Assessment of fertility among mustard-exposed residents of Sardasht, Iran: a historical cohort study

BACKGROUND: Mustard gas (HD) is an alkylating agent with mutagenic and carcinogenic effects. Previous reports have demonstrated the ability of this class of compounds to cause adverse reproductive effects, however as of the time of this writing, few correlations have been established between HD exposure and human infertility. In the present study we hypothesize that infertility among mustard-exposed individuals is higher than among the general population. METHODS: 117 couples, 90 with at least one partner, and 27 with both partners exposed to HD in June 1987, were evaluated for occurrence of infertility (defined as the failure to conceive after 12 months of unprotected intercourse). Two groups of subjects were considered in order to establish dose-responsive effect of HD on fertility. One cohort was married at the time of exposure and were evaluated in a time period 12 months from that date. The second cohort married after the date of exposure and each couple was evaluated for a year during a period following marriage. Measurements of these subjects were compared with worldwide incidence of fertility. RESULTS: A 7.5% rate of infertility was observed among couples who were married at the time of exposure; and a rate of 10.3% was noted among individuals single at exposure and subsequently married, for an overall rate of 8.3%, which compares with a worldwide rate of 10-15%. Conclusions: This study showed that within a population of HD-exposed individuals, elevated environmental levels of the agent during a time period in which couples were actively attempting to conceive, failed to correlate with increased risk of infertility. However, these results must be interpreted with caution based on experimental design which limits the definition of infertility to one 12 month time period.     

Chemical and biological assessment of a traditional chinese herbal decoction prepared from Radix Astragali and Radix Angelicae Sinensis: orthogonal array design to optimize the extraction of chemical constituents

Danggui Buxue Tang (DBT) is a simple decoction, having about 800 years of usage in China to treat menopausal irregularity in women, which contains two herbs: Radix Astragali (Huangqi) and Radix Angelicae Sinensis (Danggui). Traditionally, boiling water has been used for preparing DBT; however, the optimized conditions of extraction have not yet been determined. Here, the amounts of Radix Astragali-derived astragaloside IV, calycosin, formononetin, and Radix Angelicae Sinensis-derived ferulic acid and ligustilide were determined in DBT, which were extracted according to an orthogonal array experimental design having three variable parameters: extraction time, extraction volume and number of repeats of the extraction. Our results suggest that extraction time and number of repeats of the extraction are two crucial factors, while extraction volume is a subordinate factor. The optimized conditions for extraction were therefore established. Besides the chemical composition, the estrogenic and anti-platelet aggregation activities of DBT were determined in different groups of the extraction, and the results of bioassays were in line with the amounts of the analyzed chemical ingredients. The results provide a model system for establishing the quality assurance of the herbal preparation.     

Functional analysis of the human orthologue of the<Emphasis Type="Italic"> RSP5</Emphasis>-encoded ubiquitin protein ligase,hNedd4, in yeast

hNedd4 and Rsp5p are orthologous ubiquitin ligases that contain a catalytic Hect domain, a C2 domain and multiple WW domains that mediate interactions with proteins. hNedd4 associates with the epithelial sodium channel and mutations disrupting this interaction lead to Liddle's syndrome, a heritable hypertension. Yeast Rsp5p ubiquitinates plasma membrane receptors and transporters and regulates their endocytosis. To determine whether the human enzyme has activity in yeast, hNEDD4 was expressed in yeast from the RSP5 or GAL1/10 promoters. Ectopic hNedd4 improved the growth and partially suppressed the endocytosis defect of rsp5 mutant cells, although it did not restore the viability of the rsp5-delta strain. Wild-type cells harboring hNedd4 grew better at elevated temperature and on media containing cycloheximide. In contrast, hNedd4 WW domain mutants inhibited the growth of yeast when expressed at high levels. Our results show that hNedd4 affects cell growth, endocytosis and cycloheximide tolerance of yeast cells.     

Renal cell carcinoma,chromophobe type,with collecting duct carcinoma and sarcomatoid components

We report a case of a 72-year-old man with a chromophobe renal cell carcinoma that had both sarcomatoid and collecting duct carcinoma components. The 7-cm tumor occupied the entire lower pole of the kidney and infiltrated the renal parenchyma and the pelvic-calyceal system. Histologically, it had an area of classic chromophobe renal cell carcinoma that merged into a sarcomatoid component. Closely intermixed with the sarcomatoid component was a collecting duct carcinoma component characterized by highly pleomorphic, epithelioid cells arranged in cords, nests, and tubulomicrocystic structures. The cords, nests, and tubules were associated with a florid desmoplastic stromal response and numerous inflammatory cells. In addition, dysplastic changes were noted in adjacent nonneoplastic collecting duct epithelium. Immunohistochemical studies confirmed the presence of 3 distinct components in this patient's tumor. To the best of our knowledge, this is the first reported case of a chromophobe renal cell carcinoma with sarcomatoid and collecting duct carcinoma components.     

