Predicting the predisposition to colorectal cancer based on SNP profiles of immune phenotypes using supervised learning models.

This study explores the machine learning-based assessment of predisposition to colorectal cancer based on single nucleotide polymorphisms (SNP). Such a computational approach may be used as a risk indicator and an auxiliary diagnosis method that complements the traditional methods such as biopsy and CT scan. Moreover, it may be used to develop a low-cost screening test for the early detection of colorectal cancers to improve public health. We employ several supervised classification algorithms. Besides, we apply data imputation to fill in the missing genotype values. The employed dataset includes SNPs observed in particular colorectal cancer-associated genomic loci that are located within DNA regions of 11 selected genes obtained from 115 individuals. We make the following observations: (i) random forest-based classifier using one-hot encoding and K-nearest neighbor (KNN)-based imputation performs the best among the studied classifiers with an F1 score of 89% and area under the curve (AUC) score of 0.96. (ii) One-hot encoding together with K-nearest neighbor-based data imputation increases the F1 scores by around 26% in comparison to the baseline approach which does not employ them. (iii) The proposed model outperforms a commonly employed state-of-the-art approach, ColonFlag, under all evaluated settings by up to 24% in terms of the AUC score. Based on the high accuracy of the constructed predictive models, the studied 11 genes may be considered a gene panel candidate for colon cancer risk screening.

Assessment of Association Between the Potential Immunomodulatory Activity and Drinking Olive Leaf Tea in the Coronavirus Disease-2019 Pandemic: An Observational Study.

Objective: During the Coronavirus Disease-2019 (COVID-19) pandemic, in addition to the current measures, the healthy immune system plays an essential role and various natural agents have been recommended to boost innate immunity. The aim of this study was to investigate any association between the potential immunomodulatory activity and drinking olive leaf tea (OLT) in the COVID-19 pandemic. Design: The study was conducted among the workers in a tractor factory where OLT was served in routine. Drinking at least one cup of OLT per day for a minimum of 1 month was the inclusion criteria used in the study. The workers who had a history of vaccination and COVID-19 were excluded from the study, and lymphocyte subsets, interleukin (IL)-2, IFN-γ, COVID-19-specific IgM and IgG levels were analyzed in all the participants to determine the asymptomatic individuals among the participants and compare the immunological parameters. Results: The study was conducted among 336 workers, 183 of them were OLT drinkers and 153 were OLT nondrinkers. The results showed higher values of CD3-/CD16/56 (natural killer [NK]) cells, CD3+/CD16/56 (natural killer T [NKT]) cells, total NK (NK+NKT) cells, and serum IFN-γ, and IL-2 levels in OLT drinkers compared to the nondrinkers. Although all the OLT drinkers and nondrinkers included in the study reported no history of COVID-19, specific COVID-19 IgG levels were found positive in 60% of OLT drinkers and 38% OLT nondrinkers. Conclusions: Peripheral NK and NKT cell values and IL-2 and IFN-γ secretion levels were found higher in the OLT drinking group. There were positive correlations between the OLT drinking frequency and NK cell counts. Moreover, the number of individuals who had "asymptomatic" COVID-19 infection was higher in the OLT drinking group than in the nondrinking cohort. Clinical Trial Registration Number: The trial has been registered in the ClinicalTrials.gov database (CTR NCT05222347).

Individual and Combined Effects of CTLA4-CD28 Variants and Oxidant-Antioxidant Status on the Development of Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most frequent cancer worldwide. Research has revealed the contributions of the immune system and anti-inflammatory pathways in the development of cancer. The balance between cluster of differentiation 28 (CD28) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) signaling is important for the regulation of immune responses. The oxidant-antioxidant balance by sustaining redox control via several defense mechanisms is also an important factor for the progression of cancer. The aim of the present study was to determine the distribution of CTLA4/CD28 variants and oxidant-antioxidant status in patients with CRC. MATERIALS AND METHODS: This study enrolled 80 patients with CRC and 115 healthy controls. We used a spectrophotometric assay to detect the levels of lipid peroxidation products malon dialdehyde (MDA) and lipid hydroperoxide (LHP), and measured the concentration of protein damage products, advanced oxidation protein products (AOPP) and protein carbonyl (PCO). Additionally, antioxidant levels were detected by measuring copper, zinc, superoxide dismutase (Zn-Cu SOD) and total thiol (T-SH) levels, and advanced glycation end-products (AGEs). The CTLA4 -318C>T, CTLA4 49A>G and CD28C>T genotypes were determined by using restriction enzymes. RESULTS: AOPP and PCO levels were increased in patients with CRC as well as those of LHP, MDA and AGE, while the levels of antioxidants such as Cu-Zn SOD and T-SH were lower. Lower serum levels of CTLA4 and higher serum levels of CD28 were detected in patients and, an association of the CTLA4 -318C/T polymorphism was found in patients with CRC. CONCLUSION: Our oxidative stress was increased in patients with CRC, suggesting the contribution of this disturbed oxidative status to serum CTLA4 and CD28 levels, and to the pathogenesis of CRC.

