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Objective: The objective of this study was to investigate the impact of Gestational Yoga-YOGESTA (Gestational Yoga), on the neuropsychology, quality of life, and personality of pregnant women. Design: Open label, randomized controlled trial, used allocation concealment to allocate the treatment. Setting: Department of Obstetrics and Gynecology and Neuroscience Research Lab, Department of Neurology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. Participants: We recruited a total of 100 pregnant women visiting the Outpatient Department of Obstetrics and Gynecology. Participants were aged between 18 and 35 with uncomplicated pregnancies and they were randomly assigned to either the Yoga group (YG) or the usual care group (UCG). A total of 77 pregnant women completed both the pre- and post-survey, with 34 participants in the Yoga group and 43 in the Usual care group. Intervention: Pregnant women in their second and third trimesters were provided with a 16-week online Prenatal Yoga intervention. The intervention began after enrollment in the 2nd trimester, specifically between the 16th and 20th week, and was conducted 5 days a week until delivery, with an average intervention period of 47.18 ± 2.031 (mean ± SEM) days. Chief outcome measures: We measured Perceived stress, Depression, Anxiety, Stress, and quality of life by using standard questionnaires. Results: A total of 77 participants were included in the analysis, with 34 assigned to the Yoga group and 43 assigned to the control group. Most of the measured parameters demonstrated significant changes. The Yoga group exhibited a noteworthy decrease in perceived stress, depression, anxiety, and psychological stress, as well as an improvement in the psychological and environmental domains of QOL-BREF. Conversely, the control group demonstrated a significant increase in perceived stress, depression, anxiety, and psychological stress, along with a reduction in the physical, psychological, and social domains of QOL-BREF at the follow-up stage. Although the two groups were similar at baseline, the Yoga group showed substantial enhancements in perceived stress, depression, anxiety, physiological stress, and overall quality of life when compared to the control group at follow-up. Conclusion: The study's findings indicate that stress, anxiety, and depression are more likely to occur as gestational age progresses during pregnancy. Nevertheless, practicing Prenatal Yoga can effectively manage these changes and enhance the quality of life for expectant mothers.Clinical trial registration: Clinical Trials Registry-India, Identifier CTRI/2021/01/030827.
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Calidad de Vida , Yoga , Embarazo , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Mujeres Embarazadas , Ansiedad , Trastornos de AnsiedadRESUMEN
Uranyl ions U(VI), are the common by-product of nuclear power plants and anthropogenic activities like mining, excess utilization of fertilizers, oil industries, etc. Its intake into the body causes serious health concerns such as liver toxicity, brain damage, DNA damage and reproductive issues. Therefore, there is urgent need to develop the detection and remediation strategies. Nanomaterials (NMs), due to their unique physiochemical properties including very high specific area, tiny sizes, quantum effects, high chemical reactivity and selectivity have become emerging materials for the detection and remediation of these radioactive wastes. Therefore, the current study aims to provide a holistic view and investigation of these new emerging NMs that are effective for the detection and removal of Uranium including metal nanoparticles, carbon-based NMs, nanosized metal oxides, metal sulfides, metal-organic frameworks, cellulose NMs, metal carbides/nitrides, and carbon dots (CDs). Along with this, the production status, and its contamination data in food, water, and soil samples all across the world are also complied in this work.
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Nanopartículas del Metal , Nanoestructuras , Uranio , Nanopartículas del Metal/química , Carbono , ÓxidosRESUMEN
Cancer is a major global public health concern that affects both industrialized and developing nations. Current cancer chemotherapeutic options are limited by side effects, but plant-derived alternatives and their derivatives offer the possibilities of enhanced treatment response and reduced side effects. A plethora of recently published articles have focused on treatments based on cannabinoids and cannabinoid analogs and reported that they positively affect healthy cell growth and reverse cancer-related abnormalities by targeting aberrant tumor microenvironments (TMEs), lowering tumorigenesis, preventing metastasis, and/or boosting the effectiveness of chemotherapy and radiotherapy. Furthermore, TME modulating systems are receiving much interest in the cancer immunotherapy field because it has been shown that TMEs have significant impacts on tumor progression, angiogenesis, invasion, migration, epithelial to mesenchymal transition, metastasis and development of drug resistance. Here, we have reviewed the effective role of cannabinoids, their analogs and cannabinoid nano formulations on the cellular components of TME (endothelial cells, pericytes, fibroblast and immune cells) and how efficiently it retards the progression of carcinogenesis is discussed. The article summarizes the existing research on the molecular mechanisms of cannabinoids regulation of the TME and finally highlights the human studies on cannabinoids' active interventional clinical trials. The conclusion outlines the need for future research involving clinical trials of cannabinoids to demonstrate their efficacy and activity as a treatment/prevention for various types of human malignancies.
