89 research outputs found
Can a microscopic stochastic model explain the emergence of pain cycles in patients?
A stochastic model is here introduced to investigate the molecular mechanisms
which trigger the perception of pain. The action of analgesic drug compounds is
discussed in a dynamical context, where the competition with inactive species
is explicitly accounted for. Finite size effects inevitably perturb the
mean-field dynamics: Oscillations in the amount of bound receptors
spontaneously manifest, driven by the noise which is intrinsic to the system
under scrutiny. These effects are investigated both numerically, via stochastic
simulations and analytically, through a large-size expansion. The claim that
our findings could provide a consistent interpretative framework to explain the
emergence of cyclic behaviors in response to analgesic treatments, is
substantiated.Comment: J. Stat. Mech. (Proceedings UPON2008
Razvoj i validacija spektrofotometrijskih metoda za odreÄivanje ceftazidima u farmaceutskim doziranim pripravcima
Two spectrophotometric methods for the determination of ceftazidime (CFZM) in either pure form or in its pharmaceutical formulations are described. The first method is based on the reaction of 3-methylbenzothiazolin-2-one hydrazone (MBTH) with ceftazidime in the presence of ferric chloride in acidic medium. The resulting blue complex absorbs at λmax 628 nm. The second method describes the reaction between the diazotized drug and N-(1-naphthyl)ethylenediamine dihydrochloride (NEDA) to yield a purple colored product with λmax at 567 nm. The reaction conditions were optimized to obtain maximum color intensity. The absorbance was found to increase linearly with increasing the concentration of CFZM; the systems obeyed the Beerâs law in the range 210 and 1050 ”g mL1 for MBTH and NEDA methods, respectively. LOD, LOQ and correlation coefficient values were 0.15, 0.79 and 0.50, 2.61. No interference was observed from common excipients present in pharmaceutical formulations. The proposed methods are simple, sensitive, accurate and suitable for quality control applications.Razvijene su dvije spektrofotometrijske metode za odreÄivanje ceftazidima (CFZM), Äistog ili u farmaceutskim pripravcima. Prva metoda se temelji na reakciji 3-metilbenzotiazolin-2-on hidrazona (MBTH) sa ceftazidimom u prisutnosti ĆŸeljezovog(III) klorida u kiselom mediju. Nastaje plavi kompleks s maksimumom apsorpcije pri λmax 628 nm. Druga metoda se temelji na reakciji izmeÄu diazotiranog lijeka i N-(1-naftil)etilendiamin dihidroklorida (NEDA), pri Äemu nastaje ljubiÄasti produkt s λmax pri 567 nm. Reakcijski uvjeti su optimirani da se dobije maksimalni intenzitet boje. Apsorbancija raste linearno s poraĆĄÄu koncentracije CFZM; sustavi slijede Beerov zakon u koncentracijskom podruÄju 210 za MBTH metodu i 1050 ”g mL1 za NEDA metodu. LOD i LOQ te vrijednosti korelacijskog koeficijenta su 0,15, 0,79 i 0,50, 2,61. UobiÄajene pomoÄne tvari ne smetaju odreÄivanju ceftazidima. PredloĆŸene metode su jednostavne, osjetljive, toÄne i pogodne za primjenu u kontroli kvalitete
The contributions of muscarinic receptors and changes in plasma aldosterone levels to the anti-hypertensive effect of Tulbaghia violacea
Background: Tulbaghia violacea Harv. (Alliaceae) is used to treat various ailments, including hypertension (HTN) in
South Africa. This study aims to evaluate the contributions of muscarinic receptors and changes in plasma
aldosterone levels to its anti-hypertensive effect.
Methods: In the acute experiments, methanol leaf extracts (MLE) of T. violacea (30â120 mg/kg), muscarine (0.16
-10 ÎŒg/kg), and atropine (0.02 - 20.48 mg/kg), and/or the vehicle (dimethylsulfoxide (DMSO) and normal saline (NS))
were respectively and randomly administered intravenously in a group of spontaneously hypertensive (SHR)
weighing 300 to 350 g and aged less than 5 months. Subsequently, T. violacea (60 mg/kg) or muscarine (2.5 ÎŒg/kg)
was infused into eight SHRs, 20 min after atropine (5.12 mg/kg) pre-treatment. In the chronic (21 days) experiments,
the SHRs were randomly divided into three groups, and given the vehicle (0.2 ml/day of DMSO and NS), T. violacea
(60 mg/kg/day) and captopril (10 mg/kg/day) respectively into the peritoneum, to investigate their effects on blood
pressure (BP), heart rate (HR), and plasma aldosterone levels. Systolic BP and HR were measured using tail-cuff
plethysmography during the intervention. BP and HR were measured via a pressure transducer connecting the
femoral artery and the Powerlab at the end of each intervention in the acute experiment; and on day 22 in the
chronic experiment.
Results: In the acute experiments, T. violacea, muscarine, and atropine significantly (p < 0.05) reduced BP
dose-dependently. T. violacea and muscarine produced dose-dependent decreases in HR, while the effect of
atropine on HR varied. After atropine pre-treatment, dose-dependent increases in BP and HR were observed with
T. violacea; while the BP and HR effects of muscarine were nullified. In the chronic experiments, the T. violaceatreated
and captropril-treated groups had signicantly lower levels of aldosterone in plasma when compared to
vehicle-treated group. Compared to the vehicle-treated group, significant reduction in BP was only seen in the
captopril-treated group; while no difference in HR was observed among the groups.
Conclusion: The results obtained in this study suggest that stimulation of the muscarinic receptors and a reduction
in plasma aldosterone levels contribute to the anti-hypertesive effect of T. violacea.IS
Tuberculosis chemotherapy: current drug delivery approaches
Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance
Chronic Citalopram Administration Causes a Sustained Suppression of Serotonin Synthesis in the Mouse Forebrain
BACKGROUND:Serotonin (5-HT) is a neurotransmitter with important roles in the regulation of neurobehavioral processes, particularly those regulating affect in humans. Drugs that potentiate serotonergic neurotransmission by selectively inhibiting the reuptake of serotonin (SSRIs) are widely used for the treatment of psychiatric disorders. Although the regulation of serotonin synthesis may be an factor in SSRI efficacy, the effect of chronic SSRI administration on 5-HT synthesis is not well understood. Here, we describe effects of chronic administration of the SSRI citalopram (CIT) on 5-HT synthesis and content in the mouse forebrain. METHODOLOGY/PRINCIPAL FINDINGS:Citalopram was administered continuously to adult male C57BL/6J mice via osmotic minipump for 2 days, 14 days or 28 days. Plasma citalopram levels were found to be within the clinical range. 5-HT synthesis was assessed using the decarboxylase inhibition method. Citalopram administration caused a suppression of 5-HT synthesis at all time points. CIT treatment also caused a reduction in forebrain 5-HIAA content. Following chronic CIT treatment, forebrain 5-HT stores were more sensitive to the depleting effects of acute decarboxylase inhibition. CONCLUSIONS/SIGNIFICANCE:Taken together, these results demonstrate that chronic citalopram administration causes a sustained suppression of serotonin synthesis in the mouse forebrain. Furthermore, our results indicate that chronic 5-HT reuptake inhibition renders 5-HT brain stores more sensitive to alterations in serotonin synthesis. These results suggest that the regulation of 5-HT synthesis warrants consideration in efforts to develop novel antidepressant strategies
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