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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperinsulinemia has been shown to be associated with diabetic angiopathy. Migration and proliferation of vascular smooth muscle cells (VSMC) are the processes required for the development of atherosclerosis. In this study, we attempted to determine whether insulin affects mitogenic signaling induced by platelet-derived growth factor (PDGF) in a rat VSMC cell line (A10 cells). PDGF stimulated DNA synthesis which was totally dependent on Ras, because transfection of dominant negative Ras resulted in complete loss of PDGF-stimulated DNA synthesis. Initiation of DNA synthesis was preceded by activation of Raf-1, MEK and MAP kinases (Erk 1 and Erk2). Treatment of the cells with PD98059, an inhibitor of MAPK kinase (MEK) attenuated but did not abolish PDGF-stimulated DNA synthesis, suggesting that MAPK is required but not essential for DNA synthesis. PDGF also stimulated phosphorylation of protein kinase B (Akt/PKB) and p70 S6Kinase (p70S6K) in a wortmannin-sensitive manner. Rapamycin, an inhibitor of p70S6K, markedly suppressed DNA synthesis. Low concentrations of insulin (1-10 nmol/l) alone showed little mitogenic activity and no significant effect on MAPK activity. However, the presence of insulin enhanced both DNA synthesis and MAPK activation by PDGF. The enhancing effect of insulin was not seen in cells treated with PD98059. Insulin was without effect on PDGF-stimulated activations of protein kinase B (Akt/PKB) and p70S6K. We conclude that insulin, at pathophysiologically relevant concentrations, potentiates the PDGF-stimulated DNA synthesis, at least in part, by potentiating activation of the MAPK cascade. These results are consistent with the notion that hyperinsulinemia is a risk factor for the development of atherosclerosis.
Int J Exp Diabetes Res
PMID:Potentiation of mitogenic activity of platelet-derived growth factor by physiological concentrations of insulin via the MAP kinase cascade in rat A10 vascular smooth muscle cells. 1199 Nov 99

The aim of our in vitro experiments was to study the effects of EGF on rabbit ovarian cells, as well as the possible mechanisms of these effects. The influence of EGF on steroidogenesis, proliferation, cyclic nucleotides and MAP-kinase in rabbit granulosa cells were studied. Results of RIA showed, that EGF stimulated the release of progesterone (1-100 ng/ml), cAMP (at 100 ng/ml), cGMP (1-100 ng/ml). EGF effect on estradiol output was biphasic: at dose 1 ng/ml it inhibited, whilst at 100 ng/ml it strongly increased estradiol secretion. Immunocytochemical study demonstrated an EGF-induced (10 ng/ml) increase in the proportion of cells revealing proliferating cell nuclear antigen (41% vs 24.7% in control, p < 0.01). EGF (10 ng/ml) increased the proportion of cells with immunoreactivity to ERK-1 (more than two-fold) and ERK-3 (three-fold) members of the MAP-kinase family. Moreover, EGF induced the translocation of ERK-1 to the nucleus, whilst preferentially cytoplasmic localization of ERK-3 was not changed after EGF addition. This can indicate regulation of ERK-1 and -3 by EGF, as well as differential patterns of ERK-1 and ERK-3 expression in response to EGF in cultured granulosa cells. - These results indicate that EGF can be a stimulator of proliferation, steroidogenesis and cyclic nucleotide release by rabbit granulosa cells. Stimulation of cAMP and cGMP release, and activation of ERK-related MAP kinase in granulosa cells after EGF addition indicates the involvement of these intracellular messengers in mediating the EGF action on the ovary.
Exp Clin Endocrinol Diabetes 2002 May
PMID:Effect of epidermal growth factor (EGF) on steroid and cyclic nucleotide secretion, proliferation and ERK-related MAP-kinase in cultured rabbit granulosa cells. 1201 72

