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1.
Front Public Health ; 12: 1379326, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962764

RESUMEN

Introduction: Premarital screening (PMS) is an essential global measure that seeks to reduce the occurrence of specific genetic disorders and sexually transmitted diseases common in consanguineous marriages. Due to the lack of a nationwide study, this research was designed to comprehend how unmarried individuals perceive the risks and benefits of PMS. Method: A cross-sectional study was conducted using an online questionnaire distributed through different social media platforms, responses from the native adult population (18-49 years) Saudi Arabia was only included in the study. The questionnaire was based on the Health Belief Model (HBM) to assessing seven different constructs including susceptibility, seriousness, benefits-, barriers-, & cues- to action, self-efficacy, and social acceptance. Data frequency was represented by mean and standard deviation; chi-square and t-tests were conducted for the comparison of independent and dependent variables. A multinomial logistic regression was used to predict factors influencing decisions related to PMS. Results: 1,522 participants completed the survey, mostly 18-25 years old and most of them were women. The majority were single with 85 men and 1,370 women. Most participants (59.6%) believed their parents were related, while 40.5% did not. 122 respondents reported they had to marry within their tribe. Findings revealed significant correlations among all HBM themes, with varying strengths. Notably, a moderate positive relationship was found between the perception of benefits and cues to action, suggesting that enhancing the perceived benefits of PMS could facilitate safe marriage practices. Multinomial regression analysis revealed that demographic factors and health beliefs significantly influence individuals' intentions and behaviors toward PMS and safe marriage. Conclusion: The study concludes that by identifying and addressing barriers, and promoting positive social acceptance, PMS can significantly contribute to preventing genetic diseases and promoting safe marriage practices, although the cross-sectional design limits the establishment of causal relationships and further research is needed.


Asunto(s)
Consanguinidad , Matrimonio , Exámenes Prenupciales , Humanos , Estudios Transversales , Femenino , Masculino , Adulto , Arabia Saudita , Adolescente , Persona de Mediana Edad , Matrimonio/estadística & datos numéricos , Matrimonio/psicología , Encuestas y Cuestionarios , Exámenes Prenupciales/estadística & datos numéricos , Adulto Joven , Persona Soltera/estadística & datos numéricos , Persona Soltera/psicología , Conocimientos, Actitudes y Práctica en Salud , Modelo de Creencias sobre la Salud
2.
Front Pharmacol ; 15: 1366279, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863975

RESUMEN

Rhododendron arboreum: Sm., also known as Burans is traditionally used as an anti-inflammatory, anti-diabetic, hepatoprotective, adaptogenic, and anti-oxidative agent. It has been used since ancient times in Indian traditional medicine for various liver disorders. However, the exact mechanism behind its activity against NAFLD is not known. The aim of the present study is to investigate the molecular mechanism of Rhododendron arboreum flower (RAF) in the treatment of NAFLD using network pharmacology and molecular docking methods. Bioactives were also predicted for their drug-likeness score, probable side effects and ADMET profile. Protein-protein interaction (PPI) data was obtained using the STRING platform. For the visualisation of GO analysis, a bioinformatics server was employed. Through molecular docking, the binding affinity between potential targets and active compounds were assessed. A total of five active compounds of RAF and 30 target proteins were selected. The targets with higher degrees were identified through the PPI network. GO analysis indicated that the NAFLD treatment with RAF primarily entails a response to the fatty acid biosynthetic process, lipid metabolic process, regulation of cell death, regulation of stress response, and cellular response to a chemical stimulus. Molecular docking and molecular dynamic simulation exhibited that rutin has best binding affinity among active compounds and selected targets as indicated by the binding energy, RMSD, and RMSF data. The findings comprehensively elucidated toxicity data, potential targets of bioactives and molecular mechanisms of RAF against NAFLD, providing a promising novel strategy for future research on NAFLD treatment.

