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1.
Heliyon ; 10(9): e30148, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38720698

ABSTRACT

This study aims to analyze the impact of trade openness and Sustainable Development Goals, Financial Development, and Technology on the economic growth of Brazil, Russia, India, China and Colombia, Indonesia, Vietnam, Egypt, Turkey, South Africa countries. The present analysis employs a balanced panel data set from 1996 to 2022. This study also uses various tests, such as the Johansen-Fisher cointegration and Granger causality test. The study's findings suggest that economic growth, trade openness, Sustainable Development Goals, financial development, inflation, technology, labor forces, and financial openness have a long-term relationship among them. In the long run, a positive relationship exists between economic growth, trade openness, and the sustainable development goals index in (BRIC) and (CIVETS) countries. Based on the heterogeneous panel non-causality tests, the findings demonstrate that trade openness and Sustainable Development Goals are a unidirectional causality between trade openness, Sustainable Development Goals, and economic growth.

2.
J Allergy Clin Immunol Glob ; 3(2): 100202, 2024 May.
Article in English | MEDLINE | ID: mdl-38283085

ABSTRACT

Background: Food allergy (FA), which is a condition that has no effective cure and can result in severe life-threatening allergic reactions, remains a global public health concern; however, little is known about how FAs are currently managed in the Asia-Pacific region. Objective: The main objective of this survey was to evaluate the epidemiology of FA, as well as the availability of resources and practices for management of FA and anaphylaxis by health care providers across Asia. Methods: From June 2022 to September 2022, a questionnaire-based survey comprising 66 questions was electronically sent to member societies of the Asia Pacific Association of Allergy Asthma and Clinical Immunology by using Survey Monkey. Results: A total of 20 responses were received from 15 member countries and territories. Compared with the pediatric data, there was a lack of prevalence data for FA in adults. Except for Australia and Japan, most regions had between 0.1 and 0.5 allergists per 100,000 population and some had fewer than 0.1 allergists per 100,000 population. The perceived rate of FA in regions with a short supply of allergists was high. Although specific IgE tests and oral food challenges were available in all regions, the median wait time for oral food challenges at government facilities was 37 days (interquartile range = 10.5-60 days). Seven regions still relied on prescriptions of ampules and syringes of injectable adrenaline, and adrenaline autoinjectors were not accessible in 4 regions. Oral immunotherapy as FA treatment was available in half of the surveyed countries and territories. Conclusions: Our study offers a cross-sectional evaluation of the management practices for FA in each Asia Pacific Association of Allergy Asthma and Clinical Immunology member country or territory. Urgent actions are required to enhance allergy services, improve the accessibility and affordability of adrenaline autoinjectors, and conduct robust epidemiologic studies.

4.
BMC Pulm Med ; 23(1): 349, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37715196

ABSTRACT

BACKGROUND: Tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) may occasionally show similar cytological and biochemical picture including ADA. In such cases, differentiating TPE and MPE is challenging and needs histopathology of pleural tissue which may involve invasive procedures. The present study aims to evaluate the diagnostic accuracy of pleural fluid ADA to serum CRP (ADA/CRP) ratio to discriminate between tuberculous and malignant pleural effusion. In addition, we investigated whether the ratio ADA/CRP adds diagnostic value to ADA. METHODS: This cross-sectional study was conducted in the National Institute of Diseases of the Chest and Hospital (NIDCH), Mohakhali, Dhaka, from July 2021 to February 2022 on diagnosed patients of TPE and malignant pleural effusion MPE. A receiver operating characteristic curve (ROC) was constructed for identifying TPE. The added value of the ADA/CRP ratio to ADA was evaluated using the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). A value of p < 0.05 was considered statistically significant for all tests. RESULTS: Fifty-nine patients were enrolled in this study, of which 31 had TPE, and 28 had MPE. Pleural fluid ADA to serum CRP ratio and pleural fluid ADA level was significantly higher in patients with TPE, but there was no significant difference in serum CRP levels between patients with TPE and MPE. At cut off value of > 1.25, pleural fluid ADA to serum CRP ratio had a sensitivity of 93.8%, specificity of 85.2%, and positive and negative predictive values were 88.2% and 92% respectively, in the diagnosis of TPE and area under ROC curve (AUC) was 0.94. The NRI and IDI analyses revealed added diagnostic value of ADA/CRP to ADA. CONCLUSION: This study shows that the ADA/CRP ratio improves the diagnostic usefulness of ADA for TPE.


