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.
1. The present study examined the effect of naloxone (NAL), glycyrrhizic acid (GCA), deoxycorticosterone (DOC) and dexamethasone (DEX) on daily repeated 2 h chronic restrained stress (RS) on the locomotor activity (LA) of rats tested in the open field arena to elucidate the possible roles of opioids, glucocorticoids and mineralocorticoids in response to stress. 2. Intact and adrenalectomized (ADX) rats were either injected with 0.1 mL of NAL (0.32 microgram/100 g BW), 2.4 mg/kg DOC or 120 micrograms/kg DEX or had 1.0 mg/mL GCA dissolved in their drinking water or normal saline (for the ADX group) dissolved in their drinking water. 3. In intact groups, treatment with NAL completely blocked the stress response and treatment with GCA, DOC and DEX partially prevented the stress response. Adaptation occurred on either days 4, 5, 6 or 7 for intact rats treated with DEX, DOC, GCA or control rats, respectively. All ADX control rats died following the first 2 h RS. Adrenalectomized rats treated with DEX or DOC adapted later compared with intact rats, while rats given either GCA or NAL were unable to block or adapt to chronic RS. 4. These findings demonstrate that the stress response is primarily mediated by endogenous opioids, in that it is blocked by NAL. Both mineralocorticoids and glucocorticoids, which can act centrally to inhibit endorphins, partially blocked the stress response. The effect of GCA in intact rats was similar to that of both DEX and DOC in intact rats. Adrenalectomized rats treated with GCA (despite their lack of endogenous corticosterone) showed a stress response that was significantly different from the other ADX groups, implying that GCA had effects independent of endogenous corticosterone.
The expression and synthesis of IGF-I and IGFBP-3 have been shown to be regulated by hormones and nutrition. We study the effects of malnutrition and iodine deficiency on these growth factors and the height attainment of a group of children.
Glycyrrhizic acid (GCA) the active component of liquorice acts by inhibiting 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) which catalyses the reversible conversion of cortisol to cortisone. The aim of this study was to examine the effect of GCA on pulmonary arterial pressure. Male Sprague-Dawley rats (200g) received drinking water containing 0.1 mg/ml and 1.0 mg/ml GCA for 12 weeks. Tail blood pressure (BP) was recorded every three weeks and serum Na+ and K+ were measured at the beginning and the end of the experiment. Right atrial pressure (RAP) were measured at the end of 12 weeks just before the animals were sacrificed. Lung tissues were taken for histological examination using the elastic-van Gieson (EVG) staining method. There was a significant increase in tail BP in GCA treated rats compared to controls, for both dosages used. This was associated with an increase in serum Na+ and a decrease in K+ level. The mean RAP increased significantly from 2.69 +/- 0.23 mmHg to 4.47 +/- 0.32 mmHg (P < 0.001) in 0.1 mg/ml GCA treated rats and 6.86 +/- 0.54 mmHg (P < 0.0001) in rats receiving 1.0 mg/ml GCA in their drinking water. Histological examination showed increased thickness of pulmonary arterial wall (P < 0.0001). In conclusion GCA caused an increase in right atrial pressure as well as thickening of the pulmonary vessels suggesting pulmonary hypertension.
Corticotrophin releasing factor (CRF) and beta-endorphin (beta EP) containing neurons are shown to be present in the hypothalamus and both neurons are found at the paraventricular nucleus (PVN). Steroid hormones have been found to alter the plasma level of these neurotransmitters. Glycyrrhizic acid (GCA) is the active component of liquorice. GCA inhibits the enzyme 11 beta-hydroxysteroid dehydrogenase (11HSD) which is needed for the inactivation of the steroid pathway, so therefore would cause changes to these neurons. The aim of this study was to investigate the effects of GCA as well as deoxycorticosterone (DOC) and dexamethasone (DM) on the modulation of CRF and beta EP containing neuron at the PVN of the hypothalamus. Rats were given either DM, DOC or GCA and adrenalectomized (ADX) and given either DM or DOC. At the end of treatment rats were transfused transcardially before sacrifice and the brain were dissected for immunohistochemical analysis. We found that immunostaining of the CRF containing neurons demonstrate a reduction in the number of positive neurons in DM treated rats. DOC and GCA treated rats showed the same result as in DM rats but the reduction is less. ADX, DM, DOC and GCA treated rats did not show any changes in the number of beta EP containing neurons but naloxone increased the number of beta EP containing neurons markedly. In conclusion, GCA and DOC have similar effects on CRF and beta EP containing neurons at the PVN.
