Longitudinal anti-SARS-CoV-2 antibody immune response in acute and convalescent patients.

Despite global efforts to assess the early response and persistence of SARS-CoV-2 antibodies in patients infected with or recovered from COVID-19, our understanding of the factors affecting its dynamics remains limited. This work aimed to evaluate the early and convalescent immunity of outpatients infected with SARS-CoV-2 and to determine the factors that affect the dynamics and persistence of the IgM and IgG antibody response. Seropositivity of volunteers from Mexico City and the State of Mexico, Mexico, was evaluated by ELISA using the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein for 90 days, at different time points (1, 15, 45, 60, and 90 days) after molecular diagnosis (RT-qPCR). Gender, age range, body mass index (BMI), comorbidities, and clinical spectrum of disease were analyzed to determine associations with the dynamics of anti-SARS-CoV-2 antibodies. On 90 days post-infection, individuals with moderate and asymptomatic disease presented the lowest levels of IgM, while for IgG, at the same time, the highest levels occurred with mild and moderate disease. The IgM and IgG levels were related to the clinical spectrum of disease, BMI, and the presence/absence of comorbidities through regression trees. The results suggest that the dynamics of anti-SARS-CoV-2 IgM and IgG antibodies in outpatients could be influenced by the clinical spectrum of the disease. In addition, the persistence of antibodies against SARS-CoV-2 could be related to the clinical spectrum of the disease, BMI, and the presence/absence of comorbidities.

Jaboticabin and Related Polyphenols from Jaboticaba ( Myrciaria cauliflora) with Anti-inflammatory Activity for Chronic Obstructive Pulmonary Disease.

Myrciaria cauliflora (jaboticaba) is an edible fruit common in Brazil that has been used for treating respiratory diseases, including chronic tonsillitis and asthma. This study explores the distribution of an anti-inflammatory depside, jaboticabin, in different parts of the jaboticaba plant as well as major polyphenols from the wood of jaboticaba, some with biological activity similar to jaboticabin. The peel of the fruit was found to be the major source of jaboticabin. This is the first phytochemical study of the wood of M. cauliflora. The antioxidant-activity-guided fractionation strategy successfully identified 3,3'-dimethylellagic acid-4- O-sulfate from jaboticaba wood. This ellagic acid derivative, in a manner similar to jaboticabin, showed antiradical activity and inhibited the production of the chemokine interleukin-8 after treating the human small airway epithelial cells with cigarette smoke extract. The human intestinal Caco-2 cell studies demonstrated the jaboticabin transport in vitro. The polyphenols, jaboticabin and 3,3'-dimethyellagic acid-4- O-sulfate, from jaboticaba were both found to exhibit anti-inflammatory activities, thus suggesting the potential use of these compounds or even the fruits themselves for chronic obstructive pulmonary disease.

Chronic Hepatitis C Treatment with Direct-Acting Antiviral Agents in a Real-Life Setting.

BACKGROUND: In clinical trials, new oral direct-acting antiviral agent therapies have demonstrated a high sustained virological response rate in patients with hepatitis C virus infection. We aimed to analyze the efficacy and safety data from direct-acting antiviral agent interferon-free therapy in hepatitis C virus infection in a study performed in five different clinical settings in Mexico City; four private practice sites and one academic medical center in a real-world scenario. METHODS: Eighty-one patients were treated with seven different direct-acting antiviral agent regimens, in which the end of treatment, sustained virological response at 12 weeks post-treatment, and adverse effects were evaluated. At their discretion, attending physicians selected the treatment regimens and durations. RESULTS: In total, 70.4% of the patients were female and the mean age was 60.7 years; 74.1% had blood transfusion as a risk factor. The most common genotype was 1b (70.4%). The fibrosis stage was F3 or F4 in 55.5% of patients; liver cirrhosis was present in 44%. The overall end of treatment response was 98.8%, and the rate of sustained virological response was 96%, independent of the regimen. Three patients did not achieve sustained virological response; they had cirrhosis and were treatment-experienced, and two had hepatocarcinoma. Non-significant adverse effects during treatment were documented. CONCLUSIONS: In this real-life setting in Mexico, a rate of 96% of sustained virological response to direct-acting antiviral agents was achieved in an older population of patients with advanced fibrosis. This study provides data that may be useful in guiding health professionals and authorities in the development of health policies.

Hepatitis C screening in the general population.

