Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Depression or psychosis in a previously asymptomatic individual infected with the human immunodeficiency virus (HIV) may be psychogenic, related to brain involvement by the HIV or both. Although prognosis and treatment differ depending on etiology, computed tomography (CT) and magnetic resonance imaging (MRI) are usually unrevealing in early HIV encephalopathy and therefore cannot differentiate it from psychogenic conditions. Thirty of 32 patients (94%) with HIV encephalopathy had single-photon emission computed tomography (SPECT) findings that differed from the findings in 15 patients with non-HIV psychoses and 6 controls. SPECT showed multifocal cortical and subcortical areas of hypoperfusion. In 4 cases, cognitive improvement after 6-8 weeks of zidovudine (AZT) therapy was reflected in amelioration of SPECT findings. CT remained unchanged. SPECT may be a useful technique for the evaluation of HIV encephalopathy.
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PMID:Single-photon emission computed tomography in human immunodeficiency virus encephalopathy: a preliminary report. 186 65

An overview was presented of our approach of inhibition of de novo and salvage pathways in pyrimidine and purine metabolism. 1. Combination of acivicin, an inhibitor of de novo biosynthesis, and dipyridamole, a transport inhibitor, provided synergistic cytotoxicity in hepatoma and colon carcinoma cells. 2. AZT, a competitive inhibitor of the salvage enzyme, thymidine kinase, and 5-FU or MTX provided synergistic cytotoxicity in hepatoma 3924A. In human colon carcinoma HT-29 cells AZT and methotrexate yielded synergistic cytotoxicity and thymidine and hypoxanthine together provided protection from the action of these drugs. 3. These observations are significant because in rat hepatoma 3924A and in human cell lines HT-29, HL-60 and K562 thymidine kinase activity was 16- to 67-fold higher than that of dTMP synthase. Therefore, inhibition of dTMP synthase activity alone may provide poor responses because the salvage pathways can circumvent this block. 4. In leukemic patients treated with tiazofurin, an inhibitor of IMP dehydrogenase, the rate-limiting enzyme of GTP biosynthesis, and with allopurinol, which inhibits GPRT activity through raising plasma hypoxanthine levels, synergistic therapeutic results were obtained. The responses in sensitive patients entailed a decrease in IMP dehydrogenase activity and GTP concentration in leukemic cells and down-regulation of the ras and myc oncogenes. The down-regulation of the ras oncogene by tiazofurin through the decrease of GTP concentration has now been shown in K562, HL-60 and hepatoma cells and in patients with chronic granulocytic leukemia in blast crisis. Tiazofurin may be useful in studies on selective depression of the expression of the ras oncogene. 5. In 27 consecutive patients 50% responded positively to tiazofurin treatment. From this group, 10 out of 12 patients (83%) with chronic granulocytic leukemia in blast crisis responded to tiazofurin treatment.
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PMID:Regulation of de novo and salvage pathways in chemotherapy. 187 99

This pilot study examined the effectiveness of fluoxetine in depressed human immunodeficiency virus (HIV)-seropositive asymptomatic patients. Eight patients, participating in an AZT trial who met criteria for major depression syndrome (DSM-III-R), were treated with fluoxetine (20 or 40 mg/day) for 4 weeks. Initially, mean Hamilton Depression scores were 23.8 (range of 17-31), and improved to 6.4 (range of 3-10). All subjects maintained their remission over a 2-month follow-up. Fluoxetine treatment may be effective in treating major depression in HIV-seropositive asymptomatic patients.
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PMID:A report of eight HIV-seropositive patients with major depression responding to fluoxetine. 221 7

