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Diabetes has affected nearly half a billion people worldwide. According to current guidelines, glycemic control is essential to mitigate diabetic complications. The antihyperglycemic effects of various chemically synthesized nanoparticles have been reported in animal models. However, their impact on humans has not been previously reported. This study was conducted to biosynthesize and assess the antihyperglycemic property of silica nanoparticles (SiO2-NPs) since they are non-toxic and biocompatible. SiO2-NPs biosynthesized using the endophytic fungus Fusarium oxysporum. In this collaborative study, 26 people, either hyperglycemic or euglycemic, diagnosed at the Endocrinology Outpatients, according to the American Diabetes Association, USA, were recruited. Silica nanoparticles were characterized and assessed for in vitro antihyperglycemic property using blood samples. Particle size distribution based on TEM images confirms that the average size of silica nanoparticle is 25 nm and is monodispersed in nature. The XRD pattern shows that only one broad peak at 2θ = 220 corresponds to the plane (101) of silica nanoparticles. UV Visible spectra show the λmax at 270 nm, peaks in FTIR at 1536 cm-1, 1640 cm-1, and 3420 cm-1 for the protein cap. The mean blood glucose was 120.2 mg/dL in the 'SiO2-NP untreated' group and decreased to 97.24 mg/dL in the 'SiO2-NP treated' group. A paired t-test (P-value < 0.0001) indicates a strong relationship between antihyperglycemia and silica NP. In our study, it has been observed that the biosynthesized silica nanoparticles using the endophytic fungus Fusarium oxysporum show antihyperglycemic property in vitro.
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The list of environmental factors that trigger autoimmune diseases in genetically susceptible individuals has grown in the recent years and is far from complete. The possible intervention of the environment in triggering these diseases is ever more perceived by the clinicians. This study investigated the effect of environmental factors like organochlorine pesticides (OCPs) on proportions of different T lymphocyte subsets and their cytokine secretion in-vitro among pemphigus patients, before and after specific immunosuppressive therapy. Higher levels of OCPs like ß-HCH (isoform of hexachlorohexane), α-endosulfan (a form of endosulfan) and p,pÎ-DDE (a metabolite of o,p'-dichlorodiphenyltrichloroethane) were observed in the blood of pemphigus patients as compared to healthy controls. HCH and DDT exposure caused specific reduction in CD8+CD45RA+ and CD4+CD25+ T lymphocyte subpopulations in these patient PBMCs. A strong reduction in Th1 (IL-2 and IFN-γ) cytokines upon exposure to these OCPs in-vitro was also observed. These findings indicate that HCH and DDT have a significant impact on Th1 lymphocytes. Impaired production of these cytokines might favor infections and production of autoantibodies. We therefore speculate that the systemic absorption of the pesticide after the topical contact may be one of the factors triggering the immunological mechanism among pemphigus patients.
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Hidrocarbonetos Clorados , Pênfigo , Praguicidas , Humanos , Autoanticorpos , Citocinas , DDT , Hidrocarbonetos Clorados/toxicidade , Interleucina-2 , Praguicidas/toxicidade , Linfócitos T Auxiliares-Indutores/química , Linfócitos T Auxiliares-Indutores/metabolismoRESUMO
Background The diverse manifestations of urolithiasis provide very interesting epidemiological data. This has prompted various studies to look into the etiopathogenesis of renal stones, which is believed to be multifactorial, both exogenous and endogenous. VDR Fok1 is a risk factor for renal stone formation and could cause the formation of renal stones through the mechanism of crystal induction and crystallization in the urine. While a few recent studies have shown the role of heavy metals like cadmium and lead in the formation of renal stones, the current knowledge is still insufficient. Methods This case-control prospective study was conducted in Guru Teg Bahadur (GTB) Hospital, a tertiary care facility in Delhi with 30 cases and 30 controls. Patients visiting the department of surgery between November 2011 and April 2013 were enrolled in the study. Cases were defined as patients with renal stones diagnosed on the basis of history and radiological investigations. Controls were selected from the patients admitted to the department of surgery for reasons other than renal stones. The study protocol was approved by the Institutional Ethical Committee of the University College of Medical Sciences, GTB Hospital, Delhi. Written informed consent was obtained from all patients. A structured questionnaire was used to collect data. Metal levels were analyzed by an atomic absorption spectrophotometer (Shimadzu Flame AA-680, Shimadzu Corp., Kyoto, Japan) at Delhi University. The vitamin D receptor gene was measured using genomic DNA. Horizontal agarose gel electrophoresis was used for the quantification of the genomic DNA. Results There were 30 cases and 30 controls in the study. Stress was more prevalent among cases (63%) compared to controls (36%). Nearly 83% of cases had the ff allele of the Vitamin D receptor gene compared to 46% of controls. The median arsenic and lead levels were higher among cases compared to controls. In the unadjusted model of logistic regression, we found stressed patients had three times higher odds of developing renal stones compared to non-stressed patients (OR (95% CI): 2.98 (1.04-8.52); p=0.04). Similarly, patients with higher blood concentrations of arsenic and lead had higher odds of developing renal stones compared to those with lower concentrations. Conclusions There was a definitive role of heavy metals, including lead, cadmium, and arsenic, seen with renal stones. A significant association was seen between the ff allele of VDR polymorphism (Fok1 enzymes) and patients with renal stones. Other parameters, including male and stress factors, seem to have an important role in renal stone formation.
