Solid Lipid Nanoparticles Based on Babassu Oil and Copaiba Oleoresin: A Promising Approach for Prostate Cancer Therapy.

Solid lipid nanoparticles (SLNs) represent promising nanostructures for drug delivery systems. This study successfully synthesized SLNs containing different proportions of babassu oil (BBS) and copaiba oleoresin (COPA) via the emulsification-ultrasonication method. Before SLN synthesis, the identification and quantification of methyl esters, such as lauric acid and ß-caryophyllene, were performed via GC-MS analysis. These methyl esters were used as chemical markers and assisted in encapsulation efficiency experiments. A 22 factorial design with a center point was employed to assess the impact of stearic acid and Tween 80 on particle hydrodynamic diameter (HD) and polydispersity index (PDI). Additionally, the effects of temperature (8 ± 0.5 °C and 25 ± 1.0 °C) and time (0, 7, 15, 30, 40, and 60 days) on HD and PDI values were investigated. Zeta potential (ZP) measurements were utilized to evaluate nanoparticle stability, while transmission electron microscopy provided insights into the morphology and nanometric dimensions of the SLNs. The in vitro cytotoxic activity of the SLNs (10 µg/mL, 30 µg/mL, 40 µg/mL, and 80 µg/mL) was evaluated using the MTT assay with PC-3 and DU-145 prostate cancer cell lines. Results demonstrated that SLNs containing BBS and COPA in a 1:1 ratio exhibited a promising cytotoxic effect against prostate cancer cells, with a percentage of viable cells of 68.5% for PC-3 at a concentration of 30 µg/mL and 48% for DU-145 at a concentration of 80 µg/mL. These findings underscore the potential therapeutic applications of SLNs loaded with BBS and COPA for prostate cancer treatment.

Anti-inflammatory action of geopropolis produced by stingless bees on human peripheral blood mononuclear cells.

Natural products have been used to treat inflammatory reactions and led to the discovery of new anti-inflammatory drugs. Geopropolis (GEO) is produced by stingless bees and has been used by indigenous people to improve the immune functions. Here, a possible synergism between GEO and dexamethasone (DEX) was assessed on human peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (LPS). PBMC viability was evaluated by the MTT, apoptosis/necrosis by flow cytometry, cytokine and eicosanoids production by ELISA, and intracellular pathways by polymerase chain reaction. GEO and DEX alone or in combination did not affect cell viability. GEO in combination with lower concentrations of DEX inhibited cytokine production (TNF-α, IL-1ß, and IL-10). No effects were seen on eicosanoids nor in intracellular pathways. Despite not always being more efficient than the isolated treatments, GEO + DEX seemed to be promising and allow the use of DEX in lower concentrations, reducing adverse effects.

Use of In silico Methodologies to Predict the Bioavailability of Oral Suspensions: A Regulatory Approach.

BACKGROUND: Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability. OBJECTIVE: The aim of this work was to develop a discriminative dissolution test, which, in association with in silico methodologies, can make it possible to safely anticipate bioavailability problems. METHODS: Nimesulide and ibuprofen (BCS class II) and cephalexin (BCS class I) oral suspensions were studied. Previously, solid-state structure and particle size in active pharmaceutical ingredients were characterized and the impact of differences on solubility was evaluated for the choice of discriminative medium. Afterwards, particle size distribution (0.1 to 360 µm), dissolution profile, and in vitro permeability in Caco-2 cell of commercial suspensions, were determined. These parameters were used as input for the establishment of the in vitro-in vivo correlation (IVIVC) for the suspensions using the GastroPlus™ with Wagner-Nelson and Loo- Riegelmann deconvolution approach. RESULTS: The predicted/observed pharmacokinetic model showed good correlation coefficients (r) of 0.960, 0.950, and 0.901, respectively. The IVIVC was established for one nimesulide and two ibuprofen suspensions with r between 0.956 and 0.932, and the percent prediction error (%PE) did not exceed 15%. CONCLUSION: In this work, we have performed a complete study combining in vitro/in silico approaches with the aim of anticipating the safety and efficacy of oral pharmaceutical suspensions in order to provide a regulatory tool for this category of products in a faster and more economical way.

