Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various substances (saline solution, dextran, heparin, proteinase inhibitors, etc.) have been investigated to determine their influence on adhesion prevention, but until recently the results were controversial and lacked any implication for clinical use. The analysis of intraperitoneal plasminogen activating factor (PAA) and the fibronectin production rate of peritoneal macrophages promises new aspects of adhesion formation and prevention. The results of studies show a close correlation between ischemia/infection and the decrease of PAA as well as increased adhesion formation in patients (endometriosis) with increased fibronectin production by peritoneal macrophages.
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PMID:[Prevention of adhesions by intraperitoneal administration of substances in abdominal interventions]. 198 79

A review of the clinical features, diagnosis and management of primary and secondary dysmenorrhea updates some old views. Dysmenorrhea is painful menstruation, either cramps with no visible cause, primary dysmenorrhea, or secondary to specific pelvic pathology. Primary dysmenorrhea occurs in as many as 50% of young women, only in ovulatory cycles, and usually limited to the first 48 or 72 hours of menstruation. Secondary dysmenorrhea can be caused by any of a dozen or so disorders such as endometriosis, pelvic inflammatory disease, IUDs, irregular cycles or infertility problems, ovarian cysts, adenomyosis, uterine myomas or polyps, intrauterine adhesions or cervical stenosis. Psychological factors are now known not to cause dysmenorrhea, only to add to the reactive component of the pain. The pain is due to uterine cramps, hypoxia or ischemia, due to overproduction of prostaglandins, leukotrienes or vasopressin. Thus, primary dysmenorrhea can be treated with oral contraceptives if the women wishes to take pills for contraception and they are not contraindicated, or with non-steroidal antiinflammatory agents for the full 72 hours after pain begins. Calcium channel-blockers are also used on a research basis; transcutaneous electrical nerve stimulation is sometimes effective. If these treatments are not effective, investigation for causes of secondary dysmenorrhea is indicated, preferably for laparoscopy.
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PMID:Dysmenorrhea. 217 34

This paper summarizes what has been learned over the years about the role of eicosanoids in the pathogenesis of primary dysmenorrhea, endometriosis and menstrual migraine. The role of prostaglandins (PGs) in the pathogenesis of primary dysmenorrhea is inferred from four main observations: firstly, the clinical symptoms of primary dysmenorrhea are similar to those induced by the administration of PGF2 alpha and PGE2 for the induction of labour; secondly, the increased production of PGs by the endometrium during the luteal and menstrual phases of ovulatory cycles is consistent with the occurrence of primary dysmenorrhea mainly in ovulatory cycles; thirdly, the concentrations of PGF2 alpha and PGE2 in the endometrium and menstrual fluid of dysmenorrheic women are significantly higher than in controls; fourthly, certain PG inhibitors have been proved to be effective in the treatment of dysmenorrhea. The change in PG production can explain the major symptoms of primary dysmenorrhea, including the increased uterine contractility, uterine ischemia and the lowering of the pain threshold to chemical and physical stimuli in the pelvic nerve terminals. Moreover, recent experimental data suggest that leukotrienes (LTs) might be among the alternative pathogenetic causes of primary dysmenorrhea. The data which support a relationship between eicosanoids and endometriosis are as follows: endometriotic tissue produces PGs; the peritoneal fluid concentration of PGF2 alpha increases significantly after the induction of endometriosis in laboratory animals; the concentration of PGs in peritoneal fluid of some patients with endometriosis is greater than in controls and, finally, the number and activation of pelvic macrophages which are able to synthesize eicosanoids increase in patients with endometriosis. Possible roles for eicosanoids in the pathogenesis of infertility and secondary dysmenorrhea induced by endometriosis have been suggested. Eicosanoids are probably also involved in the pathogenesis of menstrual migraine. Different types of PGs might play a role both in the initial vasoconstriction during the prodromal phase of migraine and in the vasodilation and sensitization to pain typical of the pain phase.
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PMID:Eicosanoids in primary dysmenorrhea, endometriosis and menstrual migraine. 265 74