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Quantitative real-time polymerase chain reaction for identifying CYP2B6 gene expression was done on blood samples of 30 phenobarbitone responder and 30 non-responder neonates with seizures. CYP2B6 was observed to be significantly down regulated among phenobarbitone non-responders as compared to phenobarbitone responders (Mean (SD) DCt 17.97 (1.19) vs 15.40 (1.83); P<0.001).
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Anticonvulsivantes , Fenobarbital , Recém-Nascido , Humanos , Fenobarbital/uso terapêutico , Anticonvulsivantes/uso terapêutico , Citocromo P-450 CYP2B6 , Convulsões/tratamento farmacológico , Convulsões/genéticaRESUMO
The unregulated use of organochlorine pesticides (OCPs) has been linked to spread of breast cancer (BC), but the underlying biomolecular interactions are unknown. Using a case-control study, we compared OCP blood levels and protein signatures among BC patients. Five pesticides were found in significantly higher concentrations in breast cancer patients than in healthy controls: p',p' dichloro diphenyl trichloroethane (DDT), p'p' dichloro diphenyl dichloroethane (DDD), endosulfan II, delta-hexachlorocyclohexane (dHCH), and heptachlor epoxide A (HTEA). According to the odds ratio analysis, these OCPs, which have been banned for decades, continue to raise the risk of cancer in Indian women. Proteomic analysis of plasma from estrogen receptor-positive breast cancer patients revealed 17 dysregulated proteins, but transthyretin (TTR) was three times higher than in healthy controls, which is further validated by enzyme-linked immunosorbent assays (ELISA). Molecular docking and molecular dynamics studies revealed a competitive affinity between endosulfan II and the thyroxine-binding site of TTR, pointing towards the significance of the competition between thyroxin and endosulfan, resulting in endocrine disruption leading to breast cancer. Our study sheds light on the putative role of TTR in OCP-mediated BC, but more research is needed to decipher the underlying mechanisms that can be used to prevent the carcinogenic effects of these pesticides on women's health.
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Neoplasias da Mama , Hidrocarbonetos Clorados , Praguicidas , Humanos , Feminino , Endossulfano/análise , Neoplasias da Mama/induzido quimicamente , Pré-Albumina , Estudos de Casos e Controles , Simulação de Acoplamento Molecular , Proteômica , Praguicidas/análise , Hidrocarbonetos Clorados/análiseRESUMO
Aim: The study was designed to evaluate the modulation of mTOR complex 1 (mTORC1) and IL-6 genes following the use of mirror therapy (MT) and pregabalin in complex regional pain syndrome type-1 patients. Materials & methods: Two groups of 20 patients: MT group received MT and pregabalin, control therapy group received pregabalin. Neuropathic pain symptom inventory (NPSI), numeric rating scale - pain, modified motor activity log, SF-12 questionnaire for quality of life and IL-6 and mTORC1 expression were evaluated. Results: Group MT demonstrated a statistically significant improvement in NPSI burning, NPSI allodynia and numeric rating scale pain scores, modified motor activity log and SF-12 scores. Significant downregulation of mTORC1 and IL-6 observed in both. Conclusion: MT is a significant adjunct to pregabalin in improving motor function, quality of life and alleviating pain in complex regional pain syndrome type 1. Clinical Trial Registration: CTRI/2019/01/017272 (ClinicalTrials.gov).
