Serum IL-2 and platelet-associated immunoglobulins are good prognostic markers in immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is an acquired disease in which autoantibodies to platelets cause their sequestration and destruction by mononuclear macrophages, principally in the spleen. While most children with the disease experience a relatively short and benign clinical course, ITP in adults often lasts more than 6 months (chronic ITP) and is resistant to conventional treatment (corticosteroids, intravenous immunoglobulin, or splenectomy). This work was done to study the immunological difference between acute and chronic ITP, the effect of treatment on the studied immunological parameters, and to evaluate the role of prednisone therapy in chronic ITP. The study included 49 patients, twenty-three children with acute ITP, and twenty-six with chronic ITP. After taking the history, clinical examination was performed for all patients and control subjects. Laboratory investigations included complete blood count, bone marrow aspirate examination (patients), direct and indirect Coombs' test, antinuclear antibodies, lymphocyte phenotyping, cytokine (IL-2, IFN-gamma, and IL-6) measurement, and platelet antibodies by immunofluorescence. Results showed that acute ITP is more prevalent in preschool children and its relapse is lower when steroids are used for treatment. Platelet counts were significantly elevated in both acute and chronic ITP, especially with good response to steroids. Also, CD4 and CD4/CD8 were significantly reduced in chronic ITP with good response to therapy. Both IL-2 and IFN-gamma were significantly increased in chronic ITP when compared to acute ITP or control. Platelet associated IgM was detected more in acute than in chronic ITP, while IgG was equally detectable in both cases. This work shows that IL-2 is a good prognostic factor in chronic ITP and steroids are important for its treatment. It also shows that platelet associated IgG is a good monitoring parameter for response to treatment.     

Endothelin ETA receptor/lipid peroxides/COX-2/TGF-β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats

Background and Purpose

Cyclosporine (CSA) and non-steroidal anti-inflammatory drugs (NSAIDs) are co-prescribed for some arthritic conditions. We tested the hypothesis that this combined regimen elicits exaggerated nephrotoxicity in rats via the up-regulation of endothelin (ET) receptor signalling.

Experimental Approach

The effects of a 10 day treatment with CSA (20 mg·kg⁻¹·day⁻¹), indomethacin (5 mg·kg⁻¹·day⁻¹) or their combination on renal biochemical, inflammatory, oxidative and structural profiles were assessed. The roles of ET_A receptor and COX-2 pathways in the interaction were evaluated.

Key Results

Oral treatment with CSA or indomethacin elevated serum urea and creatinine, caused renal tubular atrophy and interstitial fibrosis, increased renal TGF-β1, and reduced immunohistochemical expressions of ET_A receptors and COX-2. CSA, but not indomethacin, increased renal ET-1, the lipid peroxidation product malondialdehyde (MDA) and GSH activity. Compared with individual treatments, simultaneous CSA/indomethacin exposure caused: (i) greater elevations in serum creatinine and renal MDA; (ii) loss of the compensatory increase in GSH; (iii) renal infiltration of inflammatory cells and worsening of fibrotic and necrotic profiles; and (iv) increased renal ET-1 and decreased ET_A receptor and COX-2 expressions. Blockade of ET_A receptors by atrasentan ameliorated the biochemical, structural, inflammatory and oxidative abnormalities caused by the CSA/indomethacin regimen. Furthermore, atrasentan partly reversed the CSA/indomethacin-evoked reductions in the expression of ET_A receptor and COX-2 protein.

Conclusions and Implications

The exaggerated oxidative insult and associated dysregulation of the ET_A receptor/COX-2/TGF-β1 signalling might account for the aggravated nephrotoxicity caused by the CSA/indomethacin regimen. The potential renoprotective effect of ET_A receptor antagonism might be exploited therapeutically.Tables of Links

Efficacy of ombitasvir/paritaprevir/ritonavir/ribavirin in management of HCV genotype 4 and end-stage kidney disease

Background

Till now, pooled data about the safety and efficacy of different direct-acting antiviral (DAAs) regimens in different renal situations are still under evaluation.

Focal and segmental glomerulosclerosis in murine models: a histological and ultrastructural characterization with immunohistochemistry correlation of glomerular CD44 and WT1 expression

Aim: Focal segmental glomerulosclerosis (FSGS) is a common progressive chronic renal disease. Podocyte injury and loss are the postulated pivotal events that trigger FSGS. In this study, the authors aim to examine the evolution of FSGS in murine models histologically, ultrastructurally and immunohistochemically with special emphasis on podocytes and parietal epithelial cells (PECs). Material and methods: FSGS resembling primary FSGS in humans was initiated in Wistar rats using intravenous Adriamycin injections. Blood and urine analysis were performed at 0, 8, and 12 weeks. Both the control kidneys and the test kidneys were harvested at 8 and 12 weeks, examined histologically and ultrastructurally and the findings correlated with the glomerular expression of immunostains specific for podocytes (WT-1) and for activated PECs (CD44). Results: FSGS developed in both 8 and 12 weeks test groups showing progressive proteinuria, podocytopathy and segmental glomerular scarring. There was a decrease in the glomerular expression of WT-1 with a concurrent increase in the glomerular expression of CD44, indicating podocyte loss with synchronous increase in activated PECs. The evolving FSGS correlated negatively with podocytes and positively with activated PECs. Conclusion: Our study shows that with podocyte injury there is podocyte effacement and loss, proteinuria, glomerular segmental adhesion and scarring, all culminating in FSGS. In addition, there is activation, hyperplasia and hypertrophy of PECs. This demonstrates that both podocyte loss and PEC activation promote FSGS. Our findings are consistent with recent investigations. More studies are required to further understand the role of these cells in the evolution of FSGS and subsequently introduce new targeted treatment modalities.     

β-Lactamase Production in Key Gram-Negative Pathogen Isolates from the Arabian Peninsula

SUMMARY

Infections due to Gram-negative bacilli (GNB) are a leading cause of morbidity and mortality worldwide. The extent of antibiotic resistance in GNB in countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Oman, and Bahrain, has not been previously reviewed. These countries share a high prevalence of extended-spectrum-β-lactamase (ESBL)- and carbapenemase-producing GNB, most of which are associated with nosocomial infections. Well-known and widespread β-lactamases genes (such as those for CTX-M-15, OXA-48, and NDM-1) have found their way into isolates from the GCC states. However, less common and unique enzymes have also been identified. These include PER-7, GES-11, and PME-1. Several potential risk factors unique to the GCC states may have contributed to the emergence and spread of β-lactamases, including the unnecessary use of antibiotics and the large population of migrant workers, particularly from the Indian subcontinent. It is clear that active surveillance of antimicrobial resistance in the GCC states is urgently needed to address regional interventions that can contain the antimicrobial resistance issue.     

Morphometric study of foramina transversaria in Jordanian population using cross-sectional computed tomography

Anatomical Science International - Foramina transversaria are bilateral landmarks of human cervical vertebrae. Morphometric analysis of foramina transversaria is valuable in both clinical and...