Showing papers by "Christina Wang published in 2005"
265 citations
TL;DR: Lower cortisol levels were associated with lower blood pressure and higher vasopressor use, and consideration should be given to monitoring cortisol levels in intubated TBI patients, particularly those receiving high-dose pentobarbital or propofol.
Abstract: Objective:To determine the prevalence, time course, clinical characteristics, and effect of adrenal insufficiency (AI) after traumatic brain injury (TBI).Design:Prospective intensive care unit–based cohort study.Setting:Three level 1 trauma centers.Patients:A total of 80 patients with moderate or se
253 citations
156 citations
TL;DR: GH response to GHRH + ARG and ITT stimulation is sensitive to BMI differences and less so to gender differences, and a higher BMI is associated with a depressed GH response to both stimulation tests.
Abstract: The aim of this study is to assess whether gender and body mass index (BMI) should be considered in developing thresholds to define GH deficiency, using GH responses to GHRH + arginine (ARG) stimulation and insulin tolerance test (ITT). Thirty-nine healthy subjects (19 males, 20 females; ages 21-50 yr) underwent GHRH + ARG, and another 27 subjects (19 males, 8 females; ages 20-49 yr) underwent ITT. Peak GH response was significantly higher (P = 0.005) after GHRH + ARG than with ITT, and this difference could not be explained by age, gender, or BMI. Peak GH response was negatively correlated with BMI in both tests (GHRH + ARG, r = -0.76; and ITT, r = -0.65). Peak GH response to GHRH + ARG was higher in females than males (P = 0.004; ratio = 2.4), but it was attenuated after eliminating the influence of BMI (P = 0.13; ratio = 1.6). No significant gender differences were found in peak GH responses to ITT, which could be due to the smaller number of female subjects studied. GH response to GHRH + ARG and ITT stimulation is sensitive to BMI differences and less so to gender differences. A higher BMI is associated with a depressed GH response to both stimulation tests. BMI should therefore be considered as a factor when defining the diagnostic cut-off points in the assessment of GH deficiency, whereas whether gender should be likewise used is inconclusive from this study.
91 citations
TL;DR: It is concluded that reduction in dietary fat intake (and increase in fiber) results in 12% consistent lowering of circulating androgen levels without changing the clearance.
Abstract: To validate our hypothesis that reduction in dietary fat may result in changes in androgen metabolism, 39 middle-aged, white, healthy men (50-60 yr of age) were studied while they were consuming their usual high-fat, low-fiber diet and after 8 wk modulation to an isocaloric low-fat, high-fiber diet. Mean body weight decreased by 1 kg, whereas total caloric intake, energy expenditure, and activity index were not changed. After diet modulation, mean serum testosterone (T) concentration fell (P < 0.0001), accompanied by small but significant decreases in serum free T (P = 0.0045), 5 alpha-dihydrotestosterone (P = 0.0053), and adrenal androgens (androstendione, P = 0.0135; dehydroepiandrosterone sulfate, P = 0.0011). Serum estradiol and SHBG showed smaller decreases. Parallel decreases in urinary excretion of some testicular and adrenal androgens were demonstrated. Metabolic clearance rates of T were not changed, and production rates for T showed a downward trend while on low-fat diet modulation. We conclude that reduction in dietary fat intake (and increase in fiber) results in 12% consistent lowering of circulating androgen levels without changing the clearance.
74 citations
TL;DR: It is concluded that adult XXY mice have testicular failure and learning deficits, similar to its human counterpart, Klinefelter syndrome.
