Science.gov

Sample records for oral carnitine therapy

  1. 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...

  2. Carnitine status and safety after administration of S-1108, a new oral cephem, to patients.

    PubMed Central

    Shimizu, K; Saito, A; Shimada, J; Ohmichi, M; Hiraga, Y; Inamatsu, T; Shimada, K; Tanimura, M; Fujita, Y; Nishikawa, T

    1993-01-01

    The metabolism and clinical safety of the pivalic acid-containing antibiotic S-1108, an orally active pro-drug cephalosporin, were investigated to assess the clinical effects, with special emphasis on the influence of carnitine consumption in 15 patients with various infectious diseases receiving S-1108 three times a day at a 300- or 600-mg total daily dose for 3 to 7 days. The free carnitine concentrations in plasma were greatly reduced to approximately 65% of pretreatment levels, and the plasma pivaloylcarnitine (the main metabolite of pivaloyloxymethyl ester) concentrations were increased during the 200-mg (three times a day) regimens but returned to the pretreatment levels within 3 to 5 days after the cessation of treatment. In three elderly patients with declining renal function (creatinine clearance rate, 31 to 50 ml/min), the acylcarnitine/free carnitine ratio increased from 0.1 to 0.4 up to 0.7 to 1.5 at day 5 during the 7-day treatment, showed a tendency to decrease, and then returned to the pretreatment ratio 4 days after discontinuation of the drug. The degree of free carnitine reduction and increase of the acylcarnitine/free carnitine ratio depended mostly on the dose and the duration of S-1108 treatment. The increased acylcarnitine/free carnitine ratio in elderly patients was due to reduction of the free carnitine concentration in plasma and mainly to the retardation of nontoxic pivaloylcarnitine excretion. This study indicated that there was a decrease in free carnitine levels in plasma, but there were no clinical symptoms or adverse effects associated with carnitine reduction in patients during the 7-day multiple administration of S-1108. PMID:8517691

  3. 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

  4. Characterisation of carnitine palmitoyltransferases in patients with a carnitine palmitoyltransferase deficiency: implications for diagnosis and therapy.

    PubMed Central

    Schaefer, J; Jackson, S; Taroni, F; Swift, P; Turnbull, D M

    1997-01-01

    OBJECTIVES: Carnitine palmitoyltransferase (CPT) deficiency is one of the most common defects of mitochondrial fatty acid oxidation. Two different enzymes (CPT-I and CPT-II) are involved. Due to problems in measuring enzyme activity, relatively little is known about the substrate specificity of each of the human enzymes. This is of considerable importance in the treatment of patients. The objectives were to establish a reliable method for the measurement of CPT activity in whole cells, to use this to characterise the substrate specificity of each enzyme, and finally, to determine if medium chain triglycerides would be of benefit in the treatment of deficient patients. METHODS: A simple permeabilisation technique was used which allows the measurement of CPT activity in a small amount of cultured skin fibroblasts or peripheral blood cells. Using this technique three patients were identified with CPT deficiency. In two of these patients, one with CPT-I deficiency and one with CPT-II deficiency, a complete substrate specificity profile of the mitochondrial carnitine acyltransferases was established for all saturated even chain acyl-CoA esters. RESULTS: For both enzymes the highest CPT activity was with C12-CoA. About 70% of total cellular carnitine octanoyltransferase activity was due to mitochondrial CPT. As CPT is involved in the transport of medium chain fatty acids the metabolic response of a patient with CPT-II deficiency to dietary medium chain triglycerides was assessed. Despite the normal production of ketone bodies there was a significant medium chain dicarboxylic aciduria in the patient, indicating a limited capacity of the CPT independent mitochondrial uptake of medium chain fatty acids. CONCLUSIONS: CPT deficiency can easily be diagnosed in permeabilised cultured skin fibroblasts. Both CPT-I and CPT-II are more active with medium chain length substrates than previously assumed. Care should therefore be taken in the treatment of these patients with medium

  5. 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

  6. 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

  7. 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

  8. 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

  9. Pharmacogenetics in Oral Antithrombotic Therapy.

    PubMed

    Maier, Cheryl L; Duncan, Alexander; Hill, Charles E

    2016-09-01

    Certain antithrombotic drugs exhibit high patient-to-patient variability that significantly impacts the safety and efficacy of therapy. Pharmacogenetics offers the possibility of tailoring drug treatment to patients based on individual genotypes, and this type of testing has been recommended for 2 oral antithrombotic agents, warfarin and clopidogrel, to influence use and guide dosing. Limited studies have identified polymorphisms that affect the metabolism and activity of newer oral antithrombotic drugs, without clear evidence of the clinical relevance of such polymorphisms. This article provides an overview of the current status of pharmacogenetics in oral antithrombotic therapy. PMID:27514462

  10. 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

  11. 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

  12. [L-carnitine therapy and myocardial function in children treated with chronic hemodialysis].

    PubMed

    Khoss, A E; Steger, H; Legenstein, E; Proll, E; Salzer-Muhar, U; Schlemmer, M; Balzar, E; Wimmer, M

    1989-01-01

    Six out of 14 chronically hemodialysed children with significantly decreased serum carnitine levels were substituted with L-carnitine (15-30 mg/kg/day-Biocarn) up to normal and above normal carnitine levels. None of these patients were digitalised. During the time of investigation plasma carnitine levels were investigated monthly and, simultaneously, three echocardiographic parameters in M-mode were quantitatively und qualitatively determined: shortening fraction (SF-%), ratio of left ventricular pre-ejection/ejection time (LVPT/LVET) and velocity of circumferential fibre shortening (Vcf). Carnitine substitution produced measurable changes in echocardiographic parameters, and a significant quantitative improvement in left ventricular function and performance: after 6 months of carnitine substitution a 24% improvement was seen, after 18 months a 44% mean improvement. No side effects of carnitine were observed; the compatibility was good. Beside these positive effects all patients reported decreased dialysis-associated spasms and polyneuropathic symptoms and increased somatic ability. PMID:2913722

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

    PubMed

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

    2000-01-01

    The efficacy, safety, and metabolic consequences of rapid weight loss in privately owned obese cats by means of a canned weight-reduction diet and the influence of orally administered L-carnitine on rate of weight loss, routine clinical evaluations, hepatic ultrasonography, plasma amino acid profiles, and carnitine analytes were evaluated. A double-blinded placebo-controlled design was used with cats randomly divided into 2 groups: Group 1 (n = 14) received L-carnitine (250 mg PO q24h) in aqueous solution and group 2 (n = 10) received an identical-appearing water placebo. Median obesity (body condition scores and percentage ideal body weight) in each group was 25%. Caloric intake was restricted to 60% of maintenance energy requirements (60 kcal/kg) for targeted ideal weight. The reducing formula was readily accepted by all cats. Significant weight loss was achieved by week 18 in each group without adverse effects (group 1 = 23.7%, group 2 = 19.6%). Cats receiving carnitine lost weight at a significantly faster rate (P < .05). Significant increases in carnitine values developed in each group (P < .02). However, significantly higher concentrations of all carnitine moieties and a greater percentage of acetylcarnitine developed in cats of group 1 (P < .01). The dietary formula and described reducing strategy can safely achieve a 20% weight reduction within 18 weeks in obese cats. An aqueous solution of L-carnitine (250 mg PO q12h) was at least partially absorbed, was nontoxic, and significantly increased plasma carnitine analyte concentrations as well as rate of weight loss. PMID:11110381

  14. Oral rehydration therapy.

    PubMed

    Sachdev, H P

    1996-08-01

    Oral rehydration solution (ORS), the best treatment of dehydration due to acute diarrhea, is the most important medical advance of this century since it is key to reducing infant and child morbidity and mortality. Pathogens responsible for acute diarrhea include those which produce enterotoxin at the intestinal mucosal surface, inducing secretion but are not invasive (e.g., Vibrio cholerae); those which invade and disrupt the mucosal lining (e.g., shigella species); and rotavirus. The World Health Organization (WHO)/UNICEF ORS is considered a universal ORS. Much research has been done on the ideal composition of an ORS. An ORS must have sufficient sodium to replace losses on a volume to volume basis, a glucose concentration that matches that of sodium to ensure its delivery to the ileum, sufficient amounts of potassium and base (e.g., sodium bicarbonate or trisodium citrate dihydrate) to correct acidosis and to enhance sodium absorption, and sufficient amounts of liquid. The risk of hypernatremia with use of the WHO/UNICEF ORS is a concern since infants and young children have an immature renal concentrating capacity, increased insensible water losses, and an impaired natriuretic response. Neonates and young infants may be prone to relatively slow correction of acidosis. It appears that the potassium content (20 mmol/l) of WHO-ORS should be higher to promote a net positive potassium retention. Too much glucose in the ORS will induce reverse osmosis of water into the gut, effectively making the ORS a dehydrating solution rather than a hydrating solution. Some carbohydrates other than glucose have proven effective glucose substitutes (e.g., sucrose, rice starch and powder, other cereals). Cereals have higher acceptability levels in developing countries. Research is investigating the nutritional benefits of supplementing ORS with micronutrients (e.g., vitamin A, folic acid, and zinc). ORS use with early refeeding has a beneficial effect on nutritional status after an

  15. 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

  16. [Oral ciprofloxacin therapy in salpingitis].

    PubMed

    De Wilde, R

    1988-01-01

    Thirty patients with clinical pelvic inflammatory disease were studied. Diagnosis was confirmed by laparoscopy. To determine the microbiological etiology, swab specimen for detection of aerobic, anaerobic and chlamydial infections were obtained from the endocervix, fimbriae and cul-de-sac. In 22 of 30 patients, microorganisms were detected. The patients received ciprofloxacin 2 X 750 mg p.o. daily at 12 hours interval for 10 days. During and after therapy, bacteriological examinations of the endocervix were performed. Based on the microbiological evaluation and clinical aspects, the bacteriological response and clinical efficacy were 86%. Laboratory analysis showed no alterations of blood values. As side effects we noticed gastrointestinal complaints (6/30), candidiasis vulvovaginalis (6/30), allergic exanthema (5/30) and non-bacterial cystitis (2/30). Oral ciprofloxacin-monotherapy proved to be safe and effective in pelvic inflammatory disease. PMID:3227738

  17. 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

  18. Carnitine transport and fatty acid oxidation.

    PubMed

    Longo, Nicola; Frigeni, Marta; Pasquali, Marzia

    2016-10-01

    Carnitine is essential for the transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent β-oxidation. It can be synthesized by the body or assumed with the diet from meat and dairy products. Defects in carnitine biosynthesis do not routinely result in low plasma carnitine levels. Carnitine is accumulated by the cells and retained by kidneys using OCTN2, a high affinity organic cation transporter specific for carnitine. Defects in the OCTN2 carnitine transporter results in autosomal recessive primary carnitine deficiency characterized by decreased intracellular carnitine accumulation, increased losses of carnitine in the urine, and low serum carnitine levels. Patients can present early in life with hypoketotic hypoglycemia and hepatic encephalopathy, or later in life with skeletal and cardiac myopathy or sudden death from cardiac arrhythmia, usually triggered by fasting or catabolic state. This disease responds to oral carnitine that, in pharmacological doses, enters cells using the amino acid transporter B(0,+). Primary carnitine deficiency can be suspected from the clinical presentation or identified by low levels of free carnitine (C0) in the newborn screening. Some adult patients have been diagnosed following the birth of an unaffected child with very low carnitine levels in the newborn screening. The diagnosis is confirmed by measuring low carnitine uptake in the patients' fibroblasts or by DNA sequencing of the SLC22A5 gene encoding the OCTN2 carnitine transporter. Some mutations are specific for certain ethnic backgrounds, but the majority are private and identified only in individual families. Although the genotype usually does not correlate with metabolic or cardiac involvement in primary carnitine deficiency, patients presenting as adults tend to have at least one missense mutation retaining residual activity. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler

  19. 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

  20. 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…

  1. Impact of inhalation therapy on oral health

    PubMed Central

    Godara, Navneet; Godara, Ramya; Khullar, Megha

    2011-01-01

    Inhalation therapy has been employed as the mainstay of the treatment in chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Beta-2 agonists, anticholinergic bronchodilators, inhaled corticosteroids, and sodium cromoglycate are often used alone or in combination in an inhaled form. Studies have shown that inhaled drugs used in the treatment have some adverse effects on the oral health based on their dosage, frequency, and duration of use. Several oral conditions such as xerostomia, dental caries, candidiasis, ulceration, gingivitis, periodontitis, and taste changes have been associated with inhalation therapy. Since the prevalence of chronic respiratory diseases is rising, it is important to provide optimal oral care to the individuals receiving inhalation therapy. This article will review the influence of inhaled drugs on the oral health of individuals and adequate management and prevention of the same. PMID:22084541

  2. Primary Carnitine Deficiency Presents Atypically with Long QT Syndrome: A Case Report.

    PubMed

    De Biase, Irene; Champaigne, Neena Lorenzana; Schroer, Richard; Pollard, Laura Malinda; Longo, Nicola; Wood, Tim

    2012-01-01

    Primary carnitine deficiency (PCD) is an autosomal recessive disorder of fatty acid oxidation caused by mutations in the SLC22A5 gene encoding for the carnitine transporter OCTN2. Carnitine uptake deficiency results in renal carnitine wasting and low plasma levels. PCD usually presents early in life either with acute metabolic crisis or as progressive cardiomyopathy that responds to carnitine supplementation. PCD inclusion in the newborn screening (NBS) programs has led to the identification of asymptomatic adult patients ascertained because of a positive NBS in their offspring. We extensively reviewed the literature and found that 15 of 42 adult published cases (35.7%) were symptomatic. Cardiac arrhythmias were present in five patients (12%). Here, we report the ascertainment and long-term follow-up of the first case of PCD presenting with long QT syndrome. The patient presented in her early twenties with a syncopal episode caused by ventricular tachycardia, and a prolonged QT interval. Arrhythmias were poorly controlled by pharmacologic therapy and a defibrillator was installed. Syncopal episodes escalated during her first pregnancy. A positive NBS in the patient's child suggested a carnitine uptake deficiency, which was confirmed by reduced carnitine transporter activity and by molecular testing. After starting carnitine supplementation, no further syncopal episodes have occurred and the QT interval returned to normal. As precaution, a low-dose metoprolol therapy and the defibrillator are still in place. Although rare, PCD should be ruled out as a cause of cardiac arrhythmias since oral carnitine supplementation is readily available and efficient. PMID:23430858

  3. 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

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

    PubMed Central

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

    2005-01-01

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

  5. Intravenous to oral antibiotic switch therapy.

    PubMed

    Cunha, Burke A.

    2001-05-01

    I.v.-to-p.o. switch therapy has become the mainstay of antibiotic therapy for the majority of patients. I.v.-to-p.o. switch therapy is inappropriate for critically ill patients who require i.v. antibiotic therapy and should not be considered in patients who have the inability to absorb drugs. These exceptions constitute a very small percentage of hospitalized patients for which i.v.-to-p.o. switch therapy is ideal. I.v.-to-p.o. switch therapy is best achieved with antibiotics that have high bioavailability that result in the same blood and tissue concentrations of antibiotic as their intravenous counterpart and have few gastrointestinal side effects. Antibiotics ideal for i.v.-to-p.o. switch programs include chloramphenicol, clindamycin, metronidazole, TMP-SMX, fluconazole, itraconazole, voriconazole, doxycycline, minocycline, levofloxacin, gatifloxacin, moxifloxacin and linezolid. Antibiotics that may be used in i.v.-to-p.o. switch programs that have lower bioavailability but are effective include beta-lactams and macrolides. For antibiotics with no oral formulation, e.g., carbapenems, equivalent coverage must be provided with an oral antibiotic from an unrelated class. Excluding gastrointestinal malabsorptive disorders, disease state is not a determinant of suitability for i.v.-to-p.o. switch programs. I.v.-to-p.o. switch programs should be used in patients with any infectious disease disorder for which there is effective oral therapy and is not limited to certain infectious diseases. Oral absorption of antibiotics is near normal in all but the most critically ill patients. Therefore, even in sick, hospitalized individuals, p.o. therapy is appropriate. I.v-to-p.o. switch therapy has several important advantages including decreasing drug cost (i.v. vs. p.o.), decreasing length of stay permitting earlier discharge and optimal reimbursement and decreasing or eliminating i.v. line phlebitis and sepsis with its cost implications. Clinicians should consider all

  6. Oral ixazomib maintenance therapy in multiple myeloma.

    PubMed

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

    2016-01-01

    Continuous therapy has proven to be an effective therapeutic strategy to improve the outcome of both young and elderly multiple myeloma patients. Remarkably, lenalidomide and bortezomib showed to play a crucial role in this setting due to their safety profile allowing long-term exposure. Ixazomib, the first oral proteasome inhibitor to be evaluated in multiple myeloma, exerts substantial anti-myeloma activity as a single agent and particularly in combination with immunomodulatory drugs and it may be an attractive option for maintenance therapy. Here we address the issue of maintenance therapy as part of a therapeutic approach of multiple myeloma patients focusing on the potential role of ixazomib. PMID:26588946

  7. Oral mucositis in myelosuppressive cancer therapy.

    PubMed

    Epstein, J B; Schubert, M M

    1999-09-01

    Because the etiology of mucositis is multifactorial , approaches to prevention and management have also been multifactorial. Effective prevention and management of mucositis will reduce the pain and suffering experienced during cancer treatment. Oropharyngeal pain in cancer patients frequently requires systemic analgesics, adjunctive medications, physical therapy, and psychologic therapy in addition to oral care and topical treatments. Good oral hygiene reduces the severity of oral mucositis and does not increase the risk of bacteremia. Current approaches to management include frequent oral rinsing with saline or bicarbonate rinses, maintaining excellent oral hygiene, and using topical anesthetics and analgesics. Cryotherapy is a potential adjunctive approach in some cases. There are a number of approaches that appear to represent viable candidates for further study. Biologic response modifiers offer the potential for prevention and for acceleration of healing. Various cytokines will enter clinical trials in the near future; these offer the potential for reduction of epithelial cell sensitivity to the toxic effects of cancer therapy or for stimulation of repair of the damaged tissue. Other approaches include the use of medications to reduce exposure of the oral mucosa to chemotherapeutic drugs that are secreted in saliva. Antimicrobial approaches have met with conflicting results, little effect being seen with chlorhexidine and systemic antimicrobials in the prevention of mucositis in radiation patients. In patients with BMT and patients with leukemia, chlorhexidine may not be effective in preventing mucositis, although there may be reduction in oral colonization by Candida. Initial studies of topical antimicrobials that affect the gram-negative oral flora have shown reductions in ulcerative mucositis during radiation therapy but have not been assessed in leukemia/BMT. Among other approaches that require further study are low-energy lasers and anti

  8. 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

  9. State of the art: Oral antiplatelet therapy.

    PubMed

    Gurbel, Paul A; 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

  10. [Management of osteoarthritis: oral therapies].

    PubMed

    Richette, Pascal

    2012-05-01

    According to the European League of Associations of Rheumatology (EULAR) and the American College of Rheumatology (ACR), acetaminophen should be used as a first-line therapy in patients with osteoarthritis, because of its safety and effectiveness. NSAID should be considered in patients unresponsive to acetaminophen, and should be prescribed at the lowest effective dose and for the shortest duration. The use of stronger analgesics, such as weak opioids and narcotic analgesics, is only indicated when other drugs, such as NSAID, have been ineffective or are contraindicated. Symptomatic slow acting drugs (avocado soybean unsaponifiable, chondroitin sulphate, diacerein, glucosamine sulphate) have mild symptomatic effects and may reduce the consumption of NSAID. PMID:22730795

  11. 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

  12. 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

  13. Oral therapy with glucose electrolyte solution.

    PubMed

    Clements, M L; Levine, M M; Black, R E; Hughes, T P; Nalin, D R; Pizarro, D; Hirschhorn, N

    1980-07-01

    Doctors Kahn and Blum based their views on oral rehydration on only 7 cases, and they fail to provide their methodological details. In their letter on oral rehydration with UNICEF/WHO (United Nations International Children's Emergency Fund/World Health Organization) glucose electrolyte solution (GES), they maintain that hyperkalemia is a danger of GES therapy, that hypernatremia will be aggravated, that therapy should not last for longer than 24 hours, that after 24 hours monitoring of plasma potassium will be needed, and that except for developing countries where material milk is used, no plan of treatment has been proposed after the first 24 hours of rehydration. The experience of Kahn and Blum is at variance with extensive data from many carefully monitored balanced studies in infants treated with GES. GES is a potent medication and needs to be used properly. Guidelines for use are listed. Kahn and Blum fail to indicate whether their 7 patients comprised their entire treatment group or only those with biochemical or clinical problems. They also fail to indicate the degree of dehydration of the infants at onset of therapy or the extent of ongoing diarrheal losses, and they do not describe the precise treatment regimen. Their mean time of treatment -- 41 hours -- was particularly long. The hyperkalemia reported by Kahn and Blum may have resulted from excessive GES administration, without a source of free water, to infants having few diarrheal stools. Proper use of GES formula rapidly rehydrates 95-98% of mildly to severely dehydrated infants, irrespective of etiology. PMID:6104241

  14. 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.

  15. Carnitine Deficiency and Pregnancy

    PubMed Central

    de Bruyn, Anouk; Jacquemyn, Yves; Kinget, Kristof; Eyskens, François

    2015-01-01

    We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, supplementation with carnitine is advised. This supplementation should be continued throughout pregnancy according to plasma concentrations. PMID:26113999

  16. Carnitine Deficiency and Pregnancy.

    PubMed

    de Bruyn, Anouk; Jacquemyn, Yves; Kinget, Kristof; Eyskens, François

    2015-01-01

    We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, supplementation with carnitine is advised. This supplementation should be continued throughout pregnancy according to plasma concentrations. PMID:26113999

  17. 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

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

    PubMed

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

    2011-09-01

    L-Carnitine is an endogenous molecule involved in fatty acid metabolism, biosynthesized within the human body using amino acids: L-lysine and L-methionine, as substrates. L-Carnitine can also be found in many foods, but red meats, such as beef and lamb, are the best choices for adding carnitine into the diet. Good carnitine sources also include fish, poultry and milk. Essentially, L-carnitine transports the chains of fatty acids into the mitochondrial matrix, thus allowing the cells to break down fat and get energy from the stored fat reserves. Recent studies have started to shed light on the beneficial effects of L-carnitine when used in various clinical therapies. Because L-carnitine and its esters help reduce oxidative stress, they have been proposed as a treatment for many conditions, i.e. heart failure, angina and weight loss. For other conditions, such as fatigue or improving exercise performance, L-carnitine appears safe but does not seem to have a significant effect. The presented review of the literature suggests that continued studies are required before L-carnitine administration could be recommended as a routine procedure in the noted disorders. Further research is warranted in order to evaluate the biochemical, pharmacological, and physiological determinants of the response to carnitine supplementation, as well as to determine the potential benefits of carnitine supplements in selected categories of individuals who do not have fatty acid oxidation defects. PMID:21561431

  19. AB081. Effects of combination therapy of Tamoxifen, L-carnitine and daily PDE5 inhibitors in the Peyronie’s disease

    PubMed Central

    Kang, Jae Il; Park, Tae Yong; Jeong, Hyeong Guk; Park, Jong Jin; Chae, Ji Yun; Kim, Jong Wook; Oh, Mi Mi; Park, Hong Seok; Kim, Je Jong; Moon, Du Geon

    2016-01-01

    Objective This study was designed to evaluate the efficacy of combination therapy of Tamoxifen, L-carnitine and daily PDE5 inhibitors and to compare with Potassium para-aminobenzoate (Potaba) monotherapy in the medical treatment of Peyronie’s disease. Methods From January 2011 to December 2014, a total of 104 patients with Peyronie’s disease enrolled in this study. Sixty-eight patients were treated with Tamoxifen 20 mg and Acetyl L-carnitine 330 mg twice a daily in addition to daily PDE5 inhibitors (Tadalafil 5 mg once daily) combination therapy (Group 1), while thirty-four patients were treated with Potassium para-aminobenzoate 12 g daily (Group 2), Pain on erection, impossibility of intercourse, plaque size, penile curvature and IIEF-5 were assessed. Plaque volume was assessed by penile ultrasonography. Results Both groups showed resolution of pain and intercourse satisfaction after treatment. The pre-treatment plaque sizes of both groups were 17.1±7.2, 17.0±5.0 mm, respectively. After treatment, those parameters significantly reduced to 13.2±5.6, 16.2±5.3 mm. In group 1, combination therapy significantly improved the angle of penile curvature, plaque size, and IIEF (P value <0.05). In group 2, the size of the plaque, penile curvature and IIEF were improved after Potassium para-aminobenzoate monotherapy. However, no significant differences were observed. Conclusion Statistically significant improvement in intercourse satisfaction, plaque size, degree of curvature and IIEF-5 was observed in combination therapy. Combination therapy may be the more effective than Potassium para-aminobenzoate monotherapy in medical treatment of Peyronie’s disease.

  20. AB093. The efficacy of medical treatment of Peyronie’s disease: Potaba monotherapy vs. combination therapy with Tamoxifen, L-carnitine, and PDE5 inhibitor

    PubMed Central

    Park, Jong Jin; Kim, Jong Wook; Moon, Du Geon

    2016-01-01

    Objective This study was designed to evaluate the efficacy of combination therapy of Tamoxifen, L-carnitine and daily PDE5 inhibitors and to compare with Potassium para-aminobenzoate (Potaba) monotherapy in the medical treatment of Peyronie’s disease. Methods From January 2011 to December 2014, a total of 104 patients with Peyronie’s disease enrolled in this study. Sixty-eight patients were treated with Tamoxifen 20 mg and Acetyl L-carnitine 330 mg twice a daily in addition to daily PDE5 inhibitors (Tadalafil 5 mg once daily) combination therapy (Group 1), while thirty-four patients were treated with Potassium para-aminobenzoate 12 g daily (Group 2), Pain on erection, impossibility of intercourse, plaque size, penile curvature and IIEF-5 were assessed. Plaque volume was assessed by penile ultrasonography. Results Both groups showed resolution of pain and intercourse satisfaction after treatment. The pre-treatment plaque sizes of both groups were 17.1±7.2, 17.0±5.0 mm, respectively. After treatment, those parameters significantly reduced to 13.2±5.6, 16.2±5.3 mm. In group 1, combination therapy significantly improved the angle of penile curvature, plaque size, and IIEF (P<0.05). In group 2, the size of the plaque, penile curvature and IIEF were improved after Potassium para-aminobenzoate monotherapy. However, no significant differences were observed. Conclusions Statistically significant improvement in intercourse satisfaction, plaque size, degree of curvature and IIEF-5 was observed in combination therapy. Combination therapy may be the more effective than Potassium para-aminobenzoate monotherapy in medical treatment of Pyeronie’s disease.

  1. 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

  2. Management of oral disease prior to radiation therapy.

    PubMed

    Schiødt, Morten; Hermund, Niels Ulrich

    2002-01-01

    Radiation therapy for malignant tumors of the head and neck is associated with significant side effects involving the oral cavity. For example, radiation therapy leads to reduced vascularity and oxygen tension of the oral hard and soft tissues and also to salivary gland dysfunction. These changes increase the risk of dental decay and oral infections and lead to reduced healing capacity following oral surgery procedures. A severe complication of radiation therapy is osteoradionecrosis of the jaw bone. The purpose of this paper is to review preradiation oral examination and treatment. Patient management regarding oral disease prior to radiation therapy has to accomplish a number of goals: (1) to identify existing oral disease and potential risk of oral disease, (2) to remove infectious dental/oral foci before the start of radiation therapy, (3) to prepare the patient for the expected side effects with information about them, (4) to establish an adequate standard of oral hygiene to meet the increased challenge, (5) to provide a plan for maintaining oral hygiene and fluoride treatment, for oral rehabilitation, and for follow-up and (6) to inform the patient about the availability of any financial support for dental treatment, and finally (7) to establish the necessary multidiciplinary collaboration within the health care system so that oral symptoms and sequelae before, during and after the radiation therapy can be reduced or alleviated. The methods used to accomplish these goals may vary between cancer centers. Each center should have a multidisciplinary team to handle such problems. After the end of radiation therapy most of the dental treatments in our patients are done by private dentists, except for some oral surgery procedures, which are performed in hospital. In our experience, the major challenge in this process is related to (1) informing of the patient, (2) timing the coordination between all the health care workers involved, (3) establishing an adequate

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

    PubMed

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

    2016-01-01

    We aimed to assess the impact of L-carnitine on plasma Lp(a) concentrations through systematic review and meta-analysis of available RCTs. The literature search included selected databases up to 31(st) January 2015. Meta-analysis was performed using fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The meta-analysis showed a significant reduction of Lp(a) levels following L-carnitine supplementation (WMD: -8.82 mg/dL, 95% CI: -10.09, -7.55, p < 0.001). When the studies were categorized according to the route of administration, a significant reduction in plasma Lp(a) concentration was observed with oral (WMD: -9.00 mg/dL, 95% CI: -10.29, -7.72, p < 0.001) but not intravenous L-carnitine (WMD: -2.91 mg/dL, 95% CI: -10.22, 4.41, p = 0.436). The results of the meta-regression analysis showed that the pooled estimate is independent of L-carnitine dose (slope: -0.30; 95% CI: -4.19, 3.59; p = 0.878) and duration of therapy (slope: 0.18; 95% CI: -0.22, 0.59; p = 0.374). In conclusion, the meta-analysis suggests a significant Lp(a) lowering by oral L-carnitine supplementation. Taking into account the limited number of available Lp(a)-targeted drugs, L-carnitine might be an effective alternative to effectively reduce Lp(a). Prospective outcome trials will be required to fully elucidate the clinical value and safety of oral L-carnitine supplementation. PMID:26754058

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

    PubMed Central

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

    2016-01-01

    We aimed to assess the impact of L-carnitine on plasma Lp(a) concentrations through systematic review and meta-analysis of available RCTs. The literature search included selected databases up to 31st January 2015. Meta-analysis was performed using fixed-effects or random-effect model according to I2 statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The meta-analysis showed a significant reduction of Lp(a) levels following L-carnitine supplementation (WMD: −8.82 mg/dL, 95% CI: −10.09, −7.55, p < 0.001). When the studies were categorized according to the route of administration, a significant reduction in plasma Lp(a) concentration was observed with oral (WMD: −9.00 mg/dL, 95% CI: −10.29, −7.72, p < 0.001) but not intravenous L-carnitine (WMD: −2.91 mg/dL, 95% CI: −10.22, 4.41, p = 0.436). The results of the meta-regression analysis showed that the pooled estimate is independent of L-carnitine dose (slope: −0.30; 95% CI: −4.19, 3.59; p = 0.878) and duration of therapy (slope: 0.18; 95% CI: −0.22, 0.59; p = 0.374). In conclusion, the meta-analysis suggests a significant Lp(a) lowering by oral L-carnitine supplementation. Taking into account the limited number of available Lp(a)-targeted drugs, L-carnitine might be an effective alternative to effectively reduce Lp(a). Prospective outcome trials will be required to fully elucidate the clinical value and safety of oral L-carnitine supplementation. PMID:26754058

  5. Striae distensae of augmented breasts after oral contraceptive therapy.

    PubMed

    Har-Shai, Y; Barak, A; Taran, A; Weissman, A

    1999-02-01

    A case of striae distensae (SD) of bilateral augmented breasts following oral contraceptive therapy is presented. Striae maturation and the prevention of additional skin marks was achieved with immediate cessation of oral contraceptive pill therapy and long-term daily topical application of tretinoin cream. It is suggested that patients who are candidates for breast augmentation surgery should be informed of the possible risk of developing SD if they are taking or planning to take the contraceptive pill. PMID:10029486

  6. Hyperammonemic Encephalopathy Caused by Carnitine Deficiency

    PubMed Central

    Zucker, Stephen D.

    2007-01-01

    Carnitine is an essential co-factor in fatty acid metabolism. Carnitine deficiency can impair fatty acid oxidation, rarely leading to hyperammonemia and encephalopathy. We present the case of a 35-year-old woman who developed acute mental status changes, asterixis, and diffuse muscle weakness. Her ammonia level was elevated at 276 μg/dL. Traditional ammonia-reducing therapies were initiated, but proved ineffective. Pharmacologic, microbial, and autoimmune causes for the hyperammonemia were excluded. The patient was severely malnourished and her carnitine level was found to be extremely low. After carnitine supplementation, ammonia levels normalized and the patient’s mental status returned to baseline. In the setting of refractory hyperammonemia, this case illustrates how careful investigation may reveal a treatable condition. PMID:18080167

  7. 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

  8. 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.

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

    SciTech Connect

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

    1991-04-01

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

  10. Current and future oral systemic therapies for psoriasis.

    PubMed

    Kelly, John B; Foley, Peter; Strober, Bruce E

    2015-01-01

    For patients with moderate to severe psoriasis, there is a large range of variably effective and safe oral, systemic medications. With appropriate monitoring, these therapies may be used as either monotherapy or in combination with other therapies. Newer drugs in the research pipeline hold significant promise. PMID:25412786

  11. Carnitine biosynthesis in mammals.

    PubMed Central

    Vaz, Frédéric M; Wanders, Ronald J A

    2002-01-01

    Carnitine is indispensable for energy metabolism, since it enables activated fatty acids to enter the mitochondria, where they are broken down via beta-oxidation. Carnitine is probably present in all animal species, and in numerous micro-organisms and plants. In mammals, carnitine homoeostasis is maintained by endogenous synthesis, absorption from dietary sources and efficient tubular reabsorption by the kidney. This review aims to cover the current knowledge of the enzymological, molecular, metabolic and regulatory aspects of mammalian carnitine biosynthesis, with an emphasis on the human and rat. PMID:11802770

  12. 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.

