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PURPOSE OF REVIEW: The purpose of this review is to describe key pharmacologic considerations to inform strategies in drug development for pediatric cancer. RECENT FINDINGS: Main themes that will be discussed include considering patient specific factors, epigenetic/genetic tumor context, and drug schedule when optimizing protocols to treat pediatric cancers. SUMMARY: Considering these factors will allow us to more effectively translate novel targeted therapies to benefit pediatric patients.
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Antineoplásicos , Neoplasias , Criança , Humanos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Desenvolvimento de Medicamentos , Terapia de Alvo Molecular/métodosRESUMO
BACKGROUND: Management of head and neck cancers requires a multidisciplinary approach where surgery followed by radio and chemotherapy is the mainstay of treatment. The above-mentioned treatment can cause mucositis, a severely debilitating side effect. This can have a significant impact on quality of life. A recent advancing mode of drug delivery is the bioadhesive system. This interacts with mucosa by adhering to it and thereby improving the efficacy of the therapeutic agent delivered. AIM AND OBJECTIVE: The purpose of this systematic review is to evaluate the effectiveness of bioadhesives in reducing oral mucositis and relieving pain associated with mucositis in head and neck cancer patients receiving radio-chemotherapy. MATERIALS AND METHOD: Studies assessing the effectiveness of bioadhesives for the treatment of radiation-induced oral mucositis were retrieved from specialized databases (PubMed/MEDLINE, Scopus, ProQuest, Google Scholar, LILACS, OpenGrey) as well as institutional repositories. Data on incidence, pain reduction, resolution, and improvement of oral mucositis using bioadhesive were compiled. A Cochrane tool was used for randomized controlled trials and a JBI tool for non-randomized controlled trials and observational studies to assess the quality of included studies. Based on the eligible study data, a meta-analysis was conducted with STATA version 16, 2019 software, and 95% confidence intervals and p values greater than 0.05. RESULTS: A total of 15 studies were included which assessed the effectiveness of bioadhesives in managing mucositis and its associated pain. Studies included in the review described either reduction, resolution, or incidence of oral mucositis respectively. A total of three meta-analyses were conducted to assess the incidence of oral mucositis and the pain associated with it, as well as the reduction in incidence. Bioadhesives showed statistically significant differences in the incidence of severe mucositis (p = 0.04). A meta-analysis comparing bioadhesives efficacy in reducing mucositis and pain associated with it found no statistically significant differences (p = 0.36). CONCLUSION: Bioadhesives are emerging as a novel drug delivery method for treating radio-chemotherapy-induced oral mucositis because of their rapid absorption and easy application. Regardless of its benefits, clinical trials comparing it with conventional treatment methods are necessary to assess its efficacy in treating oral mucositis.
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Neoplasias de Cabeça e Pescoço , Mucosite , Estomatite , Humanos , Qualidade de Vida , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Dor/etiologiaRESUMO
Background: The imaging of brain tumours has significantly improved with the use of advanced magnetic resonance (MR) techniques like diffusion tensor imaging (DTI). This study was conducted to analyse the utility of DTI-derived tensor metrics in the evaluation of intracranial gliomas with histopathological correlation and further adoption of these image-data analyses in clinical setting. Methods: A total of 50 patients with suspected diagnosis of intracranial gliomas underwent DTI along with conventional MR examination. The study correlated various DTI parameters in the enhancing part of the tumour and the peritumoral region with the histopathological grades of the intracranial gliomas. Results: The study revealed higher values of Cl (linear anisotropy), Cp (planar anisotropy), AD (axial diffusivity), FA (fractional anisotropy) and RA (relative anisotropy) and lower values of Cs (spherical anisotropy), MD (mean diffusivity) and RD (radial diffusivity) in the enhancing part of the tumour in case of high-grade gliomas. However, in the peritumoral region, the values of Cl, Cp, AD, FA and RA were less whereas values of Cs, MD and RD were more in high-grade gliomas than in the low-grade gliomas. The various cutoff values of these DTI-derived tensor metrics were found to be statistically significant. Conclusion: DTI-derived tensor metrics can be a valuable tool in differentiation between high-grade and low-grade gliomas which might be accepted in clinical practice in near future.
