ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of curcumin on pain threshold and the expressions of nuclear factor κ B (NF-κ B) and CX3C chemokine receptor 1 (CX3CR1) in spinal cord and dorsal root ganglion (DRG) of the rats with sciatic nerve chronic constrictive injury.</p><p><b>METHODS</b>One hundred and twenty male Sprague Dawley rats, weighing 220-250 g, were randomly divided into 4 groups. Sham surgery (sham) group: the sciatic nerves of rats were only made apart but not ligated; chronic constrictive injury (CCI) group: the sciatic nerves of rats were only ligated without any drug treatment; curcumin treated injury (Cur) model group: the rats were administrated with curcumin 100 mg/(kg·d) by intraperitoneal injection for 14 days after CCI; solvent control (SC) group: the rats were administrated with the solvent at the same dose for 14 days after CCI. Thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) of rats were respectively measured on pre-operative day 2 and postoperative day 1, 3, 5, 7, 10 and 14. The lumbar segment L4-5 of the spinal cord and the L4, L5 DRG was removed at post-operative day 3, 7 and 14. The change of nuclear factor κ B (NF-κ B) p65 expression was detected by Western blotting while the expression of CX3CR1 was determined by immunohistochemical staining.</p><p><b>RESULTS</b>Compared with the sham group, the TWL and MWT of rats in the CCI group were significantly decreased on each post-operative day (P<0.01), which reached a nadir on the 3rd day after CCI, and the expressions of NF-κ B p65 and CX3CR1 were markedly increased in spinal cord dorsal horn and DRG. In the Cur group, the TWL of rats were significantly increased than those in the CCI group on post-operative day 7, 10 and 14 (P<0.05) and MWT increased than those in the CCI group on post-operative day 10 and 14 (P<0.05). In addition, the administration of curcumin significantly decreased the positive expressions of NF-κ B p65 and CX3CR1 in spinal cord and DRG (P<0.05).</p><p><b>CONCLUSION</b>Our study suggests that curcumin could ameliorate the CCI-induced neuropathic pain, probably through inhibiting CX3CR1 expression by the activation of NF-κ B p65 in spinal cord and DRG.</p>
Subject(s)
Animals , Rats , Blotting, Western , CX3C Chemokine Receptor 1 , Curcumin , Pharmacology , Ganglia, Spinal , Metabolism , Lumbar Vertebrae , NF-kappa B , Metabolism , Pain Threshold , Rats, Sprague-Dawley , Receptors, Cytokine , Metabolism , Receptors, HIV , Metabolism , Sciatic Nerve , Wounds and Injuries , Metabolism , Spinal Cord , MetabolismABSTRACT
El manejo nutricional de los pacientes infectados con el virus de inmunodeficiencia humana (VIH) es desafiante; especialmente cuando los recuentos de linfocitos T CD4 son < de 200 células/mm³, debido a los episodios de pérdida de peso que experimentan los pacientes. En este estudio se plantea demostrar la relación entre los niveles de carga del VIH y los valores de linfocitos T CD4+ con los cambios de peso corporal en los pacientes ambulatorios del Centro de Atención a Pacientes con Enfermedades Infectocontagiosas (CAPEI) de la Facultad de Odontología de la Universidad Central de Venezuela. La mayoría de los pacientes que presentaba pérdida de peso tuvo linfocitos TCD4 de 200 células/mm³. Los que mantuvieron el peso o lo ganaron, presentaron contajes de linfocitos TCD4 entre 200 y 499 células/mm³ (p = 0,012). Con relación con la carga viral se encontró que los pacientes que perdieron peso, cursaban en su mayoría, con valores 1000 o 100.000 copias/ml. Al contrario, la mayor parte de los que aumentaron de peso, presentaron valores indetectables de carga viral. Estas diferencias no fueron estadísticamente significativas. Estos resultados tal vez reflejen el pronóstico de la pérdida de peso cuando el contaje de linfocitos TCD4 es de 200 células/mm³, ya que en este nivel ocurren infecciones oportunistas, favorecidas por la desnutrición, estableciéndose un círculo vicioso que aumentaría la morbi mortalidad. Evaluar el estado inmunológico nutricional en pacientes ambulatorios con infección por VIH es importante para iniciar estrategias encaso de pérdida de peso corporal
The nutritional management of patients infected with the human immunodeficiency (HIV) virus is challenging; especially when linfocitos T CD4 counts are < of 200 cells/mm³, due to episodes of weight loss experienced patients. This study raises show the relationship between the levels of the HIV load and the values of T CD4 + lymphocytes with changes in body weight in the outpatient care center for patients with diseases transmittable-contagious (CAPEI) of the Faculty of Dentistry of the University Central of Venezuela. Most of the patients who had weight loss had CD4 cell count of 200 cells/mm³ Those who maintained the weight or won it, presented between 200 and 499 CD4 cell counts cells/mm³ (p = 0.012). In relation with the viral load was found that patients who lost weight, were mostly with values 1000 or 100,000 copies/ml. On the contrary, most of those who gained weight, they were undetectable viral load values. These differences were not statistically significant. These results may reflect the prognosis of weight loss when the CD4 cell count is 200 cells/mm³, since at this level occur opportunistic infections, favored by malnutrition, establishing a vicious circle that would increase the morbidity mortality. Assess the immune status - nutrition in outpatients with HIV infection is important to initiate strategies in the event of loss of body weight
