Trastornos mentales en estudiantes de medicina humana en tres universidades de Lambayeque, Perú / Mental disorders in medical students of three universities in Lambayeque, Perú

Los trastornos de salud mental son un problema muy frecuente en la poblaci¢n actual, sobre todo en alumnos de educaci¢n superior que, de acuerdo a algunos estudios, pueden mostrar mayor predisposici¢n a problemasemocionales y psicosociales. Objetivos: Describir los trastornos mentales m s frecuentes en estudiantes demedicina de tres universidades de Lambayeque, durante el a¤o 2012. Material y m‚todos: Estudio descriptivotransversal. La poblaci¢n fue de 998 alumnos distribuidos seg£n a¤o de estudio acad‚mico, elegidos mediantemuestreo consecutivo. Se utiliz¢ el Test Mini International Neuropsychiatric Interview (MINI) como tamizaje. Serealiz¢ un an lisis descriptivo y un an lisis bivariado exploratorio determinando razones de prevalencia con un IC 95%, usando chi2 y el test de Fisher. Se us¢ el Software STATA versi¢n 11. Resultados: Se entrevist¢ un total de 284 alumnos, la media de edad fue de 21,05 ñ 3,8 a¤os, 57,4% fueron mujeres, 98,2% solteros, 61% cursaban ciencias b sicas, 6,7% ten¡an diagnóstico previo de depresi¢n y 7,4% ten¡an diagn¢stico previo de ansiedad; 140 estudiantes (49,07%) reportaron por lo menos un trastorno mental (TM). Los trastornos mentales con mayor prevalencia fueron episodio hipomaniaco (19,7%) y episodio depresivo (17,3%). En el an lisis bivariado se encontraron asociacionesentre alguna forma de trastorno mental y edad, estudiar en una universidad privada y cursar estudios de cienciasb sicas. Conclusiones: En estudiantes de medicina de Lambayeque se han encontrado prevalencias frecuentes deepisodios hipomaniaco y depresivo mayor, y de riesgo suicida. Deben conducirse mayores y m s profundos estudios de corte ep¡demiológico en este tipo de población.

Mental health disorders are a fairly frequent problem in several segments of today’s population, particularly amonghigher education students who, according to some inquiries, seem to be more prone to emotional and psychosocial problems. Objectives: To describe the most frequent mental disorders in medical students from three universities from Lambayeque, Per£, during the year 2012. Material and methods: Cross sectional study. The population under scrutiny included 998 students distributed by year of academic classes and chosen by consecutive sampling. The Mini International Neuropsychiatric Interview (MINI) for screening of mental disorders was used. A descriptive analysis and an exploratory bivariate analysis with 95 % confidence intervals using chi2 and Fisher’s tests, were performed. Software STATA version 11 was used. Results: A total of 284 students were interviewed, the average age was 21.05 ñ 3.8 years, 57.4 % were women, 98.2 % single, 61 % were enrolled in basic sciences, 6.7% had a prior diagnosis of depression, and 7.4 % h of anxiety; 140 students (49.07 %) reported at least one mental disorder. The most prevalent disorders were hypomanic episode (19.7%), and major depressive episode (17.3%). In the bivariate analysis, the presence of a mental disorder was associated with age, studyingin a private university, and being a basic science student. Conclusions: Mental disorders among medical students from Lambayeque seem to be highly prevalent, the more frequent ones being hypomanic and major depressive episodes, and suicidal risk. Morecomprehensive, extended and deeper studies of this nature are needed in this specific population.

Cardiac-specific overexpression of thioredoxin 1 attenuates mitochondrial and myocardial dysfunction in septic mice.

