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1.
Cereb Cortex ; 31(9): 4314-4328, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-33866366

RESUMO

Local field potentials (LFPs) in visual cortex are reliably modulated when the subject's focus of attention is cued into versus out of the receptive field of the recorded sites, similar to modulation of spikes. However, human psychophysics studies have used an additional attention condition, neutral cueing, for decades. The effect of neutral cueing on spikes was examined recently and found to be intermediate between cued and uncued conditions. However, whether LFPs are also precise enough to represent graded states of attention is unknown. We found in rhesus monkeys that LFPs during neutral cueing were also intermediate between cued and uncued conditions. For a single electrode, attention was more discriminable using high frequency (>30 Hz) LFP power than spikes, which is expected because LFP represents a population signal and therefore is expected to be less noisy than spikes. However, previous studies have shown that when multiple electrodes are used, spikes can outperform LFPs. Surprisingly, in our study, spikes did not outperform LFPs when discriminability was computed using multiple electrodes, even though the LFP activity was highly correlated across electrodes compared with spikes. These results constrain the spatial scale over which attention operates and highlight the usefulness of LFPs in studying attention.


Assuntos
Potenciais de Ação/fisiologia , Atenção/fisiologia , Estimulação Luminosa/métodos , Córtex Visual/fisiologia , Animais , Macaca mulatta , Masculino
2.
Indian J Crit Care Med ; 25(7): 768-772, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34316170

RESUMO

INTRODUCTION: Acute kidney injury (AKI) is defined in terms of serum creatinine (SrCrt) and urine output (UO). AKI occurs in 25% of critically ill patients, which increases the risk of morbidity and mortality. Early diagnosis of AKI is challenging, as utility of biomarkers is limited. This study is the first of its kind to estimate urinary potassium (UrK) excretion and its association with AKI in an Indian intensive care unit (ICU). AIMS AND OBJECTIVES: To study the association between UrK excretion and its ability to predict AKI in ICU patients. MATERIAL AND METHODS: During this prospective observational study, the patient's urinary indices and renal function tests were measured on day 1 of the ICU admission. UrK excretion and creatinine clearance (CrCl) were calculated from a 2-hour morning urine sample. Association between 2-hour UrK excretion and calculated CrCl and their ability to predict AKI in the subsequent 7 days was evaluated by Kidney Disease Improving Global Outcome (KDIGO)-AKI grading. RESULTS: Hundred patients admitted to ICU with a mean age of 53.59 ± 15.8 years were studied. The mean UrK excretion of 4.39 ± 2.52 was correlated linearly with CrCl and has a better prediction to AKI with the area under the receiver-operating characteristic curve value of 0.809 (CI 0.719-0.899), with a significant p-value (p <0.05). UrK excretion value of 3.49 on day 1 of ICU admission had 87% sensitivity and 74% specificity in predicting AKI. Thirty-one (31%) developed AKI, of which seven (22.58%) required renal replacement therapy (RRT), with 19% of all-cause mortality. CONCLUSION: Diagnosis of AKI with traditional methods is not promising. UrK excretion correlates well with CrCl, which can be considered as the simplest accessible marker for predicting AKI in ICUs. HOW TO CITE THIS ARTICLE: Kumar NS, Kumar GN, Misra KC, Rao M, Chitithoti S, Prakash SY. Association between Urinary Potassium Excretion and Acute Kidney Injury in Critically Ill Patients. Indian J Crit Care Med 2021;25(7):768-772.

3.
Indian J Crit Care Med ; 24(11): 1135-1136, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33384524

RESUMO

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. We present a 61-year-old uncorrected TOF patient who presented with sepsis and acute respiratory failure. At presentation, the patient had tachypnea, tachycardia, and oxygen saturation (SpO2) 64%. Chest X-ray (CXR) showed bilateral basal opacities. 2D echo revealed left ventricular dysfunction, infundibulum stenosis, pulmonary atresia, overriding of the aorta, and ventricular septal defect. A provisional diagnosis of community-acquired pneumonia with septic shock with uncorrected TOF was made. He received empirical antibiotics, ventilatory support, and supportive care. Ventilator weaning was done accepting an arbitrary baseline SpO2 of 70-75% and lactate-guided volume resuscitation led to a successful outcome. Coronary angiogram showed collaterals. This case report illustrates the dilemmas faced in treating a critically ill uncorrected TOF. To the best of our knowledge, this case could be the oldest surviving uncorrected TOF patient in the Indian population. HOW TO CITE THIS ARTICLE: Prakash SY, Kartik M, Rao M, Harde YR. Challenges Faced in Managing an Adult Uncorrected Tetralogy of Fallot Patient with Pneumonia and Septic Shock in the Intensive Care Unit. Indian J Crit Care Med 2020;24(11):1135-1136.

