Effect of ligands and additives on the palladium-promoted carbonylative coupling of vinyl stannanes and electron-poor enol triflates
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Biomedical subjects
Publications and source records attributed to C Gennari.
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The aim of this study was to assess the pattern of ultrasound (QUS) parameters and bone mineral density at different skeletal sites in patients with primary hyperparathyroidism (PHPT) before and after surgical treatment. In 22 patients (age range 28-74 years) with PHPT we measured speed of sound (SOS), attenuation (BUA) and Stiffness at the calcaneus, amplitude-dependent speed of sound (AD-SoS) at proximal phalanges, and bone mineral density at lumbar spine (BMD-LS) and at the mid-radius (BMD-MR) and ultra-distal radius (BMD-UDR) before, 1 and 2 years after surgical operation. Twenty-two age- and sex-matched healthy subjects provided control data. Before surgery, all parameters apart from SOS were significantly lower in PHPT patients than in controls. At the end of the study period, BMD-LS increased by 7.0%, BMD-UDR by 7.4% and BMD-MR by 11.0%. The changes in ultrasound parameters after surgery were lower (0.44% for SOS, 2.2% for BUA, 3.3% for Stiffness and 2.6% for AD-SoS); however, the increase was statistically significant (p < 0.05 and p < 0.01, respectively) only for Stiffness and AD-SoS. Our results indicate that parathyroidectomy increases both axial and appendicular BMD and influences QUS parameters differently at the calcaneus and at the phalanges. The combined use of BMD and QUS could improve the assessment of skeletal status in patients with PHPT before and after surgery.
In the last decade there has been a growing interest in quantitative ultrasound (QUS) techniques as a new method in the assessment of bone status in metabolic bone diseases. Many studies have shown that QUS parameters can predict vertebral and femoral fracture risk in patients with osteoporosis. However, most of the studies were performed in women, whereas few data are available for men. The aim of this study was to build up a normative database on a healthy Italian male population for QUS parameters at the phalanges. Amplitude-dependent speed of sound (AD-SoS) and three parameters (first wave amplitude, FWA; signal dynamic, SDy; time frame, TF) characterizing the graphic trace of the ultrasound signal were measured at the phalanges in 286 healthy subjects (age range 20-87 years). First, the QUS device was adapted to compensate for the difference in finger thickness between men and women. Preliminary data on 150 healthy subjects showed a significant difference between the traditional and adapted device, and the latter was independent of finger thickness variations. AD-SoS showed a significant (p<0.001) decrease with aging, expressed by a second-order polynomial equation. The peak value (2122 m/s) was observed in the fourth decade; thereafter it decreased to 1980 m/s at the ninth decade. Likewise, FWA and SDy were significantly (p<0.001) reduced after the fourth decade, whereas TF remained stable over time until the last decade. In conclusion, in men AD-SoS showed a negative trend with aging. The pattern with aging of parameters characterizing the graphic trace was different from the pattern for AD-SoS, suggesting the possibility of obtaining further information on phalanx bone physical properties which could be useful in the differential diagnosis of metabolic bone diseases and in the assessment of fracture risk.
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To assess whether aerobic exercise training is an effective and an alternative method to control blood pressure (BP) in hypertension, 32 uncomplicated, never treated patients suffering from mild-to-moderate essential arterial hypertension (EAH) were included in an aerobic exercise training program using a regular standardized cycle ergometer exercise for 3 months. In all EAH patients, before and after the exercise training period, ambulatory BP monitoring (ABPM) was performed and several metabolic variables were assessed. Before exercise, in 20 EAH patients, a 48-h ABPM showed a normal day-night rhythm, with nocturnal BP decrease, according to a dipper-type hypertension, whereas in 12 EAH patients 48-h ABPM profile indicated a nondipper-type hypertension. After exercise, EAH dippers presented a significant decrease in the daytime systolic and diastolic BP, whereas EAH nondippers did not show any change in daytime and nighttime systolic and diastolic BP. Our study confirms the controversy about the postulated BP lowering effect of dynamic exercise in EAH patients, in the sense that only EAH dipper patients seem to obtain a beneficial diurnal lowering BP effect deriving from exercise, possibly through a reduction in sympathetic tone. On the contrary, physical activity seems to fail in reducing diurnal and nocturnal BP values in EAH nondippers, suggesting that in nondipper-type hypertension, other "masking" endogenous or exogenous factors could interfere with and prevail over the adrenergic-vagal balance that modulates the day-night BP synchronism.
