Increasing heterosexual transmission of HIV‐1 subtype C in Inland Central Western Brazil

The molecular epidemiology of HIV‐1 in Brazil is complex and heterogeneous because several subtypes co‐circulate with some important regional differences. This study evaluated HIV‐1 subtypes amongst pregnant women living in the metropolitan area and in the interior cities from central western Brazil. From June 2008 to June 2010, 86.9% of confirmed cases of HIV‐1 infection amongst pregnant women (172 out of 198 cases) were recruited in Goiania/Goias state. The HIV‐1 pol gene was sequenced after nested‐PCR. HIV‐1 subtypes were assigned by REGA, phylogenetic, and bootscan analyses. The median age of participants was 26 years (15–41 years range); 58.7% of participants were diagnosed during prenatal care and 51.7% of participants came from >50 interior cities within Goias state. Amongst the 131 HIV‐1 pol sequences, 64.9% were subtype B, 13.0% were BF1 recombinant, 11.4% were subtype C, 7.6% were subtype F1, and 2.3% were BC recombinant. According to the HIV‐1 diagnosis date (1994–2010), a significant increase in subtype C and a decrease of BF1 mosaics were observed over time. All subtype C patients lived in interior cities where the highest prevalence of subtype C outside southern Brazil was observed (18.4%). Phylogenetic analysis revealed multiple independent introductions of the Brazilian subtype C clade from the southern/southeastern regions of Brazil. The HIV‐1 epidemic in women from central western Brazil infected by the heterosexual route is characterized by an unexpectedly high prevalence of subtype C viruses highly related to those circulating in southern/southeastern Brazil. These findings highlight the importance of molecular surveillance programs outside large metropolitan regions in Brazil. J. Med. Virol. 85:396–404, 2013. © 2012 Wiley Periodicals, Inc.     

Description of Leprosy Classification at Baseline among Patients Enrolled at the Uniform Multidrug Therapy Clinical Trial for Leprosy Patients in Brazil

The uniform multidrug therapy clinical trial, Brazil (U-MDT/CT-BR), database was used to describe and report the performance of available tools to classify 830 leprosy patients as paucibacillary (PB) and multibacillary (MB) at baseline. In a modified Ridley and Jopling (R&J) classification, considering clinical features, histopathological results of skin biopsies and the slit-skin smear bacterial load results were used as the gold standard method for classification. Anti-phenolic glycolipid-I (PGL-I) serology by ML Flow test, the slit skin smear bacterial load, and the number of skin lesions were evaluated. Considering the R&J classification system as gold standard, ML Flow tests correctly allocated 70% patients in the PB group and 87% in the MB group. The classification based on counting the number of skin lesions correctly allocated 46% PB patients and 99% MB leprosy cases. Slit skin smears properly classified 91% and 97% of PB and MB patients, respectively. Based on U-MDT/CT-BR results, classification of leprosy patients for treatment purposes is unnecessary because it does not impact clinical and laboratories outcomes. In this context, the identification of new biomarkers to detect patients at a higher risk to develop leprosy reactions or relapse remains an important research challenge.     

Xanthine Oxidase Activation Modulates the Endothelial (Vascular) Dysfunction Related to HgCl<Subscript>2</Subscript> Exposure Plus Myocardial Infarction in Rats

