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1.
J Pharm Policy Pract ; 14(1): 100, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34847951

RESUMO

BACKGROUND: Therapeutic drug monitoring (TDM) of Vancomycin (VCM) is required to prevent inappropriate dosage-associated bacterial resistance, therapeutic failure, and toxicities in pediatrics. Anecdotal experience and studies show that many healthcare institutions confront barriers while implementing TDM services, this study aimed to assess a pharmacist-directed VCM-TDM service for optimizing patient care in our institution. MATERIALS AND METHODS: Patients aged 1 month-18 years who received intravenous VCM were included in this quasi-experimental study. The pre-implementation phase (March-June 2018) consisted of retrospective assessment of pediatric patients, the interventional phase (July 2018 to February 2020) included educational programs and the post-implementation phase (March-June 2020) evaluated the participants based on pharmacist-directed VCM-TDM services as a collaborative-practice model including clinical and inpatient pharmacists to provide 24/7 TDM services. Outcomes of the study included the mean difference in the number of optimal (i) prescribed initial VCM doses (primary) (ii) dosage adjustments and (iii) VCM-sampling time (secondary). After ethical approval, data were collected retrospectively. RESULTS: A hundred patients were there in each phase. The number of cases who were correctly prescribed initial VCM doses was significantly higher in the post-implementation phase, mean difference of 0.22, [95% CI (0.142-0.0.358), p < 0.0001]. Patients who had correct dosage adjustments in the post-implementation phase also had higher statistical significance, mean difference of 0.29, [95% CI (0.152-0.423), p < 0.05]. More correct practices of VCM-levels timing were observed in the post-implementation phase, mean difference of 0.15, [95% CI (- 0.053-0.264), p = 0.079]. CONCLUSION: This study showed the significant role of pharmacist-directed TDM services to optimize the correct prescribing of initial VCM doses and dose adjustments.

2.
Materials (Basel) ; 14(21)2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34771863

RESUMO

Worldwide, bacterial resistance to beta-lactam antibiotics is the greatest challenge in public health care. To overcome the issue, metal-based nanoparticles were extensively used as an alternative to traditional antibiotics. However, their unstable nature limits their use. In the present study a very simple, environmentally friendly, one-pot synthesis method that avoids the use of organic solvents has been proposed to design stable, novel nanocomposites. Formulation was done by mixing biogenic copper oxide (CuO) nanomaterial with glycerol and phospholipids isolated from egg yolk in an appropriate ratio at optimum conditions. Characterization was done using dynamic light scattering DLS, Zeta potential, high performance liquid chromatography (HPLC), and transmission electron microscopy (TEM). Further, its antibacterial activity was evaluated against the extended-spectrum beta-lactamase strains based on zone of inhibition and minimal inhibitory concentration (MIC) indices. Results from this study have demonstrated the formulation of stable nanocomposites with a zeta potential of 34.9 mV. TEM results indicated clear dispersed particles with an average of 59.3 ± 5 nm size. Furthermore, HPLC analysis of the egg yolk extract exhibits the presence of phospholipids in the sample and has significance in terms of stability. The newly formed nanocomposite has momentous antibacterial activity with MIC 62.5 µg/mL. The results suggest that it could be a good candidate for drug delivery in terms of bactericidal therapeutic applications.

3.
Mol Biochem Parasitol ; 247: 111430, 2021 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-34813865

RESUMO

In this study, curcumin-nanoformulations were tested for anti-Acanthamoebic properties. Curcumin-loaded nanovesicles were synthesized, followed by characterization with Fourier transform infrared spectroscopy, ultraviolet-visible spectrophotometry, and atomic force microscopy. Using amoebicidal assay, the effects of curcumin-nanoformulations were investigated against A. castellanii belonging to the T4 genotype. To determine the effects of curcumin-nanoformulations on host cells, cytotoxicity assays were performed using human keratinocyte cells (HaCat). The results revealed that nanovesicles formulation of curcumin enhanced the anti-Acanthamoebic effects of curcumin as compared with curcumin alone. The viability decreased with increasing concentration of curcumin and/or lipid-based carrier (Noisome) (FCBR18) in a dose-dependent manner. Curcumin and curcumin-loaded nanovesicles exhibited minimal cytotoxic effects against human cells in all tested concentrations. Both concentrations of FCBR18 proved effective in inhibiting amoebae excystation. In contrast, curcumin alone showed insignificant effects against amoebae excystation. Taken together, these findings clearly showed that curcumin-loaded nanovesicles show enhanced anti-Acanthamoebic efficacy without harming human cells, and these nanotherapeutics may hold promise in the development of new formulations of anti-Acanthamoebic agents.

