Association of FAAH p.Pro129Thr and COMT p.Ala72Ser with schizophrenia and comorbid substance use through next-generation sequencing: an exploratory analysis

Objective: Individuals with schizophrenia and substance use disorders have a poor prognosis and increased psychiatric symptoms. The present study aimed to explore the association of 106 genes in individuals with schizophrenia and comorbid substance use through a next-generation sequencing (NGS) analysis and different in silico algorithms. Methods: We included 105 individuals diagnosed with schizophrenia and a family history of schizophrenia, of whom 49 (46.67%) presented comorbid substance use. Using NGS, we sequenced 106 genes previously associated with schizophrenia. Logistic regression models were used to assess differences in allele frequencies, and a generalized gene-set analysis was performed at the gene level. Functional annotations were performed using different algorithms and databases. Results: We identified a total of 3,109 variants, of which 25 were associated with schizophrenia and comorbid substance use and were located in regulatory and coding regions. We found low-frequency variants in COMT p.Ala72Ser, independently of p.Val158Met, that were associated with substance use. The endocannabinoid functional variant FAAH p.Pro129Thr was also associated with substance use. Conclusions: Genetic variants of genes related to dopaminergic and cannabinoid neurotransmitter systems were associated with comorbid substance use in schizophrenia. Nevertheless, more studies with larger sample sizes are needed to confirm our findings.

Association of FAAH p.Pro129Thr and COMT p.Ala72Ser with schizophrenia and comorbid substance use through next-generation sequencing: an exploratory analysis.

OBJECTIVE: Individuals with schizophrenia and substance use disorders have a poor prognosis and increased psychiatric symptoms. The present study aimed to explore the association of 106 genes in individuals with schizophrenia and comorbid substance use through a next-generation sequencing (NGS) analysis and different in silico algorithms. METHODS: We included 105 individuals diagnosed with schizophrenia and a family history of schizophrenia, of whom 49 (46.67%) presented comorbid substance use. Using NGS, we sequenced 106 genes previously associated with schizophrenia. Logistic regression models were used to assess differences in allele frequencies, and a generalized gene-set analysis was performed at the gene level. Functional annotations were performed using different algorithms and databases. RESULTS: We identified a total of 3,109 variants, of which 25 were associated with schizophrenia and comorbid substance use and were located in regulatory and coding regions. We found low-frequency variants in COMT p.Ala72Ser, independently of p.Val158Met, that were associated with substance use. The endocannabinoid functional variant FAAH p.Pro129Thr was also associated with substance use. CONCLUSIONS: Genetic variants of genes related to dopaminergic and cannabinoid neurotransmitter systems were associated with comorbid substance use in schizophrenia. Nevertheless, more studies with larger sample sizes are needed to confirm our findings.

Longitudinal magnetic resonance evaluation of the schizophrenia model of neonatal lesion in the ventral hippocampus.

OBJECTIVE: To evaluate the progression by means of nuclear magnetic resonance of the lesion in the schizophrenia model of lesion of the ventral hippocampal nucleus (LVNH). METHOD: Magnetic resonance imaging (MRI) were performed in male Wistar rats, from 8 days postnatal to 139 days, in animals with LNHV and without lesion (sham). The MRI were carried out on a Variant 7 T equipment. The data were analyzed with the Amira software, for a voxel-based morphometric analysis. RESULTS: We observed the presence of hypersignals with a significant enhancement in the structures analyzed in the group with LVNH, and greater volume in the lateral ventricles, presenting a larger size of the lesion on day PD96 and significantly reducing on day PD139. CONCLUSIONS: We found a cell rearrangement during the progression of the lesion, which could be the effect of the activation of immune cells.

OBJETIVO: Evaluar mediante resonancia magnética (RM) la progresión de la lesión en el modelo de esquizofrenia de lesión del núcleo del hipocampo ventral (LNHV). MÉTODO: Se realizaron RM en ratas Wistar macho, desde los 8 días posnatales hasta los 139 días, en animales con LNHV y sin lesión (sham). Las RM se realizaron con un equipo Variant de 7 T. Los datos se analizaron con el software Amira para un análisis de morfometría basada en vóxels. RESULTADOS: Observamos hiperseñales con un realce significativo en las estructuras analizadas en el grupo con LNHV, y mayor volumen en los ventrículos laterales, presentando un mayor tamaño de la lesión el día PD96 y significativamente reducido en el día PD139. CONCLUSIONES: Encontramos un reacomodo celular durante la progresión de la lesión, lo cual podría ser efecto de la activación de las células inmunitarias.

