RESUMEN
Hypertension is a rising global burden, and low- and middle-income countries account for 80% of deaths due to complications of hypertension. Hypertension can be controlled by adhering to anti-hypertensive medication. However, non-adherence is an increasing challenge. This review aims to systematically evaluate non-adherence to anti-hypertensive medication among adults in low- and middle-income countries and explore factors affecting non-adherence to anti-hypertensive medication. We performed a systematic search for studies published between 1 January 2000 and 31 August 2015. A selection process was performed for data extraction with a combination of Medical Subject Headings terms: 'hypertension' and 'adherence'. Further search criteria were: language ('english'), species ('humans'), and low- and middle-income countries. A total of 22 studies met the inclusion criteria. The pooled percentage of non-adherence when using the eight-item Morisky Medication Adherence Scale (MMAS) was 63.35% (confidence of interval (CI): 38.78-87.91) and 25.45% (CI:17.23-33.76) when using the 80 and 90% cut-off scales. The factors were classified into the five dimensions of adherence defined by the World Health Organization, and the majority of the studies reported factors from the dimension 'social and economic factors'. This systematic review demonstrated considerable variation of non-adherence to anti-hypertensive medication in low- and middle-income countries depending on the methods used to estimate non-adherence. The results showed a high non-adherence when the MMAS eight-item scale was used and low when the 80 and 90% cut-off scales were used. The majority of factors affecting non-adherence to anti-hypertensive medication fell within the World Health Organization defined dimension 'social and economic factors'.
Asunto(s)
Antihipertensivos/uso terapéutico , Países Desarrollados , Hipertensión/tratamiento farmacológico , Cumplimiento de la Medicación , HumanosRESUMEN
To investigate the impact of thymus on immunological recovery after dose-dense chemotherapy a prospective study of 17 patients diagnosed with diffuse large B-cell lymphoma (DLBCL) was conducted. Patients were monitored before, during and until 3 months after chemotherapy. The thymus was visualized using computer tomographic scans. Patients were divided into two groups according to thymic size, one group comprising of patients without detectable thymus and one group of patients with detectable thymus. Naïve CD4 and CD8 counts were measured by flow cytometry, and to measure thymic output determination of CD4+ cells containing T-cell receptor excision circles (TREC) was done. During chemotherapy, the naïve CD4 count decreased significantly as did the CD4-TREC%. Significant difference in recovery of naïve CD4 counts between patients with detectable and undetectable thymic tissue during treatment with chemotherapy was not found. CD4-TREC% was associated with lower age. It was not possible to demonstrate an association between thymic size and recovery of the naïve CD4+ cells. The study terminated 3 months after the last cycle of chemotherapy, and at that time point the naïve CD4 counts and the CD4-TREC% had not returned to pretreatment levels. However, patients with detectable thymic tissue had higher naïve CD4 counts after the first cycles of chemotherapy, suggesting that these patients may be less susceptible to infectious complications related to chemotherapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/inmunología , Timo/inmunología , Adulto , Anciano , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Recuento de Células , Citometría de Flujo , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Timo/citología , Tomografía Computarizada por Rayos XRESUMEN
Infection with human immunodeficiency virus (HIV) causes a dysregulation of the immune system. This is caused by HIV-specific as well as non-specific mechanisms and has not been explained fully. In particular, knowledge is lacking about the potential role of host-mediated immunosuppressive mechanisms. During recent years it has become evident that a subpopulation of T cells [T regulatory (T(regs))] play a major role in sustaining tolerance to self-antigens. To investigate the influence of initiation of highly active anti-retroviral therapy (HAART) on the T(reg) level in HIV-infected patients we have conducted a prospective study enrolling treatment-naive HIV-infected patients just prior to starting treatment with HAART, measuring levels of T(regs) by flow cytometry and mRNA expression of forkhead box P3 (FoxP3) at weeks 0, 4, 12 and 24 of treatment. In this prospective study neither the percentage of CD4(+)CD25(high+) nor the expression of FoxP3 changed significantly during 24 weeks of HAART. Furthermore, HIV patients have higher T(regs) measured as percentages of CD4(+)CD25(high+) cells paralleled by higher levels of FoxP3 compared with healthy controls. The elevated level of T(regs) was found to be independent of both immunological and virological status, indicating that initiation of HAART has minor effects on the T(reg) level in HIV-infected patients.
