Current Issue : January - March Volume : 2012 Issue Number : 1 Articles : 8 Articles
Metabolic urate production is the result of purine catabolism, and increase in uric acid is primarily a manifestation of increase purine catabolism once other causes are excluded. The source of purine synthesis is glucose – 6 – phosphate of HMP shunt pathway, synthesized by glucose – 6 – phosphate dehydrogenase enzyme. But a valid study depicting state of this relationship in hyperuricemia is lacking. Also allupurinol the most widely used drug in hyperuricemia may indirectly effect the enzyme activity of glucose – 6 – phosphate dehydrogenase. So the study was conducted to verify the association of carbohydrate and nucleotide metabolism in state of hyperuricemia and effect of treatment with allupurinol on this relationship. The study very effectively proves this relationship (p<<0.001) and also shows a significant effect (p<<0.001) of allupurinol treatment on the activity of enzyme glucose – 6 – phosphate dehydrogenase....
BACKGROUND:\nThe emergence of artemisinin resistance has raised concerns that the most potent antimalarial drug may be under threat. The currently recommended daily dose of artesunate (AS) is 4 mg/kg, and is administered for 3 days together with a partner antimalarial drug. This study investigated the impact of different AS doses on clinical and parasitological responses in malaria patients from an area of known artemisinin resistance in western Cambodia.\nMETHODS:\nAdult patients with uncomplicated P. falciparum malaria were randomized into one of three 7-day AS monotherapy regimens: 2, 4 or 6 mg/kg/day (total dose 14, 28 and 42 mg/kg). Clinical, parasitological, pharmacokinetic and in vitro drug sensitivity data was collected over a 7-day inpatient period and during weekly follow-up to 42 days.\nRESULTS:\n143 patients were enrolled (n?=?75, 40 and 28 to receive AS 2, 4 and 6 mg/kg/day respectively). Cure rates were high in all treatment groups at 42 days despite almost half the patients remaining parasitemic on Day 3. There was no impact of increasing AS dose on median parasite clearance times, median parasite clearance rates or on the proportion of patients remaining parasitemic on Day 3. However at the lowest dose used (2 mg/kg/d) patients with parasitemia >10,000/Ã?µL had longer median (IQR) parasite clearance times than those with parasitemia <10,000/Ã?µL (63 (48-75) vs. 84 (66-96) hours, p<0.0001). 19% of patients in the high-dose arm developed neutropenia (absolute neutrophil count <1.0Ã?â??10(9)/L) by Day 14 and resulted in the arm being halted early.\nCONCLUSION:\nThere is no pharmacodynamic benefit of increasing the daily dose of AS (4 mg/kg) currently recommended for short-course combination treatment of uncomplicated malaria, even in regions with emerging artemisinin resistance, as long as the partner drug retains high efficacy....
Although speculative and ethically controversial, cloning a dead person may be scientifically possible as more experimentation on dead animals continues. The article proposes that posthumous cloning may be justifiable in cases where the dead expressed their wishes to be cloned, or when next-of-kin seek to extend the impact of the dead on the living. Under this argument, justification for posthumous cloning does not stem from the concept of reproductive autonomy but from one�s interest in the recognition of one�s symbolic existence. Hence, posthumous cloning promotes the recognition in the symbolic existence of the dead (through the cloned), and indirectly enriches the social image, sense of identity and relational autonomy of the cloned. Seen in this way, cloning should not be regarded as an act which violates human dignity or that instrumentalizes the cloned.\r\n \r\nHowever, the article suggests the following limitation for posthumous cloning: that the nature of the relationship between the cloned and the persons preserving the symbolic existence of the dead should be the same as prior to cloning. Such a limitation would make posthumous cloning an exceptional phenomenon. Regardless of its prevalence, posthumous cloning makes us rethink our general moral opinions on cloning and the ethics of death...
BACKGROUND AND AIMS:\nThe association between hygiene and prevalence of autoimmune disease has been attributed in part to enteric helminth infection. A pilot study of experimental infection with the hookworm Necator americanus was undertaken among a group of otherwise healthy people with celiac disease to test the potential of the helminth to suppress the immunopathology induced by gluten.\nMETHODS:\nIn a 21-week, double-blinded, placebo-controlled study, we explored the effects of N. americanus infection in 20 healthy, helminth-na�¯ve adults with celiac disease well controlled by diet. Staged cutaneous inoculations with 10 and 5 infective 3(rd) stage hookworm larvae or placebo were performed at week-0 and -12 respectively. At week-20, a five day oral wheat challenge equivalent to 16 grams of gluten per day was undertaken. Primary outcomes included duodenal Marsh score and quantification of the immunodominant a-gliadin peptide (QE65)-specific systemic interferon-?-producing cells by ELISpot pre- and post-wheat challenge.\nRESULTS:\nEnteric colonisation with hookworm established in all 10 cases, resulting in transiently painful enteritis in 5. Chronic infection was asymptomatic, with no effect on hemoglobin levels. Although some duodenal eosinophilia was apparent, hookworm-infected mucosa retained a healthy appearance. In both groups, wheat challenge caused deterioration in both primary and several secondary outcomes.\nCONCLUSIONS:\nExperimental N. americanus infection proved to be safe and enabled testing its effect on a range of measures of the human autoimmune response. Infection imposed no obvious benefit on pathology....
