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Background A multidisciplinary heart team and continuum care approach seems to be the most appropriate clinical strategy in order to reduce mortality, functional decline and disability of frail and clinical complex oldest old patients affected by heart failure (HF). We analysed the independent predictors of 1 year–total mortality in our cohort of oldest old HF patients. Methods All patients aged > 85 years referred to our Heart Failure Unit of a Tertiary teaching hospital were consecutively enrolled in the study and were evaluated at first visit with a comprehensive assessment recording cardiological, geriatric and bio–humoral variables. Then we assessed with a multivariable Cox regression analysis the independent predictors of 1–year all–cause mortality. Results 87 patients were enrolled (mean age 89 ± 2.7 years, range 86–96 years); 48.9% were females, 57.9% were in NYHA class III or IV, 43.2% had HFpEF, 36.4% had an ischemic aethiology, 69.3% had a history of atrial fibrillation, 19.3% were living alone, the mean number of prescribed drugs was 8.8 ± 2.2, EVEREST congestion score was 5.2 ± 2.6, mean NT–proBNP was 8187 ± 11170 pg/ml. In the year after enrolment, 25 patients (34.1%) had more than one HF hospitalisation and 17 patients (19%) died. Among all clinical variables, living alone, having had one or more HF hospitalisation and HF–type (HFpEF, HFmrEF, HFrEF), EVEREST congestion score, trans–tricuspid gradient and tricuspid annular plane systolic excursion were significantly (p Conclusions In a cohort of HF oldest old patients tightly managed in a dedicated cardiologic and geriatric Heart Failure Unit, 1–year all–cause mortality was independently predicted by a clinical score of congestion and by living alone status.

Nowadays many particulate products are coated to avoid dust formation and breakage when subjected to forces with different magnitude and direction. In order to distinguish the influence of each force, different testers are needed. In this work Purox-S and Cellets 1000 core particles were coated in a top spray fluid bed coater by three different pre-mixed polymer coating systems (Opadry®, Kollicoat® IR and Instacoat AQUA). The repeated impact tester (RIT) was used to measure their strength toward attrition caused by low magnitude normal forces. Tangential forces may also cause rupture to the particles, so an abrasion tester was used to measure this amount of damage caused to the particles. This work provides information on the resistance of the core particles coated with different mixed polymers against attrition and abrasion.

The purpose of the present study is to obtain better understanding of the influence of the coating thickness, h , coating formulation, T g , and fluid bed temperature, T bed , variables on the resistance to attrition of the coated sodium benzoate reference particles. Three reference coating materials ( T g = 50 – 125 – 150 °C) have been sprayed by using top spray fluid bed coater. Per each coating formulation three different coating levels ( h = 1% – 5% – 9% w/w) have been obtained. The coating processes were performed at three different fluid bed temperatures ( T bed = 40 – 55 – 70 °C). The experiments have been designed according to the response surface methodology (RSM). Both single effects and interactions between single effects on the resistance to attrition (response variable) calculated by means of repeated impact tester were evaluated. From statistical analysis, the coating quantity appears to have a predominant effect on the resistance to attrition of the coated particle in these studied ranges of variables. This relationship is linear and positive, which means that an increasing quantity leads to more resistance to attrition. The interaction coating thickness – coating formulation, the interaction between the fluid bed temperature and the coating formulation and the coating formulation as well as the interaction costing thickness – fluid bed temperature were found to be very significant. On the contrary, no direct effect of the fluid bed temperature on the resistance to attrition is detected.

Hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) are important polymers in pharmaceutical, food and other industries being largely used as encapsulation agents. The characterization of two reference grades of HPMC (Pharmacoat® 603 and Pharmacoat® 615) and one reference grade of PVA (Mowiol® 4-98), through X-ray diffraction (XRD) and thermogravimetry (TG) is described. Specific analyses were performed by means of dynamic vapour sorption analysis of water adsorption/desorption from vapours at 10, 25, 40, 55 and 70 °C. Guggenheim–Anderson–de Boer (GAB), Brunauer–Emmett–Teller (BET), Park and n-layer BET models were successfully used to fit the experimental data. The glass transition temperature as function of water content was measured by means of differential scanning calorimetry (DSC). The experimental data were analysed according to Linear, Gordon–Taylor, Fox and Roos equations. XRD studies revealed amorphous structure for the Pharmacoat® 603 and Pharmacoat® 615 and crystalline for Mowiol® 4-98. Single and multi-step temperature degradation point was found for Pharmacoat® 603 and Pharmacoat® 615 and Mowiol® 4-98, respectively. The water uptake is higher for Pharmacoat® 603 and Pharmacoat® 615 than Mowiol® 4-98. The influence of temperature on water uptake is opposite for the two types of polymers. GAB and n-layer BET were found to better model Pharmacoat® 603 and Pharmacoat® 615 and Mowiol® 4-98 data, respectively. The water makes the glass transition to decrease quite drastically. Gordon–Taylor is better fitting the experimental data both for Pharmacoat® 603 and Pharmacoat® 615 and Mowiol® 4-98.

A novel spraying apparatus was developed to obtain reproducible free sprayed films. Aqueous solutions of PolyVinyl Alcohol PVA 4-98, HydroxyPropyl MethylCellulose HPMC 603 and HPMC 615 were used as reference coating materials. The apparatus is composed by a spraying system, a closed chamber containing a rotating Teflon cylinder, a pressured air supply system, a spray solution supply system, and a computerized control system. The spraying air pressure, the cylinder rotation speed, and the cylinder-spray nozzle distance were tailored in such a manner that the roughness of the obtained free films was similar to that from reference coated particles. Optimum spraying process conditions were found for all three coating materials using design of experiments. The morphology of the sprayed films obtained using the optimum conditions is evaluated by means of scanning electron microscopy (SEM), and atomic force microscopy (AFM), and then compared with those from corresponding cast films and coating layers on particles. A match was found between the morphology of sprayed films and that from the corresponding coating layer on the particle surface. The spray apparatus produced reproducible sprayed films with tuneable roughness and/or smoothness depending on the set of processing parameters.

Polymer-coated particles have been produced by top-spray fluid bed coater and both morphology and resistance to attrition have been analysed using Scanning Electron Microscope, SEM and Repeated Impact Tester, RIT respectively. Coating thickness, coated particle storage conditions and physical aging effects have been assessed. The coating thickness is found to be extremely relevant in raising the resistance to attrition. Thicker the coating and more resistant is the coated particles against attrition. This improvement is found to be more and more relevant while impact energy is increasing. The storage temperature is not influencing the morphology whereas is strongly affecting the resistance to attrition. Coated particles stored at −18 °C were found to be more resistant to attrition than ones stored at room conditions. Such differences, negligible at low energies (low numbers of impacts) increase as soon as the number of impacts and thus the energy rise. The coated particles, stored at ambient conditions, were subsequently aged in vacuum oven and the effect of aging steps was evaluated in terms of resistance to attrition. In aged coated particles were found a wasting in resistance to attrition directly proportional to the aging time. Moreover, the aging process was found to affect the breakage mechanism experienced by the coated particles during impact tests. The common attrition mechanism was found to be layer fatigue. Using the equation proposed by Tavares and King (2002) [48] as starting point, a new equation has been developed in order to fit to the resistance to attrition data. The equation takes into account the number of impacts, the velocity of the impacts, the coating thickness, the coefficient of restitution, e, of the coated particles and the mass specific fracture energy, E f,m . This equation has been successfully applied for different coating materials and different coating thicknesses.

This work demonstrates the potentiality of X-ray micro tomography as a powerful tool for morphological characterization of coated particles and, in particular, of their coating layer. X-ray micro tomography provides a high level of details at both micro and macro-scale. It was, in this work, used in the determination of density, porosity, surface/volume ratio, and thickness of the coating layer. Special emphasis was put on evaluation of the adhesion core/coating shell due to its strong influence on the acceptance and goodness of the final coated compound. Different definitions of coating thickness are evaluated. The variance of these properties is assessed within particles and between particles. A novel protocol was developed in order to segment the coating shell out from the core particles. The segmented out images were used to create 3D models of such coating shells. General aspects of theses models are discussed. The potential and limitations of X-ray micro tomography are finally highlighted based on the experimental work. Image analysis was used to determine the coating thickness applied on the core particles as complementary and reference method. As case study, two series of coated particles, prepared using top-spray fluidized bed coater, were obtained, each one employing three standard well-know coating agents.

