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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone (somatotropin) is a potent anabolic protein currently being evaluated clinically in cachexia associated with malignancy and human immunodeficiency virus (HIV) disease. Growth hormone can also lead to enhancement of lectin-mediated cellular proliferation, macrophage activation, and cytokine induction, events linked to induction of latent HIV in vitro. We thus explored the ability of recombinant human growth hormone (rhGH) to affect viral replication in acute and chronic HIV infection, and to alter transcription at the HIV-1 long terminal repeat (LTR). A clone of promonocytic cells, chronically infected with HIV-1 and susceptible to viral induction by a variety of cytokines and protein kinase C activators, was unperturbed by rhGH used over broad concentrations (10 to 500 ng/mL) and time intervals. This unresponsiveness paralleled the lack of effect of rhGH on HIV-associated trans-activation in both monocytic and CD4+ T-cell lines. In contrast, rhGH enhanced viral replication in acutely infected peripheral blood mononuclear cells (PBMC) by twofold to 20-fold, albeit having no adverse effect on the antiviral efficacy of zidovudine (AZT). Augmentation of HIV growth correlated with stimulation of cellular DNA synthetic responses and an increase in tumor necrosis factor-alpha (TNF-alpha) secretion. These data are discussed in the context of ongoing clinical trials of rhGH in HIV-seropositive individuals with wasting syndromes.
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PMID:Effect of recombinant human growth hormone on acute and chronic human immunodeficiency virus infection in vitro. 173 91

Immune cell death or dysfunction is induced by HIV infection and results in an immunocompromised state. Newer treatments are able to control viral replication to prevent massive cytoreduction. Attention must now focus on therapies that will rapidly reconstitute the immune system to provide defense against future HIV attacks as well as opportunistic infections. In addition to increasing the rate of differentiation of myeloid and lymphoid precursors from marrow stem cells, ideal therapies should improve thymic function as well. Growth hormone (GH), a member of the hematopoietic cytokine superfamily and its receptors, is expressed in multiple sites within the immune system. GH has been shown to have a stimulatory effect on the function of thymic cells, as well as other immune cell types. In this paper, we consider the use of GH to reconstitute the immune system following cytoreduction due to HIV infection.
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PMID:Growth hormone in immune reconstitution. 1022 23

Although effective treatment of antiretroviral-associated metabolic abnormalities ultimately depends on understanding the mechanisms involved, clinicians facing these problems are beginning to feel compelled to do something now to manage treatment-related metabolic complications. Diet and exercise should not be overlooked, because both can be effective in managing these complications without causing further side effects. Fibric acid derivatives such as gemfibrozil and statins can lower HIV-associated cholesterol and triglyceride levels, although further data are needed on problematic interactions between statins and protease inhibitors (PIs). Hypoglycemic agents may have some role in managing glucose abnormalities, although troglitazone cannot be recommended for fat abnormalities alone and metformin may cause lactic acidosis. Growth hormone and anabolic steroids may have some role in treating lipodystrophy, but the cost of growth hormone is prohibitive for many patients and definitive data on efficacy are lacking. Replacing a PI with a reverse transcriptase inhibitor has improved lipid and glucose levels in some studies. However, that strategy begs the question of how the nucleosides might contribute to lipodystrophy.
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PMID:How to manage metabolic complications of HIV therapy: what to do while we wait for answers. 1075 16

Growth hormone is one of the latest tools against AIDS. Serono's Serostim (somatropin) is the only growth hormone to receive Food and Drug Administration (FDA) approval to treat wasting. HIV-positive individuals show a dramatic suppression of growth hormone, and people with AIDS have practically none. The decrease in growth hormone is also associated with decreasing T-cell counts. The mechanisms in growth hormone production and their role in metabolism and nutrition are described. Serostim is very expensive, and the Serono SeroCare program has limited the cost to $36,000 per year. The program is managed by the National Organization for Rare Diseases. The method of creating growth hormone from the recombinant DNA proteins (rDNA) family is described.
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PMID:The panacea of growth hormone. 1136 26

