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Article ; Online: Computational study of the intermolecular interactions and their effect on the UV-visible spectra of the ternary liquid mixture of benzene, ethanol and propylene glycol.

Hema / Bhatt, Tara / Pant, Tarun / Dhondiyal, Charu Ch / Rana, Meenakshi / Chowdhury, Papia / Joshi, G C / Arya, Pratibha / Tiwari, Himani

Journal of molecular modeling

2020 Volume 26, Issue 10, Page(s) 268

Abstract: Quantum chemical calculations are well-equipped to provide answers to the questions regarding the different aspects of intermolecular interactions. We investigate the benzene, ethanol and 1,2 propanediol ternary mixture with theoretical as well as ... ...

Abstract	Quantum chemical calculations are well-equipped to provide answers to the questions regarding the different aspects of intermolecular interactions. We investigate the benzene, ethanol and 1,2 propanediol ternary mixture with theoretical as well as experimental UV-Vis spectroscopy. An extensive theoretical study on the molecular structure and UV-Vis spectral analysis was undertaken using density functional theory (DFT) method. Structural parameter analysis and the HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) energy gap help to describe the possible interaction between molecules in dimer and in combination. Interaction energy has been calculated from topological study. Time-dependent density functional theory (TDDFT) calculations on dimer/cluster in gas phase help to understand the effect of the molecular interaction on the overall spectral shift and related intensity variation. Our results show that in the ternary mixture, the interaction energies of the interactions are π-π interaction: 0.52-2.57 kcal/mol, Hp-π interaction: 1.15 kcal/mol and H-bonding: 2.49 to 4.46 kcal/mol. The π-π interaction and H-bonding cause red shift in absorption spectra while Hp-π interaction causes blue shift. In the ternary mixture, the strength of different kinds of interaction depends on the concentration, and as each interaction has its own effect on spectral shift, the overall experimental spectra get broader and distorted from the Gaussian shape.
Language	English
Publishing date	2020-09-14
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1284729-X
ISSN	0948-5023 ; 1610-2940
ISSN (online)	0948-5023
ISSN	1610-2940
DOI	10.1007/s00894-020-04533-y
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Article ; Online: HIV-1 transgene expression in rats induces differential expression of tumor necrosis factor alpha and zinc transporters in the liver and the lung.

Joshi, Pratibha C / Guidot, David M

AIDS research and therapy

2011 Volume 8, Page(s) 36

Abstract: Background: Highly effective antiviral treatment can suppress HIV-1 infection, but the chronic effects of HIV-1-related viral proteins, including gp120 and Tat, on organs such as the lungs can be damaging. HIV-1 transgenic rodent models are useful for ... ...

