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1.
Microbiol Res ; 286: 127818, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38970906

RESUMEN

The agricultural land in the Indian Himalayan region (IHR) is susceptible to various spells of snowfall, which can cause nutrient leaching, low temperatures, and drought conditions. The current study, therefore, sought an indigenous psychrotrophic plant growth-promoting (PGP) bacterial inoculant with the potential to alleviate crop productivity under cold and drought stress. Psychrotrophic bacteria preisolated from the night-soil compost of the Lahaul Valley of northwestern Himalaya were screened for phosphate (P) and potash (K) solubilization, nitrogen fixation, indole acetic acid (IAA) production, siderophore and HCN production) in addition to their tolerance to drought conditions for consortia development. Furthermore, the effects of the selected consortium on the growth and development of wheat (Triticum aestivum L.) and maize (Zea mays L.) were assessed in pot experiments under cold semiarid conditions (50 % field capacity). Among 57 bacteria with P and K solubilization, nitrogen fixation, IAA production, siderophore and HCN production, Pseudomonas protegens LPH60, Pseudomonas atacamensis LSH24, Psychrobacter faecalis LUR13, Serratia proteamaculans LUR44, Pseudomonas mucidolens LUR70, and Glutamicibacter bergerei LUR77 exhibited tolerance to drought stress (-0.73 MPa). The colonization of wheat and maize seeds with these drought-tolerant PGP strains resulted in a germination index >150, indicating no phytotoxicity under drought stress. Remarkably, a particular strain, Pseudomonas sp. LPH60 demonstrated antagonistic activity against three phytopathogens Ustilago maydis, Fusarium oxysporum, and Fusarium graminearum. Treatment with the consortium significantly increased the foliage (100 % and 160 %) and root (200 % and 133 %) biomasses of the wheat and maize plants, respectively. Furthermore, whole-genome sequence comparisons of LPH60 and LUR13 with closely related strains revealed genes associated with plant nutrient uptake, phytohormone synthesis, siderophore production, hydrogen cyanide (HCN) synthesis, volatile organic compound production, trehalose and glycine betaine transport, cold shock response, superoxide dismutase activity, and gene clusters for nonribosomal peptide synthases and polyketide synthetases. With their PGP qualities, biocontrol activity, and ability to withstand environmental challenges, the developed consortium represents a promising cold- and drought-active PGP bioinoculant for cereal crops grown in cold semiarid regions.

2.
Int Microbiol ; 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38760649

RESUMEN

Numerous metagenomics studies, conducted in both full-scale anaerobic digesters and household biogas plants, have shed light on the composition and activity of microbial flora essential for optimizing the performance of biogas reactors, underscoring the significance of microbial community composition in biogas plant efficiency. Although the efficiency of household biogas plants in the sub-Himalayan region has been reported, there is no literature evidence on the microbial community structure of such household biogas plants in the sub-Himalayan region. The current study evaluated the physico-chemical properties and bacterial community structure from the slurry samples of household biogas plants prevalent in the sub-Himalayan region. The slurry samples were observed to be rich in nutrients; however, their carbon and nitrogen contents were higher than the recommended standard values of liquid-fermented organic manure. The species richness and diversity indices (Chao1, Shannon, and Simpson) of household biogas plants were quite similar to the advanced biogas reactors operating at mesophilic conditions. 16S rRNA gene amplicon sequencing reveals microbial diversity, showing a higher abundance of Firmicutes (70.9%) and Euryarchaeota (9.52%) in advanced biogas reactors compared to household biogas plants. Microbial analysis shows a lack of beneficial microbes for anaerobic digestion, which might be the reason for inefficient biogas production in household biogas plants of the sub-Himalayan region. The lack of efficient bacterial biomass may also be attributed to the digester design, feedstock, and ambient temperatures. This study emphasized the establishment of efficient microbial consortia for enhanced degradation rates that may increase the methane yield in biogas plants.