Haemopoiesis is often depressed in patients suffering from acquired immune deficiency syndrome (AIDS). Although several mechanisms have been postulated to be responsible for depressed haemopoiesis in AIDS patients, the aetiology of this disorder is still unknown. We hypothesized that failure of the stromal microenvironment may account for part of the haemopoietic defect observed in patients with AIDS. We therefore studied a murine model of AIDS (MAIDS) caused by infection with LP-BM5 virus to determine the ability of bone marrow cells from immunodeficient mice to establish long-term stromal cultures. In addition, normal and MAIDS mice received AZT (2 mg/ml) in their drinking water for up to 1 month to determine the effects of AZT treatment in vivo on the ability of bone marrow cells to support haemopoiesis in long-term cultures. Decreased numbers of non-adherent cells were observed in long-term bone marrow cultures (LTBMC) of MAIDS mice when compared to cultures derived from normal mice. Decreased numbers of non-adherent cells were observed in cultures of bone marrow cells from AZT-treated normal mice, when compared to untreated normal controls. Cells from AZT-treated MAIDS mice produced the smallest number of non-adherent cells. BFU-E and CFU-G/M were decreased in cultures of MAIDS mice when compared to those of normal mice. AZT-treatment further decreased the number of colony-forming cells in both MAIDS mice and normal cultures. Stromal cell function of MAIDS mice was also assessed by inoculating non-adherent cells from normal mice onto confluent irradiated MAIDS LTBMC. Stroma from MAIDS mice was unable to support haemopoietic function of normal bone marrow cells. Polymerase chain reaction (PCR) analysis of steady state levels of cytokine mRNAs of cells from confluent cultures revealed that levels of interleukin-6 mRNA were unchanged in MAIDS mice, as compared to normal controls, but the levels of GM-CSF were decreased in MAIDS mice. These data suggest that LP-BM5 MuLV infection alters the functioning of the haemopoietic stroma and that one mechanism of this depression in haemopoiesis may be via alterations of cytokine production.
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PMID:Impaired ability of bone marrow cells from immunodeficient mice to establish long-term cultures. 791 27

Developed a Q-sort procedure to assess social, emotional, and motivational behavior associated with central nervous system disease among 180 HIV-infected pediatric patients. These ratings were factor analyzed and scales were derived based on the factor structure. Younger (M age = 1.03 years) patients with HIV-associated encephalopathy were rated as more apathetic and nonsocial in their behavior than nonencephalopathic younger patients. Older (M age = 7.8 years) encephalopathic patients had significantly higher scores on scales measuring depression, autism, and irritability compared to nonencephalopathic patients from this age group. A subgroup (26 patients) showed a significant decrease in these elevated scores after a 6-month course of AZT.
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PMID:The development of a Q-sort behavioral rating procedure for pediatric HIV patients. 815 93

We report here the results of studies examining the ability of zidovudine (AZT) to influence the establishment and maintenance of long-term marrow cultures (LTMC) using marrow from murine immunodeficient mice (MAIDS). Normal C57BL6 mice were infected with LP-BM5 (MuLV) immunodeficiency virus (10 micrograms total protein) intraperitoneally. Five weeks after viral infection, mice were sacrificed and marrow was harvested from normal non-virus-infected and virus-infected animals. LTMC were established in the presence or absence of dose escalation of AZT, that is, 10(-6), 5 x 10(-7), and 10(-7) M in vitro. Compared with controls prepared from normal bone marrow, LTMC using MAIDS-infected marrow failed to establish and subsequently release supernatant-derived mononuclear cells. The addition of AZT was ineffective in either establishing LTMC or consistently producing mononuclear cells. Measurements of erythroid (BFU-E), myeloid (CFU-GM), and megakaryocyte (CFU-Meg) precursors were all depressed and none were observed after 5 weeks of culture. Treatment with AZT failed to reverse this depression of stem cell progenitors. Microscopic examination of cultures at 10 weeks demonstrated a failure of MAIDS-LTMC to establish an adequate stromal layer compared to LTMC prepared form non-virus-infected controls. This data indicate that LP-BM5 MuLV infection alters the establishment of a normal functioning hematopoietic microenvironment or stroma. Acknowledging that important differences between MAIDS and human AIDS exist, the implications of these findings concerning the establishment of the immunodeficiency disease state in human immunodeficiency virus infection is discussed.
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PMID:Failure to establish long-term marrow cultures from immunodeficient mice (MAIDS): effect of zidovudine in vitro. 831 48