Anti-proliferative, apoptotic and signal transduction effects of hesperidin in non-small cell lung cancer cells.

PURPOSE: Hesperidin, a glycoside flavonoid, is thought to act as an anti-cancer agent, since it has been found to exhibit both pro-apoptotic and anti-proliferative effects in several cancer cell types. The mechanisms underlying hesperidin-induced growth arrest and apoptosis are, however, not well understood. Here, we aimed to investigate the anti-proliferative and apoptotic effects of hesperidin on non-small cell lung cancer (NSCLC) cells and to investigate the mechanisms involved. METHODS: The anti-proliferative and apoptotic effects of hesperidin on two NSCLC-derived cell lines, A549 and NCI-H358, were determined using a WST-1 colorimetric assay, a LDH cytotoxicity assay, a Cell Death Detection assay, an AnnexinV-FITC assay, a caspase-3 assay and a JC-1 assay, respectively, all in a time- and dose-dependent manner. As a control, non-cancerous MRC-5 lung fibroblasts were included. Changes in whole genome gene expression profiles were assessed using an Illumina Human HT-12v4 beadchip microarray platform, and subsequent data analyses were performed using an Illumina Genome Studio and Ingenuity Pathway Analyser (IPA). RESULTS: We found that after hesperidin treatment, A549 and NCI-H358 cells exhibited decreasing cell proliferation and increasing caspase-3 and other apoptosis-related activities, in conjunction with decreasing mitochondrial membrane potential activities, in a dose- and time-dependent manner. Through a GO analysis, by which changes in gene expression profiles were compared, we found that the FGF and NF-κB signal transduction pathways were most significantly affected in the hesperidin treated NCI-H358 and A549 NSCLC cells. CONCLUSIONS: Our results indicate that hesperidin elicits an in vitro growth inhibitory effect on NSCLC cells by modulating immune response-related pathways that affect apoptosis. When confirmed in vivo, hesperidin may serve as a novel anti-proliferative agent for non-small cell lung cancer.

The role of activated cytotoxic T cells in etiopathogenesis of periodontal disease: does it harm or does it heal?

The objective of this study was to determine the phenotypic profile of blood mononuclear cells, specifically CD8(+)/CD28(+) cells, in patients with generalized aggressive periodontitis (GAgP) and chronic periodontitis (CP) in peripheral blood and in blood obtained from periodontal defect site which might contribute to tissue damage. 13 GAgP, 11 chronic periodontitis (CP) and 5 healthy controls (H) were included in the study. Plaque index (PI), bleeding on probing (BoP), periodontal probing depth (PPD) and clinical attachment level (CAL) were recorded. Blood from the base of periodontal defect site and peripheral blood from the antecubital vein were obtained. Relative counts of CD45(+), CD3(+), CD4(+), CD8(+)/CD28(+), CD8(+)/CD28(-), CD19(+), CD16(+)/CD56(+)/CD3, CD3(+)/CD16(+)/CD56(+) receptors were determined with two color flow cytometry using monoclonal antibodies. BoP, PPD and CAL were significantly higher in both periodontitis groups than healthy controls (p <0.05). Activated cytotoxic T cells, CD8(+)/CD28(+) cells, were significantly elevated in GAgP and CP groups compared to HC both in blood obtained from defect site and blood obtained from systemic circulation (p <0.05). GAgP and CP patients have an increased levels of activated cytotoxic T cells as a result of inflammation which may cause severe tissue damage that lead to severe and rapid loss of periodontal tissues.

Apoptotic Effects of Quercitrin on DLD-1 Colon Cancer Cell Line.

