Effect of Human Adenovirus 36 on Response to Metformin Monotherapy in Obese Mexican Patients with Type 2 Diabetes: A Prospective Cohort Study.

Human adenovirus 36 (HAdV-36) has been associated with obesity and changes in glucose and lipid metabolism. The virus has been reported to increase insulin sensitivity and paradoxically promote weight gain. Because of its effects on metabolism, infection with the virus could alter the response to several drugs used to treat type 2 diabetes (DM2), such as metformin. The aim of this study was to test whether HAdV-36 affects the response to metformin in a group of obese patients with DM2. METHODS: In a prospective cohort study, 103 obese patients with newly diagnosed DM2 were divided into two groups based on their HAdV-36 seropositivity (+HAdV-36 and -HAdV-36). Weight, glucose, cholesterol, triglycerides, body mass index, body fat percentage, and waist and hip circumference were measured and compared in both groups at baseline and after 45 days of metformin treatment. RESULTS: Only glucose was significantly lower in the +HAdV-36 group at baseline, while all other variables were similar between the two study groups. After 45 days of follow-up, it was observed that the effect of metformin did not differ between the groups, but the variables improved significantly after treatment. CONCLUSIONS: In this study, we did not find that HAdV-36 had an effect on the response to metformin in obese patients with DM2.

Validación de un manual sobre la elaboración de una estrategia didáctica para potenciar el nivel de información sobre la COVID-19 en estudiantes de Medicina / Validation of a manual to design a didactic strategy for enhancing the level of information on COVID-19 in the medical students / Validação de um manual sobre o desenvolvimento de uma estratégia didática para aumentar o nível de informação sobre COVID-19 em estudantes de Medicina

RESUMEN Introducción: Las estrategias didácticas, en su conjunto, demandan establecer una relación dialógica, constante y triangular entre educadores, educandos y metodologías, aunque el educando ignore o no las metodologías que utiliza el docente para tal fin. Objetivo: validar un manual para el diseño y elaboración de una estrategia didáctica para potenciar el nivel de información sobre COVID-19 en estudiantes de Medicina. Método: Se elaboró un manual sobre el diseño de una estrategia didáctica empleada para incrementar el conocimiento de los estudiantes de Medicina del segundo año de la Universidad de Ciencias Médicas de Sancti Spíritus, Cuba, sobre los signos, síntomas y métodos de prevención de la COVID-19 durante el inicio de la pandemia en el país. Treinta expertos nacionales en ciencias de la educación médica emitieron sus dictámenes sobre la pertinencia de la estrategia didáctica y del manual sobre su diseño, y fueron analizados por el método Delphi. El éxito de la aplicación de la estrategia didáctica se valoró mediante la aplicación de exámenes a la población del estudio antes y después de la introducción de la estrategia didáctica en el período 2021-2022. Resultados: El consenso general de los expertos fue de Muy de acuerdo para los fundamentos que sustentan la estrategia didáctica para la educación médica superior y la calidad del manual propuesto. Conclusiones: Tanto la estrategia educativa como el manual sobre su elaboración fueron validadas por los expertos para su aplicación en la educación médica superior y, particularmente, para la detección y contención de la COVID-19.

ABSTRACT Introduction: Didactic strategies, as a whole, demand the establishment of a dialogical, constant and triangular relationship between educators, learners and methodologies, even though the learner is unaware or not of the methodologies used by the professor for purpose required. Objective: To validate a manual for designing and elaborating a didactic strategy to enhance the information level for medical students concerning COVID-19. Method: A manual based on a didactic strategy structural design was elaborated with the porpuse of increase the knowledge for the second year medical students at the Universidad de Ciencias Médicas de Sancti Spíritus, Cuba, on the signs, symptoms of COVID-19 and the prevention methods used at the beginning of the pandemic in the country. Thirty national experts in medical education sciences gave their opinions on the relevance of the didactic strategy and about the structural design of the manual, which were analyzed by the Delphi method. The success of the strategy implementation was assessed implementing tests to the studied population before and after the introduction of the didactic strategy in the period 2021- 2022. Results: The experts' opinion concerning the fundamentals underpinning the didactic strategy for higher medical education and the quality of the proposed manual was highly favorable in general consensus. Conclusions: Both the educational strategy and the elaboration of the manual were validated by the experts for its application in higher medical education and in particularly for the detection and containment of COVID-19.

