnitine and acetyl-l-carnitine with a good determination coefficient (r(2)>0.998) in the standard solution. The detection limit for l-carnitine and acetyl-l-carnitine was 4.5 fmol. The method was also successfully applied to a 1μL sample of human plasma. In the linearity calculations for determining butyrobetaine, l-carnitine and acetyl-l-carnitine in human plasma, the determination coefficients ranged from 0.996 to 0.999. Linear regression exhibited good reproducibility and a relative standard deviation better than 7.50% for the slope and 9.06% for the intercept. To characterize highly hydrophilic compounds in various samples, the proposed method provides good sensitivity for a small sample volume with a low consumption of toxic solvents.

  1. Fluorescent derivatization combined with aqueous solvent-based dispersive liquid-liquid microextraction for determination of butyrobetaine, l-carnitine and acetyl-l-carnitine in human plasma.

    PubMed

    Chen, Yi-Ching; Tsai, Chia-Ju; Feng, Chia-Hsien

    2016-09-16

    A novel aqueous solvent-based dispersive liquid-liquid microextraction (AS-DLLME) method was combined with narrow-bore liquid chromatography and fluorescence detection for the determination of hydrophilic compounds. A remover (non-polar solvent) and extractant (aqueous solution) were introduced into the derivatization system (acetonitrile) to obtain a water-in-oil emulsion state that increased the mass transfer of analytes. As a proof of concept, three quaternary ammonium substances, including butyrobetaine, l-carnitine and acetyl-l-carnitine, were also used as analytes and determined in pharmaceuticals, personal care products, food and human plasma. The analytes were derivatized with 4-bromomethylbiphenyl for fluorescence detection and improved retention in the column. The linear response was 10-2000nM for l-carnitine and acetyl-l-carnitine with a good determination coefficient (r(2)>0.998) in the standard solution. The detection limit for l-carnitine and acetyl-l-carnitine was 4.5 fmol. The method was also successfully applied to a 1μL sample of human plasma. In the linearity calculations for determining butyrobetaine, l-carnitine and acetyl-l-carnitine in human plasma, the determination coefficients ranged from 0.996 to 0.999. Linear regression exhibited good reproducibility and a relative standard deviation better than 7.50% for the slope and 9.06% for the intercept. To characterize highly hydrophilic compounds in various samples, the proposed method provides good sensitivity for a small sample volume with a low consumption of toxic solvents. PMID:27562416

  2. 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

  3. Neonatal Carnitine Palmitoyltransferase II Deficiency: A Lethal Entity.

    PubMed

    Malik, Sushma; Paldiwal, Ashutosh Abhimanyu; Korday, Charusheela Sujit; Jadhav, Shruti Sudhir

    2015-10-01

    Carnitine palmitoyltransferase II (CPTII) deficiency is a rare disorder of mitochondrial fatty acid oxidation with autosomal recessive mode of inheritance. Three classic forms of CPT II deficiency have been described namely the lethal neonatal form, severe infantile hepatocardiomuscular form and the myopathic form. We present a three-day-old female child, admitted to us for lethargy, icterus, low sugars and convulsions. Persistent non ketotic hypoglycaemia, hyperammonemia, raised liver enzymes with hepatomegaly and cardiomyopathy led to the suspicion of fatty acid oxidation defect. Tandem mass spectrometry helped to clinch the diagnosis of CPT II Deficiency in the present case. PMID:26557586

  4. Creatine, L-Carnitine, and ω3 Polyunsaturated Fatty Acid Supplementation from Healthy to Diseased Skeletal Muscle

    PubMed Central

    D'Antona, Giuseppe; Nabavi, Seyed Mohammad; Micheletti, Piero; Aquilani, Roberto; Nisoli, Enzo; Rondanelli, Mariangela; Daglia, Maria

    2014-01-01

    Myopathies are chronic degenerative pathologies that induce the deterioration of the structure and function of skeletal muscle. So far a definitive therapy has not yet been developed and the main aim of myopathy treatment is to slow the progression of the disease. Current nonpharmacological therapies include rehabilitation, ventilator assistance, and nutritional supplements, all of which aim to delay the onset of the disease and relieve its symptoms. Besides an adequate diet, nutritional supplements could play an important role in the treatment of myopathic patients. Here we review the most recent in vitro and in vivo studies investigating the role supplementation with creatine, L-carnitine, and ω3 PUFAs plays in myopathy treatment. Our results suggest that these dietary supplements could have beneficial effects; nevertheless continued studies are required before they could be recommended as a routine treatment in muscle diseases. PMID:25243159

  5. 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

  6. 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

  7. Low Level Laser Therapy to Reduce Recurrent Oral Ulcers in Behçet's Disease.

    PubMed

    Babu, D B Gandhi; Chavva, Sunanda; Waghray, Shefali; Allam, Neeharika Satya Jyothi; Kondaiah, Marella

    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

  8. Multicenter randomized controlled trial on combination therapy with 0.1% adapalene gel and oral antibiotics for acne vulgaris: comparison of the efficacy of adapalene gel alone and in combination with oral faropenem.

    PubMed

    Hayashi, Nobukazu; Kawashima, Makoto

    2012-06-01

    We conducted a randomized controlled trial in patients with acne vulgaris with moderate to severe inflammatory lesions. The patients were assigned to the following three treatment groups: group A received monotherapy with 0.1% topical adapalene gel for 4 weeks; group B received combination therapy with 0.1% topical adapalene gel and 600 mg oral faropenem for 2 weeks followed by 0.1% topical adapalene gel alone for 2 weeks; and group C received combination therapy with 0.1% topical adapalene gel and 600 mg oral faropenem for 4 weeks. The result of the analysis indicated that the percentage reduction in inflammatory lesion counts after 2 weeks of treatment was significantly higher in groups B and C than in group A (P < 0.05). After 4 weeks of treatment, group C showed significantly higher percentage reduction in inflammatory lesion counts than in groups A and B (P < 0.05), whereas no significant difference was noted between the latter two groups. Adverse reactions included dryness and irritation at the adapalene application sites that were observed in 10.1% of cases (16/158 patients) and diarrhea and loose stool because of oral faropenem that were observed in 7.5% of cases (8/106 patients). Taken together, our results suggest that combination therapy with oral antibiotics and adapalene results in earlier improvement in patients with moderate to severe inflammatory acne compared to the application of adapalene alone, and that 4 weeks of the combination therapy is preferable to 2 weeks of treatment. PMID:22168326

  9. Gene Therapy

    PubMed Central

    Baum, Bruce J

    2014-01-01

    Applications of gene therapy have been evaluated in virtually every oral tissue, and many of these have proved successful at least in animal models. While gene therapy will not be used routinely in the next decade, practitioners of oral medicine should be aware of the potential of this novel type of treatment that doubtless will benefit many patients with oral diseases. PMID:24372817

  10. Risk of Inflammatory Bowel Disease with Oral Contraceptives and Menopausal Hormone Therapy: Current Evidence and Future Directions.

    PubMed

    Khalili, Hamed

    2016-03-01

    Crohn's disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel diseases, are archetypical inflammatory disorders of the gastrointestinal tract with rising incidence worldwide. Although the role of genetic factors in disease development has been highlighted by genome-wide association studies, environmental risk factors likely play a pivotal role in development of CD and UC. Prior observational studies have suggested a link between exogenous hormone use and risk of CD and UC. Specifically, studies have shown an association between oral contraceptive use and risk of CD and menopausal hormone therapy and risk of UC. Although the exact mechanism of these associations is largely unknown, a number of hypotheses have been proposed. First, oral estrogen has been shown to modify intestinal permeability, a critical step in the pathophysiology of inflammatory bowel disease. Second, exogenous hormone use through its effect on endogenous levels of hormones may enhance the development of Th1- and Th2-mediated inflammatory diseases. Lastly, recent data have linked modification in the gut microbiome to endogenous levels of androgens, which are also known to be altered with exogenous hormone use and influence the development of autoimmune diseases. This supports the intriguing hypothesis that the gut microbiome lies at the crossroads of pathways linking exogenous hormone use with innate and adaptive immunity. Future studies should therefore focus on bridging these epidemiologic findings to disease pathogenesis through comprehensive understanding of the complex interaction between exogenous hormone use, sex steroid biomarkers, genetic risk loci, and alterations in the intestinal microbial environment in the etiology of CD and UC.

  11. 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.

  12. 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

  13. 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

  14. 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 manifestation such as pigmentation and xerostomia. Hence, we conclude that recognition, significance and treatment of these lesions in patients with HIV

  15. Amelioration of adverse effects of valproic acid on ketogenesis and liver coenzyme A metabolism by cotreatment with pantothenate and carnitine in developing mice: possible clinical significance.

    PubMed

    Thurston, J H; Hauhart, R E

    1992-04-01

    Very young children with organic brain damage, intractable seizures, and developmental retardation are at particular risk of developing fatal hepatic dysfunction coincident with valproate therapy, especially if the children are also receiving other anticonvulsant drugs. The mechanism of valproate-associated hepatic failure in these children is unclear. There are two major theories of etiology. The first concerns the manyfold consequences of depletion of CoA due to sequestration into poorly metabolized valproyl CoA and valproyl CoA metabolites. The other theory proposes that the unsaturated valproate derivative 2-n-propyl-4-pentenoic acid and/or metabolically activated intermediates are toxic and directly cause irreversible inhibition of enzymes of beta-oxidation. The present study shows for the first time that in developing mice, when panthothenic acid and carnitine are administered with valproate, at least some of the effects of valproate are mitigated. Perhaps most importantly, the beta-hydroxybutyrate concentration in plasma and the free CoA and acetyl CoA levels in liver do not fall so low. Cotreatment with carnitine alone was without effect. Findings support the CoA depletion mechanism of valproate inhibition of beta-oxidation and other CoA- and acetyl CoA-requiring enzymic reactions and stress the role of carnitine in the regulation of CoA synthesis at the site of action of pantothenate kinase. PMID:1570210

  16. Doxepin for Radiation Therapy-Induced Mucositis Pain in the Treatment of Oral Cancers

    PubMed Central

    Jayakrishnan, Ritujith; Chang, Kenneth; Ugurluer, Gamze; Miller, Robert C.

    2015-01-01

    Radiotherapy (RT), an integral part of the oncologic treatment for patients with head and neck cancer, can cause adverse side effects such as oral mucositis (OM). Pain from OM can impact a patient’s quality of life and interrupt RT treatment schedules, which decreases the probability for achieving cancer cure. Conventionally, RT-induced OM pain is treated with analgesics and/or mouthwash rinses. Doxepin, a traditional tricyclic antidepressant with analgesic and anesthetic properties when applied topically to the mucosa, has been shown to lower OM pain in multiple single-arm trials (Epstein et al.) and more recently, in a placebo-controlled crossover study (Leenstra and Miller et al.). Currently, a placebo-controlled study (Sio and Miller et al.) using doxepin for esophagitis pain caused by RT to the thorax is underway. Doxepin will also be further compared with magic mouthwash and a placebo solution in a three-arm trial (Miller and Sio et al.) with head and neck cancer patients with OM pain caused by RT. Doxepin may represent a new standard for treating RT-induced OM pain in the future. PMID:26779314

  17. A histologic assessment of a HYBENX® oral tissue decontaminant in vital pulp therapy in dogs.

    PubMed

    Rohrer, M D; Prasad, H S; Savord, E G

    2016-01-01

    The aim of this study was to assess HYBENX® Oral Tissue Decontaminant (HOTD) in treating vital pulp exposure in a canine model. The use of HOTD solution was compared to an accepted and standard regimen for vital pulp exposure, an application of a commercial calcium hydroxide product (Ca(OH)2). Both control and experimental treatments were followed by restoration with a commercial zinc oxide and eugenol obtundant intermediate restorative material and thermal insulator (ZOE). At 7 days there was 100% pulp vitality with HOTD and 50% with Ca(OH)2. New dentin formation was seen in 62.5% of the HOTD treated pulps and none of the Ca(OH)2 treatment group. The vital pulp exposures at day 21 post treatment with HOTD also showed significant improvement over Ca(OH)2 in the presence of odontoblasts, new dentin formation and pulp survivability. The presence of odontoblasts and new dentin was noted in 71% of the HOTD cases versus 50% of the survivable Ca(OH)2 cases. Furthermore, 100% of HOTD cases had vital pulps versus 62.5% of Ca(OH)2 cases. The 60-day specimens of both experimental and control techniques exhibited histologically similar appearances and were similar in outcomes. HOTD treatment at day 7 showed a significant positive difference, both in the formation of new dentin and tooth vitality. HOTD proved better for the post 21-day specimens and equivalent for the 60-day pulp specimens with no evidence of untoward tissue reactions or results.

  18. Can colorectal cancer be prevented or treated by oral hormone replacement therapy?

    PubMed Central

    Li, P.; Lin, J.E.; Schulz, S.; Pitari, G.M.; Waldman, S.A.

    2011-01-01

    Guanylyl cyclase C (GCC) is the receptor specifically expressed by intestinal cells for the paracrine hormones guanylin and uroguanylin and diarrheagenic bacterial heat-stable enterotoxins. This tissue-specific receptor coordinates lineage-dependent regulation of epithelial homeostasis, and its disruption contributes to intestinal tumorigenesis. It coordinates regenerative and metabolic circuits by restricting the cell cycle and proliferation and programming metabolic transitions central to organizing the dynamic crypt-surface axis. Further, mice deficient in GCC signaling are more susceptible to colon cancer induced by Apc mutations or the carcinogen azoxymethane. Moreover, guanylin and uroguanylin are gene products most commonly lost, early, in colon cancer in animals and humans. The role of GCC as a tumor suppressing receptor regulating proliferation and metabolism, together with the universal loss of guanylin and uroguanylin in tumorigenesis, suggests a model in which colorectal cancer is a paracrine hormone deficiency syndrome. In that context, activation of GCC reverses the tumorigenic phenotype by limiting growth of colorectal cancer cells by restricting progression through the G1/S transition and reprogramming metabolic circuits from glycolysis to oxidative phosphorylation, limiting bioenergetic support for rapid proliferation. These observations suggest a pathophysiological hypothesis in which GCC is a lineage-dependent tumor suppressing receptor coordinating proliferative homeostasis whose dysregulation through hormone loss contributes to neoplasia. The correlative therapeutic hypothesis suggests that colorectal cancer is a disease of hormone insufficiency that can be prevented or treated by oral supplementation with GCC ligands. PMID:20021465

  19. 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

  20. A critical assessment of oral care protocols for patients under radiation therapy in the regional University Hospital Network of Madrid (Spain)

    PubMed Central

    Lanzós, Isabel; Lanzós, Eduardo; Sanz, Mariano

    2015-01-01

    Background This research was aimed to critically evaluate, under the light of the available scientific evidence, the oral care protocols recommended by different hospitals in head and neck cancer (HNC) patients under radiation therapy. Material and Methods A questionnaire requesting all the relevant information for the oral care of these patients was sent to the 9 University Hospitals in Madrid. The answers were categorized and analyzed. In addition, an electronic search was conducted to identify the most relevant papers (systematic reviews [SR] and randomized clinical trials [RCTs]) assessing oral care protocols for patients treated for HNC with radiation therapy. Results Eight out of nine centers answered the questionnaire and the retrieved information was tabulated and compared. These recommendations were analyzed by a computerized search on MEDLINE and the Cochrane Oral Health Collaboration Database. The results of the analysis clearly shown a great heterogeneity, in terms of oral health care protocols, regarding the management of irradiated patients (for HNC) within the Hospitals of Madrid region. In addition, some of the recommendations lack solid scientific support. Conclusions The present survey revealed that the recommendations provided by the different hospitals were clearly different. The available evidence, supported by SR and RCTs, suggested the need of an oral assessment before cancer treatment, in order to prevent and treat dental pathologies and avoiding potential complications; during cancer treatment, it is relevant monitoring the patient in order to decrease the severity of the side effects, and to avoid any tooth extraction or surgery and special attention should be paid to mucositis, xerostomia and candidiasis; after cancer treatment, the following are relevant aspects: the risk of osteoradionecrosis, trismus, caries and the risks associated to dental implants. Key words:Head and neck cancer, supportive care in cancer, radiotherapy

  1. Effectiveness of sequential intravenous-to-oral antibiotic switch therapy in hospitalized patients with gram-positive infection: the SEQUENCE cohort study.

    PubMed

    Rodriguez-Pardo, D; Pigrau, C; Campany, D; Diaz-Brito, V; Morata, L; de Diego, I C; Sorlí, L; Iftimie, S; Pérez-Vidal, R; García-Pardo, G; Larrainzar-Coghen, T; Almirante, B

    2016-08-01

    Switching from intravenous to oral antibiotic therapy may improve inpatient management and reduce hospital stays and the complications of intravenous treatment. We aimed to assess the effectiveness of intravenous-to-oral antibiotic switch therapy and an early discharge algorithm in hospitalized patients with gram-positive infection. We performed a prospective cohort study with a retrospective comparison cohort, recruited from eight tertiary, acute-care Spanish referral hospitals. All patients included had culture-confirmed methicillin-resistant gram-positive infection, or methicillin-susceptible gram-positive infection and beta-lactam allergy and had received intravenous treatment with glycopeptides, lipopeptides, or linezolid. The study comprised two cohorts: the prospective cohort to assess the effectiveness of a sequential intravenous-to-oral antibiotic switch algorithm and early discharge, and a retrospective cohort in which the algorithm had not been applied, used as the comparator. A total of 247 evaluable patients were included; 115 in the prospective and 132 in the retrospective cohort. Forty-five retrospective patients (34 %) were not changed to oral antibiotics, and 87 (66 %) were changed to oral antibiotics without following the proposed algorithm. The duration of hospitalization was significantly shorter in the prospective cohort compared to the retrospective group that did not switch to oral drugs (16.7 ± 18.7 vs 23 ± 13.4 days, P  < 0.001). No differences were observed regarding the incidence of catheter-related bacteraemia (4.4 % vs 2.6 %, P = 0.621). Our results suggest that an intravenous-to-oral antibiotic switch strategy is effective for reducing the length of hospital stay in selected hospitalized patients with gram-positive infection.

  2. Impact of highly active antiretroviral therapy on oral manifestations of patients with human immunodeficiency virus/acquired immuno deficiency syndrome in South India

    PubMed Central

    Rao, K. V. S. Eswara; Chitturi, Ravi Teja; Kattappagari, Kiran Kumar; Kantheti, Lalith Prakash Chandra; Poosarla, Chandrasekhar; Baddam, Venkat Ramana Reddy

    2015-01-01

    Background: Human immunodeficiency virus (HIV) infection remains a global health problem, although the development of highly active antiretroviral therapy (HAART) has significantly modified the course of HIV disease into a manageable disease with improved quality-of-life mainly in the developed countries. Very few studies are available regarding effect of HAART on oral lesions in developing countries like India. Aims and Objectives: The aim was to document and compare oral lesions in HIV-seropositive patients before and after HAART. Materials and Methods: Oral manifestations were recorded in 320 HIV seropositive patients attending to the Voluntary Counseling and Confidential Testing Centre at the Government General Hospital, Guntur, before and after treating with HAART and the results were statistically analyzed using Student's t-test and Chi-square test. Results: Oral Candidiasis was significantly reduced in patients under HAART after 3 months. Furthermore, there was decreased incidence of periodontal diseases, but increased hyperpigmentation in patients undergoing HAART. Conclusion: The oral manifestations of HIV infection have changed due to the advent of HAART. Many opportunistic infections have resolved as a result of an improved immune system. Though the risk of hyperpigmentation in those with HAART has increased the prevalence of oral candidiasis and periodontal diseases were less in patients who had access to HAART. PMID:26392652

  3. Back to the future: oral targeted therapy for RA and other autoimmune diseases.

    PubMed

    O'Shea, John J; Laurence, Arian; McInnes, Iain B

    2013-03-01

    The molecular biology revolution coupled with the development of monoclonal antibody technology enabled remarkable progress in rheumatology therapy, comprising an array of highly effective biologic agents. With advances in understanding of the molecular nature of immune cell receptors came elucidation of intracellular signalling pathways downstream of these receptors. These discoveries raise the question of whether selective targeting of key intracellular factors with small molecules would add to the rheumatologic armamentarium. In this Review, we discuss several examples of this therapeutic strategy that seem to be successful, and consider their implications for the future of immune-targeted treatments. We focus on kinase inhibitors, primarily those targeting Janus kinase family members and spleen tyrosine kinase, given their advanced status in clinical development and application. We also summarize other targets involved in signalling pathways that might offer promise for therapeutic intervention in the future. PMID:23419429

  4. The use of rice seeds to produce human pharmaceuticals for oral therapy.

    PubMed

    Wakasa, Yuhya; Takaiwa, Fumio

    2013-10-01

    Rice (Oryza sativa L.) is the major staple food consumed by half of the world's population. Rice seeds have gained recent attention as bioreactors for the production of human pharmaceuticals such as therapeutic proteins or peptides. Rice seed production platforms have many advantages over animal cell or microbe systems in terms of cost-effectiveness, scalability, safety, product stability and productivity. Rice seed-based human pharmaceuticals are expected to become innovative therapies as edible drugs. Therapeutic proteins can be sequestered within natural cellular compartments in rice seeds and protected from harsh gastrointestinal environments. This review presents the state-of-the-art on the construction of gene cassettes for accumulation of pharmaceutical proteins or peptides in rice seeds, the generation of transgenic rice plants, and challenges involved in the use of rice seeds to produce human pharmaceuticals.

  5. Drug-induced sleep endoscopy as a selection tool for mandibular advancement therapy by oral device in patients with mild to moderate obstructive sleep apnoea.