Asunto(s)
Infecciones por VIH/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Anciano , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Biomarcadores/análisis , Recuento de Linfocito CD4 , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead/análisis , Factores de Transcripción Forkhead/genética , Humanos , Subunidad alfa del Receptor de Interleucina-2/inmunología , Activación de Linfocitos , Masculino , Persona de Mediana Edad , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T Reguladores/virología , Carga ViralRESUMEN
Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3 years (range 0-6.4 years). In 113 cases, the diagnosis of TB was verified by positive sputum microscopy and/or culture. Among the verified TB cases, a decreased survival rate was found in 27 patients with sCD163 levels above the upper reference limit (3.95 microg/mL). The difference in survival was significant during TB treatment (log rank, p<0.02) and after long-term follow-up (log rank, p<0.001). The decrease in survival rate during TB treatment remained significant in a multivariate Cox model controlling for human immunodeficiency virus (HIV) status, age and gender, with a mortality increase of 1.19 (95% CI, 1.04-1.36) per microg of sCD163, and a hazard ratio (HR) for sCD163 levels above the upper reference limit of 4.18 (95% CI, 1.06-16.4). The difference was not significant after excluding patients with concomitant HIV-1 and HIV-2 infection in Kaplan-Meier analyses (log rank, p 0.11). In contrast, the difference in survival remained significant in Kaplan-Meier analyses after long-term follow-up, even after excluding patients with concomitant HIV-1 and HIV-2 infection (log rank, p 0.002). In the Cox model, the mortality increase per microg of sCD163 was 1.27 (95% CI, 1.14-1.40), with an HR for elevated sCD163 levels of 2.85 (95% CI, 1.44-5.63). The HRs for concomitant HIV-1 and HIV-2 infection were 6.92 (95% CI, 3.28-14.58) and 2.48 (95% CI, 1.09-5.67), respectively. Thus, sCD163 levels appeared to be an independent predictor of survival in verified TB patients.
Asunto(s)
Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Receptores de Superficie Celular/sangre , Tuberculosis Pulmonar/diagnóstico , Adulto , Biomarcadores/sangre , Estudios de Cohortes , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Resultado del Tratamiento , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológicoRESUMEN
Hypertonic saline solutions are effective in the treatment of haemorrhagic and septic shock, elevated intracranial pressure and perioperative fluid deficits. Infusion, however, causes electrolyte and acid-base imbalance. In a randomized double-blind study, the effects of a 10-min infusion of 4 ml/kg 7.5% NaCl or 0.9% NaCl were evaluated in 14 fasting women before hysterectomy. Venous blood from the forearm was collected at baseline, 10, 20, 30, 60 and 120 min after start of the infusion for the determination of plasma electrolytes and acid-base balance. We found that 1) a median increase in plasma sodium of 11 mmol/l (range 9-13 mmol/l) and chloride of 14 mmol/l (range 9-16 mmol/l) immediately after the infusion followed by a small decrease after 2 h, 2) a minor decrease in plasma potassium in relation to the infusion followed by a significant increase of 0.3 mmol/l (range 0.1-1.4 mmol/l) above baseline after 1 h, 3) a decrease in pH of 0.05 (range 0.02-0.07) and, finally, 4) a decrease in base excess of 1.9 mmol/l (range 0.8-2.7 mmol/l). It is concluded that infusion of 7.5% NaCl in a clinical relevant dose increases plasma potassium and causes minor changes in the acid-base balance in normovolaemic women.
