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1.
Artigo em Inglês | MEDLINE | ID: mdl-38904162

RESUMO

Objective: Human Chorionic Gonadotropin (hCG) plays a crucial role in embryo implantation and in maintenance of pregnancy. An immuno-contraceptive approach involves the use of a recombinant hCGß-LTB vaccine formulated with adjuvant Mycobacterium indicus pranii (MIP), to prevent pregnancy without disturbing ovulation, hormonal profiles, and menstrual cycles in women. The present work in mice was designed to address issues encountered in clinical trials conducted with hCGß-LTB vaccine, with focus on two primary concerns. Firstly, it aimed to determine the optimal vaccine dosage required to induce a high level of anti-hCG antibodies. Secondly, it aimed to assess the safety profile of the vaccine, specifically injection site reactions in the form of nodules, observed in some of the subjects.Methods and Results: Studies undertaken indicate that a 2 µg dose of the protein version of the vaccine, administered in mice through the intramuscular route, can induce high anti-hCG titres. Furthermore, administering a booster dose enhances the antibody response. Our findings suggest that the concentration and frequency of administration of the adjuvant MIP can also be reduced without compromising vaccine efficacy.Conclusion: The issue of nodule formation at the injection site can be mitigated either by administering the vaccine along with MIP intramuscularly or injecting hCG vaccine and MIP at separate intradermal sites. Thus, protein vaccine administered at a 2µg dose via the intramuscular route addresses both efficacy and safety concerns.


The Phase I/II clinical trials initiated with the recombinant hCG vaccine in women revealed inadequate antibody titres in all subjects, alongside the development of nodules at the injection sites in some participants. Studies were undertaken in mice to propose potential strategies for mitigating injection site reactions and enhancing the antibody response. It was concluded that the optimum dose of the protein version of the vaccine to get high antibody titres, is 2 µg administered intramuscularly while upholding safety standards.

2.
Sci Rep ; 14(1): 7263, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538715

RESUMO

Agro-waste is the outcome of the under-utilization of bioresources and a lack of knowledge to re-use this waste in proper ways or a circular economy approach. In the Indian medicinal system, the root of Cyperus scariosus (CS) is used at a large scale due to their vital medicinal properties. Unfortunately, the aerial part of CS is treated as agro-waste and is an under-utilized bioresource. Due to a lack of knowledge, CS is treated as a weed. This present study is the first ever attempt to explore CS leaves as medicinally and a nutrient rich source. To determine the food and nutritional values of the neglected part of Cyperus scariosus R.Br. (CS), i.e. CS leaves, phytochemicals and metal ions of CS were quantified by newly developed HPLC and ICPOES-based methods. The content of the phytochemicals observed in HPLC analysis for caffeic acid, catechin, epicatechin, trans-p-coumaric acid, and trans-ferulic acid was 10.51, 276.15, 279.09, 70.53, and 36.83 µg/g, respectively. In GC-MS/MS analysis, fatty acids including linolenic acid, phytol, palmitic acid, etc. were identified. In ICPOES analysis, the significant content of Na, K, Ca, Cu, Fe, Mg, Mn, and Zn was observed. The TPC and TFC of the CS leaves was 17.933 mg GAE eq./g and 130.767 mg QCE eq./g along with an IC50 value of 2.78 mg/mL in the DPPH assay and better antacid activity was measured than the standard (CaCO3). The methanolic extract of CS leaves showed anti-microbial activity against Staphylococcus aureus (15 ± 2 mm), Pseudomonas aeruginosa (12 ± 2 mm) and Escherichia coli (10 ± 2 mm). In silico studies confirmed the in vitro results obtained from the antioxidant, antiacid, and anti-microbial studies. In addition, in silico studies revealed the anti-cancerous and anti-inflammatory potential of the CS leaves. This study, thus, demonstrated the medicinal significance of the under-utilized part of CS and the conversion of agro-waste into mankind activity as a pharmaceutical potent material. Consequently, the present study highlighted that CS leaves have medicinal importance with good nutritional utility and have a large potential in the pharmaceutical industry along with improving bio-valorization and the environment.


