Leishmania donovani infection activates Toll-like receptor 2, 4 expressions and Transforming growth factor-beta mediated apoptosis in renal tissues

Abstract The present study was aimed to identify the underlying mechanisms of improper renal function in Leishmania donovani infection that causes VL. Mice (BALB/c) were infected with L. donovani and different parameters for proteinuria were assessed. The levels of superoxide anion (O2 -), hydrogen peroxide (H2O2), lipid peroxidation (MDA), inflammatory cytokines, and toll-like receptor (TLR) 2 and 4 expression were found significantly elevated at 60th day in these animals and declined at 90th day post infection. However, TGF-β and caspase 3 activities were higher at 90th day in comparison to 60th day post infection. These findings suggested that exacerbated inflammatory conditions correlate with abnormal renal functions in L. donovani infection, which is further augmented by activated TLRs expressions by circulating leishmanial antigens. Further, the increased levels of TGF-β and caspase 3 at 90th day suggested TGF-β mediated apoptotic cell death of renal and other cells during later stages of disease that may eventually result in release of host and parasitic factors in urine during visceral leishmaniasis.

Vitamin A supplementation reduces the Th17-Treg – Related cytokines in obese and non-obese women

ABSTRACT Objective The objective of the present study was to investigate the effect of vitamin A supplementation on serum Th17 (IL-6, IL-17, IFNγ) and Treg (TGF-β, IL-10) related cytokines in obese and non-obese women. Subjects and methods In a randomized double blind placebo controlled design, 56 obese women were randomly assigned to receive either an oral dose of 25,000 IU retinyl palmitate or placebo per day for 4 months. Twenty eight ages matched non-obese women were also received vitamin A. At the study entry, anthropometric variables were measured and serum Th17 and Treg related cytokine profile were determined at baseline and 4 months after intervention. Results Significantly higher baseline concentrations of IL-6 were observed in obese compared with non-obese women (P < 0.05). However, the initial concentrations of other cytokines were not significantly different between groups. The mean concentrations of IL-17 and TGF-β were significantly decreased after vitamin A supplementation in non-obese and obese women respectively. Positive relationships between IL-17 and IL-10 (r = 0.42, P < 0.001), TGF-β and IL-17 (r = 0.35, P < 0.001) and between IL-10 and IFN-γ (r = 0.41, P = 0.002) in total participants were also observed. Conclusions The results of the present study showed for the first time that vitamin A supplementation reduces serum concentrations of IL-17 and TGF-β in reproductive age women. Further studies are needed to explore the possible underlying mechanisms.

Elevated IL-17 and TGF-beta serum levels: a positive correlation between T-helper 17 cell-related pro-inflammatory responses with major depressive disorder

Introduction: Depression is a mental disorder that highly associated with immune system. Therefore, this study compares the serum concentrations of IL-21, IL-17, and transforming growth factor beta [TGF-beta] between patients with major depressive disorder and healthy controls

Methods: Blood samples were collected from 41 patients with major depressive disorder and 40 healthy age-matched controls with no history of malignancies or autoimmune disorders. The subjects were interviewed face to face according to DSM-IV diagnostic criteria. Depression score was measured using completed Beck Depression Inventory in both groups. The serum concentrations of IL-21, IL-17, and TGF-beta were assessed using ELISA

Results: The mean score of Beck Depression score in the patient and control groups was 35.4 +/- 5.5 and 11.1 +/- 2.3. IL-17 serum concentrations in the patients and the control group were 10.03 +/- 0.6 and 7.6 +/- 0.6 pg/mL, respectively [P=0.0002]. TGF-beta level in the patients group was significantly higher than compare to the control group; 336.7 +/- 20.19 vs. 174.8 +/- 27.20 pg/mL, [P<0.0001]. However, the level of IL-21 was not statistically different between the two groups 84.30 +/- 4.57 vs. 84.12 +/- 4.15 pg/mL [P>0.05]

Conclusion: Considering pro-inflammatory cytokines, current results support the association of inflammatory response and depressive disorder. So, it seems that pro-inflammatory factors profile can be used as indicator in following of depression progress and its treatment impacts

Doxazosin Treatment Attenuates Carbon Tetrachloride-Induced Liver Fibrosis in Hamsters through a Decrease in Transforming Growth Factor beta Secretion

BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor beta (TGF-beta) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-beta-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.

