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1.
Proc Natl Acad Sci U S A ; 120(11): e2216774120, 2023 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-36888662

RESUMEN

Cells regularly experience fluid flow in natural systems. However, most experimental systems rely on batch cell culture and fail to consider the effect of flow-driven dynamics on cell physiology. Using microfluidics and single-cell imaging, we discover that the interplay of physical shear rate (a measure of fluid flow) and chemical stress trigger a transcriptional response in the human pathogen Pseudomonas aeruginosa. In batch cell culture, cells protect themselves by quickly scavenging the ubiquitous chemical stressor hydrogen peroxide (H2O2) from the media. In microfluidic conditions, we observe that cell scavenging generates spatial gradients of H2O2. High shear rates replenish H2O2, abolish gradients, and generate a stress response. Combining mathematical simulations and biophysical experiments, we find that flow triggers an effect like "wind-chill" that sensitizes cells to H2O2 concentrations 100 to 1,000 times lower than traditionally studied in batch cell culture. Surprisingly, the shear rate and H2O2 concentration required to generate a transcriptional response closely match their respective values in the human bloodstream. Thus, our results explain a long-standing discrepancy between H2O2 levels in experimental and host environments. Finally, we demonstrate that the shear rate and H2O2 concentration found in the human bloodstream trigger gene expression in the blood-relevant human pathogen Staphylococcus aureus, suggesting that flow sensitizes bacteria to chemical stress in natural environments.


Asunto(s)
Bacterias , Peróxido de Hidrógeno , Humanos , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/metabolismo , Bacterias/metabolismo , Microfluídica , Técnicas de Cultivo Celular por Lotes , Pseudomonas aeruginosa/genética
2.
J Bacteriol ; 205(4): e0040022, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-36951552

RESUMEN

Bacteria thrive in environments rich in fluid flow, such as the gastrointestinal tract, bloodstream, aquatic systems, and the urinary tract. Despite the importance of flow, how flow affects bacterial life is underappreciated. In recent years, the combination of approaches from biology, physics, and engineering has led to a deeper understanding of how bacteria interact with flow. Here, we highlight the wide range of bacterial responses to flow, including changes in surface adhesion, motility, surface colonization, quorum sensing, virulence factor production, and gene expression. To emphasize the diversity of flow responses, we focus our review on how flow affects four ecologically distinct bacterial species: Escherichia coli, Staphylococcus aureus, Caulobacter crescentus, and Pseudomonas aeruginosa. Additionally, we present experimental approaches to precisely study bacteria in flow, discuss how only some flow responses are triggered by shear force, and provide perspective on flow-sensitive bacterial signaling.


Asunto(s)
Caulobacter crescentus , Infecciones Estafilocócicas , Humanos , Percepción de Quorum , Factores de Virulencia , Caulobacter crescentus/genética , Pseudomonas aeruginosa/fisiología
3.
Environ Res ; 233: 116478, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37348633

RESUMEN

This study deals with the fabrication of metal ion (M = Co+2, Ni+2, and Cu+2) doped- Bi2O3 photocatalysts by solution combustion method. All the synthesized materials were characterized and analysed with the help of XRD, FESEM, EDX, HRTEM, UVDRS, Zeta potential, PL, and LCMS techniques for the structural, morphological, surface charge, optical and degradation pathways characteristics. Synthesized compounds were used for the decontamination (adsorption and degradation) of two organic pollutants namely Rhodamine B and Triclopyr. Adsorption aspects of the pollutants were studied in terms of different isotherm, kinetic and thermodynamic models. Adsorption phenomenon was best fitted with the Freundlich (R2 = 0.992) and Langmuir isotherm (R2 = 0.999) models along with pseudo second order model of kinetics for RhB and TC, respectively. Moreover, the thermodynamic parameters indicated exothermic and endothermic adsorption (ΔH ° (-7.19 kJ/mol) for RhB) and (ΔH ° (52.335 kJ/mol) for TC), respectively. Evaluated negative values of ΔG ° indicated spontaneous adsorption with most favourable at 298 K and 318 K for both the pollutants (RhB and TC) respectively. Modification with metal ions significantly improved the removal efficiency of pure Bi2O3 photocatalyst and followed the trend Co+2/Bi2O3 > Ni+2/Bi2O3 > Cu+2/Bi2O3 > Bi2O3. DFT calculations demonstrate that amongst the doped materials, only Co+2/Bi2O3 is characterized by an indirect band gap; which exhibited efficacious photocatalytic activity. Besides, the highest degradation efficiency was obtained in the case of Co+2/Bi2O3 (2 mol %); being 99.80% for RhB in 30 min and 98.50% for TC in 60 min, respectively. The doped nanostructures lead to higher absorption of visible light and more separation of light-induced charged carriers. Effect of pH of the reaction medium and role of reactive oxygen species was also examined. Finally, a probable mechanism of charge transfer and degradation of the pollutants was also presented.