Couples in the Philippines are free to choose the family planning method that best satisfies their health needs and religious beliefs. All service delivery outlets of the Philippines Department of Health and participating agencies should have all approved, safe, effective, and legal family planning methods available. Oral contraceptives (OCs), IUDs, tubal ligation, and vasectomy are at least 92% effective. OCs protect against pelvic infection and reduce the risk of ovarian and uterine cancer. Older OC users who smoke face an increased risk of blood clotting, stroke, and heart attack. The progestogen-only pill is the best OC for lactating women. The IUD can be effective for 6 years assuming no pain or other side effects. Breast feeding mothers can use the IUD safely. IUD contraindications are anemia, active cervical or pelvic infection, abnormal vaginal bleeding, and genital cancer. Condoms protect against pregnancy as well as sexually transmitted diseases, including HIV/AIDS. When practiced correctly, natural family planning methods are 70-90% effective. They are the cervical mucus method, basal body temperature method, sympto-thermal method, and breast feeding. Norplant contraceptive implants are available to Philippine women on a trial basis. They release a progestin slowly into the blood stream, suppressing ovulation and thickening cervical mucus. The long-acting contraceptive injectables are DMPA, Cycloprovera, and HRP 102. Women must receive an injection every 3 months to protect against pregnancy. The first injection should occur within the first 5 days of the menstrual cycle. Women choosing tubal ligation and men choosing vasectomy should be sure in their decision because they are permanent methods and sterilization reversal procedures are rare in the Philippines. Men with diabetes, an infection at the incision site, clotting disorders, enlarged or painful testicles, and an inguinal hernia should not have a vasectomy.
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PMID:The family planning methods. 1217 21

The use of depo-medroxyprogesterone acetate (DMPA), or Depo Provera, has been debated for the 20 years since it became available in 1967. The US Food and Drug Administration (FDA) refused to approve Depo Provera on the basis that it caused breast tumors in a controlled study of Beagle dogs and Rhesus monkeys conducted by Upjohn, the manufacturer. Depo Provera has been approved in over 60 other countries and is in use in 30 or 40 others with an estimated total of almost 5 million users. A natural hormone, progesterone, DMPA is injected intramuscularly and absorbed slowly. Common dosage is 150 mg every 3 months and usually is administered during the 1st week of the menstrual cycle. The pregnancy rate with Depo Provera is .44 pregnancies/100 women years for women receiving 100 mg every 3 months. No pregnancies were recorded in recent studies for women receiving 150 mg. Possible side effects include amenorrhea, weight gain, dizziness and headaches. The median time for contraception after the presumed duration of one's last injection is 5-1/2 months. Some countries only permit women who already have 1 child to use Depo Provera. The FDA in the US approves the use of Depo Provera for treatment of endometrial and renal cancer but accuses it of causing cancer in Beagles and Rhesus monkeys. The studies were conducted over 7 and 10-year periods, respectively, with extremely negative results including the death of 3 dogs due to "drug-induced diabetes," atrophication of adrenal glands, and malignant tumors. There were similar results for the monkey study. In the UK, the Committee for Safety in Medicine supports Upjohn's view that Beagles are unsuitable for comparison testing because "all dogs are acutely sensitive to progesterone." Groups such as the National Women's Health Network, the institute for Food and Development Policy, and "Mother Jones" have used the media to generate opposition to Depo Provera, citing a double standard for rich and poor women, developed and less developed countries. The proponents of Depo Provera criticize health activists for imposing their own standards on women in developing countries. Regarding concerns about greater risk of Acquired Immune Deficiency Syndrome (AIDS), Depo Provera can be injected with disposable needles. In response to the controversy, Upjohn withdrew its application to the FDA in September 1986 but intends to resubmit with new information from a World Health Organization report, which showed no evidence of an increased risk of cancers of the endometrium, liver, or breast.
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PMID:Depo Provera: still controversial. 1217 73

The author describes a range of contraceptive methods, and their side effects, which may be acceptable for new parents. The methods are the oral contraceptive pill, Norplant, Depo-Provera, and intrauterine devices (IUD). Natural methods and permanent contraception are options described in insets. The author notes that differences in the effectiveness rates among available types of oral contraceptive pills are small enough not to merit consideration when deciding which kind of pill may be appropriate. Combination birth control pills are taken daily at the same time for 21 out of 28 days. Combination pills are not recommended for women with a history of hypertension or other cardiovascular diseases, thrombophlebitis, migraine headaches, diabetes, active gallbladder disease, or mononucleosis. Any hormonal method may be particularly risky for smokers over age 35. The mini-pill, containing a smaller amount of progesterone and no estrogen, is taken every day and is also on a 28-day cycle. Containing no estrogen, the mini-pill is often recommended for women who are nursing, who are over age 35, or who suffer from hypertension or migraines. Both adverse and positive side effects may be experienced from use. Norplant is the brand name of a contraceptive system which releases progesterone from under the skin of a woman's upper arm over the course of a five-year period. The system has a theoretical effectiveness rate of more than 99%, although the duration of effectiveness may be less than five years in overweight women. The most common side effect is irregular bleeding, and removal is often a longer and more difficult procedure than insertion. The most commonly used injectable hormonal contraceptive is Depo-Provera, a progesterone solution which works for up to three months. The majority of users experience some side effects. Finally, IUDs are highly effective and need to be replaced only every 1-10 years depending upon how they are made. Women typically experience discomfort during IUD insertion, and they should not be used by women under age 20 years, who have never had children, or who have ever had a pelvic infection.
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PMID:Birth control for new parents. 1229 Aug 91

