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)

The etiology of chronic rejection is unknown, although acute rejection, viral infection, and initial graft ischemia have been implicated. To test the effects of infections on the process of chronic rejection, we simulated bacterial infection by the administration of the endotoxin lipopolysaccharide (LPS), a potent activator of various cell types in an established rat model of chronic rejection. Lewis recipients of Fisher 344 kidneys were treated with a single dose of LPS or vehicle 8 weeks following transplantation and grafts were examined at various time points. In the chronically rejecting controls, leukocytic infiltration and the expression of cytokines peaked at 16 weeks. In LPS-treated hosts, leukocyte infiltration and cytokine expression peaked at 12 weeks. By 16 weeks, glomeruli in LPS-treated recipients had become far more sclerotic than those in controls, mimicking the changes observed in controls at 24 weeks. We conclude that infections may play an important role in the development of chronic rejection.
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PMID:Infection-associated cellular activation accelerates chronic renal allograft rejection in rats. 863 55

Chemokine receptors play a crucial role in the recruitment of immune cells to sites of inflammation. Although chronic diseases of the brain are often accompanied by inflammatory events, there is presently no information about the occurrence and regulation of these receptors in the central nervous system (CNS). Moreover, one CC-chemokine receptor, CKR5, has recently been identified as coreceptor for HIV-1 entry into macrophages. HIV-1 target cells in brain are macrophage-related microglia, which suggests that they are infected by the same mechanism (He et al.,: Nature 385:645-649, 1997). Although rats are not susceptible to HIV-1 infection, they can be used to study chemokine receptor regulation in a variety of brain pathologies. After cloning CC-CKR5 and establishing reverse transcriptase polymerase chain reaction (RT-PCR) for its ligands macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and regulated on activation, normal T cell-expressed and secreted (RANTES), we studied expression of these four mRNAs in purified microglia and compared it with their expression in rat brain. Lipopolysaccharide (LPS)-treated microglia showed transiently increased mRNA levels of both CKR5 and its ligands. Similar data were obtained from brains of LPS-injected rats. In middle cerebral artery occluded (MCAO)-animals, RANTES mRNA was unaffected, whereas CKR5 mRNA showed a sustained rise until 96 hr after surgery. MIPs exogenously added to microglial cultures markedly reduced CKR5 mRNA expression, whereas RANTES did not. MIP mRNAs, in contrast to RANTES and CKR5 mRNAs, were undetectable in normal brain. RANTES appears to play a role distinct from MIPs in brain. In summary, upregulation of CC-chemokines and CKR5 in the CNS upon bacterial infection or in ischemia may impact on microglial activation stage and result in increased risk of HIV-1 infection.
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PMID:Cloning of rat HIV-1-chemokine coreceptor CKR5 from microglia and upregulation of its mRNA in ischemic and endotoxinemic rat brain. 967 Sep 89

Experiments were conducted to compare the impact of febrile versus nonfebrile lipopolysaccharide (LPS) induced bacterial infection at the time of global hemispheric hypoxic ischemia (GHHI) on the neural damage evoked by the GHHI insult. In the first study acute intraperitoneal (i.p.) sterile saline (SS) or LPS Escherichia coli (60 microg/kg) was given to groups of male, conscious Long Evans rats, and core (colonic, Tc) temperatures were monitored over 6 h postinjection. Peak febrile response occurred approximately 5 h after the LPS E. coli was injected. Upon sacrifice 7 days later, no hemispheric or regional brain damage occurred in the saline or LPS-injected groups of this first study. In the second study, GHHI was applied (ligation of right common carotid artery + 35 min of 12% O2) in groups of anesthetized, male Long Evans rats previously given an acute i.p. injection of sterile saline or 60 microg/kg LPS E. coli 5 h earlier. Temperatures (Tc) were monitored before, during, and 1.5 and 24 h following GHHI. The LPS-injected group was subdivided into a febrile (Tc > 38 degrees C before and (or) after GHHI) and nonfebrile (Tc < 38 degrees C before and after GHHI) subgroups. A significant correlation was found between the peak temperature rise from preinjection control values following drug administration of either saline or LPS E. coli and the resultant hemispheric damage caused by GHHI. Moreover, upon sacrifice 7 days later ipsilateral hemispheric and regional (i.e., hippocampal, thalamic) damage to GHHI of the febrile LPS E. coli group was significantly increased from respective hemispheric, hippocampal, and thalamic damage of the saline and nonfebrile, LPS groups given the same ischemic insult. Results suggest that the heightened Tc of a LPS infection at the time of global ischemia exacerbated the neural damage of GHHI, a finding similar to that reported with heightened core temperatures induced by external heating.
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PMID:Increased neural damage to global hemispheric hypoxic ischemia (GHHI) in febrile but not nonfebrile lipopolysaccharide Escherichia coli injected rats. 1010 Aug 83