Asunto(s)
Ácidos/sangre , Electrólitos/sangre , Solución Salina Hipertónica/administración & dosificación , Solución Salina Hipertónica/farmacología , Equilibrio Hidroelectrolítico/efectos de los fármacos , Adolescente , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Oxígeno/metabolismoRESUMEN
OBJECTIVES: We investigated whether the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are major regulators of glucose tolerance through the stimulation of insulin secretion, contribute to impaired glucose tolerance (IGT) among HIV-infected patients on highly active antiretroviral therapy (HAART). METHODS: Eighteen HIV-infected male patients (six lipodystrophic and 12 nonlipodystrophic) with normal glucose tolerance (NGT) were compared with 10 HIV-infected male patients (eight lipodystrophic and two nonlipodystrophic) with IGT. Plasma concentrations of GLP-1 and GIP were determined frequently during a 3-h, 75-g glucose tolerance test. Insulin secretion rates (ISRs) were calculated by deconvolution of C-peptide concentrations. RESULTS: The incremental area under the curve (incrAUC) for GLP-1 was increased by 250% in IGT patients compared with NGT patients (1455+/-422 vs. 409+/-254 pmol/L/180 min, respectively; P<0.05), whereas the incrAUC for GIP did not differ between the study groups (7689+/-1097 vs. 8041+/-998 pmol/L/180 min, respectively; not significant). In pooled study groups, the GIP incrAUC correlated positively with the ISR incrAUC without adjustment (r=0.38, P<0.05) and following adjustment for glucose incrAUC (r=0.49, P<0.01). CONCLUSIONS: Our data suggest: (1) that glucose-intolerant, HIV-infected male patients may display enhanced GLP-1 responses to oral glucose compared with normal glucose-tolerant HIV-infected male patients, which may represent a compensatory mechanism rather than explain the IGT; (2) that the GIP response may be associated with ISR independently of plasma glucose in nondiabetic HIV-infected males on HAART.
Asunto(s)
Antivirales/uso terapéutico , Glucagón/sangre , Intolerancia a la Glucosa/virología , Glucosa , Infecciones por VIH/tratamiento farmacológico , Fragmentos de Péptidos/sangre , Precursores de Proteínas/sangre , Adulto , Análisis de Varianza , Terapia Antirretroviral Altamente Activa , Área Bajo la Curva , Glucemia/análisis , Composición Corporal , Péptido C/análisis , Polipéptido Inhibidor Gástrico/sangre , Péptido 1 Similar al Glucagón , Intolerancia a la Glucosa/sangre , Prueba de Tolerancia a la Glucosa , Infecciones por VIH/sangre , Síndrome de Lipodistrofia Asociada a VIH/sangre , Síndrome de Lipodistrofia Asociada a VIH/tratamiento farmacológico , Humanos , MasculinoRESUMEN
BACKGROUND: Treatment with high doses (2-6 mg day(-1)) of human growth hormone (hGH) in patients with human immunodeficiency virus (HIV)-associated lipodystrophy syndrome (HALS) has been shown to increase concentrations of total insulin-like growth-factor-I (IGF-I) more than twofold greater than the normal upper range and is accompanied by adverse effects such as joint pain and glucose intolerance. MATERIALS AND METHODS: We performed a 16-week open-labelled prospective pilot study in six male HALS patients using a s.c. low-dose hGH, 0.7 mg day(-1), aiming to examine the impact on total and free IGF-I and fat distribution. Glucose metabolism was examined by oral glucose tolerance tests and hyperinsulinaemic euglycaemic clamps. RESULTS: Total IGF-I increased twofold (P < 0.01) and free IGF-I increased 2.5-fold (P < 0.01) to the level of the normal upper range. HDL-cholesterol increased (P = 0.01). Patients reported improvements of lipodystrophy, which was supported by a decreased waist-to-thigh ratio (P = 0.01), and waist-to-hip ratio (P = 0.06). Ratio of peripheral to trunk soft tissue mass increased (P = 0.01, measured by dual-energy X-ray absorptiometry scans) and a trend towards reduction in percentage of trunk fat was suggested (P = 0.12). Total fat mass, exercise capacity, glucose tolerance, glucose disposal rate and immune status, respectively, did not change (all P > 0.5). The patients did not complain of arthralgia or other known GH-related side-effects. CONCLUSIONS: Sixteen weeks' treatment of lipodystrophic HIV-infected patients with hGH, 0.7 mg day(-1), increased total and free IGF-I twofold and appeared safe and tolerable. The potential of low-dose hGH in the treatment of HIV-lipodystrophy awaits examination by placebo-controlled, randomized trials.
