Gene/Protein Disease Symptom Drug Enzyme Compound
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Histological changes were studied in the ovary and uterus of rats receiving different doses of Depo-Provera (DMPA) and Noristerat (NET-EN) for varying duration. The effect of DMPA on ovarian and uterine tissues was strongly progestational. The whole morphological alteration in the ovary after DMPA therapy appeared to be the atresia of the follicular apparatus with degeneration of the growing follicles. Uterine histology reflected that endometrial tissues gradually became inactive and with prolonged treatment at high doses, atrophy of the endometrium was noted. In NET-EN-treated rats, absence of mature follicles and recent corpora lutea reflected the blockade of ovulation. There was no extreme atrophy of the ovary or endometrium as found with DMPA treatment. With higher doses of NET-EN, endometrial growth was arrested.
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PMID:Histological changes in the ovary and uterus of rat after injectable contraceptive therapy. 297 Mar 68

The present work was a randomized comparative study of two injectable progestogen-only contraceptives. The first group (200 subjects) received 150 mg of depotmedroxyprogesterone acetate (Depoprovera) every 84 +/- 7 days and the second (200 subjects) received 200 mg of norethisterone enanthate (Noristerat) every 56 +/- 7 days. Acceptors of injectable contraceptives in Assiut, Egypt, were mainly women looking for fertility termination. Menstrual disruption was the main side effect among both treatment groups. Amenorrhoea was the commonest menstrual complaint and was the main reason for discontinuation in both groups. Only one pregnancy occurred during NET-EN use; two more pregnancies occurred, one in each of the two groups but there were indications that conception preceded the first injection. Menstrual irregularities were generally more frequent with DMPA users. However, DMPA had better one-year continuation rates than NET-EN (68.8 +/- 3.5 and 57.1 +/- 3.6 per 100 women, respectively).
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PMID:Acceptability of injectable contraceptives in Assiut, Egypt. 297 83

A prospective consecutive study was undertaken to compare the hemodynamic effect of two cardioplegic solutions in CABG patients after bypass, and in relation to aorta occlusion time with the support of a automatic datalogging database. A total of 249 patients were randomized. One group received Bretschneider cardioplegic HTK solution (132 patients, group I) the other group received St. Thomas cardioplegic solution (117 patients, group II). The data was divided in four periods of aortic clamp time: less than or equal to 40 min (group I 26 patients, group II 32 patients); 41-60 min (group I 49 patients, group II 47 patients); 61-80 min (group I 30 patients, group II 29 patients); and greater than 80 minutes (group I 27 pts, group II 9 patients). Anesthesia regime and therapeutic drugs and infusions were given in both groups in similar dosages. Within both groups HR, CO, PAP, PCWP increased after bypass in relation to prebypass values. SVR decreased in both groups by 30%, MAP and PVR decreased only in group I. Between group I and II differences were found in the CI (3.0 vs. 3.3 l/min/m2), MAP (70 vs. 76 mmHg), PMAR (18 vs. 16 mHg), and SVR (827 vs. 954 dyn.sec.cm-5). In significantly more of the patients in group I, sinus rhythm started spontaneously after the release of the aorta clamp (39.5% vs. 20.4%, p less than 0.005). Patients in group I needed temporarily a pacemaker after bypass in 6.3% cases (in 1.1% of patients in group II,). There was no relation of the hemodynamic data in relation to aorta occlusion time within the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical effect of Bretschneider-HTK and St. Thomas cardioplegia on hemodynamic performance after bypass measured using an automatic datalogging database system. 314 85

Progesterone and 5 alpha-pregnane-3,20-dione (5 alpha-DHP) were determined by radioimmunoassay in 242 amniotic fluid samples from 16-19 weeks of gestation. 165 samples fulfilled the criteria of the normal collective. There is a positive correlation (r = 0.359, p less than 0.001) between progesterone and 5 alpha-DHP. The mean concentration (+/- SD) of progesterone for normal pregnancies was 68.04 +/- 35.56 ng/ml, the mean for 5 alpha-DHP was 6.6 +/- 4.76 ng/ml. A slight decrease of the hormone concentrations with increase of the week of gestation was observed. 7 cases, who later developed EPH-gestosis showed a significant higher progesterone concentration (p less than 0.05). 16 women with premature labor had a significant higher 5 alpha-DHP concentration (p less than 0.05). Significantly elevated progesterone and 5 alpha-DHP values were found in 36 cases of bleedings in early pregnancy. Pregnant women older than 35 years proved to have a significant higher 5 alpha-DHP concentration (p less than 0.05). Also women, who delivered a child weighing less than 2,500 g (n = 8), showed a significant higher progesterone concentration (p less than 0.01). There was no difference in amniotic fluid progesterone and 5 alpha-DHP concentration depending on the sex of the child. The hormone concentrations of 3 cases with Morbus Langdon-Down were slightly below the mean concentration for progesterone and 5 alpha-DHP. Progesterone and 5 alpha-DHP concentrations were found to be normal in one case each of open Ductus Botalli, esophagial atresia, conjunctival bleeding with eyelid edema, teleangiectasia, Morbus Gaucher, sicklefoot, omphalocele, clubfoot, and stillbirth respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Progesterone and 5 alpha-pregnane-3,20-dione in human amniotic fluid. 359 31

