HIV-1, sexually transmitted infections, and sexual behavior trends among men who have sex with men in Lima, Peru

OBJECTIVE: To assess and estimate trends in HIV, sexually transmitted infections (STIs), and sexual behavior among men who have sex with men (MSM) in Lima, Peru. DESIGN: Second-generation HIV sentinel surveillance surveys conducted in 1996, 1998, 2000, and 2002. METHODS: Adult men reporting sex with at least 1 man during the previous year were eligible to participate. Sexual behavior and serum HIV-1 and syphilis antibodies were assessed. HIV seroincidence was estimated by a sensitive/less-sensitive enzyme immunoassay strategy. Rectal and pharyngeal swabs for Neisseria gonorrhoeae culture and a first-void urine sample for urethral leukocytes for presumptive diagnosis of urethritis were obtained. Herpes simplex virus 2 (HSV-2) antibodies were measured in 2002. RESULTS: Although HIV prevalence increased from 18.5% to 22.3% from 1996 through 2002, bacterial prevalence declined significantly for syphilis (16.0% to 12.4%), early syphilis (8.6% to 3.4%), and rectal gonorrhea (5.1% to 0.2%). High HIV seroincidence was estimated, with the lowest (4.8%) incidence in 1998. In 2002, HSV-2 seroprevalence was 51.0%. After adjustment for age, education, and self-reported sexual identity, our data suggest that a yearly increase by 6% in the prevalence of HIV occurred among MSM in Lima, with a corresponding decline in syphilis (by 9%), early syphilis (by 18%), and rectal gonorrhea (by 64%). Condom use during last sexual intercourse increased by 26% each year with the most recent male steady partner and, among non-sex workers, by 11% with the most recent casual partner. CONCLUSIONS: HIV continued to spread among MSM in Lima even when a decline in bacterial STIs and increase in condom use were estimated to occur. Intensification of medical and behavior prevention interventions is warranted for MSM in Peru.     

Stochastic resonance in the motor system: effects of noise on the monosynaptic reflex pathway of the cat spinal cord

In sensory systems, the presence of a particular nonzero level of noise may significantly enhance the ability of an individual to detect weak sensory stimuli through a phenomenon known as stochastic resonance (SR). The aim of this study was to demonstrate if such phenomenon is also exhibited by the motor system; in particular, in the Ia-motoneuron synapse of the cat spinal cord. Monosynaptic reflexes elicited by periodic electrical stimulation to the medial gastrocnemius nerve were recorded in the L(7) ventral root (or in single motoneurons) of decerebrated cats. Random stretches (mechanical noise) were applied to the lateral gastrocnemius plus soleus muscle by means of a closed-loop mechanical stimulator-transducer. In all cats, we observed the SR phenomenon. The amplitude of the monosynaptic reflexes (or number of action potentials recorded in the motoneurons) evoked by the weak electrical stimuli applied to the medial gastrocnemius nerve were an inverted U-like function of the mechanical noise applied to the lateral gastrocnemius plus soleus muscle. A significant maximum value in the amplitude of the monosynaptic responses was reached with a particular noise amplitude value. Numerical simulations on a model of the monosynaptic reflex pathway qualitatively reproduce this stochastic resonance behavior. We conclude that the monosynaptic reflex response elicited by Ia afferents is optimized by the noisy stretching of a synergistic muscle. Our study provides the first direct demonstration that the motor system, and not only the sensory systems, exhibits the SR phenomenon.     

A Novel Regulatory Defect in the Branched‐Chain α‐Keto Acid Dehydrogenase Complex Due to a Mutation in the PPM1K Gene Causes a Mild Variant Phenotype of Maple Syrup Urine Disease

This article describes a hitherto unreported involvement of the phosphatase PP2Cm, a recently described member of the branched‐chain α‐keto acid dehydrogenase (BCKDH) complex, in maple syrup urine disease (MSUD). The disease‐causing mutation was identified in a patient with a mild variant phenotype, involving a gene not previously associated with MSUD. SNP array‐based genotyping showed a copy‐neutral homozygous pattern for chromosome 4 compatible with uniparental isodisomy. Mutation analysis of the candidate gene, PPM1K, revealed a homozygous c.417_418delTA change predicted to result in a truncated, unstable protein. No PP2Cm mutant protein was detected in immunocytochemical or Western blot expression analyses. The transient expression of wild‐type PPM1K in PP2Cm‐deficient fibroblasts recovered 35% of normal BCKDH activity. As PP2Cm has been described essential for cell survival, apoptosis and metabolism, the impact of its deficiency on specific metabolic stress variables was evaluated in PP2Cm‐deficient fibroblasts. Increases were seen in ROS levels along with the activation of specific stress‐signaling MAP kinases. Similar to that described for the pyruvate dehydrogenase complex, a defect in the regulation of BCKDH caused the aberrant metabolism of its substrate, contributing to the patient's MSUD phenotype—and perhaps others.     