Body composition alterations are common in HIV infection and include AIDS wasting and lipodystrophy. Both are associated with metabolic alterations, including hypertriglyceridemia and reduced high-density lipoprotein cholesterol levels; insulin resistance and elevated low-density lipoprotein cholesterol levels are also associated with lipodystrophy. However, there is no accepted case definition for HIV-associated lipodystrophy, and patients may have one or all aspects at any given time. The inability of cross-sectional studies to capture the dynamic process of these alterations has hindered the search for a case definition. In the meantime, there are several approaches to treatment of the resulting abnormalities. Switching antiretrovirals has been most successful for improving metabolism, with little or not effect on fat distribution. Growth hormone treatment has successfully reduced visceral fat and buffalo humps but is not FDA-approved for this indication. Metformin and rosiglitazone have produced some improvement in fat distribution as well as glucose metabolism. Other methods that have been tried with varying degrees of success (and little published data) include treatment with testosterone and its derivatives, weight reduction through diet and exercise, and plastic surgery.
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PMID:HIV lipodystrophy diagnosis and management. Body composition and metabolic alterations: diagnosis and management. 1276 88

Growth hormone (GH)-secretion in HIV-lipodystrophy is impaired; however, GH-sensitivity of GH-target tissues remains to be evaluated. We measured overnight fasting concentrations of GH-sensitive insulin-like growth-factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) including GH binding protein (GHBP), a marker of GH-receptor sensitivity, in antiretroviral treated HIV-infected patients with (LIPO) and without lipodystrophy (NONLIPO) and antiretroviral naive HIV-infected patients (NAIVE). Three h GH-suppression tests using oral glucose were undertaken to determine dynamics of GH-secretion. IGF-I and IGFBP-3 were increased in LIPO compared with NONLIPO (p <0.05), but did not differ significantly between NONLIPO and NAIVE. Area under the curve of GH (AUC-GH) during the GH-suppression test was decreased in LIPO compared with NONLIPO (p <0.05). Ratio of limb to trunk fat, which was decreased in LIPO compared to NONLIPO and NAIVE (p <0.001), correlated positively with AUC-GH and rebound-GH (p <0.05). All groups displayed suppression of GH during the suppression test (p <0.05) and all groups, except LIPO, displayed a rebound of GH (p <0.05), which probably is explained by persistently increased plasma glucose in LIPO compared with NONLIPO and NAIVE (p <0.01). GHBP was inversely correlated with AUC-GH (p <0.01). Our data suggest that GH-target tissues in LIPO are at least as GH-sensitive as in HIV-infected patients without lipodystrophy.
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PMID:Different growth hormone sensitivity of target tissues and growth hormone response to glucose in HIV-infected patients with and without lipodystrophy. 1576 70

Growth hormone (GH) treatment reverses the muscle loss allegedly responsible for diminished aerobic capacity and increased fatigue in patients with HIV-associated wasting. This study examined whether submaximal measures of physical performance can be used as objective measures of the functional impact of GH treatment-induced anabolism. We randomized 27 HIV-positive men [mean (SD) age, 43.9 (7.2) yr; body mass, 71.9 (10.4) kg; BMI, 23.1 (2.8) kg/m2] with unintentional weight loss despite antiretroviral therapy to receive GH (6 mg) or placebo in a double-blinded, placebo-controlled, cross-over trial with a 3-mo washout. Lean body mass (LBM), maximum oxygen uptake (Vo2 peak), ventilatory threshold (VeT), 6-min walk test (6MWT) distance and work, profile of mood states (POMS) fatigue and vigor scores, and Nottingham health profile (NHP) energy and physical mobility scores were measured. LBM significantly increased after 3 mo of GH treatment vs. placebo (means +/- SE, 3.7 +/- 0.6 vs. 0.3 +/- 0.4 kg; P < 0.001). VeT significantly improved (17.6 +/- 3.7 vs. -5.9 +/- 2.5%; P < 0.001), but Vo2 peak did not change significantly. 6MWT distance improved (24.9 +/- 9.7 vs. 19.9 +/- 11.6 m; P > 0.05) and 6MWT work increased significantly more after 3 mo of GH treatment (33.3 +/- 8.8 vs. 16.5 +/- 7.5 kJ; P < 0.05). POMS scores of fatigue and vigor and the NHP score of energy improved, yet the changes were not statistically significant. GH treatment improved VeT linearly to the increase in LBM (r =0.43, P = 0.037) and 6MWT work (r = 0.51, P = 0.008), and the increase in 6MWT work correlated with increase in LBM (r = 0.45, P = 0.024). Improvement in 6MWT work above the median (27.3 kJ) showed a decrease in fatigue (r = -0.62, P = 0.024). We concluded that GH treatment-induced LBM gains in HIV-associated wasting were functionally relevant, as determined by effort-independent submaximal measures of cardiopulmonary exercise testing.
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PMID:Anabolic growth hormone action improves submaximal measures of physical performance in patients with HIV-associated wasting. 1588 28