Abstract: Klinefelter syndrome (XXY males) is the most common sex chromosome aneuploidy. XXY mice were generated by using a four-generation breeding scheme that involves the use of a structurally rearranged Y chromosome, Y*, yielding approximately 50% of the live-born male offspring in the fourth generation with a XXY karyotype. Adult XXY mice have small testes, decreased plasma T levels, and elevated plasma FSH levels. The testes of adult XXY mice contained small seminiferous tubules with intraepithelial vacuolization and absence of germ cells, whereas Leydig cells appeared to be more abundant than their XY littermates. Androgen receptor immunoexpression was localized in Leydig cells and peritubular myoid cells in both XY and XXY mice. Androgen receptor immunoexpression was abundant in the Sertoli cells of XY mice but nearly absent in those of XXY mice. The testicular phenotype was marked by a 23.1% decrease in testis weights in XXY pups beginning at d 7 after birth. Gonocyte numbers were similar in XY and XXY mice at d 1 of age, followed by a 62.6% decrease in the number of gonocytes in the XXY mice on d 3 and further progressive loss in spermatogonia by d 5 and 7. On d 10, only a few spermatogonia remained in the XXY mice. To determine whether the phenotype of XXY mice extended into the neurobehavioral domain, studies were conducted demonstrating impairment of learning and memory function in XXY mice. We conclude that adult XXY mice have testicular failure and learning deficits, similar to its human counterpart, Klinefelter syndrome.
70 citations
TL;DR: Temporal changes in the expression pattern of Hsp105 and Hsp60 in relation to germ cell death suggests they may be involved in key processes in regulation of germ cell apoptosis.
Abstract: To confirm that transient increase in temperature of the testis (43C for 30 minutes once daily for 2 consecutive days) could induce apoptosis of germ cells in non-human primates and to investigate the possible roles of Hsp105 and Hsp60 in regulation of germ cell loss, we conducted the study on eight cynomolgus monkeys. The sperm concentration on day 28 after heat shock decreased to 8.4% of pretreatment levels and recovered to baseline on day 144. Using the TUNEL assay, increased numbers of apoptotic spermatocytes and round spermatids were detected on days 3, 8, and 30 post heat treatment. Hsp105 and Hsp60 mRNA and protein levels were analyzed using in situ hybridization, RT-PCR, immunohistochemical and Western blot methods. Hsp105 was confined to nuclei of spermatids before treatment, decreased dramatically with the loss of spermatids on days 3, 8, and 30, before returning to baseline levels on days 84 and 144. The expression of Hsp60 was high on days 3, 8, 30 and was only detected in Sertoli cells and spermatogonia. These results suggested that exposure of the testis to heat resulted in selective, but reversible damage to the seminiferous epithelium via increased germ cell apoptosis. Temporal changes in the expression pattern of Hsp105 and Hsp60 in relation to germ cell death suggests they may be involved in key processes in regulation of germ cell apoptosis.
46 citations
TL;DR: Protection from heat-induced germ cell apoptosis was noted after pretreatment with minocycline, a second-generation tetracycline that effectively inhibits cytochrome c release and, in turn, caspase activation.
Abstract: In the present study, we determined whether a pan caspase inhibitor could prevent or attenuate heat-induced germ cell apoptosis. Groups of five adult (8 wk old) C57BL/6 mice pretreated with vehicle (DMSO) or Quinoline-Val-Asp (Ome)-CH2-O-Ph (Q-VD-OPH), a new generation broad-spectrum caspase inhibitor, were exposed once to local testicular heating (43 degrees C for 15 min) and killed 6 h later. The inhibitor (40 mg/kg body weight) or vehicle was administered intraperitoneally (i.p.) 1 h before local testicular heating. Germ cell apoptosis was detected by TUNEL assay and quantitated as number of apoptotic germ cells per 100 Sertoli cells at stages XI-XII. Compared with controls (16.8 +/- 3.1), mild testicular hyperthermia within 6 h resulted in a marked activation (277.3 +/- 21.6) of germ cell apoptosis, as previously reported by us. Q-VD-OPH at this dose markedly inhibited caspase 3 activation and significantly prevented (by 67.0%) heat-induced germ cell apoptosis. Q-VD-OPH-mediated rescue of germ cells was independent of cytosolic translocation of mitochondrial cytochrome c and DIABLO. Electron microscopy further revealed normal appearance of these rescued cells. Similar protection from heat-induced germ cell apoptosis was also noted after pretreatment with minocycline, a second-generation tetracycline that effectively inhibits cytochrome c release and, in turn, caspase activation. Collectively, the present study emphasizes the role of caspases in heat-induced germ cell apoptosis.
