RESUMEN
Candida species are amongst the commensals of the mucosal surfaces of the human body which include the oral cavity, vagina, and intestinal mucosa. Fungal infections are on the rise worldwide. The overall burden of infections due to fungi is difficult to estimate because the majority of them remain undiagnosed. The present study aims to determine the burden of antifungal resistance in low socioeconomic country, Pakistan and the frequency of ERG11 and MDR1 genes involved. A total of 636 Candida isolates were obtained from various tertiary care institutions in Lahore in the form of culture on various culture plates. Sabouraud agar culture plates were used to culture the Candida spp. Antifungal resistance was determined against Fluconazole, Itraconazole, Ketoconazole, and Nystatin via disk diffusion technique. Most resistance was observed against Fluconazole followed by Itraconazole, Ketoconazole, and Nystatin. The Candida isolates recovering from CVP tip and tissue have a high resistance profile. Candida species resistant to at least two antifungals were chosen for further ERG11 and MDR1 detection through real-time PCR. Among 255 Candida isolates, 240 contained ERG11 gene while MDR1 gene is present in 149 Candida isolates. The isolates carrying both genes were tested by the broth microdilution technique for the susceptibility against cycloheximide, all of them were able to grow in cycloheximide. The genetic determinants of antifungal resistance such as ERG11 and MDR1 are as important in the multidrug resistance against a variety of compounds and antifungal drugs.
Asunto(s)
Antifúngicos , Candida , Cicloheximida , Pruebas de Sensibilidad Microbiana , Antifúngicos/farmacología , Humanos , Candida/efectos de los fármacos , Candida/genética , Candida/clasificación , Candida/aislamiento & purificación , Cicloheximida/farmacología , Pakistán , Candidiasis/microbiología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Farmacorresistencia Fúngica Múltiple/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismoRESUMEN
Introducción: La diarrea con sangre es un motivo frecuente de admisión hospitalaria en niños, con gastroenteritis aguda; en la mayoría de los casos se tratan de infecciones leves y autolimitadas, pero pueden producirse complicaciones graves. Objetivos: Describir la etiología y características clínico- evolutivas de los niños menores de 15 años hospitalizados por diarrea con sangre en el Hospital Pediátrico, Centro Hospitalario Pereira Rossell entre los años 2012- 2023. Materiales y métodos: Estudio retrospectivo mediante revisión de historias y registros de laboratorio. Variables: demográficas, estado nutricional, hidratación, motivos de hospitalización, ingreso unidades de cuidados intensivos (UCI), enteropatógenos, tratamientos, evolución. Resultados: Se incluyeron 229 niños, mediana de edad de 8 meses; sexo masculino 61%; eutróficos 88%, bien hidratados 55%, con comorbilidades 11%, prematurez 6,5%. El motivo de hospitalización fue diarrea con sangre/disentería sin otro síntoma 45%. Se solicitó coprovirológico/coprocultivo en 98% y detección por técnicas de ácidos nucleicos en materia fecal 5,2%. Se identificó al menos un agente patógeno en 34,3%: Shigella sp. 38%; Salmonella sp. 19,5%; coinfecciones en 12%. Se indicaron antibióticos a 86%; ceftriaxona 62%, azitromicina 35%. Ingresaron a UCI 6,5% (15), presentaron complicaciones 10/14, fallo renal agudo 5 y alteraciones del medio interno 3. La mayoría presentó buena evolución. Conclusiones: La diarrea con sangre/disentería continúa siendo una causa importante de hospitalización afectando en su mayoría a niños sanos menores de 5 años. Los patógenos detectados con mayor frecuencia fueron bacterias principalmente Shigella sp., Salmonella sp. y E coli diarreogénicas. Se reportó alta prescripción de antibióticos, cumpliendo en la mayoría de los casos con las recomendaciones.