Biphosphonates are compounds that inhibit bone reabsorption mediated by osteoclasts or the progression of periodontal disease independent on the host response to pathogenic bacteria that colonize the tooth surface. The use of biphosphonates in oral implantology is still in the experimental stage. The aim of this study is to evaluate the efficacy of a non-aminobiphosphonate combined with a surfactant to increase the ability of the drug to link to the implant and bone surfaces in the development of osseointegration in rabbits. Smooth titanium implants were devised to be used on rabbit femurs. A topical administration of clodronate combined with the surfactant (Tween 20) at different concentrations was made on the implant surface and in the implant site to increase the bone and implant adhesiveness. Placebo was given to the control group. New Zealand rabbits were used and sacrificed by CO2 after 8 weeks from the implantations. A histologic and histo-morphometric analysis was carried out. Results did not show significant difference between the tests and the placebo groups. Our data are different from other similar studies obtaining statistically significant differences. These differences could depend on the efficacy of the drug used and on the procedure of application of the drug on the implant. This study demonstrates poor efficacy of clodronate applied topically to the implant and implant site during surgery to increase the percentage of osseointegration in the implant. Further studies using different fixation techniques of the drug may be necessary to confirm the present data.

The aim of the present study was to evaluate the expression and distribution of different classes of matrix metalloproteinases (MMPs) in radicular cysts and periapical granulomas.Twenty consecutive specimens of radicular cysts and 20 of periapical granulomas were selected. Expression of MMP-2, -9, -8, -13, -3 was immunohistochemically evaluated. The intensity of expression of the MMPs was evaluated using a semi-quantitative analysis: low = +; intermediate = ++; high = +++.Positive expression of MMPs was present with different distribution. MMP-9 expressed differently in the lesions. Indeed, in periapical granulomas low expression was found in endothelial cells and fibroblasts, whilst high intensities were only detected in inflammatory cells. On the contrary, in radicular cysts the high intensities were mainly present in keratinocytes and fibroblasts. MMP-8 was mainly expressed in inflammatory cells of periapical granulomas. MMP-2 and -3 presented a low intensity of expression in both groups. MMP-13 showed a variable pattern of distribution in the different cell types of the two different lesions.The present investigation supports the role of MMPs in the inflammatory process leading to the development of radicular cysts and periapical granulomas. The results of the present study suggested that the increased enlargement of radicular cysts, compared to periapical granulomas, might be related to a higher expression of MMP-9. On the other hands, the higher intensity of expression of MMP-8 in periapical granulomas could be related to an active inflammatory process. MMP-8 could play an important role in the inflammation processes during the development of periapical lesions.

The recently introduced ultrasonic osteotome procedure is an alternative to conventional rotatory burs. The aim of this study was to establish the differences between two ultrasonic osteotomes and conventional rotatory burs, in order to perform micromorphological and histological analyses of osteotomized bone surfaces. Bony samples were taken from adult bovine ribs including both the cortical and marrow bone. Soft tissues have been removed and the bone pieces were divided into four groups, to test four devices: a conventional osteotomy round bur, a Lindeman bur and piezoelectric osteotomes ES007 and the T-Black. Each device performed cuts that were examined via scanning electron microscope (SEM) and light microscopy (LM) to check respectively cut precision and bone architecture all along the defect borders. SEM analysis of specimens showed that burs created defects of greater width and with irregular edges while those produced by ultrasonic osteotomes were narrow and had mostly smooth cutting surfaces. The edges of incisions made by drills were full of bone fragments while less bone chips were observed on piezoincision’s ones. Dimensions of fragments were wider if cuts were made by burs too. LM analysis of samples showed focally, delicate bony trabecules crushed and pressed into the bone marrow in cutting made by burs. Samples cut by ultrasonic devices showed small or no smear layer and only partial or no crushed trabecules. Osteocytes seemed to be intact all along the cutting surface in all samples observed. In the present study, according to literature, ultrasonic surgery validity is confirmed. As a matter of fact, the greater the number of bone chips products, the greater the magnitude of the inflammatory process induced, as well as the possibility of a greater bone loss and delay in wound healing near the osteotomized area.