MFG-E8, a clearance glycoprotein of apoptotic cells, as a new marker of disease severity in chronic obstructive pulmonary disease

Milk fat globule epidermal growth factor 8 (MFG-E8) is an opsonin involved in the phagocytosis of apoptotic cells. In patients with chronic obstructive pulmonary disease (COPD), apoptotic cell clearance is defective. However, whether aberrant MFG-E8 expression is involved in this defect is unknown. In this study, we examined the expression of MFG-E8 in COPD patients. MFG-E8, interleukin (IL)-1β and transforming growth factor (TGF)-β levels were measured in the plasma of 96 COPD patients (93 males, 3 females; age range: 62.12±10.39) and 87 age-matched healthy controls (85 males, 2 females; age range: 64.81±10.11 years) using an enzyme-linked immunosorbent assay. Compared with controls, COPD patients had a significantly lower plasma MFG-E8 levels (P<0.01) and significantly higher plasma TGF-β levels (P=0.002), whereas there was no difference in plasma IL-1β levels between the two groups. Moreover, plasma MFG-E8 levels decreased progressively between Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and GOLD IV stage COPD. Multiple regression analysis showed that the forced expiratory volume in 1 s (FEV1 % predicted) and smoking habit were powerful predictors of MFG-E8 in COPD (P<0.01 and P=0.026, respectively). MFG-E8 was positively associated with the FEV1 % predicted and negatively associated with smoking habit. The area under the receiver operating characteristic curve was 0.874 (95% confidence interval: 0.798-0.95; P<0.01). Our findings demonstrated the utility of MFG-E8 as a marker of disease severity in COPD and that cigarette smoke impaired MFG-E8 expression in these patients.

Effects of Green Tea Application Time on Bond Strength after Enamel Bleaching

This study evaluated the effect of green tea application time on the bond strength of enamel after enamel bleaching. Enamel samples were obtained from 80 third molars and randomly divided into 7 experimental groups (G1-G7) and 1 group without treatment (G8): G1, bleached with 10% carbamide peroxide (CP); G2, CP + 10% sodium ascorbate gel (SA) for 15 min; G3, CP + SA for 30 min; G4, CP + SA for 60 min; G5, CP + 10% green tea gel (GT) for 15 min; G6, CP + GT for 30 min; G7, CP + GT for 60 min. The CP was applied onto the enamel surface for 8 h for 14 days. The SA was applied in groups 2, 3 and 4, and the GT was applied in groups 5-8 according to the above described application times. Immediately after treatment, the specimens were bonded with Adper Single Bond 2 and Filtek Z350XT. The specimens were prepared to microtensile bond strength analysis. Fracture mode analysis was performed using a stereoscopic loupe. The data were statistically analyzed by two-way analysis of variance, the Tukey's and Dunnett's tests (=5%). The means (standard deviation) were: G1, 23.3 (3.2); G2, 25.2 (3.9); G3, 26.4 (5.4); G4, 30.2 (4.5); G5, 26.6 (3.4); G6, 22.0 (5.4); G7, 31.4 (3.3); G8, 31.4 (3.2). All groups had a high percentage of adhesive failures. In conclusion, the bond strength values were higher than the value in the bleached group only when the antioxidants were applied for 60 min.

Este estudo avaliou o efeito do tempo de aplicação do chá verde na resistência de união do esmalte após o clareamento. Amostras de esmalte foram obtidas a partir de 70 terceiros molares e aleatoriamente divididas em 7 grupos experimentais (G1-G7) e um grupo sem tratamento (G8). Os 7 grupos experimentais foram tratados como segue: G1, clareado com peróxido de carbamida a 10% (PC); G2, PC + gel de ascorbato de sódio a 10% (AS) por 15 min; G3, PC + AS por 30 min; G4, PC + AS por 60 min; G5, PC + gel de chá verde a 10% (CV) por 15 min; G6, PC + CV por 30 min; G7, PC + CV por 60 min. O PC foi aplicado na superfície do esmalte por 8 h, durante 14 dias. O AS foi aplicado nos grupos 2, 3 e 4 e o CV foi aplicado nos grupos 5, 6 e 7 de acordo com os tempos de aplicação descritos acima. Imediatamente após o tratamento, foi realizado o procedimento adesivo utilizando Adper Single Bond 2 e Filtek Z350XT. Em seguida, as amostras foram preparadas para o teste de microtração. A análise do padrão de fratura foi realizada em lupa estereoscópica. Os dados foram analisados através de ANOVA (2 fatores), testes de Tukey e Dunnett (α=5%). As médias (desvio padrão) foram: G1: 23,29 (3,20); G2: 25,18 (3,95); G3: 26,41 (5,40); G4: 30,17 (4,46); G5: 26,63 (3,43); G6: 22,02 (5,41); G7: 31,40 (3,35); G8: 31,4 (3,2). Todos os grupos apresentaram maior porcentagem de falhas adesivas. Em conclusão, os valores de resistência de união foram maiores que os dos grupos clareados somente quando os antioxidantes foram aplicados por 60 min.

