The possible role of cyclic adenosine 3',5'-monophosphate (cAMP) in mediating the action of steroid hormones was investigated using the rat lung. Male rats were adrenalectomized and treated with olive oil, dexamethasone, corticosterone, deoxycorticosterone (DOC) or progesterone. At the end of 10 days, 100 micrograms isoprenaline/kg was injected intraperitoneally 5 min before the animals were killed to stimulate cAMP production. Adrenalectomy significantly decreased cAMP levels in the rat lung. Dexamethasone and corticosterone pretreatment reversed the effect of adrenalectomy whereas progesterone pretreatment but not DOC pretreatment significantly decreased lung cAMP levels. Cyclic AMP levels in normal female rats, whether pregnant or not, were not significantly different from those in male rats. We concluded that the absence of glucocorticoid, as after adrenalectomy, decreased the cAMP levels in rat lungs and that this could be reversed by either dexamethasone or corticosterone replacement. Progesterone reduced the cAMP content in rat lungs by acting as a glucocorticoid antagonist or by acting directly via progesterone receptors.
Clinical diagnosis of congenital hypothyroidism (CH) is difficult at birth without neonatal screening. In line with the priorities of the national health services in Malaysia towards preventive medicine, early diagnosis and treatment of CH is emphasised. We conducted a pilot study at Kuala Lumpur's Maternity Hospital between April 1995 and November 1995 to estimate the incidence of CH and also evaluated the problems associated with large-scale neonatal screening using a commercial TSH kit on cord bloodspots.
The clinical applications of salivary cortisol measurements were evaluated by radioimmunoassay of time-matched saliva and plasma samples. Salivary cortisol levels of normal subjects exhibited a significant (p less than 0.001) diurnal variation with a mean (+/- SD) concentration of 8.7 +/- 4.8 nmol/L at 0800-1000 h and 2.4 +/- 1.1 nmol/l at 1500-1700 h. After an overnight dexamethasone suppression test, morning salivary cortisol levels decrease to 2.7 +/- 0.7 nmol/L (p less than 0.001 vs normal). An excellent correlation (r = 0.805) of cortisol measurements with time-matched saliva and plasma samples was obtained (y = 0.03x + 0.88, p less than 0.001, n = 91). Hypercortisolism was confirmed by raised salivary cortisols in only half of patients with elevated total plasma levels, thereby indicating that salivary cortisol measurements is a better index of adrenal status.
Two cases of hypokalaemia with serum potassium levels of 1.4 mmol/L and 1.9 mmol/L causing severe periodic paralysis since childhood are presented. There were associated with muscular aches and markedly raised muscle enzymes suggesting massive rhabdomyolysis. These abnormalities were due to renal tubular acidosis with markedly acidic arterial pH. The hypokalaemia and rhabdomyolysis responded to potassium and bicarbonate replacement. We postulate these patients had sporadic distal type of renal tubular acidosis and that the hypokalaemia and acidosis had caused the rhabdomyolysis.
This is a cross-sectional study to determine the prevalence of insulin resistance and its associated factors in Hospital UKM patients with schizophrenia using the Homeostatic Model Assessment (HOMA) model. Fasting glucose and insulin from 85 patients were obtained. Fasting glucose revealed 15% of the patients were diabetic, while another 15% had impaired fasting glucose. Using the HOMA model, 68% of the patients had insulin resistance. Univariate analyses found BMI (p < 0.001) and waist circumference (p < 0.001) to be associated with insulin resistance. The statistical significance disappeared after multivariate analyses. All patients with schizophrenia should be screened and managed as a group at high risk for development of diabetes with emphasis on body weight management.