The influence of the menstrual cup on female pelvic floor muscles variables: a prospective case series.

The aim was to assess and report the effects of menstrual cup on pelvic floor muscles (PFM) function and tone, as well as check the acceptability after a period of three menstrual cycles in healthy young women. The data collected in assessments and reassessments included the International Consultation on Incontinence Questionnaire - Vaginal Symptoms (ICIQ-VS) questionnaire, evaluation of PFM function through PERFECT Scheme, PFM muscle tone, and PFM manometry (Peritron 9300®). A diary regarding the overall colletor acceptability and satisfaction was collected. Ten healthy young women completed the study. There was an improvement in the mean values of maximal voluntary contraction (MVC) (p = 0.032), a decrease in the vaginal resting pressure (VRP) (p = 0.05), and an increase in the number of repetitions of sustained muscle contractions (p = 0.042). Seven women reported some discomfort while using the vaginal cup only in the first cycle while three revealed discomfort during the whole experiment. This study provides preliminary case-based evidence that the use of the vaginal cup for a period of three menstrual cycles changes the VRP, MVC, and PFM tone, as well as improves the repetitions of PFM assessed by digital palpation. Moreover, the women reported the use of vaginal cup as a positive experience.

Propolis antiviral and immunomodulatory activity: a review and perspectives for COVID-19 treatment.

OBJECTIVES: Viral outbreaks are a frequent concern for humans. A great variety of drugs has been used to treat viral diseases, which are not always safe and effective and may induce adverse effects, indicating the need for new antiviral drugs extracted from natural sources. Propolis is a bee-made product exhibiting many biological properties. An overview of viruses, antiviral immunity, propolis safety and its immunomodulatory and antiviral action is reported, as well as perspectives for coronavirus disease 2019 (COVID-19) treatment. PubMed platform was used for data collection, searching for the keywords "propolis", "virus", "antiviral", "antimicrobial" and "coronavirus". KEY FINDINGS: Propolis is safe and exerts antiviral and immunomodulatory activity; however, clinical trials should investigate its effects on individuals with viral diseases, in combination or not with antiviral drugs or vaccines. SUMMARY: Regarding COVID-19, the effects of propolis should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs, due to its immunomodulatory and anti-inflammatory action. Propolis administration simultaneously with vaccines should be analyzed, due to its adjuvant properties, to enhance the individuals' immune response. The search for therapeutic targets may be useful to find out how propolis can help to control COVID-19.

Qualitative study of return to work following breast cancer treatment.

BACKGROUND: After 5 years' sick leave in Brazil, employees must retire due to disability. The duration from breast cancer surgery to the end of treatment should be ~9 months. However, diagnosis alone can take 6 months. Surveys administered soon after returning to work have highlighted problems regarding the slow speed of the treatment process and lack of protective legislation. AIMS: To assess the barriers and facilitators experienced and the coping strategies adopted by Brazilian women 30 days after return to work following breast cancer treatment. METHODS: A qualitative study of 12 women treated for breast cancer. The interviews were recorded, transcribed verbatim and independently analysed by two researchers using a standardized method of analysis. RESULTS: Women took an average of 583 days to return to work following breast cancer treatment. The return-to-work experience was considered good, with the physical barriers being fatigue and problems with the arms, and the work environmental barriers being related to discrimination from employers and overprotection from colleagues. Facilitators included social and emotional support given by colleagues/relatives/employers and jobs requiring more cognitive effort than physical exertion. Coping strategies were related to job role adjustments and reduction in tasks and working hours. CONCLUSIONS: Results were similar to those reported by previous studies, with the exception of the facilitators. Cognitive effort is commonly considered a barrier. However, the present study had an unusually long duration before return to work, possibly reducing the acute effects of chemotherapy on cognition.

Hypertension in seven Latin American cities: the Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study.

