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)

Primary cilia have been shown to play an important role in embryonic development as well as in postnatal life. Dysfunctional cilia are associated with situs inversus, retinal abnormalities, impaired mucociliary clearance, infertility, hydrocephalus, and congenital renal cysts. In autosomal dominant polycystic kidney disease, mutations of the ciliary proteins polycystin1 or the transient receptor potential (TRP) channel family protein polycystin2 (TRPP2) cause progressive cyst formation and destruction of the kidney. Primary cilia act as flow sensors and respond to flow-mediated bending with a prolonged intracellular calcium increase, which appears to require an intact polycystin protein complex. We have established a novel flow chamber system, which allows us to study renal epithelial cells by live cell imaging. We show that MDCK cells respond to flow by a delayed increase in intracellular calcium and that this response requires these cells to be ciliated. We show that a novel interactor of TRPP2, kidney injury molecule-1 (Kim1), which is expressed at low levels in the normal kidney and upregulated after ischemia, in renal cell cancer and in PKD is targeted to primary cilia when stably expressed in MDCK cells. We demonstrate that expression of tyrosine mutant Kim1, lacking a conserved tyrosine in the intracellular tail, abolishes the calcium increase in response to flow in a dominant negative manner. These results establish Kim1 as a novel regulatory molecule of flow-induced calcium signaling.
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PMID:Ciliary calcium signaling is modulated by kidney injury molecule-1 (Kim1). 1720 56

In spite of prompt diagnosis and either orchiectomy or preservation of the affected testis, infertility remains a significant sequel to testicular torsion. The objective of this study was to evaluate the late endocrine profile, seminal parameters, and antisperm antibody levels after testicular torsion. We also analyzed the impact of orchiectomy or detorsion on the organ fate. Of 24 patients evaluated after testicular torsion, 15 were treated with orchiectomy (group 1) and 9 were treated with orchiopexy (group 2). All subjects were assessed by semen analysis, endocrine profile (levels of follicle-stimulating hormone, luteinizing hormone, and testosterone), and seminal antisperm antibody levels. A group of 20 proven fertile men was used as the control. Median ischemia time in group 1 (48 hours) was significantly higher than in group 2 (7 hours). Both groups demonstrated decreases in sperm count and morphology compared with controls. Group 1 showed a significantly higher motility than group 2 (P = .02). Group 1 also showed a significantly better morphology by World Health Organization and Kruger criteria than group 2 (P = .01). All patients presented endocrine profiles within the normal range, and no significant differences in antisperm antibody levels were detected between the groups. However, a trend for higher levels was found in patients treated for testicular torsion, regardless of the fate of the testis. Moreover, no significant correlation was found between antisperm antibody levels and age at torsion, ischemia time, seminal parameters, or treatment applied. In conclusion, we found that after torsion patients maintain late hormonal levels within the normal range. Testicular fate did not have any correlation with the formation of antisperm antibodies. Although sperm quality was preserved in most of the patients with the exception of sperm morphology, patients treated with orchiectomy presented better motility and morphology compared with the detorsion group. Further studies may clarify whether maintenance of a severely ischemic testicle may impair testicular function.
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PMID:Late hormonal levels, semen parameters, and presence of antisperm antibodies in patients treated for testicular torsion. 1728 56

Uterine transplantation is developed as a possible future treatment for patients with absolute uterus factor infertility. Patients with the Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, patients having had hysterectomy for benign or malignant uterine/cervical diseases and patients with intrauterine adhesions are the major groups of patients, who could benefit from this procedure. There has been one attempt to transplant a human uterus, which however failed. Since then, several uterine transplantation animal models have been developed to examine various aspects of the uterus transplantation procedure and to optimize it for human use. In a mouse model, normal pregnancy rate and offspring were seen after syngeneic uterus transplantation. The tolerance for cold ischemia from the time the uterus is taken out from the donor until placed in the recipient is around 24 h, as shown in a mouse uterine transplantation model and on human uterine tissue. The rejection pattern of the transplanted uterus was tested in an allogeneic mouse model with signs of rejection after 5 to 10 days. High doses of cyclosporin A (CyA) could partly suppress rejection but pregnancies have not yet been achieved in allogeneic uterus transplants in any species. In the sheep and pig models, the vascular anastomosis technique and the tolerability to cold ischemia have been evaluated. Normal offspring have been delivered in the sheep model after autotransplantation and presently allogeneic uterine transplants in sheep treated with corticosteroids and CyA are tested. Initial studies on uterus transplantation is also now conducted in primates. It is predicted that uterus transplantation may reach a clinical stage within 2-3 years, in the event of a continuous high research activity within this field.
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PMID:Uterine transplantation: a future possibility to treat women with uterus factor infertility? 1759 42