3.
Heliyon ; 10(10): e30774, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38765040

RESUMEN

This study was aimed to investigate the learning experiences' facilitators and barriers that is encountered by the physically disabled female students during their higher education. Twenty semi-structured interviews were conducted with female students with physical disabilities aged between 19 and 33 years. Interviews were transcribed, confirmed, and analyzed after being recorded. The average age of the sample was 22.15 ± 3.48 years and one-fourth of the participants' disability was due to cerebral palsy and 35% participants used wheelchairs. All the factors promoted inclusive education and equal opportunities for both disabled and nondisabled students. This study reveals that in order to improve the learning experiences of students with disabilities (SwD) and to give them more opportunities for success, it is important to consider all the barriers discussed in this study. It can be concluded that high effort is required to transform the higher educational institutions to be more accommodating for students with disabilities.

4.
Healthcare (Basel) ; 12(2)2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38255042

RESUMEN

Lifestyle behaviors are daily habits influenced by social and environmental factors. This study examined lifestyle behaviors and their associations with sociodemographics, comorbidities, and pain in Saudi university students during the academic year 2021 and 2022. All students received the study invitation via university emails to complete an online questionnaire. The questionnaire included four sections (sociodemographics, health-related information, desired health promotion activities, and a lifestyle behavior assessment) via Health-Promoting Lifestyle Profile II (HPLP-II). The associations between study variables were assessed using Pearson's correlation and multiple linear regression. The study questionnaire was completed by 1112 students. No correlation was found between sociodemographics and lifestyle-behavior-related factors except for students in the College of Science who appeared to have good lifestyle behaviors (an increase in HPLP II total scores of 3.69). Students with mental health issues have poorer lifestyle behaviors and spend more time sitting (p < 0.00). Students without disabilities have lower scores in health responsibility, physical activity, nutrition, and stress management, while auditory disability specifically lowers health responsibility (p < 0.00). Pain was not associated with any assessed lifestyle behaviors. This study identified several significant correlations and differences between variables such as age, sedentary behavior, sleep duration, disability status, college major, and lifestyle behaviors among PNU students. These findings provide insights into the factors that influence students' health-promoting behaviors and can help guide interventions for promoting healthier lifestyles on campus. Targeted health promotion strategies at an early age could help in decreasing overall noncommunicable disease incidents later in life. The study results should be interpreted taking into consideration that the collected data were cross-sectional and self-reported. In conclusion, the findings of this study clearly demonstrate the need for specific lifestyle and health-promoting programs that are directed toward university students.

5.
Rev Med Virol ; 34(1): e2491, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37985599

RESUMEN

The immunopathology of herpes simplex virus (HSV)-associated neuroinflammation is a captivating and intricate field of study within the scientific community. HSV, renowned for its latent infection capability, gives rise to a spectrum of neurological expressions, ranging from mild symptoms to severe encephalitis. The enigmatic interplay between the virus and the host's immune responses profoundly shapes the outcome of these infections. This review delves into the multifaceted immune reactions triggered by HSV within neural tissues, intricately encompassing the interplay between innate and adaptive immunity. Furthermore, this analysis delves into the delicate equilibrium between immune defence and the potential for immunopathology-induced neural damage. It meticulously dissects the roles of diverse immune cells, cytokines, and chemokines, unravelling the intricacies of neuroinflammation modulation and its subsequent effects. By exploring HSV's immune manipulation and exploitation mechanisms, this review endeavours to unveil the enigmas surrounding the immunopathology of HSV-associated neuroinflammation. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of HSV infections.


Asunto(s)
Herpes Simple , Simplexvirus , Humanos , Enfermedades Neuroinflamatorias , Inmunidad Adaptativa , Citocinas
6.
Pathol Res Pract ; 251: 154850, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37839358

RESUMEN

MEG3, a significant long non-coding RNA (lncRNA), substantially functions in diverse biological processes, particularly breast cancer (BC) development. Within the imprinting DLK-MEG3 region on human chromosomal region 14q32.3, MEG3 spans 35 kb and encompasses ten exons. It exerts regulatory effects through intricate interactions with miRNAs, proteins, and epigenetic modifications. MEG3's multifaceted function in BC is evident in gene expression modulation, osteogenic tissue differentiation, and involvement in bone-related conditions. Its role as a tumor suppressor is highlighted by its influence on miR-182 and miRNA-29 expression in BC. Additionally, MEG3 is implicated in acute myocardial infarction and endothelial cell function, emphasising cell-specific regulatory mechanisms. MEG3's impact on gene activity encompasses transcriptional and post-translational adjustments, including DNA methylation, histone modifications, and interactions with transcription factors. MEG3 dysregulation is linked to unfavourable outcomes and drug resistance. Notably, higher MEG3 expression is associated with enhanced survival in BC patients. Overcoming challenges such as unravelling context-specific interactions, understanding epigenetic control, and translating findings into clinical applications is imperative. Prospective endeavours involve elucidating underlying mechanisms, exploring epigenetic alterations, and advancing MEG3-based diagnostic and therapeutic approaches. A comprehensive investigation into broader signaling networks and rigorous clinical trials are pivotal. Rigorous validation through functional and molecular analyses will shed light on MEG3's intricate contribution to BC progression.