    PubMed

    De Corso, E; Bastanza, G; Della Marca, G; Grippaudo, C; Rizzotto, G; Marchese, M R; Fiorita, A; Sergi, B; Meucci, D; Di Nardo, W; Paludetti, G; Scarano, E

    2015-12-01

    Nowadays oral appliance therapy is recognised as an effective therapy for many patients with primary snoring and mild to moderate obstructive sleep apnoea (OSA), as well as those with more severe OSA who cannot tolerate positive airway pressure (PAP) therapies. For this reason, it is important to focus on objective criteria to indicate which subjects may benefit from treatment with a mandibular advancement device (MAD). Various anthropometric and polysomnographic predictors have been described in the literature, whereas there are still controversies about the role of drug-induced sleep endoscopy (DISE) and advancement bimanual manoeuvre as predictor factors of treatment outcome by oral device. Herein, we report our experience in treatment of mild moderate OSA by oral appliance selected by DISE. We performed a single institution, longitudinal prospective evaluation of a consecutive group of mild moderate patients with obstructive sleep apnoea syndrome who underwent DISE. During sleep endoscopy, gentle manoeuvre of mandibular advancement less than 5 mm was performed. In 30 of 65 patients (46.2%) we obtained an unsuccessful improvement of airway patency whereas in 35 of 65 patients (53.8%) the improvement was successful and patients were considered suitable for oral device application. Because 7 of 35 patients were excluded due to conditions interfering with oral appliance therapy, we finally treated 28 patients. After 3 months of treatment, we observed a significant improvement in the Epworth medium index [(7.35 ± 2.8 versus 4.1 ± 2.2 (p < 0.05)], in mean AHI [(21.4 ± 6 events per hour versus 8.85 ± 6.9 (p < 0.05)] and in mean ODI [(18.6 ± 8 events per hour to 7 ± 5.8 (p < 0.05)]. We observed that the apnoea/hypopnoea index (AHI) improved by up to 50% from baseline in 71.4% of patients selected after DISE for MAD therapy. In the current study, mandibular advancement splint therapy was successfully prescribed on the basis not only of severity of disease, as

  6. Genetically-defined novel oral squamous cell carcinoma cell lines for the development of molecular therapies

    PubMed Central

    Fadlullah, Muhammad Zaki Hidayatullah; Chiang, Ivy Kim-Ni; Dionne, Kalen R.; Yee, Pei San; Gan, Chai Phei; Sam, Kin Kit; Tiong, Kai Hung; Ng, Adrian Kwok Wen; Martin, Daniel; Lim, Kue Peng; Kallarakkal, Thomas George; Mustafa, Wan Mahadzir Wan; Lau, Shin Hin; Abraham, Mannil Thomas; Zain, Rosnah Binti; Rahman, Zainal Ariff Abdul; Molinolo, Alfredo; Patel, Vyomesh; Gutkind, J. Silvio; Tan, Aik Choon; Cheong, Sok Ching

    2016-01-01

    Emerging biological and translational insights from large sequencing efforts underscore the need for genetically-relevant cell lines to study the relationships between genomic alterations of tumors, and therapeutic dependencies. Here, we report a detailed characterization of a novel panel of clinically annotated oral squamous cell carcinoma (OSCC) cell lines, derived from patients with diverse ethnicity and risk habits. Molecular analysis by RNAseq and copy number alterations (CNA) identified that the cell lines harbour CNA that have been previously reported in OSCC, for example focal amplications in 3q, 7p, 8q, 11q, 20q and deletions in 3p, 5q, 8p, 18q. Similarly, our analysis identified the same cohort of frequently mutated genes previously reported in OSCC including TP53, CDKN2A, EPHA2, FAT1, NOTCH1, CASP8 and PIK3CA. Notably, we identified mutations (MLL4, USP9X, ARID2) in cell lines derived from betel quid users that may be associated with this specific risk factor. Gene expression profiles of the ORL lines also aligned with those reported for OSCC. By focusing on those gene expression signatures that are predictive of chemotherapeutic response, we observed that the ORL lines broadly clustered into three groups (cell cycle, xenobiotic metabolism, others). The ORL lines noted to be enriched in cell cycle genes responded preferentially to the CDK1 inhibitor RO3306, by MTT cell viability assay. Overall, our in-depth characterization of clinically annotated ORL lines provides new insight into the molecular alterations synonymous with OSCC, which can facilitate in the identification of biomarkers that can be used to guide diagnosis, prognosis, and treatment of OSCC. PMID:27050151

  7. A histologic assessment of a HYBENX® oral tissue decontaminant in vital pulp therapy in dogs.

    PubMed

    Rohrer, M D; Prasad, H S; Savord, E G

    2016-01-01

    The aim of this study was to assess HYBENX® Oral Tissue Decontaminant (HOTD) in treating vital pulp exposure in a canine model. The use of HOTD solution was compared to an accepted and standard regimen for vital pulp exposure, an application of a commercial calcium hydroxide product (Ca(OH)2). Both control and experimental treatments were followed by restoration with a commercial zinc oxide and eugenol obtundant intermediate restorative material and thermal insulator (ZOE). At 7 days there was 100% pulp vitality with HOTD and 50% with Ca(OH)2. New dentin formation was seen in 62.5% of the HOTD treated pulps and none of the Ca(OH)2 treatment group. The vital pulp exposures at day 21 post treatment with HOTD also showed significant improvement over Ca(OH)2 in the presence of odontoblasts, new dentin formation and pulp survivability. The presence of odontoblasts and new dentin was noted in 71% of the HOTD cases versus 50% of the survivable Ca(OH)2 cases. Furthermore, 100% of HOTD cases had vital pulps versus 62.5% of Ca(OH)2 cases. The 60-day specimens of both experimental and control techniques exhibited histologically similar appearances and were similar in outcomes. HOTD treatment at day 7 showed a significant positive difference, both in the formation of new dentin and tooth vitality. HOTD proved better for the post 21-day specimens and equivalent for the 60-day pulp specimens with no evidence of untoward tissue reactions or results. PMID:27469568

  8. Impact of all oral anti-hepatitis C virus therapy: A meta-analysis

    PubMed Central

    Bansal, Siddharth; Singal, Ashwani K; McGuire, Brendan M; Anand, Bhupinder S

    2015-01-01

    AIM: To investigate the efficacy, safety, and cost of treatment of direct acting antivirals (DAAs) with and without peg interferon alfa2a (P), and/or ribavirin (R) in treating hepatitis C virus (HCV) genotype 1 patients. METHODS: MEDLINE was searched for randomized controlled trials (RCT) using DAAs for HCV treatment. Phase 1 trials and studies with investigational drugs on genotype 2 or 3, and on human immunodeficiency virus patients were excluded. Data were pooled for sustained virologic response (SVR), serious adverse effects, and drug discontinuation rate on various treatment arms in trials: P + R; 1st generation DAA (telaprevir or boceprevir) + P + R; 2nd generation DAA (sofosbuvir or simeprevir) + P + R; 2nd generation DAA + R; two 2nd generation DAA + R; and two 2nd gen DAA. Data were analyzed separately for each arm for treatment naive and non-responders (NR) to previous treatment. The cost of treatment with each regimen for achieving one SVR was also compared. RESULTS: Twenty three RCTs (n = 9354, 62% male, 11% cirrhosis) were analyzed. All oral (P free) regimens with combination of 2 DAA achieved SVR above 95%. The cost of treatment to achieve an SVR with DAA based regimens was lower for NR compared to P+R regimen. However, the cost per SVR remained higher for treatment naive patients. CONCLUSION: Second generation and emerging DAAs are promising agents in HCV treatment, with a very high level of safety and efficacy. An important drawback is their high cost. However, the present meta-analysis shows that the cost per SVR for non responders (but not for naive patients) was lower compared to P + R. This finding together with the superior safety profile and better compliance makes these drugs highly attractive. It is possible that further reduction in treatment duration may make them even more cost effective. PMID:25914781

  9. Carnitine Acetyltransferase Mitigates Metabolic Inertia and Muscle Fatigue during Exercise.

    PubMed

    Seiler, Sarah E; Koves, Timothy R; Gooding, Jessica R; Wong, Kari E; Stevens, Robert D; Ilkayeva, Olga R; Wittmann, April H; DeBalsi, Karen L; Davies, Michael N; Lindeboom, Lucas; Schrauwen, Patrick; Schrauwen-Hinderling, Vera B; Muoio, Deborah M

    2015-07-01

    Acylcarnitine metabolites have gained attention as biomarkers of nutrient stress, but their physiological relevance and metabolic purpose remain poorly understood. Short-chain carnitine conjugates, including acetylcarnitine, derive from their corresponding acyl-CoA precursors via the action of carnitine acetyltransferase (CrAT), a bidirectional mitochondrial matrix enzyme. We show here that contractile activity reverses acetylcarnitine flux in muscle, from net production and efflux at rest to net uptake and consumption during exercise. Disruption of this switch in mice with muscle-specific CrAT deficiency resulted in acetyl-CoA deficit, perturbed energy charge, and diminished exercise tolerance, whereas acetylcarnitine supplementation produced opposite outcomes in a CrAT-dependent manner. Likewise, in exercise-trained compared to untrained humans, post-exercise phosphocreatine recovery rates were positively associated with CrAT activity and coincided with dramatic shifts in muscle acetylcarnitine dynamics. These findings show acetylcarnitine serves as a critical acetyl buffer for working muscles and provide insight into potential therapeutic strategies for combatting exercise intolerance. PMID:26154055

  10. PILOT EVALUATION OF A SIMPLE ADJUNCTIVE METHOD FOR IMPROVED REMOVAL OF ORAL BIOFILM DURING CONVENTIONAL SCALING AND ROOT PLANING THERAPY.

    PubMed

    Bracke, J; Basara, M; Savord, E; Dunaway, A; Watkins, M

    2015-01-01

    Various studies have evaluated the adjunctive use of chemical and antimicrobial treatments to assist in the mechanical removal of oral microbial biofilm from tissue surfaces during scaling and root planning therapy (SRP). The current study demonstrates the elimination of two classes of surrogate molecular markers from periodontal disease sites. This suggests the current agent may be a more effective adjunctive cleansing agent for complete biofilm removal. A patient with advanced chronic periodontitis was subjected to standard SRP therapy, supplemented by irrigation with HYBENX® (HBX). Samples of gingival crevicular fluid were collected with triplicate absorbent paper points from each of three quadrants at three time points: 1) at baseline prior to treatment; 2) after irrigation with the topical agent for 20 seconds and rinsing; and 3) after SRP followed by a second irrigation/rinsing treatment with the agent. Paper points were extracted to assess the presence of 13 bacterial species known to be primarily associated with periodontal disease using DNA pyrosequencing. In addition, the presence of Matrix Metalloproteinase-8 (MMP8), as well as IL-1ß, IL-6, and TNF-alpha were also assessed by immunoassay of the paper point sample extracts. The combined adjunctive treatment indicated a complete absence of detectable bacterial DNA and the four inflammatory mediators from samples taken from the gingival sulci treated with HBX. The advantage of the current adjunctive topical treatment technique is that it is simple and easy to administer in conjunction with standard SRP techniques. It appears to provide a level of cleanliness not currently achieved with other SRP adjunctive procedures.

  11. Effects of oral motor exercises and laser therapy on chronic temporomandibular disorders: a randomized study with follow-up.

    PubMed

    Machado, Barbara Cristina Zanandréa; Mazzetto, Marcelo Oliveira; Da Silva, Marco Antonio M Rodrigues; de Felício, Cláudia Maria

    2016-07-01

    This study investigated the efficacy of combining low-level laser therapy (LLLT) with oral motor exercises (OM-exercises) for rehabilitation of patients with chronic temporomandibular disorders (TMDs). Eighty-two patients with chronic TMD and 20 healthy subjects (control group) participated in the study. Patients were randomly assigned to treatment groups: GI (LLLT + OM exercises), GII (orofacial myofunctional therapy-OMT-which contains pain relief strategies and OM-exercises), and GIII (LLLT placebo + OM-exercises) and GIV (LLLT). LLLT (AsGaAl; 780-nm wavelength; average power of 60 mW, 40 s, and 60 ± 1.0 J/cm²) was used to promote analgesia, while OM-exercises were used to reestablish the orofacial functions. Evaluations at baseline (T1), after treatment immediate (T2), and at follow-up (T3) were muscle and joint tenderness to palpation, TMD severity, and orofacial myofunctional status. There was a significant improvement in outcome measures in all treated groups with stability at follow-up (Friedman test, P < 0.05), but GIV did not show difference in orofacial functions after LLLT (P > 0.05). Intergroup comparisons showed that all treated groups had no difference in tenderness to palpation of temporal muscle compared to GC at follow-up (Kruskal-Wallis test, P < 0.01). Moreover, GI, GII, and GIII showed no difference from GC in orofacial functional condition (T2 and T3) while they differed significantly from GIV (P < 0.01). In conclusion, LLLT combined with OM-exercises was more effective in promoting TMD rehabilitation than LLLT alone was. Similar treatment results were verified with the OMT protocol. PMID:27085322

  12. Comparison of coronary angiography and early oral dipyridamole thallium-201 scintigraphy in patients receiving thrombolytic therapy for acute myocardial infarction

    SciTech Connect

    Jain, A.; Hicks, R.R.; Myers, G.H.; McCarthy, J.J.; Perry, J.R.; Adams, K.F. )

    1990-10-01

    We evaluated 50 consecutive patients who received thrombolytic therapy for acute myocardial infarction using thallium-201 single photon emission computed tomography in combination with oral dipyridamole to assess the frequency of residual myocardial ischemia. Thallium studies were performed early after myocardial infarction at a mean of 4.6 days. The time from the onset of chest pain to the administration of thrombolytic therapy was 2.6 hours (range 0.5 to 5.5). Q wave myocardial infarction was evident in 46 patients; four patients had a non-Q wave infarction (anterior infarction in 31 patients and inferior infarction in 19 patients). The serum mean peak creatinine kinase was 1503 IU/L (range 127 to 6500). Coronary angiography was performed in all patients at a mean of 3.1 days (range 2 to 10) and revealed the infarct-related vessel to be patent in 36 patients (72%). The ejection fraction was 48% (range 26% to 67%). After dipyridamole administration, 13 patients (26%) developed angina that was easily reversed with the administration of intravenous aminophylline. Systolic blood pressure decreased from 122 to 115 mm Hg (p less than 0.05) and the heart rate increased from 76 to 85 beats/min (p less than 0.05). None of the patients had significant hypotension, arrhythmias, or evidence of infarct extension. Perfusion abnormalities were present on the initial thallium images in 48 patients. Redistribution suggestive of ischemia was present in 36 patients (72%). Ischemia confined to the vascular distribution of the infarct vessel was evident in 22 patients. Seven patients had ischemia in the infarct zone as well as in a remote myocardial segment. Thus 29 patients (58%) had ischemia in the distribution of the infarct vessel. Ischemia in the infarct zone was evident in 19 of 36 patients with open infarct vessels and in 10 of 14 patients with occluded infarct vessels.

  13. Safety of Hormonal Replacement Therapy and Oral Contraceptives in Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis

    PubMed Central

    Rojas-Villarraga, Adriana; Torres-Gonzalez, July-Vianneth; Ruiz-Sternberg, Ángela-María

    2014-01-01

    Background There is conflicting data regarding exogenous sex hormones [oral contraceptives (OC) and hormonal replacement therapy (HRT)] exposure and different outcomes on Systemic Lupus Erythematosus (SLE). The aim of this work is to determine, through a systematic review and meta-analysis the risks associated with estrogen use for women with SLE as well as the association of estrogen with developing SLE. Methods and Findings MEDLINE, EMBASE, SciElo, BIREME and the Cochrane library (1982 to July 2012), were databases from which were selected and reviewed (PRISMA guidelines) randomized controlled trials, cross-sectional, case-control and prospective or retrospective nonrandomized, comparative studies without language restrictions. Those were evaluated by two investigators who extracted information on study characteristics, outcomes of interest, risk of bias and summarized strength of evidence. A total of 6,879 articles were identified; 20 full-text articles were included. Thirty-two meta-analyses were developed. A significant association between HRT exposure (Random model) and an increased risk of developing SLE was found (Rate Ratio: 1.96; 95%-CI: 1.51–2.56; P-value<0.001). One of eleven meta-analyses evaluating the risk for SLE associated with OC exposure had a marginally significant result. There were no associations between HRT or OC exposure and specific outcomes of SLE. It was not always possible to Meta-analyze all the available data. There was a wide heterogeneity of SLE outcome measurements and estrogen therapy administration. Conclusion An association between HRT exposure and SLE causality was observed. No association was found when analyzing the risk for SLE among OC users, however since women with high disease activity/Thromboses or antiphospholipid-antibodies were excluded from most of the studies, caution should be exercised in interpreting the present results. To identify risk factors that predispose healthy individuals to the development of SLE who

  14. Drug persistence with rivaroxaban therapy in atrial fibrillation patients—results from the Dresden non-interventional oral anticoagulation registry

    PubMed Central

    Beyer-Westendorf, Jan; Förster, Kati; Ebertz, Franziska; Gelbricht, Vera; Schreier, Thomas; Göbelt, Maria; Michalski, Franziska; Endig, Heike; Sahin, Kurtulus; Tittl, Luise; Weiss, Norbert

    2015-01-01

    Aims Worldwide, rivaroxaban is increasingly used for stroke prevention in atrial fibrillation (SPAF) but little is known about the rates of or reasons for rivaroxaban discontinuations in daily care. Using data from a prospective, non-interventional oral anticoagulation (NOAC) registry, we analysed rivaroxaban treatment persistence. Methods and results Persistence with rivaroxaban in SPAF was assessed in an ongoing, prospective, non-interventional registry of >2600 NOAC patients from daily care using the Kaplan–Meier time-to-first-event analysis. Reasons for and management of rivaroxaban discontinuation were assessed. Potential baseline risk factors for treatment discontinuation were evaluated using Cox regression analysis. Between October 2011 and April 2014, 1204 rivaroxaban SPAF patients were enrolled [39.3% switched from vitamin K antagonists (VKAs) and 60.7% newly treated patients]. Of these, 223 patients (18.5%) stopped rivaroxaban during follow-up (median 544 days), which translates into a discontinuation rate of 13.6 (95% CI 11.8–15.4) per 100 patient-years. Most common reasons for treatment discontinuations were bleeding complications (30% of all discontinuations), followed by other side-effects (24.2%) and diagnosis of stable sinus rhythm (9.9%). A history of chronic heart failure (HR 1.43; 95% CI 1.09–1.87; P = 0.009) or diabetes (HR 1.39; 95% CI 1.06–1.82; P = 0.018) were the only statistically significant baseline risk factors for rivaroxaban discontinuation. After discontinuation of rivaroxaban, patients received antiplatelet therapy (31.8%), VKA (24.2%), another NOAC (18.4%), heparin (9.9%), or nothing (15.7%). Conclusion Our data indicate that overall persistence with rivaroxaban therapy is high, with a discontinuation rate of ∼15% in the first year of treatment and few additional discontinuations thereafter. PMID:25694537

  15. Cryoprotective effect of L-carnitine on motility, vitality and DNA oxidation of human spermatozoa.

    PubMed

    Banihani, S; Agarwal, A; Sharma, R; Bayachou, M

    2014-08-01

    Successful cryopreservation for human spermatozoa markedly influences the reproductive outcomes of assisted reproductive technologies. But in spite of its usefulness, cryopreservation significantly decreases sperm quality. l-carnitine has been found to improve the quality of spermatozoa in selected cases with male infertility. Here, we examined the efficacy of l-carnitine in improving sperm motility and vitality and reducing sperm DNA oxidation during cryopreservation. Semen samples from infertile patients (n = 22) were collected and analysed. Cryopreservation medium supplemented with l-carnitine was mixed with the semen at a ratio of 1 : 1 (v/v). The final l-carnitine concentration in each cryovial was 0.5 mg ml(-1) per 5 × 10(6) cell ml(-1) . Controls were cryopreserved without addition of l-carnitine. After 24 h of cryopreservation, thawed sperm samples were analysed for motility, vitality and DNA oxidation. Sperm vitality was assessed by the eosin-nigrosin test, while sperm DNA oxidation was measured by flow cytometry. Addition of l-carnitine significantly improved sperm motility and vitality (P < 0.05) compared with the control. The flow cytometry experiment showed no statistical difference (P > 0.05) in the levels of DNA oxidation between samples and controls. In conclusion, l-carnitine improves human sperm motility and vitality, but has no effect on sperm DNA oxidation after cryopreservation.

  16. Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease.

