Modulation of the Circadian Rhythm and Oxidative Stress as Molecular Targets to Improve Vascular Dementia: A Pharmacological Perspective.

The circadian rhythms generated by the master biological clock located in the brain's hypothalamus influence central physiological processes. At the molecular level, a core set of clock genes interact to form transcription-translation feedback loops that provide the molecular basis of the circadian rhythm. In animal models of disease, a desynchronization of clock genes in peripheral tissues with the central master clock has been detected. Interestingly, patients with vascular dementia have sleep disorders and irregular sleep patterns. These alterations in circadian rhythms impact hormonal levels, cardiovascular health (including blood pressure regulation and blood vessel function), and the pattern of expression and activity of antioxidant enzymes. Additionally, oxidative stress in vascular dementia can arise from ischemia-reperfusion injury, amyloid-beta production, the abnormal phosphorylation of tau protein, and alterations in neurotransmitters, among others. Several signaling pathways are involved in the pathogenesis of vascular dementia. While the precise mechanisms linking circadian rhythms and vascular dementia are still being studied, there is evidence to suggest that maintaining healthy sleep patterns and supporting proper circadian rhythm function may be important for reducing the risk of vascular dementia. Here, we reviewed the main mechanisms of action of molecular targets related to the circadian cycle and oxidative stress in vascular dementia.

Influence of the Osteogenomic Profile in Response to Alendronate Therapy in Postmenopausal Women with Osteoporosis: A Retrospective Cohort Study.

BACKGROUND: Postmenopausal osteoporosis is a multifactorial disease. Genetic factors play an essential role in contributing to bone mineral density (BMD) variability, which ranges from 60 to 85%. Alendronate is used as the first line of pharmacological treatment for osteoporosis; however, some patients do not respond adequately to therapy with alendronate. AIM: The aim of this work was to investigate the influence of combinations of potential risk alleles (genetic profiles) associated with response to anti-osteoporotic treatment in postmenopausal women with primary osteoporosis. METHODS: A total of 82 postmenopausal women with primary osteoporosis receiving alendronate (70 mg administered orally per week) for one year were observed. The bone mineral density (BMD; g/cm2) of the femoral neck and lumbar spine was measured. According to BMD change, patients were divided into two groups: responders and non-responders to alendronate therapy. Polymorphic variants in CYP19, ESR1, IL-6, PTHR1, TGFß, OPG and RANKL genes were determined and profiles were generated from the combination of risk alleles. RESULTS: A total of 56 subjects were responders to alendronate and 26 subjects were non-responders. Carriers of the G-C-G-C profile (constructed from rs700518, rs1800795, rs2073618 and rs3102735) were predisposed to response to alendronate treatment (p = 0.001). CONCLUSIONS: Our findings highlight the importance of the identified profiles for the pharmacogenetics of alendronate therapy in osteoporosis.

Therapeutic Targets for Regulating Oxidative Damage Induced by Ischemia-Reperfusion Injury: A Study from a Pharmacological Perspective.

Ischemia-reperfusion (I-R) injury is damage caused by restoring blood flow into ischemic tissues or organs. This complex and characteristic lesion accelerates cell death induced by signaling pathways such as apoptosis, necrosis, and even ferroptosis. In addition to the direct association between I-R and the release of reactive oxygen species and reactive nitrogen species, it is involved in developing mitochondrial oxidative damage. Thus, its mechanism plays a critical role via reactive species scavenging, calcium overload modulation, electron transport chain blocking, mitochondrial permeability transition pore activation, or noncoding RNA transcription. Other receptors and molecules reduce tissue and organ damage caused by this pathology and other related diseases. These molecular targets have been gradually discovered and have essential roles in I-R resolution. Therefore, the current study is aimed at highlighting the importance of these discoveries. In this review, we inquire about the oxidative damage receptors that are relevant to reducing the damage induced by oxidative stress associated with I-R. Several complications on surgical techniques and pathology interventions do not mitigate the damage caused by I-R. Nevertheless, these therapies developed using alternative targets could work as coadjuvants in tissue transplants or I-R-related pathologies.