43 citations
TL;DR: Minocycline-mediated protection occurred at the mitochondria, involving the restoration of the BCL-2 levels and, in turn, suppression of cytochrome c and DIABLO release.
37 citations
TL;DR: Increased NO and germ-cell apoptosis during aging is further associated with cytosolic translocation of mitochondrial cytochrome c and poly (ADP) ribose polymerase (PARP) cleavage, thus, suggesting the involvement of NO-mediated intrinsic pathway signaling in age-related increase in germ- cell apoptosis in male Brown-Norway rats.
Abstract: We examined, using young and old Brown-Norway rats, the involvement of the nitric oxide (NO)-mediated intrinsic pathway signaling in age-related activation of male germ-cell apoptosis. Increased apoptosis of germ cells was readily observed in the normal-looking testes of old rats. Testicular NO synthase (NOS) activity, assessed by measuring the synthesis of (3)H-L-citrulline from (3)H-L-arginine, and cytokine-inducible NO synthase (iNOS) levels, assessed by western blot assay, were increased significantly by 90% and 70%, respectively, in the old rats compared to that of young animals. Immunohistochemical analysis of age-related changes in the expression of iNOS in testes confirmed our findings based on western blot assay. Increased NO and germ-cell apoptosis during aging is further associated with cytosolic translocation of mitochondrial cytochrome c and poly (ADP) ribose polymerase (PARP) cleavage, thus, suggesting the involvement of NO-mediated intrinsic pathway signaling in age-related increase in germ-cell apoptosis in male Brown-Norway rats.
29 citations
TL;DR: Signs and symptoms together with a low serum testosterone level confirm the diagnosis of male hypogonadism and androgen replacement results in improved sexual function, mood, muscle mass and bone density in most Hypogonadal men.
Abstract: Increased awareness of the clinical diagnosis of male hypogonadism has resulted in the wider use of androgen substitution therapy. Clinical signs and symptoms together with a low serum testosterone level confirm the diagnosis of male hypogonadism. Androgen replacement results in improved sexual function, mood, muscle mass and bone density in most hypogonadal men. Such benefits must be assessed against potential risks. In older men, the potential risks of androgen treatment of hypogonadism are not known. Many delivery systems for androgen substitution are now available; the preparation chosen depends on the choice of the patient and his physician. Selective androgen receptor modulators offer tissue selective biological effects and the possibility of attaining maximum efficacy and minimum adverse effects.
TL;DR: It is postulate that physiological nonuniformity of sex steroid-dependent negative feedback in particular may contribute to populational diversity in LH regulation.
Abstract: The basis for ethnicity-related distinctions in gonadotropin secretion are unknown but may have important populational and physiological implications. In male contraceptive trials, exogenous testosterone and progestins suppress spermatogenesis to a greater degree in Asian than Caucasian men. In addition, iv infusion of testosterone inhibits LH release more in Asian than Caucasian volunteers. We test the converse postulate that experimental reduction of androgen-dependent negative feedback by way of the steroidogenic inhibitor combination ketoconazole/dexamethasone will unveil ethnicity-related mechanisms of regulated LH secretion in young men. LH release was monitored by sampling blood every 10 min for 24 h followed by immunoradiometric assay, model-free pulse detection, an entropy (regulatory) statistic, and cosine regression. Statistical comparisons revealed that healthy young Asian and Caucasian men maintain comparable baseline concentrations of LH, testosterone, estradiol, SHBG, and molar testosterone to SHBG ratios. In contrast, the two ethnic groups differ prominently in each of basal, pulsatile, entropic, and 24-h rhythmic LH adaptations to short-term androgen withdrawal. Therefore, we postulate that physiological nonuniformity of sex steroid-dependent negative feedback in particular may contribute to populational diversity in LH regulation.
