Alterations of Natural Killer Cell and T-Lymphocyte Counts in Adults Infected with Human Immunodeficiency Virus through Blood and Plasma Sold in the Past in China and in Whom Infection Has Progressed Slowly over a Long Period

Natural killer (NK) cells, natural killer T (NKT) cells, and T lymphocytes were analyzed by using a flow cytometer in 225 human immunodeficiency virus (HIV)-positive individuals infected through the past sale of blood and plasma without receiving antiretroviral therapy in the People’s Republic of China. According to CD4 T-cell counts these HIV-infected adults were stratified into three groups: long-term slow progressors, HIV-infected subjects, and AIDS patients. NK cell counts in long-term slow progressors were higher compared to HIV infection and AIDS patients (P < 0.05) and lower compared to normal controls (P < 0.05), whereas NKT cell counts in slow progressors and the HIV infection group were not different from those of normal controls. NK cell counts in HIV-seropositive subjects were positively correlated with CD4 T-cell counts (P < 0.05), and NKT cell counts were positively correlated with CD4 T-cell and CD8 T-cell counts (P < 0.05). The CD8 T-cell counts were higher in slow progressors compared to those with HIV infection, AIDS patients, and normal controls. These results indicated that HIV infection causes alterations of NK cells and T cells in slow progressors, HIV-infected subjects, and AIDS patient groups, but no difference was found in NKT cell counts and percentages in slow progressors and the HIV-infected group compared to normal controls.     

Prevalence and Risk Factors of Low Bone Mineral Density in Korean HIV-Infected Patients: Impact of Abacavir and Zidovudine

Low bone mineral density (BMD) is common in HIV-infected patients. We aimed to describe the prevalence of low BMD and risk factors in Korean HIV-infected patients and to assess the effects of antiretroviral therapy (ART) on BMD. We retrospectively evaluated 224 HIV infected-patients. The prevalence of osteopenia and osteoporosis were 41.5% and 12.9%. These were much higher in 53 patients aged 50 yr and older (52.8% and 34.0%). Older age, lower body mass index, and ART > 3 months were independent risk factors for low BMD. Osteoporosis was more prevalent in patients on the abacavir-based regimen for < 1 yr than ≥ 1 yr; however, it was more prevalent in patients on the zidovudine-based regimen for ≥ 1 yr than < 1 yr (P = 0.017). Osteoporosis in patients on the abacavir-based regimen was more common in the spine than in the femur (P = 0.01). Given such a high prevalence of low BMD, close monitoring of BMD for HIV-infected patients on ART is required. The different prevalence of osteoporosis over time and affected areas between two regimens suggest they may play roles in different mechanisms in bone loss.     

Usefulness of alternate prognostic serum and plasma markers for antiretroviral therapy for human immunodeficiency virus type 1 infection

In developing countries, the usability of peripheral blood constituents that are low-cost alternatives to CD4-positive (CD4⁺) T-cell and human immunodeficiency virus type 1 (HIV-1) RNA estimation should be evaluated as prognostic markers. The aim of our study was to investigate the use of plasma levels of dehydroepiandrosterone sulfate (DHEAS), albumin, and C-reactive protein (CRP) as alternate prognostic markers for antiretroviral treatment (ART) response in place of HIV-1 load measurements. Paired blood samples were collected from 30 HIV-infected individuals before and after initiation of ART, 13 HIV-infected individuals before and after completion of antituberculosis therapy (ATT), and 10 HIV-infected individuals not on either ATT or ART. Because of the nonavailability of samples, the CRP estimation was done for samples from only 19, 9, and 8 individuals in groups 1, 2, and 3, respectively. The measurements of all three markers, i.e., DHEAS, albumin, and CRP, were carried out with commercial assays. The differences in the albumin levels before and after ART or ATT were significant (P < 0.05), while the differences in DHEAS and CRP levels were not significant (P > 0.05). When levels of DHEAS among the individuals who were followed up were analyzed, 13 (44.8%) in the ART group and 9 (69%) in the ATT group showed an increase following treatment. Prior to treatment of HIV-infected individuals, there was a significant positive correlation of CD4⁺ T-cell counts and a negative correlation of viral load with albumin and DHEAS levels (P < 0.01). Among the three plasma markers we tested, plasma albumin and, to some extent, DHEAS show promise as prognostic markers in monitoring HIV infection.     