Heavy metal exposure is associated with cardiovascular diseases such as myocardial infarction (MI). Vascular dysfunction is related to both the causes and the consequences of MI. We investigated whether chronic exposure to low doses of mercury chloride (HgCl₂) worsens MI-induced endothelial dysfunction 7 days after MI. Male Wistar rats were divided into four groups: Control (vehicle), HgCl₂ (4 weeks of exposure), surgically induced MI and combined HgCl₂-MI. Morphological and hemodynamic measurements were used to characterize the MI model 7 days after the insult. Vascular reactivity was evaluated in aortic rings. Chronic HgCl₂ exposure did not cause more heart injury than MI alone in terms of the morphological or hemodynamic parameters. Vascular reactivity increased in all groups, but the combination of HgCl₂-MI increased the vasorelaxation induced by ACh compared with the HgCl₂ and MI groups. Results showed reduced endothelial nitric oxide synthase (eNOS) protein expression in the MI group; increased iNOS activity in the HgCl₂-MI group, although without enough magnitude to reverse the reduction in NO bioavailability; and increased phenylephrine response in the HgCl₂-MI group due to an increase in ROS production, notably via xanthine oxidase (XO). Results suggest that the combination of 1 month pre-exposure of HgCl₂ before MI changed the endothelial generation of oxidative stress induced by mercury exposure from NADPH oxidase pathway to XO (xanthine oxidase)-dependent ROS production.     

Reference values for the fetal lateral ventricle atrium measurement in the second and third trimesters of pregnancy in a Brazilian population

Objective: To establish reference values for the fetal atrium lateral ventricle measurements in the second and third trimesters of pregnancy in a Brazilian population.

Methods: A retrospective cross-sectional study was performed with low-risk pregnant women who underwent ultrasound examination at 16–41 weeks of gestation. The atrium of lateral ventricle measurement was performed in the transventricular plane at the end of choroid plexus. We assessed reference curves (percentiles 5th, 50th and 95th) for the atrium of lateral ventricle measurement with gestational age (GA), using the best-fit polynomial equation, and determination coefficient (R²) and modeling the variability.

Results: The fetal atrium of lateral ventricle measurements was assessed in 519 singleton pregnancies. However, seven fetuses were excluded because of central nervous system malformations, and therefore data from 512 pregnancies were included in the analysis. The mean?±?standard deviation (range) of the fetal atrium lateral ventricle measurement (mm) was 5.1?±?1.4 (1.6–9.7). A best-fit curve was a first-degree polynomial regression: atrium lateral ventricle?=?6.455???0.049?×?GA (R²?=?0.05).

Conclusion: Reference values for the fetal atrium lateral ventricle measurements in the second and third trimesters of pregnancy in a Brazilian population were established.     

Neuromuscular junctions (NMJs): ultrastructural analysis and nicotinic acetylcholine receptor (nAChR) subunit mRNA expression in offspring subjected to protein restriction throughout pregnancy

Protein restriction during gestation can alter the skeletal muscle phenotype of offspring; however, little is known with regard to whether this also affects the neuromuscular junction (NMJ), as muscle phenotype maintenance depends upon NMJ functional integrity. This study aimed to evaluate the effects of a low protein (6%) intake by dams throughout gestation on male offspring NMJ morphology and nicotinic acetylcholine receptor (nAChR) α1, γ and ε subunit expression in the soleus (SOL) and extensor digitorum longus (EDL) muscles. Four groups of male Wistar offspring rats were studied. The offspring of dams fed low‐protein (6% protein, LP) and normal protein (17% protein, NP) diets were evaluated at 30 and 120 days of age, and the SOL and EDL muscles were collected for analysis. Morphological studies using transmission electron microscopy revealed that only SOL NMJs were affected in 30‐day‐old offspring in the LP group compared with the NP group. SOL NMJs exhibited fewer synaptic folds, the postsynaptic membranes were smooth and myelin figures were also frequently observed in the terminal axons. With regard to the expression of mRNAs encoding nAChR subunits, only 30‐day‐old LP offspring EDL muscles exhibited reduced α, γ and ε subunit expression compared with the NP group. In conclusion, our results demonstrate that a low‐protein diet (6%) imposed throughout pregnancy impairs the expression of mRNAs encoding the nAChR α, γ and ε subunits in EDL NMJs and promotes morphological changes in SOL NMJs of 30‐day‐old offspring, indicating specific differences among muscle types following long‐term maternal protein restriction.     

Effects of spironolactone in spontaneously hypertensive adult rats subjected to high salt intake

OBJECTIVE:

To evaluate the effect of spironolactone on ventricular stiffness in spontaneously hypertensive adult rats subjected to high salt intake.

