Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The balance between prostaglandin (PG)I2, a potent vasodilator and inhibitor of platelet aggregation mainly produced by endothelial cells, and thromboxane (TX)A2, a vasoconstrictor and inducer of platelet aggregation and adhesion synthesized predominantly by platelets, seems to be relevant for the regulation of vessel tone and platelet aggregation. PGE2 has vasodilating properties, too. Thus, substances affecting the biosynthesis of PG and TX may have prophylactic and therapeutic, but also detrimental effects with regard to hypertension and atherosclerosis. A mechanism of action which is related to the PG system is discussed for a number of antihypertensive agents, e.g. propranolol, angiotensin converting enzyme inhibitors, furosemide and cicletanine. The vasoprotective effect of inhibition of platelet cyclooxygenase by acetylsalicylic acid is well known. Calcium antagonists, dipyridamole, estradiol, aprotinin and interferon have also been reported to possibly exert beneficial effects on PG/TX levels, while cyclosporin A and streptokinase have shown undesirable interactions with the PG system.
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PMID:[Vasoactive drugs with an effect on the prostaglandin system]. 141 11

The effects of gamma-interferon (gamma-IFN) on protein kinase C (PKC) levels and immunosuppression in the spontaneously hypertensive rat (SHR) were examined. First, an abnormal PKC distribution was found in spleen, thymus and aorta from SHRs relative to normotensive controls. Biweekly injections of rat recombinant gamma-IFN (1000 U/kg) restored basal or resting PKC levels to those found in normotensive Wistar-Kyoto (WKY) rats. We also examined the effects of in vivo gamma-IFN treatment on nuclear PKC (nPKC) activation in purified, isolated splenocyte nuclei. It was found that basal nPKC levels were higher in untreated SHRs than gamma-IFN SHRs or WKYs. Also, while nuclei from untreated SHRs were relatively unresponsive to various immunoreactive substances and PKC activators, gamma-IFN treatment significantly restored activity. Last, the proliferative response to mitogen challenge of isolated splenocytes from untreated SHRs, gamma-IFN-treated SHRs and WKYs was studied. Although gamma-IFN treatment did not restore the proliferative response to that of WKYs, the mitogen response was significantly enhanced by treatment with gamma-IFN. The data show that gamma-IFN acts to restore normal immune function and corrects aberrant PKC levels and adds to the growing body of knowledge suggesting a role for immune dysfunction in the etiology of hypertension.
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PMID:Gamma-interferon corrects aberrant protein kinase C levels and immunosuppression in the spontaneously hypertensive rat. 146 74

Management of the pediatric renal-transplant recipient requires careful pretransplant evaluation including psychosocial assessment and cautious donor/recipient selection. Early transplantation is preferable in infants less than 1 year of age if a suitable live-related donor is available. However, cadaveric-allograft transplantation is best reserved for patients older than 3 years with donors older than 5 years. Pre-emptive transplantation is suitable for approximately one fifth of the population. Medical preparation includes careful HLA-A, -B, and -DR loci matching, interferon treatment for positive hepatitis antigenemia, and acyclovir prophylaxis for a cytomegalovirus (CMV) antibody-negative patient to a seropositive donor. Postoperative management requires close monitoring of the patient's volume status with careful fluid replacement in the form of colloid and crystalloid. Immunosuppression involves multiple drug regimens that include corticosteroids, ciclosporin, azathioprine, antilymphocyte (or -thymocyte) globulin (ALG/ATG), monoclonal antibodies (OKT3), and a ciclosporin alternative: FK-506. Long-term complications dictate management and are divided into medical, surgical, immune, and infectious categories. These are predominated by treatment of acute and chronic rejection, hypertension, and CMV infection.
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PMID:Clinical management of the pediatric renal-allograft recipient. 166 34

After liver transplantation for cancer, there is a high incidence of disease recurrence within 18 to 36 months for most tumors, although there are a small number of long-term survivors. An extended resection of the upper abdominal viscera with replacement by a liver-pancreas cluster is being tried in Pittsburgh for lesions which have not been successfully managed with liver transplantation alone. Despite a high incidence of graft reinfection after liver transplantation for hepatitis B virus (HBV) related disease, a significant proportion of patients achieve long-term survival. Hyperimmune globulin and interferon have been of little benefit in preventing reinfection. Clinical trials with a human monoclonal antibody to HBsAg are in progress. Transplantation for alcoholic liver disease has been considered controversial. However, survival after liver transplantation for Laennec's cirrhosis is comparable to survival after liver transplantation for other chronic, benign, and non-HBV related liver diseases. Sclerotherapy followed by liver transplantation is the treatment of choice for patients with acute hemorrhage from esophageal varices and end-stage liver disease. Sclerotherapy alone or followed by selective shunting is an appropriate alternative in patients with good hepatic reserve. Only 25% of infants with biliary atresia benefit from portoenterostomy. To meet the demand for small infants waiting for transplantation, several transplant programs have successfully expanded their efforts to use partial (reduced) liver grafts. Cyclosporine and low-dose prednisone remain the basis for immunosuppression after liver transplantation. However, nephrotoxicity and hypertension are frequent and troublesome side effects of cyclosporine. Triple and quadruple drug regimens have been increasingly popular in an effort to minimize cyclosporine toxicity. Phase 1 clinical trials with a new drug, FK506, recently began in Pittsburgh. Hyperacute rejection of the liver has been demonstrated in animal models and has been strongly suspected in recent clinical descriptions of acute hemorrhagic necrosis after liver transplantation. So far, only transplantation across an ABO incompatibility has been identified as a risk factor for hyperacute rejection. The new preservation solution developed by Belzer and associates at the University of Wisconsin has significantly extended the preservation time for liver grafts, and improved the quality of liver preservation.
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PMID:Changing perspectives on liver transplantation in 1988. 315 94