Assuntos
Cyperus , Extratos Vegetais/química , Espectrometria de Massas em Tandem , Antioxidantes/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/análise , Folhas de Planta/química
3.
Nat Commun ; 14(1): 6582, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37852964

RESUMO

Vascular endothelial cadherin (VE-cadherin) expressed at endothelial adherens junctions (AJs) is vital for vascular integrity and endothelial homeostasis. Here we identify the requirement of the ubiquitin E3-ligase CHFR as a key mechanism of ubiquitylation-dependent degradation of VE-cadherin. CHFR was essential for disrupting the endothelium through control of the VE-cadherin protein expression at AJs. We observe augmented expression of VE-cadherin in endothelial cell (EC)-restricted Chfr knockout (ChfrΔEC) mice. We also observe abrogation of LPS-induced degradation of VE-cadherin in ChfrΔEC mice, suggesting the pathophysiological relevance of CHFR in regulating the endothelial junctional barrier in inflammation. Lung endothelial barrier breakdown, inflammatory neutrophil extravasation, and mortality induced by LPS were all suppressed in ChfrΔEC mice. We find that the transcription factor FoxO1 is a key upstream regulator of CHFR expression. These findings demonstrate the requisite role of the endothelial cell-expressed E3-ligase CHFR in regulating the expression of VE-cadherin, and thereby endothelial junctional barrier integrity.


Assuntos
Junções Aderentes , Ubiquitina , Animais , Camundongos , Junções Aderentes/metabolismo , Ubiquitina/metabolismo , Ligases/metabolismo , Lipopolissacarídeos/farmacologia , Caderinas/genética , Caderinas/metabolismo , Endotélio/metabolismo , Ubiquitinação , Endotélio Vascular/metabolismo , Células Cultivadas
5.
Neurodegener Dis Manag ; 12(2): 77-91, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35313124

RESUMO

Aim: This subanalysis of the OPTIPARK study aimed to confirm the effectiveness and safety of opicapone in patients with Parkinson's disease and motor fluctuations in clinical practice specifically in the UK and to assess the impact of opicapone on treatment costs. Methods: Patients received opicapone added to levodopa for 6 months. Clinical outcomes were assessed at 3 and 6 months and treatment costs at 6 months. Results: Most patients' general condition improved at 3 months, with sustained improvements reported at 6 months. Opicapone improved motor and non-motor symptoms at both timepoints, was generally well tolerated and reduced total treatment costs by GBP 3719. Conclusion: Opicapone added to levodopa resulted in clinical improvements and reduced treatment costs across UK clinical practice.


Patients with Parkinson's disease (PD) often experience motor fluctuations (reduced and variable response to medication) following prolonged treatment with levodopa, which is currently the most effective treatment for the symptoms of PD. Opicapone has been developed for use in combination with levodopa to reduce the occurrence of motor fluctuations and was shown to be effective in two large clinical trials. This study describes the effectiveness, safety and cost-saving impact of opicapone when used to treat patients with PD and motor fluctuations across everyday clinical practice in the UK. Six months' treatment with opicapone was generally well tolerated, resulted in an improvement of the patients' overall PD condition and reduced treatment costs. Clinical trial registration: Registered in July 2016 at NCT02847442 (ClinicalTrial.gov).


Assuntos
Levodopa , Doença de Parkinson , Antiparkinsonianos/efeitos adversos , Inibidores de Catecol O-Metiltransferase/uso terapêutico , Custos e Análise de Custo , Método Duplo-Cego , Humanos , Levodopa/efeitos adversos , Oxidiazóis , Doença de Parkinson/tratamento farmacológico , Reino Unido
6.
Multimed Tools Appl ; 81(18): 25029-25050, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35342329