  13. 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

  14. 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

  15. 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

  16. Oral therapy for Peyronie's disease, does it work?

    PubMed

    Barrett-Harlow, Brittani; Wang, Run

    2016-06-01

    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

  17. 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

  18. Treatment of carnitine deficiency.

    PubMed

    Winter, S C

    2003-01-01

    Carnitine deficiency is a secondary complication of many inborn errors of metabolism. Pharmacological treatment with carnitine not only corrects the deficiency, it facilitates removal of accumulating toxic acyl intermediates and the generation of mitochondrial free coenzyme A (CoA). The United States Food and Drug Administration (US FDA) approved the use of carnitine for the treatment of inborn errors of metabolism in 1992. This approval was based on retrospective chart analysis of 90 patients, with 18 in the untreated cohort and 72 in the treated cohort. Efficacy was evaluated on the basis of clinical and biochemical findings. Compelling data included increased excretion of disease-specific acylcarnitine derivatives in a dose-response relationship, decreased levels of metabolites in the blood, and improved clinical status with decreased hospitalization frequency, improved growth and significantly lower mortality rates as compared to historical controls. Complications of carnitine treatment were few, with gastrointestinal disturbances and odour being the most frequent. No laboratory or clinical safety issues were identified. Intravenous carnitine preparations were also approved for treatment of secondary carnitine deficiency. Since only 25% of enteral carnitine is absorbed and gastrointestinal tolerance of high doses is poor, parenteral carnitine treatment is an appealing alternative therapeutic approach. In 7 patients treated long term with high-dose weekly to daily venous boluses of parenteral carnitine through a subcutaneous venous port, benefits included decreased frequency of decompensations, improved growth, improved muscle strength and decreased reliance on medical foods with liberalization of protein intake. Port infections were the most troubling complication. Theoretical concerns continue to be voiced that carnitine might result in fatal arrhythmias in patients with long-chain fat metabolism defects. No published clinical studies substantiate these

  19. Novel therapies for oral lichen planus.

    PubMed

    Thongprasom, Kobkan; Prapinjumrune, Chanwit; Carrozzo, Marco

    2013-11-01

    Oral lichen planus (OLP) is a chronic mucocutaneous disorder commonly found in middle-aged women. Despite the progress in research and advance in knowledge on OLP, a successful management is still difficult to achieve. The main aim of OLP treatment is to control the symptoms of the affected patients. Steroids and other immunosuppressive drugs have been recommended and widely used in the treatment of OLP. Topical corticosteroids are the mainstay of OLP treatment, but strong evidence on their effectiveness is lacking. The effectiveness of alternative ways of managing OLP has been recently reported. Topical aloe vera, topical pimecrolimus and oral curcuminoids are the most promising of the new treatment modalities. Other interesting modalities are topically applied thalidomide and amlexanox. Nevertheless, the careful assessment between the risks and benefits of these drugs is crucial and larger and well-conducted trials need to confirm the above encouraging results. PMID:23668304

  20. Implant survival rate after oral cancer therapy: a review.

    PubMed

    Javed, Fawad; Al-Hezaimi, Khalid; Al-Rasheed, Abdulaziz; Almas, Khalid; Romanos, George E

    2010-12-01

    The overall impression regarding the success of dental implants (DI) in patients having undergone oral cancer therapy remains unclear. The aim of the present review study was to assess the implant survival rate after oral cancer therapy. Databases were explored from 1986 up to and including September 2010 using the following keywords in various combinations: "cancer", "chemotherapy", "dental implant", "oral", "osseointegration", "radiotherapy", "surgery" and "treatment". The eligibility criteria were: (1) original research articles; (2) clinical studies; (3) reference list of pertinent original and review studies; (4) intervention: patients having undergone radio- and chemotherapy following oral cancer surgery; and (5) articles published only in English. Twenty-one clinical studies were included. Results from 16 studies reported that DI can osseointegrate and remain functionally stable in patients having undergone radiotherapy following oral cancer surgery; whereas three studies showed irradiation to have negative effects on the survival of DI. Two studies reported that DI can osseointegrate and remain functionally stable in patients having undergone chemotherapy. It is concluded that DI can osseointegrate and remain functionally stable in patients having undergone oral cancer treatment. PMID:21055997

  1. Exogenous pubertal induction by oral versus transdermal estrogen therapy.

    PubMed

    Kenigsberg, Lisa; Balachandar, Sadana; Prasad, Kris; Shah, Bina

    2013-04-01

    Hypogonadal adolescent girls need estrogen therapy for the induction of puberty. For years, oral conjugated estrogens have been used for this purpose, starting at a very low dose, with gradual increments over time, to allow for the maturation of the reproductive organs, in order to mimic physiologic conditions. Several concerns, mainly due to first pass through the liver, are manifest with oral estrogen therapy. With the advent of transdermal estrogens and its improved efficacy profile as well as reduced side effects, it seems reasonable to consider it for pubertal induction. The primary objective of this study was to compare and contrast oral versus transdermal estrogen with regard to metabolism and physiology and to review current available data on transdermal estrogens with respect to exogenous pubertal induction. PMID:22112543

  2. Novel Oral Therapies for Psoriasis and Psoriatic Arthritis.

    PubMed

    Yiu, Zenas Z N; Warren, Richard B

    2016-06-01

    Several classes of new oral therapy are in use or in development for the treatment of psoriasis. Despite the high efficacy of biologics, new oral therapies remain important as patients generally prefer this mode of administration and they offer an alternative risk-benefit profile. In this review, we discuss the novel modes of action of these drugs, including modulation of cellular pathways involving diverse targets such as Janus kinase, phosphodiesterase 4, sphingosine 1-phosphate, A3 adenosine receptor and rho-associated kinase 2. We review the available evidence around licensed drugs (apremilast) and drugs that are advanced (tofacitinib) or early (ponesimod, baricitinib, peficitinib, INCB039110, CF101, KD025) in the development pipeline. The key limitations of these oral therapies are their modest efficacy profile (apremilast, ponesimod) and the limitations of their safety profile (tofacitinib, ponesimod), while the evidence for the early pipeline drugs are at phase II level only. Potential niches of current unmet needs include apremilast for patients with concomitant psoriatic arthritis, as combination treatments with biologic therapies, and/or for patients in whom multiple biologic therapies have failed due to immunogenicity and secondary inefficacy. The present knowledge gap regarding these novel drugs includes the need for longer clinical trials or observational studies to evaluate safety, and randomised phase III trials for the early pipeline drugs. We conclude that further research and data are necessary to conclusively establish the role of these agents in the current psoriasis treatment paradigm. PMID:26923915

  3. 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

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

    PubMed Central

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

    2011-01-01

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

  5. 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

  6. Cancer therapy and oral mucositis. An appraisal of drug prophylaxis.

    PubMed

    Verdi, C J

    1993-09-01

    Oral mucositis as a consequence of cytotoxic therapy is a major cause of morbidity in cancer patients. Cancer therapy-induced tissue damage leading to mucositis can occur through either direct or indirect stomatotoxicity. Once mucositis has occurred, treatment consists of measures to palliate symptoms. The prevention of cancer therapy-induced oral mucositis is less standardised. Numerous drugs have been used as prophylactic agents to prevent chemo- and radiotherapy-induced mucositis. Controlled trials have shown some degree of prophylactic efficacy for sucralfate, chlorhexidine and benzydamine. Positive but non-placebo-controlled trials requiring more study have been conducted with dinoprostone (prostaglandin E2), silver nitrate, beta-carotene, pentoxifylline and lozenges containing polymixin B, tobramycin and amphotericin B. Current studies have shown a lack of efficacy with allopurinol and granulocyte colony-stimulating factor (G-CSF). Nonpharmacological methods such as oral cryotherapy and helium-neon laser treatments have shown some promise. At the present time no agent has been shown to be uniformly efficacious and can be accepted as standard therapy. Additional studies combining several agents or incorporating nonpharmacological manoeuvres for mucositis prevention are needed. PMID:8240724

  7. 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

  8. Oral Disease-Modifying Therapies for Multiple Sclerosis

    PubMed Central

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

    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

  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. 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

  14. Revisiting the Cutaneous Impact of Oral Hormone Replacement Therapy

    PubMed Central

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

    2013-01-01

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

  15. 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. PMID:27074245

  16. 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

  17. Disorders of carnitine biosynthesis and transport.

    PubMed

    El-Hattab, Ayman W; Scaglia, Fernando

    2015-11-01

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

  18. 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.

  19. Colostrum as oral immune therapy to promote neonatal health.

    PubMed

    Gephart, Sheila M; Weller, Michelle

    2014-02-01

    It is well known that the immune response is blunted and underdeveloped in the premature infant, but human milk supports the infant's growth, function, and effectiveness. Thus, own mother's colostrum (OMC) administered oropharyngeally has potential to deliver oral immune therapy (C-OIT) even before enteral feedings have begun. Colostrum interacts with lymphoid tissue in the oropharynx and gut. Colostrum as oral immune therapy is delivered by swabbing the cheeks in the first days of life. Little formal study has evaluated its effectiveness. However, small studies demonstrate that it is a practice that is safe, feasible, and well tolerated even by the smallest premature infants. Encouraging preliminary evidence supports the effect of C-OIT to reduce the time to full enteral feedings. Effects on other outcomes is unclear, in part because existing studies are underpowered to detect significant differences on outcomes like necrotizing enterocolitis, sepsis, and death. Another limitation in the evidence base is that adherence to the intervention and the number of doses of colostrum infants received in the studies is not consistently made clear. More well-designed studies are needed to demonstrate the impact on neonatal complications and how C-OIT supports the infant's immune development. Quality improvement and time series reports of differences pre- and postimplementation of OMC given orally should minimally include statistics for adherence to the intervention and/or the number of doses an infant received as a covariate. Even so, OMC is an immune therapy that poses little risk yet offers likely cost-effective benefit for vulnerable infants. PMID:24472888

  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. PMID:23225627

  1. 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. PMID:21198634

  2. 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

  3. Treatment of canine oral squamous cell carcinomas with photodynamic therapy

    PubMed Central

    McCaw, D L; Pope, E R; Payne, J T; West, M K; Tompson, R V; Tate, D

    2000-01-01

    Eleven dogs with naturally occurring oral squamous cell carcinomas were treated with photodynamic therapy (PDT) using Photochlor (HPPH) as the photosensitizer. The largest length of the tumours measured in a two-dimensional plane ranged from 0.9 to 6.8 cm. Seven of the tumours invaded underlying bone as determined by radiograph appearance. Photochlor was injected intravenously at a dose of 0.3 mg kg–1. Forty-eight hours later the tumours were treated. Tumours with a surface to base depth of greater than 1 cm were surgically reduced to less than 1 cm. Irradiation with 665 nm light with an energy density of 100 J cm–2was administered. Eight dogs were considered cured with no tumour recurrence for at least 17 months after treatment. Local treatment of oral squamous cell carcinomas with PDT appears to give results similar to those obtained with surgical removal of large portions of the mandible or maxilla. The cosmetic results with PDT are superior to those of radical surgical removal. The new sensitizer, Photochlor, appears effective for oral squamous carcinomas with results similar to those reported for other sensitizers. © 2000 Cancer Research Campaign PMID:10755404

  4. 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…

  5. 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

  6. 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 ...

  7. Intravenous/oral ciprofloxacin therapy versus intravenous ceftazidime therapy for selected bacterial infections.

    PubMed

    Gaut, P L; Carron, W C; Ching, W T; Meyer, R D

    1989-11-30

    The efficacy and toxicity of sequential intravenous and oral ciprofloxacin therapy was compared with intravenously administered ceftazidime in a prospective, randomized, controlled, non-blinded trial. Thirty-two patients (16 patients receiving ciprofloxacin and 16 patients receiving ceftazidime) with 38 infections caused by susceptible Pseudomonas aeruginosa, enteric gram-negative rods, Salmonella group B, Serratia marcescens, Pseudomonas cepacia, and Xanthomonas maltophilia at various sites were evaluable for determination of efficacy. Length of therapy varied from seven to 25 days. Concomitant antimicrobials included intravenously administered beta-lactams for gram-positive organisms, intravenous/oral metronidazole and clindamycin for anaerobes, and intravenous/local amphotericin B for Candida albicans. Intravenous administration of 200 mg ciprofloxacin every 12 hours to 11 patients produced peak serum levels between 1.15 and 3.12 micrograms/ml; trough levels ranged between 0.08 and 0.86 micrograms/ml. Overall response rates were similar for patients receiving ciprofloxacin and ceftazidime. Emergence of resistance was similar in both groups--one Enterobacter cloacae and two P. aeruginosa became resistant after ciprofloxacin therapy and two P. aeruginosa became resistant after ceftazidime therapy. The frequency of superinfection with a variety of organisms was also similar in both groups. Adverse events related to ciprofloxacin included transient pruritus at the infusion site and generalized rash leading to drug discontinuation (one patient each), and with ceftazidime adverse effects included pain at the site of infusion and the development of allergic interstitial nephritis (one patient each). Overall, intravenous/oral ciprofloxin therapy appears to be as safe and effective as intravenous ceftazidime therapy in the treatment of a variety of infections due to susceptible aerobic gram-negative organisms. PMID:2686417

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

    PubMed Central

    Darweesh, Amal Q; Fatani, Amal J

    2010-01-01

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

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

    PubMed

    Sayed-Ahmed, Mohamed M; Darweesh, Amal Q; Fatani, Amal J

    2010-01-01

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

  10. 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

  11. Implant surgery and oral anticoagulant therapy: case report

    PubMed Central

    MIRANDA, M.; BOLLERO, P.; D’OVIDIO, N.; MARSANGO, V.; BARLATTANI, A.

    2014-01-01

    SUMMARY Objectives. This work aims to assess the risks both thromboembolic that bleeding of a management protocol “non-conservative” in patients on oral anticoagulant therapy (OAT) to be undergoing implant surgery. Materials and methods. We decided to take a surgical “non-conservative” protocol, to insert four implants in the aesthetic zone, without using flapless surgery and the surgical template. In accordance with the hematologist, the value of INR is lowered and warfarin was replaced with heparin low molecular weight, to have a better coagulation’s control. Results. The modern guidelines impose a protocol of conservative management in patients with OAT, with minimally invasive surgery, flapless, and use of surgical template to reduce the risk of uncontrolled bleeding. This, thanks to the team-work between dentist and hematologist, thanks to careful adjustment of INR and the use of local haemostatic agents, were not encountered any problems with bleeding or intra or postoperative. Conclusion. Surgical treatment of patients with OAT is a real problem for the oral surgeon, to treat every time in association with the hematologist. Applying this type of surgical procedure, different from today’s guidelines, in our experience there were no post-operative complications (bleeding or bleeding); osseointegration has not been compromised and the prosthetic rehabilitation was completed successfully. PMID:25694802

  12. 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

  13. Worldwide management of oral anticoagulant therapy: the ISAM study.

    PubMed

    Pengo, Vittorio; Pegoraro, Cinzia; Cucchini, Umberto; Iliceto, Sabino

    2006-02-01

    A multicenter, observational, retrospective, cross-sectional study of patients, receiving oral anticoagulation therapy (OAT) for stroke prophylaxis in chronic non-valvular atrial fibrillation (NVAF) was conducted in the US, Canada, France, Italy and Spain according to their predominant model of care [routine medical care (RMC) or Anticoagulation Clinic care (ACC)]. The study objectives were to assess anticoagulation control (time in target range), and to describe the features of the local model of care. Consecutive patients were recruited on the basis of a minimum of 60 days of oral anticoagulant treatment over a 12 month period, and clinic and physician details were captured by means of a structured face-to-face or telephone interview. Time in therapeutic range (TTR) was calculated by using linear interpolation between INR values. A total of 1511 patients were recruited, of whom 1445 were included in the analysis of TTR. TTR was higher in ACC (69.5% and 64.9% for Italy and Spain, respectively) with respect to RMC (58.1%, 62.8% and 59.3% for the US, Canada and France, respectively). Mean intervals between INR determinations were between 3 and 4 weeks. Dose changes in case of INR outside therapeutic range were more frequent in Spain and less frequent in France. Striking differences were observed in type of VKA used, specialists involved in patient management, and dosage instructions. Studying of anticoagulation management based on local models of care highlights important discrepancies among countries and suggests further standardization of the management of this important therapy is necessary. PMID:16475046

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

    SciTech Connect

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

    1987-12-01

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

  15. 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

  16. L-carnitine ameliorates the liver inflammatory response by regulating carnitine palmitoyltransferase I-dependent PPARγ signaling.

    PubMed

    Jiang, Fang; Zhang, Zongqi; Zhang, Yi; Wu, Jianping; Yu, Li; Liu, Su

    2016-02-01

    The liver is crucial for systemic inflammation in cancer cachexia. Previous studies have shown that L-carnitine, as the key regulator of lipid metabolism, exerts an anti-inflammatory effect in several diseases, and ameliorates the symptoms of cachexia by regulating the expression and activity of carnitine palmitoyltransferase (CPT) in the liver. However, the effect of L-carnitine on the liver inflammatory response in cancer cachexia remains to be elucidated. The aim of the present study was to examine the role of the CPT I-dependent peroxisome proliferator-activated receptor (PPAR)γ signaling pathway in the ameliorative effect of L-carnitine on the liver inflammatory response. This was investigated in a colon-26 tumor-bearing mouse model with cancer cachexia. Liver sections were immunohistochemically analyzed, and mRNA and protein levels of representative molecules of the CPT-associated PPARγ signaling pathway were assessed using PCR and western blot analysis, respectively. The results showed that oral administration of L-carnitine in these mice improved hepatocyte necrosis, liver cell cord derangement and hydropic or fatty degeneration of the liver cells in the liver tissues, decreased serum levels of malondialdehyde, increased serum levels of superoxide dismutase and glutathione peroxidase, and elevated the expression levels of PPARα and PPARγ at the mRNA and protein levels. These changes induced by L-carnitine were reversed by treatment with etomoxir, an inhibitor of CPT I. The inhibitory effect of L-carnitine on the increased expression level of nuclear factor (NF)-κB p65 in the peripheral blood mononuclear cells was markedly weakened by GW9662, a selective inhibitor of PPAR-γ. GW9662 also eliminated the inhibitory effect of L-carnitine on the expression of cyclooxygenase-2 (Cox-2) in the liver, and on the serum expression levels of pro-inflammatory prostaglandin E2, C-reactive protein, tumor necrosis factor-α and interleukin-6 in the cancer cachexia

  17. 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

  18. 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…

  19. Primary Carnitine Deficiency and Cardiomyopathy

    PubMed Central

    Fu, Lijun; Huang, Meirong

    2013-01-01

    Carnitine is essential for the transfer of long-chain fatty acids from the cytosol into mitochondria for subsequent β-oxidation. A lack of carnitine results in impaired energy production from long-chain fatty acids, especially during periods of fasting or stress. Primary carnitine deficiency (PCD) is an autosomal recessive disorder of mitochondrial β-oxidation resulting from defective carnitine transport and is one of the rare treatable etiologies of metabolic cardiomyopathies. Patients affected with the disease may present with acute metabolic decompensation during infancy or with severe cardiomyopathy in childhood. Early recognition of the disease and treatment with L-carnitine may be life-saving. In this review article, the pathophysiology, clinical presentation, diagnosis, treatment and prognosis of PCD are discussed, with a focus on cardiac involvements. PMID:24385988

  20. 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

  1. The future prospects of pharmacogenetics in oral anticoagulation therapy.

    PubMed

    Kamali, Farhad; Pirmohamed, Munir

    2006-06-01

    Coumarins are the mainstay of oral anticoagulation for the treatment and prophylaxis of thromboembolic disorders. They have a narrow therapeutic index and regular monitoring is therefore required to avoid serious adverse effects. There is wide interindividual variability in dosage requirements, which makes anticoagulation response unpredictable. Current dosing titrations are haphazard and inconvenient and poor initial control leads to morbidity, and occasional mortality, because of bleeding and further thromboembolism. Recent discoveries have helped to characterize the factors that contribute to the interindividual variability in responses to coumarins. Patient and environmental factors that affect anticoagulation response to coumarins include age, body size, dietary vitamin K status, concurrent disease and drug interactions. More recently, single nucleotide polymorphisms in the 2C9 isoform of cytochrome P450 (CYP2C9) and vitamin K epoxide reductase (VKOR) have been shown to make significant contributions to the variability in coumarin dosage requirements. Polymorphisms in other genes that mediate the actions of coumarins may also contribute to this variability. Racial and cultural differences influence dosage requirements, which can be explained, at least in part, by genetic and dietary factors. Incorporation of genetic and environmental factors could help in the prediction of more individualized loading and maintenance doses for safer anticoagulation therapy. PMID:16722840

  2. Oral mucosal injury caused by cancer therapies: current management and new frontiers in research.

    PubMed

    Jensen, Siri B; Peterson, Douglas E

    2014-02-01

    This invited update is designed to provide a summary of the state-of-the-science regarding oral mucosal injury (oral mucositis) caused by conventional and emerging cancer therapies. Current modeling of oral mucositis pathobiology as well as evidence-based clinical practice guidelines for prevention and treatment of oral mucositis are presented. In addition, studies addressing oral mucositis as published in the Journal of Oral Pathology and Medicine 2008-2013 are specifically highlighted in this context. Key research directions in basic and translational science associated with mucosal toxicity caused by cancer therapies are also delineated as a basis for identifying pathobiologic and pharmacogenomic targets for interventions. This collective portfolio of research and its ongoing incorporation into clinical practice is setting the stage for the clinician in the future to predict mucosal toxicity risk and tailor therapeutic interventions to the individual oncology patient accordingly. PMID:24261541

  3. 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

  4. 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

  5. Moderate carnitine depletion and long-chain fatty acid oxidation, exercise capacity, and nitrogen balance in the rat.

    PubMed

    Heinonen, O J; Takala, J

    1994-09-01

    Carnitine plays a central role in lipid metabolism by transporting long-chain fatty acids into the mitochondria for beta-oxidation. Reduction of carnitine concentration does not automatically imply that functional carnitine deficiency exists with direct consequences on energy metabolism. In our experimental model, we reduced tissue concentrations of carnitine to levels that are comparable to those in patients with various metabolic disorders with secondary carnitine deficiency and did a study on the in vivo effects of moderate carnitine depletion on palmitate oxidation, exercise capacity, and nitrogen balance. Thirty rats were divided into a carnitine-depleted group (group I) and pair-fed controls (group II). Carnitine depletion resulting in a 48% reduction of tissue carnitine concentrations was induced by feeding ad libitum a carnitine-free oral diet consisting of parenteral nutrition solutions. Palmitate oxidation was measured by collecting expired 14CO2 after an intraperitoneal injection of [1-14C]palmitate, and exercise capacity was determined by having the rats swim to exhaustion. Despite the 48% depletion of carnitine in serum, muscle, and liver, there were no differences in cumulative palmitate oxidation in 3 h (group I, 40 +/- 7%; group II, 37 +/- 9% of injected activity), swimming time to exhaustion (group I, 8.1 +/- 2.8 h; group II, 7.7 +/- 3.6 h), or nitrogen balance (group I, 1.1 +/- 0.5 g of nitrogen/kg/d; group II, 1.2 +/- 0.5 g of nitrogen/kg/d). We conclude that carnitine depletion of 48% has no effect on palmitate oxidation, exercise capacity, or nitrogen balance in the rats studied. PMID:7808823

  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. 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

  8. 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

  9. Nimotuzumab increases the anti-tumor effect of photodynamic therapy in an oral tumor model.

    PubMed

    Bhuvaneswari, Ramaswamy; Ng, Qin Feng; Thong, Patricia S P; Soo, Khee-Chee

    2015-05-30

    Oral squamous cell carcinoma (OSCC) represents 90% of all oral cancers and is characterized with poor prognosis and low survival rate. Epidermal growth factor receptor (EGFR) is highly expressed in oral cancer and is a target for cancer therapy and prevention. In this present work, we evaluate the efficacy of photodynamic therapy (PDT) in combination with an EGFR inhibitor, nimotuzumab in oral cancer cell lines and OSCC xenograft tumor model. PDT is a promising and minimally invasive treatment modality that involves the interaction of a photosensitizer, molecular oxygen and light to destroy tumors. We demonstrated that EGFR inhibitors nimotuzumab and cetuximab exhibits anti-angiogenic properties by inhibiting the migration and invasion of oral cancer cell lines and human endothelial cells. The EGFR inhibitors also significantly reduced tube formation of endothelial cells. Chlorin e6-PDT in combination with nimotuzumab and cetuximab reduced cell proliferation in different oral cancer and endothelial cells. Furthermore, our in vivo studies showed that the combination therapy of PDT and nimotuzumab synergistically delayed tumor growth when compared with control and PDT treated tumors. Downregulation of EGFR, Ki-67 and CD31 was observed in the tumors treated with combination therapy. Analysis of the liver and kidney function markers showed no treatment related toxicity. In conclusion, PDT outcome of oral cancer can be improved when combined with EGFR inhibitor nimotuzumab. PMID:25918252

  10. Nimotuzumab increases the anti-tumor effect of photodynamic therapy in an oral tumor model

    PubMed Central

    Bhuvaneswari, Ramaswamy; Ng, Qin Feng; Thong, Patricia S.P.; Soo, Khee-Chee

    2015-01-01

    Oral squamous cell carcinoma (OSCC) represents 90% of all oral cancers and is characterized with poor prognosis and low survival rate. Epidermal growth factor receptor (EGFR) is highly expressed in oral cancer and is a target for cancer therapy and prevention. In this present work, we evaluate the efficacy of photodynamic therapy (PDT) in combination with an EGFR inhibitor, nimotuzumab in oral cancer cell lines and OSCC xenograft tumor model. PDT is a promising and minimally invasive treatment modality that involves the interaction of a photosensitizer, molecular oxygen and light to destroy tumors. We demonstrated that EGFR inhibitors nimotuzumab and cetuximab exhibits anti-angiogenic properties by inhibiting the migration and invasion of oral cancer cell lines and human endothelial cells. The EGFR inhibitors also significantly reduced tube formation of endothelial cells. Chlorin e6-PDT in combination with nimotuzumab and cetuximab reduced cell proliferation in different oral cancer and endothelial cells. Furthermore, our in vivo studies showed that the combination therapy of PDT and nimotuzumab synergistically delayed tumor growth when compared with control and PDT treated tumors. Downregulation of EGFR, Ki-67 and CD31 was observed in the tumors treated with combination therapy. Analysis of the liver and kidney function markers showed no treatment related toxicity. In conclusion, PDT outcome of oral cancer can be improved when combined with EGFR inhibitor nimotuzumab. PMID:25918252

  11. Oral proliferative verrucous leukoplakia treated with the photodynamic therapy: a case report

    PubMed Central

    Romeo, Umberto; Russo, Nicola; Palaia, Gaspare; Tenore, Gianluca; Del Vecchio, Alessandro

    2014-01-01

    Summary Aims About 60% of the oral cancer arise on a pre-existent potentially malignant disorder of oral mucosa like the oral proliferative verrucous leukoplakia. The treatment with the photodynamic therapy of these lesions represents, in the last years, an innovative, non-invasive and effective therapeutic possibility to achieve the secondary prevention of oral cancer. In the last decade, case reports have described patients with similar treated through a photochemical reaction induced by laser light. The aim of this study is to evaluate the effectiveness of the topical 5-ALA photodynamic therapy in the treatment of a case of Oral proliferative verrucous leukoplakia. Case report A female patient of 80 years old affected by white verrucous plaques on the right buccal mucosa was recruited for our case report. The right side lesion was treated with the photodynamic therapy with topical administered 5-aminolevulinic acid using the 635 nm laser light to activate the photosensitizer. Results The lesion showed complete response after 4 sessions of photodynamic therapy and no recurrence was noticed after 12 months. Conclusions The photodynamic therapy can be considered an effective treatment in the management of oral verrucous proliferative leukoplakia, but more clinical trials, with prolonged follow-up controls, are necessary to evaluate its effectiveness in the mid and long time period. PMID:25002922

  12. A systematic review of oral fungal infections in patients receiving cancer therapy

    PubMed Central

    Latortue, Marie C.; Hong, Catherine H.; Ariyawardana, Anura; D’Amato-Palumbo, Sandra; Fischer, Dena J.; Martof, Andrew; Nicolatou-Galitis, Ourania; Patton, Lauren L.; Elting, Linda S.; Spijkervet, Fred K. L.; Brennan, Michael T.

    2010-01-01

    Purpose The aims of this systematic review were to determine, in patients receiving cancer therapy, the prevalence of clinical oral fungal infection and fungal colonization, to determine the impact on quality of life and cost of care, and to review current management strategies for oral fungal infections. Methods Thirty-nine articles that met the inclusion/exclusion criteria were independently reviewed by two calibrated reviewers, each using a standard form. Information was extracted on a number of variables, including study design, study population, sample size, interventions, blinding, outcome measures, methods, results, and conclusions for each article. Areas of discrepancy between the two reviews were resolved by consensus. Studies were weighted as to the quality of the study design, and recommendations were based on the relative strength of each paper. Statistical analyses were performed to determine the weighted prevalence of clinical oral fungal infection and fungal colonization. Results For all cancer treatments, the weighted prevalence of clinical oral fungal infection was found to be 7.5% pretreatment, 39.1% during treatment, and 32.6% after the end of cancer therapy. Head and neck radiotherapy and chemotherapy were each independently associated with a significantly increased risk for oral fungal infection. For all cancer treatments, the prevalence of oral colonization with fungal organisms was 48.2% before treatment, 72.2% during treatment, and 70.1% after treatment. The prophylactic use of fluconazole during cancer therapy resulted in a prevalence of clinical fungal infection of 1.9%. No information specific to oral fungal infections was found on quality of life or cost of care. Conclusions There is an increased risk of clinically significant oral fungal infection during cancer therapy. Systemic antifungals are effective in the prevention of clinical oral fungal infection in patients receiving cancer therapy. Currently available topical antifungal

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. Combination therapy for portopulmonary hypertension with intravenous iloprost and oral bosentan.

    PubMed

    Halank, Michael; Kolditz, Martin; Miehlke, Stephan; Schiemanck, Steffen; Schmeisser, Alexander; Hoeffken, Gert

    2005-08-01

    Severe portopulmonary hypertension (PPHTN) is a rare complication of liver cirrhosis and carries a poor prognosis. In the last years, intravenous (IV) epoprostenol has been suggested to be the optimal medical treatment for PPHTN, and recently oral bosentan has been shown to be efficacious and safe in selected patients with PPHTN. We report a case of PPHTN suffering from recurrent right heart failure while on treatment with IV iloprost, which was successfully managed by combination therapy with IV iloprost plus oral bosentan, providing sustained cardiopulmonary stabilization for at least two years. This report documents the first case of a patient with PPHTN successfully treated with the combination of IV iloprost and oral bosentan over an extended period. Thus, combination therapy with IV iloprost and oral bosentan might be a promising new option for selected patients suffering from PPHTN and recurrent right heart failure. PMID:16160926

  20. 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.

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

    PubMed

    Stoopler, Eric T; Balasubramaniam, Ramesh

    2013-04-01

    Oral and perioral herpes simplex virus (HSV) infections in healthy individuals often present with signs and symptoms that are clearly recognized by oral health care providers (OHCPs). Management of these infections is dependent upon a variety of factors and several agents may be used for treatment to accelerate healing and decrease symptoms associated with lesions. This article will review the pertinent aspects of topical and systemic therapies of HSV infections for the OHCP. PMID:23705241

  2. [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

  3. Oral mini pulse therapy: report of a case and review of the literature.

    PubMed

    Kumar, Prem; Bahirwani, Shraddha; Raja, Jigna V; Pujari, Mallayya; Tuteja, Monica; Garg, Swati

    2013-06-01

    Oral lichen planus (OLP) is a chronic mucocutaneous disease with an unknown aetiology, affecting 0.5-2% of the population and with a predilection for females in fourth to fifth decade of life. Most oral lichen planus lesions are asymptomatic but the atrophic and erosive forms of OLP can cause symptoms ranging from spontaneous soreness to severe pain interfering with eating, speech and swallowing. Various drugs have been used for the treatment of OLP including corticosteroids and other immunomodulators. However, no therapy is considered as the single most effective and without side effects in the management of this enigmatic disease. This paper presents a case of successful management of extensive, symptomatic atrophic OLP with a novel treatment protocol: oral mini pulse therapy with betamethasone. In spite of using long-term systemic corticosteroids, side effects were minimal and clinically uneventful. Further controlled trials with this therapy may provide a definitive mode of treatment for severe OLP cases. PMID:23756427

  4. Oral zinc therapy for zinc deficiency-related telogen effluvium.

    PubMed

    Karashima, Tadashi; Tsuruta, Daisuke; Hamada, Takahiro; Ono, Fumitake; Ishii, Norito; Abe, Toshifumi; Ohyama, Bungo; Nakama, Takekuni; Dainichi, Teruki; Hashimoto, Takashi

    2012-01-01

    Zinc is crucial for maintaining human body homeostasis and is one of the major components of hormones, signal molecules, and enzymes. Zinc deficiency is caused by insufficient uptake of zinc from food, or caused by malabsorption syndromes, increased gastrointestinal and urinary losses, and administration of various medications. In order to test whether oral zinc administration can successfully improve zinc deficiency-related alopecia, we treated five patients with zinc deficiency-related telogen effluvium with oral zinc administration in the form of polaprezinc (Promac®). In all patients, hair loss was cured or improved. The administration of zinc for zinc deficiency-related alopecia may recover appropriate activities of metalloenzymes, hedgehog signaling, and immunomodulation, all of which are required for normal control of hair growth cycle. PMID:22741940

  5. Acute Demyelinating Disease after Oral Therapy with Herbal Extracts

    PubMed Central

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

    2011-01-01

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

  6. Use of oral rehydration therapy in acute watery diarrhoea. A practical guide.

    PubMed

    Sack, D A

    1991-04-01

    Various foods and fluids have been used in traditional treatments for diarrhoeal illnesses in infants and children for centuries. During the last 2 decades, however, with the advent of an improved scientific understanding of oral rehydration, effective treatment of dehydrating diarrhoea has been improved, expanded and simplified. The appropriate use of oral rehydration solutions depends on an appreciation of the physiological mechanisms of diarrhoeal illness. Since dehydrating diarrhoea is such a common cause of morbidity and mortality, and because oral rehydration therapy is inexpensive, effective and adaptable, it has become a powerful intervention for improvement in health care for all ages. Newer formulations using starches, cereals and/or amino acids promise to make oral rehydration therapy even more efficacious and acceptable. Nearly all developing countries now have active national diarrhoeal control programmes which facilitate rehydration therapy as the first treatment of diarrhoea while discouraging the use of other diarrhoea medicines (e.g. kaolin and pectin, antispasmodics, etc.). Industrialised countries are also increasingly using oral rather than intravenous fluids. For most patients with lesser degrees of dehydration (up to about 8%) or no detectable dehydration, oral rehydration therapy is the only form of hydration needed. The 'standard' oral replacement solution recommended by the World Health Organization has the advantage of wide experience, demonstrated safety and effectiveness and wide availability. However, rehydration is only part of the management of diarrhoea, and nutritional management (including electrolytes and glucose, alternative substrates to glucose, inclusion of starches and proteins in the solution if possible, etc.) must also be integrated into programmes for diarrhoea control. PMID:1711960

  7. Carnitine/acylcarnitine translocase and carnitine palmitoyltransferase 2 form a complex in the inner mitochondrial membrane.

    PubMed

    Console, Lara; Giangregorio, Nicola; Indiveri, Cesare; Tonazzi, Annamaria

    2014-09-01

    Carnitine/acylcarnitine translocase and carnitine palmitoyltransferase 2 are members of the carnitine system, which are responsible of the regulation of the mitochondrial CoA/acyl-CoA ratio and of supplying substrates for the ß-oxidation to mitochondria. This study, using cross-Linking reagent, Blue native electrophoresis and immunoprecipitation followed by detection with immunoblotting, shows conclusive evidence about the interaction between carnitine palmitoyltransferase 2 and carnitine/acylcarnitine translocase supporting the channeling of acylcarnitines and carnitine at level of the inner mitochondrial membrane. PMID:24898781

  8. Anticancer Activity of Apaziquone in Oral Cancer Cells and Xenograft Model: Implications for Oral Cancer Therapy

    PubMed Central

    Srivastava, Gunjan; Somasundaram, Raj Thani; Walfish, Paul G.; Ralhan, Ranju

    2015-01-01

    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 investigate the anticancer potential of Apaziquone, [EOquin, USAN, E09, 3-hydroxy-5- aziridinyl-1-methyl-2(1H-indole-4,7-dione)–prop-β-en-α-ol], a pro-drug belonging to a class of anti-cancer agents called bioreductive alkylating agents, for OSCC. Apaziquone treatment inhibited cell proliferation and induced apoptosis in OSCC cells in vitro. Apaziquone treated OSCC cells showed increased activation of Caspase 9 and Caspase 3, and Poly (ADP ribose) polymerase (PARP) cleavage suggesting induction of apoptosis by apaziquone in oral cancer cells. Importantly, apaziquone treatment significantly reduced oral tumor xenograft volume in immunocompromised NOD/SCID/Crl mice without causing apparent toxicity to normal tissues. In conclusion, our in vitro and in vivo studies identified and demonstrated the pre-clinical efficacy of Apaziquone, as a potential novel anti-cancer therapeutic candidate for oral cancer management. PMID:26208303

  9. 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

  10. 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

  11. 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.

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

    PubMed

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

    2016-03-01

    The development of Angular Cheilitis and the reactivation of Herpes Simplex Virus, could be related to a decrease in the resistance of the immune system in the infected host, being common in cancer patients receiving antineoplastic chemotherapy. The objective of the present manuscript is to report Antimicrobial Photodynamic Therapy as a treatment of infected oral lesions of patients submitted to chemotherapy. PMID:26222604

  13. 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.

