Dissecting the complexity of the memory T cell response

Memory immune responses are classically attributed to the reactivation of long-lived, antigen-specific T lymphocytes that persist in a quiescent state. Determining mechanisms for the generation of memory T cells and dissecting the functional nature of the memory T cell pool has been encumbered by an inability to distinguish recently activated effector T cells from memory T cells. We have established new activation and biochemical criteria that distinguish effector and memory T cells and have applied these criteria to follow memory generation from activated cells in vivo. We found that the resultant memory T cell pool is heterogeneous and consists of effector-like and resting memory-like subsets that differ in expression of the homing receptor, CD62L. We discuss these findings in the context of memory T cell heterogeneity identified in human and mouse systems. These results suggest that more than one type of previously activated T cell can mediate recall or memory immune responses and that elucidating the fundamental phenotypic and functional features of memory T cell subsets is therefore critical to deciphering the complex nature of the memory immune response.     

Regulation of Th17 cells by P. UF1 against systemic Listeria monocytogenes infection

Regulation of Th17 and Th1 cell responses against intracellular pathogens, including Listeria monocytogenes (L. m), is critical to limit inflammation-induced tissue damage. We recently demonstrated the ability of P. UF1 bacterium derived from the intestinal bacterial commensals of preterm infants fed human breast milk to significantly mitigate pathogen-induced inflammation limiting colonic tissue damage. Here we further elucidated the potential of P. UF1 to also regulate innate and T cells, particularly Th17 and Th1 cells, against systemic L. m infection. Data demonstrate that P. UF1 not only robustly regulated protective Th17 and Th1 cells, but also sustained regulatory T cells (Treg cells) resulting in accelerated L. m clearance. Together, regulation of pathogenic inflammation by a novel probiotic bacterium such as P. UF1 may illuminate a new strategy to specifically control Th17-Th1 cells via IL-10⁺ Treg cells to limit systemic tissue damage induced by intracellular pathogens, including L. m.     

Comparing the effects of Calendula officinalis and clotrimazole on vaginal Candidiasis: A randomized controlled trial

This triple-blind trial examined the effects of Calendula officinalis vaginal cream on the treatment of vaginal Candidiasis (primary outcome) and sexual function (secondary outcome). Married women aged 18–45 years with vaginal Candidiasis (n = 150) were recruited from April to October 2014 and randomized into Calendula and clotrimazole groups, using 5-g vaginal cream every night for seven nights. Clinical and laboratory assessments were conducted at 10–15 and 30–35 days after intervention and the female sexual function index was assessed at 30–35 days. Six women were lost to follow-up. The frequency of testing negative for Candidiasis in the Calendula group was significantly lower at the first (49% vs. 74%; odds ratio (OR) 0.32; 95% confidence interval (CI) 0.16–0.67) but higher at the second (77% vs. 34%; OR 3.1; 95% CI 1.5–6.2) follow-up compared to the clotrimazole group. The frequency of most signs and symptoms were almost equal in the two groups at the first follow-up, but were significantly lower in the Calendula group at the second follow-up. Sexual function had almost equal significant improvement in both groups. Calendula vaginal cream appears to have been effective in the treatment of vaginal Candidiasis and to have a delayed but greater long-term effect compared to clotrimazole.     

Tropisetron ameliorates early diabetic nephropathy in streptozotocin‐induced diabetic rats