4.
Trop Anim Health Prod ; 53(5): 508, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34626253

RESUMO

Nanotechnology is the discipline and technology of small and specific things that are < 100 nm in size. Because of their extremely miniscule size, any changes in their chemical and physical structure may show higher reactivity and solubility than larger particles. Nanotechnology plays a vital role in every field of life. It is considered one of the most bleeding edge field of scientific research. It has already several applications in a myriad of disciplines while its application in the field of animal production and veterinary medicine is still experimental in nature. But, in recent years, the role of nanotechnology in the aforementioned fields of scientific inquiry has shown great progress. These days, nanotechnology has been employed to revolutionize drug delivery systems and diagnose atypical diseases. Applications of nanoparticle technology in the field of animal reproduction and development of efficacious vaccines have been at the forefront of scientific endeavors. Additionally, their impacts on meat and milk quality are also being judiciously inquired in recent decades. Veterinary nanotechnology has great potential to improve diagnosis and treatment, and provide new tools to this field. This review focuses on some noteworthy applications of nanoparticles in the field of animal production and their future perspectives.


Assuntos
Nanopartículas , Nanotecnologia , Animais , Sistemas de Liberação de Medicamentos/veterinária , Leite
5.
Arch Dis Child ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257078

RESUMO

OBJECTIVE: Nutrition societies recommend using standardised parenteral nutrition (SPN) solutions. We designed evidence-based SPN formulations for neonates admitted to our neonatal intensive care unit (NICU) and evaluated their outcomes. DESIGN: This was a quality improvement initiative. Data were collected retrospectively before and after the intervention. SETTING: A tertiary-care level 3 NICU at the Aga Khan University in Karachi, Pakistan. PATIENTS: All NICU patients who received individualised PN (IPN) from December 2016 to August 2017 and SPN from October 2017 to June 2018. INTERVENTIONS: A team of neonatologists and nutrition pharmacists collaborated to design two evidence-based SPN solutions for preterm neonates admitted to the NICU. MAIN OUTCOME MEASURES: We recorded mean weight gain velocity from days 7 to 14 of life. The other outcomes were change in weight expressed as z-scores, metabolic abnormalities, PN-associated liver disease (PNALD), length of NICU stay and episodes of sepsis during hospital stay. RESULTS: Neonates on SPN had greater rate of change in weight compared with IPN (ß=13.40, 95% CI: 12.02 to 14.79) and a smaller decrease in z-scores (p<0.001). Neonates in the SPN group had fewer hyperglycemic episodes (IPN: 37.5%, SPN: 6.2%) (p<0.001), electrolyte abnormalities (IPN: 56.3%, SPN: 21%) (p<0.001), PNALD (IPN: 52.5%, SPN: 18.5%) (p<0.001) and sepsis (IPN: 26%, SPN: 20%) (p<0.05). The median length of stay in NICU was 14.0 (IQR 12.0-21.0) for the IPN and 8.0 (IQR 5.0-13.0) days for the SPN group. CONCLUSIONS: We found that SPN was associated with shorter NICU stay and greater weight gain. In-house preparation of SPN can be used to address the nutritional needs in resource-limited settings where commercially prepared SPN is not available.

6.
Microb Pathog ; 158: 105050, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34146642

RESUMO

Lumpy skin disease (LSD) is a viral disease caused by lumpy skin disease virus (LSDV), a member of Capripoxvirus, genus of Poxviridae family. It is a transboundary infection of monetary significance that primarily affects water buffaloes and cattle. LSD was known to be once endemic in Saharan regions of Africa but later on reported in central Asian and neighboring countries of Pakistan like, India, Iran and China. It is a vector borne disease and arthropods are believed to be the main perpetrators. It is discernible by its high morbidity and low mortality. Characteristic lumps on skin and high fever are considered as major signs while reduced milk production, infertility, early embryonic death and anorexia are some of the salient clinical manifestations of the disease. Additionally, nodules on mucosa of oro-pharynx, udder, genitalia and rectum are usually observed on examination. This article summarizes LSD outbreaks across Asia during last fifteen years. It is a general consensus amongst the veterinary community that disease is endemic in Pakistan as it shares borders with India, Iran and China where recent outbreaks are reported. Historically Pakistan is free of LSD, however it is at high risk of a LSDV outbreak as neighboring regions are becoming endemic. Vaccination, strict quarantine measures, limited movement of livestock along with vector control could be effective for preventing the spread of the disease. This review aims to summarize the latest developments in the epidemiology of LSD with the focus on transboundary spread, possible emergence and economic implications on Pakistan.


