Effect on growth performance, carcass traits, and myostatin gene expression in Aseel chicken fed varied levels of dietary protein in isocaloric energy diets.

A study was conducted to assess the effect of feeding different crude protein (CP) levels with isocaloric metabolizable energy (ME) diets on growth performance, carcass traits, and myostatin (MSTN) gene expression of Aseel chicken during 0 to 16 weeks of age. A total of two hundred and ten day-old Aseel chickens were randomly allotted to seven dietary treatment groups. Each group had thirty chicks distributed into three replicates of ten chicks in each. Experimental diets were formulated to have varying levels of CP, viz. 18.5, 19.0, 19.5, 20.0, 20.5, 21.0, and 21.5%, with isocaloric energy of 2800 kcal ME/kg diets of mash feed fed to birds in a completely randomized design. Different CP levels had a significant effect (P < 0.05) on the body weight gain (BWG) of Aseel chicken. At the end of 16 weeks of age, the group fed 21% CP gained 223.53 g more than the lowest CP (18.5%)-fed group. The different CP levels did not significantly (P > 0.05) influenced the feed intake of all treatment groups, but numerically highest feed intake was observed in the lowest CP (18.5%)-fed group. However, significant differences in feed efficiency (FE) appeared from the 13th week only with the 21.0% CP-fed group showing the best FE until the 16th week (3.86 to 4.06). The maximum dressing % (70.61) was observed by the 21% CP-fed group. The CP 21% diet down-regulated the MSTN gene expression in breast muscle tissue to 0.07 folds when compared to the diet of CP 20%. The best economical coordinates for maximum performance for Aseel chicken appeared to be CP of 21% and ME of 2800 kcal/kg to achieve the best FE of 3.86 at the earliest age of 13 weeks. In conclusion, 21% CP in an isocaloric diet of 2800 kcal ME/kg, in Aseel chickens, would be optimum to improve the growth performance at maximum in terms of BWG and FE up to 16 weeks of age.

CCL2, CCL3 and CCL4 gene polymorphisms in pulmonary tuberculosis patients of South India.

Polymorphisms in chemokine genes are important to determine the host-pathogen interactions which influence the chemokine levels. This study was carried out to find whether various CC chemokine gene polymorphisms, located in the promoter, exon-2 and intron-1 regions are associated with susceptibility or resistance to pulmonary tuberculosis (PTB) in south Indian population. The polymorphisms in various CC chemokine genes, MCP-1 (CCL2) [-2518A/G, 903C/T], MIP-1α (CCL3) [-2021C/T, +740A/G] and MIP-1ß (CCL4) [-5725A/C] were studied in 295 healthy controls (HCs) and 303 patients with PTB using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). The allele and genotype frequencies of CCL2, CCL3 and CCL4 were not different between HCs and patients with PTB. However, a significantly decreased frequency of CCL2 -2518GG genotype was observed in male patients with PTB [P value = 0.015, P corrected (Bonferroni correction) Pc = 0.045, odds ratio (OR) 0.43 95% CI (0.21-0.86)], and a significantly increased frequency of the same genotype was observed among female patients with PTB [P value = 0.049, Pc = 0.147, OR 2.28 95% CI (1.00-5.27)]. The results suggest that -2518GG genotype may be associated with protection in males and susceptibility to PTB in females. Moreover, we also observed differences in the haplotype frequencies of these chemokine genes between HCs and patients with PTB. However, these polymorphisms are not associated with disease independently, probably in combination with other genes, they may be associated with susceptibility or resistance to TB in south Indian population.

µ-(2,6-Bis{[3-(di-methyl-amino)-prop-yl]imino-meth-yl}-4-methyl-phenolato)-µ-hydroxido-bis-[(thio-cyanato-κN)copper(II)].

