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)

Incubation of highly enriched neurons from rat cerebral cortex with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120 for 18 h results in fragmentation of DNA at internucleosomal linkers, a feature of apoptosis. We report that neurons respond to exposure to gp120 with an increased release of arachidonic acid via activation of phospholipase A2. This process is not inhibited by antagonists of the N-methyl-D-aspartate (NMDA) receptor channels. To investigate the influence of arachidonic acid on the sensitivity of NMDA receptor towards its against, low concentrations of NMDA were coadministered with arachidonic acid. Under these conditions the NMDA-mediated cytotoxicity was enhanced. We conclude that gp120 causes an activation of phospholipase A2, resulting in an increased release of arachidonic acid which in turn sensitizes the NMDA receptor. Two compounds were found to act cytoprotectively against the deleterious effect caused by gp120 on neurons: Memantine [1-amino-3,5-dimethyladamantane] and Flupirtine [2-amino-3-ethoxycarbonylamino-6-(4-fluoro-benzyl-amino)-pyridine maleate]. Both compounds have been found to display a potent cytoprotective effect on neurons treated with the excitatory amino acid NMDA or with the human immunodeficiency virus type 1 (HIV-1) coat protein gp120. The NMDA antagonist Memantine, a drug currently used in the therapy of spasticity and Parkinson's disease, prevented the effects of gp120 at micromolar concentrations. Flupirtine was previously found to be a centrally acting, nonopiate analgesic agent which additionally possesses anticonvulsant and muscle-relaxant activity at doses similar to those producing analgesia. The cytoprotective effect of Flupirtine in vitro was significant (above 10 microM). Considering the fact that both Memantine and Flupirtine display almost no clinical side effects, these drugs may prove useful both in preventing primary infection of brain cells with the HIV virus, as well as in treating the neurological disorders often associated with the immunodeficiency syndrome such as AIDS-related dementia.
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PMID:Neurotoxicity in rat cortical cells caused by N-methyl-D-aspartate (NMDA) and gp120 of HIV-1: induction and pharmacological intervention. 882 91

Sclerosing cholangitis may be a cause of refractory pain in patients infected with the human immunodeficiency virus. We performed celiac plexus block in three such patients with sever pain from sclerosing cholangitis and a poor response to conventional analgesia. The pain had been centered in the epigastrium and/or upper-right quadrant of the abdomen for 2, 10, and 15 weeks, respectively. Computed tomography-guided celiac plexus block with absolute alcohol and bupivacaine was performed. All three patients reported complete disappearance of the pain immediately after the procedure in two cases and 3 days later in the remaining patient. All patients were discharged free of pain and without analgesics and were followed up for 2, 8, and 11 months, respectively, without recurrence of pain. Celiac plexus block deserves further trial for the treatment of severe pain associated with sclerosing cholangitis in patients with acquired immunodeficiency syndrome. The quality of life of our three patients was considerably improved with this relatively simple procedure.
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PMID:Celiac plexus block as treatment for refractory pain related to sclerosing cholangitis in AIDS patients. 883

Patients suffering from cancer and human immunodeficiency virus (HIV) disease at a teaching hospital were found to have poorly controlled pain. Many were prescribed inappropriate analgesia. A palliative care service was established to provide symptom control for patients and education for staff. Educational materials were developed, didactic teaching organized, and one-to-one education by case discussion provided to improve patient management. A repeat survey to evaluate the service showed an increase in the use of appropriate opioids, such as morphine and diamorphine, and a decrease in the use of buprenorphine and papaveretum, which are less suitable for use in chronic cancer pain. The acceptability of the guidelines and rapid availability of a palliative care opinion has improved analgesic prescribing.
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PMID:Improving analgesic prescribing in a general teaching hospital. 885 75

Opioid abuse has been postulated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) infection and AIDS. We and others have recently demonstrated that opioid enhances HIV infection of human macrophages through modulation of beta-chemokines and the CCR5 receptor and that this effect is reversed by naltrexone, a tertiary opioid antagonist. Tertiary opioid antagonists cannot be used in opioid-dependent patients because they precipitate withdrawal or reversal of analgesia. We determined whether the quaternary opioid antagonist methylnaltrexone (MNTX), now in phase III clinical trials for opioid-induced constipation, reverses the opioid-mediated enhancement of HIV infection of macrophages at clinically relevant doses. MNTX completely abrogated morphine-induced HIV Bal strain infection of macrophages. MNTX also inhibited the R5 strain (ADA) envelope-pseudotyped HIV replication induced by morphine. Furthermore, MNTX abolished morphine-mediated up-regulation of CCR5 receptor expression. The ability of MNTX to block opioid-induced CCR5 expression and HIV replication at clinically relevant doses may have additional benefit for opioid abusers with HIV infection, or patients with AIDS pain receiving opioids.
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PMID:Methylnaltrexone antagonizes opioid-mediated enhancement of HIV infection of human blood mononuclear phagocytes. 1456 41

