COVID-19 and Ivermectin: Potential threats associated with human use.

Drugs re-purposing due to COVID-19 virus has declared a number of useful candidates for treatment and prevention of the virus. Ivermectin (IVM) has gained much popularity due to a strong background of magical applications against a broad spectrum of pathogens. The in- vitro studies of ivermectin have shown promise, the thorough clinical trials of its efficacy in the treatment and prevention of SARS-CoV-2 are still warranted. Useful strategies for analyzing projected use of IVM in human coronaviruses might be developed. It may be done by concluding ongoing clinical trials and culturing lessons from IVM usage in veterinary practice. The potential toxicity and careful dosage analyses are urgently required before declaring it as an anti-SARS-CoV-2 drug candidate. This manuscript overviews the background and potential threats associated with the off-label use of IVM as prophylactic drug or treatment option against COVID-19 virus.

A comprehensive review on the applications of nano-biosensor-based approaches for non-communicable and communicable disease detection.

The outstretched applications of biosensors in diverse domains has become the reason for their attraction for scientific communities. Because they are analytical devices, they can detect both quantitative and qualitative biological components through the generation of detectable signals. In the recent past, biosensors witnessed significant changes and developments in their design as well as features. Nanotechnology has revolutionized sensing phenomena by increasing biodiagnostic capacity in terms of specificity, size, and cost, resulting in exceptional sensitivity and flexibility. The steep increase of non-communicable diseases across the world has emerged as a matter of concern. In parallel, the abrupt outbreak of communicable diseases poses a serious threat to mankind. For decreasing the morbidity and mortality associated with various communicable and non-communicable diseases, early detection and subsequent treatment are indispensable. Detection of different biological markers generates quantifiable signals that can be electrochemical, mass-based, optical, thermal, or piezoelectric. Speculating on the incumbent applicability and versatility of nano-biosensors in large disciplines, this review highlights different types of biosensors along with their components and detection mechanisms. Moreover, it deals with the current advancements made in biosensors and the applications of nano-biosensors in detection of various non-communicable and communicable diseases, as well as future prospects of nano-biosensors for diagnostics.

Antifungal and Cytotoxic Evaluation of Photochemically Synthesized Heparin-Coated Gold and Silver Nanoparticles.

Heparin-based silver nanoparticles (AgHep-NPs) and gold nanoparticles (AuHep-NPs) were produced by a photochemical method using silver nitrate and chloroauric acid as metal precursors and UV light at 254 nm. UV-Vis spectroscopy graphs showed absorption for AgHep-NPs and AuHep-NPs at 420 nm and 530 nm, respectively. TEM revealed a pseudospherical morphology and a small size, corresponding to 10-25 nm for AgHep-NPs and 1.5-7.5 nm for AuHep-NPs. Their antifungal activity against Candida albicans, Issatchenkia orientalis (Candida krusei), and Candida parapsilosis was assessed by the microdilution method. We show that AgHep-NPs were effective in decreasing fungus density, whereas AuHep-NPs were not. Additionally, the viability of human gingival fibroblasts was preserved by both nanoparticle types at a level above 80%, indicating a slight cytotoxicity. These results are potentially useful for applications of the described NPs mainly in dentistry and, to a lesser extent, in other biomedical areas.

Factores asociados al incremento de cesáreas en México, 2011-2014 / Factors associated with the increase in cesareans in Mexico, 2011-2014

Resumen Introducción: analizamos la prevalencia del parto vía cesárea en México para 2011-2014, buscando identificar algunos de los factores asociados a la presencia de cesárea durante el parto. Metodología: se realizó un análisis descriptivo y un modelo logístico multinivel con los registros de nacimientos del periodo 2011-2014, que incluye las características de la madre y del contexto. Resultados: se identificó que la presencia de factores relacionados con una mayor posibilidad de que el parto resulte en cesárea son mujeres que habitan municipios con población indígena, mayor escolaridad, mayor número de consultas prenatales, inicio temprano de estas y atenderse en clínicas privadas. También se identificó una mayor posibilidad de estancias prolongadas de hospitalización del parto si es por cesárea. Conclusiones: se observa un incremento en el número de cesáreas en hospitales públicos a partir del esquema de aseguramiento del Seguro Popular y se confirma la relación directa entre los múltiples factores analizados y la cesárea, entre ellos, mayor escolaridad, habitar en municipios predominantemente indígenas, así como en municipios con mayor índice de desarrollo humano.

