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1.
Biophys J ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39164967

RESUMEN

Transcription factors play an essential role in pattern formation during early embryo development, generating a strikingly fast and precise transcriptional response that results in sharp gene expression boundaries. To characterize the steps leading up to transcription, we performed a side-by-side comparison of the nuclear dynamics of two morphogens, a transcriptional activator, Bicoid (Bcd), and a transcriptional repressor, Capicua (Cic), both involved in body patterning along the anterior-posterior axis of the early Drosophila embryo. We used a combination of fluorescence recovery after photobleaching, fluorescence correlation spectroscopy, and single-particle tracking to access a wide range of dynamical timescales. Despite their opposite effects on gene transcription, we find that Bcd and Cic have very similar nuclear dynamics, characterized by the coexistence of a freely diffusing monomer population with a number of oligomeric clusters, which range from low stoichiometry and high mobility clusters to larger, DNA-bound hubs. Our observations are consistent with the inclusion of both Bcd and Cic into transcriptional hubs or condensates, while putting constraints on the mechanism by which these form. These results fit in with the recent proposal that many transcription factors might share a common search strategy for target gene regulatory regions that makes use of their large unstructured regions, and may eventually help explain how the transcriptional response they elicit can be at the same time so fast and so precise.

2.
BMC Infect Dis ; 24(1): 659, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956482

RESUMEN

BACKGROUND: Alveolar echinococcosis (AE) primarily affects the liver and potentially spreads to other organs. Managing recurrent AE poses significant challenges, especially when it involves critical structures and multiple major organs. CASE PRESENTATION: We present a case of a 59-year-old female with recurrent AE affecting the liver, heart, and lungs following two previous hepatectomies, the hepatic lesions persisted, adhering to major veins, and imaging revealed additional diaphragmatic, cardiac, and pulmonary involvement. The ex vivo liver resection and autotransplantation (ELRA), first in human combined with right atrium (RA) reconstruction were performed utilizing cardiopulmonary bypass, and repairs of the pericardium and diaphragm. This approach aimed to offer a potentially curative solution for lesions previously considered inoperable without requiring a donor organ or immunosuppressants. The patient encountered multiple serious complications, including atrial fibrillation, deteriorated liver function, severe pulmonary infection, respiratory failure, and acute kidney injury (AKI). These complications necessitated intensive intraoperative and postoperative care, emphasizing the need for a comprehensive management strategy in such complicated high-risk surgeries. CONCLUSIONS: The multidisciplinary collaboration in this case proved effective and yielded significant therapeutic outcomes for a rare case of advanced hepatic, cardiac, and pulmonary AE. The combined approach of ELRA and RA reconstruction under extracorporeal circulation demonstrated distinct advantages of ELRA in treating complex HAE. Meanwhile, assessing diaphragm function during the perioperative period, especially in patients at high risk of developing pulmonary complications and undergoing diaphragmectomy is vital to promote optimal postoperative recovery. For multi-resistant infection, it is imperative to take all possible measures to mitigate the risk of AKI if vancomycin administration is deemed necessary.


Asunto(s)
Atrios Cardíacos , Trasplante de Hígado , Trasplante Autólogo , Humanos , Persona de Mediana Edad , Femenino , Atrios Cardíacos/cirugía , Atrios Cardíacos/parasitología , Equinococosis/cirugía , Hígado/parasitología , Hígado/cirugía , Procedimientos de Cirugía Plástica/métodos , Equinococosis Hepática/cirugía
3.
Biophys J ; 122(18): 3783-3797, 2023 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-37559362

RESUMEN

Membrane cholesterol-rich domains have been shown to be important for regulating a range of membrane protein activities. Low-density lipoprotein receptor (LDLR)-mediated internalization of cholesterol-rich LDL particles is tightly regulated by feedback mechanisms involving intracellular sterol sensors. Since LDLR plays a role in maintaining cellular cholesterol homeostasis, we explore the role that membrane domains may have in regulating LDLR activity. We expressed a fluorescent LDLR-mEGFP construct in HEK293T cells and imaged the unligated receptor or bound to an LDL/DiI fluorescent ligand using total internal reflection fluorescence microscopy. We studied the receptor's spatiotemporal dynamics using fluorescence fluctuation analysis methods. Image cross correlation spectroscopy reveals a lower LDL-to-LDLR binding fraction when membrane cholesterol concentrations are augmented using cholesterol esterase, and a higher binding fraction when the cells are treated with methyl-ß-cyclodextrin) to lower membrane cholesterol. This suggests that LDLR's ability to metabolize LDL particles is negatively correlated to membrane cholesterol concentrations. We then tested if a change in activity is accompanied by a change in membrane localization. Image mean-square displacement analysis reveals that unligated LDLR-mEGFP and ligated LDLR-mEGFP/LDL-DiI constructs are transiently confined on the cell membrane, and the size of their confinement domains increases with augmented cholesterol concentrations. Receptor diffusion within the domains and their domain-escape probabilities decrease upon treatment with methyl-ß-cyclodextrin, consistent with a change in receptor populations to more confined domains, likely clathrin-coated pits. We propose a feedback model to account for regulation of LDLR within the cell membrane: when membrane cholesterol concentrations are high, LDLR is sequestered in cholesterol-rich domains. These LDLR populations are attenuated in their efficacy to bind and internalize LDL. However, when membrane cholesterol levels drop, LDL has a higher binding affinity to its receptor and the LDLR transits to nascent clathrin-coated domains, where it diffuses at a slower rate while awaiting internalization.


