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1.
Artigo em Inglês | MEDLINE | ID: mdl-33632373

RESUMO

Due to their effective analgesic properties, opioids are worthy of consideration for pain management in rabbits. However,this class of drugs causes undesirable effects including reduced gastrointestinal (GI) motility, reduced fecal output, and delays GI transit times and thus increases the risk of GI stasis. The risk of stasis discourages the use of opioids in rabbits, which could affect animal welfare. Gastroprokinetic agents such as cisapride are effective in promoting gastric emptying in many species, but whether this effect occurs in rabbits is unknown. This study assessed the efficacy of cisapride when administered as a single agent and in combination with buprenorphine in rabbits; efficacy was assessed by measuring GI transit times, fecal output, body weight, and food and water intake. Female New Zealand White rabbits (n = 10) were studied in a crossover,randomized design and received either vehicle and buprenorphine, cisapride and saline, cisapride and buprenorphine, or vehicle and saline (control) every 8 h for 2 d. Rabbits were anesthetized and administered radio-opaque, barium-filled spheres via orogastric tube. Feces was assessed via radiography for detection of the barium-spheres to determine GI transit time. GI transit time was significantly longer in buprenorphine groups than in control groups, regardless of the use of cisapride. Fecaloutput and food and water intake were lower for buprenorphine groups than control groups. Cisapride did not significantlyalter GI transit, fecal output, or food and water intake. In addition, treatment group did not significantly affect body weight. In conclusion, buprenorphine treatment (0.03 mg/kg TID) prolonged GI transit time and reduced fecal output and food andwater consumption in rabbits. Coadministration of buprenorphine and cisapride (0.5 mg/kg) did not ameliorate these effects,and the administration of cisapride at this dose did not appear to affect GI motility in female rabbits.

2.
J AOAC Int ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33528003

RESUMO

BACKGROUND: Ceftazidime, a third-generation cephalosporin, is widely used in the treatment of lung infections, often given as "off-label" nebulization. There is need for developing a sensitive and robust analytical method to compute aerodynamic properties of ceftazidime following nebulization. OBJECTIVE: The current study entails development of a simple, accurate and sensitive high-performance liquid chromatography method (HPLC) for ceftazidime estimation, employing the principles of analytical quality-by-design (AQbD) and Monte Carlo simulations. METHODS: Selection of critical material attributes (CMAs) affecting method performance was accomplished by factor screening exercise. Subsequently, the influential CMAs, i.e., mobile phase ratio and flow rate, were systemically optimized using a face-centred cubic design for the chosen critical analytical attributes (CAAs). The factor relationship(s) between CMAs and CAAs was explored employing 3 D-response surface and 2 D-contour plots, followed by numerical as well as graphical optimization, for establishing the optimal chromatographic conditions. The obtained method operable design region was validated by Monte Carlo simulations for defect rate analysis. RESULTS: The optimized HPLC conditions for estimating ceftazidime were acetonitrile to acetic acid solution (75:25) as mobile phase at a flow rate of 0.7 mL/min, leading to Rt of 4.5 min and peak tailing ≤ 2. Validation studies, as per ICH Q2(R1) guidance's, demonstrated high sensitivity, accuracy and efficiency of the developed analytical method with LOD of 0.075 and LOQ of 0.227 µg/mL. Application of this chromatographic method was extrapolated for determining aerodynamic performance by nebulizing ceftazidime at flow rate of 15 L/min using next-generation impactor. The study indicated superior performance, sensitivity and specificity of the developed analytical system for quantifying ceftazidime. CONCLUSIONS: Application of AQbD approach, coupled with Monte Carlo simulations, aided in developing a robust HPLC method for estimation of ceftazidime per se and on various stages of impactor.