TL;DR: A meta-analysis using the Mantel–Haenszel methods finds that the frequency of the C allele is higher within the USA study and lower within the Korean study, and this difference is mirrored by the frequencies of the CC genotypes.
Abstract: © 2005 Blackwell Publishing Ltd, Clinical Endocrinology , 63 , 232–237 When looking at the individual studies, the C allele is present at similar frequencies within the two UK Caucasian populations (75·1% and 74·8%), whereas the frequency of the C allele is higher within the USA study (82%) and lower within the Korean study (71%). This difference is also mirrored by the frequencies of the CC genotypes, where the CC genotype is reported to be 55·3% and 54·7% prevalent within the UK Caucasian populations, compared with 65% frequency within the USA population and 50% within the Korean population. A meta-analysis using the Mantel–Haenszel methods, 9
Journal Article•
TL;DR: It is demonstrated that optimum suppression of spermatogenesis through increased germ cell death is only possible in mice if total abolition of androgen action is achieved and the usefulness of acyline + flutamide treated mice as a suitable model system to study hormonal regulation of testicular germ cell apoptosis.
Abstract: As a prerequisite for studies using mutant mice, we established a mouse model for induction of male germ cell apoptosis after deprivation of gonadotropins and intratesticular testosterone (T). We employed a potent long acting gonadotropin-releasing hormone antagonist (GnRH-A), acyline, alone or in combination with an antiandrogen, flutamide for effective induction of germ cell apoptosis in mice. Combined treatment with continuous release of acyline (3 mg/kg BW/day) with flutamide (in the form of sc pellets of 25 mg) resulted in almost the same level of suppression of spermatogenesis, as judged by testis weight and by germ cell apoptotic index, in 2 weeks as that reported for rats after treatment with 1.25 mg/kg BW Nal-Glu GnRH-A for the same time period. Within the study paradigm, the maximum suppression of spermatogenesis occurred after a single sc injection of high (20 mg/kg BW) dose of acyline with flutamide. The combined treatment resulted in complete absence of elongated spermatids. Germ cell counts at stages VII-VIII showed a significant (P < 0.05) reduction in the number of preleptotene (27.1%) and pachytene spermatocytes (81.9%), and round spermatids (96.6%) in acyline + flutamide group in comparison with controls. In fact, treatment with a single high (20 mg/kg BW) dose of acyline combined with flutamide in mice achieved same or greater level of suppression, measured by germ cell counts at stages VII-VIII, in two weeks when compared with those reported after daily treatment with Nal-Glu GnRH-A for 4 weeks in rats. Both plasma and testicular T levels were markedly suppressed after administration of acyline alone either by miniosmotic pump or by a single sc injection. Addition of flutamide to acyline had no discernible effect on plasma or intratesticular T levels when compared with acyline alone. These results demonstrate that optimum suppression of spermatogenesis through increased germ cell death is only possible in mice if total abolition of androgen action is achieved and further emphasize the usefulness of acyline + flutamide treated mice as a suitable model system to study hormonal regulation of testicular germ cell apoptosis.
TL;DR: The authors believe men with low serum testosterone levels are candidates for replacement testosterone therapy after careful individual assessment of comorbidities and suggestive clinical features are required for a presumptive diagnosis of relative androgen deficiency.
TL;DR: Evidence suggests that provided hypogonadal men are carefully counselled and closely monitored during treatment testosterone therapy can be initiated after radical prostatectomy for non-metastatic prostate cancer with undetectable prostate specific antigen of long duration.
Journal Article•
TL;DR: Until more data on the efficacy and risks of testosterone (T) treatment of hypogonadal older men become available, the use of T substitution in men in this age group should be carefully considered and benefits vs risks should be discussed with the patient.