The ultrastructural response of the uterine luminal epithelium of the spayed virgin rat was studied as a parameter in screening the effects of antifertility agents which may interfere with implantation. The agents studied were bis-(p-acetoxyphenyl-2-methyl-cyclohexlidene-methane (F-6103), bis-(p-acetoxyphenyl)-2-methyl-4-methylidene-cyclohexylidene-methane (F- 6255), bis-(p-acetoxyphenyl)-1,2,3,4-tetrahydro-1-naphtylidene-methane ( F-6278), trans-(p-2-dimethylaminoethoxyphenyl) -1,2-diphenyl-1-ene (ICI- 46474), 1-(p-(2-diethylaminoethoxy) phenyl) -2-(p-methoxyphenyl-1-phenylethane (MER-25), 3-ethyl-2-methyl-4-pheny; -4-cyclohexenecarboxylic acid, sodium salt (ORF-4563), 1-(2-(p-(3,4,-dihydro-6-methoxy-2-phenyl-1-naphtyl)-phenoxy) ethyl)pyrro lidine, HCI(U-11100A), 2(p-(6-methoxy-2-phenylinden-3-yl) phenoxy)trieth ylamine, HCI (U-11555A) and 2-phenyl-1-p-(beta-pyrrolidinoethoxy) phenyl naphto(2,1-b)-furan (66/179). The substances were tested in spayed rats in spayed rats given progesterone and in spayed rats given progesterone plus estradiol-17 beta. All agents gave an estrogen-like response when given separatly. The response was most marked with the F-compounds and ORF-4563. The F-compounds and ORF-4563 changed the ultrastructure profoundly in progesterone-treated rats while the other compounds had little effect. Progesterone plus estradiol rendered the epithelium suitable for implantation. Each compound except U-1155A inhibited the attachment reaction when given before estradiol.
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PMID:Attachment reaction of rat uterine luminal epithelium. V. Suppression of the attachment reaction by some antifertility agents. 465 Jun 61

Medroxyprogesterone acetate (MPA; 5 micrograms/g body wt) or norethisterone oenanthate (NET-OEN; 4 micrograms/g body wt) was given to lactating female rats by subcutaneous injection 1 day after parturition. Each female suckled ten female pups which had been randomly allocated to her and at 21 days of age the pups were weaned. In this way female pups were exposed to either MPA or NET-OEN via milk during suckling. The patterns of LH and progesterone secretion at pro-oestrus were investigated using radioimmunoassay. When these pups reached adulthood it was found that neonatal exposure to MPA via milk significantly reduced the pro-oestrous LH peak by 45% as well as the total amount (by 27%) of LH secreted during pro-oestrus. Neonatal exposure via milk to NET-OEN had no effect on LH secretion during pro-oestrus. Pro-oestrous progesterone secretion was unaffected by either MPA or NET-OEN treatment.
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PMID:Neonatal exposure to a progestin via milk alters subsequent LH cyclicity in the female rat. 622 92

This report summarizes a survey of the management of menstrual disturbances occurring during injectable progestogen use (depot-medroxyprogesterone acetate, DMPA and norethisterone enanthate, NET-EN) by 35 investigators from 20 countries with ongoing experience with these contraceptives. A wide range of approaches are described. The most frequently emphasized aspect of management is thorough pretreatment counseling with further support and counseling at follow-up visits. Estrogens in various forms are widely used for the treatment of prolonged, frequent, or heavy bleeding episodes, but now are not usually used for induction of withdrawal bleeding episodes in women with amenorrhea. Heavy or severe bleeding appears very uncommon and figures of 1-2% are mentioned. Anecdotal information suggests that intramuscular doses or longer courses (14-21 days) of oral estrogen, including the combined pill, are more likely to successfully stop an episode of heavy bleeding than short courses. However, there are no hard data to show that a course of estrogen treatment has any beneficial effect on longterm bleeding patterns. Nevertheless, temporary cessation of spotting or light bleeding may be sufficiently reassuring to the patient to ensure continued use of the method. There appears to be little risk associated with short-term estrogen regimens currently in use. Dilatation and curettage is almost never necessary to stop an episode of bleeding, but may occasionally be recommended for diagnostic reasons. Clearly, bleeding connected with DMPA and NET--EN use are poorly understood and research is necessary to clarify pathophysiological mechanisms and improve management.
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PMID:A survey of different approaches to management of menstrual disturbances in women using injectable contraceptives. 623 Feb 12

