Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor effect and safety and endocrinological effect of a depot formulation of luteinizing hormone-releasing hormone (LH-RH) analogue ICI 118630 (Zoladex) were studied. Each depot containing 3.6 mg of ICI 118630 (corresponding to the average daily release of 120 micrograms) was subcutaneously injected 3 times at 4 week intervals to 12 prostate cancer patients in total at 4 centers from August 1984 to March 1985. Of the 12 patients, 7 showed an objective clinical response (1 CR and 6 PR patients), 3 showed no change and the remaining 2 showed PD. Overall subjective improvement was obtained in 8 of 10 patients (80.0%). Serum hormone levels (LH, FSH, and testosterone) increased immediately after injection of depot and then significantly decreased during and after 2 weeks of treatment. These changes seen in 100% of the patients were attributable to the pharmacological action of the drug. Medical castration was attained in 3.1 +/- 0.9 weeks on average. Observed side effects included gynecomastia in 1 and hyperlipidemia in 2 patients which were all mild. The trial was continued in the patients who required no special medical treatment. Changes in blood Zoladex concentrations suggested no accumulation. These findings demonstrate the safety and useful endocrinological and antitumor effects of Zoladex in prostate cancer through its pharmacological action, that is, LH-RH agonistic action.
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PMID:[Clinical effect of slow release (depot) formulation of the LH-RH analogue ICI 118630 (Zoladex) in patients with prostatic carcinoma]. 295 79

Steroid metabolism in Nagase Analbuminemia Rats (NAR), a mutant strain established from Sprague-Dawley rats, was studied. NAR are characterized by lack of serum albumin and hyperlipidemia. Total testosterone concentration in the serum of NAR was lower than that of normal rats, while the serum free testosterone, LH and FSH concentrations were similar. The half lives of 14C-labeled testosterone administered intravenously in NAR and normal Sprague-Dawley (SD) rats were 4.4 and 4.1 min, respectively. The plasma clearance rates of testosterone in NAR and normal rats were 34.7 and 39.1 ml/min per kg body weight. On Sephadex G-100 chromatography, a mixture of [3H]testosterone and normal rat serum gave two protein peaks eluted in the void volume and the albumin fraction, and the radioactivity was eluted all in the albumin fraction. In contrast, a mixture of [3H]testosterone and NAR serum gave a single protein peak eluted in the void volume and the radioactivity was mainly eluted with this protein peak. The association constants of testosterone to NAR and normal rat sera were 1.25 and 2.24 X 10(4) M-1. Enzyme activities related to the synthesis of testosterone by the testicular microsomal fractions of NAR and normal rats were examined. The activities of 3 beta-hydroxysteroid dehydrogenase, 5-ene-4-ene isomerase, 17 alpha-hydroxylase, C-17-C-20 lyase and 17 beta-hydroxysteroid dehydrogenase were lower in NAR than in normal rats. The activity for synthesis of testosterone from pregnenolone by the testicular microsomal fraction of NAR was about 40% of that of normal rats. These findings indicate that the low serum concentration of testosterone in NAR is mainly attributable to decreased biosynthesis of testosterone in the testes.
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PMID:Reduced activity of androgen biosynthesis in the testes of rats with analbuminemia. 308 76

The hormone levels in the anterior pituitary gland and serum in Nagase analbuminemia rats (NAR), a mutant strain established from Sprague-Dawley rats with hyperlipidemia, were examined. For the anterior pituitary gland, the prolactin, TSH, GH, LH and FSH contents in male NAR were significantly lower than those of normal rats. In female NAR, prolactin, TSH and LH levels were also lower than those in normal rats, whereas FSH and GH were normal. For the serum, the concentrations of TSH, total T3, total and free T4, estradiol-17 beta and testosterone were examined. The serum testosterone concentration in NAR was lower than that of normal rats. Histochemical examination of the hydroxysteroid dehydrogenase (HSD) activity of testes was made in relation to the serum testosterone level. NAR testes, which are rather small compared with those of normal rats, have lower HSD activity. A higher level of serum TSH was seen in NAR. Total and free T4 concentrations were low in the male NAR only. Estradiol-17 beta and T3 concentrations in NAR were unchanged. Changes in serum LH and FSH levels during the estrous cycle in NAR were also studied. Their patterns of change are normal.
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PMID:Hormone levels of anterior pituitary gland and serum in Nagase analbuminemia rats. 643 Jun 88

