Renal regulation of extracellular fluid volume and osmolality.

In order for our body cells to function properly, they must be surrounded in extracellular fluid that is relatively constant with regard to osmolality. The kidneys, in concert with neural and endocrine input, regulate the volume and osmolality of the extracellular fluid by altering the amount of sodium and water excreted. This is accomplished primarily through alterations in sodium and water reabsorption, the mechanisms of which differ within each nephron segment.     

HLA typing data on 100 type 1 (insulin-dependent) diabetic patients from central Italy show a negative association with DR5 rather than with DR2

HLA typing of 100 Type 1 diabetic patients from the Rome area confirmed the strong association with DR3 and DR4 and the prevalence of DR3/4 heterozygotes. However, DR5 rather than DR2 showed a significantly negative association.     

Detection of free hepatitis C virus core antigen by enzyme-linked immunosorbent assay is not suitable for screening of granulocyte colony-stimulating factor-mobilized hematopoietic progenitor donors

BACKGROUND: Recent studies have shown that hepatitis C virus (HCV) can be detected in peripheral blood mononuclear cells of patients who are negative for the presence of anti-HCV and serum HCV RNA. The aim of the study was to evaluate the prevalence of HCV viremia in granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood progenitor cell (PBPC) donors by the use of a free HCV core antigen enzyme-linked immunosorbent assay (ELISA). STUDY DESIGN AND METHODS: A total of 28 samples from consecutive PBPC donors that were mobilized with G-CSF, and 13 samples from patients presenting with leukocytosis of greater than 20 x 10(9) per L from other causes, were tested by a free HCV core antigen ELISA. Positive samples were confirmed by use of neutralization assays. The specificity of the assay was studied in 48,911 healthy blood donors negative for the presence of anti-HCV. RESULTS: The free HCV core antigen assay showed a 46.4 percent positivity in PBPC donors mobilized with G-CSF and 61.5 percent in patients exhibiting leukocytosis in the absence of G-CSF treatment. All the samples were found to be false-positive samples, and those related with growth factor treatment did not react when G-CSF was discontinued. Overall specificity by the test in freshly collected blood donor specimens was 99.62 percent. CONCLUSION: Data indicate that the free HCV core antigen ELISA is not a valid test in diagnosing HCV infection in G-CSF-treated PBPC donors. Moreover, false-positive results of this test on blood donors might be indicative of elevated white blood cell numbers. The low specificity of this assay in the PBPC mobilization setting suggests that molecular assays should be the test of choice in the screening of G-CSF-treated donors.     

A new iron(III) complex-containing sulfadiazine inhibits the proliferation and induces cystogenesis of Toxoplasma gondii

Parasitology Research - We have previously shown that metallocomplexes can control the growth of Toxoplasma gondii, the agent that causes toxoplasmosis. In order to develop new metallodrugs to...     

Sphingosine synergistically stimulates tumor necrosis factor alpha- induced prostaglandin E2 production in human fibroblasts

Sphingosine is a biologically active derivative of sphingomyelin. It affects diverse cellular functions and its mechanism(s) of action is poorly defined. Tumor necrosis factor alpha (TNF alpha) has recently been shown to rapidly induce sphingomyelin turnover, implicating this metabolic pathway in TNF alpha signal transduction. Because TNF alpha is known to induce prostaglandin E2 (PGE2) production in human fibroblasts, we tested the effect of sphingosine on TNF alpha-induced PGE2 production. We found that sphingosine enhanced TNF alpha-induced PGE2 production by as much as 18-fold over TNF alpha alone. Sphingosine appeared to stimulate TNF alpha-induced PGE2 production independent of TNF alpha-mediated interleukin 1 (IL-1) production, because anti-IL-1 antibodies and IL-1 receptor antagonist protein (IRAP) did not inhibit TNF alpha-induced PGE2 production or the stimulatory effect of sphingosine. TNF alpha stimulated PGE2 production to the same degree in normal and protein kinase C (PKC) downregulated cells in the presence and absence of sphingosine, indicating that neither TNF alpha nor sphingosine require active PKC to elicit their respective effects. The sphingosine analogues stearylamine and stearoyl-D-sphingosine had little or no effect on TNF alpha-mediated PGE2 production, supporting a specific role for sphingosine in the activation process. Short-term (1 min) exposure of cells to sphingosine dramatically increased TNF alpha-induced PGE2 production. A potential mechanism by which sphingosine could increase TNF alpha-induced PGE2 production involves enhancement of phospholipase A2 (PLA2) and/or cyclooxygenase (Cox) activity, the rate-limiting enzymes in PGE2 production. We found that both TNF alpha and sphingosine alone enhanced these enzymatic activities, and that sphingosine additively increased the effect of TNF alpha on phospholipase A2 activity. It appears that sphingosine affects TNF alpha-induced PGE2 production via a mechanism that is independent of PKC involvement, and that sphingosine may function as an endogenous second messenger capable of modulating the responsiveness of the cell to external stimuli.     

