Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inactivation of both transfusion-relevant and model viruses by modified pasteurisation (10 hours at 63 degrees C in solution) has been evaluated following the established guidelines of the EU CPMP Ad Hoc Working Party on Biotechnology/Pharmacy. This heat treatment was introduced into the manufacturing process of OCTAVI, a very high purity factor VIII concentrate stabilized only by von Willebrand factor, in the presence of a proprietary mixture of low molecular weight stabilizers. Both enveloped (human immunodeficiency virus, Sindbis virus, herpes simplex virus, pseudorabies virus) and nonenveloped viruses (poliovirus, Coxsackievirus, hepatitis A virus) were inactivated by this heating step by more than 4.7 log10. The combination of the solvent/detergent step used in the manufacture of OCTAVI with this modified pasteurization leads to a double virus-inactivated factor VIII concentrate (OCTATE) with a viral safety distinctly superior to monoinactivated products.
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PMID:Viral safety of a new highly purified factor VIII (OCTATE). 869 69

The array of clinicopathologic factors associated with acquired immune deficiency syndrome (AIDS) patients continues to increase and surprise many physicians. The recent literature contains reports of thrombotic episodes occurring in patients with human immunodeficiency virus (HIV) infection. Various abnormalities predisposing to a hypercoagulable state have also been reported in AIDS patients including the presence of antiphospholipid antibodies and the lupus anticoagulant; deficiencies of protein C, protein S, heparin cofactor II, and antithrombin and increased levels of von Willebrand factor, and d-dimers. These abnormalities correlate with the severity of HIV-associated immunosuppression as measured by the CD4 cell counts and with the presence of concurrent infectious or neoplastic diseases. The authors reviewed the medical literature and describe various abnormalities predisposing to a hypercoagulable state in AIDS patients along with the management of such complications. This issue is important because deep venous thrombosis (DVT), pulmonary embolus (PE), or thrombosis at other sites can develop in patients with AIDS who are ambulatory and have no known risk factors for pathologic thrombus formation, providing another challenge in an already difficult clinical situation. This also provides a strong rationale for careful prospective studies focusing on the prevalence and risk factors involved in the development of thromboembolic complications in patients with AIDS.
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PMID:HIV and thrombosis: a review. 1117 84

The optimal treatment of patients with von Willebrand's disease (vWD) remains to be defined. Moreover, it has not been firmly established which, if any, commonly measured parameters of von Willebrand factor (vWF) protein in the plasma are useful in guiding treatment. To better understand what guidelines physicians follow in the management of vWD, we surveyed 194 North American physicians who are members of the Hemophilia Research Society. Ninety-nine per cent of responding physicians depend on factor VIII (FVIII):C, vWF:RCo activity and vWF:AG to diagnose vWD, while only 49% use the bleeding time. The minimal goals of treatment for patients undergoing major surgery/trauma or central nervous system haemorrhage were FVIII:C and vWF:RCo activity greater than 80% while levels of more than 50% for minor surgery and dental extractions were considered adequate. Treatment of vWD was based on the type of vWD with type 1 patients being treated most often with desmopressin acetate (DDAVP) alone, types 2A and 2B patients with a combination of DDAVP and a vWF-containing FVIII product, type 3 patients with vWF-containing concentrate. Viral infections, including human immunodeficiency virus, hepatitis A, B and C viruses, and parvovirus have been seen in vWD and the efficacy of viral attenuation processes is a major criterion for the selection of treatment by physicians. Based on this survey, prospective studies need to be designed to address the clinical efficacy, safety and predictive value of laboratory monitoring of patients with vWD.
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PMID:Management of von Willebrand disease: a survey on current clinical practice from the haemophilia centres of North America. 1138 Jun 26

Von Willebrand disease (VWD) is the most commonly inherited bleeding disorder, caused by inheritance of a quantitative or qualitative abnormality of von Willebrand factor (VWF). While the majority of patients with VWD are successfully treated with adjunctive therapies or with the synthetic vasopressin analog desmopressin acetate (DDAVP), a subset of patients requires replacement therapy. In the past, cryoprecipitate was the mainstay of therapy; however, it was associated with seroconversion to hepatitis B (HBV), hepatitis C (HCV), and the human immunodeficiency virus (HIV) in treated individuals. With the advent of virucidal methodology and, more recently, nucleic acid testing (NAT) of plasma fractions, the plasma-derived concentrates containing VWF are now considered the therapeutic standard of care.
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PMID:Advances in the treatment of von Willebrand disease. 1168 20

