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Article ; Online: Chitinase and indoleamine 2, 3-dioxygenase are prognostic biomarkers for unfavorable treatment outcomes in pulmonary tuberculosis.

Kumar, Nathella Pavan / Nancy, Arul / Viswanathan, Vijay / Sivakumar, Shanmugam / Thiruvengadam, Kannan / Ahamed, Shaik Fayaz / Hissar, Syed / Kornfeld, Hardy / Babu, Subash

Frontiers in immunology

2023 Volume 14, Page(s) 1093640

Abstract: Introduction: Chitinase, Indoleamine 2,3-dioxygenesae-1 (IDO-1) and heme oxygenase-1 (HO-1) are candidate diagnostic biomarkers for tuberculosis (TB). Whether these immune markers could also serve as predictive biomarkers of unfavorable treatment ... ...

Abstract	Introduction: Chitinase, Indoleamine 2,3-dioxygenesae-1 (IDO-1) and heme oxygenase-1 (HO-1) are candidate diagnostic biomarkers for tuberculosis (TB). Whether these immune markers could also serve as predictive biomarkers of unfavorable treatment outcomes in pulmonary TB (PTB) is not known. Methods: A cohort of newly diagnosed, sputum culture-positive adults with drug-sensitive PTB were recruited. Plasma chitinase protein, IDO protein and HO-1 levels measured before treatment initiation were compared between 68 cases with unfavorable outcomes (treatment failure, death, or recurrence) and 108 control individuals who had recurrence-free cure. Results: Plasma chitinase and IDO protein levels but not HO-1 levels were lower in cases compared to controls. The low chitinase and IDO protein levels were associated with increased risk of unfavourable outcomes in unadjusted and adjusted analyses. Receiver operating characteristic analysis revealed that chitinase and IDO proteins exhibited high sensitivity and specificity in differentiating cases vs controls as well as in differentiating treatment failure vs controls and recurrence vs controls, respectively. Classification and regression trees (CART) were used to determine threshold values for these two immune markers. Discussion: Our study revealed a plasma chitinase and IDO protein signature that may be used as a tool for predicting adverse treatment outcomes in PTB.
MeSH term(s)	Adult ; Humans ; Prognosis ; Chitinases ; Tuberculosis, Pulmonary/diagnosis ; Treatment Outcome ; Biomarkers ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Tryptophan Oxygenase
Chemical Substances	Chitinases (EC 3.2.1.14) ; Biomarkers ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Tryptophan Oxygenase (EC 1.13.11.11)
Language	English
Publishing date	2023-02-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1093640
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Article: Paediatric pulmonary disease-are we diagnosing it right?

Rajendran, Priya / Thomas, Silla Varghese / Balaji, Sarath / Selladurai, Elilarasi / Jayachandran, Ganesh / Malayappan, Aravind / Bhaskar, Adhin / Palanisamy, Sivaraman / Ramamoorthy, Thirumalani / Hasini, Sindhu / Hissar, Syed

Frontiers in pediatrics

2024 Volume 12, Page(s) 1370687

Abstract: Background: It has been reported that differential diagnosis of bacterial or viral pneumonia and tuberculosis (TB) in infants and young children is complex. This could be due to the difficulty in microbiological confirmation in this age group. In this ... ...

Abstract	Background: It has been reported that differential diagnosis of bacterial or viral pneumonia and tuberculosis (TB) in infants and young children is complex. This could be due to the difficulty in microbiological confirmation in this age group. In this study, we aimed to assess the utility of a real-time multiplex PCR for diagnosis of respiratory pathogens in children with pulmonary TB. Methods: A total of 185 respiratory samples [bronchoalveolar lavage (15), gastric aspirates (98), induced sputum (21), and sputum (51)] from children aged 3-12 years, attending tertiary care hospitals, Chennai, India, were included in the study. The samples were processed by N acetyl L cysteine (NALC) NAOH treatment and subjected to microbiological investigations for Results: Out of the 185 samples tested, a total of 20 samples were positive for MTB by either one or more identification methods (smear, culture, and GeneXpert). Out of these 20 MTB-positive samples, 15 were positive for one or more bacterial or fungal pathogens, with different cycle threshold values. Among patients with negative MTB test results ( Conclusion: The results suggest that tuberculosis could coexist with other respiratory pathogens causing pneumonia. However, a large-scale prospective study from different geographical settings that uses such simultaneous detection methods for diagnosis of childhood tuberculosis and pneumonia will help in assessing the utility of these tests in rapid diagnosis of respiratory infections.
Language	English
Publishing date	2024-04-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2024.1370687
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Article ; Online: Heightened Microbial Translocation Is a Prognostic Biomarker of Recurrent Tuberculosis.