In the title compound, [Cu2(C19H31N4O)(OH)(NCS)2], the mol-ecular structure of the dinuclear complex reveals two penta-coordinated Cu(II) ions, which are bridged by the phenolate O atom of the ligand and by an exogenous hydroxide ion. The bridging atoms occupy equatorial positions in the coordination sphere of the metal atoms and complete the equatorial coordination planes with two ligand N atoms, the apical positions being occupied by thio-cyanate N atoms. The crystal structure also features π-π stacking inter-actions involving the benzene rings with a centroid-centroid distance of 3.764 (4)Å. The crystal studied was a non-merohedral twin, with a refined BASF value of 0.203 (2).

Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice.

Therapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human Fcγ receptor-Ig fusion molecules (FcγR-Igs) in mice by administering FcγR-Ig plasmid DNAs hydrodynamically and compared their effectiveness with purified molecules in blocking immune-complex (IC)-mediated inflammation in mice. The concentration of hydrodynamically expressed FcγR-Igs (CD16A(F)-Ig, CD32A(R)-Ig and CD32A(H)-Ig) reached a maximum of 130 µg ml(-1) of blood within 24 h after plasmid DNA administration. The in vivo half-life of FcγR-Igs was found to be 9-16 days and western blot analysis showed that the FcγR-Igs were expressed as a homodimer. The hydrodynamically expressed FcγR-Igs blocked 50-80% of IC-mediated inflammation up to 3 days in a reverse passive Arthus reaction model. Comparative analysis with purified molecules showed that hydrodynamically expressed FcγR-Igs are more efficient than purified molecules in blocking IC-mediated inflammation and had a higher half-life. In summary, these results suggest that the administration of a plasmid vector with the FcγR-Ig gene can be used to study the consequences of blocking IC binding to FcγRs during the development of inflammatory diseases. This approach may have potential therapeutic value in treating IC-mediated inflammatory autoimmune diseases such as lupus, arthritis and autoimmune vasculitis.

Effect of vitamin D3 on chemokine expression in pulmonary tuberculosis.

1,25 Dihydroxy vitamin D(3) (vitamin D(3)) is an immunomodulator and its deficiency has been associated with susceptibility to tuberculosis. We have studied the immunoregulatory role of vitamin D(3) on various chemokine expression in pulmonary tuberculosis. Peripheral blood mononuclear cells obtained from 21 pulmonary tuberculosis (PTB) patients and 24 healthy controls (HCs) were cultured for 48 h with culture filtrate antigen (CFA) of Mycobacterium tuberculosis with or without vitamin D(3) at a concentration 1 × 10(-7)M. The relative mRNA expression of monocyte chemoattractant protein-1 (MCP-1, CCL2), macrophage inflammatory protein-1α (MIP-1α, CCL3), macrophage inflammatory protein-1ß (MIP-1ß, CCL4), and regulated upon-activation, normal T cell-expressed and secreted (RANTES, CCL5) and IFN-γ inducible protein-10 (IP-10, CXCL10) chemokines were estimated from 48 h old macrophages using real-time polymerase chain reaction (RT-PCR). The culture supernatants were used to estimate the various chemokines including monokine induced by IFN-γ (MIG, CXCL9) levels using cytometric bead array. In HCs, vitamin D(3) significantly suppressed the MCP-1 mRNA expression of CFA stimulated cells (p=0.0027), while no such effect was observed in PTB patients. Vitamin D(3) showed no significant effect on MIP-1α, MIP-1ß and RANTES in both the study groups. The CFA induced IP-10 mRNA and protein expression was significantly suppressed by vitamin D(3) in both the study groups (p<0.05). A similar suppressive effect of vitamin D(3) was observed with MIG protein in healthy controls (p=0.0029) and a trend towards a suppression was observed in PTB patients. The suppressive effect of vitamin D(3) is more prominent in CXC chemokines rather than CC chemokines. This suggests that vitamin D(3) may down regulate the recruitment and activation of T-cells through CXC chemokines at the site of infection and may act as a potential anti-inflammatory agent.

Stromal cell-derived factor-1 (SDF-1/CXCL12) gene polymorphisms in pulmonary tuberculosis patients of south India.

