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1.
Cureus ; 16(1): e52618, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38374850

RESUMO

OBJECTIVE:  Effect of the COVID-19 pandemic on knowledge, attitude, and practices toward antenatal care among antenatal women. DESIGN:  Prospective observational study. METHOD: After taking written and informed consent, 3000 term/near-term SARS CoV2-negative antenatal women admitted to the hospital for emergency were enrolled; excluding those in advance labour or critically ill. An interview was conducted and a knowledge, attitude, and practices (KAP) questionnaire was filled out based on verbatim answers. All women were then given individualized antenatal and postnatal care as per hospital protocols and discharged accordingly. The data obtained during the study was recorded on predesigned case proforma and analysed at the end of the study using the SPSS v. 23 software, after the application of appropriate statistical tests. MAIN RESULT: All women knew about the pandemic and its signs and symptoms along with precautions to be taken. Most of the women 2652 (88.4%) thought that they were at increased risk of contracting an infection during pregnancy and 2208 (73.6%) thought that coronavirus can harm the baby and will increase the risk of pregnancy. Awareness of nearby health facilities providing antenatal care was in 71.2% and 94% were aware of functional outpatient department services but only 1.4% were aware of teleconsultation services. About 2094 women have had any ANC visits. All of them knew that taking iron, Ca and vitamin supplements and getting an ultrasound and investigations were necessary but only 1524 (50.8%) took these supplements regularly, 1752 (58.4%) got their ultrasound done and 41.6% got investigations done. Two thousand four hundred thirty-six (81.2%) women had this fear that they would contract COVID-19 infection during their visit to the hospital. All the respondents of our study wanted to have hospital delivery and knew that it was necessary to have ANC registration and none of them wanted to have home delivery. CONCLUSION: Mastering correct knowledge will foster a positive attitude among antenatal women and will not only prevent disease transmission but also improve pregnancy outcomes.

2.
Cureus ; 15(11): e48208, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38050498

RESUMO

The ultrasound diagnosis of a fetal intra-abdominal cyst is typically established during the second or third trimester in the majority of cases. They primarily arise from the gastrointestinal or genitourinary system during the development of intra-abdominal structure and if isolated may resolve spontaneously. Enteric or enterogenous or enteric duplication cysts, which are congenital developments from the intestine, are most common. This case of an enterogenous cyst is presented because of its extreme rarity, its large size, and the need for prenatal intervention. Early identification and definitive treatment are necessary for proper management of this condition.

3.
Clin Cancer Res ; 29(21): 4331-4337, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37405396

RESUMO

In April 2022, the FDA approved axicabtagene ciloleucel (axi-cel) for adults with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. Approval was based on ZUMA-7, a randomized (1:1), open-label trial in 359 patients with primary refractory LBCL (74%) or early relapse who were transplant candidates. The study compared a single course of axi-cel to standard therapy, consisting of chemoimmunotherapy followed by high-dose therapy and autologous hematopoietic stem cell transplantation (HSCT) in responding patients. Overall, 94% of the experimental arm received chimeric antigen receptor (CAR) T-cell product, and 35% of the control arm received on-protocol HSCT. The primary endpoint was event-free survival, which was significantly longer in the axi-cel arm with an HR of 0.40 (95% confidence interval, 0.31-0.51; P value < 0.0001) and estimated median of 8.3 months, versus 2.0 months with standard therapy. Among 168 recipients of axi-cel, cytokine release syndrome occurred in 92% (Grade ≥ 3, 7%), neurologic toxicity in 74% (Grade ≥ 3, 25%), prolonged cytopenias in 33%, and fatal adverse reactions in 1.8%. This is the first FDA approval of a CAR T-cell therapy for LBCL in the second-line setting and reflects a potential paradigm shift.