3.
J Biomol Struct Dyn ; 42(1): 148-162, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-36970779

RESUMEN

Acetylcholinesterase (AChE) is one of the key enzyme targets that have been used clinically for the management of Alzheimer's Disorder (AD). Numerous reports in the literature predict and demonstrate in-vitro, and in-silico anticholinergic activity of herbal molecules, however, majority of them failed to find clinical application. To address these issues, we developed a 2D-QSAR model that could efficiently predict the AChE inhibitory activity of herbal molecules along with predicting their potential to cross the blood-brain-barrier (BBB) to exert their beneficial effects during AD. Virtual screening of the herbal molecules was performed and amentoflavone, asiaticoside, astaxanthin, bahouside, biapigenin, glycyrrhizin, hyperforin, hypericin, and tocopherol were predicted as the most promising herbal molecules for inhibiting AChE. Results were validated through molecular docking, atomistic molecular dynamics simulations and Molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) studies against human AChE (PDB ID: 4EY7). To determine whether or not these molecules can cross BBB to inhibit AChE within the central nervous system (CNS) for being beneficial for the management of AD, we determined a CNS Multi-parameter Optimization (MPO) score, which was found in the range of 1 to 3.76. Overall, the best results were observed for amentoflavone and our results demonstrated a PIC50 value of 7.377 nM, molecular docking score of -11.5 kcal/mol, and CNS MPO score of 3.76. In conclusion, we successfully developed a reliable and efficient 2D-QSAR model and predicted amentoflavone to be the most promising molecule that could inhibit human AChE enzyme within the CNS and could prove beneficial for the management of AD.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Enfermedad de Alzheimer , Inhibidores de la Colinesterasa , Humanos , Simulación del Acoplamiento Molecular , Inhibidores de la Colinesterasa/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Relación Estructura-Actividad Cuantitativa , Acetilcolinesterasa/metabolismo , Simulación de Dinámica Molecular , Sistema Nervioso Central
4.
Database (Oxford) ; 20232023 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-37279783

RESUMEN

Indian Himalayan metagenome database (IHM-DB) is a web-based database consisting of information on metagenomic datasets from various databases and publications that are specifically reported from the Indian Himalayan Region (IHR). The online interface allows users to view or download the dataset-specific information for the respective states, category-wise, or according to the hypervariable region. The IHM-DB also provides an opportunity for the users to access the metagenomic publications from the IHR as well as upload their microbiome information to the website. Additionally, an open-source 16S rRNA amplicon-based automated bioinformatics pipeline, AutoQii2, allows users to analyze the single-end and paired-end raw reads. AutoQii2 provides an automated approach for performing analysis such as quality check, adapter and chimera removal and exploits the latest ribosomal database project classifier for taxonomic assignments. The source code of the AutoQii2 pipeline is available at https://gitlab.com/khatriabhi2319/autoqii2. Database URL https://ham.ihbt.res.in/ihmdb and https://fgcsl.ihbt.res.in/ihmdb.


Asunto(s)
Metagenoma , Metagenómica , ARN Ribosómico 16S/genética , Bases de Datos Factuales , Programas Informáticos
5.
Sci Rep ; 13(1): 2293, 2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36759526

RESUMEN

Metamaterials are periodic structures made by repeating a unit cell. Such a structure shows frequency-specific wave attenuation behaviour. In this work, a 2D metamaterial foundation is proposed for the seismic protection of buildings. The paramount challenge is to offer low frequency attenuation (~ 2-8 Hz), which is the dominant excitation during an earthquake. Based on the parametric study performed, a new type of metamaterial structure was proposed. It was found that the foundation consisting of repeating circular scatterers made of steel and plumbum embedded in rubber matrix can provide low and wide frequency wave attenuation from 2.6 to 7.8 Hz. The computational model of the structure was subjected to transient excitation against three pre-recorded earthquake excitations. The result showed that the novel foundation can resist the propagation of the seismic wave to the structure. Further, the response of a 2D building frame with metamaterial foundation was compared to a concrete foundation exposed to different earthquake excitations. The results are very promising as the frame vibration on the metamaterial foundation was significantly less than the same frame on the concrete foundation. The presented work opens the path to new research and development of seismic metamaterial foundation for earthquake attenuation.