TGF-B1 IN PATIENTS WITH CHRONIC HBV INFECTION

The transforming growth factor-beta[1] is an important cytokine with anti-inflammatory properties may have a role in pathogenesis of liver fibrosis. The main purpose of this study was to compare the serum levels of TGF- beta[1] in a group of chronic HBV infected [CHB] patients as well as healthy individuals and to determine the correlation between the TOF- beta[1] and stages of fibrosis in CHB patients. A case control study using forty patients with CHB as well as forty healthy individuals. ELISA technique was applied to measure the serum level of TGF- beta[1] in both patient and control groups. We used the data of the liver biopsy of CHB patients to make a correlation between TGF- beta[1] and stages of fibrosis. Our results revealed that the serum levels of TGF- beta[1] -were significantly increased in CHB patients [1958.0 +/- 730.26pg/ml] in comparison to healthy controls [944.4 +/- 5 73.24 pg/ml] [P<0.0001]. Serum levels of TGF- beta[1] -was significantly increased in F2-F3 [2600.0 +/- 472.69pg/ml] in comparison to FO-F1[1483.5 +/- 478.54 pg/ml] [P < 0.0001]. The sludy concluded that high serum levels of TGF-fl may be a mechanism by which immune response against IIBV is suppressed. The serum level of TGF- beta[1] is a potential noninvasive marker for diagnosis of liver fibrosis in CHB patients

Values of transforming growth factor beta-1, thrombopoietin and interleukin-6 in regulation of megakaryopoiesis in various platelets disorders

Megakaryopoiesis requires a highly complex series of cellular events in which a hematopoietic stem cell generates a cascade of committed progenitors and culminates with the production of circulating blood platelets. Megakaryopoiesis is regulated by several factors and cytokines that affect the proliferation and differentiation of megakaryopoietic cells. The aim of this study was to evaluate the role of some cytokines namely Thrombopoietin [TPO], Transforming growth factor [TGF-beta1] and lnterleukin 6 [IL-6] in regulation of megakaryopoiesis in various platelet disorders. This study was conducted on 72 patients with various platelet disorders; they were either thrombocytopenic [ITP "group I" or liver cirrhosis [LC] "group II" patients] or they presented with reactive thrombocytosis "group III". [According to modified Child classification group II patients was divided into three subgroups; Child A, Child B and Child C]. Twelve apparently healthy volunteers were included in the study for comparison. Estimations of serum TPO level, TGF-beta1 level and IL-6 level by ELISA technique were done for all studied groups. A highly significant increase in TPO and significant increase in IL-6 levels was noted in ITP group compared with the control group while TGF-beta1 was non significantly increased. In LC group and subgroups [Child A] a significant increase in TPO was noted on comparing with the control group but non significant increase in Child B and C; with progressive decrease of TPO level from Child A to Child B and Child C respectively. In LC group and Child C and B the TGF-beta1 was highly significantly increased on comparing with control group. Also it was significant increased in Child A when compared with control group i.e. there was progressive increase in TGF-beta1 with the progression of liver damage. A significant reduction in IL-6 was noted in LC group on comparing with the control group. A non significant reduction in IL-6 was noted in Child A, B and C group on comparing to the control group. In thrombocytosis group a significant increase in TPO, TGF-beta1 and IL-6 levels were noted compared to the control group. Estimation of serum TPO in ITP, liver cirrhosis and reactive thrombocytosis seems to be of benefit in diagnosis and evaluation of megakaryopoiesis state in these platelet disorders. Also estimation of TGF- beta1 can be used as good indicator of liver disease progress. TGF-beta1 was increased in thrombocytosis and this makes highlight to its role in feed back inhibition of megakaryopoiesis. Serum IL-6 was significantly increased in reactive thrombocytosis and this may confirm its role in stimulation of megakaryopoiesis

The Clinical Characteristics of Steroid Responsive Nephrotic Syndrome of Children according to the Serum Immunoglobulin E Levels and Cytokines