4.
Am J Otolaryngol ; 36(2): 122-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25447932

RESUMO

OBJECTIVE: The aim of this study is to validate the applicability of the PolyVinyliDene Fluoride (PVDF) nasal sensor to assess the nasal airflow, in healthy subjects and patients with nasal obstruction and to correlate the results with the score of Visual Analogue Scale (VAS). METHODS: PVDF nasal sensor and VAS measurements were carried out in 50 subjects (25-healthy subjects and 25 patients). The VAS score of nasal obstruction and peak-to-peak amplitude (Vp-p) of nasal cycle measured by PVDF nasal sensors were analyzed for right nostril (RN) and left nostril (LN) in both the groups. Spearman's rho correlation was calculated. The relationship between PVDF nasal sensor measurements and severity of nasal obstruction (VAS score) were assessed by ANOVA. RESULTS: In healthy group, the measurement of nasal airflow by PVDF nasal sensor for RN and LN were found to be 51.14±5.87% and 48.85±5.87%, respectively. In patient group, PVDF nasal sensor indicated lesser nasal airflow in the blocked nostrils (RN: 23.33±10.54% and LN: 32.24±11.54%). Moderate correlation was observed in healthy group (r=-0.710, p<0.001 for RN and r=-0.651, p<0.001 for LN), and moderate to strong correlation in patient group (r=-0.751, p<0.01 for RN and r=-0.885, p<0.0001 for LN). CONCLUSION: PVDF nasal sensor method is a newly developed technique for measuring the nasal airflow. Moderate to strong correlation was observed between PVDF nasal sensor data and VAS scores for nasal obstruction. In our present study, PVDF nasal sensor technique successfully differentiated between healthy subjects and patients with nasal obstruction. Additionally, it can also assess severity of nasal obstruction in comparison with VAS. Thus, we propose that the PVDF nasal sensor technique could be used as a new diagnostic method to evaluate nasal obstruction in routine clinical practice.


Assuntos
Técnicas de Diagnóstico do Sistema Respiratório/instrumentação , Obstrução Nasal/diagnóstico , Polivinil , Rinomanometria/instrumentação , Rinomanometria/métodos , Adulto , Análise de Variância , Estudos de Casos e Controles , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/fisiopatologia , Obstrução Nasal/fisiopatologia , Valores de Referência , Transdutores , Escala Visual Analógica
5.
J Indian Assoc Pediatr Surg ; 19(3): 178-80, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25197200

RESUMO

Megalourethra is a rare congenital disorder of anterior urethra and erectile tissue of penis. It mainly appears in two types-a milder scaphoid type and severe fusiform type. Fusiform type is commonly associated with congenital anomalies of various systems of the body. Isolated megalourethra without other congenital anomalies is extremely rare. We report one such case which was detected postnatally and successfully treated by reduction urethroplasty.

6.
bioRxiv ; 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-37609148

RESUMO

Behavioral outcome (i.e., whether a target is detected or missed) depends on attentional state and potentially other factors related to decision-making, which could in turn modulate the power and phase of neuronal oscillations. Here we investigated whether attentional state (i.e., whether attention is inside or outside the receptive fields of neurons) and behavioral outcome are distinguishable using the power and phase of local field potential (LFP) recorded from electrode arrays in area V4 of two male rhesus monkeys performing an attentional task under different cuing conditions. Since attention also strongly modulates pairwise measures such as spike count correlation and phase consistency which are typically measured across trials, we developed novel methods to obtain single-trial estimates of these measures. Surprisingly, while attentional location was best discriminated using gamma and high-gamma power, behavioral outcome was best discriminated by alpha power and steady-state visually evoked potential. Power outperformed absolute phase, although single-trial gamma phase consistency provided good attentional discriminability. Our results provide a clear dissociation between the neural mechanisms that regulate attentional focus and those that govern behavioral outcome.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38279749