Quercetin, which is the most abundant bioflavonoid compound, is mainly present in the glycoside form of quercitrin. Although different studies indicated that quercitrin is a potent antioxidant, the action of this compound is not well understood. In this study, we investigated whether quercitrin has apoptotic and antiproliferative effects in DLD-1 colon cancer cell lines. Time and dose dependent antiproliferative and apoptotic effects of quercitrin were subsequently determined by WST-1 cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, detection of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine (PS) in the plasma membrane. There were significant increases in caspase-3 activity, loss of MMP, and increases in the apoptotic cell population in response to quercitrin in DLD-1 colon cancer cells in a time- and dose-dependent manner. These results revealed that quercitrin has antiproliferative and apoptotic effects on colon cancer cells. Quercitrin activity supported with in vivo analyses could be a biomarker candicate for early colorectal carcinoma.

Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer.

BACKGROUND AND AIMS: Quercitrin (QR; quercetin-3-O-rhamnoside) has been used previously as an antibacterial agent and has been shown to inhibit the oxidation of low-density lipoproteins and prevent an allergic reaction. Furthermore, it was demonstrated that quercitrin exerts protective effects against H2O2-induced dysfunction in lung fibroblast cells. However, the mechanisms of quercitrin effects on cancer cell proliferation and apoptosis is not well understood. The aim of this study is to investigate the cytotoxic and apoptotic effects of quercitrin and the molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer (NSCLC) cell lines. METHODS: Time- and dose-dependent antiproliferative and apoptotic effects of quercitrin determined by WST-1 cell proliferation assay, lactate dehydrogenase (LDH) cytotoxicity assay, determination of nucleosome enrichment factor, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and also the localization of phosphatidylserine in the plasma membrane. Changes in whole genome gene expression levels were examined by Illumina Human HT-12v4 beadchip microarrays. RESULTS: There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to quercitrin in A549 and NCI-H358 NSCLC cells in a time- and dose-dependent manner. CONCLUSION: Our results demonstrated that genes involved in leukocyte transendothelial migration, cell adhesion and phosphatidylinositol signaling system pathways were the most statistically significant pathways in NCI-H358 and A549 cells. These results revealed that quercitrin has antiproliferative and apoptotic effects on lung cancer cells by modulating the immune response. After confirming its anticarcinogenic effects in vivo, quercitrin could be a novel and strong anticancer agent against NSCLC.

Recruitment Maneuver Does not Increase the Risk of Ventilator Induced Lung Injury.

BACKGROUND: Mechanical ventilation (MV) may induce lung injury. AIMS: To assess and evaluate the role of different mechanical ventilation strategies on ventilator-induced lung injury (VILI) in comparison to a strategy which includes recruitment manoeuvre (RM). STUDY DESIGN: Randomized animal experiment. METHODS: Thirty male Sprague-Dawley rats were anaesthetised, tracheostomised and divided into 5 groups randomly according to driving pressures; these were mechanically ventilated with following peak alveolar opening (Pao) and positive end-expiratory pressures (PEEP) for 1 hour: Group 15-0: 15 cmH2O Pao and 0 cmH2O PEEP; Group 30-10: 30 cmH2O Pao and 10 cmH2O PEEP; Group 30-5: 30 cmH2O Pao and 5 cmH2O PEEP; Group 30-5&RM: 30 cmH2O Pao and 5 cmH2O PEEP with additional 45 cmH2O CPAP for 30 seconds in every 15 minutes; Group 45-0: 45 cmH2O Pao and 0 cmH2O PEEP Before rats were sacrificed, blood samples were obtained for the evaluation of cytokine and chemokine levels; then, the lungs were subsequently processed for morphologic evaluation. RESULTS: Oxygenation results were similar in all groups; however, the groups were lined as follows according to the increasing severity of morphometric evaluation parameters: Group 15-0: (0±0.009) < Group 30-10: (0±0.14) < Group 30-5&RM: (1±0.12) < Group 30-5: (1±0.16) < Group 45-0: (2±0.16). Besides, inflammatory responses were the lowest in 30-5&RM group compared to all other groups. TNF-α, IL-1ß, IL-6, MCP-1 levels were significantly different between group 30-5&RM and group 15-0 vs. group 45-0 in each group. CONCLUSION: RM with low PEEP reduces the risk of ventilator-induced lung injury with a lower release of systemic inflammatory mediators in response to mechanical ventilation.