RESUMO Introdução: As estratégias didáticas, como um todo, demandam estabelecer uma relação dialógica, constante e triangular entre educadores, educandos e metodologias, independentemente de o educando ignorar ou não as metodologias utilizadas pelo professor para esse fim. Objetivo: Submeter um manual para a concepção e desenvolvimento de uma estratégia didática para melhorar o nível de informação sobre COVID-19 em estudantes de medicina para validação. Método: Foi elaborado um manual sobre o desenho de uma estratégia didática utilizada para aumentar o conhecimento dos alunos do segundo ano de Medicina da Universidad de Ciencias Médicas de Sancti Spíritus, Cuba, sobre os sinais, sintomas e métodos de prevenção da COVID. -19 durante o início da pandemia no país. Trinta especialistas nacionais em ciências da educação médica emitiram suas opiniões sobre a relevância da estratégia didática e do manual sobre seu desenho, e foram analisados pelo método Delphi. O sucesso da aplicação da estratégia didática foi avaliado por meio da aplicação de testes à população do estudo antes e após a introdução da estratégia didática no período 2021-2022. Resultados: O consenso geral dos especialistas foi Fortemente concordante para os fundamentos que sustentam a estratégia didática para a formação médica superior e a qualidade do manual proposto. Conclusões: Tanto a estratégia educativa como o manual sobre a sua elaboração foram validados por especialistas para a sua aplicação no ensino superior médico e, em particular, para a deteção e contenção da COVID-19.

Leptin in the Commissural Nucleus of the Tractus Solitarius (cNTS) and Anoxic Stimulus in the Carotid Body Chemoreceptors Increases cNTS Leptin Signaling Receptor and Brain Glucose Retention in Rats.

Background and Objectives: The commissural nucleus of the tractus solitarius (cNTS) not only responds to glucose levels directly, but also receives afferent signals from the liver, and from the carotid chemoreceptors (CChR). In addition, leptin, through its receptors in the cNTS, regulates food intake, body weight, blood glucose levels, and brain glucose retention (BGR). These leptin effects on cNTS are thought to be mediated through the sympathetic-adrenal system. How these different sources of information converging in the NTS regulate blood glucose levels and brain glucose retention remains largely unknown. The goal of the present study was to determine whether the local administration of leptin in cNTS alone, or after local anoxic stimulation using sodium cyanide (NaCN) in the carotid sinus, modifies the expression of leptin Ob-Rb and of c-Fos mRNA. We also investigated how leptin, alone, or in combination with carotid sinus stimulation, affected brain glucose retention. Materials and Methods: The experiments were carried out in anesthetized male Wistar rats artificially ventilated to maintain homeostatic values for pO2, pCO2, and pH. We had four groups: (a) experimental 1, leptin infusion in cNTS and NaCN in the isolated carotid sinus (ICS; n = 10); (b) experimental 2, leptin infusion in cNTS and saline in the ICS (n = 10); (c) control 1, artificial cerebrospinal fluid (aCSF) in cNTS and NaCN in the ICS (n = 10); (d) control 2, aCSF in cNTS and saline in the ICS (n = 10). Results: Leptin in cNTS, preceded by NaCN in the ICS increased BGR and leptin Ob-Rb mRNA receptor expression, with no significant increases in c-Fos mRNA in the NTSc. Conclusions: Leptin in the cNTS enhances brain glucose retention induced by an anoxic stimulus in the carotid chemoreceptors, through an increase in Ob-Rb receptors, without persistent changes in neuronal activation.

Association between genetic variant rs2267716 of CRHR2 gene with colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and one of the main causes of death around the world. Multiple lines of evidence have suggested the role of the corticotropin-releasing hormone (CRH) family in CRC induction, including the low expression of corticotropin-releasing hormone receptor 2 (CRHR2), which is an angiogenesis inhibitor and inflammatory modulator. Previous research suggests that CRHR2 expression in colonic intestinal cells can regulate migration, proliferation and apoptosis through the modulation of several pathways. The aim of this study was to analyze the association of the rs10250835, rs2267716 and rs2267717 variants of CRHR2 gene with CRC in the Mexican population in order to consider its predictive value in CRC. This cross-sectional study included a group of 187 unrelated patients with sporadic CRC and a control group of 191 healthy blood donors. DNA extraction from peripheral blood was carried out using the Miller method. Identification of the rs10250835 variant was performed using PCR-restriction fragment length polymorphism (RFLP) and the rs2267716 and rs2267717 variants using TaqMan allelic discrimination assay. The minor allele homozygous CC of the rs2267716 variant of CRHR2 showed significant difference between CRC and control group (p=0.025), as well as the GCA haplotype (p=0.007), corresponding to the rs10250835, rs2267716 and rs2267717 variants, respectively. Our results suggest that the rs2267716 variant and GCA haplotype of CRHR2 represent a risk factor for CRC development in Mexican patients.

