Screening of hepatoprotective plant components using a HepG2 cell cytotoxicity assay

The aim of this clinical study was to investigate the influence of beclomethasone dipropionate (BDP) inhalation therapy on respiratory bacterial infection in patient with an asthmatic attack. We studied 267 asthmatic attack episodes of 241 patients with/without BDP inhalation therapy. There was no difference between two groups in %peak flow, body temperature, CRP, WBC count, bacterial culture of sputum on admission. BDP inhalation therapy has little influence on respiratory bacterial infection at an asthmatic attack.     

Mechanisms of acute respiratory insufficiency in patients with hyperglycemic coma

Basic parameters of pulmonary gas exchange, central and pulmonary hemodynamics, and colloid osmotic pressure were investigated in 31 patients in diabetic hyperglycemic coma over the course of intensive care. Pulmonary gas exchange disorders were observed in all patients in the presence of increased shunting of the blood in the lungs and disorders of transcapillary liquid exchange. On the other hand, we failed to obtain data indicative of an increase in the volume of extravascular water in the lungs. However, it does not rule out the possibility of iatrogenic disorders of gas exchange during noncontrolled rehydration.     

The role of antibiotics in the treatment of periodontitis (Part 2--Controlled drug delivery)

Since last reviewing the field, controlled release products have made the jump from research to clinical practice. The potential to extend the efficacy of periodontal therapy with such products is exciting, but also needs careful evaluation. This review will look at recent developments and also will examine the eventual place for these products in periodontics.     

Absorption, disposition kinetics, and metabolic pathways of cyclohexene oxide in the male Fischer 344 rat and female B6C3F1 mouse

Cyclohexene oxide (CHO) is a monomer intermediate used in the synthesis of pesticides, pharmaceuticals, and perfumes. Although CHO has a variety of industrial uses where direct human exposure is possible, very little is known about its fate in the body. Therefore, the objectives of this study were to determine the absorption, distribution, metabolism, and excretion of cyclohexene oxide after oral, intravenous, and dermal exposure in male Fischer 344 rats and female B6C3F, mice. After intravenous administration of [14C]CHO (50 mg/kg), CHO was rapidly distributed, metabolized, and excreted into the urine. Plasma concentrations of CHO rapidly declined and were below the limit of detection within 60 min. Average (+/- SD) values for terminal disposition half-life, apparent volume of distribution at steady-state, and systemic body clearance were: 19.3 +/- 1.6 min; 0.44 +/- 0.08 liter/kg; and 31.3 +/- 0.5 ml/kg * min, respectively. After oral administration of [14C]CHO (10 and 100 mg/kg), it was found that 14C-equivalents were rapidly excreted in the urine of both species. At 48 hr, the majority of the dose (73-93%) was recovered in urine, whereas fecal elimination accounted for only 2-5% of the dose. At no time after oral administration was parent CHO detected in the blood. However, its primary metabolite cyclohexane-1,2-diol was present for different lengths of time depending on the dose. Four metabolites were detected and identified in mouse urine by MS: cyclohexane-1,2-diol; cyclohexane-1,2-diol-O-glucuronide; N-acetyl-S-(2-hydroxycyclohexyl)-L-cysteine; and cyclohexane-1,2-diol-O-sulfate. The sulfate conjugate was not present in rat urine. Topical application of [14C]CHO (60 mg/kg) provided poor absorption in both species. The majority of 14C-equivalents applied dermally were recovered from the charcoal skin trap (approximately 90% of the dose). Only 4% of the dose was absorbed, and the major route of elimination was via the urine. To evaluate the toxicity of CHO, animals were given daily doses of CHO orally and topically for 28 days. No statistically significant changes in final body weights or relative organ weights were noted in rats or mice treated orally with CHO up to 100 mg/kg or up to 60 mg/kg when given topically. Very few lesions were found at necropsy, and none were considered compound related. In conclusion, regardless of route, CHO is rapidly eliminated and excreted into the urine. Furthermore, after either oral or dermal administration, it is unlikely that CHO reaches the systemic circulation intact due to its rapid metabolism, and is therefore unable to cause toxicity in the whole animal under the test conditions used in this study.     

Nigrostriatal dopaminergic activities in dementia with Lewy bodies in relation to neuroleptic sensitivity: comparisons with Parkinson's disease

BACKGROUND: In dementia with Lewy bodies (DLB) mild extrapyramidal symptoms are associated with moderate reductions in substantia nigra neuron density and concentration of striatal dopamine. Many DLB patients treated with typical neuroleptics suffer severe adverse reactions, which result in decreased survival. METHODS: In a series of DLB cases, with and without neuroleptic sensitivity, substantia nigra neuron densities, striatal dopamine and homovanillic acid concentrations, and autoradiographic [3H]mazindol and [3H]raclopride binding (to the dopamine transporter and D2 receptor, respectively) were analyzed and compared to control and idiopathic Parkinson's disease cases. RESULTS: D2 receptors were up-regulated in neuroleptictolerant DLB and Parkinson's disease compared to DLB without neuroleptic exposure and controls. D2 receptors were not up-regulated in DLB cases with severe neuroleptic reactions. Dopamine uptake sites were reduced concomitantly with substantia nigra neuron density in Parkinson's disease compared to controls, but there was no significant correlation between substantia nigra neuron density and [3H]mazindol binding in DLB groups. There was no significant difference in substantia nigra neuron density, [3H]mazindol binding, and dopamine or homovanillic acid concentration between neuroleptic-tolerant and -sensitive groups. CONCLUSIONS: Failure to up-regulate D2 receptors in response to neuroleptic blockade or reduced dopaminergic innervation may be the critical factor responsible for neuroleptic sensitivity.     

Randomly amplified polymorphic DNA genotyping of serogroup A meningococci yields results similar to those obtained by multilocus enzyme electrophoresis and reveals new genotypes

Randomly amplified polymorphic DNA (RAPD) genotyping was applied to one representative strain of each of the 84 electrophoretic types (ETs) of Neisseria meningitidis serogroup A previously defined by multilocus enzyme electrophoresis (MEE) (J.-F. Wang et al., Infect. Immun. 60:5267-5282, 1992). Twenty-seven additional isolates comprising six ETs were also tested. MEE and RAPD genotyping yielded similar dendrograms at the subgroup level. Similar results were obtained by both methods for 18 serogroup A meningococci isolated in The Netherlands between 1989 and 1993. Ten of these isolates defined a new subgroup, designated subgroup IX. One isolate belonged to the ET-5 complex, normally associated with serogroup B strains (D. A. Caugant et al., Proc. Natl. Acad. Sci. USA 83:4927-4931, 1986). By RAPD genotyping, meningococci can be linked to previously characterized genotypes by using a computerized database, and dendrograms based on cluster analyses can easily be generated. RAPD analysis offers advantages over MEE since intermediate numbers of isolates of serogroup A meningococci can quickly be assigned to known subgroups and new subgroups can be defined.     

Effects of a unit of instruction in mental health on rural adolescents' conceptions of mental illness and attitudes about seeking help

The present study investigated the effects of a unit of instruction in mental health on rural adolescents' conceptions of mental illness and their attitudes about seeking professional help for emotional problems. Forty students enrolled in a rural Mississippi high school participated. Twenty were designated as the treatment group and twenty served as the control group. Results indicated that scores on both dependent variables (attitudes about seeking professional help and conceptions of mental illness) increased significantly for the treatment group and, further, these scores did not decrease significantly when the students were tested again twelve weeks later. The findings are discussed in the context of educating rural youth about mental illness with the express purpose of removing the stigma associated with the help-seeking process.