RESUMO

High demand and ongoing technological advancements have created a market for sensors that is both varied and rapidly evolving. Bioactive compounds are separated systematically to conduct an in-depth investigation, allowing for the profiling or fingerprinting of different Plantae kingdoms. The profiling field is significant in elucidating the complex interplay of plant traits, attributes, and environmental factors. Flexible technology advancements have enabled the creation of highly sensitive sensors for the non-destructive detection of molecules. Additionally, very specialized integrated systems that will allow multiplexed detection by integrating many hybrid approaches have been developed, but these systems are highly laborious and expensive. Electrochemical sensors, on the other hand, are a viable option because of their ability to accomplish exact compound detection via efficient signal transduction. However, this has not been investigated because of some obstacles to learning minimum metabolites' fundamentals and nonredox properties. This article reviews the electrochemical basis of plants, contrasting it with more conventional techniques and offering both positive and negative perspectives on the topic. Because few studies have been devoted to the concept of merging the domains, we've expanded the scope of this work by including pertinent non-phytochemical reports for better report comparison.

8.
Med Leg J ; : 258172231225915, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619161

RESUMO

Sudden death from haemopericardium as a result of a right atrial rupture is uncommon, most particularly when this occurs spontaneously without any prior trauma or evidence of atrial wall pathology. The deceased was a 32-year-old man. At lunchtime his symptoms of unease, giddiness and unconsciousness began and within 45 minutes he arrived at the hospital. His vitals could not be recorded in the emergency department, and after CPR, he was pronounced dead. At autopsy, an isolated right atrial rupture, without any disease of the heart wall, was discovered. The right atrium has the weakest wall and is frequently the site of spontaneous rupture brought on by increased intraluminal pressure. Both liquid blood and clotted blood were found in the pericardial cavity. Low atrial pressure encourages clot formation because it causes considerably slower blood entry into the pericardium at the time of atrial rupture compared with entry at the time of ventricular rupture. Evidence of chronic lung disease was found which explains the raised intraluminal pressure of the heart chambers. Even with no history of trauma or myocardial infarction, the Beck triad - an engorged neck vein, a muffled heart sound, and low blood pressure - should alert the emergency room staff to the possibility of cardiac tamponade because, in a very unlikely scenario, spontaneous cardial wall rupture might occur.

9.
Breast Cancer ; 31(3): 440-455, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38421553

RESUMO

Silent mating type information regulation 2 homolog 1 (SIRT1) is a class III histone deacetylase (HDAC) that is NAD + dependent and essential for metabolism, senescence, and cell survival. SIRT1 is overexpressed in several cancers, including breast cancer. SIRT1 is a well-known target gene of the estrogen receptor alpha (ER alpha) and is closely related to ER alpha deacetylation. Transcription factor Estrogen-related receptors (ERRs) share sequence homology with ERs in the DNA-binding domain, therefore, the possibility of sharing target genes between them is high. Our current research aims to gain insight into the function of ERRß in regulating the activity of SIRT1 during the progression of breast cancer. ER-positive (ER + ve) breast cancer cells and tissues had considerably enhanced SIRT1 expression. Six potential ERRE sites were identified by analysis of the 5' upstream region of SIRT1, and both in vitro and in vivo experiments supported their presence. We found SIRT1 to be up-regulated in ERRß overexpressed ER + ve breast cancer cells. Furthermore, our findings suggested that ectopic production of ERR and PCAF would increase SIRT1 activity. Our findings also indicated that ectopic production of ERRß and PCAF increased SIRT1 activity. With sufficient evidence demonstrating the substantial involvement of SIRT1 in cell proliferation, migration, and colony formation capability, we were also able to illustrate the tumorigenic role of SIRT1. Overall, our findings highlight SIRT1's tumorigenic influence on breast cancer and suggest that SIRT1 inhibitors might serve as potential therapeutic drugs for the treatment of breast cancer.