  14. Hypertension induced by pregnancy, oral contraceptives, and postmenopausal replacement therapy.

    PubMed

    Kaplan, N M

    1988-11-01

    Hypertension may develop during pregnancy or with the use of OC pills. Although the precise manner by which this rise in blood pressure occurs is unknown, appropriate management of the problem can protect against the consequences. The use of hormonal replacement therapy after menopause is not associated with a rise in blood pressure, and appears to provide significant protection against CHD. PMID:3067841

  15. Oral Parenteral Antimicrobial Therapy Administration in a Homeless Population.

    PubMed

    Hernandez, Whitney; Price, Connie; Knepper, Bryan; McLees, Margaret; Young, Heather

    2016-01-01

    Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to treat serious infections. Patients who identify themselves as homeless may receive OPAT less often, and little is known about their treatment outcomes. The purpose of this study was to describe challenges, treatment completion rates, and cost savings of OPAT in homeless patients discharged from a public safety-net hospital. PMID:26934162

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

    PubMed

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

    2008-10-01

    Infectious endocarditis is a cardiac pathology of bacterial, viral or more rarely mycotic origin developing on the surfaces of the endocardium or heart valves. Predisposing conditions are congenital malformations of the heart or valvular acquired alterations, as well as the presence of a valvular prosthesis. The microorganisms involved in the etiology and pathogenesis of the damage of such infection (bacterias, viruses or yeasts) determine the formation of the endocardic vegetations typical of this condition. Such lesions can be located on the valvular or the parietal endocardium and sometimes on the endothelium of a great artery. In despite of the elevated standards of instrumental investigations and therapeutic protocols, the bacterial endocarditis represents a pathology of wide interest, scientific and social, due to its high rate of incidence, morbility and mortality. Still now infectious endocarditis causes death in 20-30% of the patients. Although the significant progress on prevention of the infectious diseases and of the cross infections in dentistry practice, from the tartar ablation up to the oncologic oral surgery, still now the skills of oral hygiene and dentistry represent a potential threat for the development of an infectious endocarditis in predisposed patients. The authors, on the base of the revision of the literature and of their own clinical experience, show the etiology, pathophysiology and the clinical pictures related to such complex disease. PMID:19040131

  17. Light therapy: complementary antibacterial treatment of oral biofilm.

    PubMed

    Feuerstein, O

    2012-09-01

    Conventional antibacterial treatment fails to eradicate biofilms associated with common infections of the oral cavity. Unlike chemical agents, which are less effective than anticipated, owing to diffusion limitations in biofilms, light is more effective on bacteria in biofilm than in suspension. Effectiveness depends also on the type and parameters of the light. We tested the phototoxic effects of non-coherent blue light (wavelengths, 400-500 nm) and CO(2) laser (wavelength, 10.6 μm), which have different mechanisms of action on the oral bacterium Streptoccocus mutans, in biofilm and on tooth enamel. Exposure of S. mutans in biofilm to blue light had a delayed effect on bacterial viability throughout the biofilm and a sustained antibacterial effect on biofilm newly formed by previously irradiated bacteria. A synergistic antibacterial effect between blue light and H(2)O(2) may enhance the phototoxic effect, which involves a photochemical mechanism mediated by reactive oxygen species (ROS) formation. The effect of CO(2) laser irradiation on the viability of S. mutans in biofilm on enamel samples appeared to be higher in the deep layers, due to heating of the enamel surface by the absorbed energy. Biofilms do not interfere with the chemical changes resulting from irradiation, which may increase the enamel's resistance to acid attack. PMID:22899690

  18. 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

  19. Hyperbaric Oxygen Therapy-A Novel Treatment Modality in Oral Submucous Fibrosis: A Review.

    PubMed

    Kumar, M Ashwini; Radhika, Besta; Gollamudi, Nishanth; Reddy, Satya Prakash; Yaga, Uday Shankar

    2015-05-01

    Oral submucous fibrosis (OSMF) is a chronic, debilitating disease characterized by juxta epithelial fibrosis of the oral cavity and regarded as a potentially malignant disorder. Numerous treatment modalities ranging from various drugs to behavioral therapy have been tried with inconsistent results with varying degrees of success reflecting low predictability, requiring further evaluation and standardization. Novel treatment modality such as Hyperbaric oxygen therapy (HBOT) involves inhalation of 100% oxygen at increased atmospheric pressure usually ranging between 2.0 and 2.5 atmospheres for periods between 60 and 120 min. HBOT which can increase oxygen tension and delivery to oxygen-deficient tissue, is a supplementary therapy to improve hypoxic environment of OSMF and also possesses potent anti-inflammatory properties. This article enlightens on possible beneficial effects of HBOT in the management of OSMF at cellular and molecular level. PMID:26155590

  20. Nurses’ Knowledge and Education about Oral Care of Cancer Patients Undergoing Chemotherapy and Radiation Therapy

    PubMed Central

    Pai, Radhika R; Ongole, Ravikiran

    2015-01-01

    Context: Oral health awareness and oral care are crucial aspects of oncology nursing practice. However very few studies concentrate on the oral care of cancer patients undergoing cancer treatment and nursing practice in the Indian subcontinent. Most of the published studies have been conducted in the Western and European countries. Aim: This study aimed to determine the nurses’ knowledge and education about oral care in cancer patient undergoing chemotherapy and radiation therapy. Setting and design: A cross sectional descriptive survey was conducted among 158 staff nurses working in oncology related areas from 4 different hospitals of Dakshina Kannada district and Udupi district of Karnataka state, India. Statistical Analysis: descriptive and inferential statistics was used by using SPSS 16 version. Results: Majority 81 (51.3%) of the staff nurses had poor knowledge of oral care in cancer patients whereas 87 (55.1%) reported that knowledge acquired through basic education in oral care is not sufficient. Most of the staff nurses 115 (72.8%) did not receive basic education in oral care of cancer patients. There was significant association between knowledge and variables such as designation (.005), years of work experience (.040) and years of experience in cancer wards (.000) at 0.05 levels. Conclusion: Lack of knowledge suggest the need to develop and implement continuing nursing education programs on oral care specifically for patients receiving cancer treatments, for improving knowledge of staff nurses’ in order to render comprehensive care to the patients. This study also recommends the importance of inclusion of cancer patient specific oral care in the curriculum which can enhance competency of the qualified nurses in cancer wards. PMID:26009678

  1. Prevalence of oral and systemic manifestations in pediatric HIV cohorts with and without drug therapy.

    PubMed

    Jose, Renju; Chandra, Sharath; Puttabuddi, Jaishankar H; Vellappally, Sajith; Al Khuraif, Abul-Aziz A; Halawany, Hassan S; Abraham, Nimmi B; Jacob, Vimal; Hashim, Mohamed

    2013-09-01

    The prevalence of orofacial and systemic manifestations and their association with drug therapy in pediatric HIV patients is scarce in the literature. The aim of the study was to determine the prevalence of oro-facial and systemic manifestations in HIV sero-positive children with and without highly active antiretroviral therapy (HAART). The study population consisted of 100 pediatric HIV patients (n=47 on HAART and n=53 not on HAART). The majority of the children (n=56) had at least one or more oro-facial manifestation associated with HIV. Oral candidiasis was the most common oral finding present in the HAART (14/33) and non-HAART groups (19/33). Recurrent aphthous ulcers was the only significant oral finding, present more in the HAART group. The percentage of children with upper respiratory tract infection was also more in the HAART group. The other lesions which were found to be significant were seborrheic dermatitis, pulmonary tuberculosis and otitis media. There was no significant difference in the participants' oral findings based on CD4 counts in the HAART and non- HAART groups. The prevalence of oral and systemic manifestations is a persistent feature associated with pediatric HIV, though of moderate intensity in those using HAART and may vary according to individual immune status. PMID:24329176

  2. Comparison of cryotherapy and photodynamic therapy in treatment of oral leukoplakia.

    PubMed

    Kawczyk-Krupka, Aleksandra; Waśkowska, Jadwiga; Raczkowska-Siostrzonek, Agnieszka; Kościarz-Grzesiok, Anna; Kwiatek, Sebastian; Straszak, Dariusz; Latos, Wojciech; Koszowski, Rafał; Sieroń, Aleksander

    2012-06-01

    Oral leukoplakia is a pre-malignant lesion of the oral mucosa. The aim of this study is to compare the curative effects of photodynamic therapy and cryotherapy in the treatment of oral leukoplakia. The first group, treated by photodynamic therapy (δ-aminolevulinic acid (ALA), 630-635 nm wavelength), consisted of 48 patients suffering from leukoplakia. The second group consisted of 37 patients treated using cryotherapy. Analyses and comparisons of the complete responses, recurrences, numbers of procedures and adverse effects after both PDT and cryotherapy were obtained. In the first group, a complete response was obtained in 35 patients (72.9%), with thirteen recurrences observed (27.1%) over a six-month period. In the second group, a complete response was obtained in 33 patients (89.2%), and recurrence was observed in nine patients (24.3%). Photodynamic therapy and cryotherapy appear to be comparative methods of treatment that may both serve as alternatives for the traditional surgical treatment of oral leukoplakia. The advantages of PDT are connected with minimally invasive and localized character of the treatment and with not damage of collagenous tissue structures, therefore normal cells will repopulate these arrangements. PDT is more convenient for patients, less painful, and more esthetic. PMID:22594985

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-07-01

    In the recent past, numerous inflammation-mediated molecular pathways have been explored and studied as important events in carcinogenesis with respect to oral squamous cell carcinoma (OSCC). These pathways are engaged in numerous stages during tumorigenesis; which includes processes, like initiation, promotion, malignant conversion, invasion and metastasis. The inflammation-mediated/related carcinogenesis pathways reported in OSCC involves COX-2, epidermal growth factor receptor (EGFR), p38a MAP kinase, NF-kB, STAT, RhoC, PPARy, etc. Many researchers are trying to target these pathways to explore more effective therapeutic interventions in OSCC. The aim of the present paper is to briefly discuss these pathways, with special emphasis on the therapeutic utilities. The therapeutic targets for the aforementioned pathways were searched in databases pubmed and scopus with no restriction to date of publication. Articles published in English medical literature on OSCC were selected for discussion. The recent combinations, modifications in dosage and frequency, or the use of new anti-inflammatory compounds, may exemplify the next generation care for OSCC. PMID:26329416

  5. 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.

  6. 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

  7. 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

  8. A randomised, double-blind, placebo-controlled trial of L-carnitine in suspected acute myocardial infarction.

    PubMed Central

    Singh, R. B.; Niaz, M. A.; Agarwal, P.; Beegum, R.; Rastogi, S. S.; Sachan, D. S.

    1996-01-01

    In a randomised, double-blind placebo-controlled trial, the effects of the administration of oral L-carnitine (2 g/day) for 28 days were compared in the management of 51 (carnitine group) and 50 (placebo group) patients with suspected acute myocardial infarction. At study entry, the extent of cardiac disease, cardiac enzymes and lipid peroxides were comparable between the groups, although both groups showed an increase in cardiac enzymes and lipid peroxides. At the end of the 28-day treatment period, the mean infarct size assessed by cardiac enzymes showed a significant reduction in the carnitine group compared to placebo. Electrocardiographic assessment of infarct size revealed that the QRS-score was significantly less in the carnitine group compared to placebo (7.4 +/- 1.2 vs 10.7 +/- 2.0), while serum aspartate transaminase and lipid peroxides showed significant reduction in the carnitine group. Lactate dehydrogenase measured on the sixth or seventh day following infarction showed a smaller rise in the carnitine group compared to placebo. Angina pectoris (17.6 vs 36.0%), New York Heart Association class III and IV heart failure plus left ventricular enlargement (23.4 vs 36.0%) and total arrhythmias (13.7 vs 28.0%) were significantly less in the carnitine group compared to placebo. Total cardiac events including cardiac deaths and nonfatal infarction were 15.6% in the carnitine group vs 26.0% in the placebo group. It is possible that L-carnitine supplementation in patients with suspected acute myocardial infarction may be protective against cardiac necrosis and complications during the first 28 days. PMID:8746285

  9. [Geriatric dentistry: medical problems as well as disease- and therapy-induced oral disorders].

    PubMed

    Koller, M M

    1994-03-01

    As in pediatric dentistry, management of the oral problems in elderly patients does not depend on the development of new technical skills, but rather on the knowledge of: biological, psychological and social aspects of primary (physiological or age-related) and secondary (pathological or disease-related) aging; atypical presentations of disease; multiple pathological conditions (polymorbidity, polypathophysiology, polypharmacy); an underreporting of disease; the importance of functional status; the role of an interdisciplinary team; Geriatric medicine refers to social, psychological and clinical aspects of disease in older adults. Geriatric dentistry deals with the respective aspects concerning oral diseases. Chronic conditions as well as their treatment (e.g. medication) are more common with advancing age. They may have major implications for dental practice, leading to changes in oral health behavior and attitudes of the elderly patient with sometimes detrimental effects on oral health. Therefore, different concepts in prevention, diagnosis and therapy of oral diseases are required for the oral care of older adults. Two important consequences must be considered: Firstly, the medical education of the dentist and the dental team must be improved. The dental team must become a member of the group of health-care professionals caring for an aging population (geriatric medicine) to meet the heterogeneous needs of as much as 75% of our future patients. Secondly, there is great need for education of all health-care professionals dealing with elderly patients about possible negative impacts medicine can have on oral health. Identification and diagnosis of oral disease as well as preventive measures must be stressed. PMID:8153504

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

    PubMed Central

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

    1970-01-01

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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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. PMID:24164218

  16. 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.

  17. 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

  18. Bioprostethic mitral valve thrombosis due to oral contraceptive drug use and management with ultra-slow thrombolytic therapy.

    PubMed

    Yesin, Mahmut; Kalçik, Macit; Gündüz, Sabahattin; Astarcioğlu, Mehmet Ali; Gürsoy, Mustafa Ozan; Karakoyun, Süleyman; Özkan, Mehmet

    2016-03-01

    Prosthetic valve thrombosis is a severe complication, which usually occurs in inadequately anticoagulated patients. Mechanical valve thrombosis is more common than bioprosthetic valve thrombosis (BVT). Oral contraceptive drugs are associated with increased risk of thromboembolism in women. The possible association between oral contraceptive drug use and BVT has never been reported before. We present a case of obstructive BVT occurring after the use of an oral contraceptive drug and successful management with ultra-slow thrombolytic therapy. PMID:26378817

  19. Relapse After Methylprednisolone Oral Minipulse Therapy in Childhood Vitiligo: A 12-Month Follow-Up Study

    PubMed Central

    Majid, Imran; Imran, Saher

    2013-01-01

    Background: Oral minipulse (OMP) therapy with methylprednisolone is presently one of the most common oral treatments used for progressive vitiligo in children. The treatment is usually given for a period of 6 months during which majority of patients are reported to go into remission. However, there are no follow-up studies to comment upon what happens to the disease after OMP therapy is withdrawn. Aim of the study: To document the incidence of relapse over a period of 1 year after OMP therapy is stopped in children with vitiligo. Materials and Methods: The study was conducted in 180 patients of childhood vitiligo (<15 years of age) who had been on OMP therapy with oral methylprednisolone for at least 6 months and who had achieved a complete remission of their disease during the treatment period. The enrolled patients were followed up for a period of 1 year and examined clinically for any sign of reactivation of their disease over either the old lesions or at any new area of the body. Results: Forty-two patients were lost and could not complete the follow-up period of 1 year. Out of the 138 patients available at the end of 1 year, relapse was observed in 48 patients (34.8%). Rest of 90 patients remained in remission over the follow-up period of 1 year. Relapse was more common in patients below 10 years of age (47.4%) as compared with older children (25.9%). Conclusion: Relapse after using methylprednisolone OMP therapy in children with vitiligo is quite common especially in younger age groups. Studies are needed to see whether these relapses could be avoided by giving the treatment for a period longer than 6 months. PMID:23716799

  20. 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

  1. Plasminogen activation system in oral cancer: Relevance in prognosis and therapy (Review).

    PubMed

    Wyganowska-Świątkowska, Marzena; Jankun, Jerzy

    2015-07-01

    Research on carcinogenesis and progress in cancer treatment have reduced mortality of cancer patients. Mortality rates decreased by 1.5% per year from 2001 through 2010 for most types of cancer in men and women. However, oral cancer is still a significant global health problem since incidence and mortality rates are increasing. Oral cavity cancer is ranked the 8th in men and the 14th in women based on data collected between 2006 and 2010 by the National Institute of Health. Furthermore, an increasing incidence of head and neck neoplasms, particularly the tongue cancer among young adults has been reported recently. It is most likely due to increasing human papillomavirus (HPV) infection or the early start of tobacco and alcohol consumption. Treatment of oral cancer patients is mainly surgical and often leads to esthetic and functional deformities, with severe impact on the quality of life. Thus, novel form of treatments and selection of patients with high and low risk of mortality is of high priority for clinical studies. The expression of proteolytic enzymes in tumor and stromal tissues has been shown to have prognostic significance in many human cancers and inhibiting proteolysis can reduce tumor growth in many in vivo and in vitro models. Plasmin, with its activators and inhibitors are of great importance in many human malignances and collectively are called plasminogen activation system (PAS). In this comprehensive review we examine expression, possible prognostic markers and importance for therapy of the PAS members in oral cancer. Literature review suggests that overexpression of urokinase and its receptor are markers of poor outcome, thus, their inhibition can be explored in oral cancer therapy. Role of plasminogen activator inhibitor (PAI-1) is complex and depends on its concentration. Overexpression of PAI-1 favors angiogenesis, metastasis and poor prognosis, although when applied in very high concentrations it inhibits angiogenesis and tumor growth, the

  2. 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.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-12-01

    Parts 1 and 2 of this 3-part series provided an overview of the epidemiology, visible patterns, and important considerations for clinical and laboratory evaluation of acne vulgaris (AV) in adult women and reviewed the role of proper skin care and topical therapies in this patient population. In Part 3, oral therapies including combination oral contraceptives, spironolactone, antibiotics, and isotretinoin are discussed along with important considerations that clinicians should keep in mind when selecting oral agents for management of AV in adult women. PMID:26761932

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. Oral submucous fibrosis: a review of the current management and possible directions for novel therapies.

    PubMed

    Warnakulasuriya, Saman; Kerr, A Ross

    2016-08-01

    This literature review addresses the attempted interventions for the management of oral submucous fibrosis. The literature supports the use of several medical interventions, including micronutrients, antioxidants, proteolytic enzymes, immune modulators (mainly steroids), and agents to promote blood flow. However, the numbers of reported randomized controlled trials are limited. Therefore, no recommendation can be made for any specific intervention. Until now, no single molecular pathway has been identified that is either necessary or sufficient for the development of fibrosis. This has been a bar for any molecular-targeted therapies. Because areca nut (an ingredient of betel quid) plays a major etiologic role in oral submucous fibrosis, cessation of areca nut use remains pivotal in the management of this disorder. PMID:27422422

  10. 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

  11. 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

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

    PubMed Central

    Erisen, Merve

    2015-01-01

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

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

    PubMed Central

    McDonagh, Theresa; Macdougall, Iain C

    2015-01-01

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

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

    PubMed

    McDonagh, Theresa; Macdougall, Iain C

    2015-03-01

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

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

    PubMed Central

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

    1984-01-01

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

  16. 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

  17. Oral Rehydration Therapy and Feeding Replaces Total Parenteral Nutrition: A Clinical Vignette.

    PubMed

    Wright, Scott Mitchell; Noon, Muhammad Jawad; Greenough, William Bates

    2016-02-01

    A 27-year-old patient with spina bifida and a high output loss of water and electrolytes from her ileostomy was successfully liberated from dependency on total parenteral nutrition and intravenous fluid and electrolyte replacement by the use of a rice-based oral rehydration therapy (ORT). This allowed her to return home to the care of her mother. We suggest that ORT can be effective in the context of modern high-technology settings, as well as in resource-poor situations. PMID:25982236

  18. 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

  19. 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

  20. 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 ...

  1. Dramatic decrease of carnitine esters after interruption of exogenous carnitine supply in hemodialysis patients.

    PubMed

    Bene, Judit; Csiky, Botond; Wittmann, Istvan; Sulyok, Endre; Melegh, Bela

    2012-01-01

    L-carnitine supplementation is extensively used in patients on maintenance hemodialysis (HD) to improve dialysis-related clinical symptoms. In a series of studies, we investigated the dynamics of carnitine pool in carnitine-supplemented HD patients; here we report dramatic decrease with special changes of the ester profile due to interruption of the exogenous intake after the last HD session. Serum samples were collected from 18 L-carnitine-repleted end-stage renal disease (ESRD) patients before the L-carnitine supplementation, after completion of a carnitine supplementation period treatment (12 weeks, 1 g/IV/HD), right before the HD session, and 44 h after the dialysis. Levels of free carnitine (FC) and the individual esters were determined using electrospray MS/MS technique. Normally, L-carnitine supplementation causes significant elevation of all carnitine compounds to supraphysiological levels, which reaches a standard steady-state-like profile. In this study we found a dramatic decrease in the level of FC, and in short- and medium-chain acylcarnitines (ACs) 44 h after the last dialysis. At the end of this interdialytic period, FC levels increased to only 65% of the predialysis level, whereas the amounts of C2 and C3 esters recovered to only 50%. The level of C6 was 65% of the predialysis level, whereas the amount of C8 chain length ACs returned to 72% of the predialysis level. No significant change was seen in AC concentrations above C10 chain length. Omission of one single dosage of supplemental carnitine in long-term administration schemes results in dramatic decrease and reprofiling of carnitine esters even after the usual 44 h of interdialytic period. PMID:22417076

  2. 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

  3. Patients’ perspectives regarding long-term warfarin therapy and the potential transition to new oral anticoagulant therapy

    PubMed Central

    Gebler-Hughes, Elizabeth S.; Kemp, Linda

    2014-01-01

    Objectives: To examine patients’ perspectives regarding long-term vitamin K antagonist (VKA) therapy and the potential transition to new oral anticoagulants (NOACs) such as dabigatran and rivaroxaban, and to determine if factors such as residential location affect these opinions. Design, setting and participants: Patients on VKA therapy for at least 12 weeks completed a questionnaire specifically designed for the study. They were recruited while attending point-of-care international normalized ratio (INR) testing at six South Australian general practice clinics during the period July–September 2013. Main outcome measures: Opinions of current VKA therapy, level of awareness of NOACs, and ratings of potential benefits and deterrents of transition to NOACs were sought. Results: Data from 290 participants were available for analysis (response rate 95.4%). The majority of the sample (79.5%, 229/288) were either satisfied or very satisfied with current VKA therapy. The mean score for the potential benefits of transition to NOACs was 7.6 (±4.2) out of a possible 20, which was significantly lower than the mean score 10.9 (±4.5) for the perceived deterrents to transition (p < 0.001). Rural patients (82.0%, 82/100) were significantly more likely (p = 0.001) to have not heard of NOACs than metropolitan patients (50.3%, 95/189) and also perceived significant less benefits in a transition to NOACs (p = 0.001). Conclusion: When considering potential transition from VKAs to NOACs it is important for prescribers to consider that some patients, in particular those from a rural location, may not perceive a significant benefit in transitioning or may have particular concerns in this area. PMID:25436104

  4. 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

  5. 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

  6. 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. PMID:24180531

  7. Oral mycoses and other opportunistic infections in HIV: therapy and emerging problems - a workshop report.

    PubMed

    Vidya, K M; Rao, U K; Nittayananta, W; Liu, H; Owotade, F J

    2016-04-01

    Oral mycoses and other opportunistic infections are recognized features of HIV infection even after four decades of the epidemic. The therapeutic options, challenges of therapy, and evolving patterns of opportunistic infections were evaluated by the workshop. It was observed that high Candida counts and infection are still more prevalent in HIV-positive individuals even in the era of antiretroviral therapy. Furthermore, one or more non-Candida albicans are present in some HIV-positive individuals. While Candida species are more virulent in HIV infection, similar virulence may be present in other states of immunosuppression. Consequently, the interplay between host factors and virulence ultimately determines the clinical outcomes. Adverse clinical outcomes such as candidemia and other deep fungal infections are on the increase in HIV infection. Disseminated histoplasmosis and penicilliosis have been reported, especially with low CD4 counts. Even with advances in antifungal therapy, mortality and morbidity from deep fungal infections have not changed significantly. In addition, long-term exposure to common antifungal drugs such as fluconazole has led to the development of antifungal resistance in 6% to 36%. Development of new antifungal therapeutic agents and the use of alternative therapies may offer breakthrough. In addition, effective strategies to enhance the host immune status are being explored. PMID:27109283

  8. Intracerebral hemorrhage during treatment with oral anticoagulants. Risk factors, therapy and prognosis.

    PubMed

    Ernestus, R I; Speder, B; Pakos, P; Hildebrandt, G; Klug, N

    1994-01-01

    Intracerebral hemorrhage (ICH) during oral anticoagulation is a serious complication, which is mostly fatal for the multimorbid patient. In the present retrospective study of 53 patients with ICH during treatment with a cumarin derivative (Phenoprocoumon, Marcumar), we investigated the relationship between therapy and preexisting parameters such as age, location, level of consciousness, additional bleeding risks, and the degree of anticoagulation, which were assumed to be of prognostic relevance. The therapeutic management of ICH during treatment with anticoagulants was determined predominantly by location of the hematoma, patient's age, and additional bleeding risks, but less by level of consciousness and initial thromboplastin time (Quick's test). As a consequence of the individual analysis of these 5 parameters, age over 60 years, location of hematoma in the midline or ventricles, coma, additional bleeding risks such as arterial hypertension and trauma, and Quick's test below 15% at the time of bleeding were supposed to be responsible for poor prognosis. Mortality increased with a rising number of poor prognostic factors, independently of surgical or conservative treatment. In consequence, prognosis of ICH during oral anticoagulation is predominantly influenced by the number of such disadvantageous indicators and only little by therapy. PMID:8053274

  9. 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.

  10. Trichophytum rubrum endonyx onychomycosis resistant to standard oral and topical therapies.

    PubMed

    Mulvaney, Patrick M; Telang, Gladys H; Jellinek, Nat

    2015-01-01

    We present a 45 year-old man with an eight-year history of discoloration of the nail plate on his left hallux. He had been treated with two courses of oral terbinafine and topical 8% ciclopirox for presumed onychomycosis. On exam, his left great toenail contained a wide yellow-white longitudinal band involving a majority of the nail plate. No subungual debris, hyperkeratosis, or paronychial inflammation was present in the affected nail. Histopathology of the nail plate revealed numerous fungal elements arranged transversely and longitudinally, solely within the keratin layers of the nail plate; these were highlighted with periodic acid-Schiff (PAS) stain confirming endonyx onychomycosis. Cultures grew Trichophyton rubrum. All types of onychomycosis under the new classification system proposed by Hay et al. have now been associated with T. rubrum. Endonyx related to T. rubrum may be a particularly difficult infection to treat with oral or topical agents owing to the absence of robust local immune response and limited drug penetration to the interior nail plate. Physicians should be aware that this type of infection may require treatment with dual-agent therapy or alternative modalities including chemical or surgical plate avulsion or photodynamic therapy. PMID:26437286

  11. 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

  12. 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

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

    PubMed

    Kurth, Florian; 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

    2016-08-01

    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

  14. 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.

  15. 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

  16. Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management.

    PubMed

    Magoulas, Pilar L; El-Hattab, Ayman W

    2012-01-01

    established in an individual, an echocardiogram, electrocardiogram, CK concentration, liver transaminanses measurement, and pre-prandial blood sugar levels, should be performed for baseline assessment. Primary treatment involves supplementation of oral levocarnitine (L-carnitine) at a dose of 50-400 mg/kg/day divided into three doses. No formal surveillance guidelines for individuals with CDSP have been established to date, however the following screening recommendations are suggested: annual echocardiogram and electrocardiogram, frequent plasma carnitine levels, and CK and liver transaminases measurement can be considered during acute illness. Adult women with CDSP who are planning to or are pregnant should meet with a metabolic or genetic specialist ideally before conception to discuss management of carnitine levels during pregnancy since carnitine levels are typically lower during pregnancy. The prognosis for individuals with CDSP depends on the age, presentation, and severity of symptoms at the time of diagnosis; however the long-term prognosis is favorable as long as individuals remain on carnitine supplementation. PMID:22989098

  17. Mechanisms for altered carnitine content in hypertrophied rat hearts

    SciTech Connect

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

    1987-03-01

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

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

    SciTech Connect

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

    1986-03-01

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

  19. 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

  20. An Attenuated Adenovirus, ONYX-015, As Mouthwash Therapy for Premalignant Oral Dysplasia

    PubMed Central

    Rudin, Charles M.; Cohen, Ezra E.W.; Papadimitrakopoulou, Vassiliki A.; Silverman, Sol; Recant, Wendy; El-Naggar, Adel K.; Stenson, Kirsten; Lippman, Scott M.; Hong, Waun Ki; Vokes, Everett E.

    2015-01-01

    Purpose Dysplastic lesions of the oral epithelium are known precursors of oral cancer. A significant proportion of oral dysplastic lesions have functional defects in p53 response pathways. The ONYX-015 adenovirus is selectively cytotoxic to cells carrying defects in p53-dependent signaling pathways. The current study sought to establish the feasibility and activity of ONYX-015 administered topically as a mouthwash to patients with clinically apparent and histologically dysplastic lesions of the oral mucosa. Patients and Methods A total of 22 patients (19 assessable patients) were enrolled onto the study. ONYX-015 was administered on three different schedules to consecutive cohorts. Biopsies of the involved mucosa were performed to evaluate histologic response and changes in expression of putative markers of malignant potential, including p53, cyclin D1, and Ki-67. Serology was performed to measure antiadenoviral titers. Results Histologic resolution of dysplasia was seen in seven (37%) of 19 patients, and the grade of dysplasia improved in one additional patient. The majority of responses were transient. No toxicity greater than grade 2 (febrile episode in one patient) was observed. Only one of seven patients demonstrated an increase in circulating antiadenoviral antibody titer while on therapy. Although responding and resistant lesions had similar mean p53 staining at baseline, histologic response correlated with a decrease in p53 positivity over time. Significant changes in cyclin D1 or Ki-67 were not observed. Viral replication was confirmed in two of three lesions examined. Conclusion This novel approach to cancer prevention is tolerable, feasible, and has demonstrable activity. PMID:14597742

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  3. Clinical efficacy of oral risedronate therapy in Japanese patients with Paget's disease of bone.

    PubMed

    Ohara, Masaya; Imanishi, Yasuo; Nagata, Yuki; Ishii, Akira; Kobayashi, Ikue; Mori, Katsuhito; Ito, Manabu; Miki, Takami; Nishizawa, Yoshiki; Inaba, Masaaki

    2015-09-01

    Paget's disease of bone (PDB) is a chronic disorder characterized by localized bone regions with excessive bone turnover. Although oral risedronate (17.5 mg daily for 8 weeks) was recently approved in Japan, its efficacy is not well understood. We retrospectively examined the efficacy of oral risedronate in PDB patients in a clinical setting. Eleven patients whose serum alkaline phosphatase (ALP) level exceeded the upper limit of the normal range were treated. Patients whose ALP levels normalized and remained so for 12 months after therapy initiation were defined as responders. Treatment was repeated if bone pain recurred or if serum ALP levels increased at least 25% above the nadir. Six patients (55%) were responsive to the therapy. A higher prevalence of skull lesions, higher serum calcium levels at treatment initiation and antecedent treatments of bisphosphonates were predictors of resistance against the therapy. Fresh frozen serum samples obtained from some treatment sessions were evaluated for metabolic bone markers such as bone-specific ALP (BAP), type I procollagen N-terminal pro-peptide (PINP), N-treminal crosslinking telopeptide of type I collagen and C-treminal crosslinking telopeptide of type I collagen (CTX). A significant reduction of P1NP preceded that of serum ALP levels in the responders, which was followed by a similar occurrence for BAP and osteocalcin (BGP) levels. A temporary decrease in CTX levels was noted. No significant changes in markers (including ALP level) were observed in non-responder and repeat-treatment groups. P1NP levels may be more useful than ALP levels in assessing treatment efficacy. Repeat treatment effectiveness for the repeat-treatment group was limited. PMID:25319558

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

    PubMed Central

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

    2007-01-01

    We examined the effects of citric acid and l-carnitine administration on physical fatigue. In a double-blind, placebo-controlled, 3-way crossover study, 18 healthy volunteers were randomized to oral citric acid (2,700 mg/day), l-carnitine (1,000 mg/day), or placebo for 8 days. The fatigue-inducing physical task consisted of workload trials on a cycle ergometer at fixed workloads for 2 h on 2 occasions. Before the physical load, salivary chromogranin A, measured as a physiological stress marker, was lower in the group given citric acid than in the group given placebo. Also, after the physical load, the subjective feeling of fatigue assessed with a visual analogue scale was lower in the citric acid group than in the placebo group. In contrast, l-carnitine had no effect on chromogranin A or subjective fatigue. These results suggest that citric acid reduces physiological stress and attenuates physical fatigue, whereas l-carnitine does not. PMID:18299720

  5. Intracerebral Hematoma Occurring During Warfarin Versus Non-Vitamin K Antagonist Oral Anticoagulant Therapy.

    PubMed

    Takahashi, Haruhiko; Jimbo, Yasushi; Takano, Hiroki; Abe, Hiroshi; Sato, Masahito; Fujii, Yukihiko; Aizawa, Yoshifusa

    2016-07-15

    The neuroradiological findings and its outcomes of intracerebral hemorrhage (ICH) were compared between the non-vitamin K antagonist oral anticoagulant (NOAC) therapy and warfarin therapy. In the latest 3 years, 13 cases of nonvalvular atrial fibrillation on NOAC therapy were admitted for ICH. For comparison, 65 age- and gender-comparable patients with ICH on warfarin therapy were recruited. Three NOACs had been prescribed: dabigatran (n = 4), rivaroxaban (n = 2), and apixaban (n = 7). The average ages were 76 ± 9 and 78 ± 8 years in the warfarin (n = 65) and NOAC groups (n = 13), respectively. There was no difference in the clinical features, including the CHADS2 score or HAS-BLED score: 2.62 ± 1.31 versus 2.62 ± 1.33, or 1.09 ± 0.43 versus 1.00 ± 0.41, for the warfarin and NOAC groups, respectively. The volume of ICH <30 ml was found in 84.6% of the patients on NOACs, but it was found in 53.8% of the patients on warfarin (p = 0.0106). The expansion of hematoma was limited to 7 patients (10.8%) of the warfarin group. A lower hospital mortality and better modified Rankin Scale were observed in the NOAC group than in the warfarin group: 1 (7.7%) versus 27 (41.5%; p = 0.0105) and 3.2 ± 1.4 versus 4.5 ± 1.6 (p = 0.0057), respectively. In conclusion, ICH on NOAC therapy had smaller volume of hematoma with reduced rate of expansion and decreased mortality compared with its occurrence on warfarin. PMID:27289294

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2014-03-01

    Canine atopic dermatitis (CAD) is a common allergic skin disease that has been treated with subcutaneously administered interferons (IFN). Recombinant feline IFN-ω (rFeIFN-ω) was reported to be efficacious for CAD. Whether dogs develop neutralizing antibodies against rFeIFN-ω during long-term treatment and whether orally administered IFNs are efficacious in CAD is unknown. The aim of this study was to evaluate the potential development of antibodies against rFeIFN-ω in atopic dogs and to compare subcutaneous and oral IFN therapy. Twenty-six atopic dogs were randomly assigned to two groups. The first group (n=15) received eight subcutaneous injections of rFeIFN-ω (Virbagen® omega, Virbac, Carros, France) over four months, the second group (n=11) received rFeIFN-ω daily orally. Concurrent medication was permitted, except systemically acting glucocorticoids and cyclosporin, which had to be withdrawn at least two weeks prior to the study. Serum samples for antibody detection were collected before and after the study. On days 0, 60 and 120 skin lesions and pruritus were evaluated using a validated lesion score (Canine Atopic Dermatitis Extent and Severity Index=CADESI) and a validated pruritus score. Concurrent medications were recorded. For every visit a total score, consisting of CADESI, pruritus score and medication score was created. For antibody detection an indirect ELISA, using Virbagen® omega as antigen, was performed. Comparison of pruritus scores, CADESI and total scores between days 0 and 120 showed improvement in both groups, however, significant improvement could only be detected in the oral group with CADESI and total scores (61%, P=0.04 and 36%, P=0.02 respectively). Serum antibodies against rFeIFN-ω could not be detected in any of the dogs. In this study antibody production could not be demonstrated. It suggests better efficacy with oral IFN administration, which should be further verified in larger, randomized, controlled studies. PMID:24548425

  8. 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

  9. 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). PMID:18057392

  10. 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. PMID:9733667

  11. 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.

  12. 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.

  13. 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

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

    PubMed

    Holder, Renee M; Rhee, Diane

    2016-03-01

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

  15. Effect of low-level laser therapy on oral keratinocytes exposed to bisphosphonate.

    PubMed

    Lee, Jae-Yeol; Kim, In-Ryoung; Park, Bong-Soo; Kim, Yong-Deok; Chung, In-Kyo; Song, Jae-Min; Shin, Sang-Hun

    2015-02-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate therapy. However, its pathophysiology is not yet fully elucidated, and effective treatment of BRONJ remains unclear. The aim of this study is to investigate the effects of alendronate on oral keratinocytes and of low-level laser therapy (LLLT) on alendronate-treated keratinocytes, specifically by evaluating their viability, apoptosis, and wound healing function after irradiation. Oral keratinocyte cells (HaCaT) were exposed to 25 μM alendronate. Then, laser irradiation was performed with a low-level Ga-Al-As laser (λ = 808 ± 3 nm, 80 mW, and 80 mA; NDLux, Seoul, Korea) using 1.2 J/cm(2) energy dose. Viability was analyzed using MTT assay. Apoptosis was measured by Hoechst staining, caspase assay. Changes in secretion of IL-8, VEGF, and collagen type I were studied by ELISA and immunofluorescence microscopy. Scratch wound assays were also performed to measure cellular migration. Our results show that alendronate inhibits keratinocyte viability, expression of IL-8, VEGF, and collagen type I which are intimately related to healing events and cell migration while promoting apoptosis. Our results serve to demonstrate the utility of LLLT in partially overcoming the inhibitory effects of this bisphosphonate. From these results, the authors believe that the present study will provide an experimental basis for a fuller explanation of the clinical effects of LLLT as a BRONJ treatment modality. PMID:23835780

  16. The New Oral Anticoagulants for the Treatment of Venous Thromboembolism: A New Paradigm Shift in Antithrombotic Therapy

    PubMed Central

    Galanis, Taki; Keiffer, Gina; Merli, Geno

    2014-01-01

    Background Several novel oral anticoagulants have been studied for the prevention and treatment of venous thromboembolism (VTE) in different patient populations. Clinicians will increasingly encounter scenarios in which they must choose among these and conventional anticoagulants for the treatment of this potentially fatal condition. Objective To review the results of Phase III clinical trials that investigated the novel oral anticoagulants for the treatment of deep vein thrombosis and pulmonary embolism. Potential advantages and disadvantages of these anticoagulant agents with respect to each other and conventional therapy will also be explored through a case-based approach. Methods A literature search in PubMed was conducted that identified Phase III clinical trials investigating the novel oral anticoagulant agents for the treatment of VTE. Results The new oral anticoagulant agents have been shown to be as safe and effective for the treatment of VTE as conventional therapies. Conclusions These novel, oral anticoagulant agents are legitimate options for the treatment of VTE. A careful assessment of a patient׳s comorbidities, medication use, and laboratory results should be undertaken before prescribing the new oral anticoagulant agents for patients with VTE. PMID:25352938

  17. 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...