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Cannabinoides , Neoplasias , Humanos , Cannabinoides/farmacología , Células Endoteliales , Transición Epitelial-Mesenquimal , Neoplasias/tratamiento farmacológico , Microambiente Tumoral , Ensayos Clínicos como AsuntoRESUMEN
Background: Regulated breathing facilitates ventilation and reduces breathlessness. However, the effect of Yogic breathing on patients with COVID remains unclear. We aimed to evaluate the efficacy of two breathing protocols, i.e., short breathing technique (SBT) and long duration breathing technique (LBDT). Methods: Three groups including COVID-positive patients, COVID-recovered patients, and healthcare workers (HCWs) were included in the study and segregated into Yoga and control groups. SBT was administered to COVID-positive patients. Both SBT and LBDT were administered to COVID-recovered patients and HCWs. A total of 18 biochemical parameters, a 6-min walk test (6MWT), and a 1-min sit-stand test (1MSST) were assessed on 0th, 7th, and 15th days, where biochemical parameters were the primary outcome. Pre-post estimation of neuropsychological parameters (nine questionnaires) and heart rate variability (HRV) were carried out. The paired t-test or Wilcoxon rank test was applied for pre-post comparison and the Student's t-test or Mann-Whitney U test was used for group comparison. Repeated measures test was applied for data recorded at three time points. Results: A significant elevation in white blood cell (WBC) count was observed in COVID-positive intervention (p < 0.001) and control groups (p = 0.003), indicating no role of intervention on change in WBC number. WBC count (p = 0.002) and D-dimer (p = 0.002) significantly decreased in the COVID-recovered intervention group. D-dimer was also reduced in HCWs practicing Yogic breathing as compared to controls (p = 0.01). D-dimer was the primary outcome, which remained below 0.50 µg/ml (a cutoff value to define severity) in the COVID-positive yoga group (CYG) and decreased in the COVID-recovered yoga group (RYG) and the HCW yoga group (HYG) after intervention. A 6-min walk test (6MWT) showed an increase in distance covered among the COVID-positive patients (p = 0.01) and HCWs (p = 0.002) after intervention. The high-frequency power (p = 0.01) was found to be reduced in the COVID-positive intervention group. No significant change in neuropsychological parameters was observed. Conclusion: Yogic breathing lowered D-dimer, which is helpful in reducing thrombosis and venous thromboembolism in patients with COVID-19 besides lowering the chances of vaccine-induced thrombotic thrombocytopenia in vaccinated individuals. The breathing intervention improved exercise capacity in mild to moderate cases of COVID-19. Further studies can show if such breathing techniques can influence immunity-related genes, as reported recently in a study. We suggest that Yogic breathing may be considered an integrative approach for the management of patients with COVID. Trial registration: http://ctri.nic.in/Clinicaltrials/login.php, identifier: CTRI/2020/10/028195.
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COVID-19 , Yoga , Personal de Salud , Frecuencia Cardíaca/fisiología , Humanos , PulmónRESUMEN
Conventional agricultural practices rely heavily on chemical fertilizers to boost production. Among the fertilizers, phosphatic fertilizers are copiously used to ameliorate low-phosphate availability in the soil. However, phosphorus-use efficiency (PUE) for major cereals, including maize, is less than 30%; resulting in more than half of the applied phosphate being lost to the environment. Rock phosphate reserves are finite and predicted to exhaust in near future with the current rate of consumption. Thus, the dependence of modern agriculture on phosphatic fertilizers poses major food security and sustainability challenges. Strategies to optimize and improve PUE, like genetic interventions to develop high PUE cultivars, could have a major impact in this area. Here, we present the current understanding and recent advances in the biological phenomenon of phosphate uptake, translocation, and adaptive responses of plants under phosphate deficiency, with special reference to maize. Maize is one of the most important cereal crops that is cultivated globally under diverse agro-climatic conditions. It is an industrial, feed and food crop with multifarious uses and a fast-rising global demand and consumption. The interesting aspects of diversity in the root system architecture traits, the interplay between signaling pathways contributing to PUE, and an in-depth discussion on promising candidate genes for improving PUE in maize are elaborated.
