Synthesis and Purine P2X Receptor Antagonist Activity of Thiazole Derivatives

The ability of 12 new thiazole derivatives to influence the muscle contractility mediated by purine P2X receptors has been studied in vitro using isolated tissues of rats and guinea pigs. Most of the synthesized compounds did not cause significant effects, but two compounds exhibited pronounced antagonism with respect to P2X-mediated contractility response. These compounds offer a good starting point for the synthesis of new effective antagonists of P2 receptors. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 6, pp. 22 – 25, June, 2005.     

Correction of hallux valgus deformity with distal soft tissue realignment and proximal metatarsal osteotomy

Abstract Fifty moderate to severe hallux valgus deformities were corrected with a distal soft tissue realignment and proximal crescentic metatarsal osteotomy. With an average follow-up of 5.6 years, 40 feet (80%) were pain free and 42 (84%) caused no functional limitation. The average hallux valgus angle improved from 38.2° preoperatively to 12.4° at follow-up. The average intermetatarsal angle improved from 15.4° to 6.8°. The arch of motion of the first metatarsophalangeal joint was 75° preoperatively and 62° at follow-up. According to the AOFAS scoring system, 29 results (58%) were excellent, 14 (28%) good, 2 (4%) fair and 5 (10%) poor. The 5 poor results were attributed to recurrence of hallux valgus (2 cases), stiffness (1), hallux varus (1) and malunion of the osteotomy in dorsiflexion (1). The incidences of hallux varus and malunion in dorsiflexion were 8% and 14%, respectively. This technique is valuable in correction of moderate to severe hallux valgus deformities.     

Medizinische Beurteilungskriterien zu bandscheibenbedingten Berufskrankheiten der Lendenwirbelsäule (II)

The first part of this serial paper dealt with the medical criteria used in evaluation of the clinical picture caused by physical stress and the evaluation of other candidate causes and was published in issue no. 3/2005 (pp. 711–752) of Trauma and Berufskrankheit. This follow-up paper (II) presents criteria to be used in the evaluation of whether it is necessary to give up the occupations putting the spine at risk and in estimation of the degree of disability.     

Pharmacotherapy of ventricular fibrillation. A prospective study in an emergency medical service

This prospective study investigated the effects of standard pharmacotherapy in out-of-hospital ventricular fibrillation (VF) after i.v. or endobronchial (e.b.) administration of epinephrine and lidocaine. METHODS. Only patients presenting with out-of-hospital VF were included in this study, whereby VF of noncardiac origin was excluded. Cardiopulmonary resuscitation (CPR) was performed according to the guidelines of the American Heart Association. Basic life support was initiated by Emergency Medical Service (EMS) technicians. The first step of advanced life support was immediate defibrillation by the EMS physician. Epinephrine was given in doses of 2.5 mg e.b. or 1.0 mg i.v. If indicated, patients received 200-500 mg lidocaine e.b. or 100 mg i.v. The course of CPR was tape-recorded and 2-3 blood samples were taken from each patient for drug monitoring. Plasma levels of epinephrine and lidocaine were measured by high-pressure liquid and gas chromatography, respectively, and then correlated to the course of CPR. RESULTS. Forty-seven patients presented VF on arrival of the EMS physician. Restoration of spontaneous circulation was achieved in 64% (Table 3), and 30% of the patients were discharged from hospital without major neurologic deficits. Immediate defibrillation before initiation of pharmacotherapy produced a success rate of 15.8%, whereas defibrillation after drug therapy was successful in 61.5% of cases. Following e.b. instillation of 2.5 mg epinephrine (Fig. 1), median peak concentrations of epinephrine (40.2, range 4.0-79.8 ng/ml) were reached after 3-4 min and plasma levels greater than or equal to 10 ng/ml were seen for 20 min. After i.v. injection of 1.0 mg epinephrine (Fig. 2) maximum concentrations (71.6, range 4.7-104.2 ng/ml) were measured after 1-2 min and plasma levels decreased below 10 ng/ml after 10 min. Following e.b. instillation of 400-500 mg lidocaine mean lidocaine concentrations within the therapeutic range (2-5 micrograms/ml) were reached after 4-5 min and remained within these limits for 20-30 min. Peak concentrations were obtained after 12 min. Doses of 200-320 mg lidocaine e.b. failed to achieve therapeutic plasma levels (Fig. 3). Regarding the pharmacodynamic aspects of drug therapy, 22.5% of the initial survivors were resuscitated from VF without therapeutic epinephrine, presenting with mean endogenous epinephrine concentrations of 7.1 ng/ml, 51.6% of patients were resuscitated after epinephrine therapy with plasma concentrations greater than 20 ng/ml. In only 1 case could a relationship be demonstrated between the administration of lidocaine and resuscitation success. CONCLUSION. In CPR, the e.b. administration of epinephrine and lidocaine is a reliable alternative to the i.v. injection route of these drugs. Recommended doses are 2.5 mg for epinephrine and 400-500 mg for lidocaine. Resuscitation from VF requires immediate epinephrine therapy if initial defibrillation is not successful. Lidocaine has no effect on resuscitation from VF and therefore should be used specifically for antiarrhythmic therapy after restoration of spontaneous circulation.     