Study site: inpatient and outpatients, Psychiatric department, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
A patient with beta hCG-secreting germ cell carcinoma of the pineal and suprasellar regions presented with hydrocephalus, Parinaud's syndrome, hypopituitarism and polyuria. Central diabetes insipidus was strongly suspected although the water deprivation test was not diagnostic. The polyuria however, responded to ADH analogue when the hypothyroidism and hypocortisolism were treated. Pubertal development was evident and serum testosterone was normal despite the low FSH/LH, suggesting hCG stimulation of Leydig cells. This case illustrates that a beta hCG-germ cell tumour of the suprasellar region causing hypopituitarism can mask the presence of central diabetes insipidus and hypogonadotrophic hypogonadism.
This study determined the effects of palm vitamin E (TRF) diet on the levels of blood glucose, glycated hemoglobin (gHb), serum advanced glycosylation end-products (AGE) and malondialdehyde (MDA) of diabetic Sprague-Dawley rats. The rats received either control (normal rat chow), TRF diet (normal chow fortified with TRF at 1 g/kg) or Vitamin C diet (vitamin E-deficient but contained vitamin C at 45 g/kg). The animals were maintained on the respective diet for 4 weeks, made diabetic with streptozotocin (STZ), then followed-up for a further 8 weeks. At week-4, mean serum AGE levels of rats given TRF diet (0.7 +/- 0.3 units/ml) were significantly lower than those of control or Vitamin C diet rats (p pounds 0.03). The levels increased after STZ and became comparable to the other groups. At week 12, blood glucose (20.9 +/- 6.9 mM) and gHb (10.0 +/- 1.6%) of rats on TRF diet remained significantly low compared to that of control or Vitamin C diet rats (p pounds 0.03). MDA however, was not affected and remained comparable between groups throughout the study. This study showed that TRF may be a useful antioxidant; effectively prevented increase in AGE in normal rats, and caused decrease in blood glucose and gHb in diabetic rats. Further studies are needed to elucidate the mechanisms of action of TRF.
The aim of this study was to investigate the effect of altered thyroid status on 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD type 1) and type 2 (11beta-HSD type 2) bioactivity in rat kidney and colon. Male Sprague-Dawley rats (250 g) were treated with either L-thyroxine (T4) or propylthiouracil (PTU) for 4 weeks. Blood were then analysed for serum thyroxine, sodium (Na+) and potassium (K+). The kidneys and colon were assayed for 11beta-HSD type 1 and 11beta-HSD type 2 bioactivity. In T4 treated rats the serum thyroxine was significantly elevated (p<0.05) whilst PTU decreased serum thyroxine significantly (p<0.001) compared to controls. Serum Na+ and K+ were within normal limits. There were no significant changes in 11beta-HSD type 1 bioactivity in both treatment groups compared to controls. However, the 11beta-HSD type 2 bioactivity in rats given thyroxine was significantly higher in the colon (p<0.003) compared to controls. We conclude that altered thyroid status had no effect on 11beta-HSD type 1 bioactivity but 11beta-HSD type 2 bioactivity was elevated in the colon of rats given supplementary thyroxine.
Hypercholesterolemia causes endothelial dysfunction, an early feature of atherosclerosis, leading to increased production of adhesion molecules and cytokines. The aim of this study was to investigate the effects of three months of treatment with low dose atorvastatin on serum levels of adhesion molecules, interleukin-6 (IL-6) and highly sensitive C-reactive protein (hs-CRP) in patients with non-familial hypercholesterolemia. Fifty-five patients with non-familial hypercholesterolemia were randomized to treatment with atorvastatin 10 mg/day or placebo for 3 months. Soluble intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, IL-6 and hs-CRP levels were measured to assess the inflammatory activity of the endothelium. There was a significant reduction in ICAM-1 at 2 weeks (p<0.0001) with further reduction at 3 months (p<0.0001). At 3 months, there were significant reductions in VCAM-1 (p<0.02), IL-6 (p<0.0001) and hs-CRP (p<0.01), but an increase in E-selectin levels (p<0.002). Treatment with statin was an independent determinant of change in ICAM-1 (p<0.05) and IL-6 levels (p<0.05) after correcting for anthropometric indices, blood pressure and lipid profile. Low-dose atorvastatin treatment leads to reduction in proinflammatory markers of endothelial function, suggesting an attenuation of endothelial activation and improvement in endothelial function, independent of lipid lowering. This may lead to a reduction in the progression of atherosclerosis.