Asunto(s)
Neoplasias de la Mama , MicroARNs , ARN Largo no Codificante , Femenino , Humanos , Neoplasias de la Mama/genética , Proliferación Celular , Metilación de ADN , Regulación Neoplásica de la Expresión Génica/genética , MicroARNs/genética , Estudios Prospectivos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo
7.
Int J Biol Macromol ; 253(Pt 7): 127375, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37839597

RESUMEN

The intricate molecular pathways governing cancer development and progression have spurred intensive investigations into novel therapeutic targets. Glycogen Synthase Kinase-3 (GSK3), a complex serine/threonine kinase, has emerged as a key player with intricate roles in various cellular processes, including cell proliferation, differentiation, apoptosis, and metabolism. Harnessing GSK3 inhibitors as potential candidates for cancer therapy has garnered significant interest due to their ability to modulate key signalling pathways that drive oncogenesis. The review encompasses a thorough examination of the molecular mechanisms underlying GSK3's involvement in cancer progression, shedding light on its interaction with critical pathways such as Wnt/ß-catenin, PI3K/AKT, and NF-κB. Through these interactions, GSK3 exerts influence over tumour growth, invasion, angiogenesis, and metastasis, rendering it an attractive target for therapeutic intervention. The discussion includes preclinical and clinical studies, showcasing the inhibitors efficacy across a spectrum of cancer types, including pancreatic, ovarian, lung, and other malignancies. Insights from recent studies highlight the potential synergistic effects of combining GSK3 inhibitors with conventional chemotherapeutic agents or targeted therapies, opening avenues for innovative combinatorial approaches. This review provides a comprehensive overview of the current state of research surrounding GSK3 inhibitors as promising agents for cancer treatment.


Asunto(s)
Glucógeno Sintasa Quinasa 3 , Neoplasias , Humanos , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , FN-kappa B/metabolismo
8.
Artículo en Inglés | MEDLINE | ID: mdl-36078507

RESUMEN

Cerebral palsy is a common motor disorder that results in long-term impairment. The purpose of this study was to find out what factors influence Saudi mothers' compliance with their Children with Cerebral Palsy (C-CP) Home Exercise Program (HEP). A self-administered online questionnaire was used to perform this qualitative research study on a group of 113 mothers who had children with CP. The study included mothers with children from birth to 12 years old who had received a HEP prescription from a physiotherapist. The measuring instrument tool was a questionnaire with two sections: demographic characteristics and a questionnaire about the parents' adherence to the HEP. The questionnaire utilized in this study was subjected to a reliability analysis, and the derived Cronbach's alpha was found to be 0.814 for the questionnaire (which had 17 phrases). These results imply that the questionnaire is reliable. A total of 113 responses were received, with 4 incomplete responses being eliminated. The majority of mothers (66.1%) did not follow the HEP, according to the findings of this survey. The demographics of the mothers revealed that 20-25-year-old mothers were more adherent than the other age groups. The findings of this study demonstrated that the physical therapist's treatment of the mother influenced exercise compliance.