Evaluation of Medical Care for Diabetic and Hypertensive Patients in Primary Care in Mexico: Observational Retrospective Study.

INTRODUCTION: The present study evaluated the quality of medical care for patients diagnosed with diabetes mellitus (DM), hypertension (HBP), and both pathologies (DM+HBP) within a public health system in Mexico. METHODS: 45,498 patients were included from 2012 to 2015. All information was taken from the electronic medical record database. Each patient record was compared against the standard to test the quality of medical care. RESULTS: Glycemia with hypertension goals reached 29.6% in DM+HBP, 48.6% in DM, and 53.2% in HBP. The goals of serum lipids were reached by 3% in DM+HBP, 5% in DM, and 0.2% in HBP. Glycemia, hypertension, and LDL cholesterol reached 0.04%. 15% of patients had an undiagnosed disease. Clinical follow-up examinations reached 20% for foot examination and clinical eye examination. Specialty referrals reached 1% in angiology or cardiology. CONCLUSION: Goals for glycemic and hypertension reached 50% in the overall population, while serum lipids, clinical follow-up examinations, and referral to a specialist were deficient. Patients who had both diseases had more consultations, better control for hypertension and lipids, but inferior glycemic control. Overall, quality care for DM and/or HBP has not been met according to the standards.

Safety and efficacy of a COVID-19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open-label, controlled trial.

Coronavirus disease 2019 (COVID-19) is currently the major public health problem worldwide. Neutral electrolyzed saline solution that contains reactive chlorine and oxygen species may be an effective therapeutic. In the present study, the treatment efficacy of intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care vs. usual medical care alone was evaluated in ambulatory patients with COVID-19. A prospective, 2-arm, parallel-group, randomized, open-label, multi-center, phase I-II clinical trial including 214 patients was performed. The following two outcomes were evaluated during the 20-day follow-up: i) The number of patients with disease progression; and ii) the patient acceptable symptom state. Serial severe acute respiratory syndrome coronavirus 2 naso/oro-pharyngeal detection by reverse transcription-quantitative (RT-q) PCR was performed in certain patients of the experimental group. Biochemical and hematologic parameters, as well as adverse effects, were also evaluated in the experimental group. The experimental treatment decreased the risk of hospitalization by 89% [adjusted relative risk (RR)=0.11, 95% confidence interval (CI): 0.03-0.37, P<0.001] and the risk of death by 96% (adjusted RR=0.04, 95% CI: 0.01-0.42, P=0.007) and also resulted in an 18-fold higher probability of achieving an acceptable symptom state on day 5 (adjusted RR=18.14, 95% CI: 7.29-45.09, P<0.001), compared with usual medical care alone. Overall, neutral electrolyzed saline solution was better than usual medical care alone. Of the patients analyzed, >50% were negative for the virus as detected by RT-qPCR in naso/oro-pharyngeal samples on day 4, with only a small number of positive patients on day 6. Clinical improvement correlated with a decrease in C-reactive protein, aberrant monocytes and increased lymphocytes and platelets. Cortisol and testosterone levels were also evaluated and a decrease in cortisol levels and an increase in the testosterone-cortisol ratio were observed on days 2 and 4. The experimental treatment produced no serious adverse effects. In conclusion, neutral electrolyzed saline solution markedly reduced the symptomatology and risk of progression in ambulatory patients with COVID-19. The present clinical trial was registered in the Cuban public registry of clinical trials (RPCEC) database (May 5, 2020; no. TX-COVID19: RPCEC00000309).

Patient-Reported Health Outcomes After Treatment of COVID-19 with Nebulized and/or Intravenous Neutral Electrolyzed Saline Combined with Usual Medical Care Versus Usual Medical care alone: A Randomized, Open-Label, Controlled Trial.