The aim of this work is to examine the behaviour of laser treated gutta-percha (a–b) after heating, to test the validity of a new obturation technique. Samples of laser- and no laser- treated gutta-percha have been examined by the thermal/thermogravimetric analysis and compared. All samples have been submitted to four runs of heating from the temperature of 25–130 C, followed by spontaneous cooling. It was found that some samples have shown the typical behaviour of the alpha-gutta-percha; others have shown characteristics similar to the conventional beta-gutta-percha. The laser treated gutta-percha has shown a significant mass loss after the first run of heating, while the mass tends to stabilize after the third run. It has been demonstrated that the 980 nm diode laser used with cited parameters does not alters thermal behaviour of gutta-percha cones.

Polymer-coated particles have been produced by applying two grades of hydroxypropyl methylcellulose and one grade of polyvinyl alcohol onto sodium benzoate Purox-S core particles by using top-spray fluid bed coater and then stored under two different conditions, namely ambient conditions (23°C, 55% RH) and in the freezer (−18°C, 25% RH). Surface morphology has been firstly analyzed using scanning electron microscope and atomic force microscope. Resistance to attrition and viscoelastic properties have been measured by repeated impact tester (RIT) and nanoindentation, respectively. The resistance to attrition have been discussed as function of type of coating materials, breakage mechanisms, and storage temperature, and then compared with uncoated Purox-S. The storage conditions is not influencing the morphology, whereas is strongly affecting the resistance to attrition. Coated particles stored at −18°C were found to be more resistant to attrition than ones stored at room conditions. Such differences negligible at low energies (low numbers of impacts) increase as soon as the number of impacts and the energy rise. The improvement in the resistance to attrition was related to the plasticizing effect of water content. Displacement, storage modulus (E′), loss modulus (E″), and damping factor (tan δ) have been measured for all coated particles. Quasistatic and dynamic nanoindentation were found to agree very well with each other. Comparison of the nanoindentation results and the RIT results showed that tan δ, as measure of viscoelasticity and flexibility of the polymeric coating material, is related to the attrition behavior. It was found, in fact, that a higher tan δ gives more resistance to attrition. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

In recent years, gastric ulceration has been recognized as a common, possibly performancelimiting disease, of adult horses. The aim of this study was to compare endoscopic features, histological diagnosis, and mRNA levels of various cytokines (TNF-α, IL-1β, and IL-13) from horse gastric biopsies. Eleven horses suffering from equine gastric ulcer syndrome and seven horses with normal histological gastric features were assessed. No correlation between endoscopic features and histology (i.e., the gold standard) was observed. Based on histological diagnosis, a significant (p

The increasing tendency to enhance consumer products with added functionality is leading to ever more complex products. Nowadays more and more particulate products are coated to give the product specific functionalities. An appropriate approach is needed to be able to satisfy customer's requirements. In this work, three reference well-known coating agents, namely two grades of hydroxypropyl methylcellulose (HPMC) and one polyvinyl alcohol (PVA) were selected and investigated. Aqueous solutions of such polymers were obtained and viscosity and shear stress were measured function of shear rate, temperature and polymer concentration. The viscosities of the solutions appear to be mainly shear rate independent, they clearly show Newtonian behaviour. Drying and storage conditions influence on morphology and structure of the cast films were evaluated using scanning electron microscope (SEM). Dynamic mechanical thermal analysis (DMTA) experiments were carried out on HPMC and PVA cast films to assess the viscoelastic properties over wide temperature-frequency range. The time-temperature superposition principle was used to determine the shift factor, aT, and to compose a master curve. Magnitudes and profiles of storage modulus, E', loss modulus, E'', and tan delta master curves are discussed with relation to drying and storage conditions. No impact of drying temperature on the polymer properties was observed whereas the effect of storage temperature resulted to be relevant in terms of shifts in glass transition temperature and, only partially, changes in the magnitudes of E' and E''.

