Protective role of osteocalcin in diabetes pathogenesis.

In diabetes, metabolic, inflammatory, and stress-associated alterations conduce to ß-cell failure and tissue damage. Osteocalcin is a bone protein with several endocrine functions in different tissues. In this review, we gathered scientific evidence of how osteocalcin could modulate functional disorders that are altered in diabetes in an integrative way. We include adipose tissue, pancreatic function, and oxidative stress aspects. In the first section, we focus on the role of inflammatory mediators and adiponectin in energy homeostasis and insulin sensitivity. In the following section, we discuss the effect of osteocalcin in metabolic and pancreatic function and its association in insulin signaling and in ß-cell proliferation. Finally, we focus on osteocalcin action in oxidative and endoplasmic reticulum stress, and in antioxidant regulation, since ß-cells are well known by its vulnerability to stress damage. These evidences support the notion that osteocalcin could have an important role in diabetes treatment.

Leu72Met polymorphism of GHRL gene decreases susceptibility to type 2 diabetes mellitus in a Mexican population.

BACKGROUND: Type 2 diabetes mellitus (T2D) is the most frequent type of diabetes. It has a multifactorial etiology, affecting millions of people worldwide. Ghrelin gene (GHRL) encodes the ghrelin peptide, which promotes food intake, induces body weight and adipogenesis. Several single nucleotide polymorphisms (SNPs) in GHRL gene have been associated with metabolic diseases. A protective effect of the Leu72Met (rs696217) polymorphism has been described for T2D in some populations, but this effect seems to depend on the ethnicity of the patients studied. METHODS: The aim of this study was to investigate the association between the GHRL Leu72Met (rs696217) SNP with the development of T2D and serum ghrelin levels in a Western Mexican population. We performed a case-control study in which we included 284 subjects (159 with previous T2D diagnosis and 125 control subjects (CS)). Leu72Met SNP was genotyped by using PCR-RFLPs technique. Serum ghrelin levels were measured using a commercial enzyme immunoassay. Genotypic and allelic distributions were compared using Chi square test. Student T-test and Mann-Whitney U test were used to compare quantitative variables. Odds ratio (OR) was used to evaluate the association between alleles or genotypes and T2D. Multiple and logistic regression models were performed for adjustment. A two-tailed p-value ≤0.05 was considered statistically significant. RESULTS: Leu72Leu genotype was more frequent among T2D compared to CS (p < 0.05). After adjusting for age and body composition, there was a significant protective effect of the 72Met allele for T2D development (OR 0.40 IC 95% 0.23-0.70; p ≤ 0.001). Fasting serum ghrelin levels were lower in T2D than CS (p ≤ 0.0001) irrespective of age, body weight and BMI. No associations were found between genotypes and ghrelin serum levels in our population. CONCLUSIONS: The GHRL 72Met allele decreases susceptibility for T2D development in a Western Mexican population. Serum ghrelin levels are lower in T2D independently of Leu72Met polymorphism genotype.

Anti-inflammatory and antinociceptive effects of an ethanol extract from Senna septemtrionalis.

Senna septemtrionalis (Viv.) H.S. Irwin & Barneby (Fabaceae) is a medicinal plant used as a folk remedy for inflammation and pain. The objective of this study was to evaluate the anti-inflammatory and antinociceptive actions of an ethanol extract of Senna septemtrionalis aerial parts (SSE). The in vitro anti-inflammatory effects of SSE were assessed using LPS-stimulated macrophages and the subsequent quantification of the levels of cytokines (IL-6, IL-1ß, and TNF-α) with ELISA kits, nitric oxide (NO), and hydrogen peroxide (H2O2). The in vivo anti-inflammatory actions of SSE were evaluated with the TPA-induced ear oedema test and the carrageenan-induced paw oedema test. The antinociceptive actions of SSE (10-200 mg/kg p.o.) were assessed using three models: two chemical assays (formalin-induced orofacial pain and acetic acid-induced visceral pain) and one thermal assay (hot plate). SSE showed in vitro anti-inflammatory actions with IC50 values calculated as follows: 163.3 µg/ml (IL-6), 154.7 µg/ml (H2O2) and > 200 µg/ml (IL-1ß, TNF-α, and NO). SSE showed also in vivo anti-inflammatory actions in the TPA test (40% of inhibition of ear oedema) and the carrageenan test (ED50 = 137.8 mg/kg p.o.). SSE induced antinociceptive activity in the formalin orofacial pain test (ED50 = 80.1 mg/kg) and the acetic acid-induced writhing test (ED50 = 110 mg/kg). SSE showed no antinociceptive actions in the hot plate assay. The pre-treatment with glibenclamide abolished the antinociceptive action shown by SSE alone. Overall, SSE exerted in vitro and in vivo anti-inflammatory actions, and in vivo antinociceptive effects by the possible involvement of ATP-sensitive K + channels.

