Telmisartan and irbesartan therapy in type 2 diabetic patients treated with rosiglitazone: effects on insulin-resistance, leptin and tumor necrosis factor-alpha.

The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.     

Caries experience in Icelandic 12-year-old urban children between 1984 and 1991

Abstract – In order to evaluate trends in caries experience, a 20% random sample of 12-yr-old residents of Reykjavik, Iceland (252 children) was examined clinically and radiographically in 1991 under conditions consistent with those of the survey conducted in 1984. In addition to caries data, frequency of toothbrushing and use of fluoride dentifrice were recorded. The mean DFT and DPS were 3.0 and 4.1, respectively. The decrease in caries experience reached 60% with an annual fall in DPS of nearly 10%. During the 7-yr period between examinations the decline in DFT and DFS scores averaged 5.2 and 8, respectively, the annual reduction amounting to 0.7 DF teeth or 1.1 DF surfaces per child. The ratio of approximal/occlusal caries and the proportion of approximal caries were similar in both surveys. Fourteen percent of the children were free from manifest caries in 1991, but only 2% in 1984. Polarization between low and high prevalence individuals had intensified. Ninety-five percent of the children brushed their teeth regularly and 97% reported using a fluoride dentifrice.     

Evaluation of hyperforin analogues for inhibition of 5-lipoxygenase

The acylphloroglucinol hyperforin, a constituent of the herb Hypericum perforatum (St. John's wort), was recently identified as potent and direct inhibitor of 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of proinflammatory leukotrienes. In this study, naturally occurring analogues of hyperforin, isolated from H. perforatum, as well as a series of synthetic derivatives obtained by chemical modification of hyperforin by acylation, alkylation or oxidation, were analysed for the inhibition of 5-LO. The efficacies of these compounds were evaluated in intact human polymorphonuclear leukocytes, but also the inhibitory effects on isolated recombinant human 5-LO were investigated. Our data show that some of the oxidised hyperforin derivatives possess even improved efficacy, whereas alkylation and acylation have detrimental effects.     

Cardiovascular Safety and Effectiveness of Bisphosphonates: From Intervention Trials to Real-Life Data

Both osteoporosis with related fragility fractures and cardiovascular diseases are rapidly outspreading worldwide. Since they are often coexistent in elderly patients and may be related to possible common pathogenetic mechanisms, the possible reciprocal effects of drugs employed to treat these diseases have to be considered in clinical practice. Bisphosphonates, the agents most largely employed to decrease bone fragility, have been shown to be overall safe with respect to cardiovascular diseases and even capable of reducing cardiovascular morbidity in some settings, as mainly shown by real life studies. No randomized controlled trials with cardiovascular outcomes as primary endpoints are available. While contradictory results have emerged about a possible BSP-mediated reduction of overall mortality, it is undeniable that these drugs can be employed safely in patients with high fracture risk, since no increased mortality has ever been demonstrated. Although partial reassurance has emerged from meta-analysis assessing the risk of cardiac arrhythmias during bisphosphonates treatment, caution is warranted in administering this class of drugs to patients at risk for atrial fibrillation, possibly preferring other antiresorptives or anabolics, according to osteoporosis guidelines. This paper focuses on the complex relationship between bisphosphonates use and cardiovascular disease and possible co-management issues.     

Caveolin-1 expression in lung carcinoma varies according to tumour histotype and is acquired de novo in brain metastases