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Fósforo , Zea mays , Fósforo/metabolismo , Zea mays/genética , Zea mays/metabolismo , Fertilizantes , Productos Agrícolas/genética , Agricultura/métodos , Suelo/química , FosfatosRESUMEN
Pectin is a complex form of polysaccharide and is composed of several structural components that require the concerted action of several pectinases for its complete degradation. In this study, in silico and solution structure of a pectin acetyl esterase (CtPae12B) of family 12 carbohydrate esterase (CE12) from Clostridium thermocellum was determined. The CtPae12B modelled structure, showed a new α/ß hydrolase fold, similar to the fold found in the crystal structures of its nearest homologues from CE12 family, which differed from α/ß hydrolase fold found in glycoside hydrolases. In the active site of CtPae12B, two loops (loop1 and loop6) play an important role in the formation of a catalytic triad Ser15-Asp187-His190, where Ser15 acts as a nucleophile. The structural stability of CtPae12B and its catalytic site was detected by performing molecular dynamic (MD) simulation which showed stable and compact conformation of the structure. Molecular docking method was employed to analyse the conformations of various suitable ligands docked at the active site of CtPae12B. The stability and structural specificity of the catalytic residues with the ligand, 4-nitrophenyl acetate (4-NPA) was confirmed by MD simulation of CtPae12B-4NPA docked complex. Moreover, it was found that the nucleophile Ser15, forms hydrophobic interaction with 4-NPA in the active site to complete covalent catalysis. Small angle X-ray scattering analysis of CtPae12B at 3 mg/mL displayed elongated, compact and monodispersed nature in solution. The ab initio derived dummy model showed that CtPae12B exists as a homotrimer at 3 mg/mL which was also confirmed by dynamic light scattering.Communicated by Ramaswamy H. Sarma.
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Clostridium thermocellum , Clostridium thermocellum/química , Cristalografía por Rayos X , Esterasas , Glicósido Hidrolasas , Ligandos , Simulación del Acoplamiento Molecular , Pectinas , Dispersión del Ángulo Pequeño , Especificidad por Sustrato , Difracción de Rayos XRESUMEN
Membrane formation and aggregation properties of two series of (±) α-tocopherol-based cationic gemini lipids without and with hydroxyl functionalities at the headgroup region (TnS n = 3, 4, 5, 6, 8, and 12; THnS n = 4, 5, 6, 8, and 12) with varying polymethylene spacer lengths were investigated extensively while comparing with the corresponding properties of the monomeric counterparts (TM and THM). Liposomal suspensions of each cationic lipid were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential measurements, and small-angle X-ray diffraction studies. The length of the spacer and the presence of hydroxyl functionalities at the headgroup region strongly contribute to the aggregation behavior of these gemini lipids in water. The interaction of each tocopherol lipid with a model phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC)-derived vesicles, was thoroughly examined by differential scanning calorimetry (DSC) and 1,6-diphenyl-1,3,5-hexatriene (DPH)-doped fluorescence anisotropy measurements. The binding efficiency of the cationic tocopherol liposomes with plasmid DNA (pDNA) was followed by an ethidium bromide (EB) exclusion assay and zeta potential measurements, whereas negatively charged micellar sodium dodecyl sulfate (SDS)-mediated release of the pDNA from various preformed pDNA-liposomal complexes (lipoplex) was studied by an ethidium bromide (EB) reintercalation assay. The structural transformation of pDNA upon complexation with liposome was characterized using circular dichroism (CD) spectroscopic measurements. Gemini lipid-pDNA interactions depend on both the presence of hydroxyl functionalities at the headgroups and the length of the spacer chain between the headgroups. Succinctly, we performed a detailed physical-chemical characterization of the membranes formed from cationic monomeric and gemini lipids bearing tocopherol as their hydrophobic backbone and describe the role of inserting the -OH group at the headgroup of such lipids.