Assessment of the antinociceptive and ulcerogenic activity of the tapentadol-diclofenac combination in rodents.

Preclinical Research & Development The objective of the present study was to evaluate the tapentadol-diclofenac combination in three dose-ratios in the mouse acetic acid-induced visceral pain and their ulcerogenic activity on the stomachal mucous. Dose-response curves were generated for tapentadol, diclofenac, and their combination in the acetic acid-induced writhing test in mice. Moreover, the stomachs of animals were surgically removal and gastrointestinal ulcerogenic action of the combination was assessed. The isobolographic analysis, interaction index, and ANOVA were used to analyze the data. The isobolographic analysis and interaction index showed a similar antinociceptive activity for the three combinations of the analgesic mixture. Moreover, tapentadol and the proportions 1:1 or 3:1 of the analgesic combination caused a mild gastrointestinal damage. These data indicate that the systemic co-administration of tapentadol and diclofenac produced a synergistic interaction in the acetic acid-induced visceral pain test with an acceptable gastric damage profile in mice.

Participation of ATP-sensitive K+ channels and µ-opioid receptors in the antinociceptive synergism of the paracetamol-tapentadol co-administration in the formalin-induced pain assay in mice.

Preclinical Research & Development The purpose of this study was to assess the interaction and mechanisms of action of the paracetamol-tapentadol combination in the formalin-induced pain model in mice. Paracetamol (56.23-562.3 mg/kg, i.p.) or tapentadol (1-10 mg/kg, i.p.) were administered 15 min prior the intraplantar injection of formalin. The ED50 value of each drug was determined through the dose-response curves. The ED50 values were used to calculate the combinations in three fixed proportions (1:1, 1:3, and 3:1). Naloxone (1 and 5 mg/kg, i.p.), L-NAME (3 mg/kg, i.p.), or glibenclamide (10 mg/kg, i.p.) were administered before the combination of drugs to evaluate the antinociceptive mechanisms of action. The results showed that the combination 1:1 and paracetamol3-tapenadol1 ratios produced additive effects, whereas the paracetamol1-tapentadol3 proportion showed an antinociceptive synergistic interaction. Moreover, naloxone and glibenclamide reversed the antinociceptive activity of the paracetamol-tapentadol mixture. Our results indicate that the paracetamol-tapentadol combination produces an antinociceptive synergistic interaction with the possible participation of ATP-sensitive K+ channels and µ-opioid receptors in the second phase of the formalin-induced pain model in mice.

Osteocalcin levels in a healthy population of western Mexico and comparison with populations from around the world. / Niveles de referencia de osteocalcina en población sana de México.

Introduction: Osteocalcin has been shown to have an inverse relationship with blood glucose, insulin resistance and adiposity. Objective: To determine osteocalcin normal serum concentration in Mexican healthy adults and compare it with values reported in other populations. Method: Carboxylated and undercarboxylated osteocalcin serum concentrations were determined in 100 healthy adults by means of enzyme immunoassay; osteocalcin total concentration was calculated. A descriptive comparison was made with other populations' values reported in the literature. Results: Carboxylated and undercarboxylated osteocalcin median concentrations were 3.22 ng/mL and 1.61 ng/mL, respectively. Mean total osteocalcin was 7.40 ± 5.11 ng/mL. There was no significant difference between the osteocalcin values in our population and those of populations where similar quantification methods to ours were used. Conclusion: Osteocalcin total serum concentration mean in the analyzed population was 7.40 ng/mL. There are subtle variations between populations that are attributable to genetic and population factors; however, the quantification method was the only variable that was shown to significantly influence on osteocalcin levels in healthy populations.