The roughness and the purity of implant surfaces are key points in the osteointegration process. The surfaces obtained by classic methods present irregular non-reproducible patterns and furthermore contaminate the implant surface with materials other than titanium which interfere with the process of osteointegration. The aim of the present study is to evaluate, by SEM/EDX and XPS analyses, the surface microstructure and the purity of new laser-treated implant surfaces. The laser treatment of the surface allows to set parameters to determine the roughness in order to obtain a regular and repeatable surface. Furthermore, there being no contact between the implant and the machine, there is no surface contamination with elements other than titanium. In this study we used a diode-pumped solid state laser (DPSS) with Nd:YAG source operating in Q-Switching mode on titanium samples. The resulting samples were analysed by SEM/EDX and XPS to evaluate morphology and purity of the surface. The results show surfaces with very regular roughness and a total absence of contamination.

The aim of this study is to test the response of bone during cutting actions in dental procedures by sampling alkaline phosphatase (ALP) as a biological reference marker. ALP is found abundantly in bone tissue. In the first series of experiments a temporal-minimum quantity of ALP enzyme response was recorded, the observed period was 40 minutes. The ALP samples treated with piezoelectric surgery showed a rapid increase, with peak at 30 min, and then declined rapidly within the next 10 minutes. A second experiment was performed to evaluate 4 cutting instruments: drill bits high speed turbine (T1); drill bits contra-angle (T2) Piezoelectric insertions (T3), and manual instruments (controls). This second experiment was to evaluate the ALP activity at 30 min. The T1 samples produced the highest results (3,66499 +- 0,51394); control groups had a lower response (0,72793 +- 0,22353), while the T2 group produced statistically significant higher results (2,77793 +- 0,40553) than T3 (1,16608 +- 0,32676). The different values obtained for ALP in these two experiments for a short period of time (30 min) cannot be interpreted as a response of bone tissue regeneration subjected to surgical trauma. The MINIMUM trauma caused by the surgical piezoelectric instruments, in respect to conventional surgical instruments is clearly evident from the phosphatase inflammatory activity.

Cyclic AMP phosphodiesterase (cAMP PDE) seems to be important in pulp tissues. High levels of cAMP PDE have been demonstrated to be in dental pulp cells. In the present study cAMP PDE activity was analyzed in normal healthy human dental pulps, in reversible pulpitis and in irreversible pulpitis. Enzymatic cAMP PDE control values for normal healthy pulps were 12.14 +/- 3.74 nmols/mg of proteins. In reversible pulpitis the cAMP PDE activity increased almost 2.5 times. In irreversible pulpitis specimens the values increased 4.5 times compared with normal healthy pulps activity. The differences between the groups (control vs. reversible pulpitis and vs. irreversible pulpitis) were statistically significant. These results could point to a role of cAMP PDE in the initial pulp response after injury.

In the last five years we cured 81 patients divided in two groups: the first was managed inordinately, the second according to a diagnostic and therapeutic protocol.The first 23 patients were differently evaluated, before surgery, by means of traditional sialography, US, CT, CT sialography, MR, larger bore needles and FNAB. Neoplasm enucleations, atipic resections, superficial and total conservative parotidectomies were performed. The following 58 patients were evaluated and cured according to a diagnostic and therapeutic protocol.Diagnostic and therapeutic time were shortened, patients endurance improved and cost lowered.We think that many diagnostic procedures are useless and delay operation that, if possible, must be performed according to principles of radical extirpation.

Several PrP gene polymorphisms modulate sheep scrapie susceptibility. Recently, an increase of scrapie outbreaks has been reported in Italy. A vaccine containing sheep brain homogenate was used in most of the outbreaks. We investigated PrP gene polymorphisms in scrapie-affected and clinically healthy Sarda breed sheep from a flock exposed to the aforementioned vaccine, and in affected Sarda sheep from unexposed flocks. All affected animals were (Gln/Gln)171 homozygous. Moreover, we observed no variation for Ala136 and a new polymorphism (Lys to Asn) at codon 176. Our findings confirm the correlation between scrapie and (Gln/Gln)171 in breeds with no variation for Ala136.

The human DNA mismatch repair (hMMR) system plays an important role in reducing mutation and maintaining genomic stability. The MMR system in human cells is composed of at least six genes (hMSH2, hMLH1, hMSH3, hPMS1, hPMS2 and GTBP/hMSH6). In particular, hMSH2 and hMLH1 are expressed in human cells that are undergoing rapid renewal; their reduced expression has been reported in several tumors. We examined the protein expression pattern of hMSH2 and hMLH1 by immunohistochemistry in 25 ameloblastomas. All ameloblastomas expressed hMSH2 and hMLH1 proteins in the outer layer of epithelial cells. The localization of the staining was exclusively nuclear. These data suggest that the development and progression of these tumors do not depend on a defect in the hMMR system.

