Stromal cell-derived factor 1 (SDF1) genetic polymorphism in a sample of healthy individuals, seronegative individuals exposed to human immunodeficiency virus type 1 (HIV-1) and patients infected with HIV-1 from the Brazilian population

The interaction of viral and host factors is believed to determine not only the risk for initial human immunodeficiency virus type 1 (HIV-1) acquisition but also the course of the infection. Genetic polymorphisms in the chemokine receptors and their ligands were related to the susceptibility and resistance to HIV-1 infection. A polymorphism in the conserved 3' untranslated region of the stromal cell-derived factor-1 (SDF1) gene, which encodes a ligand of the CXCR4 receptor, has been related either to delayed progression to AIDS or to rapid disease progression and death. Global, regional, and ethnic distributions of frequencies of SDF1 genotypes and of the SDF1-3'A allele vary significantly. Although the HIV-1 epidemic is increasing in Brazil, little information about the frequencies of host genetic mutations related to HIV/AIDS resistance in the Brazilian population has been reported. To address this question, this study was carried out in order to determine the frequencies of the SDF1 polymorphism and the SDF1-3'A allele on 1061 genomic DNA samples purified from peripheral blood cells of 136 healthy individuals (group 1), 147 HIV-1-exposed seronegative individuals (group 2), 161 HIV-1-infected asymptomatic individuals and with CD4(+) T-cells count 350 mm(-3) (group 3), and 617 HIV-1-infected individuals with AIDS and/or CD4(+) T-cells count < 350 mm(-3) (group 4). The frequencies of the SDF1-3'A homozygous mutation were 3.7%, 6.1%, 4.3%, and 5.3% among groups 1, 2, 3, and 4, respectively (P = 0.5120). The overall frequency of the SDF1-3'A allele was 0. 1984 and did not differ among the four groups (P = 0.2744). The results underscore the global distribution of the SDF1 polymorphism and the hypothesis that the SDF1-3'A allele, itself, may not be sufficient to prevent the risk of HIV-1 infection and may be not related to the progression of the disease in the Brazilian population.     

Frequency of CCR5-Delta32 deletion in human immunodeficiency virus type 1 (HIV-1) in healthy blood donors, HIV-1-exposed seronegative and HIV-1-seropositive individuals of southern Brazilian population

The frequency of CCR5-Delta32 allele in human immunodeficiency virus type 1 (HIV-1) infection in the southern Brazilian population was determined in a cross-sectional study carried out from October 2001 to June 2004. Genomic DNA was extracted from peripheral blood cells of 134 healthy blood donors, 145 HIV-1-exposed seronegative individuals, 152 HIV-1-seropositive asymptomatic individuals, and 478 HIV-1-seropositive individuals with AIDS. A fragment with 225 base-pairs of the CCR5 gene was amplified by polymerase chain reaction. The CCR5-Delta32 homozygous deletion was observed in 2 (1.5%) blood donors and in 1 (0.7%) individual HIV-1-exposed seronegative, and was absent among all the HIV-1-seropositive individuals (Fisher's exact test, p=0.0242). The frequency of the homozygous CCR5-Delta32 deletion in the HIV-1-exposed did not differ when compared with that observed in the HIV-1 seronegative blood donors (Fisher's exact test, p=0.6093; OR: 2.18, 95% CI: 0.11-129.6). The wild-type genotype CCR5/CCR5 frequency was higher among the HIV-1-seropositive with AIDS compared to HIV-1 seropositive asymptomatic individuals (Chi-square test, p=0.0263; OR: 2.02, 95% CI: 1.03-3.97). The absence of the homozygous deletion of CCR5-Delta32 among HIV-1-seropositive individuals underscored that this genotype is an important genetic factor associated with the decreased susceptibility to HIV-1 infection. The higher frequency of heterozygosity for the CCR5-Delta32 and the CCR5-Delta32 allele in HIV-1 seropositive asymptomatic compared to HIV-seropositive with AIDS individuals also underscored that this deletion could be associated with the delay of the HIV-1 disease progression in this population. However, the low frequency of CCR5-Delta32 homozygosity observed among HIV-1-exposed seronegative individuals shows that the allele could not explain, by itself, the natural resistance to HIV-1 infection and different mechanisms of protection against HIV-1 infection that must be involved in this population.     