Assuntos
Produtos Biológicos , Linfoma Difuso de Grandes Células B , Adulto , Humanos , Antígenos CD19 , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Aprovação de Drogas
4.
Heliyon ; 9(4): e14929, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37025911

RESUMO

Human Acclimatization and therapeutic approaches are the core components for conquering the physiological variations at high altitude (≥2500 m) exposure. The declined atmospheric pressure and reduced partial pressure of oxygen at high altitudes tend to decrease the temperature by several folds. Hypobaric hypoxia is a major threat to humanity at high altitudes, and its potential effects include altitude mountain sickness. On severity, it may lead to the development of conditions like high-altitude cerebral edema (HACE) or high-altitude pulmonary edema (HAPE) and cause unexpected physiological changes in the healthy population of travelers, athletes, soldiers, and low landers while sojourning at high altitude. Previous investigations have been done on long-drawn-out acclimatization strategies such as the staging method to prevent the damage caused by high-altitude hypobaric Hypoxia. Inherent Limitations of this strategy hamper the daily lifestyle and time consuming for people. It is not suitable for the rapid mobilization of people at high altitudes. There is a need to recalibrate acclimatization strategies for improving health protection and adapting to the environmental variations at high altitudes. This narrative review details the geographical changes and physiological changes at high altitudes and presents a framework of acclimatization, pre-acclimatization, and pharmacological aspects of high-altitude survival to enhance the government efficacy and capacity for the strategic planning of acclimatization, use of therapeutics, and safe de-induction from high altitude for minimizing the life loss. It's simply too ambitious for the importance of the present review to reduce life loss, and it can be proved as the most essential aspect of the preparatory phase of high-altitude acclimatization in plateau regions without hampering the daily lifestyle. The application of pre-acclimatization techniques can be a boon for people serving at high altitudes, and it can be a short bridge for the rapid translocation of people at high altitudes by minimizing the acclimatization time.

5.
Qual Manag Health Care ; 32(3): 170-176, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36940365

RESUMO

BACKGROUND AND OBJECTIVES: Close monitoring of patients in the first 2 hours after cesarean delivery (CD) is crucial. Delays in shifting of the post-CD patients led to a chaotic environment in the postoperative ward, suboptimal monitoring, and inadequate nursing care. Our aim was to increase the percentage of post-CD patients shifted from transfer trolley to bed within 10 minutes of arrival in the postoperative ward from a baseline of 64% to 100%, and to maintain that rate for more than 3 weeks. METHODS: A quality improvement team including physicians, nurses, and workers was constituted. Problem analysis revealed lack of communication among the caregivers as the main cause of delay. The percentage of post-CD patients shifted from trolley to bed within 10 minutes of being wheeled into the postoperative ward out of the total number of post-CD patients transferred from the operation theater to the postoperative ward was taken as the outcome indicator for the project. Multiple Plan-Do-Study-Act cycles based on the Point of Care Quality Improvement methodology were undertaken to achieve the target. Main interventions were: 1) written information of patient being transferred to operation theater for CD sent to the postoperative ward; 2) stationing of a duty doctor in the postoperative ward; and 3) keeping a buffer of 1 vacant bed in the postoperative ward. The data were plotted weekly as a dynamic time series chart and signals of change were observed. RESULTS: Eighty-three percent (172 out of 206) of women were shifted in time by 3 weeks. After Plan-Do-Study-Act 4, the percentages kept improving leading to a median shift from 85.6% to 100% after 10 weeks post-initiation of the project. Sustainment was confirmed by continuing observations for 6 more weeks to ensure that the changed protocol was assimilated in the system. We found that all women were shifted within 10 minutes of their arrival in postoperative ward from trolley to bed. CONCLUSION: Providing high-quality care to patients must be a priority for all health care providers. High-quality care is timely, efficient, evidence based, and patient-centric. Delays in transfer of postoperative patients to the monitoring area can be detrimental. The point of Care Quality Improvement methodology is useful and effective in solving complex problems by understanding and fixing the various contributory factors one by one. Reorganization of processes and available manpower without any extra investment in terms of infrastructure and resources is pivotal for long term success of a quality improvement project.


Assuntos
Hospitais , Melhoria de Qualidade , Humanos , Feminino , Qualidade da Assistência à Saúde , Pacientes
6.
Hematol Oncol Clin North Am ; 36(4): 687-699, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35773050

RESUMO

The recent progress in gene and gene-modified cellular therapies has shown great promise for numerous pediatric diseases. Nevertheless, the development of these products is complicated, and the regulatory pathway is rigorous. There are, however, several opportunities for programmatic support within the Food and Drug Administration. This article highlights the life cycle of product development through approval and many of the available resources and programs to support product development.