RESUMO

Training supervised machine learning models like deep learning requires high-quality labelled datasets that contain enough samples from various categories and specific cases. The Data as a Service (DaaS) can provide this high-quality data for training efficient machine learning models. However, the issue of privacy can minimize the participation of the data owners in DaaS provision. In this paper, a blockchain-based decentralized federated learning framework for secure, scalable, and privacy-preserving computational intelligence, called Decentralized Computational Intelligence as a Service (DCIaaS), is proposed. The proposed framework is able to improve data quality, computational intelligence quality, data equality, and computational intelligence equality for complex machine learning tasks. The proposed framework uses the blockchain network for secure decentralized transfer and sharing of data and machine learning models on the cloud. As a case study for multimedia applications, the performance of DCIaaS framework for biomedical image classification and hazardous litter management is analysed. Experimental results show an increase in the accuracy of the models trained using the proposed framework compared to decentralized training. The proposed framework addresses the issue of privacy-preserving in DaaS using the distributed ledger technology and acts as a platform for crowdsourcing the training process of machine learning models.

7.
Multimed Tools Appl ; 81(16): 22185-22214, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35002472

RESUMO

Smart city management is facing a new challenge from littered face masks during COVID-19 pandemic. Addressing the issues of detection and collection of this hazardous waste that is littered in public spaces and outside the controlled environments, usually associated with biomedical waste, is urgent for the safety of the communities around the world. Manual management of this waste is beyond the capabilities of governments worldwide as the geospatial scale of littering is very high and also because this contaminated litter is a health and safety issue for the waste collectors. In this paper, an autonomous biomedical waste management framework that uses edge surveillance and location intelligence for detection of the littered face masks and predictive modelling for emergency response to this problem is proposed. In this research a novel dataset of littered face masks in various conditions and environments is collected. Then, a new deep neural network architecture for rapid detection of discarded face masks on the video surveillance edge nodes is proposed. Furthermore, a location intelligence model for prediction of the areas with higher probability of hazardous litter in the smart city is presented. Experimental results show that the accuracy of the proposed model for detection of littered face masks in various environments is 96%, while the speed of processing is ten times faster than comparable models. The proposed framework can help authorities to plan for timely emergency response to scattering of hazardous material in residential environments.

8.
ACS Nano ; 15(11): 17439-17452, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34677951

RESUMO

Extracellular vesicles (EVs) are cell-secreted particles with broad potential to treat tissue injuries by delivering cargo to program target cells. However, improving the yield of functional EVs on a per cell basis remains challenging due to an incomplete understanding of how microenvironmental cues regulate EV secretion at the nanoscale. We show that mesenchymal stromal cells (MSCs) seeded on engineered hydrogels that mimic the elasticity of soft tissues with a lower integrin ligand density secrete ∼10-fold more EVs per cell than MSCs seeded on a rigid plastic substrate, without compromising their therapeutic activity or cargo to resolve acute lung injury in mice. Mechanistically, intracellular CD63+ multivesicular bodies (MVBs) transport faster within MSCs on softer hydrogels, leading to an increased frequency of MVB fusion with the plasma membrane to secrete more EVs. Actin-related protein 2/3 complex but not myosin-II limits MVB transport and EV secretion from MSCs on hydrogels. The results provide a rational basis for biomaterial design to improve EV secretion while maintaining their functionality.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , Animais , Camundongos , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , Comunicação Celular , Transporte Biológico , Hidrogéis/farmacologia , Hidrogéis/metabolismo
9.
Exp Brain Res ; 239(7): 2063-2075, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33928399

RESUMO

There is growing interest in how social processes and behaviour might be affected in Parkinson's disease. A task which has been widely used to assess how people orient attention in response to social cues is the spatial cueing task. Socially relevant directional cues, such as a picture of someone gazing or pointing to the left or the right have been shown to cause orienting of visual attention in the cued direction. The basal ganglia may play a role in responding to such directional cues, but no studies to date have examined whether similar social cueing effects are seen in people with Parkinson's disease. In this study, patients and healthy controls completed a prosaccade (Experiment 1) and an antisaccade task (Experiment 2) in which the target was preceded by arrow, eye gaze or pointing finger cues. Patients showed increased errors and response times for antisaccades but not prosaccades. Healthy participants made most anticipatory errors on pointing finger cue trials, but Parkinson's patients were equally affected by arrow, eye gaze and pointing cues. It is concluded that Parkinson's patients have a reduced ability to suppress responding to directional cues, but this effect is not specific to social cues.