Assuntos
Doença Nodular Cutânea , Vírus da Doença Nodular Cutânea , Animais , Búfalos , Bovinos , Surtos de Doenças , Doença Nodular Cutânea/epidemiologia , Vírus da Doença Nodular Cutânea/genética , Paquistão/epidemiologia
7.
Chem Phys Lipids ; 238: 105101, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34029537

RESUMO

Stimuli-responsive or smart nanocarriers are emerging class of materials used for drug delivery and tissue engineering applications. The objective of this study was to develop environment friendly, economic and smart gelatin based hydrogel for controlled delivery of ceftriaxone. Gelatin was modified with furfuryl amine and converted to hydrogel via photo oxidation reaction, initiated with visible light in the presence of crosslinking agent (eosin Y and riboflavin) to enhance the mechanical properties and increase structural integrity of the hydrogel. The conjugated gelatin-furfuryl amine (GFA) was characterized by 1H NMR and FTIR techniques. An antimicrobial drug (ceftriaxone) was encapsulated in hydrogels systems (HG-E and HG-R) and its encapsulation efficiency was found as 88 % and 74 %, respectively. The in-vitro swelling property and release profile of the drug reveals that the behavior of hydrogel was pH dependent for both the hydrogels systems. Antibacterial study performed on HG-R hydrogel system via disc diffusion method revealed a greater zone of inhibition for Staphylococcus aureus. Findings of the presented work revealed the formation of an excellent, smart hydrogel system using Eosin-Y as cross-linker having greater encapsulation efficiency that can potentially be used for drug delivery application of ceftriaxone to enhance its therapeutic effects.

8.
J Invertebr Pathol ; 181: 107588, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33862054

RESUMO

Fungal polyketide synthases play important and differential roles in synthesizing secondary metabolites and regulating several cell events, including asexual development, environmental adaptation, and pathogenicity. This study shows the important functions of a highly reducing polyketide synthase, Pks11, in Beauveria bassiana, a filamentous fungal insect pathogen used worldwide for pest biocontrol. The deletion of pks11 led to severe defects in conidial yields on different media and a decrease of 36.27% in the mean thickness of conidial cell wall under normal conditions. Compared with the wild-type, Δpks11 showed higher tolerance to oxidation and increased sensitivity to high temperature during colony growth. Moreover, the lack of pks11 caused a decrease in conidial germination after exposure to UV radiation but did not affect the virulence of B. bassiana against Galleria mellonella larvae via typical cuticle infection. These findings concurred with the alteration in the transcript levels of some phenotype-related genes. These data suggested that pks11 played vital roles in the asexual development, cell wall integrity, and fungal responses to oxidation, high temperature, and UV irradiation of B. bassiana.


Assuntos
Beauveria/genética , Proteínas Fúngicas/genética , Policetídeo Sintases/genética , Tolerância a Radiação/genética , Esporos Fúngicos/genética , Raios Ultravioleta/efeitos adversos , Beauveria/enzimologia , Beauveria/fisiologia , Beauveria/efeitos da radiação , Parede Celular/fisiologia , Proteínas Fúngicas/metabolismo , Policetídeo Sintases/metabolismo , Esporos Fúngicos/fisiologia , Esporos Fúngicos/efeitos da radiação
9.
Molecules ; 26(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466486

RESUMO

Cyanobacteria (blue-green microalgae) are ubiquitous, Gram-negative photoautotrophic prokaryotes. They are considered as one of the most efficient sources of bioactive secondary metabolites. More than 50% of cyanobacteria are cultivated on commercial platforms to extract bioactive compounds, which have bene shown to possess anticancer activity. The chemically diverse natural compounds or their analogues induce cytotoxicity and potentially kill a variety of cancer cells via the induction of apoptosis, or altering the activation of cell signaling, involving especially the protein kinase-C family members, cell cycle arrest, mitochondrial dysfunctions and oxidative damage. These therapeutic properties enable their use in the pharma and healthcare sectors for the betterment of future generations. This review provides a baseline overview of the anti-cancerous cyanobacterial bioactive compounds, along with recently introduced nanomaterials that could be used for the development of new anticancer drugs to build a healthy future for mankind.