Complex regional pain syndrome is a form of long-term pain that involves an arm or a leg. It can develop after an injury, a surgery or a stroke. Although many drugs have been used for its treatment, the limited relief that these drugs produce along with their side effects have shifted focus to other physical and psychological modes of therapy. Mirror therapy is one such modality where the image of normal functioning limb seen in a mirror placed over the affected limb leads to pain relief in the affected limb. We have provided evidence that mirror therapy can reduce the pain of this syndrome and also decrease the levels of pain related genes in the body. This will help us to devise better treatment strategies for complex regional pain syndrome.
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Síndromes da Dor Regional Complexa , Neuralgia , Humanos , Pregabalina/uso terapêutico , Interleucina-6/uso terapêutico , Terapia de Espelho de Movimento , Qualidade de Vida , Neuralgia/tratamento farmacológico , Síndromes da Dor Regional Complexa/tratamento farmacológico , Resultado do TratamentoRESUMO
The loss of balance between regulatory T (Treg) and T helper 17 (Th17) causes loss of tolerance against desmoglein (Dsg)-3 leading to pemphigus vulgaris (PV), an autoimmune bullous skin disorder associated with autoantibodies against Dsg-3. We aimed to elucidate the complex relationship of Th17 and Treg cells, their molecules, and the underlying mechanism in the development of PV disease. Using cytokine secretion assays, Th17 and Treg cells were sorted by FACS Aria-III within Dsg-3-responsive PBMC population and homogeneous T cell clones were generated in-vitro. Different cell surface molecules like CD25, GITR, CD122, CD152, CD45RO, IL-23R, STAT3, STAT5, CD127, HLA-DR, CCR4, CCR5, CCR6 and CCR7 were studied. The functional response of Th17 and Treg cells were elucidated by measuring the levels of various cytokines released by IL-10 and IL-17 T cells. The mRNA expression of transcription factors (FoxP3 and RORγt) was also analyzed. IL-17 secreting (Th17) cells with phenotype CD4+IL-17+ were greatly increased and IL-10 secreting (Treg) cells with phenotype CD4+IL-10+ were reduced in PV cases than healthy controls. The qPCR analysis showing high expression of retinoic acid receptor-related orphan receptor gamma (RORγt) mRNA in comparison to forkhead box P3 (FoxP3) mRNA confirmed the development of pro-inflammatory Th17 response in PV. Further, the cytokine profile of pro-inflammatory and anti-inflammatory cytokines suggested defective suppressive functions in Treg cells with high inflammatory response. Our findings indicate that autoantigen Dsg-3 specifically allows the proliferation of IL-17 secreting T cells though has a negative effect on IL-10 secreting T cells leading to dysregulation of immunity in PV patients. This antagonistic relationship between Dsg-3-specific Th17 and Treg cells may be critical for the onset and persistence of inflammation in PV cases.
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Pênfigo , Linfócitos T Reguladores , Humanos , Interleucina-17/metabolismo , Interleucina-10/metabolismo , Pênfigo/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Leucócitos Mononucleares/metabolismo , Citocinas/metabolismo , Células Clonais/metabolismo , Fenótipo , Fatores de Transcrição Forkhead/metabolismo , RNA Mensageiro/metabolismo , Desmogleínas/metabolismo , Células Th17RESUMO
In recent decades, "environmental xenobiotic-mediated endocrine disruption", especially by xeno-estrogens, has gained a lot of interest from toxicologists and environmental researchers. These estrogen-mimicking chemicals are known to cause various human disorders. Pesticides are the most heavily used harmful xenobiotic chemicals around the world. The estrogen-mimicking potential of the most widely used organochlorine pesticides is well established. However, their effect is not as clearly understood among the plethora of effects these persistent xenobiotics are known to pose on our physiological system. Estrogens are one of the principal risk modifiers of various disorders, including cancer, not only in women but in men as well. Despite the ban on these xenobiotics in some parts of the world, humans are still at apparent risk of exposure to these harmful chemicals as they are still widely persistent and likely to stay in our environment for a long time owing to their high chemical stability. The present work intends to understand how these harmful chemicals may affect the risk of the development of estrogen-mediated human cancer.
