Comparison of urinary proteins in calcium stone formers and healthy individuals: a case-control study

OBJECTIVE: This study aimed at comparing the urinary protein levels in calcium stone formers with those of healthy individuals. PATIENTS AND METHODS: From January 2002 until June 2004, 100 calcium stone formers (mean age 38.6 +/- 10.3 years), who had at least two episodes of calcium stone formation, were compared with 100 healthy individuals (mean age 33.8 +/- 9.7 years). Their 24-hour urinary protein levels, using SDS-PAGE, were measured. RESULTS: The mean 24-hour urinary Tamm-Horsfall protein (THP) levels were 3.3 +/- 0.8 mg in the case group and 4.6 +/- 1.9 mg in the controls, and the difference was not statistically significant (p = 0.53). However, the THP levels in individuals with and without bacteriuria were significantly different (15.8 +/- 3.3 mg vs. 2.6 +/- 1.0 mg, p = 0.0001). The mean 24-hour urinary albumin concentrations were 163.31 +/- 15.1 mg in the case group and 74.26 +/- 4.6 mg in the controls. The mean 24-hour urinary transferrin levels were 8.09 +/- 2.7 mg in the case group and 0.40 +/- 0.3 mg in the controls. The differences were statistically significant for both albumin and transferrin (p < 0.0001 and p = 0.0063, respectively). There were no significant differences in any other mean urinary protein concentrations between cases and controls. CONCLUSIONS: The THP level in the urine of stone formers is not quantitatively different from that of healthy individuals, but it increases in association with bacteriuria. Albumin and transferrin may play a presumptive role in stone formation.     

Effect of conjugated linoleic acids,vitamin E and their combination on the clinical outcome of Iranian adults with active rheumatoid arthritis

Background: Despite beneficial effects of conjugated linoleic acids (CLAs) in animal studies, there is little information on their effects on human inflammatory and autoimmune diseases. Aim: To investigate the effects of CLAs as an adjuvant therapy on the clinical manifestations of rheumatoid arthritis (RA) in adults with an active disease. Methods: In a randomized, double‐blind placebo‐controlled trial, 87 patients with active RA were divided into four groups receiving one of the following daily supplements for 3 months: group C: CLAs 2.5 g equivalent to 2 g mixture of cis 9‐trans 11 and trans 10‐cis12 CLAs at a rate of 50/50; group E: vitamin E: 400 mg; group CE: CLAs and vitamin E at above doses; group P: placebo. Serum α‐tocopherol was determined by high‐performance liquid chromatography. Clinical data was determined by physician examination and filling the questionnaire by interview. Complete blood count (CBC), erythrocyte sedimentation rate (ESR), C‐Reactive protein (CRP) and rheumatoid factor (RF) were measured in each patient. DAS28 (diseases activity score) was also determined. Results: A 3‐month supplementation resulted significant reduction in DAS28, pain and morning stiffness in the groups C and CE compared with group P (P < 0.05). Compared with the baseline, ESR levels decreased significantly in the groups C (P ≤ 0.05), E (P ≤ 0.05) and CE (P ≤ 0.001). Group CE had significantly lower ESR levels than group P (P ≤ 0.05). CRP dropped non‐significantly in all four groups (P > 0.1). The reduction of white blood cell count was significant in group CE compared with other groups (P < 0.05). Decrease in platelet count was non‐significant in groups CE, C, and E. Changes in RF, body mass index, red blood cell count and hemoglobin were not significant in four groups, while RF decreased non‐significantly in groups CE and E. In comparison with the baseline, α‐tocopherol increased significantly in groups C (P ≤ 0.05), E (P ≤ 0.01) and CE (P ≤ 0.001) and in groups E and CE compared with group P. Conclusion: CLA supplementation resulted in significant improvement in clinical manifestation among RA patients and may be useful in their treatments.     

Dendritic cells bearing HLA-G inhibit T-Cell activation in type 1 diabetes

HLA-G is normally expressed on human trophoblast cells. It is a non-classical MHC molecule class I b. The role of HLA-G in diabetic type 1 is not known. We investigated the role of IFN-beta in induction HLA-G expression on the monocyte derived dendritic cells (DC) in diabetes type 1. Treatment of dendritic cell with IFN-beta in vitro from diabetic patients (n=20) and normal subjects (n=20) resulted to the production and expression of HLA-G on these cells from both groups. However, comparison of DC from the diabetic patients with DC from the controls revealed lower levels of HLA-G molecules in DC from diabetic patients. Using mixed lymphocyte reaction (MLR), it was found that DC expressing HLA-G mediated the inhibition of autologous T cell activation. It is concluded that IFN-beta can increase HLA-G in DC from diabetic patients; subsequently it may prevent the immune regularly pathway in the diabetic pathogenesis.     