Abstract	Background: Highly effective antiviral treatment can suppress HIV-1 infection, but the chronic effects of HIV-1-related viral proteins, including gp120 and Tat, on organs such as the lungs can be damaging. HIV-1 transgenic rodent models are useful for studying the systemic effects of these proteins independently of viral infection. We have previously shown that HIV-1 transgene expression (and therefore, HIV-1-related protein expression) in rats decreases alveolar macrophage zinc levels and phagocytic capacity by unknown mechanisms. We hypothesized that HIV-1 transgene expression induces chronic inflammation and zinc sequestration within the liver and thereby decreases zinc bioavailability in the lung. We examined the expression of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFα), the zinc storage protein, metallothionein (MT1), and the zinc exporter, ZNT1 in the livers and the lungs of wild type and HIV-1 transgenic rats ± dietary zinc supplementation. In addition, we measured zinc levels, the zinc importing protein ZIP1, and the phagocytic capacity in the alveolar macrophages. Results: HIV-1 transgene expression increased the liver-specific expression of TNFα, suggesting a chronic inflammatory response within the liver in response to HIV-1-related protein expression. In parallel, HIV-1 transgene expression significantly increased MT1 and ZNT1 expression in the liver as compared to the lung, a pattern that is consistent with zinc sequestration in the liver as occurs during systemic inflammation. Further, HIV-1 transgene expression decreased intracellular zinc levels and increased expression of ZIP1 in the alveolar macrophages, a pattern consistent with zinc deficiency, and decreased their bacterial phagocytic capacity. Interestingly, dietary zinc supplementation in HIV-1 transgenic rats decreased gene expression of TNFα, MT1, and ZNT1 in the liver while simultaneously increasing their expression in the lung. In parallel, zinc supplementation increased alveolar macrophage intracellular zinc levels and bacterial phagocytic capacity in HIV-1 transgenic rats. Conclusion: Taken together, these findings suggest that chronic HIV-1-related protein expression causes liver inflammation and zinc sequestration, which in turn limits zinc bioavailability in the lung and thereby impairs alveolar macrophage phagocytic function. Importantly, dietary zinc supplementation decreases liver inflammation and zinc sequestration and restores alveolar macrophage phagocytic function in HIV-1 transgenic rats, a result with potential clinical implications for improving lung health in HIV-1-infected individuals.
Language	English
Publishing date	2011-10-06
Publishing country	England
Document type	Journal Article
ISSN	1742-6405
ISSN (online)	1742-6405
DOI	10.1186/1742-6405-8-36
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Article ; Online: Well Behaved Class of Charge Analogue of Durgapal’s Relativistic Exact Solution

Pratibha Fuloria / B. C. Tewari / B. C. Joshi

Journal of Modern Physics, Vol 02, Iss 10, Pp 1156-

2011 Volume 1160

Abstract: We obtain a new class of charged super-dense star models after prescribing particular Forms of the metric potential and electric intensity. The metric describing the superdense stars joins smoothly with the Reissner-Nordstrom metric at the pressure free ... ...

Abstract	We obtain a new class of charged super-dense star models after prescribing particular Forms of the metric potential and electric intensity. The metric describing the superdense stars joins smoothly with the Reissner-Nordstrom metric at the pressure free boundary. The interior of the stars possess their energy density, pressure, pressure density ratio and velocity of sound to be monotonically decreasing towards the pressure free interface. In view of the surface density ρ b =2×10 14 g/cm 3 , the heaviest star occupies a mass 5.523 M ⊙ with its radius 13.98 km. In absence of the charge we are left behind with the regular and well behaved fifth model of Durgapal [1].
Keywords	Charged Fluids ; Reissener-Nordstom Metric ; General Relativity ; Physics ; QC1-999 ; Science ; Q ; DOAJ:Physics (General) ; DOAJ:Physics and Astronomy
Subject code	115
Language	English
Publishing date	2011-10-01T00:00:00Z
Publisher	Scientific Research Publishing
Document type	Article ; Online
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Article: The alcoholic lung: epidemiology, pathophysiology, and potential therapies.

Joshi, Pratibha C / Guidot, David M

American journal of physiology. Lung cellular and molecular physiology

2007 Volume 292, Issue 4, Page(s) L813–23

Abstract: Epidemiological evidence gathered only in the past decade reveals that alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome by as much as three- to fourfold. Experimental models and clinical studies are ... ...