Percepción de cambios en el ciclo menstrual posteriores a la vacunación contra SARS-CoV-2 / Perception of menstrual cycle changes following SARS-CoV-2 vaccination

Resumen OBJETIVO: Identificar si la vacunación contra la COVID-19 se asocia con cambios en el patrón menstrual. MATERIALES Y MÉTODOS: Estudio observacional y transversal anónimo efectuado entre el 4 y 29 de octubre del 2021 en un grupo de mujeres que completaron un cuestionario elaborado para saber si hubo cambios en el ciclo menstrual posteriores a la vacunación. La encuesta se aplicó durante un periodo de cuatro semanas. Para el análisis estadístico se utilizó el programa SPSS. Los cambios antes y después de la aplicación de la primera y segunda dosis de la vacuna contra COVID-19 se evaluaron con una prueba t de muestras pareadas y χ2. RESULTADOS: Se reunieron 4501 pacientes de las que se excluyeron 1815 por no cumplir con los criterios de inclusión; al final quedaron para el análisis 2686. De éstas el 37.9% (n = 1018) tuvieron cambios en el ciclo menstrual posteriores a la vacunación contra COVID-19; en 61.8% (n = 630) fueron en la cantidad del sangrado. De las mujeres que reportaron cambios en el ciclo menstrual, el 64.34% (n = 655) fueron posteriores a la aplicación de vacunas tipo ARN mensajero (35.06%; p = 0.19, IC95%: -0.35-0.19). En relación con la cantidad de dosis aplicadas 72.10% (n = 734) reportaron modificaciones en el ciclo menstrual después de la segunda vacuna (p = 0.01, IC95%: 0.58-0.98). CONCLUSIONES: La vacunación contra COVID-19 se asocia con pequeños cambios en el ciclo menstrual, sin significación estadística. Las mujeres que reciben dos dosis de la vacuna tuvieron cambios en la cantidad del sangrado.

Abstract OBJECTIVE: Identify whether vaccination against COVID-19 is associated with changes in menstrual pattern. MATERIALS AND METHODS: An anonymous observational, cross-sectional to be held from October 4 to 29, 2021 was conducted in a group of women who completed a questionnaire designed to inquire about changes in the menstrual cycle following vaccination. The survey was administered over a four-week period. SPSS software was used for statistical analysis. Changes before and after the application of the first and second doses of COVID-19 vaccine were evaluated with a paired samples t-test and 2. RESULTS: 4501 patients were collected of whom 1815 were excluded because they did not meet the inclusion criteria; in the end 2686 remained for analysis. Of these, 37.9% (n = 1018) had changes in the menstrual cycle following COVID-19 vaccination; in 61.8% (n = 630) it was in the amount of bleeding. Of the women who reported menstrual cycle changes, 64.34% (n = 655) were after application of messenger RNA vaccines (35.06%; p = 0.19, 95%CI: -0.35-0.19). In relation to the number of doses applied 72.10% (n = 734) reported modifications in the menstrual cycle after l second vaccine (p = 0.01, CI95%: 0.58-0.98). CONCLUSIONS: Vaccination against COVID-19 is associated with small changes in the menstrual cycle, without statistical significance. Women receiving two doses of vaccine had changes in the amount of bleeding.

Effect of Telmisartan in the Oxidative Stress Components Induced by Ischemia Reperfusion in Rats.

The therapeutic effects of telmisartan, an angiotensin II receptor antagonist and a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, have been demonstrated in several disorders. It has antioxidant and immune response modulator properties and has shown promising results in the treatment of an ischemia/reperfusion (I/R) lesion. In this study, a skeletal muscle (right gastrocnemius muscle) I/R lesion was induced in rats and different reperfusion times (1 h, 24 h, 72 h, 7-day, and 14-day subgroups) were assessed. Furthermore, levels of oxidative markers such as enzymatic scavengers (catalase (CAT) and superoxide dismutase (SOD)) and metabolites (nitrates and 8-oxo-deoxyguanosine) were determined. The degree of tissue injury (total lesioned fibers and inflammatory cell count) was also evaluated. We observed an increase in CAT and SOD expression levels under telmisartan treatment, with a decrease in injury and oxidative biomarker levels in the 72 h, 7-day, and 14-day subgroups. Telmisartan reduced oxidative stress and decreased the damage of the I/R lesion.