Asunto(s)
Contaminantes Químicos del Agua , Adsorción , Fotólisis , Termodinámica , Contaminantes Químicos del Agua/análisis
4.
Mycoses ; 66(3): 181-195, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36227645

RESUMEN

Apophysomyces species are an emerging cause of mucormycosis in several regions of the world, primarily affecting immunocompetent individuals. The present study addresses the global epidemiology, clinical presentation, management and outcome of mucormycosis caused by Apophysomyces spp. The study included patients diagnosed with Apophysomyces infection at our hospital between March 2019 and August 2020. In addition, cases published in PubMed and Google Scholar from inception to July 2022 were systematically searched and analysed. Only proven and probable cases that meet the eligibility criteria were included. The Indian cases were compared with those from other countries, and the results were analysed by descriptive statistics. In total, six cases of mucormycosis due to Apophysomyces spp. were diagnosed at our hospital, with additional 250 cases identified through literature search. The main underlying diseases were diabetes mellitus (24%), malignancy (3.2%) and chronic kidney disease (2.8%). The major predisposing factor was trauma (55.6%). Necrotizing fasciitis was the most common (63.2%) clinical presentation. Healthcare-associated mucormycosis accounted for 10.4% of the cases. Globally, A. elegans was the most common species (48.8%), whereas A. variabilis was predominant (86.2%) in India. Surgery was performed in 83.5% of patients. Among those treated with antifungal agents, 98% received amphotericin B and 8.1% received posaconazole. Inappropriate antifungal usage was observed in 12.7%. The overall mortality was 42.3%. A combined medical and surgical management was associated with higher survival. Our study highlights the knowledge gap among physicians regarding this infection. A timely diagnosis and aggressive management can improve the outcomes in such cases.


Asunto(s)
Mucorales , Mucormicosis , Humanos , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , India/epidemiología , Mucorales/aislamiento & purificación , Mucormicosis/diagnóstico , Mucormicosis/tratamiento farmacológico , Mucormicosis/epidemiología , Mucormicosis/microbiología , Mucormicosis/cirugía , Centros de Atención Terciaria , Salud Global/estadística & datos numéricos , Resultado del Tratamiento
5.
Postgrad Med J ; 99(1170): 318-325, 2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37227982

RESUMEN

BACKGROUND: As functional changes precede structural changes in dementia, we aimed to elucidate changes on cerebral perfusion CT (PCT) for early diagnosis of dementia; and to differentiate Alzheimer's disease (AD) from vascular dementia (VaD). We also aimed to study correlation between Montreal Cognitive Assessment (MOCA) score and PCT parameters. METHODS: We conducted a prospective case-control study enrolling 25 dementia patients (15 cases of VaD, 10 cases of AD) and 25 age-matched controls. PCT was performed on a 256-slice CT scanner. Using perfusion software, colour maps were generated for cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time and time-to-peak. These colour maps were first visually inspected for any abnormalities. Subsequently, quantitative assessment of perfusion parameters was done using symmetrical freehand region of interests drawn in bilateral frontal, temporal, parietal regions, basal ganglia and hippocampi. RESULTS: Strategic infarcts were present in 93.3% cases and white matter ischaemic changes in 100% cases of VaD. A global reduction in CBF and CBV was also observed in cases of VaD; whereas these parameters were significantly lower mainly in temporoparietal regions and hippocampi of patients with AD. There was significant positive correlation between MOCA score and various perfusion parameters in both forms of dementia. CONCLUSION: PCT is a reliable imaging modality for early diagnosis of dementia and in differentiating VaD from AD. As perfusion parameters show positive correlation with MOCA score, they could be used as a surrogate marker of cognitive status in the follow-up of patients with dementia.


