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Biomedical subjects

B B Yeap

Publications and source records attributed to B B Yeap.

7 recordsLinked to original sources

Chronic hepatitis C infection and sex hormone levels: effect of disease severity and recombinant interferon-alpha therapy.

BACKGROUND: We aimed to investigate the associations between androgen status and markers of liver disease severity and to determine the effect of interferon-alpha (IFN-alpha) treatment on sex hormone levels in the context of hepatitis C infection. METHODS: We audited liver biopsy and sex hormone data from 35 men with chronic hepatitis C and a separate group of 11 men with hepatitis C who received IFN-alpha treatment at Fremantle Hospital. RESULTS: We found that men with low fibrosis scores (0-2) on the modified Knodell histological activity index were more likely to have lower sex hormone-binding globulin (SHBG) levels (38.2 +/- 13.2 vs 66.6 +/- 43.3 nmol/L, P < 0.001) and higher free testosterone levels (380.4 +/- 102.0 vs 255.9 +/-83.0 pmol/L, P = 0.01) than those with higher fibrosis scores (3-6). SHBG directly correlated with fibrosis scores (r = 0.37, P = 0.032). Free testosterone levels inversely correlated with liver fibrosis scores (r = -0.43, P = 0.011). A transient reduction in total testosterone of 5.7 +/- 4.2 nmol/L (P = 0.014) occurred within the first 6 months of IFN-alpha therapy although free testosterone was unaffected. CONCLUSION: More severe liver disease was associated with lower free testosterone and higher SHBG. IFN-alpha therapy reduced total testosterone but not to hypogonadal levels, with no decline in free testosterone. These data suggest that liver disease in hepatitis C infection modulates androgen status indirectly via increased SHBG. Screening for androgen deficiency in the context of hepatitis C infection should selectively target men with more severe liver disease or documented higher grade fibrosis.

Adult↗

Relationship between testosterone, sex hormone binding globulin and plasma amyloid beta peptide 40 in older men with subjective memory loss or dementia.

In a group of 28 older men with either subjective memory loss or dementia, serum total testosterone and sex hormone binding globulin (SHBG) correlated inversely with plasma levels of amyloid beta peptide 40 (Abeta40, r=-0.5, P=0.01 and r=-0.4, P=0.04, respectively). Calculated free testosterone was also inversely correlated (r=-0.4, P=0.03), and all three relationships remained statistically significant after allowing for age. A similar but non-significant trend was seen with dehydroepiandrosterone sulphate (DHEAS), and neither luteinising hormone (LH) nor estradiol correlated with Abeta40. These data demonstrate that lower androgen levels are associated with increased plasma Abeta40 in older men with memory loss or dementia, suggesting that subclinical androgen deficiency enhances the expression of Alzheimer's disease-related peptides in vivo. An inverse correlation exists between SHBG and Abeta40, warranting further investigation.

Aged↗

Primary care diabetes. What options are there?

BACKGROUND: The recognised incidence of type 2 diabetes mellitus is increasing dramatically and the vital importance of good diabetes control in patients with both type 1 and type 2 diabetes is now well established. Weight reduction and oral hypoglycaemic therapy has been accompanied by new drug treatment options in type 2 diabetes, while refinements in insulin delivery are more relevant for patients with type 1 diabetes. OBJECTIVE: To review currently available drug therapies and management strategies for type 2 diabetes, and optimal insulin treatment regimens for type 1 diabetes. DISCUSSION: Weight reduction and regular exercise remain major lifestyle intervention priorities in type 2 diabetes. Metformin should be used early in overweight patients, and sulphonylureas as additive therapy. Acarbose, orlistat and the thiazolidinediones all have potential roles in the treatment of type 2 diabetes where cardiovascular risk factor reduction is also of vital importance. Insulin analogues and continuous subcutaneous insulin infusion via insulin pumps will help to optimise insulin replacement regimens for patients with type 1 diabetes mellitus.

Clinical Protocols↗

Differential posttranscriptional regulation of androgen receptor gene expression by androgen in prostate and breast cancer cells.

Androgens, via the androgen receptor (AR), modulate the growth and proliferation of prostate and breast cancer cells. However, the molecular mechanisms underlying the regulation of AR gene expression by androgen in these cells remain to be fully elucidated. To explore differences in AR gene expression between these hormone-responsive tumor cell types, we studied androgen-responsive LNCaP prostate cancer and AR positive MDA453 breast cancer cells. Dihydrotestosterone (DHT) 10 nM increased LNCaP cell proliferation and the proportion of LNCaP cells in S-phase of the cell cycle but inhibited MDA453 cell proliferation and reduced the proportion of MDA453 cells in S-phase of cell cycle. In both these cell lines, DHT decreased total AR messenger RNA (mRNA) but increased AR protein. In LNCaP cells, DHT down-regulated AR mRNA transcription but stabilized AR mRNA. In contrast, in MDA453 cells, DHT had no effect on AR mRNA transcription but destabilized AR mRNA. In summary, transcriptional down-regulation induced by androgens in LNCaP cells results in down-regulation of steady-state AR mRNA despite an androgen-induced increase in AR mRNA stability. However, in MDA453 cells, posttranscriptional destabilization of AR mRNA appears to be the predominant mechanism resulting in down-regulation of AR mRNA by androgen. These results demonstrate cell-specific and divergent regulation of AR mRNA turnover by androgen and identify a novel pathway of androgen-induced posttranscriptional destabilization and down-regulation of AR mRNA in human breast cancer cells. Furthermore, these data establish an important role for posttranscriptional pathways in the regulation of AR gene expression by androgen in human prostate and breast cancer cells.

Breast Neoplasms↗

Hyperglycemia affects cardiovascular autonomic nerve function in normal subjects.

OBJECTIVE: To evaluate the effect of acute hyperglycemia on autonomic nerve function in normal subjects. RESEARCH DESIGN AND METHODS: Six healthy volunteers ages 19-32 years underwent paired studies during euglycemia (blood glucose 5.1 +/- 0.04 mmol/l) and hyperglycemia (blood glucose 15.7 +/- 0.48 mmol/l) induced by intravenous infusion of glucose and maintained for 150 min. The order of the two studies was randomized. In each experiment, supine heart rate, heart rate variation with respiration, ratio of the maximum to minimum R-R interval after standing ("30:15" ratio), systolic blood pressure response to standing, and diastolic blood pressure response to sustained handgrip were measured. Data were analyzed using repeated measures analysis of variance. RESULTS: The supine heart rate was greater (P = 0.04) and the "30:15" ratio less (P = 0.03) during hyperglycemia than during euglycemia. Hyperglycemia had no significant effect on any of the other cardiovascular reflex tests. CONCLUSIONS: These observations indicate that acute hyperglycemia affects autonomic nerve function in healthy humans.

Adult↗