Assuntos
Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Cianobactérias/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Cianobactérias/química , Humanos , Nanopartículas/química , Preparações Farmacêuticas , Nanomedicina Teranóstica
10.
J Med Case Rep ; 15(1): 25, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33509295

RESUMO

BACKGROUND: A post-marketing surveillance study has reported an association between meropenem use and the incidence of hematologic abnormalities, including leukopenia, thrombocytopenia, hemolysis, and neutropenia, but the precise incidence in neonates is unknown. Here, we report meropenem-induced pancytopenia in a preterm neonate. CASE PRESENTATION: A preterm newborn Pakistani received intravenous meropenem 40 mg/kg every 8 hours to treat Klebsiella pneumoniae in blood cultures and suspected meningitis. The baby developed severe thrombocytopenia, with a platelet count of 22 × 103 cells/mm3, low hemoglobin level of 9.7 g/dl, and low absolute neutrophil count (ANC) of 816 cells/mm3 on days 3, 14, and 17 of meropenem therapy, respectively. Based on the blood culture and institutional guidelines, meropenem treatment was continued with monitoring and supportive care for a total of 19 days. After discontinuation of meropenem, the baby was monitored continuously for hematological changes, and low counts persisted for 3 days. ANC improved to > 1500 cells/mm3 on the fourth day, and the platelet count reached > 150 × 103 cells/mm3 for the first time on the seventh day of meropenem discontinuation. All subsequent complete blood count (CBC) reports showed improving trends. The baby was discharged on the 48th day of life (DOL), with follow-up monitoring of CBC. The baby was kept on iron supplements, and hemoglobin level of 11.2 g/dl was observed on the 59th DOL. CONCLUSION: Neonatal pancytopenia may lead to serious health complications; therefore, clinicians and pharmacists need to vigilantly monitor CBC in this vulnerable population, even when administering meropenem in septic doses for the recommended duration.


Assuntos
Neutropenia , Pancitopenia , Humanos , Recém-Nascido , Contagem de Leucócitos , Meropeném , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Pancitopenia/induzido quimicamente , Contagem de Plaquetas
11.
J Pharm Bioallied Sci ; 13(Suppl 2): S1588-S1590, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35018035

RESUMO

Background: Release of metallic ions, especially nickel and chromium, present in orthodontic fixed appliance attachments such as brackets and archwires has been a basis of concern in current years. The present study was conducted to assess nickel and chromium level in gingival crevicular fluid in patients undergoing orthodontic treatment. Materials and Methods: Forty patients undergoing fixed orthodontic treatment were divided into 2 groups of 20 each. Group I was fixed orthodontic treatment group and was given nonfluoridated toothpaste and Group II was fixed orthodontic treatment group and was given fluoridated toothpaste. The assessment of salivary nickel and chromium levels was done using inductively coupled plasma mass spectrometry. Results: In group I, there were 6 male and 14 female and in group II 7 males and 13 females. The mean nickel level (ng/ml) before treatment in group I was 0.49 and in group II was 0.52, on 7th day was 0.52 and 0.54, on 30th day was 13.4 and 100.2, and on 6th month was 0.54 and 0.52 in Group I and II, respectively. The mean chromium level (ng/ml) before treatment in Group I was 0.48 and in Group II was 0.52, on 7th day was 0.52 and 0.53, on 30th day was 40.6 and 62.4 and on 6th month was 4.9 and 0.52 in Group I and II, respectively. The difference was significant (P < 0.05). Conclusion: The release of metal ions such as nickel and chromium was more with fluoridated toothpaste as compared to nonfluoridated toothpaste in patients undergoing fixed orthodontics.

12.
Artigo em Inglês | LILACS | ID: biblio-1342199

RESUMO

Leishmaniasis is an important disease affecting global public health which is spread by sand fly having different species. Various chemical drugs are used to treat and control Leishmaniasis including pentavalent antimonials, antimicrobial and antibiotics. Due to emergence of drug resistance, these therapeutic options are losing effectiveness in attaining success. Furthermore, these drugs are expensive and have toxic effects on liver and kidneys. There has been an emerging interest and excellent response by using plant based drugs and extracts to control Leishmaniasis. Different medicinal plants including Glycyrrhiza glabra, Allium sativum, Peganum harmala and Nigella sativa have shown excellent anti-leishmanial activity. Therefore, medicinal plants can help in effective drug development against Leishmaniasis diseases in both animals and humans which will be safer and health protective.