Association between congenital heart disease and NKX2.5 gene polymorphisms: systematic review and meta-analysis.

Aim: To analyze the association of NKX2.5 gene with congenital heart disease (CHD), and to determine if the variants rs703752, rs3729753 and rs2277923 increase the risk for developing CHD. Materials & methods: PubMed, EBSCO and Web of Science databases were screened to identify eligible studies. Through a comprehensive meta-analysis software, the association between NKX2.5 gene variants and susceptibility of CHD was calculated by pooled odd ratio (ORs) and 95% CI. Results: We observed that the allelic model of rs703752 and rs2277923 increased the risk in the overall population: OR = 1.24; 95% CI: 1.00-1.55; Z p-value = 0.049; OR = 1.18; 95% CI: 0.01-1.37; Z p-value = 0.036; respectively. Conclusion: Our results suggested that the rs703752 and rs2277923 polymorphisms of the NKX2.5 gene are associated with CHD.

Risk of a syndemic between COVID-19 and dengue fever in southern Mexico.

A syndemic is the convergence of two or more diseases in the same space and time. In Mexico, the dengue epidemic is active and predominates in areas of the Pacific and the Gulf of Mexico; in turn, the COVID-19 epidemic severely affects the same areas as dengue fever. Given that both these diseases share many clinical manifestations, in areas where tropical diseases are endemic, it is important to make careful evaluations of the patient who consults for fever in order to establish a timely diagnosis. Laboratory diagnostic tests are necessary to take the pertinent measures for each patient. In Mexico, the risk of a syndemic between COVID-19 and dengue fever is high, and thus it that can collapse health systems. The states of southeastern Mexico and the Pacific region require special attention, since they have geographic, environmental and climatic conditions that favor the rapid spread of dengue and COVID-19. Simultaneous infection will worsen the epidemiological situation, and complicate the diagnosis, control and treatment of both diseases.

Una sindemia es la convergencia de dos o más enfermedades en un mismo espacio y tiempo. En México, la epidemia de dengue está activa y predomina en zonas del Pacífico y Golfo de México; por su parte, la epidemia de COVID-19 afecta severamente las mismas zonas que el dengue. Dado que estas enfermedades comparten numerosas manifestaciones clínicas, en zonas endémicas de enfermedades tropicales es importante la evaluación minuciosa del paciente que consulta por fiebre, para establecer oportunamente un diagnóstico correcto. Las pruebas de laboratorio son necesarias para llevar a cabo las medidas pertinentes en cada paciente. En México, el riesgo de sindemia de COVID-19 y dengue es alto, por lo que puede colapsar los sistemas de salud. Los estados del sureste y los colindantes con el Pacífico requieren especial atención ya que presentan condiciones geográficas, ambientales y climáticas que favorecen la rápida propagación del dengue y COVID-19. La infección simultánea empeorará la situación epidemiológica, complicará el diagnóstico, control y tratamiento de ambas enfermedades.

Riesgo de sindemia de COVID-19 y fiebre del dengue en el sur de México / Risk of a syndemic between COVID-19 and dengue fever in southern Mexico

Resumen Una sindemia es la convergencia de dos o más enfermedades en un mismo espacio y tiempo. En México, la epidemia de dengue está activa y predomina en zonas del Pacífico y Golfo de México; por su parte, la epidemia de COVID-19 afecta severamente las mismas zonas que el dengue. Dado que estas enfermedades comparten numerosas manifestaciones clínicas, en zonas endémicas de enfermedades tropicales es importante la evaluación minuciosa del paciente que consulta por fiebre, para establecer oportunamente un diagnóstico correcto. Las pruebas de laboratorio son necesarias para llevar a cabo las medidas pertinentes en cada paciente. En México, el riesgo de sindemia de COVID-19 y dengue es alto, por lo que puede colapsar los sistemas de salud. Los estados del sureste y los colindantes con el Pacífico requieren especial atención ya que presentan condiciones geográficas, ambientales y climáticas que favorecen la rápida propagación del dengue y COVID-19. La infección simultánea empeorará la situación epidemiológica, complicará el diagnóstico, control y tratamiento de ambas enfermedades.