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PURPOSE: Alignment errors in medial unicompartmental knee arthroplasty (UKA) predispose to premature implant loosening and polyethylene wear. The purpose of this study was to determine whether a novel CT-free robotic surgical assistant improves the accuracy and reproducibility of bone resections in UKA compared to conventional manual instrumentation. METHODS: Sixty matched cadaveric limbs received medial UKA with either the ROSA® Partial Knee System or conventional instrumentation. Fifteen board-certified orthopaedic surgeons with no prior experience with this robotic application performed the procedures with the same implant system. Bone resection angles in the coronal, sagittal and transverse planes were determined using optical navigation while resection depth was obtained using calliper measurements. Group comparison was performed using Student's t test (mean absolute error), F test (variance) and Fisher's exact test (% within a value), with significance at p < 0.05. RESULTS: Compared to conventional instrumentation, the accuracy of bone resections with CT-free robotic assistance was significantly improved for all bone resection parameters (p < 0.05), other than distal femoral resection depth, which did not differ significantly. Moreover, the variance was significantly lower (i.e. fewer chances of outliers) for five of seven parameters in the robotic group (p < 0.05). All values in the robotic group had a higher percentage of cases within 2° and 3° of the intraoperative plan. No re-cuts of the proximal tibia were required in the robotic group compared with 40% of cases in the conventional group. CONCLUSION: The ROSA® Partial Knee System was significantly more accurate, with fewer outliers, compared to conventional instrumentation. The data reported in our current study are comparable to other semiautonomous robotic devices and support the use of this robotic technology for medial UKA. LEVEL OF EVIDENCE: Cadaveric study, Level V.
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Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Procedimentos Cirúrgicos Robóticos , Artroplastia do Joelho/métodos , Cadáver , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Reprodutibilidade dos Testes , Procedimentos Cirúrgicos Robóticos/métodosRESUMO
BACKGROUND: Intensive Care Unit (ICU) readmissions during the same hospitalization are associated with increased hospital stays, morbidity and mortality. Whereas mortality rates in patients admitted to the ICU for the first time may range from 10 to 20% depending on various factors, readmission mortality rates can be up to 50 to 70%. Factors leading to readmission in ICU in Indian Armed Forces Hospitals have not been well studied till date. METHODS: This was a record based cross sectional descriptive study conducted at the ICU of a tertiary care Armed Forces hospital. Demographic and clinical data of ICU patients were analysed. ICU admission and discharge data for the duration of last three years were acquired from admission and discharge registers and Hospital Informatics system (HIS) software. The primary outcome was readmission rates to ICU during the same hospitalization. Secondary outcomes included diagnosis at time of index admission (first time admission) to ICU and at readmission, multiple readmissions to ICU and mortality rates in readmitted patients. RESULTS: There were 3021 admissions to the ICU during the study period. 422 patients succumbed to illness during initial admission resulting in a mortality rate of 14%. 198 patients were readmitted to the ICU. The readmission rate to the ICU was 7.8%. The mortality rate in readmitted patients was 31% as compared to the ICU mortality rate of 14%. The triggering factors for readmission were usually respiratory or cardiac decompensations. CONCLUSION: Readmission to ICU occurred in about 7.8 % of all ICU patients in our study. ICU readmissions increase the risk of adverse outcomes. Objective measures in the form of a discharge protocol incorporating the stability and work index for transfer (SWIFT Score) may help minimizing readmission to ICU. Such protocols must be in place while shifting any patients from ICU so as to improve outcomes in patients of tertiary care hospitals.
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Alta do Paciente , Readmissão do Paciente , Estudos Transversais , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção TerciáriaRESUMO
Although the roles of irisin and visfatin have been well established in diabetes mellitus, there are limited studies about their association in diabetic nephropathy. The present study was designed to assess the levels of irisin and visfatin and their association with the severity of diabetic nephropathy. 43 diabetic nephropathy cases and 43 diabetic subjects without nephropathy were enrolled in the study. Serum levels of irisin and visfatin were compared in both the groups. Irisin and visfatin were significantly increased in diabetic nephropathy cases when compared with diabetes subjects without nephropathy. eGFR was negatively correlated with visfatin (r = -0.323, p = 0.034), irisin (r = -0.324, p = 0.034), urine albumin (r = -0.443, p = 0.003) and albumin creatinine ratio (r = -0.419, p = 0.005) in patients with diabetic nephropathy. Visfatin was significantly elevated in stage IV nephropathy compared with stage III nephropathy. We conclude that irisin and visfatin are elevated in diabetic nephropathy and can be an index of its severity.