Abstract: Until more data on the efficacy and risks of testosterone (T) treatment of hypogonadal older men become available, the use of T substitution in men in this age group should be carefully considered and benefits vs risks should be discussed with the patient. Generally symptoms of hypogonadism together with low serum T levels are considered indications for treatment. For aging men, short acting preparations may be preferred and levels of serum T are maintained with in the mid adult range. Careful assessment for improvement of symptoms is the essential goal of treatment. Monitoring for manifestations of prostate disease, erythrocytosis and other adverse events of androgen treatment is critical in the management of older men with androgen replacement therapy.
[...]
TL;DR: Sexual function and parenthood are highly valued but often unstated components of the human experience and holistic medical care must screen vigilantly for dysfunction as a consequence or treatment side-effect of many common systemic diseases.
Abstract: Sexual function and parenthood are highly valued but often unstated components of the human experience. Male sexual dysfunction is common, increases with age and may occur in motivational (libidinal) and/or physical (erectile and ejaculatory) domains. 1 Sexual function is complex and not easily attributed to a single pathogenic cause. Holistic medical care must therefore screen vigilantly for dysfunction as a consequence or treatment side-effect of many common systemic diseases. 2 Testosterone is an important determinant of sexual function and its use therapeutically has long been considered due to widespread availability and low cost. However, the efficacy of testosterone therapy for sexual dysfunction has previously been thought to be most effective for young men with blood concentrations in the very low to castrate range. 3–5
TL;DR: The meeting opened with the ASA Lecture ‘‘Genes, Gender, and Germ Cells,’’ presented by David Page, PhD, from the Whitehead Institute, Massachusetts Institute of Technology, Boston, whose work has been instrumental in elucidating the contribution of genes on the Y chromosome to male development while illustrating potential mechanisms by which this chromosome has evolved to its current form in the human.
Abstract: The 30th Annual Meeting of the American Society of Andrology (ASA) was held in Seattle, Wash, April 2–4, 2005. The Annual Meeting was preceded by the Testis Workshop, held from March 31 to April 2. Dr Michael Palladino chaired the Andrology Laboratory Workshop. This full-day ‘‘Sperm Morphology Workshop,’’ held on April 2, was a laboratory-based class with hands-on training in the microscopic assessment of sperm morphology according to classification methods currently used in clinical laboratories. The program for the 30th Annual Meeting with the theme ‘‘Androgens and their Target Organs’’ featured 6 plenary lectures, 1 plenary debate, and 5 symposia. The meeting opened with the ASA Lecture ‘‘Genes, Gender, and Germ Cells,’’ presented by David Page, PhD, from the Whitehead Institute, Massachusetts Institute of Technology, Boston. In an outstanding career spanning over 20 years, Dr Page’s studies have addressed and answered fundamental questions concerning the mechanisms that underpin gonadal sexual differentiation. His work has been instrumental in elucidating the contribution of genes on the Y chromosome to male development, while illustrating potential mechanisms by which this chromosome has evolved to its current form in the human. His ASA Keynote Lecture described recent work in his laboratory that addresses the absence of information about how an ovary develops in the absence of a stimulus to become a testis. He points out that although it is clear that the somatic cell lineage, specifically the pre-Sertoli cells in the fetal gonad, drive formation of the testis, little to no information is available about how an ovary forms. As his tale of the 3 PhD students (Menke, Baltus, and Koubova) unfolded, we learned what happened when the team posed the hypothesis that the germ cells were the driver of somatic differentiation in the ovary. In an effort to identify genes involved in gender-specific gonad development, a subtractive hybridization experiment yielded predominantly somatic and male-specific genes, a disappointing blow to the original hypothesis. However, in reevaluation of the published gender-specific expression of the retinoic acid receptor-responsive gene, Stra8, Page’s team learned that this gene was both femaleand germ cell–specific in the fetal gonad, being expressed in accordance with the onset of meiotic prophase and directly