Asunto(s)
Síndrome de Lipodistrofia Asociada a VIH/tratamiento farmacológico , Hormona de Crecimiento Humana/administración & dosificación , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adulto , Terapia Antirretroviral Altamente Activa , Glucemia/metabolismo , Composición Corporal , Dieta , Ingestión de Energía , Prueba de Tolerancia a la Glucosa , Síndrome de Lipodistrofia Asociada a VIH/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios ProspectivosRESUMEN
BACKGROUND: Haemorrhagic shock is treated effectively by infusion of hypertonic saline/colloid solutions. Furthermore, previous studies found hypertonicity to affect immune responses in animals and in human blood cell cultures. It is unknown, however, whether hypertonic saline infusion affects immune responses in humans. METHODS: In a randomized double-blind study, we infused 4 ml kg-1 of 7.5% NaCl or 0.9% NaCl over 10 min in 20 fasting women before hysterectomy. We collected peripheral blood at baseline, 30, and 120 min after start of the infusion and before surgery for the determination of leucocyte and differential count; lymphocyte subtypes; neutrophil chemotaxis; elastase concentration; and the cytokine's tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1beta, IL-6, IL-8, IL-1 receptor antagonist (IL-1ra), and IL-10. Phytohaemagglutinin (PHA)-induced lymphocyte proliferation and natural killer cell cytotoxicity were measured before and 120 min after infusion. RESULTS: Compared with normal saline, infusion of hypertonic saline temporarily increased the number of B cells in peripheral blood (P < 0.01); increased the concentration of plasma elastase, a marker of neutrophil degranulation (P < 0.05); and decreased the number of circulating neutrophils (P < 0.001). No other effects were detected in the measured immunological parameters. CONCLUSION: The immunological consequences of hypertonic saline infusion seem to be modest and are unlikely to cause any clinical effects, at least in normovolaemic women.
Asunto(s)
Inmunidad/efectos de los fármacos , Solución Salina Hipertónica/farmacología , Adolescente , Adulto , Anciano , Citotoxicidad Inmunológica , Método Doble Ciego , Femenino , Citometría de Flujo , Humanos , Inmunofenotipificación , Células Asesinas Naturales/inmunología , Recuento de Leucocitos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Lactic acidosis is a feared side effect of nucleoside analog treatment, one of the cornerstones in the management of HIV infection. Precise and reliable lactate measurements are prerequisites for the diagnosis of hyperlactatemia. The effects of venous stasis, time to measurement and storage temperature on p-lactate levels, p-glucose levels, anion gap and pH were investigated. Ten HIV patients (n=8 on highly active antiretroviral therapy) and 4 healthy control subjects were studied. Blood was drawn without stasis at time 0 and with stasis for 2 and 8 min into heparin-preserved test tubes. The tubes were placed at a room temperature (25 degrees C) and on crushed ice and consecutively monitored for up to 360 min. The mean increases in p-lactate in blood kept in test tubes at 25 degrees C, measured from 0 to 60 min and from 240 to 360 min, were increased in HIV patients compared with controls (0.78 mmol/Lh +/- 0.02 vs. 0.63 mmol/Lh +/- 0.05, (p=0.009) and 0.65 mmol/Lh +/- 0.03 vs. 0.53 mmol/Lh +/- 0.05, (p=0.042)). It was found that placing the tubes on crushed ice rather than keeping them at 25 degrees C controlled glycolysis and lactate production measured over a 6-h period (0.033 mmol/Lh +/- 0.006 vs. 0.32 mmol/Lh +/- 0.01, (p<0.0001) and 0.064 mmol/Lh +/- 0.008 vs. 0.64 mmol/Lh +/- 0.02, (p<0.0001)). The total increases in lactate levels in the test tubes placed on crushed ice for 4 h and in those kept at 25 degrees C for 15 min were comparable (0.28 +/- 0.03 mmol/L vs. 0.20 +/- 0.03). Compared with storage at 25 degrees C, keeping the test tubes on crushed ice also preserved pH and anion gap over a 6-h measurement period (pH: 0.026 +/- 0.004 vs. 0.12 +/- 0.01 and anion gap: -0.8 +/- 0.4 mmol/L vs. 4.1 +/- 0.4). Two minutes of venous stasis had no influence on p-lactate levels (0.02 +/- 0.04 mmol/L, p=0.70), whereas 8 min of stasis increased p-lactate levels by 0.11 +/- 0.04 mmol/L, p=0.009. It is concluded that major errors in measurements of p-lactate, anion gap and pH can be prevented by placing test tubes on crushed ice for up to 4 h until measurement.