PURPOSE: The nephrotic syndrome (NS) is characterized by the favorable response to glucocorticoid therapy and the development of NS may be associated with dysfunctional immune systems. In order to investigate the serum immunoglobulin E (IgE) levels and cytokines activity in pediatric NS, the total of 32 steroid responsive NS patients and 5 healthy controls were enrolled in this study. MATERIALS AND METHODS: All patients were divided into two groups according to the initial serum IgE levels, such as normal and high IgE group, and their clinical characteristics were evaluated. In addition, serum levels of interleukin (IL)-4, IL-5, IL-10 and transforming growth factor (TGF)-beta were compared and correlated with serum albumin, proteinuria by means of disease severity, and cytokines. RESULTS: In the high IgE group, the higher comorbidity of allergic diseases and relapsing rate, the longer duration of steroid therapy before initial remission, and the higher serum IL-4 and IL-5 levels were found. In all patients, initially higher serum levels of IL-4 and IL-5 declined to normal levels after steroid therapy, whereas the serum IL-10 levels showed no significant difference between nephrotic phase (heavy proteinuria) and remission phase (no proteinuria) of NS. The serum TGF-beta levels of the nephrotic phase were significantly lower than those of remission phase or control group, and returned to normal control levels after steroid therapy. CONCLUSION: This study indicates that initial IgE level is associated with steroid responsiveness and disease severity, and cytokine activities may also be related to the pathogenesis of pediatric steroid responsive NS.

Experimental Murine Fascioliasis Derives Early Immune Suppression with Increased Levels of TGF-beta and IL-4

In fascioliasis, T-helper 2 (Th2) responses predominate, while little is known regarding early immune phenomenon. We herein analyzed early immunophenotype changes of BALB/c, C57BL/6, and C3H/He mice experimentally infected with 5 Fasciola hepatica metacercariae. A remarkable expansion of CD19+ B cells was observed as early as week 1 post-infection while CD4+/CD8+ T cells were down-regulated. Accumulation of Mac1+ cells with time after infection correlated well with splenomegaly of all mice strains tested. The expression of tumor necrosis factor (TNF)-alpha mRNA in splenocytes significantly decreased while that of IL-4 up-regulated. IL-1beta expression was down-modulated in BALB/c and C57BL/6 mice, but not in C3H/He. Serum levels of transforming growth factor (TGF)-beta were considerably elevated in all mice during 3 weeks of infection period. These collective results suggest that experimental murine fascioliasis might derive immune suppression with elevated levels of TGF-beta and IL-4 during the early stages of infection.

In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4+CD25+ T cells of patients with human T-lymphotropic virus type 1-associated myelopathy

HTLV-1 Tax expression exerts an inhibitory effect on the Foxp3 transcription factor in CD4+CD25+ T-regulatory cells (Treg). For a better understanding of the role of Tax mRNA in the gene expression of cellular markers we measured Tax, Foxp3, CTLA-4, GITR, TGF-β, and IL-10 mRNA in Treg cells of 50 patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP; 27 women and 23 men; mean age: 56.7 years). The control group consisted of 23 non-infected subjects (12 women and 11 men) with a mean age of 51.3 years. Real-time PCR was used to measure mRNA of Tax proteins and several cellular markers of Treg function. Determinations revealed a high level of Tax mRNA in HAM/TSP (124.35 copies/100 CD4+CD25+ T cells). Foxp3, GITR, and CTLA-4 mRNA levels were lower in HAM/TSP patients (mean ± SD, 22.07 ± 0.78, 9.63 ± 0.36, and 4.54 ± 0.39, respectively) than in non-infected controls (47.15 ± 12.94, 22.14 ± 1.91, and 21.07 ± 2.31). Both groups had similar levels of TGF-β and IL-10. An inverse relationship was found between Tax levels and Foxp3, CTLA-4, and GITR levels. Conversely, there was a direct correlation between levels of Foxp3, GITR, and CTLA-4. Disease severity and evolution time did not correlate with Tax or Foxp3 levels. The present results suggest that Tax and Foxp3 mRNA vary with the same degree of disease severity in HAM/TSP patients. Tax fluctuations may affect CTLA-4 and GITR expression via the Foxp3 pathway, causing virus-induced dysfunction of CD4+CD25+ T cells in HAM/TSP patients.

role of plasma transforming growth factor beta-1 in the development of fibrosis in patient with HCV related steatohepatitis