Assuntos
Aprovação de Drogas , Terapia Genética , Animais , Criança , Humanos , Estágios do Ciclo de Vida , Estados Unidos , United States Food and Drug Administration
7.
J Clin Oncol ; 40(30): 3501-3509, 2022 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-35613410

RESUMO

The approval of tisagenlecleucel and axicabtagene ciloleucel in 2017 marked a milestone in the development of oncology therapies. Since 2017, the breakthrough in treatment or even cure of previously intractable diseases represented by this new class of cancer treatments has continued with subsequent chimeric antigen receptor T (CAR T)-cell approvals. To date, the US Food and Drug Administration has approved five autologous CAR T-cell products for seven indications. A feature of autologous CAR T-cell products that differentiates them from traditional oncology drugs is that they need to be manufactured specifically for each patient. This feature has implications in study design, statistical analyses, and interpretation of study results. In this article, we share our experiences in the statistical review of CAR T-cell products and provide considerations for the design and statistical analyses of CAR T-cell trials. We also describe how the newly adopted estimand framework for clinical trials can help clarify nuanced issues in CAR T-cell trial design.


Assuntos
Produtos Biológicos , Receptores de Antígenos Quiméricos , Antígenos CD19/uso terapêutico , Produtos Biológicos/uso terapêutico , Humanos , Imunoterapia Adotiva/métodos , Receptores de Antígenos de Linfócitos T/uso terapêutico , Linfócitos T , Estados Unidos , United States Food and Drug Administration
8.
BMJ Open Qual ; 11(Suppl 1)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35545270

RESUMO

BACKGROUND: Antibiotic resistance is a global problem. Irrational use of antibiotics is rampant. Guidelines recommend administration of single dose of antibiotic for surgical antimicrobial prophylaxis (SSAP) for elective obstetrical and gynaecological surgeries. However, it is not usually adhered to in practice. Majority of women undergoing elective major gynaecological surgeries and caesarean sections in the department of obstetrics and gynaecology of our tertiary level heavy case load public health facility were receiving therapeutic antibiotics (for 7-10 days) instead of recommended SSAP. Our aim was to increase the SSAP in our setting from a baseline 2.1% to more than 60% within 6 months. METHODS: After root cause analysis, we formulated the departmental antimicrobial policy, spread awareness and sensitised doctors and nursing officers regarding antimicrobial resistance and asepsis through lectures, group discussions and workshops. We initiated SSAP policy for elective major surgeries and formed an antimicrobial stewardship team to ensure adherence to policy and follow processes and outcomes. The point of care quality improvement (QI) methodology was used. Percentage of patients receiving SSAP out of all low-risk women undergoing elective surgery was the process indicator and percentage of patients developing surgical site infection (SSI) of all patients receiving SSAP was the outcome indicator. The impact of various interventions on these indicators was followed over time with run charts. RESULTS: SSAP increased from a baseline 2.1%-67.7% within 6 months of initiation of this QI initiative and has since been sustained at 80%-90% for more than 2 years without any increase in SSI rate. CONCLUSION: QI methods can rapidly improve the acceptance and adherence to evidence-based guidelines in a busy public healthcare setting to prevent injudicious use of antibiotics.


Assuntos
Anti-Infecciosos , Ginecologia , Obstetrícia , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Antibioticoprofilaxia/métodos , Feminino , Humanos , Gravidez , Logradouros Públicos , Melhoria de Qualidade , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/prevenção & controle , Atenção Terciária à Saúde
9.
Clin Cancer Res ; 28(9): 1759-1764, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35046063