Abstract Introduction: The objective is to analyze the prevalence of delivery by cesarean section in Mexico among 2011-2014, to identify some of the factors associated with its occurrence. Methods: A descriptive analysis and a multilevel logistic model was conducted among the data for Birth Information Subsystem, characteristics for the mother and context. Results: Identified that the factors associated with a greater likelihood that delivery result in cesarean section, are higher levels of education, greater number of prenatal visits, an early start to prenatal visits, giving birth in private health. Also a greater likelihood of prolonged hospitalization when delivery is by cesarean section. Conclusions: An increase in the number of caesarean sections in public hospitals is observed from the Popular Insurance assurance scheme; and the direct relationship between the multiple factors analyzed and the caesarean section is confirmed, including higher education, living in predominantly indigenous municipalities, as well as in municipalities with the highest human development index.

Use of azilsartan medoxomil in the primary-care setting in Germany: A real-world evidence study
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OBJECTIVE: To evaluate azilsartan medoxomil (AZM) (Edarbi®) utilization patterns in the primary-care setting in Germany. MATERIALS AND METHODS: This is a retrospective cohort study among patients receiving AZM in the primary-care setting in Germany. Prescription patterns - including patient demographics, off-label use, use in specific populations, concomitant use of other antihypertensive drugs, and drugs potentially causing interactions with AZM - were analyzed in two periods (01/2012 - 12/2013 and 01/2014 - 11/2016) using the primary-care physician panel of German IMS® Disease Analyzer, a patient-level electronic medical records database. RESULTS: In total, 852 of 1,159 (74%) and 696 of 811 (86%) patients met the inclusion criteria for both periods, respectively. Approximately 25% of patients were aged ≥ 75 years; 1 patient was < 18 years old; ~ 50% were females. AZM was prescribed for the approved indication of essential hypertension in 83% and 68% of patients in the first and second period, while indication was missing in 12% and 26% of patients, respectively. AZM was coprescribed on the same day with other antihypertensive drugs in 23% (first period) and 37% (second period) of patients. Drugs that might cause an interaction with AZM were coprescribed on the same day in 3% of patients in both periods; overlapping prescription periods were detected in 14% (first period) and 8% (second period) of patients. Coprescription of AZM with angiotensin-converting enzyme (ACE) inhibitors (2%) or aliskiren (< 1%) on the same day was rare in both periods. Overlapping prescription periods with AZM decreased from 20 to 6% for ACE inhibitors and from 8 to 1% for aliskiren. CONCLUSION: Findings from this real-world evidence study demonstrate that AZM was generally utilized for approved indication and in accordance with the summary of product characteristics recommendations.
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Production of anti-inflammatory compounds in Sphaeralcea angustifolia cell suspension cultivated in stirred tank bioreactor.

Sphaeralcea angustifolia is a plant used for the treatment of inflammatory processes. Scopoletin, tomentin, and sphaeralcic acid were identified as the compounds with anti-inflammatory and immunomodulatory effects. Successful establishment of the cell culture in Erlenmeyer flasks has been reported previously. The aim of this study was to evaluate the ability of cells in suspension from S. angustifolia grown in a stirred tank bioreactor and demonstrate their capacity to produce bioactive compounds. Cells in suspension grown at 200 rpm reached a maximal cell biomass in dry weight at 19.11 g/L and produced 3.47 mg/g of sphaeralcic acid. The mixture of scopoletin and tomentin was only detected at the beginning of the culture (12.13 µg/g). Considering that the profile of dissolved oxygen during the cultures was lesser than 15%, it is possible that the low growth at 100 rpm could be due to oxygen limitations or to cell sedimentation. At 400 rpm, a negative effect on cell viability could be caused by the increase in the hydrodynamic stress, including the impeller tip, average shear rate, and Reynolds number. The sphaeralcic acid content in the cell suspension of S. angustifolia obtained in the bioreactor was two orders of magnitude greater than that reported for the culture grown in Erlenmeyer flasks.

