Deepika Mahajan

CD4+CD25+ Regulatory T Cells Protect against Injury in an Innate Murine Model of Chronic Kidney Disease

Studies of mechanisms of disease regulation by CD4+CD25+ regulatory T cells (Treg) have been focused on their interaction with effector T cells; however, the possibility that regulation might involve noncognate cells has not been explored in detail. This study investigated the effect of CD4+CD25+ Treg on macrophage proinflammatory properties and phenotype in vitro and found that they modulate macrophages by inhibiting their activation, leading to reduced proinflammatory cytokine production and a downregulated effector phenotype. For testing the in vivo significance of this effect, CD4+CD25+ T cells that expressed high levels of Foxp3 were reconstituted into SCID mice after induction of Adriamycin nephropathy, a noncognate model of chronic renal disease. CD4+CD25+ T cells significantly reduced glomerular and interstitial injury. In addition, there was a significant fall in the number of macrophages in both the glomeruli and interstitium of SCID mice that were reconstituted with Treg as compared with the Adriamycin alone group. Blockade of TGF-beta using neutralizing antibodies significantly impaired the protective effect of Treg. These findings delineate a TGF-beta-dependent Treg-macrophage inhibitory interaction that can explain cognate-independent protection by Treg.

PARTIAL DEPLETION OF MACROPHAGES BY ED7 REDUCES RENAL INJURY IN ADRIAMYCIN NEPHROPATHY

Background:  Because macrophages are considered to be possible effectors of disease in Adriamycin (ADR) nephrosis, we hypothesized that depletion of macrophages might protect against the initiation of renal injury. In the present study, a monoclonal antibody (ED7) directed against CD11b/CD18 integrin, which is expressed by macrophages, was used to investigate the pathogenetic effects of macrophages in ADR nephropathy.

Regular non-vigorous physical activity and cholesterol levels in the elderly.

Background: High-density lipoprotein cholesterol (HDL-C) is a powerful independent risk factor for coronary heart disease (CHD) among the elderly. Regular vigorous physical activity has been found to raise the concentration of HDL-C and thus reduce the risk of CHD. There is little data on the effect of non-vigorous activity on HDL-C in the elderly. Objective: The aim of this study was to compare CHD risk factors, especially HDL-C, in a group of elderly persons who engage in regular non-vigorous physical activity with a group of frail elderly examined in a previous study. Methods: Each subject (51 women and 19 men) had anthropometric measures taken and completed a questionnaire on lifestyle and medical history. Total cholesterol (TC), HDL-C and lipoprotein (a) were analysed. Results were compared with those of a frail group examined previously using similar methodology. Results: HDL-C, adjusted for age, body mass index (BMI) and waist-to-hip ratio (WHR), was greater among women (p < 0.01) and men (p < 0.05) who were engaged in a regular physical activity at least once a week. TC was higher among active women (p < 0.001), but there was also a trend towards a lower TC/HDL ratio. Therefore, although TC is higher in active women, this could be due to a higher proportion of the cholesterol fraction consisting of HDL-C. WHR was negatively associated with HDL-C in frail men (p < 0.05), active men (p < 0.01) and active women (p < 0.05). BMI was negatively associated with HDL-C in frail women (p < 0.05). Conclusions: This sample of elderly people who participate in regular weekly non-vigorous physical activity have a higher HDL-C than frail individuals who do little or no exercise. Since HDL-C is consistently reported to be inversely associated with CHD in the elderly, an elevation in HDL-C concentration may provide some protection to elderly persons who participate in regular nonvigorous physical activity compared to frail elderly individuals who are largely sedentary. Caution should be exercised in the interpretation of a TC only reading in active elderly women without an accompanying measure of HDL.

NSW Annual Adverse Events Following Immunisation Report, 2009

AIM This is the first annual report for NSW of adverse events following immunisation. It summarises Australian passive surveillance data for adverse events following immunisation for NSW for 2009. METHODS Analysis of de-identified information on all adverse events following immunisation reported to the Therapeutic Goods Administration. RESULTS 450 adverse events following immunisation were reported for vaccines administered in 2009; this is 32% higher than 2008 and the highest since 2003. The increase was almost entirely attributed to the commencement of the pandemic (H1N1) 2009 influenza vaccine in September 2009. Only 6% of the reported adverse events were serious in nature and the most commonly reported reactions were allergic reaction, injection site reaction, fever and headache. CONCLUSION Reports of adverse events following immunisation in 2009 were dominated by the pandemic (H1N1) 2009 influenza vaccine. A large proportion of these adverse events were reported directly to the Therapeutic Goods Administration by members of the public. Reports were predominantly mild transient events, similar to those expected from the seasonal flu vaccine.

Lipoprotein (a) in an immigrant Indian population sample in Australia.