Edible oils have different effects on lipid profiles and on the propensity for producing lipid peroxidation products. These two properties of edible oils can affect arterial structure, ultimately leading to atherosclerosis. Hypertension is said to be a predisposing factor for atherosclerosis and can accelerate its process. This paper investigates the effects of three edible oils, namely soya bean oil, palm oil and ghee, on the ultrastructure of the aortas of spontaneously hypertensive rats at the end of a 4 month feeding period. It was found that ghee produced significant structural changes to the aortic wall when compared with palm oil or soya bean oil, and that no noticeable structural differences were seen to occur on the aortas of the palm oil-fed and soya bean oil-fed groups of rats. This study suggests that the consumption of ghee, rather than palm or soya bean oil, is more likely to lead to the development of atherosclerosis.
Thirty-eight normal volunteers and 10 patients with untreated thyrotoxicosis were each given 0.5 ml of Lugol's solution daily for 10 days. On days 0, 5, 10, 15 and 20, serum levels of T4, free T4, T3 and TSH (by sensitive immunoradiometric assay) were measured. In normal subjects, the serum concentrations of free T4 declined significantly at day 10 while TSH levels were significantly increased at days 5, 10 and 15. Serum levels of T4 and T3 did not change significantly. All the observed changes took place within the limits of normal ranges for the hormones mentioned. In contrast, in the thyrotoxic subjects, both T4 and T3 were significantly decreased at days 5 and 10, while serum TSH remained below detection limit (0.14 mU/l) throughout the study. Short exposure to excessive iodide in normal subjects affects T4 and T3 release and this effect could be partially overcome by compensatory increase in TSH. In thyrotoxicosis, lack of compensatory increase in TSH results in rapid decreases in T4 and T3 levels. The integrity of the hypothalamo-pituitary-thyroidal axis may be effectively assessed by measuring TSH response to iodide suppression, using a highly sensitive immunoradiometric assay.
1. Glucocorticosteroid may relieve bronchospasm by mediating changes in the muscarinic receptor concentration and/or its affinity. 2. Cholinergic muscarinic receptors were determined by using Scatchard's plots from radioligand binding assays of 0.13-3.2 nM [3H]quinuclidinyl benzylate binding to the membrane fraction of bronchial smooth muscle (BSM). 3. The concentration of muscarinic receptor in BSM of normal rat was 57 +/- 3 fmol mg protein and the dissociation constant was 0.07 +/- 0.02 nM. Dexamethasone and corticosterone reduced muscarinic receptor concentration to 50-60% of basal with no changes in receptor affinity. No changes were found in rat treated with deoxycorticosterone. 4. These findings suggest that glucocorticoids but not mineralocorticoid relieve bronchospasm at least partly by reducing the cholinergic hypersensitivity.
The effect of ovariectomy and sex hormone/s replacement in female rats was investigated by the determination of the tumour marker enzymes gamma-glutamyltranspeptidase (GGT) and alkaline phosphatase (ALP). This was compared to ovariectomized rats receiving sex hormone replacement and treated with carcinogen. Ovariectomy significantly increased the activity of plasma GGT. Plasma and microsomal ALP and microsomal GGT were unchanged. When replacements of estrogen (E), or progesterone (Prog), or combinations of both estrogen and progesterone were given to ovariectomized rats, the activity of plasma GGT was brought to the level of normal intact females. Treatment with carcinogen increased the PGGT activities in intact rats. In ovariectomized rats receiving carcinogen, the PGGT activities were significantly lower than in intact females and rats receiving both hormone replacement and carcinogen (p < 0.01). Carcinogen treatment in case of estrogen or progesterone replacement, either individually or in combination, showed GGT activities comparable to intact females receiving carcinogen. Both plasma and microsomal ALP were not affected by carcinogen administration. These results showed that ovariectomy reduced the severity of hepatocarcinogenesis while sex hormone replacement worsened the process.
Fasting growth hormone (GH) level is an important reference level in dynamic tests of GH secretion. Other studies have demonstrated sex and age variation in the rate of GH secretion. We analysed fasting serum samples from 377 normal subjects (193 males and 184 females, age range 6 to 81 years old), using our in-house enzyme immunoassay. We found sex differences in fasting GH levels to be only significant in the prepubertal children (Tanner stage I), being higher in girls than in age-matched boys (p < 0.05). Both sexes showed age-dependent changes in fasting GH levels (p < 0.001); highest levels were achieved at puberty and subsequently declined with advancing age. Hence, the physiological sex difference and age-dependency in GH secretion can also be demonstrated in single fasting samples.
The effect of ambient temperature on the analytical and clinical performance of a glucose meter was examined. A total of 114 venous whole blood samples were analysed for glucose by a reference method, and by a glucose meter at 21-22 degrees C, room temperatures, 26-27 degrees C and 33-34 degrees C. Glucose meter readings at each temperature were compared with the reference values and evaluated by analysis of variance, Spearman's correlation, the percentage of glucose meter readings within +/- 10% of the reference value and error grid analysis. Analysis of covariance was used to determine the effect of temperature on glucose meter readings. There were no significant differences in the glucose meter readings and in accuracy of the meter readings between different temperatures. Temperature was not a significant independent determinant of the glucose meter readings. For each glucose concentration, the precision of the meter and clinical performance were comparable between the different temperatures. In conclusion, ambient temperature does not affect the accuracy, precision and clinical performance of the Omnitest Sensor.