Although some form of commercial instrument mounting arm is available, a paucity of information in the literature may cause problems in selecting the most appropriate model for an ENT department wishing to trial their invention for use in the clinic or operating theatre. The instrument mounting arm described here is based on existing designs used by hobbyists and model makers for many years but the main benefit of this innovation is its multi-purpose use in the operating theatre and cost effectiveness since it is made of aluminum alloy. It is compact, stable and easily adjustable and can incorporate an endoscope holder or an operating end piece to mount various ENT instruments that offers considerable advantages to the unassisted operator.
Vitamin E has been shown to affect bone metabolism. In this study we determined the effects of palm vitamin E and alpha-tocopherol on bone metabolism. Sprague-Dawley female rats fed with normal rat chow were divided into 4 groups and supplemented with either palm vitamin E 30 mg/kg rat weight, palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight. One group was not supplemented. Half of these rats were ovariectomised before supplementation was given for 10 months. As expected, bone mineral density of the ovariectomised rats fed on normal rat chow diet was lower compared to the intact rats. However, these changes were not seen in the supplemented group of rats. Both intact and ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight had a lower bone calcium content in both femoral and vertebral bones whilst rats fed palm vitamin E 60 mg/kg rat weight or alpha-tocopherol 30 mg/kg rat weight were able to maintain bone calcium content. Alkaline phosphatase activity was elevated in ovariectomised rats supplemented with palm vitamin E 30 mg/kg rat weight and alpha-tocopherol 30 mg/kg rat weight compared to the intact rats. Alpha-tocopherol also reduced the activity of tartrate-resistant acid phosphatase post-ovariectomy. These findings indicate that both palm vitamin E and alpha-tocopherol maintained bone mineral density in ovariectomised rats but caused conflicting effects on bone calcium content. Further study is needed in order to determine the mechanisms involved.
Thyroid hormones have been shown to be involved in the regulation of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) expression. This is a cross-sectional study to look at the effects of thyroid hormone status on the circulating levels of IGF-I and IGFBP-3 in a group of 127 patients, aged 20-80 years, who were hyperthyroid, hypothyroid, rendered euthyroid and clinically euthyroid with normal free thyroxine (fT4), but suppressed thyroid stimulating hormone (TSH) levels. TSH was measured by the IMx (Abbott) ultrasensitive assay, while radioimmunoassays for total T3 and T4 were performed using kits from ICN, USA; fT4 and fT3 using kits from DPC USA; IGF-I and IGFBP-3 using kits from Nichols Institute Diagnostics B.V., Netherlands. Differences in the levels of IGF-I between the 4 groups of patients were significant only in the patients aged 20-40. Mean (+/-SEM) IGF-I levels of hypothyroid patients (169+/-19ng/ml) was significantly lower than hyperthyroid (315+/-26 ng/ml, p=0.003), euthyroid patients (241+/-19 ng/ml, p=0.002) and patients with suppressed TSH (308+/-29 ng/ml, p=0.02). The IGF-I levels of the hyperthyroid and suppressed TSH patients were, however, comparable to age-matched normal subjects (281+/-86 ng/ml). Although there was no difference in mean IGFBP-3 levels between the 4 groups of patients, the levels in the patients aged 20-40 with hyperthyroidism (3.7+/-0.9 microg/ml) and suppressed TSH (3.9+/-1.2 microg/ml) were significantly higher (p=0.02) than age-matched normal subjects (3.1+/-0.8 microg/ml). The IGF-I levels of the thyroid patients aged 20-40 showed significant negative correlation to TSH and positive correlations to the thyroid hormones. Hence, whilst low IGF-I is associated with hypothyroidism, high IGFBP-3 is associated with hyperthyroidism. Our finding that IGFBP-3 remained significantly elevated in patients with suppressed TSH but normalised fT4 and fT3 is important as it suggests a prolonged tissue effect of thyroid hormones on IFGBP-3. As such patients have been shown to have higher risk for atrial fibrillation, the significance and possible role of IGFBP-3 in these conditions should be further elucidated in future studies.