La Leishmaniasis es una enfermedad importante que afecta la salud pública mundial y que es transmitida por las moscas de la arena, que tienen diferentes especies. Se utilizan varios medicamentos químicos para tratar y controlar la Leishmaniasis, incluidos los antimoniales pentavalentes, antimicrobianos y antibióticos. Debido a la aparición de resistencia a los medicamentos, estas opciones terapéuticas están perdiendo eficacia para lograr el éxito. Además, estos medicamentos son costosos y tienen efectos tóxicos en hígado y riñones. Ha habido un interés emergente y una excelente respuesta mediante el uso de extractos y medicamentos a base de plantas para controlar la Leishmaniasis. Diferentes plantas medicinales como Glycyrrhiza glabra, Allium sativum, Peganum harmalay Nigella sativahan mostrado una excelente actividad anti-leishmanial. Por lo tanto, las plantas medicinales pueden ayudar en el desarrollo de fármacos eficaces contra las enfermedades de la leishmaniasis tanto en animales como en seres humanos, lo que será más seguro y proteja la salud.


Assuntos
Humanos , Animais , Plantas Medicinais , Leishmaniose/tratamento farmacológico , Saúde Pública
13.
J Pharm Policy Pract ; 13(1): 74, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33292772

RESUMO

The coronavirus disease 19 (COVID-19) is rapidly spreading across the world. Pharmacy services play a vital role in public health in preventing and containing the COVID-19 pandemic. All over the world, especially in the developed countries pharmacists have responded smartly and speedily for public health, such as establishing professional protective and service guidance for pharmacy staff and services, creating and updating drug formularies, addressing the issues of drug shortages, providing public education for prevention and management of infection, contributing in drug evaluation and clinical trials. In this commentary, we review the exclusive demands from pharmacy services in Pakistan during coronavirus disease 2019 pandemic and sharing the responses of our hospital pharmacy to these demands and needs with the international pharmacy community, especially of the low and middle-income countries like Pakistan.

14.
J Pharm Policy Pract ; 13: 69, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042557

RESUMO

Background: Antibiotic resistance (ABX-R) is alarming in lower/middle-income countries (LMICs). Nonadherence to antibiotic guidelines and inappropriate prescribing are significant contributing factors to ABX-R. This study determined the clinical and economic impacts of antibiotic stewardship program (ASP) in surgical intensive care units (SICU) of LMIC. Method: We conducted this pre and post-test analysis in adult SICU of Aga Khan University Hospital, Pakistan, and compared pre-ASP (September-December 2017) and post-ASP data (April-July 2018). January-March 2018 as an implementation/training phase, for designing standard operating procedures and training the team. We enrolled all the patients admitted to adult SICU and prescribed any antibiotic. ASP-team daily reviewed antibiotics prescription for its appropriateness. Through prospective-audit and feedback-mechanism changes were made and recorded. Outcome measures included antibiotic defined daily dose (DDDs)/1000 patient-days, prescription appropriateness, antibiotic duration, readmission, mortality, and cost-effectiveness. Result: 123 and 125 patients were enrolled in pre-ASP and post-ASP periods. DDDs/1000 patient-days of all the antibiotics reduced in the post-ASP period, ceftriaxone, cefazolin, metronidazole, piperacillin/tazobactam, and vancomycin showed statistically significant (p < 0.01) reduction. The duration of all antibiotics use reduced significantly (p < 0.01). Length of SICU stays, mortality, and readmission reduced in the post-ASP period. ID-pharmacist interventions and source-control-documentation were observed in 62% and 50% cases respectively. Guidelines adherence improved significantly (p < 0.01). Net cost saving is 6360US$ yearly, mainly through reduced antibiotics consumption, around US$ 18,000 (PKR 2.8 million) yearly. Conclusion: ASP implementation with supplemental efforts can improve the appropriateness of antibiotic prescriptions and the optimum duration of use. The approach is cost-effective mainly due to the reduced cost of antibiotics with rational use. Better source-control-documentation may further minimize the ABX-R in SICU.