An ounce of prevention ... STDs and women's health

Using recent data from the U.S., the argument is reiterated that sexually transmitted diseases (STDs) have serious consequences on female morbidity, mortality, pregnancy outcome and that the cost of screening and treatment can afford significant savings. Since the rosy view of the 1950s that STDs had been eliminated with penicillin, new viral, parasitic and bacterial forms have emerged, and antibiotic-resistant classical STDs have increased yearly. 13 million new cases were reported in 1989, excluding non-reportable diseases and asymptomatic infections, such as over half of chlamydia cases. Mortality is possible from STDs, most notably from AIDS, now among the top 5 causes of death of women aged 15-44. Other fatal outcomes are cervical cancer related to human papilloma virus, accelerated by HIV, pelvic inflammatory diseases (PID) its consequences, ectopic pregnancy. Symptomatic PID affects 1 million women, resulting in 210,000 hospitalizations per year. Ectopic pregnancy accounts for 12% of maternal mortality. STDs are involved in neonatal infections with HIV, syphilis, gonorrhea, chlamydia, cytomegalovirus, and herpes. Chorioamnionitis, a finding in many miscarriages, is caused by many of the same organisms. Several studies have projected sizeable potential savings, even within the current year, by providing STD screening and treatment in family planning clinics and prenatal care, in terms of prevention of hospitalization of women, and intensive care for low birth weight, premature and infected newborns.     

Postprandial thermogenesis in lean and obese subjects after meals supplemented with medium-chain and long-chain triglycerides

The thermic effect of medium-chain triglycerides (MCTs) was studied in six lean and six obese young males by evaluating postprandial thermogenesis (PPT) after the ingestion of mixed meals containing either 38 g long-chain triglycerides (LCTs) or 30 g MCTs plus 8 g LCTs. Postabsorptive resting metabolic rate (RMR) was higher (P less than 0.05) in the obese individuals than in the lean ones. PPT, evaluated as 6-h incremental areas above RMR, was greater (P less than 0.05) in both groups after meals containing MCTs. The thermic effect of MCTs was 119.7 +/- 33.9 and 144.7 +/- 48.8 kJ/6 h in the lean and the obese subjects, respectively. The postprandial response of glucose, insulin, and free fatty acids did not depend on the type of oil contained in the meal. Our study shows that PPT is enhanced in both lean and obese subjects when LCTs in a mixed meal are replaced with MCTs.     

Serum 25-hydroxyvitamin D concentrations of free-living subjects consuming olestra

The effect of olestra on vitamin D status was assessed in a 6-wk, double-blind, placebo-controlled study involving 202 free-living adults. Subjects consumed a total of 20 g/d of olestra or triglycerides in cookies eaten at each meal. A 20-micrograms ergocalciferol capsule was taken with each morning meal. Serum 25-hydroxyergocalciferol (25-OHD2) concentrations rose from approximately 5.7 to 39.0 and 31.7 nmol/L in the placebo and olestra groups, respectively, at week 6. At week 6, 25-OHD2 contributed 46-54% to total serum 25-OHD concentration compared with 11% at baseline. The 19% decrease in serum 25-OHD2 concentrations produced by olestra in this study is equivalent to a decrease of approximately 1.2 nmol/L under nonsupplemented dietary conditions. Ingesting 20 g olestra/d in the diet is thus not expected to affect vitamin D nutritional status.     

Vitamin K in colostrum and mature human milk over the lactation period--a cross-sectional study

Vitamin K was quantitated in the milk of four groups of 15 mothers from 1 d to 6 mo postpartum in a cross-sectional study. Concentrations were 7.52 +/- 5.90 and 6.36 +/- 5.32 nmol/L (3.39 +/- 2.66 and 2.87 +/- 2.40 micrograms/L) in colostrum and mature milk, respectively. Differences between colostrum and mature milk or among samples of mature milk collected at 1, 3, and 6 mo were not statistically significant. Because of significantly increased volumes of milk over the lactation period, approximately twice as much vitamin K was delivered in mature milk as in colostrum. Within normal ranges, concentrations of vitamin K in milk were not predicted by dietary intake of vegetables or fat. Vitamin K was correlated with fat in colostrum and was localized in the lipid core of the milk fat globule but was not associated with membranes. Vitamin K in human milk is insufficient to meet recommended intakes for infants aged less than 6 mo. Population and clinical studies are needed to assess the vitamin K status of exclusively breast-fed infants and to evaluate current recommendations.