    PubMed

    Kathirvel, Elango; Morgan, Kengathevy; French, Samuel W; Morgan, Timothy R

    2013-11-01

    Mitochondrial abnormalities are suggested to be associated with the development of nonalcoholic fatty liver. Liver mitochondrial content and function have been shown to improve in oral feeding of acetyl-L-carnitine (ALC) to rodents. Carnitine is involved in the transport of acyl-coenzyme A across the mitochondrial membrane to be used in mitochondrial β-oxidation. We hypothesized that oral administration ALC with the antioxidant lipoic acid (ALC + LA) would benefit nonalcoholic fatty liver. To test our hypothesis, we fed Balb/C mice a standard diet (SF) or SF with ALC + LA or high-fat diet (HF) or HF with ALC + LA for 6 months. Acetyl-L-carnitine and LA were dissolved at 0.2:0.1% (wt/vol) in drinking water, and mice were allowed free access to food and water. Along with physical parameters, insulin resistance (blood glucose, insulin, glucose tolerance), liver function (alanine transaminase [ALT], aspartate transaminase [AST]), liver histology (hematoxylin and eosin), oxidative stress (malondialdehyde), and mitochondrial abnormalities (carbamoyl phosphate synthase 1 and electron microscopy) were done. Compared with SF, HF had higher body, liver, liver-to-body weight ratio, white adipose tissue, ALT, AST, liver fat, oxidative stress, and insulin resistance. Coadministration of ALC + LA to HF animals significantly improved the mitochondrial marker carbamoyl phosphate synthase 1 and the size of the mitochondria in liver. Alanine transaminase and AST levels were decreased. In a nonalcoholic fatty liver mice model, ALC + LA combination improved liver mitochondrial content, size, serum ALT, and AST without significant changes in oxidative stress, insulin resistance, and liver fat accumulation. PMID:24176233

  17. Reconstruction of the carnitine biosynthesis pathway from Neurospora crassa in the yeast Saccharomyces cerevisiae.

    PubMed

    Franken, Jaco; Burger, Anita; Swiegers, Jan H; Bauer, Florian F

    2015-08-01

    Industrial synthesis of L-carnitine is currently performed by whole-cell biotransformation of industrial waste products, mostly D-carnitine and cronobetaine, through specific bacterial species. No comparable system has been established using eukaryotic microorganisms, even though there is a significant and growing international demand for either the pure compound or carnitine-enriched consumables. In eukaryotes, including the fungus Neurospora crassa, L-carnitine is biosynthesized through a four-step metabolic conversion of trimethyllysine to L-carnitine. In contrast, the industrial yeast, Saccharomyces cerevisiae lacks the enzymes of the eukaryotic biosynthesis pathway and is unable to synthesize carnitine. This study describes the cloning of all four of the N. crassa carnitine biosynthesis genes and the reconstruction of the entire pathway in S. cerevisiae. The engineered yeast strains were able to catalyze the synthesis of L-carnitine, which was quantified using hydrophilic interaction liquid chromatography electrospray ionization mass spectrometry (HILIC-ESI-MS) analyses, from trimethyllysine. Furthermore, the yeast threonine aldolase Gly1p was shown to effectively catalyze the second step of the pathway, fulfilling the role of a serine hydroxymethyltransferase. The analyses also identified yeast enzymes that interact with the introduced pathway, including Can1p, which was identified as the yeast transporter for trimethyllysine, and the two yeast serine hydroxymethyltransferases, Shm1p and Shm2p. Together, this study opens the possibility of using an engineered, carnitine-producing yeast in various industrial applications while providing insight into possible future strategies aimed at tailoring the production capacity of such strains.

  18. In vivo Biocompatibility, Biodistribution and Therapeutic Efficiency of Titania Coated Upconversion Nanoparticles for Photodynamic Therapy of Solid Oral Cancers.

    PubMed

    Lucky, Sasidharan Swarnalatha; Idris, Niagara Muhammad; Huang, Kai; Kim, Jaejung; Li, Zhengquan; Thong, Patricia Soo Ping; Xu, Rong; Soo, Khee Chee; Zhang, Yong

    2016-01-01

    Despite the advantages of using photodynamic therapy (PDT) for the treatment of head and neck tumors, it can only be used to treat early stage flat lesions due to the limited tissue penetration ability of the visible light. Here, we developed near-infrared (NIR) excitable upconversion nanoparticle (UCN) based PDT agent that can specifically target epithelial growth factor receptor (EGFR) overexpressing oral cancer cells, in a bid to widen the application of PDT against thick and solid advanced or recurrent head and neck cancers. In vivo studies using the synthesized anti-EGFR-PEG-TiO2-UCNs following systemic administration displayed no major sub-acute or long term toxic effects in terms of blood biochemical, hematological or histopathological changes at a concentration of 50 mg/kg. NIR-PDT even in the presence of a 10 mm tissue phantom placed over the xenograft tumor, showed significant delay in tumor growth and improved survival rate compared to conventional chlorin-e6 (Ce6) PDT using 665 nm red light. Our work, one of the longest study till date in terms of safety (120 d), PDT efficacy (35 d) and survival (60 d), demonstrates the usefulness of UCN based PDT technology for targeted treatment of thick and bulky head and neck tumors.

  19. In vivo Biocompatibility, Biodistribution and Therapeutic Efficiency of Titania Coated Upconversion Nanoparticles for Photodynamic Therapy of Solid Oral Cancers.

    PubMed

    Lucky, Sasidharan Swarnalatha; Idris, Niagara Muhammad; Huang, Kai; Kim, Jaejung; Li, Zhengquan; Thong, Patricia Soo Ping; Xu, Rong; Soo, Khee Chee; Zhang, Yong

    2016-01-01

    Despite the advantages of using photodynamic therapy (PDT) for the treatment of head and neck tumors, it can only be used to treat early stage flat lesions due to the limited tissue penetration ability of the visible light. Here, we developed near-infrared (NIR) excitable upconversion nanoparticle (UCN) based PDT agent that can specifically target epithelial growth factor receptor (EGFR) overexpressing oral cancer cells, in a bid to widen the application of PDT against thick and solid advanced or recurrent head and neck cancers. In vivo studies using the synthesized anti-EGFR-PEG-TiO2-UCNs following systemic administration displayed no major sub-acute or long term toxic effects in terms of blood biochemical, hematological or histopathological changes at a concentration of 50 mg/kg. NIR-PDT even in the presence of a 10 mm tissue phantom placed over the xenograft tumor, showed significant delay in tumor growth and improved survival rate compared to conventional chlorin-e6 (Ce6) PDT using 665 nm red light. Our work, one of the longest study till date in terms of safety (120 d), PDT efficacy (35 d) and survival (60 d), demonstrates the usefulness of UCN based PDT technology for targeted treatment of thick and bulky head and neck tumors. PMID:27570555

  20. Fragment-based drug design and identification of HJC0123, a novel orally bioavailable STAT3 inhibitor for cancer therapy.

    PubMed

    Chen, Haijun; Yang, Zhengduo; Ding, Chunyong; Chu, Lili; Zhang, Yusong; Terry, Kristin; Liu, Huiling; Shen, Qiang; Zhou, Jia

    2013-04-01

    Fragment-based drug design (FBDD) is a promising approach for the generation of lead molecules with enhanced activity and especially drug-like properties against therapeutic targets. Herein, we report the fragment-based drug design, systematic chemical synthesis and pharmacological evaluation of novel scaffolds as potent anticancer agents by utilizing six privileged fragments from known STAT3 inhibitors. Several new molecules such as compounds 5, 12, and 19 that may act as advanced chemical leads have been identified. The most potent compound 5 (HJC0123) has demonstrated to inhibit STAT3 promoter activity, downregulate phosphorylation of STAT3, increase the expression of cleaved caspase-3, inhibit cell cycle progression and promote apoptosis in breast and pancreatic cancer cells with low micromolar to nanomolar IC50 values. Furthermore, compound 5 significantly suppressed estrogen receptor (ER)-negative breast cancer MDA-MB-231 xenograft tumor growth in vivo (p.o.), indicating its great potential as an efficacious and orally bioavailable drug candidate for human cancer therapy. PMID:23416191

  1. Oral rehydration therapy: a community trial comparing the acceptability of homemade sucrose and cereal-based solutions.

    PubMed

    Chowdhury, A M; Karim, F; Rohde, J E; Ahmed, J; Abed, F H

    1991-01-01

    Sugar-based oral rehydration therapy (ORT) for diarrhoea is promoted in many countries of the world. One programme in Bangladesh has instructed more than 13 million mothers in the preparation of a sugar-salt solution in the home; despite very high rates of correct mixing and knowledge, subsequent application was found in only some 20% of all diarrhoea episodes. Since rice is far more available in rural homes (95%) than any type of sugar (30%) and rice gruel is a widely accepted food during illness, a field trial was conducted in three areas (total population, 68,345) to compare the acceptability and use of rice-based ORT with that of sugar-based ORT. Although the mothers unanimously agreed that the rice-based solutions "stopped" the diarrhoea more quickly, they used the sugar-based solutions twice as often (in 40% of severe watery episodes) as the rice-based solutions (in 18%), because the rice-ORT was much more time-consuming and difficult to prepare. The observed reduced utilization of home-made rice-ORT makes it a poor substitute for sugar-ORT at the community level in rural Bangladesh.

  2. In vivo Biocompatibility, Biodistribution and Therapeutic Efficiency of Titania Coated Upconversion Nanoparticles for Photodynamic Therapy of Solid Oral Cancers

    PubMed Central

    Lucky, Sasidharan Swarnalatha; Idris, Niagara Muhammad; Huang, Kai; Kim, Jaejung; Li, Zhengquan; Thong, Patricia Soo Ping; Xu, Rong; Soo, Khee Chee; Zhang, Yong

    2016-01-01

    Despite the advantages of using photodynamic therapy (PDT) for the treatment of head and neck tumors, it can only be used to treat early stage flat lesions due to the limited tissue penetration ability of the visible light. Here, we developed near-infrared (NIR) excitable upconversion nanoparticle (UCN) based PDT agent that can specifically target epithelial growth factor receptor (EGFR) overexpressing oral cancer cells, in a bid to widen the application of PDT against thick and solid advanced or recurrent head and neck cancers. In vivo studies using the synthesized anti-EGFR-PEG-TiO2-UCNs following systemic administration displayed no major sub-acute or long term toxic effects in terms of blood biochemical, hematological or histopathological changes at a concentration of 50 mg/kg. NIR-PDT even in the presence of a 10 mm tissue phantom placed over the xenograft tumor, showed significant delay in tumor growth and improved survival rate compared to conventional chlorin-e6 (Ce6) PDT using 665 nm red light. Our work, one of the longest study till date in terms of safety (120 d), PDT efficacy (35 d) and survival (60 d), demonstrates the usefulness of UCN based PDT technology for targeted treatment of thick and bulky head and neck tumors. PMID:27570555

  3. Oral delivery of nanoparticles containing anticancer SN38 and hSET1 antisense for dual therapy of colon cancer.

    PubMed

    Dinarvand, M; Kiani, M; Mirzazadeh, F; Esmaeili, A; Mirzaie, Z; Soleimani, M; Dinarvand, R; Atyabi, F

    2015-01-01

    An oral delivery system intended for treatment of colon cancer in HT29 cancerous cells was investigated by encapsulating hSET1 antisense and SN38 anticancer in nanoparticles based on cysteine trimethyl chitosan (cysTMC) and carboxymethyl dextran (CMD). Studies have shown hSET1 as the main type of histone methyltransferase (HMT) complex, is significantly overexpressed in malignant cells. In this study, hSET1 antisense was employed to inhibit gene expression. Additionally, SN38 was incorporated into nanoparticles to enhance the efficiency of the system by inhibition of topoisomerase 1. CysTMC was synthetized and characterized by (1)H NMR and FTIR. Nanoparticles were prepared through complexation of CMD and cysTMC. Particle size and surface charge was 100-150 nm and 17-21 mV respectively with drug content of around 2.6%. Gel electrophoresis assay proved the stability of antisense in simulated gastric and intestinal fluids. Nanoparticles showed high mucoadhesion and glutathione responsive release. Cellular uptake was observed by confocal microscopy and quantified by flow cytometry. Cytotoxicity of NPs was assessed using MTT assay. Results showed hSET1/SN38 nanoparticles had significantly higher cytotoxicity against HT29 cells compared with nanoparticles containing SN38, free SN38 or naked hSET1. Therefore, present system could be considered an effective combination therapy of highly hydrophobic SN38 and hSET1.

  4. Oral delivery of nanoparticles containing anticancer SN38 and hSET1 antisense for dual therapy of colon cancer.

    PubMed

    Dinarvand, M; Kiani, M; Mirzazadeh, F; Esmaeili, A; Mirzaie, Z; Soleimani, M; Dinarvand, R; Atyabi, F

    2015-01-01

    An oral delivery system intended for treatment of colon cancer in HT29 cancerous cells was investigated by encapsulating hSET1 antisense and SN38 anticancer in nanoparticles based on cysteine trimethyl chitosan (cysTMC) and carboxymethyl dextran (CMD). Studies have shown hSET1 as the main type of histone methyltransferase (HMT) complex, is significantly overexpressed in malignant cells. In this study, hSET1 antisense was employed to inhibit gene expression. Additionally, SN38 was incorporated into nanoparticles to enhance the efficiency of the system by inhibition of topoisomerase 1. CysTMC was synthetized and characterized by (1)H NMR and FTIR. Nanoparticles were prepared through complexation of CMD and cysTMC. Particle size and surface charge was 100-150 nm and 17-21 mV respectively with drug content of around 2.6%. Gel electrophoresis assay proved the stability of antisense in simulated gastric and intestinal fluids. Nanoparticles showed high mucoadhesion and glutathione responsive release. Cellular uptake was observed by confocal microscopy and quantified by flow cytometry. Cytotoxicity of NPs was assessed using MTT assay. Results showed hSET1/SN38 nanoparticles had significantly higher cytotoxicity against HT29 cells compared with nanoparticles containing SN38, free SN38 or naked hSET1. Therefore, present system could be considered an effective combination therapy of highly hydrophobic SN38 and hSET1. PMID:25858880

  5. Fragment-based drug design and identification of HJC0123, a novel orally bioavailable STAT3 inhibitor for cancer therapy

    PubMed Central

    Chen, Haijun; Yang, Zhengduo; Ding, Chunyong; Chu, Lili; Zhang, Yusong; Terry, Kristin; Liu, Huiling; Shen, Qiang; Zhou, Jia

    2013-01-01

    Fragment-based drug design (FBDD) is a promising approach for the generation of lead molecules with enhanced activity and especially drug-like properties against therapeutic targets. Herein, we report the fragment-based drug design, systematic chemical synthesis and pharmacological evaluation of novel scaffolds as potent anticancer agents by utilizing six privileged fragments from known STAT3 inhibitors. Several new molecules such as compounds 5, 12, and 19 that may act as advanced chemical leads have been identified. The most potent compound 5 (HJC0123) has demonstrated to inhibit STAT3 promoter activity, downregulate phosphorylation of STAT3, increase the expression of cleaved caspase-3, inhibit cell cycle progression and promote apoptosis in breast and pancreatic cancer cells with low micromolar to nanomolar IC50 values. Furthermore, compound 5 significantly suppressed estrogen receptor (ER)-negative breast cancer MDA-MB-231 xenograft tumor growth in vivo (p.o.), indicating its great potential as an efficacious and orally bioavailable drug candidate for human cancer therapy. PMID:23416191

  6. Presence of the carcinogen N'-nitrosonornicotine in the urine of some users of oral nicotine replacement therapy products.

    PubMed

    Stepanov, Irina; Carmella, Steven G; Briggs, Anna; Hertsgaard, Louise; Lindgren, Bruce; Hatsukami, Dorothy; Hecht, Stephen S

    2009-11-01

    N'-nitrosonornicotine (NNN) is a strong carcinogen present in unburned tobacco and cigarette smoke. We here analyze data obtained in two studies, in which a biomarker of exposure to NNN--the sum of NNN and its pyridine-N-glucuronide, called total NNN--was quantified in the urine of people who had stopped smoking and used various nicotine replacement therapy (NRT) products. In 13 of 34 nicotine gum or lozenge users from both studies, total NNN at one or more time points after biochemically confirmed smoking cessation was comparable with, or considerably higher than, the baseline levels. For most of the subjects who used the nicotine patch as a smoking cessation aid, urinary total NNN at all post-quit time points was <37% of their mean baseline levels. These results indicate that endogenous formation of significant amounts of NNN may occur sporadically in some users of oral NRT. Given the carcinogenicity of NNN and the frequent use of nicotine gum as a smoking cessation aid, further studies are needed so that preventive measures can be developed. PMID:19843845

  7. In Vitro effect of low-level laser therapy on typical oral microbial biofilms.

    PubMed

    Basso, Fernanda G; Oliveira, Camila F; Fontana, Amanda; Kurachi, Cristina; Bagnato, Vanderlei S; Spolidório, Denise M P; Hebling, Josimeri; de Souza Costa, Carlos A

    2011-01-01

    The aim of this study was to evaluate the effect of specific parameters of low-level laser therapy (LLLT) on biofilms formed by Streptococcus mutans, Candida albicans or an association of both species. Single and dual-species biofilms--SSB and DSB--were exposed to laser doses of 5, 10 or 20 J/cm(2) from a near infrared InGaAsP diode laser prototype (LASERTable; 780 ± 3 nm, 0.04 W). After irradiation, the analysis of biobilm viability (MTT assay), biofilm growth (cfu/mL) and cell morphology (SEM) showed that LLLT reduced cell viability as well as the growth of biofilms. The response of S. mutans (SSB) to irradiation was similar for all laser doses and the biofilm growth was dose dependent. However, when associated with C. albicans (DSB), S. mutans was resistant to LLLT. For C. albicans, the association with S. mutans (DSB) caused a significant decrease in biofilm growth in a dose-dependent fashion. The morphology of the microorganisms in the SSB was not altered by LLLT, while the association of microbial species (DSB) promoted a reduction in the formation of C. albicans hyphae. LLLT had an inhibitory effect on the microorganisms, and this capacity can be altered according to the interactions between different microbial species.

  8. Delmopinol-induced matrix removal facilitates photodynamic therapy and chlorhexidine methods for disinfecting mixed oral biofilms

    NASA Astrophysics Data System (ADS)

    Rogers, Stephen Christopher

    It is often observed that the slimy matrixes of various bacterial-formed biofilms can limit their disinfection. This investigation demonstrated that disinfection effectiveness by either photodynamic therapy (PDT) or chlorhexidine irrigation is significantly improved by collapse of that matrix using the non-bactericidal reagent delmopinol as part of the treatment sequence. Cyclic shear-producing conditions were used to grow 4-day, whole salivary and growth media biofilms on glow-discharge-treated polystyrene (N=46) and mini-germanium internal reflection prisms to serve in a periodontal crypt model of disinfection by either methylene-blue-mediated PDT or by chlorhexidine irrigation. Assays for bacterial viability, with and without treatments, were performed by alamarBlueRTM fluorescent methods, statistically applied (ANOVA, Tukey's HSD). Multiple Attenuated Internal Reflection Infrared (MAIR-IR) assays confirmed selective removal of the predominantly polysaccharide matrix materials by the delmopinol treatment, but not by equivalent water or chlorhexidine methods. Confocal-IR microscopy showed that the delmopinol reagent, alone, caused about one-third of each wet biofilm to be removed, while bacterial re-growth was confirmed by alamarBlueRTM assay. Chlorhexidine and PDT suppression of bacterial activity without regrowth was significantly improved with the added delmopinol treatment, and is likely to provide similarly beneficial results in the effective disinfection of diverse biofilms in many settings.

  9. Intraoperative optical assessment of photodynamic therapy response of superficial oral squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Rohrbach, Daniel J.; Rigual, Nestor; Arshad, Hassan; Tracy, Erin C.; Cooper, Michelle T.; Shafirstein, Gal; Wilding, Gregory; Merzianu, Mihai; Baumann, Heinz; Henderson, Barbara W.; Sunar, Ulas

    2016-01-01

    This study investigated whether diffuse optical spectroscopy (DOS) measurements could assess clinical response to photodynamic therapy (PDT) in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the correlation between parameters measured with DOS and the crosslinking of signal transducer and activator of transcription 3 (STAT3), a molecular marker for PDT-induced photoreaction, was investigated. Thirteen patients with early stage HNSCC received the photosensitizer 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and DOS measurements were performed before and after PDT in the operating room (OR). In addition, biopsies were acquired after PDT to assess the STAT3 crosslinking. Parameters measured with DOS, including blood volume fraction, blood oxygen saturation (StO2), HPPH concentration (cHPPH), HPPH fluorescence, and blood flow index (BFI), were compared to the pathologic response and the STAT3 crosslinking. The best individual predictor of pathological response was a change in cHPPH (sensitivity=60%, specificity=100%), while discrimination analysis using a two-parameter classifier (change in cHPPH and change in StO2) classified pathological response with 100% sensitivity and 100% specificity. BFI showed the best correlation with the crosslinking of STAT3. These results indicate that DOS-derived parameters can assess the clinical response in the OR, allowing for earlier reintervention if needed.