INTRODUCTION:

High salt intake leads to cardiac hypertrophy, collagen accumulation and diastolic dysfunction. These effects are partially mediated by cardiac activation of the renin-angiotensin-aldosterone system.

METHODS:

Male spontaneously hypertensive rats (SHRs, 32 weeks) received drinking water (SHR), a 1% NaCl solution (SHR-Salt), or a 1% NaCl solution with a daily subcutaneous injection of spironolactone (80 mg.kg^-1) (SHR-Salt-S). Age-matched normotensive Wistar rats were used as a control. Eight weeks later, the animals were anesthetized and catheterized to evaluate left ventricular and arterial blood pressure. After cardiac arrest, a double-lumen catheter was inserted into the left ventricle through the aorta to obtain in situ left ventricular pressure-volume curves.

RESULTS:

The blood pressures of all the SHR groups were similar to each other but were different from the normotensive controls (Wistar  =  109±2; SHR  =  118±2; SHR-Salt  =  117±2; SHR-Salt-S  =  116±2 mmHg; P<0.05). The cardiac hypertrophy observed in the SHR was enhanced by salt overload and abated by spironolactone (Wistar  =  2.90±0.06; SHR  =  3.44±0.07; SHR-Salt  =  3.68±0.07; SHR-Salt-S  =  3.46±0.05 mg/g; P<0.05). Myocardial relaxation, as evaluated by left ventricular dP/dt, was impaired by salt overload and improved by spironolactone (Wistar  =  -3698±92; SHR  =  -3729±125; SHR-Salt  =  -3342±80; SHR-Salt-S  =  -3647±104 mmHg/s; P<0.05). Ventricular stiffness was not altered by salt overload, but spironolactone treatment reduced the ventricular stiffness to levels observed in the normotensive controls (Wistar  =  1.40±0.04; SHR  =  1.60±0.05; SHR-Salt  =  1.67±0.12; SHR-Salt-S  =  1.45±0.03 mmHg/ml; P<0.05).

CONCLUSION:

Spironolactone reduces left ventricular hypertrophy secondary to high salt intake and ventricular stiffness in adult SHRs.     

Granulocyte colony-stimulating factor improves early remodeling in isoproterenol-induced cardiac injury in rats

BackgroundGranulocyte colony-stimulating factor (G-CSF) has been used in some animal models and humans with wellestablished cardiovascular diseases. However, its effects in the initial stage of progressive non-ischemic heart failure are unknown.MethodsWistar rats (260–300 g) were divided into three groups: control (without any intervention), ISO (150 mg/kg isoproterenol hydrochloride sc, once a day for two consecutive days), and ISO-GCSF (50 μg/kg/d G-CSF for 7 days beginning 24 h after the last administration of ISO). Echocardiography was performed at baseline and after 30 days of follow-up. Subsequently, animals were anesthetized for hemodynamic analysis. The left ventricle was removed for analysis of interstitial collagen deposition and cardiomyocyte hypertrophy.ResultsIsoproterenol led to left ventricular dilation (control, 7.7 ± 0.14 mm; ISO, 8.7 ± 0.16 mm; ISO-GCSF 7.8 ± 0.09 mm; p < 0.05), myocardial fibrosis (control, 2.0 ± 0.18%; ISO, 9.1 ± 0.81%; ISO-GCSF 5.9 ± 0.58%; p < 0.05) and cardiomyocyte hypertrophy (control, 303 ± 10 μm²; ISO, 356 ± 18 μm²; ISO-GCSF 338 ± 11 μm²; p < 0.05). However, G-CSF partially prevented collagen deposition and left ventricular enlargement, with a slight effect on hypertrophy. Characterizing a compensated stage of disease, hemodynamic analysis did not change.ConclusionsG-CSF administered for 7 days was effective in preventing the onset of ventricular remodeling induced by high-dose isoproterenol with decreased collagen deposition and chamber preservation.