CXCL12 gene polymorphisms influence CXCL12 levels and may be associated with the outcome of host-pathogen interaction. Hence, the present study was carried out to find out whether CXCL12 gene polymorphisms are associated with susceptibility or resistance to pulmonary tuberculosis (PTB). Intron and 3' untranslated region (UTR) polymorphisms of CXCL12 gene were investigated among 184 patients with PTB and 187 healthy controls (HC) using polymerase chain reaction-based methods. The results revealed an increased frequency of G/A genotype of In2 +5887 [P = 0.034; odds ratio (OR) 1.66; 95% confidence intervals 1.04-2.66] and a decreased frequency of G/A genotype of 3'UTR +12197 polymorphisms (P = 0.051; OR 0.64; 95% CI 0.4-1.00) among patients than HCs. When the study subjects were categorized based on sex, significantly increased frequencies of G/A genotype (P = 0.013 P(c) = 0.039; OR 2.41) of In2 +5887 and G/G genotype (P = 0.005, P(c) = 0.015; OR 2.48) of 3'UTR +12197 polymorphisms were observed among female patients with PTB as compared to female HC. A significantly decreased frequency of the haplotype G-C-A-T (P = 0.006, P(c) = 0.030; OR 0.48) was noticed among female patients with PTB as compared to female HC. The study suggests that G/A genotype of In2 +5887 and G/G genotype of 3'UTR +12197 polymorphisms may be associated with susceptibility to PTB among females, and the haplotype G-C-A-T of CXCL12 gene may be associated with protection in females.

Synthesis of polydentate, multi metal ion sensing, unsymmetrical Schiff bases with complimented antifungal activity.

Polydentate, unsymmetrical, and multi metal ion sensing Schiff bases comprised of ferrocenecarboxaldehyde attached azomethine group at one side and aromatic aldehyde linked imine on the other side have been synthesized. Cumulative addition of different metal salts solution to receptors solution, changes the electronic spectra contrarily and for the addition of Cu2+ ions, generation of MLCT charge transfer band responsible for the coordination of metal ion with a receptor is observed. Electrochemical data (ΔEp) arrived from the cyclic voltammograms suggest a quasi-reversible process. The modest concentration of metal ions required for effective sensing by the sensory material is calculated from the Ipa values observed for metal ion added and metal free sensor solutions. Inhibition zones noticed in in vitro analysis for two fungi, two gram positive and two gram negative bacterial stains interpret that the new compounds possess high antifungal activity. Binding energy calculation using molecular docking software also ascertains the antifungal bustle.

Rare survival of high-tension electrocution shock in a crossbred Jersey cattle: a complete profile on critical care monitoring.

Background: Accidental electrocution was more common in animals and death was mostly due to shock and cardiac arrest. Survival of animals or humans could be possible if victims receive immediate medical support. Case description: A 3-year-old crossbred Jersey heifer was presented to the Emergency and Critical Care Medicine Referral Clinic of the Veterinary College and Research Institute, Orathanadu, with a history of accidental electrocution by broken high-tension overhead power transmission line during grazing in the paddy fields. The animal was dull and depressed, dark red, and some areas were charred in appearance on the dorsum and limbs. The animal showed difficulty walking due to the electrocution burn injury and was poorly responding to the surroundings. Clinical examination revealed subnormal temperature, polypnea, pale mucous membranes, ruminal atony, and arrhythmias on auscultation. Findings/treatment and outcome: On point of care (PoC) hematology testing, leukocytosis, neutrophilia, and microcytosis were observed. PoC electrolyte analysis revealed hypocalcemia (ionized calcium 0.89 mmol/L), mild hypochloremia, and severe hypokalemia (2.81 mmol/L). PoC biochemistry revealed hypoglycemia (41 mg/dl). PoC elevated levels of serum cardiac troponin (0.33 ng/dl) indicated cardiac damage. Aspartate aminotransferase (1794 U/L), CK-MB (699 U/L) and LDH (6.7 U/L) were also elevated. On PoC urinalysis, proteinuria, myoglobinuria, and glucosuria were observed. Evident clinical recovery, wound healing, and improvement in animal activities were observed. Conclusion: High-voltage electrocution injury is a serious type of accident with the potential risk of multi-organ damage and death. Early diagnosis of electrocution and immediate management enhances the expectancy of complete recovery.