Primary dysmenorrhea occurs mostly in young women with a painful bleeding pattern. In a recent study, 72% of 19-year-old women had light, 19% had medium to severe, and 8% had severe symptoms. Secondary dysmenorrhea means pathological organic alterations of the genital tract: uterus myomatosus, endometrial polyps, endometriosis, and retroflexed uterus. IUDs can also generate this condition. A certain imbalance of estradiol and progesterone results in defective prostaglandin formation in the endometrium (too much PGF2alpha and too little PGI2) as well as in abnormal and increased uterine contractility and diminished endometrial, blood supply with concomitant painful ischemia. Increased prostaglandin synthesis leads to inflammatory processes and the traumatization of the endometrium (high PGF2alpha level), but IUDs also often cause secondary dysmenorrhea. Treatment calls for the normalization of prostaglandin formation in the uterus by dietary change by increasing fatty acid intake (fish oils and plant fats), and also by the systematic addition of exogenic gestagens (Duphaston 10 mg/day po. Orgametril 5 mg/day), and by the use of the progesterone-releasing IUDs (Biograviplan and Progestasert) that lessen the contractility of the myometrium by reducing PGF2-alpha synthesis. If pregnancy is to be avoided hormonal ovulation inhibitors as optimal, since their effectiveness is over 90% (Cilest, Femovan, Marvelon, and Ortho-Novum 2 mg). If contraception is not sought, nonsteroidal antiphlogistics are recommended: ibuprofen (400 mg 3-4 times/day), naproxen (250 mg 4-5 times/day), flufenamic acid (200 mg/day tid), mefenamic acid (500 mg 3 tid or 250 mg qid), aspirin (650 mg every 4-6 hours), indomethacin (25 mg tid, although it is relatively toxic). Magnesium is a natural calcium antagonist that can influence the intracellular calcium concentration in the myometrium. THe calcium blocker nifedipin (20-40 mg po) and beta-sympathomimetics (Partusisten) also mitigate uterine contractions, but the latter can produce more side effects as a consequence of interfering in the vegetative nervous system.
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PMID:[Drug therapy of dysmenorrhea]. 289 19

A 26-year-old woman with enteric endometriosis presenting with cecocolic intussusception, a cecal mass on barium enema, and gastrointestinal hemorrhage is described. Laparotomy revealed cecocolic intussusception, ileocecal endometrial implants, and cecal mucosal ulceration presumed secondary to ischemia of the intussuscepted bowel. Histopathology showed serosal and subserosal endometrial implants without mucosal invasion. A review of the literature of endometrial bowel disease is presented.
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PMID:Ileocecal endometriosis presenting with abdominal pain and gastrointestinal bleeding. 660 98

Surgically induced endometriosis in the mouse has been described as a model to investigate the effect of environmental pollutants on the growth of endometriotic implants. The objectives of this study were to evaluate a modified surgical procedure to induce endometriosis and validate the model by comparing the effects of estrogen, 4-chlorodiphenyl ether (4-CDE) as a possible estrogenic contaminant, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a contaminant with predominantly anti-estrogenic activities, on the growth of endometrial implants. Uterine strips (1.0 x 4.0 mm2) were autotransplanted to multiple sites in the abdomen of sexually mature female B6C3F1 mice (n = 33), which were randomly assigned to the following groups: intact control (n = 4); ovariectomized (OVX, n = 9); OVX and treated with 4-CDE (n = 6); OVX and treated with 17 beta-estradiol (E2, n = 9); and OVX and treated with E2 plus TCDD (n = 5). Endometrial implants survived warm ischemia regardless of implant site and appeared as small clear spherical or ovoid fluid-filled cysts. The diameter of the endometrial cysts in the OVX animals was significantly (p < 0.0001) smaller compared with the intact animals and OVX animals replaced with E2 or 4-CDE. In contrast, TCDD treatment inhibited the growth of endometrial cysts in the presence of estrogen. We conclude that autotransplantation of uterine slices to multiple abdominal sites results in formation of endometriotic cysts that are responsive to estrogen, and that environmental contaminants possess the potential to affect the survival and growth of endometrial cysts. Therefore, we concluded that the mouse endometriosis model described in this paper has applications to investigate the possible role of environmental pollutants in the development of endometriosis.
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PMID:Morphologic characteristics of endometriosis in the mouse model: application to toxicology. 943 42

Endometrial growth and repair after menstruation are associated with profound angiogenesis. Abnormalities in these processes result in excessive or unpredictable bleeding patterns and are common in many women. It is therefore important to understand which factors regulate normal endometrial angiogenesis. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that plays an important role in normal and pathological angiogenesis. In this study we show that expression of VEGF is regulated by hypoxia in human endometrium. Culture in vitro for 24 h under hypoxic conditions resulted in a 2- to 6-fold increase in VEGF secretion by both stromal and epithelial cells isolated from human endometrium. Quantitative RT-PCR was used to measure VEGF messenger ribonucleic acid (mRNA) levels in these cells. After hypoxia, VEGF mRNA levels increased 1.8-fold in stromal cells and 3.4-fold in glandular epithelial cells. The mRNA for each VEGF splice variant increased to an equal extent. The increase in VEGF secretion by stromal and epithelial cells in response to hypoxia was not altered by treatment at the same time with estradiol or progesterone. In situ hybridization of human endometrium during menstruation, when steroid levels are low but the tissue is subject to ischemia, showed strong hybridization to VEGF mRNA in both stromal and glandular cells. These results show that local factors, such as hypoxia, can regulate VEGF expression in the endometrium. This may play an important part in normal endometrial repair after menstruation. The secretion of VEGF by endometrial cells under hypoxic conditions may also be important in the pathogenesis of endometriosis, because it would be predicted to assist revascularization of desquamated endometrial explants when they attach at ectopic sites.
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PMID:Vascular endothelial growth factor expression in human endometrium is regulated by hypoxia. 1063 17

