The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that ...evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking.
A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment.
Overall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported.
Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.
The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that ...evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking.
A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment.
Overall SVR was 98.8% (95% CI 97.35–100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported.
Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.
La combinación de sofosbuvir-velpatasvir (SOF/VEL) es una terapia antiviral de acción directa que está autorizada y disponible en México. Esto hace que la evaluación de la respuesta virológica sostenida (RVS) 12 semanas después del tratamiento, por medio de la realización de una revisión multicentro en el mundo real, sea una tarea relevante.
Se efectuó una revisión retrospectiva de los registros de 241 casos de pacientes atendidos en 20 hospitales en México para evaluar el tratamiento contra la hepatitis C con la combinación SOF/VEL (n = 231) y sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) (n = 10). El objetivo de eficacia primario fue el porcentaje de pacientes que lograron la RVS 12 semanas posterior a la finalización del tratamiento.
En general, la RVS fue de 98.8% (IC 95% 97.35 a 100%). Solo tres pacientes no lograron la RVS, de los cuales dos padecían cirrosis y una tenía historia previa de tratamiento con interferón pegilado (peg-IFN). De los subgrupos analizados, todos los casos con infección de virus de la inmunodeficiencia humana (VIH), tres con genotipo 3 y aquellos tratados con la combinación SOF/VEL/RBV, lograron RVS. Los subgrupos con tasas menores de éxito fueron los pacientes que tenían experiencia con tratamiento (96.8%) y pacientes con fibrosis F1 (95.5%). Los eventos adversos más frecuentes fueron fatiga, cefalea e insomnio. No se reportaron eventos adversos graves.
Los tratamientos con SOF/VEL y SOF/VEL/RBV fueron altamente seguros y efectivos y los resultados coinciden con los de otros estudios internacionales realizados en el mundo real.
Calcium-regulated chloride channel (CaCC) anoctamin-1 has been recently identified in neurons. In neurons, which express the Na-K-2Cl cotransporter, activation of CaCCs increases firing frequency, by ...reversion between the Cl equilibrium potential and the membrane resting potential, leading to membrane depolarization by Cl extrusion from the cell. Although there are no reports of CaCCs present in the suprachiasmatic nuclei (SCN), the fact that Na-K-2Cl cotransporter is present in SCN neurons, where it has been shown to be involved in the excitatory effects of γ-aminobutyric acid, together with the increase of neuronal firing rate induced by release of intracellular Ca after administration of 100 nM ryanodine, leads us to determine whether CaCCs are present in the SCN. Immunohistochemistry and western blots show the expression of the CaCCs anoctamin-1 protein. Quantitative PCR demonstrated the expression of anoctamin-1 mRNA in the SCN. These results clearly indicate the presence of CaCC in SCN of rats.
The purpose of this research was to investigate the possible variations to the pharmacokinetics of nimesulide by the effect of age using an animal model. An experimental, analytical, prospective and ...longitudinal study in five dogs, from birth to 730 days of age was carried out. Nimesulide
blood levels were measured in different months; concentrations were determined by HPLC-UV. Pharmacokinetic parameters were calculated by using the WinNonlin software. There were statistically significant differences (p <0.05) in most of the pharmacokinetic parameters between study of 6
months against the other three studies in different ages. Changes in the pharmacokinetic parameters of nimesulide as a result of age, are determined by the growing and maturation of the animals. Resulting data suggest that nimesulide can be used safely as a long-term analgesic in dogs, but,
the dosing regimens in humans should be different when administered at early age.
There is increasing awareness of epigenetics’s importance in understanding disease etiologies and developing novel therapeutics. An increasing number of publications in the past few years reflect the ...renewed interest in epigenetic processes and their relationship with food chemicals. However, there needs to be a recent study that accounts for the most recent advances in the area by associating the chemical structures of food and natural product components with their biological activity. Here, we analyze the status of food chemicals and their intersection with natural products in epigenetic research. Using chemoinformatics tools, we compared quantitatively the chemical contents, structural diversity, and coverage in the chemical space of food chemicals with reported epigenetic activity. As part of this work, we built and curated a compound database of food and natural product chemicals annotated with structural information, an epigenetic target activity profile, and the main source of the food chemical or natural product, among other relevant features. The compounds are cross-linked with identifiers from other major public databases such as FooDB and the collection of open natural products, COCONUT. The compound database, the “Epi Food Chemical Database”, is accessible in HTML and CSV formats at https://github.com/DIFACQUIM/Epi_food_Chemical_Database.