CCL5 (RANTES) gene polymorphisms in pulmonary tuberculosis patients of south India.

The chemokine CCL5 is known to play an important role in the formation of granuloma during infection with Mycobacterium tuberculosis. Production of CCL5 is influenced by polymorphisms in the CCL5 gene. Hence, in the present study, we investigated whether polymorphisms in the promoter and intron regions of CCL5 gene are associated with susceptibility or resistance to pulmonary tuberculosis in south Indian population. Polymorphisms in the promoter (-403G/A and -28C/G) and intron (In1.1T/C) regions of CCL5 gene were studied in 212 pulmonary tuberculosis (PTB) patients and 213 healthy controls (HCs). Allele and genotype frequencies of CCL5 gene polymorphisms were not different between PTB patients and HCs. When the haplotype and diplotype frequencies were compared, a significantly decreased frequencies of the haplotype A-C-C [P = 0.037; Odds ratio (OR): 0.57; 95% confidence interval (CI): 0.34-0.97] and the diplotype G/A-T/C (P = 0.017; OR: 0.46; 95% CI: 0.24-0.88) were observed among PTB patients when compared with HCs. However, the significant differences observed for the haplotype and the diplotype were lost when corrected for multiple comparisons [Bonferroni correction: A-C-C P corrected (P(c) ) = 0.148 and G/A-T/C P(c) = 0.136]. Though the present results suggest that the CCL5 gene haplotype A-C-C and the diplotype G/A-T/C may be associated with resistance to PTB, further studies with increased sample size may be useful to confirm this present finding as well as to understand the role of CCL5 haplotype and diplotype on genetic susceptibility to TB.

Dynamic data processing system for sports training system using internet of things.

BACKGROUND: The Internet of Things (IoT) has recently become a prevalent technological culture in the sports training system. Although numerous technologies have grown in the sports training system domain, IoT plays a substantial role in its optimized health data processing framework for athletes during workouts. OBJECTIVE: In this paper, a Dynamic data processing system (DDPS) has been suggested with IoT assistance to explore the conventional design architecture for sports training tracking. METHOD: To track and estimate sportspersons physical activity in day-to-day living, a new paradigm has been combined with wearable IoT devices for efficient data processing during physical workouts. Uninterrupted observation and review of different sportspersons condition and operations by DDPS helps to assess the sensed data to analyze the sportspersons health condition. Additionally, Deep Neural Network (DNN) has been presented to extract important sports activity features. RESULTS: The numerical results show that the suggested DDPS method enhances the accuracy of 94.3%, an efficiency ratio of 98.2, less delay of 24.6%, error range 28.8%, and energy utilization of 31.2% compared to other existing methods.

Equivalent-input-disturbance estimator-based event-triggered control design for master-slave neural networks.

This paper investigates the robust synchronization problem for a class of master-slave neural networks (MSNNs) subject to network-induced delays, unknown time-varying uncertainty, and exogenous disturbances. An equivalent-input-disturbance (EID) estimation technique is applied to compensate for the effects of unknown uncertainty and disturbances in the system output. In addition, to reduce the burden of the communication channel in the addressed MSNNs and improve the utilization of bandwidth an event-triggered control protocol is developed to obtain the synchronization of MSNNs. In particular, event-triggering conditions are verified periodically at every sampling instant in both sensors and actuators to avoid the Zeno behavior in the networks. By designing an appropriate low-pass filter in the EID estimator block, the accuracy of disturbance estimation performance is improved. Moreover, by concatenating the synchronization error, observer, and filter states as a single state vector, an augmented system is formulated. Then the tangible delay-dependent stability condition for that augmented system is established by employing the Lyapunov stability theory and reciprocally convex approach. Based on the feasible solutions of the derived stability conditions, the event-triggering parameters, controller, and observer gains are co-designed. Finally, two toy examples are given to illustrate the established theoretical findings.