This study evaluates the role of bcl-2 protein, as well as, of apoptotic bodies in the topical treatment of oral leucoplakia with 13-cis-retinoic acid (isotretinoin). To test this role, a clinical, histological and immunohistochemical study of the treated lesions was carried out, so as to verify the role of apoptosis and its genetic control mechanism of the development, progression and therapy of preneoplastic lesions.A Double-blind study was carried out on 15 patients afflicted with oral leukoplakia. They were treated daily (3 topical applications) with 0.1% isotretinoin gel or a placebo for 4 months. Afterwards, the patients treated with placebo were administered the active medication for an additional 4 month period.All the patients, with the exception of one patient who was lost to follow-up, who finished the treatment, showed a marked improvement of the dimension and the clinical aspect of the lesions (3 total remission, 11 improvement of the size and clinical appearance of the lesion of 50% or more). The immunohistochemical analysis for bcl-2 protein showed a weak positive reaction of the level in the basal membrane of the specimens collected before the pharmacological treatment; after the pharmacological treatment almost all the specimens with the exception of one, tested completely negative for bcl-2 protein. In the specimens collected before the pharmacological treatment only a few apoptotic bodies were observed, while after treatment the samples showed a noticeable increase of apoptotic bodies.A statistical analysis showed that the difference in the positive reaction to bcl-2 protein between the 2 groups is not statistically significant (p = 0.132). On the other hand, the difference in the count of apoptotic bodies between the 2 groups is statistically significant (p = 0.0193).

In this study an immunohistochemical analysis of both normal and pathological tissues was made to investigate the expression of some factors involved in genic regulation mechanisms of apoptosis.In normal mucosa, in leukoplakia, in mild and severe dysplasia and in high, mild and low grade cancer a bcl-2, p53, and Ki 67 evaluation was made using immunostaining techniques; also an evaluation of apoptotic index was carried out. Seventy-two biopsies were made in 12 patients with normal mucosa, 12 affected by leukoplakia, 12 by dysplasia (6 mild, 6 severe), 12 by low grade, 12 by mild grade and 12 by high grade cancer.tThe immunohistochemical analysis pointed out that there was weak bcl-2 expression in normal mucosa and in preneoplastic lesions and less more in severe dysplasia while bcl-2 was discreetly detectable in oral tumors. P53 was not detectable in normal mucosa and weakly expressed in preneoplastic lesions, presenting a peak in severe dysplasia. These results showed an interesting inverse relation between bcl-2 and p53 expression in severe dysplasia. Ki 67 expression results to be weak in normal mucosa, in preneoplastic lesions and in mild dysplasia, while it reaches the maximum level in severe dysplasia and in tumors.In all the samples the apoptotic index expression showed the same features of the Ki 67 protein. These results were achieved through statistically analysis carried out with the U Mann Whitney test.

The aim of this study was to report the microbiological and clinical effects of repeated subgingival administration of a 1% Chlorhexidine-gel in periodontal pockets from 10 patients with adult periodontitis. Results showed that the experimental treatment significantly improved clinical parameters (Plaque Index, Gingival Bleeding Index, and Pocket Probing Depth). Direct subgingival administration of Chlorhexidine-gel also produced a remarkable modification in the proportions of putative periodontopathic microorganisms, such as Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Veillonella parvula, Fusobacterium nucleatum, and Peptostreptococcus micros, in subgingival bacterial plaque from periodontitis patients.

Only rarely is a mature complex odontoma seen in a periapical location and in association with a primary tooth. Complex odontomas usually present as a radiopacity with a radiolucent rim. The differential diagnosis must include mature fibro-osseous lesions (e.g. cementoblastoma). Complex odontomas can be differentiated from fibro-osseous lesions because they usually present a nonhomogeneous radiopacity and almost always will present as solitary lesions. For complex odontomas located in the periapical region, the differential diagnosis must include idiopathic periapical osteosclerosis. In this case, the presence of the radiolucent rim and the presence of denser, sharper radiopacities produced by enamel distinguish the odontoma.

