[Risk factors associated with lethality on patients with central cord syndrome]. / Factores asociados a la letalidad en pacientes con síndrome medular central agudo postraumático.

Background: Central Cord Syndrome is the most common incomplete spinal cord injury, and it represents 9% of all spinal injuries of the adult. Objective: to determine the risk factors associated with lethality or/and mechanical ventilation (MV) in patients with Central Cord Syndrome (CCS). Material and Methods: upon a retrospective cohort with patients with posttraumatic CCS we evaluated at the time of emergency admission and until the hospital discharge. The dependent variable was dead or MV. We calculated incidence, relative risk (RR) with CI95% and a multivariate model for the association of statistically significant variables by means of a risk coefficient model upon the variables that evidenciated tendencies towards risk. Results: From 101 patients with CCS, 85.1% with a severe medullary canal stenosis and 9.9% required MV; the mortality was 13.9%. The only risk factor associated with dead was the use of MV with an RR of 3.6 (CI95% 1.4-9.5); the risk with tendencies towards MV was being older than 60 RR 5.4 (CI95% 0.6-44.2). Other factors demonstrated a tendency towards mortality, but they were not statistically significant. Conclusions: MV is a risk factor associated with mortality, other factors evidenciated tendencies towards mortality; being older than 60, hypertension, diabetes mellitus, narrow spinal canal, more than 20 days of hospital stay and being intervened farther than 10 days from the accident. The incidence of mortality in our sample is greater than thus reported previously on other international articles. To know and identify these and other factors will let us identify patients with a greater risk of complications.

Introducción: el síndrome medular central es la lesión medular incompleta más común y representa el 9% de las lesiones medulares del adulto. Objetivo: determinar la letalidad del síndrome medular central (SMC) y sus factores de riesgo asociados a fallecer y/o uso de ventilación mecánica (VM). Material y métodos: cohorte retrospectiva en pacientes con SMC que acuden a urgencias y valorados hasta su egreso. La variable dependiente fue VM o muerte. Se calculó la incidencia, riesgo relativo (RR) e IC95%; se usaron modelos multivariados de asociación con las variables significativas mediante un modelo de cocientes de riesgos, y aquellas que presentaron algún grado de tendencia de acuerdo con el RR por encima de 1. Resultados: se recolectó la información de una muestra de 101 pacientes con SMC que recibieron atención en la unidad entre 2015 y 2021, 85.1% presentaron estenosis medular, 9.9% de pacientes requirieron VM, la mortalidad fue de 13.9%. El factor de riesgo asociado a muerte fue la VM con RR 3.6 (IC95%: 1.4-9.5); el factor con tendencia a VM fue ser mayor de 60, RR 5.4 (IC95%: 0.6-44.2). Otros factores evidenciaron tendencia a mortalidad o VM sin significancia estadística. Conclusiones: el factor de riesgo asociado a mortalidad fue VM, otros evidencian tendencia hacia mortalidad, como ser mayor de 60 años, hipertensión arterial, diabetes mellitus, estenosis medular por debajo de los 10 milímetros, más de 20 días de estancia hospitalaria y ser intervenidos más de 10 días posterior al accidente. La mortalidad en nuestra población se encuentra muy elevada en comparación con estudios internacionales previos. Conocer los factores de riesgo ayudaran a identificar a los pacientes con mayor riesgo de muerte o VM.

Corrigendum to Article CP203292.

Cecilia Fernández Del Valle-Laisequilla, Cristian Trejo-Jasso, Juan Carlos Huerta-Cruz, Lina Marcela Barranco-Garduño, Juan Rodríguez-Silverio, Héctor Isaac Rocha-González, Juan Gerardo Reyes-García. Efficacy and safety of a fixed-dose combination of D-norpseudoephedrine, triiodothyronine, atropine, aloin, and diazepam in obese patients. Int J Clin Pharmacol Ther. 2018; 56: 531-538. doi: 10.5414/CP203292. Note from the authors: We realized only now that the affiliation of Cecilia Fernández Del Valle-Laisequilla was indicated in the title page, but due to an unintentional mistake in the final version, the affiliation was not declared in the conflict of interest section, which should read: "Cecilia Fernández Del Valle-Laisequilla is Medical Director of Productos Medix S.A. de C.V."