Asunto(s)
Colesterol , Receptores de LDL , Humanos , Colesterol/metabolismo , Clatrina/metabolismo , Fluorescencia , Células HEK293 , Lipoproteínas LDL/metabolismo , Receptores de LDL/metabolismo
4.
Pak J Med Sci ; 39(2): 467-473, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36950424

RESUMEN

Objective: To identify the breastfeeding practices in nursing mothers during the COVID-19 pandemic. Methods: This descriptive cross-sectional study was conducted in the Pediatrics and Gynecology & Obstetrics departments at two of the tertiary care hospitals in Pakistan from September 2020 to February 2021. Recently delivered mothers and mothers of children till two years of age on breastfeeding/formula feed were consecutively enrolled. Result: Of 484 participants, breastfeeding was practiced by 180 (37.2%) participants, formula-fed by 85 (17.6%), and mix feed by 219 (45.2%) participants. Out of 185 mothers who had to breastfeed previous babies, 80.2% of mothers still opted to breastfeed their newborns despite the COVID-19 pandemic. Breastfeeding practices exhibited higher incidence in illiterate mothers (aOR 0.229 95% CI 0.05-0.95, p- 0.042), housewives (aOR 0.35 95% CI 0.13-0.95 p-0.040) and shorter length of stay (aOR 0.290 95% CI 0.15-0.57, p- 0.001) while formula /mixed feeding was found higher in mothers with exposure to formula feeding in previous babies (aOR 17.842, 95% CI 8.33-38.19, p- 0.001) and mothers with pain after delivery (aOR 4.526, 95% CI 2.11-9.71, p-<0.001). Conclusion: Mothers who had to breastfeed their babies in a previous pregnancy, who were less educated, and housewives with a shorter stay in hospital have shown a stronger association with breastfeeding whereas mothers who had previous exposure to formula milk and pain after delivery have shown association to formula feed or mixed feed.

5.
Inflammopharmacology ; 30(5): 1729-1743, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35939220

RESUMEN

OBJECTIVE: The present study was designed to explore the potential anti-inflammatory and anti-arthritic effects of ellagic acid (EA) in collagen-induced arthritis (CIA). METHODS: CIA rats were treated with MTX (0.25 mg/kg body wt.) and EA (50 mg/kg b.wt.) for a period of 20 days. The effects of treatment in the rats were assessed biochemically by analyzing inflammatory mediators (NF-kB, iNOS, TNF-α, IL-1ß, IL-6 and IL-10) and oxidative stress related parameters (MPO, NO, LPO, catalase, SOD, GSH). In addition, we also assessed the expression of some inflammatory mediators TNF-α, CD8 + though immunohistochemistry in the joint tissue. RESULTS: In the present study, we found expression and synthesis of transcription factor NF-kB was prominent in CIA rats. In addition, main pro-inflammatory cytokines such as TNF-α, IL-1ß, IL-6, and the anti-inflammatory IL-10, was also stand out. Further, reactive oxygen/nitrogen species was also elevated in CIA rats. Treatment with EA ameliorates all the above mentioned inflammatory and oxidative stress related parameters to near normal. Further, we also confirmed the expression of TNF-α, CD8+ T cells through immunohistochemistry was mitigates in joint tissue of EA treated rats. We find EA significantly inhibited the developmental phase of arthritis. CONCLUSION: These results suggest that EA act as potent anti-arthritic and anti-inflammatory agent that could be used as a tool for the development of new drug for the treatment of arthritis.