Subject(s)
Pleural Effusion, Malignant , Pleural Effusion , Tuberculosis , Humans , C-Reactive Protein , Pleural Effusion, Malignant/diagnosis , Adenosine Deaminase , Cross-Sectional Studies , Bangladesh , Pleural Effusion/diagnosis
5.
Lancet Reg Health Southeast Asia ; 14: 100185, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37492418

ABSTRACT

Background: In Southeast Asia, tobacco use is a major public health threat. Tobacco users in this region may switch between or concurrently use smoked tobacco and smokeless tobacco (SLT), which makes effective tobacco control challenging. This study tracks transitions of use among different product users (cigarettes, bidis, and SLT) in Bangladesh, one of the largest consumers of tobacco in the region, and examines factors related to transitions and cessation. Methods: Four waves (2009-2015) of the International Tobacco Control (ITC) Bangladesh Survey with a cohort sample of 3245 tobacco users were analysed. Generalized Estimating Equations (GEE) models were used to explore the socioeconomic correlates of transitions from the exclusive use of cigarettes, bidis, or SLT to the use of other tobacco products or quitting over time. Findings: Among exclusive cigarette users, most remained as exclusive cigarette users (68.1%). However, rural smokers were more likely than urban smokers to transition to bidi use (odds ratio [OR] = 3.02, 95% confidence interval [CI] = 1.45-6.29); to SLT use (OR = 2.68, 95% CI = 1.79-4.02) and to quit tobacco (OR = 1.57, 95% CI = 1.06-2.33). Among exclusive bidi users, transitional patterns were more volatile. Fewer than half (43.3%) of the exclusive bidi users maintained their status throughout the waves. Those with higher socio-economic status (SES) were more likely to quit (OR = 4.16, 95% CI = 1.08-13.12) compared to low SES smokers. Exclusive SLT users either continued using SLT or quit with minimal transitions to other products (≤2%). Nevertheless, males were more likely to switch to other tobacco products; younger (OR = 2.94, 95% CI = 1.23-6.90 vs. older), more educated (OR = 1.55, 95% CI = 1.77-3.12 vs. less educated), and urban SLT users (OR = 0.52, 95% CI = 0.30-0.86 for rural vs. urban users) were more likely to quit. Interpretation: Complex transitional patterns were found among different types of tobacco product users over time in Bangladesh. These findings can inform more comprehensive and multi-faceted approaches to tackle diversified tobacco use in Bangladesh and neighbouring countries in the Southeast Asia region with similar tobacco user profiles of smoked tobacco and SLT products. Funding: This is an unfunded observational study with the use the ITC Bangladesh datasets. The ITC Bangladesh Surveys were supported by grants from the US National Cancer Institute (P01 CA138389), the International Development Research Centre (IDRC Grant 104831-003), and Canadian Institutes of Health Research (MOP-79551, MOP-115016).

6.
Tob Induc Dis ; 21: 25, 2023.
Article in English | MEDLINE | ID: mdl-36819960

ABSTRACT

INTRODUCTION: Transitions between different tobacco products are frequent among tobacco users in Bangladesh; however, the reasons leading to such transitions and why they quit are not well researched. The aim of the study is to examine perceptions and reasons reported by tobacco users in Bangladesh to transition to other products or quit. METHODS: Data from four waves (2009-2015) of the International Tobacco Control (ITC) Bangladesh Survey were used. Repeated data on perceptions and reasons for exclusive cigarette (n=520), bidi (n=130), and SLT users (n=308) to either start using other products or quit were analyzed with sampling weights. The percentages of responses across waves were used to calculate the pooled proportion data using a meta-analysis approach. RESULTS: Common reasonsig for respondents switching to other tobacco products were influence of friends/family (73.8-86.0%), and curiosity (44.4-71.3%). The perceived calming effect of smoking cigarettes and bidis (43.2-56.9%), and the impression that bidis were less harmful (52.3%) and taste better (71.2%) were major reasons for exclusive SLT users to switch products. Health concerns (16.5-62.7%) and disapproval from friends/family (29.8-56.4%) were generally the main reasons for quitting. For smoked tobacco users, doctor's advice (41.6%), package warning labels (32.3%), and price (32.4%) seemed to be the major driving factors to quit. CONCLUSIONS: Results highlight that the reasons for switching between tobacco products and quitting include social factors (e.g. friends/family) and (mis) perceptions regarding the products. Tobacco control policy could emphasize cessation support, increased price and education campaigns as key policies to reduce overall tobacco use in Bangladesh. Data from four waves (2009-2015) of the International Tobacco Control (ITC) Bangladesh Survey were used. Repeated data on perceptions and reasons for exclusive cigarette (n=520), bidi (n=130), and SLT users (n=308) to either start using other products or quit were analyzed with sampling weights. The percentages of responses across waves were used to calculate the pooled proportion data using a meta-analysis approach.