RESUMO

In March 2021, the FDA approved idecabtagene vicleucel, a chimeric antigen receptor T-cell therapy targeting the B-cell maturation antigen (BCMA), for adult patients with relapsed/refractory multiple myeloma (RRMM) after ≥4 lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 mAb. Approval was based on overall response rate (ORR), complete response (CR) rate, and duration of response (DOR) in 100 adult patients with RRMM treated with idecabtagene vicleucel in a single-arm trial. Patients received a single infusion of idecabtagene vicleucel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Of the 100 patients in the efficacy evaluable population, ORR was 72% [95% confidence interval (CI), 62-81] with stringent CR rate of 28% (95% CI, 19-38). After median follow-up of 10.7 months, median DOR was 11 months (95% CI, 10.3-11.4) in responders (partial response or better) and 19 months [95% CI, 11.4 months, not estimable (NE)] in patients who achieved stringent CR. Serious adverse reactions occurred in 67% of 127 patients evaluated for safety. Grade 3 or higher cytokine release syndrome and neurologic toxicities occurred in 9% and 4%, respectively, leading to a Risk Evaluation and Mitigation Strategy. Hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurred in 4%, with two fatalities. Prolonged cytopenia requiring hematopoietic rescue occurred in 2% (3/127), with two fatalities.


Assuntos
Imunoterapia Adotiva , Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Adulto , Antígeno de Maturação de Linfócitos B , Humanos , Imunoterapia Adotiva/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Receptores de Antígenos Quiméricos/uso terapêutico
10.
Front Plant Sci ; 11: 579037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123184

RESUMO

Priming is used to increase vigor, germination synchronization, seedling growth, and field establishment by advancing metabolic processes within seeds. Seed respiration is a good indicator of the metabolic processes that lead to transition toward germination. Onion seeds (cv. Pusa Ridhi) subjected to osmopriming (-1.5 MPa PEG6000 for 7 days), magnetopriming (100 mT for 30 min) and halopriming (150 mM KNO3 for 6 days), were evaluated at different times of imbibition to study the emergence index and respiration indices such as infrared thermal fingerprint, CO2 evolution rate, cytochrome c oxidase activity, and soluble sugars profile. Haloprimed seeds exhibited 42.5% higher emergence index as compared to unprimed control. Primed and unprimed seeds showed negative values for relative temperature (ΔT) (difference in temperature of seed and its immediate environment). Haloprimed seeds had the lowest values (-4.1 to -2.3°C) compared to other priming treatments over the germination period. Soluble sugars like raffinose, sucrose, glucose, and fructose contents were monitored and it was observed that en masse raffinose, glucose, and fructose levels were (17.5-59.9%) lower in haloprimed seeds over control. A positive correlation (r 2 = 0.504∗∗) was derived between the amount of these sugars and ΔT. Seed respiration, measured as CO2 evolution rate was more for haloprimed seeds that indicated that these soluble sugars were used as respiratory substrates. Significantly higher cytochrome c oxidase activity (40.7-89.8% and 12.5-66.6%) was observed in all primed seeds at 28 and 36 h, respectively. Among the various seed priming methods, halopriming proved to be the most effective priming treatment in onion seeds as evidenced by the higher respiration indices that resulted in faster metabolic rate and emergence index.

11.
Curr Top Med Chem ; 20(9): 770-781, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32108008

RESUMO

Alzheimer's disease (AD) is the most prevalent and severe neurodegenerative disease affecting more than 0.024 billion people globally, more common in women as compared to men. Senile plaques and amyloid deposition are among the main causes of AD. Amyloid deposition is considered as a central event which induces the link between the production of ß amyloid and vascular changes. Presence of numerous biomarkers such as cerebral amyloid angiopathy, microvascular changes, senile plaques, changes in white matter, granulovascular degeneration specifies the manifestation of AD while an aggregation of tau protein is considered as a primary marker of AD. Likewise, microvascular changes, activation of microglia (immune defense system of CNS), amyloid-beta aggregation, senile plaque and many more biomarkers are nearly found in all Alzheimer's patients. It was seen that 70% of Alzheimer's cases occur due to genetic factors. It has been reported in various studies that apolipoprotein E(APOE) mainly APOE4 is one of the major risk factors for the later onset of AD. Several pathological changes also occur in the white matter which include dilation of the perivascular space, loss of axons, reactive astrocytosis, oligodendrocytes and failure to drain interstitial fluid. In this review, we aim to highlight the various biological signatures associated with the AD which may further help in discovering multitargeting drug therapy.