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Liposomas , alfa-Tocoferol , Cationes , ADN , Lecitinas , Fosfolípidos , Plásmidos , TransfecciónRESUMEN
INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a common pediatric, neurodevelopmental disorder, with serious impacts on lives of those suffering from it. ADHD is known to be associated with social and emotional difficulties, poor self-regulation, aggression, reduced empathy, inability to regulate socially desirable behavior along with conflicts within family, and increased conflict with peers and several associated comorbid conditions. AIM: The study aims at exploring quality of life (QOL) and adjustment along with associated comorbid conditions in children diagnosed with ADHD in comparison with normal children. METHODS: A total sample of 60 children including 30 children diagnosed with ADHD and 30 normal children were selected and assessed using Vanderbilt ADHD Parent rating scale Childhood Psychopathology Measurement Schedule, KINDL QOL: Parent Questionnaire and Pre-Adolescent adjustment Scale to assess level of ADHD, comorbid psychopathologies, their QOL and adjustment respectively. RESULTS: Overall results have indicated that parents reported lesser symptom and pathology in comparisons to teachers for ADHD. Those diagnosed with ADHD had positive and significant comorbidities associated of; low intelligence with behavioral problems and high levels of conduct problems, anxiety, depression, psychotic tendencies, physical illness with emotional problems and somatization in comparison to normal and thus a poor adjusted life, with significant report of poor self-esteem and peer relations and QOL. CONCLUSION: The results of the present study has clearly stated that severe burden has been perceived by ADHD children, with a poor perceived QOL, several adjustment issues, and sufferance of one or other comorbidity. Thus, the study could help understand and emphasize the need of holistic treatment comprising medicinal and therapeutic methods, including intervention for parents, focusing exclusively on enhancing and curbing these factors.
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Continuing efforts to develop stimuli-responsive polymers (SRPs) as novel smart materials/biomaterials are anticipated to upgrade the quality life of humans. The details of the molecular, physico chemical and biophysical interactions between SRPs and proteins are not fully understood. Indeed, protein - polymer interactions play a major role in a wide range of biomedical/biomaterial applications. In this regard, we have demonstrated the influence of proteins (ß-lactoglobulin (BLG) and stem bromelain (BM) as biological stimuli) on the phase transition behavior of biomedical thermoresponsive poly(N-isopropylacrylamide) (PNIPAM). In order to predict these, we have used a set of biophysical techniques to unveil the influence of biological stimuli on the phase transition behavior of PNIPAM. Absorption spectroscopy, steady-state fluorescence spectroscopy, Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM) were operated at room temperature to examine the changes in absorbance, fluorescence intensity, molecular interactions and surface morphologies, respectively. Furthermore, temperature dependent fluorescence spectroscopy and dynamic light scattering (DLS) studies were also performed to analyze conformational changes, agglomeration behavior, particle size, coil to globule transition and phase behavior. The significant variations obtained in the phase transition temperature values, conformational changes and agglomeration behavior clearly reflects the different molecular interplay induced in presence of biological stimuli. The results demonstrated that the added proteins act as biological stimuli via preferential interactions between the amide group of the polymer and water molecules. The present study can be useful for the design and development of the next generation smart responsive materials/biomaterials.
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Polímeros/química , Bromelaínas/química , Dispersión Dinámica de Luz , Lactoglobulinas/química , Microscopía Electroquímica de Rastreo , Transición de Fase , Espectroscopía Infrarroja por Transformada de Fourier , Temperatura , Temperatura de TransiciónRESUMEN
Cephalandole A 2, a small indole alkaloid isolated from the Taiwanese orchid Cephalanceropsis gracilis (Orchidaceae), exhibits anticancer activity. Surprisingly, this natural product has not been evaluated for any other biological activity so far. To discover other novel potential of Cephalandole A 2, an efficient and economic synthetic protocol for novel Cephalandole A analogues 21a-o has been developed, in only 3 steps from using indole, and applied for their biological activity. Biological testing showed that Cephalandole A 2 and its novel analogues 21a-o exhibited potential antimicrobial and antiplatelet activity in preliminary assay. To the best of our knowledge, this is the first report of Cephalandole A 2 and its novel synthetic analogues 21a-o as a new class of antimicrobial and antiplatelet agents. In this study, 2 and other analogues i.e., 21b, 21d, 21i and 21o showed promising antimicrobial activity against the phytopathogenic bacteria and fungi. Cephalandole A 2, 21c, 21f and 21i, also showed potent antiplatelet activity.