Distribution of slow‐cycling cells in epiphyseal cartilage and requirement of β‐catenin signaling for their maintenance in growth plate

Slow proliferation is one of the characteristics of stem cells. We examined the presence, distribution, and regulation of slow‐cycling cells in the developing and growing skeleton using a pulse‐chase method with a new nucleoside derivative, 5‐ethynyl‐2′‐deoxyuridine (EdU). C57BL/6 mice received daily intraperitoneal injections of EdU from postnatal day 4 to day 7. One day after the last EdU injection, a large population of cells in articular cartilage and growth plate was labeled. Six weeks after the last injection, the number of EdU‐labeled cells dramatically decreased, but a small number of them were dominantly present in the articular surface, and the labeling index was significantly higher in the surface than that in the rest of articular cartilage. In the growth plate, most EdU‐positive cells were found in the top layer that lies immediately below the secondary ossification center. Interestingly, postnatal conditional ablation of β‐catenin in cartilage caused a complete loss of the EdU‐labeled cells in growth plate that displayed disorganization and dysfunction. Together, our data demonstrate that slow‐cycling cells do reside in specific locations and numbers in both articular cartilage and growth plate. The β‐catenin signaling pathway appears to play a previously unsuspected role in maintenance of the slow‐cycling cells. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:661–668, 2014.     

Does immobilization position after arthroscopic rotator cuff repair impact work quality or comfort?

Purpose

The purpose of this study was to quantify subjective discomfort and decrease in working performance in patients submitted to arthroscopic rotator cuff repair.

Methods

We enrolled 101 asymptomatic administrative employees (mean age 55). Subjects were asked to write a text using Microsoft Word and to make a table using Microsoft Excel, with and without shoulder braces which kept the right shoulder in neutral (brace A) and internal rotation (brace B). Total time needed to complete the tests and number of mistakes committed were annotated. Furthermore, a questionnaire to assess the subjective and interpersonal discomfort caused by the braces was compiled. Data were submitted to statistical analysis.

Results

When any brace is worn, both times and mistakes are higher than those registered without brace (p < 0.02). Both times and mistakes are higher for brace B in comparison with brace A (p < 0.02). Subjects wearing brace B had a severe/very severe discomfort degree three times higher than that registered in subjects wearing brace A. Finally, 91 % of subjects preferred brace A to brace B.

Discussion

If the choice of the brace is not supported by biological or clinical advantages, we recommend to use the brace that keeps the arm at the side, since it ensures better working performance and lower discomfort. It also received the greatest satisfaction of the respondents.

Level of evidence

IV.

     

Hemophilic Chronic Synovitis: Therapy of Hemarthrosis using Endovascular Embolization of Knee and Elbow Arteries

Purpose

Congenital hemophilia is a hereditary bleeding disorder that affects 1 in 5,000 males and is characterized by repetitive musculoskeletal bleeding episodes. Selective embolization of the knee and elbow arteries can prevent bleeding episodes. To evaluate the long-term efficacy of these procedures, we assessed the outcomes of 30 procedures performed in our center.

Methods

We performed 30 procedures in 27 hemophilic patients, including 23 knee, and 7 elbow procedures. To evaluate the efficacy of selective embolization of knee and elbow arteries in people with hemophilia, we analyzed the number of bleeding episodes during 12 months before the procedure compared with the amount of episodes that occurred 3, 6, and 12 months after embolization.

Results

Twenty-nine of 30 procedures were classified as successful. The median of 1.25 episodes per month (range 0–3) observed before the procedure was reduced to 0 (range 0–1.67; p < 0.001) at 3 months, 0.17 (range 0–1.67; p < 0.001) at 6 months, and 0.33 (range 0–1.67; p = 0.024) at 12 months. Three patients remained free of bleeding events for more than 6 months. Additionally, after the procedure there was a significant reduction in factor FVIII usage that sustained up to 12 months after the procedures. No serious adverse events were observed.

Conclusions

Selective angiographic embolization of knee and elbow arteries is a feasible procedure that can prevent repetitive bleedings, which would translate in better joint outcomes for these patients.