Introduction: Bloody diarrhea is a common reason for hospital admission in children with acute gastroenteritis; In most cases these are mild and self-limiting infections, but serious complications can occur. Goals: To describe the etiology and clinical-evolutionary characteristics of children under 15 years of age hospitalized for bloody diarrhea at the Pediatric Hospital, Centro Hospitalario Pereira Rossell between the years 2012-2023. Materials and methods: Retrospective study through review of histories and laboratory records. Variables: demographics, nutritional status, hydration, reason for hospitalization, intensive care unit (ICU) admission, enteropathogens, treatments, evolution. Results: 229 children were included, median age 8 months; male sex 61%; eutrophic 88%, well hydrated 55%, with comorbidities 11%, prematurity 6.5%. The reason for hospitalization was bloody diarrhea/dysentery without other symptoms 45%. Coprovirological/coproculture was requested in 98% and detection by nucleic acid techniques in fecal matter was requested in 5,2%. At least one pathogenic agent was identified in 34,3%: Shigella sp. 38%; Salmonella sp 19,5%; coinfections in 12%. Antibiotics were indicated for 86%; ceftriaxone 62%, azithromycin 35%. Were admitted to the ICU 6,5% (15), 10/14 had complications, 5 had acute kidney failure and 3 had alterations in the internal environment. The majority had a good evolution. Conclusions: Bloody diarrhea/dysentery continues to be an important cause of hospitalization, affecting mostly healthy children under 5 years of age. The most frequently detected pathogens were bacteria, mainly Shigella sp., Salmonella sp. and diarrheagenic E coli. High prescription of antibiotics was reported, complying in most cases with the recommendations.
Introdução: A diarreia com sangue é um motivo comum de internação hospitalar em crianças com gastroenterite aguda; Na maioria dos casos, estas são infecções leves e autolimitadas, mas podem ocorrer complicações graves. Metas: Descrever a etiologia e as características clínico-evolutivas de crianças menores de 15 anos internadas por diarreia sanguinolenta no Hospital Pediátrico Centro Hospitalario Pereira Rossell entre os anos de 2012-2023. Materiais e métodos: Estudo retrospectivo por meio de revisão de histórias e registros laboratoriais. Variáveis: dados demográficos, estado nutricional, hidratação, motivo da internação, internação em unidade de terapia intensiva (UTI), enteropatógenos, tratamentos, evolução. Resultados: foram incluídas 229 crianças, mediana de idade 8 meses; sexo masculino 61%; eutrófico 88%, bem hidratado 55%, com comorbidades 11%, prematuridade 6,5%. O motivo da internação foi diarreia sanguinolenta/disenteria sem outros sintomas 45%. O estudo coprovirologico/coprocultivo foi solicitado em 98% e a detecção por técnicas de ácidos nucleicos em matéria fecal foi solicitada em 5,2%. Pelo menos um agente patogênico foi identificado em 34,3%: Shigella sp. 38%; Salmonella sp. 19,5%; coinfecções em 12%. Os antibióticos foram indicados para 86%; ceftriaxona 62%, azitromicina 35%. Foram internados em UTI 6,5% (15), 10/14 apresentaram complicações, 5 tiveram insuficiência renal aguda e 3 apresentaram alterações no meio interno, a maioria teve boa evolução. Conclusões: A diarreia/disenteria com sangue continua a ser uma causa importante de hospitalização, afetando sobretudo crianças saudáveis ââcom menos de 5 anos de idade. Os patógenos mais frequentemente detectados foram bactérias, principalmente Shigella sp., Salmonella sp. e E. coli diarreiogênica. Foi relatada elevada prescrição de antibióticos, cumprindo na maioria dos casos as recomendações.