It has been well established that oxidative stress and inflammation are involved in the pathogenesis of diabetic nephropathy. It has been shown that tropisetron exerts anti‐inflammatory and immunomodulatory properties. The current study was designed to investigate protective effects of tropisetron on early diabetic nephropathy in streptozotocin‐induced diabetic rats. Rats were divided into six groups: (i) untreated diabetic (streptozotocin group); (ii) untreated control; (iii) diabetic rats treated with tropisetron (3 mg/kg); (iv) normal rats treated with tropisetron (3 mg/kg); (v) diabetic rats treated with granisetron (3 mg/kg); and (vi) normal rats treated with granisetron (3 mg/kg); rats began receiving treatment at the time of diabetes induction for 2 weeks. At the termination of the experiments, bodyweight, kidney index, urinary albumin excretion, and glomerular filtration rate were measured. The levels of oxidative stress markers and tumour necrosis factor‐α were also determined. Streptozotocin‐treated animals showed significant loss of bodyweight and renal enlargement and dysfunction. Diabetic rats also exhibited an increase in malondialdehyde along with a significant decrease in glutathione, superoxide dismutase activity, and catalase activity. Furthermore, the diabetic animals demonstrated a significant rise in renal cortical, urinary tumour necrosis factor‐α, and urinary albumin excretion. Both granisetron and tropisetron decreased blood glucose in diabetic animals, but this decrease was not significant for granisetron. Treatment with tropisetron, but not granisetron, prevented increases in oxidative stress and tumour necrosis factor‐α, decreased urinary cytokine excretion and albuminuria, and improved renal morphological damage. In conclusion, the present study suggests that tropisetron may be a protective agent in early diabetic nephropathy, and its action is mediated, at least in part, by anti‐oxidative and anti‐inflammatory mechanisms that appear to be independent of the 5‐HT₃ receptor.     

Osteoarticular complications of brucellosis in Hamedan, an endemic area in the west of Iran.

OBJECTIVE: To determine the frequency and clinical characteristics of osteoarticular complications of brucellosis in an endemic region in Iran. METHODS: In a prospective study we evaluated 245 patients with brucellosis diagnosed between January 2004 and December 2005. Patients included were those older than 8 years of age and who had clinical features suggestive of brucellosis and specific antibodies at significant titers, and/or positive blood or body fluid culture for Brucella species. A bone scan was performed in those with a clinical suspicion of osteoarticular involvement. RESULTS: Seventy patients (28.6%) had osteoarticular complications. Sacroiliitis was the most common complication (75.7%), followed by spondylitis (21.4%) and peripheral arthritis (8.6%). Spondylitis was the most common osteoarticular complication in the elderly. Relapses occurred in five (2%) patients, three of them with spondylitis. CONCLUSIONS: Osteoarticular disease is the most common complication of brucellosis in Western Iran. Sacroiliitis is the most common form of osteoarticular complication. With the use of a proper treatment regimen, the prospect for recovery is good.     

Acute complications of movement disorders surgery: Effects of age and comorbidities

The most common indication for movement disorder surgery is Parkinson's disease (PD), and the incidence of PD increases with age. The analysis reported here was undertaken with the primary goal of examining whether there is a relationship between peri‐operative complications and age. The Nationwide Inpatient Sample (Agency for Healthcare Research and Quality, Rockville, MD, USA) was queried for 10 years beginning in 1999 for patients undergoing deep brain stimulator insertion, pallidotomy, and thalamotomy for treatment of PD, essential tremor, and dystonia. Inpatient complications, including death, stroke (both ischemic and hemorrhagic), and other overall complications were examined. The relative risks associated with advanced age; primary diagnosis; treatment modality; the diagnoses of hypertension, diabetes, and nicotinism; and the cumulative number of comorbidities were examined. There were 5464 patients who met inclusion criteria, including 4145 patients treated for PD and 4961 patients treated with deep brain stimulation (DBS). Overall in‐hospital mortality was 0.26%, with 0.15% related to surgical factors. There was a correlation between in‐hospital mortality, increasing age, and number of medical comorbidities. After multivariate regression no factor remained predictive of mortality. Having more than 1 medical comorbidity or PD increased the risk of in‐hospital complications. Patients with PD were more likely to suffer hemorrhage or stroke. Hypertension, diabetes, nicotinism, and modality of treatment were not associated with increased mortality, hemorrhage or stroke risk, or in‐hospital mortality in univariate or multivariate analysis. Both age and medical comorbidity are correlated with in‐hospital complications, but age appears to serve as a surrogate for comorbidity. Surgery for PD appears to carry an increased risk of hemorrhage or stroke and in‐hospital complications. © 2013 International Parkinson and Movement Disorder Society