Epidemiological, immunological and virological characteristics, and disease progression of HIV-1/HCV-co-infected patients from a southern Brazilian population

A cross-sectional study was carried out in order to describe the epidemiological, immunological and virological characteristics, and the disease progression of hepatitis C virus (HCV)/human immunodeficiency virus type 1 (HIV-1)- co-infected patients from a southern Brazilian population. Of 778 HIV-1-infected individuals enrolled in the study from September 2001 to December 2003, and followed up until June 2004, 757 were tested for anti-HCV antibodies. Of these, 159 (21.0%) showed positive results for anti-HCV. Males, individuals in the 25 to 34 year age range, and individuals of lower economic levels were more likely to be seropositive for both viruses [prevalence rate (PR), 2.04; 95% confidence interval (95% CI), 1.43-2.92; p<0.001]. The anti-HCV reactivity was also associated with blood routes of transmission (PR, 2.20; 95% CI, 1.28-3.77; p<0.001), intravenous drug use (PR, 5.79; 95% CI, 4.74-7.07; p<0.001), self-reported previous sexually transmitted diseases (PR, 1.55; 95% CI, 1.18-2.04; p=0.002), VDRL positivity (PR, 2.87; 95% CI, 2.40-3.43; p<0.001), and anti-HTLV I/II reactivity (PR, 5.09; 95% CI, 4.16-6.23; p<0.001). In the follow-up period, the HCV/HIV-1-co-infected patients showed a trend toward lower CD4+ T-cell counts, higher HIV-1 RNA plasma viral load and faster disease progression than patients infected only with HIV-1, but significant differences were not observed. Although there were proportionately more deaths in the HCV/HIV-1-co-infected group, the use of highly active antiretroviral therapy (HAART) was a string predictor of increased CD4+ T-cell counts and decreased HIV-1 RNA plasma levels, suggesting that HAART is more important to the immunological and virological outcomes in HIV-1 infection than is HCV co-infection status.     

Immune-inflammatory,oxidative stress and biochemical biomarkers predict short-term acute ischemic stroke death

Metabolic Brain Disease - The aim of the study was to define new immune-inflammatory, oxidative stress and biochemical biomarkers, which predict mortality within a period of 3&nbsp;months after...     

Enteric pathways in the stomach

This report summarises the characteristics of target specific projection and neurochemical coding patterns of motor and interneuronal pathways in the gastric enteric nervous system (ENS) which are involved in the innervation of the mucosa, the circular and the longitudinal muscle. The pathways were identified by retrograde tracing and further characterised by optical and intracellular recordings of the synaptic activation of muscle motor neurones, and by recordings of pathway-specific muscle responses. All motor pathways had polarised projections consisting of ascending cholinergic and descending nitrergic populations. Thus, both muscle layers were innervated by excitatory and inhibitory motor neurones. Their projections indicated the presence of intrinsic circuits that mediate excitatory and inhibitory components of a peristaltic reflex and/or are involved in reflex mediated changes in gastric tone. Although polarised projections were also identified for interneuronal pathways, a substantial proportion of descending interneurones was cholinergic. Interneurones and longitudinal muscle motor pathways had longitudinal projection preferences whereas circular muscle motor pathways had circumferential projection preferences. Target-specific coding was primarily revealed for cholinergic populations; ChAT/ENK/+/-SP neurones projected to the muscle layers, ChAT/NPY/+/-VIP projected to the mucosa and ChAT/+/-SP/+/-5-HT/+/-Calret/+/-Calb were interneurones. Muscle strip recordings revealed the functional significance of ascending excitatory and descending inhibitory pathways to the circular muscle and the prominent influence of ascending and descending cholinergic interneurones which activated excitatory and inhibitory circular muscle motor neurones through nicotinic synapses. It is concluded that enteric pathways in the stomach have region specific features which reflect structural and functional adaptation of the gastric ENS.     

Preparation and characterization of biocompatible oil-loaded polyelectrolyte nanocapsules

The aim of this work was to develop a novel preparation method for polyelectrolyte nanocapsules. The prepared capsules have a three-layer polyelectrolyte shell and a core consisting of medium-chain triglycerides. The preparation is based on a high-pressure homogenized emulsion that is stabilized by a modified starch, followed by the stepwise addition of the additional layer components chitosan and lambda-carrageenan. Producing polyelectrolyte nanocapsules with an average size of 130 nm without alternating with separation steps resulted in an efficient preparation technique. The characterization of the nanocapsules by zeta-potential, light-scattering techniques, nuclear magnetic resonance, and transmission electron microscopy played a major role. All ingredients are nontoxic and biocompatible. These properties could be extremely useful to the food or pharmaceutical industry for incorporating lipophilic substances. The encapsulation may be beneficial regarding improved stability and protection capability of labile substances.     

