Isoflavones and functional foods alter the dominant intestinal microbiota in postmenopausal women

Dietary phytoestrogens, such as isoflavones, are used as food additives to prevent menopause-related disorders. In addition to other factors, their bioavailability strongly depends on the activity of intestinal bacteria but the underlying interactions remain poorly understood. A randomized, double-blind, placebo-controlled study was undertaken with 39 postmenopausal women to characterize changes in the dominant microbial communities of the intestinal tract after 2 mo of isoflavone supplementation with and without pro- or prebiotic. The diversity and composition of the dominant microbiota were analyzed by temporal temperature-gradient gel electrophoresis (TTGE) and fluorescent in situ hybridization. Isoflavones alone stimulated dominant microorganisms of the Clostridium coccoides-Eubacterium rectale cluster, Lactobacillus-Enterococcus group, Faecalibacterium prausnitzii subgroup, and Bifidobacterium genus. The stimulation of the Clostridium coccoides-Eubacterium rectale cluster depended on the women's equol excretion and was transient, with the exception of a prolonged bifidogenic effect. Lasting changes in the diversity of the dominant species were also observed. The probiotic strain supplied could be detected by TTGE during its passage through the intestinal tract, and ingestion of fructooligosaccharides triggered a marked and specific bifidogenic effect. In conclusion, this is the first human study that shows changes in the diversity and composition of dominant bacterial communities in response to dietary supplementation with hormone-related compounds combined with functional foods.     

1,4-Benzodiazepines as inhibitors of respiratory syncytial virus

Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower respiratory tract infections worldwide and is increasingly being recognized as a serious threat to patient groups with poorly functioning immune systems. Our approach to finding a novel inhibitor of this virus was to screen a 20 000-member diverse library in a whole cell XTT assay. Parallel assays were carried out in the absence of virus in order to quantify any associated cell toxicity. This identified 100 compounds with IC(50)'s less than 50 muM. A-33903 (18), a 1,4-benzodiazepine analogue, was chosen as the starting point for lead optimization. This molecule was moderately active and demonstrated good pharmacokinetic properties. The most potent compounds identified from this work were A-58568 (47), A-58569 (44), and A-62066 (46), where modifications to the aromatic substitution enhanced potency, and A-58175 (42), where the amide linker was modified.     

A mode of action for induction of thyroid gland tumors by Pyrethrins in the rat

Prolonged treatment with high doses of Pyrethrins results in thyroid gland tumors in the rat. To elucidate the mode of action for tumor formation, the effect of Pyrethrins on rat thyroid gland, thyroid hormone levels and hepatic thyroxine UDPglucuronosyltransferase activity was investigated. Male Sprague-Dawley CD rats were fed diets containing 0 (control) and 8000 ppm Pyrethrins and female rats diets containing 0, 100, 3000 and 8000 ppm Pyrethrins for periods of 7, 14 and 42 days and for 42 days followed by 42 days of reversal. As a positive control, rats were also fed diets containing 1200-1558 ppm sodium Phenobarbital (NaPB) for 7 and 14 days. The treatment of male rats with 8000 ppm Pyrethrins, female rats with 3000 and 8000 ppm Pyrethrins and both sexes with NaPB resulted in increased thyroid gland weights, which were associated with follicular cell hypertrophy. Thyroid follicular cell replicative DNA synthesis was increased by treatment with Pyrethrins and NaPB for 7 and/or 14 days. Treatment with Pyrethrins and NaPB increased hepatic microsomal thyroxine UDPglucuronosyltransferase activity and serum thyroid stimulating hormone levels (TSH), but reduced serum levels of either thyroxine (T4) and/or triiodothyronine (T3). The effects of Pyrethrins in female rats were dose-dependent, with 100 ppm being a no-effect level, and on cessation of treatment were essentially reversible in both sexes. The concordance between the effects of Pyrethrins and NaPB suggests that the mode of action for Pyrethrins-induced rat thyroid gland tumors is similar to that of some other non-genotoxic inducers of hepatic xenobiotic metabolism.     

Treatment of early--stages I and II--nodular, poorly differentiated lymphocytic lymphoma

Twenty-nine patients with Stages I and II nodular, poorly differentiated lymphocytic lymphoma were treated with radiation therapy or radiation therapy plus chemotherapy. Twenty-two patients with Stage I received radiation to the involved field, the other seven with Stage II received total lymphoid radiation. Complete remission was achieved in all 29. There were no differences in remission duration or survival according to treatment modality. Five of 29 (17%) patients relapsed. No relapses were observed after 5 years. Ten patients died; one patient died of lymphoma, and nine others died in continuous complete remission of various other causes. Sixty-six percent of the patients were alive at 74-160 months (median 118 months). Involved field radiation with or without chemotherapy was well tolerated, producing acceptable toxicity. Substantially more toxicity was observed after total lymphoid irradiation and although cures were also achieved, less toxic treatment programs should be investigated. The low rate of relapse observed in early stages of this lymphoma in this and in other studies is suggestive that cures might be achieved in nearly one-half of the patients presenting in early stage.     