血液中叶酸、维生素B12水平与冠状动脉病变的关系及其机理探讨

为探讨血液中叶酸、维生素B12(VB12)水平与冠状动脉病变的关系及其机理,测定了94例冠心病(CHD)患者的全血叶酸、血浆叶酸和VB12水平,与39名对照者进行对比,并对叶酸、VB12水平与发生病变的冠脉支数间的关系进行研究;随机抽取57例受试者进行血浆同型半胱氨酸(Hcy)与血脂测定,探讨叶酸、VB12水平与血浆Hcy和血脂的相关性。结果显示,CHD患者的全血叶酸、血浆叶酸和VB12水平均显著低于对照组(P<0.05),不同冠脉病变支数的患者叶酸和VB12水平无显著性差异,全血叶酸、血浆叶酸和VB12水平与Hcy呈负相关,与血脂水平无关,提示血液中较低的叶酸、VB12水平与CHD有关,叶酸与VB12水平降低导致的Hcy增高可能是CHD的一个独立的危险因素。     

Association of Vitamin B12 Deficiency and Metformin Use in Patients with Type 2 Diabetes

We evaluated the prevalence of vitamin B₁₂ deficiency and associated factors in type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients using metformin was enrolled. Vitamin B₁₂ and folate levels were quantified by chemiluminescent enzyme immunoassay. Vitamin B₁₂ deficiency was defined as vitamin B₁₂ ≤ 300 pg/mL without folate deficiency (folate > 4 ng/mL). The prevalence of vitamin B₁₂ deficiency in metformin-treated type 2 diabetes patients was 9.5% (n = 76), and the mean vitamin B₁₂ level was 662.5 ± 246.7 pg/mL. Vitamin B₁₂ deficient patients had longer duration of metformin use (P < 0.001) and higher daily metformin dose (P < 0.001) than non-deficient patients. Compared with daily metformin dose of ≤ 1,000 mg, the adjusted odds ratio for 1,000-2,000 mg, and ≥ 2,000 mg were 2.52 (95% CI, 1.27-4.99, P = 0.008) and 3.80 (95% CI, 1.82-7.92, P < 0.001). Compared with metformin use of < 4 yr, the adjusted odds ratios for 4-10 yr, and ≥ 10 yr were 4.65 (95% CI, 2.36-9.16, P < 0.001) and 9.21 (95% CI, 3.38-25.11, P < 0.001), respectively. In conclusion, our study indicates that patients with type 2 diabetes treated with metformin should be screened for vitamin B₁₂ deficiency, especially at higher dosages (> 1,000 mg) and longer durations (≥ 4 yr) of treatment.

Graphical Abstract

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Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo

The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo.     

血浆同型半胱氨酸水平与血管性痴呆的关系

目的:探讨血浆同型半胱氨酸(Hcy)、血清叶酸和维生素B12水平与血管性痴呆(VD)的关系.方法:应用反相高效液相色谱法(RP-HPLC)测定30例VD患者的血浆Hcy水平,用放射免疫法(RIA)测定其血清叶酸及维生素B12水平,并与58例非痴呆脑梗死患者和30例同龄对照比较.结果:VD组血浆Hcy水平显著高于非痴呆脑梗死组:非痴呆脑梗死组血浆Hcy水平显著高于同龄对照组;VD组血清叶酸水平明显低于非痴呆脑梗死组;非痴呆脑梗死组血清叶酸水平明显低于同龄对照组.结论:Hcy可能是VD发病的一个危险因素.     