Abstract	Epidemiological evidence gathered only in the past decade reveals that alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome by as much as three- to fourfold. Experimental models and clinical studies are beginning to elucidate the mechanisms underlying this previously unrecognized association and are revealing for the first time that chronic alcohol abuse causes discrete changes, particularly within the alveolar epithelium, that render the lung susceptible to acute edematous injury in response to sepsis, trauma, and other inflammatory insults. Recent studies in relevant animal models as well as in human subjects are identifying common mechanisms by which alcohol abuse targets both the alveolar epithelium and the alveolar macrophage, such that the risks for acute lung injury and pulmonary infections are inextricably linked. Specifically, chronic alcohol ingestion decreases the levels of the antioxidant glutathione within the alveolar space by as much as 80-90%, and, as a consequence, impairs alveolar epithelial surfactant production and barrier integrity, decreases alveolar macrophage function, and renders the lung susceptible to oxidant-mediated injury. These changes are often subclinical and may not manifest as detectable lung impairment until challenged by an acute insult such as sepsis or trauma. However, even otherwise healthy alcoholics have evidence of severe oxidant stress in the alveolar space that correlates with alveolar epithelial and macrophage dysfunction. This review focuses on the epidemiology and the pathophysiology of alcohol-induced lung dysfunction and discusses potential new treatments suggested by recent experimental findings.
MeSH term(s)	Alcoholism/complications ; Alcoholism/epidemiology ; Alcoholism/physiopathology ; Angiotensin II/physiology ; Granulocyte-Macrophage Colony-Stimulating Factor/physiology ; Humans ; Lung/physiopathology ; Macrophages, Alveolar/physiology ; Oxidative Stress/physiology ; Pulmonary Alveoli/pathology ; Pulmonary Alveoli/physiopathology ; Respiratory Distress Syndrome, Adult/epidemiology ; Respiratory Distress Syndrome, Adult/etiology ; Respiratory Distress Syndrome, Adult/physiopathology ; Signal Transduction
Chemical Substances	Angiotensin II (11128-99-7) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
Language	English
Publishing date	2007-01-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00348.2006
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Article ; Online: HIV-1 transgene expression in rats induces differential expression of tumor necrosis factor alpha and zinc transporters in the liver and the lung

Guidot David M / Joshi Pratibha C

AIDS Research and Therapy, Vol 8, Iss 1, p

2011 Volume 36

Abstract: Abstract Background Highly effective antiviral treatment can suppress HIV-1 infection, but the chronic effects of HIV-1-related viral proteins, including gp120 and Tat, on organs such as the lungs can be damaging. HIV-1 transgenic rodent models are ... ...

Abstract	Abstract Background Highly effective antiviral treatment can suppress HIV-1 infection, but the chronic effects of HIV-1-related viral proteins, including gp120 and Tat, on organs such as the lungs can be damaging. HIV-1 transgenic rodent models are useful for studying the systemic effects of these proteins independently of viral infection. We have previously shown that HIV-1 transgene expression (and therefore, HIV-1-related protein expression) in rats decreases alveolar macrophage zinc levels and phagocytic capacity by unknown mechanisms. We hypothesized that HIV-1 transgene expression induces chronic inflammation and zinc sequestration within the liver and thereby decreases zinc bioavailability in the lung. We examined the expression of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFα), the zinc storage protein, metallothionein (MT1), and the zinc exporter, ZNT1 in the livers and the lungs of wild type and HIV-1 transgenic rats ± dietary zinc supplementation. In addition, we measured zinc levels, the zinc importing protein ZIP1, and the phagocytic capacity in the alveolar macrophages. Results HIV-1 transgene expression increased the liver-specific expression of TNFα, suggesting a chronic inflammatory response within the liver in response to HIV-1-related protein expression. In parallel, HIV-1 transgene expression significantly increased MT1 and ZNT1 expression in the liver as compared to the lung, a pattern that is consistent with zinc sequestration in the liver as occurs during systemic inflammation. Further, HIV-1 transgene expression decreased intracellular zinc levels and increased expression of ZIP1 in the alveolar macrophages, a pattern consistent with zinc deficiency, and decreased their bacterial phagocytic capacity. Interestingly, dietary zinc supplementation in HIV-1 transgenic rats decreased gene expression of TNFα, MT1, and ZNT1 in the liver while simultaneously increasing their expression in the lung. In parallel, zinc supplementation increased alveolar macrophage intracellular zinc levels and bacterial phagocytic capacity in HIV-1 transgenic rats. Conclusion Taken together, these findings suggest that chronic HIV-1-related protein expression causes liver inflammation and zinc sequestration, which in turn limits zinc bioavailability in the lung and thereby impairs alveolar macrophage phagocytic function. Importantly, dietary zinc supplementation decreases liver inflammation and zinc sequestration and restores alveolar macrophage phagocytic function in HIV-1 transgenic rats, a result with potential clinical implications for improving lung health in HIV-1-infected individuals.
Keywords	pulmonary ; alveolar macrophages ; AIDS ; rodent ; inflammation ; micronutrients ; Immunologic diseases. Allergy ; RC581-607 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Allergy and Immunology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2011-10-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
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Article ; Online: Chronic alcohol ingestion in rats decreases Krüppel-like factor 4 expression and intracellular zinc in the lung.