Kumar, Nathella Pavan / Moideen, Kadar / Viswanathan, Vijay / Sivakumar, Shanmugam / Ahamed, Shaik Fayaz / Ponnuraja, C / Hissar, Syed / Kornfeld, Hardy / Babu, Subash

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2022 Volume 75, Issue 10, Page(s) 1820–1826

Abstract: Background: Microbial translocation is a known characteristic of pulmonary tuberculosis (PTB). Whether microbial translocation is also a biomarker of recurrence in PTB is not known.: Methods: We examined the presence of microbial translocation in a ... ...

Abstract	Background: Microbial translocation is a known characteristic of pulmonary tuberculosis (PTB). Whether microbial translocation is also a biomarker of recurrence in PTB is not known. Methods: We examined the presence of microbial translocation in a cohort of newly diagnosed, sputum smear, and culture positive individuals with drug-sensitive PTB. Participants were followed up for a year following the end of anti-tuberculosis treatment. They were classified as cases (in the event of recurrence, n = 30) and compared to age and gender matched controls (in the event of successful, recurrence free cure; n = 51). Plasma samples were used to measure the circulating microbial translocation markers. All the enrolled study participants were treatment naïve, HIV negative and with or without diabetes mellitus. Results: Baseline levels of lipopolysaccharide (LPS) (P = .0002), sCD14 (P = .0191), and LPS-binding protein (LBP) (P < .0001) were significantly higher in recurrence than controls and were associated with increased risk for recurrence, whereas intestinal fatty acid binding protein (I-FABP) and Endocab showed no association. Receiver operating characteristic (ROC) curve analysis demonstrated the utility of these individual microbial markers in discriminating recurrence from cure with high sensitivity, specificity, and area under the curve (AUC). Conclusions: Recurrence following microbiological cure in PTB is characterized by heightened baseline microbial translocation. These markers can be used as a rapid prognostic tool for predicting recurrence in PTB.
MeSH term(s)	Humans ; Prognosis ; Tuberculosis, Pulmonary/diagnosis ; Tuberculosis, Pulmonary/microbiology ; Tuberculosis ; Sputum/microbiology ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciac236
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Article ; Online: Sex-specific differences in systemic immune responses in MIS-C children.

Rajamanickam, Anuradha / Kumar, Nathella Pavan / Venkataraman, Aishwarya / Varadarjan, Poovazhagi / Selladurai, Elilarasi / Sankaralingam, Thangavelu / Thiruvengadam, Kannan / Selvam, Ramya / Thimmaiah, Akshith / Natarajan, Suresh / Ramaswamy, Ganesh / Putlibai, Sulochana / Sadasivam, Kalaimaran / Sundaram, Balasubramanian / Hissar, Syed / Ranganathan, Uma Devi / Babu, Subash

Scientific reports

2024 Volume 14, Issue 1, Page(s) 1720

Abstract: Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare manifestation of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection that can result in increased morbidity and mortality. Mounting evidence describes sex disparities in ... ...