Validación del instrumento Infant Malnutrition and Feeding Checklist for Congenital Heart Disease, una herramienta para identificar riesgo de desnutrición y dificultades de alimentación en lactantes con cardiopatías congénitas / Validation of the instrument “Infant Malnutrition and Feeding Checklist for Congenital Heart Disease”, a tool to identify risk of malnutrition and feeding difficulties in infants with congenital heart disease

Introducción: actualmente, se han diseñado diversas herramientas para detectar oportunamente el riesgo de desnutrición en niños hospitalizados. En aquellos con diagnóstico de cardiopatías congénitas (CC), solo existe una herramienta desarrollada en Canadá, llamada Infant Malnutrition and Feeding Checklist for Congenital Heart Disease (IMFC:CHD), la cual fue diseñada en idioma inglés. Objetivo: evaluar la validez y confiabilidad de la adaptación en español de la herramienta IMFC:CHD en lactantes con CC. Métodos: estudio transversal de validación realizado en dos etapas: la primera, de traducción y adaptación transcultural de la herramienta; y la segunda, de validación de la nueva herramienta traducida, donde se obtuvieron las evidencias de confiabilidad y validez. Resultados: en la primera etapa se obtuvo la herramienta traducida y adaptada al idioma español; para la segunda etapa se incluyeron 24 lactantes con diagnóstico de CC. Se evaluó la validez de criterio concurrente entre la herramienta de tamizaje y la evaluación antropométrica, obteniéndose un acuerdo sustancial (κ = 0,660, IC 95 %: 0,36-0,95). Para la validez de criterio predictiva, la cual fue comparada con los días de estancia hospitalaria, se obtuvo un acuerdo moderado (κ = 0,489, IC 95 %: 0,1-0,8). La confiabilidad de la herramienta se evaluó mediante consistencia externa, midiendo la concordancia interobservador, y se obtuvo un acuerdo sustancial (κ = 0,789, IC 95 %: 0,5-0,9); la reproducibilidad de la herramienta mostró un acuerdo casi perfecto (κ = 1, IC 95 %: 0,9-1,0). Conclusiones: la herramienta IMFC:CHD mostró una adecuada validez y confiabilidad, por lo que podría considerarse un recurso útil para la identificación de desnutrición grave. (AU)

Introduction: currently, various tools have been designed to timely detect the risk of malnutrition in hospitalized children. In those with a diagnosis of congenital heart disease (CHD), there is only one tool developed in Canada: Infant Malnutrition and Feeding Checklist for Congenital Heart Disease (IMFC:CHD), which was designed in English. Objective: to evaluate the validity and reliability of the Spanish adaptation of the IMFC:CHD tool in infants with CHD. Methods: cross-sectional validation study carried out in two stages. The first, of translation and cross-cultural adaptation of the tool, and the second, of validation of the new translated tool, where evidence of reliability and validity were obtained. Results: in the first stage, the tool was translated and adapted to the Spanish language; for the second stage, 24 infants diagnosed with CHD were included. The concurrent criterion validity between the screening tool and the anthropometric evaluation was evaluated, obtaining a substantial agreement (κ = 0.660, 95 % CI: 0.36-0.95) and for the predictive criterion validity, which was compared with the days of hospital stay, moderate agreement was obtained (κ = 0.489, 95 % CI: 0.1-0.8). The reliability of the tool was evaluated through external consistency, measuring theinter-observer agreement, obtaining a substantial agreement (κ = 0.789, 95 % CI: 0.5-0.9), and the reproducibility of the tool showed an almost perfect agreement (κ = 1, CI 95 %: 0.9-1.0). Conclusions: the IMFC:CHD tool showed adequate validity and reliability, and could be considered as a useful resource for the identification of severe malnutrition. (AU)

[Validation of the instrument "Infant Malnutrition and Feeding Checklist for Congenital Heart Disease", a tool to identify risk of malnutrition and feeding difficulties in infants with congenital heart disease]. / Validación del instrumento Infant Malnutrition and Feeding Checklist for Congenital Heart Disease, una herramienta para identificar riesgo de desnutrición y dificultades de alimentación en lactantes con cardiopatías congénitas.