Plasma total homocysteine concentrations in adults with growth hormone (GH) deficiency: effects of GH replacement

Growth hormone (GH) deficiency is associated with increased cardiovascular morbidity and mortality. GH treatment improves the profile of many cardiovascular risk markers in individuals with GH deficiency (GHD). The aim of the present was to assess whether GH replacement may decrease plasma total homocysteine, an independent cardiovascular risk factor, thus potentially contributing to benefits of GH replacement in adult subjects with GHD. Twenty-five patients (17 female, 8 male), mean age 39-years, with GHD were studied. GH status had been determined by an insulin tolerance test and/or arginine stimulation test. After an overnight fast, plasma insulin, IGF-1, total homocysteine (Hcy), free thyroxine (FT4), creatinine, vitamin B12, and folate were measured at baseline (V1), 3 months (V2) and then at 6 months (V3) on GH treatment. The data were analysed by hierarchical statistical models, univariate and multivariate correlation. GH treatment resulted in an increase in IGF-1 (p<0.001, p<0.001), and insulin (p=0.068, p<0.001), at each visit, respectively. Hcy levels increased from V1 to V2 (7.7+/-0.53 to 9.15+/-0.45 micromol/L; p=0.051), but this was followed by a decline at V3 (to 8.8+/-0.59), so that the overall change of Hcy levels from V1 to V3, once individuals had achieved 'adequate' GH replacement, was no longer significantly different (p=0.090). When separated by gender, at 6 months (V3) there was a small, but significant increase in Hcy in men (p=0.028), but not in women (p=0.58). There was no significant change in B12, folate, free T4 or creatinine levels. Univariate analysis revealed that only B12 and folate showed significant negative relationships with Hcy (B12: parameter= -0.013, p<0.001; folate: parameter=-1.31, p<0.001), but not between Hcy and IGF-1 (p=0.18). In a multiple variable model, both B12 and folate remained significantly negatively associated with plasma total homocysteine (p=0.018; p<0.001, respectively). In this observational study normalisation of IGF-1 levels in adult subjects with growth hormone deficiency was not associated with a fall in total homocysteine. Before firm conclusions can be drawn about the contribution of changes in plasma homocysteine concentrations to cardiovascular prognosis in adult GHD patients receiving GH replacement, further controlled studies are required.     

Triple positivity of HBsAg,anti-HCV antibody,and HIV and their influence on CD4+ lymphocyte levels in the highly HIV infected population of Abeokuta,Nigeria

BackgroundFew studies exist on hospital-based seroprevalence of triple positivity of HIV/HBV/HCV in Nigeria.ObjectivesThe study aimed at determining the triple positivity of HIV, HBsAg and HCV among HIV-infected individuals in Abeokuta, Nigeria and defining the influence of these triple infections on CD4+ counts of HIV-infected individuals as antiretroviral therapy improves in Nigeria.MethodsEnumeration of CD4+ levels in 183 HIV-infected persons was done with Partec Flow Cytometer. Seropositivity of HBsAg and anti-HCV antibody was detected with rapid kits.ResultsFrom the result obtained, significance variance (p<0.05) existed between HIV positive persons and persons who tested positive to HIV/HBV/HCV triple infection before and after the commencement of HAART. Of these infections, 31(16.9%) had HBV/HCV/HIV triple infection, while 152(83.1%) had HIV mono infection only, 56(30.6%) had HBV/HIV dual infection only and 43(23.5%) had HCV/HIV dual infection only. Significant variance (p<0.05) also existed between subjects with CD4 counts of <200 cells/µl, 200–499 cells/µl and >500 cells/µl. Highest seroprevalence of HIV (35.0%) was found in age groups 35–44 years and >65 years had the least (2.7%). Significant variance (p<0.05) also existed in the progression of CD4+ lymphocytes cells between subjects with persistent decrease (32.3%) in CD4+ lymphocytes cells and those with fluctuation in their CD4+ lymphocytes cells (12.9%) after the commencement of ART.ConclusionThe study further confirms that triple positivity of HIV/HBV/HCV infection is common in Abeokuta, Nigeria. Testing of these triple infections should be a big concern in the best choice and commencement of ART. Also, the study showed that consistent and prolonged use of HAART had a positive impact on the CD4 count of HIV-infected individuals.     