7.
Disabil Rehabil Assist Technol ; : 1-20, 2022 Nov 22.
Article in English | MEDLINE | ID: mdl-36413423

ABSTRACT

PURPOSE: We present a systematic literature review of dialogue agents for Artificial Intelligence (AI) and agent-based conversational systems dealing with cognitive disability of aged and impaired people including dementia and Parkinson's disease. We analyze current applications, gaps, and challenges in the existing research body, and provide guidelines and recommendations for their future development and use. MATERIALS AND METHODS: We perform this study by applying Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. We performed a systematic search using relevant databases (ACM Digital Library, Google Scholar, IEEE Xplore, PubMed, and Scopus). RESULTS: This study identified 468 articles on the use of conversational agents in healthcare. We finally selected 124 articles based on their objectives and content as directly related to our main topic. CONCLUSION: We identified the main challenges in the field and analyzed the typical examples of the application of conversational agents in the healthcare domain, the desired characteristics of conversational agents, and chatbot support for aged people and people with cognitive disabilities. Our results contribute to a discussion on conversational health agents and emphasize current knowledge gaps and challenges for future research.IMPLICATIONS FOR REHABILITATIONA systematic literature review of dialogue agents for artificial intelligence and agent-based conversational systems dealing with cognitive disability of aged and impaired people.Main challenges and desired characteristics of the conversational agents, and chatbot support for aged people and people with cognitive disability.Current knowledge gaps and challenges for remote healthcare and rehabilitation.Guidelines and recommendations for future development and use of conversational systems.

8.
Graefes Arch Clin Exp Ophthalmol ; 260(7): 2129-2139, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35201404

ABSTRACT

PURPOSE: Retinal microvascular endothelial dysfunction is thought to be of importance in the development of ocular vascular diseases. Obstructive sleep apnoea (OSA) causes macrovascular endothelial dysfunction, but the effect of OSA on retinal microvascular endothelial function is not known. We aimed to determine the effect of OSA on retinal microvascular function. METHODS: We conducted a multi-centre, double-blind, randomised, parallel, controlled trial in patients with known moderate-to-severe OSA, established on continuous positive airway pressure (CPAP). Participants were randomised to 14 nights of either continued CPAP or sham CPAP to generate a return of OSA. Retinal vascular responses to flickering light were measured using dynamic vessel analysis both at baseline and after 14 nights of intervention. The primary outcome was the change from baseline to follow-up in the area under the curve of the arteriolar response to flickering light, sham CPAP versus continued CPAP. RESULTS: Nineteen patients were randomised to sham CPAP, and 18 patients were randomised to continued CPAP. There was no significant effect of CPAP withdrawal and return of OSA on retinal responses, with a change in the area under the curve of the arteriole response to flickering light of + 3.8 arbitrary units (95% CI - 10.6 to + 18.2, p = 0.59), sham CPAP versus continued CPAP. CONCLUSIONS: CPAP withdrawal and a return of OSA had no significant effect on retinal microvascular responses. This contrasts with the effect of CPAP withdrawal on macrovascular endothelial function and suggests that OSA has different effects on macrovascular and microvascular endothelial function. ISRCTN 78082983, 23/10/2014, Prospectively registered.


