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1.
BMC Infect Dis ; 24(1): 659, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956482

RESUMO

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.


Assuntos
Átrios do Coração , Transplante de Fígado , Transplante Autólogo , Humanos , Pessoa de Meia-Idade , Feminino , Átrios do Coração/cirurgia , Átrios do Coração/parasitologia , Equinococose/cirurgia , Fígado/parasitologia , Fígado/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Equinococose Hepática/cirurgia
2.
Biophys J ; 122(18): 3783-3797, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37559362

RESUMO

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.


Assuntos
Colesterol , Receptores de LDL , Humanos , Colesterol/metabolismo , Clatrina/metabolismo , Fluorescência , Células HEK293 , Lipoproteínas LDL/metabolismo , Receptores de LDL/metabolismo
3.
Pak J Med Sci ; 39(2): 467-473, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36950424

RESUMO

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.

4.
Inflammopharmacology ; 30(5): 1729-1743, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35939220

RESUMO

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.


Assuntos
Artrite Experimental , Animais , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Catalase/metabolismo , Citocinas/metabolismo , Ácido Elágico/efeitos adversos , Mediadores da Inflamação/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Nitrogênio/efeitos adversos , Oxigênio/efeitos adversos , Fosforilação , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
Bull Environ Contam Toxicol ; 106(6): 996-1002, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33687536

RESUMO

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.


Assuntos
Nitrificação , Solo , Amônia , Archaea , Bactérias , Guanidinas , Japão , Neonicotinoides , Nitrocompostos , Oxirredução , Pirimidinas , Microbiologia do Solo , Estrobilurinas
6.
Wiad Lek ; 74(3 cz 2): 777-783, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33843653

RESUMO

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.


Assuntos
Autoimunidade , Resultado da Gravidez , Autoanticorpos , Feminino , Fertilização in vitro , Humanos , Gravidez , Taxa de Gravidez , Ucrânia
7.
Wiad Lek ; 74(2): 184-189, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33813469

RESUMO

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.


Assuntos
Infecções por Chlamydia , Infertilidade Feminina , Anticorpos Antibacterianos , Chaperonina 60 , Infecções por Chlamydia/complicações , Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis , Feminino , Proteínas de Choque Térmico , Humanos , Infertilidade Feminina/diagnóstico , Estudos Prospectivos
8.
J Electrocardiol ; 58: 74-79, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31770669

RESUMO

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.


Assuntos
Estudantes de Medicina , Competência Clínica , Eletrocardiografia , Humanos , Ensino , Reino Unido
9.
World J Microbiol Biotechnol ; 35(7): 104, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31236765

RESUMO

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.


Assuntos
Bactérias/classificação , Bactérias/isolamento & purificação , Biodiversidade , Cucumis sativus/microbiologia , Endófitos/classificação , Endófitos/isolamento & purificação , Microbiota , Bactérias/genética , Cucumis sativus/crescimento & desenvolvimento , DNA Bacteriano/análise , DNA Bacteriano/isolamento & purificação , Endófitos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Microbiota/genética , Filogenia , Raízes de Plantas/microbiologia , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , RNA Ribossômico 16S/genética
10.
Pak J Pharm Sci ; 32(1): 205-212, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30772810

RESUMO

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.


Assuntos
Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/efeitos dos fármacos , Nigella sativa , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Acetaminofen , Adulto , Idoso , Animais , Antioxidantes/isolamento & purificação , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citoproteção , Modelos Animais de Doenças , Feminino , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/virologia , Humanos , Fígado/metabolismo , Fígado/patologia , Masculino , Metais/sangue , Pessoa de Meia-Idade , Nigella sativa/química , Extratos Vegetais/isolamento & purificação , Coelhos , Sementes , Oligoelementos/sangue , Adulto Jovem
11.
Pak J Pharm Sci ; 30(5): 1679-1690, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29084690

RESUMO

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.