Abstract	Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare manifestation of Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) infection that can result in increased morbidity and mortality. Mounting evidence describes sex disparities in the clinical outcomes of coronavirus disease 2019 (COVID-19). However, there is a lack of information on sex-specific differences in immune responses in MIS-C. This study is an observational and cross-sectional study and we wanted to examine immune parameters such as cytokines, chemokines, acute phase proteins (APPs), growth factors, microbial translocation markers (MTMs), complement components and matrix metalloproteinases (MMPs) in MIS-C children, based on sex. Male children were associated with heightened levels of pro-inflammatory cytokines-IFNγ, IL-2, TNFα, IL-1α, IL-1β, IL-6, IL-12, G-CSF and GM-CSF, chemokines-CCL2, CCL11, CXCL1, CXCL8 and CXCL10, acute phase proteins-α-2M, CRP, growth factors VEGF and TGFα, microbial translocation markers- iFABP, LBP, EndoCAb, complement components-C1q, MBL and C3 and matrix metalloproteinases MMP-8 and MMP-9 compared to female children with MIS-C. These results indicate that the heightened immune response in males is a characteristic feature of MIS-C. These findings might explain the differential disease pathogenesis in males compared to females with MIS-C and facilitate a deeper understanding of this disease.
MeSH term(s)	Child ; Humans ; Male ; Female ; Cross-Sectional Studies ; SARS-CoV-2 ; Cytokines ; Acute-Phase Proteins ; Systemic Inflammatory Response Syndrome ; Immunity ; Matrix Metalloproteinases ; COVID-19/complications
Chemical Substances	Cytokines ; Acute-Phase Proteins ; Matrix Metalloproteinases (EC 3.4.24.-)
Language	English
Publishing date	2024-01-19
Publishing country	England
Document type	Observational Study ; Case Reports ; Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-52116-1
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Article ; Online: Clinical outcomes in children living with HIV treated for non-severe tuberculosis in the SHINE Trial.

Chabala, Chishala / Wobudeya, Eric / van der Zalm, Marieke M / Kapasa, Monica / Raichur, Priyanka / Mboizi, Robert / Palmer, Megan / Kinikar, Aarti / Hissar, Syed / Mulenga, Veronica / Mave, Vidya / Musoke, Philippa / Hesseling, Anneke C / McIlleron, Helen / Gibb, Diana / Crook, Angela / Turkova, Anna

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2024

Abstract: Background: Children living with HIV(CLWH) are at high risk of tuberculosis(TB) and face poor outcomes, despite antiretroviral treatment(ART). We evaluated outcomes in CLWH and HIV-uninfected children treated for non-severe TB in the SHINE trial.: ... ...

Abstract	Background: Children living with HIV(CLWH) are at high risk of tuberculosis(TB) and face poor outcomes, despite antiretroviral treatment(ART). We evaluated outcomes in CLWH and HIV-uninfected children treated for non-severe TB in the SHINE trial. Methods: SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, non-severe TB who were randomized to receive 4 vs 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CLWH. Results: Of 1204 enrolled, 127(11%) were CLWH, of similar age (median(IQR) 3.6(1.2, 10.3) vs. 3.5(1.5, 6.9)years, p= 0.07), but more underweight (WAZ; -2.3(-3.3, -0.8) vs -1.0(-1.8, -0.2), p<0.01) and anemic (hemoglobin 9.5(8.7, 10.9) vs 11.5(10.4, 12.3)g/dl, p<0.01) compared to HIV-uninfected children. 68(54%) CLWH were ART-naïve; baseline median CD4 count 719(241-1134) cells/mm3, CD4% 16(10-26)%). CLWH were more likely to be hospitalized (aOR=2.4(1.3-4.6)) and die (aHR(95%CI) 2.6(1.2,5.8)). HIV status, age <3 years (aHR 6.3(1.5,27.3)), malnutrition (aHR 6.2(2.4,15.9)) and hemoglobin <7g/dl(aHR 3.8(1.3,11.5) independently predicted mortality. Among children with available VL, 45% and 61% CLWH had VL<1000copies/ml at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 vs 6 months) on TB treatment outcomes by HIV status (p for interaction=0.42). Conclusions: We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CLWH treated for non-severe TB. Irrespective of TB treatment duration, CLWH had higher rates of mortality and hospitalization than HIV-uninfected counterparts.
Language	English
Publishing date	2024-04-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciae193
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Article ; Online: Downregulation of monocyte miRNAs: implications for immune dysfunction and disease severity in drug-resistant tuberculosis.