Subject(s)
Sleep Apnea, Obstructive , Continuous Positive Airway Pressure , Double-Blind Method , Humans , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/therapy
9.
Tob Induc Dis ; 19: 78, 2021.
Article in English | MEDLINE | ID: mdl-34707471

ABSTRACT

INTRODUCTION: Smokeless tobacco (ST) remains poorly regulated in Bangladesh. This study describes the prevalence and trends of ST use in Bangladesh, presents ST-related disease burden, identifies relevant policy gaps, and highlights key implications for future policy and practice for effective ST control in Bangladesh. METHODS: We analyzed secondary data from the two rounds (2009 and 2017) of The Global Adult Tobacco Survey, estimated ST-related disease burden, and conducted a review to assess differences in combustible tobacco and ST policies. In addition, we gathered views in a workshop with key stakeholders in the country on gaps in existing tobacco control policies for ST control in Bangladesh and identified policy priorities using an online survey. RESULTS: Smokeless tobacco use, constituting more than half of all tobacco use in Bangladesh, declined from 27.2% (25.9 million) in 2009 to 20.6% (22 million) in 2017. However, in 2017, at least 16947 lives and 403460 Disability-Adjusted Life Years (DALYs) were lost across Bangladesh due to ST use compared to 12511 deaths and 324020 DALYs lost in 2010. Policy priorities identified for ST control have included: introducing specific taxes and increasing the present ad valorem tax level, increasing the health development surcharge, designing and implementing a tax tracking and tracing system, standardizing ST packaging, integrating ST cessation within existing health systems, comprehensive media campaigns, and licensing of ST manufactures. CONCLUSIONS: Our analysis shows that compared to combustible tobacco, there remain gaps in implementing and compliance with ST control policies in Bangladesh. Thus, contrary to the decline in ST use and the usual time lag between tobacco exposure and the development of cancers, the ST-related disease burden is still on the rise in Bangladesh. Strengthening ST control at this stage can accelerate this decline and reduce ST related morbidity and mortality.

10.
BMJ Open Respir Res ; 8(1)2021 07.
Article in English | MEDLINE | ID: mdl-34230034

ABSTRACT

INTRODUCTION: Many respiratory clinical trials fail to reach their recruitment target and this problem exacerbates existing funding issues. Integration of the clinical trial recruitment process into a clinical care pathway (CCP) may represent an effective way to significantly increase recruitment numbers. METHODS: A respiratory support unit and a CCP for escalation of patients with severe COVID-19 were established on 11 January 2021. The recruitment process for the Randomised Evaluation of COVID-19 Therapy-Respiratory Support trial was integrated into the CCP on the same date. Recruitment data for the trial were collected before and after integration into the CCP. RESULTS: On integration of the recruitment process into a CCP, there was a significant increase in recruitment numbers. Fifty patients were recruited over 266 days before this process occurred whereas 108 patients were recruited over 49 days after this process. There was a statistically significant increase in both the proportion of recruited patients relative to the number of COVID-19 hospital admissions (change from 2.8% to 9.1%, p<0.0001) and intensive therapy unit admissions (change from 17.8% to 50.2%, p<0.001) over the same period, showing that this increase in recruitment was independent of COVID-19 prevalence. DISCUSSION: Integrating the trial recruitment process into a CCP can significantly boost recruitment numbers. This represents an innovative model that can be used to maximise recruitment without impacting on the financial and labour costs associated with the running of a respiratory clinical trial.


Subject(s)
COVID-19/therapy , Critical Pathways , Patient Selection , Randomized Controlled Trials as Topic , Hospitalization , Humans , Respiratory Therapy
11.
Article in English | MEDLINE | ID: mdl-33348533

ABSTRACT

The extent of tobacco cultivation remains substantially high in Bangladesh, which is the 12th largest tobacco producer in the world. Using data from a household survey of current, former, and never tobacco farmers, based on a multi-stage stratified sampling design with a mix of purposive and random sampling of households, this study estimated the financial and economic profitability per acre of land used for tobacco cultivation. The environmental effects of tobacco cultivation on land and water resources were estimated using laboratory tests of sample water and soil collected from tobacco-cultivating and non-tobacco cultivating areas. The study finds that tobacco cultivation turns into a losing concern when the opportunity costs of unpaid family labour and other owned resources, and the health effects of tobacco cultivation are included. Tobacco cultivation poses a significantly high environmental cost that causes a net loss to society. Nevertheless, the availability of unpaid family labour and the options of advanced credit as well as a buy back guarantee from the tobacco companies attract farmers to engage in and continue tobacco cultivation. Therefore, supply side interventions to curb the tobacco epidemic in Bangladesh need to address major drivers of tobacco cultivation to correct the wrong incentives and motivate tobacco farmers to switch to alternative livelihood options.