Assuntos
Antioxidantes/farmacologia , Plaquetas/efeitos dos fármacos , Cloroquina/análogos & derivados , Nigella sativa/química , Extratos Vegetais/farmacologia , Sementes/química , Trombocitopenia/tratamento farmacológico , Adolescente , Adulto , Animais , Antioxidantes/isolamento & purificação , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Contagem de Plaquetas , Ratos , Dengue Grave/sangue , Dengue Grave/diagnóstico , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Fatores de Tempo , Oligoelementos/sangue , Adulto Jovem
12.
Acta Pol Pharm ; 73(1): 183-96, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27008813

RESUMO

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.


Assuntos
Captopril/administração & dosagem , Derivados da Hipromelose/administração & dosagem , Polímeros/administração & dosagem , Ácidos Sulfônicos/administração & dosagem , Captopril/química , Preparações de Ação Retardada , Hidrogéis , Concentração de Íons de Hidrogênio , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
13.
AAPS PharmSciTech ; 16(6): 1281-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25771738

RESUMO

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.


Assuntos
Preparações de Ação Retardada/química , Polietilenoglicóis/química , Comprimidos/química , Teofilina/química , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Liberação Controlada de Fármacos , Derivados da Hipromelose/química , Tamanho da Partícula , Polímeros/química , Solubilidade , Viscosidade
14.
Chem Biol Interact ; 398: 111114, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38897341

RESUMO

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.


Assuntos
Artrite Experimental , Citocinas , NF-kappa B , Transdução de Sinais , Vitanolídeos , Animais , Vitanolídeos/farmacologia , Vitanolídeos/uso terapêutico , Ratos , Citocinas/metabolismo , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Experimental/patologia , NF-kappa B/metabolismo , Masculino , Transdução de Sinais/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/genética , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ratos Wistar , Modelos Animais de Doenças , Withania/química
15.
Environ Sci Pollut Res Int ; 30(16): 46204-46221, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36710308

RESUMO

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.


Assuntos
Indústrias , Organizações , Responsabilidade Social , China , Estados Unidos
16.
J Trace Elem Med Biol ; 79: 127212, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37257336

RESUMO

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.


Assuntos
Artrite Experimental , Artrite Reumatoide , Nanopartículas , Óxido de Zinco , Ratos , Animais , Óxido de Zinco/farmacologia , Óxido de Zinco/uso terapêutico , Fator de Necrose Tumoral alfa , Ciclo-Oxigenase 2/metabolismo , Ocimum sanctum/metabolismo , Citocinas/metabolismo , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Colágeno Tipo II/efeitos adversos , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/uso terapêutico , Biomarcadores
17.
Cureus ; 15(7): e41467, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37546072

RESUMO

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.

18.
Appl Biochem Biotechnol ; 195(7): 4177-4195, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36662423

RESUMO

The aim of this study was to examine the hypothesis that use of dimethyl fumarate (DMF) may mitigate arthritic symptoms in collagen-induced arthritis (CIA) rats through activation of NF-E2-related factor 2(Nrf-2) and suppression of NF-kB pathway. Arthritis in rats was induced by subcutaneous injection of collagen type II (200 µl) at the base of the tail. After induction arthritic rats were treated with DMF (25 mg/kg b.wt.) for 20 days from the day 25th to 45th. At the end of the study, serum and joint homogenate was used to assess the oxidative stress and cytokines level. In addition, mRNA expression of various genes such as NF-kB, Keap-1 (Kelch-like ECH-associated protein 1) and Nrf-2 was assayed through qRT-PCR in joint tissue. Finally, all these biochemical and molecular results were confirmed by histological and in silico study. Our results showed that decrease in the clinical severity, inflammation, and cell necrosis in DMF-treated rats. This was related with decrease in NF-kB activity and increase in activity of Nrf-2. Treatment with DMF increases the levels of endogenous antioxidant biomarkers glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) and decreases inflammation. These biochemical and molecular results were further confirmed by performing in silico study that shows DMF strongly inhibits the activation of NF-kB, and conversely at the same time increases the activity of Nrf-2 that means a significantly lower amount of inflammatory mediators and oxidants was produced. Decrease in inflammation leads to preserving the joint architecture and alleviation from clinical symptoms of arthritis. Collectively, these results indicate that Nrf-2 activation protects against arthritic symptoms.


