Showing papers by "Christina Wang published in 2003"

Semen Quality in Relation to Biomarkers of Pesticide Exposure

Abstract: We previously reported reduced sperm concentration and motility in fertile men in a U.S. agrarian area (Columbia, MO) relative to men from U.S. urban centers (Minneapolis, MN; Los Angeles, CA; New York, NY). In the present study we address the hypothesis that pesticides currently used in agriculture in the Midwest contributed to these differences in semen quality. We selected men in whom all semen parameters (concentration, percentage sperm with normal morphology, and percentage motile sperm) were low (cases) and men in whom all semen parameters were within normal limits (controls) within Missouri and Minnesota (sample sizes of 50 and 36, respectively) and measured metabolites of eight current-use pesticides in urine samples provided at the time of semen collection. All pesticide analyses were conducted blind with respect to center and case-control status. Pesticide metabolite levels were elevated in Missouri cases, compared with controls, for the herbicides alachlor and atrazine and for the insecticide diazinon [2-isopropoxy-4-methyl-pyrimidinol (IMPY)]; for Wilcoxon rank test, p = 0.0007, 0.012, and 0.0004 for alachlor, atrazine, and IMPY, respectively. Men from Missouri with high levels of alachlor or IMPY were significantly more likely to be cases than were men with low levels [odds ratios (ORs) = 30.0 and 16.7 for alachlor and IMPY, respectively], as were men with atrazine levels higher than the limit of detection (OR = 11.3). The herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and metolachlor were also associated with poor semen quality in some analyses, whereas acetochlor levels were lower in cases than in controls (p = 0.04). No significant associations were seen for any pesticides within Minnesota, where levels of agricultural pesticides were low, or for the insect repellent DEET (N,N-diethyl-m-toluamide) or the malathion metabolite malathion dicarboxylic acid. These associations between current-use pesticides and reduced semen quality suggest that agricultural chemicals may have contributed to the reduction in semen quality in fertile men from mid-Missouri we reported previously.

Endonasal transsphenoidal approach for pituitary adenomas and other sellar lesions: an assessment of efficacy, safety, and patient impressions.

Abstract: Object. The direct endonasal approach performed with the aid of an operating microscope for removal of pituitary tumors has the potential advantage over the traditional sublabial route of minimizing postoperative rhinological complications, yet maintaining a high degree of efficacy and safety. To assess the effectiveness of this procedure, tumor remission rates and surgical complications were documented, and patients' postoperative complaints were recorded using a questionnaire. Methods. One hundred consecutive patients underwent 109 endonasal operations for tumor removal. At a median follow-up period of 16 months (range 3–45 months), surgical remission rates were as follows: in 40 patients with endocrine-inactive macroadenomas, 95% for noninvasive and 40% for invasive tumors; in the 20 patients with prolactinomas, 75% for prolactinomas with an initial prolactin (PRL) level lower than 200 ng/ml, 33% for those with a PRL level between 200 and 600 ng/ml, and 0% for those with a PRL level higher than 1400 ng...

Key apoptotic pathways for heat-induced programmed germ cell death in the testis.

Abstract: Short-term exposure (43 C for 15 min) of the rat testis to mild heat results within 6 h in stage- and cell-specific activation of germ cell apoptosis. Initiation of apoptosis was preceded by a redistribution of Bax from a cytoplasmic to paranuclear localization in heat-susceptible germ cells. Here we show that the relocation of Bax is accompanied by cytosolic translocation of cytochrome c and is associated with activation of the initiator caspase 9 and the executioner caspases 3, 6, and 7 and cleavage of poly(ADP) ribose polymerase. Furthermore, early in apoptosis, a significant amount of Bax also accumulates in endoplasmic reticulum, as assessed by Western blot analyses of fractionated testicular lysates. In additional studies using the FasL-defective gld mice, we have shown that heat-induced germ cell apoptosis is not blocked, thus providing evidence that the Fas signaling system may be dispensable for heat-induced germ cell apoptosis in the testis. Taken together, these results demonstrate that the mitochondria- and possibly also endoplasmic reticulum-dependent pathways are the key apoptotic pathways for heat-induced germ cell death in the testis.

Functional role of inducible nitric oxide synthase in the induction of male germ cell apoptosis, regulation of sperm number, and determination of testes size: evidence from null mutant mice.