Predictors of Poor Retention in Care of HIV-infected Patients Receiving Antiretroviral Therapy in Korea: Five-Year Hospital-based Retrospective Cohort Study

Poor retention in care (RIC) is associated with higher antiretroviral therapy (ART) failure and worse survival. Identifying high risk patients for poor RIC is important for targeted intervention. A retrospective cohort study was conducted at a tertiary care hospital in Korea. HIV-infected patients initiating ART during 2002-2008 were included. 5 year-RIC was measured by hospital visit constancy (HVC) at 5 years after initiating ART. Among 247 enrolled patients, 179 (72.5%) remained in care, 20 (8.1%) were transferred to other hospitals, 9 (3.6%) died and 39 (15.8%) were lost to follow-up. We compared the demographic, psychosocial, and clinical characteristics between the groups with 100% HVC (n = 166, 67.2%) and ≤ 50% HVC (n = 33, 13.4%). In multivariable analysis, ART-starting age ≤ 30 years (odds ratio [OR] 4.08 vs. > 50; 95% confidence interval [CI] 1.10-15.15, P = 0.036), no non-HIV related comorbidity (OR 2.94 vs. comorbidity ≥ 1; 95% CI 1.02-8.49, P = 0.046), baseline CD4 cell count > 300 cells/μL (OR 3.58 vs. ≤ 200; 95% CI 1.33-9.65, P = 0.012) were significant predictable factors of poor RIC. HIV/AIDS care-givers should pay attention to young patients with higher baseline CD4 cell counts and no non-HIV related comorbidity.     

Prevalence of Micronutrient Deficiency after Bariatric Surgery

IntroductionWhile vitamin deficiency after bariatric surgery has been repeatedly described, few studies have focused on adequate micronutrient status. In this study, we examine the prevalence of vitamin and micronutrient deficiency for the first 3 years after surgery.MethodsOut of 1,216 patients undergoing surgery, 485 who underwent postoperative follow-up in an outpatient clinic between 2010 and 2019 were included in this evaluation (76.9% women, mean age 42 ± 12 years, mean BMI: year 1, 33.9 ± 19.2; year 2, 29.7 ± 8.7; year 3, 26.2 ± 4.0). Weight and cardiovascular risk factors as well as ferritin, vitamin B12, folic acid, 25-OH-vitamin D, vitamin A, vitamin E, zinc, copper, and selenium were evaluated. Deficits were defined as follows: ferritin <15 µg/L, vitamin B12 <197 pg/mL, folic acid <4.4 ng/mL, 25-OH-vitamin D <75 nmol/L, vitamin A <1.05 µmol/L, vitamin E <12 µmol/L, zinc <0.54 mg/L, copper <0.81 mg/L, and selenium <50 µg/L. All patients underwent dietary counselling and substitution of the respective deficits as appropriate.ResultsOne year after bariatric surgery, 485 patients completed follow-up. This number decreased to 114 patients in year 2, and 80 patients in year 3. Overall, 42.7% (n = 207) underwent sleeve gastrectomy, 43.7% (n = 211) Roux-en-Y-gastric bypass, and 13.9% (n = 67) gastric banding. The following deficits were found (year 1/2/3): ferritin, 21.6/35.0/32.5%; vitamin B12, 14.3/1.8/6.3%; folic acid, 29.7/21.6/15.3%; 25-OH-vitamin D, 70.8/67.0/57.4%; vitamin A, 13.2/8.9/12.8%; vitamin E, 0%; zinc, 1.7/0/1.5%; copper, 10.4/12.2/11.9%; selenium, 11.1/4.3/0%.ConclusionAs seen in other studies, the follow-up frequency decreased over the years. Despite intensive substitution, the extent of some deficiencies increased or did not improve. These results suggest reinforcing measures to motivate patients for regular follow-up visits, considering closer monitoring schedules, and improving supplementation strategies.     

Comparison of Human Immunodeficiency Virus Antigens as Stimulants for Lymphocyte Proliferation Assays

CD4 proliferative responses to the human immunodeficiency virus (HIV) type 1 (HIV-1) p24 (gag) antigen inversely correlate with the plasma viral load in HIV-infected subjects who control viral replication without antiretroviral therapy. Use of a single HIV-1 protein to assess CD4 proliferative responses may not reflect the global response to this pathogen. We compared the abilities of HIV p24 and gp120 antigens from two different vendors, an inactivated whole HIV-1 MN virion preparation and an HIV-1E culture supernatant antigen, to elicit proliferative responses in HIV-seropositive and HIV-seronegative donors. Peripheral blood mononuclear cells from 12 HIV-seropositive donors (each with HIV-1 loads <4,000 copies/ml of plasma, >350 CD4 T lymphocytes/mm³, and no antiretroviral therapy) and 15 HIV-seronegative donors were assessed with multiple concentrations of each stimulant by standard lymphocyte proliferation assays. Wide variations in response rates were found, with zero, three, five, and eight individuals demonstrating stimulation indices of >3 for the HIV culture antigen supernatant, gp120, p24, and inactivated whole-virus preparations, respectively. These results suggest that the use of the inactivated whole virus resulted in a more sensitive assay for detection of CD4 T-lymphocyte function in HIV-infected subjects.     