15.
Expert Opin Drug Saf ; 19(12): 1641-1649, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32892635

RESUMO

BACKGROUND: Recently intravenous (IV) and aerosolized (ASZ) colistin have been used for treating ventilator-associated pneumonia (VAP) due to colistin susceptible multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin has limited lung penetration. We compared the efficacy and safety of IV-alone versus IV+ASZ-colistin for treating VAP in neonates. METHODS: This retrospective matched case-control study was performed at NICU of the Aga Khan University Hospital, Pakistan between January 2015 and December 2018. Sixteen neonates with MDR-GNB associated VAP received IV-ASZ-colistin and were matched for date of birth, gestational age, birth weight, Apgar score, antenatal steroid history, disease severity, and duration of mechanical ventilation with 16 control neonates who received IV-colistin alone. RESULTS: Both groups had similar MDR-GNB isolates and Acinetobacter baumannii (78%) was the most common pathogen. No colistin-resistant strain was isolated. Duration of IV-colistin and concomitant antibiotics use was significantly (p < 0.05) shorter in the IV-ASZ-colistin group. Significantly (p < 0.05) higher clinical cure and microbial eradication, along with lower ventilatory requirements, mortality rate, and colistin induced nephrotoxicity and electrolyte imbalance was observed in the IV-ASZ-colistin group. CONCLUSIONS: With better lung penetration, ASZ-colistin offers effective and safe microbiological and clinical benefits as adjunctive or alternate treatment of VAP due to colistin susceptible MDR-GNB in neonates.


Assuntos
Antibacterianos/administração & dosagem , Colistina/administração & dosagem , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Respiração Artificial/estatística & dados numéricos , Administração por Inalação , Aerossóis , Antibacterianos/efeitos adversos , Estudos de Casos e Controles , Colistina/efeitos adversos , Farmacorresistência Bacteriana Múltipla , Feminino , Hospitais Universitários , Humanos , Recém-Nascido , Infusões Intravenosas , Masculino , Pneumonia Associada à Ventilação Mecânica/microbiologia , Pneumonia Associada à Ventilação Mecânica/mortalidade , Gravidez , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
16.
BMC Complement Med Ther ; 20(1): 222, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32664977

RESUMO

BACKGROUND: Statins are considered as standard drugs to control cholesterol levels, but their use is also associated with renal hypertrophy, hemorrhagic stroke, hepatomegaly, and myopathy. Murraya koenigii is an herb that is used in traditional cuisine and as a medicine in South Asia. Here we assessed the antidyslipidemic and antiatherosclerotic effects of this spice in repeated heated mix vegetable oils (RHMVO)-induced atherosclerotic models. METHODS: Aqueous extract of M. koenigii leaves (Mk LE) was prepared and its phytoconstituents were determined. Rabbits were divided into 5 groups (n = 10). Except for the control group, all the other four groups were treated with RHMVO for 16 weeks (dose = 2 ml/kg/day) to induce dyslipidemia and atherosclerosis. These groups were further treated for 10 weeks either with 300 and 500 mg/kg/day Mk LE, lovastatin, RHMVO, or left untreated. Body and organ weights were measured along with oxidative stress and tissue damage parameters. Lipid profile and hepatic function markers were studied. Atheroma measurement and histopathological examination were also performed in control and treated groups. RESULTS: Mk LE significantly (p < 0.05) attenuated RHMVO-induced dyslipidemia and atheroma formation. Furthermore, fat accumulation and lipid peroxidation in hepatic tissues were reduced by Mk LE in a dose-dependent manner. Our results indicated that the antidyslipidemic effects of Mk LE in 500 mg/kg/day dose were comparable to lovastatin. Additionally, oxidative stress markers were reduced much more significantly in Mk LE-500 than in the statin group (p < 0.05). CONCLUSIONS: This study recommends Mk LE as a potent antioxidant and lipid-lowering natural medicine that can attenuate the RHMVO-induced atherosclerotic in optimal doses and duration. Therefore, Mk LE can be accessible, cheap, and free of adverse effects alternate to statins.