BACKGROUND: Little information is available regarding hypertension, treatment, and control in urban population of Latin America. OBJECTIVE: We aimed to compare blood pressure (BP) distribution, hypertension prevalence, treatment, and control in seven Latin American cities following standard methodology. METHODS: The Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study was a cross-sectional, epidemiologic study assessing cardiovascular risk factors using stratified multistage sampling of adult populations (aged 25-64 years) in seven cities: Barquisimeto (Venezuela; n = 1848); Bogotá (n = 1553); Buenos Aires (n = 1482); Lima (n = 1652); Mexico City (n = 1720); Quito (n = 1638); and Santiago (n = 1655). The prevalence of hypertension and high normal BP were determined based on 2007 European Society of Hypertension and European Society of Cardiology definitions. RESULTS: BP increased with age in men and women; pulse pressure increased mainly in the upper age group. The hypertension prevalence ranged from 9% in Quito to 29% in Buenos Aires. One-quarter to one-half of the hypertension cases were previously undiagnosed (24% in Mexico City to 47% in Lima); uncontrolled hypertension ranged from 12% (Lima) to 41% (Mexico City). High normal BP was also evident in a substantial number of each city participants (approximately 5-15%). Majority of population has other cardiovascular risk factors despite hypertension; only 9.19% of participants have no risk factors apart from hypertension. CONCLUSION: From 13.4 to 44.2% of the populations of seven major Latin American cities were hypertensive or had high normal BP values. Most hypertensive patients have additional risk factors. Public health programs need to target prevention, detection, treatment, and control of total cardiovascular risk in Latin America.

Prevalence of the metabolic syndrome in Latin America and its association with sub-clinical carotid atherosclerosis: the CARMELA cross sectional study.

BACKGROUND: Metabolic syndrome increases cardiovascular risk. Limited information on its prevalence in Latin America is available. The Cardiovascular Risk Factor Multiple Evaluation in Latin America (CARMELA) study included assessment of metabolic syndrome in 7 urban Latin American populations. METHODS: CARMELA was a cross-sectional, population-based, observational study conducted in Barquisimeto, Venezuela; Bogota, Colombia; Buenos Aires, Argentina; Lima, Peru; Mexico City, Mexico; Quito, Ecuador; and Santiago, Chile. The prevalence of metabolic syndrome, defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and associated carotid atherosclerosis were investigated in 11,502 participants aged 25 to 64 years. RESULTS: Across CARMELA cities, metabolic syndrome was most prevalent in Mexico City (27%) and Barquisimeto (26%), followed by Santiago (21%), Bogota (20%), Lima (18%), Buenos Aires (17%), and Quito (14%). In nondiabetic participants, prevalence was slightly lower but followed a comparable ranking. Overall, 59%, 59%, and 73% of women with high triglycerides, hypertension, or glucose abnormalities, respectively, and 64%, 48% and 71% of men with abdominal obesity, hypertension, or glucose abnormalities, respectively, had the full metabolic syndrome. Prevalence of metabolic syndrome increased with age, markedly so in women. Mean common carotid artery intima-media thickness (CCAIMT) and prevalence of carotid plaque increased steeply with increasing numbers of metabolic syndrome components; mean CCAIMT was higher and plaque more prevalent in participants with metabolic syndrome than without. CONCLUSION: The prevalence of metabolic syndrome and its components by NCEP ATP III criteria was substantial across cities, ranging from 14% to 27%. CARMELA findings, including evidence of the association of metabolic syndrome and carotid atherosclerosis, should inform appropriate clinical and public health interventions.

CARMELA: assessment of cardiovascular risk in seven Latin American cities.