6.
J Med Life ; 15(10): 1305-1310, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36420278

RESUMEN

Unilateral spinal anesthesia (USpA) is a technique used to restrict the effect of the spinal block on the operative side. 10-15 degrees reverse Trendelenburg position has been used to control the height of the spinal block using hyperbaric drugs. We aimed to study the effect of the 10-degree reverse Trendelenburg position on the quality of block and hemodynamic stability in unilateral spinal anesthesia in this hospital-based, double-blind, randomized clinical trial. 60 patients of both sexes between 20-60 years of age, undergoing below-knee orthopedic surgeries, were randomized into 2 groups. In both groups, spinal anesthesia was given with 2 mL bupivacaine heavy (0.5%), and the lateral position was maintained for 10 mins. Group 2 patients were kept in a 10-degree reverse Trendelenburg position throughout the surgery. The hemodynamic parameters and block characteristics of the two groups were compared using Epi Info statistical software. The onset of sensory block was faster in Group 1 (recumbent) compared to Group 2 (reverse Trendelenburg). The two-segment regression time was longer in the second group. In group 2, 73.3% of patients reached a level at T8 or below T8, compared to 46.7% in Group 1. The duration of sensory block and anesthesia was longer in Group 2. We conclude that reverse Trendelenburg of 10 degrees immediately after spinal anesthesia significantly limits the level of sensory block and prolongs the duration of unilateral spinal anesthesia.


Asunto(s)
Anestesia Raquidea , Procedimientos Ortopédicos , Masculino , Femenino , Humanos , Anestesia Raquidea/métodos , Anestésicos Locales/farmacología , Inclinación de Cabeza , Hemodinámica
7.
Waste Manag ; 149: 42-52, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35714435

RESUMEN

The Himalayan dry toilet system prevalent in the northwestern Himalaya is a traditional practice of converting human faeces into a compost-like soil amendment. The current study evaluated night-soil compost (NSC) for agricultural use by assessing the compost quality, safety, and microbiome properties. Based on the fertility and clean indices determined by the fertility and heavy metal parameters, NSC was categorized as good quality compost with high fertilizing potential and moderate concentration of heavy metals. With respect to pathogens, the faecal coliform levels in the NSC were categorized as safe according to the U.S. Environmental Protection Agency standards. The bacterial community structure based on 16S rRNA gene amplicons revealed a diverse taxonomy with 14 phyla and 54 genera in NSC. Compared to publicly available 16S rRNA gene amplicon data, NSC exhibited predominant phyla (Proteobacteria, Bacteriodetes, Actinobacteria, and Firmicutes) similar to human faeces, cattle manure, food waste compost, vermicompost, and activated sludge. However, statistically, NSC was distinct at the genus level from all other groups. Additionally, pathogenic bacteria with antimicrobial resistance (AMR) genes in the NSC metagenome were determined by performing a standalone BLASTN against the PATRIC database. The analysis revealed 139 pathogenic strains with most pathogens susceptible to antibiotics, indicating lower AMR in the predicted strains. The phytotoxicity of NSC with Pisum sativum var. AS-10 seeds showed a germination index of > 85%, indicating NSC's non-harmful effects on seed germination and root growth. Overall, NSC from Himalayan dry toilets can be used as a soil amendment for food and non-food plants.


Asunto(s)
Compostaje , Metales Pesados , Microbiota , Eliminación de Residuos , Animales , Bacterias/genética , Bovinos , Alimentos , Humanos , ARN Ribosómico 16S/genética , Suelo/química , Microbiología del Suelo
8.
Cureus ; 14(2): e22588, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35242483