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Type 1 diabetes (T1D) that accounts for about 5-10 % of all diabetes cases results from the autoimmune destruction of the insulin-producing beta cells in the pancreas. It is characterized by severe inflammatory reaction mediated by pronounced T helper type-1 response. Parasitic infections having the ability to skew the host immune responses towards type-2 type as a part of their defense mechanism are able to induce protection against autoimmune diseases like T1D. Hence, the present study is undertaken to explore a recombinant abundant larval transcript protein of the human lymphatic filarial parasite Brugia malayi (rBmALT-2), a known anti-inflammatory molecule for its therapeutic effect on streptozotocin (STZ)-induced T1D in mice. The diabetic mice on treatment with rBmALT-2 showed a significant (p < 0.0005) decrease in their fasting blood glucose levels. By the end of the second week after the initiation of treatment with the rBmALT-2, 28 % of the diabetic mice became normal and none of them were diabetic by the end of 5th week. The anti-diabetic effect of rBmALT-2 significantly correlated with the concomitant redressal of the pancreatic histopathological damage caused by STZ assault (rho = 0.87; p < 0.0005). The sera of rBmALT-2 treated diabetic mice had increased levels of IgG1 antibodies associated with decreased IgG2a antibodies against the principal autoantigen insulin. The splenocyte proliferative response and the cytokine release in the treated mice showed marked bias against inflammation skewing the immune response to Th-2 type. From this study, it can be envisaged that that filarial proteins like rBmALT-2 with effective immunomodulatory activity and anti-diabetic effect are promising alternative therapeutic agents for T1D.
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Pregnancy-induced hypertension (PIH) has been reported as a cardiovascular (CV) risk. We assessed the sympathovagal imbalance (SVI) and the association of inflammation and oxidative stress (OS) with CV risks in PIH. A total of 125 pregnant women having a risk factor for PIH were followed till term and the incidence of PIH was observed. Retrospectively, they were divided into two groups: Group I (those who did not develop PIH, n = 82) and Group II (those who developed PIH, n = 43). Blood pressure variability (BPV) parameters including baroreflex sensitivity (BRS), spectral heart rate variability (HRV), autonomic function tests (AFTs), inflammatory markers (interleukin-6, TNF-α, interferon-γ), and OS markers were measured in both the groups. Alterations in parasympathetic and sympathetic components of AFTs were analyzed. Link of various parameters to BRS was assessed by correlation and multiple regression analysis. Parasympathetic components of AFTs were decreased from the early part of pregnancy and sympathetic components were increased toward the later part of pregnancy. Decreased BRS, the marker of CV risk, was more prominent in Group II subjects. Independent contribution of interleukin-6 (ß = 0.276, P = 0.020), TNF-α (ß = 0.408, P = 0.002), interferon-γ (ß = 0.355, P = 0.008), and thiobarbituric-acid reactive substance (ß = 0.287, P = 0.015) to BRS was found to be significant. It was concluded that sympathetic overactivity that develops more in the later part (third trimester) of pregnancy contributes to SVI and genesis of PIH. In PIH women, CV risks are present from the beginning of pregnancy that intensifies in the later part of pregnancy. Retrograde inflammation and oxidative stress contribute to the decreased BRS in PIH.