Asunto(s)
Artritis Experimental , Animales , Antiinflamatorios/uso terapéutico , Artritis Experimental/inducido químicamente , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Linfocitos T CD8-positivos/metabolismo , Catalasa/metabolismo , Citocinas/metabolismo , Ácido Elágico/efectos adversos , Mediadores de Inflamación/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , FN-kappa B/metabolismo , Nitrógeno/efectos adversos , Oxígeno/efectos adversos , Fosforilación , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
6.
Bull Environ Contam Toxicol ; 106(6): 996-1002, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33687536

RESUMEN

Pesticides to protect crops from pests are subject to rigorous risk assessment before registration in Japan. However, further information needs to be collected regarding the assessment of impacts on the natural environment. In particular, nitrifying bacteria play a role in converting ammonium salts to nitrates in soil. However, there is limited research covering the effects of insecticides on nitrification, despite several fungicides and herbicides have an inhibitory effect on nitrifying bacteria. Therefore, we investigated the effect of pesticides on the nitrification when applied to soil. The application of both pesticides promoted ammonia oxidation, and suppressed nitrite oxidation in a high-concentration treatment of dinotefuran. In addition, it was clarified that the diversity and species richness of soil bacteria was significantly reduced when the pesticides were applied to the soil, and that the specific soil bacteria (Metyhlotenera spp.) dominated the application of the pesticides.


Asunto(s)
Nitrificación , Suelo , Amoníaco , Archaea , Bacterias , Guanidinas , Japón , Neonicotinoides , Nitrocompuestos , Oxidación-Reducción , Pirimidinas , Microbiología del Suelo , Estrobilurinas
7.
Wiad Lek ; 74(2): 184-189, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33813469

RESUMEN

OBJECTIVE: The aim: To investigate the utility of testing for chlamydial heat shock protein 60 (CHSP60) antibodies in the diagnosis of tubal infertility. PATIENTS AND METHODS: Materials and methods: All the collected samples were assayed for IgM and IgG antibodies to chlamydia trachomatis and chlamydial heat shock protein 60 (CHSP60) by using immunofluorescence and enzyme-linked immunosorbent assay (ELISA) techniques, respectively. RESULTS: Results: There were no substantial differences between antibodies to C. trachomatis in females with tubal infertility (67%) and non-tubal infertility (48%). However, women with tubal infertility (45%) have more anti-CHSP60 antibodies than non-tubal infertility (9%). Antibody screening for C. trachomatis has only (63%) sensitivity and (54%) specificity for detecting tubal infertility. On the other hand, the CHSP60 antibody testing has (44%) sensitivity and 92% specificity for diagnosing tubal infertility. A positive microimmunofluorescence (MIF) titer was observed in 12 of 18 (67%) females with the tubal problem, 31 of 64 (48%) with non-tubal infertility (P=0.3, OR=2.2, 95% CI=0.71 to 8.01). The CHSP60 antibodies were found in 8 of 18 (45%) females with tubal problem & 6 of 64 (9%) women with non-tubal infertility, power factor alpha α P=0.004, OR=9.3, 95% CI=2.1 to 43.2, power= 1.002 for n= 0.05). Incorporating CHSP60 and C. trachomatis antibodies testing gives an excellent positive probability proportion of 10 to diagnose C. trachomatis associated tubal infertility. CONCLUSION: Conclusions: CHSP60 antibody testing is a more specific evaluation than antibody testing for C. trachomatis for predicting chlamydia-associated tubal infertility. Using these tests at the first infertility examination may help the immediate diagnosis for non-interceptive tubal infertility.


Asunto(s)
Infecciones por Chlamydia , Infertilidad Femenina , Anticuerpos Antibacterianos , Chaperonina 60 , Infecciones por Chlamydia/complicaciones , Infecciones por Chlamydia/diagnóstico , Chlamydia trachomatis , Femenino , Proteínas de Choque Térmico , Humanos , Infertilidad Femenina/diagnóstico , Estudios Prospectivos
8.
Wiad Lek ; 74(3 cz 2): 777-783, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33843653

RESUMEN

OBJECTIVE: The aim: This review was aimed to understand the role of different types of autoantibodies like antiphospholipid, antithyroid, antisperm, antinuclear, anti-ovarian autoantibodiesand heat shock protein HSP 60 in the process of implantation in the normal way of conceiving and IVF and also to estimate that how the presence of these autoantibodies affect the normal pregnancy outcome. PATIENTS AND METHODS: Materials and methods: This review process performed in the obstetrics and gynaecology postgraduate department, Bogomolets national medical university, Kyiv, Ukraine. It was a review of already published papers not to need the ethical board committee's approval. By following the literature review guidelines, this paper was written and searched for relevant studies regarding autoantibodies and implantation, published in medical literature till 2020 were included in this review process. The search is done for studies published till 2020 in the English language from the Medline database, including Google Scholar, PubMed, Web of Science and Cochrane library database. CONCLUSION: Conclusions: Our recent work found that the involvement of APA, ANA and/or ATA in recipients of oocyte donations did not affect their pregnancy outcomes. Some researchers did not give any clear conclusion about these risks, and some stated that the use of some immunodepressant agents could be useful to reduce the harmful effects of these autoantibodies associated with implantation failure. Each autoantibody has a different mechanism of action to create the pathological state, some have direct effect, and some indirectly impact implantation. In future, further high-quality studies need to be performed for better understanding.