Abstract A syndemic is the convergence of two or more diseases in the same space and time. In Mexico, the dengue epidemic is active and predominates in areas of the Pacific and the Gulf of Mexico; in turn, the COVID-19 epidemic severely affects the same areas as dengue fever. Given that both these diseases share many clinical manifestations, in areas where tropical diseases are endemic, it is important to make careful evaluations of the patient who consults for fever in order to establish a timely diagnosis. Laboratory diagnostic tests are necessary to take the pertinent measures for each patient. In Mexico, the risk of a syndemic between COVID-19 and dengue fever is high, and thus it that can collapse health systems. The states of southeastern Mexico and the Pacific region require special attention, since they have geographic, environmental and climatic conditions that favor the rapid spread of dengue and COVID-19. Simultaneous infection will worsen the epidemiological situation, and complicate the diagnosis, control and treatment of both diseases.

Effects of Resistant Starch Ingestion on Postprandial Lipemia and Subjective Appetite in Overweight or Obese Subjects.

Reports surrounding the role of resistant starch (RS) on postprandial lipemia in humans are scarce. The aim of the present study is to examine the effects of resistant starch on the postprandial lipemic response, subjective measures of appetite, and energy intake in overweight and obese subjects. In a randomized, single-blind, crossover study, 14 overweight/obese participants ate a high-fat breakfast (679 kcal, 58% from fat) and a supplement with native banana starch (NBS), high-amylose maize starch (HMS), or digestible maize starch (DMS) on three separate occasions. All supplements provided were matched by the available carbohydrate content, and the RS quantity in NBS and HMS supplements was identical. Appetite was estimated using visual analogue scale (VAS) and an ad libitum test meal. Postprandial glycemia, triglycerides, cholesterol, high-density lipoprotein (HDL) cholesterol, and insulin excursions did not differ between treatments. Subjective appetite measures of satiety were significantly increased after HMS; however, no effects on energy intake were observed during the ad libitum test meal. These findings suggest that a single acute dose of RS cannot be expected to improve postprandial lipemia in subjects with overweight or obesity on a high-fat meal. However, the potential benefits of long-term supplementation should not be ruled out based on these results.

EXPLORATORY ANALYSIS OF POLYGENIC RISK SCORES FOR PSYCHIATRIC DISORDERS: APPLIED TO DUAL DIAGNOSIS.

BACKGROUND: Concurrence of substance use disorders (SUDs) is high in individuals with psychiatric illnesses; more importantly, individuals with both disorders (dual diagnosis) have more severe symptoms. Psychiatric disorders have been proposed to share a genetic susceptibility with SUDs. To explore this shared genetic susceptibility, we analyzed whether any of the polygenic risk scores (PRSs) for psychiatric disorders could be associated to dual diagnosis in patients with schizophrenia (SCZ) or bipolar disorder (BD). METHODS: We included 192 individuals of Mexican ancestry: 72 with SCZ, 53 with BD, and 67 unrelated controls without psychiatric disorders. We derived calculations of PRS for autism spectrum disorders, attention-deficit/hyperactive disorder, BD, major depression, and SCZ using summary genome-wide association statistics previously published. RESULTS: We found that dual diagnosis had a shared genetic susceptibility with major depressive disorder (MDD) and SCZ; furthermore, in individuals with BD, dual diagnosis could be predicted by PRS for MDD. CONCLUSIONS: Our results reinforce the notion that individuals with dual diagnosis have a higher genetic susceptibility to develop both disorders. However, analyses of larger sample sizes are required to further clarify how to predict risks through PRS within different populations.