Insulin inhibits its own release (autofeedback), and growth hormone (GH) inhibits the GH response to a variety of stimuli. The aim of this study was to evaluate whether glucagon (G) can modify pancreatic G (IRG) release in humans. Seven healthy men received intravenous (i.v.) arginine (30 g in 30 minutes) 240 minutes after the beginning of a 0.9% NaCI saline infusion and a 2.5-, 4.0-, and 8.0-ng/kg.min-1 porcine G infusion, with each infusion lasting 360 minutes. All G infusions yielded stable and dose-related plasma IRG levels, and the 4.0- and 8.0-ng/kg.min-1 G infusions decreased plasma free fatty acids (FFA) and blood glycerol and beta-OH-butyrate levels and elicited insulin (IRI) release, and the 8.0-ng/kg.min-1 G infusion elicited GH release and increased blood glucose (BG) levels; somatostatin (SRIF) levels were not affected by G infusions. At 240 minutes, plasma IRG levels were higher during G infusion than during saline infusion, whereas serum IRI and BG levels had returned to preinfusion levels. At this point, G infusions decreased the integrated (240 to 300 minutes) IRG, IRI, BG, and SRIF responses, but not the GH response to arginine. These data indicate that prolonged G infusions decrease the IRG response to arginine; in addition, G decreases plasma FFA levels, and higher G doses stimulate IRI release and exert a self-limited hyperglycemic effect. The fact that the IRI response to arginine was decreased by G could be due to a refractoriness of beta cells to subsequent stimuli; the decreased SRIF response to arginine is likely due to G itself or to a decrease of plasma FFA levels.

The pharmacokinetics of intranasal, an intravenous infusion, and intramuscular glucagon has been studied in 5 healthy subjects and 11 patients with insulin-dependent diabetes mellitus. After infusion the elimination half-life was significantly longer in diabetics (11.9 vs 6.6 min) and the apparent volume of distribution was twice as high in diabetics (0.19 vs 0.37 l.kg-1). The metabolic clearance rates were the same in the two groups (18.9 and 21.3 ml.min-1.kg-1 in controls and in diabetics) and were about twice those previously reported. After 1 mg intranasally the Cmax of immunoreactive glucagon (IRG) was similar in diabetic and in healthy subjects. Administration of a higher dose (2 mg) to diabetic patients produced a higher plasma level, although not proportionately so. The AUC after 1 mg was also similar in controls and in diabetics. The elimination half-life in both groups was similar to the value found after i.v. infusion; it was significantly shorter in controls (5.5 min) than in diabetics (13.8 min). In both groups, mean Cmax was significantly lower than after IM glucagon, the relative bioavailability of 1 mg intranasally vs IM injection being less than 30%. After IM administration, the Cmax and AUC of IRG in controls and in diabetic patients, were identical. The apparent elimination half-life was also similar in the two groups, and was three- to four-times longer (28.6 and 31.4 min) than after infusion or intranasal administration, possibly because estimation of the t1/2 was affected by slow release of the hormone from the site of injection.

Obesity and impaired glucose tolerance (IGT) are risk factors for non insulin dependent diabetes mellitus (NIDDM) and for ischemic heart disease. Long term treatment of IGT subjects with diet and tolbutamide prevents progression of IGT to NIDDM. We have evaluated the lowest dose of glipizide, a second-generation sulfonylurea, able to improve glucose tolerance in response to oral glucose in 31 obese subjects, 12 with NIDDM, 9 with IGT and 10 with normal glucose tolerance (NGT). All subjects underwent four OGTTs, preceded by placebo and by different doses of glipizide (0.5, 1.0, 2.5 mg). Glucose tolerance was progressively improved by increasing glipizide doses in all groups, probably by peripheral mechanism and by enhanced insulin release.