OBJECTIVE: This cross-sectional, population-based observational study using stratified multistage sampling assessed the prevalence of cardiovascular risk factors and carotid plaques and measured carotid intima-media thickness in individuals living in major cities in 7 Latin American countries. PATIENTS AND METHODS: The study comprised individuals (n=11,550) aged 25 to 64 years, living in Barquisimeto, Bogota, Buenos Aires, Lima, Mexico City, Quito, and Santiago. Data on anthropometric parameters, blood pressure, fasting glucose, total and high-density lipoprotein cholesterol, triglycerides, carotid intima-media thickness, carotid plaque, and smoking status were collected through household interviews and clinical, biochemical, and sonographic measurements. RESULTS: The overall prevalence rates (ranges across cities) were as follows: hypertension (> or = 140/90 mm Hg or pharmacologic treatment), 18% (9%-29%); hypercholesterolemia (total cholesterol > or = 240 mg/dL), 14% (6%-20%); diabetes (glycemia > or = 126 mg/dL or self-reported diabetes), 7% (4%-9%); metabolic syndrome, 20% (14%-27%); obesity (body mass index > or = 30 kg/m2), 23% (18%-27%); smoking, 30% (22%-45%); and plaque, 8% (5%-14%). The mean intima-media thickness was 0.65 mm (0.60-0.74 mm). CONCLUSION: The prevalence of hypertension mirrored the world average in 3 cities but was lower in the rest. Hypercholesterolemia was highly prevalent even in countries of different socioeconomic levels. The prevalence of diabetes was similar to that in the developed countries. Tobacco use in women living in Santiago and Buenos Aires was among the world's highest. Intima-media thickness and carotid plaque prevalences varied widely.

Vigilancia de la resistencia bacteriana a los antibióticos en Venezuela / Surveillance of bacterial resistance to antibiotics in Venezuela

Los resultados presentados ponen de manifiesto las cifras de resistencia a los antibióticos en cepas bacterianas aisladas recientemente en hospitales venezolanos. La necesidad de modificaciones a los esquemas tradicionales de tratamiento quedó de manifiesto. Problemas recientes parecen ser la resistencia en gonococco, la sensibilidad disminuida a la pinicilina en neumococo, la resistencia creciente a cefalosporinas de tercera generación en bacilos Gram negativos y el incremento de resistencia a las nuevas quinolonas. El sistema de vigilancia presentado ha funcionado y representa una valiosa ayuda para la selección empírica de antibióticos. Igualmente, permite detectar precozmente cambios de patrón y, gracias a los programas existentes de computación, permite inferir mecanismos especificos de resistencia. Intentar correlacionar estos resultados con patrones de uso de antibióticos escapa del propósito del presente trabajo. Sin embargo, las cifras presentadas invitan el uso juicioso y ponderado de los mismos

Monoterapia de la hipertensión arterial leve y moderada con amlodipina, un nuevo antagonista del calcio: un estudio multicentrico / Monotherapy of mild and moderate essential hypertension, a new calcium antagonist: a multicentric study

Se estudió la actividad antihipertensiva y tolerancia de la amlodipina, como monoterapia en 37 pacientes adultos (33-70 años, promedio: 50,5 años) de ambos sexos con diagnóstico de hipertensión arterial esencial leve y moderada (PAD: 95-114 mmHg) en un diseño abierto no comparativo. Después de la administración de placebo durante 2 semanas, se inició la administración de amlodipina en dosis única (5-10 mg/día) durante 12 semanas, siendo evaluados los pacientes clínicamente cada 2 semanas, durante este período. Al finalizar el tratamiento con amlodipina, se observó una disminución significativa de la presión arterial (sentado) de 29/21 mmHg (P < 0,001), no apreciándose modificaciones significativas en la frecuencia cardíaca y peso corporal ni en los parámetros de rutina de laboratorio. Durante el tratamiento con amlodipina, se logró arterial (PAD < 90 mmHg) en 27 pacientes (84,3%). Se presentaron reacciones adversas (palpitaciones, cansancio y disnea) en un solo paciente, requiéndose la discontinuación de la terapia por su severidad. Se concluye que la amlodipina es un nuevo bloqueante de los canales de calcio que parece ser efectivo y bien tolerado como monoterapia en la hipertensión arterial esencial leve moderada

Evaluación multicéntrica venezolana del piroxicam en el tratamiento de osteoartritis y reumatismo extra-articular agudo / Venezuelan multicentric evaluation of piroxicam in the treatment of ostearthritis and acute extra-articular rheumatism