  10. Do novel oral anticoagulants do better than standard therapy in the treatment of deep vein thrombosis?

    PubMed

    Brodmann, M

    2013-08-01

    The focus of DVT treatment is the prevention of recurrence and thrombus migration by treatment with anticoagulants. The aim is to improve outcomes by reducing clot burden and by preventing thrombus propagation, in order to prevent PE and the development of long-term complication. Actually, initial therapy is parenteral anticoagulation, mainly with low molecular weight heparin followed by a vitamin K antagonist (VKA) for triggered and idiopathic DVT. The long term treatment suggestion with a VKA is for sure the most challenging therapeutic scenario, showing all the disadvantages of VKA especially in the onset phase when therapeutic levels of VKA are difficult to achieve. The difference between VKAs and NOACs is the fact, that NOACs target a specific factor in the coagulation cascade. At time now two pathways have been chosen for treatment options, the direct inhibition of active sites of thrombin and factor Xa. Routine monitoring is not required and the drugs can be administered in fixed doses, which should increase patient adherence to long term treatment. At time now, four novel anticoagulants are called to be options for DVT treatment. Rivaroxaban, apixaban and edoxaban are direct FXa inhibitors, whereas dabigtran etexilate is a direct thrombin inhibitor. PMID:23681109

  11. Metabolic engineering for high yielding L(-)-carnitine production in Escherichia coli

    PubMed Central

    2013-01-01

    Background L(-)-carnitine production has been widely studied because of its beneficial properties on various diseases and dysfunctions. Enterobacteria possess a specific biotransformation pathway which can be used for the enantioselective production of L(-)-carnitine. Although bioprocesses catalyzed by enzymes or whole cells can overcome the lack of enantioselectivity of chemical methods, current processes for L(−)-carnitine production still have severe disadvantages, such as the low yields, side reactions and the need of high catalyst concentrations and anaerobic conditions for proper expression of the biotransformation pathway. Additionally, genetically engineered strains so far constructed for L(-)-carnitine production are based on plasmids and, therefore, suffer from segregational unstability. Results In this work, a stable, high yielding strain for L(-)-carnitine production from low cost substrates was constructed. A metabolic engineering strategy was implemented in a multiple mutant for use in both growing and resting cells systems. The effect of mutations on gene expression and metabolism was analyzed to characterize the productivity constraints of the wild type and the overproducer strains. Precise deletion of genes which encode proteins of central and carnitine metabolisms were performed. Specifically, flux through the TCA cycle was increased by deletion of aceK (which encodes a bifunctional kinase/phosphatase which inhibits isocitrate dehydrogenase activity) and the synthesis of the by-product γ-butyrobetaine was prevented by deletion of caiA (which encodes a crotonobetainyl-CoA reductase). Both mutations led to improve the L(-)-carnitine production by 20 and 42%, respectively. Moreover, the highly regulated promoter of the cai operon was substituted by a constitutive artificial promoter increasing the biotransformation rate, even under aerobic conditions. Resting cells of the BW ΔaceK ΔcaiA p37cai strain produced 59.6 mmol l-1 · h-1 of L(−)-carnitine

  12. Chemotherapy-induced and/or radiation therapy-induced oral mucositis--complicating the treatment of cancer.

    PubMed

    Naidu, Maddireddy Umameshwar Rao; Ramana, Gogula Venkat; Rani, Pingali Usha; Mohan, Iyyapu Krishna; Suman, Avula; Roy, Priyadarshni

    2004-01-01

    The term mucositis is coined to describe the adverse effects of radiation and chemotherapy treatments. Mucositis is one of the most common adverse reactions encountered in radiation therapy for head and neck cancers, as well as in chemotherapy, in particular with drugs affecting DNA synthesis (S-phase-specific agents such as fluorouracil, methotrexate, and cytarabine). Mucositis may limit the patient's ability to tolerate chemotherapy or radiation therapy, and nutritional status is compromised. It may drastically affect cancer treatment as well as the patient's quality of life. The incidence and severity of mucositis will vary from patient to patient. It will also vary from treatment to treatment. It is estimated that there is 40% incidence of mucositis in patients treated with standard chemotherapy and this will not only increase with the number of treatment cycles but also with previous episodes. Similarly, patients who undergo bone marrow transplantation and who receive high doses of chemotherapy have a 76% chance of getting mucositis. Patients receiving radiation, in particular to head and neck cancers, have a 30% to 60% chance. The exact pathophysiology of development is not known, but it is thought to be divided into direct and indirect mucositis. Chemotherapy and/or radiation therapy will interfere with the normal turnover of epithelial, cells leading to mucosal injury; subsequently, it can also occur due to indirect invasion of Gram-negative bacteria and fungal species because most of the cancer drugs will cause changes in blood counts. With the advancement in cytology, a more precise mechanism has been established. With this understanding, we can select and target particular mediators responsible for the mucositis. Risk factors such as age, nutritional status, type of malignancy, and oral care during treatment will play important roles in the development of mucositis. Many treatment options are available to prevent and treat this condition, but none of

  13. Accessibility to Oral Antiviral Therapy for Patients with Chronic Hepatitis C in the United States

    PubMed Central

    Saab, Sammy; Jimenez, Melissa; Fong, Tiffany; Wu, Crystal; Bau, Sherona; Jamal, Zoha; Grotts, Jonathan; Elashoff, David

    2016-01-01

    Abstract Background: Hepatitis C (HCV) direct acting antiviral agents (DAAs) are safe, effective, and tolerable. Most contraindications to interferon-based treatment are no long applicable. The aims of this study were to understand the predictors of approval to drug accessibility. Methods: We studied all consecutive patients with HCV prescribed DAAs between October 2014 and July 2015. Data on demographic, socio-economic status, comorbidities, baseline laboratory values, and assessment of liver disease severity, insurance, and specialty pharmacy type were collected. Multivariate analyses were performed to identify predictors of prescription approval. Results: In total, 410 patients were prescribed DAAs between October 2014 and July 2015. Of those, 332 (81%) patients were insurance approved for therapy. Of the 332 patients accepted, 251 were accepted after the first prescription attempt, and 38 were accepted after the second and third attempts. The number of attempts for the other 43 approved patients was unknown. Older age (p = 0.001), employment (p = 0.001), lack of comorbidities (p = 0.02), liver transplantation (p = 0.018), and advanced liver disease (p = 0.001) were more likely associated with obtaining approval. Household income was not associated with insurance approval. In the multivariate analysis, Medicare insurance (odds ratio [OR]) 2.67, 95% confidence interval [CI] 0.96–7.20), lack of nonliver comorbidities (OR 2.72, 95% CI 1.35–5.43), and the presence of advanced liver disease (OR 1.82, 95% CI 1.04–3.24) independently predicted drug approval. Conclusion: Despite the availability of DAAs for HCV, barriers from insurance carriers continue to impair widespread use. Patients with advanced liver disease, Medicare, and without comorbidities are most likely to be insurance approved for DAAs. PMID:27350937

  14. Effectiveness of Indian Turmeric Powder with Honey as Complementary Therapy on Oral Mucositis : A Nursing Perspective among Cancer Patients in Mysore.

    PubMed

    Francis, Manjusha; Williams, Sheela

    2014-01-01

    Oral mucositis is a common, debilitating complication of cancer patients undergoing chemotherapy and radiotherapy, occurring in about 40 percent cases. Mucositis may limit the patient's ability to tolerate chemotherapy or radiation therapy, and nutrition status is compromised. The aim of the study was to assess the effect of Indian turmeric powder with honey as a complementary therapy on treatment induced oral mucositis. In the study, quasi experimental non-equivalent control group pre test post-test design was used and non-probability purposive sampling technique was adopted to select 60 cancer patients with treatment induced oral mucositis, 30 each in experimental and control group. The independent 't' value for post-test 2 and 3 (post-test 2: 2.86 for WHO OMAS and 4.58 for MPJ OMAS, post test 2: 5.42 for WHO OMAS and 7.2 for MPJ OMAS; p < 0.05) were significant between experimental and control group. It is inferred that the application of Indian turmeric and honey on treatment-induced oral mucositis is effective.

  15. New Prospective for the Management of Low-Risk Pulmonary Embolism: Prognostic Assessment, Early Discharge, and Single-Drug Therapy with New Oral Anticoagulants

    PubMed Central

    2012-01-01

    Patients with pulmonary embolism (PE) can be stratified into two different prognostic categories, based on the presence or absence of shock or sustained arterial hypotension. Some patients with normotensive PE have a low risk of early mortality, defined as <1% at 30 days or during hospital stay. In this paper, we will discuss the new prospective for the optimal management of low-risk PE: prognostic assessment, early discharge, and single-drug therapy with new oral anticoagulants. Several parameters have been proposed and investigated to identify low-risk PE: clinical prediction rules, imaging tests, and laboratory markers of right ventricular dysfunction or injury. Moreover, outpatient management has been suggested for low-risk PE: it may lead to a decrease in unnecessary hospitalizations, acquired infections, death, and costs and to an improvement in health-related quality of life. Finally, the main characteristics of new oral anticoagulant drugs and the most recent published data on phase III trials on PE suggest that the single-drug therapy is a possible suitable option. Oral administration, predictable anticoagulant responses, and few drug-drug interactions of direct thrombin and factor Xa inhibitors may further simplify PE home therapy avoiding administration of low-molecular-weight heparin. PMID:24278706

  16. Carnitine palmitoyltransferase 1C: From cognition to cancer.

    PubMed

    Casals, Núria; Zammit, Victor; Herrero, Laura; Fadó, Rut; Rodríguez-Rodríguez, Rosalía; Serra, Dolors

    2016-01-01

    Carnitine palmitoyltransferase 1 (CPT1) C was the last member of the CPT1 family of genes to be discovered. CPT1A and CPT1B were identified as the gate-keeper enzymes for the entry of long-chain fatty acids (as carnitine esters) into mitochondria and their further oxidation, and they show differences in their kinetics and tissue expression. Although CPT1C exhibits high sequence similarity to CPT1A and CPT1B, it is specifically expressed in neurons (a cell-type that does not use fatty acids as fuel to any major extent), it is localized in the endoplasmic reticulum of cells, and it has minimal CPT1 catalytic activity with l-carnitine and acyl-CoA esters. The lack of an easily measurable biological activity has hampered attempts to elucidate the cellular and physiological role of CPT1C but has not diminished the interest of the biomedical research community in this CPT1 isoform. The observations that CPT1C binds malonyl-CoA and long-chain acyl-CoA suggest that it is a sensor of lipid metabolism in neurons, where it appears to impact ceramide and triacylglycerol (TAG) metabolism. CPT1C global knock-out mice show a wide range of brain disorders, including impaired cognition and spatial learning, motor deficits, and a deregulation in food intake and energy homeostasis. The first disease-causing CPT1C mutation was recently described in humans, with Cpt1c being identified as the gene causing hereditary spastic paraplegia. The putative role of CPT1C in the regulation of complex-lipid metabolism is supported by the observation that it is highly expressed in certain virulent tumor cells, conferring them resistance to glucose- and oxygen-deprivation. Therefore, CPT1C may be a promising target in the treatment of cancer. Here we review the molecular, biochemical, and structural properties of CPT1C and discuss its potential roles in brain function, and cancer.

  17. Oral cenesthopathy.

    PubMed

    Umezaki, Yojiro; Miura, Anna; Watanabe, Motoko; Takenoshita, Miho; Uezato, Akihito; Toriihara, Akira; Nishikawa, Toru; Toyofuku, Akira

    2016-01-01

    Cenesthopathy is characterized by abnormal and strange bodily sensations and is classified as a 'delusional disorder, somatic type' or 'somatoform disorder' according to the DSM 5. The oral cavity is one of the frequent sites of cenesthopathy, thus the term 'oral cenesthopathy.' Patients with oral cenesthopathy complain of unusual sensations without corresponding abnormal findings in the oral area, such as excessive mucus secretion, a slimy sensation, or a feeling of coils or wires being present within the oral region. They usually visit multiple dentists rather than psychiatrists. Without a proper diagnosis, they repeatedly pursue unnecessary surgical procedures to remove their 'foreign body'. This sometimes creates a dilemma between the dentists and patients. The nosography of oral cenesthopathy has been discussed in some case reports and reviews but is overlooked in mainstream medicine. This review focuses on the various aspects of oral cenesthopathy. The estimated prevalence of cenesthopathy was 0.2 to 1.9 % in a study done at a Japanese university psychiatry clinic and 27 % in a study done at a Japanese psychosomatic dentistry clinic. Oral cenesthopathy do not have clear disposition, while some studies reported that elderly women were most commonly affected. Its pathophysiology has not been fully elucidated. However, recent studies have suggested a right > left asymmetrical pattern of the cerebral blood flow of patients with oral cenesthopathy. Antidepressants, antipsychotic drugs, electroconvulsive therapy, and psychotherapy might be effective in some cases, though it is known to be intractable. To date, the epidemiology, pathophysiology, etiology, classification and treatment of oral cenesthopathy are unknown due to the few reports on the disorder, though there are a few case reports. To overcome this difficult medical condition, clinico-statistical and case-control studies done under rigorous criteria and with a large sample size are required. PMID

  18. Discrepancies between Patients’ Preferences and Educational Programs on Oral Anticoagulant Therapy: A Survey in Community Pharmacies and Hospital Consultations

    PubMed Central

    Macquart de Terline, Diane; Hejblum, Gilles; Fernandez, Christine; Cohen, Ariel; Antignac, Marie

    2016-01-01

    Background Oral anticoagulation therapy is increasingly used for the prevention and treatment of thromboembolic complications in various clinical situations. Nowadays, education programs for patients treated with anticoagulants constitute an integrated component of their management. However, such programs are usually based on the healthcare providers’ perceptions of what patients should know, rather than on patients’ preferences. Objective To investigate patients’ viewpoints on educational needs and preferred modalities of information delivery. Methods We conducted an observational study based on a self-administered questionnaire. To explore several profiles of patients, the study was designed for enrolling patients in two settings: during outpatient consultations in a cardiology department (Saint Antoine Hospital, Paris, France) and in community pharmacies throughout France. Results Of the 371 patients who completed the questionnaire, 187 (50.4%) were recruited during an outpatient consultation and 184 (49.6%) were recruited in community pharmacies. 84.1% of patients were receiving a vitamin K antagonist and 15.6% a direct oral anticoagulant. Patients ranked 16 of 21 (76.2%) questionnaire items on information about their treatment as important or essential; information on adverse effects of treatment was the highest ranked domain (mean score 2.38, 95% CI 2.30–2.46). Pharmacists (1.69, 1.58–1.80), nurses (1.05, 0.95–1.16), and patient associations (0.36, 0.29–0.44), along with group sessions (0.85, 0.75–0.95), the internet (0.77, 0.67–0.88), and delivery of material at the patient’s home (1.26, 1.14–1.38), were ranked poorly in terms of delivering educational material. Conclusion This study revealed substantial discrepancies between patient preferences and current educational programs. These findings should be useful for tailoring future educational programs that are better adapted to patients, with a potential associated enhancement of their

  19. Gingiva as a new and the most accessible source of mesenchymal stem cells from the oral cavity to be used in regenerative therapies.

    PubMed

    Górski, Bartłomiej

    2016-01-01

    Since the discovery of bone marrow mesenchymal stem cells (BMMSCs), many researchers have focused their attention on new sources of mesenchymal stem cells (MSCs). Consequently, MSCs that display self-renewal capacity, multidifferentiation potential and immunomodulatory properties have been isolated from human oral tissues, including tooth, periodontal ligament, and gingiva. Oral MSCs involve dental pulp stem cells (DPSCs), stem cells from exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), dental follicle stem cells (DFCs), stem cells from apical papilla (SCAP) and gingival stem cells (GMSCs). Current research on oral stem cells is expanding at an unprecedented rate. That being the case, a plethora of in vitro differentiation assays, immunodeficient animal transplantations and preclinical trials have demonstrated that these cells exhibit strong potential for both regenerative dentistry and medicine. Oral MSCs have proved their capability to repair cornea, dental pulp, periodontal, bone, cartilage, tendon, neural, muscle and endothelial tissues without neoplasm formation as well as to treat inflammatory diseases and immune disorders. This article describes the current understanding of oral MSCs and their prospective applications in cell-based therapy, tissue engineering and regenerative medicine. Special attention is placed on GMSCs as they are easily accessible and may be obtained in a convenient and minimally invasive way. PMID:27594561

  20. Betaine and Carnitine Derivatives as Herbicidal Ionic Liquids.

    PubMed

    Pernak, Juliusz; Niemczak, Michał; Chrzanowski, Łukasz; Ławniczak, Łukasz; Fochtman, Przemysław; Marcinkowska, Katarzyna; Praczyk, Tadeusz

    2016-08-16

    This study focused on the synthesis and subsequent characterization of herbicidal ionic liquids based on betaine and carnitine, two derivatives of amino acids, which were used as cations. Four commonly used herbicides (2,4-D, MCPA, MCPP and Dicamba) were used as anions in simple (single anion) and oligomeric (two anions) salts. The obtained salts were subjected to analyzes regarding physicochemical properties (density, viscosity, refractive index, thermal decomposition profiles and solubility) as well as evaluation of their herbicidal activity under greenhouse and field conditions, toxicity towards rats and biodegradability. The obtained results suggest that the synthesized herbicidal ionic liquids displayed low toxicity (classified as category 4 compounds) and showed similar or improved efficacy against weed compared to reference herbicides. The highest increase was observed during field trials for salts containing 2,4-D as the anion, which also exhibited the highest biodegradability (>75 %). PMID:27374836

  1. Dynamic monitoring of plasma amino acids and carnitine during chemotherapy of patients with alimentary canal malignancies and its clinical value

    PubMed Central

    Wang, Xiaoyu; Wang, Jiaqi; Wang, Zhenghua; Wang, Qingjun; Li, Hua

    2015-01-01

    aminotransferase were found to be higher in eight patients with hypocarnitinemia, yet TTP, PFS, and RR (response rate) were lower. No significant difference was observed for adverse reactions. The indexes in 12 patients with citrullinemia showed no difference compared with control group. All the results showed statistically significant differences (P<0.05). Conclusion Real-time monitoring of plasma amino acids and carnitine in patients with metastatic gastrointestinal malignancies can directly reflect the body’s metabolism and nutritional status. The results provide a reference for nutrition therapy or support for patients with alimentary canal malignancies. Hypocarnitinemia is a risk factor for gastrointestinal cancer patients and affects TTP, PFS, and RR by liver function. This study shows that tandem mass spectrometry can be used to detect blood amino acids and carnitine spectrum may be used for an early diagnosis and evaluation of adverse reactions and prognosis of the digestive tract malignant tumor patients. PMID:26300648

  2. Supporting patients to self-monitor their oral anticoagulation therapy: recommendations based on a qualitative study of patients’ experiences

    PubMed Central

    Tompson, Alice; Heneghan, Carl; Fitzmaurice, David; Sutton, Stephen; Harrison, Sian; Ward, Alison

    2015-01-01

    Background Clinical trials suggest that oral anticoagulation therapy (OAT) self-monitoring is safe and effective, however little is known about the patient experience of this process. There is a lack of understanding about how best to train and support patients embarking on OAT self-monitoring. Aim To collect in-depth information about patients’ experiences of OAT self-monitoring outside of clinical trial conditions and to produce a set of recommendations on how best to support such patients. Design and setting Semi-structured qualitative interviews with patients who self-monitor and live in England. Method In total, 26 of the 267 (9.7%) who participated in the Cohort study of Anticoagulation Self-Monitoring (CASM) and were still self-monitoring after 12 months’ follow-up were interviewed. Topics discussed included experiences of OAT self-monitoring, healthcare support, training, and decision making. Framework analysis was used. Results Following initial problems using the monitoring device, interviewees described a mostly positive experience. Although less effort was expended attending monitoring appointments with health professionals, effort was required to conduct self-monitoring tests and to interpret and act on the results. Desire to self-manage was variable, especially when dosing advice systems worked promptly and reliably. Interviewees overcame patchy healthcare system knowledge and support of self-monitoring by educating themselves. Family and friends provided support with learning to use the monitor and managing OAT dosage adjustments. Conclusion Better, more-consistent training and health-service support would have alleviated a number of problems encountered by these patients who were self-monitoring. This training and support will become even more important if self-monitoring becomes more accessible to the general population of people on OAT. PMID:26077266

  3. Effectiveness of self-managed oral anticoagulant therapy in patients with recurrent venous thromboembolism. A propensity-matched cohort study.

    PubMed

    Larsen, Torben Bjerregaard; Skjøth, Flemming; Grove, Erik Lerkevang; Nielsen, Peter Brønnum; Christensen, Thomas Decker

    2016-08-30

    Patient-self-management (PSM) of oral anticoagulant therapy (OAT) with vitamin K antagonists for venous thromboembolism (VTE) has demonstrated efficacy in randomised, controlled trials. The aim of this study was to evaluate the effectiveness of PSM of OAT in everyday clinical practice. Prospectively registered patient data were obtained from databases at two hospitals, and cross-linkage with national patient registries provided detailed information on comorbidities and events. Patients with VTE performing PSM affiliated to major PSM centres were included as cases (N=444). A control group of patients on conventional treatment was propensity score selected in a ratio of 1:5 (N=2220) within matched groups. The effectiveness and safety was estimated using recurrent VTE, major bleeding events and all-cause death as outcomes. We found a lower rate of recurrent VTE among PSM patients compared to the control group with a hazard ratio (HR) of 0.63; 95 % confidence interval (CI) 0.42-0.95, whereas no difference was seen with bleeding (HR: 0.95; 95 % CI 0.44-2.02). The risk of all-cause death was lower for PSM patients (HR: 0.41; 95 % CI 0.21-0.81). A net clinical benefit analysis sums the effect on recurrent VTE and bleeding up to a weighted rate difference of 0.86 (95 % CI 0.00-1.72) in favour of PSM. In conclusion, PSM of anticoagulant treatment was associated with a statistically significant lower rate of recurrent VTE and all-cause death compared to patients on conventionally managed anticoagulant treatment. All major thromboembolic outcomes were less frequent among self-managed patients, whereas bleedings were observed with similar frequency. PMID:27412804

  4. Failure of carnitine in improving hepatic nitrogen content in alcoholic and non‐alcoholic malnourished rats

    PubMed Central

    Rodrigues, Luciana P; Portari, Guilherme Vannucchi; Padovan, Gilberto João; Jordão, Alceu Afonso; Suen, Vivian M M; Sergio Marchini, Julio

    2010-01-01

    AIMS: To investigate the effect of carnitine supplementation on alcoholic malnourished rats' hepatic nitrogen content. METHODS: Malnourished rats, on 50% protein‐calorie restriction with free access to water (malnutrition group) and malnourished rats under the same conditions with free access to a 20% alcohol/water solution (alcohol group) were studied. After the undernourishment period (4 weeks with or without alcohol), both groups were randomly divided into two subgroups, one of them nutritionally recovered for 28 days with free access to a normal diet and water (recovery groups) and the other re‐fed with free access to diet and water plus carnitine (0.1 g/g body weight/day by gavage) (carnitine groups). No alcohol intake was allowed during the recovery period. RESULTS: The results showed: i) no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. ii) Liver nitrogen content was highest in the carnitine recovery non‐alcoholic group (from 1.7 to 3.3 g/100 g, P<0.05) and lowest in alcoholic animals (about 1.5 g/100g). iii) Hepatic fat content (∼10 g/100 g, P>.05) was highest in the alcoholic animals. CONCLUSION: Carnitine supplementation did not induce better nutritional recovery. PMID:21049216

  5. Skeletal muscle carnitine loading increases energy expenditure, modulates fuel metabolism gene networks and prevents body fat accumulation in humans

    PubMed Central

    Stephens, Francis B; Wall, Benjamin T; Marimuthu, Kanagaraj; Shannon, Chris E; Constantin-Teodosiu, Dumitru; Macdonald, Ian A; Greenhaff, Paul L

    2013-01-01

    Twelve weeks of daily l-carnitine and carbohydrate feeding in humans increases skeletal muscle total carnitine content, and prevents body mass accrual associated with carbohydrate feeding alone. Here we determined the influence of l-carnitine and carbohydrate feeding on energy metabolism, body fat mass and muscle expression of fuel metabolism genes. Twelve males exercised at 50% maximal oxygen consumption for 30 min once before and once after 12 weeks of twice daily feeding of 80 g carbohydrate (Control, n= 6) or 1.36 g l-carnitine + 80 g carbohydrate (Carnitine, n= 6). Maximal carnitine palmitolytransferase 1 (CPT1) activity remained similar in both groups over 12 weeks. However, whereas muscle total carnitine, long-chain acyl-CoA and whole-body energy expenditure did not change over 12 weeks in Control, they increased in Carnitine by 20%, 200% and 6%, respectively (P < 0.05). Moreover, body mass and whole-body fat mass (dual-energy X-ray absorptiometry) increased over 12 weeks in Control by 1.9 and 1.8 kg, respectively (P < 0.05), but did not change in Carnitine. Seventy-three of 187 genes relating to fuel metabolism were upregulated in Carnitine vs. Control after 12 weeks, with ‘insulin signalling’, ‘peroxisome proliferator-activated receptor signalling’ and ‘fatty acid metabolism’ as the three most enriched pathways in gene functional analysis. In conclusion, increasing muscle total carnitine in healthy humans can modulate muscle metabolism, energy expenditure and body composition over a prolonged period, which is entirely consistent with a carnitine-mediated increase in muscle long-chain acyl-group translocation via CPT1. Implications to health warrant further investigation, particularly in obese individuals who have a reduced reliance on muscle fat oxidation during low-intensity exercise. PMID:23818692

  6. L-carnitine-supplemented parenteral nutrition improves fat metabolism but fails to support compensatory growth in premature Korean infants.