The atherogenic potential of soybean oil (Sb) and palm oil (PO) was compared by measuring lipid profile, lipid peroxidation (LP) and activity of the antioxidant enzyme glutathione peroxidase (GSHPx) in rat sera and liver and heart homogenates. Male Rattus norwegicus rats were fed a basal diet, or basal diet fortified with 20% weight/ weight Sb or PO for 4 or 9 months. There was no difference in high density lipoprotein cholesterol:low density lipoprotein cholesterol ratio between the two groups, but triglyceride concentrations were higher in the PO fed rats compared to the Sb fed rats, although the difference diminished after 9 months. No differences in serum LP and GSHPx activity were seen between the two groups. In the liver and heart, LP was lower in PO after 4 months feeding, but the reverse was seen after 9 months. Liver and heart GSHPx activity was higher in the PO group after both treatment periods. In conclusion, both PO and Sb fed rats appeared comparable in their lipid profile, but the PO food had a temporary beneficial effect on the LP process in liver and heart. GSHPx activity however did not correlate well with LP in liver and heart, suggesting involvement of other antioxidants.
The effects of long-term administration of tocotrienol on hepatocarcinogenesis in rats induced by diethyl nitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated by the determination of plasma and liver gamma-glutamyl transpeptidase (GGT), cytosolic glutathione reductase (GSSG-Rx), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST). Twenty-eight male Rattus norwegicus rats (120-160g) were divided according to treatments into four groups: control group, tocotrienol - supplemented diet group (30mg/kg food), DEN/AAF-treated group and DEN/AAF treated plus tocotrienol-supplemented-diet group (30mg/kg food). The rats were sacrificed after nine months. The results obtained indicated no difference in the morphology and histology of the livers of control and tocotrienol-treated rats. Greyish-white neoplastic nodules (two per liver) were found in all the DEN/ AAF treated rats (n-10) whereas only one nodule was found in one of the carcinogen treated rats receiving tocotrienol supplementation (n-6). Histological examination showed obvious cellular damage for both the DEN/AAF-treated rats and the tocotrienol-supplemented rats but were less severe in the latter. Treatment with DEN/AAF caused increases in GGT, GSH-Px, GST and GSSG-Rx activities when compared to controls. These increases were also observed when tocotrienol was supplemented with DEN/AAF but the increases were less when compared to the rats receiving DEN/AAF only.
Fasting serum growth hormone (GH) levels of different groups of diabetic patients were measured and compared to age-matched normal subjects. Insulin-dependent diabetes mellitus (IDDM) children (aged 12-17 years) were found to have significantly lower fasting GH levels than age-matched normal children (p < 0.001). In the adult age groups of 18-44 and 45-76 years, the IDDM patients showed increased fasting GH levels compared to age-matched normal subjects (p < 0.06 and p < 0.001 respectively) and non-insulin-dependent diabetes mellitus (NIDDM) patients (p < 0.05 and p < 0.001 respectively). The fasting GH levels of IDDM patients of the age group 18-44 years also showed significant correlations with glycated haemoglobin (r = 0.510, p = 0.002) and fasting blood sugar levels (r = 0.571, p = 0.01).
1. Sex steroids have been shown to regulate the biosynthesis of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). 2. In vitro studies showed that oestradiol (E2) or testosterone (T) can interfere with the bioassay of enzyme activity, but not progesterone (P4). 3. For in vivo studies, the activity of 11 beta-HSD in the testis of normal and adrenalectomized (ADX) adult male Wistar rats was determined following a daily IM injection of sex steroids for 7 days. 4. The 11 beta-HSD activity was significantly reduced (P < 0.01) either by E2 or T in normal and ADX rats. The enzyme activity in normal rats given both T and E2 was even lower (P < 0.001) than when E2 was given alone. 5. P4 given to normal and ADX rats increased the enzyme activity higher than normal (P < 0.001). 6. The presence of corticosteroids influenced the effects of E2, but not of T and P4, on 11 beta-HSD activity. 7. E2 and T downregulate 11 beta-HSD activity, whereas P4 increased it. E2 did not act through lowering T level.