Asunto(s)
Autoinmunidad , Resultado del Embarazo , Autoanticuerpos , Femenino , Fertilización In Vitro , Humanos , Embarazo , Índice de Embarazo , Ucrania
9.
J Electrocardiol ; 58: 74-79, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31770669

RESUMEN

PURPOSE: Interpreting a twelve­lead electrocardiogram (ECG) is a basic, albeit essential skill for most healthcare professionals to attain. Despite its importance, evidence suggests that the competency of healthcare professionals to interpret ECGs can be improved. We evaluated the effectiveness of a national interactive workshop designed to improve ECG interpretation in the UK medical student cohort. METHODS: UK medical students who attended a national workshop were asked to complete a pre- and post- workshop test which comprised of 20 ECGs which showed a variety of pathologies relating to conduction disturbances, tachycardia and acute coronary syndromes. The workshop was interactive and consisted of 6 h of ECG tutorials, divided into hourly sessions which covered all key topics such as 'basic electrophysiology' and 'electro-conduction problems'. Pre- and post-workshop test scores were compared by difference in means using the paired two-tailed t-test. RESULTS: A total of 145 participants completed the pre-test and of those 44 completed both the pre and post-test. The mean pre-test and post-test scores were 9.7/20 questions (48.9%) and 11.2/20 questions (56.2%) respectively, with a mean improvement of 1.5/20 (7.3%) from pre- to post-test (+7.3%, 95% CI: +1.8 to +12.8%, p = 0.01). CONCLUSION: A national ECG workshop which emphasizes activity-based learning may be effective in improving the competency of medical students to interpret ECGs. Further exploration with multi-center controlled studies involving a diverse cohort of students and analyses to determine their cost-effectiveness is warranted.


Asunto(s)
Estudiantes de Medicina , Competencia Clínica , Electrocardiografía , Humanos , Enseñanza , Reino Unido
11.
World J Microbiol Biotechnol ; 35(7): 104, 2019 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-31236765

RESUMEN

Endophytic bacterial diversity in plants presents the level of interaction between culturable and non-culturable endophytic bacteria, thereby providing an appropriate insight into the endophytic environment. This study was conducted to determine the trend of culturable and non-culturable endophytic bacteria at two different sites encompassing four consecutive growth stages. For culturable endophytic bacteria, isolation was carried out using the dilution plate technique, and the obtained colonies were compared using PCR-restriction fragment length polymorphism (RFLP). Different RFLP-types were identified to their nearest neighbour using 16S rRNA sequencing. The non-culturable endophytic bacterial diversity was obtained by next generation sequencing. Results suggested a similar trend among the culturable and non-culturable bacteria for observed operational taxonomic units and diversity indices. It is noticeable that the endophytic bacteria inhabiting in stage 1 disappeared, and instead, different endophytic bacteria appeared. Moreover, the temporal persistence of certain culturable and non-culturable bacteria was also observed. In conclusion, the endophytic bacterial diversity in cucumber initially increased with the plant growth and then decreased at a later stage. Furthermore, it was suggested that plants regulate the number and diversity of endophytes throughout the lifecycle of plants.


Asunto(s)
Bacterias/clasificación , Bacterias/aislamiento & purificación , Biodiversidad , Cucumis sativus/microbiología , Endófitos/clasificación , Endófitos/aislamiento & purificación , Microbiota , Bacterias/genética , Cucumis sativus/crecimiento & desarrollo , ADN Bacteriano/análisis , ADN Bacteriano/aislamiento & purificación , Endófitos/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Microbiota/genética , Filogenia , Raíces de Plantas/microbiología , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , ARN Ribosómico 16S/genética
12.
Pak J Pharm Sci ; 32(1): 205-212, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30772810