There are hormones from 2 sources which determine the menstrual cycle. The pituitary produces luteinizing hormone and follicle stimulating hormone and the ovaries secrete estrogen and progesterone. For clinical use, a cheap source of progesterone has been found in the Mexican yam. Since the 1st oral contraceptives were tested in Puerto Rico in the late 1950s, there has been a trend toward reducing the dosage. Estrogen prevents ovulation in 95-98% of patients. Other factors are also involved. Although it is estimated that 80-100 million women in the world today use oral contraceptives, this method is not always followed for long periods. From 25 to 60% discontinue the use within the 1st year. Increased risk of unfavorable side effects occurs in those with high blood pressure, migraine headaches, diabetes, epilepsy, undiagnosed genital bleeding, or gallbladder disease. Women over age 40 run a greater risk of heart attacks. Intravenous blood clots are the major risk. Severe abdominal, chest, or leg pains, severe headaches, and eye problems may be symptoms of blood clots. With the 21-day package the user takes a pill a day for 3 weeks and then none during menstruation. The sequential type of medication is no longer used. Minipills are taken every day. Missing taking pills is the most common cause of failure of the method. Estrogen replacement therapy for menopausal women is a temporary treatment to relieve physical distress. Depo-Provera, containing a long-acting progesterone agent, may be injected every 3 months instead of daily oral contraceptives. When progesterone is used with an IUD it acts locally. Hormones to maintain pregnancy are no longer used. Use of hormones as a test for pregnancy has been discontinued. Estrogen-progesterone injections given to inhibit milk production may cause serious side effects.
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PMID:The pills: oral contraceptives and other hormones. 1230 26

This "Ask the Experts" column addresses two concerns related to use of Depo-Provera. The first question relates to the clinical significance of frequent urination. Two of the three experts assert that frequent urination in a Depo-Provera user is unlikely to be related to method use; urinary tract infection and diabetes are more probable causes. The third notes that hypoestrogenicity could be a factor and suggests examination of the vagina for atrophy, which could cause the tissue around the urethra to become atrophic. The second question addresses techniques for confirming menopause in Depo-Provera users. The experts concur that measurement of follicle-stimulating hormone in perimenopausal Depo-Provera users lacks predictive value. Recommended, instead, is continuation of Depo-Provera with supplemental estrogen until the woman is in her mid-50s. At that time, conventional hormone replacement therapy can be initiated.
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PMID:Frequent urination and Depo-Provera. Ask the experts. 1232 8

About 600 injections per year are administered in a Luxembourg family planning center using 3 types of long acting progestatives: Depo Provera 150 and 450 and Norigest. The method is no longer reserved for women with completed families and the mentally handicapped since its reversibility has been proven. Patients seeking this type of contraception must meet the same criteria as for oral contraceptives except that women with contraindications for estrogens may tolerate progestatives. Long acting progestatives offer the safety of minipills along with high effectiveness since the risk of forgetting a pill is removed. Some women with cardiac disease, diabetes, and circulatory problems are able to use injectables, but caution should be exercised with hypertensives and the obese because of possible weight gain. Women with coagulation problems or suspected fibromas should be excluded. Administered postpartum, pure progestatives do not affect lactation. Menstrual cycles are completely disturbed, with irregular and unpredictable bleeding until amenorrhea appears after 3-6 months. Women who are psychologically unable to accept amenorrhea should not use this method, as they are more likely to experience undesirable side effects. Return of fertility upon termination of use poses no problem and usually occurs after 6-10 months, even after a single injection. Treatment with a sequential contraceptive beginning on the day when the next injection would have been given may help to reestablish menstruation. The physician should determine through a preliminary interview the couple's psychological readiness for this type of contraception. A careful medical history and gynecological examination should be done to rule out contraindications, and treatment should begin in the 1st 3 days of the cycle. Irregular and prolonged bleeding after 6 months of use can be treated with oral administration of estrogen, or by proceeding to the next injection ahead of schedule. Administration of a mild diuretic is rarely necessary for water retention. Pregnancy during use of the method is very rare but usually occurs after the 2nd or 3rd treatment and may be detected only in the 3rd or 4th month. Uterine size should be assessed at each treatment for the 1st year. Short term local treatment with estrogen rapidly restores vaginal lubrication when necessary. No serious incidents have occurred with use of long acting progestatives at this clinic.
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PMID:[Indications and medical survey of long acting progestatives used for contraception (author's transl)]. 1233 49