Subject(s)
Agriculture/economics , Nicotiana , Bangladesh/epidemiology , Farmers , Farms , Humans
12.
ERJ Open Res ; 4(3)2018 Jul.
Article in English | MEDLINE | ID: mdl-30083549

ABSTRACT

Strategic @ERSTalk-@WHO alliance to address tobacco use by training health professionals on brief advice resulted in establishing smoking cessation in real care settings with quit rates higher than the literature and high propensity for wider dissemination http://ow.ly/lWDF30krq5V.

13.
Indian J Public Health ; 61(Suppl 1): S18-S24, 2017 09.
Article in English | MEDLINE | ID: mdl-28928314

ABSTRACT

Despite the high prevalence of smokeless tobacco (SLT) use among adults in Bangladesh, SLT was not included in the Tobacco Control Law till 2013. Information on SLT use among Bangladeshi people is inadequate for policymaking and implementing effective control measures. With the aim to identify the prevalence and trends of different SLT products, health and economic impacts, manufacture, and sale of and policies related to SLT in Bangladesh, we carried out a literature review, which involved literature search, data extraction, and synthesis. Evidence suggests that in Bangladesh, SLTs range from unprocessed to processed or manufactured products including Sada Pata, Zarda, Gul, and Khoinee. Over 27% of Bangladeshi adults aged 15 years and older use SLT in one form or other. SLT use is associated with age, sex, education, and socioeconomic status. SLT consumption has reportedly been associated with increased prevalence of heart diseases, stroke, and oral cancer and led to around 320,000 disability adjusted life years lost in Bangladesh in 2010. No cessation service is available for SLT users in public facilities. Compared to cigarettes, taxation on SLT remains low in Bangladesh. The amendment made in Tobacco Control Law in 2013 requires graphic health warnings to cover 50% of SLT packaging, ban on advertisement of SLT products, and restriction to sale to minors. However, implementation of the law is weak. As the use of SLT is culturally accepted in Bangladesh, culturally appropriate public awareness program is required to curb SLT use along with increased tax and cessation services.


Subject(s)
Tobacco Use/epidemiology , Tobacco Use/trends , Tobacco, Smokeless , Adolescent , Bangladesh/epidemiology , Health Knowledge, Attitudes, Practice , Humans , Mass Media , Social Class , Tobacco Use Cessation , Tobacco, Smokeless/economics , Tobacco, Smokeless/legislation & jurisprudence , Tobacco, Smokeless/poisoning
14.
J Org Chem ; 82(13): 6528-6540, 2017 07 07.
Article in English | MEDLINE | ID: mdl-28641002

ABSTRACT

Samarium(II) iodide-water and samarium(II) iodide-water-amine complexes have been recognized as valuable reagents for the selective generation of aminoketyl radicals from amides and derivatives. The resulting aminoketyl radicals can undergo reduction or reductive cyclization pathways, providing a powerful method for (i) direct synthesis of alcohols from amides by the challenging N-C bond scission and (ii) synthesis of nitrogen-containing heterocycles via polarity reversal of the amide bond. This report describes mechanistic investigation into samarium(II) iodide-water and samarium(II) iodide-water-amine-mediated generation of benzylic aminoketyl radicals from aromatic primary, secondary, and tertiary amides (benzamides). The mechanistic experiments suggest that the rate and selectivity of the reduction is closely dependent on the water concentration and the type of amide undergoing the reduction. The data also suggest that benzylic aminoketyl radicals generated in the reduction of benzamides are significantly more dependent on the electronic effects of α-substitution than the corresponding aminoketyl radicals generated by single-electron transfer to unactivated aliphatic amides; however, little variation in terms of steric influence of N-substituents is observed. These observations will have implications for the design of reductive processes involving Sm(II)-mediated reduction of amides and reductive umpolung cyclizations via aminoketyl radicals as a key step.

