Growth Hormone Improves Growth Retardation Induced by Rapamycin without Blocking Its Antiproliferative and Antiangiogenic Effects on Rat Growth Plate

Rapamycin, an immunosuppressant agent used in renal transplantation with antitumoral properties, has been reported to impair longitudinal growth in young individuals. As growth hormone (GH) can be used to treat growth retardation in transplanted children, we aimed this study to find out the effect of GH therapy in a model of young rat with growth retardation induced by rapamycin administration. Three groups of 4-week-old rats treated with vehicle (C), daily injections of rapamycin alone (RAPA) or in combination with GH (RGH) at pharmacological doses for 1 week were compared. GH treatment caused a 20% increase in both growth velocity and body length in RGH animals when compared with RAPA group. GH treatment did not increase circulating levels of insulin-like growth factor I, a systemic mediator of GH actions. Instead, GH promoted the maturation and hypertrophy of growth plate chondrocytes, an effect likely related to AKT and ERK1/2 mediated inactivation of GSK3β, increase of glycogen deposits and stabilization of β-catenin. Interestingly, GH did not interfere with the antiproliferative and antiangiogenic activities of rapamycin in the growth plate and did not cause changes in chondrocyte autophagy markers. In summary, these findings indicate that GH administration improves longitudinal growth in rapamycin-treated rats by specifically acting on the process of growth plate chondrocyte hypertrophy but not by counteracting the effects of rapamycin on proliferation and angiogenesis

Nutritional profile and obesity: results from a random‑sample population‑based study in Córdoba, Argentina

Introduction Obesity is a chronic, heterogeneous, multifactorial disease, which has sharply increased in prevalence in both developed and developing countries. This study aimed to estimate the prevalence of obesity and to identify socio-demographic risk factors associated with it, with special emphasis on diet. Methods Nutritional status, demographic characteristics, lifestyle habits, and food consumption patterns derived from a Food Frequency Questionnaire were investigated. Exhaustive exploratory analyses were performed in order to describe dietary patterns, and logistic regression models were used for odds ratio estimation. Results The study included 4328 subjects, over 18 years old and resident in Cordoba city. The prevalence of overweight and obesity was 34 and 17 %, respectively, with 60 % in men and 45 % in women of BMI ≥ 25. Obesity risk factors were high intake of sodium, refined grains, starchy vegetables, and snacks. A lower risk of overweight and obesity was associated with an adequate, moderate intake of meats, eggs, alcoholic beverages, sugar and sweets, milk, yogurt, and pulses. Conclusions A high intake of snacks, refined grains, starchy vegetables and sodium and low intake of yogurt, milk, pulses, and whole grains seem to be associated with the emergence and high prevalence of obesity in Cordoba, Argentina.publishedVersionFil: Aballay, Laura Rosana. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Escuela de Nutrición. Estadística y Bioestadística; ArgentinaFil: Aballay, Laura Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: De la Quintana, Ana Gabriela. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Escuela de Nutrición; Argentina.Fil: Díaz, María del Pilar. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Escuela de Nutrición. Estadística y Bioestadística; Argentina.Fil: Díaz, María del Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Osella, Alberto R. Hospital Saverio de Bellis. Laboratorio de Epidemiologia y Bioestadística; Italia

Ulnar-sided wrist pain. II. Clinical imaging and treatment

Pain at the ulnar aspect of the wrist is a diagnostic challenge for hand surgeons and radiologists due to the small and complex anatomical structures involved. In this article, imaging modalities including radiography, arthrography, ultrasound (US), computed tomography (CT), CT arthrography, magnetic resonance (MR) imaging, and MR arthrography are compared with regard to differential diagnosis. Clinical imaging findings are reviewed for a more comprehensive understanding of this disorder. Treatments for the common diseases that cause the ulnar-sided wrist pain including extensor carpi ulnaris (ECU) tendonitis, flexor carpi ulnaris (FCU) tendonitis, pisotriquetral arthritis, triangular fibrocartilage complex (TFCC) lesions, ulnar impaction, lunotriquetral (LT) instability, and distal radioulnar joint (DRUJ) instability are reviewed

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Measurement of jet-substructure observables in top quark, W boson and light jet production in proton-proton collisions at √s=13 TeV with the ATLAS detector

A measurement of jet substructure observables is presented using data collected in 2016 by the ATLAS experiment at the LHC with proton-proton collisions at s√ = 13 TeV. Large-radius jets groomed with the trimming and soft-drop algorithms are studied. Dedicated event selections are used to study jets produced by light quarks or gluons, and hadronically decaying top quarks and W bosons. The observables measured are sensitive to substructure, and therefore are typically used for tagging large-radius jets from boosted massive particles. These include the energy correlation functions and the N-subjettiness variables. The number of subjets and the Les Houches angularity are also considered. The distributions of the substructure variables, corrected for detector effects, are compared to the predictions of various Monte Carlo event generators. They are also compared between the large-radius jets originating from light quarks or gluons, and hadronically decaying top quarks and W bosons

Human rheumatoid synoviocytes express functional P2X7 receptors

10noreservedHuman type B synoviocytes are involved in joint injury during rheumatic diseases by producing inflammatory mediators such as interleukin-6 (IL-6). The increased level of purine and pirimidine nucleotides in the synovial fluid of rheumatoid arthritis (RA) patients could activate the large family of P2 receptors. Thus, we investigated the presence of P2 receptors in human type B synoviocytes from rheumatoid joints, also evaluating whether the P2X7 receptor is involved in IL-6 release. Reverse transcriptase polymerase chain reaction analysis revealed messenger ribonucleic acid (mRNA) expression for the P2X1, P2X2, P2X4, P2X5, P2X6, P2X7, P2Y1, P2Y4, P2Y11, P2Y12, P2Y13, and P2Y14 but not the P2X3, P2Y2, and P2Y6 receptors. The expression of the P2X7 receptor was confirmed by Western blot analysis. Adenosine triphosphate (ATP) and the P2X7 receptor agonist 2'-3'-O-(4-benzoylbenzoyl)ATP (BzATP) triggered an increase in intracellular calcium, thereby suggesting the expression of functional P2 receptors, including the P2X7 receptor. Moreover, BzATP treatment upregulated both IL-6 mRNA and protein expression. Synoviocytes spontaneously released low quantities of IL-6; the incubation with BzATP induced the release of larger amounts of the cytokine, and such a release was blunted by the P2X7 antagonist oxidized ATP. The selective P2X1 and P2X3 receptor agonist alpha,beta-methylene ATP did not affect IL-6 release. Finally, BzATP failed to induce a significant uptake of the large-molecule YO-PRO, thus suggesting the lack of pore formation after P2X7 receptor stimulation. In conclusion, among the different P2 receptors expressed on human RA type B synoviocytes, the P2X7 receptor may modulate IL-6 release but not inducing changes in cell membrane permeability.mixedCaporali, F.; Capecchi, PIER LEOPOLDO; Gamberucci, Alessandra; Lazzerini, PIETRO ENEA; Pompella, G.; Natale, M.; Lorenzini, S.; Selvi, E.; Galeazzi, Mauro; LAGHI PASINI, FrancoCaporali, F.; Capecchi, PIER LEOPOLDO; Gamberucci, Alessandra; Lazzerini, PIETRO ENEA; Pompella, G.; Natale, M.; Lorenzini, S.; Selvi, E.; Galeazzi, Mauro; LAGHI PASINI, Franc