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Background: Organochlorine pesticides (OCPs) have been long linked to type 2 diabetes mellitus (T2DM); however, this relation at the molecular level has not been explored yet. Endoplasmic reticulum (ER) stress and pro-inflammatory pathways are considered vital ones in the pathogenesis of T2DM. We aimed to investigate the existence of any association between OCPs, ER stress, and pro-inflammatory pathways in subjects with known T2DM. Methods: Seventy subjects each with T2DM and normal glucose tolerance were recruited from the surgery department. Their visceral adipose tissue was collected intraoperatively. OCP concentration, ER stress, and pro-inflammatory markers were analyzed and compared between two study groups. Results: We found 18 OCPs and their metabolites in visceral adipose tissue samples of study participants. The levels of δ-HCH, heptachlor, endrin, and p,p'DDT were significantly higher in the T2DM group and were also positively correlated with fasting and postprandial plasma glucose levels (p < 0.01). We observed a positive association of δ-HCH (p < 0.01), heptachlor (p < 0.05), and endrin (p < 0.05) with central adiposity and ER stress markers. However, we failed to establish the correlation of OCPs with any of the pro-inflammatory markers. Conclusion: The existence and simultaneous complex correlation of OCPs with ER stress may explain their role in the pathogenesis of T2DM, revealing the persistence of the gene-environment interaction in the etiology of T2DM.
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Diabetes Mellitus Tipo 2 , Praguicidas , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Estresse do Retículo Endoplasmático , Marcadores Genéticos , HumanosRESUMO
Aim: To carry out a case-control study of the association of GST gene polymorphisms in pediatric asthma-related oxidative stress. Materials & methods: Asthma patients (n = 250) and age-matched healthy subjects (n = 250) DNA were genotyped for GSTM1/GSTT1 (+/+, +/-, -/+ and -/-) frequencies using multiplex-PCR and plasma oxidative stress markers (examined spectrophotometrically). Results: Asthma patients had significantly more common null-genotype GSTM1-/GSTT1- (10.4%; p = 0.002) and elevated levels of malondialdehyde, protein carbonyl and 8-hydroxy-2-deoxyguanosine as compared with controls. In addition, the level of plasma glutathione, GST activity and ferric-reducing ability were significantly decreased as compared with controls. Conclusion: Our data revealed significant associations between GSTM1-/GSTT1- genotype and oxidative stress markers in asthmatic children, which may very likely contribute to increased incidence of bronchial asthma.
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Asma , Predisposição Genética para Doença , Glutationa Transferase/genética , Asma/epidemiologia , Asma/genética , Estudos de Casos e Controles , Criança , Genótipo , Glutationa Transferase/metabolismo , Humanos , Polimorfismo Genético/genética , Fatores de RiscoRESUMO
Engineered well-ordered hybrid nanomaterials are symbolically at a pivotal point, just ahead of the long-anticipated transformation of the human race. Incorporating newer carbon nanomaterials like graphene quantum dots (GQDs) with tetrapyrrolic porphyrins (Pp) and phthalocyanines (Pc) is crucial for achieving exquisite molecular nanoarchitectures that are superior to their individual components. The outcomes of this, particularly in the case of graphene quantum dot-porphyrin/phthalocyanine (GQD-Pp/Pc) hybrids, remain comprehensively unexplored to date. Interestingly, GQD-Pp/Pc hybrids provide a modern strategy to regulate matter by utilising intramolecular and organisational properties to create well-defined nanocomposites via a synergistic enhancement effect. The high molar absorption coefficient and enhanced energy transfer, hole and electron transfer abilities capabilities allow Pp and Pc to exhibit a wide spectrum of photophysical and photochemical features. However, their low biostability, non-specific tumor-targeting properties, hydrophobicity, and low cellular internalisation efficiency limit their extensive biomedical utility. Conjugating Pp/Pc to nanocarriers such as GQDs improves their targeted delivery, immunological tolerance, and longevity. Due to the zero-order release kinetics of GQDs, they can assist in maintaining a steady rate of photosensitiser (PS) delivery at the desired site. To completely rationalise the functionalization of GQD-Pp/Pc species at interfaces, we investigate the current prominence and future potential of porphyrin-related graphene nanosystems, especially GQDs, for the development of various applications. This encouraging report demonstrates how GQD-Pp/Pc species can be used to examine new phenomena at the multidisciplinary level. Notably, a customised hybrid system optimises amendable and diverse functional properties, yielding a ray of hope in the fields of photodynamic therapy (PDT), photocatalysis, solar cells, sensing, and beyond via various photo-physicochemical approaches such as electron transfer, catalytic transformation, light-harvesting, and axial/peripheral ligation of adducts. Gratifyingly, the covalent and non-covalent coupling of functional molecular units at interfaces enable new properties to be generated in hybrid systems.