Hepatitis C virus [HCV] is a major public health problem worldwide, which causes high rate of chronic liver disease such as liver cirrhosis and hepatocellular carcinoma. Plasma transforming growth factor Beta-1 [TGFB-1] is a member of large family of peptides, which has a major regulatory role in hepatic fibrosis and cirrhosis. The study evaluated the role of transforming growth factor Beta-1 [TGFB-1] in induction of fibrosis in liver parasites-free HCV patients with related steatohepatitis. Thirty HCV patients who were clinically and serologically positive were selected. They were diagnosed as fatty liver by abdominal ultrasonography; steatohepatitis and confirmed by histopathological biopsies examination. ELISA evaluated plasma transforming growth factor Beta-1 [TGFB-1] level. Also, 12 cross-matched subjects clinically, parasitologically and serologically free were used as a controls. The level of plasma transforming growth factor Beta-1 [TGFB-1] was highly elevated in the patients versus controls with mean +/- SD 18739.86 +/- 18539.46 and 6465 +/- 1142 respectively [P < 0.001]. The TGFB-1 level in HCV related steato-hepatitis was elevated in all grades in contrast to controls [P < 0.05], without relation between the TGFB-1 levels and steatohepatitis severity. The TGFB-1 level showed high significant difference in all stages of fibrosis in patients in contrast to controls and the TGFB-1 level was very high when fibrosis started in stage I [P < 0.01] and tended to decrease in fibrosis of stage 2 and 3 [P < 0.05]. There was highly significant positive correlation between TGFB-1 and body mass index [BMI] r = 0.774

Lupus nephropathy: clinical, immunohistochemistry and quantitative morphometric analysis studies

Lupus nephritis includes a wide range of parenchymal injuries and severity. Better predictors to outcome are needed for patients newly diagnosed with lupus nephritis, so that an appropriate management strategy may be selected. This study aimed to determine whether the ratio of hepatocyte growth factor [HGF] to transforming growth factor beta 1 [TGF beta1] in lupus nephritis could be a prognostic factor for response to therapy with cyclophosphamide and steroids at six months. Also, to determine whether a simple automated system for objective scoring of biopsies of lupus nephritis could be a prognostic factor for response to therapy with cyclophosphamide and steroids at 6 months. Consequently, renal biopsy findings and clinical parameters of thirty parasites-free patients with new onset lupus nephritis were recorded. Histopathologic, clinical, immune-histochemical and morphometric data at baseline served to define the predictive value for outcome after 6 months of therapy. The results showed a significant positive relationship between response to therapy and HGF IS [P= 0.007], HGF ES [P= 0.026], HGF IS/ TGFbeta1 IS ratio [P= 0.022] and HGF ES/ TGFbeta1 ES ratio [P= 0.001]. A significant inverse relationship was proved between response to therapy and TGFbeta1 IS [P= 0.025] as well as TGFbeta1 ES [P= 0.017]. Also, a significant inverse relationship was present between response to therapy and nuclear index, tubular index and matrix index [P = 0.03, 0.03 and 0.029 respectively]

Host immune response to Toxoplasma gondii and Ascaris lumbricoides in a highly endemic area: evidence of parasite co-immunomodulation properties influencing the outcome of both infections

Toxoplasmosis and ascaridiasis evoke polar Th-1 and Th-2 host immune responses, respectively. A study to investigate the specific cytokine profile production by in vitro cultures of peripheral blood mononuclear cells from individuals living under precarious sanitary conditions in a highly endemic area for the parasites Toxoplasma gondii and Ascaris lumbricoides was conducted. High levels of both IFN-³ (Th-1) and IL-13 (Th-2) were observed in groups of co-infected individuals presenting toxoplasmic ocular lesions. Significantly lower IL-10 and TGF-² levels were produced by co-infected individuals in comparison with groups of individuals not infected with A. lumbricoides and either positive or negative for T. gondii living under good sanitary conditions (control groups). The possible influence of co-parasitism on the clinical presentation of ocular toxoplasmosis is discussed.

role of Thrombomodulin, IL-12, transforming growth factor-beta2 in early onset preeclamsia: a potential biomarker for disease severity

