Atrial dimension reference values in healthy participants using the biplane/monoplane method for clinical and research use.

AIM: To provide reference values of the dimensions of the left and right atrium (RA) obtained using the biplane and monoplane methods, respectively, on two- and four-chamber views, which represent the standard projections acquired in clinical practice, and correlation with body surface area (BSA), age, and gender. MATERIALS AND METHODS: Healthy volunteers, M:F = 1:1, including five participants per gender and age decile from 20 to 70 years, who underwent cardiovascular magnetic resonance imaging (CMR) were enrolled prospectively. Normal atrial reference values were calculated for male and female subpopulations and stratified by age. Atrial areas and volumes were assessed both as absolute values and indexed to BSA. Differences among genders and correlation with age were assessed. Intra- and interobserver reproducibility were assessed in a subpopulation. RESULTS: Fifty participants (mean age 43.3 ± 14 years, 25 men) were evaluated. Image analysis took <1 minute for each subject (mean time 30 ± 5 seconds). Intra- and interobserver reproducibility were excellent (ICC >0.85 for all datasets). RA areas were significantly higher in males (p=0.0001). The left atrial (LA) surface did not show significant differences among genders. Atrial areas normalised to BSA did not show significant gender differences. Both right and left absolute atrial volumes turned out to be significantly higher in males (p=0.0001 and p=0.0047, respectively), and normalised to BSA remained significantly different only for the RA (p=0.0006). Neither atrial volume nor areas showed significant correlation with age. CONCLUSIONS: The monoplane method is a fast and reproducible technique to assess atrial dimensions. Absolute atrial dimensions show significant variations among genders. Gender-specific reference ranges for atrial dimensions are recommended.

Transjugular intrahepatic portosystemic shunt in non-cirrhotic portal hypertension related to cystic fibrosis in a lung transplant patient.

Liver involvement is not uncommon in patients with cystic fibrosis (CF). Even if serious complications as non-cirrhotic portal hypertension, cirrhosis and liver failure rarely occur, they are associated with impaired survival and reduced quality of life. Herein, we have reported the first case of a patient with CF and non-cirrhotic portal hypertension who underwent transjugular intrahepatic portosystemic shunt placement for recurrent variceal bleeding after bilateral lung transplantation, and we have reviewed the available literature pertaining to this field.

Aerosol optical properties in the Arctic: The role of aerosol chemistry and dust composition in a closure experiment between Lidar and tethered balloon vertical profiles.

A closure experiment was conducted over Svalbard by comparing Lidar measurements and optical aerosol properties calculated from aerosol vertical profiles measured using a tethered balloon. Arctic Haze was present together with Icelandic dust. Chemical analysis of filter samples, aerosol size distribution and a full set of meteorological parameters were determined at ground. Moreover, scanning electron microscopy coupled with energy-dispersive X-ray (SEM-EDS) data were at disposal showing the presence of several mineralogical phases (i.e., sheet silicates, gypsum, quartz, rutile, hematite). The closure experiment was set up by calculating the backscattering coefficients from tethered balloon data and comparing them with the corresponding lidar profiles. This was preformed in three subsequent steps aimed at determining the importance of a complete aerosol speciation: (i) a simple, columnar refractive index was obtained by the closest Aerosol Robotic Network (AERONET) station, (ii) the role of water-soluble components, elemental carbon and organic matter (EC/OM) was addressed, (iii) the dust composition was included. When considering the AERONET data, or only the ionic water-soluble components and the EC/OM fraction, results showed an underestimation of the backscattering lidar signal up to 76, 53 and 45% (355, 532 and 1064 nm). Instead, when the dust contribution was included, the underestimation disappeared and the vertically-averaged, backscattering coefficients (1.45 ±â€¯0.30, 0.69 ±â€¯0.15 and 0.34 ±â€¯0.08 Mm-1 sr-1, at 355, 532 and 1064 nm) were found in keeping with the lidar ones (1.60 ±â€¯0.22, 0.75 ±â€¯0.16 and 0.31 ±â€¯0.08 Mm-1 sr-1). Final results were characterized by low RMSE (0.36, 0.08 and 0.04 Mm-1 sr-1) and a high linear correlation (R2 of 0.992, 0.992 and 0.994) with slopes close to one (1.368, 0.931 and 0.977, respectively). This work highlighted the importance of all the aerosol components and of the synergy between single particle and bulk chemical analysis for the optical property characterization in the Arctic.