RESUMEN

INTRODUCTION: The primary goal of spinal anesthesia in lower limb surgeries is to achieve a successful sensory and motor block. Adequate level of spinal block for lower limb orthopedic surgery is T10. Due to multiple factors affecting the level of spinal anesthesia, it is not always easy to control the level of spinal anesthesia.We proposed that maintaining patients in a 10° reverse Trendelenburg position after spinal anesthesia can significantly control the height of the sensory block, resulting in stable hemodynamics. MATERIALS AND METHODS: This study is a single centric, prospective, single-blinded randomized clinical trial (CTRI/2018/08/015455) conducted in a tertiary care center in Sub-Himalayan region in India from July 2018 to June 2019. Total 60 patients fulfilling our inclusion and exclusion criteria were recruited in the study and were divided into two groups. In the supine group, patients were positioned in the supine position, and in the Trendelenburg group, patients were positioned in a 10° reverse Trendelenburg position after administering spinal anesthesia with 12.5 mg bupivacaine heavy. The two groups were compared in terms of sensory block, motor block, and analgesia duration. Heart rate, blood pressure, mean arterial pressure, and hypotension were also compared between the two groups. RESULTS: Duration of sensory block, motor block, and analgesia were significantly higher in patients of the reverse Trendelenburg group (group T) compared to the supine group (group S). In group T, 26.6% had a sensory block level above T8, whereas in group S, 86.6% of patients had a sensory block level above T8. No hypotension was observed in the Trendelenburg group, which was present in 33% of patients in the supine group (group S). CONCLUSION: Ten-degree reverse Trendelenburg position immediately after giving spinal anesthesia significantly limits the level of sensory block and provides better hemodynamic stability, and can be more beneficial, especially in geriatric patients and other high-risk patients for lower limb surgeries.

9.
Indian J Anaesth ; 66(12): 842-848, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36654901

RESUMEN

Background and Aims: TheProSeal™ laryngeal mask airway (PLMA) and I-Gel™ are second-generation supraglottic airway devices (SADs). The Baska mask is a SAD having a non-inflatable cuff with a tendency to increase the perilaryngeal seal with an increase in airway pressures. This study compared the efficacy of I-Gel™, PLMA and Baska mask with respect to airway dynamics in patients scheduled for laparoscopic surgeries under general anaesthesia (GA). Methods: Ninety patients, of American Society of Anesthesiologists physical status I and II, aged 20-65 years scheduled for laparoscopic cholecystectomy under GA were enroled. The patients were randomised into three groups: Group P (n = 30): airway secured using PLMA, Group I (n = 30): airway secured using I-Gel™ and Group B (n = 30): airway secured using Baska mask. The primary outcome was the change in dynamic compliance, and the secondary outcomes included insertion time, changes in peak inspiratory pressure (PIP) and oropharyngeal leak pressure (OLP) at different time intervals. Results: After insertion of the SADs, the dynamic compliance was highest in group B and least in the group I (p = 0.01). The maximum decrease in dynamic compliance was observed in group I. The insertion time for SAD placement was more in group P. The group B had least PIP as compared to groups P, I at insertion. After carboperitonium, groups P and B had comparable PIP, and group I had highest PIP (p = 0.001). OLP was highest in group B, whereas group I had least OLP. Conclusion: The airway dynamics are better maintained with Baska mask as compared to the PLMA and I-Gel™.