3.
J Nanobiotechnology ; 19(1): 19, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430888

RESUMO

BACKGROUND: Incidence of pulmonary aspergillosis is rising worldwide, owing to an increased population of immunocompromised patients. Notable potential of the pulmonary route has been witnessed in antifungal delivery due to distinct advantages of direct lung targeting and first-pass evasion. The current research reports biomimetic surface-active lipid-polymer hybrid (LPH) nanoparticles (NPs) of voriconazole, employing lung-specific lipid, i.e., dipalmitoylphosphatidylcholine and natural biodegradable polymer, i.e., chitosan, to augment its pulmonary deposition and retention, following nebulization. RESULTS: The developed nanosystem exhibited a particle size in the range of 228-255 nm and drug entrapment of 45-54.8%. Nebulized microdroplet characterization of NPs dispersion revealed a mean diameter of ≤ 5 µm, corroborating its deep lung deposition potential as determined by next-generation impactor studies. Biophysical interaction of LPH NPs with lipid-monolayers indicated their surface-active potential and ease of intercalation into the pulmonary surfactant membrane at the air-lung interface. Cellular viability and uptake studies demonstrated their cytocompatibility and time-and concentration-dependent uptake in lung-epithelial A549 and Calu-3 cells with clathrin-mediated internalization. Transepithelial electrical resistance experiments established their ability to penetrate tight airway Calu-3 monolayers. Antifungal studies on laboratory strains and clinical isolates depicted their superior efficacy against Aspergillus species. Pharmacokinetic studies revealed nearly 5-, 4- and threefolds enhancement in lung AUC, Tmax, and MRT values, construing significant drug access and retention in lungs. CONCLUSIONS: Nebulized LPH NPs were observed as a promising solution to provide effective and safe therapy for the management of pulmonary aspergillosis infection with improved patient compliance and avoidance of systemic side-effects.

4.
Food Chem ; 335: 127505, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32739823

RESUMO

Dysregulation of glucose homeostasis result in hyperglycemia and pigmented rice, unique combination of high quality starch and phenolics has the potential in regulating it. In this study, pigmented rice was characterized in terms of nutraceutical starch (NS) and phenolic content. Further the effect of rice phenolics on carbolytic enzyme inhibition, glucose uptake, hepatic glucose homeostasis and anti-glycation ability was analyzed in vitro. The most relevant effect on enzyme inhibition (α-amylase: IC50-42.34 µg/mL; α-glucosidase: IC50:63.89 µg/mL), basal uptake of glucose (>39.5%) and anti-glycation ability (92%) was found in red rice (RR), than black rice (BR). The role of RR phenolics in regulating glucose homeostasis was deciphered using hepatic cell line system, which found up-regulation of glucose transporter 2 (GLUT2) and glycogen synthase 2 (GYS2); while expression of gluconeogenic genes were found down regulated. To our knowledge this study is the first report validating the role of starch-phenolic quality towards anti-hyperglycemic effect of RR.


Assuntos
Glucose/metabolismo , Homeostase , Hiperglicemia/metabolismo , Fígado/metabolismo , Oryza/química , Proantocianidinas/análise , Amido/análise , Transporte Biológico/efeitos dos fármacos , Suplementos Nutricionais/análise , Inibidores de Glicosídeo Hidrolases/farmacologia , Homeostase/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fenol/análise , Fenol/farmacologia , alfa-Amilases/antagonistas & inibidores
5.
Physiol Plant ; 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33280130

RESUMO

The ATP-binding cassette (ABC) transporters belong to a large protein family predominantly present in diverse species. ABC transporters are driven by ATP hydrolysis and can act as exporters as well as importers. These proteins are localized in the membranes of chloroplasts, mitochondria, peroxisomes and vacuoles. ABC proteins are involved in regulating diverse biological processes in plants, such as growth, development, uptake of nutrients, tolerance to biotic and abiotic stresses, tolerance to metal toxicity, stomatal closure, shape and size of grains, protection of pollens, transport of phytohormones, etc. In mitochondria and chloroplast, the iron metabolism and its transport across the membrane are mediated by ABC transporters. Tonoplast-localized ABC transporters are involved in internal detoxification of metal ion; thus protecting against the DNA impairment and maintaining cell growth. ABC transporters are involved in the transport of secondary metabolites inside the cells. Microorganisms also engage a large number of ABC transporters to import and expel substrates decisive for their pathogenesis. ABC transporters also suppress the seed embryonic growth until favorable conditions come. This review aims at giving insights on ABC transporters, their evolution, structure, functions and roles in different biological processes for helping the terrestrial plants to survive under adverse environmental conditions. These specialized plant membrane transporters ensure a sustainable economic yield and high-quality products, especially under unfavorable conditions of growth. These transporters can be suitably manipulated to develop 'Plants for the Future'.