Infertility,blood mercury concentrations and dietary seafood consumption: a case-control study

Objective To compare blood mercury concentrations of infertile couples with those of fertile couples in Hong Kong, and to examine the relationship between blood mercury concentrations and seafood consumption.
Design Case–control study.
Setting In vitro fertilisation (IVF) Unit and Antenatal Unit of a university teaching hospital.
Sample One hundred fifty-seven infertile couples attending IVF treatment and 26 fertile couples attending antenatal care without known occupational exposure to mercury.
Methods Mercury concentrations in whole blood were measured by cold vapour atomic absorption spectrophotometry. A dietitian recorded the quantity of seafood consumption among infertile couples via a food-frequency questionnaire. Blood mercury concentrations and quantity of seafood consumption were compared between infertile and fertile couples.
Main outcome measures Whole blood mercury concentrations, quantity of seafood consumption.
Results Infertile couples had higher blood mercury concentrations than fertile couples. 'Infertile males with abnormal semen' and 'infertile females with unexplained infertility' also had higher blood mercury concentrations than their fertile counterparts. Blood mercury concentrations were positively correlated with quantity of seafood consumption. Infertile subjects with elevated blood mercury concentrations consumed a larger amount of seafood.
Conclusion Higher blood mercury concentration is associated with male and female infertility. Higher seafood consumption is associated with elevated blood mercury concentrations in our infertile population.     

Exercise and intestinal polyp development in APCMin mice

PURPOSE: Epidemiological evidence suggests that physical activity protects against colon cancer. We previously used a mouse predisposed to intestinal polyps (APCMin) to evaluate this association and found the suggestion of fewer polyps in exercised males but not females. The present study was designed to further explore the potential exercise x sex interaction on polyp development and to begin to look at potential mechanisms. METHODS: Six-week-old APCMin mice (N = 60 males; 60 females) were randomly assigned to one of two groups by sex: treadmill running at 20 m.min-1, 5% grade, 45 min.d-1, 5 d.wk-1 (EX) or nonrunning controls (CON) (N = 30 per group). EX mice ran in running wheels while in quarantine (weeks 0-3), followed by treadmill running weeks 3-8. Body weights were measured weekly. Urine was collected at 5 wk and fasting blood at 7.5 wk. Body composition was measured, serum was frozen, and polyp number and size were measured at sacrifice. RESULTS: EX resulted in lower body weights (P < 0.01) and reduced fat mass (P < 0.01). Fasting glucose was lower in EX (P < 0.01), and leptin was lower in EX (P = 0.05) compared with CON. EX did not affect serum insulin-like growth factor-1 or urinary corticosterone. Total polyp number and size were not statistically different between groups; however, there were fewer jejunal polyps in EX (3.6 +/- 0.7, mean +/- SE) versus CON males (5.2 +/- 0.8; P = 0.04) and an even larger difference when only the consistent runners were kept in the analysis (2.7 +/- 0.5 in EX; P = 0.01). CONCLUSION: Despite favorable changes in body composition, blood glucose, and leptin, 8 wk of running resulted in only minor changes related to polyp development in male but not female APCMin mice.     

Modeled evidence of force reduction at the extensor carpi radialis brevis origin with the forearm support band

PURPOSE: Although the forearm support band has been hypothesized to reduce force and thus inflammation and degeneration at the extensor carpi radialis brevis (ECRB) origin, little evidence exists to support an actual effect. We present both a cadaveric and clinical model that show the effect and principles of the forearm support band. METHOD: The cadaver model measured forces at the ECRB origin as various pressures were applied to the forearm support band and while the ECRB tendon was loaded distally. For clinical correlation support band pressure during rest and activity was measured in healthy individuals. RESULTS: Our results revealed an increased forearm support band effect with increased band pressure and a decreased relative effect with increased force applied distally. For clinical correlation the support band pressure during activity was measured in 21 healthy volunteers while controlling for the application pressure in 2 common support band designs. This resulted in activity pressures ranging from 43 to 192 mm Hg dependent on the starting pressure of application. CONCLUSIONS: Although further clinical evaluation is necessary to determine the most appropriate clinical indications and application pressures for the forearm support band these combined results suggest that the forearm support band may be most effective when applied to 30 to 50 mm Hg at rest, resulting in up to 120 mm Hg pressure during activity. According to our model this would result in a force reduction at the ECRB origin of approximately 13% to 15% throughout a range of activity levels.