Prevalence of Drug-Resistant Tuberculosis in HIV-Positive and Diabetic Patients in Sinaloa, Mexico: A Retrospective Cross-Sectional Study.

Tuberculosis (TB) is a disease caused by the bacillus Mycobacterium tuberculosis (MTB). Human immunodeficiency virus (HIV) infection and type 2 diabetes mellitus (T2DM) are among the main risk factors for the development of TB and increase the risk of drug-resistant TB developing (DR-TB). The aim of this study was to estimate the prevalence of DR-TB in patients with HIV or T2DM in Sinaloa, Mexico. This was an observational and cross-sectional study. The analysis was conducted using the clinical data of patients registered on the National Epidemiological Surveillance System for TB (SINAVE/PUI-TB) platform with a presumed diagnosis of TB during 2019 to 2021 in Sinaloa, Mexico. The prevalence of DR-TB was estimated in HIV and T2DM patients, as well as the odds ratios for their sociodemographic variables, using the Chi-square test. There were 2, 4, and 4 TB-HIV cases and 2, 6, and 9 TB-T2DM cases during 2019, 2020, and 2021, respectively, whereas there were 2 and 1 DRTB-HIV and DRTB-T2DM cases, respectively. The results indicated that the WHO guidelines for DR-TB were not properly applied to this high-risk population. Hence, the appropriate application of guidelines for TB and DR-TB detection in these patients needs to be immediately implemented by the State health system.

Design, synthesis, in silico, and in vitro evaluation of benzylbenzimidazolone derivatives as potential drugs on α-glucosidase and glucokinase as pharmacological targets.

Benzimidazolones have shown biological activities, including antihyperglycemic and hypoglycemic, by inhibiting or activating of α-glu and GK. The aim of this study is the rational design of compounds using in silico assays to delimitate the selection of structures to synthesize and the in vitro evaluation of benzimidazolone derivatives in blood glucose control. A docking of 23 benzimidazolone derivatives was performed; selecting the compounds with better in silico profiles to synthesize by microwave-irradiation/conventional heat and evaluate in enzymatic in vitro evaluation. Compounds 2k, 2m, 2r, and 2s presented the best in silico profiles, showing good affinity energy (-10.9 to -8.6 kcal mol-1) and binding with catalytic-amino acids. They were synthesized at 70 °C and 24 h using DMF as the solvent and potassium carbonate (yield: 22-38%). The results with α-glu showed moderate inhibition of 2k (14 ± 1.23-29 ± 0.45), 2m (12 ± 2.21-36 ± 0.30), 2r (7 ± 2.21-13 ± 1.34), and 2s (11 ± 0.74-35 ± 2.95) at evaluated concentrations (0.1 to 100 µg mL-1). The GK activation assay showed an enzymatic activity increase; compound 2k increased 1.31 and 2.83 more than normal activity, 2m (2.13-fold), 2s (2.86 and 3.74-fold) at 100 and 200 µg mL-1 respectively. The present study showed that the 2s derivative presents moderate potential as an α-glu inhibitor and a good activator potential of GK, suggesting that this compound is a good candidate for blood glucose control through antihyperglycemic and hypoglycemic mechanisms.

Chitosan as an Outstanding Polysaccharide Improving Health-Commodities of Humans and Environmental Protection.

Public health, production and preservation of food, development of environmentally friendly (cosmeto-)textiles and plastics, synthesis processes using green technology, and improvement of water quality, among other domains, can be controlled with the help of chitosan. It has been demonstrated that this biopolymer exhibits advantageous properties, such as biocompatibility, biodegradability, antimicrobial effect, mucoadhesive properties, film-forming capacity, elicitor of plant defenses, coagulant-flocculant ability, synergistic effect and adjuvant along with other substances and materials. In part, its versatility is attributed to the presence of ionizable and reactive primary amino groups that provide strong chemical interactions with small inorganic and organic substances, macromolecules, ions, and cell membranes/walls. Hence, chitosan has been used either to create new materials or to modify the properties of conventional materials applied on an industrial scale. Considering the relevance of strategic topics around the world, this review integrates recent studies and key background information constructed by different researchers designing chitosan-based materials with potential applications in the aforementioned concerns.

In Silico Prediction of Hub Genes Involved in Diabetic Kidney and COVID-19 Related Disease by Differential Gene Expression and Interactome Analysis.