6.
Sci Total Environ ; : 143790, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33280861

RESUMO

In dairy grazing systems, livestock urine patches are hotspots that contribute to global warming, both directly through nitrous oxide (N2O) emissions, and indirectly, through nitrate leaching. However, under warm-dry temperate environments, N2O emission factors (EFs) have not been thoroughly evaluated, accounting for the influence of urinary nitrogen (N) concentration and urine volume, and emissions measurement approach through different urine application methods. Here we quantified and compared N2O emissions and EFs on a moderately well-drained sandy loam soil from urine patches established in naturally expanding effective area (NEEA), representing urine volumes of 2, 3 and 4 L m-2 (equivalent to urine -N loadings of 141, 211 and 282 kg N ha-1), and using the uniformly wetted area (UWA) with urine applied at 10 L m-2 (709 kg N ha-1), under two different soil moistures (below field capacity, BFC; field capacity, FC). The results showed that cumulative N2O emissions in the NEEA urine patches were 0.36-0.52 kg N2O-N ha-1 over 146 days (early-winter to late-spring). In the UWA urine patches, cumulative N2O emissions were 2.3 times higher at FC (1.96 kg N2O-N ha-1) than BFC (0.87 kg N2O-N ha-1). The EFs were similar between UWA (0.09%) and NEEA (0.07-0.10%) at BFC but were significantly higher (P < 0.05-0.1) in UWA (0.26%) than NEEA (0.09-0.16%) at FC. The EFs in NEEA were not affected by urine-N loadings under BFC and FC, ranging between 0.07 and 0.16%. The relatively high versus low urine-N loadings in NEEA enhanced pasture herbage and N-uptake responses under both soil moistures. However, there were no differences in apparent N-use efficiency (ranging from 27 to 39%) across the treatments. The EFs observed in this study are much lower than the existing Australian cattle urine annual EF of 0.4%, and further examination to determine a more accurate EF for the industry is required.

7.
Cells ; 10(1)2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33374255

RESUMO

Siglecs (sialic acid-binding immunoglobulin-like lectins) are single-pass cell surface receptors that have inhibitory activities on immune cells. Among these, Siglec-8 is a CD33-related family member selectively expressed on human mast cells and eosinophils, and at low levels on basophils. These cells can participate in inflammatory responses by releasing mediators that attract or activate other cells, contributing to the pathogenesis of allergic and non-allergic diseases. Since its discovery in 2000, initial in vitro studies have found that the engagement of Siglec-8 with a monoclonal antibody or with selective polyvalent sialoglycan ligands induced the cell death of eosinophils and inhibited mast cell degranulation. Anti-Siglec-8 antibody administration in vivo to humanized and transgenic mice selectively expressing Siglec-8 on mouse eosinophils and mast cells confirmed the in vitro findings, and identified additional anti-inflammatory effects. AK002 (lirentelimab) is a humanized non-fucosylated IgG1 antibody against Siglec-8 in clinical development for mast cell- and eosinophil-mediated diseases. AK002 administration has safely demonstrated the inhibition of mast cell activity and the depletion of eosinophils in several phase 1 and phase 2 trials. This article reviews the discovery and functions of Siglec-8, and strategies for its therapeutic targeting for the treatment of eosinophil- and mast cell-associated diseases.

8.
Indian Heart J ; 72(6): 547-551, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33357643

RESUMO

INTRODUCTION: Infective endocarditis (IE) is the most dreaded complication of intravenous drug abuse (IVDA). IVDA is present in significant proportions in India. Since there is scarcity of Indian data on IVDA associated IE, we report a study comparing IVDA to non IVDA associated IE. We compare differences in clinical profile, microbiology, echocardiography and clinical outcome from a tertiary care hospital. METHODS: A total of 133 patients admitted from 1st January 2017 to 31st December 2019 who met the Modified Duke ''definitive'' criteria for IE were included. Detailed Information was collected regarding demography, clinical data and laboratory investigations. All patients underwent transthoracic echocardiography and trans-esophageal echocardiogram wherever necessary. RESULTS: Among a total of 133 patients, 54 patients (40.6%) were iv drug abusers. Patients in IVDA-group were younger, mostly males, more likely to have concomitant HCV and HIV infections compared to non IVDA-group. Chronic comorbidities such as DM and CKD were more common in non IVDA-group. Rate of positive blood culture was higher in IVDA-group compared to non IVDA-group (74.1%v/s 32.9%,p < 0.001) with different microbiological profile. Percentage of Methicillin resistant staphylococcus aureus (42.6%v/s17.7%,p = 0.003) and pseudomonas related IE (18.5%v/s2.5%,p = 0.003) was significantly higher among IVDA-group. IVDA-group most commonly had tricuspid valve involvement Whereas mitral and aortic valve were most commonly involved valve in non IVDA-group. Mortality was slightly higher among IVDA-group compared to non IVDA-group, though statistically non-significant. Left sided valve involvement and Congestive heart failure were independent predictors of mortality. CONCLUSION: IVDA-IE is a significant problem in India. Demographic, microbiological and echocardiographic profile is quite different in IVDA and non IVDA-group. There is urgent need to conduct larger studies.