Actividad in vitro del tedizolid y de antibióticos de comparación en aislamientos de Staphylococcus aureus resistentes a meticilina en infecciones de piel y tejidos blandos en siete hospitales de Colombia / In vitro activity of tedizolid and other comparator drugs in methicillin-resistant Staphylococcus aureus isolates in skin and soft tissue infections in seven Colombian hospitals

Introducción. Staphylococcus aureus resistente a meticilina (SARM) causa infecciones graves de la piel y los tejidos blandos en los hospitales y, en los últimos años, en la comunidad. El tedizolid es una nueva oxazolidinona cuya potencia in vitro ha demostrado ser mayor que la del linezolid frente a este microorganismo. Objetivo. Conocer la actividad antimicrobiana del tedizolid y de algunos antibióticos de comparación en aislamientos de SARM causante de infecciones de piel y tejidos blandos en hospitales de Colombia. Materiales y métodos. Se hizo un estudio multicéntrico prospectivo y descriptivo a lo largo de doce meses en siete hospitales de tercer nivel de Colombia. Se recolectaron aislamientos de SARM de pacientes adultos con infección de piel y tejidos blandos. Se determinó la concentración inhibitoria mínima (CIM) mediante la técnica de ETEST® (bioMérieux) del tedizolid, el linezolid, la vancomicina, la daptomicina, el trimetoprim-sulfametoxazol y la clindamicina. Resultados. Se obtuvieron aislamientos de SARM de 102 pacientes, de los cuales 56 (54,9 %) eran hombres; el promedio de edad fue de 46,8 años. La infección tuvo origen en la comunidad en 77 casos (75,4 %). El tipo de muestra que predominó fue el absceso (69 pacientes: 67,6 %). Todos los aislamientos fueron sensibles a tedizolid, linezolid, daptomicina, trimetoprim-sulfametoxazol y vancomicina. La actividad in vitro del tedizolid fue mayor que la del linezolid. Los intervalos de la CIM del tedizolid oscilaron entre 0,125 µg/ml y 0,5 µg/ml en tanto que los del linezolid fluctuaron entre 1 µg/m y 2 µg/ml. Conclusiones. Las cepas circulantes de SARM en Colombia presentaron una gran sensibilidad al tedizolid, por lo cual sería una alternativa terapéutica para las infecciones de piel y tejidos blandos en nuestro medio.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) causes severe skin and soft tissue infections in hospitals and, more recently, in the community. Tedizolid is a new second-generation oxazolidinone derivative having greater in vitro potency than linezolid against this type of microorganism. Objectives: To evaluate the antimicrobial activity of tedizolid and other comparator antibiotics in MRSA isolates causing skin and soft tissue infections in Colombian hospitals. Materials and methods: We conducted a prospective, multi-center descriptive study in seven tertiary-level hospitals in Colombia along a 12-month period. MRSA isolates were collected from adult patients with skin and soft tissue infections. Tedizolid, linezolid, vancomycin, daptomycin, trimethoprimsulfamethoxazole, and clindamycin minimum inhibitory concentration (MIC) was determined by ETEST® (bioMérieux). Results: MRSA isolates were obtained from 102 patients with an average age of 46.8 years of whom 56 (54.9%) were men. Infection was community-acquired in 77 cases (75.4%). Abscess-related samples predominated (69 patients: 67.6%). All isolates were susceptible to tedizolid, linezolid, daptomycin, trimethoprim-sulfamethoxazole, and vancomycin. Tedizolid had greater in vitro activity than linezolid. Tedizolid MIC intervals ranged from 0.125 µg/mL to 0.5 µg/mL while those of linezolid ranged from 1µg/mL to 2µg/mL. Conclusions: MRSA strains circulating in Colombia are highly susceptible to tedizolid and can be considered a therapeutic alternative for hospitals and/or community-acquired skin and soft tissue infections.