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Grafite , Nanocompostos , Porfirinas , Pontos Quânticos , Grafite/química , Humanos , Isoindóis , Pontos Quânticos/químicaRESUMO
Introduction: A randomized controlled study was conducted to assess modulation of signal transduction genes (PKA, PKC and ERK) following integrated multimodal approach encompassing pulsed radiofrequency treatment (PRF) of dorsal root ganglion and pregabalin in thoracic postherpetic neuralgia (PHN). Clinical variables such as pain intensity and quality of life were also explored. Material & methods: A total of 40 Patients of PHN were recruited. 20 patients randomly assigned to each of the two groups, group PP administered PRF with pregabalin and group SP administered pregabalin alone. Results: Significant downregulation of PKA and ERK observed in group PP at end of 10th week (p < 0.05). A significantly positive correlation demonstrated between Visual analog scale scores and signal transduction genes expression in PHN patients. Conclusion: Downregulation of all three signal transduction genes was observed following the integrated multimodal approach; however, significant downregulation was observed with PKA and ERK only. A positive correlation observed between signal transduction gene expression and visual analog scale scores signify their role in the pathogenesis of PHN.
People who had nerve pain after recovering from a herpes attack (postherpetic neuralgia) were treated with pulsed radiofrequency (PRF) treatment of the dorsal root ganglion, which involves stimulating a nerve cluster at the base of the spine with radio waves, along with oral pregabalin therapy, or with pregabalin alone. Certain pain genes such PKA, PKC and ERK were found to be suppressed after the combined treatment with PRF and pregabalin. The suppression of these genes was also associated with the self-reported pain scores of the participants in the study.
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Neuralgia Pós-Herpética , Tratamento por Radiofrequência Pulsada , Gânglios Espinais , Expressão Gênica , Humanos , Neuralgia Pós-Herpética/tratamento farmacológico , Pregabalina/farmacologia , Pregabalina/uso terapêutico , Qualidade de Vida , Transdução de Sinais , Resultado do TratamentoRESUMO
BACKGROUND: Exposure to dichlorodiphenyltrichloroethane (DDT), a potent lipophilic organochlorine pesticide, has long been linked as a risk factor for type 2 diabetes mellitus (T2DM). However, its presence in the adipose tissues of the T2DM subjects has not been explored in the Indian population, where this long-banned pesticide is still in use. The present study was conducted to evaluate the possible association of DDT and its metabolites in obese and non-obese T2DM subjects. METHODS: Subjects with normal glucose tolerance (n = 50) and T2DM (n = 50) were divided into equal numbers in obese and non-obese groups. Their plasma glucose levels, HbA1c, and lipid profile were measured. The adipose tissues were collected intraoperatively, and DDT and its metabolites were measured using a gas chromatograph equipped with an electron capture detector. RESULTS: Obese subjects, irrespective of their glycemic status, and T2DM subjects had higher concentrations of DDT. p, p' DDT was found to increase the odds for diabetes, and o, p' DDT for central obesity. p, p' DDD was also strongly correlated with central obesity, glycemic parameters, and triglycerides. CONCLUSION: The excess deposition of p, p' DDD, o, p' DDT, and p, p' DDT in obese subjects may proceed to T2DM by disrupting triglycerides and glycemic parameters.
