Benzodiazepines Inhibit in Vitro Free Radical Formation from Human Neutrophils Induced by Fmlp and A23187.

Diazepam (DZP) inhibited in vitro in a concentration-dependent manner superoxide anion generation and chemiluminescence from human neutrophils stimulated by the formylated oligopeptide FMLP and by the calcium ionophore A23187.

The dose-dependent inhibitory effect of DZP on A23187-dependent superoxide generation in the presence of Ca⁺⁺ 0.6 mM was highly antagonized by increasing extracellular Ca⁺⁺ concentration to 1.5 mM and to 2.0 mM.

Ro 5-4864, a specific ligand for peripheral type benzodiazepine (BZ) binding site, inhibited superoxide generation induced by FMLP, while clonazepam (CNZ), which is selective for brain sites, did not possess any activity. Ro 15-1788, a central type BZ receptor antagonist, did not show any antagonistic activity on DZP-dependent inhibition.

A new physiological property for substances presenting an affinity for peripheral type BZ binding sites is supposed. The inhibitory effect of BZ on neutrophil functions seemed to be associated with a Ca⁺⁺-involving mechanism.     

Concordance among three self-reported measures of medication adherence and pharmacy refill records.

OBJECTIVE: To evaluate the level of agreement among three previously validated self-reported medication adherence measures and pharmacy refill records (RRs). DESIGN: Cross-sectional study. SETTING: Five primary care physician office sites in rural northeast Georgia. PARTICIPANTS: 139 adult patients with one or more of these chronic diseases: hypertension, diabetes mellitus, hypercholesterolemia, hypothyroidism, or a condition requiring hormone replacement therapy. INTERVENTIONS: Study participants completed the Brief Medication Questionnaire (BMQ), the Medication Adherence Survey (MAS), and the Medical Outcomes Study (MOS) instruments; pharmacy RRs for the medication or medications being used to treat the target disease were obtained from pharmacies used by the study participants. MAIN OUTCOME MEASURES: Adherence to medication therapy for target disease. RESULTS: Participants were nearly all white (98.6%), consistent with the Appalachian area in which the study was conducted, and mostly women (71.9%). While 91.4% of study participants reported taking their study medication most or all of the time, RRs showed mean adherence rates of 82.6%, 82.1%, 79.1%, 74.6%, and 69.8% for diabetes mellitus, hypertension, hypothyroidism, hypercholesterolemia, and hormone replacement therapy, respectively. Moderate correlations of .234, .261, and .213 were found between RRs and the MAS, MOS, and BMQ belief screen, respectively. Spearman correlations ranged from .091 between RRs and the BMQ regimen subscale to .313 between MOS and MAS. Pearson chi-square tests showed that only the BMQ belief subscale was significant in this study. CONCLUSION: Because of the weak to moderate concordance found among validated measures of adherence, the selection of a useful adherence measure in pharmacy practice is difficult. These findings underscore the difficulty in both assessing patients' medication-taking behavior and assessing and comparing the results of adherence research. The development of valid and reliable measures for easily assessing medication adherence behavior in community pharmacies is needed.     

Clinical study on pharmacological interaction between nimesulide and warfarin.

This article describes the pharmacological interaction between nimesulide, a recently introduced non-steroidal anti-inflammatory drug, and warfarin, an indirect anticoagulant. The aim of the study was to demonstrate if nimesulide could potentiate the activity of this anticoagulant drug, as previously shown by some authors. Ten patients, who were taking 5 mg/day of warfarin, were treated with nimesulide 100 mg twice a day, for seven days: the association of the two drugs did not alter, in a statistical way, neither prothrombin time, nor partial thromboplastin time, nor fibrinogenemia, nor bleeding time. The findings showed that, in a short-term treatment, there was no bleeding risk in combining warfarin with nimesulide.     