Elevated plasma homocysteine levels in centenarians are not associated with cognitive impairment

Background: Previous reports have shown elevated plasma total homocysteine (tHcy) levels in elderly person with impaired cognition. Objective: To study the association between cognitive status and plasma tHcy levels in centenarians. Design: Cross-sectional survey. Setting: Centenarians living in two northern Italian provinces. Participants: Thirteen cognitively normal centenarians, ten cognitively impaired not-demented centenarians, and 34 demented centenarians with a clinical diagnosis of Alzheimer's disease (AD). Measurements: Blood levels of homocysteine's biological determinants vitamin B12, folate, and vitamin B6. Results. Elevated plasma tHcy levels (>17 μmol/l) were common in the general population (77% of normal centenarians, 100% of cognitively impaired not-demented centenarians, 82% of AD centenarians). Demented centenarians had the lowest folate serum levels. Low or borderline vitamin B12 serum levels (<221 pmol/l) and low vitamin B6 plasma levels (<11.7 nmol/l) were found in 33 and 66% of all centenarians independently of cognitive status. Among demented centenarians only plasma tHcy correlated inversely with both serum vitamin B12 and folate. No significant difference was found for plasma tHcy levels among the three diagnostic groups, even after adjusting for B vitamin levels. Conclusions: Hyperhomocysteinemia is very common among centenarians, probably due to vitamin deficiencies, but does not seem to be associated with cognitive impairment.     

N-homocysteinylation of tau and MAP1 is increased in autopsy specimens of Alzheimer's disease and vascular dementia

The pathomechanisms that associate a deficit in folate and/or vitamin B12 and the subsequent hyperhomocysteinemia with pathological brain ageing are unclear. We investigated the homocysteinylation of microtubule-associated proteins (MAPs) in brains of patients with Alzheimer's disease or vascular dementia, and in rats depleted in folate and vitamin B12, Cd320 KO mice with selective B12 brain deficiency and H19-7 neuroprogenitors lacking folate. Compared with controls, N-homocysteinylated tau and MAP1 were increased and accumulated in protein aggregates and tangles in the cortex, hippocampus and cerebellum of patients and animals. N-homocysteinylation dissociated tau and MAPs from β-tubulin, and MS analysis showed that it targets lysine residues critical for their binding to β-tubulin. N-homocysteinylation increased in rats exposed to vitamin B12 and folate deficit during gestation and lactation and remained significantly higher when they became 450 days-old, despite returning to normal diet at weaning, compared with controls. It was correlated with plasma homocysteine (Hcy) and brain expression of methionine tRNAsynthetase (MARS), the enzyme required for the synthesis of Hcy–thiolactone, the substrate of N-homocysteinylation. Experimental inactivation of MARS prevented the N-homocysteinylation of tau and MAP1, and the dissociation of tau and MAP1 from β-tubulin and PSD95 in cultured neuroprogenitors. In conclusion, increased N-homocysteinylation of tau and MAP1 is a mechanism of brain ageing that depends on Hcy concentration and expression of MARS enzyme. Its irreversibility and cumulative occurrence throughout life may explain why B12 and folate supplementation of the elderly has limited effects, if any, to prevent pathological brain ageing and cognitive decline. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Association of hyperhomocysteinemia with genetic variants in key enzymes of homocysteine metabolism and methotrexate toxicity in rheumatoid arthritis patients

Objectives

The study investigated the association between plasma homocysteine, folate and vitamin B12 with 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TYMS 2R → 3R) and methionine synthase (MTR A2756G) polymorphisms and methotrexate (MTX) treatment and toxicity in Tunisian Rheumatoid arthritis (RA) patients.