Background: Coronavirus disease (COVID-19) is currently the main public health problem worldwide. The administration of neutral electrolyzed saline, a solution that contains reactive species of chlorine and oxygen (ROS), may be an effective therapeutic alternative due to its immunomodulating characteristics, in systemic inflammation control, as well as in immune response improvement, promoting control of the viral infection. The present study evaluated the efficacy of treatment with intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care versus usual medical care alone, in ambulatory patients with COVID-19. Methods: A prospective, 2-arm, parallel group, randomized, open-label, phase I-II clinical trial included 39 patients in the control group (usual medical care alone) and 45 patients in the experimental group (usual medical care + intravenous and/or nebulized electrolyzed saline, with dose escalation). Two aspects were evaluated during the twenty-day follow-up: i) the number of patients with disease progression (hospitalization or death); and ii) the Patient Acceptable Symptom State (PASS), a single-question outcome that determines patient well-being thresholds for pain and function. Biochemical and hematologic parameters, as well as adverse effects, were evaluated in the experimental group. Results: The experimental treatment decreased the risk for hospitalization by 92% (adjusted RR=0.08, 95% CI: 0.01-0.50, P=0.007), with a 43-fold increase in the probability of achieving an acceptable symptom state on day 5 (adjusted RR= 42.96, 95% CI: 9.22-200.0, P<0.001). Intravenous + nebulized administration was better than nebulized administration alone, but nebulized administration was better than usual medical care alone. Clinical improvement correlated with a decrease in C-reactive protein, and aberrant monocytes and an increase of lymphocytes, and platelets. Cortisol and testosterone levels were also evaluated, observing a decrease in cortisol levels and an increment of testosterone-cortisol ratio, on days 2 and 4. Conclusions: The experimental treatment produced no serious adverse effects. In conclusion, intravenous and/or nebulized neutral electrolyzed saline importantly reduced the symptomatology and risk of progression (hospitalization and death), in ambulatory patients with COVID-19. Trial registration: Cuban Public Registry of Clinical Trials (RPCEC) Database RPCEC00000309. Registered: 05. May 2020. https://rpcec.sld.cu/en/trials/RPCEC00000309-En.

One-step nested RT-PCR for COVID-19 detection: A flexible, locally developed test for SARS-CoV2 nucleic acid detection.

INTRODUCTION: Due to the coronavirus pandemic, identifying the infected individuals has become key to limiting its spread. Virus nucleic acid real-time RT-PCR testing has become the current standard diagnostic method but high demand could lead to shortages. Therefore, we propose a detection strategy using a one-step nested RT-PCR. METHODOLOGY: The nucleotide region in the ORF1ab gene that has the greatest differences between the human coronavirus and the bat coronavirus was selected. Primers were designed after that sequence. All diagnostic primers are species-specific since the 3´ end of the sequence differs from that of other species. A primer set also creates a synthetic positive control. Amplified products were seen in a 2.5% agarose gel, as well as in an SYBR Green-Based Real-Time RT-PCR. RESULTS: Amplification was achieved for the positive control and specific regions in both techniques. CONCLUSIONS: This new technique is flexible and easy to implement. It does not require a real-time thermocycler and can be interpreted in agarose gels, as well as adapted to quantify the viral genome. It has the advantage that if the coronavirus mutates in one of the key amplification nucleotides, at least one pair can still amplify, thanks to the four diagnostic primers.

Adenovirus 5 produces obesity and adverse metabolic, morphological, and functional changes in the long term in animals fed a balanced diet or a high-fat diet: a study on hamsters.

Adenovirus 5 (Ad-5) infection is a common cause of acute respiratory infections and the main vector used in gene therapy. There are few studies on the relationship of Ad-5 to obesity. In the present study, we evaluated the chronic effects of Ad-5 infection on golden (Syrian) hamsters fed either a balanced diet (BD) or a high-fat diet (HFD). After a single inoculation with Ad-5 (1 × 107 pfu), the body weight of the animals was measured weekly. Medium-term (22 weeks) serum biochemical analyses and long-term (44 weeks) liver morphology, adiposity, and locomotive functionality (movement velocity) assessments were carried out. In the animals fed the BD, adenovirus infection produced hyperglycemia and hyperlipidemia. In the long term, it produced a 57% increase in epididymal pad fat and a 30% body weight gain compared with uninoculated animals. In addition, morphological changes related to non-alcoholic fatty liver disease (NAFLD) were observed. The animals fed the HFD had similar but more severe changes. In addition, the hamsters presented an obesity paradox: at the end of the study, the animals that had the most morphological and functional changes (significantly reduced movement velocity) had the lowest body weight. Despite the fact that an HFD appears to be a more harmful factor in the long term than adenovirus infection alone, infection could increase the severity of harmful effects in individuals with an HFD. Epidemiological studies are needed to evaluate the effect of adenovirus as a precursor of chronic liver and cardiovascular diseases, including the chronic effects of gene therapy.