We investigated the effect of antiretroviral therapy on vascular activation in 41 human immunodeficiency (HIV)--infected patients receiving a regimen that included either at least 1 protease inhibitor (PI; n = 21) or a nonnucleoside reverse-transcriptase inhibitor (NNRTI; n = 20). A control group of 21 healthy subjects was included for comparison. Levels of endothelial markers (soluble vascular cell adhesion molecule [sVCAM]--1, soluble intercellular adhesion molecule--1, and von Willebrand factor) were higher in HIV-infected persons before treatment than in control subjects and decreased significantly after 5--13 months of treatment. Levels of sVCAM-1 and von Willebrand factor correlated significantly with initial virus load. d-dimer concentrations also decreased significantly after initiation of treatment. PI- and NNRTI-containing regimens had similar effects. Therapy did not reduce levels of the soluble platelet (sP) activation markers sP-selectin and CD40 ligand. The inhibition of markers of vascular activation may counterbalance sequelae of therapy-induced dyslipidemia and potentially prevent development of atherosclerosis in HIV-infected patients.
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PMID:Antiretroviral therapy reduces markers of endothelial and coagulation activation in patients infected with human immunodeficiency virus type 1. 1186 97

The endothelium participates in haemostasis, inflammation, blood pressure regulation and other physiological systems. Consequently, endothelial dysfunction has been related to hypertension, thrombosis and atherosclerosis. Both von Willebrand factor (vWF) and tissue-type plasminogen activator (t-PA) are synthesized by the endothelium and their plasma levels increased during endothelium activation or injury. So far, they are well-known markers of endothelial cell function. Many circumstances activate or damage the endothelium, such as viruses, bacterium and inflammation. Circulating vWF and t-PA were studied in 92 unselected human immunodeficiency virus-1 (HIV-1)-infected patients [27 patients with and 65 patients without acquired immunodeficiency syndrome (AIDS)] and correlated with plasma levels of pro-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-6), viral load, CD4 T-cell count and infectious status. HIV-1-infected patients had significantly higher plasma levels of vWF (152 versus 90%), tumour necrosis factor-alpha (31.3 versus 9.0 pg/ml) and interleukin-6 (3.5 versus 1.9 pg/ml) but not t-PA (5.9 versus 4.2 ng/ml) than the control group. These two endothelial markers correlated significantly with viral load and interleukin-6 levels in HIV-1-infected patients. The highest levels of vWF and t-PA were found in patients with AIDS. In conclusion, endothelial cell perturbation is present in HIV infection and may be a consequence of different mechanisms such as viral load, cytokines and advanced diseases.
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PMID:Viral load and disease progression as responsible for endothelial activation and/or injury in human immunodeficiency virus-1-infected patients. 1254 23

Many circumstances can induce activation and/or injury of the endothelium that plays a role in the development of vascular complications. Raised plasma levels of endothelial markers such as von Willebrand factor (vWF), soluble thrombomodulin (sTM) and soluble vascular cell adhesion molecule-1 (sVCAM-1) have a prognostic and/or diagnostic value. Human immunodeficiency virus-infected patients (HIV+) have a clustering of conditions that activate or injure the endothelium. Highly active antiretroviral treatment produces adverse effects such as dyslipemia, insulin resistance (IR) and body fat changes (named lipodystrophy syndrome) which may contribute to aggravate their endothelial perturbation. The aim of this study was to measure lipid profile, insulin resistance status, and endothelial markers in 38 HIV+ naive of antiretroviral treatment and 63 HIV+ under highly active antiretroviral treatment (33 with lipodystrophy syndrome and 30 without it). Body fat distribution was also evaluated by dual-energy X-ray absorptiometry (DEXA) analysis. Thirty-one HIV negative subjects were used as controls. We looked for association between variables. Insulin resistance status was a common finding in the four groups. Lipodystrophic patients presented an atherothrombotic lipid profile [elevated levels of triglycerides (TG), low-density lipoprotein cholesterol (LDL-chol) and apolipoprotein-B (APO-B)] and a strong loss of fat in legs and arms (lipoatrophy). All endothelial markers evaluated in our naive patients were higher as compared to control group. sVCAM-1 in HIV+ under therapy without lipodystrophy syndrome showed significantly decreased levels as compared to naive group (487 vs. 666 ng/ml) and vWF and sTM tended to diminish although they did not show a significant difference (130% vs. 170%, 41 vs. 45 ng/ml, respectively). Lipodystrophic patients showed a tendency to increased levels of endothelial activation markers (sVCAM-1: 500 ng/ml and vWF: 154%) together with significantly increased levels of an endothelial injury marker (sTM: 50 ng/ml) with respect to HIV+ under therapy without lipodystrophy syndrome. Plasma levels of sTM, as an endothelial injury marker, correlated with peripheral lipoatrophy (rho = -0.357) in lipodystrophic patients. In conclusion, despite the beneficial immunology effect of highly active antiretroviral treatment and the apparent decrease in the endothelial perturbation, the patients who develop lipodystrophy present altered endothelial markers and other risk factors, such as IR and dyslipemia, which turn them into a high atherothrombotic risk group.
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PMID:Endothelial markers and HIV infection in the era of highly active antiretroviral treatment. 1289 23