Assuntos
Sinais (Psicologia) , Doença de Parkinson , Fixação Ocular , Humanos , Tempo de Reação , Movimentos Sacádicos
10.
J Cell Signal ; 2(1): 47-51, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33644778

RESUMO

Acute respiratory distress syndrome (ARDS) is the major cause of mortality among hospitalized acute lung injury (ALI) patients. Lung macrophages play an important role in maintaining the tissue-fluid homeostasis following injury. We recently showed that circulating monocytes recruited into the alveolar space suppressed the stimulator of type 1 interferon genes (STING) signaling in alveolar macrophages through sphingosine-1-phosphate (S1P). We used CD11b-DTR mice to deplete CD11b+ monocytes following LPS or Pseudomonas aeruginosa infection. Depletion of CD11b+ monocytes leads to the persistent inflammatory injury, infiltration of neutrophils, activation of STING signaling and mortality following lung infection. We demonstrated that adoptively transferred SPHK2-CD11b+ monocytes into CD11b-DTR mice after pathogenic infection rescue lung inflammatory injury.

11.
Int J Cardiovasc Imaging ; 37(3): 871-880, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33047178

RESUMO

Ethnic-specific normal reference ranges for various echocardiographic measurements are essential for accurate diagnostic interpretation and clinical decision-making. Unfortunately, such normative data for Indians is lacking. A total of 880 healthy volunteers (mean age 39.7 ± 12.3 years, 63.8% men) from six centers across different regions of India were enrolled in this study. Comprehensive transthoracic echocardiographic study was performed in all subjects, in accordance with the existing guideline recommendations. Cardiac chamber dimensions [Left ventricular (LV) end-diastolic diameter and volume; right ventricular (RV) basal diameter, left atrial volume] were obtained and indexed to body surface area. LV ejection fraction, LV global longitudinal strain (LVGLS) and measures of RV systolic function were also obtained. The subjects were divided into 3 age groups (35 years or less, 36-55 years and 56 years or above) for analysis. Age- and gender-specific reference values for various clinically relevant echocardiographic parameters were derived. Compared with women, men had larger cardiac chamber dimensions and volumes, but not when indexed. In contrast, the women had higher LV systolic function, but right ventricular systolic function was not different. The indexed LV volumes in our study were much smaller than those recommended in the American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) 2015 chamber quantification guidelines but were similar to those reported in the Indian patients included in the recent World Alliance Societies of Echocardiography (WASE) Normal Values Study. LVGLS was also comparable with the WASE data. INDEA study is the first, multi-centric study to provide normal echocardiographic references values for Indian adults. Our findings underscore the need to follow India-specific reference values, instead of those recommended by the ASE/EACVI, which are largely applicable to the western populations.


Assuntos
Função do Átrio Esquerdo , Ecocardiografia Doppler , Coração/diagnóstico por imagem , Volume Sistólico , Função Ventricular Esquerda , Adolescente , Adulto , Fatores Etários , Idoso , Superfície Corporal , Feminino , Voluntários Saudáveis , Coração/fisiologia , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores Raciais , Valores de Referência , Fatores Sexuais , Adulto Jovem
12.
Indian J Crit Care Med ; 24(10): 932-937, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33281317