Testicular torsion is a urological syndrome caused mainly by a twist in the spermatic cord. It constitutes a surgical emergency and affects newborns, children and adolescent boys. The torsion must be treated promptly to avoid loss of function of ipsilateral and contralateral testis. This syndrome often leads to infertility of the ipsilateral (torted) and contralateral (not torted) testis,but the mechanisms of cellular injury remain still incompletely understood. The primary pathophysiologic event in testicular torsion is ischemia followed by reperfusion; thus, testicular torsion/detorsion is an ischemia/reperfusion (I/R) injury to the testis. Testicular torsion and detorsion causes morphological and biochemical changes by both ischemia and reperfusion of the tissues. These I/R injury is associated with overgeneration of reactive oxygen species (ROS) and reactive nitrogen species (RNS), and also with a common mechanism to other organs such as brain, heart and kidneys. Although the results are not conclusive and the molecular mechanism by which antioxidants control male fertility have not yet been clearly identified, several antioxidant enzymes and antioxidant drugs have been studied to prevent such I/R injury in testis. As a result, antioxidant therapy may represent a new non-hormonal option within a broader therapeutic strategy in men with ROS-mediated infertility such as testicular torsion.
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PMID:Testicular torsion, oxidative stress and the role of antioxidant therapy. 1766 92

Whether induced by infection, inflammation, ischemia, and/or surgical injury, peritoneal adhesions are the leading cause of pelvic pain, bowel obstruction, and infertility. Although some patients develop limited scar tissues, others for unknown reasons develop severe adhesions from seemingly equal procedures. Additionally in the same patient, adhesions develop at one surgical site but not in another. The mechanisms underlying the predisposition to form scars as well as their site specificity are unknown. Because a large number of intraperitoneal surgical procedures are performed each day, many patients are at risk of developing postoperative adhesions. As such, understanding the nature of molecular events and their mechanisms of action is essential, and in the absence of such information, attempts to prevent patients from developing adhesions will remain an empirical process. An unprecedented advancement in surgical techniques have resulted in minimizing peritoneal tissue injury that cause adhesion formation. Increased understanding of the cellular and molecular events that lead to scar tissue formation has also 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. This article attempts to highlight some of the key molecules (i.e., the transforming growth factor family and its regulatory mechanisms) that are recognized to regulate peritoneal wound repair and adhesion formation. Such understanding of peritoneal biology not only will assist us to better manage patients with adhesions but also will assist those with endometriosis and malignant diseases that affect the peritoneal cavity.
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PMID:TGF-beta system: the principal profibrotic mediator of peritoneal adhesion formation. 1875 7

Postoperative intra-abdominal and pelvic adhesions are the leading cause of infertility, chronic pelvic pain, and intestinal obstruction. It is generally considered that some people are more prone to develop postoperative adhesions than are others. Unfortunately, there is no available marker to predict the occurrence or the extent and severity of adhesions preoperatively. Ischemia has been thought to be the most important insult that leads to adhesion development. Furthermore, a deficient, suppressed, or overwhelmed natural immune system has been proposed as an underlying mechanism in adhesion development. The type of surgical approach (laparoscopy or laparotomy) and closure of peritoneum in gynecologic surgeries and cesarean section have been debated as important factors that influence the development and extent of postoperative adhesions. In this article, we have reviewed the current state of adhesion development and the effects of barrier agents in prevention of postoperative adhesions.
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PMID:Postoperative adhesions: from formation to prevention. 1875 8

