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 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

One hundred and seventy-six patients with mesangial IgA nephropathy have been studied retrospectively. Mean follow up from apparent onset of the disease was 9.3 years and with follow up from the diagnostic renal biopsy of 4.6 years. Our aim was to evaluate the prognostic significance of sex, age and type of symptoms at onset. The degree of proteinuria, presence of hypertension or decreased renal function, histological lesions and IFL pattern at the time of the diagnostic renal biopsy were recorded. 17 of the patients developed End Stage Renal Failure (ESRF) during the study. According to the Logrank test (renal survival) and Cox stepwise proportional hazard model, severity of glomerular mesangial lesions and degree of proteinuria are the most important indicators of a poor prognosis. The significance of all other parameters disappear after correction for histological lesions and degree of proteinuria. Our conclusion is that a semiquantitative light microscopical examination is an excellent prognostic index in IgA nephropathy, as is a simple determination of protein excretion in the urine.
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PMID:IGA nephropathy: a retrospective evaluation of prognostic indices in 176 patients. 292 79

In recent years, several laboratories have suggested that chronic hepatitis C virus (HCV) infection is strongly associated with type II cryoglobulinemia (CG) and/or membranoproliferative glomerulonephritis (MPGN). We report here a case of MPGN due to type II CG probably associated with chronic HCV infection, and discuss the pathogenesis and treatment of such cases. A 60-year-old-female was referred to us from a local hospital because of progressive peripheral edema, purpura on the lower limbs, pleural effusion, ascites, hypertension, and renal failure. Laboratory findings indicated proteinuria, abnormal urinary sediments, normochromic normocytic anemia and azotemia. Other laboratory findings included positive rheumatoid factor, elevated serum IgM, hypocomplementemia and elevated circulating immune complexes. Cryoglobulin was detected and found to consist of a mixture of a monoclonal IgM kappa with polyclonal IgG. Renal biopsy showed MPGN. These observations suggested a close association between MPGN and type II CG. We did not find any causes of type II CG except for positive HCV antibody and HCV RNA. Therefore, we made the diagnosis of type II CG associated with chronic HCV infection. Symptoms related to CG was responsiveness to steroid, but development of liver dysfunction developed. Treatment with alfa-interferon (alpha IFN) was added and thereafter, the liver dysfunction improved. However, the serum Cryo level was not reproducibly lowered. While in this case it was unclear whether IFN therapy was beneficial, several reports in addition to the findings of this case suggest a close relation between HCV infection and type II CG and MPGN.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of membranoproliferative glomerulonephritis due to type II cryoglobulinemia probably associated with hepatitis C virus infection]. 819 26

Pentoxifylline (PTX) has recently been shown to modulate TNF-alpha production and to reduce the incidence and severity of all major complications after BMT, including mucositis, veno-occlusive disease, renal insufficiency, hypertension, and graft-versus-host disease. To analyze in detail the effect of PTX on immune complications after BMT, we investigated the immunomodulatory effect of PTX on immune responses in vitro. The continuous presence of PTX significantly reduced the proliferative response of PBMC to PHA stimulation and to alloantigens in a dose-dependent manner. Starting at concentrations of 100 micrograms/ml, PTX was able to inhibit and, at 1000 micrograms/ml, completely block mitogen-induced proliferation. Maximal inhibition of more than 90% (91 +/- 4%) was also observed at PTX concentrations of 1000 micrograms/ml in the mixed lymphocyte culture (MLR) and by addition on day 0. However, lower but still significant suppression (13 +/- 7%) was achieved at concentrations of 10 micrograms/ml PTX. The inhibitory capacity of PTX was increased by mAbs against TNF-alpha (34 +/- 5% additional suppression at 100 micrograms/ml PTX) and not reversed by the addition of rTNF-alpha. The effect of PTX on the generation of CTLs in vitro was studied in the cell-mediated lymphotoxicity assay. PTX (100 micrograms/ml) significantly inhibited (P = 0.0178) the in vitro generation of CTLs when PTX was added to the culture on day 0. PTX also showed profound modulatory properties in the NK assay, with a reduction of 23 +/- 3% in specific lysis at 10 micrograms/ml PTX and maximal reductions of 88 +/- 3% at 1000 micrograms/ml PTX. Immunomodulatory properties of PTX were not only associated with blockage of TNF-alpha, as shown by decreased mRNA expression and TNF-alpha values in the culture supernatants, but also with an impaired production of other cytokines and secondary messages such as IFN-gamma and neopterin. PTX treatment, however, did not affect IFN-alpha or IL-1 beta production, and IL-6 release was even increased. PTX, therefore, has profound immunomodulatory properties in vitro, which are associated with selective inhibition of cytokine release and can be enhanced by the addition of mAbs against TNF-alpha, but not reversed by the addition of rTNF-alpha.
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PMID:Immune response modulation by pentoxifylline in vitro. 833 42