Sepsis-induced myocardial dysfunction is associated with increased oxidative stress and mitochondrial dysfunction. Current evidence suggests a protective role of thioredoxin-1 (Trx1) in the pathogenesis of cardiovascular diseases. However, it is unknown yet a putative role of Trx1 in sepsis-induced myocardial dysfunction, in which oxidative stress is an underlying cause. Transgenic male mice with Trx1 cardiac-specific overexpression (Trx1-Tg) and its wild-type control (wt) were subjected to cecal ligation and puncture or sham surgery. After 6, 18, and 24h, cardiac contractility, antioxidant enzymes, protein oxidation, and mitochondrial function were evaluated. Trx1 overexpression improved the average life expectancy (Trx1-Tg: 36, wt: 28h; p=0.0204). Sepsis induced a decrease in left ventricular developed pressure in both groups, while the contractile reserve, estimated as the response to ß-adrenergic stimulus, was higher in Trx1-Tg in relation to wt, after 6h of the procedure. Trx1 overexpression attenuated complex I inhibition, protein carbonylation, and loss of membrane potential, and preserved Mn superoxide dismutase activity at 24h. Ultrastructural alterations in mitochondrial cristae were accompanied by reduced optic atrophy 1 (OPA1) fusion protein, and activation of dynamin-related protein 1 (Drp1) (fission protein) in wt mice at 24h, suggesting mitochondrial fusion/fission imbalance. PGC-1α gene expression showed a 2.5-fold increase in Trx1-Tg at 24h, suggesting mitochondrial biogenesis induction. Autophagy, demonstrated by electron microscopy and increased LC3-II/LC3-I ratio, was observed earlier in Trx1-Tg. In conclusion, Trx1 overexpression extends antioxidant protection, attenuates mitochondrial damage, and activates mitochondrial turnover (mitophagy and biogenesis), preserves contractile reserve and prolongs survival during sepsis.

Defective leptin-AMP-dependent kinase pathway induces nitric oxide release and contributes to mitochondrial dysfunction and obesity in ob/ob mice.

AIMS: Obesity arises on defective neuroendocrine pathways that increase energy intake and reduce mitochondrial metabolism. In the metabolic syndrome, mitochondrial dysfunction accomplishes defects in fatty acid oxidation and reciprocal increase in triglyceride content with insulin resistance and hyperglycemia. Mitochondrial inhibition is attributed to reduced biogenesis, excessive fission, and low adipokine-AMP-activated protein kinase (AMPK) level, but lateness of the respiratory chain contributes to perturbations. Considering that nitric oxide (NO) binds cytochrome oxidase and inhibits respiration, we explored NO as a direct effector of mitochondrial dysfunction in the leptin-deficient ob/ob mice. RESULTS: A remarkable three- to fourfold increase in neuronal nitric oxide synthase (nNOS) expression and activity was detected by western blot, citrulline assay, electronic and confocal microscopy, flow cytometry, and NO electrode sensor in mitochondria from ob/ob mice. High NO reduced oxygen uptake in ob/ob mitochondria by inhibition of complex IV and nitration of complex I. Low metabolic status restricted ß-oxidation in obese mitochondria and displaced acetyl-CoA to fat synthesis; instead, small interference RNA nNOS caused a phenotype change with fat reduction in ob/ob adipocytes. INNOVATION: We evidenced that leptin increases mitochondrial respiration and fat utilization by potentially inhibiting NO release. Accordingly, leptin administration to ob/ob mice prevented nNOS overexpression and mitochondrial dysfunction in vivo and rescued leptin-dependent effects by matrix NO reduction, whereas leptin-Ob-Rb disruption increased the formation of mitochondrial NO in control adipocytes. We demonstrated that in ob/ob, hypoleptinemia is associated with critically low mitochondrial p-AMPK and that, oppositely to p-Akt2, p-AMPK is a negative modulator of nNOS. CONCLUSION: Thereby, defective leptin-AMPK pathway links mitochondrial NO to obesity with complex I syndrome and dysfunctional mitochondria.

Interrelationship between oxygen-related variables in patients with acute myocardial infarction: an interpretative review.

The high mortality rate of cardiogenic shock in acute myocardial infarction (AMI) implies that debate over the correct haemodynamic management is still unresolved. The purpose of this review is to re-evaluate the reciprocal relationships between oxygen-related variables and response to treatment in a large number of patients with AMI. A MEDLINE search of reports published between 1970 and 2008 was performed. Twelve clinical reports including 453 patients with AMI and 989 sets of oxygen delivery and oxygen consumption expressed in ml min⁻¹ m⁻² and oxygen extraction ratio were selected. While processing this data, we found an early down-regulation in oxygen demand linked to a decrease in oxygen supply. This mechanism is also supported in some studies by a critically low oxygen uptake that was not associated with lactic acidosis.