Asunto(s)
Enfermedad de Alzheimer , Encéfalo , Humanos , Encéfalo/diagnóstico por imagen , Estudios de Casos y Controles , Pronóstico , Tomografía Computarizada por Rayos X/métodos , Enfermedad de Alzheimer/diagnóstico por imagen , Perfusión
6.
J Prosthet Dent ; 2023 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-36610846

RESUMEN

STATEMENT OF PROBLEM: Prosthetic intervention with a speech aid prosthesis (SAP) along with speech therapy has been reported to improve speech outcomes in patients with persisting velopharyngeal insufficiency (VPI). However, little is known regarding the impact of this treatment on different speech parameters over time in adult patients with VPI. PURPOSE: The purpose of this retrospective study was to evaluate the change in speech parameters after rehabilitation with an SAP and speech therapy in adult patients with VPI using subjective and objective tests. MATERIAL AND METHODS: Patients above 16 years of age who had received prosthetic treatment for VPI and had complete speech assessment records between 2017 and 2020 were included in the analysis. After completion of the prosthetic treatment, speech therapy comprising 2 sessions per week of 45 minutes was provided by a speech pathologist. Speech evaluation was performed using tests that included speech intelligibility calculation, nasal pinch test, audible nasal air emissions, acoustic analysis, and the nasalance check. Assessments were done at 4 time intervals: T0: without an SAP; T1: 1 week with an SAP; T2: 1 month with an SAP; and T3: 3 months with an SAP. A descriptive analysis was followed by a comparison between groups using the Friedman test for subjective assessments and repeated measures ANOVA for objective tests (α=.05). RESULTS: Of 10 individuals who had received an SAP, 5 participants, 2 men and 3 women with a mean age of 38 years were included in the analysis. Statistically significant improvement in mean scores was observed from T0 to T3 concerning speech intelligibility (P<.001), hypernasality (P<.001), audible nasal air emission (P<.001), mean fundamental frequency (P=.034), shimmer percentage (P=.004), and nasalance (P=.004). Improvement in jitter percentage was not statistically significant (P=.218). CONCLUSIONS: An SAP along with speech therapy should be considered as a conservative and effective treatment option for addressing speech issues in adult patients with VPI.

7.
Folia Phoniatr Logop ; 75(2): 67-80, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35917799

RESUMEN

INTRODUCTION: This paper attempts to describe the neuropsychological differences between subgroups of tinnitus with normal hearing. METHODS: The study compared 150 normal-hearing participants with and without tinnitus in the 18-55 age-group. The participants completed nine neuropsychological tests, namely, Rey's auditory verbal learning test (RAVLT), Rey complex figure test (RCFT), digit vigilance test (DVT), Verbal N-back test (N Back), controlled oral word association test (COWA), animal names test (ANT), digit symbol substitution test (DSST), Wechsler digit span test (DST), and Stroop test. RESULTS: Poor verbal memory was demonstrated by a unilateral tinnitus group (p = 0.0001) for the total RAVLT score, immediate score, delayed recall, hits, and omissions). Significant deficits were observed in working memory functioning by the unilateral and bilateral tinnitus participants (p < 0.001) for one-back and two-back hit and error scores). In addition, there was a significant impairment in the auditory attention of single-sided tinnitus participants (p < 0.03, 0.02). Selective attention was affected in bilateral tinnitus participants (p < 0.05). DISCUSSION/CONCLUSION: Tinnitus, whether unilateral or bilateral, has an effect on working memory. The RAVLT and DST results, on the other hand, demonstrated that unilateral tinnitus suffers from significant deficits in auditory memory and attention, whereas bilateral tinnitus suffers from selective attention issues. When treating individuals with unilateral and bilateral tinnitus, these findings must be addressed.


Asunto(s)
Acúfeno , Humanos , Memoria a Corto Plazo , Aprendizaje Verbal , Pruebas Neuropsicológicas , Audición
8.
Indian J Med Res ; 155(3&4): 387-396, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-36124513

RESUMEN

Background & objectives: Obesity is a rising pandemic in childhood. There is scarcity of evidence on the efficacy of yoga in achieving weight loss in overweight/obese children. The objective of this study was to assess the efficacy of family-based comprehensive yoga intervention in the reduction of body mass index (BMI) in overweight/obese children, in comparison to standard dietary and lifestyle counselling and control group. Methods: This was an open-label randomized controlled study. Children aged 8-15 yr who were overweight or had obesity were randomized to one of the three arms for 18 wk; standard weight management (group 1), yoga with dietary modification (group 2) and control (no intervention; group 3). Reduction in BMI and improvement in physiological, biochemical and psychological parameters from baseline to 18 wk was compared between the three arms. Late follow up was also done at 6-12 months. Results: A total of 165 children with mean±standard deviation (SD) age of 11.6±1.8 yr and mean BMI 26.3±4.2 kg/m2 were enrolled. Outcome analysis at 18 wk was performed for 109 children. Improved diet quality and reduced intake were observed in both intervention arms. The median (IQR) reduction in BMI in standard and yoga arms was similar [-1.4 (-3.1, -0.5) kg/m2 and -1.2 (-2.3, -0.6) kg/m2, respectively], while it increased by +0.3 (-0.3, 0.1) in the control arm. In the yoga arm, mean systolic BP reduced from 118 (10) to 114 (8) mmHg, (P=0.019). In the standard arm, significant improvement in psychological scores was noted. In group 3, the mean fasting glucose increased from 93±10 to 102±12 mg/dl (P<0.001). Interpretation & conclusions: The findings of the present study suggest that yoga in conjunction with dietary modification is equally effective as the standard weight management for BMI reduction in the paediatric age group.


