Representative study for the evaluation of age- and gender-specific anthropometric parameters and blood pressure in an adolescent Hungarian population

BACKGROUNDS/AIMS: To assess the age- and gender-specific anthropometric parameters and blood pressure in Hungarian adolescents. METHODS: A cross-sectional study was performed between 1997 and 2000. Altogether 6,345 secondary school students (aged 15-18 years) were involved in the study. The representative sampling sites were selected randomly. In the capital city 3-stage and in the counties 4-stage stratified groups were assigned for the studies. Statistical analysis was performed using SPSS for Windows 9.0. RESULTS: The age- and gender-specific percentile distributions are given with regard to body weight, body height, body mass index (BMI), waist circumference, waist-to-hip ratio and arterial blood pressure values. Elevated blood pressure values were found at the first recording in 14.1% of the boys and in 2.5% of the girls. Since it is well known that the arterial blood pressure (ABP) may exhibit considerable intra- individual fluctuation with time, we therefore categorized normotensive and hypertensive students on the basis of the mean ABP values calculated from data obtained during the course of the three separate consecutive measurement periods at least 2 weeks apart. After that, the incidence of high blood pressure was 7.5% in boys and 1.1% in girls. CONCLUSION: The age- and gender-specific cutoff values thus formed may serve as reference values to assess the risk of developing nutrition-related noninfectious diseases in the future on the basis of the present percentile distribution of BMI. The present study also provides data on the prevalence of hypertension in the 15- to 18-year-old age group.     

Transient receptor potential canonical channel 1 impacts on mechanosignaling during cell migration

Cell migration is crucial for many important physiological and pathophysiological processes ranging from embryogenesis to tumor metastasis. It requires the coordination of mechanical forces generated in different regions of the migrating cell. It has been proposed that stretch-activated, Ca²⁺-permeable channels are involved in mechanosignaling during cell migration. To date, the molecular identity of these channels is only poorly defined. Here, we investigated the contribution of TRPC1 channels to mechanosignaling during cell migration. We used primary cultures of synovial fibroblasts from TRPC1^?/? mice and the wild-type littermates or Madin?CDarby canine kidney (MDCK-F) cells with increased or decreased TRPC1 expression. TRPC1^?/? fibroblasts have the same migratory phenotype as siTRPC1 MDCK-F cells, with a largely increased projected cell area and impaired directionality. Measurements of the intracellular Ca²⁺ concentration ([Ca²⁺]_i) were combined with time-lapse video microscopic cell migration experiments. Cells were seeded on elastic silicone membranes. Uniaxial stretch elicits a graded elevation of the [Ca²⁺]_i in TRPC1-expressing cells. In contrast, TRPC1^?/? fibroblasts or siTRPC1 MDCK-F cells do not react to 0.4?%, and the response to 4?% stretch is attenuated. Similarly, siTRPC1 MDCK-F cells do not alter their direction of migration upon mechanical stimulation, which contrasts the behavior of TRPC1-overexpressing cells which turn into the direction of stretch. Impaired mechanosignaling in siTRPC1 MDCK-F cells leads to accelerated lamellipodial protrusions. Finally, artificially decreasing membrane tension with the detergent deoxycholate impairs the migration of TRPC1-overexpressing cells, but not of siTRPC1 cells. Taken together, our findings indicate that TRPC1 channels are linked to mechanosignaling during cell migration.     

Intracardiac echocardiography in a case with previous failed cavotricuspid isthmus ablation

The Eustachian ridge (ER) can present an obstacle to cavotricuspid isthmus (CTI) ablation. We describe a case, where intracardiac echocardiography revealed a prominent ER as a likely reason for a previous failed CTI ablation and guided the looping of the ablation catheter around the ER, resulting in an ultimately successful ablation.     

Calcification of articular cartilage in human osteoarthritis

Objective

Hypertrophic chondrocyte differentiation is a key step in endochondral ossification that produces basic calcium phosphates (BCPs). Although chondrocyte hypertrophy has been associated with osteoarthritis (OA), chondrocalcinosis has been considered an irregular event and linked mainly to calcium pyrophosphate dihydrate (CPPD) deposition. The aim of this study was to determine the prevalence and composition of calcium crystals in human OA and analyze their relationship to disease severity and markers of chondrocyte hypertrophy.

Methods

One hundred twenty patients with end‐stage OA undergoing total knee replacement were prospectively evaluated. Cartilage calcification was studied by conventional x‐ray radiography, digital‐contact radiography (DCR), field‐emission scanning electron microscopy (FE‐SEM), and synovial fluid analysis. Cartilage calcification findings were correlated with scores of knee function as well as histologic changes and chondrocyte hypertrophy as analyzed in vitro.

Results

DCR revealed mineralization in all cartilage specimens. Its extent correlated significantly with the Hospital for Special Surgery knee score but not with age. FE‐SEM analysis showed that BCPs, rather than CPPD, were the prominent minerals. On histologic analysis, it was observed that mineralization correlated with the expression of type X collagen, a marker of chondrocyte hypertrophy. Moreover, there was a strong correlation between the extent of mineralization in vivo and the ability of chondrocytes to produce BCPs in vitro. The induction of hypertrophy in healthy human chondrocytes resulted in a prominent mineralization of the extracellular matrix.

Conclusion

These results indicate that mineralization of articular cartilage by BCP is an indissociable process of OA and does not characterize a specific subset of the disease, which has important consequences in the development of therapeutic strategies for patients with OA.