Asunto(s)
Humanos , Masculino , Femenino , Recién Nacido , Lactante , Preescolar , Niño , Adolescente , Infecciones por Rotavirus/complicaciones , Infecciones por Campylobacter/complicaciones , Diarrea Infantil/etiología , Diarrea Infantil/sangre , Disentería/etiología , Disentería/sangre , Infecciones por Enterobacteriaceae/complicaciones , Infecciones por Rotavirus , Infecciones por Rotavirus/tratamiento farmacológico , Infecciones por Campylobacter/diagnóstico , Infecciones por Campylobacter/tratamiento farmacológico , Niño Hospitalizado/estadística & datos numéricos , Estudios Retrospectivos , Infecciones por Enterobacteriaceae/diagnóstico , Infecciones por Enterobacteriaceae/tratamiento farmacológicoRESUMEN
The antioxidant activity and the inhibitory potential of α-amylase of lyophilized hydroethanolic extracts of Conocarpus erectus leaves obtained by ultrasonication were determined. The most potent extract was subjected to ultra-high performance liquid chromatography system equipped with mass spectrometer for metabolite identification. The identified metabolites were docked in α-glucosidase to assess their binding mode. The results revealed that 60% ethanolic extract exhibited highest ferric reducing antioxidant power (4.08 ± 0.187 mg TE/g DE) and α-amylase inhibition (IC50 58.20 ± 1.25 µg/mL. The metabolites like ellagic acid, 3-O-methyl ellagic acid, ferujol, 5, 2 Ì-dihydroxy-6,7,8-trimethyl flavone and kaempferol glucoside were identified in the extract and subjected to molecular docking studies regarding α-amylase inhibition. The comparison of binding affinities revealed 3-O-methyl ellagic acid as most effective inhibitor of α-amylase with binding energy of -14.5911 kcal/mol comparable to that of acarbose (-15.7815 kcal/mol). The secondary metabolites identified in the study may be extended further for functional food development with antidiabetic properties.
Se determinó la actividad antioxidante y el potencial inhibidor de la α-amilasa de extractos hidroetanólicos liofilizados de hojas de Conocarpus erectus obtenidos por ultrasónicación. El extracto más potente se sometió a un sistema de cromatografía líquida de ultra alto rendimiento equipado con un espectrómetro de masas para la identificación de metabolitos. Los metabolitos identificados se acoplaron en α-glucosidasa para evaluar su modo de unión. Los resultados revelaron que el extracto etanólico al 60% exhibió el mayor poder antioxidante reductor férrico (4.08 ± 0.187 mg TE/g DE) e inhibición de la α-amilasa (IC50 58.20 ± 1.25 µg/mL. Los metabolitos como el ácido elágico, 3-O-metil elágico ácido, ferujol, 5, 2 Ì-dihidroxi-6,7,8-trimetil flavona y kaempferol glucósido se identificaron en el extracto y se sometieron a estudios de acoplamiento molecular con respecto a la inhibición de la α-amilasa. La comparación de las afinidades de unión reveló 3-O-metil El ácido elágico como inhibidor más eficaz de la α-amilasa con una energía de unión de -14,5911 kcal/mol comparable a la de la acarbosa (-15,7815 kcal/mol). Los metabolitos secundarios identificados en el estudio pueden ampliarse aún más para el desarrollo funcional de alimentos con propiedades antidiabéticas.
Asunto(s)
Extractos Vegetales/química , alfa-Amilasas/antagonistas & inhibidores , Myrtales/química , Antioxidantes/química , Benzopiranos/análisis , Técnicas In Vitro , Extractos Vegetales/farmacología , Hojas de la Planta/química , Simulación del Acoplamiento Molecular , Antioxidantes/farmacologíaRESUMEN
Search for safe antioxidants and novel nutraceuticals urged to evaluate the antioxidant, anti-acetylcholine esterase and anti-lipoxygenase activity of various leaf extracts of Conocarpus lancifolius. Extraction was optimized from freeze dried plant extracts quenched with liquid nitrogen using water, ethanol, methanol, hexane, ethyl acetate and chloroform. Maximum extract yield, total phenolic contents and total flavonoid contents were obtained in case of ethanolic extraction. The highest 2,2-diphenyl-1-picrylhydrazylradical scavenging in terms of IC50 value of 55.26 µg/mL was observed for ethanolic leaf extract. The acetylcholine esterase and lipoxygenase inhibitory activities (IC50) were also observed for ethanolic extract. These findings for ethanolic extract were statistically significant when compared with other extracts (ρ<0.05). The haemolytic % values indicated that all extracts were associated with very low or negligible toxicity. The epicatechin, isorhamnetin, rutin, scopoleptin, skimmianine, quercetin-3-O-α-rhamnoside, quercetin-3-O-ß-glucoside, cornoside, creatinine, choline, pyruvic acid, α-hydroxybutyric acid, phyllanthin and hypophyllanthin were identified as major functional metabolites in ethanolic leaf extract of C. lancifoliusby 1H-NMR. The identified metabolites were probably responsible for the pharmacological properties of C.lancifolius. The findings may be utilized as pharmacological leads for drug development and food fortification.