9.
Contemp Clin Trials Commun ; 20: 100664, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33145451

RESUMO

Background: Effectiveness and safety of pharmaceuticals is the prime concern of every osteoarthritis (OA) treatment. Chronic administration of NSAIDs, especially in case of geriatrics, through oral route tend to compromise the patient's safety, whereas topical treatments are not found to be effective owing their poor ability to deliver drug molecules.Thus, the present study deals with a randomized, double-blind, controlled trial conducted on patients with knee osteoarthritis (OA) for comparing the performance of a novel topical gel (liposomal gel) of diclofenac with a placebo and a marketed gel. Methods: The patients were treated and evaluated for 6 weeks as per the Western Ontario McMaster Universities (WOMAC) Index for OA. Patients were also observed for any adverse events. All the results were analyzed statistically using Kruskal-Wallis test, followed by Student's t-test at p ≤ 0.05. Results: Patients treated with liposomal gel showed statistically significantly improvements in treatment in comparison to the other tested formulations. All the treatments were found to be well tolerated with no report of adverse event. The results unequivocally demonstrated the superiority of the diclofenac liposomal gel, in the relieving the symptoms of OA of the knee, in comparison to placebo and marketed gel. Conclusion: From above results it was revealed that the drug in liposome have higher therapeutic potential. Thus, this can be a safe and effective option for the management of chronic OA especially for geriatric patients.

10.
Colloids Surf B Biointerfaces ; 197: 111429, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33130524

RESUMO

Bioactives are documented to exhibit diverse pharmacological activities, however, their low and inconsistent bioavailability primarily pose serious impediment against their potential therapeutic usage. Efforts, therefore, have been undertaken to systematically develop nanostructured lipidic carriers of chrysin, a vital flavonoid, employing Capmul PG-12 (i.e., liquid lipid), glyceryl monostearate (i.e., solid lipid), stearylamine, Phospholipid S-100 (i.e., cosurfactant) and Poloxamer 188 (i.e., surfactant). NLCs were formulated using hot-melt dispersion-high pressure homogenization method and optimized using Face-Centred Cubic Design. Afterwards, stearylamine was conjugated with biotin as ligand through EDC-NHS coupling reaction and biotin-staerylamine complex formation was ratified using H-1NMR and FTIR. It was further used instead of SA for the preparation of biotin-conjugated-optimized NLCs (Bio-NLCs). Mean particle size of consequent Bio-NLCs was found to be 246.4 nm and zeta potential as 11.4 mV. In vitro release studies indicated sustained drug release characteristics from NLCs over 48 h. Cell line studies conducted on coumarin6-loaded Bio-NLCs in demonstrated remarkably superior cellular uptake over naive NLCs and pure dye. Marked improvement in absorption parameters was observed during in vivo pharmacokinetics for Bio-NLCs and NLCs vis-à-vis pure chrysin suspension. However, the improvement for naive NLCs was relatively lower than that of Bio-NLCs. Almost 5.20-folds augmentation in Cmax (p < 0.005), 8.94-folds in AUC0-24 (p < 0.001), 7.46-folds in AUC0-∞ (p < 0.001) and 7.25-folds in Ka (p < 0.01), signify improved degree of drug absorption and retention of Bio-NLCs. Stability studies indicated the robustness of Bio-NLCs, when stored under refrigerated storage conditions for 3 months. By and large, the current work demonstrates high potential of Bio-NLCs for distinctly improved biopharmaceutical performance of chrysin.