Rosetting of activated human T lymphocytes with autologous erythrocytes. Definition of the receptor and ligand molecules as CD2 and lymphocyte function-associated antigen 3 (LFA-3).

CD2, also known as LFA-2, T11, and the E rosette receptor, is a T lymphocyte surface protein functionally important in adhesion to target cells and T cell triggering. LFA-3 is a widely distributed cell surface protein that functions in adhesion on target cells. We find that LFA-3 is expressed on human E, and that CD2 is a receptor for LFA-3 that mediates T cell adhesion to human E. Pretreatment of T lymphocytes with CD2 mAb or of E with LFA-3 mAb inhibits rosetting. Purified CD2 molecules bind to human E and inhibit rosetting. 125I-CD2 binding to E is inhibited by LFA-3 mAb; reciprocally, binding of LFA-3 mAb to human E is inhibited by pretreatment with purified CD2. Higher concentrations of CD2 aggregate human E; aggregation is inhibited by mAb to LFA-3.

Deficiency of lymphocyte function-associated antigen 3 (LFA-3) in paroxysmal nocturnal hemoglobinuria. Functional correlates and evidence for a phosphatidylinositol membrane anchor.

Lymphocyte function-associated antigen 3 (LFA-3) is a widely distributed cell surface glycoprotein that binds to the T lymphocyte CD2 surface glycoprotein. This interaction mediates CTL-target cell conjugate formation and adhesion of thymocytes to thymic epithelial cells. CD2 is also the E rosette receptor of T lymphocytes and mediates rosetting with autologous E by binding to LFA-3. We describe deficient expression of LFA-3 on E from paroxysmal nocturnal hemoglobinuria (PNH) patients. PNH is an acquired defect affecting phosphatidylinositol-anchored membrane proteins, of which decay-accelerating factor (DAF) is most important in the clinical symptoms of PNH. LFA-3-negative, weakly positive, and positive populations were found among PNH E. There was a good correlation with DAF deficiency. PNH E exhibited decreased binding of 125I-CD2 and rosetting with a human T lymphoma cell line. PNH E readily incorporated purified LFA-3, restoring LFA-3 expression and the CD2 binding and rosetting activity to normal levels. The expression of DAF was not restored after the incorporation of purified LFA-3 into PNH E, showing that LFA-3 and DAF are different molecules. Phosphatidylinositol-specific phospholipase C (PIPLC) treatment of a B lymphoma cell line released 35% of the cell surface LFA-3 and 62% of DAF. LFA-3 on E was resistant to PIPLC. However, when LFA-3 purified from human E was reconstituted in sheep E or human E and subjected to PIPLC treatment, 40-50% of LFA-3 was released from the cell membrane. The results show that LFA-3 is attached to the cell membrane by a phosphatidylinositol glycolipid moiety, and confirm previous findings (37-41) that LFA-3 is a cell adhesion molecule that mediates adhesion by interacting with CD2 antigen.

Interferon gamma gene +874A/T polymorphism and intracellular interferon gamma expression in pulmonary tuberculosis.

We investigated whether IFN-gamma gene +874(A/T) polymorphism influences intracellular interferon gamma expression in T-cell subsets of normal healthy subjects (NHS) and pulmonary tuberculosis patients (PTB). Peripheral blood mononuclear cells were stimulated with live Mycobacterium tuberculosis (MTB) and the intracellular IFN-gamma expression was studied using flow cytometry. Genotyping of IFN-gamma gene +874(A/T) was done using allele specific polymerase chain reaction. Significantly increased IFN-gamma expressing CD3+CD4+ and CD3+CD8+ T cells were observed in NHS with AA genotype compared to TT genotype in unstimulated (p=0.0308 and p=0.0157) and MTB stimulated (p=0.0494 and p=0.0287) cultures and this difference was not observed in PTB patients. The present study suggests that the variant genotypes of IFN-gamma (+874) may be associated with altered expression of IFN-gamma at the intracellular level and play an immunoregulatory role at the site of M. tuberculosis infection.