Nano based drug delivery systems: recent developments and future prospects.

Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner. Nanotechnology offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines. Recently, there are a number of outstanding applications of the nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic agents etc.) in the treatment of various diseases. The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (e.g., natural products) and selective diagnosis through disease marker molecules. The opportunities and challenges of nanomedicines in drug delivery from synthetic/natural sources to their clinical applications are also discussed. In addition, we have included information regarding the trends and perspectives in nanomedicine area.

In vitro activity of tedizolid and other comparator drugs in methicillin-resistant Staphylococcus aureus isolates in skin and soft tissue infections in seven Colombian hospitals / Actividad in vitro del tedizolid y de antibióticos de comparación en aislamientos de Staphylococcus aureus resistentes a meticilina en infecciones de piel y tejidos blandos en siete hospitales de Colombia.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) causes severe skin and soft tissue infections in hospitals and, more recently, in the community. Tedizolid is a new second-generation oxazolidinone derivative having greater in vitro potency than linezolid against this type of microorganism. Objectives: To evaluate the antimicrobial activity of tedizolid and other comparator antibiotics in MRSA isolates causing skin and soft tissue infections in Colombian hospitals. Materials and methods: We conducted a prospective, multi-center descriptive study in seven tertiary-level hospitals in Colombia along a 12-month period. MRSA isolates were collected from adult patients with skin and soft tissue infections. Tedizolid, linezolid, vancomycin, daptomycin, trimethoprim-sulfamethoxazole, and clindamycin minimum inhibitory concentration (MIC) was determined by ETEST® (bioMérieux). Results: MRSA isolates were obtained from 102 patients with an average age of 46.8 years of whom 56 (54.9%) were men. Infection was community-acquired in 77 cases (75.4%). Abscess-related samples predominated (69 patients: 67.6%). All isolates were susceptible to tedizolid, linezolid, daptomycin, trimethoprim-sulfamethoxazole, and vancomycin. Tedizolid had greater in vitro activity than linezolid. Tedizolid MIC intervals ranged from 0.125 µg/mL to 0.5 µg/mL while those of linezolid ranged from 1µg/mL to 2µg/mL. Conclusions: MRSA strains circulating in Colombia are highly susceptible to tedizolid and can be considered a therapeutic alternative for hospitals and/or community-acquired skin and soft tissue infections.

Introducción. Staphylococcus aureus resistente a meticilina (SARM) causa infecciones graves de la piel y los tejidos blandos en los hospitales y, en los últimos años, en la comunidad. El tedizolid es una nueva oxazolidinona cuya potencia in vitro ha demostrado ser mayor que la del linezolid frente a este microorganismo.Objetivo. Conocer la actividad antimicrobiana del tedizolid y de algunos antibióticos de comparación en aislamientos de SARM causante de infecciones de piel y tejidos blandos en hospitales de Colombia.Materiales y métodos. Se hizo un estudio multicéntrico prospectivo y descriptivo a lo largo de doce meses en siete hospitales de tercer nivel de Colombia. Se recolectaron aislamientos de SARM de pacientes adultos con infección de piel y tejidos blandos. Se determinó la concentración inhibitoria mínima (CIM) mediante la técnica de ETEST® (bioMérieux) del tedizolid, el linezolid, la vancomicina, la daptomicina, el trimetoprim-sulfametoxazol y la clindamicina.Resultados. Se obtuvieron aislamientos de SARM de 102 pacientes, de los cuales 56 (54,9 %) eran hombres; el promedio de edad fue de 46,8 años. La infección tuvo origen en la comunidad en 77 casos (75,4 %). El tipo de muestra que predominó fue el absceso (69 pacientes: 67,6 %). Todos los aislamientos fueron sensibles a tedizolid, linezolid, daptomicina, trimetoprim-sulfametoxazol y vancomicina. La actividad in vitro del tedizolid fue mayor que la del linezolid. Los intervalos de la CIM del tedizolid oscilaron entre 0,125 µg/ml y 0,5 µg/ml en tanto que los del linezolid fluctuaron entre 1 µg/m y 2 µg/ml.Conclusiones. Las cepas circulantes de SARM en Colombia presentaron una gran sensibilidad al tedizolid, por lo cual sería una alternativa terapéutica para las infecciones de piel y tejidos blandos en nuestro medio.