O Direito humano à saúde e o seu subfinanciamento

Esta cartilha integra o programa formativo na área de "Financiamento da Saúde no Brasil", desenvolvido pelo Centro de Educação e Assessoramento Popular - CEAP em parceria com o Centro Nordestino de Medicina Popular - CNMP, com apoio do Ministério da Saúde. Neste processo, realizamos também um Seminário sobre o tema em Florianópolis-SC e outro em Camaragibe-PE em 2008, além de um curso de três etapas em cada uma destas duas Regiões, em 2009. A formação deu-se junto ao Fórum Sul da Saúde e à Rede de Usuários do SUS do Nordeste1 , e teve como objetivo principal capacitar lideranças sociais e conselheiros da saúde para desempenharem com mais subsídios o seu papel de controle da política pública da saúde no Brasil. Buscamos, também, fortalecer os espaços e processos organizativos de luta pelo direito humano à saúde, que permitem ampliar nossa ação para além dos espaços institucionais do SUS. Além de ser um instrumento complementar desta rica experiência formativa, pretendemos com esta publicação atingir um público muito maior, especialmente as lideranças que acreditam e lutam pela implementação e pela qualificação do SUS em todos os cantos do país. Esta luta, sabemos, exige dos movimentos sociais e dos militantes da causa, uma agenda política intensa para tornar a seguridade social um direito efetivo de todos e todas.

Oxido nítrico y circulación / Nitric oxide and circulation

Nitric oxide (NO) is a fascinating ubiquitous molecule with multiple complex roles in biological systems, such as intra and inter cell communications. Endothelial physiology relies on its endothelium derived relaxing factor (EDRF) properties as originally described. NO exhibits physiological vasodilator effects, mediated in part by its binding to the heme group of guanylyl cyclase to produce cGMP that relaxes vascular smooth muscle by lowering cytoplasmic Ca2' levels. So me experiments from several laboratories have very recently established that red blood cells provide a novel vasodilator activity NO mediated in which hemoglobin acts as an O2 sensor and O2-responsive NO signal transducer, thereby regulating both peripheral and pulmonary vascular tone. Haemoglobin through its oxygen binding function adjusts NO bioavailability at the microcirculation and in turn, red blood cells can cause microvessels to dila­te or constrict, with S-nitroso-haemoglobin as an intermediate. But other groups demonstrated that SNO­Hb is not essential for the physiologic coupling of erythrocyte deoxygenation with increased NO bioactivity in vivo. A third group emphasized the role of nitrites and the nitrite reductase activity of hemoglobin as the source of vasodilators in the microcirculation. As blood transfusion in the setting of acute coronary syndromes seemed to be associated with higher mortality, some authors linked those phenomena to the S-nitrosohemoglobin deficiency in banked blood, a mechanism that could explain its loss of physiological activity. In adition to the peripheric actions, the regulatory function of NO on cardiac efficiency also contributes to its key role in the circulation.

Control of muscle mitochondria by insulin entails activation of Akt2-mtNOS pathway: implications for the metabolic syndrome.

BACKGROUND: In the metabolic syndrome with hyperinsulinemia, mitochondrial inhibition facilitates muscle fat and glycogen accumulation and accelerates its progression. In the last decade, nitric oxide (NO) emerged as a typical mitochondrial modulator by reversibly inhibiting citochrome oxidase and oxygen utilization. We wondered whether insulin-operated signaling pathways modulate mitochondrial respiration via NO, to alternatively release complete glucose oxidation to CO(2) and H(2)O or to drive glucose storage to glycogen. METHODOLOGY/PRINCIPAL FINDINGS: We illustrate here that NO produced by translocated nNOS (mtNOS) is the insulin-signaling molecule that controls mitochondrial oxygen utilization. We evoke a hyperinsulinemic-normoglycemic non-invasive clamp by subcutaneously injecting adult male rats with long-lasting human insulin glargine that remains stable in plasma by several hours. At a precise concentration, insulin increased phospho-Akt2 that translocates to mitochondria and determines in situ phosphorylation and substantial cooperative mtNOS activation (+4-8 fold, P<.05), high NO, and a lowering of mitochondrial oxygen uptake and resting metabolic rate (-25 to -60%, P<.05). Comparing in vivo insulin metabolic effects on gastrocnemius muscles by direct electroporation of siRNA nNOS or empty vector in the two legs of the same animal, confirmed that in the silenced muscles disrupted mtNOS allows higher oxygen uptake and complete (U-(14)C)-glucose utilization respect to normal mtNOS in the vector-treated ones (respectively 37+/-3 vs 10+/-1 micromolO(2)/h.g tissue and 13+/-1 vs 7.2+/-1 micromol (3)H(2)O/h.g tissue, P<.05), which reciprocally restricted glycogen-synthesis by a half. CONCLUSIONS/SIGNIFICANCE: These evidences show that after energy replenishment, insulin depresses mitochondrial respiration in skeletal muscle via NO which permits substrates to be deposited as macromolecules; at discrete hyperinsulinemia, persistent mtNOS activation could contribute to mitochondrial dysfunction with insulin resistance and obesity and therefore, to the progression of the metabolic syndrome.