12.
BMC Genomics ; 22(1): 307, 2021 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-33910515

RESUMEN

BACKGROUND: Night-soil compost (NSC) has traditionally been conserving water and a source of organic manure in northwestern Himalaya. Lately, this traditional method is declining due to modernization, its unhygienic conditions, and social apprehensions. Reduction in the age-old traditional practice has led to excessive chemical fertilizers and water shortage in the eco-sensitive region. In the current study, a bacterium has been analyzed for its safety, cold-adaptation, efficient degradation, and plant growth-promoting (PGP) attributes for its possible application as a safe bioinoculant in psychrotrophic bacterial consortia for improved night-soil composting. RESULTS: Glutamicibacter arilaitensis LJH19, a psychrotrophic bacterium, was isolated from the NSC of Lahaul valley in northwestern Himalaya. The strain exhibited amylase (186.76 ± 19.28 U/mg), cellulase (21.85 ± 0.7 U/mg), and xylanase (11.31 ± 0.51 U/mg) activities at 10 °C. Possessing efficient hydrolytic activities at low-temperature garners the capability of efficient composting to LJH19. Additionally, the strain possessed multiple PGP traits such as indole acetic acid production (166.11 ± 5.7 µg/ml), siderophore production (85.72 ± 1.06% psu), and phosphate solubilization (44.76 ± 1.5 µg/ml). Enhanced germination index and germination rate of pea seeds under the LJH19 inoculation further supported the bacterium's PGP potential. Whole-genome sequencing (3,602,821 bps) and genome mining endorsed the cold adaptation, degradation of polysaccharides, and PGP traits of LJH19. Biosynthetic gene clusters for type III polyketide synthase (PKS), terpene, and siderophore supplemented the endorsement of LJH19 as a potential PGP bacterium. Comparative genomics within the genus revealed 217 unique genes specific to hydrolytic and PGP activity. CONCLUSION: The physiological and genomic evidence promotes LJH19 as a potentially safe bio-inoculant to formulate psychrotrophic bacterial consortia for accelerated degradation and improved night-soil compost.


Asunto(s)
Compostaje , Genómica , Micrococcaceae , Desarrollo de la Planta , Suelo
13.
Front Microbiol ; 12: 626964, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33776957

RESUMEN

Cereal-based traditional fermented beverages (TFBs) are prevalent among India's ethnic community, and lugri is one such TFB popular among the tribal people of the Lahaul valley in North-Western Himalaya. Previous studies have reported that lugri harbors probiotics and contains amino acids and vitamins but comprehensive substrate-specific exploration of lugri for probiotic attributes is unexplored. The present study selected three substrate-based lugri (wheat, rice, and barley) to study their biochemical properties and explore potential probiotics. This study screened the best probiotic strains for antioxidant studies and the fermentative process. A biochemical analysis determined that rice-based lugri had a higher alcohol content, electric conductivity, crude protein, and lower pH than barley and wheat-based lugri. A total of 134 distinct morphotypes were screened, and 43 strains were selected based on their qualitatively superior acid and bile tolerance. Rice-based undistilled lugri harbored the most probiotics, with 22 out of 43 strains isolated. All 43 bacterial isolates exhibited properties like cell surface hydrophobicity, cell-auto aggregation, ß-galactosidase, and exopolysaccharide production, supporting them as possible probiotics. Based on antibiotic susceptibility, hemolytic activity, and biofilm formation, all the bacterial strains were found to be non-pathogenic. Taxonomically, they ranged among eight distinct genera and 10 different species. Statistically, 12 isolates were found to be the most promising probiotic, and eight strains were isolated from rice-based undistilled lugri. Furthermore, the antioxidant activity of the promising isolates was tested, based on free-radical scavenging ability toward 2,2-diphenyl-1-picrylhydrazyl (4.39-16.41%) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (15.29-57.74%). The strain Lacticaseibacillus paracasei LUL:01 showed the best antioxidant activity and probiotic attributes, and hence was used for the production of fermented milk. The strain LUL:01 fermented the sterile milk within 18 h, and the viable count remained above the legal requirement of 6 log10 CFU/ml during 28 days storage at 4°C. The strain represents a suitable candidate for applying probiotic functional food formulation with several health benefits.

14.
Genomics ; 113(3): 1448-1457, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33744342

RESUMEN

The medicinal herb, Picrorhiza kurroa Royle ex Benth has become endangered because of indiscriminate over-harvesting. Although micropropagation has been attempted for mass propagation of the plant, survival of in vitro plantlets under green house/open field poses a major challenge. Biopriming of micropropagated plantlets with plant growth-promoting rhizobacteria (PGPR) are among the successful methods to combat this problem. Serratia quinivorans PKL:12 was the best-characterized PGPR from rhizospheric soil of P. kurroa as it increased the vegetative growth and survival of the micropropagated plantlets most effectively. Complete genome (5.29 Mb) predicted genes encoding proteins for cold adaptation and plant growth-promoting traits in PKL:12. Antibiotic and biosynthetic gene cluster prediction supported PKL:12 as a potential biocontrol agent. Comparative genomics revealed 226 unique genes with few genes associated with plant growth-promoting potential. Physiological and genomic evidence supports S. quinivorans PKL:12 as a potential agent for bio-hardening of micropropagated P. kurroa plantlets in cold regions.