Relation between conversion degree and cytotoxicity of a flowable bulk-fill and three conventional flowable resin-composites.

OBJECTIVE: The aim of this study is to evaluate if the cytotoxic effects of the Surefil SDR flow, bulk fill flowable composite resin and three conventional flowable materials (Venus Diamond Flow, Filtex Supreme XTE Flowable and Enamel plus HRi Flow) correlated with the conversion degree (DC); hardness and depth of cure are also assessed. MATERIALS AND METHODS: Disks of each materials--cured using LED lamp--are utilized to evaluate DC (by FT-IR technique), amount of leached monomers (by HPLC technique), hardness (by Vickers hardness tester) and cytotoxicity (by MTT test). RESULTS: All tested materials show light cytotoxic effects, independently from DC values. Both the latter parameter and the hardness, in fact, change in function of thickness and type of material. HPLC results show that the monomers amount leached from each specimen is influenced by thickness but it is always very low which justifies the absence of any cytotoxic effect. CONCLUSIONS: Our findings suggest that there are not statistically significant differences in cytotoxicity in all experimental conditions, notwithstanding the differences in hardness and in degree of conversion.

Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations.

Here we summarized what is known at the present about function, structure and effect of mutations in the human prolidase. Among the peptidases, prolidase is the only metalloenzyme that cleaves the iminodipeptides containing a proline or hydroxyproline residue at the C-terminal end. It is relevant in the latest stage of protein catabolism, particularly of those molecules rich in imino acids such as collagens, thus being involved in matrix remodelling. Beside its intracellular functions, prolidase has an antitoxic effect against some organophosphorus molecules, can be used in dietary industry as bitterness reducing agent and recently has been used as target enzyme for specific melanoma prodrug activation. Recombinant human prolidase was produced in prokaryotic and eukaryotic hosts with biochemical properties similar to the endogenous enzyme and represents a valid tool both to better understand the structure and biological function of the enzyme and to develop an enzyme replacement therapy for the prolidase deficiency (PD). Prolidase deficiency is a rare recessive disorder caused by mutations in the prolidase gene and characterized by severe skin lesions. Single amino acid substitutions, exon splicing, deletions and a duplication were described as causative for the disease and are mainly located at highly conserved amino acids in the sequence of prolidase from different species. The pathophysiology of PD is still poorly understood; we offer here a review of the molecular mechanisms so far hypothesized.

Alterations of energy metabolism and glutathione levels of HL-60 cells induced by methacrylates present in composite resins.

OBJECTIVES: Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA) are largely present in auto- or photopolymerizable composite resins. Since the polymerization reaction is never complete, these molecules are released into the oral cavity tissues and biological fluids where they could cause local adverse effects. The aim of this work was to verify the hypothesis that the biological effects of HEMA, TEGDMA and Bis-GMA - at a non-cytotoxic concentration - depend on the interaction with mitochondria and exert consequent alterations of energy metabolism, GSH levels and the related pathways in human promyelocytic cell line (HL-60). METHODS: The biological effects of methacrylic monomers were determined by analyzing the following parameters: GSH concentration, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activity, oxygen and glucose consumption and lactate production along with cell differentiation and proliferation. RESULTS: All monomers induced both cellular differentiation and decrease in oxygen consumption. Cells treated with TEGDMA and Bis-GMA showed a significant enhancement of glucose consumption and lactate production. TEGDMA and HEMA induced GSH depletion stimulating G6PDH and GR activity. CONCLUSIONS: All the monomers under study affect the metabolism of HL-60 cells and show differentiating activity. Since alterations in cellular metabolism occurred at compound concentrations well below cytotoxic levels, the changes in energy metabolism and glutathione redox balance could be considered as potential mechanisms for inducing clinical and sub-clinical adverse effects and thus providing useful parameters when testing biocompatibility of dental materials.

Molecular characterisation of six patients with prolidase deficiency: identification of the first small duplication in the prolidase gene and of a mutation generating symptomatic and asymptomatic outcomes within the same family.