Early onset Preeclampsia is a pregnancy specific heterogeneous syndrome with genetic predisposition ranging from hypertension, proteinuria and edema to severe preeclampsia with complications. A defective implantation and placentation, circulating factors including proinflammatory molecules, cytokines and adhesion molecules have been implicated in the pathogenesis of preeclampsia. Was to assess the clinical value of assaying maternal serum concentration of thrombomodulin [TM] interleukin-12 [IL-12] and transforming growth factor beta-2 [TGF-beta 2], in normotensive, mild and severe preeclamptic pregnant women, and to evaluate the correlation between these factors and the blood pressure, uric acid and creatinine. The second objective was to look for differences between mild and severe early onset preeclampsia, compared with a healthy pregnant and non pregnant cross sectional investigated groups. Serum TM, IL-12 and TGF-beta 2 were measured using enzyme linked immunoassay [ELISA] and enzyme immunoassay respectively in 45 women with preeclampsia divided into 24 mild and 21 severe preeclamptic patients and compared with 21 pregnant normotensive and 20 non pregnant controls. Serum uric acid and creatinine were measured as well. Severe preeclamptic women had significantly increased levels of TM [p<0.01], IL-12 [p<0.01] and TGF-beta 2 p<0.01] compared with women with normal pregnancy and non pregnant women. Serum creatinine and uric acid co1Icentrations were significantly higher in severe preeclamptic patients [1.35 +/- 0.17mg/dL, 7.43 +/- 0.74mg/dL, respectively, mean +/- SD] and did not change significantly in mild preeclamptic women compared with those of healthy normotensive pregnant women. Significant positive correlations existed between serum TGF-beta 2 concentrations and mean arterial blood pressure, TM. serum creatinine and uric acid concentrations in severe pre peclamptic patients. Conclusion: Increase concentration of thrombomodulin, II-12 and TGF-beta 2, in severe preeclamptic patient might explain the shallow placentation, endothelial cell dysfunction and renal involvement described in severe preeclampsia. Measurement of maternal plasma of TM, IL-l2, TGF-beta 2 levels in preeclampsia can be useful biomarker for the assessment of the severity of the disease

Relationship between serum cytokines profiles and hepatic fibrosis in Schistosomiasis mansoni: an experimental study

Forty of eighty mice [10 each group] were infected with S. mansoni cercariae and sacrificed at 3 weeks [G-A], 6 weeks [G-B], 12 weeks [G-C] and 16 weeks [G-D] post infection [P.I]. The other forty mice were used as control groups of ten mice each. There were highly significant difference between egg counts after 12 weeks and 16 weeks of infection compared to 6 weeks P.I. The maximum egg count and mature eggs were in 6[th] week P.I while dead eggs reached the peak at 16[th] weeks P.I. Liver egg counts showed maximum followed by intestinal and then, stool egg counts. A highly significant differences in hydroxy-proline, TGF-Bland DL-4 of infected than in controls and their peak at 16 weeks P.I. A significant difference in the EFN-gamma in the infected than in controls with peak occurred at 6 weeks P.I. and declined after that reaching a low level at 16 weeks P.I. A highly significant positive correlation was between TGF-Bland IL4 and significant negative correlation between IFN- gamma and both IL4 and TGF-B1. A highly significant and significant negative correlation between TGF-B1 and egg count at 12 and 16 weeks P.I respectively. Negative correlation was between IL-4 and egg count at 16 weeks P.I. But, significant positive correlation was between IFN- gamma with the egg count at 16 weeks P.I. A significant negative correlation was between TGF-B1 and oogram at 6 and 16 weeks P.I, but highly significant positivity was between IFN- gamma and oogram at 16 weeks P.I. A significant negative correlation was between IL-4 and oogram at 16 weeks P.I. A significant positive correlation was between levels of hydroxyproline and TGF-B1 at 12 and 16 weeks P.I. Highly significant negative correlation between hydroxyproline and IFN- gamma was at 12 weeks P.I with significant and highly significant positive correlation between hydroxyproline and IL4 at 12 and 16 weeks-P.I

Citocinas e proteínas de fase aguda do soro como marcadores de regressão da resposta inflamatória ao tratamento da tuberculose pulmonar / Cytokines and acute phase serum proteins as markers of inflammatory regression during the treatment of pulmonary tuberculosis