    PubMed

    Seong, So-Hui; Cho, Soo-Chul; Park, Yongsoon; Cha, Youn-Soo

    2010-04-01

    We have previously shown that pregnant Korean mothers often have especially poor carnitine status, which may be responsible for the suboptimal carnitine levels of newborn Korean infants. This study tested the hypothesis that carnitine obtained from premature infant formula alone is adequate in sustaining optimal lipid metabolism and growth in premature infants. Accordingly, we investigated the effects of parenteral carnitine supplementation on carnitine status, growth parameters, and lipid metabolism in premature infants by measuring serum lipid profiles, carnitine and beta-hydroxybutyrate concentrations, and body weight, size, and length. Twenty-five low-birth weight Korean infants were randomly assigned to control (LCNS, n = 12) or L-carnitine-supplemented (10 mg/[kg d], LCS, n = 13) groups. On day 9, the triacylglycerol concentration was lower in the LCS group; but the high-density lipoprotein cholesterol concentration and free, acyl, and total carnitine and beta-hydroxybutyrate were significantly increased compared with the LCNS group. The ratio of acyl carnitine to free carnitine was significantly lower on day 5 in the LCS compared with the LCNS group. Body weight, height, Apgar score (1 and 5 minute), head circumference, and chest circumference were recorded on day 0; and body weight was measured again on days 5 and 9. Infant formula intake was recorded every day. There was no significant difference in body weight or growth parameters between the groups from days 0 to 9.Therefore, we concluded that, in low-birth weight infants, the addition of 10 mg/(kg d) supplemental carnitine significantly improves lipid profiles and serum carnitine level but does not enhance growth. PMID:20534325

  7. The new insight into oral drug delivery system based on metal drugs in colon cancer therapy through β-lactoglobulin/oxali-palladium nanocapsules.

    PubMed

    Ghalandari, Behafarid; Divsalar, Adeleh; Saboury, Ali Akbar; Parivar, Kazem

    2014-11-01

    Many efforts have been made to improve the targeting and potential applications of oral drug delivery systems. In this paper, we have demonstrated and investigated how biopolymer nanocapsules can be used as a novel oral drug delivery system for metal-based drug delivery in colon cancer therapy. In this work, β-lactoglobulin nanocapsules containing oxali-palladium were chosen to be synthesized and investigated for the use in colon cancer therapy. These nanocapsules were fabricated in three different pHs (3, 4.5 and 7) and investigated both in the presence and absence of low methoxyl pectin. The results obtained from these experiments indicated that the soluble and stable β-lactoglobulin nanocapsules which contained oxali-palladium had the ability to be formed at a size smaller than 200 nm when in the presence of low methoxyl pectin and at pH 4.5. The in vitro release data indicated that the maximum release occurs at pH 7.0 and 7.5. There lease mechanism demonstrated an anomalous diffusion with a predominant contribution from erosion. Finally, it can be concluded that the β-LG nanocapsules containing oxali-palladium complexed with low methoxyl pectin can be a very promising candidate for the use in oral drug delivery for colon cancer treatment. PMID:25190224

  8. [Co-delivery of paclitaxel and cyclosporine by a novel liposome-silica hybrid nano-carrier for anti-tumor therapy via oral route].

    PubMed

    Deng, Li; Su, Ting-Ting; Huang, Xing-Liang; Wang, Ya-Hua; Li, Chong

    2014-01-01

    In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug pair. Optimization of the preparation of the drug-loading formulation and characterization of its physicochemical parameters and drug release profile were performed in vitro. Then in vivo pharmacodynamics and pharmacokinetics studies were performed. The results showed that the obtained formulation has a small particle size (mean diameter of 100.2 +/- 15.2 nm), a homogeneous distribution [the polydispersity index was (0.251 +/- 0.018)] and high encapsulation efficiency (90.15 +/- 2.47) % and (80.64 +/- 3.52) % for paclitaxel and cyclosporine respectively with a mild and easy preparation process. A sequential drug release trend of cyclosporine prior to palictaxel was observed. The liposome-silica hybrid nano-carrier showed good biocompatibility in vivo and co-delivery of cyclosporine and paclitaxel significantly enhanced the oral absorption of paclitaxel with improved anti-tumor efficacy, suggesting a promising approach for multi-drug therapy against tumor and other serious diseases via oral route. PMID:24783515

  9. Oral Appliances Therapy

    MedlinePlus

    ... Membership Directory Membership Directory Publications & Research JDSM, Dialogue Journal of Dental Sleep Medicine Dialogue Archive Dialogue Accreditation Application, Standards Accredited Facilities ...

  10. L-Carnitine supplementation decreases DNA damage in treated MSUD patients.

    PubMed

    Mescka, Caroline Paula; Guerreiro, Gilian; Hammerschmidt, Tatiane; Faverzani, Jéssica; de Moura Coelho, Daniella; Mandredini, Vanusa; Wayhs, Carlos Alberto Yasin; Wajner, Moacir; Dutra-Filho, Carlos Severo; Vargas, Carmen Regla

    2015-05-01

    Maple syrup urine disease (MSUD) is an inherited disorder caused by severe deficient activity of the branched-chain α-keto acid dehydrogenase complex involved in the degradation pathway of branched-chain amino acids (BCAAs) and their α-ketoacid derivatives. MSUD patients generally present ketoacidosis, poor feeding, ataxia, coma, psychomotor delay, mental retardation and brain abnormalites. Treatment consists of dietary restriction of the BCAA (low protein intake) supplemented by a BCAA-free amino acid mixture. Although the mechanisms of brain damage in MSUD are poorly known, previous studies have shown that oxidative stress may be involved in the neuropathology of this disorder. In this regard, it was recently reported that MSUD patients have deficiency of l-carnitine (l-car), a compound with antioxidant properties that is used as adjuvant therapy in various inborn errors of metabolism. In this work, we investigated DNA damage determined by the alkaline comet assay in peripheral whole blood leukocytes of MSUD patients submitted to a BCAA-restricted diet supplemented or not with l-car. We observed a significant increase of DNA damage index (DI) in leukocytes from MSUD patients under BCAA-restricted diet as compared to controls and that l-car supplementation significantly decreased DNA DI levels. It was also found a positive correlation between DI and MDA content, a marker of lipid peroxidation, and an inverse correlation between DI and l-car levels. Taken together, our present results suggest a role for reactive species and the involvement of oxidative stress in DNA damage in this disorder. Since l-car reduced DNA damage, it is presumed that dietary supplementation of this compound may serve as an adjuvant therapeutic strategy for MSUD patients in addition to other therapies. PMID:25867118

  11. Combination effect of Pentoxifylline and L-carnitine on idiopathic oligoasthenoteratozoospermia

    PubMed Central

    Moslemi Mehni, Najme; Ketabchi, Ali Asghar; Hosseini, Ebrahim

    2014-01-01

    Background: Pentoxifylline (PX) is a methyl xanthine derivative that influences the sperm motion characteristics and L-carnitine (L-C) is an amino acid that is naturally produced in the body. In general, separate administration of PX and L-C has been reported to be effective on preserving sperm motility in vitro, and also when is consumed orally by the Idiopathic oligoasthenoteratozoospermia (IOAT) patients. Objective: The aim of this study was to evaluate any possible effect of a combination of L-C and PX on sperm characteristics and improving the type of assisted reproductive techniques (ART) in a group of patients with unexplained oligoasthenoteratozoospermia. Materials and Methods: Two hundred twelve infertile men with IOAT in a double-blind, placebo-controlled, randomized clinical trial were allocated for this study. They randomized to four groups. Group I received PX/ and L-C (each one, twice daily), group II, PX and placebo, group III, L-C with the placebo, and group IV, received placebo tablets. Finally, we compared pre and post intervention sperm parameters and ART procedures between groups. Results: While the use of PX and L-C are only improved sperm motility, but their combined uses improved all sperm parameters, especially the sperm count. Also the combination of PX and L-C was effective on improving the ART procedures (p<0.01). Conclusion: Our results demonstrate that the combination use of PX and L-C is useful in improving of sperm parameters in IOAT patients and also, improve ART procedures in this group of patients. PMID:25709639

  12. Phase II Evaluation of Early Oral Estramustine, Oral Etoposide and Intravenous Paclitaxel in Combination with Hormone Therapy in Patients with High-Risk Metastatic Adenocarcinoma of the Prostate: Southwest Oncology Group (SWOG) S0032

    PubMed Central

    Smith, David C.; Tangen, Cathy M.; Hussain, Maha H.A.; Van Veldhuizen, Peter J.; Harrer, Grant W.; Stuart, Robert K.; Mills, Glenn M.; Vogelzang, Nicholas J.; Thompson, Ian M.

    2012-01-01

    Background This multicenter cooperative group single arm trial assessed the efficacy of a multiagent taxane-based chemotherapy in combination with hormonal therapy in men with metastatic androgen-dependent prostate cancer. Methods Forty-one patients with newly diagnosed metastatic prostate cancer involving both the axial and appendicular skeletons or viscera were enrolled. Thirty-five were treated with combined androgen blockade and up to 4 cycles of oral estramustine (280 mg orally 3 times per day) and etoposide (50 mg/m2 daily) for 14 days of each 21 day cycle, with paclitaxel (135 mg/m2 IV over 1 hour) on day 2 of each cycle. Chemotherapy was started within 30 days of initiation of hormonal therapy. Patients were followed to determine progression-free survival. Results The median progression-free survival for the evaluable population was 13 months (95% CI 10–16 mo) with a median overall survival of 38 months (95% CI 28–49 mo). The main toxicities were myelosuppression with 9 patients with ≥ grade 3 neutropenia, and 1 with grade 4 thrombocytopenia. One patient died with neutropenic infection. Four episodes of thrombosis embolism occurred (3 grade 4, 1 grade 3) with one episode of grade 4 cardiac ischemia. Conclusions Administration of chemotherapy to this population is feasible with moderate toxicity. This is a high-risk population with poor prognosis and this study serves as a basis for ongoing phase III trials assessing this approach in metastatic prostate cancer. PMID:21334731

  13. A comparison of different oral therapies versus no treatment for erectile dysfunction in 196 radical nerve-sparing radical prostatectomy patients.

    PubMed

    Natali, A; Masieri, L; Lanciotti, M; Giancane, S; Vignolini, G; Carini, M; Serni, S

    2015-01-01

    We retrospectively analyzed the effects on the erectile function (EF) of no treatment (NT), and an oral therapy (OT; on-demand therapy (OD) or a regimented rehabilitation (RR) program with phosphodiesterase type 5 inhibitors (PDE5-Is)), in a cohort of 196 consecutive patients following nerve-sparing radical retropubic prostatectomy (NSRRP). Patients undergoing bilateral NSRRP (BP; n = 147) and unilateral NSRRP (UP; n = 49), chose between OT (PDE5-Is OD or RR program) and NT. Patients who chose OD therapy received PDE5-Is (100 mg sildenafil, 20 mg tadalafil and vardenafil), whereas patients who chose the RR program received 100 mg sildenafil or 20 mg vardenafil three times a week, or 20 mg tadalafil twice a week at bedtime. The t-test for unpaired data and Fisher test were used for univariate analyses, logistic regression multivariate analysis was used to test the accuracy of available variables to predict EF recovery after radical prostatectomy. Potency rates were significantly correlated with the surgical technique and with OT when compared to NT (P < 0.02), respectively 68.7% for BP (61% with no therapy and 71% with PDE5-Is) and 44% for UP (29% with no therapy and 51% with PDE5-Is), while no statistically significative differences were found between OD and rehabilitation protocols (72% with rehabilitation and 70% with OD therapy in BP, 52% with rehabilitation and 50% with OD therapy in UP; P = NS). Early OT with PDE5-Is (OD or RR program) was superior to NT in recovery of EF in NSRRP. Furthermore, an RR program with PDE5-Is did not appear to be superior to OD therapy. PMID:25056808

  14. Low-level laser therapy for treatment of chemotherapy-induced oral mucositis in childhood: a randomized double-blind controlled study.

    PubMed

    Amadori, Francesca; Bardellini, Elena; Conti, Giulio; Pedrini, Nicola; Schumacher, Richard Fabian; Majorana, Alessandra

    2016-08-01

    The aim of this study was to verify if low-level laser therapy could be useful to reduce chemotherapy-related oral mucositis grading and pain in childhood undergoing chemotherapy. A randomized double-blind clinical trial was carried out. Patients from 3 to 18 years of age undergoing cancer therapy and presenting OM grade 2 or more were eligible for this study. Patients were randomly divided in two groups: group A received laser therapy from the day of OM diagnosis and other 3 consecutive days (830 nm wavelength, power 150 mW, spot size 1 cm(2), 30 s per cm(2), energy density 4.5 J/cm(2)); group B received sham therapy (placebo) with the same timing. Two blind clinicians performed OM scoring and pain evaluation at day 1 (immediately before the beginning of laser treatment-T0), day 4 (after finishing laser therapy cycle-T1) and at day 7 (T2) as follow-up. A total of 123 patients were included in the study. Group A was composed of 62 children while group B is 61; in both groups, there was a progressive reduction in grade of OM, and at day 7, not every mucosal lesion disappeared. The difference in the decline of OM grading between the two groups resulted not statistically significant (p = 0.07). A statistically significant difference in pain reduction between two groups both at T1 and at T2 (p < 0.005) was observed. This study demonstrated the efficacy of LLLT in reducing pain due to chemotherapy-induced oral mucositis in children, while no significant benefit was noted in reducing OM grade. PMID:27272517

  15. Novel localization of OCTN1, an organic cation/carnitine transporter, to mammalian mitochondria

    SciTech Connect

    Lamhonwah, Anne-Marie; Tein, Ingrid . E-mail: ingrid.tein@sickkids.ca

    2006-07-14

    Carnitine is a zwitterion essential for the {beta}-oxidation of fatty acids. We report novel localization of the organic cation/carnitine transporter, OCTN1, to mitochondria. We made GFP- and RFP-human OCTN1 cDNA constructs and showed expression of hOCTN1 in several transfected mammalian cell lines. Immunostaining of GFP-hOCTN1 transfected cells with different intracellular markers and confocal fluorescent microscopy demonstrated mitochondrial expression of OCTN1. There was striking co-localization of an RFP-hOCTN1 fusion protein and a mitochondrial-GFP marker construct in transfected MEF-3T3 and no co-localization of GFP-hOCTN1 in transfected human skin fibroblasts with other intracellular markers. L-[{sup 3}H]Carnitine uptake in freshly isolated mitochondria of GFP-hOCTN1 transfected HepG2 demonstrated a K {sub m} of 422 {mu}M and Western blot with an anti-GFP antibody identified the expected GFP-hOCTN1 fusion protein (90 kDa). We showed endogenous expression of native OCTN1 in HepG2 mitochondria with anti-GST-hOCTN1 antibody. Further, we definitively confirmed intact L-[{sup 3}H]carnitine uptake (K {sub m} 1324 {mu}M), solely attributable to OCTN1, in isolated mitochondria of mutant human skin fibroblasts having <1% of carnitine acylcarnitine translocase activity (alternate mitochondrial carnitine transporter). This mitochondrial localization was confirmed by TEM of murine heart incubated with highly specific rabbit anti-GST-hOCTN1 antibody and immunogold labeled goat anti-rabbit antibody. This suggests an important yet different role for OCTN1 from other OCTN family members in intracellular carnitine homeostasis.

  16. l-carnitine as a Potential Additive in Blood Storage Solutions: A Study on Erythrocytes.

    PubMed

    Soumya, R; Carl, H; Vani, R

    2016-09-01

    Erythrocytes undergo various changes during storage (storage lesion) that in turn reduces their functioning and survival. Oxidative stress plays a major role in the storage lesion and antioxidants can be used to combat this stress. This study elucidates the effects of l-carnitine (LC) on erythrocytes of stored blood. Blood was obtained from male Wistar rats and stored (4 °C) for 20 days in CPDA-1 (citrate phosphate dextrose adenine) solution. Samples were divided into-(i) controls (ii) LC 10 (l-carnitine at a concentration of 10 mM) (iii) LC 30 (l-carnitine at a concentration of 30 mM) and (iv) LC 60 (l-carnitine at a concentration of 60 mM). Every fifth day, the biomarkers (haemoglobin, hemolysis, antioxidant enzymes, lipid peroxidation and protein oxidation products) were analysed in erythrocytes. Hemoglobin and protein sulfhydryls were insignificant during storage indicative of the maintenance of hemoglobin and sulfhydryls in all groups. Superoxide dismutase and malondialdehyde levels increased initially and decreased towards the end of storage. The levels of catalase and glutathione peroxidase were lower in experimentals than controls during storage. l-carnitine assisted the enzymes by scavenging the reactive oxygen species produced. Hemolysis increased in all groups with storage, elucidating that l-carnitine could not completely protect lipids and proteins from oxidative stress. Hence, this study opens up new avenues of using l-carnitine as a component of storage solutions with combinations of antioxidants in order to maintain efficacy of erythrocytes.

  17. [Should we add antiplatelet therapy to oral anticoagulation in patients with atrial fibrillation and vascular disease? Review of available evidence].

    PubMed

    Andreu, José Manuel; Roldán, Vanessa; García-Navarro, Miguel; Ruipérez, Juan Antonio; Valdés, Mariano; Marín, Francisco

    2012-01-01

    Current recommendation is to add antiplatelet drug to oral anticoagulation in patients with atrial fibrillation (AF) and vascular disease. However, it is debatable to join both antithrombotic drugs in stable vascular disease.

  18. Point of care monitoring of oral anticoagulant therapy in children: comparison of CoaguChek Plus and Thrombotest methods with venous international normalised ratio.

    PubMed

    Ignjatovic, Vera; Barnes, Chris; Newall, Fiona; Hamilton, Simone; Burgess, Janet; Monagle, Paul

    2004-10-01

    This paper reports the outcome of a research protocol aimed at optimising warfarin monitoring in a tertiary pediatric centre. The Thrombotest INR was the standard monitoring test employed to manage oral anticoagulant therapy in children at the Royal Children's Hospital (RCH), Melbourne. This study compares the results of this standard method to the novel CoaguChek INR monitor and the "gold standard" technique of venous INR sampling. The objectives were to determine 1) if point-of-care techniques of measuring the INR (Thrombotest and CoaguChek) are accurate and reliable compared to INR results obtained from venous sampling, processed in an accredited laboratory, and 2) if INR results generated by POC devices can be safely used to manage oral anticoagulant therapy in children. 18 children (10 females and 8 males) participated in the study. Ages ranged from 9 months to 21 years (Mean 11.9 years; SD 5.03 years). The agreement between CoaguChek and venous INR measurements (r = 0.885) was shown to be higher compared to Thrombotest and venous INR (r = 0.700). Compared to the venous INR, values obtained with Coaguchek and Thrombotest crossed into or out of the therapeutic range in 25% and 36% of cases respectively. In 88% of the CoaguChek cases and 57% Thrombotest cases, the difference from the venous result was less than 0.5. The CoaguChek method of INR monitoring is a more accurate and reliable method compared to Thrombotest, in the pediatric population tested, and can be safely used to manage oral anticoagulant therapy in children.

  19. A Prospective Study Comparing the Long-term Effectiveness of Injectable Risperidone Long-acting Therapy and Oral Aripiprazole in Patients with Schizophrenia

    PubMed Central

    Macfadden, Wayne; Ma, Yi-Wen; Thomas Haskins, J.; Bossie, Cynthia A.