RESUMO

BACKGROUND: Post-intensive care survivors have decreased quality-of-life scores and prolonged cognitive dysfunction due to baseline factors and events related to intensive care unit admission, which remain largely unrecognized. MATERIALS AND METHODS: A prospective observational cohort study to assess the quality of life and occurrence of cognitive dysfunction, 3 and 6 months following discharge from the intensive care unit, was carried out. We enrolled 136 adults presenting to the intensive care unit with no prior cognitive dysfunction or depression and followed up and assessed them with repeatable battery for the assessment of neuropsychological status (RBANS) and quality of life with short Form-36 (SF-36) health survey. RESULTS: The incidence and prevalence of cognitive dysfunction was 100% at 3 and 6 months, respectively, as assessed by RBANS with a global cognition scores at 3 and 6 months of 71 (IQR 68.5-73) and 74 (IQR 72-86), respectively. Higher Charlson's comorbidity score, increased severity of illness, longer duration of mechanical ventilation, pain, delirium, coma, and hospital stay were associated with statistically significant lower scores at 3 months. The median SF-36 mental component score (MCS) and physical component score (PCS) at 3 months were 38.4 and 32.5 and at 6 months were 38.2 and 32.6, respectively. Poor score was associated significantly with advancing age, poor functional parameters at baseline as evidenced by clinical frailty, poor baseline Katz ADL scores, increased severity of illness, longer duration of mechanical ventilation, occurrence and duration of delirium, coma, pain, and usage of sedatives with or without analgesics. CONCLUSION AND CLINICAL SIGNIFICANCE: Patients discharged from the intensive care unit are at high risk for persistent cognitive impairment and poor quality of life score. Poor baseline patient characteristics and events occurring in ICU are associated with worse cognition and quality of life scores. There is an urgent need to prevent, diagnose, and manage these patients by optimizing intensive care practices. HOW TO CITE THIS ARTICLE: Balasubramanian V, Suri JC, Ish P, Gupta N, Behera D, Gupta P, et al. Neurocognitive and Quality-of-life Outcomes Following Intensive Care Admission: A Prospective 6-month Follow-up Study. Indian J Crit Care Med 2020;24(10):932-937.

14.
Indian J Crit Care Med ; 24(8): 677-682, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33024374

RESUMO

INTRODUCTION: Obstetric patients are a special group of patients whose management is challenged by concerns for fetal viability, altered maternal physiology, and diseases specific to pregnancy. MATERIALS AND METHODS: A prospective analysis of all obstetric patients admitted to the critical care department was done to assess reasons for transfer to the critical care unit (CCU) and the interventions required for management of these patients. RESULTS: Between June 2013 and September 2017, obstetric admission comprised 95 women (5.9%) of the total critical care admissions. There were 77 patients (81.1%) who were discharged from the hospital and 18 patients (18.9%) died. In most of the cases, the primary reasons for shifting the patient to the CCU were severe preeclampsia with pulmonary edema (22.1%), eclampsia (8.4%), acute respiratory distress syndrome (ARDS) (14.7%), and hypovolemic shock in antepartum hemorrhage (APH) and postpartum hemorrhage (PPH) (10.5 and 13.7%, respectively). It was seen that 73 patients (76.8%) required ventilator support, 58 patients (57.4%) required vasopressor support, and intensive hemodynamic monitoring and blood/blood products were transfused in 55 patients (54.5%). The need for ventilator support was more in patients with a lower PaO2/FiO2 and a higher APACHE II score. Patients with a high severity of illness score and a lower PaO2/FiO2 had higher odds of requiring vasopressors. Low hemoglobin at the time of transfer to the CCU and a prolonged hospital stay were found to predict the need for blood transfusion. CONCLUSION: Obstetric patients are susceptible to critical illnesses but timely management improves the outcome of these young women. HOW TO CITE THIS ARTICLE: Suri J, Kumar R, Gupta A, Mittal P, Suri JC. A Prospective Study of Clinical Characteristics and Interventions Required in Critically Ill Obstetric Patients. Indian J Crit Care Med 2020;24(8):677-682.