Introduction: Introduction: currently, various tools have been designed to timely detect the risk of malnutrition in hospitalized children. In those with a diagnosis of congenital heart disease (CHD), there is only one tool developed in Canada: Infant Malnutrition and Feeding Checklist for Congenital Heart Disease (IMFC:CHD), which was designed in English. Objective: to evaluate the validity and reliability of the Spanish adaptation of the IMFC:CHD tool in infants with CHD. Methods: cross-sectional validation study carried out in two stages. The first, of translation and cross-cultural adaptation of the tool, and the second, of validation of the new translated tool, where evidence of reliability and validity were obtained. Results: in the first stage, the tool was translated and adapted to the Spanish language; for the second stage, 24 infants diagnosed with CHD were included. The concurrent criterion validity between the screening tool and the anthropometric evaluation was evaluated, obtaining a substantial agreement (κ = 0.660, 95 % CI: 0.36-0.95) and for the predictive criterion validity, which was compared with the days of hospital stay, moderate agreement was obtained (κ = 0.489, 95 % CI: 0.1-0.8). The reliability of the tool was evaluated through external consistency, measuring the inter-observer agreement, obtaining a substantial agreement (κ = 0.789, 95 % CI: 0.5-0.9), and the reproducibility of the tool showed an almost perfect agreement (κ = 1, CI 95 %: 0.9-1.0). Conclusions: the IMFC:CHD tool showed adequate validity and reliability, and could be considered as a useful resource for the identification of severe malnutrition.

Introducción: Introducción: actualmente, se han diseñado diversas herramientas para detectar oportunamente el riesgo de desnutrición en niños hospitalizados. En aquellos con diagnóstico de cardiopatías congénitas (CC), solo existe una herramienta desarrollada en Canadá, llamada Infant Malnutrition and Feeding Checklist for Congenital Heart Disease (IMFC:CHD), la cual fue diseñada en idioma inglés. Objetivo: evaluar la validez y confiabilidad de la adaptación en español de la herramienta IMFC:CHD en lactantes con CC. Métodos: estudio transversal de validación realizado en dos etapas: la primera, de traducción y adaptación transcultural de la herramienta; y la segunda, de validación de la nueva herramienta traducida, donde se obtuvieron las evidencias de confiabilidad y validez. Resultados: en la primera etapa se obtuvo la herramienta traducida y adaptada al idioma español; para la segunda etapa se incluyeron 24 lactantes con diagnóstico de CC. Se evaluó la validez de criterio concurrente entre la herramienta de tamizaje y la evaluación antropométrica, obteniéndose un acuerdo sustancial (κ = 0,660, IC 95 %: 0,36-0,95). Para la validez de criterio predictiva, la cual fue comparada con los días de estancia hospitalaria, se obtuvo un acuerdo moderado (κ = 0,489, IC 95 %: 0,1-0,8). La confiabilidad de la herramienta se evaluó mediante consistencia externa, midiendo la concordancia interobservador, y se obtuvo un acuerdo sustancial (κ = 0,789, IC 95 %: 0,5-0,9); la reproducibilidad de la herramienta mostró un acuerdo casi perfecto (κ = 1, IC 95 %: 0,9-1,0). Conclusiones: la herramienta IMFC:CHD mostró una adecuada validez y confiabilidad, por lo que podría considerarse un recurso útil para la identificación de desnutrición grave.

Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions.

The loss of function melanocortin 4-receptor (MC4R) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5-9.7), p = 0.005]. Regarding interventions, in the dietary restriction group only two patients were MC4R Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: -4.0 kg (-2.9%) in patient 1, and -1.8 kg (-1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (-2.9 kg; -2.8%). Phentermine treatment produced similar weight loss in six carriers (-12.7 kg; 15.5%) and 18 non-carriers (-11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single MC4R loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional MC4R allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in MC4R Ile269Asn mutation carriers.

Metformin improves the weight reduction effect of mazindol in prediabetic obese Mexican subjects.