  18. Successful use of oral linezolid as a single active agent in endocarditis unresponsive to conventional antibiotic therapy.

    PubMed

    Ravindran, V; John, J; Kaye, G C; Meigh, R E

    2003-08-01

    Treatment of resistant gram-positive endocarditis is difficult. We report a case of resistant Staphylococcus epidermidis endocarditis that failed to respond to conventional antibiotic therapy but was treated successfully with an oral regimen of a new antibiotic, linezolid as a single active agent. This case report demonstrates the use of linezolid as an effective alternative to conventional antibiotics in such cases. PMID:12860152

  19. 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

  20. 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

  1. 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

  2. Efficacy of oral single dose therapy with artemisinin-naphthoquine phosphate in uncomplicated falciparum malaria.

    PubMed

    Tun, Thein; Tint, Hla Soe; Lin, Khin; Kyaw, Thar Tun; Myint, Moe Kyaw; Khaing, Win; Tun, Zaw Win

    2009-09-01

    All artemisinin-based combination therapies (ACTs), recommended by the World Health Organization, are 3-day regimens. A considerable level of non-compliance on ACTs has been reported from some countries. The study aimed to assess the therapeutic efficacy of single dose treatment with new generation ACT containing artemisinin plus naphthoquine. An oral single dose of eight tablets (400 mg of naphthoquine+1000 mg artemisinin) of the combination drug was administered to adult uncomplicated falciparum malaria patients. Observations of fever, parasite clearance and reappearance, and other clinical manifestations were made on Days 0, 1, 2, 3, 7, 14, 21 and 28. Fifty-three adult falciparum positive cases, with fever or history of fever within the previous 24 h, were included in the final evaluation of the study. Mean fever clearance time, parasite clearance time were 18.2+/-8.6 h and 34.6+/-14.3 h, respectively. Adequate clinical and parasitological response was achieved in 52 cases, the rate being 98.1% (95% CI, 91.1-99.9). One patient was classified as late parasitological failure because of the reappearance of falciparum parasite on Day 14. The drug was well tolerated and no adverse reactions were detected in the patients. Since it is a single dose therapy, health workers can administer the drug as directly observed treatment. PMID:19464245

  3. 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

  4. 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

  5. Absence of Hepatitis B Resistance Mutants before Introduction of Oral Antiviral Therapy

    PubMed Central

    Moehlen, Martin; De Medina, Maria; Hill, Mary; Jeffers, Lennox; Schiff, Eugene R.; Martin, Paul

    2013-01-01

    Introduction. The aim of this study was to assess whether hepatitis B virus drug resistant mutations antedated the widespread use of nucleos(t)ide analogues in treatment naïve patients. A number of reports have suggested that drug resistant mutants can be detected in apparently treatment naïve patients. Study. Fifty deidentified serum samples collected from 1986 to 1992 from patients with replicative chronic HBV infection at the University of Miami were genotyped and tested for resistance mutations using a line probe assay InnoLiPA HBV DR v2/v3. Serum HBV DNA was measured. All patients had documented chronic HBV infection with a detectable viral load, HBeAg seropositivity, and absence of HIV infection. Results. Of the 50 individuals included, 86% were male, mean age was 40 ± 12 years, and mostly genotype A. The mean HBV DNA was 126 pg/mL (range 6.4 to 557.0). No mutations were identified. Conclusions. The absence of drug induced mutations in these sera collected several years prior to the introduction of oral antiviral therapy suggests that these mutations do not occur in treatment naïve populations. Detection of drug resistance in an apparently treatment naïve subject suggests either unrecognized prior antiviral therapy or infection by an inoculum from a treatment experienced patient. PMID:27335823

  6. Use of Oral Anticoagulation Therapy in Atrial Fibrillation after Stroke: Results from a Nationwide Registry

    PubMed Central

    Jespersen, Stine Funder; Christensen, Louisa M.; Christensen, Anders; Christensen, Hanne

    2013-01-01

    Background. The knowledge is still sparse about patient related factors, influencing oral anticoagulation therapy (OAC) rates, in stroke patients with atrial fibrillation (AF). Aims. To assess the use of OAC in ischemic stroke patients diagnosed with AF and to identify patient related factors influencing the initiation of OAC. Methods. In the nationwide Danish Stroke Registry we identified 55,551 patients admitted with acute ischemic stroke from 2003 to 2011. Frequency analysis was used to assess the use of OAC in patients with AF, and logistic regression was used to determine independent predictors of OAC. Results. 17.1% (n = 9,482) of ischemic stroke patients had AF. OAC prescription rates were increasing, and in 2011 46.6% were prescribed OAC, 42.5% had a contraindication, and 3.7% were not prescribed OAC without a stated contraindication. Younger age, less severe stroke, and male gender were positive predictors of OAC, while excessive alcohol consumption, smoking, and institutionalization were negative predictors of OAC (P values < 0.05). Conclusions. Advanced age, severe stroke, female gender, institutionalization, smoking, and excessive alcohol consumption were associated with lower OAC rates. Contraindications were generally present in patients not in therapy, and the assumed underuse of OAC may be overestimated. PMID:24349774

  7. Radiographic features of oral cholecystograms of 448 symptomatic gallstone patients: implications for nonsurgical therapy.

    PubMed

    Plaisier, P W; Brakel, K; van der Hul, R L; Bruining, H A

    1994-02-01

    Since radiographic findings on oral cholecystography (OCG) have implications for the eligibility for nonsurgical therapy of elderly patients, we investigated the OCGs of 448 symptomatic gallstone patients (109 male, 339 female; mean age, 49.8 +/- 14 (range, 21-88)). Opacification of the gallbladder was found in 323 cases (72.1%). Calcifications of gallstones were found in 85 opacified gallbladders (26.3%). Solitary and multiple stones were calcified in 35.3% and 18.2%, respectively (P < 0.0005). When divided into two groups (< or = 40 years and > 40 years), there was a significant increase in calcifications (P < 0.02) and a non-significant increase in opacification with increasing age. It is concluded that age is a determinant for calcification of gallstones and not opacification of the gallbladder. Since multiple stones are proportionately observed more in clinical studies than in epidemiologic studies, it is suggested that multiplicity of stones predisposes to biliary complaints. That solitary stones are more likely to be calcified than multiple stones, adds to the hypothesis that solitary and multiple stones have a different pathogenesis. Elderly patients, in whom non-surgical therapy is most likely to be indicated and cost-effective, are less likely to be suitable for this form of treatment, since age is a determinant for stone calcification. PMID:8168584

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

    PubMed

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

    2015-01-01

    The management of type 2 diabetes mellitus (T2DM) by primary care physicians (PCPs) has become increasingly complex due to limitations on consultation time, an increasing array of drug treatment options, and issues of comorbidities and polypharmacy. Diabetes is a progressive condition and treatment with a single glucose-lowering agent can only address limited pathophysiologic targets and does not provide adequate glycemic control in many cases. Consequently, most patients with T2DM will eventually require treatment with multiple glucose-lowering medications. Oral combination therapy in T2DM may be given as multiple-pills, or as single-pill, fixed-dose combinations (FDCs), the latter of which offer convenience, ease of administration, and a reduction in the medication burden. Therefore, FDCs can potentially improve patients' treatment adherence and optimize achievement and maintenance of glycemic targets. However, cost factors also need to be considered. An understanding of the issues associated with the use of combination therapy in T2DM will help PCPs to guide patient-centered decision making and promote the effective management of T2DM. PMID:26439384

  9. Combination therapy with insulin and oral agents: optimizing glycemic control in patients with type 2 diabetes mellitus.

    PubMed

    Yki-Järvinen, Hannele

    2002-01-01

    The United Kingdom Prospective Diabetes Study (UKPDS) showed that tight glycemic control with any of several therapeutic regimens has the potential to significantly reduce the risk for long-term microvascular complications of type 2 diabetes. An important question that remains to be answered is what is the best approach to optimizing glycemic control in patients with this disease. This article reviews results of studies in which insulin was used alone or in combination with oral antidiabetic agents for treatment of patients with type 2 diabetes. Analysis of comparative studies (13 in insulin-naive and 26 in previously insulin-treated patients) showed that combination therapy involving one to two insulin injections per day plus oral therapy is usually more effective than insulin monotherapy for achieving and maintaining glycemic control. Combination treatment for type 2 diabetes can be significantly improved by newly developed preparations that lack the major limitations of older products. Once-daily administration of isophane insulin (NPH insulin) is limited by a 15-18-h duration of action and a peak effect that occurs about 6 h after injection. Insulin glargine, a new insulin analogue developed using recombinant DNA technology, has a flat pharmacodynamic profile and a 24-h duration of action. Results from a recent comparative study indicate that insulin glargine plus oral therapy may provide better post-dinner glucose control as well as less symptomatic and nocturnal hypoglycemia than oral therapy combined with NPH insulin. The studies reviewed in the present article support the conclusion that combination therapy with insulin glargine combined with one or more oral antidiabetic agents may be the treatment of choice for achieving glycemic control in patients with type 2 diabetes. PMID:12324990

  10. Combined therapeutic use of oral alitretinoin and narrowband ultraviolet-B therapy in the treatment of hailey-hailey disease.

    PubMed

    Vanderbeck, Kaitlin A; Giroux, Lyne; Murugan, Nirosha J; Karbowski, Lukasz M

    2014-02-17

    Hailey-Hailey disease (HHD) is a chronic familial bullous disease characterized by recurrent blisters and erosions typically at friction-prone areas of the body accompanied by acantholysis upon histologic examination. There are a number of therapies used in the management of HHD. Its symptoms have been effectively treated with antimicrobial therapies, corticosteroids and other agents such as cyclosporine and prednisone. However, such treatments are not always effective. Therefore, there is a need for new treatments for the management of HHD. In this report, a patient with long-standing HHD responsive only to high levels of prednisone is described. After the successful tapering and cessation of oral prednisone the patient began a new combination therapy of complementary doses of oral alitretinoin, and narrowband UVB therapy, which yielded a favorable response within 2-3 weeks. After 6 weeks, a mono-therapy of daily (30 mg) oral alitretinoin was sufficient to maintain successful near-complete remission of the disease. PMID:25386331

  11. Combined Therapeutic Use of Oral Alitretinoin and Narrowband Ultraviolet-B Therapy in the Treatment of Hailey-Hailey Disease

    PubMed Central

    Vanderbeck, Kaitlin A.; Giroux, Lyne; Murugan, Nirosha J.; Karbowski, Lukasz M.

    2014-01-01

    Hailey-Hailey disease (HHD) is a chronic familial bullous disease characterized by recurrent blisters and erosions typically at friction-prone areas of the body accompanied by acantholysis upon histologic examination. There are a number of therapies used in the management of HHD. Its symptoms have been effectively treated with antimicrobial therapies, corticosteroids and other agents such as cyclosporine and prednisone. However, such treatments are not always effective. Therefore, there is a need for new treatments for the management of HHD. In this report, a patient with long-standing HHD responsive only to high levels of prednisone is described. After the successful tapering and cessation of oral prednisone the patient began a new combination therapy of complementary doses of oral alitretinoin, and narrowband UVB therapy, which yielded a favorable response within 2-3 weeks. After 6 weeks, a mono-therapy of daily (30 mg) oral alitretinoin was sufficient to maintain successful near-complete remission of the disease. PMID:25386331

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

    PubMed Central

    OZTURK, MEHMET ADNAN; KARDAS, ZEHRA; KARDAS, FATİH; GUNES, TAMER; KURTOGLU, SELİM

    2016-01-01

    The aim of the present study was to investigate the efficacy of L-carnitine therapy on the occurrence and prognosis of respiratory distress syndrome (RDS). A single blind, randomized controlled trial study was conducted on 130 infants with gestational ages of 28–36 weeks. Infants were assigned to experimental groups (groups 1 and 2) and control groups (groups 3 and 4). Groups 1 and 3 consisted of infants with RDS, and groups 2 and 4 groups were composed of infants without RDS. The experimental groups were treated with carnitine. No statistically significant differences in serum carnitine levels were detected between the study and the control groups on day 1 of treatment (P=0.06). However, on day 7 of treatment, serum carnitine levels in the experimental groups were significantly increased (P=0.02), as compared with the control groups. The surfactant requirement value, which is how many rounds of surfactant therapy were required, was 1.56±0.97 in group 1, and 2.12±0.99 in group 3 (P<0.001). The mean duration of mechanical ventilation required was 3.04±3.60 days in group 1, and 4.73±5.63 days in group 3 (P<0.001). The present results indicate that carnitine supplementation in premature infants with RDS may help to increase carnitine levels, thus decreasing the duration of mechanical ventilation and surfactant requirement. PMID:26998047

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

    PubMed

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

    2014-02-01

    Recombinant-Feline Interferon-Omega (rFeIFN-ω) is an immune-modulator licensed for use subcutaneously in Feline Immunodeficiency virus (FIV) therapy. Despite oral protocols have been suggested, little is known about such use in FIV-infected cats. This study aimed to evaluate the clinical improvement, laboratory findings, concurrent viral excretion and acute phase proteins (APPs) in naturally FIV-infected cats under oral rFeIFN-ω therapy (0.1 MU/cat rFeIFN-ω PO, SID, 90 days). 11 FIV-positive cats were treated with oral rFeIFN-ω (PO Group). Results were compared to previous data from 7 FIV-positive cats treated with the subcutaneous licensed protocol (SC Group). Initial clinical scores were similar in both groups. Independently of the protocol, rFeIFN-ω induced a significant clinical improvement of treated cats. Concurrent viral excretion and APP's variation were not significant in the PO Group. Oral rFeIFN-ω can be an effective alternative therapy for FIV-infected cats, being also an option for treatment follow-up in cats submitted to the licensed protocol. PMID:24332273

  14. 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

  15. Downregulation of oxidative and nitrosative apoptotic signaling by L-carnitine in Ifosfamide-induced Fanconi syndrome rat model.

    PubMed

    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

  16. 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

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

    PubMed Central

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

    2016-01-01

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

  18. Intracellular in vitro probe acylcarnitine assay for identifying deficiencies of carnitine transporter and carnitine palmitoyltransferase-1.

    PubMed

    Purevsuren, Jamiyan; Kobayashi, Hironori; Hasegawa, Yuki; Yamada, Kenji; Takahashi, Tomoo; Takayanagi, Masaki; Fukao, Toshiyuki; Fukuda, Seiji; Yamaguchi, Seiji

    2013-02-01

    Mitochondrial fatty acid oxidation (FAO) disorders are caused by defects in one of the FAO enzymes that regulates cellular uptake of fatty acids and free carnitine. An in vitro probe acylcarnitine (IVP) assay using cultured cells and tandem mass spectrometry is a tool to diagnose enzyme defects linked to most FAO disorders. Extracellular acylcarnitine (AC) profiling detects carnitine palmitoyltransferase-2, carnitine acylcarnitine translocase, and other FAO deficiencies. However, the diagnosis of primary carnitine deficiency (PCD) or carnitine palmitoyltransferase-1 (CPT1) deficiency using the conventional IVP assay has been hampered by the presence of a large amount of free carnitine (C0), a key molecule deregulated by these deficiencies. In the present study, we developed a novel IVP assay for the diagnosis of PCD and CPT1 deficiency by analyzing intracellular ACs. When exogenous C0 was reduced, intracellular C0 and total AC in these deficiencies showed specific profiles clearly distinguishable from other FAO disorders and control cells. Also, the ratio of intracellular to extracellular C0 levels showed a significant difference in cells with these deficiencies compared with control. Hence, intracellular AC profiling using the IVP assay under reduced C0 conditions is a useful method for diagnosing PCD or CPT1 deficiency. PMID:23143007

  19. 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. PMID:27000012

  20. Differential effects of oral and transdermal menopausal hormone therapy on prostacyclin and thromboxane in platelets

    PubMed Central

    Raz, Limor; Hunter, Larry W.; Jayachandran, Muthuvel; Heit, John A.; Miller, Virginia M.

    2014-01-01

    Abstract Menopausal hormone therapies (MHT) may increase thrombotic risk but modulate endothelial function and reduce development of vascular lesions. This study compared effects of MHT on prostanoid‐modulated adenosine triphosphate (ATP) secretion from platelets in relationship with endothelial reactive hyperemia (RH) index and carotid intima medial thickness (CIMT). Participants were healthy, recently menopausal women of the Kronos Early Estrogen Prevention Study (KEEPS) randomized to one of three treatments: oral conjugated equine estrogen (oCEE, 0.45 mg/day), transdermal 17β‐estradiol (tE2, 50 μg/day) each with intermittent oral progesterone or placebo pills and patch (PL). Prostacyclin and thromboxane A2 were assessed by quantification of their stable metabolites (6‐keto‐prostaglandin F1α, 6‐k‐PGF1α; thromboxane B2, TXB2), using ELISA. Dense granule ATP secretion from activated platelets was determined by bioluminescence; RH and CIMT were determined by fingertip tonometry and ultrasound, respectively. After 48 months of treatment, platelet content of 6‐k‐PGF1α and TXB2 was significantly lower in oCEE compared to the PL. Inhibition of ATP secretion by exogenous activation of cAMP associated with platelet 6‐k‐PGF1α (r = −0.41, P = 0.04) and TXB2 (r = 0.71, P = 0.0005) only in the oCEE group. Serum and platelet content of 6‐k‐PGF1α and TXB2 associated positively in the PL and tE2 groups. Serum 6‐k‐PGF1α positively associated with RH in the oCEE group (r = 0.73, P = 0.02), while serum TXB2 positively associated with CIMT in the tE2 group (r = 0.64, P = 0.01). Thus, oCEE and tE2 differentially affect prostanoid‐mediated platelet secretory pathways but alone would not account for an increased thrombotic risk for oral MHT. Furthermore, platelet‐derived prostanoids may contribute to RH and vascular remodeling in healthy menopausal women. PMID:24760527

  1. Differential effects of oral and transdermal menopausal hormone therapy on prostacyclin and thromboxane in platelets.

    PubMed

    Raz, Limor; Hunter, Larry W; Jayachandran, Muthuvel; Heit, John A; Miller, Virginia M

    2014-01-01

    Abstract Menopausal hormone therapies (MHT) may increase thrombotic risk but modulate endothelial function and reduce development of vascular lesions. This study compared effects of MHT on prostanoid-modulated adenosine triphosphate (ATP) secretion from platelets in relationship with endothelial reactive hyperemia (RH) index and carotid intima medial thickness (CIMT). Participants were healthy, recently menopausal women of the Kronos Early Estrogen Prevention Study (KEEPS) randomized to one of three treatments: oral conjugated equine estrogen (oCEE, 0.45 mg/day), transdermal 17β-estradiol (tE2, 50 μg/day) each with intermittent oral progesterone or placebo pills and patch (PL). Prostacyclin and thromboxane A2 were assessed by quantification of their stable metabolites (6-keto-prostaglandin F1α, 6-k-PGF1α; thromboxane B2, TXB2), using ELISA. Dense granule ATP secretion from activated platelets was determined by bioluminescence; RH and CIMT were determined by fingertip tonometry and ultrasound, respectively. After 48 months of treatment, platelet content of 6-k-PGF1α and TXB2 was significantly lower in oCEE compared to the PL. Inhibition of ATP secretion by exogenous activation of cAMP associated with platelet 6-k-PGF1α (r = -0.41, P = 0.04) and TXB2 (r = 0.71, P = 0.0005) only in the oCEE group. Serum and platelet content of 6-k-PGF1α and TXB2 associated positively in the PL and tE2 groups. Serum 6-k-PGF1α positively associated with RH in the oCEE group (r = 0.73, P = 0.02), while serum TXB2 positively associated with CIMT in the tE2 group (r = 0.64, P = 0.01). Thus, oCEE and tE2 differentially affect prostanoid-mediated platelet secretory pathways but alone would not account for an increased thrombotic risk for oral MHT. Furthermore, platelet-derived prostanoids may contribute to RH and vascular remodeling in healthy menopausal women. PMID:24760527

  2. Oral rehydration therapy: efficacy of sodium citrate equals to sodium bicarbonate for correction of acidosis in diarrhoea.

    PubMed Central

    Islam, M R; Samadi, A R; Ahmed, S M; Bardhan, P K; Ali, A

    1984-01-01

    Forty patients with moderate degrees of dehydration and acidosis because of acute watery diarrhoea were successfully treated randomly with either WHO recommended oral rehydration solution containing 2.5 g sodium bicarbonate or an oral solution containing 2.94 g sodium citrate in place of sodium bicarbonate per litre of oral rehydration rehydration solution. Efficacies were compared by measuring oral fluid intake, stool and vomitus output, change in body weight, hydration status, and rate of correction of acidosis during a period of 48 hours. Seventy five per cent (21 cases) in the citrate group and 83% (19 cases) in the bicarbonate group were successfully rehydrated (p greater than 0.05). There were no significant differences in intake, output, gain in body weight, fall in haematocrit and plasma specific gravity, and correction of acidosis between the two groups of patients within 48 hours after initiation of therapy. The solution with sodium citrate base was as effective as WHO-oral rehydration solution for management of diarrhoea. This study shows the efficacy, safety, and acceptability of citrate containing oral rehydration solution for rehydration and correction of acidosis in diarrhoea. PMID:6086466

  3. Carnitine metabolism and deficit--when supplementation is necessary?

    PubMed

    Evangeliou, A; Vlassopoulos, D

    2003-06-01

    Carnitine is an ammo acid derivative found in high energy demanding tissues (skeletal muscles, myocardium, the liver and the suprarenal glands). It is essential for the intermediary metabolism of fatty acids. Carnitine is indispensable for beta-oxidation of long-chain fatty acids in the mitochondria but also regulates CoA concentration and removal of the produced acyl groups. AcylCoAs act as restraining factor for several enzymes participating in intermediary metabolism. Transformation of AcylCoA into acylcarnitine is an important system for removing the toxic acyl groups. Although primary deficiency is unusual, depletion due to secondary causes, such as a disease or a medication side effect, can occur. Primary carnitine deficiency is caused by a defect in plasma membrane carnitine transporter in muscle and kidneys. Secondary carnitine deficiency is associated with several inborn errors of metabolism and acquired medical or iatrogenic conditions, for example in patients under valproate and zidovuline treatment. In cirrhosis and chronic renal failure, carnitine biosynthesis is impaired or carnitine is lost during hemodialysis. Other chronic conditions like diabetes mellitus, heart failure, Alzheimer disease may cause carnitine deficiency also observed in conditions with increased catabolism as in critical illness. Preterm neonates develop carnitine deficiency due to impaired proximal renal tubule carnitine re-absorption and immature carnitine biosynthesis. Carnitine stabilizes the cellular membrane and raises red blood cell osmotic resistance but has no metabolic influence on lipids in dialysis patients. L-Carnitine has been administered in senile dementia, metabolic nerve diseases, in HIV infection, tuberculosis, myopathies, cardiomyopathies, renal failure anemia and included in baby foods and milk. PMID:12769764

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

    PubMed

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

    2016-04-01

    Current research for the first time demonstrated that endothelial dysfunction and hepatic injury in mice were induced by ingestion of 3% l-carnitine water for consecutive 10 weeks. Interestingly, oral administration of dietary raffinose family oligosaccharides (RFOs) at 400 and 800mg/kgbw significantly reduced the impact of l-carnitine on the serum total cholesterol, triglycerides, high- and low-density lipoproteins, alanine aminotransferase, aspartate amino-transferase, NO, endothelin-1 and C-reactive protein. Furthermore, l-carnitine-induced elevation of hepatic lipid contents and malonaldehyde formation, and the inhibition of SOD and GSH-Px activities in mice were markedly ameliorated by oral administration of RFOs. Moreover, histopathology of H&E and Oil Red O staining of the liver also confirmed the protective effect of RFOs against hepatic steatosis and oxidative injury induced by high l-carnitine diet in mice. These findings for the first time suggest that RFOs may alleviate endothelial dysfunction and liver injury from ingestion of high l-carnitine diet. PMID:26769087

  5. 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

  6. 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

  7. 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

  8. Reported and actual prescription of oral rehydration therapy for childhood diarrhoeas by retail pharmacists in Nigeria.

    PubMed

    Igun, U A

    1994-09-01

    This study documented what retail pharmacists and operators of patent medicine shops prescribe for childhood diarrhoeas in Borno State in the northeastern part of Nigeria. Data was generated by a combination of open and confederates survey of 135 pharmacies and patent medicine shops in the state. The study found that retail pharmacies and patent medicine shop operators, in the overwhelming majority routinely prescribe drugs, particularly, antibiotics, for both watery and bloody diarrhoea. Very few of the pharmacists and almost none of the patent medicine shop operators prescribed any form of oral rehydration therapy (ORT) for watery diarrhoea. There was very high discrepancy between what respondents told interviewers they usually prescribe and what was actually prescribed to confederates in their facilities. It is suggested that the non-prescription of ORT by the majority of facilities could be accounted for by pharmacists' permissive attitude to the norms. This permissive attitude was generated by the profit motive and reinforced by mothers' expectations. The study conclude that more operators can be made to prescribe ORT by instituting incentives for those who prescribe and overt sanctions for those who do not. PMID:7973875

  9. Assessment of predictive molecular variables in feline oral squamous cell carcinoma treated with stereotactic radiation therapy.

    PubMed

    Yoshikawa, H; Ehrhart, E J; Charles, J B; Custis, J T; LaRue, S M

    2016-03-01

    This study evaluated molecular characteristics that are potentially prognostic in cats with oral squamous cell carcinoma (SCC) that underwent stereotactic radiation therapy (SRT). Survival time (ST) and progression-free interval (PFI) were correlated with mitotic index, histopathological grades, Ki67 and epidermal growth factor receptor expressions, tumour microvascular density (MVD), and tumour oxygen tension (pO(2)). Median ST and PFI were 106 and 87 days, respectively (n = 20). Overall response rate was 38.5% with rapid improvement of clinical symptoms in many cases. Patients with higher MVD or more keratinized SCC had significantly shorter ST or PFI than patients with lower MVD or less keratinized SCC (P = 0.041 and 0.049, respectively). Females had significantly longer PFI and ST than males (P ≤ 0.016). Acute toxicities were minimal. However, treatment-related complications such as fractured mandible impacted quality of life. In conclusion, SRT alone should be considered as a palliative treatment. MVD and degree of keratinization may be useful prognostic markers. PMID:23815402

  10. 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

  11. 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.

  12. Oral rehydration therapy in the second decade of the twenty-first century.

    PubMed

    Binder, Henry J; Brown, Ian; Ramakrishna, B S; Young, Graeme P

    2014-03-01

    Oral rehydration solution (ORS) was established as the cornerstone of therapy for dehydration secondary to acute infectious diarrhea approximately 40 years ago. The efficacy of ORS is based on the ability of glucose to stimulate Na and fluid absorption in the small intestine via a cyclic AMP-independent process. Despite the establishment that ORS is the primary reason for the substantial reduction in morbidity and mortality from diarrhea in children in developing countries, the use of ORS has lagged for many reasons. This review highlights efforts to establish a major reformulation of ORS following the demonstration that short-chain fatty acids (SCFA) stimulate colonic Na and fluid absorption by a cyclic AMP-independent mechanism. The addition of high-amylose maize starch (HAMS), a microbially-fermentable (or 'resistant') starch, to ORS results in delivery of non-absorbed carbohydrate to the colon where it is fermented to SCFA. To date, three randomized controlled trials with a HAMS-ORS in south India have demonstrated a substantial decrease in diarrhea duration in both adults and children hospitalized for acute diarrhea. Significant efforts are now underway to establish this dual-action, modified HAMS-hypoosmolar ORS solution as the standard ORS for the treatment of dehydration from acute diarrhea. PMID:24562469

  13. [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

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

    PubMed

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

    2013-10-01

    The aim of this study was to analyze contributions by integrative community therapy to behavior changes in users of Psychosocial Care Centers (CAPS). This was a comprehensive-interpretative study with a qualitative approach, based on thematic oral history. The study site was the Caminhar Center in João Pessoa, Paraíba State, Brazil. The study material was produced with interviews conducted with six subjects and was discussed using thematic analysis as proposed by Minayo, providing the basis for two major thematic lines: integrative community therapy as a liberating praxis and changes that make the difference. The subjects' stories revealed significant changes in the personal, professional, and community fields, based on their inclusion in the integrative community therapy circles, a strategy that promoted the recovery of processes of natural socialization that constitute human life. The use of integrative community therapy was clearly related to proposals for the participants' psychosocial integration and rehabilitation. PMID:24127097

  15. Oral vasodilator therapy in patients with moderate to severe portopulmonary hypertension as a bridge to liver transplantation.

    PubMed

    Raevens, Sarah; De Pauw, Michel; Reyntjens, Koen; Geerts, Anja; Verhelst, Xavier; Berrevoet, Frederik; Rogiers, Xavier; Troisi, Roberto I; Van Vlierberghe, Hans; Colle, Isabelle

    2013-04-01

    Portopulmonary hypertension (POPH) is a part of group 1 pulmonary hypertension (pulmonary hypertension associated with portal hypertension). Liver transplantation (LTx) may be curative, but is usually restricted to patients with mild-to-moderate POPH. The presence of severe POPH may be a contraindication to transplantation because of the elevated risk of peritransplantation and post-transplantation morbidity and mortality. This report describes a series of seven patients with onset of moderate (two patients) or severe (five patients) POPH before LTx, of whom six were treated with oral vasodilator therapy for POPH. Although previous studies recommend aggressive parenteral prostacyclin therapy (epoprostenol), we describe the opportunity to treat cases of severe POPH with an oral phosphodiesterase type 5 inhibitor (sildenafil) and/or an endothelin receptor antagonist (bosentan/ambrisentan) as a bridge to successful LTx in selected patients. PMID:23242127

  16. Assessment of ghrelin and leptin receptor levels in postmenopausal women who received oral or transdermal menopausal hormonal therapy*

    PubMed Central

    Ruszkowska, Barbara; Sokup, Alina; Kulwas, Arleta; Socha, Maciej W.; Góralczyk, Krzysztof; Góralczyk, Barbara; Rość, Danuta

    2012-01-01

    Objective: In postmenopausal women, an increased leptin concentration and reduced levels of ghrelin and adiponectin were observed. The aim of this study was to evaluate the concentrations of the active form of ghrelin, total ghrelin, leptin receptor, lipoprotein(a) (Lp(a)), and plasminogen activator inhibitor type 1 (PAI-1) in postmenopausal women who received oral or transdermal menopausal hormonal therapy (MHT). Methods: The study involved 76 healthy women: 46 women aged from 44 to 58 years who received oral (26) or transdermal (20) MHT; the control group consisted of 30 women aged from 44 to 54 years who did not receive MHT. The plasma concentrations of total ghrelin, the active form of ghrelin, Lp(a), and PAI-1:Ag were measured by enzyme-linked immunosorbent assay (ELISA). The concentration of the leptin receptor was measured by enzyme immunometric assay (EIA). Results: We observed a significantly higher concentration of total ghrelin and the active form of ghrelin in women who received transdermal MHT in comparison with those who took oral MHT. We also found a significantly lower concentration of total ghrelin in women who received oral MHT compared with the control group. A higher concentration of PAI-1:Ag was found in the group of women who took transdermal MHT in comparison with those who took oral MHT and with the control group. The differences were statistically significant. Additionally, we found a significant negative correlation between the concentrations of total ghrelin and PAI-1:Ag and a positive correlation between the concentrations of total ghrelin and leptin receptor in women who received transdermal MHT. Conclusions: The study showed that women who used transdermal MHT had higher levels of total ghrelin than women who took oral MHT. This indicates a beneficial effect of the transdermal route of MHT. However, transdermal therapy was associated with adverse effects with regard to the observed higher levels of PAI-1:Ag, which in turn, can lead to

  17. Phase I trial of low-dose oral Clofarabine in myelodysplastic syndromes patients who have failed frontline therapy.

    PubMed

    Rudrapatna, Venkatesh K; Morley, Kimberly; Boucher, Kenneth M; Pierson, Andrew S; Shull, Christian T; Kushner, James P; Shami, Paul J

    2015-08-01

    We investigated protracted low-dose oral Clofarabine for the treatment of myelodysplastic syndromes (MDS). Adults with an International Prognostic Scoring System (IPSS) score of INT-1 or higher who had failed first line therapy were eligible. INT-1 patients had to be transfusion-dependent. We started with oral Clofarabine at 5mg (fixed dose) daily for 10 consecutive days on a 28-day cycle. Toxicity prompted a modification to 1mg PO daily for 10 days and then 1mg PO daily for 7 days. Patients received treatment indefinitely until loss of response or unacceptable toxicity. Nine patients (5 women) were enrolled and evaluable (median age 65 years; range 55-81). A 10-day regimen of oral Clofarabine at 5mg/day induced Grade IV pancytopenia. A dose of 1 mg/day for 7/28 days was very well tolerated without significant toxicity. Three patients had responses (2 with responses lasting up to 21 and 51 cycles) defined as stable disease in spite of no significant change on bone marrow evaluation. Low-dose oral Clofarabine (1mg daily for 7/28 days) proved both effective and safe for patients with MDS who had failed prior therapy. This patient population is particularly sensitive to more protracted Clofarabine treatment schedules. PMID:26038120

  18. 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

  19. 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

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

    PubMed Central

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

    2015-01-01

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

  1. 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

  2. Carnitine deficiency provokes cisplatin-induced hepatotoxicity in rats.

    PubMed

    Al-Majed, Abdulhakeem A

    2007-03-01

    This study investigates whether or not carnitine deficiency is a risk factor and could contribute to cisplatin-induced liver toxicity. A total of 60 adult male Wistar albino rats were divided into six groups. The first three groups were injected intraperitoneally with normal saline, propionyl-l-carnitine (500 mg/kg), and d-carnitine (500 mg/kg), respectively, for 10 successive days. The fourth, fifth and sixth groups were injected intraperitoneally with the same doses of normal saline, propionyl-l-carnitine and d-carnitine, respectively, for 5 successive days before and after a single dose of cisplatin (7 mg/kg). Administration of the standard nephrotoxic dose of cisplatin did not produce any changes in serum alanine transaminase and gamma-glutamyl transferase and no morphological changes in liver tissues. However, it did produce a significant increase in thiobarbituric acid reactive substances and total nitrate/nitrite and a significant decrease in reduced glutathione content in liver tissues. On the other hand, combined treatment with cisplatin and d-carnitine induced a dramatic increase in serum alanine transaminase and gamma-glutamyl transferase, as well as progressive reduction in total carnitine and ATP content in liver tissue. Moreover, histopathological examination of liver tissues confirmed the biochemical data, where cisplatin and d-carnitine combination showed signs of liver injury manifested as focal necro-inflammatory changes and portal inflammation. Interestingly, in carnitine supplemented rats using propionyl-l-carnitine, cisplatin did not produce any biochemical and histopathological changes in liver tissues. In conclusion, data from this study suggest for the first time that (1) carnitine deficiency is a risk factor and could precipitate cisplatin-induced hepatotoxicity, (2) oxidative stress is not the main cause of cisplatin-related hepatotoxicity and (3) propionyl-l-carnitine prevents the development of cisplatin-induced liver injury. PMID

  3. Inhibition of carnitine synthesis protects against left ventricular dysfunction in rats with myocardial ischemia.

    PubMed

    Aoyagi, T; Sugiura, S; Eto, Y; Yonekura, K; Matsumoto, A; Yokoyama, I; Kobayakawa, N; Omata, M; Kirimoto, T; Hayashi, Y; Momomura, S