Chronic hepatitis C virus (HCV) infection is quite prevalent in long-term hemodialysis (HD) patients. Patients who are candidates for renal transplantation might be treated, before grafting, with interferon-alpha (IFN-alpha). Among 39 HCV-positive long-term HD patients treated with IFN-alpha, we observed three cases of reversible posterior leukoencephalopathy syndrome (PLES). PLES included headaches in three patients, confusion in three patients, cortical blindness in two patients, visual hallucinations in one patient, seizures in three patients, and respiratory distress in one patient in a context of fluid overload and severe hypertension in all cases. The three patients were receiving IFN-alpha and recombinant erythropoietin therapies simultaneously for de novo anemia. Contrast-enhanced computed tomography scan or magnetic resonance imaging showed low-density areas in the occipital lobes (in three patients), frontal lobes (in one patient), and temporal lobes (in one patient). After withdrawal of IFN-alpha and recombinant erythropoietin therapies, hemodiafiltration, and symptomatic treatment of seizures and hypertension, PLES was reversible within 1 week in one patient, 10 days in one patient, and 2 months in the third patient. Our case reports show the occurrence of reversible PLES in HCV-positive long-term HD patients treated with IFN-alpha. Physicians caring for HCV-positive long-term HD patients treated with IFN-alpha need to be particularly cautious when these patients receive simultaneously recombinant erythropoietin and when IFN-alpha therapy induces a weight loss, which indicates a reduction in dry weight.
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PMID:Reversible posterior leukoencephalopathy syndrome in hepatitis C virus-positive long-term hemodialysis patients. 1127 99

Interferon-alpha (IFN-alpha) has been widely used for treatment of chronic hepatitis C in Japan. In general, cardiovascular adverse reactions are rare in association with IFN-alpha therapy. Here, a 64-year-old man with chronic active hepatitis C complained of fatigue, palpitation and depression, and developed atrial fibrillation with prominent negative T waves during IFN-alpha therapy. Echocardiogram showed septal and apical hypertrophy. Three days after discontinuation of IFN-alpha, subjective symptoms and atrial fibrillation subsided. It is unclear whether or not IFN-alpha induced the giant negative T waves with apical hypertrophy. We might observe the developing course of hepatitis C virus (HCV)-related myocardial hypertrophy by chance. Cardiovascular toxicity should be carefully monitored during IFN-alpha therapy even in patients with minor cardiac disease, such as premature ventricular contracture (PVC) and mild hypertension.
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PMID:Giant negative T waves during interferon therapy in a patient with chronic hepatitis C. 1130 Jan 66

In the conventionally treated group of patients with chronic myelogenous leukemia (CML) the prognosis has been significantly improved by interferon-alpha (IFN-alpha). Several side effects in association with IFN-alpha treatment have been reported. Here we present the first case of a CML patient with reversible pulmonary artery hypertension (PAH) during IFN-alpha therapy. The patient received IFN-alpha-2b (up to 10 million U/day) for 6 months until he started to complain of dyspnea on exertion and an afebrile non-productive cough. An echocardiography and right heart catheterization showed signs of right heart failure with PAH (80 mmHg). A reduced carbon monoxide diffusion capacity and partial respiratory insufficiency were noted. Inflammatory markers were not elevated and pulmonary infiltrates could not be detected. Respiratory infections, thromboembolic causes or autoimmune diseases were carefully ruled out. IFN-alpha was suspected as causative agent, because experimental investigations in sheep showed that IFN-alpha can stimulate the thromboxane cascade which resulted in transient PAH. A reduced pulmonary diffusion capacity had been observed secondary to PAH. After discontinuation of IFN-alpha, our patient's clinical status improved rapidly. After 6 months the pulmonary artery pressure had returned to near normal values (35 mmHg) and the pulmonary diffusion capacity was normal. It took one year until the electrocardiogram reverted to the pre-IFN-alpha pattern. PAH should be included in the differential diagnosis of patients treated with IFN-alpha who complain of exertional dyspnea in the absence of inflammatory signs.
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PMID:Pulmonary artery hypertension during interferon-alpha therapy for chronic myelogenous leukemia. 1144 36