    2010-01-01

    Objective: To test the hypothesis that long-term maintenance with injectable risperidone long-acting therapy is superior to oral daily aripiprazole in stable patients with schizophrenia. Design: This two-year, rater-blinded, open-label, multicenter study (NCT00299702) randomized subjects to injectable risperidone long-acting therapy (25–50mg, injected every 2 weeks) or oral aripiprazole (5–30mg/day), with study visits every two weeks. Subjects who met relapse criteria or discontinued study drug could remain in the study. Setting: Clinical trial. Participants: Stable subjects with schizophrenia not adequately benefiting from current treatment who experienced two or more relapses in the past two years. If recently relapsed, subjects were stabilized (per clinician judgment) for two or more months before entry. Measurements: Primary endpoints: time to relapse and time in remission. Safety assessments included adverse event reporting. Results: Of 355 subjects randomized, 349 were in the intent-to-treat analysis set. Data inspection revealed that 53 (14.9%) randomized subjects deviated from inclusion/exclusion criteria, most commonly not meeting stability requirements. At baseline, mean (standard deviation [SD]) Positive and Negative Syndrome Scale total score was 68.9 (14.6); 115 (33.0%) intent-to-treat subjects met remission criteria. Approximately 29 percent in each group discontinued the study before completing two years. No significant between-group differences were noted in time to relapse or time in remission. No new tolerability issues were identified. Conclusion: Results failed to demonstrate superiority with injectable risperidone long-acting therapy versus oral aripiprazole. The study design did not allow for valid conclusions of equivalence or noninferiority. Although this study attempted to mimic a real-world treatment setting for stable patients, the broad study population, the lack of patient selection for nonadherence, biweekly visits, regular

  20. Effects of L-carnitine against H2O2-induced oxidative stress in grass carp ovary cells (Ctenopharyngodon idellus).

    PubMed

    Wang, Qiuju; Ju, Xue; Chen, Yuke; Dong, Xiaoqing; Luo, Sha; Liu, Hongjian; Zhang, Dongming

    2016-06-01

    This study was designed in vitro to investigate the effects of L-carnitine against H2O2-induced oxidative stress in a grass carp (Ctenopharyngodon idellus) ovary cell line (GCO). GCO cells were pre-treated with different concentrations of L-carnitine, followed by incubation with 2.5 mM H2O2 for 1 h to induce oxidative damage. The results indicated that adding L-carnitine at concentrations of 0.01-1 mM into the medium for 12 h significantly increased cell viability. Pre-treatment with L-carnitine at concentrations of 0.1-5 mM for 12 h significantly inhibited 2.5 mM H2O2-induced cell viability loss. The significant decreases in the level of reactive oxygen species and cell apoptosis were observed in 0.5 mM L-carnitine group compared to the H2O2 group. Malondialdehyde values of all of the L-carnitine groups were significantly lower than those of the H2O2 group, while total glutathione levels of all of the L-carnitine groups were significantly higher than of the H2O2 group. The activity of antioxidant enzymes, such as total superoxide dismutase (0.1 and 0.5 mM L-carnitine), catalase (0.5 mM L-carnitine) and γ-glutamyl cysteine synthetase (0.5 and 1 mM L-carnitine), was significantly increased. In addition, pre-treatment of L-carnitine in GCO cells exposed to 2.5 mM H2O2 significantly increased the mRNA expression of copper, zinc superoxide dismutase, catalase (0.5 mM L-carnitine), glutamate cysteine ligase catalytic subunit (0.1-1 mM) and glutathione peroxidase (0.1 mM L-carnitine). In conclusion, L-carnitine promotes GCO cell growth and improves antioxidant function, it plays a protective role against oxidative stress induced by H2O2 in GCO cells, and the appropriate supplemental amount of L-carnitine is 0.1-1 mM.

  1. The Study of Hemodialysis Effectiveness on the Change Rate of Lipid Peroxidation and L-Carnitine Level in Hemodialysis Patients

    PubMed Central

    Isfahani, Maryam; Sheikh, Nasrin

    2010-01-01

    Carnitine is a small molecule widely present in all cells from prokaryotic to eukaryotic. It is an important element in β-oxidation of fatty acids. Carnitine is a scavenger of oxygen free radicals in mammalian tissues. Lack of carnitine in a hemodialysis patient can lead to carnitine deficiency. Oxidation of fatty acids and lipid metabolism are severly affected by carnitine deficiency. Oxidative stress is defined as imbalance between formation of free radicals and antioxidative defense mechanisms. It has been proposed to play a role in many disease states. In hemodialysis patients multiple factors can lead to a a high susceptibility to oxidative stress. The aim of this study was to determine hemodialysis effectiveness on the change rate of serum L-carnitine and lipid peroxidation. 27 patients with chronic renal failure (24-80 yrs) who undergo hemodialysis for 6-12 months were selected (M= 17, F= 10). Malondialdehyde (MDA), as an indicator of lipid peroxidation was measured colorimetrically with a standard thiobarbituric acid (TBA) method. L-carnitine was measured with enzymatic UV method (ROCHE, Spectronic Genesis 2, 340 nm). The weight mean of L-carnitine before and after hemodialysis was 7.67±3.6 mg/l and 2.07±1.6 mg/l, respectively (P<0.001). The weight mean of pre-hemodialysis MDA was 4.17±1.24 µmol/l, following hemodialysis -4.98±1.2 µmol/l (P<0.001). Results showed that 55.6% of patients suffered from carnitine defciency. Serum carnitine was found to be decreased markedly after hemodialysis (P<0.001). Our findings indicated that oxidative stress in these patients is further exacerbated by hemodialysis, as evidenced by increased lipid peroxidation. The relationship between serum L-carnitine and MDA before and after hemodialysis was observed (r=0.82; p<0.001; r=0.75; p<0.001).

  2. Determining and surveying the role of carnitine and folic acid to decrease fatigue in β-thalassemia minor subjects.

    PubMed

    Tabei, Seyed Mohammad Bagher; Mazloom, Maryam; Shahriari, Mahdi; Zareifar, Soheila; Azimi, Ali; Hadaegh, Amirhossein; Karimi, Mehran

    2013-11-01

    Beta-thalassemia minor (BTM) patients usually experience fatigue, bone pain complaint, and muscle weakness. Carnitine is an essential protein for transportation of long-chain fatty acids to the matrix for beta-oxidation. BTM patients have abnormally low plasma carnitine concentrations, which results in deficient ATP production. Carnitine and folic acid together may have a role in preventing bone pain complaint and fatigue in these patients. The aim of this study is to determine the effect of carnitine and folic acid supplementation in subjects with BTM. Seventy three BTM (mean age 11.06 ± 5.46 years) and 23 healthy controls (mean age 8.48 ± 3.78 years) were enrolled in the study. Fasting blood was drawn to determine baseline free and total carnitine levels, red blood cell folate concentration, and hemoglobin level. BTM were divided into three groups and received different types of supplementation for 3 months: Group 1, 50 mg/kg/day carnitine; Group 2, 50 mg/kg/day carnitine plus 1 mg/day folic acid; and Group 3, 1 mg/day folic acid. Controls did not receive supplementation. Laboratory parameters were again evaluated after 3 months' supplementation. A detailed quality of life questionnaire was designed to investigate muscle symptoms before and after supplementation. Free and total plasma carnitine concentration and hemoglobin levels in BTM subjects increased significantly after carnitine supplementation (P < .0001). Bone pain complaint and muscle weakness decreased with carnitine. Red blood cell folate level increased after folic acid supplementation. Carnitine and folic acid supplementation resulted in a decrease in bone pain complaint and muscle weakness in cases with β-thalassemia minor.

  3. Reiki therapy for postoperative oral pain in pediatric patients: Pilot data from a double-blind, randomized clinical trial

    PubMed Central

    Kundu, Anjana; Lin, Yuting; Oron, Assaf P.; Doorenbos, Ardith Z.

    2014-01-01

    Purpose To examine the effects of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. Methods This was a double-blind, randomized controlled study of children undergoing dental procedures. Participants were randomly assigned to receive either Reiki therapy or the control therapy (sham Reiki) preoperatively. Postoperative pain scores, opioid requirements, and side effects were assessed. Family members were also asked about perioperative care satisfaction. Multiple linear regressions were used for analysis. Results Thirty-eight children participated. The blinding procedure was successful. No statistically significant difference was observed between groups on all outcome measures. Implications Our study provides a successful example of a blinding procedure for Reiki therapy among children in the perioperative period. This study does not support the effectiveness of Reiki as an adjuvant therapy to opioid therapy for postoperative pain control in pediatric patients. PMID:24439640

  4. Effects of feeding L-carnitine to gilts through day 70 of gestation on litter traits and the expression of insulin-like growth factor system components and L-carnitine concentration in foetal tissues.

    PubMed

    Brown, K R; Goodband, R D; Tokach, M D; Dritz, S S; Nelssen, J L; Minton, J E; Higgins, J J; Lin, X; Odle, J; Woodworth, J C; Johnson, B J

    2008-12-01

    We investigated the influence of supplemental L-carnitine on foetal blood metabolites, litter characteristics, L-carnitine concentration in skeletal muscle and insulin-like growth factor (IGF) axis components in foetal hepatic and skeletal muscle tissues at day 40, 55 and 70 of gestating gilts. A total of 59 gilts (body weight = 137.7 kg) received a constant feed allowance of 1.75 kg/day and a top-dress containing either 0 or 50 ppm of L-carnitine starting on the first day of breeding through the allotted gestation length. Foetuses from the gilts fed diets with L-carnitine tended to be heavier (p = 0.06) and the circulating IGF-II tended to be lower (p = 0.09) at day 70, compared with the foetuses from the control gilts. Insulin-like growth factor-I messenger RNA (mRNA) was lower (p = 0.05) in hepatic tissue in the foetuses collected from gilts fed L-carnitine. Free and total carnitine concentration increased (p < 0.05) in the skeletal muscle from the foetuses collected from gilts fed supplemental L-carnitine. This study showed that L-carnitine had beneficial effects on the average foetal weight at day 70 of gestation, associated with changes in the foetal IGF system.

  5. Acceleration of gluconeogenesis from propionate by dl-carnitine in the rat kidney cortex

    PubMed Central

    Weidemann, M. J.; Krebs, H. A.

    1969-01-01

    1. The rate of gluconeogenesis from propionate in rat kidney-cortex slices was stimulated up to 3·5-fold by dl-carnitine and by bicarbonate, and was inhibited by inorganic phosphate or high concentrations of propionate (above 3mm). 2. The stimulatory effect of carnitine was dependent on the bicarbonate concentration and could be replaced at low propionate concentration by addition of 25mm-bicarbonate–carbon dioxide buffer. At low bicarbonate concentration the carnitine concentration can be rate-limiting. 3. All observations are in accordance with the view that the action of carnitine is in principle the same as that established for other fatty acids in other tissues, namely that carnitine promotes the appearance of propionyl-CoA within the mitochondrion by acting as a carrier. 4. The accelerating effects of carnitine and bicarbonate and the inhibitory effect of phosphate can be explained on the basis of the known properties of key enzymes of propionate metabolism, i.e. the reversibility of the reactions leading to the formation of methylmalonyl-CoA from propionyl-CoA. 5. 5mm-Propionate caused a five- to ten-fold fall in the free CoA content of the tissue. This fall can account for the inhibition of respiration and gluconeogenesis caused by high propionate concentration. 6. Relatively large quantities of propionyl-l-carnitine (15% of the propionate removed) were formed when dl-carnitine was present; thus the `activation' of propionate proceeded at a faster rate than the carboxylation of propionyl-CoA. The metabolism of added propionyl-l-carnitine was accompanied by glucose synthesis. 7. The appearance of radioactivity from [2-14C]propionate in both glucose and carbon dioxide was as expected on account of the randomization of C-2 and C-3 of propionate, i.e. the formation of succinate as an intermediate. 8. The maximum rate of glucose synthesis from propionate (93·3±3·3μmoles/g. dry wt./hr.) was not affected by dietary changes aimed at varying the rate of

  6. Acceleration of gluconeogenesis from propionate by Dl-carnitine in the rat kidney cortex.

    PubMed

    Weidemann, M J; Krebs, H A

    1969-01-01

    1. The rate of gluconeogenesis from propionate in rat kidney-cortex slices was stimulated up to 3.5-fold by dl-carnitine and by bicarbonate, and was inhibited by inorganic phosphate or high concentrations of propionate (above 3mm). 2. The stimulatory effect of carnitine was dependent on the bicarbonate concentration and could be replaced at low propionate concentration by addition of 25mm-bicarbonate-carbon dioxide buffer. At low bicarbonate concentration the carnitine concentration can be rate-limiting. 3. All observations are in accordance with the view that the action of carnitine is in principle the same as that established for other fatty acids in other tissues, namely that carnitine promotes the appearance of propionyl-CoA within the mitochondrion by acting as a carrier. 4. The accelerating effects of carnitine and bicarbonate and the inhibitory effect of phosphate can be explained on the basis of the known properties of key enzymes of propionate metabolism, i.e. the reversibility of the reactions leading to the formation of methylmalonyl-CoA from propionyl-CoA. 5. 5mm-Propionate caused a five- to ten-fold fall in the free CoA content of the tissue. This fall can account for the inhibition of respiration and gluconeogenesis caused by high propionate concentration. 6. Relatively large quantities of propionyl-l-carnitine (15% of the propionate removed) were formed when dl-carnitine was present; thus the ;activation' of propionate proceeded at a faster rate than the carboxylation of propionyl-CoA. The metabolism of added propionyl-l-carnitine was accompanied by glucose synthesis. 7. The appearance of radioactivity from [2-(14)C]propionate in both glucose and carbon dioxide was as expected on account of the randomization of C-2 and C-3 of propionate, i.e. the formation of succinate as an intermediate. 8. The maximum rate of glucose synthesis from propionate (93.3+/-3.3mumoles/g. dry wt./hr.) was not affected by dietary changes aimed at varying the rate of caecal

  7. Anticancer activity of pyrithione zinc in oral cancer cells identified in small molecule screens and xenograft model: Implications for oral cancer therapy.

    PubMed

    Srivastava, Gunjan; Matta, Ajay; Fu, Guodong; Somasundaram, Raj Thani; Datti, Alessandro; Walfish, Paul G; Ralhan, Ranju

    2015-10-01

    Oral squamous cell carcinoma (OSCC) patients diagnosed in late stages have limited chemotherapeutic options, underscoring the great need for development of new anticancer agents for more effective disease management. We aimed to identify novel anticancer agents for OSCC using quantitative high throughput assays for screening six chemical libraries consisting of 5170 small molecule inhibitors. In depth characterization resulted in identification of pyrithione zinc (PYZ) as the most effective cytotoxic agent inhibiting cell proliferation and inducing apoptosis in OSCC cells in vitro. Further, treatment with PYZ reduced colony forming, migration and invasion potential of oral cancer cells in a dose-dependent manner. PYZ treatment also led to altered expression of several key components of the major signaling pathways including PI3K/AKT/mTOR and WNT/β-catenin in OSCC cells. In addition, treatment with PYZ also reduced expression of 14-3-3ζ, 14-3-3σ, cyclin D1, c-Myc and pyruvate kinase M2 (PKM2), proteins identified in our earlier studies to be involved in development and progression of OSCCs. Importantly, PYZ treatment significantly reduced tumor xenograft volume in immunocompromised NOD/SCID/Crl mice without causing apparent toxicity to normal tissues. Taken together, we demonstrate in vitro and in vivo efficacy of PYZ in OSCC. In conclusion, we identified PYZ in HTS assays and demonstrated in vitro and in vivo pre-clinical efficacy of PYZ as a novel anticancer therapeutic candidate in OSCC. PMID:26115765

  8. Obesity and lipid stress inhibit carnitine acetyltransferase activity[S

    PubMed Central

    Seiler, Sarah E.; Martin, Ola J.; Noland, Robert C.; Slentz, Dorothy H.; DeBalsi, Karen L.; Ilkayeva, Olga R.; An, Jie; Newgard, Christopher B.; Koves, Timothy R.; Muoio, Deborah M.

    2014-01-01

    Carnitine acetyltransferase (CrAT) is a mitochondrial matrix enzyme that catalyzes the interconversion of acetyl-CoA and acetylcarnitine. Emerging evidence suggests that this enzyme functions as a positive regulator of total body glucose tolerance and muscle activity of pyruvate dehydrogenase (PDH), a mitochondrial enzyme complex that promotes glucose oxidation and is feedback inhibited by acetyl-CoA. Here, we used tandem mass spectrometry-based metabolic profiling to identify a negative relationship between CrAT activity and muscle content of lipid intermediates. CrAT specific activity was diminished in muscles from obese and diabetic rodents despite increased protein abundance. This reduction in enzyme activity was accompanied by muscle accumulation of long-chain acylcarnitines (LCACs) and acyl-CoAs and a decline in the acetylcarnitine/acetyl-CoA ratio. In vitro assays demonstrated that palmitoyl-CoA acts as a direct mixed-model inhibitor of CrAT. Similarly, in primary human myocytes grown in culture, nutritional and genetic manipulations that promoted mitochondrial influx of fatty acids resulted in accumulation of LCACs but a pronounced decrease of CrAT-derived short-chain acylcarnitines. These results suggest that lipid-induced antagonism of CrAT might contribute to decreased PDH activity and glucose disposal in the context of obesity and diabetes. PMID:24395925

  9. Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases.

    PubMed

    Breitkreutz, R; Babylon, A; Hack, V; Schuster, K; Tokus, M; Böhles, H; Hagmüller, E; Edler, L; Holm, E; Dröge, W

    2000-01-01

    Abnormally low intramuscular glutamate and glutathione (GSH) levels and/or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency virus (SIV) infection and may contribute to the development of cachexia. We tested the hypothesis that an impaired mitochondrial energy metabolism may compromise the Na+-dependent glutamate transport. A randomized double-blind clinical trial was designed to study the effects of L-carnitine, i.e. an agent known to enhance mitochondrial integrity and function, on the glutamate transport and plasma glutamate level of cancer patients. The effect of carnitine on the intramuscular glutamate and GSH levels was examined in complementary experiments with tumour-bearing mice. In the mice, L-carnitine treatment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels. The carnitine-treated group in the randomized clinical study showed also a significant decrease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extremities. Further studies may be warranted to determine the effect of L-carnitine on the intramuscular GSH levels in cancer patients.

  10. Role of Carnitine Acetyl Transferase in Regulation of Nitric Oxide Signaling in Pulmonary Arterial Endothelial Cells

    PubMed Central

    Sharma, Shruti; Sun, Xutong; Agarwal, Saurabh; Rafikov, Ruslan; Dasarathy, Sridevi; Kumar, Sanjiv; Black, Stephen M.

    2013-01-01

    Congenital heart defects with increased pulmonary blood flow (PBF) result in pulmonary endothelial dysfunction that is dependent, at least in part, on decreases in nitric oxide (NO) signaling. Utilizing a lamb model with left-to-right shunting of blood and increased PBF that mimics the human disease, we have recently shown that a disruption in carnitine homeostasis, due to a decreased carnitine acetyl transferase (CrAT) activity, correlates with decreased bioavailable NO. Thus, we undertook this study to test the hypothesis that the CrAT enzyme plays a major role in regulating NO signaling through its effect on mitochondrial function. We utilized the siRNA gene knockdown approach to mimic the effect of decreased CrAT activity in pulmonary arterial endothelial cells (PAEC). Our data indicate that silencing the CrAT gene disrupted cellular carnitine homeostasis, reduced the expression of mitochondrial superoxide dismutase-and resulted in an increase in oxidative stress within the mitochondrion. CrAT gene silencing also disrupted mitochondrial bioenergetics resulting in reduced ATP generation and decreased NO signaling secondary to a reduction in eNOS/Hsp90 interactions. Thus, this study links the disruption of carnitine homeostasis to the loss of NO signaling observed in children with CHD. Preserving carnitine homeostasis may have important clinical implications that warrant further investigation. PMID:23344032

  11. Crystal Structures of Murine Carnitine Acetyltransferase in Ternary Complexes with Its Substrates

    SciTech Connect

    Hsiao,Y.; Jogl, G.; Tong, L.

    2006-01-01

    Carnitine acyltransferases catalyze the reversible exchange of acyl groups between coenzyme A (CoA) and carnitine. They have important roles in many cellular processes, especially the oxidation of long-chain fatty acids in the mitochondria for energy production, and are attractive targets for drug discovery against diabetes and obesity. To help define in molecular detail the catalytic mechanism of these enzymes, we report here the high resolution crystal structure of wild-type murine carnitine acetyltransferase (CrAT) in a ternary complex with its substrates acetyl-CoA and carnitine, and the structure of the S554A/M564G double mutant in a ternary complex with the substrates CoA and hexanoylcarnitine. Detailed analyses suggest that these structures may be good mimics for the Michaelis complexes for the forward and reverse reactions of the enzyme, representing the first time that such complexes of CrAT have been studied in molecular detail. The structural information provides significant new insights into the catalytic mechanism of CrAT and possibly carnitine acyltransferases in general.

  12. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

    PubMed Central

    Koeth, Robert A.; Wang, Zeneng; Levison, Bruce S.; Buffa, Jennifer A.; Org, Elin; Sheehy, Brendan T.; Britt, Earl B.; Fu, Xiaoming; Wu, Yuping; Li, Lin; Smith, Jonathan D.; DiDonato, Joseph A.; Chen, Jun; Li, Hongzhe; Wu, Gary D.; Lewis, James D.; Warrier, Manya; Brown, J. Mark; Krauss, Ronald M.; Tang, W. H. Wilson; Bushman, Frederic D.; Lusis, Aldons J.; Hazen, Stanley L.