RESUMEN

Synthetic drugs are associated with adverse side-effects and rapid increase in resistance to most of them inspires to evaluate plants for their therapeutic values. We have been aimed to suggest the medicinal use of Nigella sativa seed aqueous extract to minimize the severity of liver damage via its antioxidant properties and its role in maintenance of cell ion-homeostasis. Annoyances in serum levels of some antioxidants and trace metals in human hepatitis C infected patients were compared with that from acetaminophen-induced hepatotoxic rabbits. Serum analysis of human patients and that of hepatotoxic rabbits have exhibited the same trend of incidence of liver marker enzymes, antioxidant levels, and trace metal concentrations, except for the serum levels of cobalt. Significance of pre-/ or post-treatment of Nigella sativa to acetaminophen induced-hepatotoxic rabbit has also evaluated. NS post-treatment to rabbits has been found effective in normalizing the levels (P<0.001) of serum liver markers; especially the ALP levels, and the antioxidants; with significant effect on the serum catalase levels. However, NS pre-treatment has shown its role (P<0.001) in maintaining the serum nickel and cobalt concentrations. Therefore, we suggest the use of Nigella sativa seeds as pre-/ or post-treatment therapy, and also as supplement to the normal medications of liver infection to normalize the status of cell antioxidants and trace metal concentrations.


Asunto(s)
Antioxidantes/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Hígado/efectos de los fármacos , Nigella sativa , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Acetaminofén , Adulto , Anciano , Animales , Antioxidantes/aislamiento & purificación , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citoprotección , Modelos Animales de Enfermedad , Femenino , Hepatitis C Crónica/sangre , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/virología , Humanos , Hígado/metabolismo , Hígado/patología , Masculino , Metales/sangre , Persona de Mediana Edad , Nigella sativa/química , Extractos Vegetales/aislamiento & purificación , Conejos , Semillas , Oligoelementos/sangre , Adulto Joven
13.
Pak J Pharm Sci ; 30(5): 1679-1690, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29084690

RESUMEN

Dengue infection is rapidly spreading in most of the countries of south Asia. It is of utmost importance to explore the plants with "anti-thrombocytopenic activity" the dreadful response of dengue fever. The present study was conducted to investigate the potential of aqueous extract of Nigella sativa (black cumin) seeds in alleviating the severity of dengue disease by raising the platelet count (PLT). Serum samples of thirty patients with dengue hemorrhagic fever (DHF) were analysed for different biochemical parameters. When compared with control groups, the patients were found with very low PLT count (7.62 fold), reduced antioxidant levels; catalase (1.4 fold), ascorbic acid (1.1 fold), bilirubin (1.06 fold), and severe deficiency of micronutrient concentrations; cobalt (2.27 fold), iron (2.35 fold) and nickel (71.46 fold). Similar parameters were studied in albino rats to observe the changes in serum levels of biochemical markers, after administration of single dose of choloroquine phosphate (IM, 1.5 mL saline). The drug successfully induced thrombocytopenia along with significant decrease in levels of antioxidants and trace metals. Administration of N. sativa aqueous seed extract (15.25 mg/kg/bw) for 12 days resulted in an increase in PLT count (1.59 fold) as compared to control group. N. sativa post-treatment was found effective in elevating the serum levels of catalase, ascorbic acid, and bilirubin (1.06, 1.58 and 0.4 folds respectively). However, the N. sativa pre-treatment was useful in increasing the levels of micronutrients; iron, nickel and cobalt when compared to quinine-induced group. From the above findings it was suggested that N. sativa seed aqueous extract supplementation would be a promising solution for declined PLT count and associated consequences.


Asunto(s)
Antioxidantes/farmacología , Plaquetas/efectos de los fármacos , Cloroquina/análogos & derivados , Nigella sativa/química , Extractos Vegetales/farmacología , Semillas/química , Trombocitopenia/tratamiento farmacológico , Adolescente , Adulto , Animales , Antioxidantes/aislamiento & purificación , Estudios de Casos y Controles , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Recuento de Plaquetas , Ratas , Dengue Grave/sangre , Dengue Grave/diagnóstico , Trombocitopenia/sangre , Trombocitopenia/inducido químicamente , Factores de Tiempo , Oligoelementos/sangre , Adulto Joven
14.
Acta Pol Pharm ; 73(1): 183-96, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27008813