Curry-McCoy, Tiana V / Guidot, David M / Joshi, Pratibha C

Alcoholism, clinical and experimental research

2012 Volume 37, Issue 3, Page(s) 361–371

Abstract: Background: Chronic alcohol ingestion alters the dynamic balance between granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor beta1 (TGFβ1) signaling within the alveolar space and, in parallel, impairs alveolar ... ...

Abstract	Background: Chronic alcohol ingestion alters the dynamic balance between granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor beta1 (TGFβ1) signaling within the alveolar space and, in parallel, impairs alveolar macrophage and epithelial cell function by inhibiting expression of the zinc importer ZIP4 and decreasing zinc bioavailability in the alveolar compartment. As the transcription factor Krüppel-like factor 4 (KLF4 ) binds to ZIP4 , we hypothesized that alcohol exposure and consequent perturbations in GM-CSF and TGFβ1 signaling could decrease cellular KLF4 expression and/or binding as a mechanism by which it inhibits ZIP4 expression and decreases cellular zinc levels. Methods and results: Alcohol exposure in vitro or chronic ingestion in vivo decreased KLF4 expression in alveolar macrophages and epithelial cells. Treatment with GM-CSF or TGFβ1 showed an enhancing or dampening effect on KLF4 expression and binding, respectively. Further, treatment of a rat alveolar macrophage cell line with alcohol in vitro for 4 weeks decreased the expression of the zinc transporters ZIP4 and ZNT1, and of the zinc storage protein metallothionein 1. In parallel, treating these macrophages with KLF4 siRNA decreased ZIP4 expression and decreased cellular zinc and phagocytic capacity to levels equivalent to those following alcohol exposure. In epithelial monolayers, transepithelial electrical resistance (TER) was significantly decreased by alcohol ingestion as compared with control diets, and it was restored by in vitro GM-CSF treatment. In contrast, in vitro TGFβ1 treatment of the epithelial monolayers from control-fed rats significantly decreased TER as compared with untreated control monolayers. Conclusions: Taken together, these results suggest that within the alveolar space, chronic alcohol exposure decreases KLF4 and ZIP4 expression and consequently decreases zinc transport into cells, which, in turn, impairs their function. Furthermore, the dynamic decrease in the relative influence of GM-CSF versus TGFβ1 could mediate the zinc deficiency and consequent cellular dysfunction that characterize the "alcoholic lung" phenotype.
MeSH term(s)	Alcohol Drinking/genetics ; Alcohol Drinking/metabolism ; Alcohol Drinking/pathology ; Animals ; Cation Transport Proteins/antagonists & inhibitors ; Cation Transport Proteins/biosynthesis ; Cation Transport Proteins/genetics ; Cell Line ; Cells, Cultured ; Down-Regulation/genetics ; Intracellular Fluid/metabolism ; Kruppel-Like Transcription Factors/antagonists & inhibitors ; Kruppel-Like Transcription Factors/biosynthesis ; Kruppel-Like Transcription Factors/genetics ; Lung/metabolism ; Macrophages, Alveolar/metabolism ; Macrophages, Alveolar/pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Zinc/metabolism ; Zinc Fingers/genetics
Chemical Substances	Cation Transport Proteins ; GKLF protein ; Kruppel-Like Transcription Factors ; Slc39a4 protein, mouse ; Slc39a4 protein, rat ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2012-09-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	428999-7
ISSN	1530-0277 ; 0145-6008
ISSN (online)	1530-0277
ISSN	0145-6008
DOI	10.1111/j.1530-0277.2012.01946.x
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Article ; Online: Chronic alcohol ingestion exacerbates lung epithelial barrier dysfunction in HIV-1 transgenic rats.