Subject(s)
Humans , Male , Female , Body Mass Index , HIV , Lymphocytes/immunology , Weight Loss/immunology , Receptors, HIV , Viremia/immunology , Allergy and ImmunologyABSTRACT
El objetivo del trabajo fue determinar la participación del coreceptor CCR5 y su ligando CCL3L1 en relación a una de las características del fenotipo del HIV-1, el tropismo viral. Los resultados que obtuvimos así como otras investigaciones que estamos desarrollando tienen implicancias clínicas y terapéuticas en los niños HIV-1 infectados. Para lograr el objetivo hemos evaluado en forma conjunta y combinada los datos que habíamos obtenido a lo largo de casi 15 años en relación a las variantes genéticas del CCR5, en particular la mutación Δ32 y su ligando CCL3L1 en función del número de copias del gen en los niños HIV-1 infectados por transmisión vertical que son asistidos en el Hospital Garrahan, investigando la probable asociación de ellas con el tropismo viral. Hallamos que los niños en primoinfección tienen una proporción considerable de variantes HIV-1 SI que emplean como co-receptor al CXCR4 en lugar del CCR5. Otro hecho relevante fue que la presencia de las variantes SI predominaron en los niños heterocigotas para la variante genética CCR5Δ32. En este último grupo encontramos además que estaba significativamente asociado con un número de copias del CCL3L1 alto (≥2). Probablemente ambos factores participan favoreciendo la reducción en el número de moléculas del co-receptor CCR5 expresadas en la superficie celular facilitado la infección por las variantes X4. Aunque las variantes SI en la etapa crónica alcanzan a un 40% no parecieran asociadas con el genotipo CCR5Δ32 ni con el número de copias del CCL3L1. En resumen, hemos demostrado que las variantes SI X4 T-trópicas del HIV-1 pueden estar presentes en los estadios muy tempranos de la infección viral sugiriendo que puede ser transmisible verticalmente. Además, el genotipo CCR5Δ32 en el contexto de copias altas del CCL3L1 en el niño HIV-1 infectado, contribuyen a un mayor riesgo a ser infectado por variantes SI en primoinfección. Este hecho no pareciera suceder en la etapa crónica de la infección viral.
The aim of the study was to assess the role of co-receptor CCR5 and its ligand CCL3L1 in viral tropism, one of the char-acteristics of the HIV-1 phenotype. The results of this study as well as those found in our other ongoing research have clini-cal and therapeutic consequences for HIV-1 Infected children. For the aim of the study we collected and evaluated the data obtained over a period of almost 15 years on genetic variants of CCR5, specially the 32 mutation and its ligand CCL3L1 (MIP-1 P), in relation to the number of copies of the gene in HIV-1-mother-to-child infected children seen at the pediatric hospital J.P. Garrahan, to investigate a probable association with viral tropism. We found that children with a primary in-fection have a considerable number of HIV-1 SI (syncytium-inducing, i.e. cytopathic) variants that use CXCR4 instead of CCR5 as a co-receptor. Another relevant finding was that SI variants were predominant in children that were homozygous for the genetic CCR5 32 variant. In this latter group we additionally found that this was significantly associated with a high number of CCL3L1 copies ( 2). Both factors may play a favorable role in the decrease of the number of molecules of the CCR5 co-receptor expressed on the cell surface that facilitate infection through X4 variants. Although in the chronic stage SI variants reach 40%, they do not seem to be associated with either the CCR5 32 genotype or the number of CCL3L1 copies. In sum-mary, we have shown that SI X4 T-tropic variants of HIV-1 may be present in very early stages of viral infection suggesting that they may be transmitted from mother to child. In addition, the CCR5 32 genotype in the setting of a high number of CCL3L1 copies in an HIV-1 infected child contribute to a higher risk of being infected by SI variants in primary infection, however, this mechanism does not seem to occur in the chronic stage of viral infection.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , HIV-1 , Infectious Disease Transmission, Vertical , Receptors, HIV , Viral Tropism , ArgentinaABSTRACT
Introducción. Hasta el año 2000, la prevalencia de VIH/sida en Colombia era de 0,4 La intensificación del conflicto armado ha coincidido con un aumento en la incidencia del virus. El presente estudio está enfocado en determinar la existencia de un vínculo entre el aumento de las tasas de VIH/sida y el conflicto armado en el país de 2002 a 2008. Métodos. Se realizó un estudio descriptivo retrospectivo. La población de estudio fueron hombres y mujeres entre los 15 y 59 años, residentes en el territorio nacional, a los cuales se les diagnosticó infección por el virus de la inmunodeficiencia adquirida (VIH) durante el periodo 2002-2008. Las variables fueron seleccionadas del índice de riesgo de situación humanitaria. Los datos fueron analizados en tablas de análisis bivariado...
