Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00627 (MAP)
 15,705 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recent literature relating to the pathogenesis of diabetic retinopathy, with or without nephropathy, is critically reviewed. Particular attention is given to the (GH) growth hormone hypothesis. The various procedures of hypophysectomy are discussed including the possible ways of suppressing GH production or overproduction by drugs, especially with (MAP) medroxyprogesterone acetate. Personal results obtained with long-term administration of MAP in depot form on alternate days in 10 patients with advanced retinopathy are described. An inconstant and barely significant suppression of the GH response to insulin-induced hypoglycemia was noted in 6 cases showing that a complete pituitary inactivation had not been achieved. Therefore, the modifications observed in the fundus picture seem to have no relationship with such a condition. The features involved were Microaneurysms and Hemorrhages and Exudates. New vessels and retinitis proliterans were unaffected. Subjective improvement in visual acuity appeared to be more frequent with various possible explanations. MAP was without appreciable effect on the clinical and metabolic course of the diabetes or on renal function in cases of concomitant nephropathy. In light of these preliminary results, further investigation seems to be justified. (author's modified) (summary in ENG).
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PMID:[Trial treatment of diabetic retinopathy by inhibition of pituitary somatotropin secretion with MAP]. 112 48

We have analyzed the inheritance of maturity-onset diabetes of the young (MODY) on chromosome 20 in a large multigeneration family, the R.-W. family, and in two other MODY families. Of the four branches of the R.-W. pedigree which have been studied, two have documented early onset of non-insulin-dependent diabetes mellitus (NIDDM), while there is no evidence of early onset in the other two branches. The early-onset branches have apparently inherited the same D20S16 allele from the affected parent, while another D20S16 allele was inherited in the two branches without evidence of early onset. A test for homogeneity, the M-test, using the results of two-point linkage analysis with D20S16 indicates heterogeneity between early- and late-onset branches of the R.-W. family (P less than or equal to .014). In addition, analysis strongly suggests that MODY as expressed in the EDI and WIS families is unlinked to loci on chromosome 20 (P less than or equal to .018-.004). Comparable results are seen when the data are analyzed by the HOMOG program. Three polymorphic loci-D20S16, D20S17, and ADA--show no recombination with the MODY locus when two-point linkage analysis is used in the early-onset branches of the family. The multipoint lod score in the early-onset branches of the R.-W. family is 10.16, with the most likely location being between D20S4 and D20S17. Multipoint linkage analysis using the CHROMPICS option of the program CRI-MAP has been used to follow inheritance of the MODY disease locus. This analysis has identified two cases of possible nonpenetrance in the early-onset branches of the family (odds of at least 156:1), as determined by the appearance of apparent isolated double crossovers at the MODY locus in these unaffected individuals.
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PMID:Linkage analysis of maturity-onset diabetes of the young (MODY): genetic heterogeneity and nonpenetrance. 153 97

In this article, we analyze the blood pressure (BP) threshold for the start of antihypertensive treatment in insulin-dependent diabetes mellitus (IDDM) patients, with particular emphasis on those with persistent microalbuminuria or proteinuria (incipient and overt nephropathy, respectively). In such individuals, there is a clear increase in the prevalence of hypertension and in actual measured BP values that is not observed in normoalbuminuric patients. In 94 young healthy adults (less than 45 yr of age), average mean +/- SD arterial pressure (MAP; diastolic + 1/3 pulse pressure) was approximately 90.0 +/- 8.1 mmHg, closely corresponding to large population studies. In microalbuminuric IDDM patients, MAP values between approximately 105 and approximately 95 mmHg have been found in different studies, and the level has progressively decreased in various studies between 1984 and 1990 with similar BP-measuring techniques. Somewhat higher values are seen in patients with proteinuria, who are also consistently characterized by reduced glomerular filtration rate (GFR). A clear correlation is found between MAP plotted against the increased rate of microalbuminuria (%/yr) in incipient nephropathy and against fall rate of GFR (ml.min-1.mo-1) in proteinuric patients. In the natural history of renal disease, different cutoff points in MAP for start of progression are observed: greater than 95 mmHg for the start of progression of microalbuminuria and greater than 105 mmHg for the decrease in GFR. During antihypertensive treatment, there is reduction or no progression in microalbuminuria with MAP of approximately 90-95 mmHg and only a limited fall in GFR with MAP of approximately 100 mmHg. However, certain antihypertensive drugs (angiotensin-converting enzyme inhibitors) may have specific renoprotective actions, reducing microalbuminuria at rather low BP levels or even independent of BP reduction. The optimal way of monitoring BP may be by 24-h ambulatory recording.
Diabetes Care 1991 Nov
PMID:Renal factors influencing blood pressure threshold and choice of treatment for hypertension in IDDM. 174 53