11.
N Engl J Med ; 383(17): 1624-1634, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33085861

RESUMO

BACKGROUND: Eosinophilic gastritis and duodenitis are characterized by gastrointestinal mucosal eosinophilia, chronic symptoms, impaired quality of life, and a lack of adequate treatments. Mast-cell activity may contribute to the pathogenesis of the conditions. AK002 (lirentelimab) is an anti-Siglec-8 antibody that depletes eosinophils and inhibits mast cells and that has shown potential in animal models as a treatment for eosinophilic gastritis and duodenitis. METHODS: In this phase 2 trial, we randomly assigned adults who had symptomatic eosinophilic gastritis, eosinophilic duodenitis, or both conditions in a 1:1:1 ratio to receive four monthly infusions of low-dose AK002, high-dose AK002, or placebo. The primary end point was the change in gastrointestinal eosinophil count from baseline to 2 weeks after the final dose; to maximize statistical power, we evaluated this end point in the placebo group as compared with the combined AK002 group. Secondary end points were treatment response (>30% reduction in total symptom score and >75% reduction in gastrointestinal eosinophil count) and the change in total symptom score. RESULTS: Of the 65 patients who underwent randomization, 43 were assigned to receive AK002 and 22 were assigned to receive placebo. The mean percentage change in gastrointestinal eosinophil count was -86% in the combined AK002 group, as compared with 9% in the placebo group (least-squares mean difference, -98 percentage points; 95% confidence interval [CI], -121 to -76; P<0.001). Treatment response occurred in 63% of the patients who received AK002 and in 5% of the patients who received placebo (difference, 58 percentage points; 95% CI, 36 to 74; P<0.001). The mean change in total symptom score was -48% with AK002 and -22% with placebo (least-squares mean difference, -26 percentage points; 95% CI, -44 to -9; P = 0.004). Adverse events associated with AK002 were similar to those with placebo, with the exception of higher percentages of patients having mild-to-moderate infusion-related reactions with AK002 (60% in the combined AK002 group and 23% in the placebo group). CONCLUSIONS: In patients with eosinophilic gastritis or duodenitis, AK002 reduced gastrointestinal eosinophils and symptoms. Infusion-related reactions were more common with AK002 than with placebo. (Funded by Allakos; ENIGMA ClinicalTrials.gov number, NCT03496571.).


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Duodenite/tratamento farmacológico , Enterite/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Eosinófilos , Gastrite/tratamento farmacológico , Lectinas/antagonistas & inibidores , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos B/imunologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Duodenite/complicações , Enterite/complicações , Eosinofilia/complicações , Feminino , Gastrite/complicações , Trato Gastrointestinal/imunologia , Humanos , Infusões Intravenosas/efeitos adversos , Lectinas/imunologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Egypt Heart J ; 72(1): 70, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33064222

RESUMO

BACKGROUND: The COVID-19 pandemic brought restriction to the movement of people due to the implementation of lockdown across various regions around the world. In India, most of the patients belong to rural areas and hence were unable to come for a follow-up visit. Hence, we reached out to patients on oral anticoagulation using telemedicine with aim of communicating with the patient concerning drug compliance, titration of dose of anticoagulation, health education, and identification of high-risk patients needing referral to the nearest health facility/our institute. This study was conducted at the Hero DMC heart institute (a tertiary care center for cardiac diseases). The study design is cross-sectional and involves a comparison of the pre-COVID-19 phase with the COVID-19 phase. We asked a five-component (Likert scale) questionnaire from patients for satisfaction after the consult. All symptoms, need for hospitalization and clinical events were recorded. The events were compared in both groups. RESULTS: We contacted 628 patients through telemedicine and 600 patients gave consent for participation in the study. For comparison, we analyzed data of 614 patients in the pre-COVID-19 phase. The mean age during the pre-COVID-19 phase was 55.27 + 17.09 years and the COVID-19 phase was 56.97 + 15.09 years with males more than females in both groups. There was no significant difference in the number of patients on oral anticoagulants and novel oral anticoagulants (NOAC). However, there were higher number of  patients on antiplatelets in the pre-COVID phase (p value0.01). 37% in the pre-COVID-19 phase and 40.31 % in the COVID-19 phase were noted to have out of target range INR (International normalized ratio). There was no difference in the number of bleeding or thromboembolic events seen. Patient response as assessed by a questionnaire (Likert scale) showed that >75% of patients were satisfied. CONCLUSION: Through telemedicine, we were able to approach our patients on oral anticoagulation and achieved titration of anti-coagulation, and health education similar to pre-COVID-19 times. During pandemics, telemedicine offers a promising option for patient management with chronic cardiac conditions. It also provides us an opportunity for the management of patients on oral anticoagulation involving titration of drug dosages (anti-coagulation), identification of high-risk patients, and health education.