OBJETIVO: Analisar o padrão de citocinas pró- e antiinflamatórias e da resposta de fase aguda (RFA) como marcadores de resposta ao tratamento da tuberculose pulmonar. MÉTODOS: Determinação dos níveis de interferon-gama (IFN-γ), tumor necrosis factor-alpha (TNF-α, fator de necrose tumoral-alfa), interleucina-10 (IL-10) e transforming growth factor-beta (TGF-β, fator transformador de crescimento-beta), pelo método ELISA, em sobrenadante de cultura de células mononucleares do sangue periférico e monócitos, assim como dos níveis de proteínas totais, albumina, globulinas, alfa-1-glicoproteína ácida (AGA), proteína C reativa (PCR) e velocidade de hemossedimentação (VHS) em 28 doentes com tuberculose pulmonar, em três tempos: antes (T0), aos três meses (T3) e aos seis meses (T6) de tratamento, em relação aos controles saudáveis, em um único tempo. RESULTADOS: Os pacientes apresentaram valores maiores de citocinas e RFA que os controles em T0, com diminuição em T3 e diminuição (TNF-α, IL-10, TGF-β, AGA e VHS) ou normalização (IFN-γ e PCR) em T6. CONCLUSÕES: PCR, AGA e VHS são possíveis marcadores para auxiliar no diagnóstico de tuberculose pulmonar e na indicação de tratamento de indivíduos com baciloscopia negativa; PCR (T0 > T3 > T6 = referência) pode também ser marcador de resposta ao tratamento. Antes do tratamento, o perfil Th0 (IFN-γ, IL-10, TNF-α e TGF-β), indutor de e protetor contra inflamação, prevaleceu nos pacientes; em T6, prevaleceu o perfil Th2 (IL-10, TNF-α e TGF-β), protetor contra efeito nocivo pró-inflamatório do TNF-α ainda presente. O comportamento do IFN-γ (T0 > T3 > T6 = controle) sugere sua utilização como marcador de resposta ao tratamento.

OBJECTIVE: To evaluate the pattern of pro-inflammatory cytokines, anti-inflammatory cytokines and the acute phase response (APR) as markers of the response to treatment of pulmonary tuberculosis. METHODS: Twenty-eight patients with pulmonary tuberculosis were evaluated at three time points: pretreatment (T0), treatment month 3 (T3) and treatment month 6 (T6). Levels of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukine-10 (IL-10) and transforming growth factor-beta (TGF-β) were determined using ELISA in the supernatant of peripheral blood mononuclear cell and monocyte culture. Levels of total protein, albumin, globulins, C-reactive protein (CRP), alpha-1-acid glycoprotein (AAG) and erythrocyte sedimentation rate (ESR) were also determined. All of these parameters were also evaluated, only once, in a group of healthy controls. RESULTS: In relation to controls, patients presented cytokine levels and APR that were higher at T0, lower at T3 and either lower (TNF-α, IL-10, TGF-β, AAG and ESR) or normal (IFN-γ and CRP) at T6. CONCLUSIONS: For individuals with negative smear sputum microscopy, CRP, AAG and ESR are potential markers of pulmonary tuberculosis and of the need for treatment; CRP (T0 > T3 > T6 = reference) can also be a marker of treatment response. In the patients, the Th0 profile (IFN-γ, IL-10, TNF-α and TGF-β), inducer of and protector against inflammation, predominated at T0, whereas the Th2 profile (IL-10, TNF-α and TGF-β), protecting against the harmful pro-inflammatory effect of the remaining TNF-α, predominated at T6. The behavior of IFN-γ (T0 > T3 > T6 = controls) suggests its use as a marker of treatment response.

Inflammation markers in healthy and periodontitis patients: a preliminary data screening

Advances in diagnostic research are moving towards methods whereby the periodontal risk can be identified and quantified by objective measures using biomarkers. Patients with periodontitis may have elevated circulating levels of specific inflammatory markers that can be correlated to the severity of the disease. The purpose of this study was to evaluate whether differences in the serum levels of inflammatory biomarkers are differentially expressed in healthy and periodontitis patients. Twenty-five patients (8 healthy patients and 17 chronic periodontitis patients) were enrolled in the study. A 15 mL blood sample was used for identification of the inflammatory markers, with a human inflammatory flow cytometry multiplex assay. Among 24 assessed cytokines, only 3 (RANTES, MIG and Eotaxin) were statistically different between groups (p<0.05). In conclusion, some of the selected markers of inflammation are differentially expressed in healthy and periodontitis patients. Cytokine profile analysis may be further explored to distinguish the periodontitis patients from the ones free of disease and also to be used as a measure of risk. The present data, however, are limited and larger sample size studies are required to validate the findings of the specific biomarkers.