Asunto(s)
Parálisis Cerebral , Adulto , Parálisis Cerebral/terapia , Niño , Terapia por Ejercicio , Femenino , Humanos , Madres , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Adulto Joven
9.
Artículo en Inglés | MEDLINE | ID: mdl-36078678

RESUMEN

Background: Children with Down Syndrome (C-DS) have language, cognitive and communication difficulties, in addition to consistent physical inactivity that contributes to poor health and higher-disability-adjusted life years. The purpose of this study was to determine the correlation between the use of electronic technology and levels of physical activity in C-DS in the Riyadh region of Saudi Arabia. Methods: A cross-sectional study was conducted with 49 mothers, where each had a child (6-12 years of age) with Down Syndrome (DS), and who were recruited using purposive sampling from three DS centers in Riyadh, Saudi Arabia. The Children's Physical Activity Questionnaire and Research Questionnaire on the Impact of Technology on Children were used. Descriptive statistics were used to describe the demographics. Pearson's correlation, Student's t-test and the Chi-square test were used to assess the association between technology use, physical activity levels and socio-demographic variables. Results: There was no significant correlation between physical activity and the use of technology by C-DS. However, there was a negative correlation between a high level of physical activity and technology use (R = -0.037). Although, no significant correlation between the mother's characteristics and technology use was found; there was a significantly positive correlation (p = 0.05) between the education level of mothers and the technology use by C-DS. Nonetheless, there was no association between the physical activity level and the gender of the child with DS. Conclusions: This study found that no significant relationship exists between the use of electronic gadgets and the level of physical activity in C-DS.


Asunto(s)
Síndrome de Down , Niño , Estudios Transversales , Síndrome de Down/epidemiología , Síndrome de Down/psicología , Ejercicio Físico , Femenino , Humanos , Madres/psicología , Tecnología
10.
Nutr Cancer ; 72(1): 170-181, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31088230

RESUMEN

Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and occurs frequently in patients with liver cirrhosis. HCC is the leading cause of cancer-related mortality around the globe.Aim: This study assessed the effects of thiamin in the anticancer activity of methotrexate (MTX) in diethyl nitrosamine (DEN) induced hepatocellular Carcinoma in Wistar strain male rats.Method: Fifty rats were randomly segregated in five groups with 10 rats in each group. HCC was induced by single intraperitoneal (i.p) dose of DEN (200 mg/kg) and HCC promoter phenobarbital was used in the basal diet (0.05%) for 5 days per week until the termination of the study in all the rats except for the normal control (NC) group. Disease control (DC) was given no treatment, while DM (DEN + MTX) and DT (DEN + thiamin) groups were given MTX (5 mg/kg, i.p per week for 16 weeks) and thiamin (25 mg/kg, orally, daily for 16 weeks), respectively. DMT (DEN + MTX + thiamin) group was given the combined dose of MTX and thiamin. Histopathological study was carried out to confirm the liver function tests such as α-feto protein (AFP), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TB), and total protein (TP) along with antioxidants vascular endothelial growth factor (VEGF), lipid per-oxidation (LPO), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT).Results: Results showed that liver biomarkers and antioxidants parameters were still abnormal in the DC group while DM group showed significant restoration, but DT group showed less significant normalization. DMT showed mild recovery of these parameters.Conclusion: The mechanism of action of MTX and thiamin is antiparallel to each other and hence their concomitant administration may lead to inefficient anticancer activity of MTX.


Asunto(s)
Alquilantes/toxicidad , Carcinoma Hepatocelular/tratamiento farmacológico , Dietilnitrosamina/toxicidad , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Metotrexato/farmacología , Estrés Oxidativo/efectos de los fármacos , Tiamina/farmacología , Animales , Antimetabolitos Antineoplásicos/farmacología , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/patología , Dieta/efectos adversos , Modelos Animales de Enfermedad , Quimioterapia Combinada , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Complejo Vitamínico B/farmacología
11.
Arch Physiol Biochem ; 125(3): 270-275, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29663832

RESUMEN

HCC has been reported to be immensely occurring carcinoma worldwide. Recent days the mortality occurred due to liver cancer has also been found to be increased at an alarming speed affecting mostly the young patients. The aim of the current study was to decipher the role of calcium and vitamin K3 in the treatment of chemically induced hepatocarcinogenesis in the male Wistar rats. Liver cancer was induced via a subnecrogenic dose of 160 mg/kg body weight, diethylnitrosamine (DENA) when associated with fasting/refeeding in male Wistar rats. It elevated the serum glutamate oxaloacetate (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), bilirubin, total cholesterol (CH), triglycerides (TG), alfa-fetoprotein (AFP) and reduced high-density lipoprotein (HDL). Histopathological examination of liver tissue showed marked carcinogenicity of the chemical carcinogen. Food, water intake and animal weights were also assessed, respectively. The animals exposed to DENA showed a significant decrease in the body weight. The elevated levels of serum SGOT, SGPT, ALP, AFP, TC and TG were restored by administration of calcium and Vit K (ad libitum) combination at higher dose than the normal dietary requirement (3 mg/kg) daily for 12 weeks p.o. Physiological and biochemical analysis showed the beneficial effects of calcium and vitamin K3 combination in the animals exposed to DENA. The results deciphered the beneficial effects of calcium and vitamin K3 in combination.