Asunto(s)
Obesidad Infantil , Yoga , Adolescente , Niño , Glucosa , Humanos , Sobrepeso , Obesidad Infantil/terapia , Pérdida de Peso
9.
Postgrad Med J ; 2022 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-37076646

RESUMEN

BACKGROUND: As functional changes precede structural changes in dementia, we aimed to elucidate changes on cerebral perfusion CT (PCT) for early diagnosis of dementia; and to differentiate Alzheimer's disease (AD) from vascular dementia (VaD). We also aimed to study correlation between Montreal Cognitive Assessment (MOCA) score and PCT parameters. METHODS: We conducted a prospective case-control study enrolling 25 dementia patients (15 cases of VaD, 10 cases of AD) and 25 age-matched controls. PCT was performed on a 256-slice CT scanner. Using perfusion software, colour maps were generated for cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time and time-to-peak. These colour maps were first visually inspected for any abnormalities. Subsequently, quantitative assessment of perfusion parameters was done using symmetrical freehand region of interests drawn in bilateral frontal, temporal, parietal regions, basal ganglia and hippocampi. RESULTS: Strategic infarcts were present in 93.3% cases and white matter ischaemic changes in 100% cases of VaD. A global reduction in CBF and CBV was also observed in cases of VaD; whereas these parameters were significantly lower mainly in temporoparietal regions and hippocampi of patients with AD. There was significant positive correlation between MOCA score and various perfusion parameters in both forms of dementia. CONCLUSION: PCT is a reliable imaging modality for early diagnosis of dementia and in differentiating VaD from AD. As perfusion parameters show positive correlation with MOCA score, they could be used as a surrogate marker of cognitive status in the follow-up of patients with dementia.

10.
Int J Neuropsychopharmacol ; 24(5): 400-408, 2021 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-33515455

RESUMEN

BACKGROUND: Several lines of evidence suggest the abnormalities of protein kinase C (PKC) signaling system in mood disorders and suicide based primarily on the studies of PKC and its isozymes in the platelets and postmortem brain of depressed and suicidal subjects. In this study, we examined the role of PKC isozymes in depression and suicide. METHODS: We determined the protein and mRNA expression of various PKC isozymes in the prefrontal cortical region (Brodmann area 9) in 24 normal control subjects, 24 depressed suicide (DS) subjects, and 12 depressed nonsuicide (DNS) subjects. The levels of mRNA in the prefrontal cortex were determined by quantitative real-time reverse transcription PCR, and the protein expression was determined by western blotting. RESULTS: We observed a significant decrease in mRNA expression of PKCα, PKCßI, PKCδ, and PKCε and decreased protein expression in either the membrane or the cytosol fraction of PKC isozymes PKCα, PKCßI, PKCßII, and PKCδ in DS and DNS subjects compared with normal control subjects. CONCLUSIONS: The current study provides detailed evidence of specific dysregulation of certain PKC isozymes in the postmortem brain of DS and DNS subjects and further supports earlier evidence for the role of PKC in the platelets and brain of the adult and teenage depressed and suicidal population. This comprehensive study may lead to further knowledge of the involvement of PKC in the pathophysiology of depression and suicide.


Asunto(s)
Trastorno Depresivo Mayor/enzimología , Corteza Prefrontal/enzimología , Proteína Quinasa C/metabolismo , Suicidio Completo , Adulto , Autopsia , Femenino , Humanos , Isoenzimas/metabolismo , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Adulto Joven
11.
J Psychiatry Neurosci ; 46(5): E538-E547, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34588173