Asunto(s)
Acidosis Láctica/diagnóstico , Conservación de la Sangre , Infecciones por VIH/sangre , Ácido Láctico/sangre , Acidosis Láctica/etiología , Adulto , Glucólisis , Infecciones por VIH/complicaciones , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , TemperaturaRESUMEN
Hematologic and immunologic functions were examined in 19 HIV-negative infants of HIV-positive mothers and 19 control infants of HIV-negative mothers. Control infants were selected to match for gestational age, weight, and mode of delivery. Cord blood was obtained from all infants and used for flow cytometric determination of lymphocyte subsets, including the naive CD4 count. Furthermore, to determine thymic output, cord blood mononuclear cells were used for determination of T-cell receptor excision circles (TRECs). Evaluation of progenitor cell function was done by means of colony-forming cell assay and fetal thymic organ cultures (FTOCs). Lower naive CD4 counts (459.3 +/- 68.9 vs 1128.9 +/- 146.8 cells/microL, P <.001) and reduced thymic output in infants of HIV-positive mothers were found (frequency of CD4(+) cells with TRECs was 3.6% +/- 0.7% compared with 14.3% +/- 2.2% in controls, P <.001). In combination with lower red blood cell counts in infants of HIV-positive mothers, this finding suggested impairment of progenitor cell function. Indeed, progenitors from infants of HIV-positive mothers had decreased cloning efficiency (15.7% +/- 2.6% vs 55.8% +/- 15.9%, P =.009) and seemed to generate fewer T cells in FTOCs. In conclusion, lower numbers of naive CD4(+) cells and reduced thymic output in HIV-negative infants of HIV-positive mothers may be due to impaired progenitor cell function.
Asunto(s)
Recuento de Linfocito CD4 , Seronegatividad para VIH/inmunología , Seropositividad para VIH/inmunología , Células Madre Hematopoyéticas/fisiología , Timo/inmunología , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Recuento de Células , Ensayo de Unidades Formadoras de Colonias , Citocinas/sangre , Recuento de Eritrocitos , Femenino , Sangre Fetal/química , Sangre Fetal/citología , Citometría de Flujo , Seropositividad para VIH/tratamiento farmacológico , Células Madre Hematopoyéticas/inmunología , Células Madre Hematopoyéticas/patología , Humanos , Recién Nacido , Interferón gamma/sangre , Interleucina-2/sangre , Interleucina-4/sangre , Intercambio Materno-Fetal , Técnicas de Cultivo de Órganos , Embarazo , Zidovudina/efectos adversos , Zidovudina/uso terapéuticoRESUMEN
This randomized, placebo-controlled trial examine the long-term effect of granulocyte colony-stimulating factor (G-CSF) on absolute numbers of CD34+ progenitor cells and progenitor cell function in human immunodeficiency virus (HIV)-infected patients. G-CSF (300 microg filgrastim) or placebo was given three times weekly for 12 weeks to 30 HIV-infected patients that had been treated with HAART for at least 24 weeks and not yet achieved CD4 counts above 350 CD4+ cells/microl. Blood samples were collected at weeks 0, 2, 4, 8, and 12, and again 12 weeks after termination of the G-CSF treatment. Significant increase in absolute numbers of circulating CD34+ cells was detected in the treatment group (P = 0.006). The function of progenitor cells was examined in vitro using a colony-forming unit (CFU) assay, and increase in the number of CFU/ml was detected (P = 0.005). In order to estimate the effect of G-CSF on in vivo function of progenitors the white-blood count was determined. Significant increase in white-blood count was found (P < 0.001), while hemoglobin and platelet count decreased (P = 0.001 and P = 0.013, respectively). Significant increase in the CD4 count occurred, but correlation between the numbers of progenitors and the CD4 count was not found. These data suggest that G-CSF mainly increases the number and differentiation of myeloid progenitors.