Leptin in the Commissural Nucleus Tractus Solitarii Increases the Glucose Responses to Carotid Chemoreceptors Activation by Cyanide.

Leptin is a protein hormone that plays a key role in the regulation of energy balance and glucose homeostasis. Leptin and all leptin receptor isoforms are present in the carotid bodies, but its precise function in glucose regulation and metabolism is not yet known. The aim of this study was to determine whether exogenous leptin, microinjected into the commissural nucleus tractus solitarii (cNTS), preceding sodium cyanide (NaCN) injection into the circulatory isolated carotid sinus (ICS), in vivo, modifies hyperglycemic reflex (HR) and brain glucose retention (BGR). In anesthetized Wistar rats (sodium pentobarbital, i.p. 3.3 mg/100 g/saline, Pfizer, Mex), arterial and venous blood samples were collected from silastic catheters implanted in the abdominal aorta and jugular sinus. Exogenous leptin (50 ng/20 nL of aCSF) or leptin vehicle (20 nL of aCSF) microinjected (stereotaxically) into the cNTS 4 min before NaCN (5 µg/100 g/50 µL saline into ICS) (experimental 1 [E1] and control 1[C1] groups, respectively) significantly increased HR and BGR compared with their basal values, but the increase was bigger in the E1 group. When leptin or aCSF were injected into the cNTS before saline (E2 and C2 groups, respectively) glucose responses did not vary when compared with their basal levels. Leptin and its receptors in the cNTS cells probably contribute to their sensitization during hypoxia.

Polimorfismo rs4285184 del gen MGAT1 como factor de riesgo de obesidad en la población mexicana / The rs4285184 polymorphism of the MGAT1 gene as a risk factor for obesity in the Mexican population

Antecedentes y objetivo: La obesidad es un factor que contribuye a la morbilidad de ciertas enfermedades, y a la mortalidad mundial. MGAT1 es una glucosiltransferasa implicada en la síntesis de los oligosacáridos ligados a proteínas y lípidos, y es posible que sus polimorfismos estén implicados en la etiología de la obesidad. Investigamos la asociación entre el polimorfismo rs4285184 del gen MGAT1 y la obesidad en adultos del estado de Colima, México. Métodos: Se realizó un estudio caso-control que incluyó a 244 sujetos. Todos ellos fueron agrupados con arreglo a su porcentaje de grasa corporal, determinado mediante impedancia bioeléctrica, y fueron genotipados para el polimorfismo rs4285184 del gen MGAT1 mediante PCR-RFLP. Se analizaron los resultados para buscar su asociación con el porcentaje de grasa corporal. Resultados: El alelo G reflejó una frecuencia del 49,19% y el 38,75% para los casos y controles, respectivamente (p= 0,020) (OR 1,53; IC 95% 1,068-2,193). La frecuencia del genotipo A/G + G/G fue del 75% en los pacientes obesos, cifra significativamente superior en comparación al 57,5% del grupo control (p = 0,004) (OR 2.217; IC 95% 1,287-3,821). Conclusiones: La presencia del polimorfismo rs4285184 del gen MGAT1 incrementó el riesgo de desarrollar grasa corporal asociada a la obesidad en la población mexicana (AU)