Prolidase deficiency (PD) is a rare autosomal recessive connective tissue disorder caused by mutations in the prolidase gene. The PD patients show a wide range of clinical outcomes characterised mainly by intractable skin ulcers, mental retardation and recurrent respiratory infections. Here we describe five different PEPD mutations in six European patients. We identified two new PEPD mutant alleles: a 13 bp duplication in exon 8, which is the first reported duplication in the prolidase gene and a point mutation resulting in a change in amino acid E412, a highly conserved residue among different species. The E412K substitution is responsible for the first reported phenotypic variability within a family with severe and asymptomatic outcomes.

In vitro comparison of the cytotoxicity of two orthodontic composite resins.

AIM: Several studies have reported that dental resin-based materials release substances with biological activity: for this reason in this study we evaluated the in vitro cytopathic effects of a self-curing and a light-curing orthodontic composite resins by a cytotoxicity test. METHODS: The cytotoxic potential of specimens, prepared according to the manufacturer instructions, was evaluated using the thiazolyl blue tetrazolium bromide (MTT) assay on the mouse fibroblast cell line (3T3 Swiss) with 2 cells-material contact systems: the 24 h extracts method and the indirect toxicity method. RESULTS: The results obtained in this study elicit a close agreement between the 2 procedures; from the data obtained in the reported experimental conditions, it was possible to establish that the examined chemical-cured material is more cytotoxic than the light-cured one. CONCLUSIONS: From a clinical point of view, the photo-polymerizable resins are undoubtedly more useful in the daily practice, because of the larger precision of the bonding obtainable by the greater period available for setting the brackets before their lock. The results obtained in this study, even considering the limits of the in vitro tests, represent a further favourable feature of the light-curing composite resins. However, further investigations about the influence of polymerization methods of the materials on the biological effects are suggested to contribute to the determination of the best clinical operative conditions.

Gastric pH, sevelamer hydrochloride and omeprazole.

AIMS: Sevelamer hydrochloride is a polymer containing multiple amines (40% amine hydrochloride) separated by one carbon from the polymer backbone, and it is not absorbed by the intestine. These amines are partially protonated and interact with phosphate molecules through ionic and hydrogen bonding, therefore reducing phosphate absorption and lowering serum phosphate concentration. Alterations of gastric pH, in particular excessive alkalinization, could interfere with sevelamer phosphate binding capacity. CASE HISTORY: A 30-year-old dialysis patient affected by secondary hyperparathyroidism started sevelamer treatment, 4.8 g/day, with a basal serum phosphate of 6.9 mg/dl. The patient was also treated with omeprazole (20 mg/day) because of chronic gastritis. Phosphate levels normalized (4.2 mg/dl), but after four months of follow-up serum phosphate unexpectedly increased to 7.2 mg/dl. We found out that in the same period she had autonomously increased the dosage of omeprazole to 80 mg/day, due to worsening of dyspepsia. Gastric pH measurement showed a median level of 4.1, rather than the normal values of 1 - 2, indicating excessive pharmacological alkalinization. When omeprazole was reduced to the correct dose of 20 mg/day, we observed a rapid decrease of phosphate levels. CONCLUSION: This case report highlights the influence of gastric pH on sevelamer phosphate binding capacity. The high dose of omeprazole and the consequent excessive increase in gastric pH was probably responsible for a decreased phosphate binding capacity of sevelamer. When patients taking appropriate doses of sevelamer do not respond to treatment, a potential interaction with drugs determining an increase of gastric pH should be considered.

[Breathing sleep disturbances and occupational medicine: study of 20 clinical cases]. / Disturbi respiratori del sonno e medicina del lavoro: considerazioni su 20 casi clinici.