13.
Mol Microbiol ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068046

RESUMO

Several GntR/FadR transcriptional regulators govern sugar acid metabolism in bacteria. Although effectors have been identified for a few sugar acid regulators, the mode of effector binding is unknown. Even in the overall FadR subfamily, there are limited details on effector-regulator interactions. Here, we identified the effector-binding cavity in Escherichia coli DgoR, a FadR subfamily transcriptional repressor of D-galactonate metabolism that employs D-galactonate as its effector. Using a genetic screen, we isolated several dgoR superrepressor alleles. Blind docking suggested eight amino acids corresponding to these alleles to form a part of the effector-binding cavity. In vivo and in vitro assays showed that these mutations compromise the inducibility of DgoR without affecting its oligomeric status or affinity for target DNA. Taking Bacillus subtilis GntR as a representative, we demonstrated that the effector-binding cavity is similar among FadR subfamily sugar acid regulators. Finally, a comparison of sugar acid regulators with other FadR members suggested conserved features of effector-regulator recognition within the FadR subfamily. Sugar acid metabolism is widely implicated in bacterial colonization and virulence. The present study sets the basis to investigate the influence of natural genetic variations in FadR subfamily regulators on their sensitivity to sugar acids and ultimately on host-bacterial interactions.

14.
Glob Chang Biol ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068483

RESUMO

Despite increasing recognition of the critical role of coastal wetlands in mitigating climate change, sea-level rise, and salinity increase, soil organic carbon (SOC) sequestration mechanisms in estuarine wetlands remain poorly understood. Here, we present new results on the source, decomposition, and storage of SOC in estuarine wetlands with four vegetation types, including single Phragmites australis (P, habitat I), a mixture of P. australis and Suaeda salsa (P + S, habitat II), single S. salsa (S, habitat III), and tidal flat (TF, habitat IV) across a salinity gradient. Values of δ13 C increased with depth in aerobic soil layers (0-40 cm) but slightly decreased in anaerobic soil layers (40-100 cm). The δ15 N was significantly enriched in soil organic matter at all depths than in the living plant tissues, indicating a preferential decomposition of 14 N-enriched organic components. Thus, the kinetic isotope fractionation during microbial degradation and the preferential substrate utilization are the dominant mechanisms in regulating isotopic compositions in aerobic and anaerobic conditions, respectively. Stable isotopic (δ13 C and δ15 N), elemental (C and N), and lignin composition (inherited (Ad/Al)s and C/V) were not completely consistent in reflecting the differences in SOC decomposition or accumulation among four vegetation types, possibly due to differences in litter inputs, root distributions, substrate quality, water-table level, salinity, and microbial community composition/activity. Organic C contents and storage decreased from upstream to downstream, likely due to primarily changes in autochthonous sources (e.g., decreased onsite plant biomass input) and allochthonous materials (e.g., decreased fluvially transported upland river inputs, and increased tidally induced marine algae and phytoplankton). Our results revealed that multiple indicators are essential to unravel the degree of SOC decomposition and accumulation, and a combination of C:N ratios, δ13 C, δ15 N, and lignin biomarker provides a robust approach to decipher the decomposition and source of sedimentary organic matter along the river-estuary-ocean continuum.

15.
Dis Markers ; 2020: 5068067, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963636

RESUMO

6,12-Diphenyl-3,9-diazatetraasterane-1, 5, 7, 11-tetracarboxylate (DDTC) has been synthesized by the photodimerization of 4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate. The potential of theercvantitumor activity and mechanism were investigated in vitro using MTT assay in human lung cancer cell line A549, ovarian cancer cell lines SKOV3 and A2780, breast cancer cell line MCF-7, gastric cancer cell line BGC-823, colon cancer cell line HT29, prostate cancer cell line DU145, and liver cancer cell line SMMC7721. The results show that DDTC can inhibit the growth of ovarian cancer SKOV3 and A2780 cells. The best IC50 value is approximately 5.29 ± 0.38 and 4.29 ± 0.39 µM, respectively. DDTC induced the cell cycle arrest in the G2 phase by flow cytometric analysis. The migration and invasion of ovarian cancer SKOV3 and A2780 cells were inhibited by DDTC. DDTC could increase the expression protein level of E-cadherin in A2780 cells and ascend the expression protein and mRNA levels of E-cadherin in SKOV3 cells. DDTC could also decrease the protein and mRNA expression of EMT (epithelial-to-mesenchymal transition) markers of N-cadherin and Vimentin. mRNA and protein expression level of checkpoint kinase 1 (Chk1) were significantly increased and expressions of cyclin-dependent kinase (CDK1) and cell division cycle 25a (Cdc25a) were decreased in the SKOV3 and A2780 cell lines. Moreover, DDTC induced apoptosis by the cleavage and activation of caspase 3 and caspase 9.