The effect of montelukast sodium on serum arginase levels in patients with seasonal allergic rhinitis.

BACKGROUND: Nitric oxide (NO) imbalance appears to be important in the pathogenesis of allergic rhinitis. NO is synthesized from l-arginine by NO synthase (NOS). Competing with NOS for l-arginine is arginase, which catalyzes the hydrolysis of arginine to urea and ornithine. Therefore, increased serum arginase activity could potentially limit NO production catalyzed by inducible NOS, thus contributing to allergic rhinitis. This study was designed to investigate the effect of the cysteinyl leukotriene type 1 receptor antagonist, montelukast sodium on serum arginase levels in patients with seasonal allergic rhinitis. METHODS: Twenty-five patients with seasonal allergic rhinitis (SAR; treatment group) and 16 nonasthmatic patients without allergic rhinitis (control group) were included in the study. Serum arginase levels and the mean total nasal symptoms scores were measured before and after oral montelukast sodium (10 mg) was administered daily for 4 weeks to the treatment group. RESULTS: Serum arginase levels and the mean total nasal symptoms scores were significantly lower in the treatment group after montelukast sodium administration compared with the baseline levels (p = 0.001). Serum arginase levels were significantly lower in the treatment group compared with the control group (p = 0.01). There was no statistically significant difference between the serum arginase levels of the treatment group before treatment and the control group (p = 0.05). There was a weak correlation between the mean total nasal symptoms scores and serum arginase levels in the treatment group before montelukast sodium administration (rs = 0.40; p = 0.05). CONCLUSION: Montelukast sodium may reduce serum arginase levels and total nasal symptoms scores of patients with SAR. Additional studies that compare the effectiveness of nasal corticosteroid and montelukast sodium on serum arginase levels should be conducted.

Potential adjuvant effects of Nigella sativa seeds to improve specific immunotherapy in allergic rhinitis patients.

OBJECTIVE: To investigate the effects of Nigella sativa seed supplementation on symptom levels, polymorphonuclear leukocyte (PMN) functions, lymphocyte subsets and hematological parameters of allergic rhinitis. SUBJECTS AND METHODS: Twenty-four patients randomly selected from an experimental group of 31 (mean age 34 years) sensitive to house dust mites with allergic rhinitis and a control group of 8 healthy volunteers (mean age 23 years) were treated with allergen-specific immunotherapy in conventional doses for 30 days. After a month of immunotherapy, 12 of the 24 patients and the 8 healthy volunteers were given N. sativa seed supplementation (2 g/day orally) for 30 days. The remaining 12 patients continued only on immunotherapy during the same period. The other 7 patients were given 0.1 ml saline solution subcutaneously once a week as a placebo. The symptom scores, PMN functions, lymphocyte subsets and other hematological parameters were evaluated before and after all treatment periods. RESULTS: There was a statistically significant increase in the phagocytic and intracellular killing activities of PMNs of patients receiving specific immunotherapy, especially after the addition of N. sativa seed. The CD8 counts of patients receiving specific immunotherapy plus N. sativa seed supplementation significantly increased compared to patients receiving only specific immunotherapy. PMN functions of healthy volunteers significantly increased after N. sativa seed supplementation compared to baseline. CONCLUSION: N. sativa seed supplementation during specific immunotherapy of allergic rhinitis may be considered a potential adjuvant therapy.

Can immune parameters be used as predictors to distinguish between pulmonary multidrug-resistant and drug-sensitive tuberculosis?

INTRODUCTION: Despite the development and wide implementation of Directly Observed Therapy Strategies (DOTS), multidrug-resistant tuberculosis (MDR-TB) remains a serious global health threat. In this study, the role of host immune response in patients with MDR-TB is investigated and compared with that of patients with smear-positive drug-sensitive tuberculosis (SP-TB). MATERIAL AND METHODS: 27 patients with SP-TB, 20 patients with MDR-TB, and 20 healthy controls were included in the study. Immune parameters were determined by flow cytometry using monoclonal antibodies in order to compare the percentage values of these markers in the two study groups and the control group. RESULTS: The levels of lymphocyte subgroups in the gate of CD45(+)/CD14(-) lymphocyte: CD45(+), CD3(+), CD4(+), NK, CD3/HLA-DR, CD 95(+) cells were significantly lower; by contrast CD23(+), CD25(+), CD19(+), CD4(+)/CD8(+), HLA-DR cells were found to be lower, but not significantly so in patients with MDR-TB, compared to levels in patients in the SP-TB and control groups. Besides these findings, the levels of NKT cells and (γ)δ TCR(+) cells were significantly higher in the MDR-TB than in the healthy control and SP-TB group. CONCLUSIONS: The lower levels of CD3/ HLA-DR, CD4 (+), Fas (+), and NK, and the higher level of NKT together with (γ)δ T cells in patients with MDR-TB compared to those in SP-TB may indicate a profound immune suppression in MDR-TB patients and thereby may denote an accumulation in the bacterial load. Our findings may shed light on the pathogenesis and prognosis of MDR tuberculosis, and may point towards the use of flow cytometry findings as an aid to early diagnosis in MDR-TB patients.