Assuntos
Neoplasias da Mama , Regulação Neoplásica da Expressão Gênica , Receptores de Estrogênio , Sirtuína 1 , Feminino , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Carcinogênese , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células MCF-7 , Receptores de Estrogênio/metabolismo , Sirtuína 1/metabolismo , Sirtuína 1/genética
10.
Med Leg J ; : 258172241230207, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38690611

RESUMO

Acute rheumatic fever-related acquired heart disease in children and young adults is a worldwide issue, but it poses a serious public health threat in developing nations like India. We present a case report of a young adult who collapsed suddenly during a routine walk and was declared dead in an emergency ward on arrival. There was no significant past medical history. On autopsy, massive cardiomegaly and a "butter and bread" appearance of the pericardium, along with findings suggestive of mitral stenosis and aortic regurgitation, raised suspicion about rheumatic heart disease. Rheumatic carditis was confirmed by a microscopic examination that showed Aschoff bodies in the left ventricle, mitral valve and interventricular septum, in addition to uncommon Anitschkow cells in the left ventricle. A sudden death due to undiagnosed rheumatic carditis causing such massive cardiomegaly is rare. This case highlights the need to keep rheumatic carditis as a cause of sudden death.

11.
J Clin Orthop Trauma ; 52: 102424, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38766386

RESUMO

Introduction: Effective management of postoperative pain in total knee arthroplasty (TKA) poses a significant challenge for surgeons. Achieving rapid recovery without pain and promoting early ambulation in immediate and early postoperative periods are essential for patient satisfaction. There are many pain management protocols including nerve blocks. Nerve blocks procedures were done using USG and anaesthetist dependent. This cadaveric study aimed to define the VMO (Vastus medialis obliquus) triangle to target the 'safe zone' of the saphenous nerve during TKA: A surgeon's friendly technique. Methods: 12 formalin-fixed embalmed cadaveric lower limbs were dissected to explore anatomy, trajectory, the relation of saphenous nerve and measured the distances from the nearby palpable bony landmarks. Results: The average distance to target the saphenous nerve i.e target point from midpoint of superior pole of the patella was 10.6cm, the average angle to target the saphenous nerve is the angle between the line joining the medial epicondyle to the midpoint of the superior pole of the patella is found to be 64.2°. The average distance from midpoint of superior pole patella to medial epicondyle is found to be 8.1cm. Therefore, triangle so formed using these three points (1. Medial epicondyle, 2. The midpoint of superior pole of the patella, 3. Target point of the saphenous nerve) is called a VMO triangle. Conclusions: The saphenous nerve course, relations, and the distances from intraoperative bony landmarks for the VMO triangle during TKA which is a reproducible triangle so may be useful for arthroplasty surgeons to achieve successful saphenous nerve block and to avoid related complications during total knee arthroplasty (TKA).

12.
Curr Mol Med ; 23(8): 726-736, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37606033

RESUMO

BACKGROUND: Fungal infections have become a worldwide problem due to their involvement in numerous diseases. The risk factors for fungal infections are multiple surgeries, transplant therapies, frequent administration of antibiotics, cancer treatments, and prosthetic devices. The problem of resistance in fungi against drug therapies is widespread, becoming a severe health-related problem. OBJECTIVE: The study's objective was to identify molecular targets that may open new paths for fungal treatment. METHODS: Several research and review articles were studied to gather information regarding the novel mechanism of antifungal drugs. However, identifying novel targets is challenging due to the similarities between host and fungal cells. Although, the plasma membrane and cell wall of fungus offer various drug targets that may target to fight against microbial infections. Unfortunately, biofilm formation and over-expression of protein are a few mechanisms through which fungi develop resistance. RESULTS: Despite these problems, several approaches have been working to prevent and treat fungal infections. Modifying the chemical structure of antifungal drugs may also improve their activity and pharmacokinetics. In this review article, we have discussed the molecular targets and novel techniques to be used for the development of antifungal drugs. In addition, different strategies to overcome resistance in fungi have also been described. CONCLUSION: This article may be helpful for the researchers working on the discovery and development of new antifungal works for resistance to fungal diseases.