Assuntos
Aterosclerose/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Murraya , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Óleos Vegetais/efeitos adversos , Animais , Modelos Animais de Doenças , Temperatura Alta , Masculino , Extratos Vegetais/química , Folhas de Planta , Coelhos
17.
Expert Opin Drug Saf ; 19(9): 1209-1217, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32544349

RESUMO

OBJECTIVES: Amphotericin-B (d-AmB) has a broader anti-fungal spectrum and is used for neonatal invasive-fungal-infections especially invasive-candidiasis (IC). To prevent d-AmB-induced nephrotoxicity, renal protective effect of fluid and electrolyte management has been established among adults; in this study, the authors determined this effect among neonates. METHODS: In this retrospective cohort study, the authors reviewed neonatal medical records, admitted to neonatal intensive care unit and received d-AmB therapy. Patients were divided into, renal-insufficiency-group (RIG) and the non-renal-insufficiency-group (NIG). RESULTS: A total of 90 cases were analyzed, 41 composed RIG and 49 NIG. Renal insufficiency (RI) was developed on 1.7 (0.84) and 7.8 (1.21) days of d-AmB therapy in 26 (63%) and 15 (37%) cases respectively. Bivariate and multivariate analysis demonstrate that >4 m Eq/kg/d sodium intake across all-time points was significantly (p < 0.0001) associated with reduced risk of RI [(phase-I: AOR: 0.96; 95% CI: 0.91-0.99), (phase-II: AOR: 0.84; 95% CI: 0.68-0.92) and (phase-III: AOR: 0.90; 95% CI: 0.86-0.95)]. While adequate fluid intake reduced the likelihood of RI if started before and initial 2 days of d-AmB therapy. CONCLUSIONS: Adequate hydration before and 48 hours after d-AmB therapy and >4 mEq/kg/day sodium intake before and through d-AmB therapy may protect neonatal RI.


Assuntos
Anfotericina B/efeitos adversos , Antifúngicos/efeitos adversos , Infecções Fúngicas Invasivas/tratamento farmacológico , Insuficiência Renal/induzido quimicamente , Anfotericina B/administração & dosagem , Antifúngicos/administração & dosagem , Estudos de Coortes , Eletrólitos/metabolismo , Feminino , Hidratação/métodos , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Paquistão , Insuficiência Renal/epidemiologia , Insuficiência Renal/prevenção & controle , Estudos Retrospectivos , Sódio/administração & dosagem , Atenção Terciária à Saúde
18.
Lipids Health Dis ; 19(1): 69, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32284066

RESUMO

BACKGROUND: Hepatic diseases are one of the chief reasons for worldwide morbidity and mortality. The increased incidence in Asian countries is driving researchers to explore preventive ways from nature. It is more practical to go with healthy routine edibles like vegetable oils to avoid environmental and chemical hepatic injuries. With the use of thermally oxidized oils overproduction of reactive oxygen species (ROS) with overwhelmed cellular antioxidants defense system results in oxidative stress, the known cause of cardiovascular diseases (CVDs), cancers and neurodegenerative disorders. Little is investigated about the effect of daily used oxidized cooking oils on hepatic function changes with oxidative stress especially in the animal model that mimics the human situation. METHODS: In this study, healthy adult male rabbits of local strain were divided into 4 groups (n = 12). First, two sets of rabbits were treated with 1 and 2 ml/kg/day of repeatedly heated mix vegetable oils (RHMVO) respectively. The third set of rabbits was given 1 ml/kg/day of single time heated mix vegetable oils (STHMVO) and the fourth set of rabbits served as controls and fed with normal rabbit diet to for 16 weeks. Serum liver function markers including total-protein, albumin, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) along with the activity of hepatic antioxidant-enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) for lipid peroxidation were compared among different groups of rabbits. Histopathological examination was performed for all four groups. RESULTS: Significantly (p < 0.05) elevated hepatic enzymes and MDA levels, with lower total protein, serum albumin, GPx, SOD and CAT levels were found in high and low doses RHMVO treated groups, in comparison to control. In the STHMVO group, all mentioned markers were insignificantly changed. Accumulation of liver fat in low and high dose oil-treated groups was further confirmed under the microscopic examination of liver tissues, presented significant fat accumulation in liver tissues, in addition, 40-60% increased oxidative stress compared to control, in a dose-dependent manner. CONCLUSIONS: These results conclude that consumption of thermally oxidized mix vegetable oils for longer duration can impair the liver function and destroy its histological structure significantly through fat accumulation and oxidative stress both in high as well as low doses.