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OBJECTIVES: The aim of this study is to study the modulation of extracellular signal-regulated protein kinase (ERK) and tissue inhibitors of matrix metalloproteases 1 (TIMP 1) gene in patients with neuropathic pain (NP). MATERIALS AND METHODS: In the present, cross-sectional, observational study, 2 ml of venous baseline sample was withdrawn from all the patients with neuropathic (NP) or non NP (NNP) soon after their diagnosis or on their first visit to the pain clinic. A real-time quantitative polymerase chain reaction experiment was conducted to measure the mRNA expression of TIMP1 and ERK genes in blood samples. The Delta Ct, Delta Ct, and fold change analysis of both the genes were conducted between patients with NP and NNP. RESULTS: A total of 285 patients with chronic pain were assessed, out of which, 153 patients had NP and 132 had NNP. The average duration of chronic pain was 11 months for 285 patients. The mRNA expression of TIMP1 gene is significantly down regulated (2.65-fold) (P (-f. 01), and the mRNA expression level of ERK is significantly up regulated (2.03-fold) (P (-f. 01) in NP patients when compared with NNP. CONCLUSION: The mRNA expression of TIMP1 gene is significantly down regulated, and ERK is significantly up regulated in patients with NP. Further, multicentric trials with larger sample size are recommended to confirm this finding.
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Chronic kidney disease of unknown etiology (CKDu), manifested clinically as tubulo interstitial fibrosis, has emerged as the second major cause of chronic kidney disease (CKD) in the Indian subcontinent and various agrochemicals have been implicated in its occurance. Among the agrochemicals organochlorine pesticides particularly endosulfan is well known for its toxicity and recent residue analysis have shown its presence in the blood samples of general population. In this present study, we have investigated the consequences of endosulfan exposure at a concentration (0.01 µM) equivalent to their highest reported presence in human blood sample of some CKDu patients, to human renal proximal tubular epithelial (HK-2) cell line with regard to ROS generation and expression of profibrotic and epithelial to mesenchymal (EMT) markers in order to find out endosulfan's ability to induce profibrotic changes in renal cell. We demonstrated a significant increase in intracellular ROS generation and increased expression of TGF-ß1 when cells were incubated with ß-endosulfan (0.01 µM) indicating occurrence of oxidative stress and fibrotic process. Again, decreased expression of epithelial marker E-cadherin and increase in the expression of mesenchymal marker α-smooth muscle actin (α-SMA) suggest possible onset of EMT process. Pre-treatment with 5 mM concentration of anti-oxidant N-acetyl cysteine partially attenuated the above process. In conclusion, these findings suggest possible involvement of ß-endosulfan in the development of CKDu through oxidative stress and profibrotic signaling.
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Endossulfano , Insuficiência Renal Crônica , Endossulfano/toxicidade , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal , Fibrose , Humanos , Rim/patologia , Túbulos Renais Proximais/patologia , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/patologia , Fator de Crescimento Transformador beta1RESUMO
OBJECTIVE: This study was designed to explore the efficacy and feasibility of cognitive behavioral therapy (CBT) along with pregabalin and compare it with pregabalin monotherapy for the management of neuropathic pain in post-herpetic neuralgia (PHN) patients and to explore the modulation of messenger RNA (mRNA) expression of interleukin (IL)-6 and mammalian target of rapamycin-1 (mTORC1) genes in these patients. DESIGN: Randomized controlled pilot study. METHODS: The patients aged >18 years of age with an established diagnosis of PHN with evident allodynia and hyperalgesia who had pain for at least 3 months after healing of rash with pain intensity ≥4/10 on NRS-Pain Scale were enrolled. The trial was registered with the Clinical Trials Registry-India (CTRI/2019/03/018014). A detailed baseline assessment regarding type and duration of pain and disability using pain-relevant self-report questionnaires was done. Two mL venous blood samples were collected for gene expression studies at base line and at end of 12 weeks of treatment. Patients were randomized into one of the two groups. Group PR received pregabalin and Group CP received CBT along with pregabalin. The pain intensity was measured using numeric rating scale (NRS)-Pain scale, neuropathic component of the pain by using Neuropathic Pain Symptom Inventory (NPSI) and Pain Detect Questionnaire (PDQ), sleep interference by NRS-Sleep, pain-related catastrophic thoughts by using Pain Catastrophizing Scale (PCS), depression and quality of life using Beck Depression Inventory-II (BDI-II) and Short Form-12 (SF-12), respectively. The research funding was supported by the intramural grant from the institution. RESULTS: A total of 40 patients with 20 in each group were included. Following integrated approach encompassing CBT and Pregabalin, group CP had significant downregulation of mRNA expression of IL-6; however, no such correlation was observed with mTOR expression. A significant decline in the intensity of pain, NPSI scoring for burning, allodynia, and pain-related catastrophizing were observed; also a significant improvement in depressive symptoms and quality of life were observed with the use of CBT. CONCLUSIONS: A significant downregulation of mRNA expression of IL-6 was observed; however, no significant correlation was observed between NRS pain score and ΔCt values of mRNA expression of both mTORC1 gene and IL-6 gene at baseline and at the end of 12th week. In addition, we note a significant decrease in pain intensity, depressive symptoms, and pain-related catastrophizing while improving QOL was observed with the use of CBT as a clinical adjunct along with pregabalin in PHN patients.