Sixty three and fifty nine non-insulin dependent diabetes mellitus (NIDDM) patients in rural (land resettlement scheme) and urban areas respectively were studied to determine factors associated with diabetic control. The anthropometric and metabolic data (HbA1 and fructosamine levels) were analysed. After adjusting for gender, age, body mass index (BMI) and food intake, the fructosamine level which correlates with short term diabetic control, was significantly lower among patients in urban areas compared to patients in rural areas (p < 0.05). However, for longer term diabetic control (HbA1 level) the difference was not statistically significant (p > 0.05). The socio-economic status, level of education, BMI and types of food did not correlate with diabetic control in either group of patients. More diabetes education is needed together with socio-economic development and changes in lifestyles to enhance compliance towards health and dietary regimens and to achieve better metabolic control.
A cross-sectional study was carried out to determine the prevalence of diabetes mellitus and its relationship with age, physical activity, nutritional status and diet amongst rural Malays in Kuala Selangor. By simple random sampling 360 subjects were selected for the study. Besides guided questionnaires, subjects also underwent a 2 hours post prandial (2HPP) test to determine the diabetic status as recommended by WHO. The crude prevalence of diabetes mellitus was 14.6% which increases with age. The prevalence of diabetes adjusted for age was 12.2%. Physical activity status seemed to be a significant risk factor for diabetes. A greater proportion of diabetics was obese and their mean fat intake was higher than normal subjects (p < 0.05). The prevalence of diabetes mellitus in this study was significantly higher compared with data from 1984 (3.9%), representing a marked increment of 212.8 per cent over a 10-year period.
The effects of castration with/ without testosterone replacement in male rats, and ovarectomy with oestrogen replacement in female rats, on serum lipids were studied. Simultaneous feeding with diets fortified with 20% weight/ weight (w/ w) soybean oil (Sb) or palm oil (P0) were done to determine the influence of these oils on serum lipids in castrated and sex hormone replaced rats. Two month old male and female Rattus norwegicus rats were given the above treatment for 4 months, and their sera assayed for lipid profile. Castration increased HDL-cholesterol (HDLchol) and total cholesterol (Tchol) concentrations. Testosterone or oestrogen replacement in male and female rats respectively increased HDLchol and decreased LDL-cholesterol (LDLchol) concentrations. Testosterone replacement also decreased Tchol concentration back to noncastrated levels, and reduced serum triglycerides (TG) to lower than non-castrated levels. Addition of Sb or P0 to the diet increased the LDLchol in the testosterone or oestrogen replaced male and female rats, but there was no difference between the two groups. P0 raised serum TG of the testosterone replaced group compared to control and Sb groups. In conclusion, testosterone and oestrogen were found to have favourable effects on serum lipids. Sb and P0 did not differ in their effects on lipoprotein cholesterol and Tchol, but P0 raised serum TG as compared to Sb.
In this study we examined the incidence of hypercalcaemia among patients with tuberculosis in Malaysia. Serum calcium concentration and other calcium metabolism parameters were studied in 43 newly diagnosed tuberculous patients from the Kuala Lumpur General Hospital and the National Tuberculosis Centre. Forty-four patients admitted to the medical wards of the General Hospital, Kuala Lumpur were recruited as controls. The incidence of hypercalcaemia was found to be only 1/43 (2.3%). There was no significant difference between the mean serum calcium and other calcium metabolism parameters between the patients and the controls. Despite earlier reported incidences of 30-50%, this study showed that hypercalcaemia in tuberculosis is uncommon in Malaysia.