During 2004, in the Center for Sleep Disorders, a questionnaire including Epworth sleepiness scale (ES) was administered to 120 subjects; 20 male subjects of this group with elevated score (ES >14) were selected and submitted to polysomnography. Subjects, all in working age, were represented by 3 (15%) shift-workers, 9 (45%) drivers, 17 (85%) industrial workers (among those 5 building workers) and 3 (15%) employers. By polysomnography, moderatelsevere OSAHS was diagnosed in all subjects (40% moderate, 60% severe). CPAP (Continuous Positive Airway Pressure) therapy led to an improvement of clinical symptoms since the first month. Counselling of Occupational Medicine Physician with the Center for Sleep Disorders, was useful to direct the action of Competent Doctor, especially for jobs requiring high vigilance (drivers or shift-worker). The pass certificate for jobs with an high risk (alone, in high places, heavy means drivers) cannot avoid to evaluate this pathology, that is often associated to other related risk factors (obesity, hypertension, diabetes), because it compromises both the specific suitability and the protection of common health and safety.

[Evaluation of risks of biomechanical overload of the upper limb in physical kinesis therapists]. / Valutazione del rischio da sovraccarico biomeccanico dell'art superiore nei tecnici di fisiokinesiterapia.

Physical therapists are at risk for work-related musculoskeletal disorders (WMSDs). Contributing risk factors are job-task, mental stress and biomechanical overload, due to fixed and incorrect postures of neck, upper limbs and back. The purpose of this study was to investigate, by questionnaire and the use of muscle superficial EMG recording and analysis, the workload in the physical therapist activity, in order to provide suitable preventive measures.

[Longitudinal study of a population exposed to risk of biomechanical overload of the upper limb]. / Studio longitudinale su una popolazione esposta a rischio di sovraccarico biomeccanico dell'arto superiore.

One of the most important factors of the work-related musculoskeletal disorders of the upper extremities (WMSDs) is the biomechanical overload. The purpose of this study is to evaluate the possibility of the worker fitting to the job, to decrease the upper limb repetitive stress. In order to this aim, we have collected and compared, in different controls at the distance of two years, the clinical-anamnestic and instrumental data of a cohort of workers in a car industry.

Biodegradable microspheres for prolidase delivery to human cultured fibroblasts.

Prolidase deficiency (PD) is a rare autosomal recessive disorder caused by inadequate levels of the cytosolic exopeptidase prolidase (E.C. 3.4.13.9), for which there is not, as yet, a resolutive cure. We have investigated whether biodegradable microspheres loaded with prolidase could release active enzyme inside cells, to consider this system as a possible therapeutic approach for prolidase deficiency. Poly(lactide-co-glycolide) microspheres were prepared, modifying the classical double emulsion solvent evaporation method to mitigate the burst effect of the enzyme from the microspheres. Ex-vivo experiments were performed, by incubating microencapsulated prolidase with cultured fibroblasts from PD patients and from controls, to determine the amount of active enzyme delivered to the cells. The microparticulate drug delivery system described carried small amounts of active prolidase inside fibroblasts, ensuring a response to the intracellular accumulation of X-Pro dipeptides, the mechanism that is supposed to be responsible for the development of clinical manifestations of this disorder in man. A positive result of the presence of active enzyme inside cells was an improvement in fibroblast shape.

Cytotoxicity of a new endodontic filling material.

In vitro cell cultures have been widely used as a means of evaluating cytotoxicity of root canal filling materials. Following ANSI/ADA spec. no. 41, the aim of the present study was to investigate the biological compatibility of a new sealer (FibreFill) and compare it with some commercially available endodontic sealers (Bioseal and Acroseal). Mouse 3T3 fibroblasts were seeded and cultured and subsequently extracts of the cements were added. After 24 hours incubation, the cellular vitality of fibroblasts was evaluated by the neutral red uptake test (NRU), which measures the membrane permeability. Data were collected and statistically analysed. Results showed that all tested materials exhibited mild cytotoxic effects, which are compatible with normal clinical use, and no statistically significant difference was noted between FibreFill and the other tested materials. Therefore, selection amongst these sealers should be based on other factors.

Human salivary peptides derived from histatins.