Effect of jaggery on the quality and intake levels of maize silage.

Silage, which is anaerobically fermented green fodder, is valued throughout the world as a source of animal feed during lean months. Several farms in India use carbohydrate sources like jaggery or molasses at 2% for preparation of silage, and this increases cost of production. The present study was undertaken to assess the effect of jaggery on quality and intake of maize silage, with an objective to find out whether additional carbohydrate source is essential in preparation of silage using green maize. Three silage types, one without jaggery (A), the second with 1% jaggery (B), and the third with 2% jaggery (C) were prepared in cylindrical bins under similar conditions. They were compared for colour, pH, lactic acid bacteria count, lactic acid content, proximate composition and silage intake by sheep. Silage type C with 2% jaggery was significantly different from the other two types with values of 3.98 and 805.66 g for pH and mean silage intake, respectively. Even though the values of pH and dry matter intake for all three silage types were within normal levels, silage type C was significantly superior in terms of fermentation and palatability. The method of preparation followed could be ideal for small holder farmers requiring less quantity of silage.

Effect of 1, 25 dihydroxyvitamin D(3) on matrix metalloproteinases MMP-7, MMP-9 and the inhibitor TIMP-1 in pulmonary tuberculosis.

Matrix metalloproteinases (MMPs) play a vital role in the pathogenesis of several inflammatory diseases including tuberculosis through tissue remodeling. 1, 25(OH)(2)D(3) has several well recognized biological functions including suppression of MMP production. The influence of 1, 25(OH)(2)D(3) on MMP-7, MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1), production was studied in 43 pulmonary tuberculosis (PTB) patients and 44 healthy controls (HC). Peripheral blood mononuclear cells (PBMCs) were cultured with culture filtrate antigen (CFA) of Mycobacterium tuberculosis (MTB) and live MTB with or without 1, 25(OH)(2)D(3) (10(-7) M) for 48 h and the culture supernatants were assayed for MMP-7, MMP-9, TIMP-1 and cytokines IFN-gamma and TNF-alpha using ELISA. In HC and PTB, the levels of MMP-7, MMP-9 and TIMP-1 were not altered by CFA and live MTB stimulation in both groups. However, a significant decrease in the spontaneous production of MMP-7 (p=0.007), and an increase in MMP-9 (p=0.07) and TIMP-1 (p=0.0001) were observed in PTB patients as compared to HC. Vitamin D(3) significantly reduced the MMP-7 (p=0.0001) and MMP-9 (p=0.0001) and increased the TIMP-1 (p=0.005) level in antigen stimulated and unstimulated cultures of PTB as compared to HC. A significant positive correlation between MMP-9 and IFN-gamma was observed in unstimulated cultures of both HC (p=0.05) and PTB patients (p=0.0007). The present study suggests that 1, 25(OH)(2)D(3) suppresses the production of MMPs and enhances the level of TIMP-1 in tuberculosis. The present study suggests that 1, 25(OH)(2)D(3) may probably play an important role in the pathological process in tuberculosis by downregulating the levels of MMPs and upregulating the levels of TIMPs.

Plasma 1,25 dihydroxy vitamin D3 level and expression of vitamin d receptor and cathelicidin in pulmonary tuberculosis.