Vaginal delivery is a natural process that usually does not require significant medical intervention. Management guided by current knowledge of the relevant screening tests and normal labor process can greatly increase the probability of an uncomplicated delivery and postpartum course. All women should be screened for group B streptococcus; women who test positive should be treated with antibiotics during labor. Routine human immunodeficiency virus screening of all pregnant women, and treatment with antiretroviral medication for those who test positive, can reduce perinatal transmission of the infection. Once a woman is in labor, management should focus on the goal of delivering a healthy newborn while minimizing discomfort and complications for the mother. In a patient who tests negative for group B streptococcus, delaying admission to the labor ward until she is in active labor decreases the number of possible medical interventions during labor and delivery. Once a patient has been admitted to the hospital, providing her with continuous emotional support can improve delivery outcomes and the birthing experience. Epidural analgesia is effective for pain control and should not be discontinued late in labor to reduce the need for operative vaginal delivery. Epidurals prolong labor, but do not increase the risk of cesarean delivery. Research has shown that labor may not progress as rapidly as historically reported; this should be considered before intervening for dystocia. Routine episiotomy increases morbidity and should be abandoned. Once the infant has been delivered, active management of the third stage of labor decreases the risk of postpartum hemorrhage.
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PMID:Spontaneous vaginal delivery. 2000 Feb 97

The recent approval by the US Food and Drug Administration of 2 medications--methylnaltrexone and alvimopan--introduces a new class of therapeutic entities to clinicians. These peripherally acting mu-opioid receptor antagonists selectively reverse opioid actions mediated by receptors outside the central nervous system, while preserving centrally mediated analgesia. Methylnaltrexone, administered subcutaneously, has been approved in the United States, Europe, and Canada. In the United States, it is indicated for the treatment of opioid-induced constipation in patients with advanced illness (eg, cancer, AIDS) who are receiving palliative care, when response to laxative therapy has not been sufficient. Alvimopan, an orally administered medication, has been approved in the United States to facilitate recovery of gastrointestinal function after bowel resection and primary anastomosis. Clinical and laboratory studies performed during the development of these drugs have indicated that peripheral receptors mediate other opioid effects, including decreased gastric emptying, nausea and vomiting, pruritus, and urinary retention. Laboratory investigations with these compounds suggest that opioids affect fundamental cellular processes through mechanisms that were previously unknown. These mechanisms include modifications of human immunodeficiency virus penetration, tumor angiogenesis, vascular permeability, and bacterial virulence.
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PMID:Development of peripheral opioid antagonists' new insights into opioid effects. 1882 66

Membrane-permeable peptide carriers are attractive drug delivery tools. Among such carriers, the protein transduction domain (PTD) of the human immunodeficiency virus-type 1 Tat protein is most frequently used and has been successfully shown to deliver a large variety of cargoes. The Tat PTD can facilitate the uptake of large, biologically active molecules into mammalian cells, and recent studies have shown that it can mediate the delivery of different cargoes into tissues throughout a living organism. Given that the Tat PTD-mediated delivery is size-independent, this technology could make previously non-applicable large molecules usable to modulate biological function in vivo and treat human diseases. It is likely that the peptide carrier-mediated intracellular delivery process encompasses multiple mechanisms, but endocytic pathways are the predominant internalization routes. Tat PTD has been successfully used in preclinical models for the study of cancer, ischemia, inflammation, analgesia, and anesthesia. Our recent studies have shown that intraperitoneally injected fusion Tat peptide Tat-PSD-95 PDZ2 can be delivered into the spinal cord to dose-dependently disrupt protein-protein interactions between PSD-95 and NMDA receptors. This peptide significantly inhibits chronic inflammatory pain and reduces the threshold for halothane anesthesia. The ability of the Tat PTD to target any cell is advantageous in some respects. However, the drug delivery system will be more attractive if we can modify the Tat PTD to deliver cargo only into desired organs to avoid possible side effects.
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PMID:Tat-Mediated Peptide Intervention in Analgesia and Anesthesia. 2071 10

