The effect of caffeine on the pharmacokinetics of acetaminophen in man

The influence of caffeine (60 mg) was studied on the pharmacokinetic characteristics of acetaminophen (500 mg single dose) in ten healthy male human volunteers in a complete cross-over design. A high-performance liquid chromatography (HPLC) method was used to analyse serum drug concentrations. Caffeine caused a highly significant (p < 0.01) increase in AUC and AUMC, a significant (p < 0.05) increase in C_max, and a significant (p < 0.05) decrease in clearance (Cl/F) of acetaminophen. We conclude that caffeine taken in doses commonly available commercially or in a cup of coffee can significantly potentiate the therapeutic potential of acetaminophen in man.     

Serial dexamethasone suppression test results during antidepressant therapy: Relationship to diagnosis and clinical change

Thirty-two outpatients with major depression of mild to moderate severity were given a 1 mg dexamethasone test (DST) after 1 week of placebo. Those who failed to show a response to placebo began a 6-week course of desipramine treatment. Severity ratings and the DST were repeated during biweekly visits. DST results robustly validated Winokur's familial subtyping and the primary/secondary distinction only when multiple results were considered. The use of multiple DSTs doubled the sensitivity of this test to primary depression and to familal pure depressive disorder without affecting specificity. Based on these data, a single abnormal DST result is considerably more meaningful than a single normal one. This finding may have particular importance to outpatients.     

Effect of dehydration on the disposition kinetics of erythromycin in rabbits.

The effect of water deprivation on the physiologic, biochemical, and disposition parameters of erythromycin was investigated in rabbits. The packed cell volume, plasma glucose, and total lipid concentration increased significantly in dehydration. The pharmacokinetic parameters of erythromycin after intravenous administration also changed, suggesting a need for monitoring toxicity of erythromycin in the water-deprived population.     

Hydrogen sulfide provides cardioprotection against myocardial/ischemia reperfusion injury in the diabetic state through the activation of the RISK pathway

Background

Nitric oxide (NO) is currently administered using devices that maintain constant inspired NO concentrations. Alternatively, devices that deliver a pulse of NO during the early phase of inspiration may have use in optimizing NO dosing efficiency and in extending application of NO to long-term use by ambulatory, spontaneously breathing patients. The extent to which the amount of NO delivered for a given pulse sequence determines alveolar concentrations and uptake, and the extent to which this relationship varies with breathing pattern, physiological, and pathophysiological parameters, warrants investigation.

Methods

A mathematical model was used to analyze inhaled nitric oxide (NO) transport through the conducting airways, and to predict uptake from the alveolar region of the lung. Pulsed delivery was compared with delivery of a constant concentration of NO in the inhaled gas.

Results

Pulsed delivery was predicted to offer significant improvement in uptake efficiency compared with constant concentration delivery. Uptake from the alveolar region depended on pulse timing, tidal volume, respiratory rate, lung and dead space volume, and the diffusing capacity of the lung for NO (D_LNO). It was predicted that variation in uptake efficiency with breathing pattern can be limited using a pulse time of less than 100 ms, with a delay of less than 50 ms between the onset of inhalation and pulse delivery. Nonlinear variation in uptake efficiency with D_LNO was predicted, with uptake efficiency falling off sharply as D_LNO decreased below ~50-60 ml/min/mm Hg. Gas mixing in the conducting airways played an important role in determining uptake, such that consideration of bulk convection alone would lead to errors in assessing efficiency of pulsed delivery systems.

Conclusions

Pulsed NO delivery improves uptake efficiency compared with constant concentration delivery. Optimization of pulse timing is critical in limiting intra- and inter-subject variability in dosing.     

Studies on the protective effect of dietary fish oil on cisplatin induced nephrotoxicity in rats

Cisplatin (CP) is a major antineoplastic drug for the treatment of solid tumors, however, dose dependent nephrotoxicity remains the major concern for its long term use. Several agents/strategies were attempted to prevent CP nephrotoxicity but were not found suitable for clinical practice. Dietary fish oil (FO) enriched in ω-3 fatty acids has been shown to prevent/reduce the progression of certain types of cancers, cardiovascular and renal disorders. The present study was undertaken to see whether FO can prevent CP-induced nephrotoxic and other deleterious effects. Rats were prefed experimental diets for 10days and then received a single dose of CP (6mg/kg body weight) intraperitoneally while still on diet. Serum/urine parameters, enzymes of carbohydrate metabolism, brush border membrane (BBM) and oxidative stress in rat kidney were analyzed. CP nephrotoxicity was recorded by increased serum creatinine and blood urea nitrogen. CP decreased the activities of metabolic enzymes, antioxidant defense system and BBM enzymes. In contrast, FO alone increased enzyme activities of carbohydrate metabolism and brush border membrane (BBM). FO feeding to CP treated rats markedly enhanced resistance to CP-elicited deleterious effects. Dietary FO supplementation ameliorated CP induced specific metabolic alterations and oxidative damage due to its intrinsic biochemical antioxidant properties.     

Throughput and delay analysis of IEEE 802.15.6-based CSMA/CA protocol

The IEEE 802.15.6 is a new communication standard on Wireless Body Area Network (WBAN) that focuses on a variety of medical, Consumer Electronics (CE) and entertainment applications. In this paper, the throughput and delay performance of the IEEE 802.15.6 is presented. Numerical formulas are derived to determine the maximum throughput and minimum delay limits of the IEEE 802.15.6 for an ideal channel with no transmission errors. These limits are derived for different frequency bands and data rates. Our analysis is validated by extensive simulations using a custom C+?+ simulator. Based on analytical and simulation results, useful conclusions are derived for network provisioning and packet size optimization for different applications.