Assuntos
Antifúngicos , Micoses , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Terapia de Alvo Molecular , Micoses/tratamento farmacológico , Antibacterianos , Membrana Celular
13.
Comb Chem High Throughput Screen ; 26(7): 1385-1399, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35927817

RESUMO

BACKGROUND: Nature has bestowed mother Earth with an array of herbals utilized as therapeutics for various human ailments since the origin of life. Bryonia laciniosa (family: Cucurbitaceae) is one such herb, which finds its mention in various traditional systems of medicine and has attracted current researchers due to its significant therapeutic value. OBJECTIVE: The current article aims to present a literature metasynthesis on Bryonia laciniosa. METHODS: The authors performed scholarly searches for peer-reviewed findings on Bryonia laciniosa and incorporated all the data related to the phytochemical and therapeutic profile of the drug. RESULTS: This compilation comprises of Phytochemical and Pharmacological profile of Bryonia laciniosa elaborating its traditional significance and recent researches related to its biological activities. The plant exhibits its potential as an antimicrobial, anti-inflammatory, analgesic, antipyretic, anticonvulsant, anti-asthmatic, anticancer, antioxidant, antidiabetic, and aphrodisiac agent. It also displays its benefits in wound healing and ulcerative colitis. CONCLUSION: The presence of flavonoids, saponins, terpenoids, anthocyanins, coumarins, alkaloids, polyphenols, tannins and emodins in this plant is responsible for its various pharmacological activities. The retrospective study provides direction for existing research as well as future studies to support the domain of pharmaceutical and medical sciences.


Assuntos
Bryonia , Extratos Vegetais , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Fitoterapia , Bryonia/química , Antocianinas , Estudos Retrospectivos , Compostos Fitoquímicos/farmacologia
14.
Curr Opin Neurobiol ; 76: 102589, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35751949

RESUMO

We review recent efforts to decode visual spatial attention from different types of brain signals, such as spikes and local field potentials (LFPs). Combining signals from more electrodes improves decoding, but the pattern of improvement varies considerably depending on the signal as well as the task (for example, decoding of sensory stimulus/motor intention versus location of attention). We argue that this pattern of results conveys important information not only about the usefulness of a particular brain signal for decoding attention, but also about the spatial scale over which attention operates in the brain. The spatial scale, in turn, likely depends on the extent of underlying mechanisms such as normalization, gain control via excitation-inhibition interactions, and neuromodulatory regulation of attention.


Assuntos
Interfaces Cérebro-Computador , Córtex Motor , Potenciais de Ação/fisiologia , Encéfalo , Córtex Motor/fisiologia , Movimento/fisiologia
15.
Cureus ; 14(6): e25908, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35844315

RESUMO

Introduction Acute pancreatitis (AP) is one of the most common emergency room presentations, with an annual worldwide incidence of 150-420 cases per million and a 30-50% mortality rate. Unfortunately, predicting prognosis in AP patients at an early admission phase is difficult. The Waterlow score is a semi-quantitative composite score devised to stratify the risk of developing pressure sores in in-patient settings. Components such as age, gender, nutritional status, body mass index, mobility, smoking status, comorbidities, surgery, use of medications, neurological status, and continence, all combine to generate a single numerical figure between 2 and 64 to overcome the difficulty of the composite scoring systems such as the Ranson score, Glassgow score, Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) and its modification (Portsmouth or P-POSSUM), Simplified Acute Physiology Score (SAPS 2), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Bedside index for severity in acute pancreatitis (BISAP). Aim This study aimed to validate the Waterlow score as a surrogate marker in predicting in-patient mortality, length of hospital stay (LOHS), intensive care unit (ICU) admissions, and AP complications compared to the Ranson score and serum CRP levels. Method A prospective case series analysis was conducted from August 2018 to November 2019 at a tertiary care center in central Gujarat. This study included 51 newly diagnosed patients with AP or acute on chronic pancreatitis on accrual. Out of 51 patients, four were excluded from our study, as three were discharged against medical advice (DAMA) and one other absconded from the ward premises. The study group comprised 47 patients diagnosed with AP, out of which 40 patients were male (85.1%) and seven were females (14.9%). The mean age of the population was 37.5 ± 13.0 years. Microsoft Excel calculated the standard deviation and mean for data entry. All statistical analyses were made with MedCalc software version 19.1.3 (MedCalc Software Ltd., Ostend, Belgium). Result When the Waterlow score, Ranson score, and serum C-reactive protein (CRP) levels were plotted against inpatient mortality, the area under the curve (AUC) was found to be 0.85, 0.80, and 0.98, respectively. The plot of CRP lay closest to the vertical axis. On plotting the receiver operator characteristic (ROC) curve of all three markers of AP severity, the area under the graph was calculated to be 0.81 (Waterlow score), 0.81 (Ranson score), and 0.82 (serum CRP), respectively. Nearly all three markers performed similarly. Waterlow score offers a high sensitivity but poor specificity in sorting outpatients at risk of adverse outcomes. It was observed that the Waterlow score could significantly predict mortality, ICU admissions, and LOHS in this study population. In contrast, the Ranson score and serum CRP levels could not indicate LOHS. A risk assessment tool based upon a subset of Waterlow parameters with additional variables may perform better than a tool based solely on Waterlow risk factors. Conclusion This study showed no correlation between the Waterlow score, the rate of local complications (p = 0.9513), and the incidences of surgical interventions (p = 0.9915). Therefore, a risk assessment tool based upon a subset of Waterlow parameters with additional variables may perform better than a tool based solely on Waterlow risk factors.