2-Deoxy-d-ribose-induced oxidative stress causes apoptosis in human monocytic cells: Prevention by pyridoxal-5′-phosphate

Hyperglycemia-induced oxidative stress plays a crucial role in the pathogenesis of diabetic complications. Although some clinical evidences suggest the use of pyridoxal-5'-phosphate (PLP) in diabetes with nephropathy, the exact mechanism of PLP has not been fully understood. In the present study, the effect of PLP on 2-deoxy-D-ribose (dRib)-induced oxidative damages and apoptosis on human monocytic cells (U937) was investigated. U937 cells exposed to dRib (30 mM) exhibited abnormal properties, including loss pf cell viability, overproduction of reactive oxygen species (ROS), glutathione depletion and some biochemical features of apoptosis. Treatment with PLP at two effective concentrations (100 and 250 microM) strongly inhibited ROS production and glutathione depletion in dRib-treated U937 cells. The extent of Lipid peroxidation and protein oxidation was also decreased in the presence of PLP. In addition, PLP suppressed dRib-induced apoptotic criteria such as sub-G1 apoptotic population and annexin-V staining. The use of N-acetylcysteine (NAC), a thiol antioxidant and GSH precursor, prevented the extent of apoptosis. The results demonstrate that dRib induces the generation of ROS leading to dRib-mediated apoptosis which can be attenuated by PLP through antioxidant mechanisms.     

HLA class II allele and haplotype frequencies in iranian patients with acute myelogenous leukemia and control group

Previous studies have demonstrated some significant differences in HLA allele frequencies in leukemic patients and normal subjects. We have analyzed HLA class II alleles and haplotypes in 60 Iranian patients with acute myelogenous leukemia (AML) and 180 unrelated normal subjects. Blood samples were collected after obtaining informed consents. From the patients and control DNA extraction and HLA typing were performed using PCR-SSP method. Significant positive association with the disease was found for HLA-DRB1*11 allele (35% vs. 24.7%, p=0.033). Two alleles including HLA-DRB4 and -DQB1*0303 were found to be significantly decreased in patients compared to controls. Regarding haplotype analysis, no significant association was found between case and control groups. It is suggested that HLA-DRB1*11 allele plays as a presumptive predisposing factor while the HLA-DRB4 and -DQB1*0303 alleles are suggested as protective genetic factors against acute myelogenous leukemia. Larger studies are needed to confirm and establish the role of these associations with acute myelogenous leukemia.     

CCR7+ Central and CCR7− Effector Memory CD4+ T Cells in Human Cutaneous Leishmaniasis

Purpose

The profile of central (=T_CM) and effector (=T_EM) memory CD4⁺ T cell subsets and the possible role as surrogate markers of protection is studied in the volunteers with history of cutaneous leishmaniasis (HCL).

Methods

Profile of T cell subsets based on CCR7/CD45RA expressions and phenotypic changes after soluble Leishmania antigen (SLA) stimulation were analyzed. Then, sorted CD4⁺CD45RO^?CD45RA⁺ naïve T, CD4⁺CD45RO⁺CD45RA^?CCR7^? T_EM, CD4⁺CD45RO⁺CD45RA^?CCR7⁺ T_CM subsets were cultured with SLA for proliferation, cytokine production and intracellular cytokine assays.

Results

In the HCL and control volunteers, the mean frequencies of CD4⁺CD45RA⁺CCR7⁺ naïve T cells and CD4⁺CD45RA^?CCR7^? T_EM cells were higher than the other subsets before culture. Frequency of naïve T cells and CD4⁺CD45RA^?CCR7⁺ T_CM cells was significantly decreased (P?=?0.01 for naïve T and P?<?0.05 for T_CM cells) and frequency of T_EM cells was significantly increased after SLA stimulation compared to before culture (P?<?0.001). By CFSE labeling, CD4⁺CD45RO⁺CD45RA^?CCR7⁺ T_CM cells showed more proliferation potential than CD4⁺CD45RO⁺CD45RA^?CCR7^? T_EM cells. Stimulation of the T_EM cells in HCL volunteers induced a significantly higher IFN-γ production (P?=?0.04) with higher number of intracellular IFN-γ positive cells (P?=?0.032) than the same cells from controls. A significantly higher number of T_CM cells produced IL-2 in HCL volunteers compared with controls (P?<?0.05). Most of the intracellular IFN-γ positive T_EM cells were proliferating CFSE-dim populations (P?<?0.05).

Conclusions

A combination of Leishmania-reactive IFN-γ producing CD4⁺CD45RO⁺CD45RA^?CCR7^? T_EM and Leishmania-reactive IL-2 producing CD4⁺CD45RO⁺CD45RA^?CCR7⁺ T_CM are identified in individuals with history of CL which might play a role in protective recall immune response against Leishmania infection.