Human saliva from a healthy donor was subjected to fractionation by gel chromatography and six pools were collected and analysed by MALDI-TOF-MS and HPLC-ESI-MS. Three peptides, corresponding to 888.3, 687.3, and 524.1 amu and SNYLYDN, YLYDN, and LYDN sequences (determined by automated Edman sequencing), were isolated from pool 4. YLYDN was not previously described in human saliva. The peptides show the common C-terminal sequence of histatin 3 and histatin 1. To exclude the possibility that the three peptides were an artifact of the purification procedure, nine samples of human saliva were collected from healthy donors, immediately acidified with 0.2% TFA, and analysed by RP-HPLC-ESI-MS. The three peptides were detected in all the analyzed samples. SNYLYDN was always found at a concentration higher than that of YLYDN and LYDN. A correlation analysis performed on quantitative data indicated that the three peptides derive only from histatin 3. Other already known histatins also were searched for in the chromatogram. Histatins 1, 2, 3, 5, 6, 7, 8, and 10 were observed, although not in all samples analyzed, whereas other minor histatins were not detected.

Therapeutic apheresis exchange in two patients with prolidase deficiency.

BACKGROUND: Prolidase deficiency is a rare genetic disorder for which a cure has not yet been found. OBJECTIVES: To assess the effectiveness of apheresis exchange as a new therapeutic approach. METHODS: Apheresis exchanges were repeated monthly for four consecutive months, in parallel, on two patients, replacing prolidase-deficient red blood cells with normal filtered cells. Prolidase activity and urinary dipeptides were determined at regular intervals. RESULTS: The constant presence of active prolidase inside cells allowed a continuous, although partial, degradation of imidodipeptides, with a concomitant improvement of skin ulceration. CONCLUSIONS: Apheresis exchange could be a reasonable way of obtaining a clinical improvement in these patients.

Surfactant apoprotein A modulates interleukin-8 and monocyte chemotactic peptide-1 production.

Previous studies have shown that surfactant apoprotein A (SP-A) and natural or synthetic surfactant can modulate the release of pro-inflammatory cytokines from alveolar mononuclear phagocytes. The aim of this study was to assess whether SP-A or Surfactant (Surf) from patients with pulmonary alveolar proteinosis (PAP) can affect the release of two chemokines (interleukin (IL)-8 and monocyte chemtactic peptide (MCP)-1) from human monocytes and rat lung type-II cells. In addition IL-8 and MCP-1 levels were assessed in the brochoalveolar lavage fluid (BALF) of seven patients with PAP and compared with those in a group of control subjects (n=5). SP-A, tested over a wide range of concentrations, significantly increased IL-8 and MCP-1 release from monocytes. SP-A retained its activity after collagenase digestion, but was not active after heat treatment. The release of IL-8 by monocytes was also stimulated by Surf. Finally, median BALF IL-8 and MCP-1 levels in PAP patients were significantly higher than in controls (9.50 and 9.51 pg x mL(-1) in controls versus 151.95 and 563.70 pg x mL(-1) in PAP, respectively) and significantly correlated with SP-A concentrations in BALF. Overall the results of this study support the view that the high content of alveolar surfactant apoprotein A may contribute to the upregulation of chemokine release in pulmonary alveolar proteinosis, thus contributing to airway inflammation.

Urinary desmosine excretion in acute exacerbations of COPD: a preliminary report.

Desmosine (DES) is an elastin-derived, cross-link amino acid, which is not metabolized; hence, its urinary levels reflect elastin breakdown. We hypothesized that elastin degradation should increase as a result of increased lung inflammation during an acute exacerbation of COPD and should decrease after recovery. To test this hypothesis we measured DES in three urine samples from nine COPD subjects during the first 5 days of an acute exacerbation and at 2 months after recovery. We also measured forced expiratory volume in 1 sec (FEV1) to monitor the effects ofthe exacerbation on ventilatory function. The mean (SD) FEV1 was 45 (15)% predicted during the exacerbation and 57.8 (16)% predicted 2 months later (P=0.00001). The mean (SD) DES excretion was 25.3 (9) microg g(-1) creatinine at day 1;23.5 (9) at day 3 and 24 (9) at day 5 of the exacerbation. The mean (SD) urinary DES excretion 60 days after discharge was 20.9 (7) microg g(-1) creatinine (P=0.049) in comparison with the mean of the three acute-phase values. The size of the increase in desmosine excretion during exacerbation is small, 3.2 microg g(-1) creatinine or 16% of the recovery desmosine value. We conclude that there is a small but statistically significant increase in lung elastin breakdown in the body during an acute exacerbation of COPD.