Methods

A total of 185 patients with RA were included. Homocysteine (Hcy) was assessed by fluorescence polarization immunoassay, and folate and vitamin B12 were measured by chemiluminescence immunoassays. The genetic polymorphisms were analyzed by PCR or PCR-RFLP. Hyperhomocysteinemia (HHC) was considered for Hcy?>?15 µmol/L.

Results

MTHFR C677T polymorphism was associated with HHC in RA patients (multi-adjusted OR, 95% CI 2.18, [1.07–4.57]; p?=?0.031). No association was detected with the remaining polymorphisms. Plasma Hcy, folate, and vitamin B12 did not differ according to each polymorphism, or with MTX treatment or toxicity. However, HHC was more prevalent in patients with than those without MTX toxicity (32.7 vs. 16.7%; p?=?0.035).

Conclusions

The MTHFR 677TT genotype is an independent risk factor for HHC in Tunisians RA patients. HHC could be a useful marker of MTX toxicity in RA patients.

     

Concentrations of Circulating β-Chemokines Do Not Correlate with Viral Load in Human Immunodeficiency Virus-Infected Individuals

The CC or β-chemokines MIP-1α, MIP-1β, and RANTES are the primary components of human immunodeficiency virus type 1 (HIV-1)-suppressive soluble factors in vitro. We studied the relationship between the concentrations of MIP-1α, MIP-1β, and RANTES in plasma and HIV viral load in HIV-infected subjects. The HIV-positive patient group (n = 140) had significantly lower concentrations of all three β-chemokines (MIP-1α, P < 0.0005; MIP-1β, P < 0.005; RANTES, P < 0.0005) than the control group (n = 58 for MIP-1α, n = 27 for MIP-1β, and n = 59 for RANTES). In addition, we divided the patient group into three subgroups (high, moderate, and low) based on the number of HIV-1 RNA copies in the plasma (as measured by quantitative HIV RNA PCR). Again, all three subgroups had significantly lower concentrations of the β-chemokines than the HIV-negative control group. However, there was no significant difference in plasma β-chemokine concentrations among the three subgroups within the patient group (P < 0.3). Although our results demonstrate that HIV-infected individuals had significantly lower concentrations of circulating β-chemokines than healthy uninfected control subjects, we found no correlation between the concentrations of β-chemokines in plasma and HIV-1 viral load in HIV-infected individuals.     

Inflammatory Responses in Blood Samples of Human Immunodeficiency Virus-Infected Patients with Pulmonary Infections

We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1β (IL-1β), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-α) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-α, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1β, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-α levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).     

Polymorphisms in the methylenetetrahydrofolate reductase and methionine synthase reductase genes and homocysteine levels in Brazilian children

Hyperhomocysteinemia is a risk factor for thrombosis, and methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms, folate, and B12 levels could contribute to plasma homocysteine (Hcy) variation. Although well established in adults, few studies have been performed in childhood. In this study, we investigated association of polymorphisms C677T and A1298C in the MTHFR gene and A66G in the MTRR gene with Hcy levels in children. These polymorphisms, as well as Hcy, folate, and vitamin B12 levels were investigated in 220 normal children with ages ranging from 1 to 8 years. Plasma Hcy, folate, and vitamin B12 levels were normal in all children. None of the polymorphisms could be considered an independent risk factor for hyperhomocysteinemia during childhood. The median Hcy levels in 37 children (17%) doubly heterozygous for C677T and A1298C mutations in the MTHFR gene were not different from the other genotypes. However, the association of the different genotypes with Hcy, folate, and vitamin B12 levels demonstrated significant P-values. The folate levels demonstrated a statistically significant decrease (P = 0.0477) from the C677T mutation in the MTHFR gene (TT genotype) when compared to the other groups. Folate was the only independent risk factor for hyperhomocysteinemia. Thus, monitoring the concentrations of folate would be more helpful for evaluating hyperhomocysteinemia and for preventing cardiovascular disease.     