Drug-induced liver injury (DILI) is a rare clinical condition, the incidence is estimated from 14 to 19 cases per 100,000 population per year, it is responsible of 3 to 5% of jaundice ...hospitalizations, and it is the most frequent cause of acute liver failure in many of the western countries. Neobuxbaumia tetetzo is a species of flowering plant of the Cactaceae family, endemic to Mexico, distributed in Puebla and Oaxaca, and has been used within Mexican cuisine, without studies that establish the safety of its consumption, which predisposes to undocumented adverse effects, including probable liver injury.
The patient is a 19-year-old male, high school student and employee of a private company, single, originally from Tehuacán, Puebla, resident of Mexico City. Non-relevant family hereditary background. He denied experiencing any chronic degenerative diseases, allergies or traumas, but reported complications during an appendectomy in May of 2019. Has positive alcoholism, consuming it occasionally in social events; last consumption was seven months prior to the onset of symptoms. He denied the use of drugs, food supplements and herbalism. He began in June 30th of 2020 with asthenia, hyporexia, adinamia, nausea and unquantified fever, pain in epigastrium of moderate intensity, generalized pruritus, conjunctival jaundice and coluria were added, progressed to generalized jaundice, required hospitalization in August 2020. The laboratory results are Total Bilirubin 38.5 mg/dL, Direct bilirubin 26 mg/dL, ALT 60, AST 63, AP 329, GGT 33, General urine test that evidenced bilirubins 6 and urobilinogen 8. An ultrasonography and an abdominal tomography were performed, both reporting vesicular lithiasis, without obstruction or dilation of the bile duct. Subsequently, cholangioresonance was carried out on September 9, 2020, reporting liver gland with homogeneous parenchyma, bile duct without intra and extrahepatic dilation, gallbladder with the presence of lithic of 6.5 mm. Cholecystectomy and liver biopsy were performed, with histopathological result of gallbladder with chronic cholecystitis. Liver biopsy reporting: Hepatic parenchyma with preserved architecture, with few plasmatic and eosinophilic cells, and presence of severe intracanalicular and intracytoplasmic cholestasis corresponding to regenerative changes of grade 0 fibrosis on the Metavir scale and focal microvesicular steatosis, without regeneration nodules. Within its approach, serology Anti-Sm, IgM vs. CMV, IgM vs. Rubella, IgM vs. Toxoplasma, ANAs, anti Ro, SCL70 antibodies, HBV, HCV were negative.
The only finding observed in the clinical case of our patient that we can appreciate is the elevation of bilirubin. After ruling out the main and possible causes that affected the health of our patient, it was decided to re-interrogate him and it was found that the patient had an antecedent of consumption of N. tetetzo, this highlights the importance of the clinical history in the approach of DILI and the need for of a clinician to contemplate this possibility. Although in this case, a RUCAM score of 6 points was calculated which makes the diagnosis possible, the score was created in order to avoid biopsy given that it is invasive; and before an anatomopathological finding compatible with DILI it is doubtful whether it is worth rechallenging the patient to the consumption of N. tetetzo to objectify the condition of bilirubins before exposure, there is a risk of acute liver failure, which creates an ethical dilemma and violates the principle of non-maleficence.
The authors declare that there is no conflict of interest.
Searching, retrieving, and analyzing chemical information are among the main tasks faced by students and professionals in chemistry-related scientific disciplines. Currently, freely available modules ...developed in programming languages, such as Python, allow efficient data management and facilitate the obtaining of information and knowledge from the data. This article describes an electronic handbook generated on the GitBook platform to introduce the Python programming language and the analysis, computational representation, and visualization of chemical data. This manual explores the most common molecular representations of low molecular weight organic compounds and their applications in various contexts. It also illustrates the acquisition of chemical data from large public molecular databases such as ChEMBL and PubChem and the analysis and visualization of chemical information using concepts such as chemical space. The GitBook is freely available (https://difacquim.gitbook.io/quimioinformatica/) and is expected to foster open science and facilitate learning for chemistry students at the undergraduate and graduate levels, as well as professionals interested in chemical data analysis and visualization.