Lymphocyte subgroups and natural killer cell activity in recurrent herpetic stromal keratitis.

PURPOSE: Although the role of natural killer cells in the defense against certain viral infections has been published, little is known about the role of lymphocyte subgroups in recurrent herpetic stromal keratitis. Accordingly, serum levels of major immunoglobulins (IgG, IgA, and IgM) and IgG subgroups, the lymphocyte subgroups, and natural killer cell activity were investigated in patients with recurrent herpetic stromal keratitis. METHODS: Eleven patients with recurrent herpetic stromal keratitis and 10 healthy subjects were included. A delayed-type hypersensitivity skin test was performed in addition to the determination of serum immunoglobulin levels, IgG subgroups, peripheral blood lymphocyte percentages, and natural killer cell activity in both groups. RESULTS: The result of the delayed-type hypersensitivity skin test was positive in all patients with recurrent herpetic stromal keratitis and healthy subjects. No significant difference was obtained in serum immunoglobulin levels and IgG subgroups between the patients and healthy subjects. Among the cell surface antigens (CD3, CD4, CD8, CD16, CD19, and CD20), only CD8+ (i.e., cytotoxic) T-lymphocyte percentages were significantly increased (P=0.003), and the CD4:CD8 ratio was significantly decreased in the patients compared to the healthy subjects (P=0.021). There was no significant difference in the expression of CD16+ natural killer cells between both groups, despite a significantly lower natural killer cell activity in patients with recurrent herpetic stromal keratitis (P=0.011). CONCLUSIONS: These results indicate that human cytotoxic T cells show a difference in numbers and natural killer cell activity that may affect the prognosis of recurrent herpetic stromal keratitis.

Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow.

Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1alpha are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin-biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK(+) cells was 236 (range, 20-847) per 5 x 10(4) enriched BM cells. The presence of CK(+) cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (>236 CK(+) per 5 x 10(4) enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.

Nigella sativa (black seed) oil does not affect the T-helper 1 and T-helper 2 type cytokine production from splenic mononuclear cells in allergen sensitized mice.

Nigella sativa Linn. (Ranunculaceae) is known to have beneficial effects on a wide range of diseases including asthma. However, the mechanism of action in asthma and other allergic diseases is not entirely clear. The present study was planned to evaluate the effects of Nigella sativa on cytokine production of splenic mononuclear cells in ova-sensitized mice. Nineteen two-month-old BALB/c mice were given 0.3 mL of Nigella sativa oil by oro-eosophageal cannula once a day for a month. The control group consisting of 10 mice took 0.3 mL of 0.9% saline solution by the same route for the same period. In the third week of the study, all mice were sensitized by means of intraperitoneal injections of 20 microg of ovalbumin (OVA-Grade VI, Sigma). Ova injections were repeated three times with 7-day intervals. After another week, all mice were sacrificed by means of cervical dislocation. Then the splenic mononuclear cells (MNCs) of mice were cultured with OVA or Concavalin A (Con-A). From the culture supernatants, IL-4, IL-10 and IFN-gamma were assessed by means of ELISA. The cytokine production of splenic MNCs of mice that were given Nigella sativa for 30 days was not significantly different than those who took saline solution instead. In conclusion, Nigella sativa oil seems not to have an immunomodulatory effect on Th1 and Th2 cell responsiveness to allergen stimulation.

Effects of body temperature on ventilator-induced lung injury.