RESUMEN

BACKGROUND: Abnormalities of inflammation have been implicated in the pathophysiology of depression and suicide, based on observations of increased levels of proinflammatory cytokines in the serum of people who were depressed and died by suicide. More recently, abnormalities in cytokines and innate immunity receptors such as toll-like receptors have also been observed in the postmortem brains of people who were depressed and died by suicide. In addition to toll-like receptors, another subfamily of innate immunity receptors known as NOD-like receptors containing pyrin (NLRPs) are the most widely present NOD-like receptors in the central nervous system. NLRPs also form inflammasomes that play an important role in brain function. We studied the role of NLRPs in depression and suicide. METHODS: We determined the protein and mRNA expression of NLRP1, NLRP3 and NLRP6 and the components of their inflammasomes (i.e., adaptor molecule apoptosis-associated speck-like protein [ASC], caspase1, caspase3, interleukin [IL]-1ß and IL-18) postmortem in the prefrontal cortex of people who were depressed and died by suicide, and in healthy controls. We determined mRNA levels using quantitative polymerase chain reaction, and we determined protein expression using Western blot immunolabelling. RESULTS: We found that the protein and mRNA expression levels of NLRP1, NLRP3, NLRP6, caspase3 and ASC were significantly increased in people who were depressed and died by suicide compared to healthy controls. LIMITATIONS: Some people who were depressed and died by suicide were taking antidepressant medication at the time of their death. CONCLUSION: Similar to toll-like receptors, NLRP and its inflammasomes were upregulated in people who were depressed and died by suicide compared to healthy controls. Innate immunity receptors in general - and NLRPs and inflammasomes in particular - may play an important role in the pathophysiology of depression and suicide.


Asunto(s)
Depresión/inmunología , Inmunidad Innata , Inflamasomas , Proteínas NLR/inmunología , Pirina , Suicidio Completo , Adulto , Autopsia , Encéfalo/metabolismo , Citocinas/metabolismo , Femenino , Humanos , Inflamasomas/metabolismo , Masculino , ARN Mensajero , Receptores Toll-Like/metabolismo
12.
Middle East Fertil Soc J ; 26(1): 1, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33437145

RESUMEN

BACKGROUND: COVID-19 is the most recent zoonotic outbreak of coronaviruses. Mostly, it invades the cells of the respiratory system by binding to the receptor angiotensin-converting enzyme 2 (ACE2) which is also present in other organs like the kidney, testis, ovaries, breast, heart, and intestine, rendering them prone to be infected. The reproductive potential is a must for the sustenance of any species and it is our prime duty to safeguard the reproductive system of the present generation from such a deadly virus. The previously reported coronaviruses like severe acute respiratory syndrome coronavirus (SARS-CoV) had a detrimental impact on reproductive organs. There is a dearth of sufficient research to provide substantial evidence for the harmful effects of this novel virus on the reproductive system. Hence, our review compiles the knowledge available until now to boost research in this regard and to take the necessary steps in time. MAIN BODY OF ABSTRACT: Here we tried to compile all the data available on the effect of SARS-CoV-2 on the reproductive system as well as vertical transmission of the virus. All related articles published from February to August 2020 were reviewed and thoroughly analyzed. SARS-CoV-2 has been found to affect the sperm concentration and motility, thus degrading the fertility of males. In females, it is suspected that this virus affects the oocyte quality and ovarian function, resulting in infertility or miscarriage. Traces of SARS-CoV-2 virus have also been found in the breast milk of the infected mothers and the semen of infected males. Vertical transmission of SARS-CoV-2 has also been reported in some cases. CONCLUSION: Based on the literature review, SARS-CoV-2 seems to have the potential of affecting both male and female reproductive tracts. This review brings together the findings and observations made in the area of reproductive health during the current pandemic. The reproductive system of the young population is preordained for subsequent disorders, infertility, reduced sperm count, and motility. Therefore, the research and medical practices should focus on possible vulnerability being posed by SARS-CoV-2 to the gametes and future generations. We, hereby, recommend close monitoring of young and pregnant COVID-19 patients concerning reproductive health with utmost priority.

13.
Indian J Crit Care Med ; 23(12): 590-592, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31988552

RESUMEN

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is capable of causing a wide range of infections. Colonized healthcare workers (HCWs) and contaminated hand-touch surfaces act as a potential source of MRSA in hospitals. This study was conducted to detect the carriage of MRSA in the hands of HCWs during patient care to check awareness among HCWs to follow proper hand hygiene protocol. MATERIALS AND METHODS: This study was a cross-sectional point prevalence study done in wards and intensive care units (ICUs) of a tertiary care hospital. Hand cultures were collected from HCWs after the clinical rounds, without prior information about the procedure. It was done on three consecutive days to include maximum HCWs from the hospital. Cultures were taken before and after the use of alcohol-based hand rub. Hand cultures were obtained by asking HCWs to touch the surface of chromogenic screening agar for MRSA with their fingertips and thumbs of both the hands. RESULTS: Of a total of 62 HCWs screened, 32 (51.61%) were positive for MRSA. Among these, seven were doctors. After using alcohol-based hand rub, six HCWs were still positive for MRSA. Another important finding on this screening agar was detection of Candida on the hands of HCWs. CONCLUSION: Regular monitoring of hand hygiene compliance is vital to prevent the spread of nosocomial infections. The MRSA screening agar is rapid, simple, cost-effective, and useful to identify the carriage of not only MRSA but also Candida (in the wake of nosocomial outbreaks with Candida auris) in the hands of HCWs. Further studies are required to evaluate the transmission rate of MRSA from HCWs to patients in Indian hospitals. HOW TO CITE THIS ARTICLE: Sharma A, Kalita JM, Nag VL. Screening for Methicillin-resistant Staphylococcus aureus Carriage on the Hands of Healthcare Workers: An Assessment for Hand Hygiene Practices. Indian J Crit Care Med 2019;23(12):590-592.