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Antiinfecciosos/farmacología , Benzoxazinas/farmacología , Indoles/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Animales , Benzoxazinas/síntesis química , Indoles/síntesis química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , ConejosRESUMEN
This study examines the spatio-temporal trends obtained from decade long (Jan 2003-Dec 2014) satellite observational data of Atmospheric Infrared Sounder (AIRS) and Measurements of Pollution in the Troposphere (MOPITT) on carbon monoxide (CO) concentration over the Indo-Gangetic Plains (IGP) region. The time sequence plots of columnar CO levels over the western, central and eastern IGP regions reveal marked seasonal behaviour, with lowest CO levels occurring during the monsoon months and the highest CO levels occurring during the pre-monsoon period. A negative correlation between CO levels and rainfall is observed. CO vertical profiles show relatively high values in the upper troposphere at â¼200 hPa level during the monsoon months, thus suggesting the role of convective transport and advection in addition to washout behind the decreased CO levels during this period. MOPITT and AIRS observations show a decreasing trend of 9.6 × 1015 and 1.5 × 1016 molecules cm-2 yr-1, respectively, in columnar CO levels over the IGP region. The results show the existence of a spatial gradient in CO from the eastern (higher levels) to western IGP region (lower levels). Data from the Census of India on the number of households using various cooking fuels in the IGP region shows the prevalence of biomass-fuel (i.e. firewood, crop residue, cowdung etc.) use over the eastern and central IGP regions and that of liquefied petroleum gas over the western IGP region. CO emission estimates from cooking activity over the three IGP regions are found to be in the order east > central > west, which support the existence of the spatial gradient in CO from eastern to the western IGP region. Our results support the intervention of present Indian government on limiting the use of biomass-fuels in domestic cooking to achieve the benefits in terms of the better air quality, household health and regional/global climate change mitigation.
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Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Monóxido de Carbono/análisis , Clima , Culinaria , Monitoreo del Ambiente/métodos , Petróleo/análisis , Estaciones del Año , Biomasa , IndiaRESUMEN
Metoprolol succinate is a very potent drug for the treatment of hypertension but suffers from poor bioavailability due to its erratic absorption in lower GI tract. Therefore, in the present study, it was hypothesized that by formulating mucoadhesive particles, the residence time in the GIT and release of drug may be prolonged that will enhance the bioavailability of metoprolol succinate. Metoprolol succinate loaded chitosan microparticles were prepared by ionic gelation method. The optimized microparticles were coated with sodium alginate to form a layer over chitosan microparticles to increase the mucoadhesive strength and to release the drug in controlled manner. Coated and uncoated microparticles were evaluated for particle size, zeta potential, morphology, entrapment efficiency, drug loading and in vitro drug release. The coated microparticles showed comparatively less drug release in the 0.1 N HCl while sustained release in PBS (pH 6.8) as compared to uncoated microparticles. The in vivo study on albino rats demonstrated an increase in bioavailability of the coated microparticles as compared to marketed formulation. From the study it can be concluded that alginate coated chitosan microparticles could be a useful carrier for the oral delivery of metoprolol succinate.