This study was performed to quantitate and characterize the mononuclear phagocytes (MPs) in human immunodeficiency virus encephalopathy (HIVE) by immunohistochemistry in an effort to gain insights into potential mechanisms of central nervous system (CNS) accumulation. Single- and double-labeled studies using antibodies against CD14, CD16, CD68, proliferating cell nuclear antigen (PCNA), Ki-67, von Willebrand factor, and HIV-1 p24 were performed using brain tissue from patients with HIVE, HIV-1 infection without encephalitis, and seronegative controls. A substantial increase in MPs was observed in CNS tissue from patients with HIVE, relative to seronegative controls and patients with acquired immune deficiency syndrome but without encephalitis, as determined by CD68 and CD16 immunohistochemistry. A large proportion of CD16+ MPs in HIVE CNS tissue were PCNA+, but do not appear to be proliferating, based on limited Ki-67 positivity. Although virtually all cells positive for HIV-1 p24 were PCNA+, there were many PCNA+ cells where HIV-1 p24 expression was not detected. PCNA positivity was also observed in some endothelial cells and ependymal cells in HIVE CNS. Our results would support a role for HIV-1-induced alterations in MP trafficking and homeostasis in the pathogenesis of HIVE.
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PMID:Macrophage/microglial accumulation and proliferating cell nuclear antigen expression in the central nervous system in human immunodeficiency virus encephalopathy. 1516 43

N-Ethyl-maleimide-sensitive factor (NSF) plays a critical role in the regulation of exocytosis. NSF regulates exocytosis by interacting with a complex containing soluble NSF attachment protein receptor (SNARE) molecules, hydrolyzing ATP, and disassembling the SNARE complex. We hypothesized that peptide inhibitors of NSF would decrease exocytosis. We now report the development of a novel set of peptides that block exocytosis by inhibiting NSF activity. These NSF inhibitors are fusion polypeptides composed of an 11 amino acid human immunodeficiency virus transactivating regulatory protein (TAT) domain fused to a 22 amino acid NSF domain. These TAT-NSF fusion polypeptides cross endothelial cell membranes, inhibit NSF hydrolysis of ATP, decrease NSF disassembly of SNARE molecules, and block exocytosis of von Willebrand factor. Control peptides have no effect on exocytosis. TAT-NSF inhibitors administered to mice prolong the bleeding time. Blood concentrations of these TAT-NSF peptides rapidly decrease within 5 min after injection and then remain constant from 10 to 60 min after injection. These TAT-NSF compounds may be useful in the treatment of a variety of diseases in which exocytosis plays a prominent role, including myocardial infarction, stroke, thrombosis, and autoimmune disorders.
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PMID:A novel class of fusion polypeptides inhibits exocytosis. 1567

Human immunodeficiency virus (HIV) infection is a risk factor for thrombotic microangiopathy (TMA). We sought whether a severe deficiency in ADAMTS13, the enzyme specifically involved in the cleavage of von Willebrand factor, was associated with specific presenting features and outcome in HIV-associated TMA. In this prospective, multicentre, case-control study, 29 patients of 236 in the French Network on TMA had an HIV-associated TMA. Seventeen patients with severe ADAMTS13 deficiency (ADAMTS13 <5% HIV(+) group) were compared to 12 patients with a detectable ADAMTS13 activity (ADAMTS13 >or=5% HIV(+) group). HIV(+) patients were also compared to 62 patients with idiopathic TMA, either with (45 patients, ADAMTS13 <5% idiopathic group) or without (17 patients, ADAMTS13 >or=5% idiopathic group) severe ADAMTS13 deficiency. ADAMTS13 <5% HIV(+) patients had less AIDS-related complications than ADAMTS13 >or=5% HIV(+) patients (23.5% versus 91.6%, respectively, P = 0.0005) and their median CD4(+) T cell count was higher (P = 0.05). TMA-associated death rate was higher in ADAMTS13 >or=5% HIV(+) patients than in ADAMTS13 <5% HIV(+) patients (50% versus 11.7%, respectively, P = 0.04). In ADAMTS13 <5% patients, TMA-associated death rate was comparable between HIV(+) and idiopathic patients (15.5% in idiopathic patients, P-value was non-significant). By contrast, TMA-associated death rate in ADAMTS13 >or=5% HIV(+) patients was higher than in idiopathic patients (11.7% in idiopathic patients, P = 0.04). In conclusion, HIV-associated TMA with severe ADAMTS13 deficiency have less AIDS-related complications and a higher CD4(+) T cell count. TMA prognosis is better and comparable to this of idiopathic forms.
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PMID:Human immunodeficiency virus-associated thrombotic microangiopathies: clinical characteristics and outcome according to ADAMTS13 activity. 1878 60


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