Activation of glial cells and neuro-glial interactions are emerging as key mechanisms underlying chronic pain. Accumulating evidence has implicated 3 types of glial cells in the development and maintenance of chronic pain: microglia and astrocytes of the central nervous system (CNS), and satellite glial cells of the dorsal root and trigeminal ganglia. Painful syndromes are associated with different glial activation states: (1) glial reaction (ie, upregulation of glial markers such as IBA1 and glial fibrillary acidic protein (GFAP) and/or morphological changes, including hypertrophy, proliferation, and modifications of glial networks); (2) phosphorylation of mitogen-activated protein kinase signaling pathways; (3) upregulation of adenosine triphosphate and chemokine receptors and hemichannels and downregulation of glutamate transporters; and (4) synthesis and release of glial mediators (eg, cytokines, chemokines, growth factors, and proteases) to the extracellular space. Although widely detected in chronic pain resulting from nerve trauma, inflammation, cancer, and chemotherapy in rodents, and more recently, human immunodeficiency virus-associated neuropathy in human beings, glial reaction (activation state 1) is not thought to mediate pain sensitivity directly. Instead, activation states 2 to 4 have been demonstrated to enhance pain sensitivity via a number of synergistic neuro-glial interactions. Glial mediators have been shown to powerfully modulate excitatory and inhibitory synaptic transmission at presynaptic, postsynaptic, and extrasynaptic sites. Glial activation also occurs in acute pain conditions, and acute opioid treatment activates peripheral glia to mask opioid analgesia. Thus, chronic pain could be a result of "gliopathy," that is, dysregulation of glial functions in the central and peripheral nervous system. In this review, we provide an update on recent advances and discuss remaining questions.
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PMID:Glia and pain: is chronic pain a gliopathy? 2379 84

Infection of the nervous system with the human immunodeficiency virus (HIV-1) can lead to cognitive, motor and sensory disorders. HIV-related sensory neuropathy (HIV-SN) mainly contains the HIV infection-related distal sensory polyneuropathy (DSP) and antiretroviral toxic neuropathies (ATN). The main pathological features that characterize DSP and ATN include retrograde ("dying back") axonal degeneration of long axons in distal regions of legs or arms, loss of unmyelinated fibers, and variable degree of macrophage infiltration in peripheral nerves and dorsal root ganglia (DRG). One of the most common complaints of HIV-DSP is pain. Unfortunately, many conventional agents utilized as pharmacologic therapy for neuropathic pain are not effective for providing satisfactory analgesia in painful HIV-related distal sensory polyneuropathy, because the molecular mechanisms of the painful HIV-SDP are not clear in detail. The HIV envelope glycoprotein, gp120, appears to contribute to this painful neuropathy. Recently, preclinical studies have shown that glia activation in the spinal cord and DRG has become an attractive target for attenuating chronic pain. Cytokines/chemokines have been implicated in a variety of painful neurological diseases and in animal models of HIV-related neuropathic pain. Mitochondria injured by ATN and/or gp120 may be also involved in the development of HIV-neuropathic pain. This review discusses the neurochemical and pharmacological mechanisms of HIV-related neuropathic pain based on the recent advance in the preclinical studies, providing insights into novel pharmacological targets for future therapy.
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PMID:The Molecular and Pharmacological Mechanisms of HIV-Related Neuropathic Pain. 2440 74

Capsaicin 8% patch (Qutenza) is mainly used to treat postherpetic neuralgia and human immunodeficiency virus-associated neuropathy. However, evidence of the efficacy of Qutenza in other forms of neuropathic pain is lacking. A 24-year old Libyan man, with no previous medical history, sustained multiple wounds in the right side of the chest and back after a bomb explosion. The patient experienced pain, which persisted in a wide location around the surgical intervention for a long time, beyond the usual course of natural healing of an acute pain and was different from that suffered preoperatively. The characteristics of the pain included burning, electric shock-like sensation, tingling, and numbness, and it was paroxysmal. The pain was associated with hyperalgesia and intense allodynia in a wide area, approximately of 1,100 cm2. Our initial treatment strategy included pregabalin, tramadol, and duloxetine. However, our patient's pain responded to treatment with capsaicin 8% patch when the initial treatments showed only minimal effectiveness regarding the intensity of pain. Interestingly, the most important finding was that capsaicin 8% patch showed a more than 80% reduction of the area of allodynia associated with the pain, when other treatments failed. Moreover, although recent data showed that in patients who respond to Qutenza, analgesia starts within a few days of treatment and lasts on average 5 months, our patient showed an initial response within 7 days of treatment but a longer duration of more than 18 months. Although further controlled studies are needed to explore the efficacy of the capsaicin 8% patch in patients who experience posttraumatic neuropathic pain, we encourage clinicians to try the capsaicin 8% patch when alternative treatments fail.
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PMID:Posttraumatic and postsurgical neuropathic pain responsive to treatment with capsaicin 8% topical patch. 2465 88


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