Assuntos
Comportamento Alimentar , Calefação , Lipídeos/química , Fígado/patologia , Óleos Vegetais/toxicidade , Animais , Antioxidantes/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Malondialdeído/metabolismo , Estado Nutricional , Coelhos , Fatores de Tempo , Ganho de Peso
19.
Arch Dis Child ; 105(9): 830-836, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32198160

RESUMO

OBJECTIVE: Infections with multidrug-resistant organisms (MDROs) such as Gram-negative bacteria have high morbidity and mortality with limited treatment options. Colistin, an antibiotic active against MDRO, was rarely used due to frequent adverse effects, but its use has now been recommended among adults. In this study, we determined the efficacy of colistin for the treatment of sepsis in neonates. DESIGN/SETTING/PATIENTS/OUTCOMES: We conducted a retrospective record review of all neonates admitted to the neonatal intensive care unit of Aga Khan University Hospital, Karachi, Pakistan, between June 2015 and June 2018, who had sepsis and received colistin by intravenous, inhalation and/or intrathecal routes. Predictors of colistin efficacy, for neonatal survival and microbial clearance, were assessed using multiple logistic regression. RESULTS: 153 neonates received colistin; 120 had culture-proven sepsis; and 93 had MDR-GNB (84 colistin-sensitive). 111 (72.5%) neonates survived and were discharged from hospital; 82.6% had microbial clearance. Neonates with colistin-sensitive bacteria (adjusted OR (AOR)=3.2, 95% CI 2.8 to 4.0), and those in which colistin therapy started early (AOR=7.2, 95% CI 3.5 to 13.6) were more likely to survive. Neonates with increased gestational age (AOR=1.9, 95% CI 1.5 to 3.0), higher weight (AOR=5.4, 95% CI 3.3 to 11.8) and later onset of sepsis (AOR=4.3, 95% CI 2.0 to 9.0) had higher survival. Adverse events included nephrotoxicity in 5.2%; 13.7% developed seizures and 18.3% had electrolyte imbalance. CONCLUSIONS: Colistin therapy was associated with survival among neonates suffering from MDR-GNB sepsis. The frequency of side effects was moderate.


Assuntos
Antibacterianos/uso terapêutico , Colistina/uso terapêutico , Sepse Neonatal/tratamento farmacológico , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Recém-Nascido , Masculino , Paquistão/epidemiologia , Estudos Retrospectivos , Centros de Atenção Terciária/estatística & dados numéricos
20.
Chem Phys Lipids ; 228: 104894, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32126217

RESUMO

Numerous nanotechnological approaches have been widely practiced to improve the bioavailability of less aqueous soluble drugs; phospholipid based vesicles (liposomes) being the most widely applied drug delivery system. However; due to stability issues, large scale production limitations, sterilization and long term storage problems; non-ionic surfactant based vesicles (niosomes) are considered their excellent counterparts. Niosomes are vesicles of non-ionic surfactants having the ability to carrying both hydrophilic and hydrophobic drugs in their inner aqueous or lipid bilayer compartments. In this research work, triazole based non-ionic surfactant (TBNIS) was synthesized and characterized by different spectroscopic techniques and then screened for biocompatibility using NIH 3T3 cell line, blood hemolysis assay and acute toxicity in mice. The synthesized surfactant was then checked for niosomes' formation, Amphotericin B loading and entrapment efficiency, drug release, stability and bioavailability of the drug was assessed and compared with free drug solution. The synthesized surfactant was found biocompatible and caused less blood hemolysis, greater cell vial ability and negligible toxicity in animals. The size of drug loaded niosomal vesicles of TBNIS based surfactant was 179.9 ± 3.23 nm with smaller size distribution i.e. 0.29 ± 0.02. The triazole based surfactant vesicles showed 88.76 ± 3.45 % drug entrapment efficiency, sustained drug release profile and stability. The drug in TBNIS based vesicles has greater oral bioavailability 0.099 ± 0.03 as compared to plan drug solution 0.012 ± 0.023 µg/mL. Results of this study suggests that the newly synthesized triazole based surfactant can be used in drug delivery for improving bioavailability of less water soluble drugs like Amphotericin B.


Assuntos
Materiais Biocompatíveis/síntese química , Sistemas de Liberação de Medicamentos , Tensoativos/química , Triazóis/síntese química , Animais , Materiais Biocompatíveis/farmacocinética , Materiais Biocompatíveis/farmacologia , Disponibilidade Biológica , Hemólise/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Células NIH 3T3 , Triazóis/farmacocinética , Triazóis/farmacologia
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