A 47-year-old woman was evaluated for congenital dwarfism, primary amenorrhoea due to hypogonadotrophic hypogonadism, severe hyperlipidaemia with pancreatitis, and overt diabetes mellitus associated with severe insulin resistance requiring 2.5-3 units of insulin per kilogram body weight. Chromosomal analysis with trypsin banding was normal and biochemical evaluation revealed low oestrogen levels, inappropriately low gonadotrophins, very low IGF-I concentrations and GH concentrations unresponsive to insulin or L-dopa administration. Prolactin, pituitary-adrenal and pituitary-thyroid axes were normal. Dynamic testing with GnRH and GHRH produced increases in FSH, LH and GH concentrations. A MRI of the brain revealed no discernible hypothalamic abnormalities and a small pituitary. The presence of congenital combined growth hormone and gonadotrophin deficiency on the basis of a suprapituitary defect suggests the existence of common or related pathways regulating GnRH and GHRH synthesis or secretion and may have contributed to the ultimate development of insulin resistance and hyperlipidaemia.
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PMID:Isolated combined growth hormone and gonadotrophin deficiency due to hypothalamic dysfunction, associated with insulin resistance. 755 20

Because of their efficacy and ease of use, oral contraceptives (OCs) have become the most widespread contraceptive in France and the world. OCs also have the advantages of reversibility and increasing safety and innocuity due to lower doses of ethinyl estradiol (EE) and improved progestins. The contraceptive effect of OCs depends primarily on suppression of ovulation, endometrial atrophy, and modifications in the cervical mucus rendering it inhospitable to sperm. The three major types of OCs are combined pills of either standard or low dose, sequential pills, and low-dose progestins. Higher dose progestins may also be used for contraception but they are usually reserved for treatment of uterine and mammary pathology. Standard-dose combined OCs contain 50 mcg of EE, while low-dose formulations contain 20-40 mcg. Combined pills are monophasic, biphasic, or triphasic. The advantages of combined OCs are their great efficacy and antigonadotropic power, which allows total steroid doses to be reduced. They may however cause cycle problems due to endometrial atrophy. The long-term administration of EE alone for the first cycle phase with sequential pills has been shown to increase risks of breast disorders, endometrial dysplasia and uterine cancer. Sequential pills are now used only for short-term treatment in specific indications. Low-dose progestins provide a low and continuous dose of progestin. Ovulation is not always inhibited, and persisting secretion of LH and FSH involves some follicular maturation. Contraceptive efficacy relies solely on local effects on the cervical mucus, endometrial atrophy, and decreased tubal motility. The failure rate and incidence of ectopic pregnancy are higher and cycle problems are frequent. The only advantage is the absence of estrogen for women with contraindications. The side effects of combined OCs may include alterations of glucose tolerance and of lipid profiles, increases of blood pressure, modifications in coagulation factors leading to increased thromboembolic risk proportional to the estrogen dose, and increased risk of biliary lithiasis and certain types of jaundice. Combined OCs have not been formally proven to increase risk of cervical cancer, and they are known to have protective effects against ovarian tumors. Most adolescents tolerate standard-dose combined OCs quite well. Low-dose combined pills or high-dose progestins may be appropriate for women over 40. Combined OCs are contraindicated in cases of hypertension, although low-dose progestins may be prescribed. Combined OCs are contraindicated for many diabetics and in all cases of hyperlipidemia and in smokers over 35.
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PMID:[Oral contraception]. 827 87

The ES 300 system, a fully automated multichannel immunoassay analyzer, was evaluated simultaneously for 9 weeks in four major centers. Precision, accuracy, carryover, comparison to in-house methods, and interferences were assessed for the following 17 tests: T4, T3, FT4, TSH, TBK, TBG, LH, FSH, prolactin, HCG, digoxin, cortisol, ferritin, IgE, insulin, AFP, and CEA. All centers reported good intra-lab and inter-lab precision. Accuracy was judged to be good based on correlation with in-house methods and recovery of target values in commercial and proficiency control materials. Linearity was evaluated for 14 analytes. Method biases were observed for T3 and insulin that were attributed to differences in standardization. No significant interferences from bilirubin, lipemia, and hemolysis were observed for all methods except insulin and AFP. Featuring random access capability, low daily maintenance, and high throughput, the ES 300 system performed well and met the stated claims of the manufacturer.
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PMID:A multicenter evaluation of the Boehringer Mannheim ES 300 immunoassay system. 844 40

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used for the treatment of hyperlipidemia, and recent in vitro and animal data suggest that statins promote bone formation and increase bone strength. We examined the relationship between sustained continuous delivery of statin and fracture healing rates in adult male animals with femoral segmental fractures. Because statin affects the production of cholesterol we also evaluated the influence of statin, on adrenal and testicular steroidogenesis and the morphology of the reproductive tract tissues in animals receiving statin for a period of 12 weeks post surgery. Simvastatin significantly increased fracture healing and without significant influence on the body weights and the weights of the reproductive organs. Basal plasma LH, FSH and testosterone levels were not affected by active treatment with simvastatin. Reproductive tissue morphology was unchanged by local sustained release of statin. In conclusion, long-term simvastatin treatment delivered at a fracture target site did not influence testicular reproductive and endocrine function, but was able to effectively heal complicated segmental fracture.
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PMID:Evaluation of the male reproductive organs after treatment with continuous sustained delivery of statin for fracture healing. 1585 82