Exploratory analysis of polygenic risk scores for psychiatric disorders: Applied to dual diagnosis

Background Concurrence of substance use disorders (SUDs) is high in individuals with psychiatric illnesses; more importantly, individuals with both disorders (dual diagnosis) have more severe symptoms. Psychiatric disorders have been proposed to share a genetic susceptibility with SUDs. To explore this shared genetic susceptibility, we analyzed whether any of the polygenic risk scores (PRSs) for psychiatric disorders could be associated to dual diagnosis in patients with schizophrenia (SCZ) or bipolar disorder (BD). Methods We included 192 individuals of Mexican ancestry: 72 with SCZ, 53 with BD, and 67 unrelated controls without psychiatric disorders. We derived calculations of PRS for autism spectrum disorders, attention-deficit/hyperactive disorder, BD, major depression, and SCZ using summary genome-wide association statistics previously published. Results We found that dual diagnosis had a shared genetic susceptibility with major depressive disorder (MDD) and SCZ; furthermore, in individuals with BD, dual diagnosis could be predicted by PRS for MDD. Conclusions Our results reinforce the notion that individuals with dual diagnosis have a higher genetic susceptibility to develop both disorders. However, analyses of larger sample sizes are required to further clarify how to predict risks through PRS within different populations.

Association between APOE polymorphisms and lipid profile in Mexican Amerindian population.

BACKGROUND: Apolipoprotein E (ApoE) is a glycoprotein that plays an important role in lipid homeostasis at both cerebral and systemic levels. Moreover, the differential distribution of APOE gene alleles among different populations, means that ApoE isoforms could have different effects on lipids metabolism. The present study aims to evaluate the relationship between APOE gene alleles and the lipid profile in a Mexican Amerindian (MA) population. METHODS: This study included 1997 MA individuals of different ethnicities distributed throughout different states of Mexico. All individuals underwent anthropometric measurements as well as laboratory tests including fasting glucose (FG), total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). TaqMan® probe genotyping assays were used to genotype APOE. The Kruskal-Wallis test was performed to determine the correlation between APOE gene alleles and genotypes and the biochemical variables measured. RESULTS: Among the biochemical variables analyzed, only the HDL-C and LDL-C levels showed statistical differences (p-value < .05) between individuals carrying different APOE alleles. For HDL-C, individuals carrying the E2 allele had higher HDL-C levels, followed by individuals carrying the E3 allele and carriers of the E4 allele presented the lowest levels of HDL-C (E2 > E3 > E4). This relationship was inversed for LDL-C levels (E2 < E3 < E4). Nevertheless, the difference of HDL-C levels between APOE-E3 and APOE-E4 carriers remained only in obese individuals. CONCLUSIONS: Our results suggest that APOE gene genotypes play an important role in the differential modulation of lipid profiles in the MA population with obesity.

Identification of gene ontology and pathways implicated in suicide behavior: Systematic review and enrichment analysis of GWAS studies.

Multiple large-scale studies such as genome-wide association studies (GWAS) have been performed to identify genetic contributors to suicidal behaviors (SB). We aimed to summarize and analyze the information obtained in SB GWAS, to explore the biological process gene ontology (GO) of genes associated with SB from GWAS, and to determine the possible implications of the genes associated with SB in Kyoto encyclopedias of genes and genomes (KEGG) biological pathways. The articles included in the analysis were obtained from PubMed and Scopus databases. Enrichment analyses were performed in Enrichr to evaluate the KEGG pathways and GO of the genes associated with SB of GWAS. The findings of biological process GO analysis showed 924 GO involved in genes related with SB; of those, the regulation of glucose import in response to insulin stimulus, regulation of protein localization to plasma membrane, positive regulation of endopeptidase activity, heterotypic cell-cell adhesion, regulation of cardiac muscle cell contraction, positive regulation of protein localization to plasma membrane, and positive regulation of protein localization to cell periphery biological process GO showed significant statistical association. Furthermore, we obtained 130 KEGG pathways involved in genes related with SB, which Aldosterone synthesis and secretion, Rap1 signaling pathway and arrhythmogenic right ventricular cardiomyopathy pathways showed a significant statistical association. These findings give a better perspective of the biological participation of genes associated with SB, which will be important to perform adequate strategies to prevent and treat SB.

Prevalence and correlations between suicide attempt, depression, substance use, and functionality among patients with limb amputations.