Fan, Xian / Joshi, Pratibha C / Koval, Michael / Guidot, David M

Alcoholism, clinical and experimental research

2011 Volume 35, Issue 10, Page(s) 1866–1875

Abstract: Background: Alcohol abuse and HIV-1 infection frequently coexist, and these individuals are at high risk for serious lung infections and respiratory failure. Although alcohol ingestion and HIV-1 transgene expression have been shown to independently ... ...

Abstract	Background: Alcohol abuse and HIV-1 infection frequently coexist, and these individuals are at high risk for serious lung infections and respiratory failure. Although alcohol ingestion and HIV-1 transgene expression have been shown to independently cause oxidative stress and disrupt alveolar epithelial barrier function in experimental models, their interactive effects have not been examined. Methods and results: In this study, we determined that chronic alcohol ingestion (12 weeks) exacerbated the already significant defects in alveolar epithelial paracellular permeability and lung liquid clearance in HIV-1 transgenic rats. Further, immunocytochemical analyses of tight junction protein expression in primary alveolar epithelial cells showed that occludin and zonula occludens-1 localization within the plasma membrane was more disrupted than in either condition alone, consistent with the observed defects in epithelial barrier function. Interestingly, expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), the transcription factor required to activate the antioxidant-response element, was decreased in primary alveolar epithelial cells isolated from HIV-1 transgenic rats. In parallel, exposing lung epithelial cells in vitro to either alcohol or the HIV-related protein gp120 also decreased Nrf2 expression. Importantly, treatment with procysteine, which increases thiol antioxidants including glutathione, improved tight junction protein localization in the plasma membrane and restored alveolar epithelial barrier function in alcohol-fed HIV-1 transgenic rats. Conclusions: These results provide novel evidence that HIV-related proteins and alcohol together causes more barrier dysfunction in the lung epithelium than either stress alone. However, these significant effects on the alveolar barrier can be mitigated by augmenting the thiol antioxidant pool, a strategy with potential clinical applications in subjects who are highly vulnerable to lung disease because of coexistent alcohol abuse and HIV infection.
MeSH term(s)	Alcoholism/metabolism ; Alcoholism/pathology ; Alcoholism/physiopathology ; Animals ; Antioxidants/physiology ; Central Nervous System Depressants/metabolism ; Central Nervous System Depressants/pharmacology ; Central Nervous System Depressants/toxicity ; Comorbidity ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Epithelial Cells/pathology ; Epithelium/drug effects ; Epithelium/metabolism ; Epithelium/pathology ; Epithelium/physiopathology ; Ethanol/metabolism ; Ethanol/pharmacology ; Ethanol/toxicity ; Glutathione/metabolism ; HIV Envelope Protein gp120/metabolism ; HIV Infections/metabolism ; HIV Infections/pathology ; HIV-1 ; Lung/drug effects ; Lung/metabolism ; Lung/pathology ; Lung/physiopathology ; Lung Diseases/metabolism ; Lung Diseases/pathology ; Lung Diseases/physiopathology ; Male ; Membrane Proteins/biosynthesis ; NF-E2-Related Factor 2/biosynthesis ; NF-E2-Related Factor 2/metabolism ; Occludin ; Pyrrolidonecarboxylic Acid/pharmacology ; Rats ; Rats, Inbred F344 ; Rats, Transgenic ; Thiazolidines/pharmacology ; Tight Junctions/metabolism ; Tight Junctions/pathology ; Time Factors
Chemical Substances	Antioxidants ; Central Nervous System Depressants ; HIV Envelope Protein gp120 ; Membrane Proteins ; NF-E2-Related Factor 2 ; OCLN protein, human ; Occludin ; Ocln protein, rat ; Thiazolidines ; gp120 protein, Human immunodeficiency virus 1 ; Ethanol (3K9958V90M) ; Glutathione (GAN16C9B8O) ; Pyrrolidonecarboxylic Acid (SZB83O1W42) ; 2-oxothiazolidine-4-carboxylic acid (X7063P804E)
Language	English
Publishing date	2011-05-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	428999-7
ISSN	1530-0277 ; 0145-6008
ISSN (online)	1530-0277
ISSN	0145-6008
DOI	10.1111/j.1530-0277.2011.01531.x
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Article: Genomic revolution: Transforming tuberculosis diagnosis and treatment with the use of Whole Genome Sequencing - A consensus statement.