Accumulative evidence suggests that alterations due to mutations or genetic polymorphisms in the TCF7L2 and CCND1 genes, which are components of the Wnt signaling pathway, contributes to ...carcinogenesis. The present study was designated to clarify whether common single nucleotide polymorphisms (SNPs) of the transcription factor 7- like 2 (TCF7L2) and cyclin D1 (CCND1) genes are associated with colorectal cancer risk in Mexican patients. A case-control study including 197 colorectal cancer patients and 100 healthy subjects was conducted in a Mexican population. Identification of polymorphisms was made by the polymerase chain reaction-restriction fragment length polymorphism methodology. The association was calculated by the odds ratio (OR) test. The results demonstrate that patients with the T/T genotype for the rs12255372 polymorphism of the TCF7L2 gene present an increased colorectal cancer risk (OR=2.64, P=0.0236). Also, the risk analysis for Tumor-Nodule-Metastasis (TNM) stage and tumor location showed association with this polymorphism under the over-dominant model of inheritance (OR=1.75, P=0.0440). A similar relation was observed for the genotype T/T of the rs7903146 polymorphism and the rectal location of cancer (OR=7.57, P=0.0403). For the rs603965 polymorphism of the CCND1 gene, we observed a protection effect for the colon cancer location under the dominant model (OR=0.49, P=0.0477). These results reveal a significant role of the analyzed polymorphisms in the TCF7L2 and CCND1 genes on the susceptibility or protection for developing colorectal cancer in the Mexican population.
Acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) continues to be a public health problem. In 2020, 680,000 people died from HIV-related causes, and 1.5 ...million people were infected. Antiretrovirals are a way to control HIV infection but not to cure AIDS. As such, effective treatment must be developed to control AIDS. Developing a drug is not an easy task, and there is an enormous amount of work and economic resources invested. For this reason, it is highly convenient to employ computer-aided drug design methods, which can help generate and identify novel molecules. Using the de novo design, novel molecules can be developed using fragments as building blocks. In this work, we develop a virtual focused compound library of HIV-1 viral protease inhibitors from natural product fragments. Natural products are characterized by a large diversity of functional groups, many sp
atoms, and chiral centers. Pseudo-natural products are a combination of natural products fragments that keep the desired structural characteristics from different natural products. An interactive version of chemical space visualization of virtual compounds focused on HIV-1 viral protease inhibitors from natural product fragments is freely available in the supplementary material.
Aging is a physiological decline process. The number of older adults is growing around the world; therefore, the incidence of cognitive impairment, dementia, and other diseases related to aging ...increases. The main cellular factors that converge in the aging process are mitochondrial dysfunction, antioxidant impairment, inflammation, and immune response decline, among others. In this context, these cellular changes have an influence on the kynurenine pathway (KP), the main route of tryptophan (Trp) catabolism. KP metabolites have been involved in the aging process and neurodegenerative diseases. Although there are changes in the metabolite levels with age, at this time, there is no study that has evaluated cognitive decline as a consequence of Trp catabolism fluctuation in aging. The aim of this study was to evaluate the relation between the changes in Trp catabolism and cognitive impairment associated with age through KP metabolites level alterations in women over 50 years of age. Seventy-seven nondemented women over 50 years old were examined with a standardized cognitive screening evaluation in Spanish language (Neuropsi), Beck anxiety inventory (BAI), and the geriatric depression scale (GDS). Also, serum levels of Trp, kynurenine (Kyn), kynurenic acid (KYNA), and 3-hydroykynurenine (3-HK) and the glutathione ratio (GSH/GSSG) were measured. Results showed a negative correlation between age and Trp levels and a positive correlation between age and KYNA/Trp and 3-HK/Trp ratios. The level of cognitive impairment showed a significant positive association with age and with kynurenine pathway activation and a significant negative correlation with Trp levels. The GSH/GSSG ratio correlated positively with Trp levels and negatively with Kyn/Trp and 3-HK/Trp ratios. The depression score correlated negatively with Trp and positively with the 3-HK/Trp ratio. We concluded that KP activation increases with age and it is strongly associated with the level of cognition performance in nondemented women over 50 years of age.
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