Most patients undergoing limb amputations suffer significant emotional changes. The aim of this study was to estimate the prevalence of suicide attempts and depression in a sample of Mexican patients with limb amputations and, second, to determine whether the patients' functionality correlates with the presence of depression. We studied 40 patients who had undergone a limb amputation. The suicide attempt was evaluated using the Suicide Intent Scale. The depression was assessed using the Hamilton Depression Rating Scale, whereas the functionality of the patients was measured using the Functional Independence Measure. In this sample, 90% were men, whereas only 10% were women. In terms of the suicide behavior, we identified suicide attempts in 27.5% of the patients. The rate of depression was 92.5%. In the Functional Independence Measure, we observed that 57.5% of the patients showed complete dependence. Finally, a significant correlation was found between depression and functionality (r=-0.75, P<0.001). The findings of the present study highlight the high incidence of suicide attempts and depression in Mexican patients with limb amputations. Also, we identified a correlation between the lack of functional independence and depression. Therefore, holistic interventions are necessary in these patients: rehabilitation therapy to increase their functionality, and psychological and pharmacology therapy to decrease suicidal behavior and depression. Finally, more studies using larger samples are necessary to obtain conclusive results.

The role of the Cys23Ser (rs6318) polymorphism of the HTR2C gene in suicidal behavior: systematic review and meta-analysis.

The polymorphisms of the serotonin receptor 2C (HTR2C) gene have been proposed to influence suicidal behavior. The aim of our study was to explore the role of the HTR2C gene variant Cys23Ser (rs6318) in the pathogenesis of suicidal behavior through a systematic review and meta-analysis. The search was performed using EBSCO and PubMed databases. To be included in the analysis, the studies had to evaluate suicidal behavior (attempted, ideation, or completed suicide). The results of the meta-analysis were expressed as odds ratios (ORs). Because HTR2C lies on chromosome X, pooled ORs were calculated, respectively, for each of the models used, namely: allelic, homozygous, dominant, and recessive for the female group and allelic for the male group. The meta-analysis comprised 3867 individuals, including 1668 cases and 2199 controls. The HTR2C Cys23Ser (rs6318) polymorphism did not show a significant association with suicidal behavior either in women (OR: 0.75; 95% confidence interval: 0.55-1.00) or in men (OR: 0.89; 95% confidence interval: 0.64-1.23). Similarly, nonsignificant associations were observed for all of the genetic models used in any of the populations/subgroups studied. Our findings suggest that the rs6318 (Cys23Ser) polymorphism is not associated with suicidal behavior. However, because of the study limitations, we suggest more researches should be performed, increasing the sample sizes and statistical power, to determine the association between the rs6318 variant and suicidal behavior.

Acute Consumption of Resistant Starch Reduces Food Intake but Has No Effect on Appetite Ratings in Healthy Subjects.

Previous studies have shown the benefits of native banana starch (NBS) supplementation in improving glucose metabolism and reducing body weight (BW) in humans. However, the effect of this starch on appetite regulation is unknown. The aim of this study was to examine the effects of NBS rich resistant starch on subjective measurements of appetite, energy intake, and appetite hormones in healthy subjects. Postprandial glucose and insulin responses were also assessed. In a randomized, single-blind, crossover study, 28 healthy young subjects consumed a beverage containing either 40 g of NBS or 40 g of digestible corn starch (DCS) on two separate occasions. Effects on appetite were estimated using visual analogue scales (VAS) and satiety hormone responses. At the end of the intervention, participants were provided with a pre-weighed ad libitum homogeneous test meal. After a washout period of 1 week, subjects received the alternative treatment. NBS supplementation induced a reduction in food intake, glucose area under the curve (AUC)-180 min, and insulin AUC-180 min. However, there was no associated effect on the subjective appetite ratings or gut hormones. NBS supplementation may help to reduce meal size and control BW.

Decrease in brain-derived neurotrophic factor at plasma level but not in serum concentrations in suicide behavior: A systematic review and meta-analysis.