RESUMEN

A super-absorbent hydrogel was developed by crosslinking of 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) and acrylic acid with hydroxypropyl methylcellulose (HPMC) for controlled release drug delivery of captopril, a well known antihypertensive drug. Acrylic acid and AMPS were polymerized and crosslinked with HPMC by free radical polymerization, a widely used chemical crosslinking method. N,N'-methylenebisacrylamide (MBA) and potassium persulfate (KPS) were added as cross-linker and initiator, respectively. The hydrogel formulation was loaded with captopril (as model drug). The concentration of captopril was monitored at 205 nm using UV spectrophotometer. Equilibrium swelling ratio was determined at pH 2, 4.5 and 7.4 to evaluate the pH responsiveness of the formed hydrogel. The super-absorbent hydrogels were evaluated by FTIR, SEM, XRD, and thermal analysis (DSC and TGA). The formation of new copolymeric network was determined by FTIR, XRD, TGA and DSC analysis. The hydrogel formulations with acrylic acid and AMPS ratio of 4: 1 and lower amounts of crosslinker had shown maximum swelling. Moreover, higher release rate of captopril was observed at pH 7.4 than at pH 2, because of more swelling capacity of copolymer with increasing pH of the aqueous medium. The present research work confirms the development of a stable hydrogel comprising of HPMC with acrylic acid and AMPS. The prepared hydrogels exhibited pH sensitive behav-ior. This superabsorbent composite prepared could be a successful drug carrier for treating hypertension.


Asunto(s)
Captopril/administración & dosificación , Derivados de la Hipromelosa/administración & dosificación , Polímeros/administración & dosificación , Ácidos Sulfónicos/administración & dosificación , Captopril/química , Preparaciones de Acción Retardada , Hidrogeles , Concentración de Iones de Hidrógeno , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier
15.
AAPS PharmSciTech ; 16(6): 1281-9, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25771738

RESUMEN

Polyethylene oxide has been researched extensively as an alternative polymer to hydroxypropyl methylcellulose (HPMC) in controlled drug delivery due to its desirable swelling properties and its availability in a number of different viscosity grades. Previous studies on HPMC have pointed out the importance of particle size on drug release, but as of yet, no studies have investigated the effect of particle size of polyethylene oxide (polyox) on drug release. The present study explored the relationship between polymer level and particle size to sustain the drug release. Tablets produced contained theophylline as their active ingredient and consisted of different polyethylene oxide particle size fractions (20-45, 45-90, 90-180 and 180-425 µm). It was shown that matrices containing smaller particle sizes of polyox produced harder tablets than when larger polyox particles were used. The release studies showed that matrices consisting of large polyox particles showed a faster release rate than matrices made from smaller particles. Molecular weight (MW) of the polymer was a key determining step in attaining sustained release, with the high MW of polyox resulting in a delayed release profile. The results showed that the effect of particle size on drug release was more detrimental when a low concentration of polyox was used. This indicates that care must be taken when low levels of polyox with different particle size fractions are used. More robust formulations could be obtained when the concentration of polyox is high. Differential scanning calorimetry (DSC) traces showed that particle size had no major effect on the thermal behaviour of polyox particles.


Asunto(s)
Preparaciones de Acción Retardada/química , Polietilenglicoles/química , Comprimidos/química , Teofilina/química , Rastreo Diferencial de Calorimetría/métodos , Química Farmacéutica/métodos , Liberación de Fármacos , Derivados de la Hipromelosa/química , Tamaño de la Partícula , Polímeros/química , Solubilidad , Viscosidad
16.
Sci Total Environ ; 951: 175552, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39151632

RESUMEN

In order to assess the risk of pesticides to aquatic ecosystems, five single-dose pesticides including chlorpyrifos, pymetrozine, dinotefuran, azoxystrobin, and acetochlor that are frequently used in developing countries, were selected. Based on the principle of conservative risk assessment, application amounts for different dosage forms were recommended, the Top-Rice model and risk quotient method were used to evaluate the aquatic ecological risk of the aforementioned single-dose pesticide products. The results showed that predicted peak environmental concentration ranges after application on rice were 110.52-564.25 µg/L for chlorpyrifos, 20.79-114.6 µg/L for pymetrozine, 21.81-114.02 µg/L for dinotefuran, 16.52-56.94 µg/L for azoxystrobin, and 167.22-2184.01 µg/L for acetochlor in different seasons of Changsha, Hangzhou, Nanning in China, and Lahore and Faisalabad in Pakistan. Under the current conditions of registered administration, the acute and chronic risks posed by chlorpyrifos to fish and invertebrates were deemed alarming, and those by pymetrozine and dinotefuran were considered acceptable. The acute risk of exposure of azoxystrobin to vertebrates such as fish, and invertebrates such as daphnia and shrimp is alarming, whereas the chronic risk to vertebrates, invertebrates, and algae was acceptable. The acute exposure risk posed by acetochlor was deemed worrying, and in the case of chronic exposure, only 36 % of the simulation group exhibited a risk quotient below 1, indicating no risk. These findings imply that the ecological risks of using registered chlorpyrifos and acetochlor products on rice cannot be ignored. It should be noted that the analysis method and model employed in this study were intentionally conservative to ensure a comprehensive assessment of the potential risks associated with the use of registered pesticide products. However, the model failed to consider influential factors like photolysis of pesticides on the soil surface, thereby introducing a certain degree of conservativeness in the evaluation results.