Semen lactoferrin promotes CCL20 production by epithelial cells: Involvement in HIV transmission

AIM: To study the effect of seminal plasma on Chemokine(C-C motif) ligand 20(CCL20) production by epithelial cells and its relationship with lactoferrin.METHODS: HEC-1A cells, a cell line derived from a monostratified endocervical epithelium, were incubated with samples of seminal plasma(diluted 1:10 in culture medium) recovered from human immunodeficiency virus(HIV) seronegative(HIV-) or HIV seropositive(HIV+) subjects. Recombinant human interleukin 1 beta(IL-1β) was used as positive control, and culture medium only as negative control. The measurement of CCL20 production in the supernatants of HEC-1A cells and of lactoferrin in seminal plasma was determined by enzyme-linked immunosorbent assay techniques. A fractionation of seminal plasma proteins was performed by ion exchange chromatography on a pool of seminal plasma specimens from HIV- subjects. Each fraction was tested for its ability to stimulate the production of CCL20 by HEC-1A cells and for its lactoferrin concentration. The HIV viral load in seminal plasma samples from HIV+ patients was measured using the HIV-Monitor kit(Roche Diagnostic Systems, Branchburg, NJ, United States).RESULTS: The positive control IL-1β was responsible for an increase of 11.36 ± 3.36 times in the production of CCL20. Stimulation of HEC-1A cells was performed in 34 seminal plasma samples(22 from HIV+ subjects and 12 from HIV- subjects). The mean production of CCL20 by HEC-1A in presence of seminal plasma from HIV- and HIV+ subjects was respectively 5.38 ± 0.91 and 7.57 ± 3.26 times higher than that obtained with the untreated cells(P 0.05 between the two groups). Using the same 34 specimens of seminal plasma, no correlation was observed between the concentration of total proteins in seminal plasma and their ability to stimulate the secretion of CCL20 by HEC-1 cells. In contrast, the ability to produce CCL20 by HEC-1A cells correlated to the concentration of lactoferrin in the seminal plasma samples(r coefficient = 0.56; CI: 0.26-0.76; P 0.001). After fractionation by ion exchange chromatography, the seminal plasma fractions exhibiting the highest concentrations of lactoferrin were responsible for the greatest stimulation of CCL20 production by HEC-1A cells(r coefficient = 0.89; CI: 0.78-0.95; P 0.0001). CONCLUSION: Lactoferrin present in seminal plasma correlated with an increased production of CCL20 by HEC-1A cells and therefore could facilitate HIV entry through the genital mucosa.     

Effect of Interleukin-28B Polymorphism on Interleukin-28 Expression and Immunological Recovery amongst HIV-1-Infected Individuals Following Antiretroviral Therapy

Purpose: Type III interferon is well known to have diverse antiviral and immunomodulatory activities. Studies describing the association of interleukin (IL)-28 polymorphisms in treatment-experienced HIV participants are limited. This study was aimed to determine the association of IL-28B gene polymorphisms with immunological recovery in HIV patients on 6–9 months of antiretroviral therapy (ART). Methods: Eighty treatment-naive HIV patients were recruited, of which 48 patients were followed up after 6–9 months of ART. Whole blood samples were collected before and after 6–9 months of ART. CD4, CD8 and CD3 counts were enumerated flow cytometry. IL-28B polymorphisms (rs12979860 and rs8099917) were profiled by polymerase chain reaction (PCR)-restriction fragment length polymorphism. The IL-28 mRNA and plasma HIV-1 viral load were estimated using real-time PCR and plasma IL-28 level by ELISA. Results: The CD4, CD4/CD3%, IL-28 mRNA and reversal of CD4/CD8 ratio were significantly increased following 6–9 months of ART (P < 0.01). The rs12979860 CC genotype and rs12979860:rs8099917 (CC: TT) haplotype showed significant association with higher CD4+ T-cell count amongst treatment-naive HIV-infected individuals (P < 0.05). In addition, there was a significant association of rs12979860 CC genotype with increase in CD4/CD3% following 6–9 months of ART. IL-28 mRNA showed correlation with the HIV-1 viral load, and there was a significant increase in the IL-28 mRNA expression following 6–9 months of ART. Conclusion: Our preliminary findings suggest that IL-28 polymorphisms could influence both immunological recovery and therapeutic response in HIV infection. Hence, functional studies are warranted to understand the mechanistic basis of IL-28-mediated host genetic influence on HIV therapeutic response.