The increased levels of tumor necrosis factor-alpha (TNF-alpha) seen in patients with acquired immune deficiency syndrome (AIDS) may contribute to the AIDS-related wasting syndrome. TNF also induces expression of human immunodeficiency virus (HIV) through activation of the transcription factor NF-kappa B, which binds to the viral long terminal repeat (LTR). Because TNF can decrease the antiretroviral activity of zidovudine (AZT) in vitro, pentoxifylline (PTX) may increase the efficacy of AZT. PTX decreases HIV replication in acutely infected cells and inhibits gene expression controlled by the HIV-1 LTR. The antiretroviral activity of PTX is associated with decreased binding of NF-kappa B to its recognition sequences. Therefore, PTX may inhibit HIV expression indirectly by diminishing TNF production and directly, by decreasing activity of NF-kappa B. PTX, and an inhibitor of the viral transactivator TAT, Ro24-7429, may inhibit HIV gene expression in a cooperative fashion. The first clinical study of PTX in AIDS patients was conducted by us through the AIDS Clinical Trial Group of the National Institutes of Health. AIDS patients on antiretroviral therapy received PTX 400 or 800 mg three times daily for 8 weeks. TNF assays included TNF mRNA levels in peripheral blood mononuclear cells (PBMCs) and inducible TNF protein levels in the supernatant of PBMCs cultured in the presence of 0.1 microgram/ml lipopolysaccharide (LPS). The median change in TNF mRNA was a 30% decrease. There was a median and significant 40% decrease in the production of inducible TNF protein. HIV load decreased in 10 patients and increased in four patients, but did not change in the group as a whole. Others have extended our initial observations in HIV-infected patients. In a placebo-controlled trial, TNF production by unstimulated PBMCs decreased by 52% in the PTX arm and increased by 7.2% in the placebo arm. In a study comparing AZT, PTX, or a combination of the two, viral load after treatment was ninefold above baseline in the AZT or PTX alone arm, compared to only twofold in the combination arm. In a quality of life trial, PTX was associated with improvement in depression, anger, and social and cognitive function: a placebo effect, however, was not ruled out. PTX 400 mg three times daily is safe and well tolerated. PTX decreases PBMC TNF expression in HIV-infected patients, measured as protein in culture supernatant or as mRNA, and may decrease viral replication. Further studies of HIV-infected persons are needed to ascertain the benefit of PTX as an adjunct either to inhibitors of reverse transcriptase (e.g., AZT) or of transcription (e.g., TAT inhibitor).
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PMID:Pentoxifylline for the treatment of HIV infection and its complications. 869 54

We determined the in vivo ability of infused human recombinant hemoglobin 1.1 (hr-Hb) and erythropoietin to rescue the hematopoietic activity from the suppressive effects of AZT in normal and in a murine model of AIDS (MAIDS) mice. Mice were fed with AZT for 8 weeks with or without treatment in the last 4 weeks by administering various concentrations of hr-Hb and/or erythropoietin (Epo). Blood parameters, body weight (BW) and erythroid burst-forming units (BFU-E) for all mice were determined. AZT-treated normal and MAIDS mice showed a significant decrease in hematocrit (64 and 78.1%), hemoglobin (27.2 and 45.5%), BW (17.5 and 35.5%), number of white (66.9 and 42.1%) and red blood cells (65.5 and 38%), and the number of BFU-E (73 and 59%), whereas the AZT-treated normal and MAIDS mice that received hr-Hb (5 mg/kg BW/day) and/or Epo (2 U/mouse/day) showed significant alleviation of AZT cytotoxicity. This was evident by the recovery in all blood indices examined, the number of BFU-E and the BW of mice treated. BFU-E recovery in MAIDS (97%) was greater than that in normal mice (63%) as compared to their controls. hr-Hb produced a similar response as the combination, however recovery was slightly better with the latter in some hematological parameters. Higher concentrations of hr-Hb (10-15 mg) did not result in a more significant increase in most blood indices. Our results indicate that infusion with hr-Hb can alleviate AZT toxicity in normal and in immunodeficient mice, and that hr-Hb may be clinically useful in preventing severe bone marrow depression brought about by various drugs or agents such as AZT.
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PMID:Effect of blood substitute, recombinant hemoglobin, on in vivo hematopoietic recovery from AZT toxicity. 928 3