delivery within the oral cavity – investigation of lectin binding to oral mucosa. J Drug Target 1997; 5: 45-55. 15 Nicholls T.J, Green KL, Rogers DJ, Cook DJ, Smart JD. An investigation of lectin binding and retention within the precorneal region of the rat. In: Van Driessche E, Fischer J, Beeckmans S, Bog-Hansen TC, eds. Lectins: biology, biochemistry, clinical biochemistry. Vol 11. Hellerup: Textop, 1996: 311-5. 16 Nicholls TJ, Green KL, Rogers DJ, Cook DJ, Wolowacz S, Smart JD. Lectins in ocular drug delivery: an investigation of lectin binding sites on the corneal and conjunctival surfaces. Int J Pharm 1996; 138: 175-83. 17 Möckel B, Schwarz T, Zinke H, Eck J, Langer M, Lentzen H. Effects of mistletoe lectin I on human blood cell lines and peripheral blood cells. Drug Res 1997; 47: 1145-51. 18 Lorea P, Goldschmidt D, Darro F, Salmon I, Bovin N, Gabius H-J, Kiss R. Danguy A. In vitro characterisation of lectin-induced alterations on the proliferative activity of three human melanoma cell lines. Melanoma Res 1997; 7: 353-63. as >30 mg/dL – as an important independent risk factor for CHD. A meta-analysis of 27 studies shows a clear association between Lp(a) and CHD. Increased LDL-C, or increased Lp(a), increases the risk of CHD two-fold; but if the patient has both then the risk increases six-fold. Most studies show that Lp(a) is largely under genetic control and is resistant to dietary or lipid lowering intervention, other than treatment with niacin or hormone replacement therapy. Levels of Lp(a) range from <0.1 mg/dL to >100 mg/dL and are known to vary markedly with ethnicity. Only limited studies have been carried out on Lp(a) levels in people of Indian origin, and include Indian groups in Singapore, the USA and in India itself. The values obtained range from means of 8.7 mg/dL and 9.2 mg/dL in the USA and India, respectively, to 20.1 mg/dL in Singapore and 34.1 mg/dL for one small group in the USA. Clearly, the distribution of Lp(a) in Indian population groups needs further investigation. The aim of this study is to investigate the level and distribution of Lp(a) in an Indian immigrant population in Australia and to determine the stability of this Lp(a) after 12-months’ storage at -80 ̊C. The study sample consisted of 50 volunteers (25 men, 25 women; age range: 23-75 years) who had migrated to Australia from India over the past 20 years. Anthropometric measurements (weight, height, hip and waist circumference) were taken without shoes and over light clothing. Following overnight fasting, venous blood samples were collected into EDTA tubes and centrifuged at 1500 rpm for 10 min. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides were analysed on a Reflotron reflectance photometric analyser (Boehringer Mannheim, Germany) within 2 h of collection. LDL-C was estimated using the Friedewald formula. Immunoturbidimetric analyses of apoprotein A1 (apo A1) and apoprotein B (apo B) were carried out on plasma using a Turbitime system (Behring Diagnostics, Australia). Lp(a) was determined by a sandwich enzyme-linked immunosorbent assay (ELISA). Nunc-Immuno microplates (Nalge Nunc International, Denmark) were coated with 150 mL sheep anti-human Lp(a) antiserum (7.6 μg/mL; Immuno AG, Vienna) in phosphate-buffered saline (PBS; pH 7.4) overnight at room temperature (RT) with gentle shaking. Unbound antiserum was tipped out and the wells washed (x4) with PBS containing 5 g/L Tween 20. All the free sites were blocked by treating the wells with 200 μL 5 g/L bovine serum albumin (BSA) in PBS for 1 h. The wells were then washed as before and then incubated for 2 h with controls and plasma samples (100 μL) diluted 1 in 10 000 with dilution buffer (PBS containing 5 g/L Tween 20 and 5 g/L BSA) and the appropriate standards. After 2 h the wells were washed as before and 100 μL rabbit anti-human Lp(a) serum (Dade Behring, Germany), diluted 1 in 1250 with dilution buffer, was added. The plates were incubated for 2 h at RT and then washed (x4). To each well was added 100 μL diluted (1 in 5000) horseradish peroxidase (HRPO)conjugated goat anti-rabbit-IgG (Sigma-Aldrich, USA) and the plates were incubated for 2 h at RT. After washing as before, the reaction was developed by adding 100 μL substrate (0.4 mg/mL OPD [Sigma-Aldrich, USA] in 0.05 mol/L phosphate citrate buffer [pH 5.0] containing 0.03% sodium perborate [Sigma-Aldrich, USA]) per well. The reaction was allowed to proceed in the dark for 109

The seroepidemiology of pertussis in NSW: fluctuating immunity profiles related to changes in vaccination schedules

The pertussis epidemic experienced in NSW in 2008-2009 was likely to be in part due to changes in diagnostic practice since 2007, which amplified disease notifications. We used population-based seroepidemiology as a less biased means of interpreting age-specific pertussis infection patterns in NSW from three serosurveys undertaken in 1997-98 (during an epidemic), 2002 (post-epidemic) and 2007 (inter-epidemic), using a standardised pertussis toxin IgG enzyme-linked immunosorbent assay (ELISA). There was a decrease in the proportion of high anti-pertussis toxin IgG titres (>62.5ELISAUnits/mL) across all age groups in the 2007 serosurvey compared to the previous two serosurveys. In the 2007 serosurvey, the proportion of undetectable (<5ELISAUnits/mL) anti-pertussis toxin IgG titres increased in many age groups. The seroepidemiological profiles of the three serosurveys demonstrate fluctuating immunity profiles related to changes in vaccination schedules.

NSW Annual Report Describing Adverse Events Following Immunisation, 2010

AIM This report summarises Australian passive surveillance data for adverse events following immunisation in NSW for 2010. METHODS Analysis of de-identified information on all adverse events following immunisation reported to the Therapeutic Goods Administration. RESULTS 424 adverse events following immunisation were reported for vaccines administered in 2010; this is 6% lower than 2009 but 24% higher than 2008 and the second highest number since 2003. A total of 274 (65%) adverse events involved seasonal or pandemic influenza vaccines. Reports were predominantly of mild transient events: the most commonly reported reactions were fever, allergic reaction, injection site reaction, malaise and headache. Only 9% of the reported adverse events were serious in nature, including eight reports of febrile convulsions in children following seasonal influenza vaccine. CONCLUSION The large number of reports in 2010 is attributable to the high rates of fever and febrile convulsions in children after vaccination with 2010 seasonal trivalent influenza vaccine, as well as pandemic (H1N1) 2009 influenza vaccine.