PURPOSE: To evaluate the effects of body temperature on ventilator-induced lung injury. MATERIAL AND METHODS: Thirty-four male Sprague-Dawley rats were randomized into 6 groups based on their body temperature (normothermia, 37 +/- 1 degrees C; hypothermia, 31 +/- 1 degrees C; hyperthermia, 41 +/- 1 degrees C). Ventilator-induced lung injury was achieved by ventilating for 1 hour with pressure-controlled ventilation mode set at peak inspiratory pressure (PIP) of 30 cmH2O (high pressure, or HP) and positive end-expiratory pressure (PEEP) of 0 cmH2O. In control subjects, PIP was set at 14 cmH2O (low pressure, or LP) and PEEP set at 0 cmH2O. Systemic chemokine and cytokine (tumor necrosis factor alpha , interleukin 1 beta , interleukin 6, and monocyte chemoattractant protein 1) levels were measured. The lungs were assessed for histological changes. RESULTS: Serum chemokines and cytokines were significantly elevated in the hyperthermia HP group compared with all 3 groups, LP (control), normothermia HP, and hypothermia HP. Oxygenation was better but not statistically significant in hypothermia HP compared with other HP groups. Cumulative mean histology scores were higher in hyperthermia HP and normothermia HP groups compared with control and normothermia HP groups. CONCLUSIONS: Concomitant hyperthermia increased systemic inflammatory response during HP ventilation. Although hypothermia decreased local inflammation in the lung, it did not completely attenuate systemic inflammatory response associated with HP ventilation.

Levels of tumour necrosis factor-alpha and IL-1alpha in newly diagnosed and multidrug resistant tuberculosis.

BACKGROUND: The pro-inflammatory cytokines tumour necrosis factor (TNF)-alpha and IL-1alpha play key roles in host defence against tuberculosis (TB) but there is little knowledge of their levels in multidrug resistant TB (MDR-TB). The aim of the present study was to investigate the levels of TNF-alpha and IL-1alpha and their relationship with the levels of T helper (CD4+), T suppressor (CD8+) and total lymphocytes (CD45+) in newly diagnosed TB (N-TB) and MDR-TB. METHODOLOGY: This study assessed 19 N-TB patients (M/F : 17/2) and 11 MDR-TB patients (M/F : 10/1). Serum TNF-alpha and IL-1alpha were assessed by ELISA. Lymphocyte expression of CD45, CD4, CD8, CD3, CD23, CD19 and CD95 were determined by flow cytometry. RESULTS: The levels of TNF-alpha, IL-1alpha, and CD4, CD4/CD8, CD45, CD19, CD23 and CD95 positive lymphocytes were lower in MDR-TB than in N-TB patients (P < 0.05). Statistically, there was a positive correlation between TNF-alpha and IL-1alpha (r = 0.92) for both MDR-TB and N-TB. For both groups, both TNF-alpha and IL-1alpha correlated with CD4+ lymphocytes (r = 0.48). TNF-alpha and IL-1alpha showed negative correlations with CD8+ lymphocytes (r = -0.81, r = -0.73) (P < 0.01) in MDR-TB patients. CONCLUSION: The lower levels of cytokines and numbers of T helper lymphocytes in MDR-TB compared with N-TB implies that the immune profiles of the two groups are different, and may be important in the natural history of the disease.

[The role of supplementation or inhibition of nitric oxide production in burn injury to reduce ischemic damage]. / Yanikta nitrik oksit üremtiminin desteklenmesi veya azaltilmasinin iskemik hasari azaltmadaki rolü.

BACKGROUND: To determine the role of nitric oxide (NO) which is vasodilator agent and inflammatory cytokine, in burn injury. METHODS: Rats were divided into 5 groups, and a 30 % burn was inflicted. In addition to sham control and burn control groups, other 3 groups were given L-Arginine, and L-nitro-L-Arginine methylester (L-NAME), and both. Neutrophil and hematocrit percentage in blood, NO, TNF-alpha and malondialdehyde (MDA) levels in plasma and neutrophil infiltration in the lung were evaluated at 24 hours after thermal injury. RESULTS: The inhibition of NO production with L-NAME treatment significantly decreased these parameters when compared to burned control group. MDA was decreased significantly in all groups which were given drugs. CONCLUSION: The induction and inhibition of NO production both reduced lipid peroxidation but induction increased the mortality, plasma TNF-alpha and neutrophil in the blood. Inhibition of NO production is found more useful after thermal injury in rats.