Se insta a la búsqueda de antioxidantes seguros y nuevos nutracéuticos para evaluar la actividad antioxidante, anti-acetilcolina esterasa y anti-lipoxigenasa de varios extractos de hojas de Conocarpus lancifolius. La extracción se optimizó a partir de extractos de plantas liofilizados enfriados con nitrógeno líquido usando agua, etanol, metanol, hexano, acetato de etilo y cloroformo. En el caso de extracción etanólica se obtuvo el rendimiento máximo de extracto, el contenido de fenoles totales y el contenido de flavonoides totales. La mayor eliminación de radicales 2,2-difenil-1-picrilhidrazilo en términos de valor de CI50 de 55,26 µg/mL se observó para el extracto de hoja etanólico. También se observaron las actividades inhibidoras de la acetilcolina esterasa y lipoxigenasa (CI50) para el extracto etanólico. Estos hallazgos para el extracto etanólico fueron estadísticamente significativos en comparación con otros extractos (ρ<0.05). Los valores del % hemolítico indicaron que todos los extractos estaban asociados con una toxicidad muy baja o insignificante. Se identificaron la epicatequina, isorhamnetina, rutina, escopoleptina, skimmianina, quercetina-3-O-α-ramnosido, quercetina-3-O-ß-glucósido, cornosido, creatinina, colina, ácido pirúvico, ácido α-hidroxibutírico, filantrina e hipofillantina. como metabolitos funcionales principales en el extracto etanólico de hojas de C. lancifoliuspor 1H-NMR. Los metabolitos identificados probablemente fueron responsables de las propiedades farmacológicas de C. lancifolius. Los hallazgos pueden utilizarse como pistas farmacológicas para el desarrollo de fármacos y la fortificación de alimentos.
Asunto(s)
Extractos Vegetales/farmacología , Combretaceae/química , Antioxidantes/farmacología , Fenoles/análisis , Flavonoides/análisis , Técnicas In Vitro , Extractos Vegetales/química , Inhibidores de la Colinesterasa/farmacología , Inhibidores de la Colinesterasa/química , Depuradores de Radicales Libres , Inhibidores de la Lipooxigenasa/farmacología , Inhibidores de la Lipooxigenasa/química , Etanol , Antioxidantes/químicaRESUMEN
Abstract Introduction The prevalence of deafness is high in Pakistan. Knowledge regarding the clinical features of patients with profound hearing loss will not only help identify the cause but will also help in the strategic planning for public health interventions. Objective The present study was conducted to cover in detail the clinical aspects of children with hearing loss, that is, age at presentation, associated deficits and disorders, possible cause of the disease, associated family history, and role of consanguineous marriage. Methods The present study was performed from November 2016 to September 2018. All of the patients under 6 years of age with profound bilateral hearing loss who would benefit from cochlear implantation were included in the study. Detailed history was taken. The developmental skills were assessed for all areas, and the patients were scored regarding their motor, manipulative, visual, language, social and self-care skills according to the Schedule of Growing Skills II. Detailed family history was taken from the parents of the affected children. The Statistical Package for the Social Sciences (SPSS) software, version 20.0, was used for the statistical analysis. Results The mean age of the children to be treated was 3.2 ± 1.25 years. Most patients (51.5%) had a positive family history of disease. Consanguineous marriage was common; the parents of 76.9% of the patients were first-degree relatives. Most patients (90.8%) had associated language impediments. In total, four (Ł3.07%) patients had global developmental delay. Conclusion Consanguineous marriage pattern plays an important role in diseases running in families. Development in these children is strongly linked to their age at the consultation.