Asunto(s)
Biomarcadores/análisis , Calcio/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Vitamina K 3/uso terapéutico , Vitaminas/uso terapéutico , Alquilantes/toxicidad , Animales , Carcinoma Hepatocelular/inducido químicamente , Carcinoma Hepatocelular/patología , Caspasa 3/metabolismo , Dietilnitrosamina/toxicidad , Neoplasias Hepáticas Experimentales/inducido químicamente , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratas , Ratas Wistar
12.
Artif Cells Nanomed Biotechnol ; 46(sup1): 66-78, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29226729

RESUMEN

PURPOSE: The aim of the study to formulate and statistically optimize sitagliptin-loaded eudragit nanoparticles (SIT-NPs) and evaluate the in-vitro pharmaceutical quality and in-vivo anti-diabetic assessment. METHOD: SIT-NPs were prepared by using combination method of solvent evaporation and nano-precipitation techniques. The influence of different independent variables as eudragit RL100 concentration (%), tween 80 concentration (%) and sonication time (min) were evaluated on dependent variables like particle size (nm), drug loading (%) and in-vitro drug release (%). Further, the optimized formulation was evaluated for surface morphology, CLSM, ex-vivo permeation study and in-vivo anti-diabetic activity and stability study. RESULTS: The developed SIT-NPs formulations showed particle size range (135.86-193.45 nm), drug loading (6.36-8.76%) and prolonged drug release over 24 h. The prepared SIT-NPs were found to be nearly spherical with smooth surface. The comparative in-vitro release study and CLSM study results revealed that SIT-NPopt showed significantly (p < .05) enhanced release and permeation as compared to SIT free solution (SIT-Fs). The in-vivo anti-diabetic assessment revealed that SIT-NPopt able to reduce the blood sugar level (BSL) for a prolonged period of time. Further, the stability study data showed the formulations were found stable at both temperature and having the shelf life of 488 d. CONCLUSIONS: This research has shown that SIT-NPs based on experimental design offers a new and better approach to delivering SIT, thus encouraging further development of this formulation.


Asunto(s)
Composición de Medicamentos/métodos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Nanopartículas/química , Polímeros/química , Fosfato de Sitagliptina/química , Fosfato de Sitagliptina/farmacología , Administración Oral , Animales , Diabetes Mellitus/tratamiento farmacológico , Portadores de Fármacos/química , Liberación de Fármacos , Estudios de Factibilidad , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/uso terapéutico , Tamaño de la Partícula , Permeabilidad , Ratas , Ratas Wistar , Fosfato de Sitagliptina/administración & dosificación , Fosfato de Sitagliptina/uso terapéutico
13.
Biomed Pharmacother ; 97: 652-655, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29101809

RESUMEN

Evaluation of diphenhydramine in talc induced type 2 diabetes mellitus was done in Wistar rats. Oral administration of Talc (10mg/kg)carried out for 21days increased the levels of serum glutamate pyruvate transaminase (SGPT), glutamate oxaloacetate transaminase (SGOT), serum creatinine, blood glucose, urea, uric acid and triglycerides (TGs), but when the animals were treated with diphenhydramine (DPH), the levels of the aforementioned biochemical parameters decreased significantly (p<0.0001). The level of serum cholesterol and high density lipoprotein (HDL) was found to be reduced in Diabetes Mellitus (DM) control and when it was treated with DPH control animals, these makers increased significantly. The study done on DM and Diphenhydramine suggests that Talc increases the blood glucose level at a dose of 10mg/kg (0.14gm) and Diphenhydramine (1mg/kg)reduces the increased blood glucose level. These finding simply that diphenhydramine may be useful in the management of talc induced diabetes.