Abstract: Inducible nitric oxide synthase (iNOS) through its product, nitric oxide (NO), may contribute to the induction of germ cell apoptosis. Using adult iNOS-deficient mice, we characterized the reproductive hormonal profile and the testicular phenotype. Although there was no difference in body weight, mean testis weights in mutant mice were 30.77% higher, and testicular sperm count was 65.51% higher than control animals. No significant differences were apparent in plasma LH, FSH, and testosterone levels between these mice. Compared with wild-type mice, histomorphometric analysis showed that the mutant mice had a 39.63% increase in the number of pachytene spermatocytes and 33.79% in round spermatids, with no apparent changes in the number of preleptotene spermatocytes and spermatogonia. The incidence of spontaneous germ cell apoptosis detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay was lower at stages I-IV and XI-XII of iNOS-mutant mice compared with wild-type animals. The rate of germ cell proliferation estimated by quantitative assessment of the bromodeoxyuridine labeled preleptotene spermatocytes showed no significant change between wild-type and iNOS-deficient mice. When applying testicular warming (43 C for 15 min) to mice, the rate of germ cell apoptosis was elevated predominantly at early (I-IV) and late (XI-XII) stages, and less during stages V-VI, VII-VIII, and IX-X at 2 and 6 h after heat exposure in the wild-type mice. In contrast, the rate of apoptosis in mutant mice was markedly decreased at early and late stages 2 and 6 h after heat exposure. Pachytene spermatocytes and early round spermatids were most susceptible to heat-induced apoptosis in both mutant and control animals. Our studies demonstrate that: 1) deficiency of iNOS results in failure to eliminate a small portion of pachytene spermatocytes and round spermatids by apoptosis, resulting in a remarkable increase in testis weight and sperm output; 2) deficiency of iNOS confers partial resistance to heat-induced germ cell apoptosis. These experiments suggest that iNOS plays a physiological role in regulation of germ cell number and in determining testicular size.

A simple self-report diary for assessing psychosexual function in hypogonadal men

Abstract: To examine the performance of a self-report diary to assess psychosexual function in hypogonadal men, 2 groups of eugonadal men and 2 groups of hypogonadal men were asked to record and score parameters for sexual desire, sexual enjoyment, sexual performance, sexual activity, and positive and negative moods daily for 7 days before a clinic visit (data set 1 and 2). The hypogonadal men were also assessed after testosterone replacement and some of the eugonadal men were studied while they were on placebo treatment. In this retrospective analysis, sexual function parameters (sexual desire, performance, and activity score) in the diary discriminated between the hypogonadal and eugonadal men with all measures significantly lower in hypogonadal men (all parameters P <.0001). Significant improvements in sexual desire and performance as well as sexual activity scores (P <.0001 for all parameters) in hypogonadal men after testosterone treatment were readily detected within 30 days. Mood and functional parameters did not show any change over time in eugonadal men on placebo treatment. The mood parameters assessed by the diary showed an excellent correlation with those assessed by the Profile of Mood States. Mood parameters were not clearly different between eugonadal and hypogonadal men at baseline. With testosterone treatment positive mood parameters were significantly increased (P <.0028 and.0001 set in data 1 and 2, respectively), and negative mood parameters improved in hypogonadal men (P <.0003 in data set 2). We conclude that this simple self-report diary is useful in assessing the sexual function and mood profile of hypogonadal subjects in clinical research.

Three-year follow-up of androgen treatment in hypogonadal men: preliminary report with testosterone gel.

Abstract: Transdermal testosterone gels represent an effective alternative to injectable testosterone preparations. Short-term (6 months) data demonstrated positive effects on muscle, bone, fat, libido and mood. This report provides a preliminary analysis of longer-term treatment with a testosterone gel (AndroGel or Testogel) in a group of men aged 19-67 years of age. The positive effects of testosterone treatment on all of the above parameters persisted in this 3-year follow-up. The benefits occurred independent of age (equally in the older and younger subjects). The positive effects of transdermal testosterone gel on bone mineral density previously identified at 6 months of treatment, continued with time. The positive effects on bone mineral density were greater in the spine than the hip. There were minimal effects on lipid levels. Levels of prostate-specific antigen (PSA) increased with testosterone treatment but, in general, remained in the normal range. Three subjects (1.8%) were shown to have elevated PSA and biopsy-proven prostate cancer. It was not possible to determine if this incidence is above the background rate. Monitoring for prostate disease through PSA measurements and digital rectal examination is recommended for hypogonadal men in the older age groups when treated with testosterone.