The short term cardiac side-effects of AZT (3'-azido-3'-deoxythymidine, zidovudine) was studied in rats to understand the biochemical events contributing to the development of AZT-induced cardiomyopathy. Developing rats were treated with AZT (50 mg/kg/day) for 2 wk and the structural and functional changes were monitored in the cardiac muscle. AZT treatment provoked a surprisingly fast appearance of cardiac malfunctions in developing animals characterized by prolonged RR, PR and QT intervals and J point depression. Electron microscopy showed abnormal mitochondrial structure but the cardiomyocyte had normal myofibers. The AZT treatment of rats significantly increased ROS and peroxynitrite formation in heart tissues as determined by the oxidation of nonfluorescent dihydrorhodamine123 and dichlorodihydro-fluorescein diacetate (H2DCFDA) to fluorescent dyes, and induced single-strand DNA breaks. Lipid peroxidation and oxidation of cellular proteins determined from protein carbonyl content were increased as a consequence of AZT treatment. Activation of the nuclear poly-ADP-ribose polymerase and the accelerated NAD+ catabolism were also observed in AZT-treated animals. Western blot analysis showed that mono-ADP-ribosylation of glucose regulated protein (GRP78/BIP) was enhanced by AZT treatment, that process inactivates GRP78. In this way moderate decrease in the activity of respiratory complexes was detected in the heart of AZT-treated animals indicating a damaged mitochondrial energy production. There was a significant decrease in creatine phosphate concentration resulting in a decrease in creatine phosphate/creatine ratio from 2.08 to 0.58. ATP level remained close to normal but the total extractable ADP increased with 45%. The calculated free ATP/ADP ratio decreased from 340 to 94 in the heart of AZT-treated rats as a consequence of increased free ADP concentration. It was assumed that the increased free ADP in AZT-treated cardiomyocyte may help cells to compensate the defective ATP production in damaged mitochondria by activating the ATP synthesis in undamaged mitochondria. Southern blot analysis did not show decreased quantity of mtDNA deriving from AZT-treated rat hearts indicating that under our experimental conditions AZT-induced heart abnormalities are not the direct consequence of the mtDNA depletion. These data show that ROS-mediated oxidative damages, activated ADP-ribosylation reactions and accelerated NAD+ catabolism play basic roles in the development of AZT-induced cardiomyopathy in our animal model and indicated that these ROS-mediated processes can be important factors in the development of myopathy and cardiomyopathy in zidovudine-treated AIDS patients.
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PMID:Role of reactive oxygen species and poly-ADP-ribose polymerase in the development of AZT-induced cardiomyopathy in rat. 989 21

How a weakened immune system affects the female's reproductive system is explained. The female's endocrine system controls the menstrual and reproductive systems, and the immune system attacks harmful substances and organisms. The hypothalamus stimulates the pituitary gland to produce the hormones FSH and LH, which in turn signal the ovaries to produce estrogen and progesterone. These hormones cause a mature egg to be released. If fertilized, the egg remains within the uterus; if not, menstruation occurs. HIV-positive females often complain of menstrual cycle changes, such as irregular periods, depression, or pain. The virus, other complications, or medications, such as AZT, may cause these symptoms. Estrogen therapy may help those with suppressed immune systems who have premature menopause. Oral contraceptives offer protection against pregnancy, but not HIV. It is not known if the pill reacts adversely with AIDS treatment drugs. Lists are provided showing the pros and cons of oral contraceptives and hormone therapy.
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PMID:[Women, immunity and sexual hormones]. 1136 3


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