Asunto(s)
Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Difenhidramina/uso terapéutico , Talco/toxicidad , Animales , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Difenhidramina/farmacología , Evaluación Preclínica de Medicamentos/métodos , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar
14.
Mol Cell Biochem ; 444(1-2): 187-196, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29204817

RESUMEN

Hepatocellular carcinoma (HCC) is the fifth leading cause of death and is generally typified by elevated liver enzyme biomarkers, antioxidants, and chronic inflammation of hepatocytes. Although currently available drugs have shown remarkable alleviation of the cancerous condition, but at the same time they present a more severe challenge of toxic effects due to chemotherapy. Therefore, in order to bring more patient-compliant therapy, we aimed to refurbish the use of a COX inhibitor, oxyphenbutazone (OPB), with low dose of methotrexate (MTX) to treat diethyl nitrosamine (DENA)-induced HCC in Wistar rats and in Hep3B cells. Hep3B cells were subjected to assays like in vitro cytotoxicity, DNA synthesis, and caspase activity. The combination index was also evaluated, succeeding the cytotoxicity assay, to analyze the possible synergism. For in vivo study, Wistar strain male rats were given single intraperitoneal dose of DENA (200 mg/kg) and were supplied with sodium phenobarbital (0.1% in tap water) for promoting tumorigenesis throughout the study. MTX (2.5 and 5.0 mg/kg/week, ip) and OPB (70 mg/kg/week, po in two divided doses) were administered to the treatment groups from 3rd week till the termination of study. Several biochemical parameters including biomarkers of liver function, antioxidant enzymes, and histopathological examination of liver cells were tested. Significant synergism was witnessed in the cytotoxicity assay when Hep3B cells received varied dose combination treatment of MTX (0.25, 0.5, or 1.0 µmol/L) and OPB (2.5, 5.0, or 7.5 µmol/L). MTX (0.5 and 1.0 µmol/L) in combination with OPB (5.0 or 7.5 µmol/L) inhibited the cell proliferation as BrdU incorporation was quite low in DNA synthesis analysis, as well as caspase-9/-3 cascade was activated which led to apoptosis of cancer cells. Co-treatment with MTX and OPB exerted potential anticancer activity in rats than either of the drugs alone. Administration of combination therapy harmonized the DENA-induced elevation of serum biochemical parameters, including but not limited to, α-fetoprotein (AFP), alanine- and aspartate-aminotransferase, alkaline phosphatase, vascular endothelial growth factor (VEGF), and antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and lipid per oxidation (LPO). All these results were optimally substantiated by histopathological examination. As evident COX-2 catalyzes the synthesis of PGE2, needed in the activation of Wnt/ß-catenin pathway, which in turn is responsible for activating the transcriptional proteins required for higher degree of cell division and thence growth. Therefore, inhibition of COX-2 by our novel combination infers that even low doses of MTX can elucidate noticeable anticancer activity when paired with OPB.


Asunto(s)
Citotoxinas/farmacología , Dinoprostona/metabolismo , Oxifenilbutazona/farmacología , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismo , Animales , Línea Celular Tumoral , Humanos , Masculino , Ratas , Ratas Wistar
15.
Arch Biochem Biophys ; 623-624: 58-63, 2017 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-28501584

RESUMEN

Present study, was an effort to scrutinize the molecular and biochemical role of ibuprofen and thiamine combination in diethylnitrosamine (DEN)-induced HCC in Wistar rats. Single intraperitoneal injection of DEN (200 mg/kg) was used for induction of HCC in rats. The rats were divided into eight various groups. DEN induced rats were treated with pure ibuprofen (40 mg/kg) and thiamine in combination for the period of 12th weeks. The protocol was terminated after the 16th week. Exposure of DEN up-regulated the levels of different serum biochemical parameters, antioxidant enzyme level, Alfa-fetoprotein (AFP) and reduced the level of High density lipoprotein (HDL) in Wistar rats along with the alteration in pro-inflammatory cytokines viz., interlukin-6 (IL-6), Tumor necrosis factor (TNF-α) and Interleukin-1ß (IL-1ß) with decrease in body weight. Macroscopic evaluation, revealed DEN group rats confirmed the expansion of hepatic nodules, which were reduced by the individual treatment of ibuprofen and thiamine, but the synergistic treatment of ibuprofen and thiamine confirm the significant reduction of hepatic nodules. Further, this combination possesses the significant chemoprotective effect in DEN-induced HCC by restoring the hepatic enzymes and other biomarkers along with an alteration in pro-inflammatory cytokines. The above result concludes that ibuprofen and thiamine combination possess potent anti-cancerous activity.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Anticarcinógenos/uso terapéutico , Ibuprofeno/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Hígado/efectos de los fármacos , Tiamina/uso terapéutico , Complejo Vitamínico B/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/farmacología , Anticarcinógenos/farmacología , Citocinas/análisis , Dietilnitrosamina , Sinergismo Farmacológico , Ibuprofeno/farmacología , Interleucina-1beta/análisis , Hígado/patología , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Tiamina/farmacología , Complejo Vitamínico B/farmacología
16.
Curr Pharm Des ; 22(28): 4420-4429, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27356778