Introduction: Up until 2000 the overall estimated prevalence of HIV/AIDS in Colombia was 0.4. The intensification of the armed conflict has coincided with a rise in the prevalence of HIV/AIDS. This study was focused on determining the relationship between the rise in HIV/AIDS and the armed conflict t in Colombia (2002-2008). Methods: The present research was descriptive and retrospective. The population studied was men and women in the 15-59 age range resident in the Colombian territory, who were diagnosed as HIV (+) from January 2002 to December 2008. Variables of the study were chosen from the Humanitarian Situation Risk Index. The dates were analysed in bivariate tables...
Subject(s)
Humans , HIV , Receptors, HIV , ColombiaABSTRACT
Pacientes infectados pelo HIV1 apresentam aumentada permeabilidade intestinal, a qual permite a passagem para a circulação sanguínea de produtos microbianos, fenômeno conhecido por translocação microbiana. Dentre os produtos translocados são encontrados vários ligantes dos receptores do tipo Toll (TRL). A ativação de TLR desencadeia uma complexa cascata de sinalização, induz a síntese de diversas citocinas, e modula a função de células dendríticas (CDs), macrófagos e linfócitos, células-alvo da infecção pelo HIV1. Estudos experimentais mostram que a ativação de TLRs influencia a replicação do HIV1, como, por exemplo, a ativação de TLR4 e TLR3 resulta em diminuição da replicação viral. No entanto, os estudos relacionados à ativação de TLR2 e HIV1 são escassos. Assim, em nosso estudo, resolvemos analisar o efeito da ativação de TLR2 sobre a replicação do HIV1 em PBMCs e macrófagos primários humanos infectados in vitro. Para isto, PBMCs e macrófagos obtidos de doadores saudáveis foram infectados pelo HIV1 e em seguida expostos ao Zymosaqn ou Pam3CSK4, ambos ligantes de TLR2, e a replicação viral foi avaliada pela detecção da proteína viral p24 nos sobredanantes de cultura. Vimos que tanto o Zymosan quanto o Pam3CSK4 inibem de forma potente (até 90 porcento) a replicação do isolado Ba L (trópico para CCR5) de HIV1 em PBMCs e macrófagos, assim como isolados primários trópicos para CCR5 e CXCR4. o tratamento das células com os ligantes de TLR2 antes da infecção também induziu a queda da replicação viral. Ambos os ligantes de TLR2 induziram aumento da produção das beta quimiocinas CCL3, CCL4 e CCL5 em macrófagos e PBMCs, e de IL10 em macrófagos. A imuno-neutralização das beta quimiocinas diminuiu expressivamente o seu efeito inibitório sobre a replicação do HIV1. sugerindo que estas moléculas participam da inibição da replicação do HIV1 resultante da ativação de TLR2. no entanto, a neutralização do receptor de IL10 não produziu resultados semelhantes. A expressão dos receptores celulares CD4, CCR5 e CXCR4 não foi alterada quando macrófagos e PBMCs foram tratados com Pam3CSK4. observamos, ainda, que a proteína quinase R (PKR) é ativada por Pam3CSK4 tanto em macrófagos quanto em PBMCs. Estes resultados mostram que a ativação de TLR2 resulta em uma potente inibição da replicação do HIV1 em PBMCs e macrófagos, e sugerem que as beta quimiocinas estão envolvidas neste fenômeno. Nossos achados ressaltam o papel anti-HIV1 resultante da ativação de TLR2, e indicam que novos estudos devem ser realizados para esclarecer, com maior profundidade, os mecanismos envolvidos neste processo.