Introducción: Se ha demostrado que la osteocalcina tiene una relación inversa con la glucemia, resistencia a la insulina y adiposidad. Objetivo: Determinar la concentración sérica normal de osteocalcina en adultos sanos mexicanos y compararlos con los reportados en otras poblaciones. Método: Se determinó la concentración sérica de osteocalcina carboxilada y pobremente carboxilada en 100 adultos sanos mediante inmunoensayo enzimático; se calculó la concentración de osteocalcina total. Se hizo una comparación descriptiva con valores de otras poblaciones reportadas en la literatura. Resultados: Las medianas de las concentraciones de osteocalcina carboxilada y pobremente carboxilada fueron 3.22 ng/mL y 1.61 ng/mL, respectivamente; la media de osteocalcina total fue 7.40 ± 5.11 ng/mL. No hubo diferencia significativa entre los valores de osteocalcina total en nuestra población y los de poblaciones en las que se utilizaron métodos de cuantificación similares al nuestro. Conclusión: La concentración sérica promedio de osteocalcina total en la población analizada fue de 7.40 ng/mL. Las variaciones sutiles entre poblaciones son atribuibles a factores genéticos y poblacionales, sin embargo, el método de cuantificación fue el único que se comprobó influye significativamente en los niveles de osteocalcina en poblaciones sanas.

Association of A-604G ghrelin gene polymorphism and serum ghrelin levels with the risk of obesity in a mexican population.

Obesity is a metabolic disorder that has a multifactorial etiology and affects millions of people worldwide. Ghrelin, a hormone coded by the GHRL gene, plays a role in human body composition and appetite. Single nucleotide polymorphisms (SNPs) of the GHRL gene have been associated with obesity and metabolic disorders. To evaluate the association of A-604G SNP of GHRL promoter region with serum ghrelin levels and the risk of obesity in a Mexican population. Two hundred and fifty individuals were enrolled and classified as obese or control subjects (CS) according to BMI. DNA samples, anthropometric measurements and biochemical parameters were obtained from all subjects. The A-604G SNP was genotyped using PCR-RFLPs technique. Ghrelin levels were measured using a commercial enzyme immunoassay. The G/G genotype was more frequent among obese individuals (p < 0.0001) when compared to CS. The G/A genotype and A allele were associated with protection against obesity (OR 0.29, p < 0.0001; OR 0.39, p < 0.0001 respectively), the A allele remained significant after adjusting for age and gender (OR: 0.25, p < 0.0001). Serum ghrelin levels were higher in obese patients (p = 0.004) than in CS, however, significance was lost after adjustment for age (p = 0.088). The G/G genotype was associated with higher levels of serum ghrelin (p = 0.02) independently of the effect of age. The G/G genotype of the A-604G SNP in the GHRL gene is associated with altered serum ghrelin levels and obesity. The A allele was also associated with protection against obesity in this study.

Role and New Insights of Pirfenidone in Fibrotic Diseases.

Pirfenidone (PFD) is a non-peptide synthetic molecule issued as a broad-spectrum anti-fibrotic drug with the ability to decrease TGF-ß1, TNF-α, PDGF and COL1A1 expression, which is highly related to prevent or remove excessive deposition of scar tissue in several organs. Basic and clinical evidence suggests that PFD may safely slow or inhibit the progressive fibrosis swelling after tissue injuries. Furthermore, a number of evidence suggests that this molecule will have positive effects in the treatment of other inflammatory diseases. This review contains current research in which PFD has been used as the treatment of several diseases, and focus mainly in the outcomes related to improve inflammation and fibrogenesis. Therefore, the main goal of this review is to focus on the novel findings of PFD efficacy rather than deepen in the chemical aspects of the molecule.

Skinfold Thickness as a Cardiometabolic Risk Predictor in Sedentary and Active Adult Populations.