The concordance rate of monozygotic twins showed that the occurrence of ulcerative colitis required both internal and environmental conditions. Genetic studies revealed that IBD1 locus on chromosome 16 and IBD2 locus on chromosome 12 showed highly suspicious susceptibility for inflammatory bowel disease. The other possible internal factors include antineutrophil cytoplasmic antibodies and mucin abnormality. Many environmental factors have been reported to cause relapse. These are viral and bacterial infection, medicine such as antibiotics, non-steroidal anti-inflammatory drugs and aminosalicylates, colonic ischemia, post-examination state, psychological stress, winter season, travel and overwork.
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PMID:[Influencing factors on occurrence and relapse in ulcerative colitis]. 1057 4

Fournier's disease is a potentially fatal acute, gangrenous infection of the scrotum, penis, or perineum associated with a synergistic bacterial infection of the subcutaneous fat and superficial fascia. Thrombosis of small subcutaneous arterioles with resultant ischemia contributes to the rapid extension of the infection. During a 12-year period, the clinical and operative records of 14 patients with Fournier's gangrene were analyzed. All patients were treated with broad spectrum antibiotics and serial surgical debridements. Nine patients had polymicrobial isolates from the initial wound culture; two patients had Group A Streptococcus species as the sole isolate. The etiology of the infection was identified in 12 patients. Five patients died for an overall mortality of 38 per cent. The mean age of survivors was 51 years compared with 75 years for nonsurvivors (P<0.05). The last six patients in this series survived. The mean hospital stay was 29 days. Four patients (31%) had a prior history of diabetes; however, 11 patients (85%) had elevated serum glucose levels (>120 mg/dL) on admission. All patients were hypoalbuminemic on admission. Survivors had an average serum creatinine on admission of 1.28 mg/dL compared with 3.1 mg/dL for nonsurvivors. Although supportive care is required in these patients, the mainstay for treatment of Fournier's gangrene entails an aggressive approach with frequent and extensive soft tissue debridements to control the invasive nature of the infection with delayed wound coverage once the infection has been controlled. Elderly patients with evidence of renal dysfunction on admission have a poor prognosis despite aggressive therapy.
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PMID:The continuing challenge of Fournier's gangrene in the 1990s. 1059 65

P-selectin is a major component in the early interaction between platelets, endothelial cells, and inflammatory cells in the initial phases of the innate immune response. The major ligand for P-selectin is P-selectin glycoprotein ligand-1 (PSGL-1) and this ligand is expressed on the surface of monocyte, lymphocyte, and neutrophil membranes. A truncated form of recombinant human P-selectin glycoprotein ligand-1 has been covalently linked to immunoglobulin G (rPSGL-Ig) and this fusion peptide functions as a competitive inhibitor of PSGL-1. As an inhibitor of neutrophil-endothelial cell adherence, rPSGL-Ig is in early clinical development for the treatment of ischemia reperfusion injury. To determine the potential for deleterious effects from inhibition in P-selectin-mediated neutrophil attachment in the presence of bacterial infection, the effects of therapeutic doses of rPSGL-Ig were tested in three standard laboratory sepsis models. The experimental models included: the murine systemic Listeria monocytogenes infection model, the Pseudomonas aeruginosa bacteremia model in neutropenic rats, and the cecal ligation and puncture (CLP)-induced peritonitis model in rats. Recombinant human PSGL-Ig had no adverse effects on mortality or immune clearance in systemic bacterial infection in any of the three infection models. The PSGL-1 inhibitor did significantly decrease local neutrophil infiltration and bacterial clearance in the peritoneum following CLP, but this did not increase the systemic levels of proinflammatory cytokines, the quantitative levels of bacteremia, or the overall mortality rate following CLP. The results indicate that rPSGL-Ig did not exacerbate infection in these experimental sepsis models.
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PMID:Evaluation of the safety of recombinant P-selectin glycoprotein ligand-immunoglobulin G fusion protein in experimental models of localized and systemic infection. 1130 27

Skin and soft-tissue abscesses, a common problem among injection drug users (IDUs), result in serious morbidity for the patient and costly hospitalizations for incision and drainage; however, there has been little etiologic or preventive epidemiologic research on this problem. We performed a case-control study that enrolled 151 IDUs who had been given a new diagnosis of abscess requiring incision and drainage (cases) and 267 IDUs who did not have abscess or other bacterial infection during the previous year and who were stratum-matched to cases according to age, sex, and race (controls). Subcutaneous or intramuscular, instead of intravenous, injection is a major risk factor for abscess among IDUs. The injection of a cocaine and heroin mixture, or "speedball," may predispose patients to develop abscess by inducing soft-tissue ischemia. Cleaning the skin with alcohol before injection was found to have a protective effect. Neither human immunodeficiency virus nor human T-lymphotropic virus type II seropositivity was significantly associated with abscess.
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PMID:Risk factors for skin and soft-tissue abscesses among injection drug users: a case-control study. 1138 92