Acetylcholinesterase and neuropathy target esterase in chickens treated with acephate

Reports that near-lethal doses of the pesticide methamidophos (O,S-dimethyl phosphoramidothioate) caused a delayed neurotoxicity (OPIDN) in humans and that another phosphoramidate, isofenphos, caused OPIDN in the hen at high doses, prompted a study of the abilities of acephate (O,S-dimethyl acetylphosphoramidothioate) to inhibit brain acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in vivo. Hens were treated orally with 5-700 mg/kg of acephate, or im with 50-200 micrograms/kg of diisopropyl-fluorophosphate (DFP, positive control) and sacrificed 24 hr later. Brain homogenates were assayed for AChE as an estimate of acute toxicity, for NTE to indicate acephate's potential to cause OPIDN, and for residues of acephate and its metabolite methamidophos. A range finding study confirmed the LD50 level for acephate was approximately 800 mg/kg. Regression analyses indicated an ID50 (a dose that inhibits 50% of activity) for acephate inhibition of AChE of 10 mg/kg and an extrapolated ID50 for inhibition of NTE of 1300 mg/kg, almost twice the LD50. In contrast, ID50 values for DFP were similar for AChE (146 micrograms/kg) and NTE (132 micrograms/kg). Brain methamidophos levels were 10 to 16 percent of the total acephate plus methamidophos brain concentration. The lower the dose of acephate, the higher was the relative percentage of methamidophos. The results show acephate is a more potent inhibitor of AChE than it is of NTE in hens and suggest it would be difficult to administer a single dose of acephate sufficient to cause OPIDN without killing the animal.     

Consumption of salted fish and other risk factors for nasopharyngeal carcinoma (NPC) in Tianjin, a low-risk region for NPC in the People's Republic of China

The dietary habits, occupational exposures, use of tobacco and alcohol, and medical history were compared among 100 patients with histologically confirmed nasopharyngeal carcinoma (NPC) in Tianjin City, People's Republic of China, and 300 neighborhood controls who were individually matched to the patients with regard to age (within 5 yr), sex, and race (Han). Exposure to salted fish was significantly associated with an increased risk of NPC. Four characteristics of exposure to salted fish independently contributed to the increased risk: (a) earlier age at first exposure, (b) increasing duration of consumption, (c) increasing frequency of consumption, and (d) cooking the fish by steaming it rather than frying, grilling, or boiling it. In addition, significant associations were observed for consumption in childhood of salted shrimp paste (increased risk) and carrots (reduced risk), and the three dietary effects (i.e., those from consumption of salted fish, salted shrimp paste, and carrots) were independent of each other. None of the non-dietary factors studied were significantly associated with NPC risk.     

Multi-society guideline for reprocessing flexible gastrointestinal endoscopes. Society for Healthcare Epidemiology of America.

Flexible gastrointestinal endoscopy is a valuable diagnostic and therapeutic tool for the care of patients with gastrointestinal and pancreaticobiliary disorders. Compliance with accepted guidelines for the reprocessing of gastrointestinal endoscopes between patients is critical to the safety and success of their use. When these guidelines are followed, pathogen transmission can be effectively prevented. Increased efforts and resources should be directed to improve compliance with these guidelines. Further research in the area of gastrointestinal endoscope reprocessing should be encouraged. The organizations that endorsed this guideline are committed to assisting the FDA and manufacturers in addressing critical infection control issues in gastrointestinal device reprocessing.     

Abnormal refractoriness in patients with Parkinson''s disease after brief withdrawal of levodopa treatment.

Two pairwise matched groups of patients with mild to moderate Parkinson's disease and a group of normal age matched controls were used to investigate the effects on simple and choice reaction time (RT) of brief withdrawal of levodopa therapy. Comparisons within and across these groups disclosed a selective effect of levodopa withdrawal. After about 12 hours of levodopa deprivation, patients exhibited an exaggeration of normal refractoriness, the well established tendency for RT to increase progressively as the delay between a response and the next imperative signal is reduced below 0.5 s. Increased refractoriness was at least as great for simple as choice RT. Choice RT on trials involving repetition (as opposed to alternation) of the previous response, however, showed no tendency towards greater impairment by brevity of the recovery period or by withdrawal of medication, eliminating an effector based account. With longer recovery periods, RT was unaffected by medication; indeed, unmedicated patients were as fast as normal subjects under these conditions. Even at the briefest delays, fully medicated patients did not differ from normal controls. The paper concludes with a critical review of chronometric studies of medication effects in Parkinson's disease.