Studies report that increased body fat can lead to health risks for individuals. However, some methods used for analyzing adiposity did not identify its distribution in the human body because they are typically measured using bioimpedance scales. This study aims to associate the presence of cardiometabolic risk factors in sedentary and active adult populations through anthropometric methods based on skinfold thickness measurements. A cross-sectional study was conducted on 946 adults aged between 18 and 79 years with prior informed consent. Clinical, anthropometric, and biochemical parameters, as well as some cardiometabolic risk factors, were evaluated. Almost half of the population (45.1%; n = 427) is sedentary. A significant association was found between the sum of the skinfolds (bicipital, tricipital, subscapular, and suprailiac) and the cardiometabolic risk factors evaluated, highlighting the cardiovascular risk associated with abdominal obesity, risk of insulin resistance, as well as the development of hyperglycemia, and hypertriglyceridemia. The bicipital fold was thicker (19.67 mm) in the population with a sedentary lifestyle than in the physically active population (18.30 mm). Furthermore, the skinfolds that predict higher metabolic risks were suprailiac and subscapular in sedentary and active populations. Thus, these skinfold measurements could be considered in assessing the adult population for early cardiometabolic risk detection, even in healthy and physically active people.

SARS-CoV-2: Air pollution highly correlated to the increase in mortality. The case of Guadalajara, Jalisco, México.

Objectives: To determine whether air pollution or changes in SARS-CoV-2 lineages lead to an increase in mortality. Methods: Descriptive statistics were used to calculate rates of infection (2020-2021). RT-PCR was used to compare viral loads from October 2020 to February 2021. Next-generation sequencing (NGS) (n = 92) was used to examine and phylogenetically map SARS-CoV-2 lineages. A correlative "air pollution/temperature" index (I) was developed using regression analysis. PM2.5, PM10, O3, NO2, SO2, and CO concentrations were analyzed and compared to the mortality. Results: The mortality rate during the last year was ∼32%. Relative SARS-CoV-2 viral loads increased in December 2020 and January 2021. NGS revealed that approximately 80% of SARS-CoV-2 linages were B.1.243 (33.7%), B1.1.222 (11.2%), B.1.1 (9%), B.1 (7%), B.1.1.159 (7%), and B.1.2 (7%). Two periods were analyzed, the prehigh- and high-mortality periods and no significant lineage differences or new lineages were found. Positive correlations of air pollution/temperature index values with mortality were found for IPM2.5 and IPM10. INO2. ISO2, and ICO but not for O3. Using ICO, we developed a model to predict mortality with an estimated variation of ∼±5 deaths per day. Conclusion: The mortality rate in the MZG was highly correlated with air pollution indices and not with SARS-CoV-2 lineage.

Genetic polymorphisms of genes coding to alcohol-metabolizing enzymes in western Mexicans: association of CYP2E1*c2/CYP2E1*5B allele with cirrhosis and liver function.

BACKGROUND: Alcoholic cirrhosis constitutes a major public health problem in the world where ADH1B, ALDH2, and CYP2E1 polymorphisms could be playing an important role. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy control individuals (C) and patients with alcoholic cirrhosis (AC) from western Mexico. METHODS: Ninety C and 41 patients with AC were studied. Genotype and allele frequency were determined through polymerase chain reaction-restriction fragment length polymorphisms. RESULTS: Polymorphic allele distribution in AC was 1.6%ADH1B*2, 0.0%ALDH2*2, and 19.5%CYP2E1*c2; in C: 6.1%ADH1B*2, 0%ALDH2*2, and 10.6%CYP2E1*c2. CYP2E1*c2 polymorphic allele and c1/c2 genotype frequency were significantly higher (p < 0.05 and p < 0.01, respectively) in patients with AC when compared to C. Patients with AC, carrying the CYP2E1*c2 allele, exhibited more decompensated liver functioning evaluated by total bilirubin and prothrombin time, than c1 allele carrying patients (p < 0.05). Cirrhosis severity, assessed by Child's Pugh score and mortality, was higher in patients carrying the c2 allele, although not statistically significant. CONCLUSIONS: In this study, CYP2E1*c2 allele was associated with susceptibility to AC; meanwhile, ADH1B*2 and ALDH2*2 alleles were not. CYP2E1*c2 allele was associated with AC severity, which could probably be attributed to the oxidative stress promoted by this polymorphic form. Further studies to clearly establish CYP2E1*c2 clinical relevance in the development of alcohol-induced liver damage and its usefulness as a probable prognostic marker, should be performed. Also, increasing the number of patients and including a control group conformed by alcoholic patients free of liver damage may render more conclusive results. These findings contribute to the understanding of the influence of gene variations in AC development among populations, alcohol metabolism, and pharmacogenetics.