Aims:  To study caveolin-1 (Cav-1) expression in metastatic lung carcinomas.
Methods and results:  Cav-1 expression was investigated in a series of 121 lung carcinomas and it was shown that 18/121 tumours (14.9%) were Cav-1+. None of the pure bronchioloalveolar carcinomas proved to be positive, vs. 42.8% of the large cell carcinomas (neuroendocrine subtype excluded). Adenocarcinomas (8.5%), large cell neuroendocrine carcinomas (20%) and squamous cell carcinomas (29.6%) displayed an intermediate percentage of positive cases, suggesting a gradient of Cav-1 expression according to tumour histotype-related aggressiveness. Moreover, the percentage of Cav-1+ tumours with distant metastases was almost double that of non-metastatic tumours (17.8% vs. 8.1%), irrespective of the histotype. In 34 tumours metastatic to the brain, primary and secondary lesions were compared and 53% of brain metastases were Cav-1+ vs. 20.6% of primaries, indicating a de novo acquisition of Cav-1 expression. This pattern was exclusive to the brain, as it was not acquired in adrenal metastases. In our series, the presence of epidermal growth factor receptor amplification, determined by fluorescence in situ hybridization, was not related to Cav-1 reactivity.
Conclusions:  Cav-1 immunoreactivity in lung carcinoma is histotype-dependent and acquired de novo in brain metastases, suggesting a site-specific phenotypic shift in secondary lesions.     

Hepatitis B virus and hepatitis C virus infections in children

PURPOSE OF REVIEW: To analyse the most relevant recent information on efficacy, duration and coverage of anti-hepatitis B virus vaccination; correlates of mother-to-child hepatitis C virus transmission; the natural history and outcomes of hepatitis B and C virus infections in children; the efficacy and safety of specific therapies. RECENT FINDINGS: Insufficient hepatitis B virus vaccine coverage and incomplete or delayed vaccine cycles need improvement in many countries. Hepatitis B virus mutants may explain some fulminant hepatitis in perinatally infected infants and vaccine failures. No interventions to prevent vertical hepatitis C virus transmission have been identified. Spontaneous clearance of hepatitis B is lower in children than in adults, while the rates appear to be similar for hepatitis C. The disease progression is slower for both infections in childhood. Several studies support the efficacy and safety of interferons and lamivudine in chronic hepatitis B or of interferons and ribavirin in chronic hepatitis C in children, but the optimal therapy remains unclear. SUMMARY: There are doubts as to the long-term persistence of anti-hepatitis B immunization in low-endemicity areas. Routine hepatitis C virus testing in pregnancy is not recommended as there are no available prophylactic measures. Although hepatitis B and C virus infections are usually asymptomatic or with mild manifestations in childhood, concerns around their long-term clinical impact suggest the need for early treatment. Children should preferably be treated in the context of targeted trials for a better understanding of the efficacy and tolerance of drugs currently used in adults.     

Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene

Rearrangements of the RET receptor tyrosine kinase gene generating RET/PTC oncogenes are specific to papillary thyroid carcinoma (PTC), the most frequent thyroid tumor. Here, we show that the RET/PTC1 oncogene, when exogenously expressed in primary normal human thyrocytes, induces the expression of a large set of genes involved in inflammation and tumor invasion, including those encoding chemokines (CCL2, CCL20, CXCL8, and CXCL12), chemokine receptors (CXCR4), cytokines (IL1B, CSF-1, GM-CSF, and G-CSF), matrix-degrading enzymes (metalloproteases and urokinase-type plasminogen activator and its receptor), and adhesion molecules (L-selectin). This effect is strictly dependent on the presence of the RET/PTC1 Tyr-451 (corresponding to RET Tyr-1062 multidocking site). Selected relevant genes (CCL20, CCL2, CXCL8, CXCR4, L-selectin, GM-CSF, IL1B, MMP9, UPA, and SPP1/OPN) were found up-regulated also in clinical samples of PTC, particularly those characterized by RET/PTC activation, local extrathyroid spread, and lymph node metastases, when compared with normal thyroid tissue or follicular thyroid carcinoma. These results, demonstrating that the RET/PTC1 oncogene activates a proinflammatory program, provide a direct link between a transforming human oncogene, inflammation, and malignant behavior.     