15.
J Clin Hypertens (Greenwich) ; 22(7): 1154-1162, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32558208

RESUMO

Women are underrepresented in groups of patients seeking hypertension care in India. The present paper reports trends in office and ambulatory blood pressure measurement (OBPM, ABPM) and 24-h heart rate (HR) with sex in 14,977 subjects untreated for hypertension (aged 47.3 ± 13.9 years, males 69.4%) visiting primary care physicians. Results showed that, for systolic blood pressure (SBP), females had lower daytime ABPM (131 ± 16 vs. 133 ± 14 mm Hg, P < .001) but higher nighttime ABPM (122 ± 18 vs. 121 ± 16 mm Hg, P < .001) than males. Females had higher HR than men at daytime (80 ± 11 vs 79 ± 11.5 bpm) and nighttime (71 ± 11 vs 69 ± 11), respectively (all P < .001). Dipping percentages for SBP (7.4 ± 7.3 vs 9.3 ± 7.4%), DBP (10.1 ± 8.6 vs. 12.3 ± 8.9%), and HR (10.7 ± 7.9 vs. 12.8 ± 9.2%) were lower (P < .001) for females than for males, respectively. Females more often had isolated nighttime hypertension as compared to males (14.9%, n = 684% vs 10.6%, n = 1105; P < .001). BP patterns and HR showed clear differences in sex, particularly at nighttime. As females were more often affected by non-dipping and elevated nighttime SBP and HR than males, they should receive ABPM, at least, as frequently as men to document higher risk necessitating treatment.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Adulto , Pressão Sanguínea , Ritmo Circadiano , Feminino , Frequência Cardíaca , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade
17.
Indian Heart J ; 72(1): 27-31, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32423557

RESUMO

BACKGROUND: Acute decompensated heart failure (ADHF) is a growing public health problem in the community. Limited and often contradictory data are available from small studies published from India. Objective of this study was to report clinical characteristics, outcome, and discharge treatment strategies of these patients from a single community hospital. METHODS: In this observational prospective study from a multispeciality community hospital from North India, data were collected to include demographics, clinical characteristics, management strategies, and prognosis in 428 patients with ADHF admitted for more than two consecutive years (January 2017 through December 2018). RESULTS: The study included 428 patients (mean age 61 ± 14 years) of whom 59% were male. ADHF with reduced left ventricular ejection fraction (HFrEF) was present in 77% subjects; Preserved (≥50%) and midrange ejection fraction (41-49%) with ADHF was observed in 12% and 11% patients, respectively. Ischemic etiology was noticed in 69% of the population. Prior myocardial revascularisation was observed in 47% of all and in 71% of those with ischemic heart disease. Major comorbidities included type 2 diabetes mellitus (60.7%), arterial hypertension (51%), anemia (54%), chronic kidney disease (29%), atrial fibrillation (16%), and hypothyroidism (9%). Mean hospital stay was 4.5 ± 3.2 days (inter-quartile range: 2-9 days). In-hospital mortality was 8.4% (36 patients) and there were additional 17% deaths over 6 months after discharge. At-discharge medication in those with HFrEF included anti-renin-angiotensin agents (57%), beta-adrenergic receptor blocking agents in 53%, mineralocorticoid receptor antagonists in 34%, ivabradine in 21%, and digoxin in 5%. Angiotensin-neprilysin inhibitor was prescribed to 21% patients at discharge. Ferric carboxymaltose use was in 7.5% of all despite a high prevalence of anemia (54%). Vaccination status at discharge was not available in majority. CONCLUSION: The commonest cause of ADHF presenting to this community hospital was HFrEF of ischemic etiology. It is associated with significant in-hospital mortality. There is substantial under-use of guideline-recommended chronic heart failure therapies at hospital discharge. These data provide useful information which can be used to improve patient care and formulate future strategies for management of ADHF.


Assuntos
Insuficiência Cardíaca/epidemiologia , Hospitais Comunitários/estatística & dados numéricos , Cooperação do Paciente , Volume Sistólico/fisiologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
18.
Cell Rep ; 30(12): 4096-4109.e5, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32209471

RESUMO

Acute lung injury (ALI) is a lethal inflammatory lung disorder whose incidence is on the rise. Alveolar macrophages normally act to resolve inflammation, but when dysregulated they can provoke ALI. We demonstrate that monocyte-derived macrophages (CD11b+ macrophages) recruited into the airspace upregulate the anti-inflammatory function of alveolar macrophages by suppressing their stimulator of type 1 interferon gene (STING) signaling. Depletion of CD11b+ macrophages in mice (macrophagedep mice) after endotoxin or after Pseudomonas aeruginosa causes expansion of the inflammatory alveolar macrophage population, leading to neutrophil accumulation, irreversible loss of lung vascular barrier function, and lethality. We show that CD11b+ macrophages suppress alveolar macrophage-STING signaling via sphingosine kinase-2 (SPHK2) generation of sphingosine-1-phosphate (S1P). Thus, adoptive transfer of wild-type (WT) or STING-/-, but not SPHK2-/-, CD11b monocytes from murine bone marrow into injured macrophagedep mice rescue anti-inflammatory alveolar macrophages and reverse lung vascular injury. SPHK2-induced S1P generation in CD11b+ macrophages has the potential to educate alveolar macrophages to resolve ALI.