Asunto(s)
Agricultura , Oryza , Plaguicidas , Medición de Riesgo , Plaguicidas/análisis , Desarrollo Sostenible , Contaminantes Químicos del Agua/análisis , China , Monitoreo del Ambiente , Animales
17.
Chem Biol Interact ; 398: 111114, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38897341

RESUMEN

Withaferin A, a steroid lactone from Withania somnifera, exhibits anti-inflammatory, immunomodulatory, and antioxidant properties. This study investigated the effects of withaferin A on collagen-induced arthritis (CIA) rats, focusing on NF-κB p65 regulation and cytokine release. Withaferin A (50 mg/kg b.wt., orally) or methotrexate (0.25 mg/kg b.wt., i.p., as a reference drug) was given to CIA rats daily for 20 days postarthritis induction. Joints were removed from nonarthritic and arthritic rats to assess the levels of NO, MPO, interleukin (IL)-1ß, IL-6, IL-10, TNF-α, COX-2, and NF-κB via ELISA. Furthermore, the mRNA expression of IL-1ß, IL-10, TNF-α, COX-2, iNOS, and NF-κB was also assessed through qPCR. Treatment with withaferin A significantly inhibited the levels of inflammatory cytokines and the transcription factor NF-κB; suppressed the expression of IL-1ß, IL-10, TNF-α, COX-2, iNOS, and NF-κB in the joint tissue of CIA rats; and reduced cartilage and bone destruction, as shown by H&E staining. To confirm the results obtained from biochemical and molecular studies and to determine the molecular target of withaferin A, we performed a molecular simulation of the potential targets of withaferin A, which identified the NF-κB pathway as its target. These results suggested that withaferin A effectively attenuated rheumatoid arthritis progression by inhibiting the activation of the NF-κB pathway and the downstream secretion of inflammatory cytokines.


Asunto(s)
Artritis Experimental , Citocinas , FN-kappa B , Transducción de Señal , Witanólidos , Animales , Witanólidos/farmacología , Witanólidos/uso terapéutico , Ratas , Citocinas/metabolismo , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Artritis Experimental/patología , FN-kappa B/metabolismo , Masculino , Transducción de Señal/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/genética , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Ratas Wistar , Modelos Animales de Enfermedad , Withania/química
18.
Environ Sci Pollut Res Int ; 30(16): 46204-46221, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36710308

RESUMEN

Corporate social responsibility turned into a global sensation from the inception of the twenty-first century in the corporate world and grabbed immense engrossment from all stakeholders in their decision-making process. Capital structure and corporate governance practices are the well-mellowed facets of corporate finance literature. In this study, the moderating role of corporate social responsibility (CSR) between corporate governance and leverage of the US and Chinese listed firms has been established, with a further extension of analyzing the moderating role of CSR between corporate governance and leverage in high vs low leveraged firms and high CSR vs low CSR firms as the novelty of this study and has never been examined in both economies and globally. The data of 1989 Chinese-listed firms from 28 sectors of the economy and 6640 US-listed firms from 27 sectors of the economy has been taken from 2001 to 2019 and analyzed through fixed effect regression and system generalized method of moment (GMM). Results of the study reveal that CSR and corporate governance are negatively associated with the leverage of both Chinese and US firms. Moreover, the moderating role of CSR has established between corporate governance and leverage negative relationship. The moderating role of CSR in the relationship of leverage and corporate governance is established only in low-leveraged firms whereas it is insignificant in high-leveraged firms. System GMM confirms the signs and significance of the regression results; that is why regression results are robust and reliable, and there is no endogeneity problem in our model. The study also gives an insight for future research on high- and low-leveraged firms and firms with more CSR score than less CSR score with other dimensions such as firm performance and firm value variables.