Asunto(s)
Recuento de Células Sanguíneas/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/farmacología , Infecciones por VIH/fisiopatología , Hematopoyesis/efectos de los fármacos , Movilización de Célula Madre Hematopoyética , Neutropenia/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hemoglobinas/análisis , Humanos , Recuento de Leucocitos/efectos de los fármacos , Masculino , Neutropenia/etiología , Recuento de Plaquetas/efectos de los fármacos , Proteínas Recombinantes , Factores de TiempoRESUMEN
No clear association between human disease and TT virus (TTV) has been documented. A possible pathogenic role of TTV was investigated in patients infected with human immunodeficiency virus (HIV). TTV serum concentrations were estimated in 185 HIV-infected patients by dilution polymerase chain reaction. Of these, 149 (76%) were TTV-positive, compared with 18 (7%) of 252 Danish blood donors (P<. 001). Of the HIV-infected patients who were TTV-positive, 72 (51%) had high TTV viremia (>/=5 times the highest concentration observed among blood donors, i.e., >/=3.5x105 TTV/mL of serum). High TTV viremia was associated with decreased survival (P<.001; relative hazard [RH], 2.0). There was a correlation between lower CD4+ T cell counts and higher TTV titers (P<.01). In a Cox regression model, CD4+ T cell count (P<.001), age (P<.001), HIV viral load (P<.001), beta2 microglobulin (P<.02), and high TTV viremia (P<.01; RH, 1.9) were independent predictors of survival. TTV is suspected to be an opportunistic pathogen with an independent influence on HIV progression.
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Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones por Virus ADN/epidemiología , Virus ADN/aislamiento & purificación , Infecciones Oportunistas Relacionadas con el SIDA/mortalidad , Infecciones Oportunistas Relacionadas con el SIDA/virología , Adolescente , Adulto , Anciano , Donantes de Sangre , Infecciones por Virus ADN/mortalidad , Dinamarca/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Tasa de Supervivencia , Factores de TiempoRESUMEN
HIV infection is characterized by the loss of CD4+ T cells as well as the loss of T-cell function, leading to severe immunodeficiency. The proliferative capacity of T cells measured in vitro as responses to antigens and mitogens is severely reduced during HIV infection. An increased level of the intracellular second messenger adenosine 3',5'-cyclic monophosphate (cAMP) has been shown to cause impaired proliferative capacity of peripheral blood mononuclear cells (PBMC) from HIV-infected individuals in vitro. Sumatriptan, a 5HT1d receptor agonist, inhibits the activity of adenylyl cyclases, the enzymes responsible for regulation of the intracellular levels of cAMP. In a preliminary study sumatriptan increased the proliferative responses of PBMC to a polyclonal activator in vitro in 9 of 10 HIV-seropositive individuals (p=0.007), and in 7 of 9 healthy blood donors (p=0.05). This was probably due to a decrease in the intracellular level of cyclic AMP.