Food Consumption and Metabolic Risks in Young University Students.

The purpose of this study was to analyze the association between components of the diet, metabolic risks, and the serum concentrations of adiponectin and interleukin-6 (IL-6). With prior informed consent, an analytical cross-sectional study was carried out with 72 students in their first year of university. The subjects had a mean age of 19.2 ± 1.0 years and body mass index of 23.38 ± 4.2, and they were mainly women (80.6%). Sociodemographic, anthropometric, and dietary data and metabolic risk factors were evaluated, and biochemical parameters and adipocytokines were also considered. The data were analyzed using means, ranges, and correlations, as well as principal components. In general, the protein, fat, and sodium intake were higher than the international dietary recommendations, and deficiencies in vitamins B5 and E, potassium, phosphorus, selenium, and zinc were observed. The most frequently observed metabolic risks were insulin resistance and hypoalphalipoproteinemia. IL-6 was positively correlated with lipid and protein intake. Adiponectin showed a positive correlation with high-density lipoprotein and a negative correlation with insulin, weight, and waist, while the adiponectin pattern was similar to that of vitamins E and A, which decreased with increasing intake of calories, macronutrients, and sodium. In general, a hypercaloric diet that was high in protein, fat, and sodium and deficient in vitamins, mainly fat-soluble, was associated with a lower concentration of adiponectin and a higher concentration of IL-6, which favor the presence of metabolic risks, including insulin resistance. Intervention studies are required to evaluate the dietary intake of metabolic markers in young people without comorbidities, which will lay the foundation for implementing prevention strategies.

Effect of Ursolic Acid on Insulin Resistance and Hyperinsulinemia in Rats with Diet-Induced Obesity: Role of Adipokines Expression.

Excess of visceral adipose tissue (VAT) characteristic of obesity leads to a proinflammatory state disrupting the insulin signaling pathway, triggering insulin resistance (IR) and inflammation, the main processes contributing to obesity comorbidities. Ursolic acid (UA), a pentacyclic triterpenoid occurring in a variety of plant foods, exhibits anti-inflammatory properties. The aim of this study was to evaluate UA effects on IR, hyperinsulinemia, and inflammation in experimental diet-induced obesity. Forty male Wistar rats were randomly assigned to eight groups (n = 5). One group was used for time 0. Three groups were labeled as OBE (control): receiving high-fat diet (HFD; fat content 45.24% of energy) during 3, 6, or 9 weeks; three groups UA-PREV: exposed to simultaneous HFD and UA during 3, 6, or 9 weeks to evaluate UA preventive effects; one group UA-REV: receiving HFD for 6 weeks, followed by simultaneous HFD and UA for three additional weeks to analyze UA reversal effects. Measurements were performed after 3, 6, or 9 weeks of treatment. Adiposity was calculated by weighing VAT after sacrifice. Serum markers were quantified through colorimetric and enzyme-linked immunosorbent assay methods. VAT adipokines RNAm expression was evaluated by quantitative reverse transcriptase-polymerase chain reaction. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests. UA significantly decreased adiposity, IR, hyperinsulinemia, triacylglycerides, and cholesterol levels, and also VAT mRNA expression of MCP-1 (monocyte chemoattractant protein-1), IL (interleukin)-1ß and IL-6, concomitantly increasing adiponectin levels. UA metabolic effects demonstrated in this study support its potential therapeutic utility to improve IR, hyperinsulinemia, and inflammation observed in obesity and diabetes.

Establishment of a cut-point value of serum TNF-alpha levels in the metabolic syndrome.