Dicentric (17;18) in a case of atypical B-cell chronic lymphocytic leukemia

We report a new dic(17;18)(p11.2;p11.2) in a 61-year-old male patient diagnosed with atypical B-cell chronic lymphocytic leukemia. The dic(17;18)(p11.2;p11.2) was detected in 90%, 10%, and 100% of metaphases in the peripheral blood, bone marrow, and lymph node, respectively. Fluorescence in situ hybridization studies with chromosome 17 and 18 centromeric probes revealed the presence of two normal centromeres of both chromosomes 17 and 18. The centromere of one chromosome 17 was found together with the centromere of one chromosome 18, confirming the dicentric nature of the rearrangement. In addition, with the use of a 17p13.1 region probe, monosomy of the 17p13 region, where the Tp53 gene is located, was observed.     

HTLV infection among foreign pregnant women living in Spain

Background

The overall seroprevalence of HTLV infection among pregnant women in Spain is below 0.02% and accordingly universal antenatal screening is not recommended. However, as the number of immigrants has significantly increased during the last decade, this population might warrant specific considerations.

Objective

To evaluate the seroprevalence of HTLV infection among immigrant pregnant women living in Spain.

Methods

From January 2009 to December 2010 a cross-sectional study was carried out in all foreign pregnant women attended at 14 Spanish clinics. All were tested for HTLV antibodies using a commercial enzyme-immunoassay, being reactive samples confirmed by Western blot or PCR.

Results

A total of 3337 foreign pregnant women were examined. Their origin was as follows: Latin America 1579 (47%), North Africa 507 (16%), East Europe 606 (18%), Sub-Saharan Africa 316 (9%), North America and West Europe 116 (3.5%) and Asia and Australia 163 (5%). A total of 7 samples were confirmed as HTLV positive, of which 6 were HTLV-1 and 1 HTLV-2. HTLV-1 infection was found in 5 women coming from Latin America and 1 from Morocco. The only woman with HTLV-2 came from Ghana. The overall HTLV seroprevalence was 0.2%, being 0.3% among Latin Americans and 0.2% among Africans. It was absent among women coming from other regions.

Conclusions

The seroprevalence of HTLV infection among foreign pregnant women in Spain is 0.2%, being all cases found in immigrants from Latin America and Africa. Given the benefit of preventing vertical transmission, antenatal screening should be recommended in pregnant women coming from these regions.     

Reduction of metastasis using a non-volatile buffer

The tumor microenvironment is acidic as a consequence of upregulated glycolysis and poor perfusion and this acidity, in turn, promotes invasion and metastasis. We have recently demonstrated that chronic consumption of sodium bicarbonate increased tumor pH and reduced spontaneous and experimental metastases. This occurred without affecting systemic pH, which was compensated. Additionally, these prior data did not rule out the possibility that bicarbonate was working though effects on carbonic anhydrase, and not as a buffer per se. Here, we present evidence that chronic ingestion of a non-volatile buffer, 2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA) with a pK _a of 6.9 also reduced metastasis in an experimental PC3M prostate cancer mouse model. Animals (n = 30) were injected with luciferase expressing PC3M prostate cancer cells either subcutaneously (s.c., n = 10) or intravenously (i.v., n = 20). Four days prior to inoculations, half of the animals for each experiment were provided drinking water containing 200 mM IEPA buffer. Animals were imaged weekly to follow metastasis, and these data showed that animals treated with IEPA had significantly fewer experimental lung metastasis compared to control groups (P < 0.04). Consistent with prior work, the pH of treated tumors was elevated compared to controls. IEPA is observable by in vivo magnetic resonance spectroscopy and this was used to measure the presence of IEPA in the bladder, confirming that it was orally available. The results of this study indicate that metastasis can be reduced by non-volatile buffers as well as bicarbonate and thus the effect appears to be due to pH buffering per se.     