Contrast medium in power Doppler ultrasound for assessment of synovial vascularity: comparison with arthroscopy

OBJECTIVE: To evaluate the reliability of contrast-unenhanced power Doppler (CUPD) and contrast-enhanced power Doppler (CEPD) ultrasound (US) assessment of synovial vascularity of knee joint synovitis by prospective comparison with the "gold standard," arthroscopy. METHODS: A total of 18 knees of 17 patients with refractory rheumatoid and psoriatic knee joint synovitis were examined by US. Recognition of PD synovial vessel flow and its spatial arrangement in relation to the pannus/cartilage interface (P/CI) or fluid/synovium interface (F/SI) were studied by CUPD- and CEPD-US after a single intravenous bolus of galactosel palmitic acid (Levovist). Arthroscopy video recordings were reanalyzed by computer image analysis to assess synovial vascular marking. CUPD and CEPD flow signal scores were compared with each other and with corresponding vascular marking scores. Using villous vascular marking as reference, CUPD and CEPD sensitivity and specificity were measured. Interobserver variability was evaluated. RESULTS: Compared with the unenhanced PD method, contrast administration increased the PD flow signal score in 13/18 knees (72.2%), allowing increased detection of F/SI PD flow signal configuration (p < 0.018) and of the coexistence of P/CI and F/SI PD imaging (p < 0.0078). With arthroscopy as reference, contrast-enhanced PD was found to be more useful than the unenhanced method, showing more reproducible PD signal scores (p = 0.05 vs p = nonsignificant), as well as higher sensitivity (80% vs 30%), but lower specificity (62% vs 87%), in the recognition of increased vascularity of synovial villi. Interobserver agreement was 100%. CONCLUSION: The prospective comparison with arthroscopy showed the reliability of the CEPD method in synovial vessel recognition and its potential clinical usefulness in assessment of knee joint synovitis.     

Growing Strong and Healthy with Mister Bone: An Educational Program to Have Strong Bones Later in Life

Optimal peak bone mass and bone health later in life are favored by a sufficient calcium intake in infancy, childhood and adolescence. The purpose of this study was to test a new educational program created to monitor and to improve calcium and vitamin D intake in children. Nutritional habits in children were evaluated through a food frequency questionnaire (FFQ) to assess the intake of calcium, vitamin D, dairy products, and total caloric energy at baseline and after seven months of exposure to a unique educational program applied between November 2013 and May 2014 in 176 schoolchildren (48% male, 52% female) attending the fourth and fifth grades of two selected primary schools in Florence, Italy. A significant increase of calcium (from 870 ± 190 to 1100 ± 200 mg/day, p < 0.05), and vitamin D (from 3.6 ± 1.53 to 4.1 ± 2 µg/day) intake in children was documented after the educational program. The amount of specific foods important for bone health consumed, such as milk and vegetables, increased significantly, both in male and female children (p < 0.05). The proposed educational program appears to be effective in modifying calcium intake in children, with a significant increase in the consumption of dairy products and vegetables, but without a significant change in the total caloric intake.     

Generation of non MHC restricted killing in non-cytotoxic T-lymphocytes from leukaemia patients

Experiments were undertaken to determine whether the depression of natural killer (NK) activity previously observed in the peripheral blood lymphocytes (PBL) of leukaemia patients in remission extended to NK-like precursors in the blood. T-lymphocytes (E+) from leukaemia patients and normal subjects were depleted of IgG Fc-receptor-bearing (gamma FcR) fresh NK cells by passage over immune complex-coated monolayers. gamma FcR - E + PBL were cultured alone or with DAUDI cells. On day 5 of culture, cytotoxicity toward the NK-sensitive cell lines K562 and MOLT-4 was evaluated in the responder lymphocytes of leukaemia patients and controls. Negligible NK-like cytotoxicity was found in both FcR - E + PBL responder populations cultured alone. By contrast, stimulation with DAUDI induced high levels of K562 and MOLT-4 cytotoxicity in leukaemia as well as in normal responder cells. Complement-mediated cytotoxicity experiments using various McAb demonstrated that in both normal and leukaemia cultures NK-like effectors react with the pan-T OKT3 McAb and with the OKT11 McAB directed to the SRBC receptor, but not with Leu 1 1b and OKM1 McAbs, directed against antigens expressed on peripheral blood NK cells. Fractionation of the responder cells on discontinuous Percoll gradients showed that most of this activity was present in the highly dividing blast cell fraction.