Diabetic kidney disease (DKD) is a frequently chronic kidney pathology derived from diabetes comorbidity. This condition has irreversible damage and its risk factor increases with SARS-CoV-2 infection. The prognostic outcome for diabetic patients with COVID-19 is dismal, even with intensive medical treatment. However, there is still scarce information on critical genes involved in the pathophysiological impact of COVID-19 on DKD. Herein, we characterize differential expression gene (DEG) profiles and determine hub genes undergoing transcriptional reprogramming in both disease conditions. Out of 995 DEGs, we identified 42 shared with COVID-19 pathways. Enrichment analysis elucidated that they are significantly induced with implications for immune and inflammatory responses. By performing a protein-protein interaction (PPI) network and applying topological methods, we determine the following five hub genes: STAT1, IRF7, ISG15, MX1 and OAS1. Then, by network deconvolution, we determine their co-expressed gene modules. Moreover, we validate the conservancy of their upregulation using the Coronascape database (DB). Finally, tissue-specific regulation of the five predictive hub genes indicates that OAS1 and MX1 expression levels are lower in healthy kidney tissue. Altogether, our results suggest that these genes could play an essential role in developing severe outcomes of COVID-19 in DKD patients.

Effect of 4-hydroxychalcone as preventive and curative treatment in Wistar rats with liver injury.

The increasing prevalence and complications related to liver diseases (caused by infection, toxic agents, or metabolic syndrome), together with insufficient existence of treatments, make evident the need for better therapeutic alternatives. Therefore, the aim of this study was to determine the effect of 4-hydroxychalcone (4-HC) as preventive and curative treatment in acute and chronic liver injury, respectively. Liver damage was induced with carbon tetrachloride (CCl4) in Wistar rats. Rats were divided into two groups: (1) acute liver injury and (2) chronic liver injury. In turn, each group was divided into four subgroups: (i) control (water); (ii) dimethyl sulfoxide 10%; (iii) CCl4; and (iv) 4-HC. The pre-treatment with 4-HC decreased transaminases, IL-6 serum levels, and hepatic malondialdehyde, increased IL-10 serum levels and hepatic glutathione, and decreased liver damage (necrosis, steatosis, and inflammatory infiltrate). In contrast, treatment with 4-HC after the induction of chronic liver injury decreased IL-6 serum levels and liver damage (steatosis, inflammatory infiltrate, ballooning cells, steatofibrosis, and fibrosis degree). Thus, the 4-HC treatment is proposed as a preventive treatment against acute liver injury; moreover, these results suggested the potential of 4-HC as a curative treatment against chronic liver injury, but other scheme treatments must be evaluated in future.

Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain rats.

In the present study the interaction of cannabinoid, PhAR-DBH-Me [(R, Z)-18-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-18-oxooctadec-9-en-7-ylphenyl-acetate] and tramadol in two neuropathy models, as well as their possible toxic effects, was analyzed. The anti-allodynic effect of PhAR-DBH-Me, tramadol, or their combination, were evaluated in neuropathic rats. Furthermore, the effective dose 35 (as the 35 % of the anti allodynic effect) was calculated from the maximum effect of each drug. Moreover, the isobolographic analysis was performed to determine the type of interaction between the drugs. A plasma acute toxicity study was carried out to assess the hepatic, renal, and heart functions after an individual or combined administration of the drugs, as well as histology using the hematoxylin-eosin or Masson-trichome method. PhAR-DBH-Me, tramadol, and their combination produced an antiallodynic effect on spinal nerve ligation (SNL) and cisplatin-induced neuropathic pain in rats. Moreover, PhAR-DBH-Me and tramadol combination showed a synergistic interaction in neuropathic pain rats induced by SNL but not for cisplatin-induced neuropathy. On the other hand, changes in renal and hepatic functions were not observed. Likewise, analysis of liver, kidney and heart histology showed no alterations compared with controls. Results show that the combination of PhAR-DBH-Me and tramadol attenuates the allodynia in SNL rats; the acute toxicology analysis suggests that this combination could be considered safe in administered doses.

Evaluation of sucrose-enriched diet consumption in the development of risk factors associated to type 2 diabetes, atherosclerosis and non-alcoholic fatty liver disease in a murine model.

Overconsumption of sucrose, the main contributor of the total added sugar intake in the world, has been associated with negative metabolic effects related to non-communicable diseases. However, this relationship continues to be a controversial topic and further studies are needed. The aim of this study was to evaluate the sucrose-enriched diet consumption in the development of risk factors associated with type 2 diabetes, atherosclerosis and non-alcoholic fatty liver disease in a murine model. Sucrose-enriched diet-fed rats showed a decrease in food, lipids and protein intake as well as in serum total cholesterol levels, an increase in carbohydrates intake, glucose, insulin, triglycerides, VLDL-c and HDL-c levels and a greater degree of insulin resistance, steatosis and non-alcoholic steatohepatitis. Our results show that sucrose-enriched diet consumption during 25 weeks contribute to the development of risk factors associated with type 2 diabetes, atherosclerosis and non-alcoholic fatty liver disease in male Wistar rats.

Synthesis and molecular docking studies of imines as α-glucosidase and α-amylase inhibitors.