Glucoamylase activity from the thermophilic fungus Scytalidium thermophilum. Biochemical and regulatory properties

A glucoamylase activity produced by the thermophilic fungus Scytalidium thermophilum was purified 6.8‐fold by ion exchange chromatography. The protein exhibited a molecular mass of about 86 kDa (7% PAGE and SDS‐PAGE), or 68.5 kDa (Bio Sil SEC‐400 FPLC). The pI of the enzyme was 8.4. Optima of pH and temperature, with starch or maltose as substrates were, 6.5/60 °C and 5.0/55 °C, respectively. The enzyme had a half‐life of 22 min at 55 °C with starch as substrate, and it was fully stable with maltose. Maltase activity was activated by 10 mM Ba⁺⁺ (7.8%); Mn⁺⁺ (12.4%) or Mg⁺⁺ (28%). The enzyme contained approximately 25.5% carbohydrate. K_m and V_max values for starch and maltose were 0.28 mg/ml, 67.2 U/mg protein and 1.40 mg/ml, 5.61 U/mg protein, respectively. The products of hydrolysis of starch, detected by thin layer chromatography, showed only glucose after 30 min, indicating a glucoamylase activity. The amino terminal sequence of the purified protein showed 93% homology with a glucoamylase activity purified from Humicola grisea var. thermoidea.     

miR-320c Regulates SERPINA1 Expression and Is Induced in Patients With Pulmonary Disease

IntroductionAlpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3′UTR region of SERPINA1 gene. In this study we explore the involvement of miR-320c, a member of this family, in this disease.MethodsFirstly in vitro studies were carried out to demonstrate regulation of SERPINA1 gene by miR-320. Furthermore, the expression of miR-320c was analyzed in the blood of 98 individuals with different AAT serum levels by using quantitative PCR and expression was correlated to clinical parameters of the patients. Finally, HL60 cells were used to analyze induction of miR-320c in inflammatory conditions.ResultsOverexpression of miR-320 members in human HepG2 cells led to inhibition of SERPINA1 expression. Analysis of miR-320c expression in patient's samples revealed significantly increased expression of miR-320c in individuals with pulmonary disease. Additionally, HL60 cells treated with the pro-inflammatory factor lipopolysaccharide (LPS) showed increase in miR-320c expression, suggesting that miR-320c responds to inflammation.ConclusionOur findings demonstrate that miR-320c inhibits SERPINA1 expression in a hepatic cell line and its levels in blood are associated with lung disease in a cohort of patients with different AAT serum levels. These results suggest that miR-320c can play a role in AAT regulation and could be a biomarker of inflammatory processes in pulmonary diseases.     

Unilateral Dichotomy of Nipple (Intraareolar Polythelia) and Areola: Report of a Case and Surgical Correction

An unusual case of intraareolar polythelia with two nipples is presented. The dichotomy affected not only the nipple, but also the areola. No other breast malformation existed. Surgical correction was performed by transposition flaps sutured to one another in the center of the areola. The anatomic and functional results were satisfactory.     

Neuronal Nitric Oxide Synthase is a Key Factor in Doxorubicin-Induced Toxicity to Rat-Isolated Cortical Neurons

Doxorubicin (DOX) is neurotoxic to serum-free cultures of rat cortical neurons in a biphasic concentration manner. For concentrations up to 0.5 μM, cell death follows an apoptotic pattern, while for higher concentrations apoptosis is inhibited and necrosis becomes dominant. Considering the potential toxic effects of DOX resulting from its redox-cycling, in this study we investigated the generation of reactive species and subsequent oxidative stress effects, formation of quinoproteins, activation of NF-kB, depletion of energy levels and consequent cell death in cultures of primary rat cortical cells challenged with this antitumour drug. The influence of neuronal nitric oxide synthase (nNOS) on DOX-induced neuronal cell damage was subsequently evaluated. The exposure of rat cortical primary cell cultures to DOX resulted in a significant generation of ROS/RNS, activation of NF-kB, depletion of GSH levels, depletion of ATP, and cell death, in a concentration biphasic manner. Doxorubicin also significantly increased protein-bound quinone products in neurons in a concentration-dependent manner. Inhibition of nNOS decreased neuronal cell death induced by DOX in a significant way, at the first phase of the biphasic curve. In conclusion, this study shows, for the first time, a clear involvement of nNOS and subsequent ROS/RNS generation as crucial signalling mediators of DOX-induced neurotoxicity on isolated cortical neurons. Inhibition of ROS/RNS formation, modulation of NOS isoforms and modulation of NF-kB activation could be of beneficial in preventing damage in the CNS caused by DOX.