[Analysis of the impact of mortality due to suicides in Mexico, 2000-2012]. / Análisis del impacto de la mortalidad por suicidios en México, 2000-2012.

The objective of this study was to analyze the burden of disease due to suicide in Mexico using years of life lost (YLL) between 2000 and 2012 by sex, age group (for those under 85 years of age) and jurisdiction. Vital statistics on mortality and population estimates were used to calculate standardized mortality rates and years of life lost due to suicide. Between 2000 and 2012 a sustained increase in the suicide mortality rate was observed in Mexico. The age group with the highest rate was 85 years of age or older for men, and 15-19 years of age for women. The highest impact in life expectancy due to suicide occurred at 20 to 24 years of age in men and 15 to 19 years of age in women. The states with the highest mortality due to suicide were located in the Yucatan Peninsula (Yucatan, Quintana Roo and Campeche). Mortality due to suicide in Mexico has increased continually. As suicides are preventable, the implementation of health public policies through timely identification, integral prevention strategies and the detailed study of associated risk factors is imperative.

Análisis del impacto de la mortalidad por suicidios en México, 2000-2012 / Analysis of the impact of mortality due to suicides in Mexico, 2000-2012

El objetivo del presente artículo es analizar la carga de la mortalidad por suicidios en México, a partir del indicador de años de vida perdidos (AVP), entre 2000 y 2012, por sexo, grupos de edad (para menores de 85 años de edad) a nivel nacional y por entidad federativa. Se emplearon estadísticas vitales de mortalidad y estimaciones de población para calcular tasas estandarizadas de mortalidad y los años de vida perdidos por suicidios. Entre 2000 y 2012 se dio un incremento sostenido de la tasa de mortalidad por suicidios. En hombres, el grupo de edad con las mayores tasas fue el de 85 años y más; para mujeres el de 15-19 años. El mayor impacto en la esperanza de vida se dio entre los 20 y 24 años en hombres y entre los 15 y 19 años para mujeres. Los estados con la mayor mortalidad se ubican en la península de Yucatán (Yucatán, Quintana Roo y Campeche). La mortalidad por suicidio en México se ha incrementado de manera constante. Los suicidios son prevenibles, por lo que es fundamental implementar políticas públicas en salud a través de acciones de identificación oportuna, estrategias integrales de prevención y el estudio detallado de los factores de riesgo asociados.

The objective of this study was to analyze the burden of disease due to suicide in Mexico using years of life lost (YLL) between 2000 and 2012 by sex, age group (for those under 85 years of age) and jurisdiction. Vital statistics on mortality and population estimates were used to calculate standardized mortality rates and years of life lost due to suicide. Between 2000 and 2012 a sustained increase in the suicide mortality rate was observed in Mexico. The age group with the highest rate was 85 years of age or older for men, and 15-19 years of age for women. The highest impact in life expectancy due to suicide occurred at 20 to 24 years of age in men and 15 to 19 years of age in women. The states with the highest mortality due to suicide were located in the Yucatan Peninsula (Yucatan, Quintana Roo and Campeche). Mortality due to suicide in Mexico has increased continually. As suicides are preventable, the implementation of health public policies through timely identification, integral prevention strategies and the detailed study of associated risk factors is imperative.

Heparin assisted photochemical synthesis of gold nanoparticles and their performance as SERS substrates.

Reactive and pharmaceutical-grade heparins were used as biologically compatible reducing and stabilizing agents to photochemically synthesize colloidal gold nanoparticles. Aggregates and anisotropic shapes were obtained photochemically under UV black-light lamp irradiation (λ = 366 nm). Heparin-functionalized gold nanoparticles were characterized by Scanning Electron Microscopy and UV-Vis spectroscopy. The negatively charged colloids were used for the Surface Enhanced Raman Spectroscopy (SERS) analysis of differently charged analytes (dyes). Measurements of pH were taken to inspect how the acidity of the medium affects the colloid-analyte interaction. SERS spectra were taken by mixing the dyes and the colloidal solutions without further functionalization or addition of any aggregating agent.