Subject(s)
Humans , Acquired Immunodeficiency Syndrome , Chemokines , HIV , Receptors, HIVABSTRACT
Human immunodeficiency virus (HIV) infects the host cells by the fusion of viral and cell membranes. Blocking the combining between HIV and the receptors can prevent HIV from entering the host cells. We designed an invasion-inhibitor for HIV-1 targeting dendritic cell (DC), including 2 important HIV-1 receptors CD4 and CCR5, and 2 molecules Flt3-L and Mip-3alpha. With the synthetic gene of the inhibitor, 2 eukaryotic expression vectors pABK-CKR5-CD4/Flt3L-Mip3alpha (pABK-HIV-MF) and pABK-CKR5-CD4 (pABK-HIV-MT) were constructed and transfected into HEK 293 cells for expression. Results from RT-PCR, immunofluorescent assay, ELISA and Western blot approved that the invasion-inhibitor for HIV-1 was successfully and exactly expressed in the eukaryotic cells. Current study formed a solid base for the further research on the function of inhibitors for HIV-1 and elimination targeting DC.
Subject(s)
Humans , Artificial Gene Fusion , CD4 Antigens , Genetics , Chemokine CCL20 , Genetics , Dendritic Cells , Allergy and Immunology , Metabolism , Genetic Vectors , Genetics , HEK293 Cells , HIV Envelope Protein gp120 , Genetics , HIV-1 , Physiology , Receptors, CCR5 , Genetics , Receptors, HIV , Transfection , fms-Like Tyrosine Kinase 3 , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate HIV-1 co-receptor usage in patients experienced anti-retroviral therapy (ART) in Anhui and Henan province of China.</p><p><b>METHODS</b>A total of 45 HIV-1 infected individuals who have experienced ART and 109 un-experienced ART patients from Anhui and Henan province, which were called as treatment group and treatment-negative group, were selected as study subjects. HIV-1 strains were isolated from peripheral blood mononuclear cells of whole blood from patients. HIV-1 p24 in the culture supernatant was measured using a commercial enzyme-linked immunosorbent assay (ELISA) kit. HIV-1 co-receptor usage was identified using Ghost cell lines expressing CD4 and the chemokine receptor CCR5 or CXCR4.</p><p><b>RESULTS</b>Among 45 HIV strains from the treatment group, 22 (48.9%) strains used CCR5 as a co-receptor (R5 tropic strain), 21 (46.7%) strains used CXCR4/CCR5 as a co-receptor (X4/R5 duel tropic strain), and 2 (4.4%) used only CXCR4 as a co-receptor (X4 tropic strain). In 109 strains from treatment-negative group, 96 (88.1%) strains used CCR5 as a co-receptor (R5 tropic strain), 13 (11.9%) strains used CCR5/CXCR4 as a co-receptor use (X4/R5 strain). A significant difference was found between two groups in X4 co-receptor usages (χ(2) = 27.30, P < 0.05). Furthermore, after treated with AZT + DDI + NVP, the HIV-1 CXC4/CCR5 utilization was 59.09% (13/22), meanwhile after treated with D4T + DDI + NVP, the HIV-1 CXC4/CCR5 utilization was 43.48% (10/23), which the difference was not statistical significant (χ(2) = 1.10, P = 0.30).</p><p><b>CONCLUSION</b>HIV-1 CXCR4/CCR5 co-receptor utilization was higher in ART patients than treatment-negative patients.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Acquired Immunodeficiency Syndrome , Drug Therapy , Metabolism , Antiviral Agents , Therapeutic Uses , Cells, Cultured , HIV-1 , Receptors, CCR5 , Metabolism , Receptors, CXCR4 , Metabolism , Receptors, HIV , MetabolismABSTRACT
PURPOSE: The aim of the present study was to investigate the expression and the infiltration characteristics of fractalkine (CX3CL1)/ its receptor (CX3CR1) positive cells and macrophages in cisplatininduced ARF (CisARF). METHODS: Cisplatin (30 mg/kg) was injected intraperitoneally into wild-type C57BL/6 mice. Time course of CX3CL1 expression/CX3CR1 positive cells and macrophage infiltration in CisARF was investigated by using immunofluorescence for CX3CL1, CX3CR1 and CD 11b in the outer medullary region. And we performed a study whether there was a significant difference of macrophages infiltration between wild type and caspase-1- deficient mice, which was protective against CisARF. RESULTS: (1) Renal dysfunction was the most severe on day 3. (2) The intensity of immunofluorecence staining for CX3CL1 showed that there was a significantly increased expression in the tubulointerstitium rather than blood vessels in cisplatin-treated mice. There were no differences in CX3CR1 positive cells between vehicle and cisplatin-treated mice. (3) Macrophages infiltration was augmented from day 2 after cisplatin administration and preceded the development of CisARF. Macrophages infiltration in caspase-1 -/- mice was significantly lower than wild- type mice in CisARF. CONCLUSION: Our data demonstrated that CX3CL1 expression and macrophage infiltration in CisARF precedes the development of ARF, especially in the tubulointerstitium rather than blood vessels. However, recent reports showed that the blockade of CX3CR1 positive cells and depletion of macrophages could not be protective against CisARF. Therefore, further study is required to determine the role of other inflammatory cells such as natural killer cells in CisARF.