[Efficacy of absorbance ratio of ELISA antibodies [corrected] for hepatitis C virus of 3th generation in the prediction of viremia evaluated by PCR]. / Eficacia del cociente de absorbancia de un análisis inmunoenzimático de tercera generación para anticuerpos al virus de hepatitis C en la predicción de viremia por reacción en cadena de polimerasa.

BACKGROUND: In order to decrease the burden of suffering and the costs derived from confirmatory molecular assays, a better strategy is badly needed to decrease the rate of false positive results of the enzyme-linked immunoassay (ELISA) for detection of hepatitis C virus (HCV) antibodies (Anti). OBJECTIVE: To establish the best cutoff of the S/CO rate in subjects with a positive result of a microparticule, third generation ELISA assay for Anti-HCV, for predicting viremia as detected by polymerase chain reaction (PCR) assay. METHODS: Using the result of the PCR assay as "gold standard", a ROC curve was build with the results of the S/CO rate values in subjects with a positive result for ELISA HCV assay. RESULTS: Fifty two subjects (30 male, 22 female, 40 +/- 12.5 years old) were included. Thirty four (65.3%) had a positive RNA HCV PCR assay. The area under the curve was 0.99 (95% CI: 0.98-1.0). The optimal cutoff for the S/CO rate was established in 29: sensitivity: 97%; specificity: 100%: PPV: 100%; NPV: 94%. CONCLUSIONS: Setting the cutoff of the S/CO in 29 results in a high predictive value for viremia as detected by PCR in subjects with a positive ELISA HVC assay. This knowledge may result in a better decision taking for the clinical follow up of those subjects with a positive result in the ELISA screening assay for HCV infection.

The biological significance of mtNOS modulation.

In the last years, nitric oxide synthases (NOS) have been localized in mitochondria. At this site, NO yield directly regulates the activity of cytochrome oxidase, O(2) uptake and the production of reactive oxygen species. Recent studies showed that translocated neuronal nitric oxide synthase (nNOS) is posttranslationally modified including phosphorylation at Ser 1412 (in mice) and myristoylation in an internal residue. Different studies confirm that modified nNOS alpha is the main modulable isoform in mitochondria. Modulation of mtNOS was observed in different situations, like adaptation to reduced O(2) availability and hypoxia, adaptation to low environmental temperature, and processes linked to life and death by effects on kinases and transcription factors. We present here evidence about the role of mtNOS in the analyzed conditions.

Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase.

Although transcriptional effects of thyroid hormones have substantial influence on oxidative metabolism, how thyroid sets basal metabolic rate remains obscure. Compartmental localization of nitric-oxide synthases is important for nitric oxide signaling. We therefore examined liver neuronal nitric-oxide synthase-alpha (nNOS) subcellular distribution as a putative mechanism for thyroid effects on rat metabolic rate. At low 3,3',5-triiodo-L-thyronine levels, nNOS mRNA increased by 3-fold, protein expression by one-fold, and nNOS was selectively translocated to mitochondria without changes in other isoforms. In contrast, under thyroid hormone administration, mRNA level did not change and nNOS remained predominantly localized in cytosol. In hypothyroidism, nNOS translocation resulted in enhanced mitochondrial nitric-oxide synthase activity with low O2 uptake. In this context, NO utilization increased active O2 species and peroxynitrite yields and tyrosine nitration of complex I proteins that reduced complex activity. Hypothyroidism was also associated to high phospho-p38 mitogen-activated protein kinase and decreased phospho-extracellular signal-regulated kinase 1/2 and cyclin D1 levels. Similarly to thyroid hormones, but without changing thyroid status, nitric-oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester increased basal metabolic rate, prevented mitochondrial nitration and complex I derangement, and turned mitogen-activated protein kinase signaling and cyclin D1 expression back to control pattern. We surmise that nNOS spatial confinement in mitochondria is a significant downstream effector of thyroid hormone and hypothyroid phenotype.

An unusual triosephosphate isomerase from the early divergent eukaryote Giardia lamblia.