INTRODUCTION: Vitamin D(3), which exerts its effect through vitamin D receptor (VDR), is known for its potent immunomodulatory activities. Associations between low serum vitamin D(3) levels and increased risk of tuberculosis have been reported. STUDY SUBJECTS AND METHODS: Plasma 1,25 dihydroxy vitamin D(3) levels (1,25(OH)(2) D(3)) and ex vivo levels of VDR protein from peripheral blood mononuclear cells were studied in 65 pulmonary tuberculosis (PTB) patients and 60 normal healthy subjects (NHS) using enzyme-linked immunosorbent assay-based methods. Using real-time polymerase chain reaction (PCR), induction of VDR, cathelicidin, and CYP27B1 mRNA were studied in live Mycobacterium tuberculosis-stimulated macrophage cultures treated with or without 1,25 dihydroxy vitamin D(3). VDR and CYP27B1 (-1077 A/T) gene polymorphisms were studied using PCR-based methods. RESULTS: 1,25(OH)(2) D(3) were significantly increased (p = 0.0004), while ex vivo levels of VDR protein were significantly decreased in PTB patients (p = 0.017) as compared to NHS. 1,25(OH)(2) D(3) levels were not different between variant genotypes of CYP27B1. A trend towards decreased levels of VDR protein was observed among NHS with BsmI BB and TaqI tt genotypes compared to NHS with other genotypes. Relative quantification of mRNA using real-time PCR revealed increased VDR mRNA expression in live M. tuberculosis-stimulated culture in PTB patients (p < 0.01) than normal healthy subjects. Cathelicidin mRNA expression was significantly increased in vitamin D(3)-treated cultures compared to unstimulated and M. tuberculosis-stimulated culture in both patients (p < 0.001) and NHS (p < 0.05). CONCLUSIONS: The present study suggests that PTB patients may have increased 1,25(OH)(2) D(3) levels, and this might lead to downregulation of VDR expression. Decreased VDR levels could result in defective VDR signaling. Moreover, addition of 1,25(OH)(2) D(3) might lead to increased expression of cathelicidin which could enhance the immunity against tuberculosis.

5' regulatory and 3' untranslated region polymorphisms of vitamin D receptor gene in south Indian HIV and HIV-TB patients.

INTRODUCTION: Vitamin D receptor (VDR) gene polymorphisms in the 5' regulatory region (Cdx2 and A-1012G), coding region (FokI), and 3' untranslated region (UTR; BsmI, ApaI, and TaqI) were studied to find out whether these polymorphisms are associated with susceptibility to or protection against HIV-1 and development of tuberculosis (TB) in human immunodeficiency virus (HIV)-1-infected patients. STUDY SUBJECTS AND METHODS: The study was carried out in 131 HIV patients without TB (HIV+ TB-) and 113 HIV patients with TB (HIV+ TB+; includes 82 patients with pulmonary TB (HIV+ PTB+) and 31 with extra pulmonary TB), 108 HIV-negative pulmonary TB patients (HIV- PTB+), and 146 healthy controls. RESULTS: Among the 5' regulatory and coding region polymorphisms, significantly increased frequency of G/A genotype of Cdx-2 was observed in HIV+ TB- group compared to controls (p = 0.012, odds ratio (OR) 1.89 95% confidence interval (CI) 1.14-3.15). In the 3' UTR genotypes, a decreased frequency of b/b genotype of BsmI in total HIV patients (p = 0.014, OR 0.54 95% CI 0.32-0.89) and increased frequencies of A/A genotype of ApaI in HIV+ TB+ patients (p = 0.041, OR 1.77 95% CI 1.02-3.06) and t/t genotype of TaqI in HIV+ PTB+ patients (p = 0.05, OR 2.32 95% CI 0.99-5.46) were observed compared to controls. Haplotype analysis revealed significantly increased frequencies of 3' UTR haplotype B-A-t in HIV+ TB+ and HIV+ PTB+ groups (Pc = 0.030, OR 1.75 95% CI 1.14-2.66) and decreased frequencies of b-A-T haplotype in total HIV patients (Pc = 0.012, OR 0.46 95% CI 0.27-0.77), HIV+ TB- (p = 0.031 OR 0.48 95% CI 0.25-0.89), and HIV+ PTB+ groups (Pc = 0.04, OR 0.47 95% CI 0.23-0.89) compared to controls. CONCLUSIONS: The results suggest that VDR gene 3' UTR haplotype b-A-T may be associated with protection against HIV infection while B-A-t haplotype might be associated with susceptibility to development of TB in HIV-1-infected patients.