Imine functionality is found in many compounds with important biological activity. Thus, the development of novel synthetic approaches for imines is important. In this work, it is propose an easy, eco-friendly and straightforward synthesis pathway of aryl imines under microwave irradiation catalyzed by Alumina-sulfuric acid. In addition, the in vitro enzymatic inhibition, antioxidant activity and molecular docking studies were performed. The aryl imines were isolated with yields in the range of 37-94%. All aryl imines synthesized were evaluated for in vitro inhibitory potential against α-glucosidase and α-amylase enzymes and the results exhibited that the most of the compounds displayed inhibitory activity against both enzymes. The (E)-1-(4-nitrophenyl)-N-(pyridin-2-yl)methanimine (3d) was 1.15-fold more active than acarbose against α-amylase whilst the (E)-1-phenyl-N-(pyridin-2-yl)methanimine (3c) displayed similar activity that acarbose against α-glucosidase. The molecular docking studies in α-glucosidase and α-amylase reveal that aryl imines mainly establish an H-bond with the R2-subtituent and hydrophobic interactions with the R1-subtituent. The docking analysis reveals these synthetic aryl imines 3d-i interact in same active site than acarbose drug in both enzymes.

Therapeutic effect of treatment with metformin and/or 4-hydroxychalcone in male Wistar rats with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Despite the impact of this pathology in the population, nowadays there is no specific treatment for this disease, focusing its treatment on risks factors. However, it is imperative the existence of a specific treatment, due to this, the aim of this study was to determine the therapeutic effect of treatment with metformin, 4-hydroxychalcone or co-treatment on male Wistar rats with NAFLD. Wistar rats were divided into two groups with free access to either tap water or 50% sucrose (NAFLD) during 25 weeks. After 20 weeks of induction each were divided into four groups that received daily p.o. administration of: i) saline solution (1 ml); ii) metformin (200 mg/kg/day); iii) 4-hydroxychalcone (80 mg/kg/day) and i.v.) co-treatment (metformin plus 4-hydroxychalcone at the doses mentioned above), for 5 weeks. In healthy rats: metformin and co-treatment modified food and total caloric intake and induced diarrhea; but none of the treatments changed the other parameters evaluated. Meanwhile in rats with NAFLD: i) metformin inhibited hepatic total cholesterol and TGF-ß, increased diarrhea frequency, and slightly decreased liver steatosis, and fibrosis; ii) 4-hydroxychalcone decreased IL-6, TNF-α and TGF-ß, increased IL-10, and markedly decreased liver steatosis and fibrosis; and iii) co-treatment markedly decreased food intake, total caloric intake, and body weight, increased diarrhea; increased IL-10, showing and intermediate effect on decrease TNF-α, TGF-ß, liver steatosis and fibrosis. Our results showed that 4-hydroxychalcone treatment was the most effective among the treatments tested against NAFLD.

Potential vascular α1-adrenoceptor blocking properties of metformin in rat aorta and tail artery.

Metformin is a widely used drug for the treatment of type 2 Diabetes Mellitus. Several studies have also suggested that metformin decreases blood pressure; although an interaction with α-adrenoceptors has been proposed, this mechanism needs to be further investigated. Since α1-adrenoceptors play a significant role to regulate vascular tone, this study has analysed the potential ability of metformin to block α1-adrenoceptors in rat aorta and tail artery. For this purpose, the contractile responses induced by noradrenaline, methoxamine, and phenylephrine were determined in the absence or presence of metformin in rat aorta and tail artery rings. In both arteries, noradrenaline, methoxamine, and phenylephrine produced concentration-dependent contractile responses. Interestingly, the contractile responses to noradrenaline, methoxamine, and phenylephrine were significantly and differentially blocked by metformin (1, 3.1 and/or 10 mM) but not by vehicle. These results suggest that metformin is capable to block α1-adrenoceptors and may explain, at least in part, the anti-hypertensive effect observed in several clinical trials.

Histopathological and biochemical changes in the development of nonalcoholic fatty liver disease induced by high-sucrose diet at different times.

The high intake of sweetened drinks is associated with obesity and insulin resistance. These pathologies are directly related to the development of nonalcoholic fatty liver disease (NAFLD), considered a condition of metabolic syndrome (MS). Due to their increasing worldwide prevalence, experimental animal models have been developed to gain a better understanding of its physiopathology; notwithstanding, few studies have evaluated its progression in association with MS and ingestion of sweetened drinks. Therefore, the aim of this study was to understand the pathophysiologic characteristics of NAFLD related to sucrose concentration and time of ingestion in rats. Wistar rats were divided into 2 groups with free access to either tap water or 30% sucrose, and euthanized at 12, 16, or 20 weeks; and 2 additional groups were given free access to either 40% or 50% sucrose and were euthanized at 20 weeks. Biochemical parameters and levels of serum cytokines were measured, and histology was performed. Ingestion of 30% sucrose induced liver steatosis until 16 weeks (grade 2) and 20 weeks (grade 3). Meanwhile, during 20 weeks, 40% sucrose induced grade 5 of nonalcoholic steatohepatitis (NASH) and 50% sucrose induced grade 6 of NASH and fibrosis. This study demonstrated that increasing time of induction and concentration of sucrose ingestion resulted in a higher grade of NAFLD.