INTRODUCTION: Suicide is known as a major health concern worldwide. There is evidence for the role of brain-derived neurotrophic factor (BDNF) in suicide behavior. Therefore, this factor has been proposed as a biomarker for suicide behavior. Clinical studies have measured BDNF concentrations at central and peripheral levels. As a consequence, the aim of this study was to assess BDNF levels in blood plasma and serum to see whether there is a difference in concentrations in patients with suicide behavior when compared to those in controls, using a meta-analysis approach. METHODS: We conducted a systematic review and meta-analysis. The search strategy was performed using three databases: PubMed, EBSCO and ScienceDirect. The meta-analysis included a total of nine case-control studies, six measured the BDNF level in serum and three in plasma in suicide behavior. RESULTS: A decrease in BDNF levels in plasma was observed (d = -0.73, 95% CI -1.42 to -0.03 pg/ml). In the case of serum concentrations, no BDNF differences were encountered between cases and controls (d = 0.09, 95% CI -0.31 to 0.13 ng/ml, p(Q) = .92). CONCLUSIONS: According to the results found in the present meta-analysis, the plasma BDNF level could be suggest as a potential biomarker in suicide behavior. However, since the number of studies included in the analysis is limited, a larger number is necessary to determine conclusively the role of BDNF as a biomarker in suicide behavior.

Isobolographic Analyses of Proglumide-Celecoxib Interaction in Rats with Painful Diabetic Neuropathy.

Preclinical Research The aim of the present study was to analyze the antihyperalgesic and antiallodynic interaction between the non-selective cholecystokinin (CCK) antagonist receptor, proglumide, and the selective cyclooxygenase-2 inhibitor, celecoxib in streptozotocin (STZ)-induced diabetic rats. Hyperalgesia was evaluated in the formalin test and tactile allodynia using von Frey filaments. Isobolographic analyses were employed to define the nature of the compound interactions, using a fixed dose ratio (0.5:0.5). Proglumide (20-160 mg/kg) and celecoxib (0.3-30 mg/kg) in these fixed dose ratio combinations induced dose-dependent antihyperalgesia and an antiallodynic effect in diabetic rats. ED40 values were calculated for the treatments and an isobologram was constructed. Theoretical ED40 values for combination proglumide-celecoxib estimated from the isobolograms for antihyperalgesic and antiallodynic activity (30.50 ± 1.90 mg/kg and 45.81 ± 4.55 mg/kg, respectively) were obtained, while experimental ED40 values for this antihyperalgesic and antiallodynic combined effect (13.83 ± 0.65 mg/kg and 17.74 ± 3.57 mg/kg; respectively) were significantly different. Coadministration of proglumide-celecoxib showed an interaction index value of 0.45 ± 0.03 for the antihyperalgesic effect and 0.39 ± 0.08 for the antiallodynic activity, indicating a synergistic interaction. These data suggest that proglumide and celecoxib can interact synergistically to reduce hyperalgesic and allodynic behaviors in diabetic neuropathy. This combination could be useful to treat neuropathic pain in diabetic patients. Drug Dev Res 78 : 116-123, 2017. ©2017 Wiley Periodicals, Inc.

Protective Action of Carica papaya on ß-Cells in Streptozotocin-Induced Diabetic Rats.

The aim of the present study was to investigate the effect of C. papaya L. leaf extract (CPLE) on pancreatic islets in streptozotocin (STZ)-induced diabetic rats, as well as on cultured normal pancreatic cells with STZ in the medium. CPLE (3-125 mg/Kg) was administered orally for 20 days, while a group of diabetic rats received 5 IU/Kg/day of insulin. At the end of the treatment the rats were sacrificed. Blood was obtained to assess glucose and insulin levels. The pancreas was dissected to evaluate ß cells by immunohistochemistry. In addition, normal pancreatic cells were cultured in a medium that included CPLE (3-12 mg). One half of the cultured cells received simultaneously CPLE and STZ (6 mg), while the other half received CPLE and five days later the STZ. After three days of incubation, insulin was assayed in the incubation medium. The CPLE administered to diabetic rats improved the fasting glycemia and preserved the number and structure of pancreatic islets. However, when CPLE was added to pancreatic cells in culture along with STZ, the insulin concentration was higher in comparison with the cells that only received STZ. In conclusion, the CPLE preserves the integrity of pancreatic islets, improves the basal insulin secretion and protects cultured cells from the adverse effects of STZ.

Effects of Acute Ingestion of Native Banana Starch on Glycemic Response Evaluated by Continuous Glucose Monitoring in Obese and Lean Subjects.