14.
Bioorg Med Chem ; 26(1): 215-224, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29195794

RESUMEN

The present study reports the effect of indanone derivatives on scopolamine induced deficit cholinergic neurotransmission serving as promising leads for the therapeutics of cognitive dysfunction. Eleven compounds 54-64 have been designed, synthesised and evaluated against behavioural alterations using step down passive avoidance protocol at a dose of 0.5 mg/kg with Donepezil (1) as the reference standard. All the synthesised compounds were evaluated for their in vitro acetylcholinesterase (AChE) inhibition at five different concentrations using mice brain homogenate as the source of the enzyme. Compounds 54, 56, 59 and 64 displayed appreciable activity with an IC50 value of 14.06 µM, 12.30 µM, 14.06 µM and 12.01 µM, respectively towards acetylcholinesterase inhibition. The molecular docking study performed to predict the binding mode of the compounds suggested that these compounds could bind appreciably to the amino acids present at the active site of recombinant human acetylcholinesterase (rhAChE). The behavioural, biochemical and in silico pharmacokinetic studies were in concordance with each other.


Asunto(s)
Acetilcolinesterasa/metabolismo , Reacción de Prevención/efectos de los fármacos , Inhibidores de la Colinesterasa/farmacología , Disfunción Cognitiva/tratamiento farmacológico , Diseño de Fármacos , Indanos/farmacología , Animales , Inhibidores de la Colinesterasa/administración & dosificación , Inhibidores de la Colinesterasa/química , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Indanos/administración & dosificación , Indanos/química , Ratones , Simulación del Acoplamiento Molecular , Estructura Molecular , Escopolamina , Relación Estructura-Actividad
15.
BMC Pregnancy Childbirth ; 18(1): 428, 2018 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-30373537

RESUMEN

BACKGROUND: Postpartum Hemorrhage remains the leading cause of maternal mortality. To prevent PPH, Misoprostol tablet in a dose of 600 micrograms is recommended for use immediately after childbirth in home deliveries wherein the use of oxytocin is difficult. The current article describes an implementation of "community based advance distribution of Misoprostol program" in India which aimed to design an operational framework for implementing this program. METHODS: The intervention was carried out in Janjheli block in Mandi district of the state of Himachal Pradesh which is a mountainous terrain with limited geographical access and reported 90% home deliveries in the year 2014-15. An operational framework to implement program activities was designed which was based on WHO HSS building blocks. Key implementing steps included- Ensuring local ownership through program leadership, forecasting and procurement of 600 mcg misoprostol tablets, training, branding and communication, community engagement and counselling, recording and reporting, monitoring, supportive supervision and feedback mechanisms. RESULTS: Over the one year of implementation, 512 home deliveries were reported, out of which 89% received the tablets and 84% consumed the tablet within one minute of delivery. No incidence of PPH in tablet consuming mothers was reported. On account of periodic counselling and effective community engagement the intervention also contributed to better tracking of pregnancies till delivery and institutional delivery rates which increased to 93% from 45% and 57% from 11% respectively as compared to the preceding year. CONCLUSIONS: The model has successfully shown the use of single misoprostol tablets of 600 mcg, first time in this program. We also demonstrated a HSS based operational framework, based on which the program is being scaled to additional blocks in Himachal Pradesh as well as to other states of India.


Asunto(s)
Atención a la Salud/métodos , Misoprostol/administración & dosificación , Oxitócicos/administración & dosificación , Hemorragia Posparto/prevención & control , Femenino , Humanos , India , Servicios de Salud Materna/estadística & datos numéricos , Misoprostol/efectos adversos , Oxitócicos/efectos adversos , Parto , Embarazo , Evaluación de Programas y Proyectos de Salud/métodos
16.
BMC Complement Altern Med ; 18(1): 268, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-30285727