En el presente trabajo se evaluó eficacia y tolerancia del Piroxicam en 633 pacientes, 428 (67%) de los cuales concluyeron el ensayo. Del total evaluado, 234 presentaban osteoartritis (OA) y 194 reumatismo extra-articular agudo (REA). En 217 pacientes (92.7%) con OA, que recibieron 20 mg diarios v.o. de Piroxicam por 30 días, la eficacia fue evaluada como excelente o buena, con mejoría mayor del 75% para el dolor, la rigidez y la inflamación. En 191 pacientes (98.4%) con REA, que recibieron 40 mg Piroxicam v.o. en los dos primeros días seguido de 20 mg diarios por 5 a 12 días más, la eficacia fue clasificada como excelente o buena, con mejoría de un 90% en el dolor, la limitación funcional y la inflamación. En 233 pacientes (99.6%) con OA y en 193 pacientes (99.4%) con REA, no hubo efectos secundarios o fueron de leve intensidad, encontrándose principalmente en el tracto gastrointestinal. Sólo un paciente de cada grupo suspendió el tratamiento por los efectos secundarios. Concluimos que el Piroxicam es una droga eficaz y bien tolerada en el tratamiento de la OA y el REA

Experiencia con prazosin como monoterapia de la hipertension arterial leve y moderada: su efecto sobre lípidos y lipoproteinas plasmáticos encomparación con propanolol / Experience with prazosin as montherapy of mild and moderate essential hypertension: effect on plasma lipids and lipoproteins in comparasion with propanolol

Se evaluó la actividad antihipertensiva y tolerancia del prazosin (PRZ), un bloqueador adrenérgico alfa-1 selectivo, en 164 pacientes adultos de ambos sexos, con edad comprendida entre 21-28 años con diagnóstico de hipertensión arterial esencial (HTA) leve y moderada (presión arterial diastólica 90-104 mmHg y 105-114 mmHg, respectivamente) en un diseño abierto multicéntrico no comparativo. Se administró placebo por dos semanas y luego se inició el tratamiento con PRZ a la dosis de 1-10 mg/día, durante 8 semanas. La administración de PRZ se tradujo en un significado descenso de la presión arterial sistólica (PAS y presión arterial diastólica (PAD) en posición supina y de pie, de 23/21 y 26.1/21.6 mmHg respectivamente, al cabo de 8 semanas (p<0.01). No se observaron cambios significativos en la frecuencia cardíaca o en el peso corporal. 44 pacientes (26.8%) manifestaron efectos indeseables al tratamiento con PRZ (principalmente debilidad y mareos) que obligaron a la descontración de la terapia en 10 de ellos (6.1%). Se alcanzó el control de las cifras tensionales (PAD 90 mmHg) en el 80.8% de los pacientes con HTA levs y en el 67.9% de los pacientes con HTA moderada al cabo de 5 semanas de terapia

Piroxicam en el tratamiento sintomático de la dismenorrea primaria: un estudio multicéntrico venezolano / Piroxicam in the symptomatic treatment of primary dysmenorrhea: a multicenter Venezuelan study

Se evaluó la actividad analgésica y tolerancia del Piroxicam (P) en 69 pacientes con diagnóstico de dismenorrea primaria en un diseño multicéntrico abierto no-comparativo. Luego de un período basal sin droga activa se administró P a la dosis de 40 mg/día x 2 días seguidos de 20 mg/día x 2 días durante dos ciclos menstruales consecutivos. A 42 pacientes se les administró un tercer ciclo de tratamiento con P. La administración de P se tradujo en un significativo descenso de la intensidad del dolor (62.2% a 72.8% p < 0.001) en los diferentes días del ciclo menstrual. Un 79.1% de los pacientes manifestaron sentirse asintomáticos al cabo de 2 ciclos de tratamiento con P. No hubo cambios significativos en la reducción del dolor durante el tercer ciclo de tratamiento con P en comparación con el segundo ciclo. Piroxicam fue bien tolerado. Se observaron efectos secundarios en solo 7 pacientes (10.1%), 2 de ellos presentaron rash cutáneo que obligó a la suspensión del tratamiento. La evaluación global de la terapia con P fue excelente y buena en el 92% de los pacientes tratados. Piroxicam es útil en el tratamiento sintomático de la dismenorrea primaria administrado en dosis única diaria