<Emphasis Type="Italic">C-reactive protein</Emphasis> +1444CT (rs1130864) genetic polymorphism is associated with the susceptibility to systemic lupus erythematosus and C-reactive protein levels

The T rare allele of +1444CT (rs1130864) polymorphism of C-reactive protein (CRP) has been associated with increased CRP levels in some inflammatory conditions, but its role on systemic lupus erythematosus (SLE) susceptibility and on CRP levels in SLE patients remains uncertain. The objective of the study was to evaluate the association between the rs1130864 CRP polymorphism with SLE susceptibility, disease activity, and CRP levels in SLE Brazilian patients. The study enrolled 176 SLE patients and 137 controls. SLE disease activity was assessed using the SLE Disease Activity Index (SLEDAI). The rs1130864 CRP polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism. SLE patients presented higher body mass index (p = 0.046) and CRP levels (p = 0.017) than controls. The genotype and allele frequencies of patients differed from controls [CC vs. CT = odds ratio (OR) 1.730, 95% confidence interval (CI) 1.068–2.803, p = 0.035; CC vs. TT = OR 3.667, 95% CI 1.410–9.533, p = 0.009; C vs. T = OR 1.883, 95% CI 1.299–2.728, p = 0.001)]. Patients carrying the T allele presented higher CRP levels (p = 0.009), were more frequent Caucasians (p = 0.018), and with no use of immunosuppressive treatment (p = 0.004) than those carrying the C allele. However, the SLEDAI and anti-double-stranded DNA positivity did not differ from those carrying T vs. C allele (p = 0.595 and p = 0.243, respectively). The rs1130864 CRP polymorphism was associated with SLE susceptibility and CRP levels, but not with disease activity, suggesting that this polymorphism may play a role in the pathophysiology of SLE through increasing the CRP that, probably, plays an inflammatory role in SLE pathophysiology.     

Vitamin D deficiency is associated with acute ischemic stroke,C-reactive protein,and short-term outcome

The aim of this study was to investigate whether vitamin D deficiency (VDD) is associated with acute ischemic stroke, inflammatory markers, and short-term outcome. 168 acute ischemic stroke patients and 118 controls were included. The modified Rankin Scale (mRS) was applied up to 8 h of admission (baseline) and after three-months follow-up, and blood samples were obtained up to 24 h of admission to evaluate serum levels of 25-hydroxivitamin D [25(OH)D] and inflammatory markers. Vitamin D levels classified the individuals in sufficient (VDS?≥?30.0 ng/mL), insufficient (VDI 20.0–29.9 ng/mL), and deficient (VDD?<?20.0 ng/mL) status. Patients had lower levels of 25(OH)D, higher frequency of VDD (43.45% vs. 5.08%, OR: 16.64, 95% CI: 5.66–42.92, p?<?0.001), and higher inflammatory markers than controls (p?<?0.05). Patients with VDD showed increased high sensitivity C-reactive protein (hsCRP) levels than those with VDS status (p?=?0.043); those with poor outcome presented with lower 25(OH)D levels than those with good outcome (p?=?0.008); moreover, 25(OH)D levels were negatively correlated with mRS after three-months follow-up (r?=??0.239, p?=?0.005). The associations between VDD and higher hsCRP levels and between 25(OH)D levels and poor outcome at short-term in acute ischemic stroke patients suggest the important role of vitamin D in the inflammatory response and pathophysiology of this ischemic event.

     

Growth-related effects of oxidant-induced stress on cultured RPE and choroidal endothelial cells

Mounting evidence suggests that oxidative stress caused by reactive oxygen intermediates is a significant mechanism in the pathogenesis of age-related macular degeneration (AMD). Although vascular endothelial growth factor (VEGF) and other cytokines are involved in choroidal neovascularization (CNV) it is largely unknown whether oxidative stress may predispose the eye to increased levels of proangiogenic factors. In an in vitro study we have determined viability and proliferation of both human retinal pigment epithelial (RPE) cells and bovine choroidal endothelial cells (CECs) and assessed the release of basic fibroblast growth factor (bFGF) and VEGF from RPE cells after exposing them to oxidative stress. Permanent presence of tert-butyl-hydroperoxide (tBH), a pro-oxidative stressor, in the cell cultures resulted in decreasing viability and proliferation of RPE cells and CECs. Loss of RPE cell viability was associated with activation of apoptosis by tBH in a dose-dependent manner. The antioxidant, N-acetyl-l-cysteine (NAC), and secreted soluble mediators of RPE cells were appropriate to attenuate the effects of tBH-mediated oxidative stress. RPE cells exposed to tBH were found to release increasing amounts of bFGF but not VEGF after 24 h of culture, thereby supporting proliferation of CECs. These findings suggest that oxidative stress compromises the viability of RPE cells and CECs. However, increased bFGF levels concomitantly released from RPE cells may attenuate the CEC-directed effect, protect CECs from oxidative insults, and are likely to promote CNV.