RESUMEN

BACKGROUND: Glutamate, the major excitatory neurotransmitter of CNS acts as a neurotoxin at higher concentrations. Prolonged activation of glutamate receptors results in progressive neuronal damage by aggravating calcium influx, inducing mitochondrial damage and oxidative stress. Excitotoxic cell death is associated with the pathogenesis of various neurodegenerative disorders such as trauma, brain injury and neurodegenerative diseases. The current study was designed to investigate the neuroprotective and neuroregenerative potential of Tinospora cordifolia against glutamate-induced excitotoxicity using primary cerebellar neuronal cultures as a model system. METHODS: Monosodium salt of glutamate was used to induce neurotoxic injury in primary cerebellar neurons. Four extracts including Hexane extract, Chloroform extract, Ethyl acetate, and Butanol extract were obtained from fractionation of previously reported aqueous ethanolic extract of T. cordifolia and tested for neuroprotective activity. Out of the four fractions, Butanol extract of T. cordifolia (B-TCE) exhibited neuroprotective potential by preventing degeneration of neurons induced by glutamate. Expression of different neuronal, apoptotic, inflammatory, cell cycle regulatory and plasticity markers was studied by immunostaining and Western blotting. Neurite outgrowth and migration were also studied using primary explant cultures, wound scratch and gelatin zymogram assay. RESULTS: At molecular level, B-TCE pretreatment of glutamate-treated cultures normalized the stress-induced downregulation in the expression of neuronal markers (MAP-2, GAP-43, NF200) and anti-apoptotic marker (Bcl-xL). Further, cells exposed to glutamate showed enhanced expression of inflammatory (NF-κB, AP-1) and senescence markers (HSP70, Mortalin) as well as the extent of mitochondrial damage. However, B-TCE pretreatment prevented this increase and inhibited glutamate-induced onset of inflammation, stress and mitochondrial membrane damage. Furthermore, B-TCE was observed to promote regeneration, migration and plasticity of cerebellar neurons, which was otherwise significantly inhibited by glutamate treatment. CONCLUSION: These results suggest that B-TCE may have neuroprotective and neuroregenerative potential against catastrophic consequences of glutamate-mediated excitotoxicity and could be a potential therapeutic candidate for neurodegenerative diseases.


Asunto(s)
Ácido Glutámico/toxicidad , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Tinospora/química , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Cerebelo/citología , Cerebelo/efectos de los fármacos , Cerebelo/fisiología , Plasticidad Neuronal/efectos de los fármacos , Neuronas/citología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar
17.
Int Tinnitus J ; 22(1): 77-83, 2018 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-29993222

RESUMEN

OBJECTIVES: This research was conducted to investigate the presenting features of tinnitus in subjects with normal hearing thresholds as compared to the ones with hearing loss. METHODOLOGY: Sample population comprised of 175 subjects with tinnitus, in the age range of 18 to 55 years, segregated into two groups: G1 (75 subjects) having normal hearing with tinnitus and G2 (100 subjects) having hearing loss with tinnitus. All the subjects underwent conventional audiometric testing along with a thorough evaluation of all the parameters of tinnitus. RESULTS AND CONCLUSION: Significantly large number of males reported with tinnitus as compared to females. Tinnitus was most prevailing in left ear and these subjects sought intervention earlier than right tinnitus subjects. G1 subjects reported earlier as compared to G2 subjects. Males looked out for specialist's advice earlier than females in both the groups. Large number of subjects in both groups reported with sudden onset and continuous tinnitus.


Asunto(s)
Pérdida Auditiva/epidemiología , Acúfeno/epidemiología , Adulto , Audiometría de Tonos Puros , Umbral Auditivo/fisiología , Femenino , Audición , Pérdida Auditiva/complicaciones , Pérdida Auditiva/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Distribución por Sexo , Factores Sexuales , Acúfeno/complicaciones , Acúfeno/fisiopatología , Adulto Joven
18.
Mol Cell Biochem ; 427(1-2): 91-101, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28004351

RESUMEN

Sleep is a profound regulator of cellular immunity, and the curtailment of sleep in present day lifestyle leads to disruption of neuro-immune-endocrine interactions. No therapeutic remedy is yet known for the amelioration of detrimental effects caused by sleep deprivation (SD). The current study was aimed to elucidate the effects of acute SD on immune function and its modulation by water extract from leaves of Withania somnifera (ASH-WEX). Three groups of animals, i.e. Vehicle-Undisturbed sleep (VUD), Vehicle-Sleep deprived (VSD) and ASH-WEX fed sleep deprived (WSD) rats were tested for their anxiety-like behaviour and further used for the study of inflammatory and apoptotic markers expression in piriform cortex and hippocampus regions of the brain. VSD animals showed high level of anxiety in elevated plus maze test, which was ameliorated in WSD group. The stress induced expression of inflammatory and immune response markers GFAP, TNFα, IL-6, OX-18 and OX-42 in VSD animals was found to be modulated by ASH-WEX. Further, the stress induced apoptosis was suppressed in WSD group as indicated by expression of NF-κB, AP-1, Bcl-xL and Cytochrome c. This study provides scientific validation to the anxiolytic, anti-inflammatory and anti-apoptotic properties of ASH-WEX, which may serve as an effective dietary supplement for management of SD induced stress and associated functional impairments.