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Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Hipertensão Induzida pela Gravidez/fisiopatologia , Inflamação/sangue , Estresse Oxidativo , Nervo Vago/fisiopatologia , Adulto , Biomarcadores/sangue , Citocinas/sangue , Feminino , Humanos , Hipertensão Induzida pela Gravidez/metabolismo , Inflamação/fisiopatologia , Gravidez , Fatores de RiscoRESUMO
A feeding trial was designed to assess the effect of super dosing of phytase in corn-soya-based diets of broiler chicken. One hundred and sixty-eight day-old broilers were selected and randomly allocated to four dietary treatment groups, with 6 replicates having 7 chicks per treatment group. Two-phased diets were used. The starter and finisher diet was fed from 0 to 3 weeks and 4 to 5 weeks of age respectively. The dietary treatments were consisted of normal phosphorus (NP) group without any phytase enzyme (4.5 g/kg available/non-phytin phosphorus (P) during starter and 4.0 g/kg during finisher phase), three low-phosphorus (LP) groups (3.2 g/kg available/non-phytin P during starter and 2.8 g/kg during finisher phase) supplemented with phytase at 500, 2500, 5000 FTU/kg diet, respectively, to full fill their phosphorus requirements. The results showed that super doses of phytase (at 2500 FTU and 5000 FTU/kg) on low-phosphorus diet improved feed intake, body weight gain, ileal digestibility (serine, aspartic acid, calcium, phosphorus), blood P levels and bone minerals such as calcium (Ca), P, magnesium (Mg) and zinc (Zn) content. It could be concluded that super doses of phytase in low-phosphorus diet were beneficial than the normal standard dose (at 500 FTU/kg) of phytase in diet of broiler chicken.
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6-Fitase/farmacologia , Ração Animal/análise , Densidade Óssea/efeitos dos fármacos , Galinhas/crescimento & desenvolvimento , Glycine max/química , Zea mays/química , 6-Fitase/administração & dosagem , Fenômenos Fisiológicos da Nutrição Animal , Animais , Cálcio da Dieta/administração & dosagem , Cálcio da Dieta/metabolismo , Galinhas/fisiologia , Dieta/veterinária , Relação Dose-Resposta a Droga , Feminino , Masculino , Fósforo na Dieta/administração & dosagem , Fósforo na Dieta/metabolismoRESUMO
OBJECTIVES: Increased fructose consumption causes dyslipidemia and fatty liver in postmenopausal women, both independent risk factors for cardiovascular disease. This study explored the potential mechanisms by which amla (Emblica officinalis) reduced hypercholesterolemia and hypertriglyceridemia and prevented fatty liver in a fructose-fed, ovariectomized rat model of menopause. METHODS: Sham-operated and ovariectomized rats were put on a chow or high fructose diet. They were further divided into groups with or without amla. After 18 weeks of treatment, livers were harvested and subjected to Western blot and histological analyses. RESULTS: In all groups, amla increased the protein expression of liver farnesoid X receptor (FXR) and liver X receptor (LXR), key proteins involved in lipid metabolism. Fructose-fed rats developed fatty liver and amla prevented this. Here amla produced an exceptional rise in LXR and insulin-induced gene-2 (Insig-2) which prevented the maturation of sterol regulatory element-binding protein-1 and steroyl CoA desaturase-1, responsible for triglyceride synthesis. Amla also increased the protein expression of ATP binding cassette transporter A1 (ABCA1), involved in high density lipoprotein (HDL) synthesis as well as low density lipoprotein receptor (LDLR) responsible for uptake of LDL cholesterol. Besides this, amla increased the protein expression of peroxisome proliferator activated receptor α (PPARα) involved in ß oxidation of fatty acids. CONCLUSIONS: Amla increased the protein expression of liver FXR, LXRα, PPARα and their downstream proteins Insig-2, ABCA1 and LDLR. This property of amla to modulate some of the key proteins involved in lipid metabolism promises its usefulness as a preventive agent for dyslipidemia and hepatic steatosis.