Recent studies have shown the predictive power of abdominal distribution of adipose tissue for the development of cardiovascular disease, stroke, diabetes as well as strong associations to the previously known risk factors for these endpoints. The reason for the accumulation of abdominal fat might be due to an imbalance between cortisol and sex steroid hormones. Cortisol receptor density seems to be particularly high in abdominal adipose tissue, leading to expression of lipoprotein lipase activity primarily here. Progesterone and testosterone seems to counteract this, the former perhaps through competition with the cortisol receptor. Accumulation of intraabdominal fat, particularly in the tissues drained by the portal circulation, probably leads to high free fatty acid concentrations in the portal vein, because of the high lipolytic sensitivity of these tissues. This in turn seems to inhibit hepatic clearance of portal insulin, leading to peripheral hyperinsulinemia, insulin resistance, perhaps hypertension as well as hyperlipidemia via drive by free fatty acids of lipoprotein synthesis in the liver. These are risk factors for diabetes, cardiovascular disease and stroke. It is of interest that subjects with abdominal adipose tissue have several factors leading to increased cortisol and low sex steroid hormone secretion, including stress, high alcohol consumption and smoking. This might provide some of the background to this syndrome.
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PMID:Obesity and adipose tissue distribution as risk factors for the development of disease. A review. 214 Jan 8

Researchers followed 68 women who attended the Family Welfare Clinic at the Kenyatta National Hospital in Nairobi, Kenya to determine if the low estrogen combined oral contraceptive (OC) Microgynon, a progestogen only OC, and Depo-Provera induce changes in the oral glucose test. These women did not take any steroidal contraceptives before entry into the study. Blood glucose levels were significantly higher after 60, 90 and 120 minutes than the control levels for women taking Microgynon. In addition, the mean areas under the glucose curves were substantially elevated after 1, 3, and 6 months above the control (p.002, .005, and .01 respectively). The only significant change in blood glucose levels in women taking the progestogen only OC occurred at 30 minutes after 6 months. Yet the mean areas under the curve were significantly higher than the control after ,1 2, and 3 months (p.005, .05 and .002 respectively). As for Depo-Provera, significantly lowered blood glucose levels only occurred after 1 month at 30, 50, and 90 minutes although no significant changes occurred after 1, 3, and 6 months in the mean areas under the glucose curves. Metabolic change occurred earlier and more often in Microgynon users than progestogen only OC users. This could be due to the progestogen levonorgestrel which has been shown to interrupt glucose metabolism. These changes could possible adversely effect women who are predisposed to developing diabetes, since 1 woman did develop a diabetic curve after 1 month of using Microgynon. Nevertheless no pattern towards abnormal glucose tolerance existed. Standard deviations of areas under the curves indicated that the number of women who develop glucose intolerance may increase with duration of use.
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PMID:The effect of low-oestrogen combined pill, progestogen-only pill and medroxyprogesterone acetate on oral glucose tolerance test. 214 46

