Transsulfuration pathway: a targeting neuromodulator in Parkinson's disease.

The transsulfuration pathway (TSP) is a metabolic pathway involving sulfur transfer from homocysteine to cysteine. Transsulfuration pathway leads to many sulfur metabolites, principally glutathione, H2S, taurine, and cysteine. Key enzymes of the TSP, such as cystathionine ß-synthase and cystathionine γ-lyase, are essential regulators at multiple levels in this pathway. TSP metabolites are implicated in many physiological processes in the central nervous system and other tissues. TSP is important in controlling sulfur balance and optimal cellular functions such as glutathione synthesis. Alterations in the TSP and related pathways (transmethylation and remethylation) are altered in several neurodegenerative diseases, including Parkinson's disease, suggesting their participation in the pathophysiology and progression of these diseases. In Parkinson's disease many cellular processes are comprised mainly those that regulate redox homeostasis, inflammation, reticulum endoplasmic stress, mitochondrial function, oxidative stress, and sulfur content metabolites of TSP are involved in these damage processes. Current research on the transsulfuration pathway in Parkinson's disease has primarily focused on the synthesis and function of certain metabolites, particularly glutathione. However, our understanding of the regulation of other metabolites of the transsulfuration pathway, as well as their relationships with other metabolites, and their synthesis regulation in Parkinson´s disease remain limited. Thus, this paper highlights the importance of studying the molecular dynamics in different metabolites and enzymes that affect the transsulfuration in Parkinson's disease.

Comportamiento informativo en las bibliotecas de la Facultad de Estudios Superiores Zaragoza de la Universidad Nacional Autónoma de México, antes y durante la pandemia por SARS-CoV-2

Se estudia el comportamiento informativo de alumnos y docentes de la Facultad de Estudios Superiores Zaragoza (FESZ), de la Universidad Nacional Autónoma de México (UNAM), durante la pandemia ocasionada por el SARS-CoV-2, en la Biblioteca Digital UNAM ante el cierre total de las bibliotecas, lo que limitó la consulta presencial de libros y revistas impresas. Se llevó a cabo una investigación cuantitativa con la técnica de análisis de datos estadísticos a partir de las bitácoras de acceso a la Biblioteca Digital (BIDI UNAM) que en suma contempló 15,597 accesos, en comparación a dos periodos, antes y durante la pandemia, obteniendo como resultado un incremento en los accesos, sumado al impulso de estrategias de alfabetización informacional para el uso y aprovechamiento de los recursos de información, mismos que pueden ser integrados en los procesos de enseñanza y aprendizaje, fortaleciendo el modelo educativo de la FESZ.

The informational behavior of students and professors of the Facultad de Estudios Superiores Zaragoza (FESZ) of the Universidad Nacional Autónoma de México (UNAM) during the pandemic caused by SARS-CoV-2, is studied in the Biblioteca Digital UNAM (BIDI UNAM) before the total closure of libraries, which limited the consultation of printed books and journals. A quantitative research was carried out with the statistical data analysis technique from the access logs to the BIDI UNAM, wich in total included 15,597 accesses, compared to two periods, before and during the pandemic, obtaining as a result an increase in accesses, in addition to the promotion of information literacy strategies for the use and exploitation of information resources, which can be integrated into the teaching and learning processes, strengthening the educational model of the FESZ.

The Effect of 600 mg Alpha-lipoic Acid Supplementation on Oxidative Stress, Inflammation, and RAGE in Older Adults with Type 2 Diabetes Mellitus.

Alpha-lipoic acid (ALA) has been used as a dietary supplement at different doses in patients with diabetes mellitus type 2 (T2DM) due to its antioxidant, anti-inflammatory, and hypoglycemic effects. However, the reports on the effects of ALA are controversial. For this reason, the purpose of the present study was to determine the effect of 600 mg/day of ALA on the markers of oxidative stress (OxS) and inflammation and RAGE in older adults with T2DM. A quasiexperimental study was carried out with a sample of 135 sedentary subjects (98 women and 37 men) with a mean age of 64 ± 1 years, who all had T2DM. The sample was divided into three groups: (i) experimental group (EG) with 50 subjects, (ii) placebo group (PG) with 50 subjects, and control group (CG) with 35 subjects. We obtained the following measurements in all subjects (pre- and posttreatment): glycosylated hemoglobin (HbA1c), receptor for advanced glycation end products (RAGE), 8-isoprostane, superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant status (TAS), and inflammatory (CRP, TNF-α, IL-6, IL-8, and IL-10) markers. Regarding the effect of ALA on HbA1c, a decrease was observed in the EG (baseline 8.9 ± 0.2 vs. posttreatment 8.6 ± 0.3) and the PG (baseline 8.8 ± 0.2 vs. posttreatment 8.4 ± 0.3) compared to the CG (baseline 8.8 ± 0.3 vs. six months 9.1 ± 0.3) although the difference was not statistically significant (p < 0.05). There was a statistically significant decrease (p < 0.05) in the blood concentration of 8-isoprostane in the EG and PG with respect to the CG (EG: baseline 100 ± 3 vs. posttreatment 57 ± 3, PG: baseline 106 ± 7 vs. posttreatment 77 ± 5, and CG: baseline 94 ± 10 vs. six months 107 ± 11 pg/mL). Likewise, a statistically significant decrease (p < 0.05) in the concentration of the RAGE was found in the EG (baseline 1636 ± 88 vs. posttreatment 1144 ± 68) and the PG (baseline 1506 ± 97 vs. posttreatment 1016 ± 82) compared to CG (baseline 1407 ± 112 vs. six months 1506 ± 128). A statistically significant decrease was also observed in all markers of inflammation and in the activity of SOD and GPx in the CG with respect to the EG and PG. Our findings suggest that the administration of ALA at a dose of 600 mg/day for six months has a similar effect to that of placebo on oxidative stress, inflammation, and RAGE in older adults with T2DM. Therefore, higher doses of ALA should be tried to have this effect. This trial is registered with trial registration number ISRCTN13159380.