The glucagon-like peptides (GLP-1 and GLP-2) are proglucagon-derived peptides cosecreted from gut endocrine cells in response to nutrient ingestion. GLP-1 acts as an incretin to lower blood glucose via stimulation of insulin secretion from islet beta cells. GLP-1 also exerts actions independent of insulin secretion, including inhibition of gastric emptying and acid secretion, reduction in food ingestion and glucagon secretion, and stimulation of beta-cell proliferation. Administration of GLP-1 lowers blood glucose and reduces food intake in human subjects with type 2 diabetes. GLP-2 promotes nutrient absorption via expansion of the mucosal epithelium by stimulation of crypt cell proliferation and inhibition of apoptosis in the small intestine. GLP-2 also reduces epithelial permeability, and decreases meal-stimulated gastric acid secretion and gastrointestinal motility. Administration of GLP-2 in the setting of experimental intestinal injury is associated with reduced epithelial damage, decreased bacterial infection, and decreased mortality or gut injury in rodents with chemically induced enteritis, vascular-ischemia reperfusion injury, and dextran sulfate-induced colitis. GLP-2 also attenuates chemotherapy-induced mucositis via inhibition of drug-induced apoptosis in the small and large bowel. GLP-2 improves intestinal adaptation and nutrient absorption in rats after major small bowel resection, and in humans with short bowel syndrome. The actions of GLP-2 are mediated by a distinct GLP-2 receptor expressed on subsets of enteric nerves and enteroendocrine cells in the stomach and small and large intestine. The beneficial actions of GLP-1 and GLP-2 in preclinical and clinical studies of diabetes and intestinal disease, respectively, has fostered interest in the potential therapeutic use of these gut peptides. Nevertheless, the actions of the glucagon-like peptides are limited in duration by enzymatic inactivation via cleavage at the N-terminal penultimate alanine by dipeptidyl peptidase IV (DP IV). Hence, inhibitors of DP IV activity, or DP IV-resistant glucagon-like peptide analogues, may be alternative therapeutic approaches for treatment of human diseases.
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PMID:Biological actions and therapeutic potential of the glucagon-like peptides. 1183 66

It is conceivable that VEGF inhibition may prevent edema formation at the early stages of diabetic retinopathy. Once the retina is irreversibly ischemic or new vessels have formed, however, antagonizing VEGF may lead to retinal necrosis due to chronic ischemia. An alternative approach would be the induction of neovascular maturation. Once the new vessels become mature, retina ischemia resolves. There would be no edema, hemorrhage, or retinal detachment. Acute administration of an angiogenic molecule called angiopoietin-1 protects vasculature from leaking [103]. Angiopoietins bind to the endothelial cell-specific receptor Tie 2 and play an important role is vascular development, especially vessel maturation. The proposed mechanisms include recruiting pericytes and organizing vascular matrix [103]. Since VEGF is constitutively expressed at low levels in normal eyes [46], it may contribute to the maintenance of vascular integrity. Thus, oversuppression of VEGF expression may be harmful to the retinal vasculature. Inhibiting VEGF action may need to be delivered in a tightly regulated manner such that complete inhibition may be avoided both to maintain basal levels and to provide rapid reversal of inhibition when acute angiogenic responses are desired [72]. VEGF is involved in normal angiogenic processes in adults such as cardiac collateral circulation, wound healing and menstrual cycle [27]. Local drug delivery seems to be more appealing than systemic administration to avoid the side effects. Some VEGF antagonists, such as VEGF receptor chimeric protein and the VEGF neutralizing antibodies are large molecules with poor diffusion into tissues. Repetitive invasive procedures such as intravitreal injection seem to be impractical due to potential complications of retinal detachment and bacterial infection. Recent progress on transscleral delivery of bioactive proteins and DNAs to the choroid and retina provides promising future on local delivery of therapeutic agents [12,13].
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PMID:Vascular endothelial growth factor gene regulation and action in diabetic retinopathy. 1206 83

Actinomycosis is a granulomatous suppurative bacterial disease caused by anaerobic actinomyces, which presents primarily with the cervico-facial, thoracic, abdominal or pelvic form. Cutaneous involvement is well documented and it is usually secondary to local extension or exceptionally to ematogenous spreading from visceral sites. Primary cutaneous actinomycosis is very rare and usually associated with external trauma and/or local ischemia. We report on the case of a primary cutaneous actinomycosis of the forehead in a 59-year-old man with diabetes mellitus who had had a preceding cranial trauma and several cutaneous reconstructive surgical procedures. The patient was treated successfully with combined antibiotic therapy.
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PMID:Primary cutaneous actinomycosis of the forehead. 1270 79


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