Arora, V K / Jindal, S K / Katiyar, S K / Behra, Digambar / Talwar, Deepak / Sarin, Rohit / Dhar, Raja / Mehta, Parthiv / Bhargava, Salil / Singhal, Pratibha / Joshi, Shashank / Tiwaskar, Mangesh / Nikam, Chaitali / Chatterjee, Anirvan / Vora, Agam

The Indian journal of tuberculosis

2023 Volume 70, Issue 4, Page(s) 383–389

Abstract: Tuberculosis (TB) is a preventable, treatable, and curable disease. However, in 2020, 9∙9 million people were estimated to have developed tuberculosis, and 1.5 million people were estimated to have died from it. Whereas in India, 2.6 million were ... ...

Abstract	Tuberculosis (TB) is a preventable, treatable, and curable disease. However, in 2020, 9∙9 million people were estimated to have developed tuberculosis, and 1.5 million people were estimated to have died from it. Whereas in India, 2.6 million were diagnosed with TB and 436,000 succumbed to TB in 2019. India (26%) is the major contributor to the global drop in TB cases. The COVID-19 pandemic has substantially reduced access to services for the diagnosis and treatment of TB, resulting in an increase in deaths and a reversal in global progress. [1] Presently, TB incidence is falling at a rate of 2% per year, obstructed mainly by the rearing pandemic of drug-resistant tuberculosis (DRTB). Particularly concerning is multi-drug resistant TB (MDRTB), defined as resistance towards isoniazid (INH) and rifampicin (RIF). [2] The World Health Organization (WHO) targeted to reduce worldwide TB incidence by 90% until 2035. (1) Early initiation of effective treatment based on susceptibility patterns of the Mycobacterium tuberculosis complex (MTBC) is considered key to successful TB control in countries with high DRTB incidence. Worldwide MDRTB treatment outcomes are poor, with cure rates less than 60% (2) due to the lack of comprehensive Drug Susceptibility Testing (DST) in most high MDRTB burden countries. This is leading to the inadequate anti-TB activity of the provided regimens (3-5), unlike regimens advised for DST assure optimal results. (6) In addition to resistances to the established regimens, the resistance to the newer DRTB drugs is increasing. On World TB Day 2022, Academy of Advanced Medical Education, Thyrocare Technologies Limited and HyastackAnalytics - IITB along with expert pulmonologist and renowned physicians from India convened for an advisory board meeting in Delhi on 20th March 2022 to discuss the role of Whole Genome Sequencing (WGS) in the diagnosis and management of TB. Objectives and specific topics relating to WGS in MDRTB were discussed, each expert shared their views, which led to a group discussion with a commitment to putting the patient first, and increasing their collective efforts, the organizations recognized that it is possible to make this goal a reality. The organizations involved in the discussion have declared their commitment to engaging in collaborative efforts to tackle DRTB detection efficiently. They advocate for strengthening access to WGS TB services, controlling and preventing TB, improving surveillance and drug resistance management, and investing in research and development. This Round Table serves as a framework to build on and ensure that the goal of ending TB is achievable with WGS services wherever needed. Post discussion, a uniform consensus was said to be arrived if more than 80% board members agreed to the statement. The present paper is the outcome of aspects presented and discussed in the advisory board meeting.
MeSH term(s)	Humans ; Antitubercular Agents/therapeutic use ; Antitubercular Agents/pharmacology ; Microbial Sensitivity Tests ; Pandemics ; Mycobacterium tuberculosis/genetics ; Tuberculosis/diagnosis ; Tuberculosis/drug therapy ; Tuberculosis/epidemiology ; Tuberculosis, Multidrug-Resistant/diagnosis ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Multidrug-Resistant/epidemiology ; Genomics ; Whole Genome Sequencing
Chemical Substances	Antitubercular Agents
Language	English
Publishing date	2023-10-19
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	603129-8
ISSN	0019-5707 ; 0019-5705
ISSN	0019-5707 ; 0019-5705
DOI	10.1016/j.ijtb.2023.10.002
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Article ; Online: Alcohol ingestion disrupts alveolar epithelial barrier function by activation of macrophage-derived transforming growth factor beta1.