Seven patients with refractory multiple myeloma (readily evaluable for response) were treated in a Phase II trial with poly(I,C)-LC using a 3 times per week intravenous schedule. Serial immunologic testing included assessment of natural killer (NK) cell activity, antibody-dependent cytotoxicity, delayed hypersensitivity, and in vitro mitogen responses. One patient had a partial response (PR) of 6-month duration, and 3 other patients had objective responses (less than PR). Significant interferon induction occurred, but levels dropped substantially with serial dosing. Major toxicity included hypertension, hypotension, fever, and myelosuppression. The demonstration of modulation of myeloma progression in this refractory population was encouraging.
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PMID:Poly(I,C)-LC as an interferon inducer in refractory multiple myeloma. 393 57

A study was carried out to establish the maximum tolerated dose of human lymphoblastoid interferon and to define its side effects when given by intramuscular injection. Pyrexia limited the initial dose to a maximum of 3 megaunits/m2 body surface area, but tolerance to this effect developed over 4 to 5 days and the dose was then increased to 5 to 7.5 megaunits/m2; subjective disturbance prevented further increase in dose, but 2.5 to 5.0 megaunits/m2 daily was well tolerated and appears suitable for long-term administration. Other side effects were hypertension, hypotension, myelosuppression, and disturbance of liver-function tests. All toxic effects were reversible on stopping the interferon. Two patients showed evidence of tumour regression, indicating that further trials are justified to define the extent of anticancer activity.
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PMID:Initial evaluation of human lymphoblastoid interferon in patients with advanced malignant disease. 615 64

Natural killer cytotoxicity of peripheral blood lymphocytes in normal pregnancy and edema-proteinuria-hypertension (EPH) gestosis was investigated and compared to natural killer cytotoxicity in lymphocytes of normal nonpregnant control donors. These lymphocytes were also compared for their ability to respond to interferon treatment in vitro. Natural killer activity was found to be only slightly decreased in normal pregnant women but was found to be increased in patients with EPH gestosis. Interferon treatment of peripheral lymphocytes caused strong enhancement of natural killer activity in lymphocytes of normal pregnant women but resulted in only weak activities in lymphocytes from patients with EPH gestosis. We consequently concluded that pre-natural killer lymphocyte subpopulations from patients with EPH gestosis have already been activated by a presently still unknown stimulator.
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PMID:Activity of natural killer cells in normal pregnancy and edema-proteinuria-hypertension gestosis. 618 96

We evaluated the distribution and fate of homologous radioactive Hepatic-binding-protein (125I-HBP) in the rabbit after intravenous (iv) injection and the possibility that this protein may induce interferon production. We demonstrated that only 9% of the injected 125I-HBP remained in the circulation 30 min after injection. The 125I-HBP-Asialoorosomucoid complex displayed a longer half-life than the HBP alone, while 125I-Asialoorosomucoid had a very short half-life and only 1% of the dose was found in the circulation after iv administration. Ten min after iv injection of 125I-HBP the major amount of radioactivity was present in the liver and less in the kidneys and lung. HBP, after iv administration, does not stimulate interferon production and this fact is probably due to its rapid catabolism.
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PMID:Short circulatory residence of the hepatic binding protein. 620 22

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical toxicity of the interferons. 751 63

Fifty patients treated with interferon for chronic type C hepatitis, chronic type B hepatitis and renal cell carcinoma were examined for retinal complications. Retinal hemorrhages or cotton wool spots were observed in 23 (46%) of the patients. Retinal hemorrhages without cotton wool spots were found in 14 patients, cotton wool spots without retinal hemorrhages in 5 patients, and both hemorrhages and cotton wool spots in four patients. These findings were potentially reversible. There was one case of branch retinal artery occlusion and one case with microaneurysm. Red blood cell count decreased significantly in the patients with retinopathy compared with those without retinopathy (p < 0.05%). Patients with diabetes, hypertension, retinal arterial sclerosis, and anemia were at risk for retinopathy.
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PMID:[Interferon-induced retinal changes]. 751 88


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