BACKGROUND: A significant number of patients infected with hepatitis C virus remain unaware of their infection, as this is a silent disease for many years. Patients are frequently detected at advance stages of the disease. OBJECTIVE: To identify the prevalence and viremic stage of hepatitis C among a general population cohort. METHODS: Anti-hepatitis C virus detection and viral RNA were offered without cost to individuals who voluntarily considered it relevant to be examined, as part of the World Hepatitis Day annually from 2007-2014. RESULTS: A total of 32,945 individuals were analyzed; 57% were female and 43% male. Of them, 75.7% were between 21-50 years old. In 59%, the sample was obtained at their work place and in 41% at the facilities of 12 private laboratories. Anti-hepatitis C virus was positive in 194 patients (0.58%), of which 129 (66%) were confirmed positive by polymerase chain reaction. The overall prevalence of viremic cases in the sample was 0.39%. CONCLUSIONS: Adequate estimation of the prevalence of anti-hepatitis C virus and viremic population, not only among high-risk groups but also in the general population, is central to the allocation of resources in an effort to reduce the consequences of the disease.

Effective use of FibroTest to generate decision trees in hepatitis C.

AIM: To assess the usefulness of FibroTest to forecast scores by constructing decision trees in patients with chronic hepatitis C. METHODS: We used the C4.5 classification algorithm to construct decision trees with data from 261 patients with chronic hepatitis C without a liver biopsy. The FibroTest attributes of age, gender, bilirubin, apolipoprotein, haptoglobin, alpha2 macroglobulin, and gamma-glutamyl transpeptidase were used as predictors, and the FibroTest score as the target. For testing, a 10-fold cross validation was used. RESULTS: The overall classification error was 14.9% (accuracy 85.1%). FibroTest's cases with true scores of F0 and F4 were classified with very high accuracy (18/20 for F0, 9/9 for F0-1 and 92/96 for F4) and the largest confusion centered on F3. The algorithm produced a set of compound rules out of the ten classification trees and was used to classify the 261 patients. The rules for the classification of patients in F0 and F4 were effective in more than 75% of the cases in which they were tested. CONCLUSION: The recognition of clinical subgroups should help to enhance our ability to assess differences in fibrosis scores in clinical studies and improve our understanding of fibrosis progression.

[Statistical and prognostic correlation of serum levels of basal inhibin to response and follicular quality in assisted reproduction]. / Correlación estadística y pronóstica de la concentración sérica de inhibina basal con la respuesta y calidad folicular en reproducción asistida.

BACKGROUND: Inhibin B is a direct marker of ovarian reserve and one of the earliest markers of ovarian aging. It has been used in assisted reproduction programs as a serum marker that can identify an altered follicular reserve and predict a good or poor response to the stimulation with exogenous gonadotropins. OBJECTIVE: To correlate inhibin B levels with follicular response and quality of oocytes obtained through ovarian stimulation controlled in an in vitro fertilization cycle (IVFET), as well as relate it with variables such as: fertilization percentage and pregnancy rates. PATIENTS AND METHODS: In a prospective and transversal study we included 71 patients that entered the IVFET program (February-April 2005). We determined inhibin B levels at the third day of the cycle and evaluated the follicular response and the oocyte quality during the ovarian stimulation, as well as fertilization and pregnancy rates. Statistical analysis was made with Spearman's and ANOVA tests. RESULTS: We observed a positive correlation between inhibin levels and quantity of developed follicles (0.457), number of captured oocytes (0.390), and quantity of metaphase II oocytes (0.324). We observed better oocyte quality in women with inhibin levels > 251 pg/ mL, and we considered that the ones that had levels < 50 pg/mL had poor follicular response (19.71%). There was no correlation with fertilization and pregnancy rates. CONCLUSIONS: In the early follicular phase inhibin B has direct correlation with ovarian reserve. Its high levels are related to better follicular response and oocyte quality. This enzyme levels are not useful as a predictive factor of pregnancy in IVFET cycles.

[Correlation between follicle levels of superoxide dismutase and oocyte quality, fertilization rates and embryo development]. / Correlación entre las concentraciones intrafoliculares de la superóxido dismutasa y la calidad ovocitaria, las tasas de fertilización y el desarrollo embrionario.

BACKGROUND: The intraovarian oxidative balance is important during oocyte development, and fertilization. It has been proposed that one of the most important enzymes in the follicle is the superoxide dismutase (SOD). OBJECTIVE: To correlate levels and percentage of SOD activity in follicular liquid with quality, fertilization and embryo development in a group of patients submitted to in vitro fertilization. MATERIAL AND METHODS: We obtained 120 follicular liquids from oocytes aspirated in 41 patients during an IVF program and then we followed the development of each oocyte separately. We measured the activity and concentration of SOD in the follicular liquid, and we evaluated the following variables: quality and maturity in the oocytes, as well as fertilization rate, segmentation rate and pregnancy. The statistical analysis was made with ANOVA test and Pearson test. RESULTS: In the analysis of the results, we observed a higher percentage of activity in the SOD in oocytes with good quality (3 and 4) in comparison with poor quality oocyte (1 and 2) (89 and 82% vs 75 and 61% p<0.05). We observed higher concentrations and activity of SOD in oocytes with a good fertilization rate and segmentation (p<0.05). When we analyzed the variables in function of pregnancy, we observed that the embryos that were transferred and developed pregnancy had higher concentrations and activity of SOD than embryos that did not develop pregnancy. CONCLUSIONS: Elevated levels and high percentage in the activity of SOD are associated with a better quality in the oocyte, and a good embryo development, influenced by the oxidative balance.