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Alginatos , Portadores de Fármacos , Metoprolol , Alginatos/química , Alginatos/farmacocinética , Alginatos/farmacología , Animales , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Evaluación Preclínica de Medicamentos , Ácido Glucurónico/química , Ácido Glucurónico/farmacocinética , Ácido Glucurónico/farmacología , Ácidos Hexurónicos/química , Ácidos Hexurónicos/farmacocinética , Ácidos Hexurónicos/farmacología , Masculino , Metoprolol/química , Metoprolol/farmacocinética , Metoprolol/farmacología , Ratas , Ratas WistarRESUMEN
Cell-permeable small molecules that enhance the stability of the G-quadruplex (G4) DNA structures are currently among the most intensively pursued ligands for inhibition of the telomerase activity. Herein we report the design and syntheses of four novel benzimidazole-carbazole conjugates and demonstrate their high binding affinity to G4 DNA. S1 nuclease assay confirmed the ligand mediated G-quadruplex DNA protection. Additional evidence from Telomeric Repeat Amplification Protocol (TRAP-LIG) assay demonstrated efficient telomerase inhibition activity by the ligands. Two of the ligands showed IC50 values in the sub-micromolar range in the TRAP-LIG assay, which are the best among the benzimidazole derivatives reported so far. The ligands also exhibited cancer cell selective nuclear internalization, nuclear condensation, fragmentation, and eventually antiproliferative activity in long-term cell viability assays. Annexin V-FITC/PI staining assays confirm that the cell death induced by the ligands follows an apoptotic pathway. An insight into the mode of ligand binding was obtained from the molecular dynamics simulations.
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Bencimidazoles/química , Carbazoles/química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Neoplasias/tratamiento farmacológico , Telomerasa/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Técnicas de Química Sintética , Dicroismo Circular , Diseño de Fármacos , Evaluación Preclínica de Medicamentos/métodos , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , G-Cuádruplex , Humanos , Concentración 50 Inhibidora , Ligandos , Simulación de Dinámica Molecular , Estructura Molecular , Neoplasias/genética , Neoplasias/patología , Espectrometría de Fluorescencia , Telómero/genéticaRESUMEN
Oral mucositis is one of the major side effects of cancer chemotherapy (30-76%) and radiotherapy (over 50%). Current palliative treatments of oral mucositis include specialized agents like pelifermin, platelet derived factors etc. or oral hygienic agents which suffered from various drawbacks like systemic side effect, least effect owing to fast wash out of buccal mucosa, patient unfriendly delivery systems, and mere symptomatic relief. In this research work, N-succinyl chitosan gel delivery system of microemulsified eugenol, honey and sodium hyaluronate was prepared to explore their multiple and synergistic effects on various pathological factors of oral mucositis. N-succinyl chitosan was synthesized in our laboratory and loaded with microemulsified eugenol (10% v/v), honey (10% v/v) and sodium hyaluronate (0.2% w/v) to prepare orogel with optimum pH, spreadability, mucoadhesion strength, and viscosity. In vitro eugenol release from N-succinyl chitosan gel after 8 hours in PBS (pH-6.4) was found to be 87.45±0.14%, which was better in comparison to that released from chitosan gel. Ex vivo penetration studies using rat buccal mucosal tissue also suggested better J-efflux of eugenol through N-succinyl chitosan in comparison to chitosan gel with enhancement ratio (ER) of 1.71. The antimicrobial effect of N-succinyl chitosan based orogel against S. aureus and C. albicans efficacy was found to be statistically high in comparison to chitosan based orogel as well as marketed formulation of chlorhexidine (p<0.05). The N-succinyl chitosan orogel in 5-fluoro uracil induced oral mucositis animal (Wistar rats) model showed enhanced survival ratio, weight gain and high tissue regeneration activity than chitosan gel formulation within 15 days. The formulation was successful in elevating the survival and reducing the inflammation in the oral mucosa of animals compared to disease control (p<0.05) and hence suggesting the potential of N-succinyl chitosan orogel in the treatment of oral mucositis.