16.
Chemosphere ; 254: 126863, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32957281

RESUMO

In urban set up, increasing combustion and processing activities have contaminated the air with toxic heavy metals which are generally enriched on atmospheric particulate matter. Vegetation around urban area act as a sink where such metal enriched particles generally deposit on the foliar surfaces, however, role of vegetation in uptake of metals adhered on the atmospheric particulate matter is yet not explored properly and is important to study to evaluate their role as bio-remediator. The undertaken work examines the foliar surface of Morus alba for its potential to deposit and accumulate atmospheric heavy metals. Further, to understand foliar uptake mechanism and translocation of atmospheric metal enriched on particulate matter a simulated experiment was conducted by labeling the known particle size (45 µm and 120 µm) with radio labeled 65Zn, applied on the tagged leaf with two particle loads, 25 mg and 50 mg. The study showed that owing to its rough foliar surface with trichomes and grooves, Morus alba efficiently trap heavy metal enriched particles and was capable of accumulating metals from particulate matter into different plant parts. It was recorded that 65Zn adhered on different size particles was taken up by tagged leaf of mulberry and majorly translocated to the lower stem and roots. It was also inferred from the study that both particle size and particle load significantly affect the foliar uptake and translocation of atmospheric heavy metal. The study focuses on the fact that urban avenue trees are capable of taking up atmospheric heavy metals and can play a crucial role in improving air quality.


Assuntos
Poluentes Atmosféricos/metabolismo , Morus/metabolismo , Material Particulado/farmacocinética , Zinco/farmacocinética , Poluentes Atmosféricos/farmacocinética , Poluição do Ar , Biodegradação Ambiental , Tamanho da Partícula , Material Particulado/análise , Material Particulado/química , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Traçadores Radioativos , Radioisótopos de Zinco/farmacocinética
17.
Sci Total Environ ; 740: 140403, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32927559

RESUMO

Waste amendments, such as steel slag and biochar, have been reported as a strategy for improving soil fertility, crop productivity, and carbon (C) sequestration in agricultural lands. However, information regarding the subsequent effects of steel slag and biochar on C cycling and the underlying microbial mechanisms in paddy soils remains limited. Hence, this study aimed to examine the effect of these waste amendments (applied in 2015-2017) on total soil CO2 emissions, total and active soil organic C (SOC) contents, and microbial communities in the early and late seasons in a subtropical paddy field. The results showed that despite the exogenous C input from these waste amendments (steel slag, biochar and slag + biochar), they significantly (P < 0.05) decreased total CO2 emissions (e.g., by 41.9-59.6% at the early season), compared to the control soil. These amendments also significantly (P < 0.001) increased soil salinity and pH. The increased soil pH had a negative effect (r = -0.37, P < 0.05) on microbial biomass C (MBC). The biochar and slag + biochar treatments (cf. control) significantly (P < 0.001) increased SOC contents in the both seasons. The amendments altered the soil microbial community structure that associated with soil C cycling: (1) all three amendments increased the relative abundance of Agromyces and Streptomyces, which was associated with higher soil pH (cf. control); and (2) biochar and slag + biochar treatments caused a higher relative abundance of Sphingomonas, which was supported by high SOC contents under those amendments. Overall, this study demonstrated that the steel slag and biochar amendments altered microbial community composition due to changes in key soil properties, such as salinity, pH and SOC contents, with implications for increasing soil C stocks while mitigating CO2 emissions in the paddy field.