The clinical use of estrogens and progestogens for menopausal women is reviewed, discussing the indications, results of studies on effectiveness of various agents o each target organ, contraindications, risk-benefit ratio, and types of drug preparations available and used in European countries. The indications for menopausal hormone replacement are primarily to prevent myocardial infarction and osteoporosis, and also to treat early menopause, urogenital atrophy, and severe skin, mucous membrane and psychic disorders. Mechanisms of action of estrogens and progestins, and anticipated results are detailed for each of the indications. Contraindications typical of oral contraceptives usually do not apply for hormone replacement. For example, only severe acute liver disease, current thromboembolism, endometrial cancer other than I, and breast cancer within 3-5 years of primary treatment are contraindications. Neither cervical, ovarian or vulvar cancer, diabetes, varicose veins, hypertension, nor history of liver disease or thromboembolism are contraindications: in some cases progestins or transdermal estrogens are recommended. Estrogen side effects suggest overdosage. Progesterone or its derivatives rather than oral contraceptive progestins are prescribed. There is a clear benefit, comparing cost of medication to that of treating consequences of estrogen deficiency. The preparations currently used in Europe include oral micronized estradiol, conjugated estrogens, transdermal patches, local vaginal estrogens, and injectable estradiol esters for those who cannot tolerate oral or transdermal agents. Preparations should contain progesterone unless the woman has had a hysterectomy. Combinations designed to avoid withdrawal bleeding are available.
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PMID:Clinical use of oestrogens and progestogens. 221 69

Insulin and insulin-like growth factors have been implicated in the stimulation of ovarian steroidogenesis. To assess the effect of diabetes mellitus on this process, a comparison was made of progesterone production by cultured granulosa cells (50,000 cells/well) from 11 individual follicles of nondiabetic and 6 individual follicles of diabetic women. Diabetic metabolic control was fair [HbA1C 6.8, 8.7 (nl 5.0-7.5)]. Cells were collected by laparoscopic follicular aspiration after ovulation induction and isolated by Percoll gradient centrifugation. Progesterone production was measured after culture with hCG (10 IU/mL) or insulin (100 microU/mL). In both nondiabetic and diabetic groups on day 4, hCG significantly stimulated progesterone production (1,686 +/- 1,268 ng/mL to 4,123 +/- 2,825 ng/mL and 1,059 +/- 249 ng/mL to 1,506 +/- 245 ng/mL, respectively). In nondiabetic follicles, insulin also stimulated progesterone production on days 4 (2366 +/- 1032 ng/mL to 3699 +/- 1582 ng/mL; P less than .05) and 7 (987 +/- 475 ng/mL to 1858 +/- 929 ng/mL; P less than .05); this response was not noted in diabetic granulosa cells. We suggest that insulin-stimulated progesterone production by granulosa cells isolated in the presence of fair diabetic metabolic control is impaired.
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PMID:Progesterone production from granulosa cells of individual human follicles derived from diabetic and nondiabetic subjects. 256 16

The injection of 25 mg/kg i.p. cyclosporin (CsA) for 3 wk caused marked functional and morphological deteriorations of pancreatic islet cells in Wistar rats that were prevented by the combined administration of p-aminobenzoic acid-N-D-mannoside sodium salt (K-MAP). In this article, the toxic effect of CsA on pancreatic islet cells and the preventive effect of K-MAP on CsA-associated islet cell toxicity were investigated. Prolonged hyperglycemia and depressed insulin secretion after the glucose challenge observed in CsA-treated rats could be prevented by the combined administration of 300 and 900 mg/kg K-MAP. Cytoplasmic vacuolizations and a decrease in the number of mitochondria, intact endoplasmic reticula, secretory granules, and insulin-positive cells, as revealed by peroxidase-antiperoxidase staining, could also be prevented by the administration of 900 mg/kg K-MAP. This preventive effect of K-MAP on CsA-associated islet cell toxicity may suggest the combined use of K-MAP with CsA in pancreas transplantation and treatment of insulin-dependent diabetes.
Diabetes 1989 Jan
PMID:Modulation of prostaglandin metabolism by K-MAP and prevention of toxic effect of cyclosporin on pancreatic islet cells. 264 33