Curry-McCoy, Tiana V / Venado, Aida / Guidot, David M / Joshi, Pratibha C

Respiratory research

2013 Volume 14, Page(s) 39

Abstract: Background: Chronic alcohol abuse causes oxidative stress and impairs alveolar epithelial barrier integrity, thereby rendering the lung susceptible to acute edematous injury. Experimentally, alcohol-induced oxidative stress increases the expression of ... ...

Abstract	Background: Chronic alcohol abuse causes oxidative stress and impairs alveolar epithelial barrier integrity, thereby rendering the lung susceptible to acute edematous injury. Experimentally, alcohol-induced oxidative stress increases the expression of transforming growth factor β1 (TGFβ1) in the lung; however, we do not know the precise contribution of various alveolar cells in this process. In the present study, we focused on cell-cell interactions between alveolar macrophages and epithelial cells and the potential mechanisms by which TGFβ1 may become activated in the alveolar space of the alcoholic lung. Methods: Primary alveolar macrophages and epithelial cells were isolated from control- and alcohol-fed Sprague-Dawley rats. Expression of TGFβ1 and the epithelial integrin αvβ6 were examined by real time PCR and either immunocytochemistry or flow cytometry. Alveolar epithelial cells were cultured on transwell supports in the presence of macrophage cell lysate from control- or alcohol-fed rats or in the presence of viable macrophages ± alcohol. Epithelial barrier function was assessed by transepithelial resistance (TER) and paracellular flux of Texas Red dextran. Results: TGFβ1 expression was increased in alveolar macrophages from alcohol-fed rats, and TGFβ1 protein was predominantly membrane-bound. Importantly, alveolar macrophage cellular lysate from alcohol-fed rats decreased TER and increased paracellular dextran flux in primary alveolar epithelial cell monolayers as compared to the lysates from control-fed rats. Alcohol-induced epithelial barrier dysfunction was prevented by anti-TGFβ1 antibody treatment, indicating the presence of bioactive TGFβ1 in the macrophage lysate. In addition, co-culturing macrophages and epithelial cells in the presence of alcohol decreased epithelial barrier function, which also was prevented by anti-TGFβ1 and anti-αvβ6 treatment. In parallel, chronic alcohol ingestion in vivo, or direct treatment with active TGFβ1 in vitro, increased the expression of αvβ6 integrin, which is known to activate TGFβ1, in alveolar epithelial cells. Conclusions: Taken together, these data suggest that interactions between alveolar epithelial cells and macrophages contribute to the alcohol-mediated disruption of epithelial barrier function via the expression and activation of TGFβ1 at points of cell-cell contact.
MeSH term(s)	Administration, Oral ; Animals ; Cell Communication ; Cells, Cultured ; Epithelial Cells/cytology ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Ethanol/administration & dosage ; Ethanol/toxicity ; Macrophage Activation/drug effects ; Macrophage Activation/physiology ; Macrophages/cytology ; Macrophages/drug effects ; Macrophages/metabolism ; Male ; Pulmonary Alveoli/cytology ; Pulmonary Alveoli/metabolism ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1/metabolism
Chemical Substances	Transforming Growth Factor beta1 ; Ethanol (3K9958V90M)
Language	English
Publishing date	2013-04-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-9921
ISSN (online)	1465-993X
ISSN	1465-9921
DOI	10.1186/1465-9921-14-39
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Article ; Online: Treatment outcomes of retinal vein occlusion in clinical practice in Nepal.