Organochlorine Pesticides in Gonad, Brain, and Blood of Mice in Two Agricultural Areas of Sinaloa.

The adverse effect of pesticides on non-target wildlife and human health is a primary concern in the world, but in Mexico, we do not know which wildlife species are at the greatest risk. The aim of this study was to determine organochlorine pesticides in mice of two agricultural fields in Sinaloa, Culiacan and Guasave. Procedures of extraction, analysis, and quantification were followed according to the modified EPA 8081b method. In three mouse tissues (gonad, brain, and blood), γBHC and decachlorobiphenyl with a frequency higher than 50% and endosulfan sulfate with 43% were observed. The wildlife fauna living in agricultural areas are at great risk due to: (1) diversity of the chemicals used for pest control, like mice, and (2) variety of organochlorine pesticides in direct or indirect contact with non-target organisms, affecting the health of animals and humans (toxic effects and accumulation).

Synthesis of new quinazolin-2,4-diones as anti-Leishmania mexicana agents.

The quinazolin-2,4-dione moiety is found in many compounds with important biological activities making it a target for its synthesis. In this work, a one-pot three-step synthesis of new quinazolin-2,4-diones from phthalic anhydrides and their activity against Leishmania mexicana are described. The new quinazolin-2,4-diones were isolated with yields in the range of 32-70 %. All compounds displayed lower cytotoxicity in RAW 264.7 macrophage over miltefosine. Compound 6,7-dichloro-3-phenylquinazoline-2,4(1H,3H)-dione (6e) displayed an attractive profile which includes anti-Leishmania mexicana activity ([Formula: see text] [Formula: see text]M), much lower cytotoxic activity ([Formula: see text] [Formula: see text]M) and a high selective index ([Formula: see text]) proving to be superior to miltefosine.

Protective effect of thymic humoral factor on porcine serum-induced hepatic fibrosis and liver damage in Wistar rats.

INTRODUCTION: Immunomodulatory drugs have been reported to have anti-inflammatory and anti-fibrotic properties. Thymic humoral factor (THF), a peptide produced in the thymus, causes a potent immunomodulatory effect on different components of the immune system. OBJECTIVE: To evaluate the effect of THF on different stages of liver damage and fibrosis induced in rats through the administration of porcine serum (PS). MATERIAL AND METHODS: PS-induced liver fibrosis models serve as a primarily immunological mechanism in the development of liver damage and fibrosis. RESULTS: The intraperitoneal administration of THF in rats with PS-induced liver damage produced a reduction of ALT and AST after 60 days. Histopathological changes in liver sections showed an improved histological appearance and lower % of fibrosis after 60 days in liver damaged rats that received THF treatment. Serum IL-6 levels were visibly reduced by THF administration after 60 days and in comparison with rats that did not receive the treatment. This was due to an increment in serum IL-10 levels caused by the administration of THF, which appears to reduce the inflammatory process by decreasing immune response. CONCLUSION: THF had beneficial effects in combating liver damage and fibrosis processes in an autoimmune model of PS-induced liver fibrosis in rats.

Use of a graft of demineralized bone matrix along with TGF-ß1 leads to an early bone repair in dogs.

Tibia fractures are common in small animal practice. Over the past decade, improvements to animal internal fracture fixation have been developed. TGF-ß1 has been shown to be crucial in the development, induction and repair of bone. In present study, we investigate the effect of local application of a graft demineralized bone matrix (DBM) along with TGF-ß1 in a model of open osteotomy induced experimentally in dogs. Tibia fracture was brought about by using an open osteotomy model in young male dogs. Fracture repair was evaluated by a histological and biochemical analysis. Collagen content, proteolytic activity and urokinase-type plasminogen activator (uPA) expression were analyzed at the end of the study. Radiographic analysis, alkaline phosphatase and hematological evaluation were performed weekly. At the fifth week, there was an improvement and restoration of bone architecture in animals treated with a graft containing TGF-ß1 (5 ng/ml) compared with the control and graft groups, as was evidenced by the presence of an early formation of wide callus and bone regeneration. In addition, local application of TGF-ß1 led to an increase in collagen and proteolytic activity. More immunopositive osteoclast and mesenchymal cells were found in bone tissue from animals treated with TGF-ß1 as compared with the control group. No changes in alkaline phosphatase, hematological and clinical parameters were observed. This study shows that the combined use of DBM along with TGF-ß1 is able to improve and accelerate the bone repair.