OBJECTIVE: Obesity is the strongest risk factor for type 2 diabetes (T2D). We aimed to explore 7% weight reduction rates of mazindol alone or combined with metformin in non-diabetic obese Mexican subjects who had additional risk factors for T2D. MATERIALS AND METHODS: In this randomized double-blind study, 137 participants received 1 mg mazindol (n = 65) alone or combined with 500 mg metformin (n = 72), twice a day, for 6 months. RESULTS: Mazindol and mazindol-metformin were similarly effective. However, when subjects were subclassified into non-diabetics and prediabetics, according to glycated hemoglobin (HbA1c) - < 5.7% and 5.7 - 6.4%, respectively - and/or fasting plasma glucose (FPG) - < 100 mg/dL and 100 - 125 mg/dL, respectively -, differences were evident. Prediabetics in the mazindol-metformin group had a higher rate of 7% weight reduction (78.4%, n = 37) compared to prediabetics treated with mazindol (48.3%, n = 29). Furthermore, mazindol-metformin treatment induced significant reductions in fasting plasma insulin, HOMA-IR, and HbA1c in prediabetics compared to mazindol. No differences were found in any parameter between non-diabetics treated with mazindol (n = 36) and mazindol-metformin (n = 35). CONCLUSION: Our results highlight the effectiveness of mazindol-metformin to achieve higher rates of 7% weight reduction and to improve the glycemic profile in prediabetic obese subjects, which could be useful to prevent or delay T2D in these subjects.

Combined First Month Body Weight Loss and Development of Tolerance as Predictors of 6-Month Efficacy of Mazindol in Mild and Moderate Obese Subjects.

The weight loss response to anti-obesity drugs is highly variable and poorly understood, which does not allow us to know, in advance, in which subjects the drug will be effective and in which it will not. The objective of this study was to explore the body weight reduction in kilograms in the first month (1mo-BWRkg) and the development of tolerance as predictors of 6-month efficacy for treatment with 1 mg mazindol twice a day. One hundred ninety-six obese subjects were individually or jointly analyzed. Approximately 60% of subjects developed tolerance to mazindol and achieved increasing proportional levels of 6-month efficacy according to 1mo-BWRkg intervals (<1 kg, 1 to <2 kg, 2 to <4 kg and ≥4 kg). Both moT and 1mo-BWRkg were significantly correlated with the mean percentage body weight reduction (BWR%) after 6-months of treatment. The qualitative analysis of both predictors on the progressive efficacy of mazindol was used to classify patients according to expected efficacy (inefficient, slightly effective, partially effective, or fully effective), based on the mean percentage efficacy and the number of subjects reaching a BWR% of <5%, 5 to <10%, 10 to <15% or ≥15%. In conclusion, combined 1mo-BWRkg and moT were early predictors for the progressive efficacy of 6-month mazindol anti-obesity therapy. This finding represents progress in predictive, preventive, and personalized medicine which could serve for estimating the expectations of individual efficacy with the use of the drug. and highlights the basic principle of personalized medicine, "one size does not fit all".

GPR55 and GPR119 Receptors Contribute to the Processing of Neuropathic Pain in Rats.

Orphan G-protein-coupled receptors (GPCR) comprise a large number of receptors which are widely distributed in the nervous system and represent an opportunity to identify new molecular targets in pain medicine. GPR55 and GPR119 are two orphan GPCR receptors whose physiological function is unclear. The aim was to explore the participation of spinal GPR55 and GPR119 in the processing of neuropathic pain in rats. Mechanical allodynia was evaluated using von Frey filaments. Protein localization and modulation were measured by immunohistochemistry and western blotting, respectively. Intrathecal administration of CID16020046 (selective GPR55 antagonist) or AS1269574 (selective GPR119 agonist) produced a dose-dependent antiallodynic effect, whereas O1062 (GPR55 agonist) and G-protein antagonist peptide dose-dependently prevented the antiallodynic effect of CID16020046 and AS1269574, respectively. Both GPR55 and GPR119 receptors were expressed in spinal cord, dorsal root ganglia and sciatic nerve, but only GPR119 was downregulated after 14 days of spinal nerve ligation. Data suggest that GPR55 and GPR119 participate in the processing of neuropathic pain and could be useful targets to manage neuropathic pain disorders.

DNA Methylation Levels of the TBX5 Gene Promoter Are Associated with Congenital Septal Defects in Mexican Paediatric Patients.