Background and objective: Obesity is a factor that contributes to the morbidity of certain diseases and to worldwide mortality. MGAT1 is a glycosyltransferase involved in the synthesis of protein-bound and lipid-bound oligosaccharides and its polymorphisms are possibly involved in the etiology of obesity. We investigated the association of the rs4285184 polymorphism of the MGAT1 gene with obesity in adults in the State of Colima, Mexico. Methods: A case-control study was conducted that included 244 subjects. All of them were grouped according to their percentage of body fat, determined through bioelectrical impedance, and they were genotyped for the rs4285184 polymorphism of the MGAT1 gene through PCR-RFLP. The results were analyzed for their association with the percentage of body fat. Results: The G allele had a frequency of 49.19 and 38.75% for the cases and controls, respectively (P = .020) (OR 1.53; 95% CI 1.068-2.193). The frequency of the A/G + G/G genotype was 75% in the obese patients, which was significantly higher compared with the 57.5% of the control group (P = .004) (OR 2.217; 95% CI 1.287-3.821). Conclusions: The presence of the rs4285184 polymorphism of the MGAT1 gene increased the risk for developing body fat associated with obesity in the Mexican population (AU)

The rs4285184 polymorphism of the MGAT1 gene as a risk factor for obesity in the Mexican population. / Polimorfismo rs4285184 del gen MGAT1 como factor de riesgo de obesidad en la población mexicana.

BACKGROUND AND OBJECTIVE: Obesity is a factor that contributes to the morbidity of certain diseases and to worldwide mortality. MGAT1 is a glycosyltransferase involved in the synthesis of protein-bound and lipid-bound oligosaccharides and its polymorphisms are possibly involved in the etiology of obesity. We investigated the association of the rs4285184 polymorphism of the MGAT1 gene with obesity in adults in the State of Colima, Mexico. METHODS: A case-control study was conducted that included 244 subjects. All of them were grouped according to their percentage of body fat, determined through bioelectrical impedance, and they were genotyped for the rs4285184 polymorphism of the MGAT1 gene through PCR-RFLP. The results were analyzed for their association with the percentage of body fat. RESULTS: The G allele had a frequency of 49.19 and 38.75% for the cases and controls, respectively (P=.020) (OR 1.53; 95% CI 1.068-2.193). The frequency of the A/G+G/G genotype was 75% in the obese patients, which was significantly higher compared with the 57.5% of the control group (P=.004) (OR 2.217; 95% CI 1.287-3.821). CONCLUSIONS: The presence of the rs4285184 polymorphism of the MGAT1 gene increased the risk for developing body fat associated with obesity in the Mexican population.

The D9N, N291S, and T495G Polymorphisms of the Lipoprotein Lipase Gene Are Not Associated with Cerebral Infarction.

BACKGROUND: Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein metabolism and its polymorphisms are possibly implicated in the etiology of ischemic cerebrovascular disease (CVD). The aim of this work was to determine the association of the of D9N, N291S, and T495G polymorphisms of the LPL gene as a risk factor for the development of CVD. METHODS: A case-control study was conducted that included 100 patients with CVD and 120 healthy controls. All the subjects were genotyped for the D9N, N291S, and T495G polymorphisms of the LPL gene through polymerase chain reaction-restriction fragment length polymorphism, and the results were analyzed for their association with CVD. RESULTS: The D9N genotype was not significantly correlated with CVD; the odds ratio (OR) between the control subjects and CVD patients was .29 (95% confidence interval [CI], .03-2.66; P = .27). The N291S polymorphism was not significantly correlated with CVD either; the OR between the control subjects and CVD patients was 1.2 (95% CI, .07-19.46; P = .89). And the T495G mutation was not significantly correlated with CVD; the OR between the control subjects and the CVD patients was 1.21 (95% CI, .7-2.08; P = .48). CONCLUSIONS: In the present study, the D9N, N291S, and T495G polymorphisms of the LPL gene were not risk factors for the development of CVD.

Effects of the SLCO1B1 *1 and SLCO1B1 *5 polymorphisms on IL-6 and IL-10 levels in patients under pravastatin treatment prior to inguinal hernia repair.