Neuroprotection in stroke by complement inhibition and immunoglobulin therapy.

Activation of the complement system occurs in a variety of neuroinflammatory diseases and neurodegenerative processes of the CNS. Studies in the last decade have demonstrated that essentially all of the activation components and receptors of the complement system are produced by astrocytes, microglia, and neurons. There is also rapidly growing evidence to indicate an active role of the complement system in cerebral ischemic injury. In addition to direct cell damage, regional cerebral ischemia and reperfusion (I/R) induces an inflammatory response involving complement activation and generation of active fragments, such as C3a and C5a anaphylatoxins, C3b, C4b, and iC3b. The use of specific inhibitors to block complement activation or their mediators such as C5a, can reduce local tissue injury after I/R. Consistent with therapeutic approaches that have been successful in models of autoimmune disorders, many of the same complement inhibition strategies are proving effective in animal models of cerebral I/R injury. One new form of therapy, which is less specific in its targeting of complement than monodrug administration, is the use of immunoglobulins. Intravenous immunoglobulin (IVIG) has the potential to inhibit multiple components of inflammation, including complement fragments, pro-inflammatory cytokine production and leukocyte cell adhesion. Thus, IVIG may directly protect neurons, reduce activation of intrinsic inflammatory cells (microglia) and inhibit transendothelial infiltration of leukocytes into the brain parenchyma following an ischemic stroke. The striking neuroprotective actions of IVIG in animal models of ischemic stroke suggest a potential therapeutic potential that merits consideration for clinical trials in stroke patients.

Effect of 1,25 dihydroxyvitamin D3 on intracellular IFN-gamma and TNF-alpha positive T cell subsets in pulmonary tuberculosis.

We studied the immunomodulatory effect of 1,25(OH)(2)D(3) on single cell expression of IFN-gamma and TNF-alpha cytokines in T cell subsets of pulmonary tuberculosis (PTB) patients (n=22) and normal healthy subjects (n=22). Peripheral blood mononuclear cells (PBMCs) were cultured with live Mycobacterium tuberculosis (MTB) with or without 1,25(OH)(2)D(3) (10(-7)M) for 48 h. T cell subsets positive for IFN-gamma and TNF-alpha were enumerated by flow cytometry and the culture supernatants were assayed for both the cytokines using ELISA. In both NHS and PTB patients, a significantly reduced percentage of IFN-gamma and TNF-alpha expressing CD3+, CD3+CD4+ and CD3+CD8+ T cells were observed in cultures stimulated with live MTB and treated with 1,25(OH)(2)D(3) compared to cultures without 1,25(OH)(2)D(3) (NHS; CD3+ IFN-gamma+: p<0.0001; CD3+TNF-alpha+: p=0.0292 and PTB; CD3+ IFN-gamma+: p=0.0292; CD3+ TNF-alpha+: p=0.0028). The levels of IFN-gamma and TNF-alpha in the culture supernatants of 1,25(OH)(2)D(3) treated cultures were also found to be significantly decreased in both groups (NHS; IFN-gamma: p=0.0001; TNF-alpha: p<0.0001) and (PTB; IFN-gamma: p<0.0001; TNF-alpha: p<0.0001). A positive correlation was observed between IFN-gamma and TNF-alpha expressing CD3+CD8+ T cells in MTB stimulated cultures treated with or without 1,25(OH)(2)D(3) in NHS (p=0.0001; p=0.001, respectively) and PTB patients (p=0.002; p=0.005, respectively). The present study revealed the suppressive effect of 1,25(OH)(2)D(3) on single cell expression of IFN-gamma and TNF-alpha by CD3+CD4+ and CD3+CD8+ T cells in pulmonary tuberculosis. This suppressive effect of 1,25(OH)(2)D(3) on proinflammatory and Th1 cytokine positive cells might have a role in reducing inflammation at the site of infection.