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Terapia Cognitivo-Comportamental , Neuralgia Pós-Herpética , Neuralgia , Analgésicos/uso terapêutico , Estudos de Viabilidade , Humanos , Lactente , Interleucina-6 , Neuralgia/tratamento farmacológico , Neuralgia/genética , Neuralgia Pós-Herpética/tratamento farmacológico , Projetos Piloto , Pregabalina/uso terapêutico , Qualidade de Vida , RNA Mensageiro , Serina-Treonina Quinases TOR , Resultado do Tratamento , Ácido gama-AminobutíricoRESUMO
Exposure to organochlorine pesticides (OCPs) may be a risk factor for breast cancer (BC). Their role may be more relevant in developing countries such as India, where an abundance of these products is used for agricultural purposes. The present study compares OCP tissue levels in patients who underwent BC surgery (group A) or patients who had surgery for excision of breast fibroadenoma (group B). We perform OCP level quantification using a PerkinElmer, Inc. (Waltham, MA) gas chromatograph (GC) that is equipped with a 63Ni selective electron-capture detector. Significantly higher breast tissue OCP levels are present in the study population, indicating significant exposure. We detect 18 different types of OPCs in study subjects, with six OPCs (γ-hexachlorocyclohexane [HCH], δ-HCH, endrin, endosulfan-II, p,p'-dichlorodiphenyldichloroenthane [DDD], and p,p'-dichlorodiphenyltrichloroenthane [DDT]) present in all subjects. Endosulfan-II, p,p'-DDT, and p,p'-DDD tissue levels are significantly higher in BC patients than in those with fibroadenoma. Higher tissue levels of OCPs (α-HCH) are significantly associated with the presence of extracapsular spread (1.42 vs. 0.91; p = 0.04) and higher disease stage (early BC vs. locally advanced BC; 18.90 vs. 11.90; p = 0.04). The present pilot study indicates higher OCP tissue levels in northern India BC patients compared to patients with fibroadenoma.
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Neoplasias da Mama/metabolismo , Fibroadenoma/metabolismo , Hidrocarbonetos Clorados/metabolismo , Praguicidas/metabolismo , Adulto , Feminino , Humanos , Índia , Pessoa de Meia-Idade , Projetos PilotoRESUMO
BACKGROUND: Organochlorine pesticides (OCPs) exposure may induce an endocrine disruption which may lead to the risk of developing diabetes through alteration and disturbance of glucose metabolism, insulin resistance, and destruction of ß-cells. The present study determines the recent trend of OCPs residue in blood samples and their association with the known risk factors responsible for developing the risk of diabetes among the North Indian population. METHODS: Blood sample of 300 patients (100 each of normal glucose tolerance [NGT], prediabetes and newly detected diabetes mellitus [DM]) between the age group of 30 to 70 years were collected. OCPs residue in whole blood samples was analyzed by using gas chromatography equipped with a 63Ni selective electron capture detector. RESULTS: Significantly higher levels of ß-hexachlorocyclohexane (HCH), dieldrin, and p,p'-dichloro-diphenyl-dichloroethylene (DDE) were found in the prediabetes and newly detected DM groups as compared to NGT group. Insulin resistance showed to be significantly positive correlation with ß-HCH and dieldrin. Also, fasting and postprandial glucose levels were significantly positively correlated with levels of ß-HCH, dieldrin, and p,p'-DDE. Further, when OCPs level was adjusted for age and body mass index (BMI), it was found that ß-HCH, dieldrin, and p,p'-DDE levels in blood increases the risk of diabetes by 2.70, 2.83, and 2.55 times respectively. Moreover, when we adjust OCPs level based on BMI categories (BMI <23, ≥23, and ≤25, and >25 kg/m2); ß-HCH and p,p'-DDE showed a significant risk of developing newly detected DM with BMI >25 and ≥23 and ≤25 kg/m2. CONCLUSION: The OCPs level present in the environment may be responsible for biological, metabolic, and endocrine disruptions within the human body which may increase the risk of developing newly detected DM. Hence, OCPs exposure can play a crucial role in the etiology of diabetes.