Avanços no diagnóstico da doença periodontal levam a métodos nos quais o risco e atividade da doença periodontal podem ser identificados e quantificados por biomarcadores. Pacientes com periodontite podem apresentar elevados níveis circulatórios de marcadores inflamatórios específicos que podem ser correlacionados com a severidade da doença. Portanto, o objetivo desse estudo foi avaliar as diferenças nos níveis séricos de biomarcadores inflamatórios em pacientes saudáveis e com doença periodontal. Foram incluídos no estudo 25 pacientes (8 saudáveis e 17 com periodontite crônica). Uma amostra de 15 mL de sangue foi obtida para identificar os marcadores inflamatórios simultaneamente utilizando Array de proteínas através de citometria de fluxo. De 24 citocinas inflamatórias analisadas, apenas 3 (RANTES, MIG e Eotaxina) apresentaram diferenças estatisticamente significantes (p<0,05) entre os dois grupos. Conclui-se que alguns marcadores inflamatórios selecionados apresentam diferença de concentração em pacientes com periodontite e saudáveis. A análise do perfil de citocinas pode ser utilizada tanto para distinguir pacientes periodontais de pacientes saudáveis, como para medir o risco à doença. Contudo, mais estudos com número maior de amostras são necessários para validar os achados sobre os biomarcadores específicos.

Association of transforming growth factor-beta 1 [TGF-beta1] and monocyte chemoattractant protein-1 [MCP-1] with type II diabetic nephropathy

To estimate the levels of serum transforming growth factor-beta 1 [TGF-beta1], and urinary moncyte chemoattractant protin-1 [MCP-1] throughout the course of diabetic nephropathy [DN], and to find their possible relationship. Also, to assess the relationship between their levels and parameters of renal injury such as albumin/creatinine ratio [ACR] and estimated glomerular filtration rate [eGFR]. Serum TGF-beta1, urinary MCP-1, estimated glomerular filtration rate [eGFR] [as a parameter of renal injury] and glycosylated hemoglobin [HbA1C] [as an index of glycemic control] were measured in 60 patients with type II diabetes mellitus with different degrees of nephropathy [20 with normoalbuminuria, 20 with microalbuminuria and 20 with macroalbuminuria] and compared with 20 matched healthy control subjects. Both levels of serum TGF-beta1 and urinary MCP-1 were significantly higher in patients with micro- and macroalbuminuria [137.8 +/- 69.5 and 329.25 +/- 41.46 ng/dl, respectively for TGF-beta1] [167.41 +/- 50.23 and 630.87 +/- 318.10] ng/g creatinine, respectively for MCP-1] as compared with normoalbuminuric patients and healthy controls [33.25 +/- 17.5 and 29.64 +/- 10.57 ng/dl. respectively for TGF-beta1] [63.85 +/- 21.15 and 61.50 +/- 24.81] ng/g creatinine, respectively for MCP-1] p<0.001. There was a positive significant correlation between levels of serum TGF-beta1 and those of urinary MCP-1 [r=0.73, p<0.001]. Serum TGF-beta1 and urinary MCP-1 correlated positively with HbA 1C [r= 0.49 and 0.55, respectively, p<0.05 for both] and inversely with eGFR [r= -0.69 and -0.60, respectively, p<0.001 for both]. The progression of diabetic nephropathy may he associated with increased levels of serum TGF-beta1 and urinary MCP-1 that are closely- inked to renal damage and the degree of glycemic control. Thus, it seems possible that adequate glvcemic control and TGF-beta1 and MCP-1 antagonists might be helpful in attenuating the progression of nephropathy in diabetic patients

Transforming growth factor- beta 1 in patients with angiographically proven coronary heart disease

Transforming growth factor- beta 1 [TGF- beta 1] is a multifunctional cytokine that exhibits vasculoprotective properties. Production and plasma levels of TGF- beta 1 are influenced by polymorphisms in the TGF- beta 1 gene. A T-C transition at nucleotide 29 of the TGF- beta 1 gene results in a Leu-Pro substitution at amino acid 10 of the signal peptide. We investigated whether the T29-C polymorphism of TGF- beta 1 is associated with myocardial infarction among a sample of Egyptian coronary artery diseased males. The study population consisted of 90 patients with angiographically proven myocardial infarction and 30 control individuals without signs or symptoms of myocardial infarction. Polymorphism-related genotypes were determined with allele-specific PCR [polymerase chain reaction]. In this study; we found no differences between patients with MI and healthy subjects regarding the genotype and allele frequencies of codon 10 TGF- beta 1 polymorphism. Thus, our results indicate that this polymorphism does not appear to predispose to the development of MI. There was an agreement between genotypes observed and those predicted by the Hardy-Weinberg equilibrium in the control group [Codon 10, x[2] goodness of fit was not significant = 0.777, p; 0.87]. Negative association findings in this study did not exclude that TGF- beta 1 is a susceptibility locus for myocardial infarction, but further study on a larger scale is needed