Sampath, Pavithra / Moorthy, Manju / Menon, Athul / Madhav, Lekshmi / Janaki, Aishwarya / Dhanapal, Madhavan / Natarajan, Alangudi Palaniappan / Hissar, Syed / Ranganathan, Uma Devi / Ramaswamy, Gopalakrishna / Bethunaickan, Ramalingam

Frontiers in immunology

2023 Volume 14, Page(s) 1197805

Abstract: Background: Monocyte miRNAs govern both protective and pathological responses during tuberculosis (TB) through their differential expression and emerged as potent targets for biomarker discovery and host-directed therapeutics. Thus, this study examined ... ...

Abstract	Background: Monocyte miRNAs govern both protective and pathological responses during tuberculosis (TB) through their differential expression and emerged as potent targets for biomarker discovery and host-directed therapeutics. Thus, this study examined the miRNA profile of sorted monocytes across the TB disease spectrum [drug-resistant TB (DR-TB), drug-sensitive TB (DS-TB), and latent TB] and in healthy individuals (HC) to understand the underlying pathophysiology and their regulatory mechanism. Methods: We sorted total monocytes including three subsets (HLA-DR Results: The outcome was the differential expression of 107 miRNAs particularly the downregulation of miRNAs in the active TB groups (both drug-resistant and drug-sensitive). The miRNA profile revealed differential expression signatures: i) decline of miR-548m in DR-TB alone, ii) decline of miR-486-3p in active TB but significant elevation only in LTB iii) elevation of miR-132-3p only in active TB (DR-TB and DS-TB) and iv) elevation of miR-150-5p in DR-TB alone. The directionality of functions mediated by monocyte miRNAs from Gene Set Enrichment Analysis (GSEA) facilitated two phenomenal findings: i) a bidirectional response between active disease (activation profile in DR-TB and DS-TB compared to LTB and HC) and latent infection (suppression profile in LTB vs HC) and ii) hyper immune activation in the DR-TB group compared to DS-TB. Conclusion: Thus, monocyte miRNA signatures provide pathological clues for altered monocyte function, drug resistance, and disease severity. Further studies on monocyte miRNAs may shed light on the immune regulatory mechanism for tuberculosis.
MeSH term(s)	Humans ; Monocytes ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Leukocytes, Mononuclear ; Down-Regulation ; Tuberculosis ; HLA-DR Antigens ; Tuberculosis, Multidrug-Resistant/drug therapy ; Tuberculosis, Multidrug-Resistant/metabolism ; Patient Acuity
Chemical Substances	MicroRNAs ; HLA-DR Antigens
Language	English
Publishing date	2023-06-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1197805
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Article ; Online: Cytokine upsurge among drug-resistant tuberculosis endorse the signatures of hyper inflammation and disease severity.

Sampath, Pavithra / Rajamanickam, Anuradha / Thiruvengadam, Kannan / Natarajan, Alangudi Palaniappan / Hissar, Syed / Dhanapal, Madhavan / Thangavelu, Bharathiraja / Jayabal, Lavanya / Ramesh, Paranchi Murugesan / Ranganathan, Uma Devi / Babu, Subash / Bethunaickan, Ramalingam

Scientific reports

2023 Volume 13, Issue 1, Page(s) 785

Abstract: Tuberculosis (TB) elimination is possible with the discovery of accurate biomarkers that define the stages of infection. Drug-resistant TB impair the current treatment strategies and worsen the unfavourable outcomes. The knowledge on host immune ... ...