    1997-10-01

    During myocardial ischemia, inhibition of the carnitine-mediated transportation of fatty acid may be beneficial because it facilitates glucose utilization and prevents an accumulation of fatty acid metabolites. We orally administered 3-(2,2,2-trimethyl hydrazinium) propionate (MET), an inhibitor of carnitine synthesis, for 20 days to rats. Then we evaluated left ventricular (LV) function during brief ischemia by using a buffer-perfused isovolumic heart model. After 15 min of reoxygenation after the transient ischemia, LV peak systolic pressure (PSP) almost completely returned to the baseline level in rats given MET (96 +/- 4%), whereas it was only partially (77 +/- 16%) recovered in the placebo-treated rats. We induced myocardial infarction in other rats by ligating the left anterior descending coronary artery. Then the animals were given MET for 20 days, and LV function was compared. In the placebo-treated rats (with myocardial infarction, but without drug treatment), LVPSP was lower than that in the sham group [108 +/- 19 (n = 10) vs. 136 +/- 15 mm Hg (n = 13); p < 0.05], and the time constant (T) of LV pressure decay was elongated (36 +/- 4 vs. 30 +/- 7 ms; p < 0.05). In MET-treated groups, however, neither PSP nor T differed from those in the sham group. In conclusion, inhibition of the carnitine-mediated transportation of fatty acid by MET protected against left ventricular dysfunction in acute and chronic myocardial ischemia. PMID:9335406

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

    PubMed Central

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

    2004-01-01

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

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

    PubMed

    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

  6. 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

  7. A new concept for bisphosphonate therapy: a rationale for the development of monthly oral dosing of ibandronate.

    PubMed

    Reginster, Jean-Yves; Felsenberg, Dieter; Cooper, Cyrus; Stakkestad, Jacob A; Miller, Paul D; Kendler, David L; Adami, Silvano; McClung, Michael R; Bolognese, Michael A; Civitelli, Roberto; Dumont, Etienne; Bonvoisin, Bernard; Recker, Robert R; Delmas, Pierre D

    2006-02-01

    Oral daily and weekly bisphosphonates represent the current mainstay of treatment for postmenopausal osteoporosis (PMO). However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long term. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Such regimens require high potency agents, which can be given at low effective doses and that also have good tolerability. Ibandronate is a potent, nitrogen-containing bisphosphonate with proven efficacy when given intermittently to estrogen-depleted beagle dogs, rats and cynomolgus monkeys. Clinically, a pivotal prospective study has established that oral ibandronate has significant vertebral fracture efficacy in PMO, whether given daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months; extended between-dose interval>2 months). Both oral regimens were well tolerated, which is noteworthy as patients with a history of gastrointestinal (GI) disturbance were not specifically excluded. As a result of these findings, a large, multinational, randomized, double-blind study (Monthly Oral iBandronate In LadiEs: MOBILE) is currently exploring the non-inferiority of once-monthly oral ibandronate (100 or 150 mg) to the oral daily ibandronate (2.5 mg) regimen with proven anti-fracture efficacy, in terms of lumbar spine bone mineral density (BMD) change. As with the trials investigating the weekly administration of other bisphosphonates, vertebral fracture efficacy will be inferred if the study demonstrates the non-inferiority of once-monthly ibandronate to the proven oral daily regimen in terms of spinal BMD change. The availability of this once-monthly ibandronate regimen is expected to offer benefits in terms of convenience (by having to follow dosing recommendations once a month vs. once daily or weekly) and potentially tolerability (by reducing the potential for upper GI irritation that

  8. [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

  9. A multicenter evaluation of oral pressure therapy for the treatment of obstructive sleep apnea

    PubMed Central

    Colrain, Ian M.; Black, Jed; Siegel, Lawrence C.; Bogan, Richard K.; Becker, Philip M.; Farid-Moayer, Mehran; Goldberg, Rochelle; Lankford, D. Alan; Goldberg, Andrew N.; Malhotra, Atul

    2013-01-01

    Objective We aimed to evaluate the impact of a novel noninvasive oral pressure therapy (OPT) (Winx®, ApniCure) system on polysomnographic measures of sleep-disordered breathing, sleep architecture, and sleep stability in obstructive sleep apnea (OSA). Subjects and methods A 4-week, multicenter, prospective, open-label, randomized, crossover, first-night order of control vs treatment, single-arm trial was conducted in five American Academy of Sleep Medicine (AASM) – accredited sleep clinics and one research laboratory. Sixty-three subjects (analysis cohort) were studied from a screening cohort of 367 subjects. The analysis cohort was 69.8% men, ages 53.6 ± 8.9 years (mean ± SD), body mass index of 32.3 ± 4.5 kg/m2, with mild to severe OSA. At treatment initiation, subjects received random assignment to one night with and one without (control) treatment, and they were assessed again following 28 nights of treatment. Breathing and sleep architecture were assessed each night based on blind scoring by a single centralized scorer using AASM criteria. Results Average nightly usage across the take-home period was 6.0 ± 1.4 h. There were no severe or serious device-related adverse events (AEs). Median apnea–hypopnea index (AHI) was 27.5 events per hour on the control night, 13.4 events per hour on the first treatment night, and 14.8 events per hour after 28 days of treatment. A clinically significant response (treatment AHI ≤10/h and ≤50% of control values) was seen in 20 of the 63 subjects evaluated. Rapid eye movement percentage (REM%) was significantly increased, and N1%, stage shifts to N1 sleep, overall stage shifts, total awakenings, and arousals per hour were all significantly reduced at both treatment nights compared to controls. Mean Epworth sleepiness scale (ESS) was significantly reduced from 12.1 to 8.6 (Cohen d effect size, 0.68) in those untreated for two or more weeks prior to OPT study participation and remained unchanged in subjects who

  10. 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

  11. The status of ORT (oral rehydration therapy) in Bangladesh: how widely is it used?

    PubMed

    Chowdhury, A M; Karim, F; Sarkar, S K; Cash, R A; Bhuiya, A

    1997-03-01

    During 1980-1990 BRAC, a Bangladeshi non-governmental organization, taught over 12 million mothers how to prepare oral rehydration therapy (ORT) at home with lobon (common salt) and gur (unrefined brown sugar). This was followed by a strong promotion and distribution of prepackaged ORS by various agencies including the government. In 1993 we assessed knowledge of ORT preparation, its local availability and its use for the management of diarrhoea. Over 9000 households in 90 villages were revisited; 306 government outreach health workers, 296 drug sellers, and 237 village doctors were interviewed; 152 government facilities and 495 pharmacies/shops were visited. ORT prepared by mothers in a sub-sample of the households was analyzed for chloride content and interviewers collected information on use of ORT for diarrhoeal episodes occurring in the preceding two weeks. The data quality was assessed through a resurvey of sample respondents within two weeks of the first interview. Over 70% of the mothers could prepare a chemically 'safe and effective' ORS. A significant proportion of these mothers were very young at the time of the mass campaigns using house to house teaching, implying an intergenerational transfer of the knowledge on ORT. ORT was found to be used in 60% of all diarrhoeal episodes, but the rate varied with the type of diarrhoea, being highest for daeria (severe watery diarrhoea) and lowest for amasha (dysentery). Drug sellers and village doctors now recommend ORT much more frequently than before. Members of the medical profession (qualified and unqualified) still lag behind in prescribing the use of ORT. The availability of pre-packaged ORS in rural pharmacies has improved enormously. There is convincing evidence that the widescale promotion in the past of ORS for dehydration in diarrhoea has led to this marked improvement today. Nevertheless the use of rice-based ORS, culturally appropriate messages and the promotion of ORS with food offer opportunities to

  12. Effects of Oral Anticoagulant Therapy in Medical Inpatients ≥65 Years With Atrial Fibrillation.

    PubMed

    Bo, Mario; Sciarrillo, Irene; Li Puma, Federica; Badinella Martini, Marco; Falcone, Yolanda; Iacovino, Marina; Grisoglio, Enrica; Menditto, Elena; Fonte, Gianfranco; Brunetti, Enrico; Maggiani, Guido; Isaia, Giovanni Carlo; Gaita, Fiorenzo

    2016-02-15

    In this retrospective cohort observational study, we investigated mortality, ischemic, and hemorrhagic events in patients ≥65 years with atrial fibrillation consecutively discharged from an Acute Geriatric Ward in the period 2010 to 2013. Stroke and bleeding risk were evaluated using CHA2DS2-VASC (congestive heart failure/left ventricular dysfunction, hypertension, aged ≥75 years, diabetes mellitus, stroke/transient ischemic attack/systemic embolism, vascular disease, aged 65 to 74 years, gender category) and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) scores. Co-morbidity, cognitive status, and functional autonomy were evaluated using standardized scales. Independent associations among clinical variables, including use of vitamin K antagonist-based oral anticoagulant therapy (OAT), all-cause mortality, and fatal and nonfatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching. Of 980 patients discharged (mean age 83 years, 60% women, roughly 30% cognitively impaired or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.8 and 2.1, respectively), 505 (51.5%) died during a mean follow-up period of 571 days; ischemic and hemorrhagic stroke occurred in 82 (12.3%) and 13 patients (1.3%), respectively, and major bleedings in 43 patients (4.4%). Vitamin K antagonists' use was independently associated with reduced mortality (odds ratio 0.524) and with a nonsignificant reduction in incidence of ischemic stroke, without excess in bleeding risk. Similar findings were observed in the 2 propensity score-matched cohorts of patients. In conclusion, among vulnerable patients with atrial fibrillation ≥65 years with high

  13. A cross sectional study of oral submucous fibrosis in central India and the effect of local triamcinolone therapy.

    PubMed

    Ameer, N T; Shukla, Rakesh Kumar

    2012-09-01

    The use of processed arecanut is on the increase. In the impending danger of increased occurrence of oral submucous fibrosis and subsequent oral cancer following this habit is colossal. So an attempt is made to clinically evaluate the condition and to evaluate the effect of triamcinolone on this condition. Using the clinical data collected from the patients presenting in the ENT OPD of NSCB Medical College Hospital, Jabalpur, a cross sectional study was done and the effect of intralesional triamcinolone on this condition is noted by biweekly submucosal injections of 40 mg triamcinolone for 12 weeks and followed up for 1 year. The effect of therapy was evaluated subjectively by improvement in symptoms and objectively by increase in mouth opening. The age of occurrence and sex predilection also showed a significant change with more young males being affected by the condition. There was no significant correlation between effect of triamcinolone therapy and duration of addiction but a significant correlation (P < 0.0001) was noted with the frequency of addiction per day. A significant improvement in mouth opening is observed following local triamcinolone therapy. The results imply that the exposure and the frequency of chewing habits, and not mere the duration that is significant in producing the condition and affecting the treatment outcome. Local triamcinolone therapy has good effect in the initial stages of the disease. The fact that more youngsters are being affected needs serious consideration. PMID:23998027

  14. 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. PMID:26932256

  15. 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

  16. 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.

  17. 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

  18. Oral manifestations of human immunodeficiency virus in children: An institutional study at highly active antiretroviral therapy centre in India

    PubMed Central

    Ponnam, Srinivas Rao; Srivastava, Gautam; Theruru, Kotaih

    2012-01-01

    Context: More than 1000 children are newly infected with Human immunodefi ciency virus (HIV) every day, and of these more than half will die as a result of AIDS due to lack of access to HIV treatment. HIV disease varies considerably in children. Among those infected prenatally, some experience few or no symptoms for years, whereas in others the disease progresses rapidly. The risk factors that influence the development of such oral manifestations include, low CD4+ T cell count, xerostomia and lack of highly active antiretroviral therapy (HAART). Aims: To identify the oral manifestations of HIV in children receiving HAART. Materials and Methods: The study comprised 95 children receiving HAART. 95 HIV +ve children not receiving HAART and 95 HIV –ve children were also included for comparing the manifestations of HIV. Statistical Analysis Used: Statistical analysis was done using Fisher's Chi-square test. Probability value (P value) was obtained for the three groups. Results: The manifestations of HIV that were observed in children receiving HAART include dental caries (26%), periodontal diseases (23%), candidiasis (19%), hyperpigmentation (17%), ulcerative stomatitis (9%) and one case of mucocele. These manifestations were compared with HIV +ve children not receiving HAART and HIV –ve children to find manifestations with statistical significance. Conclusions: We conclude that HAART had increased the disease-free states in HIV +ve children on HAART promising them better life span. The incidence of oral lesions can further come down with adequate oral hygiene measures in HIV-infected children. PMID:22923890

  19. The influence of chronic L-carnitine supplementation on the formation of preneoplastic and atherosclerotic lesions in the colon and aorta of male F344 rats.

    PubMed

    Empl, Michael T; Kammeyer, Patricia; Ulrich, Reiner; Joseph, Jan F; Parr, Maria K; Willenberg, Ina; Schebb, Nils H; Baumgärtner, Wolfgang; Röhrdanz, Elke; Steffen, Christian; Steinberg, Pablo

    2015-11-01

    L-Carnitine, a key component of fatty acid oxidation, is nowadays being extensively used as a nutritional supplement with allegedly "fat burning" and performance-enhancing properties, although to date there are no conclusive data supporting these claims. Furthermore, there is an inverse relationship between exogenous supplementation and bioavailability, i.e., fairly high oral doses are not fully absorbed and thus a significant amount of carnitine remains in the gut. Human and rat enterobacteria can degrade unabsorbed L-carnitine to trimethylamine or trimethylamine-N-oxide, which, under certain conditions, may be transformed to the known carcinogen N-nitrosodimethylamine. Recent findings indicate that trimethylamine-N-oxide might also be involved in the development of atherosclerotic lesions. We therefore investigated whether a 1-year administration of different L-carnitine concentrations (0, 1, 2 and 5 g/l) via drinking water leads to an increased incidence of preneoplastic lesions (so-called aberrant crypt foci) in the colon of Fischer 344 rats as well as to the appearance of atherosclerotic lesions in the aorta of these animals. No significant difference between the test groups regarding the formation of lesions in the colon and aorta of the rats was observed, suggesting that, under the given experimental conditions, L-carnitine up to a concentration of 5 g/l in the drinking water does not have adverse effects on the gastrointestinal and vascular system of Fischer 344 rats. PMID:25164827

  20. Low-dose oral methotrexate as second-line therapy for persistent trophoblast after conservative treatment of ectopic pregnancy.

    PubMed

    Bengtsson, G; Bryman, I; Thorburn, J; Lindblom, B

    1992-04-01

    The aim of this study was to evaluate the efficacy of methotrexate as second-line treatment for ectopic pregnancy. Oral methotrexate was used in 15 patients with evidence of persistent trophoblast after conservative laparoscopic surgery for tubal pregnancy. The treatment was successful in 14 of 15 cases, and the mean time for decline of serum hCG to nonpregnant levels was 24 days. In the remaining case, hCG continued to rise. Side effects were noticed, even at a low dosage, but only in those subjects not receiving citrovorum rescue. As an alternative to a second operation, oral methotrexate appears to be an effective and well-tolerated therapy for persistent trophoblast. PMID:1532446

  1. The role of carnitine in the perinatal period.

    PubMed

    Kępka, Alina; Chojnowska, Sylwia; Okungbowa, Osazee E; Zwierz, Krzysztof

    2014-01-01

    Carnitine (2-hydroxy-4-trimethylammonium butyrate, vitamin BT) is a small hydrophilic molecule derived from protein-bound lysine, not degraded in the body but excreted via urine, bile and breast milk. Carnitine stimulates the catabolism of long-chain fatty acids (FAs), by transporting them to mitochondria for oxidation, and the intracellular decomposition of branched-chain ketoacids. It also helps to excrete toxic exogenous and nontoxic endogenous organic acids via urine. It further participates in the production of pulmonary surfactant, inhibits free radicals production and demonstrates other antioxidant properties. After delivery, infants dramatically increase energy demands for movement, growth, differentiation and maintenance of the body temperature that strongly depend on FAs oxidation which is facilitated by carnitine. At early stages of life, carnitine biosynthesis is less efficient than in adults and immature infants have less carnitine tissue reserves than term infants. Carnitine supplementation is recommended in newborns with aciduria, childhood epilepsy associated with valproate-induced hepatotoxicity, in kidney-associated syndromes, and premature infants receiving total parenteral nutrition. Concentrations of carnitine and acylcarnitines in neonatal blood have been postulated a useful tool for the diagnosis of type 1 diabetes, as well as the detection and monitoring of many inherited and acquired metabolic disorders. Taking into account the complex metabolic role of cellular FAs transporters, further studies are needed on indications and contraindications for carnitine supplementation in different clinical settings during early developmental period. PMID:25874778

  2. 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.

  3. 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

  4. 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

  5. Oral drugs in multiple sclerosis therapy: an overview and a critical appraisal.

    PubMed

    D'Amico, Emanuele; Leone, Carmela; Caserta, Cinzia; Patti, Francesco

    2015-01-01

    Multiple sclerosis (MS) is characterized by demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of MS resulted in the introduction of numerous effective drugs with diverse mechanisms of actions, routes of administration and benefit-risk profiles. New oral drugs recently approved for MS treatment has led to significant achievements in MS management. The oral route of administration promotes patient satisfaction and increases therapeutic compliance; but their introduction has raised concerns regarding safety and tolerability; and a thorough analysis of the benefit/risk ratio is required. This article reviews the mechanisms of action, safety and efficacy of the licensed and experimental oral drugs in MS. Moreover, we put into perspective the disease, drug and patient-related factors that should be taken into account when considering the appropriate oral drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS. PMID:26098146

  6. 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. PMID:22899691

  7. Predictors of obstructive sleep apnoea-hypopnea severity and oral appliance therapy efficacy by using lateral cephalometric analysis.

    PubMed

    Sakamoto, Y; Yanamoto, S; Rokutanda, S; Naruse, T; Imayama, N; Hashimoto, M; Nakamura, A; Yoshida, N; Tanoue, N; Ayuse, T; Yoshimine, H; Umeda, M

    2016-09-01

    Obstructive sleep apnoea-hypopnea (OSAH) is a common disorder characterised by repetitive complete or partial closure of the upper airway during sleep, which results in sleep fragmentation and oxygen desaturation. There is growing interest in the use of oral appliances (OAs) to treat OSAH. The purpose of this study was to clarify the cephalometric factors that are associated with OSAH severity and that predict the outcome of OA therapy. Two hundred nine patients with OSAH were recruited and analysed retrospectively. They had a polysomnographically documented apnoea-hypopnea index (AHI) of more than five respiratory events per hour. Lateral skull radiographs were used for cephalometric analysis. Only 67 of the 209 recruited patients underwent a second polysomnography (PSG) to evaluate the efficacy of OA therapy. In all recruited patients, the angle formed by the subspinal point (A) to the nasion (N) to the supramental point (B) (i.e. ANB angle) and the distance between the mandibular plane and hyoid bone (MP-H) were predictive factors of OSAH severity. In only 67 patients underwent PSG with an OA, the mean rate of decrease in the AHI was 47·8 ± 29·1%. OA therapy effectively treated OSAH in some patients with a very severe form of OSAH. However, patients who had a high position of the hyoid bone had a poor response to OA therapy. This study suggested that cephalometric analysis is useful for predicting OSAH severity and OA therapy efficacy. PMID:27132249

  8. 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

  9. Oral Gentamicin Gut Decontamination for Prevention of KPC-Producing Klebsiella pneumoniae Infections: Relevance of Concomitant Systemic Antibiotic Therapy

    PubMed Central

    Tascini, Carlo; Sbrana, Francesco; Flammini, Sarah; Tagliaferri, Enrico; Arena, Fabio; Leonildi, Alessandro; Ciullo, Ilaria; Amadori, Francesco; Di Paolo, Antonello; Ripoli, Andrea; Lewis, Russell; Rossolini, Gian Maria

    2014-01-01

    Gut colonization represents the main source for KPC-producing Klebsiella pneumoniae (KPC-Kp) epidemic dissemination. Oral gentamicin, 80 mg four times daily, was administered to 50 consecutive patients with gut colonization by gentamicin-susceptible KPC-Kp in cases of planned surgery, major medical intervention, or need for patient transfer. The overall decontamination rate was 68% (34/50). The median duration of gentamicin treatment was 9 days (interquartile range, 7 to 15 days) in decontaminated patients compared to 24 days (interquartile range, 20 to 30 days) in those with persistent colonization (P < 0.001). In the six-month period of follow-up, KPC-Kp infections were documented in 5/34 (15%) successfully decontaminated patients compared to 12/16 (73%) persistent carriers (P < 0.001). The decontamination rate was 96% (22/23) in patients receiving oral gentamicin only, compared to 44% (12/27) of those treated with oral gentamicin and concomitant systemic antibiotic therapy (CSAT) (P < 0.001). The multivariate analysis confirmed CSAT and KPC-Kp infection as the variables associated with gut decontamination. In the follow-up period, KPC-Kp infections were documented in 2/23 (9%) of patients treated with oral gentamicin only and in 15/27 (56%) of those also receiving CSAT (P = 0.003). No difference in overall death rate between different groups was documented. Gentamicin-resistant KPC-Kp strains were isolated from stools of 4/16 persistent carriers. Peak gentamicin blood levels were below 1 mg/liter in 12/14 tested patients. Oral gentamicin was shown to be potentially useful for gut decontamination and prevention of infection due to KPC-Kp, especially in patients not receiving CSAT. The risk of emergence of gentamicin-resistant KPC-Kp should be considered. PMID:24419337

  10. Oral gentamicin gut decontamination for prevention of KPC-producing Klebsiella pneumoniae infections: relevance of concomitant systemic antibiotic therapy.

    PubMed

    Tascini, Carlo; Sbrana, Francesco; Flammini, Sarah; Tagliaferri, Enrico; Arena, Fabio; Leonildi, Alessandro; Ciullo, Ilaria; Amadori, Francesco; Di Paolo, Antonello; Ripoli, Andrea; Lewis, Russell; Rossolini, Gian Maria; Menichetti, Francesco

    2014-01-01

    Gut colonization represents the main source for KPC-producing Klebsiella pneumoniae (KPC-Kp) epidemic dissemination. Oral gentamicin, 80 mg four times daily, was administered to 50 consecutive patients with gut colonization by gentamicin-susceptible KPC-Kp in cases of planned surgery, major medical intervention, or need for patient transfer. The overall decontamination rate was 68% (34/50). The median duration of gentamicin treatment was 9 days (interquartile range, 7 to 15 days) in decontaminated patients compared to 24 days (interquartile range, 20 to 30 days) in those with persistent colonization (P<0.001). In the six-month period of follow-up, KPC-Kp infections were documented in 5/34 (15%) successfully decontaminated patients compared to 12/16 (73%) persistent carriers (P<0.001). The decontamination rate was 96% (22/23) in patients receiving oral gentamicin only, compared to 44% (12/27) of those treated with oral gentamicin and concomitant systemic antibiotic therapy (CSAT) (P<0.001). The multivariate analysis confirmed CSAT and KPC-Kp infection as the variables associated with gut decontamination. In the follow-up period, KPC-Kp infections were documented in 2/23 (9%) of patients treated with oral gentamicin only and in 15/27 (56%) of those also receiving CSAT (P=0.003). No difference in overall death rate between different groups was documented. Gentamicin-resistant KPC-Kp strains were isolated from stools of 4/16 persistent carriers. Peak gentamicin blood levels were below 1 mg/liter in 12/14 tested patients. Oral gentamicin was shown to be potentially useful for gut decontamination and prevention of infection due to KPC-Kp, especially in patients not receiving CSAT. The risk of emergence of gentamicin-resistant KPC-Kp should be considered. PMID:24419337

  11. Active sites residues of beef liver carnitine octanoyltransferase (COT) and carnitine palmitoyltransferase (CPT-II).

    PubMed Central

    Nic a'Bháird, N; Yankovskaya, V; Ramsay, R R

    1998-01-01

    The carnitine acyltransferases which catalyse the reversible transfer of fatty acyl groups between carnitine and coenzyme A have been proposed to contain a catalytic histidine. Here, the chemical reactivity of active site groups has been used to demonstrate differences between the active sites of beef liver carnitine octanoyltransferase (COT) and carnitine palmitoyltransferase-II (CPT-II). Treatment of CPT-II with the histidine-selective reagent, diethyl pyrocarbonate (DEPC), resulted in simple linear pseudo-first-order kinetics. The reversal of the inhibition by hydroxylamine and the pKa (7.1) of the modified residue indicated that the residue was a histidine. The order of the inactivation kinetics showed that 1mol of histidine was modified per mol of CPT-II.When COT was treated with DEPC the kinetics of inhibition were biphasic with an initial rapid loss of activity followed by a slower loss of activity. The residue reacting in the faster phase of inhibition was not a histidine but possibly a serine. The modification of this residue did not lead to complete loss of activity suggesting that a direct role in catalysis is unlikely. It was deduced that the residue modified by DEPC in the slower phase was a lysine and indeed fluorodinitrobenzene (FDNB) inactivated COT with linear pseudo-first-order kinetics. The COT peptide containing the FDNB-labelled lysine was isolated and sequenced. Alignment of this sequence placed it 10 amino acids downstream of the putative active-site histidine. PMID:9480926

  12. 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

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

    ClinicalTrials.gov

    2016-03-11

    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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. Epigenetic Modifications and Accumulation of DNA Double-Strand Breaks in Oral Lichen Planus Lesions Presenting Poor Response to Therapy.

    PubMed

    Dillenburg, Caroline S; Martins, Marco A T; Almeida, Luciana O; Meurer, Luise; Squarize, Cristiane H; Martins, Manoela D; Castilho, Rogerio M

    2015-07-01

    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

  19. 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

  20. 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

  1. 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

  2. Effectiveness of oral health education versus nicotine replacement therapy for tobacco cessation- a parallel randomized clinical trial

    PubMed Central

    Saha, Sabyasachi; Krishna-Reddy, Vamsi; Mohd, Shafaat; Narang, Ridhi; Sood, Poonam

    2016-01-01

    Background India has millions of tobacco users. It is the leading cause of deaths due to oral cancer and hence needs effective strategies to curb it. Hence the aim of present study was to evaluate and compare the effectiveness of Oral Health Education (OHE) and Nicotine Replacement Therapy (NRT) in tobacco cessation. Material and Methods The clinical trial consisted of Manohar Lal Kapoor (MLK) factory workers (n= 40) giving history of tobacco consumption (smoking/smokeless) within past 30 days. They were randomized into OHE (n=20) and NRT (n=20) groups. Baseline evaluation (demographic, smoking/ smokeless behaviour) was done. Fagerstrom test was used for Nicotine Dependence (FTND) and to assess nicotine addiction level. Follow up was done at an interval of 1week, 2 weeks, 1 month, 2 months and 3 months to assess the reduction in the mean FTND score. “Nano-CheckTM Rapid Nicotine test” was used for the qualitative detection of cotinine in human urine. Appropriate statistical analysis was performed (Paired and Unpaired t test). Results In both OHE and NRT group there was a significant reduction (p< 0.00001) in mean Fagerstrom score at every follow up but when both the groups were compared mean Fagerstrom score reduction was more in NRT than OHE at all time interval though it was not statistically significant (p>0.05). Conclusions NRT is better than OHE when both the groups were compared. However, it was found that any intervention given to tobacco users either NRT or OHE is helpful for the patients in the process of quitting tobacco. Key words:Tobacco cessation, nicotine replacement therapy, oral health education, fagerstrom test, urine cotinine. PMID:26855709

  3. Decision-making about the use of non-vitamin K oral anticoagulant therapies for patients with atrial fibrillation.

    PubMed

    Eckman, Mark H

    2016-02-01

    Until recently, vitamin K antagonists, warfarin being the most commonly used agent in the United States, have been the only oral anticoagulant therapies available to prevent stroke in patients with atrial fibrillation (AF). In the last 5 years four new, non-vitamin K oral anticoagulants, the so-called NOACs or novel oral anticoagulants, have come to market and been approved by the Federal Drug Administration. Despite comparable if not superior efficacy in preventing AF-related stroke, and generally lower risks of major hemorrhage, particularly intracranial bleeding, the uptake of these agents has been slow. A number of barriers stand in the way of the more widespread use of these novel agents. Chief among them is concern about the lack of antidotes or reversal agents. Other concerns include the need for strict medication adherence, since missing even a single dose can lead to a non-anticoagulated state; out-of-pocket costs for patients; the lack of easily available laboratory tests to quantitatively assess the level of anticoagulant activity when these agents are being used; contraindications to use in patients with severe chronic kidney disease; and black-box warnings about the increased risk of thromboembolic events if these agents are discontinued prematurely. Fortunately, a number of reversal agents are in the pipeline. Three reversal agents, idarucizumab, andexanet alfa, and aripazine, have already progressed to human studies and show great promise as either antidotes for specific drugs or as universal reversal agents. The availability of these reversal agents will likely increase the clinical use of the non-vitamin K oral anticoagulants. In light of the many complex and nuanced issues surrounding the choice of an optimal anticoagulant for any AF patient, a patient-centered/shared decision-making approach will be useful. PMID:26343041

  4. Oral delivery of taurocholic acid linked heparin-docetaxel conjugates for cancer therapy.

    PubMed

    Khatun, Zehedina; Nurunnabi, Md; Reeck, Gerald R; Cho, Kwang Jae; Lee, Yong-Kyu

    2013-08-28

    We have synthesized taurocholic acid (TCA) linked heparin-docetaxel (DTX) conjugates for oral delivery of anticancer drug. The ternary biomolecular conjugates formed self-assembly nanoparticles where docetaxel was located inside the core and taurocholic acid was located on the surface of the nanoparticles. The coupled taurocholic acid in the nanoparticles had enhanced oral absorption, presumably through the stimulation of a bile acid transporter of the small intestine. The oral absorption profile demonstrated that the concentration of the conjugates in plasma is about 6 fold higher than heparin alone. An anti-tumor study in MDA-MB231 and KB tumor bearing mice showed significant tumor growth inhibition activity by the ternary biomolecular conjugates. Ki-67 histology study also showed evidence of anticancer activity of the nanoparticles. Finally, noninvasive imaging using a Kodak Molecular Imaging System demonstrated that the nanoparticles were accumulated efficiently in tumors. Thus, this approach for oral delivery using taurocholic acid in the ternary biomolecular conjugates is promising for treatment of various types of cancer. PMID:23665255

  5. Diagnosis and indications for low-intensity laser therapy of the pathology of the oral cavity mucosa of patients with hematologic and gastroenteric diseases

    NASA Astrophysics Data System (ADS)

    Kunin, Anatoly A.; Minakov, E. V.; Sutscenko, A. V.; Vornovsky, V. A.; Dunaeva, S. V.; Stepanov, Nicolay N.; Shumilovitch, Bogdan R.

    1996-11-01

    In the recent years low intensity laser irradiation is made use of in stomatology with the view of treating numerous diseases of the oral cavity mucosa and parodontium. The oral cavity mucosa lesions caused by the internal organs diseases, especially those of blood and the gastroenteric tract, constitute a particular group. Such diseases are usually manifested by an inflammation, erosions, ulcers, hemorrhages. An abundant microflora of the oral cavity and diminished immunity of the patients contribute to the possibility of septicaemia development. Laser therapy of the oral cavity mucosa lesions according to strictly defined indications promotes rapid healing of ulcers, arresting the oral cavity mucosa inflammation, providing a reduction in bleeding and presents a safe prophylactic means of stomatogenic sepsis.

  6. 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…

  7. 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

  8. The neurobiology of acetyl-L-carnitine.

    PubMed

    Traina, Giovanna

    2016-01-01

    A large body of evidence points to the positive effects of dietary supplementation of acetyl-L-carnitine (ALC). Its use has shown health benefits in neuroinflammation, which is a common denominator in a host of neurodegenerative diseases. ALC is the principal acetyl ester of L-Carnitine (LC), and it plays an essential role in intermediary metabolism, acting as a donor of acetyl groups and facilitating the transfer of fatty acids from cytosol to mitochondria during beta-oxidation. Dietary supplementation of ALC exerts neuroprotective, neurotrophic, antidepressive and analgesic effects in painful neuropathies. ALC also has antioxidant and anti-apoptotic activity. Moreover, ALC exhibits positive effects on mitochondrial metabolism, and shows promise in the treatment of aging and neurodegenerative pathologies by slowing the progression of mental deterioration. In addition, ALC plays neuromodulatory effects on both synaptic morphology and synaptic transmission. These effects are likely due to affects of ALC through modulation of gene expression on several targets in the central nervous system. Here, we review the current state of knowledge on effects of ALC in the nervous system. PMID:27100509

  9. Considerations for long-term anticoagulant therapy in patients with venous thromboembolism in the novel oral anticoagulant era

    PubMed Central

    Toth, Peter P

    2016-01-01

    Background Patients who have had a venous thromboembolic event are generally advised to receive anticoagulant treatment for 3 months or longer to prevent a recurrent episode. Current guidelines recommend initial heparin and an oral vitamin K antagonist (VKA) for long-term anticoagulation. However, because of the well-described disadvantages of VKAs, including extensive food and drug interactions and the need for regular anticoagulation monitoring, novel oral anticoagulants (NOACs) have become an attractive option in recent years. These agents are given at fixed doses and do not require routine coagulation-time monitoring. The NOACs are discussed in this review with regard to the needs of patients on long-term anticoagulation. Methods Current guidelines from Europe and North America that refer to the treatment of deep vein thrombosis and/or pulmonary embolism are included, as well as published randomized Phase III clinical trials of NOACs. PubMed searches were used for sourcing case studies of long-term anticoagulant treatment, and results were filtered for human application and screened for relevance. Conclusion NOAC-based therapy showed a similar efficacy and safety profile to heparins/VKAs but without the need for regular anticoagulation monitoring or dietary adjustments, and can be taken as a fixed-dose regimen once or twice daily. This represents a significant step forward in facilitating the management of long-term anticoagulation therapy. Furthermore, in the EINSTEIN studies, improved patient satisfaction was documented with the NOAC rivaroxaban, which may result in better adherence to therapy and an overall reduction in the incidence of recurrent venous thromboembolism. PMID:26929637

  10. 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

  11. Tibolone, transdermal estradiol or oral estrogen-progestin therapies: effects on circulating allopregnanolone, cortisol and dehydroepiandrosterone levels.

    PubMed

    Pluchino, N; Genazzani, A D; Bernardi, F; Casarosa, E; Pieri, M; Palumbo, M; Picciarelli, G; Gabbanini, M; Luisi, M; Genazzani, A R

    2005-03-01

    The aim of the present study was to evaluate, in healthy postmenopausal women, the impact of tibolone (2.5 mg), transdermal estradiol (50 microg) (TE) and different oral estrogen-progestin regimens, conjugated equine estrogens (0.625 mg) plus medroxyprogesterone acetate (5 mg) (CEE + MPA) and estradiol (2 mg) plus norethisterone acetate (1 mg) (E2 + NETA) on circulating estradiol, progesterone, allopregnanolone, cortisol and dehydroepiandrosterone (DHEA) levels. Blood samples were collected before and after 1, 3, 6 and 9 months of treatment in 85 postmenopausal women. Estradiol levels increased (p < 0.001) in the TE, CEE + MPA and E2 + NETA groups after 1 month of therapy, but did not change in the tibolone group during the entire follow-up period. Both E2 + NETA and tibolone treatments induced an increase in progesterone levels (p < 0.05) after 1 year of therapy. Allopregnanolone levels showed an increase in all estrogen-based groups, being significant after 3 months of treatment (p < 0.01). Patients receiving tibolone showed a significant increase in allopregnanolone levels at 3 months (p < 0.05), but lower than in the other groups. Cortisol levels decreased significantly in the TE and CEE + MPA groups after 6 months and 12 months of treatment, respectively. Neither tibolone nor E2 + NETA treatments modified circulating cortisol levels. DHEA levels significantly (p < 0.05) decreased after 6 months of TE or estrogen-progestin therapies independently of the presence or the type of progestin used. In contrast, DHEA remained stable throughout the 12 months of treatment with tibolone. The increase of allopregnanolone, a steroid with sedative and anxiolytic properties, in response to these different treatments could underlie, at least in part, the central effects that hormone replacement therapy and tibolone have on anxiety, mood and behavior. Unlike estrogen-based therapy, tibolone treatment did not reduce the DHEA milieu in the menopause, and thus did not enhance the

  12. Benzydamine hydrochloride in prevention and management of pain in oral mucositis associated with radiation therapy

    SciTech Connect

    Epstein, J.B.; Stevenson-Moore, P.

    1986-08-01

    Benzydamine hydrochloride rinse reduced pain associated with radiation mucositis when it was used during the course of radiation therapy. Fewer patients using benzydamine rinse required systemic analgesics. All patients using benzydamine tolerated the rinse well and continued with regular rinsing throughout the course of radiation therapy. Benzydamine hydrochloride is currently undergoing clinical trials in the United States for application for approval from the Food and Drug Administration.

  13. 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. PMID:19395269

  14. 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

  15. [Therapy education for patients receiving oral anti-coagulants vitamin K antagonists].