Assuntos
Doença de Alzheimer/classificação , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Angiopatia Amiloide Cerebral/metabolismo , Placa Amiloide/metabolismo , Fatores Etários , Apolipoproteínas E/metabolismo , Axônios/metabolismo , Líquido Extracelular/metabolismo , Feminino , Genética , Sistema Glinfático/metabolismo , Humanos , Masculino , Microglia/metabolismo , Microvasos/metabolismo , Emaranhados Neurofibrilares/metabolismo , Oligodendroglia/metabolismo , Estresse Oxidativo , Agregação Patológica de Proteínas/metabolismo , Fatores Sexuais , Proteínas tau/metabolismo
12.
Blood Adv ; 3(23): 4002-4020, 2019 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-31809537

RESUMO

To address the global burden of sickle cell disease and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to patient-reported outcome, pain (non-patient-reported outcomes), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the end-organ considerations, measurement of cure, and low-resource settings panels as well as relevant findings and recommendations from the biomarkers panel.


Assuntos
Anemia Falciforme/fisiopatologia , Cardiopatias/etiologia , Pneumopatias/etiologia , Insuficiência Renal Crônica/etiologia , Cardiopatias/patologia , Humanos , Pneumopatias/patologia , Insuficiência Renal Crônica/patologia
13.
3 Biotech ; 9(5): 183, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31065483

RESUMO

Grain softness has been a major trait of interest in wheat because of its role in producing flour suitable for making high-quality biscuits, cookies, cakes and some other products. In the present study, marker-assisted backcross breeding scheme was deployed to develop advanced wheat lines with soft grains. The Australian soft-grained variety Barham was used as the donor parent to transfer the puroindoline grain softness gene Pina-D1a to the Indian variety, DBW14, which is hard grained and has PinaD1bPinbD1a genes. Foreground selection with allele-specific PCR-based primer for Pina-D1a (positive selection) was used to identify heterozygous BC1F1 plants. Background selection with 173 polymorphic SSR primers covering all the 21 chromosomes was also carried out, in the foreground-selected BC1F1 plants. BC1F2 plants were selected by ascertaining the presence of Pina-D1a (positive selection) and absence of Pina-D1b (negative selection). Using the approach of positive, negative and background selection with molecular markers, 15 BC1F2 and 31 BC2F1 plants were finally selected. The 15 BC1F2 plants were selfed and the 31 BC2F1 plants were further backcrossed and selfed to raise BC3F1 and BC2F2 progenies, respectively. A part of the BC2F2 seed of each of the 31 plants was analyzed for grain hardness index (GHI) with single-kernel characterization system. The GHI varied from 12.1 to 37.1 in the seeds borne on the 31 BC2F1 plants. The reasons for this variation and further course of action are discussed.

14.
J Food Sci Technol ; 56(4): 1696-1707, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30996405

RESUMO

The aim of this study was to screen Indian cultivated wheat varieties and list out the parameters/genes required to be improved for an end-product. Therefore, 30 Indian wheat varieties under cultivation by farmers were screened for 14 physico-chemical and rheological parameters, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) for high molecular weight glutenin subunits (HMW-GS), DNA based molecular markers for low molecular weight glutenin subunits (LMW-GS) and puroindolines (Pin) genes. Based on grain texture, sedimentation value, farinographic, alveographic, HMW-GS and LMW-GS and biscuit making parameters, HS490 was found to be a highly suited for biscuit and soft wheat products. HI1563 and DBW14 were also found to possess characteristics such as low protein, low to medium SDS-sedimentation value and combination of 2*, 7+8 and 2+12 (HMW-GS). DBW14 also had LMW alleles desirable for biscuit quality. DBW14 needs to be improved for grain softness to make it suitable for biscuit quality while both grain softness and LMW alleles need to be improved for HI1563 to improve its biscuit spread factor and alveographic indices for extensible gluten. Rest varieties showed moderate to very strong gluten but the gluten lacked extensibility. Only four varieties K307, DBW39, NI5439 and DBW17 possessed high flour protein and moderately strong gluten. They had more balanced deformation energy (W) and configuration ratio (P/L) combination suggestive of strong and extensible gluten needed for raised bread making. Marker assisted backcross breeding is suggested as solution to produce end-use specific varieties where appropriate alleles at only a few loci need to be incorporated.