Abstract	Tuberculosis (TB) elimination is possible with the discovery of accurate biomarkers that define the stages of infection. Drug-resistant TB impair the current treatment strategies and worsen the unfavourable outcomes. The knowledge on host immune responses between drug-sensitive and drug-resistant infection is inadequate to understand the pathophysiological differences and disease severity. The secreted proteins, cytokines display versatile behaviour upon infection with Mycobacterium tuberculosis (MTB) and their imbalances often tend to assist disease pathology than protection. Therefore, studying these soluble proteins across TB infection spectrum (drug-resistant TB, drug-sensitive TB, and latent TB) may unveil the disease mediated responses and unique stage specific cytokine signatures. Thus, we sought to determine the plasma cytokine levels from healthy, latently infected, drug-sensitive, and drug-resistant TB individuals. Our study revealed top 8 cytokines (IL-17, IL-1α, IL-2, IL-10, IL-5, IFN-γ, TNF-α and IL-6) and their biomarker abilities to discriminate different stages of infection.
MeSH term(s)	Humans ; Cytokines ; Antigens, Bacterial ; Tuberculosis ; Latent Tuberculosis ; Mycobacterium tuberculosis ; Tuberculosis, Multidrug-Resistant/drug therapy ; Inflammation ; Patient Acuity
Chemical Substances	Cytokines ; Antigens, Bacterial
Language	English
Publishing date	2023-01-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-27895-8
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Article ; Online: Plasma chemokines CXCL10 and CXCL9 as potential diagnostic markers of drug-sensitive and drug-resistant tuberculosis.

Scientific reports

2023 Volume 13, Issue 1, Page(s) 7404

Abstract: Tuberculosis (TB) diagnosis still remains to be a challenge with the currently used immune based diagnostic methods particularly Interferon Gamma Release Assay due to the sensitivity issues and their inability in differentiating stages of TB infection. ... ...

Abstract	Tuberculosis (TB) diagnosis still remains to be a challenge with the currently used immune based diagnostic methods particularly Interferon Gamma Release Assay due to the sensitivity issues and their inability in differentiating stages of TB infection. Immune markers are valuable sources for understanding disease biology and are easily accessible. Chemokines, the stimulant, and the shaper of host immune responses are the vital hub for disease mediated dysregulation and their varied levels in TB disease are considered as an important marker to define the disease status. Hence, we wanted to examine the levels of chemokines among the individuals with drug-resistant, drug-sensitive, and latent TB compared to healthy individuals. Our results demonstrated that the differential levels of chemokines between the study groups and revealed that CXCL10 and CXCL9 as potential markers of drug-resistant and drug-sensitive TB with better stage discriminating abilities.
MeSH term(s)	Humans ; Chemokine CXCL10 ; Mycobacterium tuberculosis ; Tuberculosis/diagnosis ; Tuberculosis/drug therapy ; Latent Tuberculosis ; Chemokines ; Tuberculosis, Multidrug-Resistant/diagnosis ; Tuberculosis, Multidrug-Resistant/drug therapy ; Biomarkers ; Chemokine CXCL9
Chemical Substances	Chemokine CXCL10 ; Chemokines ; Biomarkers ; Chemokine CXCL9 ; CXCL9 protein, human ; CXCL10 protein, human
Language	English
Publishing date	2023-05-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-34530-z
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Article ; Online: Acute Phase Proteins Are Baseline Predictors of Tuberculosis Treatment Failure.

Kumar, Nathella Pavan / Moideen, Kadar / Nancy, Arul / Viswanathan, Vijay / Thiruvengadam, Kannan / Sivakumar, Shanmugam / Hissar, Syed / Kornfeld, Hardy / Babu, Subash

Frontiers in immunology

2021 Volume 12, Page(s) 731878

Abstract: Systemic inflammation is a characteristic feature of pulmonary tuberculosis (PTB). Whether systemic inflammation is associated with treatment failure in PTB is not known. Participants, who were newly diagnosed, sputum smear and culture positive ... ...