Asunto(s)
Picrorhiza , Plantas Medicinales , Genómica , Picrorhiza/genética , Picrorhiza/metabolismo , Plantas Medicinales/genética , Serratia
16.
J Clin Diagn Res ; 11(4): UC16-UC21, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28571239

RESUMEN

INTRODUCTION: The effect of adding dexmedetomidine (α2-adrenoceptor agonist) to local anaesthetics in brachial plexus blocks has been evaluated, however there has been no consensus regarding the ideal dose of dexmedetomidine. Without ultrasound axillary block has been considered as the safest approach for brachial block. AIM: To evaluate the efficacy of two doses of dexmedetomidine (0.5 µg/kg and 1 µg/kg) as an adjuvant to lignocaine in patients undergoing forearm surgeries under axillary brachial plexus block. MATERIALS AND METHODS: This prospective randomized controlled study was conducted on 104 adult patients, American Society of Anaesthesiologists (ASA) physical status 1 or 2. They were randomized and given following drug formulations, Group L (n=35) received 23 ml of 2% lignocaine with adrenaline + 7 ml of saline, Group LD0.5 (n=34) received 23 ml of 2% lignocaine with adrenaline + 0.5 µg/kg of dexmedetomidine diluted in saline to make a volume of 7 ml, Group LD1 (n=35) was given 23 ml of 2% lignocaine with adrenaline + 1 µg/kg of dexmedetomidine diluted in saline to make volume of 7 ml, the total volume of drug being 30 ml in each group and concentration of lignocaine 1.5%. The duration of postoperative analgesia and demand for rescue analgesia were the primary outcomes and block characteristics taken as secondary outcome. RESULTS: Sensory and motor block onset times were shorter in Group L than in group LD0.5, LD1 (p < 0.05). Sensory and motor blockade durations were longer in Group LD1, LD0.5 than Group L (p<0.01). Duration of analgesia was longer in Group LD1 than in group LD0.5 and least in Group L (p<0.05). CONCLUSION: Dexmedetomidine (0.5 µg/kg and 1 µg/kg) as an adjuvant in axillary brachial plexus increases the duration of postoperative analgesia and delays the requirement of first dose of analgesic in a dose dependent manner and 1 µg/kg seems to be the near ideal dose of dexmedetomidine as an adjuvant in axillary block.

17.
Int J Biol Macromol ; 96: 687-696, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28041915

RESUMEN

The complex pathophysiology involved in migraine necessitates the drug treatment to act on several receptors simultaneously. The present investigation was an attempt to discover the unidentified anti-migraine activity of the already marketed drugs. Shared featured pharmacophore modeling was employed for this purpose on six target receptors (ß2 adrenoceptor, Dopamine D3, 5HT1B, TRPV1, iGluR5 kainate and CGRP), resulting in the generation of five shared featured pharmacophores, which were further subjected to virtual screening of the ligands obtained from Drugbank database. Molecular docking, performed on the obtained hit compounds from virtual screening, indicated nystatin to be the only active lead against the receptors iGluR5 kainate receptor (1VSO), CGRP (3N7R), ß2 adrenoceptor (3NYA) and Dopamine D3 (3PBL) with a high binding energy of -11.1, -10.9, -10.2 and -12kcal/mole respectively. The anti-migraine activity of nystatin was then adjudged by fabricating its brain targeted chitosan nanoparticles. Its brain targeting efficacy, analyzed qualitatively by confocal laser scanning microscopy, demonstrated a significant amount of drug reaching the brain. The pharmacodynamic models on Swiss male albino mice revealed significant anti-migraine activity of the nanoformulation. The present study reports for the first time the therapeutic potential of nystatin in migraine management, hence opening avenues for its future exploration.