Cardiovascular diseases and type 2 diabetes are the major causes of mortality in Mexico. Metabolic syndrome (MS) is a cluster of factors that increase the risk to develop such diseases. Previous studies have shown that MS is associated with high tumor necrosis factor (TNF-alpha) levels. In fact, TNF-alpha has been proposed to be a useful marker for clinical diagnosis of inflammation at an early stage. Therefore, we analyzed TNF-alpha concentrations in Mexican individuals with or without MS and related these levels to the associated MS components. Clinical, anthropometric, and biochemical data were analyzed in 41 healthy and 39 MS individuals. Individuals were similarly grouped by age and gender.The serum TNF-alpha levels measured by a highly sensitive enzyme-linked immunosorbent assay (ELISA) kit were increased significantly in MS subjects compared with healthy individuals (P<0.001). The assay showed 78.1% sensitivity and 61.5% specificity with a cut-point level of 1.36 pg/mL. TNF-alpha levels higher than the cut-point value were correlated with insulin resistance indices. These findings support the hypothesis that serum TNF-alpha concentration could be a useful marker for early MS diagnosis. Nevertheless, we suggest the establishment of specific cut-point values in each studied population to evaluate potential clinical applications.

Interactions between DRD2/ANKK1 TaqIA Polymorphism and Dietary Factors Influence Plasma Triglyceride Concentrations in Diabetic Patients from Western Mexico: A Cross-sectional Study.

This study aimed to screen relevant interactions between DRD2/ANKK1 TaqIA polymorphism and dietary intakes with reference to phenotypical features in patients with T2D from western Mexico. In this cross-sectional study, a total of 175 T2D patients were enrolled. Dietary intake was evaluated using 3-day food records and appropriate software. Glycemic and blood lipid profiles were measured by standardized methods. Genotyping of the DRD2/ANKK1 TaqIA polymorphism was performed by the RFLP method. Gene-diet interactions regarding anthropometric and metabolic phenotypes were screened by adjusted multiple linear regression analyses. Genotype frequencies of the DRD2/ANKK1 TaqIA polymorphism were A1A1 (16.0%), A1A2 (52.6%), and A2A2 (31.4%). Statistically significant interactions between the DRD2/ANKK1 TaqIA genotypes and dietary factors in relation to blood triglyceride (TG) levels were found. Carriers of the A1 allele (A1A1 homozygotes plus A1A2 heterozygotes) were protected from TG increases by maltose intake (P int. = 0.023). Instead, A2A2 homozygotes were susceptible to TG rises through consumptions of total fat (P int. = 0.041), monounsaturated fatty acids (P int. = 0.001), and dietary cholesterol (P int. = 0.019). This study suggests that the interactions between DRD2/ANKK1 TaqIA polymorphism and dietary factors (sugar and fats) influence TG levels in diabetic patients.

Partial traumatic amputation of an upper limb with excellent functional recovery: A 13-year follow-up clinical case.

Introducción: Se han publicados pocos informes sobre el seguimiento a largo plazo de la reparación quirúrgica de una amputación parcial. Algunos estudios de largo plazo han registrado tasas similares de discapacidad entre los pacientes con amputaciones y los sometidos a operación reconstructiva. Objetivo: Informar un caso clínico de una amputación traumática parcial de una extremidad superior con recuperación funcional después de 13 años de seguimiento. Caso clínico: Paciente masculino de ocho años con traumatismo grave en la extremidad superior izquierda, desprendimiento de los músculos bíceps y tríceps y una fractura diafisaria oblicua del húmero distal. La fractura se fijó de manera transitoria con alambres de Kirschner de 2.0 mm, seguido de inmovilización con aparato de Sarmiento y al final se realizó reducción abierta y fijación interna con placa de compresión dinámica de 3.5 mm. La integridad muscular y neurovascular permitió la reparación microquirúrgica del nervio radial y la rehabilitación neuromuscular. Conclusiones: Este informe clínico representa un caso de una recuperación funcional excelente atestiguada a través de un periodo de seguimiento de 13 años.