Controlled release of glibenclamide from monolithic silica subdermal implants produced by the sol-gel process and its use for hyperglycaemia treatment in a murine model.

Glibenclamide is an anti-hyperglycaemic drug that is commonly used for the treatment of type 2 diabetes mellitus and has promising new medical indications. However, this drug is associated with high rates of serious hypoglycaemic episodes as a result of its pharmacological activity. Administering the drug through controlled release delivery systems could reduce the incidence of these episodes. In this study, glibenclamide silica monolithic xerogel implants for subdermal application (GMSIx) were developed using the sol-gel technique for matrix synthesis with TEOS with different drying conditions (environmental, 60, 90, and 120 °C, which were named as GMSIE, GMSI60, GMSI90, and GMSI120, respectively). The inclusion of the drug in monoliths was monitored by DSC, FTIR, and PXRD. The effect of drying conditions on the morphology, moisture content, hardness, dosage uniformity, surface characteristics, and drug release mechanism of glibenclamide from the matrices was systematically investigated. Oral Glucose Tolerance Tests were performed with mice to evaluate the efficacy of the GMSI in maintaining blood glucose levels. Glibenclamide was completely included in a non-crystalline solid form in the matrixes. The moisture content, hardness, dosage uniformity, and surface characteristics depend on the drying conditions. The monolithic matrices showed a mesoporous surface with high surface area, and a narrower pore size distribution occurred for GMSI60. GMSIE and GMSI60 showed non-Fickian anomalous Korsmeyer-Peppas glibenclamide release kinetics. GMSI90 and GMSI120 showed controlled release of the drug through dissolution. When GMSI60 was administered to mice, glucose blood levels were effectively maintained despite a high oral glucose load in the animals, showing a sustained effect of the drug released from this new sol-gel drug delivery system.

Increased acetylcholine esterase activity produced by the administration of an aqueous extract of the seed kernel of Thevetia peruviana and its role on acute and subchronic intoxication in mice.

BACKGROUND: The real mechanism for Thevetia peruviana poisoning remains unclear. Cholinergic activity is important for cardiac function regulation, however, the effect of T. peruviana on cholinergic activity is not well-known. OBJECTIVE: To study the effect of the acute administration of an aqueous extract of the seed kernel of T. peruviana on the acetylcholine esterase (AChE) activity in CD1 mice as well its implications in the sub-chronic toxicity of the extract. MATERIALS AND METHODS: A dose of 100 mg/kg of the extract was administered to CD1 mice and after 7 days, serum was obtained for ceruloplasmin (CP) quantitation and liver function tests. Another group of mice received a 50 mg/kg dose of the extract 3 times within 1 h time interval and AChE activity was determined for those animals. Heart tissue histological preparation was obtained from a group of mice that received a daily 50 mg/kg dose of the extract by a 30-days period. RESULTS: CP levels for the treated group were higher than those for the control group (Student's t-test, P ≤ 0.001). AChE activity in the treated group was significantly higher than the control group (Tukey test, control vs. T. peruviana, P ≤ 0.001). Heart tissue histological preparations showed leukocyte infiltrates and necrotic areas, consistent with infarcts. CONCLUSION: The increased levels of AChE and the hearth tissue infiltrative lesions induced by the aqueous seed kernel extract of T. peruviana explains in part the poisoning caused by this plant, which can be related to an inflammatory process.

The effect of the aqueous extract of Helietta parvifolia A. Gray (Rutaceae) stem bark on carrageenan-induced paw oedema and granuloma tissue formation in mice.

AIMS OF STUDY: Despite the ethnopharmacological relevance of Helietta parvifolia A. Gray (Rutaceae) in Mexico, we found no significant pharmacological studies of this plant in the scientific literature. The aim of the present study was to establish the anti-inflammatory effect of an aqueous extract of the stem bark of Helietta parvifolia in mice. MATERIALS AND METHODS: The anti-inflammatory activity of the aqueous extract of the stem bark of Helietta parvifolia was evaluated using carrageenan-induced paw oedema in mice, and the cotton pellet granuloma method. RESULTS: An extract dose ranging from 20 to 80 mg/kg p.o. showed a non-significant effect over the initial phase of carrageenan-induced oedema. However, it showed a significant inhibition of oedema after 3h, which can be related to the inhibition of the release of kinin-like substances. An ID(50) value of 47.4 mg/kg was obtained for the plant extract. The extract also suppressed granulomatous tissue formation during chronic inflammation. The inhibitory values were 19.2, and 22.2, corresponding to 40 and 80 mg/kg doses of extract respectively. CONCLUSIONS: Aqueous extract showed a statistically significant anti-inflammatory effect in mice during the late phase of acute inflammation and during chronic inflammation. However, the exact mechanism(s) of anti-inflammatory effects of Helietta parvifolia observed in this study remains unclear.