Subject(s)
Animals , Mice , Acute Kidney Injury , Blood Vessels , Chemokine CX3CL1 , Cisplatin , Fluorescent Antibody Technique , Killer Cells, Natural , Macrophages , Receptors, Cytokine , Receptors, HIV , Renal InsufficiencyABSTRACT
La coinfección con sífilis en el paciente infectado con VIH-1 ha aumentado en los últimos años. La sífilis se ha asociado con activación inmunológica, pero el efecto de la misma sobre los parámetros inmunovirológicos en esta población aún son controversiales. El objetivo es evaluar el efecto de la sífilis en el contaje de células TCD4+ y la carga viral del paciente VIH+. Se realizó un estudio retrospectivo, multicéntrico, de casos y controles, extrayendo de las historias clínicas de los pacientes VIH+ que asistieron a control en los últimos 10 años, los reportes de contaje de células TCD4+ y carga viral, antes, durante y después del diagnóstico de sífilis para compararlos entre sí y con un grupo control. 48 pacientes VIH+ diagnosticados con sífilis conformaron el grupo de estudio y 56 sin sífilis, el grupo control. 14 (29%) pacientes con sífilis secundaria, 33 (69%) latente y 1 (2%) primaria. 38 (80%) recibían TARV en el momento de la sífilis. 24 (70%) elevaron sus valores de TCD4+ durante la enfermedad y 27(59%) posterior a ella, con una media de elevación de 19,41 celulas x mm³ (p=0,43) y 23,74 células x mm³ (p=0,28) respectivamente. Las determinaciones de carga viral se elevaron durante la enfermedad en 8 (38%) pacientes con una media de elevación de 64688 copias ARN-VIH/ml (4,96 log10) (p=0,03), y disminuyeron en 13 (45%) con una media de -1163 copias de ARN/ml (3,06 log10) (p=0,99) posteriormente. La sífilis en el paciente VIH+ estuvo asociada a elevaciones significativas en la carga viral y a cambios no significativos en el contaje de células TCD4+ durante la enfermedad.
Syphilis co-infection in HIV-1 patients has increased in recent years. Syphilis has been linked to immunoactivation, however, its effect on immunovirological parameters in this population is still controversial. Objective evaluate the effect of syphilis on the TCD4+ cell count andviral load of the HIV+ patient. A retrospective, multicenter case-control study was conducted by extracting the TCD4+ cell counts and viral load before, during, and after diagnosis of syphilis, from the clinical records of HIV+ patients who attended check-ups in the past 10 years, in order to compare them among themselves and against a control group. Seroprevalence of HIV/Syphilis co-infection was 18%. 48 HIV+ patients diagnosed with syphilis formed the study group, while 56, without syphilis, the control group. 14 (29%) had secondary, 33 (69%) latent and 1 (2%) primary syphilis. 38 (80%) received ART at the time of their syphilis. Of 24 (70%) the TCD4+ values increased during illness, and of 27 (59%) they increased subsequently, with a mean increase of 19.41 cell/mm³ (p=0.43) and 23.74 cell/mm³ (p=0.28) respectively. Measurements of the viral load increased in 8 (38%) patients during the disease with a mean increase of 64,688 HIV RNA copies/ml (4.96 log10) (p=0.03); and in 13 they decreased subsequently (45%) with a mean of -1,163 RNA copies/ml (3.06 log10) (p=0.99). Syphilis in the HIV+ patient was linked to significant increases in the viral load and to non-significant changes in the TCD4+ cell count during the disease.