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Quitosano/química , Sistemas de Liberación de Medicamentos , Eugenol/química , Miel , Ácido Hialurónico/química , Mucosa Bucal/metabolismo , Animales , Quitosano/administración & dosificación , Eugenol/administración & dosificación , Geles , Ácido Hialurónico/administración & dosificación , Técnicas In Vitro , Absorción por la Mucosa Oral , Ratas Wistar , Estomatitis/tratamiento farmacológico , PorcinosRESUMEN
BACKGROUND: The secretory proteins of Mycobacterium tuberculosis (M. tuberculosis) have been known to be involved in the virulence, pathogenesis as well as proliferation of the pathogen. Among this set, many proteins have been hypothesized to play a critical role at the genesis of the onset of infection, the primary site of which is invariably the human lung. METHODOLOGY/PRINCIPAL FINDINGS: During our efforts to isolate potential binding partners of key secretory proteins of M. tuberculosis from a human lung protein library, we isolated peptides that strongly bound the virulence determinant protein Esat6. All peptides were less than fifty amino acids in length and the binding was confirmed by in vivo as well as in vitro studies. Curiously, we found all three binders to be unusually rich in phenylalanine, with one of the three peptides a short fragment of the human cytochrome c oxidase-3 (Cox-3). The most accessible of the three binders, named Hcl1, was shown also to bind to the Mycobacterium smegmatis (M. smegmatis) Esat6 homologue. Expression of hcl1 in M. tuberculosis H37Rv led to considerable reduction in growth. Microarray analysis showed that Hcl1 affects a host of key cellular pathways in M. tuberculosis. In a macrophage infection model, the sets expressing hcl1 were shown to clear off M. tuberculosis in much greater numbers than those infected macrophages wherein the M. tuberculosis was not expressing the peptide. Transmission electron microscopy studies of hcl1 expressing M. tuberculosis showed prominent expulsion of cellular material into the matrix, hinting at cell wall damage. CONCLUSIONS/SIGNIFICANCE: While the debilitating effects of Hcl1 on M. tuberculosis are unrelated and not because of the peptide's binding to Esat6-as the latter is not an essential protein of M. tuberculosis-nonetheless, further studies with this peptide, as well as a closer inspection of the microarray data may shed important light on the suitability of such small phenylalanine-rich peptides as potential drug-like molecules against this pathogen.
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Antígenos Bacterianos/química , Proteínas Bacterianas/química , Pulmón/microbiología , Mycobacterium tuberculosis/patogenicidad , Péptidos/química , Fenilalanina/química , Clonación Molecular , ADN Complementario/metabolismo , Complejo IV de Transporte de Electrones/química , Perfilación de la Expresión Génica , Biblioteca de Genes , Vectores Genéticos , Humanos , Análisis por Matrices de Proteínas , Unión Proteica , Técnicas del Sistema de Dos HíbridosRESUMEN
The reversibility of osteopenia secondary to isolated Ca deficiency (CaDef) is still not clear. We studied the effect of severe CaDef on Ca homeostasis and bone accrual in a 'hypercalcaemic' animal, the rabbit, during the post-weaning period and its reversibility on Ca supplementation. Male Belgian 5-week-old rabbit pups were fed CaDef diet (0.026 % Ca) for 10 weeks. As compared with those fed with a normal chow diet (0.45 % Ca), CaDef pups developed significant hypocalcaemia (P < 0.05), hypocalciuria (urinary Ca 76 (SEM 12) v. 17 (SEM 1) mg/l; P < 0.005), hypophosphataemia (serum inorganic P 100 (SEM 6) v. 65 (SEM 4) mg/l; P < 0.005), secondary hyperparathyroidism (SHPT) (serum intact parathyroid hormone human equivalent 18.2 (SEM 1.4) v. 125.0 (SEM 4.5) pg/ml; P < 0.001) and elevated serum calcitriol levels (34.0 (SEM 3.9) v. 91.0 (SEM 1.0) pg/ml; P < 0.005). Elevated urinary C-terminal telopeptide of class I collagen (P < 0.005) and total serum alkaline phosphatase (P < 0.005) suggested increased bone turnover. There was a significantly lower gain in bone mineral density (BMD) and bone mineral content (BMC) in the whole body and lumbar spine in vivo, and various sub-regions of the femur and tibia in vitro. Supplementation of adequate Ca (0.45 % Ca) after 15 weeks on the normal diet resulted in rapid catch-up growth, and resolution of SHPT. Rapid gain in various BMD and BMC parameters continued at 30 weeks of age, and both were comparable with those in rabbits on a normal diet. We conclude that Ca deficiency-induced SHPT and poor bone accrual in growing rabbit pups are rapidly reversible with Ca supplementation. The present study indicates that early intervention may be a more appropriate window period for human nutritional corrective measures.