Auxological and endocrinological complications frequently occur in children with connatal HIV infection. These complications seem to be related both to the infection itself and the antiretroviral therapy. Many children consequently show height-weight and pubertal retardation without any evidence of hormonal deficit. We studied 10 children with connatal HIV infection who were enrolled in this analysis and followed up for 7 years in order to evaluate their height-weight growth, pubertal maturation, bone age progression and hormonal pattern [basal Growth hormone (GH) and GH after Clonidine or Insulin stimulation, Insulin-like Growth Factor 1 (IGF-1), Insulin-like Growth Factor Binding Protein 3 (IGFBP-3), FSH, LH, ACTH and Cortisol, TSH, fT4, T4, T3, Ab-TGO, Leptin]. Three children showed a height lower than 3rd centile during the first two years of their life and in prepubertal age, with recurring improvement in their growth rate. Weight growth was very compromised in one girl, remaining firmly lower than 3rd centile during the follow-up. Three children presented a weight lower than 3rd centile until they were two years old. However, a height growth rate higher than 10th centile was found in nine children throughout the follow-up, while it was pathological in five children. The blood level of Leptin was higher at the beginning of the study: 0.82 - 11.68 ng/l (M+/-DS: 3.29+/-4.15) than at its conclusion: 0.2 - 3 ng/l (M+/-DS: 1.65+/-1.01). There was a statistically significant correlation between leptinemia and the CD4/CD8 count (p: 0.010; r: 0.916) and the CDC classification (p: 0.006; r: 0.937), indicating a strong relationship with the degree of virological and immunological impairment. The authors stress the importance of a careful height-weight growth rate control in HIV-infected children, as it reflects the clinical and virological course of the disease. Adequate control of the infection allows physiological growth in most patients. Moreover, we emphasize the utility of IGFBP-3 and IGF-1 measurements, since they represent growth markers which are more exact and better capable of reproduction than GH.
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PMID:[Hormonal, auxological and clinical follow-up in children with connatal HIV infection: personal records]. 1712 27

Growth hormone (GH) is a major regulatory factor for overall body growth as evidenced by the height extremes in people with abnormal circulating GH levels or GH receptor (GHR) disruptions. GH also affects metabolism, cardiac and immune function, mental agility and aging. Currently, GH is being used therapeutically for a variety of clinical conditions including promotion of growth in short statured children, treatment of adults with GH deficiency and HIV-associated wasting. To help reveal previous unrecognized functions of GH, better understand the known functions of GH, and avoid adverse consequences that are often associated with exogenous GH administration, careful delineation of the molecular mechanisms whereby GH induces its diverse effects is needed. GH is a peptide hormone that is secreted into the circulation by the anterior pituitary and acts upon various target tissues expressing GHR. GH binding of GHR activates the tyrosine kinase Janus kinase 2 (JAK2), thus initiating a multitude of signaling cascades that result in a variety of biological responses including cellular proliferation, differentiation and migration, prevention of apoptosis, cytoskeletal reorganization and regulation of metabolic pathways. A number of signaling proteins and pathways activated by GH have been identified, including JAKs, signal transducers and activators of transcription (Stats), the mitogen activated protein kinase (MAPK) pathway, and the phosphatidylinositol 3'-kinase (PI3K) pathway. Although these signal transduction pathways have been well characterized, the manner by which GH activates these pathways, the downstream signals induced by these pathways, and the cross-talk with other pathways are not completely understood. Recent findings have added vital information to our understanding of these downstream signals induced by GH and mechanisms that terminate GH signaling, and identified new GH signaling proteins and pathways. This review will highlight some of these findings, many of which are unexpected and some of which challenge previously held beliefs about the mechanisms of GH signaling.
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PMID:Recent advances in growth hormone signaling. 1730 65