Patients with a history of recurrent candidiasis and who were using Depo-Provera (medroxyprogesterone acetate, DMPA) for contraception were reviewed in order to determine the time relationship between episodes of proven candidiasis, episodes of pruritus vulvae suggestive of this infection (but unproven), and injection of DMPA. Recently, patients were included in the study who had been given DMPA specifically to prevent recurrences of candidiasis even when the drug's contraceptive action was unnecessary, such as after sterilization. In all cases, the infection was initially treated with a vaginal candidacide, most commonly 1 week of an imidazole. The patients ranged in age from 19-37 years at the time of the 1st injection. Diabetes had been eliminated in all the cases. DMPA was given intramuscularly at a dose of 150 mg every 12 weeks. Prior to 1983, an estrogen supplement was prescribed in most cases in an effort to produce monthly menstrual periods. Estrogen supplementation is no longer used routinely, with amenorrhea the aim, although it is occasionally given to women who experience breakthrough bleeding. Candidal infection was considered proven when the branching filaments of the species were seen on a stained vaginal smear or when the species were cultured in a laboratory from a vaginal swab taken a symptomatic patient. With the exception of 2 patients, clinical candidiasis did not occur within the time in which 150 mg of intramuscular DMPA is known to suppress ovulation in all women, i.e., 12 weeks -- except in the presence of exogenous estrogen (cases 1, 2, and 14) and in one case (15) in which the patient had an unplanned conception prior to the injection. Both patients who experienced clinical despite the use of DMPA alone (cases 8 and 13) asked remain on the drug because believe it was responsible for their longest remissions in the past few years. The study seemed to provide evidence that DMPA will prevent a recurrence of clinical candidiasis in many women who are prone to this condition. The study further indicated that estrogens may predispose women to this infection.
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PMID:Depo-Provera in the treatment of recurrent vulvovaginal candidiasis. 294 26

Synthetic progestins derived from nortestosterone provide a promising contraceptive alternative for women with contraindications for estrogens. Progesterone and synthetic progestins reduce vasodilatation and edema induced by estrogens and stop estrogen-dependent cellular multiplication in target tissue. Progestins have 2 kinds of contraceptive affect: antigonadotropic action at sufficient doses, and peripheral action at lower doses. The cervical mucus is modified in composition and volume, becoming hostile to sperm; the endometrial mucus atrophies; and tubal motility is slowed. High dose progestins are administered from the 5th or 10th to the 25th cycle day, with the earlier date preferred for women with shorter cycles. They are an ideal method for women with endometrial hyperplasia or benign breast disease or histories of breast or uterine cancer, as well as for women over 40 with dysovulatory cycles. Contraindications to high dose progestins include obesity, hypertension, lipid metabolic anomalies, and diabetes. Low dose progestin-only pills are administered at the exact same time each day including during menstruation. They are attractive for some women because they contain no estrogen, a reduced progestin dose causing fewer headaches and less somnolence, and fewer metabolic effects. Low dose progestins are indicated for lactating women, those with contraindications to estrogens such as obesity, hypertension, hyperlipidemia, and diabetes, and those with renal or cardiac insufficiency with valvulopathy. Low dose progestins are also indicated for nulliparas and other women for whom IUDS are contraindicated. Women using low dose progestins should never take drugs that act as enzymatic inductors, which speed hepatic degradation of steroids and reduce their efficiency. A resulting pregnancy is likely to be extrauterine because of slowed tubal transport. The failure rate of low dose progestins ranges from .9-3%, with higher failure rates among younger women. About 30% of users initially experience spotting, which despite its usual disappearance after 2-3 months of use is the most common reason for discontinuing the method. Low dose progestins have no metabolic or vascular effects, but they may cause a relative hyperestrogenism is some users. Other modes of administration of progestin contraception include continuous high doses, never justified solely for contraception. Trimonthly injections of medroxyprogesterone acetate of norethindrone enanthate provide contraception through a long lasting antigonadotropic effect. Metrorrhagia and amenorrhea are among possible side effects. The method is used primarily in developing countries where its ease of use is a major advantage. Subcutaneous implants releasing continuous doses of levonorgestrel provide contraceptive protection for over 5 years. The cumulative failure rate is 1.7 at 5 years. Metabolic tolerance is good. The major side effect is menstrual irregularity.
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PMID:[Progestational contraception]. 365 94


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