The authors describe the molecular mechanisms determining some skeletal diseases, in particular those due to a well-defined, single genic defect. In fact, they examine the hereditary disorders due to mutations in the genes encoding the different collagen types and the hereditary diseases secondary to the defects in: a) the structural proteins of cartilage; b) the enzymes and the sulfate transporters of proteoglycans; c) the transcription factors; d) the growth factors. At the end, the authors emphasize the importance of the genetic studies on animal models, for understanding the etiopathogenesis of many human hereditary disorders.
Reverse-turn inducing bicyclic lactams were incorporated into the substrate sequence recognized by farnesyl transferase to create inhibitors of RAS farnesylation. While the free peptides did not show any effect on the farnesylation, their Fmoc-protected counterparts impede the transformation of RAS with IC50's in the low micromolar range.
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The aims of this study were to identify risk factors for hip fracture in men aged 50 years or more. We identified 730 men with hip fracture from 14 centers from Portugal, Spain, France, Italy, Greece and Turkey during the course of a prospective study of hip fracture incidence and 1132 age-stratified controls selected from the neighborhood or population registers. The questionnaire examined aspects of work, physical activity past and present, diseases and drugs, height, weight, indices of co-morbidity and consumption of tobacco, alcohol, calcium, coffee and tea. Significant risk factors identified by univariate analysis included low body mass index (BMI), low sunlight exposure, a low degree of recreational physical activity, low consumption of milk and cheese, and a poor mental score. Co-morbidity including sleep disturbances, loss of weight, impaired mental status and poor appetite were also significant risk factors. Previous stroke with hemiplegia, prior fragility fractures, senile dementia, alcoholism and gastrectomy were associated with significant risk, whereas osteoarthrosis, nephrolithiasis and myocardial infarction were associated with lower risks. Taking medications was not associated with a difference in risk apart from a protective effect with the use of analgesics independent of co-existing osteoarthrosis and an increased risk with the use of anti-epileptic agents. Of the potentially 'reversible' risk factors, BMI, leisure exercise, exposure to sunlight and consumption of tea and alcohol and tobacco remained independent risk factors after multivariate analysis, accounting for 54% of hip fractures. Excluding BMI, 46% of fractures could be explained on the basis of the risk factors sought. Of the remaining factors low exposure to sunlight and decreased physical activity accounted for the highest attributable risks (14% and 9% respectively). The use of risk factors to predict hip fractures had relatively low sensitivity and specificity (59.6% and 61.0% respectively). We conclude that lifestyle factors are associated with significant differences in the risk of hip fracture. Potentially remediable factors including a low degree of physical exercise and a low BMI account for a large component of the total risk.
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We studied 21 patients (11 men and 10 women) with osteogenesis imperfecta (OI) and 21 age- and sex-matched controls. In all patients we measured serum levels of total alkaline phosphatase (ALP), type I procollagen carboxy-terminal propeptide (PICP), osteocalcin (BGP), urinary excretion of hydroxyproline (HOP/Cr), and pyridinoline crosslinks (Pyr/Cr). Bone mineral density was measured at the distal radius (BMD-R) and at the lumbar spine (BMD-LS) by dual X-ray absorptiometry (DXA). Ultrasound parameters were also performed at the calcaneous with the Achilles device and at the phalanxes with DBM Sonic 1200. A significant reduction (P < 0.001) in BMD and in ultrasound parameters was found in OI patients compared with normals. PICP was significantly reduced in the OI patients compared with controls (P < 0.001); other markers of bone turnover were higher in OI than in controls, but the difference did not reach the statistical significance. A significant correlation (P < 0.05) was found between PICP and BMD at the lumbar spine and between PICP and ultrasound parameters at the calcaneous. On the basis of our data, we conclude that patients with OI show low values of BMD and ultrasound parameters; therefore in these patients, not only is bone mass disturbed but also bone quality. The reduced levels of PICP in OI patients confirm that most OI patients have defects in collagen I biosynthesis. These defects may contribute to the fragility of OI bone by interfering with complete mineralization and/or normal tissue structure. PICP may be considered a useful marker in the clinical management of OI.