16.
J Food Biochem ; 46(12): e14452, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36165437

RESUMO

Sesquiterpenes are important in human health because they can treat viral infection, cardiovascular disease, and cancer. Sesquiterpenes have also been shown to increase the sensitivity of tumor cells to conventional pharmacological therapies, in addition to their antiviral effects. The present review article was drafted with an intention to gather information regarding sesquiterpenes and its medicinal importance. The role of sesquiterpenes in the endogenous production of sesquiterpenes by plants and fungi, as well as the mechanisms by which they are effective against viral infection, are discussed in this review. Different online libraries such as PUBMED, Sciencedirect, MEDLINE were assessed to gather information, additionally, books, magzagines, journals, and scientific newspapaers were also studied to make this article more informative. This review examines novel synthesis mechanisms, their cyclization, purification techniques, and the diverse ecological roles sesquiterpenes play in the plant producer, which varies according to the plant and the chemical under consideration. In this article, we have discussed the consequences of sesquiterpenes and their properties for future crop productivity. We have addressed the many forms of sesquiterpenes that have been shown to have antiviral activity in various diseases. The consequences of sesquiterpenes and their properties are very useful for future crop productivity. We have addressed the many forms of sesquiterpenes that have been shown to have antiviral activity in the treatment of various diseases. PRACTICAL APPLICATIONS: Novel synthesis mechanisms, their cyclization, purification techniques, and the diverse ecological roles of sesquiterpenes will be very helfpul in drug development process. Sesquiterpene lactones are shown in this review to have qualities that warrant further scientific investigation in order to stimulate preclinical and clinical trials leading to the creation of novel medications. For antiviral drug development, the sesquiterpenes are a good prospective lead molecule because they can suppress viral replication by disrupting vRNA production and viral protein production.


Assuntos
Sesquiterpenos , Viroses , Humanos , Estudos Prospectivos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Viroses/tratamento farmacológico , Plantas , Antivirais/farmacologia
17.
Cell Death Dis ; 11(8): 703, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32839427

RESUMO

Estrogen-related receptor beta (ERRß) is downregulated in breast cancer cells and its overexpression in breast cancer patients is positively correlated with an improved prognosis and prolonged relapse-free survival. Here, we unravelled a molecular mechanism for ERRß downregulation in breast cancer. We found that ERRß is a key substrate of the SCF complex and that NEDDylation can activate the Cullin subunits of the SCF complex to target ERRß for degradation in breast cancer. Consistently, using in vitro and in vivo models, we demonstrated that MLN4924, a specific small molecule inhibitor of NEDDylation, can restore ERRß expression and culminate in a reduction in cell proliferation and migration of breast cancer cells. We also showed that increased ERRß expression promotes the upregulation of its target genes, including the tumour suppressors p21Cip1/Waf1 and E-cadherin, involved in cell proliferation and migration arrest at the gene promoter level. Interestingly, this tumour suppressive role of ERRß does not depend on the expression of ERα in breast cancer. Moreover, our data revealed that the ERRß recruits the transcription co-activator p300 to its targeted gene promoters to upregulate their expression. Collectively, our work revealed that restoration of ERRß expression using the NEDDylation inhibitor MLN4924 can be a novel and effective strategy for breast cancer treatment.