16.
Arch Ophthalmol ; 125(6): 783-8, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17562989

ABSTRACT

OBJECTIVE: To investigate the role of very late antigen 1 (VLA-1) (also known as integrin receptor alpha(1)beta(1)) in corneal transplantation inflammation and allograft survival. METHODS: Cell infiltration and vasculogenesis (both angiogenesis and lymphangiogenesis) associated with allodisparate corneal transplantation were assessed in VLA-1-deficient conditions and controls by immunofluorescent microscopic studies. Corneal allograft survival was also assessed after anti-VLA-1 antibody treatment and in VLA-1 knockout recipient mice. RESULTS: Anti-VLA-1 antibody treatment leads to a profound reduction in the granulocytic, monocytic, and T-cell infiltration after corneal transplantation. In addition, corneal angiogenesis and lymphangiogenesis were both significantly suppressed in VLA-1 knockout mice. Remarkably, universal graft survival was observed in both anti-VLA-1 antibody treatment and knockout mice. CONCLUSIONS: Very late antigen 1 blockade markedly reduces inflammation and inflammation-induced tissue responses, including vasculogenic responses, associated with corneal transplantation and promotes allograft survival. CLINICAL RELEVANCE: These studies offer insights into important integrin-mediated mechanisms of corneal transplant-related inflammation and provide possible new integrin-based immunotherapies for transplant rejection.


Subject(s)
Cornea/physiology , Corneal Transplantation , Graft Survival/physiology , Integrin alpha1beta1/physiology , Animals , Corneal Neovascularization/prevention & control , Gene Silencing , Glycoproteins/metabolism , Lymphangiogenesis , Macrophage-1 Antigen/metabolism , Male , Membrane Transport Proteins , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Fluorescence , Platelet Endothelial Cell Adhesion Molecule-1/metabolism , Receptors, Chemokine/metabolism , T-Lymphocytes/immunology , Transplantation, Homologous
18.
Transplantation ; 81(11): 1577-82, 2006 Jun 15.
Article in English | MEDLINE | ID: mdl-16770247

ABSTRACT

BACKGROUND: Murine models of high-risk and low-risk corneal transplantation were used to determine the role of keratocyte apoptosis in the failure of orthotopic allogeneic corneal transplants. MATERIALS AND METHODS: Normal (low-risk, low-rejecting) and inflamed/vascularized (high-risk, high-rejecting) BALB/c recipient beds received fully mismatched C57BL/6 corneal allografts. Apoptosis was detected in the corneal stroma at various time points using an in situ terminal deoxynucleotide tranferase-mediated dUTP nick-end labeling assay, and ex vivo via Western analysis for active caspase-3. Apoptosis was also measured in a (donor-type) C57BL/6 keratocyte cell line after stimulation of Fas or via use of various pro-inflammatory cytokines. RESULTS: Significantly more apoptotic cells were present in the stroma of rapidly rejecting high-risk corneal allografts compared with low-risk grafts. Apoptotic cells were shown to be nearly uniformly CD45 and hence of a non-hematopoetic lineage. Apoptosis, however, was not present in highly inflamed but ungrafted corneas. Apoptosis was induced in keratocytes in vitro by dual stimulation with agonistic Fas mAb and either interleukin-1beta or tumor necrosis factor-alpha. CONCLUSION: Apoptosis of resident non-bone marrow-derived fibroblastic cells of the corneal stroma is strongly correlated with the failure of corneal allografts, particularly in the highly inflamed microenvironment of the high-risk allograft.


Subject(s)
Apoptosis/physiology , Corneal Stroma/cytology , Corneal Stroma/transplantation , Corneal Transplantation/immunology , Fibroblasts/physiology , Graft Rejection/physiopathology , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , Apoptosis/drug effects , Blotting, Western , Caspase 3 , Caspases/analysis , Cell Line , Fibroblasts/enzymology , Fluorescent Antibody Technique , Graft Rejection/pathology , Inflammation/pathology , Inflammation/physiopathology , Interleukin-1/pharmacology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Receptors, Tumor Necrosis Factor/immunology , Transplantation, Homologous/pathology , Transplantation, Homologous/physiology , Tumor Necrosis Factor-alpha/pharmacology , fas Receptor
19.
Mol Vis ; 11: 632-40, 2005 Aug 29.
Article in English | MEDLINE | ID: mdl-16145544