Assuntos
Artrite , NF-kappa B , Ratos , Animais , NF-kappa B/metabolismo , Fumarato de Dimetilo/farmacologia , Fumarato de Dimetilo/uso terapêutico , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Inflamação/tratamento farmacológico , Glutationa/metabolismo , Artrite/tratamento farmacológico
19.
J Orthod Sci ; 12: 82, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38234657

RESUMO

BACKGROUND: Static friction force between the orthodontic brackets and wire impacts the sliding mechanics that affect teeth movements and treatment duration. This sliding media is jam-packed with released metal ions from the fixed appliances. This study aimed to assess the static frictional force and surface topography of stainless steel (SS) and I archwires in dry conditions and in media fully with metal ions that were released from fixed appliances. METHODS: In this research study, a set of 60 as-received straight archwires specimens (5 cm wire) were employed and categorized into two groups based on the material type [30 super elastics new I archwires gauge (0.018 × 0.014 inch) and 30 SS archwires 0.018 × 0.022" as a control]. The archwires' static friction force was measured while sliding a loaded Roth SS brackets (0.018") on the archwire using a universal tensile testing machine in dry and metal ions released media, while the surface topography was assessed using a noncontact AFM machine. RESULTS: The static friction of I archwire was significantly lower than the SS wire in dry condition. Metal ions media released from fixed appliances significantly reduced the Static friction compared to dry and wet conditions with deionized water for both wires. An Atomic Force Microscope machine surface roughness reports revealed that the highest mean of all three roughness parameters was found in the SS group, followed by I archwires in descending order. Additionally, metal ions media significantly reduce all roughness parameters.

20.
N Engl J Med ; 360(20): 2055-65, 2009 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-19439741

RESUMO

BACKGROUND: Older women with breast cancer are underrepresented in clinical trials, and data on the effects of adjuvant chemotherapy in such patients are scant. We tested for the noninferiority of capecitabine as compared with standard chemotherapy in women with breast cancer who were 65 years of age or older. METHODS: We randomly assigned patients with stage I, II, IIIA, or IIIB breast cancer to standard chemotherapy (either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide plus doxorubicin) or capecitabine. Endocrine therapy was recommended after chemotherapy in patients with hormone-receptor-positive tumors. A Bayesian statistical design was used with a range in sample size from 600 to 1800 patients. The primary end point was relapse-free survival. RESULTS: When the 600th patient was enrolled, the probability that, with longer follow-up, capecitabine therapy was highly likely to be inferior to standard chemotherapy met a prescribed level, and enrollment was discontinued. After an additional year of follow-up, the hazard ratio for disease recurrence or death in the capecitabine group was 2.09 (95% confidence interval, 1.38 to 3.17; P<0.001). Patients who were randomly assigned to capecitabine were twice as likely to have a relapse and almost twice as likely to die as patients who were randomly assigned to standard chemotherapy (P=0.02). At 3 years, the rate of relapse-free survival was 68% in the capecitabine group versus 85% in the standard-chemotherapy group, and the overall survival rate was 86% versus 91%. Two patients in the capecitabine group died of treatment-related complications; as compared with patients receiving capecitabine, twice as many patients receiving standard chemotherapy had moderate-to-severe toxic effects (64% vs. 33%). CONCLUSIONS: Standard adjuvant chemotherapy is superior to capecitabine in patients with early-stage breast cancer who are 65 years of age or older. (ClinicalTrials.gov number, NCT00024102.)


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Capecitabina , Quimioterapia Adjuvante/efeitos adversos , Cisplatino/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Metástase Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Receptores de Estrogênio/análise , Análise de Sobrevida
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