    PubMed

    Satger, Bernadette; Blaise, Sophie; Fontaine, Michèle; Yver, Jacqueline; Allenet, Benoît; Baudrant, Magali; Pernod, Gilles; Bosson, Jean-Luc

    2009-12-01

    The vitamin K antagonists (VKA) remain to this day the only oral form of therapeutic anticoagulation. Approximately 1% of the French population, mainly elderly, is treated with these anticoagulants. Oral anticoagulants have significant risks of iatrogenic complications; indeed they are the leading cause of such drug-induced complications, predominantly hemorrhages. AFSSAPS (French Drug and Medical Products Agency) clinical practice recommendations, repeatedly disseminated, emphasize the education of patients receiving VKAs. Managing oral anticoagulant treatment is challenging, with a significant risk of under- or overdosing and consequently, thrombosis or hemorrhage. The therapeutic window is narrow, multiple drug-interactions are possible, and the specific dose required for a particular individual to achieve appropriate International Normalized Ratio (INR) levels is unpredictable. The literature contains few randomized controlled trials about the efficacy of education for patients treated with oral anticoagulants. These education programs are not standardized and are therefore varied and difficult to compare. Nevertheless, studies demonstrate the importance of patient education programs in reducing the risk of hemorrhage and achieving better treatment stability. The Grenoble region hospital-community network for vascular diseases (GRANTED) has developed an education program for these patients, consisting of individual sessions for the patient and/or a friend or family member (either at a health care facility or at the patient's home), telephone support and group sessions, and using educational tools and supports. There is also a link with the general practitioner who receives a report. This approach makes it possible to adapt the educational message to individual patients and their daily lives, as well as directly involving them in the management of their treatment. PMID:19815369

  16. 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

  17. Oral Solubilized Ursodeoxycholic Acid Therapy in Amyotrophic Lateral Sclerosis: A Randomized Cross-Over Trial

    PubMed Central

    Min, Ju-Hong; Hong, Yoon-Ho; Sung, Jung-Joon; Kim, Sung-Min; Lee, Jung Bok

    2012-01-01

    To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial. PMID:22323869

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

    PubMed

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

    2016-08-01

    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, 30mg/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 (10mg/kg/d i.p), HFD+STZ diabetic group received L-carnitine (0.6g/kg/d i.p), and HFD+STZ diabetic group received glibenclamide (5mg/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

  19. 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

  20. 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

  1. Multiple disturbances of free fatty acid metabolism in noninsulin-dependent diabetes. Effect of oral hypoglycemic therapy.

    PubMed Central

    Taskinen, M R; Bogardus, C; Kennedy, A; Howard, B V

    1985-01-01

    To assess the mechanisms for the elevation of free fatty acids in noninsulin-dependent diabetes, free fatty acid metabolism and lipid and carbohydrate oxidation were compared in 14 obese diabetic Pima Indians and in 13 age-, sex-, and weight-matched nondiabetics. The studies were repeated in 10 of the diabetics after 1 mo of oral hypoglycemic therapy. Fasting plasma glucose concentrations were elevated in diabetics (242 +/- 14 vs. 97 +/- 3 mg/dl, P less than 0.01) and decreased to 142 +/- 12 (P less than 0.01) after therapy. Fasting free fatty acid concentrations were elevated in diabetics (477 +/- 26 vs. 390 +/- 39 mumol/liter, P less than 0.01) and declined to normal values after therapy (336 +/- 32, P less than 0.01). Although free fatty acid transport rate was correlated with obesity (r = 0.75, P less than 0.001), the transport of free fatty acid was not higher in diabetics than in nondiabetics and did not change after therapy. On the other hand, the fractional catabolic rate for free fatty acid was significantly lower in untreated diabetics (0.55 +/- 0.04 vs. 0.71 +/- 0.06 min-1, P less than 0.05); it increased after therapy to 0.80 +/- 0.09 min-1, P less than 0.05, and was inversely correlated with fasting glucose (r = -0.52, P less than 0.01). In diabetics after therapy, lipid oxidation rates fell significantly (from 1.35 +/- 0.06 to 1.05 +/- 0.01 mg/min per kg fat-free mass, P less than 0.01), whereas carbohydrate oxidation increased (from 1.21 +/- 0.10 to 1.73 +/- 0.13 mg/min per kg fat-free mass, P less than 0.01); changes in lipid and carbohydrate oxidation were correlated (r = 0.72, P less than 0.02), and in all subjects lipid oxidation accounted for only approximately 40% of free fatty acid transport. The data suggest that in noninsulin-dependent diabetics, although free fatty acid production may be elevated because of obesity, the elevations in plasma free fatty acid concentrations are also a result of reduced removal, and fractional clearance of free

  2. Tumor lysis syndrome in a chronic lymphocytic leukemia patient with pleural effusion after oral fludarabine and cyclophosphamide therapy.

    PubMed

    Nakazawa, Hideyuki; Nishina, Sayaka; Mimura, Yuto; Kawakami, Toru; Senoo, Yasushi; Sakai, Kaoko; Nakazawa, Ko; Kitano, Kiyoshi

    2014-06-01

    Tumor lysis syndrome (TLS) is a rare complication of the treatment for chronic lymphocytic leukemia (CLL). Since the advent of new therapeutic agents with higher response rates, however, TLS has been observed with increasing frequency. An 84-year-old woman with a nine-year history of untreated CLL presented with exacerbating dyspnea due to pleural effusion. CLL cells without Richter transformation were observed in the pleural effusion at a high concentration, as well as in lymph nodes and bone marrow. After 5 days of oral fludarabine and cyclophosphamide (FC) therapy, the patient developed TLS, which necessitated rescue with hemodialysis. Although transient exacerbation of pleurisy occurred, the effusion cytology ameliorated, and she eventually achieved complete remission after additional two courses of FC and rituximab. Sequestration of fludarabine in the pleural effusion may be attributable to the development of TLS. PMID:24584911

  3. [Clinical Investigation of the Effects of Filgrastim BS1 on Neutropenia Following Oral Cancer Chemotherapy (TPF Therapy)].

    PubMed

    Uchiyama, Kimio; Yamada, Manabu; Tamate, Shusuke; Iwasaki, Konomi; Mitomo, Keisuke; Nakayama, Seiichi

    2015-09-01

    The time for the neutrophil count to recover after subcutaneous injection of filgrastim BS1 or lenograstim was studied in patients suffering from neutropenia following preoperative combined chemotherapy using docetaxel, nedaplatin, or cisplatin (in divided doses for 5 days)and 5-fluorouracil for oral cancer. 1. There was no significant difference in the minimum leukocyte and neutrophil counts after chemotherapy. 2. There was no significant difference in the maximum leukocyte and neutrophil counts after chemotherapy. 3. Time for leukocytes to recover from their minimum count(>4,000/mm3)or for neutrophils to recover from their minimum count(>2,000/mm3)and the number of days on which treatment was administered tended to be shorter in the filgrastim BS1 group. Thus, it was concluded that filgrastim BS1 is just as effective as other prior G-CSF agents in treating patients suffering from neutropenia following chemotherapy(TPF therapy). PMID:26469162

  4. Successful treatment of oral verrucous hyperplasia with photodynamic therapy combined with cryotherapy--report of 3 cases.

    PubMed

    Chang, Yu-Chao; Yu, Chuan-Hang

    2014-06-01

    Our previous study showed successful treatment of a large oral verrucous hyperplasia (OVH) with topical 5-aminolevulinic acid-mediated photodynamic therapy combined with cryotherapy (ALA-PDT). In this case series, we extended this combined method for another three OVH lesions in three different patients. The clinical procedure was conducted as follows: the OVH lesions were irradiated with a 635-nm laser 1.5h after topical application of 20% ALA on the lesion for a total of 1000 s, which consisted of five 3-min and one 100-s irradiations separated by five 3-min rests. Cryogun cryotherapy was then performed on the lesion after ALA-PDT. The tumor was cleared after 1-6 treatments. No recurrence of the lesion was found after a follow-up period of 6-24 months. We suggest that our combined treatment protocol may be effective in treating OVH lesions. PMID:24561304

  5. Photodynamic Therapy with 3-(1’-hexyloxyethyl) pyropheophorbide a (HPPH) for Cancer of the Oral Cavity

    PubMed Central

    Rigual, Nestor; Shafirstein, Gal; Cooper, Michele T.; Baumann, Heinz; Bellnier, David A.; Sunar, Ulas; Tracy, Erin C.; Rohrbach, Daniel J.; Wilding, Gregory; Tan, Wei; Sullivan, Maureen; Merzianu, Mihai; Henderson, Barbara W.

    2013-01-01

    Purpose The primary objective was to evaluate safety of 3-(1’-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Experimental Design Patients with histologically proven oral dysplasia, carcinoma in situ (CiS ) or early stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies employed an HPPH dose of 4 mg/m2 and light doses from 50 to 140 J/cm2. Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of signal transducer and activator of transcription 3 (STAT3) were assessed as potential indicators of PDT effective reaction. Results Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and CiS, and 82% for SCCs lesions at 140 J/cm2. The responses in the CiS/dysplasia cohort are not durable. The PDT induced STAT3 cross-links is significantly higher (P=0.0033) in SCC than in CiS/dysplasia for all light-doses. Conclusion HPPH-PDT is safe for the treatment of CiS/dysplasia and early stage cancer of the oral cavity. Early stage oral HNSCC appears to respond better to HPPH-PDT in comparison to premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT mediated photoreaction. PMID:24088736

  6. 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

  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. A fusion protein derived from plants holds promising potential as a new oral therapy for type 2 diabetes.

    PubMed

    Choi, Jeehye; Diao, Hong; Feng, Zhi-Chao; Lau, Arthur; Wang, Rennian; Jevnikar, Anthony M; Ma, Shengwu

    2014-05-01

    The incretin hormone glucagon-like peptide-1 (GLP-1) is recognized as a promising candidate for the treatment of type 2 diabetes (T2D), with one of its mimetics, exenatide (synthetic exendin-4) having already been licensed for clinical use. We seek to further improve the therapeutic efficacy of exendin-4 (Ex-4) using innovative fusion protein technology. Here, we report the production in plants a fusion protein containing Ex-4 coupled with human transferrin (Ex-4-Tf) and its characterization. We demonstrated that plant-made Ex-4-Tf retained the activity of both proteins. In particular, the fusion protein stimulated insulin release from pancreatic β-cells, promoted β-cell proliferation, stimulated differentiation of pancreatic precursor cells into insulin-producing cells, retained the ability to internalize into human intestinal cells and resisted stomach acid and proteolytic enzymes. Importantly, oral administration of partially purified Ex-4-Tf significantly improved glucose tolerance, whereas commercial Ex-4 administered by the same oral route failed to show any significant improvement in glucose tolerance in mice. Furthermore, intraperitoneal (IP) injection of Ex-4-Tf showed a beneficial effect in mice similar to IP-injected Ex-4. We also showed that plants provide a robust system for the expression of Ex-4-Tf, producing up to 37 μg prEx-4-Tf/g fresh leaf weight in transgenic tobacco and 137 μg prEx-4-Tf/g freshweight in transiently transformed leaves of N. benthamiana. These results indicate that Ex-4-Tf holds substantial promise as a new oral therapy for type 2 diabetes. The production of prEx-4-Tf in plants may offer a convenient and cost-effective method to deliver the antidiabetic medicine in partially processed plant food products. PMID:24373324

  9. 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

  10. Angiotensin inhibition in severe heart failure: acute central and limb hemodynamic effects of captopril with observations on sustained oral therapy.

    PubMed

    Faxon, D P; Halperin, J L; Creager, M A; Gavras, H; Schick, E C; Ryan, T J

    1981-05-01

    The systemic, pulmonary, and limb circulatory responses to the angiotensin-converting enzyme inhibitor, captopril, were determined in 10 patients with severe, chronic heart failure. Immediate effects include sustained reductions in arterial pressure and pulmonary capillary wedge pressure and improvement in cardiac output, as reported with other vasodilator drugs. Calf vascular resistance did not change despite substantial lowering of total systemic vascular resistance, indicating that arteriolar dilatation occurred on a selective basis. Transient reduction in mean right atrial pressure paralleled slight calf venodilatation, but effects upon the resistance vasculature predominated. Plasma renin activity and norepinephrine concentrations increased after therapy in the acute phase as plasma aldosterone levels consistently fell. During maintenance oral treatment over 7 to 15 months (median, 11.5 months), patients displayed symptomatic benefit, improved functional capacity, and greater exercise tolerance. No major adverse reactions developed. These findings suggest that angiotensin converting enzyme inhibition with captopril in congestive heart failure patients improved cardiocirculatory function through selective arteriolar dilatation. The reordering of regional blood flow which appears to result from release of angiotensin-mediated vasoconstriction, as well as the suppression of aldosterone, may underlie the prolonged benefit observed in these patients. This oral vasodilator appears to represent an effective adjunct for the treatment of advanced, chronic heart failure refractory to conventional measures. PMID:7013458

  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. Impact of oral beta-blocker therapy on mortality after primary percutaneous coronary intervention for Killip class 1 myocardial infarction.

    PubMed

    Hioki, Hirofumi; Motoki, Hirohiko; Izawa, Atsushi; Kashima, Yuichirou; Miura, Takashi; Ebisawa, Souichirou; Tomita, Takeshi; Miyashita, Yusuke; Koyama, Jun; Ikeda, Uichi

    2016-05-01

    The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PCI), which has become the mainstay of treatment for AMI, is associated with a lower mortality than fibrinolysis. The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear. We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure. The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (ALPS-AMI) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infarction. We prospectively tracked cardiovascular events for 3 years in 444 ALPS-AMI patients (median age 66 years; 18.2 % women) who had Killip class 1 on admission and were discharged alive. The primary endpoint was all-cause mortality. The 3-year follow-up was completed in 413 patients (93.0 %). During this follow-up, 21 patients (4.7 %) died. In Kaplan-Meier analysis, patients on beta-blockers had a significantly lower incidence of all-cause mortality (2.7 vs. 7.3 %, log-rank p = 0.025). After adjusting for the calculated propensity score for using beta-blockers, their use remained an independent predictor of all-cause mortality (hazard ratio 0.309; 95 % confidence interval 0.116-0.824; p = 0.019). In the statin era, the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission. PMID:25863805

  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. Anti-oxidative therapy with oral dapsone improved HCV antibody positive annular elastolytic giant cell granuloma.

    PubMed

    Igawa, K; Maruyama, R; Katayama, I; Nishioka, K

    1997-05-01

    A 72-year-old fisherman who was positive for the HCV antibody developed an annular, erythematous, infiltrated lesions on sun-exposed areas. The lesions were diagnosed as annular elastolytic giant cell granuloma both clinically and histologically. Topical corticosteroid and cryotherapy with liquid nitrogen for several months failed to improve the lesions. We then started dapsone, a known anti-oxidant, at 50 mg/day. A month later, the margins of the erythematous lesions faded, and the infiltration gradually decreased. No recurrence has been observed for one year after the start of the therapy. Anti-oxidative therapy appears to be effective for annular elastolytic giant cell granuloma and could be an alternate therapy for refractory granulomatous disease. PMID:9198323

  15. Oral antiplatelet therapy for atherothrombotic disease: overview of current and emerging treatment options

    PubMed Central

    Fintel, Dan J

    2012-01-01

    Clinical presentations of atherothrombotic vascular disease, such as acute coronary syndromes, ischemic stroke or transient ischemic attack, and symptomatic peripheral arterial disease, are major causes of morbidity and mortality worldwide. Platelet activation and aggregation play a seminal role in the arterial thrombus formation that precipitates acute manifestations of atherothrombotic disease. As a result, antiplatelet therapy has become the cornerstone of therapy for the prevention and treatment of atherothrombotic disease. Dual antiplatelet therapy with aspirin and a P2Y12 adenosine diphosphate (ADP) receptor inhibitor, such as clopidogrel or prasugrel, is the current standard-of-care antiplatelet therapy in patients with acute coronary syndromes managed with an early invasive strategy. However, these agents are associated with several important clinical limitations, including significant residual risk for ischemic events, bleeding risk, and variability in the degree of platelet inhibition. The residual risk can be attributed to the fact that aspirin and P2Y12 inhibitors block only the thromboxane A2 and ADP platelet activation pathways but do not affect the other pathways that lead to thrombosis, such as the protease-activated receptor-1 pathway stimulated by thrombin, the most potent platelet agonist. Bleeding risk associated with aspirin and P2Y12 inhibitors can be explained by their inhibitory effects on the thromboxane A2 and ADP pathways, which are critical for protective hemostasis. Interpatient variability in the degree of platelet inhibition in response to antiplatelet therapy may have a genetic component and contribute to poor clinical outcomes. These considerations underscore the clinical need for therapies with a novel mechanism of action that may reduce ischemic events without increasing the bleeding risk. PMID:22393298

  16. Oral health knowledge deficit: A barrier for seeking periodontal therapy? A pilot study

    PubMed Central

    Hosadurga, Rajesh; Boloor, Vinita; Kashyap, Rajesh

    2015-01-01

    Context: In developing countries many chronic conditions including periodontitis are on the rise. Oral health attitudes and beliefs are important factors affecting oral health behavior. Aims: The aim of this pilot study was to assess the existing knowledge about periodontal disease and its impact on treatment seeking behavior in a group of population visiting the out-patient Department of Periodontics, Yenepoya Dental College, India. This study also attempted to identify deficit in the knowledge if present. Settings and Design: This is a written questionnaire based pilot study. 143 subjects (89 male and 54 female) agreed to participate in the study. Simple random sampling was used for recruitment. Subjects and Methods: A written questionnaire consisting of 18 questions was given to the patients. Only one correct answer was present and the score given was + 1. The knowledge of the subjects was reflected by their ability to select a correct answer from the number of distractors (multiple choices, prespecified answers). Statistical Analysis Used: SPSS software version 15.0 is used for all statistical analysis. The Chi-square test was employed to assess the passive knowledge of the participants in relation to their age. Results: We found a deficit in the knowledge in all the topics investigated. No consistent relationship between age and gender was found. Female respondents had better knowledge about oral hygiene compared to males. Conclusion: We made an attempt to assess the knowledge of periodontitis among the participants of this study. Knowledge deficit was found in the population surveyed. This knowledge deficit could be one of the reasons why patients do not seek periodontal treatment routinely unless there are acute symptoms. There is urgent need to educate the patients about the periodontal disease, the need for the treatment of periodontitis and advanced treatment modalities available. PMID:26644723

  17. Rifaximin vs conventional oral therapy for hepatic encephalopathy: A meta-analysis

    PubMed Central

    Eltawil, Karim M; Laryea, Marie; Peltekian, Kevork; Molinari, Michele

    2012-01-01

    AIM: To characterize the efficacy of rifaximin in the management of hepatic encephalopathy (HE) as several randomized controlled studies have shown contradictory results on its effectiveness in comparison to other oral agents. METHODS: We performed a systematic review and random effects meta-analysis of all eligible trials identified through electronic and manual searches. Twelve randomized controlled trials met the inclusion criteria with a total of 565 patients. RESULTS: The clinical effectiveness of rifaximin was equivalent to disaccharides or other oral antibiotics [odds ratio (OR) 0.96; 95% CI: 0.94-4.08] but with a better safety profile (OR 0.27; 95% CI: 0.12-0.59). At the completion of treatment protocols, patients receiving rifaximin showed lower serum ammonia levels [weighted mean difference (WMD) = -10.65; 95% CI: -23.4-2.1; P = 0.10], better mental status (WMD = -0.24; 95% CI: -0.57-0.08; P = 0.15) and less asterixis (WMD -0.1; 95% CI -0.26-0.07; P = 0.25) without reaching statistical significance. On the other hand, other psychometric outcomes such as electroencephalographic response and grades of portosystemic encephalopathy were superior in patients treated with rifaximin in comparison to the control group (WMD = 0.21, 95% CI: -0.33-0.09, P = 0.0004; and WMD = -2.33, 95% CI: -2.68-1.98, P = 0.00001, respectively). Subgroup and sensitivity analysis did not show any significant difference in the above findings. CONCLUSION: Rifaximin appears to be at least as effective as other conventional oral agents for the treatment of HE with a better safety profile. PMID:22371636

  18. Incidence, clinical impact and risk of bleeding during oral anticoagulation therapy

    PubMed Central

    Rubboli, Andrea; Becattini, Cecilia; Verheugt, Freek WA

    2011-01-01

    Bleeding is the most important complication of oral anticoagulation (OAC) with vitamin K-antagonists. Whilst bleeding is unavoidably related to OAC, it may have a great impact on the prognosis of treated subjects by leading to discontinuation of treatment, permanent disability or death. The yearly incidence of bleeding during OAC is 2%-5% for major bleeding, 0.5%-1% for fatal bleeding, and 0.2%-0.4% for intracranial bleeding. While OAC interruption and/or antagonism, as well as administration of coagulation factors, represent the necessary measures for the management of bleeding, proper stratification of the individual risk of bleeding prior to start OAC is of paramount importance. Several factors, including advanced age, female gender, poor control and higher intensity of OAC, associated diseases and medications, as well as genetic factors, have been proven to be associated with an increased risk of bleeding. Most of these factors have been included in the development of bleeding prediction scores, which should now be used by clinicians when prescribing and monitoring OAC. Owing to the many limitations of OAC, including a narrow therapeutic window, cumbersome management, and wide inter- and intra-individual variability, novel oral anticoagulants, such as factor Xa inhibitors and direct thrombin inhibitors, have been recently developed. These agents can be given in fixed doses, have little interaction with foods and drugs, and do not require regular monitoring of anticoagulation. While the novel oral anticoagulants show promise for effective thromboprophylaxis in atrial fibrillation and venous thromboembolism, definitive data on their safety and efficacy are awaited. PMID:22125670

  19. An effective oral vitamin D replacement therapy in persons with spinal cord injury

    PubMed Central

    Bauman, William A.; Emmons, Racine R.; Cirnigliaro, Christopher M.; Kirshblum, Steven C.; Spungen, Ann M.

    2011-01-01

    Background/objective Vitamin D deficiency is prevalent in chronic spinal cord injury (SCI). A 3-month course of oral vitamin D3 to ‘normalize’ serum vitamin D levels was investigated. Design Prospective drug-intervention study. Setting VA Medical Center; private rehabilitation facility. Methods Seven individuals with chronic SCI and vitamin D deficiency completed 3 months of oral vitamin D3 (i.e. cholecalciferol) supplementation. At screening, baseline, and months 1 and 3, blood was collected for serum calcium, 25 hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), and N-telopeptide (NTx); 24-hour urine for calcium, creatinine, and NTx was performed. Oral vitamin D3 (2000 IU daily) and elemental calcium (1.3 g daily) were prescribed for 90 days. The results are expressed as mean ± standard deviation (SD). Analysis of variance with a Fisher's post-hoc analysis was performed to test for differences between study visits. Subjects were classified as deficient (<20 ng/ml), relatively deficient (20–30 ng/ml), or not deficient (>30 ng/ml) in 25(OH)D. Results Serum 25(OH)D levels were greater at months 1 and 3 than at baseline (26 ± 6 and 48 ± 17 vs. 14 ± 2 ng/ml; P = 0.005). Six of seven subjects were no longer deficient [25(OH)D >30 ng/ml] by month 3. Serum iPTH levels were significantly decreased at month 1 and month 3; serum NTx levels were significantly lower at month 3 than at baseline. Serum and urinary calcium levels remained within the normal range. Conclusion A daily prescription of 2000 IU of oral vitamin D3 for 3 months safely raised serum 25(OH)D levels into the normal range in persons with chronic SCI on calcium supplementation. PMID:22118252

  20. Inadequate response or intolerability to oral methotrexate: Is it optimal to switch to subcutaneous methotrexate prior to considering therapy with biologics?

    PubMed

    Yadlapati, Sujani; Efthimiou, Petros

    2016-05-01

    Methotrexate (MTX) is considered an anchor drug in the treatment of rheumatoid arthritis. It is also the first-line therapy in a multitude of rheumatologic conditions. Low-dose oral MTX is the preliminary modality of treatment for rheumatoid arthritis due to its affordability, favorable outcomes, and limited risks. However, patients refractory to low-dose MTX therapy may require larger doses of oral MTX. Several studies in the past have demonstrated variability in bioavailability of oral MTX at high doses. This warrants a subsequent switch to parenteral MTX. Widely used among the parenteral preparations of MTX is subcutaneous (SC) MTX. SC MTX provides dependable efficacy, predictable bioavailability, sustained clinical outcomes, and minimal GI adverse effects. It is useful either singularly or in combination therapy regimens. Although SC MTX and intramuscular MTX have similar pharmacokinetics, SC MTX may be preferred by most patients. Development of prefilled syringes and auto-injectors have enabled self-administration of the medication providing the patients with a sense of independence and improved general well-being. Hence, SC MTX can prove to be more efficacious in patients refractory to oral MTX therapy or in patients experiencing severe gastrointestinal adverse effects. PMID:26936262

  1. 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)

  2. 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…

  3. 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. PMID:15815632

  4. 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

  5. [Cryotherapy, combined drug therapy and radiotherapy in the treatment of oral cavity cancer: 3 years' experience].

    PubMed

    Vercellino, V; Goia, F; Gandolfo, S; Camoletto, D

    1980-01-01

    The medium-term (three years) result of a multidisciplinary association treatment of carcinoma of the oral cavity has been reviewed. Treatment was Cryosurgery-polychemotherapy-ratiotherapy and the technique has been described along with the times of association in an introduction that has already been published in this review (see bibliography). Thirty patients were treated with the association because they refused or could not be submitted to surgery at the intital therapeutic action. All these patients present fairly extensive lesions and a three-year follow-up. Results were positive: 56.6% of patients showed disappearance of any objective or subjective sign of cancer and, in all cases, appreciable remission in terms of both extent and duration. The easiness of the technique is confirmed as well as the excellent conversation of the anatomical structures involved. However, a critical review of cases presenting partial failure suggest a classifications of oral carcinomatous lesions (for therapeutic purposes only) on the basis of which the condition can be treated with cryo-polychemo-radiotherapy alone or with a variation of this which provides for the addition of local exersis. PMID:6935521

  6. Long-term therapy with oral treprostinil in pulmonary arterial hypertension failed to lead to improvement in important physiologic measures: results from a single center.

    PubMed

    Chin, Kelly Marie; Ruggiero, Rosechelle; Bartolome, Sonja; Velez-Martinez, Mariella; Darsaklis, Konstantina; Kingman, Martha; Harden, Scarlet; Torres, Fernando

    2015-09-01

    Sustained-release oral treprostinil, an oral prostacyclin, led to significant improvement in 6-minute walk distance (6MWD) versus placebo in treatment-naive patients with pulmonary arterial hypertension (PAH) but failed to lead to significant improvement in two 16-week trials in patients receiving background PAH therapies (FREEDOM studies). Long-term studies are lacking. Our objective was to evaluate 6MWD, functional class, hemodynamics, and other long-term outcomes during oral treprostinil administration in PAH. Patients receiving oral treprostinil through the FREEDOM studies at our institution were included and were followed for up to 7 years. The primary end point was change in pulmonary vascular resistance (PVR) at first follow-up catheterization. Other end points included 6MWD, functional class, and other hemodynamic results. Thirty-seven patients received oral treprostinil for a median of 948 days, with 81%, 61%, and 47% continuing therapy at 1, 2, and 3 years, respectively. Mean treprostinil dose at 3, 12, and 24 months was 4.3 ± 2.3, 8.6 ± 3.2, and 11.7 ± 5.8 mg/24 h, respectively. Compared with pretreatment values, there was no significant change in 6MWD at 3 or 12 months, no improvement in functional class at 12 months, and no significant change in hemodynamics at the first follow-up catheterization (N = 34). Oral treprostinil dose was inversely associated with change in PVR (r = -0.42, P < 0.05), and change in PVR was numerically better among patients in the highest dosing quartile. No significant improvement in 6MWD, functional class, or hemodynamics versus pretreatment values was seen with long-term oral treprostinil therapy, potentially because of inability to achieve a clinically effective dose. PMID:26401252

  7. Long-term therapy with oral treprostinil in pulmonary arterial hypertension failed to lead to improvement in important physiologic measures: results from a single center

    PubMed Central

    Ruggiero, Rosechelle; Bartolome, Sonja; Velez-Martinez, Mariella; Darsaklis, Konstantina; Kingman, Martha; Harden, Scarlet; Torres, Fernando

    2015-01-01

    Abstract Sustained-release oral treprostinil, an oral prostacyclin, led to significant improvement in 6-minute walk distance (6MWD) versus placebo in treatment-naive patients with pulmonary arterial hypertension (PAH) but failed to lead to significant improvement in two 16-week trials in patients receiving background PAH therapies (FREEDOM studies). Long-term studies are lacking. Our objective was to evaluate 6MWD, functional class, hemodynamics, and other long-term outcomes during oral treprostinil administration in PAH. Patients receiving oral treprostinil through the FREEDOM studies at our institution were included and were followed for up to 7 years. The primary end point was change in pulmonary vascular resistance (PVR) at first follow-up catheterization. Other end points included 6MWD, functional class, and other hemodynamic results. Thirty-seven patients received oral treprostinil for a median of 948 days, with 81%, 61%, and 47% continuing therapy at 1, 2, and 3 years, respectively. Mean treprostinil dose at 3, 12, and 24 months was 4.3 ± 2.3, 8.6 ± 3.2, and 11.7 ± 5.8 mg/24 h, respectively. Compared with pretreatment values, there was no significant change in 6MWD at 3 or 12 months, no improvement in functional class at 12 months, and no significant change in hemodynamics at the first follow-up catheterization (N = 34). Oral treprostinil dose was inversely associated with change in PVR (r = −0.42, P < 0.05), and change in PVR was numerically better among patients in the highest dosing quartile. No significant improvement in 6MWD, functional class, or hemodynamics versus pretreatment values was seen with long-term oral treprostinil therapy, potentially because of inability to achieve a clinically effective dose. PMID:26401252

  8. Community Case Management of Childhood Diarrhea in a Setting with Declining Use of Oral Rehydration Therapy: Findings from Cross-Sectional Studies among Primary Household Caregivers, Kenya, 2007

    PubMed Central

    Olson, Christine K.; Blum, Lauren S.; Patel, Kinnery N.; Oria, Prisca A.; Feikin, Daniel R.; Laserson, Kayla F.; Wamae, Annah W.; Bartlett, Alfred V.; Breiman, Robert F.; Ram, Pavani K.

    2011-01-01

    We sought to determine factors associated with appropriate diarrhea case management in Kenya. We conducted a cross-sectional survey of caregivers of children < 5 years of age with diarrhea in rural Asembo and urban Kibera. In Asembo, 61% of respondents provided oral rehydration therapy (ORT), 45% oral rehydration solution (ORS), and 64% continued feeding. In Kibera, 75% provided ORT, 43% ORS, and 46% continued feeding. Seeking care at a health facility, risk perception regarding death from diarrhea, and treating a child with oral medications were associated with ORT and ORS use. Availability of oral medication was negatively associated. A minority of caregivers reported that ORS is available in nearby shops. In Kenya, household case management of diarrhea remains inadequate for a substantial proportion of children. Health workers have a critical role in empowering caregivers regarding early treatment with ORT and continued feeding. Increasing community ORS availability is essential to improving diarrhea management. PMID:22144458

  9. 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

  10. Neuropsychological changes in demented patients treated with acetyl-L-carnitine.

    PubMed

    Sinforiani, E; Iannuccelli, M; Mauri, M; Costa, A; Merlo, P; Bono, G; Nappi, G

    1990-01-01

    The study was carried out on 24 patients suffering from mild to moderate dementia. The diagnosis of dementia was made according to DMS III criteria. Patients with cerebrovascular pathologies were excluded by using Hachinski Ischaemic Score less than or equal to 4 and computerized tomography parameters. Patients with depression (Hamilton Rating Scale for Depression greater than or equal to 18) were excluded. All the patients, after a wash-out period of two weeks were treated on a simple blind method with acetyl-L-carnitine (No. = 12 patients) and piracetam (12 patients) by intravenous route (two weeks) followed by an oral one for further 10 weeks. A battery of clinical neuropsychological tests was applied to evaluate the cognitive, attentive and behavioural aspects. The results, analysed by non-parametric variance analysis (Friedman Test) show a statistically significant improvement of the behavioural profile, of attention and of psychomotricity in the patients treated with acetyl-L-carnitine. No significant improvement was found in the piracetam group. PMID:2387665

  11. 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

  12. 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

  13. Improvement of regressive autism symptoms in a child with TMLHE deficiency following carnitine supplementation.

    PubMed

    Ziats, Mark N; Comeaux, Mathew S; Yang, Yaping; Scaglia, Fernando; Elsea, Sarah H; Sun, Qin; Beaudet, Arthur L; Schaaf, Christian P

    2015-09-01

    Disorders of carnitine biosynthesis have recently been associated with neurodevelopmental syndromes such as autism spectrum disorder (ASD). A 4-year-old male with autism and two episodes of neurodevelopmental regression was identified to have a mutation in the TMLHE gene, which encodes the first enzyme in the carnitine biosynthesis pathway, and concurrent carnitine deficiency. Following carnitine supplementation, the patient's regression ended, and the boy started gaining developmental milestones. This case report suggests that deficits in carnitine biosynthesis may be responsible for some cases of regression in individuals with ASD, and that testing for the respective biochemical pathway should be considered. Furthermore, this case suggests that carnitine supplementation may be useful in treating (and potentially preventing) regressive episodes in patients with carnitine deficiency. Further work to better define the role of disorders of carnitine biosynthesis in autism spectrum disorder is warranted. PMID:25943046

  14. 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

  15. 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.

  16. 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.

  17. Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy.

    PubMed

    Maas, Angela H E M; Euler, Mia von; Bongers, Marlies Y; Rolden, Herbert J A; Grutters, Janneke P C; Ulrich, Lian; Schenck-Gustafsson, Karin

    2015-12-01

    A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained. PMID:26358933

  18. Phase I and pharmacologic study of oral Ftorafur and x ray therapy in advanced gastrointestinal cancer

    SciTech Connect

    Byfield, J.E.; Sharp, T.R.; Hornbeck, C.L.; Frankel, S.S.; Floyd, R.A.; Griffiths, J.C.

    1985-03-01

    The authors have treated 15 patients with advanced gastrointestinal carcinoma with a cyclical regimen of combined Ftorafur (N/sub 1/-((2-furanidyl-))-5-Fluorouracil, a 5-FU pro-drug) and external beam radiation. The most common toxicity in general, and the most common limiting toxicity was nausea and vomiting, in contrast to oral FT alone where diarrhea is more prominent. Stomatitis was seen only once and no other form of serious toxicity was encountered. Two-thirds of the patients responded in subjective terms (pain relief). There was 1 partial response of FT alone (pulmonary metastases outside the treatment field). The sole patient whose treatment field was outside the abdomen (chest portals for esophageal carcinoma) developed pneumonitis which contributed to his death. No other delayed effects were noted. Serum FT levels were related to the infested dose and in the microgram range while serum 5-FU levels were in the nanogram range indicating slow decomposition of FT into 5-FU.

  19. Study on Biopharmaceutics Classification and Oral Bioavailability of a Novel Multikinase Inhibitor NCE for Cancer Therapy

    PubMed Central

    Yang, Yang; Fan, Chun-Mei; He, Xuan; Ren, Ke; Zhang, Jin-Kun; He, Ying-Ju; Yu, Luo-Ting; Zhao, Ying-Lan; Gong, Chang-Yang; Zheng, Yu; Song, Xiang-Rong; Zeng, Jun

    2014-01-01

    Specific biopharmaceutics classification investigation and study on phamacokinetic profile of a novel drug candidate (2-methylcarbamoyl-4-{4-[3- (trifluoromethyl) benzamido] phenoxy} pyridinium 4-methylbenzenesulfonate monohydrate, NCE) were carried out. Equilibrium solubility and intrinsic dissolution rate (IDR) of NCE were estimated in different phosphate buffers. Effective intestinal permeability (Peff) of NCE was determined using single-pass intestinal perfusion technique in rat duodenum, jejunum and ileum at three concentrations. Theophylline (high permeability) and ranitidine (low permeability) were also applied to access the permeability of NCE as reference compounds. The bioavailability after intragastrical and intravenous administration was measured in beagle dogs. The solubility of NCE in tested phosphate buffers was quite low with the maximum solubility of 81.73 μg/mL at pH 1.0. The intrinsic dissolution ratio of NCE was 1 × 10−4 mg·min−1·cm−2. The Peff value of NCE in all intestinal segments was more proximate to the high-permeability reference theophylline. Therefore, NCE was classified as class II drug according to Biopharmaceutics Classification System due to its low solubility and high intestinal permeability. In addition, concentration-dependent permeability was not observed in all the segments, indicating that there might be passive transportation for NCE. The absolute oral bioavailability of NCE in beagle dogs was 26.75%. Therefore, dissolution promotion will be crucial for oral formulation development and intravenous administration route will also be suggested for further NCE formulation development. All the data would provide a reference for biopharmaceutics classification research of other novel drug candidates. PMID:24776763

  20. Fosfomycin: A First-Line Oral Therapy for Acute Uncomplicated Cystitis.

    PubMed

    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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. Quality of life related to oral mucositis of patients undergoing haematopoietic stem cell transplantation and receiving specialised oral care with low-level laser therapy: a prospective observational study.