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Fígado Gorduroso/prevenção & controle , Frutose/administração & dosagem , Receptores Nucleares Órfãos/fisiologia , Phyllanthus emblica/química , Extratos Vegetais/administração & dosagem , Receptores Citoplasmáticos e Nucleares/fisiologia , Animais , Modelos Animais de Doenças , Ácido Graxo Sintases/metabolismo , Fígado Gorduroso/induzido quimicamente , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/análise , Fígado/química , Fígado/patologia , Receptores X do Fígado , Menopausa , Tamanho do Órgão/efeitos dos fármacos , Receptores Nucleares Órfãos/análise , Ovariectomia , Ratos , Ratos Wistar , Receptores Citoplasmáticos e Nucleares/análise , Proteína de Ligação a Elemento Regulador de Esterol 1/análiseRESUMO
Consumption of aflatoxin B1 (AFB1) contaminated feed by poultry affects the health of broiler birds causing severe economic losses. The use of phytochemicals is a safe, effective, alternative and practical approach to combat the toxic effect of AF in broilers. Resveratrol, a polyphenol derived from red grapes, berries and peanuts, exerts anti-inflammatory, antioxidant and immunomodulatory effects. Our study was aimed at evaluating the possible protective effects of resveratrol against the adverse effects of AFB1 in broiler birds. A feeding trial of 42 days of duration was undertaken in a completely randomized design with five dietary treatments: G1-AFB1(1.0 ppm); G2-CTR (basal diet alone); G3-AFB1(1.0 ppm)+Resv 0.5%; G4-AFB1(1.0 ppm)+Resv 1%; and G5-Resv 1%. Gain in body weight (BWG) and feed intake (FI) was observed to be highest (p < 0.05) in the AFB1 birds followed by the control group. Feed conversion ratio was lowest in G2-CTR birds and failed to record any significant variation (p > 0.05) between groups as well as within groups. Birds fed resveratrol at both 0.5% and 1.0% levels in combination with AFB1 as well as alone along with basal diet had lower BWG and FI between the fourth and fifth week and also at the fifth week (p < 0.05). No variation (p > 0.05) was obtained in the FCR of AFB1 and resveratrol group of broiler birds. AFB1 feeding significantly increased the activities of aspartate-(AST) and alanine-(ALT) amino transferase, superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.05) but lowered glucose, cholesterol and triglyceride levels in serum. Supplementation of resveratrol helped in increasing the activities of the oxidative enzymes and in improving the plasma total antioxidant capacity (TAOC) and total protein (TP) significantly (p < 0.05) and protein values. The livers of AFB1 group showed degeneration of hepatocytes, bile duct hyperplasia and microgranuloma formation. In resveratrol supplemented birds, the severity and degree of the liver lesions was far less. Apoptotic proteins failed to show any variation in expression between AFB1, control and resveratrol group of birds. The inclusion of resveratrol in broiler diets enhanced antioxidant status of birds indicating the protective effect of resveratrol against AFB1-induced toxicity. So, we advice use of resveratrol as a feed additive to control aflatoxicosis in poultry farms.
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Aflatoxina B1/toxicidade , Doenças das Aves Domésticas/induzido quimicamente , Estilbenos/farmacologia , Ração Animal/análise , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Biomarcadores/sangue , Galinhas , Dieta/veterinária , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Doenças das Aves Domésticas/prevenção & controle , Resveratrol , Estilbenos/administração & dosagem , Aumento de Peso/efeitos dos fármacosRESUMO
It is known that there is a significant interplay of insulin resistance, oxidative stress, dyslipidemia, and inflammation in type 2 diabetes mellitus (T2DM). The study was undertaken to investigate the effect of turmeric as an adjuvant to anti-diabetic therapy. Sixty diabetic subjects on metformin therapy were recruited and randomized into two groups (30 each). Group I received standard metformin treatment while group II was on standard metformin therapy with turmeric (2 g) supplements for 4 weeks. The biochemical parameters were assessed at the time of recruitment for study and after 4 weeks of treatment. Turmeric supplementation in metformin treated type 2 diabetic patient significantly decreased fasting glucose (95 ± 11.4 mg/dl, P < 0.001) and HbA1c levels (7.4 ± 0.9 %, P < 0.05). Turmeric administered group showed reduction in lipid peroxidation, MDA (0.51 ± 0.11 µmol/l, P < 0.05) and enhanced total antioxidant status (511 ± 70 µmol/l, P < 0.05). Turmeric also exhibited beneficial effects on dyslipidemia LDL cholesterol (113.2 ± 15.3 mg/dl, P < 0.01), non HDL cholesterol (138.3 ± 12.1 mg/dl, P < 0.05) and LDL/HDL ratio (3.01 ± 0.61, P < 0.01) and reduced inflammatory marker, hsCRP (3.4 ± 2.0 mg/dl, P < 0.05). Turmeric supplementation as an adjuvant to T2DM on metformin treatment had a beneficial effect on blood glucose, oxidative stress and inflammation.