This study investigated whether bone turnover influences the response to alendronate in women with postmenopausal osteoporosis. One hundred postmenopausal osteoporotic women were randomized to receive either alendronate (10 mg/day) plus calcium (1000 mg/day) (n = 50) or calcium alone (n = 50). Vertebral and radial bone density, measured by DXA, and markers of bone turnover were assessed at baseline and after 1 and 2 years. At the end of treatment, alendronate users showed an increase of 5.0% and 2.3%, respectively, at the lumbar spine and ultradistal radius; in the group treated only with calcium, bone mineral density (BMD) decreased by 1.6% at the lumbar spine and 1.3% at the ultradistal radius. The difference between the two groups was significant (P < 0.001). The patients were divided into high (HT) or low (LT) bone turnover groups, as assessed by 24-hour whole body retention (WBR%) of (99m)Tc-methylene-diphosphonate. The response to alendronate treatment was greater in HT patients compared with LT patients. In fact, at the end of the study period, BMD at the lumbar spine had increased by 7.9% in HT patients and by 3.0% in LT patients; the difference between the two groups was significant (P < 0.001). No significant difference between the two groups was found for BMD at the ultradistal radius. In conclusion, the present study demonstrates that 2-year treatment with alendronate has highly positive effects on bone mass at both the lumbar spine and ultradistal radius. The increase in bone mass, especially at the axial level, is influenced by bone turnover. Therefore, the evaluation of bone turnover may be useful in predicting the response to alendronate treatment.
Renal osteodystrophy (ROD) can be characterized by both high (HT) and low (LT) bone turnover states. Although bone biopsy remains the "gold standard" to diagnose ROD, noninvasive tools for the diagnosis and follow-up of such bone disease are desirable. Recently, ultrasound (US) techniques, proposed to assess skeletal status, have been shown to be correlated not only with bone density but also with bone quality. We have investigated 98 patients on chronic hemodyalisis (HD) and 98 healthy, sex- and age-matched subjects. Amplitude-dependent speed of sound (AD-SOS) and ultrasound bone profile score (UBPS) at phalanxes and speed of sound (SOS), broadband ultrasound attenuation (BUA), and a quantitative ultrasound index (QUI/stiffness) at the heel were performed in both groups. In all subjects intact parathyroid hormone (PTH), total alkaline phosphatase (T-ALP), bone isoenzyme alkaline phosphatase (B-ALP), and carboxy-terminal telopeptide of type I collagen (ICTP) were assessed. All US parameters were significantly lower in the hemodialysis group than in control subjects. Moreover, among US parameters only AD-SOS and UBPS showed a significant correlation with PTH, T-ALP, and B-ALP. Dialytic age showed a modest, but significant correlation only with US parameters at the phalanxes. On the basis of bone biochemical markers, we considered a group with high and a group with normal to low bone turnover. AD-SOS and UBPS, but not SOS, BUA, and stiffness were significantly (p < 0.01) lower in the high bone turnover than in low bone turnover group. Furthermore, in the high bone turnover group, parameters of the US phalanxes strongly correlated with B-ALP. Our results seem to demonstrate that US parameters are a useful tool in the assessment of skeletal status in patients on maintenance dialysis.
A double-blind, placebo-controlled, randomized, prospective two-center study was carried out to assess the effects of tibolone + fluoride versus placebo + fluoride therapy on trabecular and cortical bone in postmenopausal osteoporotic women. Ninety-four subjects (mean age 61.1 years, postmenopausal 13.5 years on average) with low bone mineral density (BMD) at baseline were randomized to 2.5 mg of tibolone (Org OD 14, Livial) plus 26.4 mg of fluoride (Fluocalcic) or placebo plus 26.4 mg of fluoride daily over 2 years; 55 (58.5%) subjects completed the study, the main reason for discontinuation being untoward gastrointestinal effects. BMD at the lumbar spine was measured by both dual photon absorptiometry (DPA) and dual-energy X-ray absorptiometry (DXA), and at the hip by DXA at 6-month intervals. Baseline values (DXA, g/cm2) for tibolone + fluoride and placebo + fluoride groups were 0.733 and 0.744 for the lumbar spine, and 0.761 and 0.788 for the hip. Change from baseline and percentage change from baseline were calculated for the intent-to-treat and completers groups. An analysis of variance (ANOVA) model or Wilcoxon test was used for statistical evaluation. There was a mean increase in BMD at the lumbar spine measured by DPA of 25.3% and 12.3% in tibolone + fluoride and placebo + fluoride groups, respectively (p = 0.01); with DXA, respective changes were 32.6% and 14.0% (p = 0.013). Data on BMD at the hip showed mean increases of 7.9% and 2.6% for the tibolone + fluoride and placebo + fluoride groups, respectively. We conclude that combined tibolone + fluoride treatment induces a highly significant increase in BMD at the lumbar spine without simultaneous loss of the cortical bone allowing for a meaningful reduction of the fluoride dose when given in combination with tibolone.