We describe a treatment made with interferon-alpha (IFN-alpha) plus ribavirin of two patients with membranoproliferative glomerulonephritis (MPGN) induced by hepatitis C virus (HCV): case # 1 was a 22-yr-old woman with leg and facial edema, hypertension and proteinuria, whose liver biopsy revealed chronic active hepatitis; and case # 2 was a 42-yr-old man with anasarca, hypertension and proteinuria, whose liver biopsy indicated cirrhosis. Both had anti-HCV, HCV-RNA and cryoglobulins. IFN-alpha (3 million units (MU), 3 times/week) and ribavirin (1 g/day) were administered for 12 months. The drugs were well tolerated by both patients. Serum alanine aminotransferase (ALT) levels normalized and HCV-RNA became negative. Cryoglobulins disappeared and an improvement in renal disease was seen after 6 months of therapy. However, after 9 months, case # 2 presented ALT elevation, and proteinuria was detected. Two years after the end of therapy, both patients were negative in repeated HCV-RNA and cryoglobulin tests. Case # 1 was asymptomatic, with normal liver and renal tests, and case # 2 had normal blood pressure, with mild edema of the ankles. Based on the evolution of these two cases, the association of IFN-alpha and ribavirin may be a therapeutic option for patients with MPGN related to HCV.
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PMID:Therapy with interferon-alpha plus ribavirin for membranoproliferative glomerulonephritis induced by hepatitis C virus. 1455 46

Recent advances in the treatment of colorectal cancer (CRC) include the incorporation of new drugs to treat a disease where only one drug was known to be active. Oxaliplatin and irinotecan have been incorporated into 5-fluorouracil (5-FU)-based regimens where they have increased response rates and survival. Targeted therapies against the epidermal growth factor pathway and the vascular endothelial growth factor (VEGF) pathway are also on the forefront of oncology research, and are beginning to play a role in the treatment of CRC. Current research efforts are trying to optimize the integration of targeted therapies into chemotherapy regimens such as IFL (irinotecan/bolus 5-FU/leucovorin [LV]), FOLFIRI (irinotecan/infusional 5-FU/LV), and FOLFOX (oxaliplatin/infusional 5-FU/LV). In this article, the incorporation of the monoclonal antibody bevacizumab into the IFL regimen will be reviewed in detail. Bevacizumab targets VEGF-A, an important angiogenesis signaling factor commonly expressed in metastatic CRC. The addition of bevacizumab to the IFL regimen significantly increased response rates, median time to progression, and overall survival in patients receiving first-line treatment for CRC, thus leading the Food and Drug Administration to approve bevacizumab for the treatment of CRC in combination with 5-FU-based regimens. Bevacizumab treatment is associated with an increased rate of hypertension. In addition, there may be slight (1%-2%) but relevant increased risks related to gastrointestinal perforations and cardiovascular events. A modest increased risk of wound healing complications was observed in patients who underwent surgery while still receiving, or shortly after receiving, bevacizumab. Bevacizumab plus 5-FU is also a highly active first-line regimen. The role of bevacizumab with other first-line combination regimens, as well as its activity in the second-line setting, is now being determined by ongoing clinical trials.
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PMID:Integrating the anti-VEGF-A humanized monoclonal antibody bevacizumab with chemotherapy in advanced colorectal cancer. 1547 81

Bevacizumab is a recombinant humanized monoclonal antibody that targets vascular endothelial growth factor (VEGF). It is thought that bevacizumab inhibits the formation of new blood vessels. Two clinical trials show that the addition of bevacizumab to a regimen of either fluorouracil plus leucovorin (FL) or FL combined with irinotecan (IFL), significantly improves response rate and time to tumour progression and increases overall survival for patients with advanced colorectal cancer (ACC). Thromboembolic events are the most clinically significant adverse events, but hypertension, hemorrhage and gastrointestinal perforation are other potential safety concerns. More studies are needed to compare the combination of bevacizumab plus IFL to other chemotherapy regimens used in the treatment of ACC. The addition of bevacizumab to 5-fluorouracil-based chemotherapy regimens will significantly increase the costs of palliation for ACC.
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PMID:Bevacizumab for advanced colorectal cancer. 1561 52


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