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BACKGROUND: India has the highest burden of acute coronary syndromes worldwide. Apart from certain lipid alterations that have been established to be definite risk factors, low level of adiponectin, high levels of resistin, and IL-6 have been shown to be risk factors for cardiovascular events. Insulin resistance is also a significant predictor of poor outcome in patients admitted with ACS. METHODS: 69 male patients with ACS and 70 age-matched healthy males were recruited in the study. Insulin, total adiponectin, resistin, and IL-6 levels were assayed in all study subjects. Indices of insulin resistance and novel adipokine indices were calculated using standard formulae. Multiple logistic regression analysis was done to find out the best predictor of ACS. RESULTS: Resistin, IL-6, insulin resistance indices, AR index, and IRAR index were found to be significantly higher, while insulin sensitivity indices and total adiponectin were found to be lower in cases, as compared with controls (p < 0.001). Insulin resistance was found to be higher in the admission sample, when compared to the fasting sample in patients with ACS (p = 0.01). On multivariate logistic regression analysis, HOMA-IR and AR index were found to be significantly associated with ACS. AR index was the best independent predictor of ACS, with the highest odds ratio (AR index: adjusted OR 17.528, p < 0.0001 versus HOMA-IR: adjusted OR 1.146, p = 0.001). CONCLUSIONS: The present results implicate that adipokines are significantly associated with pathogenesis of ACS, warranting adequate and early appropriate treatment to reverse this metabolic dysregulation. In our study, AR index was the best predictor of ACS. Hence, the novel AR index might be useful in routine clinical practice for screening persons with increased risk of future development of ACS.
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Síndrome Coronariana Aguda/sangue , Adiponectina/sangue , Resistina/sangue , Síndrome Coronariana Aguda/epidemiologia , Adulto , Glicemia/análise , Estudos Transversais , Humanos , Índia/epidemiologia , Insulina , Resistência à Insulina , Interleucina-6/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Graduate medical students often get less opportunity for clarifying their doubts and to reinforce their concepts after lecture classes. The Medical Council of India (MCI) encourages group discussions among students. We evaluated the effect of identifying mistakes in a given set of wrong statements and their correction by a small group discussion by graduate medical students as a revision exercise. METHODS: At the end of a module, a pre-test consisting of multiple-choice questions (MCQs) was conducted. Later, a set of incorrect statements related to the topic was given to the students and they were asked to identify the mistakes and correct them in a small group discussion. The effects on low, medium and high achievers were evaluated by a post-test and delayed post-tests with the same set of MCQs. RESULTS: The mean post-test marks were significantly higher among all the three groups compared to the pre-test marks. The gain from the small group discussion was equal among low, medium and high achievers. The gain from the exercise was retained among low, medium and high achievers after 15 days. CONCLUSION: Identification of mistakes in statements and their correction by a small group discussion is an effective, but unconventional revision exercise in biochemistry.
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Bioquímica/educação , Educação de Pós-Graduação em Medicina , HumanosRESUMO
Trace metal concentrations were determined in particulate matter (PM10) in ambient air of four purposively selected residential areas in Ibadan, Nigeria namely Bodija market (BM), Ojo Park (OP), Oluyole Estate (OE) and University of Ibadan (UI). PM10 was determined in the morning (7-10 a.m.) and afternoon (2-5 p.m.) for 12 weeks in the dry season months of January-March using a volumetric sampler following standard procedures and levels compared with WHO guideline limits. Glass-fibre filter papers exposed to the particulate matter were digested using appropriate acid mixtures, and the digest analysed for trace metals including Ni, Cr, Mn, Zn, and Pb using ICPMS method and levels compared with WHO limits. Data was analysed using ANOVA and Pearson correlation test at 5 % level of significance. The highest mean PM10 concentrations 502.3 ± 39.9 µg/m(3) were recorded in the afternoon period at BM, while the lowest concentration 220.6 ± 69.9 µg/m(3) was observed in the morning hours at UI. There was a significant difference between the PM10 levels across the various locations (p < 0.05), and all the levels were higher than WHO limit of 50 µg/m(3). The highest levels of Ni, Zn and Pb were recorded at BM, which also had the highest PM10 burden. The trend in Pb levels across the locations was BM > UI > OP > OE with the highest level 5.70 µg/m(3) in BM nearly fourfolds WHO limits of 1.5 µg/m(3). There was a significant correlation between PM10 and Ni (p < 0.05).Urban communities with increased human activities especially motor traffic recorded both higher levels of PM10 and toxic trace metals. There is need to carry out source apportionment to establish the origin of these trace metals in future studies.