The TBX5 gene regulates morphological changes during heart development, and it has been associated with epigenetic abnormalities observed in congenital heart defects (CHD). The aim of this research was to evaluate the association between DNA methylation levels of the TBX5 gene promoter and congenital septal defects. DNA methylation levels of six CpG sites in the TBX5 gene promoter were evaluated using pyrosequencing analysis in 35 patients with congenital septal defects and 48 controls. Average methylation levels were higher in individuals with congenital septal defects than in the controls (p < 0.004). In five CpG sites, we also found higher methylation levels in patients than in the controls (p < 0.05). High methylation levels were associated with congenital septal defects (OR = 3.91; 95% CI = 1.02-14.8; p = 0.045). The analysis of Receiver Operating Characteristic (ROC) showed that the methylation levels of the TBX5 gene could be used as a risk marker for congenital septal defects (AUC = 0.68, 95% CI = 0.56-0.80; p = 0.004). Finally, an analysis of environmental factors indicated that maternal infections increased the risk (OR = 2.90; 95% CI = 1.01-8.33; p = 0.048) of congenital septal defects. Our data suggest that a high DNA methylation of the TBX5 gene could be associated with congenital septal defects.

Weight Loss at First Month and Development of Tolerance as Possible Predictors of 30 mg Phentermine Efficacy at 6 Months.

The efficacy of anti-obesity drugs usually does not consider the high degree of interindividual variability in responses to the drug which could affect the decision to withdraw the drug early due to ineffectiveness or to continue therapy according to specific expectations of success. The aim of this study was to analyze body weight loss in kilograms during the first month (1 mo-BWLkg) of treatment with 30 mg phentermine and development of tolerance to phentermine, on its 6-month efficacy. One hundred sixty-six subjects with obesity were individually or jointly analyzed in the study. Subjects with 1 mo-BWLkg of <1 kg, 1-3 kg, 3-5 kg, and ≥5 kg reached 6-month mean percentage body weight reductions (BWR%) of approximately 3%, 5%, 10%, and 15%, respectively. Development of late tolerance (4-6 months) to phentermine had a lower impact than early tolerance (2-3 months). Subjects with 1 mo-BWLkg < 3 kg who developed early tolerance did not achieve relevant BWR% (≥5%) at month 6, while the rest of the subgroups achieved increasing and progressive BWR%, according to their 1 mo-BWLkg range and time of onset of tolerance. The 1 mo-BWLkg and development of tolerance to phentermine could be useful to predict the expected 6-month efficacy trends in obese patients treated with 30 mg phentermine.

Three- and six-month efficacy and safety of phentermine in a Mexican obese population.

OBJECTIVE: Mexico has the second largest prevalence of obesity among adults worldwide, a condition especially affecting the low-income population. There is a pressing need to improve therapeutic options for weight loss. Phentermine is an old and low-cost agent given as an adjuvant therapy for obesity for a 12-week period, at an initial dose of 15 mg or 30 mg. However, there are no precise guidelines on the suitability of both the starting dose and the continuation of treatment for 6 months. The aim of this study was to evaluate the 3- and 6-month efficacy and safety of phentermine in obese Mexican patients to elucidate the aforementioned. MATERIALS AND METHODS: In this prospective, multi-center, open-label study, 932 obese adults received 15 mg or 30 mg phentermine once daily for 6 months. RESULTS: 30 mg phentermine was more effective than 15 mg phentermine in improving anthropometric variables in the 3-month follow-up, but not after completing the 6-month treatment period. Nearly 40% of 3-month non-responders reached a body weight reduction of at least 5% at 6 months. Conversely, ~ 65% and 25% of 3-month responders maintained or improved, respectively, their body weight reduction with long-term phentermine. Potential tolerance as weight regain was ~ 10% from 3 to 6 months. None of the doses increased cardiovascular risk, although mild-to-moderate adverse events were more frequent with 30 mg phentermine. CONCLUSION: 30 mg phentermine was more effective than 15 mg phentermine after 3 months, but not at 6 months of treatment. An important number of subjects could benefit following the therapy from 3 to 6 months.