    2013-01-01

    Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk. PMID:23563705

  13. Characterization of L-carnitine transport by rat kidney brush-border-membrane vesicles.

    PubMed Central

    Stieger, B; O'Neill, B; Krähenbühl, S

    1995-01-01

    In the presence of a 100 mM Na+ gradient, transport of L-carnitine into rat renal brush-border-membrane vesicles was linear over 30 s and showed an overshoot at 5 min. The uptake of L-carnitine was clearly less active in the presence of other cations such as Li+, K+, Cs+ or choline. In the presence of a Na+ gradient, L-carnitine uptake after 20 s was much higher for chloride as an anion than for SCN-, NO3-, gluconate or SO4(2-). In comparison with conditions with inside positive or no membrane potential, transport was higher in vesicles with an inside negative membrane potential, suggesting an electrogenic mechanism. The kinetic characterization of the Na(+)-dependent portion of L-carnitine transport revealed two transport systems with Km values of 17.4 +/- 3.9 microM and 15.0 +/- 6.0 mM, respectively. The transport could be inhibited in a concentration-dependent fashion by structural analogues such as butyrobetaine, L-acetylcarnitine, trimethyl-lysine and D-carnitine, but not by L-arginine or glycinebetaine. PMID:7626031

  14. Effect of carnitine on muscular glutamate uptake and intramuscular glutathione in malignant diseases

    PubMed Central

    Breitkreutz, R; Babylon, A; Hack, V; Schuster, K; Tokus, M; Böhles, H; Hagmüller, E; Edler, L; Holm, E; Dröge, W

    2000-01-01

    Abnormally low intramuscular glutamate and glutathione (GSH) levels and/or a decreased muscular uptake of glutamate by the skeletal muscle tissue have previously been found in malignant diseases and simian immunodeficiency virus (SIV) infection and may contribute to the development of cachexia. We tested the hypothesis that an impaired mitochondrial energy metabolism may compromise the Na+-dependent glutamate transport. A randomized double-blind clinical trial was designed to study the effects of L -carnitine, i.e. an agent known to enhance mitochondrial integrity and function, on the glutamate transport and plasma glutamate level of cancer patients. The effect of carnitine on the intramuscular glutamate and GSH levels was examined in complementary experiments with tumour-bearing mice. In the mice, L -carnitine treatment ameliorated indeed the tumour-induced decrease in muscular glutamate and GSH levels and the increase in plasma glutamate levels. The carnitine-treated group in the randomized clinical study showed also a significant decrease in the plasma glutamate levels but only a moderate and statistically not significant increase in the relative glutamate uptake in the lower extremities. Further studies may be warranted to determine the effect of L -carnitine on the intramuscular GSH levels in cancer patients. © 2000 Cancer Research Campaign PMID:10646895

  15. A Substrate Pharmacophore for the Human Organic Cation/Carnitine Transporter Identifies Compounds Associated with Rhabdomyolysis

    PubMed Central

    Ekins, Sean; Diao, Lei; Polli, James E.

    2012-01-01

    The human Organic Cation/Carnitine Transporter (hOCTN2), is a high affinity cation/carnitine transporter expressed widely in human tissues and is physiologically important for the homeostasis of L-carnitine. The objective of this study was to elucidate the substrate requirements of this transporter via computational modelling based on published in vitro data. Nine published substrates of hOCTN2 were used to create a common features pharmacophore that was validated by mapping other known OCTN2 substrates. The pharmacophore was used to search a drug database and retrieved molecules that were then used as search queries in PubMed for instances of a side effect (rhabdomyolysis) associated with interference with L-carnitine transport. The substrate pharmacophore was comprised of two hydrogen bond acceptors, a positive ionizable feature and ten excluded volumes. The substrate pharmacophore also mapped 6 out of 7 known substrate molecules used as a test set. After searching a database of ~800 known drugs, thirty drugs were predicted to map to the substrate pharmacophore with L-carnitine shape restriction. At least 16 of these molecules had case reports documenting an association with rhabdomyolysis and represent a set for prioritizing for future testing as OCTN2 substrates or inhibitors. This computational OCTN2 substrate pharmacophore derived from published data partially overlaps a previous OCTN2 inhibitor pharmacophore and is also able to select compounds that demonstrate rhabdomyolysis, further confirming the possible linkage between this side effect and hOCTN2. PMID:22339151

  16. [Quality of life and problems posed by hypoglycemia in type 2 diabetes mellitus during oral hypoglycemic therapy].

    PubMed

    Ionova, T I; Odin, V I; Nikitina, T P; Kurbatova, K A; Shablovskaia, N E

    2013-01-01

    Quality of life characteristics, hypoglycemic episodes and patients' attitude toward them were estimated in the patients with type 2 diabetes mellitus based on the modern recommendations for the patient-oriented treatment with metformin in combination with sulfonylurea derivatives (M+S) therapy, traditional approach, n = 83) and metformin in combination with vildagliptin (M+V therapy, innovative approach, n = 111). M+V therapy ensured a higher quality of life than M+S therapy based on all SF-36 scales. Quality of life parameters corresponded to population norms in most patients given M+V therapy and only in 52% of those treated with M+S. The frequency of hypoglycemic episodes, related concerns, and other problems associated with this condition were less apparent in case of M+V therapy. Transition from M+S to M+V therapy resulted in the improvement of quality of life and reduction in the frequency of hypoglycemia. Quality of life did not change after transition to M+S therapy while the frequency of hypoglycemia and the number of related problems increased. HbA1c levels were similar in both groups (0.8% difference). According to patients' reports M+V therapy is more efficient than M+S; these data allow to comprehensively evaluate the efficacy of therapy and monitor the health state of diabetic patients in the course of treatment. PMID:24437153

  17. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using...

  18. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using...

  19. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using...

  20. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using...

  1. 21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Newborn screening test system for amino acids... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using...

  2. Essentials of oral cancer

    PubMed Central

    Rivera, César

    2015-01-01

    Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators. PMID:26617944

  3. Essentials of oral cancer.

    PubMed

    Rivera, César

    2015-01-01

    Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators. PMID:26617944

  4. Treatment of naturally occuring hemangiopericytoma and oral squamous cell carcinoma in dogs using surgery and photodynamic therapy with HPPH as a photosensitizer

    NASA Astrophysics Data System (ADS)

    Payne, John T.; McCaw, Dudley L.; Rogers, Kevin J.; Tompson, Robert V.

    1995-05-01

    Pyropheophorbide-a-hexyl ether (HPPH) is a new photosensitizer for use with photodynamic therapy (PDT) that has shown promise in laboratory animals. PDT, using this drug, is being used to treat canine patients afflicted with hemangiopericytoma and oral squamous cell carcinoma (SCC) at the University of Missouri-Columbia College of Veterinary Medicine. To date, 11 dogs with hemangiopericytoma and 5 dogs with oral SCC have been treated using a combination of surgery and PDT. Thus far, there have been no serious complications attributable to the treatment. Two dogs have had recurrences of the hemangiopericytoma and there have been no recurrences of SCC with a median follow time of 5 months. Both recurrent hemangiopericytomas were in patients with large tumors that had previous surgery. This study is ongoing and no conclusions have been reached; however several observations are noted. It appears that PDT using HPPH is safe is dogs, and may decrease the recurrence rate of Hemangiopericytomas. In dogs with oral SCC, the treatment is effective is causing necrosis and sloughing of the tumor tissue, and recurrences have not been noted on follow-ups up to 6 months.

  5. Effects of Photodynamic Therapy with Blue Light and Curcumin as Mouth Rinse for Oral Disinfection: A Randomized Controlled Trial

    PubMed Central

    Leite, Diego Portes Vieira; Parmesano, Thiago Nogueira; Fontana, Carla Raquel; Bagnato, Vanderlei Salvador

    2014-01-01

    Abstract Objective: The purpose of this study was to evaluate the effects of the antimicrobial photodynamic therapy (a-PDT) with blue light and curcumin on oral disinfection during the 2 h after treatment. Background data: a-PDT is a technique that can potentially affect the viability of bacterial cells, with selective action targeting only areas with photosensitizer accumulation. Materials and methods: A randomized controlled trial was undertaken. Twenty-seven adults were randomly divided into three groups: (1) the PDT group, which was treated with the drug, curcumin, and blue light (n=9); (2) the light group, which was treated only with the blue light, and no drug (n=9) and; (3) the curcumin group, which was treated only with the drug, curcumin, and no light (n=9). The irradiation parameters were: blue light-emitting diode (LED) illumination (455±30 nm), 400 mW of average optical power, 5 min of application, illumination area of 0.6 cm2, 600 mW/cm2 of intensity, and 200 J/cm2 of fluence. A curcumin concentration of 30 mg/L was used. The saliva samples were collected for bacterial counts at baseline and after the experimental phases (immediately after treatment, and 1 and 2 h after treatment). Serial dilutions were performed, and the resulting samples were cultured on blood agar plates in microaerophilic conditions. The number of colony-forming units (CFU) was determined. Results: The PDT group showed a significant reduction of CFU immediately after treatment (post-treatment) with PDT (5.71±0.48, p=0.001), and 1 h (5.14±0.92, p=0.001) and 2 h (5.35±0.76, p=0.001) after treatment, compared with pretreatment (6.61±0.82). There were no significant changes for the light group. The curcumin group showed a significant increase of CFU 1 h after treatment (6.77±0.40, p=0.02) compared with pretreatment (5.57±0.91) falling to baseline values at 2 h after treatment (5.58±0.70). Conclusions: The PDT group showed significant difference in

  6. L-carnitine effectively improves the metabolism and quality of platelet concentrates during storage.

    PubMed

    Deyhim, Mohammad Reza; Mesbah-Namin, Seyed Alireza; Yari, Fatemeh; Taghikhani, Mohammad; Amirizadeh, Naser

    2015-04-01

    Human platelets undergo structural and biochemical alternations during storage which are collectively called platelet storage lesion (PSL). PSL is characterized as metabolic and functionally changes. It causes decrease in platelet recovery and survival. Here, we evaluated the effect of L-carnitine (LC) on the metabolism, function, and mitochondrial metabolic activity of platelet during storage. Platelet-rich plasma was used to prepare platelet concentrate (PC) in Iranian Blood Transfusion Organization. For this purpose, ten PC bags from healthy donors were stored at 22 °C with gentle agitation in the presence or absence of LC. The effects of LC (15 mM) on the platelet quality were assessed by analyzing the levels of glucose, lactate, ATP, and lactate dehydrogenase (LDH) activity. Platelet aggregations induced by arachidonate and ristocetin were analyzed by aggregometer. Platelet mitochondrial melablolic activity was measured by tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay; platelet count and mean platelet volume were also determined by a hematology analyzer during 5 days of PC storage. The results indicated that LC could significantly decrease lactate concentration and glucose consumption accompanied with the increased oxygen consumption in stored PC. LDH activity also less significantly increased in LC-treated PC on days 2 and 5 of storage. Platelet aggregation in response to the ristocetin and arachidonate was significantly higher in LC-treated PC than that in untreated PC on day 5 of storage. Finally, platelet mitochondrial metabolic activity less significantly decreased in LC-treated PC compared to the control group on days 2 and 5 of storage. It seems that LC would be a good additive to reduce PSL and improve the platelet metabolism and quality of the stored PC for platelet transfusion therapy.

  7. Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    SciTech Connect

    D. W. Nigg

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  8. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies

    PubMed Central

    2013-01-01

    Background Standard treatment for venous thromboembolism (VTE) consists of a heparin combined with vitamin K antagonists. Direct oral anticoagulants have been investigated for acute and extended treatment of symptomatic VTE; their use could avoid parenteral treatment and/or laboratory monitoring of anticoagulant effects. Methods A prespecified pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE studies compared the efficacy and safety of rivaroxaban (15 mg twice-daily for 21 days, followed by 20 mg once-daily) with standard-therapy (enoxaparin 1.0 mg/kg twice-daily and warfarin or acenocoumarol). Patients were treated for 3, 6, or 12 months and followed for suspected recurrent VTE and bleeding. The prespecified noninferiority margin was 1.75. Results A total of 8282 patients were enrolled; 4151 received rivaroxaban and 4131 received standard-therapy. The primary efficacy outcome occurred in 86 (2.1%) rivaroxaban-treated patients compared with 95 (2.3%) standard-therapy-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.66–1.19; pnoninferiority < 0.001). Major bleeding was observed in 40 (1.0%) and 72 (1.7%) patients in the rivaroxaban and standard-therapy groups, respectively (hazard ratio, 0.54; 95% CI, 0.37–0.79; p = 0.002). In key subgroups, including fragile patients, cancer patients, patients presenting with large clots, and those with a history of recurrent VTE, the efficacy and safety of rivaroxaban were similar compared with standard-therapy. Conclusion The single-drug approach with rivaroxaban resulted in similar efficacy to standard-therapy and was associated with a significantly lower rate of major bleeding. Efficacy and safety results were consistent among key patient subgroups. Trial registration EINSTEIN-PE: ClinicalTrials.gov, NCT00439777; EINSTEIN-DVT: ClinicalTrials.gov, NCT00440193. PMID:24053656

  9. Protein ingestion acutely inhibits insulin-stimulated muscle carnitine uptake in healthy young men1

    PubMed Central

    Shannon, Chris E; Nixon, Aline V; Greenhaff, Paul L; Stephens, Francis B

    2016-01-01

    Background: Increasing skeletal muscle carnitine content represents an appealing intervention in conditions of perturbed lipid metabolism such as obesity and type 2 diabetes but requires chronic l-carnitine feeding on a daily basis in a high-carbohydrate beverage. Objective: We investigated whether whey protein ingestion could reduce the carbohydrate load required to stimulate insulin-mediated muscle carnitine accretion. Design: Seven healthy men [mean ± SD age: 24 ± 5 y; body mass index (in kg/m2): 23 ± 3] ingested 80 g carbohydrate, 40 g carbohydrate + 40 g protein, or control (flavored water) beverages 60 min after the ingestion of 4.5 g l-carnitine tartrate (3 g l-carnitine; 0.1% 2[H]3-l-carnitine). Serum insulin concentration, net forearm carnitine balance (NCB; arterialized-venous and venous plasma carnitine difference × brachial artery flow), and carnitine disappearance (Rd) and appearance (Ra) rates were determined at 20-min intervals for 180 min. Results: Serum insulin and plasma flow areas under the curve (AUCs) were similarly elevated by carbohydrate [4.5 ± 0.8 U/L · min (P < 0.01) and 0.5 ± 0.6 L (P < 0.05), respectively] and carbohydrate+protein [3.8 ± 0.6 U/L · min (P < 0.01) and 0.4 ± 0.6 L (P = 0.05), respectively] consumption, respectively, compared with the control visit (0.04 ± 0.1 U/L · min and −0.5 ± 0.2 L). Plasma carnitine AUC was greater after carbohydrate+protein consumption (3.5 ± 0.5 mmol/L · min) than after control and carbohydrate visits [2.1 ± 0.2 mmol/L · min (P < 0.05) and 1.9 ± 0.3 mmol/L · min (P < 0.01), respectively]. NCB AUC with carbohydrate (4.1 ± 3.1 μmol) was greater than during control and carbohydrate-protein visits (−8.6 ± 3.0 and −14.6 ± 6.4 μmol, respectively; P < 0.05), as was Rd AUC after carbohydrate (35.7 ± 25.2 μmol) compared with control and carbohydrate consumption [19.7 ± 15.5 μmol (P = 0.07) and 14.8 ± 9.6 μmol (P < 0.05), respectively]. Conclusions: The insulin

  10. Determination of free and total carnitine with a random-access chemistry analyzer.

    PubMed

    Wan, L; Hubbard, R W

    1998-04-01

    Carnitine deficiency presents as a major problem in fatty acid oxidation. The use of a plasma carnitine assay can rapidly help to describe this deficiency. The method we describe here requires two simple steps of sample preparation, followed by automated analysis with the Beckman Synchron CX4 random-access chemistry analyzer. The goal of this method development was to reduce the cost of analysis and to allow a greater number of laboratories to perform this assay on demand within 1 h for both free and total carnitine. The method has a linearity of 0-150 micromol/L and a detection limit of 5 micromol/L. The inter- and intraday CVs are <20%. The method agreed closely with both the widely used RIA and spectrophotometric methods.

  11. Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

    SciTech Connect

    Deusing, Dorothé Jenni Beyrer, Melanie Fitzenberger, Elena Wenzel, Uwe

    2015-05-08

    Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation.

  12. PPAR-γ Regulates Carnitine Homeostasis and Mitochondrial Function in a Lamb Model of Increased Pulmonary Blood Flow

    PubMed Central

    Rafikov, Ruslan; Kumar, Sanjiv; Hou, Yali; Oishi, Peter E.; Datar, Sanjeev A.; Raff, Gary; Fineman, Jeffrey R.; Black, Stephen M.

    2012-01-01

    Objective Carnitine homeostasis is disrupted in lambs with endothelial dysfunction secondary to increased pulmonary blood flow (Shunt). Our recent studies have also indicated that the disruption in carnitine homeostasis correlates with a decrease in PPAR-γ expression in Shunt lambs. Thus, this study was carried out to determine if there is a causal link between loss of PPAR-γ signaling and carnitine dysfunction, and whether the PPAR-γ agonist, rosiglitazone preserves carnitine homeostasis in Shunt lambs. Methods and Results siRNA-mediated PPAR-γ knockdown significantly reduced carnitine palmitoyltransferases 1 and 2 (CPT1 and 2) and carnitine acetyltransferase (CrAT) protein levels. This decrease in carnitine regulatory proteins resulted in a disruption in carnitine homeostasis and induced mitochondrial dysfunction, as determined by a reduction in cellular ATP levels. In turn, the decrease in cellular ATP attenuated NO signaling through a reduction in eNOS/Hsp90 interactions and enhanced eNOS uncoupling. In vivo, rosiglitazone treatment preserved carnitine homeostasis and attenuated the development of mitochondrial dysfunction in Shunt lambs maintaining ATP levels. This in turn preserved eNOS/Hsp90 interactions and NO signaling. Conclusion Our study indicates that PPAR-γ signaling plays an important role in maintaining mitochondrial function through the regulation of carnitine homeostasis both in vitro and in vivo. Further, it identifies a new mechanism by which PPAR-γ regulates NO signaling through Hsp90. Thus, PPAR-γ agonists may have therapeutic potential in preventing the endothelial dysfunction in children with increased pulmonary blood flow. PMID:22962578

  13. Direct Injection LC-MS-MS Analysis of Opiates, Methamphetamine, Buprenorphine, Methadone and Their Metabolites in Oral Fluid from Substitution Therapy Patients.

    PubMed

    Liu, Hsiu-Chuan; Lee, Hsi-Tzu; Hsu, Ya-Ching; Huang, Mei-Han; Liu, Ray H; Chen, Tai-Jui; Lin, Dong-Liang

    2015-01-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed, validated and applied to simultaneous analysis of oral fluid samples for the following 10 analytes: methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, morphine, codeine, 6-acetylmorphine, 6-acetylcodeine, amphetamine, and methamphetamine. The oral fluid sample was briefly centrifuged and the supernatant was directly injected into the LC-MS-MS system operated under reverse-phase chromatography and electrospray ionization (ESI). Deuterated analogs of the analytes were adopted as the internal standards and found to be effective (except for buprenorphine) to compensate for potential matrix effects. Each analytical run took <10 min. Linearity range (r(2) > 0.99) established for buprenorphine and the other nine analytes were 5-100 and 1-100 ng/mL. Intra- and interday precision (% CV) ranges for the 10 analytes were 0.87-12.2% and 1.27-12.8%, while the corresponding accuracy (%) ranges were 91.8-113% and 91.9-111%. Limits of detection and quantitation established for these 10 analytes were in the ranges of 0.1-1.0 and 0.25-1.0 ng/mL (5 ng/mL for buprenorphine). The method was successfully applied to the analysis of 62 oral fluid specimens collected from patients participating in methadone and buprenorphine substitution therapy programs. Analytical results of methadone and buprenorphine were compared with data derived from GC-MS analysis and found to be compatible. Overall, the direct injection LC-MS-MS method performed well, permitting rapid analysis of oral fluid samples for simultaneous quantification of methadone, buprenorphine, opiate and amphetamine drug categories without extensive sample preparation steps. PMID:25935159

  14. Effect of L-carnitine on exercise performance in patients with mitochondrial myopathy

    PubMed Central

    Gimenes, A.C.; Bravo, D.M.; Nápolis, L.M.; Mello, M.T.; Oliveira, A.S.B.; Neder, J.A.; Nery, L.E.

    2015-01-01

    Exercise intolerance due to impaired oxidative metabolism is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still uncertain whether L-carnitine supplementation is beneficial for patients with MM. The aim of our study was to investigate the effects of L-carnitine on exercise performance in MM. Twelve MM subjects (mean age±SD=35.4±10.8 years) with chronic progressive external ophthalmoplegia (CPEO) were first compared to 10 healthy controls (mean age±SD=29±7.8 years) before they were randomly assigned to receive L-carnitine supplementation (3 g/daily) or placebo in a double-blind crossover design. Clinical status, body composition, respiratory function tests, peripheral muscle strength (isokinetic and isometric torque) and cardiopulmonary exercise tests (incremental to peak exercise and at 70% of maximal), constant work rate (CWR) exercise test, to the limit of tolerance [Tlim]) were assessed after 2 months of L-carnitine/placebo administration. Patients with MM presented with lower mean height, total body weight, fat-free mass, and peripheral muscle strength compared to controls in the pre-test evaluation. After L-carnitine supplementation, the patients with MM significantly improved their Tlim (14±1.9 vs 11±1.4 min) and oxygen consumption (V˙O2) at CWR exercise, both at isotime (1151±115 vs 1049±104 mL/min) and at Tlim (1223±114 vs 1060±108 mL/min). These results indicate that L-carnitine supplementation may improve aerobic capacity and exercise tolerance during high-intensity CWRs in MM patients with CPEO. PMID:25714882

  15. Oral mucosal stigmata in hereditary-cancer syndromes: From germline mutations to distinctive clinical phenotypes and tailored therapies.