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Material Particulado/análise , Poluentes Atmosféricos/análise , NigériaRESUMO
In the title compound, C13H12N2OS, the planes of the thio-phene and phenyl rings are nearly perpendicular to each other, making a dihedral angle of 86.42â (12)°. In the crystal, mol-ecules are linked by C-Hâ¯O hydrogen bonds, forming a helical chain along the b-axis direction.
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In the title compound, C14H11FO2, the two benzene rings are not coplanar, with a dihedral angle of 57.45â (12)° between their planes. In the crystal, mol-ecules are linked by an O-Hâ¯O hydrogen bond, forming a 21 helical chain along the b axis.
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In the title compound, C14H11FO2, the dihedral angles beteen the central C3O ketone residue and the fluoro- and hy-droxy-substituted benzene rings are 50.44â (9) and 12.63â (10)°, respectively. The planes of the benzene rings subtend a dihedral angle of 58.88â (9)° and an intra-molecular O-Hâ¯O hydrogen bond closes an S(6) ring. No directional inter-actions beyond van der Waals packing contacts were identified in the crystal structure.
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This study explores the pharmacological potential of chalcones through a multidisciplinary approach, including synthesis, quantum theory, molecular electrostatics, and density functional theory (DFT) calculations. The synthesized compound, analyzed via single crystal X-ray diffraction, crystallized in the triclinic system (space group P-1) with C-Hâ¯O interactions stabilizing its structure. Hirshfeld surface analysis confirms these interactions, with H-H contacts dominating (45.1 %). Molecular electrostatics analysis reveals charge distribution, and a 3.10 eV HOMO-LUMO energy gap indicates bioactivity. Molecular docking identifies the compound (3a) showed a maximum Gscore of HTNF-α (-9.81 kcal/mol); Tubulin (-7.96 kcal/mol); COX2 (-7.88 kcal/mol), EGFR (-6.72 kcal/mol), and VEGFR1(-2.50 kcal/mol). Where compound (3c) showed maximum binding at the putative binding site with dock scores for VEGFR2 (-9.24 kcal/mol). This research not only advances molecular science but also holds promise for diverse applications, including drug design. The significance of this study lies in its comprehensive exploration of the pharmacological potential of chalcones using a multidisciplinary approach. Through the integration of synthesis, quantum theory, molecular electrostatics, and density functional theory (DFT) calculations, we have extensively explored the structural and biochemical characteristics of these compounds. This investigation has revealed valuable insights that have the potential to lead to significant advancements in the fields of molecular science and drug design. Moreover, the molecular docking studies shed light on the compound's interaction with various biological targets. The significant binding affinities observed for these targets underscore the potential therapeutic relevance of the synthesized compound in diverse disease conditions.
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PURPOSE: The importance of cellular context to the synergy of DNA damage response (DDR)-targeted agents is important for tumors with mutations in DDR pathways, but less well-established for tumors driven by oncogenic transcription factors. In this study, we exploit the widespread transcriptional dysregulation of the EWS-FLI1 transcription factor to identify an effective DDR-targeted combination therapy for Ewing sarcoma. EXPERIMENTAL DESIGN: We used matrix drug screening to evaluate synergy between a DNA-PK inhibitor (M9831) or an ATR inhibitor (berzosertib) and chemotherapy. The combination of berzosertib and cisplatin was selected for broad synergy, mechanistically evaluated for Ewing sarcoma selectivity, and optimized for in vivo schedule. RESULTS: Berzosertib combined with cisplatin demonstrates profound synergy in multiple Ewing sarcoma cell lines at clinically achievable concentrations. The synergy is due to loss of expression of the ATR downstream target CHEK1, loss of cell-cycle check-points, and mitotic catastrophe. Consistent with the goals of the project, EWS-FLI1 drives the expression of CHEK1 and five other ATR pathway members. The loss of CHEK1 expression is not due to transcriptional repression and instead caused by degradation coupled with suppression of protein translation. The profound synergy is realized in vivo with a novel optimized schedule of this combination in subsets of Ewing sarcoma models, leading to durable complete responses in 50% of animals bearing two different Ewing sarcoma xenografts. CONCLUSIONS: These data exploit EWS-FLI1 driven alterations in cell context to broaden the therapeutic window of berzosertib and cisplatin to establish a promising combination therapy and a novel in vivo schedule. See related commentary by Ohmura and Grünewald, p. 3358.