Introduction: There are just a few reports that deal with long-term outcomes of a partial amputation surgical repair. Long-term studies have reported similar rates of disability among patients with amputations and those that have been undergoing reconstructive surgery. Objective: The purpose of this report is describing a clinical case of a patient with partial traumatic amputation of an upper limb with an excellent functional recovery after 13 years of follow-up. Clinical case: The case of an 8 year old male patient with severe trauma to the upper left limb is described. The lesions included an oblique diaphyseal open fracture of the distal region of the humerus, along with detachment of the biceps and triceps muscles. The fracture was fixed transiently with 2.0 mm Kirschner's wire followed by immobilization with Sarmiento's brace, and finally, open reduction and internal fixation with a 3.5 mm dynamic compression plate were performed. The muscular and neurovascular integrity allowed microsurgical repair of the radial nerve and neuromuscular rehabilitation. Conclusion: This clinical report represents a case with an excellent functional recovery witnessed through a 13-year follow-up period.

Serum ghrelin and obestatin levels in HIV-infected patients: Effect of 36 weeks of antiretroviral treatment.

INTRODUCTION: Patients with HIV+ often present lipid disturbances. The role of ghrelin and obestatin in these lipid disturbances is not clear. The effect of antiretroviral (ART) drugs on those molecules is also unknown. This study measured ghrelin and obestatin levels, as well as metabolic markers, in patients with HIV+ before and after 36 weeks of ART. MATERIAL AND METHODS: Twenty HIV-positive, ART-naïve patients who started a scheme consisting of tenofovir/emtricitabine+lopinavir/ritonavir were enrolled. Plasma samples were collected before and after 36 weeks of treatment. Serum ghrelin and obestatin levels were quantitated by ELISA; glucose, cholesterol, and triglyceride levels were measured by colorimetric and enzymatic methods, and cardiovascular risk was calculated by the atherogenic index of plasma (AIP). RESULTS: All patients completed 36 weeks of ART. Total cholesterol (p<0.001), LDL-C (p=0.019), HDL-C (p=0.003), VLDL-C (p=0.002), and triglyceride levels (p=0.021) significantly increased after treatment. AIP revealed increased cardiovascular risk at baseline, which remained high after treatment. There was a statistically significant increase in obestatin level in the unpaired and paired analyses, while ghrelin levels only showed a trend to increase. Changes in ghrelin and obestatin levels positively correlated, but no correlation was seen with any metabolic parameter. CONCLUSION: After 36 weeks of ART, patients showed an altered lipid profile, but there were no significant changes in cardiovascular risk. Ghrelin and obestatin levels increased after 36 weeks of ART, but the increase was only significant for obestatin. Changes in ghrelin and obestatin positively correlate.

Pharmacological Control of Complications Following to Third Molar Removal: Evidence Based on A Meta-Analysis.

AIMS: The purpose of this meta-analysis was to evaluate the clinical efficacy of non-steroidal anti-inflammatory drugs and dexamethasone on the trismus, postsurgical pain, facial swelling, as well as the analgesic consumption after third molar surgery. MATERIAL AND METHODS: The reports were identified in the most important medical databases. Those studies that met the requirements were fully assessed according to the inclusion and exclusion criteria. The quality of each report was evaluated with the Oxford Quality Scale and using the Cochrane Collaboration's risk of bias tool. Each meta-analysis was done using the technique of mean difference and 95% confidence intervals employing a random effects model with the Review Manager 5.3., from the Cochrane Library. Significant statistical difference was accepted when the p value was less than 0.05 on the test of overall effect (Z value). RESULTS: Qualitative evaluation was done using the data of 330 patients extracted from seven articles and the quantitative assessment with data of 200 patients from three reports. It was not observed difference among non-steroidal anti-inflammatory drugs and dexamethasone in any of the clinical effectiveness indicators. CONCLUSION: The outcomes of our meta-analysis indicate that non-steroidal anti-inflammatory drugs and dexamethasone have good therapeutic effect for the management of inflammatory complications following to third molar surgery.

[Combination of noise plus weight-bearing accelerates consolidation time in tibial shaft fractures: A preliminary report]. / La combinación de ruido más carga de peso acelera la consolidación en las fracturas de la diáfisis tibial: Un informe preliminar.