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Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Activación de Linfocitos/efectos de los fármacos , Agonistas de Receptores de Serotonina/farmacología , Sumatriptán/farmacología , Adulto , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Estudios de Casos y Controles , AMP Cíclico/metabolismo , Infecciones por VIH/metabolismo , Humanos , Técnicas In Vitro , Mitógenos de Phytolacca americana/farmacologíaRESUMEN
This study was conducted to determine the impact of immune activation, cytokine production and apoptosis on the naive CD4+ cell count and the function of hematopoietic progenitor cells during the initial phase of highly active antiretroviral therapy (HAART). Blood samples from 11 HIV-infected patients were collected prior to HAART and after 4 and 12 weeks of therapy. Flow cytometry was used to determine the naive CD4+ count and activated T cells. The cloning efficiency of progenitor cells was determined using a colony-forming cells assay. Finally, apoptosis and cytokine production were determined. During the study period, the naive CD4+ count and the cloning efficiency increased significantly. Immune activation was found in HIV-infected patients and decreased during HAART. The level of immune activation correlated negatively with both the naive CD4+ count and the function of progenitor cells. A negative correlation was found between apoptosis and the naive CD4+ count. Alterations in cytokine production during HAART or correlation between cytokine production and the naive CD4+ count or the cloning efficiency of progenitor cells were not detected. In conclusion, immune activation in HIV-infected patients treated with HAART is inversely correlated with the function of progenitor cells and the naive CD4+ count.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Células Madre Hematopoyéticas/fisiología , Fármacos Anti-VIH/administración & dosificación , Apoptosis , Antígenos CD4/análisis , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/fisiología , Citocinas/sangre , Citometría de Flujo , Infecciones por VIH/sangre , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Masculino , Factores de Tiempo , Carga ViralRESUMEN
PURPOSE: Previous studies have shown that agents modulating the cAMP/PKA pathway have a beneficial effect on immune reconstitution in HIV-infected individuals. Here we evaluate the effect of buspirone on immune function as measured by CD4 and CD8 T-cell counts, CD4/CD8 T-cell ratio, HIV viral load, and response to pokeweed mitogen (PWM) in antiretroviral naive HIV-1-infected individuals. METHOD: Twenty-three HIV-infected patients with CD4 T-cell counts above 300 per microL were enrolled in a 6-month double-blinded placebo controlled trial. No patients received antiretroviral therapy during the study. Blood samples were drawn prior to treatment, after 1 week, 1 month, 3 months, and 6 months, and as a follow-up sample 1 month after completion of study. RESULTS: A significant decrease in CD8+ T-cell counts (p =.02) and an increase in CD4/CD8 ratio (p =.0003) in buspirone-treated patients compared to placebo-treated patients was observed. There were no significant differences in CD4 T-cell counts, HIV viral load, or proliferative response to PWM between those receiving placebo and those receiving buspirone. CONCLUSION: Buspirone treatment leads to significant changes in CD8 T-cell count and in CD4/CD8 ratio. Thus, agents affecting the adenosine 3', 5'-cyclic monophosphate/protein kinase A type 1 (cAMP/PKA-1) pathway may be candidates for positive immune modulation in patients with HIV-1 infection.
Asunto(s)
Buspirona/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , VIH-1/fisiología , Adulto , Relación CD4-CD8 , Método Doble Ciego , Femenino , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Agonistas de Receptores de Serotonina/uso terapéutico , Carga ViralRESUMEN
In this study, the effect of recombinant interleukin-2 (rIL-2) on the function of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients was examined. Using polymerase chain reaction (PCR), an impaired ability of PBMC from 8 patients to respond upon mitogen stimulation with expression of IL-2 and IL-2 receptor (IL-2R) messenger ribonucleic acid (mRNA) was found compared with healthy donors (p = 0.02 and p = 0.05, respectively). Flow cytometry was used to determine the expression of p55 interleukin-2 alpha-receptor (CD25) after phytohaemagglutinin (PHA)-stimulation. Induced CD25 expression in response to stimulation was lower in patient cells than in donor cells (in CD4+ (p = 0.01) and in CD8+ (p = 0.03)). After rlL-2 treatment, the functionality of ex vivo expanded PBMC from patients was restored to the level found in donors. Finally, the induced gene expressions for IL-2 and IL-2R were positively correlated (p < 0.0001), suggesting that the activation of the IL-2 and IL-2R genes in humans may share a common activation pathway, as has been found in monkeys infected by simian immunodeficiency virus (SIV). These results indicate the existence of a reversible IL-2 and IL-2R defect at the pretranscriptional or transcriptional level in PBMC from patients. This may help explain the T-cell anergy found during HIV-infection.