12B75, 274150; Abacavir sulfate/lamivudine, Abatacept, Ad2/HIF-1alpha, Adalimumab, Adefovir, Adefovir dipivoxil, AGN-201904-Z, AIDSVAX, Albinterferon alfa-2b, Alemtuzumab, Aliskiren fumarate, Alvimopan hydrate, Amlodipine besylate/atorvastatin calcium, Amlodipine besylate/Olmesartan medoxomil, Ammonium tetrathiomolybdate, Amodiaquine, Apaziquone, Aprepitant, Arsenic trioxide, Artesunate/Amodiaquine, Ascorbic acid, Atazanavir sulfate, Atazanavir/ritonavir, Atomoxetine hydrochloride, Atrigel-Leuprolide, Axitinib; Bevacizumab, Binodenoson, Bortezomib, Bovine lactoferrin; Calcipotriol/betamethasone dipropionate, Carisbamate, Certolizumab pegol, Ciclesonide, Conivaptan hydrochloride, CP-690550, CP-751871, Cypher; Dapivirine, Darbepoetin alfa, Darunavir, Dasatinib, del-1 Genemedicine, Denosumab, Desloratadine, Dexlansoprazole, DiabeCell, Drospirenone/ethinylestradiol, DTaP-HepB-IPV, Duloxetine hydrochloride, Dutasteride; Eculizumab, Eldecalcitol, Eletriptan, Emtricitabine, Entecavir, Eritoran tetrasodium, Ertapenem sodium, Escitalopram oxalate, Eslicarbazepine acetate, Esomeprazole magnesium, Estradiol acetate, Eszopiclone, ETEC vaccine, Etoricoxib, Exenatide, Ezetimibe; Fluticasone furoate, Fosmidomycin, Fosmidomycin/clindamycin; Glutamine; Heat Shock Protein 10, Hepatitis B hyperimmunoglobulin, HIV vaccine, Hochuekki-to, Human Albumin, Human papillomavirus vaccine; Immune globulin subcutaneous [human], IMP-321, Interferon omega, ISIS-301012, Istaroxime; Japanese encephalitis virus vaccine; Latanoprost/timolol maleate, Lenalidomide, Linaclotide acetate, Lumiracoxib, LY-517717; Malaria vaccine, MAS-063D, Meningitis B vaccine, Mepolizumab, Methylnaltrexone bromide, Micafungin sodium, MK-0822A, Morphine glucuronide, Morphine hydrochloride, Mycophenolic acid sodium salt; Natalizumab, Nesiritide, Norelgestromin/ethinyl estradiol, NT-201; Oblimersen sodium, Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide, Omalizumab, Otamixaban; Paclitaxel nanoparticles, Panitumumab, Panobinostat, Parathyroid hormone (human recombinant), Parecoxib sodium, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pegvisomant, PI-88, Pimecrolimus, Pneumococcal 7-valent conjugate vaccine, Pneumococcal 9-valent conjugate vaccine, Pneumococcal conjugate vaccine, Poloxamer-188, Prasugrel, Pregabalin, Prulifloxacin; R-109339, Ramipril/amlodipine, Ranolazine, Rasburicase, rHA influenza vaccine, Ro-50-3821, Rosuvastatin calcium, Rotavirus vaccine, Rotigotine, Ruboxistaurin mesilate hydrate; Satavaptan, SC-75416, Solifenacin succinate, Sorafenib, Sugammadex sodium, Sunitinib malate, Synthetic conjugated estrogens B; Tadalafil, Talnetant, Taxus, Tegaserod maleate, Telbivudine, Temsirolimus, Tenofovir disoproxil fumarate, Tetomilast, Tiotropium bromide, Tipifarnib, Tofimilast, Tremelimumab, Trimethoprim; Udenafil, Urocortin 2; Valdecoxib, Vernakalant hydrochloride; XP-828L.
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PMID:Gateways to clinical trials. 1798 11


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