1. The effects of corticosteroid pretreatment on acetylcholine (ACH)-induced contraction of bronchial smooth muscle (BSM) were studied. 2. ACH dose-response curves for dexamethasone (DM)- and corticosterone (B)-treated but not deoxycorticosterone (DOC)-treated BSM were significantly shifted to the right; this provides evidence that glucocorticoid treatment reduced the sensitivity of BSM to ACH. 3. Morphine enhanced BSM contraction in response to ACH by 20%. DM suppressed this enhancement. 4. These findings correlated well with the reduction of muscarinic receptor numbers in BSM by glucocorticoids in our previous study. In addition, glucocorticoids reduced the sensitivity of BSM to opioids.
11Beta-hydroxysteroid dehydrogenase (11beta-HSD) Type I enzyme is found in testis and liver. In Leydig cell cultures, 11beta-HSD activity is reported to be primarily oxidative while another report concluded that is primarily reductive. Hepatic 11beta-HSD preferentially catalyzes reduction and the reaction direction is unaffected by the external factors. Recent analysis of testicular 11beta-HSD revealed two kinetically distinct components. In the present study, various steroid hormones or glycyrrhizic acid (GCA), given for 1 week, or thyroxine given for 5 weeks to normal intact rats had different effects on the 11beta-HSD oxidative activity in testis and liver. Deoxycorticosterone, dexamethasone, progesterone, thyroxine, and clomiphene citrate increased testicular 11beta-HSD oxidative activity, but decreased hepatic enzyme activity except for deoxycorticosterone (unchanged). Corticosterone and testosterone decreased 11beta-HSD oxidative activity in testis but not that of liver (which was unchanged). Estradiol, GCA and adrenalectomy lowered oxidative activity of 11beta-HSD in testis and liver, but the degrees of reduction were different. The in vivo effects of glucocorticoids too were different, even in the same organ. Dexamethasone, a pure glucocorticoid, has greater affinity for glucocorticoid receptors (GR) than corticosterone. The direct effects of dexamethasone via GR in increasing testicular 11beta-HSD oxidative activity may override its indirect effects. Possibly, the reverse occurs with corticosterone treatment, as it has both glucocorticoid and mineralocorticoid effects. Because both organs have Type I isoenzyme, the difference in 11beta-HSD oxidative activities of these two organs could be attributable to the presence of an additional isozyme in testis or differences in tissue-specific regulatory mechanisms.
1. alpha-Tocopherol (alpha-T) and gamma-tocotrienol (gamma-T) were supplemented continuously for 8 weeks in the diets of normal rats and rats chemically induced with cancer using diethylnitrosamine (DEN), 2-acetylaminofluorene (AAF) and partial hepatectomy. Hepatocarcinogenesis was followed by determining the plasma gamma-glutamyl-transpeptidase (GGT) and alkaline phosphatase (ALP) activities as well as placental glutathione S-transferase (PGST) and GGT activities histochemically, at 4-week intervals. 2. Male Rattus norvegicus were supplemented alpha-T and gamma-T at two different doses of 30 and 300 mg/kg diet. The supplementation was started at three different times: simultaneously with DEN administration; 4 weeks; and 8 weeks after DEN administration. 3. Elevation of plasma GGT activities and formation of PGST and GGT positive foci were attenuated significantly (P < 0.05) when alpha-T and gamma-T were supplemented simultaneously with cancer induction. Supplementation begun 4 and 8 weeks after cancer induction did not affect plasma enzyme activities and formation of enzyme-positive foci. 4. alpha-T was more effective than gamma-T, and a lower dose of 30 mg/kg was found to be more effective in reducing the severity of hepatocarcinogenesis.
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.
The aim of this study was to determine ethnic differences and predictors of the perception of quality of life (QOL) in a multiethnic Malaysian population with type 2 diabetes.
To construct a type-2 diabetes specific quality of life (QOL) tool for Asian populations that is valid and reliable across different ethnicities, languages, and socio-economic backgrounds.
1. Male Sprague-Dawley rats were made either hyper- or hypothyroid with thyroxine or 4-methyl-2-thiouracil, respectively. Bronchial smooth muscle (BSM) contractility and lung cyclic adenosine 3',5'-monophosphate (cAMP) content were measured in both conditions. 2. Bronchial smooth muscle contractility was significantly weaker in hyperthyroid rats, while the BSM contractility of hypothyroid rats was the same as controls. 3. The cAMP content of hyperthyroid rat lungs was similar to controls but was decreased in hypothyroid rats. 4. These studies demonstrated that both the hyper- and hypothyroid states affect respiration, although the mechanisms involved with different for each condition.
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.