[Activation in the metaloproteinases complex in the follicle-embryonic generative capability]. / Activación en el complejo de metaloproteinasas en la capacidad generativa folículo-embrionaria.

OBJECTIVE: To evaluate the impact of the enzymatic inhibition complex of metaloproteinases [TIMP(MMP-3 stromelisine-1)] in follicle/genesis processes and their ovule/embryonic subsequent development in stimulated cycles. TYPE OF STUDY: Prospective longitudinal in research center. MATERIALS AND METHODS: A total of 20 patients were evaluated in vitro fertilization cycles measuring matrix metaloproteinases concentrations in days 3 and 12 of ovarian stimulation, as well as in the follicular liquid at the moment of ovarian retrieval. The determination of [TIMP/(MMP-3 stromelisine-1)] was done by ELISA and monoclonal antibodies type of immunoassay methods. For its statistical evaluation were applied linear regression models ( r/r2 ) and Kolmogorov-Smirov test comparing the two groups where values were expressed in agreement at its mean, standard deviation and a significance of p < 0.05. RESULTS: For regression models was found a positive correlation between basal FSH and the age of patients [(r2 = 0.26)(p = 0.003)], dividing groups in older and younger patients than 35 years; it was observed significant difference in metaloproteinases concentration as in serum concentration (days 3 and 12 of stimulation) as in the follicular liquid. A decrease in the 14% [(TIMP/(MMP-3/stromelisine-1)] complex concentration was increasing in accordance at the female patients age. CONCLUSIONS: The matrix metaloproteinases complex study has allowed observing a status not only in the ovular quality but in the embryonic development and fertilization processes too.

The evaluation of forty-three plant species for in vitro antimycobacterial activities; isolation of active constituents from Psoralea corylifolia and Sanguinaria canadensis

Extracts from forty-three plant species were selected on account of reported traditional uses for the treatment of TB and/or leprosy. These were assayed for antimycobacterial activities. A simple in vitro screening assay was employed using two model species of mycobacteria, M. aurum and M. smegmatis. Crude methanolic extracts from three of the plants, C. mukul, P. corylifolia and S. canadensis, were found to have significant antimycobacterial activity against M. aurum only (MIC=62.5 microg/ml). Bioassay guided fractionation led to the isolation of two known benzophenanthridine alkaloids, sanguinarine (1) and chelerythrine (2), from the roots S. canadensis and the known phenolic meroterpene, bakuchiol (3) from the seeds of P. corylifolia. The fractionation of the resin of C. mukul lead to a decrease in antimycobacterial activity and hence further work was not pursued. Compound (2) was the most active against M. aurum and M. smegmatis (IC(50)=7.30 microg/ml [19.02 microM] and 29.0 microg/ml [75.56 microM], respectively). M. aurum was the most susceptible organism to all three compounds. No significant difference in antimycobacterial activity was observed when the two alkaloids were tested for activity in media of differing pH values. The activities of the pure compounds against M. aurum were comparable with those against M. bovis BCG with compound (2) being the most active (M. bovis BCG, IC(50)=14.3 microg/ml [37.3 microM]). These results support the use of these plants in traditional medicine.

Efecto de los niveles de interleucina-6 intrafolicular en la secreción de estradiol y progesterona de pacientes tratadas con fertilización in vitro y transferencia de embriones / Effect of the follicul on inter leuking-6 over secretion of either estradiol and progesterone in patients undergone to in vitro fertilization and embryo transfer

El objetivo del estudio fue evaluar la relación entre los niveles intrafoliculares de Interleucina-6 (IL-6) y las concentraciones séricas de estradiol y progesterona en pacientes que reciben hiperestimulación ovárica controlada. Se midieron los niveles intrafoliculares de IL-6 en 15 pacientes tratadas con fertilización in vitro y transferencia de embriones y fueron correlacionados con los valores séricos de estradiol y progesterona. Hubo correlación negativa entre los niveles intrafoliculares de IL-6 y el estradiol y la progesterona. Cuatro de las pacientes lograron el embarazo (tasa de embarazo 26.6 por ciento), una de ellas presentó un aborto espontáneo. Como conclusión, se establece que los niveles elevados de IL-6 en el folículo pueden ser debido a una reacción a la hiperestimulación ovárica controlada y en cierto sentido, a un mecanismo de defensa. Tomando en cuenta la reducción en los niveles de estradiol relacionados con la elevación de IL-6, es probable que exista una reducción sutil en la acción de la aromatasa por acción de la IL-6 y otras citocinas.