Asunto(s)
Encéfalo/efectos de los fármacos , Quitosano/química , Portadores de Fármacos/química , Trastornos Migrañosos/tratamiento farmacológico , Nanopartículas/química , Nistatina/química , Nistatina/farmacología , Animales , Bradiquinina/farmacología , Encéfalo/metabolismo , Evaluación Preclínica de Medicamentos , Liberación de Fármacos , Aseo Animal/efectos de los fármacos , Hiperalgesia/complicaciones , Masculino , Ratones , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/metabolismo , Simulación del Acoplamiento Molecular , Terapia Molecular Dirigida , Nistatina/metabolismo , Nistatina/uso terapéutico , Tamaño de la Partícula , Fotofobia/inducido químicamente , Fotofobia/complicaciones , Conformación Proteica , Programas Informáticos
18.
Environ Toxicol ; 31(7): 808-19, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25534813

RESUMEN

Deltamethrin (DLM) is a well-known pyrethroid insecticide used extensively in pest control. Exposure to DLM has been demonstrated to cause apoptosis in various cells. However, the immunotoxic effects of DLM on mammalian system and its mechanism is still an open question to be explored. To explore these effects, this study has been designed to first observe the interactions of DLM to immune cell receptors and its effects on the immune system. The docking score revealed that DLM has strong binding affinity toward the CD45 and CD28 receptors. In vitro study revealed that DLM induces apoptosis in murine splenocytes in a concentration-dependent manner. The earliest markers of apoptosis such as enhanced reactive oxygen species and caspase 3 activation are evident as early as 1 h by 25 and 50 µM DLM. Western blot analysis demonstrated that p38 MAP kinase and Bax expression is increased in a concentration-dependent manner, whereas Bcl 2 expression is significantly reduced after 3 h of DLM treatment. Glutathione depletion has been also observed at 3 and 6 h by 25 and 50 µM concentration of DLM. Flow cytometry results imply that the fraction of hypodiploid cells has gradually increased with all the concentrations of DLM at 18 h. N-acetyl cysteine effectively reduces the percentage of apoptotic cells, which is increased by DLM. In contrast, buthionine sulfoxamine causes an elevation in the percentage of apoptotic cells. Phenotyping data imply the effect of DLM toxicity in murine splenocytes. In brief, the study demonstrates that DLM causes apoptosis through its interaction with CD45 and CD28 receptors, leading to oxidative stress and activation of the mitochondrial caspase-dependent pathways which ultimately affects the immune functions. This study provides mechanistic information by which DLM causes toxicity in murine splenocytes. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 808-819, 2016.


Asunto(s)
Caspasas/efectos de los fármacos , Insecticidas/toxicidad , Mitocondrias/enzimología , Nitrilos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Piretrinas/toxicidad , Transducción de Señal/efectos de los fármacos , Bazo/efectos de los fármacos , Acetilcisteína/farmacología , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Glutatión/metabolismo , Sistema Inmunológico/efectos de los fármacos , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/inmunología , Simulación del Acoplamiento Molecular , Nitrilos/antagonistas & inhibidores , Piretrinas/antagonistas & inhibidores , Transducción de Señal/inmunología , Bazo/citología
19.
Eur J Med Chem ; 85: 147-78, 2014 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-25084143

RESUMEN

Malaria has emerged as a major health problem worldwide after the appearance of resistant strains of Plasmodium falciparum to the most of antimalarial drugs. The development of resistance by the parasite against first line as well as second line antimalarial drugs has drawn attention to develop new drugs to alleviate the disease burden. Therefore, there is a great need for new antimalarial drugs with improved attributes over older therapies. This review is primarily addressed to description of the recent advances in the synthesis of heterocyclic compound as antimalarial agents which can facilitate the development of more potent and effective antimalarial agents.


Asunto(s)
Antimaláricos/síntesis química , Técnicas de Química Sintética/métodos , Antimaláricos/química , Compuestos Heterocíclicos/química , Humanos
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