Abstract	Systemic inflammation is a characteristic feature of pulmonary tuberculosis (PTB). Whether systemic inflammation is associated with treatment failure in PTB is not known. Participants, who were newly diagnosed, sputum smear and culture positive individuals with drug-sensitive PTB, were treated with standard anti-tuberculosis treatment and classified as having treatment failure or microbiological cure. The plasma levels of acute phase proteins were assessed at baseline (pre-treatment). Baseline levels of C-reactive protein (CRP), alpha-2 macroglobulin (a2M), Haptoglobin and serum amyloid P (SAP) were significantly higher in treatment failure compared to cured individuals. ROC curve analysis demonstrated the utility of these individual markers in discriminating treatment failure from cure. Finally, combined ROC analysis revealed high sensitivity and specificity of 3 marker signatures comprising of CRP, a2M and SAP in distinguishing treatment failure from cured individuals with a sensitivity of 100%, specificity of 100% and area under the curve of 1. Therefore, acute phase proteins are very accurate baseline predictors of PTB treatment failure. If validated in larger cohorts, these markers hold promise for a rapid prognostic testing for adverse treatment outcomes in PTB.
MeSH term(s)	Acute-Phase Proteins/metabolism ; Adult ; Antitubercular Agents/therapeutic use ; Biomarkers/blood ; C-Reactive Protein/metabolism ; Cohort Studies ; Female ; Haptoglobins/metabolism ; Humans ; Male ; Middle Aged ; Pregnancy-Associated alpha 2-Macroglobulins/metabolism ; Prospective Studies ; ROC Curve ; Serum Amyloid P-Component/metabolism ; Treatment Failure ; Tuberculosis, Pulmonary/blood ; Tuberculosis, Pulmonary/drug therapy ; Tuberculosis, Pulmonary/microbiology
Chemical Substances	Acute-Phase Proteins ; Antitubercular Agents ; Biomarkers ; HP protein, human ; Haptoglobins ; Pregnancy-Associated alpha 2-Macroglobulins ; Serum Amyloid P-Component ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2021-11-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.731878
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Article ; Online: Effect of anti-tuberculosis treatment on the systemic levels of tissue inhibitors of metalloproteinases in tuberculosis - Diabetes co-morbidity.

Kumar, Nathella Pavan / Moideen, Kadar / Viswanathan, Vijay / Sivakumar, Shanmugam / Hissar, Syed / Kornfeld, Hardy / Babu, Subash

Journal of clinical tuberculosis and other mycobacterial diseases

2021 Volume 23, Page(s) 100237

Abstract: Objectives: To study the association of Tissue inhibitors of matrix metalloproteinases (TIMP) levels with tuberculosis-diabetes comorbidity (TB-DM) comorbidity at baseline and in response to anti-TB treatment (ATT).: Methods: We examined the levels ... ...

Abstract	Objectives: To study the association of Tissue inhibitors of matrix metalloproteinases (TIMP) levels with tuberculosis-diabetes comorbidity (TB-DM) comorbidity at baseline and in response to anti-TB treatment (ATT). Methods: We examined the levels of TIMP-1, -2, -3 and -4 in pulmonary tuberculosis alone (TB) or TB-DM at baseline and after ATT. Results: TIMP-1, -3 and -4 were significantly increased in TB-DM compared to TB at baseline and after ATT. ATT resulted in a significant reduction in TIMP-2 and -3 levels and a significant increase in TIMP-1 in both TB and TB-DM. TIMP-1, -3 and -4 were also significantly increased in TB-DM individuals with bilateral, cavitary disease and also exhibited a positive relationship with bacterial burden in TB-DM and HbA1c in all TB individuals. Within the TB-DM group, those known to be diabetic before incident TB (KDM) exhibited higher levels of TIMP-1, -2, -3 and -4 at baseline and TIMP-2 at post-treatment compared to those newly diagnosed with DM (NDM). KDM individuals on metformin treatment exhibited lower levels of TIMP-1, -2 and -4 at baseline and of TIMP-4 at post-treatment. Conclusions: TIMP levels were elevated in TB-DM, associated with disease severity and bacterial burden, correlated with HbA1c levels and modulated by duration of DM and metformin treatment.
Language	English
Publishing date	2021-04-22
Publishing country	England
Document type	Journal Article
ISSN	2405-5794
ISSN (online)	2405-5794
DOI	10.1016/j.jctube.2021.100237
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