    PubMed

    Bezinelli, L M; Eduardo, F P; Neves, V D; Correa, L; Lopes, R M G; Michel-Crosato, E; Hamerschlak, N; Biazevic, M G H

    2016-07-01

    Oral mucositis is a painful condition that occurs in 80% of patients who undergo haematopoietic stem cell transplantation (HSCT). Our objective was to determine the impact of mucositis on quality of life (QoL) of patients subjected to HSCT treated with low-level laser therapy (LLLT). Patients were evaluated: (1) on the first day of treatment; (2) 5 days after autologous or 8 days after allogeneic transplantation; (3) once bone marrow had integrated; and (4) 30 days after discharge. Clinical evaluation was performed using the World Health Organization criteria; oral health QoL was measured using the Oral Health Impact Profile (OHIP-14); and mucositis symptoms with the Patient-Reported Oral Mucositis Symptom (PROMS) scale. The higher the score, the lower the patient's QoL. The OHIP-14 responses showed that at D + 5/D + 8, all domains had the highest scores, while at times 1 and 4, the scores were lower. In the PROMS scale, all domains scored worst at time 2, and the differences between the scores at the four times were statistically significant. The study has shown that QoL improves over time in patients undergoing LLLT therapy for mucositis prevention. PMID:26087364

  6. 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

  7. Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells.

    PubMed

    Wang, Xiaomei; Su, Jin; Sherman, Alexandra; Rogers, Geoffrey L; Liao, Gongxian; Hoffman, Brad E; Leong, Kam W; Terhorst, Cox; Daniell, Henry; Herzog, Roland W

    2015-04-01

    Coagulation factor replacement therapy for the X-linked bleeding disorder hemophilia is severely complicated by antibody ("inhibitor") formation. We previously found that oral delivery to hemophilic mice of cholera toxin B subunit-coagulation factor fusion proteins expressed in chloroplasts of transgenic plants suppressed inhibitor formation directed against factors VIII and IX and anaphylaxis against factor IX (FIX). This observation and the relatively high concentration of antigen in the chloroplasts prompted us to evaluate the underlying tolerance mechanisms. The combination of oral delivery of bioencapsulated FIX and intravenous replacement therapy induced a complex, interleukin-10 (IL-10)-dependent, antigen-specific systemic immune suppression of pathogenic antibody formation (immunoglobulin [Ig] 1/inhibitors, IgE) in hemophilia B mice. Tolerance induction was also successful in preimmune mice but required prolonged oral delivery once replacement therapy was resumed. Orally delivered antigen, initially targeted to epithelial cells, was taken up by dendritic cells throughout the small intestine and additionally by F4/80(+) cells in the duodenum. Consistent with the immunomodulatory responses, frequencies of tolerogenic CD103(+) and plasmacytoid dendritic cells were increased. Ultimately, latency-associated peptide expressing CD4(+) regulatory T cells (CD4(+)CD25(-)LAP(+) cells with upregulated IL-10 and transforming growth factor-β (TGF-β) expression) as well as conventional CD4(+)CD25(+) regulatory T cells systemically suppressed anti-FIX responses. PMID:25700434

  8. 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

  9. Root-Canal Therapy: A Means of Treating Oral Pain and Infection

    PubMed Central

    Levine, Mitchell

    1988-01-01

    What is root-canal treatment? This article shows how endodontic treatment (root-canal therapy) can preserve teeth that would otherwise be extracted, and how tooth-pulp pathology can be diagnosed. Some clinical examples illustrate how non-dental infections can masquerade as dental problems, and vice versa. ImagesFigure 1Figure 2Figure 3aFigure 3bFigure 3cFigure 4aFigure 4bFigure 4cFigure 5Figure 6aFigure 6bFigure 7Figure 8aFigure 8bFigure 9Figure 10Figure 11aFigure 11b PMID:21253195

  10. 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

  11. Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever

    PubMed Central

    Mendenhall, Michelle; Russell, Andrew; Smee, Donald F.; Hall, Jeffery O.; Skirpstunas, Ramona; Furuta, Yousuke; Gowen, Brian B.

    2011-01-01

    Background Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed. Methodology/Principal Findings Here, we used a model of acute arenaviral infection in outbred guinea pigs based on challenge with an adapted strain of Pichindé virus (PICV) to further preclinical development of T-705 (Favipiravir), a promising broad-spectrum inhibitor of RNA virus infections. The guinea pig-adapted passage 19 PICV was uniformly lethal with an LD50 of ∼5 plaque-forming units and disease was associated with fever, weight loss, thrombocytopenia, coagulation defects, increases in serum aspartate aminotransferase (AST) concentrations, and pantropic viral infection. Favipiravir (300 mg/kg/day, twice daily orally for 14 days) was highly effective, as all animals recovered fully from PICV-induced disease even when therapy was initiated one week after virus challenge when animals were already significantly ill with marked fevers and thrombocytopenia. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in peak serum virus titers and AST concentrations in favipiravir-treated animals. Moreover, a sharp decrease in body temperature was observed shortly after the start of treatment. Oral ribavirin was also evaluated, and although effective, the slower rate of recovery may be a sign of the drug's known toxicity. Conclusions/Significance Our findings support further development of favipiravir for the treatment of severe arenaviral infections. The optimization of the experimental favipiravir treatment regimen in the PICV guinea pig model will inform critical future studies in the same species based

  12. 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

  13. 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. PMID:27180242

  14. Systemic oxygen therapy versus oral enalapril for treatment of diabetic macular ischemia: a randomized controlled trial.

    PubMed

    Sharifipour, Farideh; Razzaghi, Mohammadreza; Ramezani, Alireza; Azarmina, Mohsen; Yaseri, Mehdi; Soheilian, Roham; Soheilian, Masoud

    2016-04-01

    The purpose of this study was to evaluate the structural and functional effects of systemic oxygen therapy and enalapril in patients with diabetic macular ischemia (DMI). This randomized clinical trial consisted of 105 eyes with DMI divided into three groups. Group I received systemic oxygen by face mask at a flow rate of 10 L/min; Group II received 5 mg enalapril daily; and Group III received placebo tablets for 3 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT) measured by optical coherence tomography (OCT), extent of foveal avascular zone (FAZ) on fluorescein angiograms, and electroretinograms (ERG) were obtained at baseline and after 3 and 6 months. Overall, 102 patients completed the study. Baseline characteristics were not significantly different among groups. Significant improvement in BCVA and decrease in CMT and FAZ occurred at months 3 and 6 in oxygen group compared to deterioration in enalapril and control groups (All P values <0.001). ERG parameters were significantly better in oxygen group compared to enalapril group at months 3 and 6 and better than those in control group at month 3. Normobaric oxygen therapy for 3 months in DMI decreased CMT and FAZ and improved BCVA and ERG parameters. Enalapril did not show any favorable effect. PMID:26292645

  15. Histological Evaluation of Wound Healing Process after Photodynamic Therapy of Rat Oral Mucosal Ulcer

    PubMed Central

    Deyhimi, Parviz; Khademi, Heidar; Birang, Reza; Akhoondzadeh, Mohammad

    2016-01-01

    Statement of the Problem When the body defense is compromised, wounds can act as a route for entrance and colonization of microorganisms in the body. Photodynamic therapy with methylene blue is known as a promising antimicrobial modality. Purpose The present study aimed to investigate the effects of this procedure on wound healing processes. Materials and Method In this experimental study, 48 male Wistar rats were recruited. Experimental wounds were surgically made on their buccal mucosa. Based on the treatment modality, they were divided into 3 groups (n=16) of control (CG), laser (LG), photosensitizer+ laser (PLG) by methylene blue (MB). The treatment procedure in the two latter groups was done in days 1-4 and 6-9. After sacrificing on 2, 4, 7 and 14-day follow-ups, the microscopic grade of healing of the wounds was assigned on each interval according to histological grading criteria. Results A qualitative result was obtained that showed a healing progression in PLG at day 2 of follow-up. At day 4 of follow-up, no difference was seen in healing stage among the groups. However on day 7 of follow-up, samples of the LG showed a lower degree of healing compared with the other two groups. Likewise, on day 14 of follow- up, both PLG and LG showed lower degree of healing than CG. Conclusion This study qualitatively showed that MB- mediated photodynamic therapy would have an inhibitory effect on healing process after 14 days of the wound creation. PMID:26966708

  16. [Exploring an optimal approach to the use of oral hypoglycemic agents based on CGM results: implications for combination therapy with oral hypoglycemic agents].

    PubMed

    Mori, Yutaka

    2011-08-01

    In the treatment of type 2 diabetes aimed at prevention of cardiovascular events impacting the prognosis of affected patients, it is critically important not only to lower HbAlc values but to find a way to improve postprandial hyperglycemia without causing hypoglycemia thus minimizing drastic glycemic variations or to maintain favorable glycemic control with daily glycemic variations in mind. In other words, it is no longer adequate to emphasize quantitative reductions in HbAlc as in conventional therapeutic approaches but qualitative glycemic control that takes daily glycemic variations into account is becoming of increasing importance to the management of type 2 diabetes. On the other hand, the 6 oral hypoglycemic agent (OHA) classes currently available for clinical use, i.e., biguanides (BGs), thiazolidinediones (TZDs), alpha-glucosidase inhibitors, sulfonylureas (SUs), fast-acting insulin secretagogues (glinides) and DPP-4 inhibitors, appear to vary from class to class or even from agent from agent within a class in regard to their impact on daily glycemic variations. In our CMG-based study of their impact on glycemic variations, it was demonstrated that BGs and TZDs improve hyperglycemia during nighttime and before breakfast more effectively than they do postprandial glycemic excursions; that, of the insulin secretagogues, glinides reduce daily glycemic variations as do alpha-glucosidase inhibitors, while SUs do not affect them very much; and that DPP-4 inhibitors lower not only mean glucose levels which are deemed equivalent to HbAlc values but also narrow the range of glycemic variations. Thus, OHAs can be broadly classified into those that primarily reduce 24-hour mean glucose levels as equivalent to HbAlc values and those that primarily narrow the range of glycemic variations. Therefore, with either of these agents as monotherapy, it is next to impossible to achieve reductions in HbAlc with a narrow range of glycemic variations, and combination therapy

  17. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester

    PubMed Central

    Hashim, Sami A.; VanItallie, Theodore B.

    2014-01-01

    Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer’s disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson’s disease. PMID:24598140

  18. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.

    PubMed

    Hashim, Sami A; VanItallie, Theodore B

    2014-09-01

    Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer's disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson's disease. PMID:24598140

  19. 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

  20. 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

  1. Blood supply to the oral and maxillofacial tissues following radiation therapy: a prospective ultrasonographic study.

    PubMed

    Semergidis, T; Vairaktaris, E; Iatrou, I; Carageorgis, P; Martis, C

    1996-02-01

    In this prospective clinical study of the early radiation effects on blood supply to the mouth and face, 44 patients (31 men-13 women, mean age 63.4 yrs) with oral tumors underwent surgery and adjuvant postoperative radiotherapy with conventional fractionation (mean dose at the neck approximately equal to 50 Gy). Blood flow parameters 1 cm below the bifurcation of the common carotid artery (mean velocity time averaged, lumen diameter, resistivity index-RI) as well as perivascular reaction, were recorded on Color Doppler Imaging video tapes in a series of five consecutive examinations up to six months postirradiation. There were no statistically significant changes shown between the initial and follow-up examinations for any of the parameters investigated. There was no difference in blood flow between the ipsilateral (operated-irradiated) and contralateral side of the neck. Results did not seem to correlate with known vascular disease risk factors such as sex, arterial pressure, cholesterol levels, smoking and diabetes. After the effect of age was controlled, flow measurements remained statistically stable. Radiation dosage did not appear to influence carotid flow parameters. Perivascular reaction had the highest peak immediately postirradiation but regressed with time. This study suggests that therapeutic radiation of the neck at this dose level may not have important effects on the maxillofacial region blood supply for approximately eight months postoperatively; however, these patients should be closely evaluated for symptoms or signs of carotid artery lesions on a long-term basis. PMID:8707937

  2. Intranasal budesonide spray as an adjunct to oral antibiotic therapy for acute sinusitis in children.

    PubMed

    Yilmaz, G; Varan, B; Yilmaz, T; Gürakan, B

    2000-01-01

    We investigated the clinical value of intranasal budesonide in acute sinusitis in 52 children with acute maxillary sinusitis. We randomly divided them into two groups: group 1 received oral pseudoephedrine (2 x 30 mg) and cefaclor (40 mg/kg) for 10 days, and group 2 received intranasal budesonide (2 x 100 microg) and cefaclor (40 mg/kg) for 10 days. Symptoms of headache, cough, and nasal stuffiness and signs of nasal discharge were graded before and after treatment. The patients whose symptoms and signs completely normalized after treatment were considered to have recovered, and those with persisting symptoms and signs after treatment as having not recovered. The results of the two treatment groups were compared. The recovery rate of the children in group 2 were significantly higher than those in group 1 (P < 0.05). No adverse drug effects were determined during the study period. These findings suggest that topical steroids may be a useful adjunctive agent in the treatment of acute sinusitis of children without apparent side effects and can possibly hasten the resolution of symptoms. PMID:10923938

  3. 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

  4. New oral anticoagulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis

    PubMed Central

    Oldgren, Jonas; Wallentin, Lars; Alexander, John H.; James, Stefan; Jönelid, Birgitta; Steg, Gabriel; Sundström, Johan

    2013-01-01

    Background Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting. Methods and results All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7–14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59–0.84], but increased clinically significant bleeding (HR: 1.79; 1.54–2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80–0.95), but more than doubled the bleeding (HR: 2.34; 2.06–2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies. Conclusion In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with

  5. Production of L-carnitine by secondary metabolism of bacteria

    PubMed Central

    Bernal, Vicente; Sevilla, Ángel; Cánovas, Manuel; Iborra, José L

    2007-01-01

    The increasing commercial demand for L-carnitine has led to a multiplication of efforts to improve its production with bacteria. The use of different cell environments, such as growing, resting, permeabilized, dried, osmotically stressed, freely suspended and immobilized cells, to maintain enzymes sufficiently active for L-carnitine production is discussed in the text. The different cell states of enterobacteria, such as Escherichia coli and Proteus sp., which can be used to produce L-carnitine from crotonobetaine or D-carnitine as substrate, are analyzed. Moreover, the combined application of both bioprocess and metabolic engineering has allowed a deeper understanding of the main factors controlling the production process, such as energy depletion and the alteration of the acetyl-CoA/CoA ratio which are coupled to the end of the biotransformation. Furthermore, the profiles of key central metabolic activities such as the TCA cycle, the glyoxylate shunt and the acetate metabolism are seen to be closely interrelated and affect the biotransformation efficiency. Although genetically modified strains have been obtained, new strain improvement strategies are still needed, especially in Escherichia coli as a model organism for molecular biology studies. This review aims to summarize and update the state of the art in L-carnitine production using E. coli and Proteus sp, emphasizing the importance of proper reactor design and operation strategies, together with metabolic engineering aspects and the need for feed-back between wet and in silico work to optimize this biotransformation. PMID:17910757

  6. Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial

    PubMed Central

    Kamal, S. M. Mostafa; Arifuzzaman, Abu Saleh Mohammad; Rahim, Zeaur; Khan, Lamia; Haq, Md. Ahsanul; Zaman, Khaliqu; Bergman, Peter; Brighenti, Susanna; Gudmundsson, Gudmundur H.; Agerberth, Birgitta; Raqib, Rubhana

    2015-01-01

    Background Development of new tuberculosis (TB) drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3) and 4-phenyl butyrate (PBA) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects. Objective To examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients. Methods Adult TB patients (n = 288) were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D3 (25(OH)D3) in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM) were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OH)D3. Results At week 4, 71% (46/65) of the patients in the PBA+vitD3-group (p = 0.001) and 61.3% (38/62) in the vitD3-group (p = 0.032) were culture negative compared to 42.2% (27/64) in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group (p = 0.001) and 2.2 times higher in vitD3-group (p = 0.032) compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034). Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01). Conclusion Adjunct therapy with PBA+vitD3 or vitD3 or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy

  7. Associated oral lesions in human immunodefeciency virus infected children of age 1 to 14 years in anti retroviral therapy centers in Tamil Nadu

    PubMed Central

    Kumar, R Krishna; Mohan, G; Reddy, N Venugopal; Rao, V Arun Prasad; Shameer, M; Christopher, Ananthi

    2013-01-01

    Aim: To evaluate the prevalence of oral lesions status in human immunodeficiency virus (HIV) infected children of age 1 to 14 years in Anti Retro viral therapy (ART) centres in Tamil Nadu. Materials and Methods: A of total 326 HIV infected children, age 1 to 14 years of which 174 male children and 152 female children were examined for Oral lesions in the Department of Pedodontics and Preventive Dentistry, Rajah Muthiah Dental College and Hospital, Annamalai University in association with the ART centers in Villupuram, Vellore and HIV Homes in Thiruvannamalai, Trichy and Salem in Tamil Nadu towns. Statistical Analysis: Statistical Package for Social Science for Windows (version 11 code: 3000135939012345). Result: Of the total 326 children, 201 (61.65%) had oral lesions. (68 [20.86%] with Oral Candidiasis [OC], 54 [16.56%] with Angular Cheilitis, 27 [8.28%] with Necrotizing Ulcerative Gingivitis [NUG], 25 [7.66%] with Necrotizing Ulcerative Periodontitis [NUP], 18 [5.53%] with Linear Gingival Erythema [LGE] and 9 [2.76%] with Apthous Ulcer.) Conclusion Among the oral lesions in HIV infected children, OC 20.86% was the predominant oral lesion followed by Angular Chelitis 16.56%, NUG 8.28%, NUP 7.66%, LGE5.53% and Apthous Ulcer 2.76%. PMID:24403790

  8. 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

  9. Electrophysiological Studies into the Safety of the Anti-diarrheal Drug Clotrimazole during Oral Rehydration Therapy

    PubMed Central

    Lexmond, Willem S.; Rufo, Paul A.; Fiebiger, Edda; Lencer, Wayne I.

    2015-01-01

    Background and Aims Morbidity and mortality from acute diarrheal disease remains high, particularly in developing countries and in cases of natural or man-made disasters. Previous work has shown that the small molecule clotrimazole inhibits intestinal Cl- secretion by blocking both cyclic nucleotide- and Ca2+-gated K+ channels, implicating its use in the treatment of diarrhea of diverse etiologies. Clotrimazole, however, might also inhibit transporters that mediate the inwardly directed electrochemical potential for Na+-dependent solute absorption, which would undermine its clinical application. Here we test this possibility by examining the effects of clotrimazole on Na+-coupled glucose uptake. Materials and Methods Short-circuit currents (Isc) following administration of glucose and secretagogues were studied in clotrimazole-treated jejunal sections of mouse intestine mounted in Ussing chambers. Results Treatment of small intestinal tissue with clotrimazole inhibited the Cl- secretory currents that resulted from challenge with the cAMP-agonist vasoactive intestinal peptide (VIP) or Ca2+-agonist carbachol in a dose-dependent fashion. A dose of 30 μM was effective in significantly reducing the Isc response to VIP and carbachol by 50% and 72%, respectively. At this dose, uptake of glucose was only marginally affected (decreased by 14%, p = 0.37). There was no measurable effect on SGLT1-mediated sugar transport, as uptake of SGLT1-restricted 3-O-methyl glucose was equivalent between clotrimazole-treated and untreated tissue (98% vs. 100%, p = 0.90). Conclusion Treatment of intestinal tissue with clotrimazole significantly reduced secretory responses caused by both cAMP- and Ca2+-dependent agonists as expected, but did not affect Na+-coupled glucose absorption. Clotrimazole could thus be used in conjunction with oral rehydration solution as a low-cost, auxiliary treatment of acute secretory diarrheas. PMID:26405813

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

    PubMed

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

    2016-04-01

    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

  11. 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

  12. Protective effects of L-carnitine and homogenized testis tissue on the testis and sperm parameters of busulfan-induced infertile male rats

    PubMed Central

    Dehghani, Farzaneh; Hassanpour, Ashraf; Poost-pasand, Aghdas; Noorafshan, Ali; Karbalay-Doust, Saeid

    2013-01-01

    Background: Busulfan(Bus) is a chemotherapy drug that is widely used for cancer treatment. However, administration of busulfan may cause temporary or permanent sterility in male patients. Therefore, reduction of this side is necessary. Objective: evaluation of the protective effects of L-carnitine and testis homogenized tissue(THT) on sperm parameters and the testis structure after busulfan treatment. Materials and Methods: Twenty rats were divided four groups. Group I (Control) received a single dose of DMSO and 1mL of distilled water (I.P.). Group II (Bus) received a single of busulfan (10 mg/kg) plus 1 ml of the distilled water(I.P.). Group III (Bus+THT) received busulfan plus 1mL of THT daily by oral gavages. Group IV (Bus+L-car) received a single dose of busulfan plus 100 mg/kg/day L-carnitine(I.P.). after 48 dayst, the Stereological technique was used for the estimating volume and diameter of testis, seminiferous tubules and interstitial tissue, flagella length, germinal epithelium height and spermatoginic cell number. Semen analysis was used for the assessment of sperm parameters. Results: THT increased volume of testis (6.5%), seminiferous tubule and interstitial tissue volume (6.5%), 6.9% and 11.7% respectively), germinal epithelium height (13%), sperm count (7.5%), and decreased sperm with abnormal morphology (1%) in comparison with the L-carnitine in busulfan treated group. Conclusion: It seems the use of L-carnitine and THT decreases side effects of busulfan on the male reproductive system. However, in our study, THT is more effective than L-carnitine and leads to the recovery testis structure and sperm parameters after treatment with busulfan. This article extracted from M.Sc. thesis. (Ashraf Hassanpour) PMID:24639808

  13. 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.

  14. Impact of reducing dosing frequency on adherence to oral therapies: a literature review and meta-analysis

    PubMed Central

    Srivastava, Kunal; Arora, Anamika; Kataria, Aditi; Cappelleri, Joseph C; Sadosky, Alesia; Peterson, Andrew M

    2013-01-01

    Objectives To assess the impact of reduced frequency of oral therapies from multiple-dosing schedules to a once-daily (OD) dosing schedule on adherence, compliance, persistence, and associated economic impact. Methods A meta-analysis was performed based on relevant articles identified from a comprehensive literature review using MEDLINE® and Embase®. The review included studies assessing adherence with OD, twice-daily (BID), thrice-daily (TID), and four-times daily (QID) dosing schedules and costs associated with optimal/suboptimal adherence among patients with acute and chronic diseases. Effect estimates across studies were pooled and analyzed using the DerSimonian and Laird random-effect model. Results Forty-three studies met inclusion criteria, and meta-analyzable data were available from 13 studies. The overall results indicated that OD schedules were associated with higher adherence rates (odds ratio [OR] 3.07, 95% confidence interval [CI] 1.80–5.23; P < 0.001 for OD versus > OD dosing) and compliance rates (OR 3.50, 95% CI 1.73–7.08; P < 0.001 for OD versus > OD dosing); persistence rates showed the same direction but were not statistically significant (OR 1.43, 95% CI 0.62–3.29; P = 0.405 for OD versus BID dosing). Results for each of the conditions were consistent with those observed overall with respect to showing the benefits of less frequent dosing. From a health economic perspective, higher adherence rates with OD relative to multiple dosing in a number of conditions were consistently associated with corresponding lower costs of health care resources utilization. Conclusion Current meta-analyses suggested that across acute and chronic disease states, reducing dosage frequency from multiple dosing to OD dosing may improve adherence to therapies among patients. Improving adherence may result in subsequent decreases in health care costs. PMID:23737662

  15. 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.

  16. 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

  17. Cerebrospinal fluid carnitine levels in patients with Alzheimer's disease.

    PubMed

    Rubio, J C; de Bustos, F; Molina, J A; Jiménez-Jiménez, F J; Benito-León, J; Martín, M A; Campos, Y; Ortí-Pareja, M; Cabrera-Valdivia, F; Arenas, J

    1998-03-01

    We assessed free carnitine (FC) and acylcarnitine esters (AC) in both cerebrospinal fluid (CSF) and plasma from 24 patients with diagnostic criteria for Alzheimer's disease (AD), and from 28 healthy matched-controls. We found no significant correlation between FC and AC levels in CSF. FC and AC levels in CSF did not differ significantly between AD patients and controls, but plasma FC levels were significantly lower in AD patients. CSF and plasma FC and AC levels did not correlate with age, age at onset of AD, duration of AD, and scores of the Minimental State Examination of Folstein. Although these results suggest that CSF carnitine levels are apparently unrelated with the risk for AD, the trend of the FC/AC ratio to be higher in AD patients might suggest the possibility of a lower carnitine acetyltransferase activity in AD, as previously reported in some brain areas. PMID:9562266

  18. Hormone replacement therapy and oral contraceptives and risk of oesophageal adenocarcinoma: a systematic review and meta-analysis.

    PubMed

    Lagergren, Katarina; Lagergren, Jesper; Brusselaers, Nele

    2014-11-01

    There is an unexplained strong male predominance in the aetiology of oesophageal adenocarcinoma (OAC). The hypothesis that oestrogens are protective, deserves attention. A potential protective influence of exogenous oestrogen exposure, that is, hormone replacement therapy (HRT) and oral contraceptives (OC) has been addressed only in studies of limited statistical power, and the individual studies have not provided conclusive results. We conducted a systematic literature search and meta-analysis on HRT and OC and the risk of OAC. We used the databases PubMed and the Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by the Mantel-Haenszel random-effect method. A total of five studies were included. Compared to never users, ever users of HRT had a statistically significantly decreased risk of OAC (pooled OR = 0.75; 95% CI: 0.58-0.98), and ever users of OC had a borderline significantly decreased risk of this cancer (pooled OR = 0.76; 95% CI: 0.57-1.00). In conclusion, HRT and OC use seems to be associated with a decreased risk of OAC. However, further research is warranted. PMID:24676860

  19. 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

  20. 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

  1. Heat generation and transfer behaviors of ti-coated carbon steel rod adaptable for ablation therapy of oral cancer.

    PubMed

    Naohara, Takashi; Aono, Hiromichi; Maehara, Tsunehiro; Hirazawa, Hideyuki; Matsutomo, Shinya; Watanabe, Yuji

    2013-01-01

    For the purpose of developing a novel ablation therapy for oral cancer, the heat generation and transfer properties of a Ti-coated carbon steel rod with 20-mm length and 1.8-mm outer diameter were investigated by means of a high-frequency induction technique at 300 kHz. The heat generation measurement performed using water (15 mL) revealed that the difference of the inclination angles (θ = 0°, 45° and 90°) relative to the magnetic flux direction only slightly affects the heating behavior, exhibiting the overlapped temperature curves during an induction time of 1200 s. These results suggest that the effect of the shape magnetic anisotropy is almost eliminated, being convenient for the precise control of the ablation temperature in clinical use. In the experiments utilizing a tissue-mimicking phantom, the heat transfer concentrically occurred in the lateral direction for both the planar surface and a 10-mm deep cross-section. However, the former exhibited a considerably lower increase in temperature (ΔT), probably due to the effect of heat dissipation to the ambient air. No significant heat transfer was found to occur to the lower side of the inserted Ti-coated carbon steel rod, which is situated in the longitudinal direction. PMID:24955829

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

    PubMed Central

    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. PMID:1860151

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. Oral Cancer

    MedlinePlus

    ... won't heal Bleeding in your mouth Loose teeth Problems or pain with 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

  9. Efficacy of cryotherapy associated with laser therapy for decreasing severity of melphalan-induced oral mucositis during hematological stem-cell transplantation: a prospective clinical study.

    PubMed

    de Paula Eduardo, Fernanda; Bezinelli, Leticia Mello; da Graça Lopes, Roberta Marques; Nascimento Sobrinho, Jairo Jose; Hamerschlak, Nelson; Correa, Luciana

    2015-09-01

    Melphalan followed by hematopoietic stem-cell transplantation (HSCT) is the standard treatment for multiple myeloma and other hematopoietic neoplasms. However, high doses of melphalan cause severe oral mucositis (OM). The objective was to verify the efficacy of cryotherapy plus laser therapy on reduction of OM severity. HSCT patients undergoing melphalan chemotherapy (n = 71) were randomly divided into two groups according to OM treatment: oral cryotherapy performed with ice chips for 1 h 35 min followed by low-level laser therapy (InGaAIP, 660 nm, 40 mW, 6 J/cm(2) ) (n = 54) and laser therapy alone with the same protocol (n = 17). A control group (n = 33) was composed of HSCT patients treated with melphalan who received no specific treatment for OM. OM scores and clinical information were collected from D0 to D + 11. The cryotherapy/laser therapy group showed the lowest OM scores (maximum Grade I) and the lowest mean number of days (8 days) with OM in comparison with the other groups (p < 0.001). OM Grades III and IV were present with high frequency only in the control group. The association of cryotherapy with laser therapy was effective in reducing OM severity in HSCT patients who underwent melphalan conditioning. PMID:24519448

  10. 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. PMID:26182820

  11. 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

  12. 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

  13. L-Carnitine L-tartrate (LCLT) and dehydroepiandrosterone sulfate (DHEAS) affect red and white blood cells in aged Sprague-Dawley rats.

    PubMed

    Strasser, Alois; Dedoyard, Anne; Lohninger, Alfred; Niedermüller, Hans

    2007-01-01

    Supplementation with either L-carnitine or DHEAS was separately suggested to counteract age-related declines. However, little is known about any interactive effects of these substances, independently promoting mitochondrial energy metabolism, in older individuals. We thus studied the effects of 3 months of daily oral combined supplementation with LCLT and DHEAS on red (RBCs) and white blood cells (WBCs) in male Sprague-Dawley rats by determining RBC and WBC counts, lymphocyte proliferation and interleukin-2 (IL-2) synthesis in spleen lymphocytes after Concanavalin A (ConA) stimulation. Supplementation with LCLT in addition to DHEAS decreased RBCs and increased platelets in the blood of 25-month-old Sprague-Dawley rats, whereas supplementation with DHEAS alone shifted the balance from segmented neutrophile granulocytes to large lymphocytes in differential WBC counts. Based on these results, interactive effects of supplementation with L-carnitine and DHEAS on RBCs and platelets are suggested. PMID:16930745

  14. 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

  15. 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

  16. Effects of ciprofibrate and 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) on the distribution of carnitine and CoA and their acyl-esters and on enzyme activities in rats. Relation between hepatic carnitine concentration and carnitine acetyltransferase activity.

    PubMed Central

    Bhuiyan, A K; Bartlett, K; Sherratt, H S; Agius, L

    1988-01-01

    The effects of feeding the peroxisome proliferators ciprofibrate (a hypolipidaemic analogue of clofibrate) or POCA (2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate) (an inhibitor of CPT I) to rats for 5 days on the distribution of carnitine and acylcarnitine esters between liver, plasma and muscle and on hepatic CoA concentrations (free and acylated) and activities of carnitine acetyltransferase and acyl-CoA hydrolases were determined. Ciprofibrate and POCA increased hepatic [total CoA] by 2 and 2.5 times respectively, and [total carnitine] by 4.4 and 1.9 times respectively, but decreased plasma [carnitine] by 36-46%. POCA had no effect on either urinary excretion of acylcarnitine esters or [acylcarnitine] in skeletal muscle. By contrast, ciprofibrate decreased [acylcarnitine] and [total carnitine] in muscle. In liver, ciprofibrate increased the [carnitine]/[CoA] ratio and caused a larger increase in [acylcarnitine] (7-fold) than in [carnitine] (4-fold), thereby increasing the [short-chain acylcarnitine]/[carnitine] ratio. POCA did not affect the [carnitine]/[CoA] and the [short-chain acylcarnitine]/[carnitine] ratios, but it decreased the [long-chain acylcarnitine]/[carnitine] ratio. Ciprofibrate and POCA increased the activities of acyl-CoA hydrolases, and carnitine acetyltransferase activity was increased 28-fold and 6-fold by ciprofibrate and POCA respectively. In cultures of hepatocytes, ciprofibrate caused similar changes in enzyme activity to those observed in vivo, although [carnitine] decreased with time. The results suggest that: (1) the reactions catalysed by the short-chain carnitine acyltransferases, but not by the carnitine palmitoyltransferases, are near equilibrium in liver both before and after modification of metabolism by administration of ciprofibrate or POCA; (2) the increase in hepatic [carnitine] after ciprofibrate or POCA feeding can be explained by redistribution of carnitine between tissues; (3) the activity of carnitine

  17. The Impact of Initiating Biphasic Human Insulin 30 Therapy in Type 2 Diabetes Patients After Failure of Oral Antidiabetes Drugs

    PubMed Central

    Gu, Yunjuan; Hou, Xuhong; Zhang, Lei; Pan, Jiemin; Cai, Qingxia; Bao, Yuqian

    2012-01-01

    Abstract Background The present study evaluated the efficacy of biphasic human insulin 30 (BHI 30) in type 2 diabetes patients who had failed in therapy with two or more oral antidiabetes drugs (OADs). Methods This open-label, nonrandomized, 4-month, multicenter, clinical observational study was conducted in Shanghai, China. A total of 660 insulin-naive type 2 diabetes patients with poor glycemic control (glycosylated hemoglobin [HbA1c] ≥7.5%), despite treatment with two or more OADs for more than 6 months, were recruited and received BHI 30 monotherapy or BHI 30 plus OAD(s) (metformin only, α-glucosidase inhibitor only, or both). Results Among the 660 subjects, 644 completed the 4-month study. At the end of the study, the median level of HbA1c decreased by 2.0% (from 9.1% to 7.0%) in the BHI 30 monotherapy group and also 2.0% (from 9.5% to 7.3%) in the BHI 30 plus OAD group. More patients achieved the HbA1c <7.0% target in the BHI 30 monotherapy group than in the BHI 30 plus OAD(s) group (47.9% vs. 35.3%, P=0.002). Compared with the expenses of the prior treatment strategy, the median daily cost decreased by 39.8% (4.5 yuan, Chinese RMB) at the end point in the BHI 30 monotherapy group but increased by 20.0% (2.2 yuan) in the BHI 30 plus OAD(s) group (P<0.0001). Moreover, patients in the BHI 30 plus OAD(s) group had fewer minor hypoglycemic episodes than in the BHI 30 monotherapy group (mean of 1.06 vs. 2.77 per patient per year, P<0.0001). Conclusions Short-term BHI 30 therapy can improve glycemic control in insulin-naive type 2 diabetes patients after failure of two or more OADs. With higher baseline glucose level, the BHI 30 plus OAD(s) group had lower pharmacoeconomic efficacy than the BHI 30 monotherapy group despite having fewer hypoglycemia events. PMID:22047050

  18. 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.

  19. Crystal structure of rat carnitine palmitoyltransferase II (CPT-II)

    PubMed Central

    Hsiao, Yu-Shan; Jogl, Gerwald; Esser, Victoria; Tong, Liang

    2010-01-01

    Carnitine palmitoyltransferase II (CPT-II) has a crucial role in the β-oxidation of long-chain fatty acids in mitochondria. We report here the crystal structure of rat CPT-II at 1.9 Å 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. PMID:16781677

  20. Role of Oral Antibiotics in Treatment of Breastfeeding Women with Chronic Breast Pain Who Fail Conservative Therapy

    PubMed Central

    Burgess, Kelly; Hawn, Thomas R.; Zyzanski, Steven

    2014-01-01

    Abstract Background: Although breast pain remains a common cause of weaning, controversy exists regarding the etiology of chronic pain. Prospective studies are needed to define optimal treatment regimens. We evaluated patient history, exam, and bacterial cultures in breastfeeding women with chronic breast pain. We compared pain resolution and breastfeeding complications in patients responding to conservative therapy (CTX) (n=38) versus those in patients failing CTX and receiving oral antibiotic treatment (OTX) (n=48). Subjects and Methods: We prospectively enrolled 86 breastfeeding women with breast pain lasting greater than 1 week and followed up patients through 12 weeks. Results: Higher initial breast (p=0.012) and nipple pain severity (p=0.004), less response to latch correction (p=0.015) at baseline visit, and breastmilk Staphylococcus aureus growth (p=0.001) were associated with failing CTX. Pain type was not associated with failure of CTX. When culture results were available at 5 days, breast pain remained higher (p<0.001) in patients failing CTX and starting antibiotics. OTX patients then had more rapid breast pain reduction between 5 and 14 days (score of 3.1 vs. 1.3; p<0.001). By 4 weeks there was no difference (1.8/10 vs. 1.4/10; p=0.088) in breast pain level between groups. Median length of OTX was 14 days. At 12 weeks, weaning frequency (17% vs. 8%; p=0.331) was not statistically different. Conclusions: Initial pain severity and limited improvement to latch correction predicts failure of CTX. S. aureus growth is more common in women failing CTX. For those women not responding to CTX, OTX matched to breastmilk culture may significantly decrease their pain and is not associated with increased complications. PMID:24387034

  1. 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

  2. Accuracy of ultrasound and oral cholecystography in assessing the number and size of gallstones: implications for non-surgical therapy.