BACKGROUND: Most antigens reach the immune system through mucosae. Gastrointestinal mucosa is a barrier for alimentary antigens. Inflammatory processes, such as Helicobacter pylori-associated gastritis, could alter the integrity of the gastric barrier, increase the mucosal permeability, and enhance crossing of food antigens which may stimulate allergic reactions. PURPOSE: The aim of this study was to establish whether patients with symptomatic food allergy and detectable immunoglobulin E (IgE) to alimentary antigens were infected by Helicobacter pylori more often than controls, and to determine the phenotype of the infecting Helicobacter pylori. PATIENTS AND METHODS: Thirty-eight consecutive patients with symptomatic food allergy and serum IgE to alimentary antigens, and 53 consecutive age-matched controls (subjects without food allergy and detectable levels of IgE anti-alimentary antigens) living in the same area and attending the same institution were investigated serologically to determine the prevalence of Helicobacter pylori infection, and an immune response to CagA, a marker of the most pathogenic strains. IgE to alimentary allergens were measured by a commercial kit. RESULTS: The prevalence of Helicobacter pylori infection in patients with food allergy and controls was similar (42.1% and 47.1%, respectively). Anti-CagA antibodies in Helicobacter pylori-infected persons were detected in 62.5% of patients with food allergy, and 28.0% of controls (p = 0.030, odds ratio = 4.29, RR = 2.23). The mean IgE level to the most common alimentary antigens was increased in CagA-positive, with respect to the CagA-negative, patients. CONCLUSIONS: The enhanced mucosal and inflammatory lesions commonly found in individuals infected by CagA-positive Helicobacter pylori strains could increase the epithelial permeability and render non-selective the passage of allergens which, in atopic persons, could directly stimulate an IgE response. Infection by CagA-positive Helicobacter pylori may increase the risk of food allergy.
UNLABELLED: H. pylori infection is putatively associated with extra-digestive disorders and may also play a role in the development of autoimmune thyroid diseases (ATD). It was recently found that monoclonal antibodies to an H. pylori strain with cagA-positivity reacted with follicular cells of the thyroid gland, and that an H. pylori organism possessing the cag pathogenicity island carried a gene encoding for an endogenous peroxidase. The aims of this study was (1); To ascertain whether the infection by strains endowed with an increased inflammatory potential (those expressing CagA) could further enhance the risk of developing ATD (2); To verify the possible existence of an immune cross-reactivity between autoantibodies to peroxidase and thyroglobulin and H. pylori antigens (3). To establish whether thyroid colloid antigens could cross-react with an anti-H. pylori serum. The study was partly designed retrospectively. We examined 41 consecutive women with ATD, and, as a control, 33 consecutive age- and socio-economic class-matched women without autoimmune thyroid disorders, living in the same area as patients, occurred at the same institution in the same period (six months). Both patients and controls were examined serologically for H. pylori infection and CagA status by Western blotting. Some serum samples were absorbed with H. pylori to determine whether the antibody levels decreased. Colloid proteins were resolved electrophoretically and matched with a hyperimmune serum raised in rabbits against a CagA-positive H. pylori. Thirty-two patients (78.0%) tested seropositive for H. pylori infection, vs. 16 controls (48.4%) (P = 0.008, OR = 3.78, RR = 1.61). The prevalence of anti-CagA antibodies was 71.8% in infected patients, and 50% in infected controls (P = 0.161, n.s.). The overall prevalence of infection by CagA-positive H. pylori was significantly higher in patients with ATD (23/41, or 56.0%) than that in controls (8/33, or 24.2%) (P = 0.006, OR = 3.99, RR = 2.31). The other tests gave negative or inexplicable results. IN CONCLUSION: CagA-positive H. pylori infection increases the risk of ATD development.