Asunto(s)
Ansiolíticos/farmacología , Factores Inmunológicos/farmacología , Extractos Vegetales/farmacología , Hojas de la Planta/química , Privación de Sueño/tratamiento farmacológico , Withania/química , Animales , Ansiolíticos/química , Femenino , Factores Inmunológicos/química , Extractos Vegetales/química , Ratas , Ratas Wistar , Privación de Sueño/metabolismo , Privación de Sueño/patología
19.
J Environ Biol ; 37(1): 115-9, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26930868

RESUMEN

Current study presents the effect of irrigation with different concentrations (20, 40, 60, 80 and 100%) of untreated and treated brewery-distillery effluent on germination behaviour of marigold (Tagetes erecta L. var. Pusa Basanti). The 100% untreated effluent showed acidic pH (4.80) and higher values of BOD (1500.00 mg l(-1)), COD (4000.00 mg l(-1)), chloride (1742.20 mg l(-1)), TSS (900.00 mg l(-1)) as compared to that of treated effluent. Tagetes seeds were exposed to different concentrations of effluent and the results revealed maximum values of germination parameters viz., percent germination, peak value, germination value, germination index, speed of germination and vigour index at 20% untreated and 60% treated effluent concentrations, whereas the values for negative germination parameters viz., delay index, germination period and percent inhibition were minimum at 20% untreated and 60% treated effluent concentrations.


Asunto(s)
Riego Agrícola , Germinación/fisiología , Residuos Industriales , Semillas/fisiología , Tagetes/fisiología , Industria de Alimentos , Eliminación de Residuos Líquidos
20.
Photosynth Res ; 125(1-2): 305-19, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25366828

RESUMEN

Investigations were carried to unravel mechanism(s) for higher tolerance of floating over submerged leaves of long leaf pondweed (Potamogeton nodosus Poir) against photoinhibition. Chloroplasts from floating leaves showed ~5- and ~6.4-fold higher Photosystem (PS) I (reduced dichlorophenol-indophenol â†’ methyl viologen â†’ O2) and PS II (H2O â†’ parabenzoquine) activities over those from submerged leaves. The saturating rate (V max) of PS II activity of chloroplasts from floating and submerged leaves reached at ~600 and ~230 µmol photons m(-2) s(-1), respectively. Photosynthetic electron transport rate in floating leaves was over 5-fold higher than in submerged leaves. Further, floating leaves, as compared to submerged leaves, showed higher F v/F m (variable to maximum chlorophyll fluorescence, a reflection of PS II efficiency), as well as a higher potential to withstand photoinhibitory damage by high light (1,200 µmol photons m(-2) s(-1)). Cells of floating leaves had not only higher mitochondria to chloroplast ratio, but also showed many mitochondria in close vicinity of chloroplasts. Electron transport (NADH â†’ O2; succinate â†’ O2) in isolated mitochondria of floating leaves was sensitive to both cyanide (CN(-)) and salicylhydroxamic acid (SHAM), whereas those in submerged leaves were sensitive to CN(-), but virtually insensitive to SHAM, revealing the presence of alternative oxidase in mitochondria of floating, but not of submerged, leaves. Further, the potential of floating leaves to withstand photoinhibitory damage was significantly reduced in the presence of CN(-) and SHAM, individually and in combination. Our experimental results establish that floating leaves possess better photosynthetic efficiency and capacity to withstand photoinhibition compared to submerged leaves; and mitochondria play a pivotal role in protecting photosynthetic machinery of floating leaves against photoinhibition, most likely by oxidation of NAD(P)H and reduction of O2.


Asunto(s)
Transporte de Electrón , Complejo de Proteína del Fotosistema I/metabolismo , Complejo de Proteína del Fotosistema II/metabolismo , Hojas de la Planta/fisiología , Potamogetonaceae/fisiología , Clorofila/metabolismo , Cloroplastos/metabolismo , Fluorescencia , Luz , Mitocondrias/enzimología , Proteínas Mitocondriales/metabolismo , Oxidorreductasas/metabolismo , Fotosíntesis , Hojas de la Planta/efectos de la radiación , Proteínas de Plantas/metabolismo , Potamogetonaceae/efectos de la radiación
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