Subject(s)
Humans , Male , Female , Viral Load/methods , Viral Load , HIV , Receptors, HIV/blood , Receptors, HIV/therapeutic use , Syphilis/pathology , HematologyABSTRACT
<p><b>BACKGROUND</b>To investigate variant genotyping of CCR2-64I, SDF1-3'A and CCR5Delta32 in HIV-1 infected Chinese Long-term nonprogressors and to study their association with disease progression.</p><p><b>METHODS</b>The genotypes of CCR2-64I, SDF1-3'A and CCR5Delta32 were detected by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) assay in seventeen HIV-1 infected Chinese Long-term nonprogressors (LTNPs) and thirty-nine Chinese typical progressors (TPs).</p><p><b>RESULTS</b>The frequency of CCR2-64I and SDF1-3'A in LTNPs are 50% and 62.5%, higher than those (23.08% and 33.33%) in TPs. Only one heterozygous CCR5 mutant was detected in LTNPs, and no CCR5 mutant in TPs.</p><p><b>CONCLUSION</b>Variant genotyping of CCR2-64ISDF1-3'A and CCR5Delta32 may be protective factors for delaying disease progression in HIV-1 infected Chinese LTNPs.</p>
Subject(s)
Humans , Chemokine CXCL12 , Genetics , China , Gene Frequency , Genotype , HIV Infections , Genetics , Pathology , Virology , HIV Long-Term Survivors , HIV-1 , Physiology , Host-Pathogen Interactions , Mutation , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Receptors, CCR2 , Genetics , Receptors, CCR5 , Genetics , Receptors, HIV , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To explore genetic polymorphisms CCR5 of HIV coreceptor and CCR2 in Chinese Yi Ethnic group in Sichuan.</p><p><b>METHODS</b>Genomic DNA samples were obtained from 119 healthy individuals and 88 HIV-1 infected individuals of Chinese Yi Ethnic group in Sichuan. Polymerase chain reaction (PCR), cloning and gene sequencing techniques were employed to identify the genotype of CCR5Delta32; PCR-restriction fragment length polymorphism (RFLP) and gene sequencing were employed to identify the CCR2-64I alleles.</p><p><b>RESULTS</b>At CCR5 locus, 2 heterozygotes (CCR5-wt/Delta32) and none homozygote (CCR5-Delta32/Delta32) were observed in 119 healthy individuals, allelic frequency of CCR5-Delta32 was 0.84%; No mutant was found in 88 HIV-1 infected individuals. At CCR2 locus, 26 heterozygotes (CCR2-64V/64I) and two homozygotes (CCR2-64I/64I) were observed in healthy individuals but the allelic frequency CCR2-64I was 12.61%. Among infected individuals, 12 heterozygotes (CCR2-64V/64I) and 7 homozygotes (CCR2-64I/64I) were observed and the allelic frequency CCR2-64I was 13.27%. Statistical analysis revealed that the differences of both loci between healthy and infected individuals were insignificant. Both loci were consistent with the Hardy-Weinberg equilibrium in the two different groups.</p><p><b>CONCLUSION</b>The polymorphism of CCR5Delta32 and CCR2-64I alleles from Chinese Yi Ethnic group was detected which was of significance for the evaluation of genetic resistance to HIV-1 infection in Chinese population.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Alleles , Base Sequence , China , Ethnology , HIV Infections , Virology , HIV-1 , Genetics , Molecular Sequence Data , Polymorphism, Genetic , Receptors, CCR5 , Genetics , Receptors, HIV , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the V249I and T280M allelic polymorphisms of human immunodeficiency virus (HIV) coreceptor CX3CR1 in HIV-1 infected and uninfected population of Chinese indigenous Han and Uygur people and to probe the association between I249-M280 haplotype and HIV-1 susceptibility as well as AIDS progression.</p><p><b>METHODS</b>Genomic DNA of 223 Uygur subjects and 316 Han subjects were purified from PBMC. I249 and M280 allelic frequencies were identified by polymerase chain reaction (PCR)/nest polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. All data were tested by chi(2) or u statistics analysis.</p><p><b>RESULTS</b>Allelic frequencies of I249 and M280 were 16.1% and 13.3% in Uygur people, and 3.3% and 2.4% in Han people. No obvious difference existed between three groups of either ethnic group. However the allelic frequencies of HIV infected population were higher than those of general population, and those of general population higher than those of HIV-1 high-risk group. There was a strong linkage between I249 and M280 (P almost zero).</p><p><b>CONCLUSIONS</b>I249 mutation was the sine qua non of M280 mutation, and most I249 alleles were accompanied by M280. The frequency of I249-M280 haplotype in Uygur population (13.3%) was adjacent to Caucasian people (15.8%), and that of I249-T280 haplotype (2.8%) was obviously lower than Caucasian people (12.5%); while both of them in Han people were much lower (0.9% and 2.4%). I249-M280 haplotype could accelerate AIDS progression according to Faure et al, while might be associated with HIV-1 susceptibility.</p>