The age- and sex-related levels of plasma lipids, lipoproteins and apolipoproteins in a random population sample of 2875 Hong Kong Chinese Adults (1397 men and 1478 women aged 25-74) and their implications on cardiovascular risk assessment are reported. Total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides increased with age in both sexes. Postmenopausal women had the worst profiles. They also showed higher triglyceride and non-high density lipoprotein (non-HDL)-cholesterol and had higher percentage of values greater than the desirable limits, compared with men of the same age groups. Overall 39% of men and 29% of women had non-HDL cholesterol of 4.2 mmol/L or greater. Apolipoproteins A-I and B followed the same trends as HDL-cholesterol and LDL-cholesterol, respectively. Apolipoprotein E (apo E) allele frequencies were: epsilon2 8.7, epsilon3 80.4 and epsilon4 10.9% with the genotype having a significant effect on plasma apo E concentration (p < 0.001). Carriers of the epsilon2 allele had higher apo E values than those homozygous for E3. Lipoprotein(a) levels were higher in women than men (geometric mean 152 versus 102 mg/L, p < 0.05) and in women with FSH above versus below 40 IU/L (185 versus 136 mg/L, p < 0.05). With respect to the NCEP ATP-III 2001 guidelines, the prevalence of hyperlipidemia in the Hong Kong population approached those in high CHD prevalence Caucasian communities. Local management guidelines and community-wide programs to reduce fat intake, increase regular moderate exercise and reduce the prevalence of overweight and obesity are urgently required, and hormone replacement therapy for postmenopausal women might be warranted.
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PMID:Plasma lipid, lipoprotein and apolipoprotein levels in a random population sample of 2875 Hong Kong Chinese adults and their implications (NCEP ATP-III, 2001 guidelines) on cardiovascular risk assessment. 1647 54

The nephrotic syndrome is a renal disease characterized by proteinuria, hypoproteinemia, edema and hyperlipidemia. It has been reported that female nephrotic rats are characterized by loss of the oestrus cycle, follicle atresia, low gonadotropin and steroid concentrations; particularly, undetectable estradiol levels. Therefore, to determine the mechanisms involved in the ovarian steroidogenesis impairment, in this present study we evaluated the ovarian expression of the essential steroidogenesis components: cytochrome P450 side cholesterol chain cleavage enzyme (P450scc) and steroidogenic acute regulatory protein (StAR). The experiments were conducted in the rat experimental model of nephrosis induced by puromycin aminonucleoside (PAN) and in control groups. The evaluation of the expression of P450scc and StAR mRNA were performed during the acute phase of nephrosis as well as after the exogenous administration of 1 or 4 doses of human chorionic gonadotrophin (hCG), or a daily dose of FSH or FSH+hCG for 10 days. In addition, serum hormone concentrations, intra-ovarian steroid content, and the reproductive capacity were determined. The results revealed a decreased expression of mRNA of P450scc enzyme and StAR during nephrosis, and eventhough they increased after gonadotropins treatment, they did not conduce to a normal cycling rat period or fertility recovery. This study demonstrates that the mechanism by which ovarian steroid biosynthesis is altered during acute nephrosis involves damage at the P450scc and StAR mRNA synthesis and processing.
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PMID:Steroidogenic impairment due to reduced ovarian transcription of cytochrome P450 side-chain-cleavage (P450scc) and steroidogenic acute regulatory protein (StAR) during experimental nephrotic syndrome. 1657 60

Albright hereditary osteodystrophy (AHO) is a genetic disorder caused by heterozygous inactivating mutations in GNAS, the gene that encodes the alpha-chain of Gs (G alpha s). This syndrome is associated with short stature, obesity, brachydactyly, and subcutaneous ossifications. Patients with GNAS mutations on maternally-inherited alleles are resistant to multiple G-protein-coupled hormones, including parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), luteinizing hormone/follicle-stimulating hormone (LH/FSH), and glucagon. This variant of AHO, termed pseudohypoparathyroidism (PHP) type 1a, is due to tissue-specific paternal imprinting of G alpha s. We investigated whether patients with PHP type 1a exhibited evidence of resistance to growth hormone releasing hormone (GHRH) (1), another hormone requiring G alpha s function. In addition, G alpha s transcripts are imprinted in the pituitary somatotrophs responsible for growth hormone (GH) secretion which could thereby influence GHRH-dependent stimulation of somatotrophs. We therefore hypothesized that patients with PHP type 1a may be GH deficient which could contribute to the obesity and short stature in this condition. We found that GH deficiency is common in PHP type 1a (69%) with a prevalence that is much greater than in the general population (0.03%). We propose that GH status be evaluated in all patients with this condition. Treatment with recombinant GH could lead to improvements in height in children, as well as other physical (eg, obesity, hyperlipidemia, osteoporosis, reduced renal function) and psychological (fatigue and diminished sense of well-being) parameters in GH-deficient PHP type 1a patients of all ages.
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PMID:Short stature, obesity, and growth hormone deficiency in pseudohypoparathyroidism type 1a. 1667 31


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