Asunto(s)
Industrias , Organizaciones , Responsabilidad Social , China , Estados Unidos
19.
J Trace Elem Med Biol ; 79: 127212, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37257336

RESUMEN

BACKGROUND AND OBJECTIVE: Rheumatoid arthritis is a chronic progressive autoimmune disorder, characterised by destruction of cartilage and under line bones. Though exact etiology of rheumatoid arthritis (RA) remains unknown. It is believed that alteration in control of cellular or molecular responses is involved in the chronic inflammation. Earlier in RA patients it was observed the circulating RA specific biomarkers and immunoglobulin deposits in the synovial joints. Zinc Oxide Nanoparticles (ZnO NPs) is used as an anti-inflammatory and anticancer agent, however there is nil/very less scientific data shows the anti-arthritic activity of green synthesis ZnO nanoparticles (Ocimum sanctum water extract in-situ synthesis of ZnO NPs having active compound Caffeic acid and Rosmerinic acid). Hence, the present activity was planned to assess the anti-arthritic activity of ZnO NPs in CIA rats. METHODS: Arthritis in rats were induced by subcutaneous injection of collagen type II (CII) (200 µl) at the base of tail on day 0 followed by booster dose on day 14. ZnO NPs were given (2 mg/kg b.wt./day) orally for 20 days. At the end of the study serum, joint homogenate was used to assess the level of biomarkers (RF, a-CCP, a-CII and CRP) and inflammatory mediators. In addition, m-RNA expression of various genes such as Nuclear factor-kB (NF-kB), inflammatory mediators like tumour necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) etc. were assayed in joint tissue. Finally all these biochemical and molecular results were confirmed by microscopic study of joint tissue. RESULTS: ZnO NPs, treated rats showed decrease in inflammation and clinical severity. This was related with decrease in the level of biomarkers (like RF, a-CCP and CRP), inflammatory mediators (TNF-α, COX-2) and activity of transcription factor NF-kB. All these findings were positively correlated with microscopic analysis of joint tissue that showed reduced inflammation and bone erosion in treated group. CONCLUSION: This study validates the anti-arthritic activity of ZnO NPs as it mitigates the arthritis related symptoms in CIA rats.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Nanopartículas , Óxido de Zinc , Ratas , Animales , Óxido de Zinc/farmacología , Óxido de Zinc/uso terapéutico , Factor de Necrosis Tumoral alfa , Ciclooxigenasa 2/metabolismo , Ocimum sanctum/metabolismo , Citocinas/metabolismo , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Artritis Reumatoide/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Colágeno Tipo II/efectos adversos , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/uso terapéutico , Biomarcadores
20.
Cureus ; 15(7): e41467, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37546072

RESUMEN

Introduction Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Early detection and timely treatment have provided successful repair of the anomaly in the developed world. However, in the developing world, there is still a burden of uncorrected TOF patients reaching adulthood. The goal of this study is to determine whether there is any difference in postoperative complications between adult and pediatric populations following surgical correction for TOF. Methods This study involved all those patients who received primary or secondary surgical repair for TOF in our facility between January 2017 and December 2020. The patients were split according to their age into the pediatric group if they were under 18 years and the adult group if they were 18 years or older. Patients with absent pulmonary valve or pulmonary atresia were not included in this study. Patients with large major aortopulmonary collateral arteries (MAPCA) were also excluded from this study. All patients underwent total correction through a median sternotomy approach. The ventricular septal defect was closed with a Bard knitted fiber patch. The right ventricular outflow tract (RVOT) was augmented by excising muscle bands or fibrous bands in the RVOT. If the annulus was smaller than the 3.5 z score, then a transannular patch was done using an autologous pericardium. The main pulmonary artery was augmented in every surgery using an autologous pericardial patch. All patients were shifted to the ICU on the ventilator and were extubated after fulfillment of the extubation criteria. Postoperative complications measured included re-opening, re-intubation, prolonged ventilation (>24 hours), and mortality within the index hospital admission. The clinical data of all patients were prospectively collected and analyzed using the chi-square test and t-test. A p-value of less than or equal to 0.05 was considered significant. Results The total number of patients was 134. This included 83 males (60.1%). A total of 114 patients who were aged below 18 years were included in the pediatric group, and 20 patients aged equal to or more than 18 years were included in the adult group. The mean average perfusion time in minutes in the adult group was 125.8 and in the pediatric group, it was 98.79. Similarly, the mean average of the cross-clamp time was also longer in the adult group at 89.55 minutes versus 69.63 minutes in the pediatric group. Overall, in the adult group, three (15%) patients had postoperative complications, while in the pediatric group, a total of 14 (11.9%) patients had postoperative complications (p = 0.001). However, there was no significant difference in the number of re-openings (8.5% vs. 10%; p = 0.8). The total mortality observed was 16 (11.59%). This included 14 (11.9%) in the pediatric group and two (10%) in the adult group. There was no significant difference between the two groups (p = 0.8). Conclusions Surgical repair of TOF can be performed in both adult and pediatric populations with acceptable outcomes. The mortality rate was found to be slightly greater in the pediatric population compared to the adults. However, it can be seen that the number of postoperative complications is greater in adults. Further research is needed to optimize outcomes for both pediatric and adult patients with TOF.

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