15.
J Phys Chem B ; 122(45): 10306-10314, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30351107

RESUMO

The important cyclization reaction of antioxidant drug N-acetyl-l-cysteine (NAC) has been monitored in vitro at basic pH with the help of time series Raman spectroscopy. The thiazoline ring formation of NAC at acidic pH is a well-known reaction and has been studied extensively. However, the formation of a thiazolidine ring from NAC at basic pH has not been investigated precisely till date. The effect of basicity of the medium on the rate of cyclization has been investigated by studying the reaction at five different basic pH values. Raman signatures of cyclization have been observed with the passage of time and are found to appear faster as the basicity of the medium increases. Ab initio calculations have been done to understand the plausible mechanism of the reaction at basic pH. It is observed that formation of a thiazolidine ring from NAC occurs primarily in four steps, which involve proton abstraction from the thiol (SH) group of NAC and subsequent formation of an S-C bond by a nucleophilic attack of the C-S group on the protonated C-O-H group in NAC. Correlation of the theoretically calculated results with experimental Raman spectral analysis has led to a detailed and proper understanding of this important biochemical reaction.


Assuntos
Acetilcisteína/química , Antioxidantes/química , Tiazolidinas/síntese química , Ciclização , Concentração de Íons de Hidrogênio , Modelos Químicos , Análise Espectral Raman
16.
Spectrochim Acta A Mol Biomol Spectrosc ; 190: 177-180, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-28922644

RESUMO

The α and γ polymorphs of drug pyrazinamide have been detected with the help of temperature dependent Raman spectroscopic technique. Pyrazinamide is a very useful drug used for the treatment of tuberculosis (TB) and plays a significant role in destroying the dormant tubercle bacilli which are not destroyed by other common TB drugs. Temperature dependent Raman spectra suggest polymorphic phase change from α→γ form of pyrazinamide between 145 and 146°C. In situ Raman spectra of pyrazinamide between 145 and 146°C show the conversion of α→γ form by the shift in CO stretching vibration accompanied by several other changes. The phase change is characterized by the breaking of two linear NH⋯O type hydrogen bonds associated with CO stretching vibration in α dimer and formation of one linear NH⋯N type hydrogen bond along with a weak intramolecular CH⋯O type hydrogen bond in the γ dimer.


Assuntos
Modelos Moleculares , Pirazinamida/química , Teoria Quântica , Análise Espectral Raman , Temperatura , Dimerização , Conformação Molecular , Vibração , Difração de Raios X
17.
J Med Chem ; 59(7): 3418-26, 2016 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-27007481

RESUMO

The metabolic transformation of antirheumatic fluorescent drug leflunomide into its active metabolite teriflunomide through isoxazole ring opening has been monitored in vitro using steady state and time domain fluorescence spectroscopy and density functional theory. During metabolic reaction, absorption of leflunomide split into two bands resembling absorption spectra of teriflunomide. The fluorescence spectra reveal slow conversion of leflunomide to E and Z forms of teriflunomide in aqueous medium, which becomes faster at basic pH. The E form, which is more potent as a drug, becomes more stable with an increase in the basicity of the medium. Both molecules are associated with charge transfer due to twisting in the lowest singlet excited state. Excited state charge transfer followed by proton transfer was also observed in the Z form during the ring opening of leflunomide. Quantum yield and radiative decay rates have been observed to decrease for the metabolite because of an increase in nonradiative decay channels.


Assuntos
Crotonatos/química , Crotonatos/metabolismo , Fluorescência , Isoxazóis/química , Isoxazóis/metabolismo , Teoria Quântica , Toluidinas/química , Toluidinas/metabolismo , Antirreumáticos/química , Antirreumáticos/metabolismo , Hidroxibutiratos , Técnicas In Vitro , Leflunomida , Modelos Moleculares , Nitrilas , Prótons , Espectrometria de Fluorescência
18.
Life Sci ; 151: 330-338, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26979773