    PubMed

    Ponti, Giovanni; Tomasi, Aldo; Manfredini, Marco; Pellacani, Giovanni

    2016-05-10

    Numerous familial tumor syndromes are associated with distinctive oral mucosal findings, which may make possible an early diagnosis as an efficacious marker for the risk of developing visceral malignancies. In detail, Familial Adenomatous Polyposis (FAP), Gardner syndrome, Peutz-Jeghers syndrome, Cowden Syndrome, Gorlin Syndrome, Lynch/Muir-Torre Syndrome and Multiple Endocrine Neoplasia show specific lesions of the oral mucosa and other distinct clinical and molecular features. The common genetic background of the above mentioned syndromes involve germline mutations in tumor suppressor genes, such as APC, PTEN, PTCH1, STK11, RET, clearly implied in both ectodermal and mesodermal differentiation, being the oral mucosal and dental stigmata frequently associated in the specific clinical phenotypes. The oral and maxillofacial manifestations of these syndromes may become visible several years before the intestinal lesions, constituting a clinical marker that is predictive for the development of intestinal polyps and/or other visceral malignancies. A multidisciplinary approach is therefore necessary for both clinical diagnosis and management of the gene-carriers probands and their family members who have to be referred for genetic testing or have to be investigated for the presence of visceral cancers. PMID:26850131

  16. First Japanese Case of Carnitine Palmitoyltransferase II Deficiency with the Homozygous Point Mutation S113L.

    PubMed

    Shima, Atsushi; Yasuno, Tetsuhiko; Yamada, Kenji; Yamaguchi, Miyoko; Kohno, Ryuichi; Yamaguchi, Seiji; Kido, Hiroshi; Fukuda, Hidetoshi

    2016-01-01

    Carnitine palmitoyltransferase II (CPT II) deficiency is a rare inherited disorder related to recurrent episodes of rhabdomyolysis. The adult myopathic form of CPT II deficiency is relatively benign and difficult to diagnose. The point mutation S113L in CPT2 is very common in Caucasian patients, whereas F383Y is the most common mutation among Japanese patients. We herein present a case of CPT II deficiency in a Japanese patient homozygous for the missense mutation S113L. The patient showed a decreased frequency of rhabdomyolysis recurrence after the administration of a diet containing medium-chain triglyceride oil and supplementation with carnitine and bezafibrate. PMID:27629963

  17. Supplementation with l-carnitine downregulates genes of the ubiquitin proteasome system in the skeletal muscle and liver of piglets.

    PubMed

    Keller, J; Ringseis, R; Koc, A; Lukas, I; Kluge, H; Eder, K

    2012-01-01

    Supplementation of carnitine has been shown to improve performance characteristics such as protein accretion in growing pigs. The molecular mechanisms underlying this phenomenon are largely unknown. Based on recent results from DNA microchip analysis, we hypothesized that carnitine supplementation leads to a downregulation of genes of the ubiquitin proteasome system (UPS). The UPS is the most important system for protein breakdown in tissues, which in turn could be an explanation for increased protein accretion. To test this hypothesis, we fed sixteen male, four-week-old piglets either a control diet or the same diet supplemented with carnitine and determined the expression of several genes involved in the UPS in the liver and skeletal muscle. To further determine whether the effects of carnitine on the expression of genes of the UPS are mediated directly or indirectly, we also investigated the effect of carnitine on the expression of genes of the UPS in cultured C2C12 myotubes and HepG2 liver cells. In the liver of piglets fed the carnitine-supplemented diet, the relative mRNA levels of atrogin-1, E214k and Psma1 were lower than in those of the control piglets (P < 0.05). In skeletal muscle, the relative mRNA levels of atrogin-1, MuRF1, E214k, Psma1 and ubiquitin were lower in piglets fed the carnitine-supplemented diet than that in control piglets (P < 0.05). Incubating C2C12 myotubes and HepG2 liver cells with increasing concentrations of carnitine had no effect on basal and/or hydrocortisone-stimulated mRNA levels of genes of the UPS. In conclusion, this study shows that dietary carnitine decreases the transcript levels of several genes involved in the UPS in skeletal muscle and liver of piglets, whereas carnitine has no effect on the transcript levels of these genes in cultivated HepG2 liver cells and C2C12 myotubes. These data suggest that the inhibitory effect of carnitine on the expression of genes of the UPS is mediated indirectly, probably via modulating

  18. Thermochemoradiation Therapy Using Superselective Intra-arterial Infusion via Superficial Temporal and Occipital Arteries for Oral Cancer With N3 Cervical Lymph Node Metastases

    SciTech Connect

    Mitsudo, Kenji; Koizumi, Toshiyuki; Iida, Masaki; Iwai, Toshinori; Oguri, Senri; Yamamoto, Noriyuki; Itoh, Yoshiyuki; Kioi, Mitomu; Hirota, Makoto; Tohnai, Iwai

    2012-08-01

    Purpose: To evaluate the therapeutic results and histopathological effects of treatment with thermochemoradiation therapy using superselective intra-arterial infusion via the superficial temporal and occipital arteries for N3 cervical lymph node metastases of advanced oral cancer. Methods and Materials: Between April 2005 and September 2010, 9 patients with N3 cervical lymph node metastases of oral squamous cell carcinoma underwent thermochemoradiation therapy using superselective intra-arterial infusion with docetaxel (DOC) and cisplatin (CDDP). Treatment consisted of hyperthermia (2-8 sessions), superselective intra-arterial infusions (DOC, total 40-60 mg/m{sup 2}; CDDP, total 100-150 mg/m{sup 2}) and daily concurrent radiation therapy (total, 40-60 Gy) for 4-6 weeks. Results: Six of 9 patients underwent neck dissection 5-8 weeks after treatment. In four of these 6 patients, all metastatic lymph nodes, including those at N3, were grade 3 (non-viable tumor cells present) or grade 4 (no tumor cells present) tumors, as classified by the system by Shimosato et al (Shimosato et al Jpn J Clin Oncol 1971;1:19-35). In 2 of these 6 patients, the metastatic lymph nodes were grade 2b (destruction of tumor structures with a small amount of residual viable tumor cells). The other 3 patients did not undergo neck dissection due to distant metastasis after completion of thermochemoradiation therapy (n=2) and refusal (n=1). The patient who refused neck dissection underwent biopsy of the N3 lymph node and primary sites and showed grade 3 cancer. During follow-up, 5 patients were alive without disease, and 4 patients died due to pulmonary metastasis (n=3) and noncancer-related causes (n=1). Five-year survival and locoregional control rates were 51% and 88%, respectively. Conclusions: Thermochemoradiation therapy using intra-arterial infusion provided good histopathologic effects and locoregional control rates in patients with N3 metastatic lymph nodes. However, patients with N3

  19. Successful Treatment of Primary Cutaneous Mucormycosis Complicating Anti-TNF Therapy with a Combination of Surgical Debridement and Oral Posaconazole.

    PubMed

    Camargo, Jose F; Yakoub, Danny; Cho-Vega, Jeong Hee

    2015-10-01

    Lipid formulations of amphotericin B remain the first-line antifungal therapy for invasive mucormycosis. Posaconazole is an alternative for salvage therapy, but its use as primary therapy is not recommended due to the paucity of clinical data. Here we describe the case of a 57-year-old diabetic woman receiving etanercept and prednisone for the treatment of psoriatic arthritis who developed primary cutaneous mucormycosis after a minor gardening injury. Infection was successfully treated with aggressive surgical debridement followed by a 6-week course of the new delayed-release tablet formulation of posaconazole and temporary withholding of anti-TNF treatment. Primary antifungal therapy with posaconazole can be considered in selected cases of cutaneous mucormycosis. PMID:26112998

  20. Oral beta-glucan adjuvant therapy converts nonprotective Th2 response to protective Th1 cell-mediated immune response in mammary tumor-bearing mice.

    PubMed

    Baran, Jarek; Allendorf, Daniel J; Hong, Feng; Ross, Gordon D

    2007-01-01

    Beta (1-3)-D-glucans were identified almost 40 years ago as biological response modifiers that stimulated tumor rejection. In vitro studies have shown that beta-glucans bind to a lectin domain within complement receptor type 3 (CR3), or to, more recently described dectin-1 a beta-glucan specific receptor, acting mainly on phagocytic cells. In this study, we assessed the intracellular cytokine profiles of peripheral blood lymphocytes from mice bearing mammary tumors receiving i.v. anti-tumor mAbs combined or not with whole glucan particle suspension given orally (WGP, 400 microg every 24 hours). The proportions of T cells producing IL-4 and IFNgamma were determined by flow cytometry. The proportion of T cells producing IL-4 was significantly higher in tumor-bearing mice not receiving beta-glucan-enhanced therapy. Conversely, T cells from mice undergoing beta-glucan-enhanced therapy showed increased production of the Th1 cytokine IFNgamma. The switch from a Th2 to a Th1 response after WGP therapy was possibly mediated by intestinal mucosal macrophages releasing IL-12.

  1. The evaluation of clinical therapy effects of oral western medicine combined with magnetic pulse acupoint stimulation in treating elderly patients with coronary heart disease

    PubMed Central

    Fu, Xin; Guo, Li; Jiang, Zheng-Ming; Xu, Ai-Guo

    2015-01-01

    Objective: Treat the patients suffered from coronary heart disease with oral western medicine, combining with magnetic pulse acupoint stimulation, and observe the therapeutic effects of such combination therapy method. Methods: 56 old people with coronary heart disease are randomly divided into a treatment group and a control group. Both groups of patients are treated by the routine drugs, in addition, the patients of the treatment group are treated by magnetic pulse therapy additionally. Compare clinical symptoms, blood lipid and blood rheological indexes of the patients in the two groups when they are selected and after 30 days’ treatment. Results: after 30 days’ treatment, it is found that clinical symptoms, blood lipid and blood rheological indexes of the patients in the treatment group are significantly improved compared with those when they are selected and those of the control group (P<0.05). Conclusion: patients with coronary heart disease, treated by pulsed magnetic therapy and the conventional drug intervention, had relieved synptom, improve blood lipid and heart blood supply function. PMID:26309664

  2. Retrospective Audit: Does Prior Assessment by Oral and Maxillofacial Surgeons Reduce the Risk of Osteonecrosis of The Jaw in Patients Receiving Bone-Targeted Therapies for Metastatic Cancers to the Skeleton?--Part II.

    PubMed

    Turner, Bruce; Ali, Sacha; Pati, Jhumur; Nargund, Vinod; Ali, Enamul; Cheng, Leo; Wells, Paula

    2016-01-01

    Men who receive bone-targeted therapy for metastatic prostate cancer are at increased risk of osteonecrosis of the jaw (ONJ). Development of ONJ has been associated with the administration of bone-targeted therapies in association with other risk factors. ONJ can be distressing for a patient because it can cause pain, risk of jaw fracture, body image disturbance, difficultly eating, and difficulty maintaining good oral hygiene. The aim of this article is to report results of an audit of prior assessment by oral and maxillofacial surgeons (OMFS) before initiation of bone-targeted therapies and whether it may reduce the risk of ONJ in patients receiving bone-targeted therapies for advanced cancers. PMID:27501592

  3. Regulation of Genes Involved in Carnitine Homeostasis by PPARα across Different Species (Rat, Mouse, Pig, Cattle, Chicken, and Human)

    PubMed Central

    Ringseis, Robert; Wen, Gaiping; Eder, Klaus

    2012-01-01

    Recent studies in rodents convincingly demonstrated that PPARα is a key regulator of genes involved in carnitine homeostasis, which serves as a reasonable explanation for the phenomenon that energy deprivation and fibrate treatment, both of which cause activation of hepatic PPARα, causes a strong increase of hepatic carnitine concentration in rats. The present paper aimed to comprehensively analyse available data from genetic and animal studies with mice, rats, pigs, cows, and laying hens and from human studies in order to compare the regulation of genes involved in carnitine homeostasis by PPARα across different species. Overall, our comparative analysis indicates that the role of PPARα as a regulator of carnitine homeostasis is well conserved across different species. However, despite demonstrating a well-conserved role of PPARα as a key regulator of carnitine homeostasis in general, our comprehensive analysis shows that this assumption particularly applies to the regulation by PPARα of carnitine uptake which is obviously highly conserved across species, whereas regulation by PPARα of carnitine biosynthesis appears less well conserved across species. PMID:23150726

  4. The protective effect of L-carnitine against hippocampal damage due to experimental formaldehyde intoxication in rats.

    PubMed

    Ozmen, E; Ozsoy, S Y; Donmez, N; Ozsoy, B; Yumuşak, N

    2014-07-01

    We investigated the protective effects of L-carnitine on hippocampus tissue damage in rats during experimental formaldehyde (FA) intoxication. Male Wistar albino rats were assigned into four groups: (1) control (C), (2) formaldehyde (FA), (3) formaldehyde + 0.5 g/kg of L-carnitine (FA + 0.5 LC) (4) formaldehyde + 1 g/kg L-carnitine (FA + 1 LC). At the end of the 14 day trial period, animals were sacrificed by decapitation under anesthesia. The hippocampus tissue samples were extracted to measure MDA, GSH and SOD activity. Neuronal degeneration was assessed based on histopathological (hematoxylin and eosin) and immunohistochemical (anti-ubiquitin) examination. To detect oxidative stress, specimens were reacted with anti-Cu/Zn-SOD antibody. After administering L-carnitine with FA to the animals, the activities of SOD and GSH increased, but the levels of MDA decreased in hippocampus tissue. Neuronal degeneration was observed in the FA group. L-carnitine administration reduced neuronal degeneration and histological structure was similar to controls. After FA application, degenerated hippocampus neurons were stained with anti-ubiquitin and Cu/Zn-SOD antibodies; weakly positive staining was observed in L- carnitine-treated groups. L-carnitine may be useful for preventing oxidative damage in the hippocampus tissue due to formaldehyde intoxication.

  5. Isolation of soluble scFv antibody fragments specific for small biomarker molecule, L-Carnitine, using phage display.

    PubMed

    Abou El-Magd, Rabab M; Vozza, Nicolas F; Tuszynski, Jack A; Wishart, David S

    2016-01-01

    Isolation of single chain antibody fragment (scFv) clones from naïve Tomlinson I+J phage display libraries that specifically bind a small biomarker molecule, L-Carnitine, was performed using iterative affinity selection procedures. L-Carnitine has been described as a conditionally essential nutrient for humans. Abnormally high concentrations of L-Carnitine in urine are related to many health disorders including diabetes mellitus type 2 and lung cancer. ELISA-based affinity characterization results indicate that selectants preferentially bind to L-Carnitine in the presence of key bioselecting component materials and closely related L-Carnitine derivatives. In addition, the affinity results were confirmed using biophysical fluorescence quenching for tyrosine residues in the V segment. Small-scale production of the soluble fragment yielded 1.3mg/L using immunopure-immobilized protein A affinity column. Circular Dichroism data revealed that the antibody fragment (Ab) represents a folded protein that mainly consists of β-sheets. These novel antibody fragments may find utility as molecular affinity interface receptors in various electrochemical biosensor platforms to provide specific L-Carnitine binding capability with potential applications in metabolomic devices for companion diagnostics and personalized medicine applications. It may also be used in any other biomedical application where detection of the L-Carnitine level is important. PMID:26608419

  6. An ATP-dependent L-carnitine transporter in Listeria monocytogenes Scott A is involved in osmoprotection.

    PubMed Central

    Verheul, A; Rombouts, F M; Beumer, R R; Abee, T

    1995-01-01

    Listeria monocytogenes is a gram-positive, psychotrophic, food-borne pathogen which is able to grow in osmotically stressful environments. Carnitine (beta-hydroxy-L-tau-N-trimethyl aminobutyrate) can contribute significantly to growth of L. monocytogenes at high osmolarity (R. R. Beumer, M. C. te Giffel, L. J. Cox, F. M. Rombouts, and T. Abee, Appl. Environ. Microbiol. 60:1359-1363, 1994). Transport of L-[N-methyl-14C]carnitine in L. monocytogenes was shown to be energy dependent. Analysis of cell extracts revealed that L-carnitine was not further metabolized, which supplies evidence for its role as an osmoprotectant in L. monocytogenes. Uptake of L-carnitine proceeds in the absence of a proton motive force and is strongly inhibited in the presence of the phosphate analogs vanadate and arsenate. The L-carnitine permease is therefore most likely driven by ATP. Kinetic analysis of L-carnitine transport in glucose-energized cells revealed the presence of a high-affinity uptake system with a Km of 10 microM and a maximum rate of transport (Vmax) of 48 nmol min-1 mg of protein-1. L-[14C]carnitine transport in L. monocytogenes is significantly inhibited by a 10-fold excess of unlabelled L-carnitine, acetylcarnitine, and tau-butyrobetaine, whereas L-proline and betaine display, even at a 100-fold excess, only a weak inhibitory effect. In conclusion, an ATP-dependent L-carnitine transport system in L. monocytogenes is described, and its possible roles in cold adaptation and intracellular growth in mammalian cells are discussed. PMID:7768820

  7. Photoaffinity labelling of carnitine acetyltransferase with S-(p-azidophenacyl)thiocarnitine.

    PubMed Central

    Mauro, J M; Lewis, R V; Barden, R E

    1986-01-01

    A photolabile reagent, p-azidophenacyl-DL-thiocarnitine, was synthesized and tested as a photoaffinity label for carnitine acetyltransferase (EC 2.3.1.7) from pigeon breast. p-Azidophenacyl-DL-thiocarnitine is an active-site-directed reagent for this acetyltransferase, since it is a competitive inhibitor (Ki 10 microM) versus carnitine. U.v. irradiation of a mixture of p-azidophenacyl-DL-thiocarnitine and enzyme produces irreversible inhibition. Acetyl-DL-carnitine protects the enzyme from inhibition by photoactivated p-azidophenacyl-DL-thiocarnitine. In the presence of 30 mM-2-mercaptoethanol as a scavenger, the relationship between loss of activity and photoincorporation of reagent suggests that one molecule of reagent is incorporated per molecule of inhibited enzyme. However, peptide maps of enzyme labelled with p-azidophenacyl[14C]thiocarnitine indicate that several (about six) tryptic peptides (of a possible 60-65) are modified. The presence of 5 mM-acetyl-DL-carnitine significantly decreases the incorporation of reagent in each labelled tryptic peptide. PMID:3800901

  8. Metabolomic analysis reveals that carnitines are key regulatory metabolites in phase transition of the locusts.

    PubMed

    Wu, Rui; Wu, Zeming; Wang, Xianhui; Yang, Pengcheng; Yu, Dan; Zhao, Chunxia; Xu, Guowang; Kang, Le

    2012-02-28

    Phenotypic plasticity occurs prevalently and plays a vital role in adaptive evolution. However, the underlying molecular mechanisms responsible for the expression of alternate phenotypes remain unknown. Here, a density-dependent phase polyphenism of Locusta migratoria was used as the study model to identify key signaling molecules regulating the expression of phenotypic plasticity. Metabolomic analysis, using high-performance liquid chromatography and gas chromatography-mass spectrometry, showed that solitarious and gregarious locusts have distinct metabolic profiles in hemolymph. A total of 319 metabolites, many of which are involved in lipid metabolism, differed significantly in concentration between the phases. In addition, the time course of changes in the metabolic profiles of locust hemolymph that accompany phase transition was analyzed. Carnitine and its acyl derivatives, which are involved in the lipid β-oxidation process, were identified as key differential metabolites that display robust correlation with the time courses of phase transition. RNAi silencing of two key enzymes from the carnitine system, carnitine acetyltransferase and palmitoyltransferase, resulted in a behavioral transition from the gregarious to solitarious phase and the corresponding changes of metabolic profiles. In contrast, the injection of exogenous acetylcarnitine promoted the acquisition of gregarious behavior in solitarious locusts. These results suggest that carnitines mediate locust phase transition possibly through modulating lipid metabolism and influencing the nervous system of the locusts. PMID:22328148

  9. Metabolomic analysis reveals that carnitines are key regulatory metabolites in phase transition of the locusts

    PubMed Central

    Wu, Rui; Wu, Zeming; Wang, Xianhui; Yang, Pengcheng; Yu, Dan; Zhao, Chunxia; Xu, Guowang; Kang, Le

    2012-01-01

    Phenotypic plasticity occurs prevalently and plays a vital role in adaptive evolution. However, the underlying molecular mechanisms responsible for the expression of alternate phenotypes remain unknown. Here, a density-dependent phase polyphenism of Locusta migratoria was used as the study model to identify key signaling molecules regulating the expression of phenotypic plasticity. Metabolomic analysis, using high-performance liquid chromatography and gas chromatography–mass spectrometry, showed that solitarious and gregarious locusts have distinct metabolic profiles in hemolymph. A total of 319 metabolites, many of which are involved in lipid metabolism, differed significantly in concentration between the phases. In addition, the time course of changes in the metabolic profiles of locust hemolymph that accompany phase transition was analyzed. Carnitine and its acyl derivatives, which are involved in the lipid β-oxidation process, were identified as key differential metabolites that display robust correlation with the time courses of phase transition. RNAi silencing of two key enzymes from the carnitine system, carnitine acetyltransferase and palmitoyltransferase, resulted in a behavioral transition from the gregarious to solitarious phase and the corresponding changes of metabolic profiles. In contrast, the injection of exogenous acetylcarnitine promoted the acquisition of gregarious behavior in solitarious locusts. These results suggest that carnitines mediate locust phase transition possibly through modulating lipid metabolism and influencing the nervous system of the locusts. PMID:22328148

  10. L-carnitine supplementation in humans. The effects on physical performance.

    PubMed

    Cerretelli, P; Marconi, C

    1990-02-01

    The use of supplementary L-carnitine by athletes has become rather widespread over the recent years even in the absence of unequivocal results from human experimental studies that might support this practice. To justify the above procedure, the most commonly purported reasons are that L-carnitine administration could hypoth