RESUMEN

Methicillin-Resistant Staphylococcus aureus (MRSA) is a Gram-positive bacterium which causes community and hospital-acquired infections. Synthetic drug/antibiotic treatment for MRSA-related infections is becoming less effective and natural products may be an emerging new alternative for future antibacterial drug development. Alkaloids are a class of natural compounds which are known for their phytochemistry and pharmacology. This review focuses on 32 alkaloids isolated from various plants that showed marked antibacterial activity against MRSA by acting through different mechanisms such as inhibition of pyruvate kinase, Quorum quenching effect, alteration in efflux pump in MRSA and intercalating of bacterial DNA, to name just a few. In addition, the use of recent plant alkaloids against clinical isolates of MRSA has also been discussed.

17.
J Pharm Bioallied Sci ; 6(3): 180-4, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25035637

RESUMEN

INTRODUCTION: Rabeprazole, a member of substituted benzimidazoles, inhibits the final step in gastric acid secretions. This drug claims to cause fastest acid separation (due to higher pKa), and more rapidly converts to the active species to aid gastric mucin synthesis. The most significant pharmacological action of Rabeprazole is dose dependent suppression of gastric acid secretion; without anticholinergic or H2-blocking action. It completely abolishes the hydrochloric acid secretion as it is powerful inhibitor of gastric acid. Rabeprazole is acid labile and hence commonly formulated as an enteric coated tablet. The absorption of rabeprazole occurs rapidly as soon as tablet leaves the stomach. AIM: In the present study an attempt was made to formulate and evaluate Rabeprazole sustained release matrix tablet using wet granulation technique incorporating various polymers like HPMC-E15, Carbopol934, and sodium carboxymethyl cellulose (CMC). MATERIALS AND METHODS: The Formulated tablets were evaluated for different physicochemical properties like rheological properties, weight variation, thickness, hardness, % friability, in vitro release studies and drug content. RESULTS: Studies revealed that all the physicochemical parameters comply with the official standards. The in vitro release studies exhibits the release up to 90%, over a prolonged period of time which confirms the extended release profile of formulation, having better bioavailability as well as decreased dosing frequency with reduced doses. CONCLUSION: The sustained release matrix tablets of rabiprazole shown better bioavailability, efficacy and potency, when compared with official standards.

18.
Mol Cell Biochem ; 384(1-2): 279-85, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24052147

RESUMEN

Sulfonamides have been reported to possess substantial antitumor activity as they act as carbonic anhydrase inhibitors. In addition, selenium appears to have a protective effect at various stages of cancer due to its antioxidant property, enhanced carcinogen detoxification, inhibition of cell invasion, and by inhibiting angiogenesis. Here, in the present study we aimed to evaluate and synergize the cytotoxic activity of sulfonamide and selenium (SM+SE) as effective therapy in the treatment of DENA-induced HCC. Hepatocarcinogeneis was induced by a single intraperitoneal injection of diethylnitrosamine (DENA) (200 mg/kg) in phosphate buffer. 30 Male Wistar rats used in this study were divided randomly into five equal groups (n = 6). DENA-administered animals showed significant alteration (p < 0.001) in liver-specific enzymes-glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), and Alpha fetoproteins (AFP), and also induced severe histopathological changes in the hepatic tissues. Interestingly, treatment with (SE+SE) (SM 30 mg/kg + SE 3 mg/kg) significantly reduced (P < 0.001, P < 0.001, P < 0.001, P < 0.001) the elevated AFP, SGOT, SGPT, and ALP levels, respectively, suggesting that combination therapy of SM+SE has a potential to treat DENA-induced liver damage.