Assuntos
Antígeno CD11b/metabolismo , Inflamação/patologia , Lisofosfolipídeos/metabolismo , Macrófagos Alveolares/metabolismo , Proteínas de Membrana/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Esfingosina/análogos & derivados , Transferência Adotiva , Animais , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Pulmão/irrigação sanguínea , Pulmão/patologia , Macrófagos Alveolares/microbiologia , Camundongos Endogâmicos C57BL , Nucleotídeos Cíclicos/metabolismo , Pseudomonas aeruginosa/fisiologia , Transdução de Sinais , Esfingosina/metabolismo , Células U937
19.
J Hypertens ; 38(7): 1262-1270, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32195821

RESUMO

OBJECTIVE: India Heart Study (IHS) is aimed at investigating the agreement between office blood pressure measurement (OBPM) and self (S)BPM in a hypertension-naive population. METHODS: A total of 18 918 individuals (aged 42.6 ±â€Š11.7 years, 62.7% men), visiting 1237 primary care physicians across India, underwent OBPM. They performed SBPM for a period of 1 week using a validated oscillometric BP monitor that was preprogrammed to adhere to a guideline-based SBPM-schedule and blinded to the results. Thereafter, individuals underwent a second OBPM. Available laboratory results were obtained. Thresholds for elevated OBPM and SBPM were 140/90 and 135/85 mmHg, respectively. RESULTS: On the basis of first-visit OBPM and SBPM, there were 5787 (30.6%) individuals with normotension; 5208 (27.5%) with hypertension; 4485 (23.7%) with white-coat hypertension (WCH) and 3438 (18.2%) with masked hypertension. Thus, a diagnosis contradiction between SBPM and first-visit OBPM was seen in 9870 (41.9%) individuals. On the basis of second-visit OBPM, the normotension, hypertension, WCH and masked hypertension prevalence values were 7875 (41.6%); 4857 (25.7%); 2397 (12.7%) and 3789 (20.0%). There was poor agreement (kappa value 0.37) between OBPM of visit 1 and 2 with a diagnosis difference in 6027 (31.8%) individuals. The majority of masked hypertension and WCH individuals had BP values close to thresholds. CONCLUSION: There was a poor agreement between OBPM of visit1 and visit 2. Likewise, the agreement between OBPM at both visits and SBPM was poor. SBPM being considered to have a better correlation with patient prognosis should be the preferred method for diagnosing hypertension.


Assuntos
Determinação da Pressão Arterial/métodos , Pressão Sanguínea , Hipertensão/diagnóstico , Autocuidado , Adulto , Feminino , Humanos , Hipertensão/fisiopatologia , Índia/epidemiologia , Masculino , Hipertensão Mascarada/diagnóstico , Pessoa de Meia-Idade , Visita a Consultório Médico , Oscilometria , Prevalência , Atenção Primária à Saúde , Reprodutibilidade dos Testes , Hipertensão do Jaleco Branco/diagnóstico
20.
Cureus ; 11(9): e5612, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31700725

RESUMO

Hydatid disease is a common disease in developing countries. The usual presentations include lung and liver cysts. Herein, we present a case of extrapulmonary, intrathoracic hydatid cyst with chest wall and spinal cord involvement, with the patient having symptoms of neurological compression and chest pain. Contrast-enhanced computed tomography (CECT) showed a large, septated, cystic mass which was eroding third, fourth and fifth ribs posteriorly, undermining the transverse process and pushing the spinal cord to the right through the intervertebral foramen. The diagnosis was confirmed by aspiration cytology. The patient was treated with albendazole as she refused surgery, which showed complete resolution of symptoms within one month.

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