BACKGROUND: Different genetic variants in the SLCO1B1 gene have been shown to have functional importance in individual variability in pravastatin pharmacokinetics, resulting in different inflammatory responses to surgical inguinal hernia repair. The aim of this study was to determine IL-6 and IL-10 serum concentrations in the presence and absence of the SLCO1B1*1 and SLCO1B1*5 polymorphisms in patients under pravastatin treatment that underwent inguinal hernia repair. METHODS: The study included 26 subjects that were under pravastatin treatment (40 mg/day) at least 1 month prior to inguinal hernia repair open technique. All the subjects were genotyped for the SLCO1B1*1 and SLCO1B1*5 polymorphisms through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and their preoperative and postoperative serum IL-6 and IL-10 levels were quantified through the ELISA technique. The IL-6 and IL-10 levels were analyzed in the presence or absence of the mutated polymorphism for SLCO1B1*1 and SLCO1B1*5. RESULTS: The SLCO1B1*1 polymorphism had a frequency of 38.5% and the SLCO1B1*5 polymorphism had a frequency of 19.2%. The preoperative and postoperative serum concentrations of IL-6 were 0.252 pg/ml ± 0.19 and 0.206 pg/ml ± 0.20, respectively, with a p = 0.525, whereas the preoperative and postoperative serum concentrations for IL-10 were 4.943 pg/ml ± 3.13 and 4.611 pg/ml ± 3.01, respectively, with a p = 0.004. CONCLUSIONS: The patients under pravastatin treatment presented with lower postoperative IL-10 levels with respect to the baseline concentration (p = 0.004), regardless of the presence or absence of the two polymorphisms.

Carnitine palmitoyltransferase 1B 531K allele carriers sustain a higher respiratory quotient after aerobic exercise, but ß3-adrenoceptor 64R allele does not affect lipolysis: a human model.

Carnitine palmitoyltransferase IB (CPT1B) and adrenoceptor beta-3 (ADRB3) are critical regulators of fat metabolism. CPT1B transports free acyl groups into mitochondria for oxidation, and ADRB3 triggers lipolysis in adipocytes, and their respective polymorphisms E531K and W64R have been identified as indicators of obesity in population studies. It is therefore important to understand the effects of these mutations on ADRB3 and CPT1B function in adipose and skeletal muscle tissue, respectively. This study aimed to analyze the rate of lipolysis of plasma indicators (glycerol, free fatty acids, and beta hydroxybutyrate) and fat oxidation (through the non-protein respiratory quotient). These parameters were measured in 37 participants during 30 min of aerobic exercise at approximately 62% of maximal oxygen uptake, followed by 30 min of recovery. During recovery, mean respiratory quotient values were higher in K allele carriers than in non-carriers, indicating low post-exercise fatty acid oxidation rates. No significant differences in lipolysis or lipid oxidation were observed between R and W allele carriers of ADRB3 at any time during the aerobic load. The substitution of glutamic acid at position 531 by lysine in the CPT1B protein decreases the mitochondrial beta-oxidation pathway, which increases the non-protein respiratory quotient value during recovery from exercise. This may contribute to weight gain or reduced weight-loss following exercise.

A280V polymorphism in the histamine H3 receptor as a risk factor for migraine.

BACKGROUND AND AIMS: Activation of histamine H3 receptors blocks the release of peptides responsible for headache. Our objective was to investigate the association between the genotypes of A280V polymorphism in the H3 receptor and migraine risk. METHODS: We evaluated the frequency of the genotypes of A280V, polymorphism A280V and allelic variants of H3 receptor in 147 migraine patients and 186 healthy controls using a PCR-RLFP method. RESULTS: V allele frequency was 6.46% and 2.68% for the cases and controls, respectively (p = 0.02) (OR 2.67; 95% CI 1.20-5.93). The frequency of V/V + V/A genotypes was 12.92% in migraine patients, significantly higher when compared to the 3.22% frequency in the control group (p = 0.001) (OR 4.45; 95% CI 1.7-11.46). CONCLUSIONS: The results of this study suggest that V-allele genotypes in the H3 receptor gene are related to migraine risk in the Mexican population. We propose the hypothesis that the V-allele genotypes in the H3 receptor gene increase the population of inactive receptors, enhancing the inhibition of the negative feedback mechanism on the H3 receptor and increasing histamine release, which correlates with migraine attacks in susceptible patients. The case-control study reinforces the role of histamine in migraine pathogenesis.

Association between human papillomavirus in men and their sexual partners and uterine cervical intraepithelial neoplasia.