Assuntos
Neoplasias da Mama/metabolismo , Receptor beta de Estrogênio/metabolismo , Proteína NEDD8/antagonistas & inibidores , Neoplasias da Mama/genética , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas Culina/metabolismo , Ciclopentanos/farmacologia , Progressão da Doença , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Recidiva Local de Neoplasia/genética , Pirimidinas/farmacologia , Receptores de Estrogênio/metabolismo , Ubiquitinas/metabolismo
18.
Indian J Otolaryngol Head Neck Surg ; 71(Suppl 3): 1935-1939, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31763271

RESUMO

A new nasal sensor has been designed using Polyvinylidene fluoride (PVDF) film using its piezoelectric property to measure nasal patency. The aim of this study is to determine the intra- and intersession reliability of the new PVDF nasal sensor measurement of unilateral and combined nasal parameters in a group of healthy subjects. Two identical nasal sensors: for right nostril (RN) and left nostril (LN) were designed using piezoelectric natured PVDF films. Twenty subjects were studied. To evaluate the repeatability, total three sets of PVDF sensor measurements were recorded, two sets were taken 5 min apart during same session without repositioning the PVDF nasal sensors and two more sets were taken during 1 h apart successively, by repositioning the PVDF nasal sensor. Intraclass correlation coefficients (ICC) of PVDF sensor measurements for intra- and intersession showed a high and greater repeatability over time for all the combined (mean) and unilateral (RN and LN) values. In both healthy and patients, ICC values for both intra- and intersession measurements were ≥ 0.80 confirming strong reliability and also almost all of the coefficients of variation for the same parameters were low (below 10%). PVDF sensor measurements showed good intra- and intersession repeatability and can be recommended for the objective monitoring of nasal patency during diagnosis and follow-up of conditions.

19.
Indian J Nucl Med ; 33(1): 43-47, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29430114

RESUMO

CONTEXT: Instillation or application of the radiotracer over the tear film is one of the important parts of dacroscintigraphy. Our study explains the value of an improvised dropper technique so that desired amount of radioactivity in desired volume can be instilled over the tear film. AIM: The aim of the study is to introduce a simple and convenient instillation method based on dropper technique for performing dacroscintigraphy. This improvised dropper technique can be used so that desired amount of radioactivity in desired volume can be instilled over the tear film. The objectives of this experiment are to measure the volume and activity of each drop from the dropper. SETTINGS AND DESIGN: Experiment of volume and activity measurement standardization was carried out in two parts. In the first part, we calculated the volume of each drop indirectly to standardize the volume of drop. In the second part, we standardized the activity in each drop by measuring it in a dose calibrator. SUBJECTS AND METHODS: In this study, we used a common pediatric dropper of approximately 1 ml capacity, radioactivity (99mTcO4 pertechnetate), sample vial (container), vial holder, a pair of nonsterile gloves, dose calibrator, etc., Experiments of volume and radioactivity standardization were carried out in two parts. The first part of experiment calculated volume of each drop indirectly, and in the second, we standardized the activity in each drop by measuring it in dose calibrator. Statistical analysis used: Analysis of variance test was used to calculate the correlation of readings by same individual as well as among the three individuals. RESULTS: After analysis of result obtained, it was understood that there was no significant difference found in volume and activity of each drop in the readings recorded by same individual as well as among the three individuals. The calculated activity and observed activity were 86.64 and 79.16 µCi, respectively. The difference was only 8.63% lying within acceptable limits.

20.
Methods Mol Biol ; 1645: 227-238, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28710632

RESUMO

Androsta-1,4-diene-3,17-dione (androstadienedione, ADD) is key intermediate for the organic synthesis of a variety of female sex hormones such as estrone, estradiol, estriol and other related derivatives. De novo synthesis of this molecule is not yet reported in any form of living system, i.e., microbial, plant, and animal. The structural complexities due to presence of several chiral carbon centers create significant hurdles in chemical synthesis of such molecules. Microbe-mediated biotransformation offer a highly reliable, cost-effective, and relatively non hazardous way for commercial manufacturing of steroidal key intermediates. Currently microbial biotransformations are extensively being exploited for large-scale production of basic intermediates such as androstenedione (AD), ADD, and several types of hydroxylated derivatives of androstane compounds. In this chapter several aspects of microbial biotransformation process of AD to ADD are discussed.


Assuntos
Androstenodiona/biossíntese , Bactérias/metabolismo , Biotransformação , Engenharia Metabólica/métodos , Androstadienos/química , Androstenodiona/química , Bactérias/química , Bactérias/genética , Carbono/química , Estradiol/biossíntese , Estradiol/química , Estrona/biossíntese , Estrona/química
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