A randomized comparative trial of 832 women receiving (NET-EN) norethisterone enanthate and 846 women receiving (DMPA) depot medroxyprogesterone acetate injections at 12 week intervals was conducted in 10 centers. The pregnancy rate with NET-EN was significantly higher than with DMPA. The termination rate for amenorrhea was substantially lower with NET-EN than DMPA, whereas the discontinuation rates for bleeding problems were similar with the 2 drugs. Analysis of bleeding patterns among continuing and discontinuing users suggests that women tolerated frequent bleeding episodes, but found prolonged bleeding or prolonged bleeding-free intervals unacceptable. Bleeding for more than 30 days during an injection interval and complete amenorrhea for a whole injection interval were jointly associated with 43.7% of all terminations among NET-EN users and 64.5% of all terminations among DMPA users. In future efforts to improve the acceptability of long acting injectable contraceptives, more attention should be given to the control of prolonged amenorrhea and prolonged bleeding.
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PMID:Vaginal bleeding disturbances associated with the discontinuation of long-acting injectable contraceptives. From the World Health Organization Special Programme for Research, Development, and Research Training in Human Reproduction; Task Force on Long-acting Systemic Agents for the Regulation of Fertility. 700 25

Exposure to solar ultraviolet (UV) light is a major cause of skin cancer, the most common human neoplasm. The earth's upper atmosphere absorbs the high energy UV-C wavelengths (100-280 nm), while allowing transmission of UV-B (280-320 nm) and UV-A (320-400 nm). It is therefore UV-B and to some extent UV-A, that contributes to most human skin malignancies. We report that the exposure of cultured keratinocytes or skin to UV-C radiation causes activation of MAP kinases (ERK and JNK). In contrast, the solar radiation associated with skin cancer (UV-B) was an ineffective activator of the ERK and JNK signal transduction pathways. Therefore, while exposure of epidermal cells to UV-C radiation under laboratory conditions causes marked activation of MAP kinase signal transduction pathways, only a low level of MAP kinase signaling is involved in the response of skin to biologically relevant solar radiation.
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PMID:Differential effects of UV-B and UV-C components of solar radiation on MAP kinase signal transduction pathways in epidermal keratinocytes. 747 12

Human monoblastoid leukemia U937 cells differentiate to monocyte/macrophage upon treatment with phorbol ester, 12-o-tetradecanoylphorbol-13-acetate (TPA). Previous studies, including our own, have demonstrated that drug-induced differentiation of leukemia cells is associated with genetic and enzymatic activations of protein tyrosine phosphatases (PTPases). In this study, to further investigate a relationship between PTPase activation and leukemic differentiation, we established TPA-resistant U937 variant UT16 cells. Unlike known TPA-resistant cells whose resistance is mainly due to lack or down modulation of protein kinase C (PKC), UT16 cells showed TPA-induced activation of PKC, Raf-1, and ERK/MAP kinases similar to the parental U937 cells. Interestingly, however, UT16 cells exhibited altered binding activity of AP-1 complexes, decreased ability to induce c-jun and c-fos gene expressions, and failure to differentiate to a monocytic lineage. Based on these observations, UT16 cells could be considered a novel type of TPA-resistant cell. Among UT16 cells, most of TPA-inducible PTPase genes, PTP-1C, PTP-MEG2, P19-PTP, HPTP epsilon, and PTP-U1, did not respond to TPA. Consistently, TPA increased PTPase enzymatic activity in U937 but not in UT16 cells. Taken together, activation of PTPases is well correlated with TPA-induced differentiation of U937 cells. These findings indicate that gene expression and enzymatic activity of some PTPase isozymes described here are regulated by a TPA-mediated signaling event and are likely to be used as biomarkers for the monocytic differentiation of myeloid leukemia cells.
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PMID:Phorbol ester-resistant monoblastoid leukemia cells with a functional mitogen-activated protein kinase cascade but without responsive protein tyrosine phosphatases. 747 24


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