ABSTRACT

PURPOSE: To determine the differential gene expression of chemokine species and leukocyte infiltration of grafts in the early pre-rejection postoperative period after high-risk (HR) compared to normal-risk (NR) corneal transplantation. METHODS: Fully mismatched and syngeneic corneal grafts were performed in NR (avascular) and HR (vascularized) recipient beds of BALB/c murine hosts. Gene expression levels of a panel of chemokines were determined by a multiprobe ribonuclease protection assay system. The profiles of infiltrating cells into the corneal grafts at the same times were determined immunohistochemically. RESULTS: Compared to NR transplantation, HR eyes exhibited significantly higher mRNA levels for macrophage inflammatory protein (MIP)-2 and monocyte chemotactic protein-1 (MCP-1) on day 1, and for eotaxin on days 1 and 3 after transplantation. By day 6 after transplantation, still well before graft rejection, significantly higher levels of RANTES, eotaxin, MIP-1alpha, MIP-1beta, MIP-2, and MCP-1 were detected in HR eyes. The overexpression of MIPs in HR eyes correlated with a significant increase in the number of infiltrating macrophages (p<0.01), and neutrophils (p<0.05) in HR compared to NR recipients. Low levels of eosinophil and mast cell infiltration were observed in all grafts, with a modest increase in mast cell infiltration (p<0.05) in HR compared to NR grafts. CONCLUSIONS: These results suggest that increased expression of gene products for select chemokines, in particular those that mediate recruitment of innate immune cells, in the early period after HR corneal transplantation is related to the enhanced leukocytic infiltration of grafts observed in HR keratoplasty.


Subject(s)
Chemokines/genetics , Corneal Neovascularization/surgery , Corneal Transplantation , Gene Expression Regulation/physiology , Leukocytes/physiology , Animals , Chemokines/metabolism , Corneal Neovascularization/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , RNA, Messenger/metabolism , Risk Factors , Transplantation, Isogeneic
20.
J Immunol ; 173(7): 4464-9, 2004 Oct 01.
Article in English | MEDLINE | ID: mdl-15383577

ABSTRACT

Corneal grafts were until recently considered entirely devoid of resident APCs, giving rise to the tenet that alloantigen recognition is mediated exclusively by the indirect (host APC-dependent) pathway. The recent discovery of a resident myeloid corneal dendritic cell population that is normally MHC class II(-) but can readily up-regulate class II expression during inflammation led us to hypothesize that under certain conditions the direct pathway of allosensitization becomes operative. To test this, corneal allotransplants were performed in either inflamed (high-risk (HR)) or uninflamed (low-risk (LR)) host beds in mice, and the frequencies of host T cells activated via the direct pathway were determined. We found that directly primed CD4(+) T cells were detected in the HR but not LR setting, and these cells displayed a clear Th1 phenotype by 2 wk after grafting. Moreover, the use of MHC class II knockout donor tissue led to significantly enhanced survival of HR but not LR allografts. Finally, we show that donor corneal APC demonstrate high expression of CD40, CD80, and CD86 costimulatory molecules when derived from HR but not LR grafts. These data are the first to report that a functional donor APC-dependent direct response is elicited in corneal transplant hosts when the graft bed is inflamed and underscore the relevance of the graft microenvironment in dictating the pathway of allosensitization.


Subject(s)
Cornea/blood supply , Cornea/immunology , Corneal Transplantation/immunology , Corneal Transplantation/pathology , Signal Transduction/immunology , Animals , Antigen-Presenting Cells/immunology , Antigen-Presenting Cells/metabolism , Antigen-Presenting Cells/pathology , Antigens, CD/biosynthesis , B7-1 Antigen/biosynthesis , B7-2 Antigen , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD40 Antigens/biosynthesis , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cornea/pathology , Graft Survival/genetics , Graft Survival/immunology , Histocompatibility Antigens Class II/genetics , Interferon-gamma/biosynthesis , Interleukin-2/biosynthesis , Membrane Glycoproteins/biosynthesis , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Postoperative Complications/immunology , Postoperative Complications/pathology , Risk Factors , Signal Transduction/genetics , Th1 Cells/immunology , Th1 Cells/metabolism , Th2 Cells/immunology , Th2 Cells/metabolism , Time Factors
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