OBJECTIVES: To determine whether the presence of human papillomavirus (HPV) in men is a risk factor in the development of intraepithelial cervical neoplasia in their sexual partners and to corroborate HPV frequency and type. MATERIALS AND METHODS: A case-control study was carried out in the city of Colima, Mexico, from October 2004 to September 2005. It included the male sexual partners of females presenting with intraepitheleal neoplasia and with negative cervical uterine cytology. The study was approved by the local ethics committee, and participants signed a letter of informed consent. Samples were taken from the penis with a cytobrush and were analyzed by polymerase chain reaction (PCR) with type-specific HPV consensus primers. Statistical analysis was carried out using averages, percentages, and chi-square test for association. RESULTS: Twenty-one patients and 40 controls were analyzed. Eight were excluded due to DNA degradation. Chi-square test was utilized to find association between risk factor (HPV in men) in men whose sexual partners were women with premalignant lesions and normal Papanicolaou test. There was no statistical significance; OR was 2.5, CI was 0.38-16.41, and P = 0.37 (Fisher's exact test). There was no significant difference between the two study groups. Four HPV-positive cases (19%) were obtained from the case group, and two HPV-positive cases (6%) were obtained from the control group. The six positive samples had low-grade virus. There was no association between HPV in men and the cervical intraepitheleal neoplasia of their sexual partners. CONCLUSIONS: In the present study, HPV in men was not found to be a risk factor in the development of cervical uterine lesions. The viruses that were found were low risk. The sample size employed was not large enough to be able to determine any differences between both study groups.

[Prevalence and cervical human papilloma virus associated factors in patients with rheumatoid arthritis]. / Prevalencia y factores asociados con infección por virus del papiloma humano cervical en pacientes con artritis reumatoide.

BACKGROUND: Nevertheless its association with cervicouterine cancer, there is no information about cervical human papillomavirus infection prevalence in patients with rheumatoid arthritis. OBJECTIVE: To evaluate human papillomavirus infection prevalence through molecular biology tests, and to analyze this infection related factors in patients with rheumatoid arthritis. MATERIAL AND METHOD: Analytic, transversal study to 250 patients: 61 women with rheumatoid arthritis selected from a rheumatologic external consult of a second level hospital, and 189 healthy women, with cervical cytology, of a first level hospital. They were polled to find infection risk factors. They were exfoliated to get cervix cells to extract its DNA and detect human papillomavirus (chain reaction of polymerase with specific consensus markers), and identification of restriction enzyme in high and low risks viruses. Prevalence was calculated, and adjusted factors analysis was performed through logistic regression with odds ratio and confidence intervals of 95%. RESULTS: Prevalence of papillomavirus infection in patients with rheumatoid arthritis was 30%, and in control group was 24%, with an odds ratio of 0.8 (CI 95% 0.42-1.6, p = 0.5). Ninety-four percent of the most frequent viral types in women with rheumatoid arthritis were high risk (mainly types 16, 58, and 18). Factors associated with higher human papillomavirus adjusted to rheumatoid arthritis were: more than one sexual partner (OR = 5.8 CI 95% 1.1-31.1, p = 0.04), more than one sexual intercourse weekly (OR = 6.7, CI 95% 0.9-51.6, p = 0.06), circumcised sexual partner (OR = 9.0, CI 95% 1.2-64.4, p = 0.02). Patients and controls had same values of marital status. Seventy-four percent of controls worked, compared to 44% of women with rheumatoid arthritis (p < 0.01). CONCLUSION: One out of three women with rheumatoid arthritis has human papillomavirus infection and 94% has the high-risk viral type. Infection associated factors mainly includes sexual partner ones; due to high risk of cervical dysplasia, it is necessary the early detection of the infection and surveillance.

Polymorphism in the matrix metalloproteinase-2 gene promoter is associated with cervical neoplasm risk in Mexican women.

Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity on matrix proteins, and previous studies have revealed a strong association between the MMP-2 -1306C-->T polymorphism and the risk of several types of cancer. Our study looked at whether this polymorphism contributed to the development of cervical neoplasia by analyzing 54 patients with invasive squamous cell cervical cancer, 100 patients with cervical intraepithelial neoplasia, and 126 control subjects. The MMP-2 CC genotype was more frequent in the cancer patients when compared with the control group (OR 2.57; 95% CI 1.15-5.86). The association of cervical cancer with the CC genotype was more pronounced in women who had first coitus at an early age (OR 3.96; 95% CI 1.46-11.06). The CC genotype was associated with intraepithelial neoplasia only in women with first coitus at 19 years old or younger. The data suggest that the MMP-2 -1306C-->T polymorphism contributes to the development of squamous cell cervical cancer in the population studied, especially in women who had first coitus at an early age.