Assuntos
Oryza , Solo , Dióxido de Carbono/análise , Carvão Vegetal , Microbiologia do Solo , Aço
18.
J Assoc Physicians India ; 68(10): 34-38, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32978923

RESUMO

Objective: Recent studies have shown that lower serum chloride is associated with diuretic resistance and increased mortality in heart failure. Impact of lower admission chloride on duration of stay in acute decompensated heart failure (ADHF) has not been studied previously. Methods: In this retrospective analysis, we studied the effect of admission serum chloride on the duration of hospital stay in patients admitted with ADHF. A total of 167 patients were studied. Serum chloride levels were divided into tertiles - <96 meq/L (tertile 1), 96-101 meq/L (tertile 2), and >101 meq/L (tertile 3) based on the distribution of serum chloride levels in our patients. Results: The median lengths of hospital stay in tertiles 1, 2, and 3 were 8(Interquartile range :6 -11), 7 (Interquartile range :5 -10.50), and 6 days(Interquartile range :4.25 - 8), respectively (p = 0.011). Admission serum chloride levels were inversely associated with duration of stay (R2 linear = 0.074, p = 0.001). On multiple linear regression analysis, serum chloride remained independent predictor of increased hospital stay (p=0.003) while association with serum sodium was not significant (p=0.07). 1 unit increase in chloride level was associated with 1.3% (p=0.003) decrease in hospital stay (95% CI: 2.2% to 0.5%). Conclusion: This retrospective analysis suggests that admission serum chloride levels are independently and inversely associated with increased duration of stay. This is independent of admission sodium levels. Thus serum chloride, rather than sodium, is an important poor prognostic marker in heart failure patients.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Hospitalização , Doença Aguda , Biomarcadores , Diuréticos , Humanos , Tempo de Internação , Prognóstico , Estudos Retrospectivos
19.
Crit Rev Ther Drug Carrier Syst ; 37(2): 135-159, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865903

RESUMO

Nail psoriasis is a chronic condition which causes pain and functional impairment; thus, it restricts the activities of daily living and worsens the quality of life. Different chemotherapeutic options are available for treating nail psoriasis such as systemic, intralesional, and topical therapies. However, current chemotherapy suffers from several limitations and to overcome them, new advancements are being made worldwide. Various reports have been published on current progress in the treatment of nail psoriasis such as clinical efficacy studies of novel antipsoriatic agents and novel formulation strategies for current chemotherapy. There are several novel nail formulations for the treatment of nail disorders, particularly onychomycosis, such as vesicular colloidal structure (liposomes, niosomes, transfersomes, ethosomes, etc.) and nonvesicular colloidal structures (nano-emulgel, nanocapsules, thermosensitive gel, etc.) These formulations can also prove beneficial for the treatment of nail psoriasis, and will be heavily explored in the near future. This review provides a brief introduction to the disease, its pathogenesis, and its treatment modalities. The review also throws light onto progress and future perspectives in nail psoriasis treatment.

20.
Crit Rev Ther Drug Carrier Syst ; 37(3): 229-269, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749139

RESUMO

Nanostructured drug delivery formulations have lately gained enormous attention, contributing to their systematic development. Issuance of quality by design (QbD) guidelines by ICH, FDA, and other federal agencies, in this regard, has notably influenced the overall development of drug products, enabling holistic product and process understanding. Owing to the applicability of QbD paradigms, a science lately christened as formulation by design (FbD) has been dedicated exclusively to QbD-enabled drug product development. Consisting of the principal elements of design of experiments (DoE), quality risk management (QRM), and QbD-enabled product comprehension as the fundamental tools in the implementation of FbD, a variety of drug nanocargos have been successfully developed with FbD paradigms and reported in the literature. FbD aims to produce novel and advanced systems utilizing nominal resources of development time, work effort, and money. A systematic FbD approach envisions the entire developmental path through pivotal milestones of risk assessment, factor screening and optimization (both using appropriate experimental designs), multivariate statistical and optimum search tools, along with response surface modeling, usually employing suitable computer software. The design space is one of the fundamental elements of FbD providing the most sought-after regulatory flexibility to pharma companies, postapproval. The present paper provides a bird's eye view of the fundamental aspects of FbD terminology, methodology, and applications in the development of a wide range of nanocargos, as well as a discussion of trends from both technological and regulatory perspectives.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Desenho de Fármacos , Nanoestruturas/química , Portadores de Fármacos/administração & dosagem , Composição de Medicamentos , Humanos , Nanoestruturas/administração & dosagem , Controle de Qualidade
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