In this article, Dr. Andrew M. Kaunitz, associate professor of obstetrics and gynecology at the University of Florida Health Sciences Center in Jacksonville, gives suggestions for prescribing Depo-Provera. While Depo-Provera works as a contraceptive primarily by inhibiting ovulation, it has other antifertility effects, such as endometrial atrophy and cervical mucus thickening, which help prevent pregnancy in case ovulation does occur. A usual dose of Depo-Provera, 150 mg given intramuscularly every 3 months, has a contraceptive efficacy rate of 99.6%--the highest rate for any hormonal method. Kaunitz explains that the initial injection of the drug should take place within 7 days of the beginning of menses to ensure that there is no pregnancy. Efficacy is highest up to 12 weeks after injection, even though ovulation does not take place 14 weeks after the drug is administered. In the event that the patient is more than 2 weeks late in receiving her second or subsequent injection, Kaunitz recommends obtaining a pregnancy test. Because of possible adverse effects on carbohydrate metabolism and lipoprotein levels, Kaunitz suggests that women at high risk of cardiovascular disease or diabetes receive a lower dose of the drug, 100 mg. Similarly, very small women (those weighing under 100 lbs) may also require a smaller dose. Even at a lower dose, says Kaunitz, Depo-Provera remains highly effective, with a failure rate of 1%. Kaunitz also emphasizes prescribing Depo-Provera only to women who want a long-term contraceptive (at least 2 years), since although it does not affect fertility permanently, it does take longer for fertility to return than with oral contraceptives or Norplant.
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PMID:Prescribing tips for Depo-Provera. 1234 62

The bulk of the experimental data suggest beneficial effects of estrogen (both premenopausal use of OCs and postmenopausal use of ERT-HRT). An intriguing finding from the monkey studies is that social subordination, which induces estrogen deficiency in female monkeys, accelerates atherosclerosis premenopausally and predicts extent of postmenopausal atherosclerosis. This effect can be inhibited by exogenous estrogen, premenopausally. The results suggest that more effort on detecting and regulating premenopausal ovarian dysfunction may be justified. A complication in understanding estrogen action may be the result of varying extents of arterial damage. For example, primary prevention studies in both postmenopausal animals and women have provided strong evidence of atheroprotection with a variety of estrogens. In contrast, the results of secondary prevention studies [10,12] have in general suggested little cardioprotection with either ERT or HRT. Studies in rabbits suggest the antiatherogenic effect of estrogen may not be present when the endothelium is damaged [64]. The state of the endothelium may be critical for some estrogen actions. For those effects of estrogen that require the ER, be it ERalpha or ERbeta, the presence of the receptor may vary with age, disease state, or type of hormone therapy. If continuous combined HRT therapy decreases ER in the artery as it does in the uterus, this may eliminate those estrogen actions requiring the ER, but not others. Older women who have not been exposed to estrogens for many years may be more sensitive to some estrogen effects, and may need lower doses of ERT-HRT. Recent reports suggest that lower doses of estrogens maintain beneficial effects on lipoproteins and coagulation factors [95], while also requiring lower doses of progestogens to protect the uterus [96]. These beneficial findings are very promising in light of the improvements in CHD risk and decreased stroke risk reported with low-dose estrogens [5]. It ill be interesting to see if CRP is increased with lower doses of estrogens and whether these changes are associated with increased early risk of CHD. Perhaps older women with CHD are also more obese, may have diabetes, and may be more susceptible to inflammatory and thrombotic effects of higher doses of estrogens. There are many questions left unanswered. It is hoped that some of the answers may come from the WHI, which is a large prospective trial assessing ERT and HRT. The age range is also relatively large and may be able to determine if older women respond differently than younger women. Some initial data from the WHI have been made available suggesting a small increased risk in the first 2 years and a trend for decreasing risk in the last months of the first 2 years [34]. Just recently, the CEE + MPA arm of the study was stopped early by the data and-safety monitoring board as the overall health risks exceeded benefits with increases in both breast cancer and CVD [97]. The remainder of the study groups including an estrogen-only arm, are expected to continue until 2005.
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PMID:Reproductive hormones and cardiovascular disease mechanism of action and clinical implications. 1235 69


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