Testicular torsion is a common syndrome that could lead to infertility. We investigated the therapeutic effects of lycopene, an antioxidant caretenoid, on testicular ischemia/reperfusion (IR) injury that resembles testicular torsion. Male Wistar albino rats were divided into three groups: sham (n = 6), IR (n = 18), and ischemia/reperfusion with lycopene (IRL, n = 18). Left testicular artery and vein was occluded for 1 h, followed by reperfusion of 3 h, 24 h or 30 days in IR and IRL animals. Either corn oil (vehicle) or lycopene (4 mg/kg) was administrated once daily by gavage to IR or IRL animals, respectively, 5 min after ischemia. Sham-operated animals were treated with vehicle by gavage 5 min after the operation. IR decreased sperm motility and concentration in both ipsilateral and contralateral testes and increased abnormal sperm rate in ipsilateral testis after 30 days of reperfusion. Treatment with lycopene increased the motility in bilateral testes and decreased the rate of abnormal sperm in ipsilateral testis to the sham level, but did not increase sperm concentration in bilateral testes. IR increased the activities of catalase and glutathione peroxidase and the level of reduced glutathione by 24 h of reperfusion, but malondialdehyde remained unchanged. Lycopene treatment restored the enzyme activities but not the reduced glutathione level. Lycopene treatment also ameliorated the IR-induced tissue damage in bilateral testes. In conclusion, the therapeutic antioxidant effect of lycopene on germ cells could serve as a promising intervention to oxidative stress-associated infertility problems, such as testicular torsion.
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PMID:Lycopene, an antioxidant carotenoid, attenuates testicular injury caused by ischemia/reperfusion in rats. 1947 70

Uterine transplantation may be a possible treatment option in the future for absolute uterine infertility. The tolerance of human uterine tissue to cold ischemic preservation is one of the issues that need to be resolved. The objective of this study was to assess the morphological changes in human uterine tissue after cold ischemic preservation in a transplant solution. Small tissue samples of human uteri were subjected to cold ischemia (2-8 degrees C for up to 48 hours) in Celsior transplant solution. Histological analysis by light and electron microscopy was used to assess evidence of cold ischemic injury. Histological examination did not show any major changes of the uterine tissue after 48-hour cold preservation; whereas, electron microscopy after 24 hours confirmed unchanged structural integrity of the uterine myoendometrium. The human uterus is morphologically resistant toward cold ischemia in Celsior preservation solution for up to 24 hours and may be suitable for transplantation purposes.
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PMID:Cold ischaemic preservation of human uterine tissue. 2008 47

"Lipid mediators" represent a class of bioactive lipids that are produced locally through specific biosynthetic pathways in response to extracellular stimuli. They are exported extracellularly, bind to their cognate G protein-coupled receptors (GPCRs) to transmit signals to target cells, and are then sequestered rapidly through specific enzymatic or non-enzymatic processes. Because of these properties, lipid mediators can be regarded as local hormones or autacoids. Unlike proteins, whose information can be readily obtained from the genome, we cannot directly read out the information of lipids from the genome since they are not genome-encoded. However, we can indirectly follow up the dynamics and functions of lipid mediators by manipulating the genes encoding a particular set of proteins that are essential for their biosynthesis (enzymes), transport (transporters), and signal transduction (receptors). Lipid mediators are involved in many physiological processes, and their dysregulations have been often linked to various diseases such as inflammation, infertility, atherosclerosis, ischemia, metabolic syndrome, and cancer. In this article, I will give an overview of the basic knowledge of various lipid mediators, and then provide an example of how research using mice, gene-manipulated for a lipid mediator-biosynthetic enzyme, contributes to life science and clinical applications.
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PMID:Lipid mediators in life science. 2132 48

Oxidative stress is widely implicated in failed reproductive performance, including infertility, miscarriage, diabetes-related congenital malformations, and preeclampsia. Maternal obesity is a strong risk factor for preeclampsia, and in a recent study we observed oxidative stress in the oocytes of obese animals before pregnancy as well as in early-stage embryos. This adds to the growing evidence that investigators need to focus more on the preconceptual period in efforts to prevent pregnancy disorders, including those related to oxidative stress. Our research has also focused on the role of free radicals and antioxidant capacity in preeclampsia. By measuring markers of lipid peroxidation and antioxidant capacity, we obtained unequivocal evidence for oxidative stress in this disorder. Partial failure of the process of placentation has been implicated, and recent findings suggest that ischemia-reperfusion in the placenta may contribute to oxidative stress in trophoblasts. Endoplasmic reticulum stress in the placenta may also play a role. Randomized controlled trials have been conducted by our group as well as others to determine whether early supplementation with vitamins C and E in women at risk of preeclampsia is beneficial, but these trials have shown no evidence that these supplements can prevent preeclampsia. Whether this indicates that an inappropriate antioxidant strategy was used or supplementation was administered too late in gestation to be beneficial is not known. Other potential approaches for preventing preeclampsia through amelioration of oxidative stress include the use of supplements in the preconceptual period, selenium supplements, antiperoxynitrite strategies, and statins.
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PMID:Role of oxidative stress and antioxidant supplementation in pregnancy disorders. 2161 60


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