Asunto(s)
Infecciones por VIH/inmunología , Infecciones por VIH/terapia , Interleucina-2/uso terapéutico , Leucocitos Mononucleares/efectos de los fármacos , Linfocitos/efectos de los fármacos , Receptores de Interleucina-2/efectos de los fármacos , Adulto , Recuento de Linfocito CD4 , ADN Complementario/biosíntesis , Femenino , Citometría de Flujo , Humanos , Interleucina-2/genética , Masculino , Persona de Mediana Edad , Fitohemaglutininas/farmacología , Reacción en Cadena de la Polimerasa , ARN Mensajero/efectos de los fármacos , ARN Mensajero/inmunología , Proteínas RecombinantesRESUMEN
An obstacle to stem cell gene therapy for AIDS is the limited numbers of hematopoietic progenitors available. Granulocyte colony-stimulating factor (G-CSF) is used for mobilization of progenitors, but little is known about the functional characteristics of mobilized progenitors, and immature and T cell progenitors may not be mobilized. This study examined the effect of G-CSF on the function of progenitors. Ten human immunodeficiency virus-infected patients received G-CSF (filgrastim, 300 microgram/day) for 5 days. Absolute numbers of immature and T cell progenitors did not increase. The ability of CD34+ progenitor cells to generate lymphocytes was examined by use of thymic organ cultures. The mean number of lymphocytes generated per CD34+ cell on day 0 was 0.72 and on day 4 was 0.09 (P<.003). The number of CD4+ cells generated per CD34+ cell was significantly reduced after G-CSF treatment. Thus, G-CSF increased the number of mature progenitor cells but did not increase T cell progenitors.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Infecciones por VIH/inmunología , VIH-1 , Células Madre Hematopoyéticas/efectos de los fármacos , Linfocitos T/fisiología , Animales , Antígenos CD34/análisis , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Células Cultivadas , Filgrastim , Citometría de Flujo , Infecciones por VIH/tratamiento farmacológico , Células Madre Hematopoyéticas/fisiología , Humanos , Masculino , Ratones , Ratones Noqueados , Técnicas de Cultivo de Órganos , Proteínas Recombinantes , Timo/inmunologíaAsunto(s)
Vacunas contra el SIDA , Vacunas contra el SIDA/química , Proteína gp120 de Envoltorio del VIH/química , Proteína gp120 de Envoltorio del VIH/inmunología , Proteína gp120 de Envoltorio del VIH/metabolismo , Humanos , Fusión de Membrana , Conformación Molecular , Receptores del VIH/química , Receptores del VIH/inmunología , Receptores del VIH/metabolismoRESUMEN
BACKGROUND: In patients scheduled for vascular surgery, atherosclerotic disease is highly prevalent. Haemodynamic reactions are often aggravated when spinal analgesia is used in this population. No randomized studies have been conducted comparing single shot (SS) with continuous spinal analgesia (CSA) for vascular patients. We did a prospective randomized study comparing haemodynamics when SS versus CSA was performed. METHODS: Sixty patients were randomized to have SS or CSA. The power of the study was 0.90. Patients in the SS group received 17.5 mg bupivacaine and in the CSA group 5 mg was given initially and incremental doses of 2.5 mg were given until an analgesic level of T-11 was reached. Mean arterial pressures (MAP) were measured invasively. ST-analysis was done continuously. Postoperatively, the patients were interviewed using a standardized questionnaire. Back pain, neurologic sequelae and post-dural puncture headache (PDPH) were investigated. RESULTS: There was no significant difference between the analgesic levels (T-7/T-8), the decrease in MAP, the number of patients needing ephedrine and the total amount of ephedrine given in the two groups. The motor blockade was more pronounced in the SS group (P < 0.001) and the total amount of bupivacaine used was 17.5 mg compared to 7.5 mg (5-17.5) in the CSA group (P < 0.001). One patient suffered PDPH which was slight and responded to a nonsteroidal anti-inflammatory drug. Two patients in each group had transient paraesthesias in the legs. There were technical problems with the spinal catheter in 4 patients, and these were excluded from the study. CONCLUSION: In this study we found no difference in the haemodynamic response to SS or CSA in patients scheduled for vascular surgery of the legs. SS is easier to apply and is recommended when the duration of surgery allows for it.