Subject(s)
Humans , Alleles , Asian People , Genetics , CX3C Chemokine Receptor 1 , China , Epidemiology , Ethnology , Chromosomes, Human, Pair 3 , Ethnicity , HIV Infections , Epidemiology , Genetics , Virology , HIV-1 , Genetics , Haplotypes , Membrane Proteins , Genetics , Metabolism , Point Mutation , Polymorphism, Restriction Fragment Length , Receptors, Chemokine , Genetics , Metabolism , Receptors, HIV , Genetics , Physiology , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of fractalkine (FKN) and its receptor CX3CR1 in cardiac allografts and the effect of Cyclosporin A (CsA).</p><p><b>METHODS</b>Three groups of rats underwent heterotopic cardiac transplantation, 45 cases in each group and 5 cases in control group: SD to SD regarded as isograft group (group A), Wistar to SD divided into CsA untreated allograft group (group B) and CsA treated allograft group (group C), normal SD rats as control group. The FKN mRNA expression was detected by one-step RT-PCR method and the expression of FKN and CX3CR1 protein was detected by standard ABC immunohistochemical technique.</p><p><b>RESULTS</b>The expression of FKN mRNA and protein was weak in both isografts and normal heart specimens. The changes of FKN mRNA expression were correlated with the process of acute allograft rejection. The peak of FKN mRNA expression (0.8 +/- 0.26) appeared on the seventh day after transplantation, which could be down-regulated by CsA significantly (t = 2.390, P < 0.05). FKN protein was located in endothelia cells and its receptor CX3CR1 was located in infiltrating mononuclear cells in allografts.</p><p><b>CONCLUSIONS</b>Upregulation of FKN and its receptor was significantly correlated with the trafficking of mononuclear cells which play an important role in acute allograft rejection. It may be one of the important mechanisms of CsA to intervene the acute rejection by inhibiting the activation of the FKN-CX3CR1 pathway.</p>
Subject(s)
Animals , Male , Rats , Acute Disease , CX3C Chemokine Receptor 1 , Chemokine CX3CL1 , Chemokines, CX3C , Genetics , Metabolism , Cyclosporine , Pharmacology , Graft Rejection , Allergy and Immunology , Pathology , Heart Transplantation , Allergy and Immunology , Pathology , Immunohistochemistry , Membrane Proteins , Genetics , Metabolism , RNA, Messenger , Metabolism , Rats, Sprague-Dawley , Rats, Wistar , Receptors, Cytokine , Genetics , Metabolism , Receptors, HIV , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transplantation, HomologousABSTRACT
<p><b>OBJECTIVE</b>To screen human monoclonal Fab fragments against HIV-1 gp120 peptide binding chemokine receptor.</p><p><b>METHODS</b>A synthesized polypeptide containing 23 amino acid residues of the gp120 antigen epitope binding chemokine receptor was coated as the solid-phase antigen. After biopanning from the HIV-1 phage Fab antibody library, the acquired positive clones were tested and sequenced.</p><p><b>RESULTS</b>One clone of human phage Fab monoclonal antibody against HIV-1 gp120 polypeptide was acquired. It has high affinity, specificity and inhibition rate and it belongs to IgG I subclass and kappa type. Its Vh H and V kappa were derived from Vh III and V kappa III.</p><p><b>CONCLUSIONS</b>The human phage Fab fragment against HIV-1 gp120 antigen site binding chemokine receptor was acquired.</p>
Subject(s)
Humans , Amino Acid Sequence , Antibodies, Monoclonal , Genetics , Antibodies, Viral , Genetics , Bacteriophages , Genetics , Cloning, Molecular , HIV Envelope Protein gp120 , Immunoglobulin Fab Fragments , Genetics , In Vitro Techniques , Molecular Sequence Data , Peptide Library , Receptors, Chemokine , Metabolism , Receptors, HIV , Allergy and ImmunologyABSTRACT