An abnormal glycemic profile, including postprandial glycemia and acute glucose spikes, precedes the onset of overt diabetes in obese subjects. Previous studies have shown the beneficial effects of chronic native banana starch (NBS) supplementation. In this study, we examined the effects of acute ingestion of NBS on glycemic profiles by means of continuous glucose monitoring in obese and lean subjects. In a crossover study, obese and lean subjects consumed beverages containing either 38.3 g of NBS or 38.3 g of digestible corn starch (DCS) twice daily during 4 days. On day 5, a 3-h meal tolerance test (MTT) was performed to evaluate glucose and insulin responses. After 1 week of washout period, treatments were inverted. NBS supplementation reduced the 48-h glycemia AUC in lean, obese, and in the combined group of lean and obese subjects in comparison with DCS. Postprandial glucose and insulin responses at MTT were reduced after NBS in comparison with DCS in all groups. However, no changes were observed in glycemic variability (GV) indexes between groups. In conclusion, acute NBS supplementation improved postprandial glucose and insulin responses in obese and lean subjects during 48 h of everyday life and at MTT. Further research to elucidate the mechanism behind these changes is required.

Celecoxib reduces hyperalgesia and tactile allodynia in diabetic rats.

BACKGROUND: In the present study we determined the antihyperalgesic and antiallodynic effect of celecoxib in diabetic rats as well as the possible participation of opioid receptors in the mechanism of action of celecoxib in these rats. METHODS: Experimental diabetes was induced by streptozotocin. Formalin (0.5%) was used to produce hyperalgesia in non-diabetic and diabetic rats. von Frey filaments were used to determine the 50% withdrawal threshold in diabetic rats. RESULTS: Oral administration of celecoxib (0.3-30 mg/kg) reduced formalin-induced nociceptive behavior during phase 2. Systemic pre-treatment (-10 min) with naltrexone (3mg/kg) prevented celecoxib-induced antihyperalgesia in formalin-treated diabetic rats. Furthermore, naltrexone as well as the δ and κ opioid receptor antagonists naltrindole (3mg/kg) and 5'-guanidino naltrindole (1mg/kg), respectively, fully prevented celecoxib-induced antihyperalgesia (10mg/kg) in formalin-treated non-diabetic and diabetic rats. Furthermore, celecoxib (0.3-30 mg/kg) produced an antiallodynic effect in diabetic rats. Pre-treatment with naltrexone (3mg/kg) fully prevented the antiallodynic effect of celecoxib at 0.3, 3 and 10mg/kg. In contrast, this dose of naltrexone only partially prevented the antiallodynic effect of celecoxib 30 mg/kg. Naltrexone and naltrindole (3mg/kg), but not 5'-guanidino naltrindole (1mg/kg), fully prevented the antiallodynic effect of celecoxib in diabetic rats. CONCLUSIONS: Data suggest that celecoxib produces an antihyperalgesic and antiallodynic effect in diabetic rats. These effects seem to result from activation of µ, δ and κ opioid receptors for antinociception and µ and δ for antiallodynia. Celecoxib could be useful to treat neuropathic pain in diabetic patients.

Association study between the MDR1 gene and clinical characteristics in schizophrenia

Objective: Schizophrenia is a complex psychiatric disorder, characterized by disturbed patterns of thought and affecting 0.3-2.0% of the world population. Previously, the multidrug resistance 1 (MDR1) gene has been associated with schizophrenia in treatment response studies in psychotic patients. The aim of this study was to determine the association between MDR1 gene polymorphisms and clinical characteristics in patients with schizophrenia. Methods: Positive and negative symptoms of schizophrenia were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) in 158 Mexican patients with schizophrenia. Analyses of MDR1 gene polymorphisms were performed using TaqMan technology. A multivariate ANOVA was performed with MDR1 polymorphisms and gender as independent variables. Results: Males with the G/G genotype of MDR1 rs2032582 presented significantly higher levels of delusions (p = 0.02). When comparing female vs. male groups, the difference was statistically significant (p = 0.0003). Analyses of the MDR1 gene rs1045642 variant showed no significant differences. Conclusion: Our findings suggest that male carriers of the G allele of variant rs2032582 exhibit greater severity of delusions; however, these results should be taken as preliminary, and replication studies in other populations of different ethnic origins are required to confirm these findings. .