Sphaeralcic acid and tomentin, anti-inflammatory compounds produced in cell suspension cultures of Sphaeralcea angustifolia.

Sphaeralcea angustifolia, an endangered plant species in Mexico, is employed to treat inflammatory processes and as a wound healing remedy. Scopoletin (1) was reported as one of the main bioactive compounds in this plant. Here, we isolated and identified compounds with anti-inflammatory properties from the suspension-cultured cells of S. angustifolia. The CH2Cl2 : CH3OH extract of the cells exhibited anti-inflammatory properties in acute inflammation models. Two compounds were isolated, 5-hydroxy-6,7-dimethoxycoumarin, named tomentin (2), and 2-(1,8-dihydroxy-4-isopropyl-6-methyl-7-methoxy)-naphthoic acid, denominated as sphaeralcic acid (3). Their structures were determined by spectroscopic and spectrometric analyses. The anti-inflammatory effects of both compounds were also evaluated. At a dose of 45 mg/kg, compound 2 inhibited the formation of λ-carrageenan footpad edema at 58 %, and compound 3 at 66 %. Local application of compound 2 (225 mM per ear) or 3 (174 mM per ear) inhibited the phorbol ester-induced auricular edema formation by 57 % or 86 %, respectively. The effect of compound 3 was dose-dependent and the ED50 was 93 mM.

Cross-linked enzyme aggregates (CLEAs) of selected lipases: a procedure for the proper calculation of their recovered activity.

In the last few years, synthesis of carrier-free immobilized biocatalysts by cross-linking of enzyme aggregates has appeared as a promising technique. Cross-linked enzyme aggregates (CLEAs) present several interesting advantages over carrier-bound immobilized enzymes, such as highly concentrated enzymatic activity, high stability of the produced superstructure, important production costs savings by the absence of a support, and the fact that no previous purification of the enzyme is needed. However, the published literature evidences that a) much specific non-systematic exploratory work is being done and, b) recovered activity calculations in CLEAs still need to be optimized. In this context, this contribution presents results of an optimized procedure for the calculation of the activity retained by CLEAs, based on the comparison of their specific activity relative to their free enzyme counterparts. The protocol implies determination of precipitable protein content in commercial enzyme preparations through precipitation with ammonium sulphate and a protein co-feeder. The identification of linear ranges of activity versus concentration/amount of protein in the test reaction is also required for proper specific activity determinations. By use of mass balances that involve the protein initially added to the synthesis medium, and the protein remaining in the supernatant and washing solutions (these last derived from activity measurements), the precipitable protein present in CLEAs is obtained, and their specific activity can be calculated. In the current contribution the described protocol was applied to CLEAs of Thermomyces lanuginosa lipase, which showed a recovered specific activity of 11.1% relative to native lipase. The approach described is simple and can easily be extended to other CLEAs and also to carrier-bound immobilized enzymes for accurate determination of their retained activity.

Microbiological and Pharmacological Evaluation of the Micropropagated Rubus liebmannii Medicinal Plant.

Rubus liebmannii is an endemic species from Mexico used in traditional medicine primarily to treat dysentery and cough. The in vitro activity against Giardia lamblia and Entamoeba histolytica that produces the ethanolic extract of the aerial parts of the plant led us to expand the pharmacological and phytochemical research of this species. Gastrointestinal disorders including amebiasis remain one of the health problems that need to be addressed and it is of interest to find alternatives that improve their treatment. Also, it is important to emphasize that R. liebmannii grows wild in the country and is not found in abundance; therefore, alternatives that avoid overexploitation of the natural resource are mandatory. Ongoing with the evaluation of the potentialities that R. liebmannii possesses for treating infectious gastrointestinal diseases, the aim of the present study was to evaluate the biological effects and the chemical composition of the micropropagated plant.