Synergistic anticonvulsant effect of valproic acid and ethosuximide on pentylenetetrazole-induced epileptic phenomena in rats

The possible synergistic effect of valproic acid and ethosuximide in combination on pentylenetetrazole-induced epilepsy was investigated in rats. Valproic acid and ethosuximide administered intraperitoneally both showed dose-dependent anti-epileptic activity towards pentylenetetrazole-induced myoclonias and tonic-clonic seizures. The valproic acid-ethosuximide combination had a synergistic pharmacological effect. Against myoclonias combined valproic acid-ethosuximide produced a non-significant decrease in the effective dose of both drugs compared with treatment with either drug alone. In the case of tonic-clonic seizures the protective effect against the seizures was significantly increased by combined treatment compared with treatment with either drug alone. Neither plasma concentrations nor any other pharmacokinetic parameters were significantly changed when the same doses of valproic acid and ethosuximide were given, singly or in combination.     

Effects of prostaglandin A1 on renal handling of salt and water in congestive heart failure

Prostaglandin A1 (PGA1) was infused at the rate of 1/microgram/kg/min in 10 patients with decompensated heart failure under conditions of water loading (5 patients) or water deprivation (5 patients). During water loading, PGA1 increased urinary excretion of sodium, potassium, chloride, calcium, and magnesium, as well as free-water clearance. During water deprivation, it increased free-water reabsorption. Gomerular filtration rate was increased slightly by PGA1 only when it was given with an infusion of hypertonic mannitol during water deprivation. This selective action of PGA1, which increased the excretion but not the reabsorption of free water, suggests its use to correct certain hypo-osmolar conditions. The site of action of PGA1 on the kidney seems to be in the tubules and mainly in the proximal tubules. These findings might be important in the understanding of the role of renal prostaglandins.     

Nitroprusside in vitro inhibits platelet aggregation and intracellular calcium translocation. Effect of haemoglobin

The biologically final active compound of nitrovasodilators is now supposed to be nitric oxide (NO), a labile substance identical to EDRF. The effects of nitroprusside on platelet functions were studied in vitro. Platelet aggregation induced by several stimuli (ADP, collagen, arachidonic acid and PAF) was inhibited by increasing concentrations of the drug (1-50 uM); interestingly, the potency of nitroprusside is higher when PAF is employed as stimulating agent in comparison with the other agonists (ED50 = 2 uM for ADP, 2.5 uM for A.A., 4.5 uM for collagen and 0.3 uM for PAF-induced aggregations). The concomitant addition of haemoglobin is able to reverse the inhibitory effect of nitroprusside, according to the view that haemoglobin possesses a high affinity for NO, thus antagonizing the effect of this compound. Nitroprusside was also able to inhibit intracellular calcium translocation, as studied with the Quin 2 technique, induced by PAF and arachidonic acid. Fron these observations the hypothesis may be suggested that nitroprusside inhibits platelet functions by mimicking the endogenous NO, and that the intracellular calcium metabolism is involved in the inhibitory activity of the drug.     

Methylation of α‐Amino Acids and Derivatives Using Trimethylsilyldiazomethane

A study of the methylation of N‐nosyl‐α‐amino acids and derivatives with trimethylsilyldiazomethane is here reported. Trimethylsilyldiazomethane allows the chemo‐specific methylation of the carboxyl function of N‐nosyl‐α‐amino acids in high yields and purity. This method provides a practical route to N‐methyl‐α‐amino acids avoiding the use of the more toxic and explosive diazomethane. This simple and safe methylation methodology of α‐amino acids and derivatives is not limited to organic synthesis and involves the use of a commercially available reagent as well.     

Nevirapine plasma exposure affects both durability of viral suppression and selection of nevirapine primary resistance mutations in a clinical setting

The relationship between nevirapine plasma concentrations and the durability of both viral suppression (VS) and selection of nevirapine primary resistance mutations (PRMs) was evaluated. A nevirapine trough concentration (Ctrough) of >4,300 ng/ml was found to predict longer VS. Patients with nevirapine Ctrough s ranging from 3,100 to 4,300 ng/ml had higher probabilities of developing PRMs than those with nevirapine Ctrough s below and above this concentration interval.