Evaluation of the Antinociceptive, Antiallodynic, Antihyperalgesic and Anti-Inflammatory Effect of Polyalthic Acid.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very commonly used, but their adverse effects warrant investigating new therapeutic alternatives. Polyalthic acid, a labdane-type diterpenoid, is known to produce gastroprotection, tracheal smooth muscle relaxation, and antitumoral, antiparasitic and antibacterial activity. This study aimed to evaluate the antinociceptive, antiallodynic, antihyperalgesic and anti-inflammatory effect of polyalthic acid on rats. Moreover, the effectiveness of treating hyperalgesia with a combination of polyalthic acid and naproxen was analyzed, as well as the type of drug-drug interaction involved. Nociception was examined by injecting 1% formalin into the right hind paw and thermal hyperalgesia and inflammation by injecting a 1% carrageenan solution into the left hind paw of rats. Allodynia was assessed on an L5/L6 spinal nerve ligation model. Polyalthic acid generated significant antinociceptive (56-320 mg/kg), antiallodynic (100-562 mg/kg), and antihyperalgesic and anti-inflammatory (10-178 mg/kg) effects. Antinociception mechanisms were explored by pretreating the rats with naltrexone, ODQ and methiothepin, finding the effect blocked by the former two compounds, which indicates the participation of opioid receptors and guanylate cyclase. An isobolographic analysis suggests synergism between polyalthic acid and naproxen in the combined treatment of hyperalgesia.

Efficacy and safety of the metformin-mazindol anorectic combination in rat.

The current study investigates the anorectic interaction and safety of the mazindol-metformin combination in rats. Isobologram and interaction index were used to determine anorectic interaction between mazindol and metformin in the sweetened milk model. The safety profile of the mazindol-metformin combination was determined by measuring anxiety, blood pressure, hematic biometry and blood chemistry. An acute dose of mazindol and metformin administered per os, individually or as a mixture, has reduced the milk consumption in rats in a dose-dependent manner. Theoretical effective dose 40 (ED40t) did not differ from the experimental effective dose 40 (ED40e) obtained with the mazindol-metformin mixture in the anorexia experiments, by Student's t-test. In addition, the interaction index confirmed the additive anorectic effect between both drugs. A single oral dose of ED40e mazindol-metformin mixture induced anxiolysis in the elevated plus-maze test. Moreover, oral administration of mazindol-metformin combination for 3 months significantly decreased glycemia, but not blood pressure nor other parameters of hematic biometry and blood chemistry. Results suggest that mazindol-metformin combination exerts an additive anorectic effect, as well as anxiolytic and hypoglycemic properties. Mazindol-metformin combination might be useful in obese patients with anxiety disorders or diabetes risk factors.

Abnormal fluid distribution and low handgrip strength index as predictors of mortality in Mexican patients with chronic heart failure.

OBJECTIVES: In patients with heart failure, fluid alteration and low muscle strength frequently coexist because of their reduced physical activity and sedentary behavior; however, few studies have evaluated the effects of this coexistence on the prognosis of these patients. The aim of this study was to examine the independent association between fluid alteration and the low handgrip strength (HGS) index with mortality in patients with chronic heart failure. METHODS: This observational study included 546 (53.3% male) stable outpatients with heart failure. The presence of an abnormal fluid distribution was determined with a bioelectrical impedance ratio (200/5 kHz) ≥0.85. Handgrip strength (HGS) was measured with a hand dynamometer, and the HGS index was calculated by dividing the HGS (kg) by the squared height (meters). A low HGS index was defined if men had <10.1 and women <7.95 kg/m2. The primary outcome was all-cause mortality. RESULTS: The mean age of the study population was 60.75 ± 17 y, and 30% were classified with a low HGS index, 9.5% with an abnormal fluid distribution, and 29% with both. During the 36 mo of follow-up, 16.5% of the participants reached the endpoint. In men but not in women, coexistence of a low HGS index and abnormal fluid distribution were independently associated with all-cause mortality with a hazard ratio of 2.8 (95% confidence interval, 1.25-6.4; P = 0.01). CONCLUSIONS: In men with heart failure, co-existence of a low HGS index and abnormal fluid distribution was independently associated with all-cause mortality.

Possible involvement of peripheral TRP channels in the hydrogen sulfide-induced hyperalgesia in diabetic rats.