     

The small ubiquitin‐like modifier mediates the resistance of prosthesis‐loosening fibroblast‐like synoviocytes against fas‐induced apoptosis

Objective

To study the expression of small ubiquitin‐like modifier 1 (SUMO‐1) in aseptic loosening of prosthesis implants and to investigate its role in regulating the susceptibility of prosthesis‐loosening fibroblast‐like synoviocytes (FLS) to Fas‐induced apoptosis.

Methods

Specimens of aseptically loosened tissue were obtained at revision surgery, and the expression of SUMO‐1 was analyzed by in situ hybridization. SUMO‐1 levels in FLS were determined by quantitative polymerase chain reaction and Western blot analysis. Immunohistochemistry and confocal microscopy were used to study the subcellular localization of SUMO‐1. The functional role of SUMO‐1 in Fas‐induced apoptosis of prosthesis‐loosening FLS was investigated by small interfering RNA–mediated knockdown of SUMO‐1 and by gene transfer of the nuclear SUMO‐specific protease SENP1.

Results

SUMO‐1 was expressed strongly in aseptically loosened tissue and was found prominently at sites adjacent to bone. Prosthesis‐loosening FLS expressed levels of SUMO‐1 similar to the levels expressed by rheumatoid arthritis (RA) FLS, with SUMO‐1 being found mainly in promyelocytic leukemia protein nuclear bodies. Knockdown of SUMO‐1 had no effect on spontaneous apoptosis but significantly increased the susceptibility of prosthesis‐loosening FLS to Fas‐induced apoptosis. Gene transfer of the nuclear SUMO‐specific protease SENP1 reverted the apoptosis‐inhibiting effects of SUMO‐1.

Conclusion

These data suggest that SUMO‐1 is involved in the activation of both RA FLS and prosthesis‐loosening FLS by preventing these cells from undergoing apoptosis. Modification of nuclear proteins by SUMO‐1 contributes to the antiapoptotic effects of SUMO‐1 in prosthesis‐loosening FLS, providing evidence for the specific activation of sumoylation during their differentiation. Therefore, SUMO‐1 may be an interesting target for novel strategies to prevent aseptic prosthesis loosening.

     

The glucocorticoid dexamethasone programs human dendritic cells for enhanced phagocytosis of apoptotic neutrophils and inflammatory response

GCs are powerful anti-inflammatory compounds inhibiting inflammatory cell recruitment and production of proinflammatory cytokines. We have recently found that DCs, the key players of T cell priming and polarization, respond to allogeneic apoptotic neutrophils with proinflammatory cytokine release and Th1 cell activation. Here, we show that monocyte-derived human DCs develop their capacity to engulf apoptotic cells by up-regulating a set of apoptophagocytic genes. This gene expression pattern was reprogrammed when differentiation took place in the presence of the synthetic GC Dex, which increased the expression of phagocytosis receptors MERTK and CD14, the bridging molecule C1QA, DNASE2, and ADORA3. The increased phagocytosis was attenuated by the addition of ADORA3 antagonist and could not be observed when bone marrow-derived DCs of ADORA3 KO mice were treated with Dex. The GC-treated human DCs loaded with allogeneic apoptotic neutrophils secreted, in response to LPS and IFN-γ, the inflammatory cytokine TNF-α. Furthermore, the Dex-treated DCs could activate autologous T lymphocytes toward Th1 effector cells, and this was enhanced by their exposure to allogeneic apoptotic neutrophils.     

Efficacy of omeprazole in functional dyspepsia: double-blind, randomized, placebo-controlled trials (the Bond and Opera studies)

Background:

The efficacy of H₂-receptor antagonists in functional dyspepsia is equivocal and the therapeutic place of proton pump inhibitors in functional dyspepsia is unknown.

Aim:

To evaluate the efficacy of proton pump inhibitor therapy in functional dyspepsia.

Methods:

Patients (n = 1262) with a clinical diagnosis of functional dyspepsia (persistent or recurrent epigastric pain or discomfort for at least 1 month and a normal upper gastrointestinal endoscopy) were randomized to receive omeprazole 20 mg, 10 mg or identical placebo, for 4 weeks. Symptoms were assessed using validated measures. Helicobacter pylori status was determined pre-entry by a ¹³C-urea breath test.

Results:

On an intention-to-treat analysis (n=1248), complete symptom relief was observed in 38% on omeprazole 20 mg, compared with 36% on omeprazole 10 mg and 28% on placebo (P = 0.002 and 0.02, respectively). Among those with ulcer-like and reflux-like dyspepsia, complete symptom relief was achieved in 40% and 54% on omeprazole 20 mg, and 35% and 45% on omeprazole 10 mg, respectively, compared with 27% and 23% on placebo (all P < 0.05, except omeprazole 10 mg in ulcer-like dyspepsia, P = 0.08). There was no significant benefit of omeprazole over placebo in dysmotility-like dyspepsia. Symptom relief was similar in H. pylori-positive and negative cases.

Conclusions:

Omeprazole is modestly superior to placebo in functional dyspepsia at standard (20 mg) and low doses (10 mg) but not in patients with dysmotility-like dyspepsia.

     

Glucocorticoid hormone differentially modulates the in vitro expansion and cytokine profile of thymic and splenic Treg cells

Objective

Functional disturbances in regulatory T cells (Treg) have been described in autoimmune diseases, and their potential therapeutic use is intensively studied. Our goal was to investigate the influence of glucocorticoid hormone on the in vitro differentiation of Treg cells from thymic and splenic CD4⁺ T cells under different conditions to establish methods for generating stable and functionally suppressive iTregs for future use in adoptive transfer experiments.