Introduction: Long bones fractures are responsible for prolonged periods of incapacity and economic losses. New therapies for shortening the time of consolidation are needed. Thus, the purpose of this clinical study was to evaluate the efficacy of noise plus weight-bearing over the bone consolidation of tibial shaft fractures. Methods: In this clinical trial, 12 patients with tibial shaft fractures were recruited during a 24-month period. Participants were treated with intramedullary nails and randomized to two groups: an experimental group and a control group. Both groups underwent a rehabilitation program consisting of two daily walking sessions with progressive weight-bearing. Simultaneously, the experimental group received a noise stimulus on the fracture site with intensities of 0.1-0.6 N and frequencies of 0.1-50 Hz. Radiographic consolidation was evaluated by Radiographic Unión Scale of Tibia. Results: X-ray consolidation was achieved at 18.6 ± 3.6 weeks and 27.2 ± 6.9 weeks, for experimental and control group, respectively (p < 0.05). Recovery of mobility ranges in the knee and ankle was faster in the experimental group than in the control group. Conclusions: This new method to stimulate fracture consolidation has the following advantages: it is effective, portable, easy to use, and inexpensive.

Introducción: Las fracturas de huesos largos son causa de períodos prolongados de incapacidad y pérdidas económicas. Se necesitan nuevas terapias para acortar el tiempo de consolidación. Por lo tanto, el objetivo de este estudio clínico fue evaluar la eficacia del ruido más el soporte de peso sobre la consolidación ósea de las fracturas de la diáfisis tibial. Método: En este ensayo clínico, 12 pacientes con fracturas de la diáfisis tibial fueron reclutados durante un período de 24 meses. Los participantes fueron tratados con clavos intramedulares y luego aleatorizados a dos grupos: un grupo experimental y un grupo control. Ambos grupos se sometieron a un programa de rehabilitación que consta de dos sesiones diarias de caminata con soporte progresivo de peso. Simultáneamente, el grupo experimental recibió un estímulo de ruido en el sitio de la fractura con intensidades de 0.1-0.6 N y frecuencias de 0.1-50 Hz. La consolidación radiográfica se evaluó mediante la escala RUST. Resultados: La consolidación radiográfica se logró a las 18.6 ± 3.6 semanas en el grupo experimental y a las 27.2 ± 6.9 semanas en el grupo control (p < 0.05). La recuperación de los rangos de movilidad en la rodilla y el tobillo fue más rápida en el grupo experimental que en el grupo control. Conclusiones: Este nuevo método para estimular la consolidación de fracturas tiene las siguientes ventajas: es eficaz, portátil, fácil de usar y económico.

Distribution of --844 G/A and Hind III C/G PAI-1 polymorphisms and plasma PAI-1 levels in Mexican subjects: comparison of frequencies between populations.

Several polymorphisms have been described in the PAI-1 gene including the -844 G/A and Hind III C/G polymorphisms. These polymorphisms have been associated with different diseases such as preeclampsia and cardiovascular diseases. The allele and genotype frequencies of both PAI-1 polymorphism where investigated in Mexican subjects and compared with other healthy worldwide populations. The hematological and biochemical parameters where classified according each genotype in our studied group. One hundred Mexican subjects were recruited. Demographic data and hematological and biochemical parameters were collected, and genomic DNA isolation was performed in all the participants. Screening of both polymorphisms studied was made by polymerase chain reaction and restriction analysis. Levels of plasminogen activator inhibitor-1 in plasma were measured by ELIS-ARA plasminogen activator inhibitor antigen kit. The -844 and Hind III genotypes frequencies were as follows: 49% (G/G), 40% (G/A), 11% (A/A) and 50% (C/C), 44% (C/G), 6% (G/G), respectively. The wild-type genotypes (G/G and C/C) were significantly higher with respect to the compared populations. In addition, a significant increase of apolipoprotein A1 in the carriers of G/A -844 and C/G Hind III genotypes was observed. However, when the plasma plasminogen activator inhibitor levels were analyzed with respect to each genotype and haplotype, no significant differences were found.