BACKGROUND: Peripheral diabetic neuropathy can be painful and its symptoms include hyperalgesia, allodynia and spontaneous pain. Hydrogen sulfide (H2S) is involved in diabetes-induced hyperalgesia and allodynia. However, the molecular target through which H2S induces hyperalgesia in diabetic animals is unclear. The aim of this study was to determine the possible involvement of transient receptor potential (TRP) channels in H2S-induced hyperalgesia in diabetic rats. RESULTS: Streptozotocin (STZ) injection produced hyperglycemia in rats. Intraplantar injection of NaHS (an exogenous donor of H2S, 3-100 µg/paw) induced hyperalgesia, in a time-dependent manner, in formalin-treated diabetic rats. NaHS-induced hyperalgesia was partially prevented by local intraplantar injection of capsazepine (0.3-3 µg/paw), HC-030031 (100-316 µg/paw) and SKF-96365 (10-30 µg/paw) blockers, at 21 days post-STZ injection. At the doses used, these blockers did not modify formalin-induced nociception. Moreover, capsazepine (0.3-30 µg/paw), HC-030031 (100-1000 µg/paw) and SKF-96365 (10-100 µg/paw) reduced formalin-induced nociception in diabetic rats. Contralateral injection of the highest doses used did not modify formalin-induced flinching behavior. Hyperglycemia, at 21 days, also increased protein expression of cystathionine-ß-synthase enzyme (CBS) and TRPC6, but not TRPA1 nor TRPV1, channels in dorsal root ganglia (DRG). Repeated injection of NaHS enhanced CBS and TRPC6 expression, but hydroxylamine (HA) prevented the STZ-induced increase of CBS protein. In addition, daily administration of SKF-96365 diminished TRPC6 protein expression, whereas NaHS partially prevented the decrease of SKF-96365-induced TRPC6 expression. Concordantly, daily intraplantar injection of NaHS enhanced, and HA prevented STZ-induced intraepidermal fiber loss, respectively. CBS was expressed in small- and medium-sized cells of DRG and co-localized with TRPV1, TRPA1 and TRPC6 in IB4-positive neurons. CONCLUSIONS: Our data suggest that H2S leads to hyperalgesia in diabetic rats through activation of TRPV1, TRPA1 and TRPC channels and, subsequent intraepidermal fibers loss. CBS enzyme inhibitors or TRP-channel blockers could be useful for treatment of painful diabetic neuropathy.

Antiallodynic interaction and motor performance of the pregabalin/thioctic acid and pregabalin/α-tocopherol combinations in neonatal streptozotocin-induced diabetic rats.

Painful peripheral neuropathy can be associated with nerve damage caused by diabetes mellitus. Although pregabalin is the first-line therapy for peripheral neuropathy, it shows substantial discontinuation rates, mainly because of nervous system side effects as motor incoordination. Multimodal therapy may improve the motor side effect profile of pregabalin. The aim of this study was to evaluate the interaction of pregabalin + thioctic acid or pregabalin + α-tocopherol on allodynia and motor performance in neonatal streptozotocin-induced diabetic rats. Efficacy of drugs separately or in combination was tested by tactile allodynia using von Frey filaments. Isobolographic and interaction index analysis were used to determine the antiallodynic interaction between pregabalin and either thioctic acid or α-tocopherol. Motor performance was measured using a rotarod test. Pregabalin, thioctic acid, and α-tocopherol reduced, in a dose-dependent fashion, tactile allodynia. Pregabalin + thioctic acid and pregabalin + α-tocopherol combinations also dose-dependently reduced allodynic behavior in diabetic rats. Isobolographic analysis revealed an additive interaction for both combinations. Consistently, the interaction indices confirmed the additive effect between pregabalin + thioctic acid and pregabalin + α-tocopherol. In addition, the administration of either combination improved motor incoordination induced by pregabalin. Data suggests that thioctic acid or α-tocopherol could positively impact the therapeutic profile of pregabalin, because they might be useful for reducing motor incoordination associated to pregabalin in patients with peripheral neuropathy.