Assuntos
Intolerância à Glucose , Hidrocarbonetos Clorados , Resistência à Insulina , Praguicidas , Estado Pré-Diabético , Adulto , Idoso , Intolerância à Glucose/induzido quimicamente , Intolerância à Glucose/diagnóstico , Intolerância à Glucose/epidemiologia , Humanos , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/toxicidade , Pessoa de Meia-Idade , Praguicidas/efeitos adversos , Praguicidas/análise , Estado Pré-Diabético/induzido quimicamente , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologiaRESUMO
Organochlorine pesticides (OCPs) are well known synthetic pesticides widely used in agricultural practices and public health program. Higher toxicity, slow degradation, and bioaccumulation are the significant challenges of OCPs. Due to its uses in agricultural and public health, contamination of drinking water and water table also increases day by day. Contaminated drinking water has become a significant issue and alarming signal for public health globally. The purpose of this study was to assess the recent trend of organochlorine pesticides (OCPs) level in drinking water and blood samples of the North Indian population and also to find out its association with glucose intolerance, lipid metabolism, and insulin resistance, which are known risk factors of type 2 diabetes mellitus (T2DM). A case-control study was conducted on 130 Non-Glucose intolerance (NGT), 130 pre-diabetes and 130 recently diagnosed T2DM subjects of the age group of 30-70 years. Patients consuming drinking water from the same source for at least ten years were included in this study for blood and water samples collection. Significantly higher levels of α-HCH, ß-HCH, γ-HCH, p,p'-DDE, and o,p'-DDT were found in groundwater samples. However, in tap water samples, the level of α-HCH was found to be slightly higher than the permissible limit of 0.001. Among all recruited subjects consuming contaminated groundwater, 42% had T2DM, 38% pre-diabetes, and the remaining 20% were found normal. We also observed that OCP contamination in groundwater is higher than tap and filter water. The levels of ß-HCH, p,p'-DDE, and o,p'-DDT were higher in the pre-diabetes and T2DM group than the NGT group. With an increase of OCPs level in groundwater, the blood OCPs level tends to increase T2DM risk. It depicts that the elevated OCPs level in consumed groundwater may contribute to increased risk for the development of T2DM after a certain period of exposure.
Assuntos
Diabetes Mellitus Tipo 2 , Água Potável , Hidrocarbonetos Clorados , Praguicidas , Adulto , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Monitoramento Ambiental , Humanos , Hidrocarbonetos Clorados/análise , Índia/epidemiologia , Pessoa de Meia-Idade , Praguicidas/análise , Fatores de RiscoRESUMO
Concerning the climate crisis, energy disaster, and greenhouse effects, microalgae have paved the way for consideration as a biofuel feed material. The advent of polymeric materials with unique architecture at nanoscale, in combination with microalgae, has given direction for the bioeconomic yield of highly valued compounds, essentially lipid. Herein, we discuss the paramount significance of exotic hydrogel matrix (HM) with efficient violet light absorption, far-red emission, CO2-adsorbing capability and catalyst-free condition that could increase the photosynthesis activity, alleviating the microalgal growth for the effective augmentation of lipid, protein, and chlorophyll. The intrinsic morphological and structural features of HM were revealed by a suite of characterizations that confirm its hollow tubular architecture. Fluorescence intensity measurement confirmed the electron transfer from HM to Chlorella sorokiniana, accelerating the photosynthetic rate for the improved production of lipids (98%), proteins (60%), and chlorophyll a (121%), compared to untreated C. sorokiniana control cells. Moreover, by visualizing the Nile red (NR) fluorescence response from C. sorokiniana/HM cells, a high lipid content was observed with a larger cell size (14.6 µm) compared to control cells (8.7 µm). Fatty acid methyl esters (FAMEs), obtained from C. sorokiniana/HM, were noted with a large-scale volume of C16:C18 fatty acids (>80%). We, therefore, envisage that HM plays a significant role in enhancing the generation of lipids and proteins from C. sorokiniana. These outcomes assure a qualitative transit in the bioenergy domain.