Whether induced by infection, inflammation, ischemia, and/or surgical injury, peritoneal adhesions are the leading cause of pelvic pain, bowel obstruction and infertility. It is clear that while postsurgical peritoneal wounds heal without adhesions in some patients, others develop severe scarring from seemingly equal procedures; in addition, in the same patient, adhesions can develop at one surgical site and not in another. The mechanisms underlying the predisposition to form adhesions as well as their site specificity are completely unknown. However, a large number of intraperitoneal surgical procedures are performed each day in the USA, and thus many patients are at risk of developing postoperative adhesions. Therefore, understanding of adhesion formation at the molecular level is essential and in the absence of such information, attempts to prevent patients from developing adhesions will remain an empirical process. The unprecedented advancement in molecular biology during the past decade has led to the identification of many biologically active molecules with the potential of regulating inflammatory and immune responses, angiogenesis and tissue remodeling, events that are central to normal peritoneal wound healing and adhesion formation. Although, the insight into their importance in the development of tissue fibrosis has substantially increased, their major roles in peritoneal biological functions and adhesion formation remain at best speculative. This article reviews the clinical implications of adhesions and attempts to highlight some of the key molecules i.e. growth factors, cytokines, chemokines, proteases and extracellular matrix, that are recognized to regulate inflammation, fibrinolysis, angiogenesis, and tissue remodeling, events that are central to peritoneal wound repair and adhesion formation. Finally, the article discusses the potential application and site specific delivery of several active compounds that are developed to alter the local inflammatory and immune response i.e., cytokine/chemokine network, targeted gene delivery and development of a new generation of biomaterials to prevent adhesion formation. Such understanding of peritoneal biology not only assist us to better manage patients with adhesion, but also those with endometriosis and malignant diseases that affect the peritoneal cavity.
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PMID:Peritoneal molecular environment, adhesion formation and clinical implication. 1189 50

Severe hemolysis or myolysis occurring during pathological states, such as sickle cell disease, ischemia reperfusion, and malaria results in high levels of free heme, causing undesirable toxicity leading to organ, tissue, and cellular injury. Free heme catalyzes the oxidation, covalent cross-linking and aggregate formation of protein and its degradation to small peptides. It also catalyzes the formation of cytotoxic lipid peroxide via lipid peroxidation and damages DNA through oxidative stress. Heme being a lipophilic molecule intercalates in the membrane and impairs lipid bilayers and organelles, such as mitochondria and nuclei, and destabilizes the cytoskeleton. Heme is a potent hemolytic agent and alters the conformation of cytoskeletal protein in red cells. Free heme causes endothelial cell injury, leading to vascular inflammatory disorders and stimulates the expression of intracellular adhesion molecules. Heme acts as a pro-inflammatory molecule and heme-induced inflammation is involved in the pathology of diverse conditions; such as renal failure, arteriosclerosis, and complications after artificial blood transfusion, peritoneal endometriosis, and heart transplant failure. Heme offers severe toxic effects to kidney, liver, central nervous system and cardiac tissue. Although heme oxygenase is primarily responsible to detoxify free heme but other extra heme oxygenase systems also play a significant role to detoxify heme. A brief account of free heme toxicity and its detoxification systems along with mechanistic details are presented.
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PMID:Free heme toxicity and its detoxification systems in human. 1591 43

It is widely known that angiogenesis plays a key role in endometriotic lesion formation and development. Antiangiogenic treatments aimed at inhibiting new vessel formation have proven efficient in experimental models. However, as antiangiogenic strategies do not target pre-existing pericyte-protected vessels, they require chronic administration and are likely to be beneficial for early-stage disease only or to prevent recurrence after surgery. Moreover, they may have detrimental effects on reproductive function. Vascular-disrupting agents (VDAs) have emerged as a promising new tool for the treatment of tumors. VDAs target established blood vessels, resulting in tumor ischemia and necrosis. These agents may therefore be more efficient against advanced disease. Two major types of VDAs are being developed for cancer: ligand-directed VDAs using antibodies, peptides and growth factors to deliver toxic effectors to tumor endothelium; and small-molecule VDAs exploiting physiological differences between tumor and normal endothelium to induce acute vascular shutdown. The ongoing evolution in genomics and proteomics is revolutionizing the discovery of novel endothelial markers. Several studies suggest that the vasculature of endometriotic lesions may have particular pathophysiological properties, which could be exploited for the development of selective VDAs. The aim of this review is to explore the merits and limitations of vascular therapy for the treatment of endometriosis.
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PMID:Antiangiogenic and vascular-disrupting agents in endometriosis: pitfalls and promises. 1843 Jul 58


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