Bhandari, Sanjeeb / Poudel, Manish / Paudyal, Indira / Joshi, Pratibha L / Shrestha, Chunu / Paudyal, Govinda / Pradhan, Eli

BMC ophthalmology

2021 Volume 21, Issue 1, Page(s) 92

Abstract: Background: This study evaluated the treatment outcomes of retinal vein occlusion (RVO) in a routine clinical practice in Nepal.: Methods: This was a retrospective analysis of observational data of patients with RVO who attended the retina clinic of ... ...

Abstract	Background: This study evaluated the treatment outcomes of retinal vein occlusion (RVO) in a routine clinical practice in Nepal. Methods: This was a retrospective analysis of observational data of patients with RVO who attended the retina clinic of the Tilganga Institute of Ophthalmology from 1 November 2017 to 31 October 2018. The main outcome was the mean change in visual acuity (VA) at 12 months from the start of treatment. Other outcomes of interest were the mean change in central subfield thickness (CST) and the number of treatments over 12 months. Results: A total of 99 eyes (of 99 patients) with RVO (60 - branch RVO [BRVO] and 39 - central RVO [CRVO] were available for the analysis. Eyes with CRVO had worse VA and CST at baseline. Eyes in both groups were similar for age, associated factors for RVO, duration of vision loss and the presence of ischemia at baseline. The mean (95% Confidence Interval [CI]) VA change at 12 months for BRVO was - 0.35 (- 0.46, - 0.23) logMAR (p < 0.001) from a mean (SD) of 0.75 (0.42) logMAR at baseline with 63% achieving VA < 0.3 logMAR while for CRVO it was - 0.35 (- 0.46, - 0.23) logMAR (p = 0.19) from 1.13 (0.61) logMAR at baseline and VA < 0.3 logMAR in 36%. The mean (95% CI) change in CST over 12 months was - 114 (- 189, - 40) μm (p = 0.003) from a mean (SD) of 423 (151) μm at baseline for BRVO and - 184(- 276, - 91) μm (p < 0.001) from 519 (213) μm for CRVO. Patients in both groups received a median of 2 bevacizumab injections over 12 months. Around 37% eyes were lost before 12 months' observation. The mean VA and CST trajectory in these eyes at their last visit was similar to those that completed 12 months. Conclusion: The outcomes of RVO over the 12 months were inferior and the number of treatments fewer than those of the clinical trials and other reports from routine clinical practice. Future studies to identify the treatment barriers are warranted to improve the treatment outcomes in our patients.
MeSH term(s)	Angiogenesis Inhibitors/therapeutic use ; Humans ; Intravitreal Injections ; Macular Edema/drug therapy ; Nepal/epidemiology ; Retinal Vein Occlusion/drug therapy ; Retinal Vein Occlusion/epidemiology ; Retrospective Studies ; Treatment Outcome
Chemical Substances	Angiogenesis Inhibitors
Language	English
Publishing date	2021-02-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2050436-6
ISSN	1471-2415 ; 1471-2415
ISSN (online)	1471-2415
ISSN	1471-2415
DOI	10.1186/s12886-021-01857-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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