The attempt has been made to identity the lowest dose of glipizide, a second generation sulphonylurea, capable of improving glucose tolerance in overweight and obese subjects with various degrees of glucose tolerance. Thirty one obese subjects, 12 with non insulin dependent diabetes mellitus (NIDDM), 9 with impaired glucose tolerance (IGT) and 10 with normal glucose tolerance (NGT) each underwent four OGTTS (75 g), at 1 week intervals, after administration in random order of placebo or glipizide 0.5, 1.0 or 2.5 mg 30 min before glucose. Glucose tolerance in all groups was progressively improved by the increasing doses of glipizide and was normalized by 1.0 mg glipizide in impaired glucose tolerance (IGT) and by 2.5 mg glipizide in NIDDM. Insulin release was not significantly affected by glipizide in the three groups of subjects. The data indicate that it is possible, at least in acute experiments, to improve glucose tolerance in overweight and obese subjects with IGT, with NGT and with NIDDM, with doses of glipizide that do not affect insulin release.

This randomized controlled clinical trial was designed to compare the clinical outcomes of guided tissue regeneration with calcium sulfate graft and membrane (CS) versus guided tissue regeneration with collagen membrane (CM) or open flap debridement (OFD) only in terms of clinical attachment gain in periodontal intrabony defects.Fifty-one systemically healthy, non-smoking subjects affected by moderate to severe chronic periodontitis were recruited. The subjects had one deep intrabony defect with a probing depth (PD)or =6 mm and were randomly divided into three equal groups (17 subjects per group). Subjects were surgically treated with OFD (OFD group), OFD with CS (CS group), or OFD and CM (CM group). One year after surgical treatment, a complete clinical examination and a surgical reentry were performed. The pre- and post-therapy clinical parameters, including PD, clinical attachment level (CAL), gingival recession (GR), and intrasurgical parameters (defect bone level [DBL]), were compared.After 1 year, the clinical and intrasurgical parameters showed statistically significant changes from baseline within each group for all of the evaluated parameters (PD and CAL, P0.001; GR and DBL, P0.05). Differences (PD, CAL, and DBL, P0.001; GR, P0.05) were also seen across the three groups. The CM and CS groups had significantly smaller PD, CAL, and DBL values than subjects treated with only OFD. Groups treated with regenerative techniques had a significantly greater PD reduction and CAL and DBL gain compared to the OFD group. No significant differences were seen between CM and CS. Conversely, the CM group showed a significantly greater GR increase compared to OFD and CS.Both regenerative treatments produced additional clinical benefits over OFD alone. Moreover, the use of CS may minimize post-surgical recession.

The main therapeutic approaches for inflammatory periodontal diseases include the mechanical treatment of root surfaces. Multi-center clinical trials have demonstrated that the adjunctive use of a chlorhexidine (CHX) chip is effective in improving clinical results compared to scaling and root planing (SRP) alone. However, some recent studies failed to confirm these clinical results, nor have any data been reported regarding the capability of the CHX chip in affecting the activity of alkaline phosphatase (ALP) in the gingival crevicular fluid (GCF). This enzyme has been related to a condition of destructive activity of periodontitis. The aim of this study is to provide further data on the clinical and biochemical effects of CHX chips when used as an adjunct to SRP. Eighty-two systemically healthy patients, aged 31-63, with moderate and advanced periodontitis were recruited from the departments of Periodontology of the University of Chieti. In each patient 2 experimental sites, located in two symmetric quadrants, were chosen with a probing depth ofor = 5 mm and bleeding on probing. The 2 sites were selected randomly at the split-mouth level; control sites received SRP alone, and test sites SRP plus 1 CHX chip. Clinical indices, including probing depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), and the ALP activity in GCF were evaluated at baseline and after 6 months. Alkaline phosphatase activity was assayed spectrophotometrically. The PPD and CAL were significantly lower at 6 months as compared to the baseline scores in both treatments (p less than 0.01). The PPD reduction was 2.7 mm in the CHX+SRP group and 1.9 mm in the SRP alone group. The CHX+SRP group showed a significantly greater gain of clinical attachment (mean: 1.4 mm) in comparison with the SRP group (mean: 0.9; p less than 0.05). No differences were observed in the decrease of the percent of BOP-positive sites between the experimental groups. Conversely, the CHX+SRP group underwent a significantly greater decrease (p less than 0.01) of the GCF-ALP activity 6 months after treatment in comparison with the SRP alone group. The adjunctive use of the CHX chip resulted in a significant improvement of pocket reduction and clinical attachment gain as compared with SRP alone. These results were concomitant with a significantly greater reduction of the GCF-ALP activity levels.