    PubMed

    Brakel, K; Laméris, J S; Nijs, H G; Ginai, A Z; Terpstra, O T

    1992-09-01

    Prior to non-surgical therapy of gallstones it is important to assess their number and size. In order to evaluate the accuracy of ultrasound (US) and oral cholecystography (OCG) in counting and measuring gallstones, a prospective blind study was conducted to compare the results of US (n = 99) and OCG (n = 36), either alone or in combination (n = 34), with the number and size of gallstones retrieved after cholecystectomy. The number of gallstones was accurately estimated by US and OCG in 74% and 69% of the cases, respectively. In assessing the presence of up to three, five or 10 gallstones both US and OCG proved reliable. In measuring the size of gallstones, there was 19% accuracy with US compared with only 3% with OCG. With an accepted measurement error of 3 mm these values increased to 80% for US and 44% for OCG. US proved more reliable than OCG in discriminating gallstones smaller or larger than 10 mm and smaller or larger than 20 mm, but with US, detection of gallstones larger than 30 mm was problematic. Both US and OCG underestimated gallstone size. The combination of both techniques did not significantly improve the assessment of either number or size of gallstones compared with the results obtained with US or OCG alone. It is concluded that (1) both US and OCG have some limitations in assessing the number and size of gallstones, (2) the combination of both examinations does not improve accuracy, and (3) patient selection for non-surgical treatment of gallstones can be started by US alone. PMID:1393414

  3. Effect of L-carnitine on the hepatic transcript profile in piglets as animal model

    PubMed Central

    2011-01-01

    Background Carnitine has attracted scientific interest due to several health-related effects, like protection against neurodegeneration, mitochondrial decay, and oxidative stress as well as improvement of glucose tolerance and insulin sensitivity. The mechanisms underlying most of the health-related effects of carnitine are largely unknown. Methods To gain insight into mechanisms through which carnitine exerts its beneficial metabolic effects, we fed piglets either a control or a carnitine supplemented diet, and analysed the transcriptome in the liver. Results Transcript profiling revealed 563 genes to be differentially expressed in liver by carnitine supplementation. Clustering analysis of the identified genes revealed that most of the top-ranked annotation term clusters were dealing with metabolic processes. Representative genes of these clusters which were significantly up-regulated by carnitine were involved in cellular fatty acid uptake, fatty acid activation, fatty acid β-oxidation, glucose uptake, and glycolysis. In contrast, genes involved in gluconeogenesis were down-regulated by carnitine. Moreover, clustering analysis identified genes involved in the insulin signaling cascade to be significantly associated with carnitine supplementation. Furthermore, clustering analysis revealed that biological processes dealing with posttranscriptional RNA processing were significantly associated with carnitine supplementation. Conclusion The data suggest that carnitine supplementation has beneficial effects on lipid and glucose homeostasis by inducing genes involved in fatty acid catabolism and glycolysis and repressing genes involved in gluconeogenesis. PMID:22040461

  4. 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

  5. Carnitine palmitoyltransferase 2 and carnitine/acylcarnitine translocase are involved in the mitochondrial synthesis and export of acylcarnitines.

    PubMed

    Violante, Sara; Ijlst, Lodewijk; Te Brinke, Heleen; Tavares de Almeida, Isabel; Wanders, Ronald J A; Ventura, Fátima V; Houten, Sander M

    2013-05-01

    Acylcarnitines are commonly used in the diagnosis of mitochondrial fatty acid β-oxidation disorders (mFAODs). It is generally assumed that this plasma acylcarnitine profile reflects the mitochondrial accumulation of acyl-CoAs. The identity of the enzymes and the mitochondrial and plasmalemmal transporters involved in the synthesis and export of these metabolites have remained undefined. We used lentiviral shRNA to knock down the expression of medium-chain acyl-CoA dehydrogenase (MCAD) in control and carnitine palmitoyltransferase 2 (CPT2)-, carnitine/acylcarnitine translocase (CACT)-, and plasmalemmal carnitine transporter (OCTN2)-deficient human fibroblasts. These cell lines, including mock-transduced controls, were loaded with decanoic acid and carnitine, followed by the measurement of the acylcarnitine profile in the extracellular medium. In control fibroblasts, MCAD knockdown markedly increased the production of octanoylcarnitine (3-fold, P<0.01). OCTN2-deficient cell lines also showed extracellular accumulation of octanoylcarnitine (2.8-fold, P<0.01), suggesting that the cellular export of acylcarnitines does not depend on OCTN2. In contrast, in CPT2- and CACT-deficient cells, the accumulation of octanoylcarnitine in the medium did not significantly increase in the MCAD knockdown. Similar results were obtained using pharmacological inhibition of CPT2 in fibroblasts from MCAD-deficient individuals. This shows that CPT2 and CACT are crucial for mitochondrial acylcarnitine formation and export to the extracellular fluids in mFAOD. PMID:23322164

  6. Expression of Cu,Zn-SOD, Mn-SOD and GST-pi in oral cancer treated with preoperative radiation therapy.

    PubMed

    Terakado, N; Shintani, S; Nakahara, Y; Mihara, M; Tomizawa, K; Suzuki, K; Taniguchi, N; Matsumura, T

    2000-01-01

    Radical scavengers play an important role in cancer cells defending themselves against free radicals which occur with irradiation. SOD (Cu,Zn, Mn-) and GST-pi are radical scavengers with an effect on radiation therapy. We investigated the correlation between radiation effects and expression of Cu,Zn-, Mn-SOD and GST-pi in 34 cases of oral cancer, treated with preoperative radiation therapy. In this study, 22 cases out of 34 were classified as effective and 12 cases as non-effective. Expression of Cu,Zn, Mn-SOD and GST-pi were observed in 13 (38.2%), 10 (29.4%) and 20 (58.8%) cases, respectively. Regarding the value of radiation sensitivity from expression of these proteins in the biopsy samples, no significant correlation was found between those expressions and histological effectiveness of preoperative radiation therapy. But interestingly, in 11 out of 12 of the non-effective cases, strong staining of Cu, Zn-SOD and GST-pi were shown at the residual cancer cells after preoperative radiation therapy. These results suggested that the expression of SOD (Cu,Zn-, and Mn-) and GST-pi may be not useful markers for predicting the effects of radiation therapy. However, Cu, Zn-SOD and GST-pi were increased by irradiation and may play an important role in radiation resistance and cancer cell regeneration after radiation therapy. PMID:10948348

  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. 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 ...

  9. Effects of exercise on L-carnitine and lipid metabolism in African catfish (Clarias gariepinus) fed different dietary L-carnitine and lipid levels.

    PubMed

    Ozorio, Rodrigo O A; Van Ginneken, Vincent J T; Bessa, Rui J B; Verstegen, Martin W A; Verreth, Johan A J; Huisman, Elbertus A

    2010-04-01

    African catfish (Clarias gariepinus) were fed four isonitrogenous diets (34 % crude protein), each containing one of two lipid (100 or 180 g/kg) and two L-carnitine (15 or 1000 mg/kg) levels. After 81 d of feeding, thirty-two fish (body weight 32 g) from each dietary group were randomly selected, sixteen fish were induced to a 3-h swim (speed of 1.5 body length (BL)/s), while the other sixteen fish were kept under resting condition. Fish fed 1000 mg L-carnitine accumulated 3.5 and 5 times more L-carnitine in plasma and muscle, respectively, than fish fed the 15 mg L-carnitine. Muscle L-carnitine content was significantly lower in exercised fish than in rested fish. High dietary lipid level (fish oil) led to an increase in muscle n-3 PUFA content and a decrease in SFA and MUFA content. In liver, the increase in dietary lipid level resulted in an increased levels of both n-6 and n-3 PUFA. L-carnitine supplementation significantly decreased n-3 PUFA content. Exercise decreased n-3 PUFA in both muscle and liver. Plasma lactate and lactate dehydrogenase, normally associated with increased glycolytic processes, were positively correlated with exercise and inversely correlated with dietary L-carnitine level. L-carnitine supplementation reduced significantly the RQ from 0.72 to 0.63, and an interaction between dietary L-carnitine and lipid was observed (P < 0.03). Our results indicate that an increase in fatty acids (FA) intake may promote FA oxidation, and both carnitine and exercise might influence the regulation of FA oxidation selectivity. PMID:19930769

  10. Expression of oral secretory leukocyte protease inhibitor in HIV-infected subjects with long-term use of antiretroviral therapy

    PubMed Central

    Nittayananta, Wipawee; Kemapunmanus, Marisa; Yangngam, Supaporn; Talungchit, Sineepat; Sriplung, Hutcha

    2012-01-01

    BACKGROUND The objectives of this study were to determine 1) expression of oral secretory leukocyte protease inhibitor (SLPI) in HIV-infected subjects compared to non-HIV controls, 2) the oral SLPI expression in HIV-infected subjects with ART compared to those without ART, and 3) factors associated with the expression of oral SLPI. METHODS Oral tissues and samples of both un-stimulated and stimulated saliva were collected from HIV-infected subjects with and without ART, and non-HIV individuals. The expression of SLPI mRNA in the tissue was determined by quantitative real-time PCR. Salivary SLPI protein was detected using ELISA. Chi-square test and logistic regression analysis were performed to determine the association between HIV/ART status and the expression of oral SLPI. RESULTS One hundred and fifty-seven HIV-infected subjects were enrolled; 99 on ART (age range 23–57 yr, mean 39 yr), 58 not on ART (age range 20–59 yr, mean 34 yr), and 50 non-HIV controls (age range 19–59 yr, mean 36 yr). The most common ART regimen was 2 NRTIs+1 NNRTI. The expression of oral SLPI in stimulated saliva was significantly decreased with HIV infection (p< 0.001). The expression was also significantly different with respect to ART use (p=0.007). Smoking, CD4+ cell count, and HIV viral load were the factors associated with the oral SLPI expression. CONCLUSION The expression of oral SLPI is altered by HIV infection and use of ART. Thus, oral SLPI may be the useful biomarker to identify subjects at risk of infections and malignant transformation due to HIV infection and long-term ART. PMID:23126266

  11. Systematic Evaluation of Key L-Carnitine Homeostasis Mechanisms during Postnatal Development in Rat

    PubMed Central

    2012-01-01

    Background The conditionally essential nutrient, L-carnitine, plays a critical role in a number of physiological processes vital to normal neonatal growth and development. We conducted a systematic evaluation of the developmental changes in key L-carnitine homeostasis mechanisms in the postnatal rat to better understand the interrelationship between these pathways and their correlation to ontogenic changes in L-carnitine levels during postnatal development. Methods mRNA expression of heart, kidney and intestinal L-carnitine transporters, liver γ-butyrobetaine hydroxylase (Bbh) and trimethyllysine hydroxylase (Tmlh), and heart carnitine palmitoyltransferase (Cpt) were measured using quantitative RT-PCR. L-Carnitine levels were determined by HPLC-UV. Cpt and Bbh activity were measured by a spectrophotometric method and HPLC, respectively. Results Serum and heart L-carnitine levels increased with postnatal development. Increases in serum L-carnitine correlated significantly with postnatal increases in renal organic cation/carnitine transporter 2 (Octn2) expression, and was further matched by postnatal increases in intestinal Octn1 expression and hepatic γ-Bbh activity. Postnatal increases in heart L-carnitine levels were significantly correlated to postnatal increases in heart Octn2 expression. Although cardiac high energy phosphate substrate levels remained constant through postnatal development, creatine showed developmental increases with advancing neonatal age. mRNA levels of Cpt1b and Cpt2 significantly increased at postnatal day 20, which was not accompanied by a similar increase in activity. Conclusions Several L-carnitine homeostasis pathways underwent significant ontogenesis during postnatal development in the rat. This information will facilitate future studies on factors affecting the developmental maturation of L-carnitine homeostasis mechanisms and how such factors might affect growth and development. PMID:22805277

  12. Gbu Glycine Betaine Porter and Carnitine Uptake in Osmotically Stressed Listeria monocytogenes Cells

    PubMed Central

    Mendum, Mary Lou; Smith, Linda Tombras

    2002-01-01

    The food-borne pathogen Listeria monocytogenes grows actively under high-salt conditions by accumulating compatible solutes such as glycine betaine and carnitine from the medium. We report here that the dominant transport system for glycine betaine uptake, the Gbu porter, may act as a secondary uptake system for carnitine, with a Km of 4 mM for carnitine uptake and measurable uptake at carnitine concentrations as low as 10 μM. This porter has a Km for glycine betaine uptake of about 6 μM. The dedicated carnitine porter, OpuC, has a Km for carnitine uptake of 1 to 3 μM and a Vmax of approximately 15 nmol/min/mg of protein. Mutants lacking either opuC or gbu were used to study the effects of four carnitine analogs on growth and uptake of osmolytes. In strain DP-L1044, which had OpuC and the two glycine betaine porters Gbu and BetL, triethylglycine was most effective in inhibiting growth in the presence of glycine betaine, but trigonelline was best at inhibiting growth in the presence of carnitine. Carnitine uptake through OpuC was inhibited by γ-butyrobetaine. Dimethylglycine inhibited both glycine betaine and carnitine uptake through the Gbu porter. Carnitine uptake through the Gbu porter was inhibited by triethylglycine. Glycine betaine uptake through the BetL porter was strongly inhibited by trigonelline and triethylglycine. These results suggest that it is possible to reduce the growth of L. monocytogenes under osmotically stressful conditions by inhibiting glycine betaine and carnitine uptake but that to do so, multiple uptake systems must be affected. PMID:12406761

  13. Preference for oral anticoagulation therapy for patients with atrial fibrillation in Europe in different clinical situations: results of the European Heart Rhythm Association Survey.

    PubMed

    Larsen, Torben Bjerregaard; Potpara, Tatjana; Dagres, Nikolaos; Proclemer, Alessandro; Sciarrafia, Elena; Blomström-Lundqvist, Carina

    2015-05-01

    The purpose of this European Heart Rhythm Association Survey was to assess the clinical practice in relation to the use of oral anticoagulation therapy for patients with atrial fibrillation (AF) in Europe. Of special interest were patients undergoing percutaneous coronary intervention (PCI), cardioversion procedures, catheter ablation, surgery, and those suffering from anticoagulation-related bleeding. Of 38 responding centres, non-vitamin K antagonist oral anticoagulants (NOACs) were used for stroke prophylaxis and were preferred (33.3%) or considered equal (48.5%) to vitamin K antagonists (VKAs). Only 3% did not use NOACs at all. There were some practice differences regarding the use of NOACs in combination with dual antiplatelet therapy in AF patients undergoing PCI, and only 12% preferred using NOACs in this setting. Bare metal stents were preferred rather than drug-eluting stents in AF patients at high bleeding risk. There were clear practice differences between centres regarding the use of triple therapy. Most of the major bleeding events would be handled using symptomatic and supportive measures (e.g. mechanical compression, fluid replacement, blood transfusion, prothrombin complex concentrate, or recombinant Factor VIIa). More than 80% of the centres offer either VKA or NOAC for at least 3 weeks before and after cardioversion and 70% offer either VKA or NOAC before and after AF catheter ablation. Patients treated with an NOAC were routinely re-assed in most centres. PMID:25926476

  14. Combined oral pulse and topical corticosteroid therapy for severe alopecia areata in children: a long-term follow-up study.

    PubMed

    Lalosevic, Jovan; Gajic-Veljic, Mirjana; Bonaci-Nikolic, Branka; Nikolic, Milos

    2015-01-01

    There are no widely accepted therapy protocols for severe alopecia areata (AA). We treated 65 children/adolescents with AA affecting >30% of scalp. Fourty-three percent of patients had AA plurifocalis (AAP). Fifty-seven percent had AA subtotalis (AAS), AAP+ophiasis (AAP+OPH), and alopecia totalis/universalis (AT/AU). Long-term follow-up (median 96 months) data were available for 69% of patients. Oral dexamethasone (prednisolone 5 mg/kg equivalent) was given once in 4 weeks. Patients received 6, 9, or 12 pulses. Clobetasol propionate 0.05% ointment under plastic wrap occlusion was applied 6 days a week. Hair growth was assessed on a scale ranging 0-100% of regrowth in individual AA lesions. Regrowth >50% was considered good response. Six to twelve months months after the therapy, 56.9% of patients had >75% of hair regrowth. In AAP, 65.5% had complete regrowth. 61.5% of all patients were considered good responders. Significantly, higher percentage of good responders was found in AA lasting ≤12 months. No patients had serious side effects. There was no change in stability of the hair status at the long-term follow-up. Most AA patients had beneficial effects with this protocol. Best results were in AAP and AAP+OPH. Combined topical and oral pulse corticosteroid therapy of AA in children shows long-lasting results, without serious side effects. PMID:26179196

  15. 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

  16. Continuous hormone replacement therapy for menopause combining nomegestrol acetate and gel, patch, or oral estrogen: a comparison of amenorrhea rates.

    PubMed

    Blanc, B; Cravello, L; Micheletti, M C; d'Ercole, C; Zartarian, M

    1998-01-01

    This open-label, prospective, randomized, multicenter trial compared the incidence of amenorrhea in 54 postmenopausal women (mean age, 54.9 +/- 0.6 years) who underwent six 4-week cycles of continuous hormone replacement therapy combining a progestin-nomegestrol acetate 2.5 mg/d--plus one of three estrogens: percutaneous 17beta-estradiol gel (1.5 mg/d, group A), transdermal 17beta-estradiol patch (50 microg/d, group B), or oral estradiol valerate (2 mg/d, group C). Based on an intent-to-treat analysis, the rate of amenorrhea varied significantly according to which estrogen preparation was used. Calculated cycle by cycle, rates of amenorrhea were 67% to 83% for group A, 25% to 56% for group B, and 53% to 61% for group C. Overall rates of persistent amenorrhea were not statistically different between groups for cycles 1 through 3, but for cycles 4 through 6, significantly more women in groups A and C (67% and 46%, respectively) experienced amenorrhea than did those in group B (12%). Amenorrhea rates for the entire six-cycle period were 78% for group A, 48% for group B, and 60% for group C. These differences were not statistically significant. The differences in rates could not be attributed to endometrial atrophy, since when measured by transvaginal sonography, endometrial thickness did not differ significantly between groups. Of the original population, 7% withdrew prematurely because of bleeding. The data for all three groups confirmed that in two out of three women, the occurrence of amenorrhea during the first three cycles predicted continuation of amenorrhea during subsequent cycles and that for 51% of women, < or =10 days of bleeding during the first three cycles predicted amenorrhea during the last three cycles. Calculated as a function of the number of women included in the trial, the percentage of amenorrheic women (evaluated cycle by cycle or for the second three-cycle period) was highest when the progestin was combined with percutaneous 17beta

  17. Carnitine-acylcarnitine translocase deficiency, clinical, biochemical and genetic aspects.

    PubMed

    Rubio-Gozalbo, M E; Bakker, J A; Waterham, H R; Wanders, R J A

    2004-01-01

    The carnitine-acylcarnitine translocase (CACT) is one of the components of the carnitine cycle. The carnitine cycle is necessary to shuttle long-chain fatty acids from the cytosol into the intramitochondrial space where mitochondrial beta-oxidation of fatty acids takes place. The oxidation of fatty acids yields acetyl-coenzyme A (CoA) units, which may either be degraded to CO(2) and H(2)O in the citric acid cycle to produce ATP or converted into ketone bodies which occurs in liver and kidneys. Metabolic consequences of a defective CACT are hypoketotic hypoglycaemia under fasting conditions, hyperammonemia, elevated creatine kinase and transaminases, dicarboxylic aciduria, very low free carnitine and an abnormal acylcarnitine profile with marked elevation of the long-chain acylcarnitines. Clinical signs and symptoms in CACT deficient patients, are a combination of energy depletion and endogenous toxicity. The predominantly affected organs are brain, heart and skeletal muscle, and liver, leading to neurological abnormalities, cardiomyopathy and arrythmias, skeletal muscle damage and liver dysfunction. Most patients become symptomatic in the neonatal period with a rapidly progressive deterioration and a high mortality rate. However, presentations at a later age with a milder phenotype have also been reported. The therapeutic approach is the same as in other long-chain fatty acid disorders and includes intravenous glucose (+/- insulin) administration to maximally inhibit lipolysis and subsequent fatty acid oxidation during the acute deterioration, along with other measures such as ammonia detoxification, depending on the clinical features. Long-term strategy consists of avoidance of fasting with frequent meals and a special diet with restriction of long-chain fatty acids. Due to the extremely low free carnitine concentrations, carnitine supplementation is often needed. Acylcarnitine profiling in plasma is the assay of choice for the diagnosis at a metabolite level

  18. 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. PMID:27241631

  19. Determination of L-carnitine in food supplement formulations using ion-pair chromatography with indirect conductimetric detection.

    PubMed

    Kakou, Aikaterini; Megoulas, Nikolaos C; Koupparis, Michael A

    2005-04-01

    A novel method for the determination of L-carnitine in food supplement formulations was developed and validated, using ion-pair chromatography with indirect conductimetric detection. The chromatographic method was based on a non-polar (C18) column and an aqueous octanesulfonate (0.64 mM) eluent, acidified with trifluoroacetic acid (5.2 mM). The retention time was 5.4 min and the asymmetry factor 0.65. A linear calibration curve from 10 to 1000 microg/ml (r= 0.99998), with a detection limit of 2.7 microg/ml (25 microl injection volume), a repeatability %RSD of 0.8 (40 microg/ml, n = 5) and reproducibility %RSD of 2.6 were achieved. The proposed method was applied for the determination of carnitine in oral solutions and capsules. No interference from excipients was found and the only pretreatment step required was the appropriate dilution with the mobile phase. Recovery from spiked samples was ranged from 97.7 to 99.7% with a precision (%RSD, n = 3) of 0.01-2.1%. PMID:15830947

  20. L-carnitine as an ergogenic aid for patients with chronic obstructive pulmonary disease submitted to whole-body and respiratory muscle training programs.

    PubMed

    Borghi-Silva, A; Baldissera, V; Sampaio, L M M; Pires-DiLorenzo, V A; Jamami, M; Demonte, A; Marchini, J S; Costa, D

    2006-04-01

    The effects of adding L-carnitine to a whole-body and respiratory training program were determined in moderate-to-severe chronic obstructive pulmonary disease (COPD) patients. Sixteen COPD patients (66 +/- 7 years) were randomly assigned to L-carnitine (CG) or placebo group (PG) that received either L-carnitine or saline solution (2 g/day, orally) for 6 weeks (forced expiratory volume on first second was 38 +/- 16 and 36 +/- 12%, respectively). Both groups participated in three weekly 30-min treadmill and threshold inspiratory muscle training sessions, with 3 sets of 10 loaded inspirations (40%) at maximal inspiratory pressure. Nutritional status, exercise tolerance on a treadmill and six-minute walking test, blood lactate, heart rate, blood pressure, and respiratory muscle strength were determined as baseline and on day 42. Maximal capacity in the incremental exercise test was significantly improved in both groups (P < 0.05). Blood lactate, blood pressure, oxygen saturation, and heart rate at identical exercise levels were lower in CG after training (P < 0.05). Inspiratory muscle strength and walking test tolerance were significantly improved in both groups, but the gains of CG were significantly higher than those of PG (40 +/- 14 vs 14 +/- 5 cmH2O, and 87 +/- 30 vs 34 +/- 29 m, respectively; P < 0.05). Blood lactate concentration was significantly lower in CG than in PG (1.6 +/- 0.7 vs 2.3 +/- 0.7 mM, P < 0.05). The present data suggest that carnitine can improve exercise tolerance and inspiratory muscle strength in COPD patients, as well as reduce lactate production. PMID:16612469

  1. 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

  2. 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

  3. 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

  4. Carnitine transporter OCTN2 and carnitine uptake in bovine kidney cells is regulated by peroxisome proliferator-activated receptor β/δ

    PubMed Central

    2014-01-01

    Background Peroxisome proliferator-activated receptor α (PPARα), a central regulator of fatty acid catabolism, has recently been shown to be a transcriptional regulator of the gene encoding the carnitine transporter novel organic cation transporter 2 (OCTN2) in cattle. Whether PPARβ/δ, another PPAR subtype, which has partially overlapping functions as PPARα and is known to share a large set of common target genes with PPARα, also regulates OCTN2 and carnitine transport in cattle is currently unknown. To close this gap of knowledge, we studied the effect of the PPARβ/δ activator GW0742 on mRNA and protein levels of OCTN2 and carnitine uptake in the presence and absence of the PPARβ/δ antagonist GSK3787 in the bovine Madin-Darby bovine kidney (MDBK) cell line. Findings Treatment of MDBK cells with GW0742 caused a strong increase in the mRNA level of the known bovine PPARβ/δ target gene CPT1A in MDBK cells indicating activation of PPARβ/δ. The mRNA and protein level of OCTN2 was clearly elevated in MDBK cells treated with GW0742, but the stimulatory effect of GW0742 on mRNA and protein level of OCTN2 was completely blocked by GSK3787. In addition, GW0742 increased Na+-dependent carnitine uptake, which is mediated by OCTN2, into MDBK cells, whereas treatment of cells with the PPARβ/δ antagonist completely abolished the stimulatory effect of GW0742 on carnitine uptake. Conclusions The present study shows for the first time that gene expression of the carnitine transporter OCTN2 and carnitine transport are regulated by PPARβ/δ in bovine cells. These novel findings extend the knowledge about the molecular regulation of the OCTN2 gene and carnitine transport in cattle and indicate that regulation of OCTN2 gene expression and carnitine transport is not restricted to the PPARα subtype. PMID:24716857

  5. Gut microbiota metabolism of L-carnitine and cardiovascular risk.

    PubMed

    Ussher, John R; Lopaschuk, Gary D; Arduini, Arduino

    2013-12-01

    In recent years, a number of studies have alluded to the importance of the intestinal microflora in controlling whole-body metabolic homeostasis and organ physiology. In particular, it has been suggested that the hepatic production of trimethylamine-N-oxide (TMAO) from gut microbiota-derived trimethylamine (TMA) may enhance cardiovascular risk via promoting atherosclerotic lesion development. The source of TMA production via the gut microbiota appears to originate from 2 principle sources, either phosphatidylcholine/choline and/or L-carnitine. Therefore, it has been postulated that consumption of these dietary sources, which are often found in large quantities in red meats, may be critical factors promoting cardiovascular risk. In contrast, a number of studies demonstrate beneficial properties for l-carnitine consumption against metabolic diseases including skeletal muscle insulin resistance and ischemic heart disease. Furthermore, fish are a significant source of TMAO, but dietary fish consumption and fish oil supplementation may exhibit positive effects on cardiovascular health. In this mini-review we will discuss the discrepancies regarding L-carnitine supplementation and its possible negative effects on cardiovascular risk through potential increases in TMAO production, as well as its positive effects on metabolic health via increasing glucose metabolism in the muscle and heart. PMID:24267266

  6. 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. PMID:19538826

  7. 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.

  8. 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

  9. 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.

  10. Effectiveness and tolerability of treatment intensification to basal–bolus therapy in patients with type 2 diabetes on previous basal insulin-supported oral therapy with insulin glargine or supplementary insulin therapy with insulin glulisine: the PARTNER observational study

    PubMed Central

    Pfohl, Martin; Siegmund, Thorsten; Pscherer, Stefan; Pegelow, Katrin; Seufert, Jochen

    2015-01-01

    Background Due to the progressive nature of type 2 diabetes mellitus (T2DM), antidiabetic treatment needs to be continuously intensified to avoid long-term complications. In T2DM patients on either basal insulin-supported oral therapy (BOT) or supplementary insulin therapy (SIT) presenting with HbA1c values above individual targets for 3–6 months, therapy should be intensified. This study investigated effectiveness and tolerability of an intensification of BOT or SIT to a basal–bolus therapy (BBT) regimen in T2DM patients in daily clinical practice. Methods This noninterventional, 8-month, prospective, multicenter study evaluated parameters of glucose control, occurrence of adverse events (eg, hypoglycemia), and acceptance of devices in daily clinical practice routine after 12 and 24 weeks of intensifying insulin therapy to a BBT regimen starting from either preexisting BOT with insulin glargine (pre-BOT) or preexisting SIT with ≥3 daily injections of insulin glulisine (pre-SIT). Results A total of 1,530 patients were documented in 258 German medical practices. A total of 1,301 patients were included in the full analysis set (55% male, 45% female; age median 64 years; body mass index median 30.8 kg/m2; pre-BOT: n=1,072; pre-SIT: n=229), and 1,515 patients were evaluated for safety. After 12 weeks, HbA1c decreased versus baseline (pre-BOT 8.67%; pre-SIT 8.46%) to 7.73% and 7.66%, respectively (Δ mean −0.94% and −0.80%; P<0.0001). At week 24, HbA1c was further reduced to 7.38% and 7.30%, respectively (Δ mean −1.29% and −1.15%; P<0.0001), with a mean reduction of fasting blood glucose values in both treatment groups by more than 46 mg/dL. An HbA1c goal of ≤6.5% was reached by 17.9% (pre-BOT) and 18.6% (pre-SIT), and an HbA1c ≤7.0% by 46.1% (pre-BOT) and 43.0% (pre-SIT) of patients. During 24 weeks, severe as well as serious hypoglycemic events were rare (pre-BOT: n=5; pre-SIT: n=2; pretreated with both insulins: n=1). Conclusion Intensifying

  11. 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

  12. 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…

  13. Carnitine levels in skeletal muscle of malnourished patients before and after total parenteral nutrition.

    PubMed

    Sandstedt, S; Larsson, J; Cederblad, G

    1986-11-01

    Carnitine is necessary for the transport of long-chain fatty acids across the mitochondrial membrane. Carnitine is derived from the diet and from endogenous synthesis from lysine and methionine. About 98% of the body's carnitine pool is located in skeletal muscle tissue. Skeletal muscle carnitine levels were determined in two groups of malnourished patients, eight patients with anorexia nervosa with a weight loss of 32.4% +/- 1.8 (mean +/- SEM) and six surgical patients with major gastrointestinal disorders and a weight loss of 15.2% +/- 2.7. Their hepatic and kidney functions were normal. On admission, the muscle carnitine levels were 16.9 +/- 4.0 mumol/g dry weight (mean +/- SD) for the surgical patients and 20.8 +/- 5.0 mumol/g dry weight for the anorexia nervosa patients, which corresponded to carnitine levels seen in healthy subjects. No statistical significance was found between the two groups. Total parenteral nutrition was given to the surgical patients for 2 weeks and to the anorexia nervosa patients for 3-5 weeks. No statistical difference in muscle carnitine levels was found in either group after nutritional support. These malnourished patients had no decreased muscle carnitine levels on admission and maintained them during several weeks of total parenteral nutrition. PMID:16831776

  14. 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

  15. Inhibition of gene expression of carnitine palmitoyltransferase I and heart fatty acid binding protein in cyclophosphamide and ifosfamide-induced acute cardiotoxic rat models.

    PubMed

    Sayed-Ahmed, Mohamed M; Aldelemy, Meshan L; Al-Shabanah, Othman A; Hafez, Mohamed M; Al-Hosaini, Khaled A; Al-Harbi, Naif O; Al-Sharary, Shakir D; Al-Harbi, Mohamed M

    2014-09-01

    This study investigated whether cyclophosphamide (CP) and ifosfamide (IFO) therapy alters the expression of the key genes engaged in long-chain fatty acid (LCFA) oxidation outside rat heart mitochondria, and if so, whether these alterations should be viewed as a mechanism during CP- and IFO-induced cardiotoxicity. Adult male Wistar albino rats were assigned to one of the six treatment groups: Rats in group 1 (control) and group 2 (L-carnitine) were injected intraperitoneal (i.p.) with normal saline and L-carnitine (200 mg/kg/day), respectively, for 10 successive days. Animals in group 3 (CP group) were injected i.p. with normal saline for 5 days before and 5 days after a single dose of CP (200 mg/kg, i.p.). Rats in group 4 (IFO group) received normal saline for 5 successive days followed by IFO (50 mg/kg/day, i.p.) for 5 successive days. Rats in group 5 (CP-carnitine supplemented) were given the same doses of L-carnitine as group 2 for 5 days before and 5 days after a single dose of CP as group 3. Rats in group 6 (IFO-carnitine supplemented) were given the same doses of L-carnitine as group 2 for 5 days before and 5 days concomitant with IFO as group 4. Immediately, after the last dose of the treatment protocol, blood samples were withdrawn and animals were killed for biochemical, histopathological and gene expression studies. Treatment with CP and IFO significantly decreased expression of heart fatty acid binding protein (H-FABP) and carnitine palmitoyltransferase I (CPT I) genes in cardiac tissues. Moreover, CP but not IFO significantly increased acetyl-CoA carboxylase2 mRNA expression. Conversely, IFO but not CP significantly decreased mRNA expression of malonyl-CoA decarboxylase. Both CP and IFO significantly increased serum lactate dehydrogenase, creatine kinase isoenzyme MB and malonyl-CoA content and histopathological lesions in cardiac tissues. Interestingly, carnitine supplementation completely reversed all the biochemical, histopathological and

  16. 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

  17. 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

  18. [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

  19. A factor in human seminal plasma which affects carnitine accumulation in bovine epididymal sperm.

    PubMed

    Carter, A L; Cho, S H; Bishop, E R; Boldt, J

    1988-05-01

    This study was initiated to determine whether factors are present in human sperm-free seminal plasma (HSP) that regulate the uptake and release of carnitine from sperm. Bovine caput epididymal sperm cells accumulated more carnitine than caudal sperm cells. A significant reduction in carnitine uptake by caput sperm was observed in the presence of HSP from normal subjects, but not from three subjects with reduced motility. A factor has been isolated from HSP that inhibits carnitine uptake by caput sperm and has the following properties: it is nondialyzable, stable to freeze-thawing, soluble in 60% ammonium sulfate, and has an approximate molecular weight of 158 kd. These data are consistent with the existence of a relatively high molecular weight protein in HSP responsible for the preservation of carnitine concentrations in sperm. PMID:3360180

  20. L-Carnitine Protect against Cyclophosphamide Induced Skeletal and Neural Tube Malformations in Rat Fetuses.

    PubMed

    Khaksary Mahabady, Mahmood; Najafzadeh Varzi, Hossein; Zareyan Jahromi, Saeedeh

    2015-11-01

    Cyclophosphamide (CP) is a mustard alkylating agent used in the treatment of a number of neoplastic diseases and as an immunosuppressant for the prevention of xenograft rejection. There are many reports that the teratogenic effects of cyclophosphamide can be prevented by application of antioxidant drugs and stimulation of the maternal immune system. Also, there is some evidence that L-carnitine is antioxidant. Therefore, in this study, the prophylactic effect of L-carnitine on teratogenic effects of CP was evaluated. This study was performed on 31 pregnant rats divided into 5 groups. Control group received normal saline and test groups received L-carnitine (500 mg/kg), CP (15 mg/kg), CP (15 mg/kg) plus L-carnitine (250 mg/kg) and CP (15 mg/kg) plus L-carnitine (500 mg/kg) intraperitoneally at 9th day of gestation. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red-Alcian blue method. Cleft palate, spina bifida, and exencephaly incidence were 55.55%, 33.34% and 27.77% in fetuses of mice that received only CP. Cleft palate, spina bifida, exencephaly incidence were 21.42%, 4.76% and 9.52% in the group which received CP plus L-carnitine (250 mg/kg), respectively. However, cleft palate, spina bifida, and exencephaly incidence were 8%, 0% and 8% range in the group received CP plus L-carnitine (500 mg/kg), respectively. In addition, skeletal anomalies incidence including limbs, vertebrae, and sternum defects were decreased by L-carnitine. The mean of weight and length of animals' fetuses received L-carnitine were significantly greater than those received only CP. In conclusion, L-carnitine significantly decreased teratogenicity induced by CP; but this subject needs more detailed evaluation. PMID:26786992