Asunto(s)
Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Selenio/uso terapéutico , Sulfametoxazol/uso terapéutico , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Antiinfecciosos/uso terapéutico , Antioxidantes/uso terapéutico , Aspartato Aminotransferasas/metabolismo , Bilirrubina/sangre , Glucemia , Quimioprevención , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Invasividad Neoplásica , Neovascularización Patológica/tratamiento farmacológico , Ratas , Ratas Wistar , alfa-Fetoproteínas/metabolismo
19.
Arch Gynecol Obstet ; 288(4): 747-57, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23793551

RESUMEN

PURPOSE: Ectopic pregnancy (EP) presents a major health problem for women of child-bearing age. EP refers to the pregnancy occurring outside the uterine cavity that constitutes 1.2-1.4 % of all reported pregnancies. All identified risk factors are maternal: pelvic inflammatory disease, Chlamydia trachomatis infection, smoking, tubal surgery, induced conception cycle, and endometriosis. These developments have provided the atmosphere for trials using methotrexate as a non-surgical treatment for EP. The diagnosis measure of EP is serum human chorionic gonadotropin, urinary hCGRP/i-hCG, progesterone measurement, transvaginal ultrasound scan, computed tomography, vascular endothelial growth factor, CK, disintegrin and metalloprotease-12 and hysterosalpingography. The treatment option of EP involves surgical treatment by laparotomy or laparoscopy, medical treatment is usually systemic or through local route, or by expectant treatment. RESULTS: It was concluded that review data reflect a decrease in surgical treatment and not an actual decline in EP occurrence so that further new avenues are needed to explore early detection of the EP.


Asunto(s)
Embarazo Ectópico , Abortivos no Esteroideos/uso terapéutico , Femenino , Humanos , Laparoscopía , Metotrexato/uso terapéutico , Embarazo , Embarazo Ectópico/diagnóstico , Embarazo Ectópico/etiología , Embarazo Ectópico/terapia , Factores de Riesgo , Salpingectomía , Salpingostomía , Espera Vigilante
20.
Mol Cell Biochem ; 378(1-2): 275-81, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23512523

RESUMEN

The present study was designed to evaluate the hepatoprotective effects of newly isolated stigmast-4, 20 (21), 23-trien-3-one (STO) against carbon tetrachloride-induced hepatic injury in Wistar albino rats. Hepatotoxicity was induced by the administration of a single intraperitoneal dose of CCl4 (0.5 mL/kg CCl4 in olive oil) in experimental rats. Three different doses (2.5, 5.0, and 10 mg/kg, p.o) of STO was administered to the test groups during whole experimental protocol. Changes in the activity of serum ALT, AST, ALP, TB, and TP, anti-oxidant enzymes like SOD, CAT, GPx, GST, and LPO were studied in CCl4-induced hepatocellular carcinogenesis. The altered levels of serum ALT, AST, ALP, TB, and TP restored toward normalization significantly by STO in a dose dependant manner. The biochemical observations were supplemented with histopathological examination of rat liver sections. Meanwhile, it also produced a significant and dose-dependent reversal of CCl4-diminished activity of anti-oxidant enzymes like SOD, CAT, GPx, GST, and the reduced CCl4-elevated level of LPO. STO significantly prevented the increased levels of serum markers, also suppressed the free radical processes by scavenging hydroxyl radicals. It also modulates the levels of LPO and markedly increases the endogenous anti-oxidant enzymes level in CCl4-induced hepatic injury.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Estigmasterol/análogos & derivados , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Biomarcadores/sangre , Tetracloruro de Carbono , Catalasa/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Evaluación Preclínica de Medicamentos , Glutatión Peroxidasa/sangre , Glutatión Transferasa/sangre , Hígado/efectos de los fármacos , Hígado/patología , Ratas , Ratas Wistar , Estigmasterol/farmacología , Estigmasterol/uso terapéutico , Superóxido Dismutasa/sangre
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