Chemokine receptors are G protein-coupled receptors that mediate migration and activation of leukocytes as an important part of a protective immune response to injury and infection. In addition, chemokine receptors are used by HIV-1 to infect CD4 positive cells. The structural bases of chemokine receptor recognition and signal transduction are currently being investigated. High-resolution X-ray diffraction and NMR spectroscopy of chemokines indicate that all these peptides exhibit a common folding pattern, in spite of its low degree of primary-sequence homology. Chemokines' functional motifs have been identified by mutagenesis studies, and a possible mechanism for receptor recognition and activation is proposed, but high-resolution structure data of chemokine receptors is not yet available. Studies with receptor chimeras have identified the putative extracellular domains as the major selectivity determinants. Single-amino acid substitutions in the extracellular domains produce profound changes in receptor specificity, suggesting that motifs in these domains operate as a restrictive barrier to a common activation motif. Similarly HIV-1 usage of chemokine receptors involves interaction of one or more extracellular domains of the receptor with conserved and variable domains on the viral envelope protein gp 120, indicating a highly complex interaction. Elucidating the structural requirements for receptor interaction with chemokines and with HIV-1 will provide important insights into understanding the mechanisms of chemokine recognition and receptor activation. In addition, this information can greatly facilitate the design of effective inmunomodulatory and anti-HIV-1 therapeutic agents
Subject(s)
Humans , CD4-Positive T-Lymphocytes/virology , HIV/metabolism , Receptors, Chemokine/chemistry , Receptors, Chemokine/physiology , Receptors, Chemokine/metabolism , Receptors, HIV/metabolismABSTRACT
Esta revisäo aborda recentes descobertas dque esclareceram a natureza das moléculas acessórias obrigatoriamente utilizadas pelo HIV para infectar células humanas, elucidando mecanismos de resistência à infecçäo e abrindo perspectivas de novos alvos para drogas e vacinas. Um ano após a descoberta do HIV, a molécula CD4 foi identificada como receptor primário utilizado no processo de infecçäo dos linfócitos T. Entretanto, há mais de uma década se sabia que só esta molécula näo era suficiente e que o HIV precisava de moléculas adicionais, ou co-receptores, para permitir a infecçäo da célula-alvo. Em 1996, vários grupos de pesquisa descobriram que receptores para citocinas, das quais bem caracterizadas...
Subject(s)
Humans , Receptors, HIV , HIV-1/chemistry , Chemokines/analysis , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/therapySubject(s)
Humans , Chemokines/therapeutic use , HIV Infections/drug therapy , Receptors, CXCR4 , Receptors, HIV , T-LymphocytesABSTRACT
El presente artículo de revisión se centra en las consideraciones fundamentales sobre la biología molecular del virus de la inmunodeficiencia humana, el principal de los retrovirus que infectan a los hombres, destacando sus aspectos constitutivos así como genéticos y las alteraciones con la célula huésped. Se presenta además los aspectos morfofuncionales básicos de los linfocitos T CD4 y las interacciones que a nivel de membrana se producen para favorecer la infección por el virus y que explican su fisiopatología. Finalmente, se destacan los eventos intracelulares que conducen a la replicación y ensamblaje viral que producen la muerte celular y explican la inmunosupresión del huésped
Subject(s)
Humans , HIV Infections/immunology , HIV Infections/physiopathology , HIV/genetics , Molecular Biology , DNA/physiology , Genes, env/physiology , Genes, gag/physiology , Genes, Regulator/physiology , Genes, vif/physiology , Genes, vpr/physiology , Genes, vpu/physiology , Receptors, Antigen, T-Cell, alpha-beta/physiology , Receptors, HIV/physiology , Retroviridae Infections/physiopathology , T-Lymphocytes/physiologyABSTRACT
Guía de atención y cuidados en su domicilio para los pacientes enfermos de SIDA o son portadores del virus VIH. Los capítulos de la guía son: I. Introducción: al familiar, amigo o compañero del que vive con VIH/SIDA II. Información básica sobre SIDA para el enfermo y sus familiares III. El SIDA y la sociedad en la que vivimos IV. Cuando llega la noticia a casa V. Emociones y sentimientos del paciente y su familia VI. Cómo ayudar al paciente en casa VII. ¿Existe el riesgo de contagio al convivir y cuidar a quien vive con VIH/SIDA? VIII. Sexualidad y la pareja IX. Higiene en casa X. Algunos consejos para la alimentación XI. ¿Qué hacer ante los primeros síntomas? XII. Mitos y realidades de los tratamientos contra el SIDA XIII. ¿Qué hacer cuando el paciente empeora? XIV. Momento de entregarse XV. Muerte XVI. La familia ante la muerte XVII. ¿Qué hacer y a dónde acudir en caso de fallecimiento? XVIII. Aspectos jurídicos y derechos humanos XIX. Carta de despedida XX. Directorio de utilidad