RESUMO

AIM AND MAIN METHOD: The medicinal properties of fermented papaya preparation (FPP) derived from Carica papaya fruit was investigated in order to determine its ability to modulate the progression of N-methyl-N-nitrosourea induced hepatocellular carcinoma in Balb/c mice. KEY FINDINGS: As well as reducing the physical symptoms associated with N-methyl-N-nitrosourea (MNU)-induced hepatocellular carcinoma, supplementation of Balb/c mice with 500mg FPP/kg BW for 92days normalized the blood cell count, led to an increased activity of several key antioxidant enzymes (SOD: +20%, CAT: +81%, GPx: +66.1%, GR: +54.4%; P<0.001 vs. MNU control), increased the ferrous reducing antioxidant potential (+36.7%, P<0.001 vs. MNU control) and reduced the extent of lipid peroxidation in the liver by 44.3% (P<0.001 vs. MNU control). SIGNIFICANCE: Results demonstrated the ability of FPP to preserve the integrity of liver against oxidative damage and protect hepatocytes against irreversible DNA structural modifications induced by MNU, highlighting its potential role as an immune-defense modulator during hepatocarcinoma.


Assuntos
Carica/química , Progressão da Doença , Fermentação , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Metilnitrosoureia , Preparações de Plantas/farmacologia , Preparações de Plantas/uso terapêutico , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Contagem de Células Sanguíneas , Frutas , Hemoglobinas/metabolismo , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Neoplasias Hepáticas Experimentais/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Preparações de Plantas/química
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 154: 200-206, 2016 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-26529636

RESUMO

Study of copper complex of creatinine and urea is very important in life science and medicine. In this paper, spectroscopic and structural study of a newly synthesized heteroligand complex of copper with creatinine and urea has been discussed. Structural studies have been carried out using DFT calculations and spectroscopic analyses were carried out by FT-IR, Raman, UV-vis absorption and fluorescence techniques. The copper complex of creatinine and the heteroligand complex were found to have much increased water solubility as compared to pure creatinine. The analysis of FT-IR and Raman spectra helps to understand the coordination properties of the two ligands and to determine the probable structure of the heteroligand complex. The LIBS spectra of the heteroligand complex reveal that the complex is free from other metal impurities. UV-visible absorption spectra and the fluorescence emission spectra of the aqueous solution of Cu-Crn-urea heteroligand complex at different solute concentrations have been analyzed and the complex is found to be rigid and stable in its monomeric form at very low concentrations.


Assuntos
Complexos de Coordenação/química , Cobre/química , Creatinina/análogos & derivados , Ureia/análogos & derivados , Complexos de Coordenação/síntese química , Creatinina/síntese química , Ligantes , Modelos Moleculares , Teoria Quântica , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman , Ureia/síntese química
20.
Food Funct ; 7(1): 594-609, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26574664

RESUMO

The hepatoprotective potential of edible mushrooms from Mauritius, namely Pleurotus sajor-caju and Agaricus bisporus was evaluated using an N-methyl-N-nitrosourea (MNU)-induced hepatocarcinogenesis Balb/c mice model. Mushroom extracts restored normal weight in MNU treated mice over a 3 month supplementation period. Blood parameter analyses indicated a clear modulation of hemoglobin concentration, leukocyte, platelet, lymphocyte, neutrophil, monocyte and eosinophil counts in MNU-induced mice (p < 0.05). Mushroom extract supplementation effectively reduced oxidative damage in MNU-primed mice, which was marked by a significant decrease in the extent of lipid peroxidation (p < 0.05) and a concomitant increase in the enzymatic antioxidant levels, primarily catalase, superoxide dismutase, glutathione reductase and peroxidase, and FRAP values (p < 0.05). DNA protective effects of the extracts were confirmed by Raman spectroscopy, where, the MNU-DNA interaction, as evidenced by an intense peak at 1254 cm(-1), was normalized. The findings demonstrate hepatoprotective, immunomodulatory and anti-carcinogenic effects and suggest the use of mushrooms as potential dietary prophylactics in cancer chemoprevention.


Assuntos
Agaricales/química , Antineoplásicos/uso terapêutico , Carcinogênese/induzido quimicamente , Neoplasias Hepáticas/induzido quimicamente , Metilnitrosoureia/toxicidade , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória
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