Efficacy and safety of a fixed-dose combination of D-norpseudoephedrine, triiodothyronine, atropine, aloin, and diazepam in obese patients
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OBJECTIVE: A fixed-dose combination (FDC) of D-norpseudoephedrine, tri-iodothyronine, atropine, aloin, and diazepam is used in Mexico for the short-term treatment of obesity; however, its efficacy and safety have been scarcely studied. The aim of this study was to analyze the efficacy and safety of this FDC in Mexican adult overweight and obese patients by a prospective, uncontrolled, multicenter, phase IV open-label study. MATERIALS AND METHODS: 3,290 patients with a body mass index (BMI) ˃ 27 kg/m2 were included in the current study. Primary outcome was the absolute body weight loss, whilst secondary outcomes were the improvement of anthropometric and cardiometabolic parameters as well as the description of adverse events. RESULTS: The FDC decreased the body weight and BMI by -9.0 ± 5.6 kg and -3.4 ± 2.2 kg/m2, respectively, at 6 months. In addition, 43.3% and 14.3% of subjects achieved at least 5% or 10% weight loss at 6 months, respectively. The FDC also significantly improved waist circumference, hip circumference, body fat, visceral fat, systolic blood pressure, diastolic blood pressure, diabetes risk, and mortality risk, at 3 and 6 months. Moreover, the FDC seems to have better results in the following order: obese grade 3 ≈ obese grade 2 ˃ obese grade 1 ˃ overweight patients. Mild mouth dryness, anxiety, and headache were the main reported adverse events. CONCLUSION: Data suggest that the FDC is effective and well tolerated for the short-term therapy of overweight and obesity in Mexican patients.
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Histopathology of murine toxoplasmosis under treatment with dialyzable leukocyte extract.

BACKGROUND: Dialyzable leukocyte extracts (DLEs) contain molecules smaller than 10 kDa with biological activity in receptor organisms. Primarily, they participate in the regulation of the Th1 immune response, which is essential for the control of several intracellular infections, such as toxoplasmosis. This disease is associated with congenital infection, encephalitis or systemic infections in immunocompromised individuals. The clinical course of this infection fundamentally depends on a well-regulated immune response and timely treatment with the appropriate drugs. OBJECTIVE: The aim of this study was to evaluate the effect of treatment with a leukocyte extract, derived from crocodile lymphoid tissue, on the histopathology and brain parasite load in NIH mice that had been infected with cysts of Toxoplasma gondii (ME-49 strain). METHODS: The treatment was applied during the acute and chronic stages of the infection. Histopathological changes were evaluated in the ileum, liver and spleen at one, four and eight weeks after infection and in the brain at week 8. The parasite load was evaluated by counting the cysts of T. gondii found in the brain. FINDINGS: Compared to the control mouse group, the mice infected with T. gondii and under treatment with DLE showed less tissue damage, mainly at the intestinal, splenic and hepatic levels. In addition, a greater percentage of survival was observed, and there was a considerable reduction in the parasite load in the brain. CONCLUSIONS: The results suggest that DLE derived from crocodile is a potential adjunctive therapy in the conventional treatment of toxoplasmosis.

Histopathology of murine toxoplasmosis under treatment with dialyzable leukocyte extract

BACKGROUND Dialyzable leukocyte extracts (DLEs) contain molecules smaller than 10 kDa with biological activity in receptor organisms. Primarily, they participate in the regulation of the Th1 immune response, which is essential for the control of several intracellular infections, such as toxoplasmosis. This disease is associated with congenital infection, encephalitis or systemic infections in immunocompromised individuals. The clinical course of this infection fundamentally depends on a well-regulated immune response and timely treatment with the appropriate drugs. OBJECTIVE The aim of this study was to evaluate the effect of treatment with a leukocyte extract, derived from crocodile lymphoid tissue, on the histopathology and brain parasite load in NIH mice that had been infected with cysts of Toxoplasma gondii (ME-49 strain). METHODS The treatment was applied during the acute and chronic stages of the infection. Histopathological changes were evaluated in the ileum, liver and spleen at one, four and eight weeks after infection and in the brain at week 8. The parasite load was evaluated by counting the cysts of T. gondii found in the brain. FINDINGS Compared to the control mouse group, the mice infected with T. gondii and under treatment with DLE showed less tissue damage, mainly at the intestinal, splenic and hepatic levels. In addition, a greater percentage of survival was observed, and there was a considerable reduction in the parasite load in the brain. CONCLUSIONS The results suggest that DLE derived from crocodile is a potential adjunctive therapy in the conventional treatment of toxoplasmosis.