Objective. Data from randomized clinical trials with metabolic outcomes can be used to address concerns about potential issues of cardiovascular safety for newer drugs for type 2 diabetes. This meta-analysis was designed to assess cardiovascular safety of GLP-1 receptor agonists. Design and Methods. MEDLINE, Embase, and Cochrane databases were searched for randomized trials of GLP-1 receptor agonists (versus placebo or other comparators) with a duration =12 weeks, performed in type 2 diabetic patients. Mantel-Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for major cardiovascular events (MACE), on an intention-to-treat basis, excluding trials with zero events. Results. Out of 36 trials, 20 reported at least one MACE. The MH-OR for all GLP-1 receptor agonists was 0.74 (0.50ââ?¬â??1.08), p = . 1 2 (0.85 (0.50ââ?¬â??1.45), p = . 5 5, and 0.69 (0.40ââ?¬â??1.22), p = . 2 0, for exenatide and liraglutide, resp.). Corresponding figures for placebo-controlled and active comparator studies were 0.46 (0.25ââ?¬â??0.83), \r\np = . 0 0 9, and 1.05 (0.63ââ?¬â??1.76), p = . 8 4, respectively. Conclusions. To date, results of randomized trials do not suggest any detrimental effect of GLP-1 receptor agonists on cardiovascular events. Specifically designed longer-term trials are needed to verify the possibility of a beneficial effect....
Objectives: The pH values of external aqueous medium relative to the roots of 70 single rooted teeth filled with Ca(OH)2 in to various vehicles was evaluated in the present study.\nMethods and Material: After root canal instrumentation and smear layer removal the samples were randomly divided into three control groups (5 samples each) and six experimental groups (10 samples each). The control groups were water control, dissolution control and sealing control. Experimental groups were filled with: Group I- Ca(OH)2-Normal Saline; Group II- Ca(OH)2-Local Anesthetic; Group III- Ca(OH)2-Propylene Glycol; Group IV-Ca(OH)2-Camphorated paramonochlorophenol; Group V- Ca(OH)2-Glycerine and Group VI- Ca(OH)2 Plus Points (CHPP). All the samples were immersed in glass vialsââ?¬â?¢ containing distilled water maintained at 37Ã?°C. Digital pH meter was used to analyze the pH changes at specific time intervals up to 28 days. \nStatistical analysis used: Statistical evaluation was carried out using one way-Anova and Tukey HSD tests.\nResults: Results revealed that nonsetting Ca(OH)2 formulations produced significantly higher pH elevation than the Calcium Hydroxide Plus Points with Ca(OH)2ââ?¬â?? CMCP combination giving the highest values.\nConclusions: The results indicated that CMCP when used as a vehicle facilitates sustained release of hydroxyl ions from calcium hydroxide medicament in the root canal system....
Background. Intermittent application of chemotherapy and tyrosine kinase inhibitors may avoid antagonism between the two classes of drugs. This hypothesis was tested in a Phase II clinical trial. Patients and Methods. Eligible patients were nonsmokers or light smokers, chemo-naÃ?¯ve, with metastatic adenocarcinoma of the lung. Treatment: 4 to 6 cycles of gemcitabine 1250?mg/m2 on days 1 and 4, cisplatin 75?mg/m2 on day 2, and erlotnib 150 mg daily on days 5ââ?¬â??15, followed by erlotinib as maintenance. Results. 24 patients entered the trial. Four pts had grade 3 toxicity. Complete remission (CR) and partial remission (PR) were seen in 5?pts and 9?pts, respectively (response rate 58%). Median time to progression (TTP) was 13.4 months and median overall survival (OS) was 23 months. When compared to patients with negative or unknown status of EGFR mutations, 8 patients with EGFR gene activating mutations had significantly superior experience: 4 CR and 4 PR, with median TTP 21.5 months and OS 24.2 months (p < . 0 5). Conclusions. Intermittent schedule with gemcitabine, cisplatin and erlotinib has mild toxicity. For patients who are positive for EGFR gene activating mutations, this treatment offers excellent response rate, time to progression and survival....
Symptoms after human infection with the helminth Trichuris suis have not previously been described. Exposure to helminths has been suggested as immune therapy against allergy and autoimmune diseases. We randomized adults with allergic rhinitis to ingest a dose of 2500 T. suis eggs or placebo every 21 days for 168 days (total 8 doses) in a double-blind clinical trial. In a previous publication, we reported a lack of efficacy and a high prevalence of adverse gastrointestinal reactions. The aim of the present study was to present a detailed description of the adverse event data and post-hoc analyses of gastrointestinal reactions. Adverse events and severity (mild, moderate, severe) were recorded daily by subjects, classified by organ using MedDRA 10.0, and event rates compared between subjects on T. suis treatment vs. subjects on placebo. T. suis-specific serum IgG antibodies were measured by a fluoroenzymeimmunoassay (Phadia ApS). During 163 days complete follow-up, subjects ingesting T. suis eggs (N = 49) had a three to 19-fold higher rate of events (median duration, 2 days) with gastrointestinal reactions (moderate to severe flatulence, diarrhea, and upper abdominal pain) compared with placebo subjects (N = 47). The highest incidence of affected subjects was seen from the first few days and until day 42 (3rd dose): 63% vs. 29% for placebo; day 163: 76% vs. 49% for placebo. Seroprevalences increased concurrently in the T. suis group: Day 59, 50%; day 90, 91%; day 170, 93%. The combined duration of episodes with onset before day 42 was =14 days in 80% of affected subjects. Age, gender, total IgE, and recent intestinal symptoms at baseline did not predict gastrointestinal side effects. In conclusion, during the first 2 months, repeated ingestions of 2500 T. suis eggs caused frequent gastrointestinal reactions lasting up to 14 days, whereas 4 months further treatment mainly provoked a subclinical stimulation....
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