Recombinant triosephosphate isomerase from the parasite Giardia lamblia (GlTIM) was characterized and immunolocalized. The enzyme is distributed uniformly throughout the cytoplasm. Size exclusion chromatography of the purified enzyme showed two peaks with molecular weights of 108 and 55 kDa. Under reducing conditions, only the 55-kDa protein was detected. In denaturing gel electrophoresis without dithiothreitol, the enzyme showed two bands with molecular weights of 28 and 50 kDa; with dithiotretitol, only the 28-kDa protein was observed. These data indicate that GlTIM may exist as a tetramer or a dimer and that, in the former, the two dimers are covalently linked by disulfide bonds. The kinetics of the dimer were similar to those of other TIMs. The tetramer exhibited half of the kcat of the dimer without changes in the Km. Studies on the thermal stability and the apparent association constants between monomers showed that the tetramer was slightly more stable than the dimer. This finding suggests the oligomerization is not related to enzyme thermostability as in Thermotoga maritima. Instead, it could be that oligomerization is related to the regulation of catalytic activity in different states of the life cycle of this mesophilic parasite.

Nitric oxide, complex I, and the modulation of mitochondrial reactive species in biology and disease.

Mitochondria are the specialized organelles for energy metabolism but also participate in the production of O(2) active species, cell cycle regulation, apoptosis and thermogenesis. Classically, regulation of mitochondrial energy functions was based on the ADP/ATP ratio, which dynamically stimulates the transition between resting and maximal O(2) uptake. However, in the last years, NO was identified as a physiologic regulator of electron transfer and ATP synthesis by inhibiting cytochrome oxidase. Additionally, NO stimulates the mitochondrial production of O(2) active species, primarily O(2)(-) and H(2)O(2), and, depending on NO matrix concentration, of ONOO(-), which is responsible for the nitrosylation and nitration of mitochondrial components. By this means, alteration in mitochondrial complexes restricts energy output, further increases O(2) active species and changes cell signaling for proliferation and apoptosis through redox effects on specific pathways. These mechanisms are prototypically operating in prevalent generalized diseases like sepsis with multiorgan failure or limited neurodegenerative disorders like Parkinson's disease. Complex I appears to be highly susceptible to ONOO(-) effects and nitration, which defines an acquired group of mitochondrial disorders, in addition to the genetically induced syndromes. Increase of mitochondrial NO may follow over-expression of nNOS, induction and translocation of iNOS, and activation and/or increased content of the newly described mtNOS. Likewise, mtNOS is important in the modulation of O(2) uptake and cell signaling, and in mitochondrial pathology, including the effects of aging, dystrophin deficiency, hypoxia, inflammation and cancer.

Modulation of mitochondrial nitric oxide synthase and energy expenditure in rats during cold acclimation.

To preserve thermoneutrality, cold exposure is followed by changes in energy expenditure and basal metabolic rate (BMR). Because nitric oxide (NO) modulates mitochondrial O(2) uptake and energy levels, we analyzed cold effects (30 days at 4 degrees C) on rat liver and skeletal muscle mitochondrial NO synthases (mtNOS) and their putative impact on BMR. Cold exposure delimited two periods: A (days 1-10), with high systemic O(2) uptake and weight loss, and B (days 10-30), with lower O(2) uptake and fat deposition. mtNOS activity and expression decreased in period A and then increased in period B by 60-100% in liver and skeletal muscle (P < 0.05). Conversely, mitochondrial O(2) uptake remained initially high in the presence of l-arginine and later fell by 30-50% (P < 0.05). On this basis, the estimated fractional contribution of liver plus muscle to total BMR varied from 40% in period A to 25% in period B. The transitional modulation of mtNOS in rat cold acclimation could participate in adaptive responses that favor calorigenesis or conservative energy-saving mechanisms.

beta-Adrenergic stimulation controls the expression of a thioesterase specific for very-long-chain fatty acids in perfused hearts.

Arachidonic acid is not freely stored in the cells. A number of different pathways for the mobilization of this compound have been proposed, including a novel mechanism that involves the release of arachidonic acid from arachidonoyl-CoA by a thioesterase with substrate specificity for very-long-chain fatty acids. In rat heart, the acyl-CoA thioesterase activity can be regulated by a mechanism that involves beta-adrenoceptors. In this paper we demonstrate that beta-adrenergic agonists also regulate the acyl-CoA thioesterase mRNA levels. Isoproterenol (10(-7)M)-a concentration known to exert physiological responses-increases in a time-dependent manner the acyl-CoA thioesterase mRNA levels, an effect blocked by a specific beta-adrenoceptor antagonist. In addition, our results show that cAMP is involved in this process. The acyl-CoA thioesterase mRNA levels are also increased by fasting, but not by di(2-ethylhexyl)phthalate, a peroxisome proliferator. These results may suggest the existence of a beta-adrenoceptor-activated regulatory pathway for arachidonic acid release in cardiac tissue.