RESUMEN
Introduction The prevalence of deafness is high in Pakistan. Knowledge regarding the clinical features of patients with profound hearing loss will not only help identify the cause but will also help in the strategic planning for public health interventions. Objective The present study was conducted to cover in detail the clinical aspects of children with hearing loss, that is, age at presentation, associated deficits and disorders, possible cause of the disease, associated family history, and role of consanguineous marriage. Methods The present study was performed from November 2016 to September 2018. All of the patients under 6 years of age with profound bilateral hearing loss who would benefit from cochlear implantation were included in the study. Detailed history was taken. The developmental skills were assessed for all areas, and the patients were scored regarding their motor, manipulative, visual, language, social and self-care skills according to the Schedule of Growing Skills II. Detailed family history was taken from the parents of the affected children. The Statistical Package for the Social Sciences (SPSS) software, version 20.0, was used for the statistical analysis. Results The mean age of the children to be treated was 3.2 ± 1.25 years. Most patients (51.5%) had a positive family history of disease. Consanguineous marriage was common; the parents of 76.9% of the patients were first-degree relatives. Most patients (90.8%) had associated language impediments. In total, four (L3.07%) patients had global developmental delay. Conclusion Consanguineous marriage pattern plays an important role in diseases running in families. Development in these children is strongly linked to their age at the consultation.
RESUMEN
Resealed erythrocytes have been explored in various dimensions of drug delivery, owing to their high biocompatibility and inability to initiate immune response. The present research was designed to evaluate the drug delivery potential of erythrocytes by loading a hydrophobic anti-malarial drug, Artemether. Three different loading techniques were applied to achieve maximum optimized drug loading. A HPLC method was validated for drug quantification in erythrocytes. The relatively high loading was achieved using hypotonic treatment was 31.39% as compared to other two methods. These, drug loaded erythrocytes were characterized for membrane integrity via ESR showing higher ESR values for drug loaded cells as compared to normal cells. Moreover, microscopic evaluation was done to observe morphological changes in erythrocytes after successful loading which showed swollen cells with slight rough surface as compared to smooth surface of normal cells. Drug release was studied for 8 h which showed more than 80% release within 3-7 h from erythrocytes treated with different hypotonic methods. Overall, the study revealed a potential application of erythrocytes in delivery of hydrophobic drugs using hypotonic treatment as compared to other methods.
Asunto(s)
Eritrocitos/clasificación , Liberación de Fármacos , Arteméter/administración & dosificación , Preparaciones Farmacéuticas/administración & dosificación , Cromatografía Líquida de Alta Presión/métodosRESUMEN
OBJECTIVE: The effectiveness of Haemophilus influenzae type b (Hib) vaccine in preventing severe pneumonia in Asian children has been questioned, and many large Asian countries yet to introduce Hib conjugate vaccine in immunization programs. The primary objective of this study was to assess Hib conjugate vaccine effectiveness (VE) on radiologically-confirmed pneumonia in children born after introduction of Hib conjugate vaccine in Pakistan. STUDY DESIGN: A matched case-control study enrolled cases of radiologically-confirmed pneumonia in several hospitals serving low-income populations during 2009-2011. Cases were matched by age and season with 3 hospital and 5 neighborhood controls. Pneumonia was diagnosed using standardized World Health Organization criteria for chest radiograph interpretation. Matched OR were estimated for VE. RESULTS: A total of 1027 children with radiologically-confirmed pneumonia were enrolled; 975 cases, 2925 hospital controls, and 4875 neighborhood controls were analyzed. The coverage for 3 doses of diphtheria-tetanus-pertussis-hepatitis B-Hib conjugate vaccine was 13.7%, 18%, and 22.7% in cases, hospital controls and neighborhood controls, respectively. Estimated Hib VE for radiologically-confirmed pneumonia was 62% with 3 doses of vaccine using hospital controls and 70% using neighborhood controls. CONCLUSIONS: Hib conjugate vaccine prevented a significant fraction of radiologically-confirmed pneumonia in children in Pakistan. Maximizing impact on child survival needs improved immunization coverage.