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1.
Prog Orthod ; 23(1): 12, 2022 Apr 11.
Article in English | MEDLINE | ID: mdl-35399128

ABSTRACT

BACKGROUND: Since their introduction in orthodontics, clear aligners have been appreciated by patients, including adults, for their comfort and low aesthetic impact. Despite the enormous mobilization of financial resources all over the world aimed at producing new product lines, few clinical studies or high-quality evidence have been produced regarding the real effectiveness of such treatment. Given the few limited kinds of research on the subject, this study aims to produce and critically evaluate other data, to establish the concrete reliability of clear aligners in orthodontic therapy. RESULTS: Significant sample sizes were obtained for intrusion, vestibulo/lingual (V/L) crown tipping, and rotation. The overall accuracy for rotation resulted in 86%, ranging from 96% for maxillary central incisors to 70.4% for mandibular first premolars. The intrusion was registered only for anterior teeth; mean predictability was 92%, with the worst result being 86.7% for mandibular canines and the best being 98% for mandibular central incisors. V/L tipping was the most accurate movement: 93.1% of the prescribed movement was completed. Maxillary central incisors showed the lowest accuracy (80.7%), while mandibular central incisors were the highest (97.5%). CONCLUSIONS: The present study provided reassuring data in support of the accuracy of the Invisalign® system. Vestibulo/lingual tipping was the most predictable movement, while rotation of canines, premolars, and lateral incisors were the least predictable. Intrusion resulted highly predictable up to 2 mm. When careful treatment planning follows a correct diagnosis, together with the use of auxiliary features and refinements, the planned results can be achieved in a clinically successful way. Authors believe that there is a major need for greater samples to overcome bias related to variables if we want to answer the unsolved questions, such as the predictability of severe malocclusions treatment.


Subject(s)
Orthodontic Appliances, Removable , Tooth Movement Techniques , Cuspid , Humans , Incisor , Orthodontic Appliance Design , Reproducibility of Results , Tooth Movement Techniques/methods
2.
Plant Methods ; 16: 61, 2020.
Article in English | MEDLINE | ID: mdl-32377221

ABSTRACT

BACKGROUND: Reproductive success in seed plants depends on a healthy fruit and seed set. Normal seed development in the angiosperms requires the production of functional female gametophytes. This is particularly evident in seedless cultivars where defects during megagametophyte's developmental processes have been observed through cytohistological analysis. Several protocols for embryo sac histological analyses in grapevine are reported in literature, mainly based on resin- or paraffin-embedding approaches. However their description is not always fully exhaustive and sometimes they consist of long and laborious steps. The use of different stains is also documented, some of them, such as hematoxylin, requiring long oxidation periods of the dye-solution before using it (from 2 to 6 months) and/or with a differentiation step not easy to handle. Paraffin-embedding associated to examination with light microscope is the simplest methodology, and with less requirements in terms of expertise and costs, achieving a satisfactory resolution for basic histological observations. Safranin O and fast green FCF is an easy staining combination that has been applied in embryological studies of several plant species. RESULTS: Here we describe in detail a paraffin-embedding method for the examination of grapevine ovules at different phenological stages. The histological sample preparation process takes 1 day and a half. Sections of 5 µm thickness can be obtained and good contrast is achieved with the safranin O and fast green FCF staining combination. The method allows the observation of megasporogenesis and megagametogenesis events in the different phenological stages examined. CONCLUSIONS: The histological sample preparation process proposed here can be used as a routine procedure to obtain embedded ovaries or microscope slides that would require further steps for examination. We suggest the tested staining combination as a simple and viable technique for basic screenings about the presence in grapevine of a normally and fully developed ovule with embryo sac cells, which is therefore potentially functional.

3.
Euro Surveill ; 24(23)2019 06.
Article in English | MEDLINE | ID: mdl-31186078

ABSTRACT

Between October and December 2018, several clinicians in Norway reported an increase in scabies diagnoses. We compared data from the Norwegian Syndromic Surveillance System on medical consultations for mite infestations with scabies treatment sales data to investigate this reported increase. From 2013 to 2018, consultations and sales of scabies treatments had almost increased by threefold, particularly affecting young adults 15-29 years. We recommend to increase awareness among clinicians to ensure timely diagnosis and treatment.


Subject(s)
Mite Infestations/epidemiology , Scabies/epidemiology , Adolescent , Adult , Aged , Child , Child, Preschool , Disease Outbreaks , Humans , Incidence , Infant , Infant, Newborn , Middle Aged , Norway/epidemiology , Scabies/diagnosis , Sentinel Surveillance , Young Adult
4.
Epidemiol Infect ; 145(10): 2072-2080, 2017 07.
Article in English | MEDLINE | ID: mdl-28446259

ABSTRACT

The annual incidence of listeriosis in Italy is lower (0·19-0·27 per 100 000 inhabitants per year) than in Europe (0·34-0·52 per 100 000 inhabitants per year). Since the observed incidence of listeriosis may be biased downward for underdiagnosis or under-reporting, this work aims to estimate the real incidence of listeriosis during a 9-year period in the Lombardy region, Italy. Data on listeriosis cases were collected from national mandatory notification system (MAINF) and Laboratory-based Surveillance System (LabSS). The two sources were cross-matched and capture-recapture method was applied to estimate the number of undetected cases and the real incidence of invasive listeriosis. Five hundred and eighty invasive listeriosis cases were detected by the two sources between 2006 and 2014: 50·2% were identified only via MAINF, 16·7% were recorded only via LabSS, overlaps occurred in 192 cases (33·1%). The mean annual incidence detected only by MAINF was 0·56 per 100 000 inhabitants, which rose to 0·67 per 100 000 considering also the cases detected by LabSS. The capture-recapture method allowed to estimate an incidence of 0·84 per 100 000. The high incidence of listeriosis may be due to improved sensitivity of the surveillance system, but also reflect a real increase, associated with an increased population at risk.


Subject(s)
Listeria monocytogenes/physiology , Listeriosis/epidemiology , Population Surveillance , Female , Humans , Incidence , Italy/epidemiology , Listeriosis/microbiology , Male
5.
Waste Manag ; 48: 209-217, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26586420

ABSTRACT

This paper evaluates the effect of ultrasonication on anaerobic biodegradability of lignocellulosic residues. While ultrasonication has been commonly applied as a pre-treatment of the feed substrate, in the present study a non-conventional process configuration based on recirculation of sonicated digestate to the biological reactor was evaluated at the lab-scale. Sonication tests were carried out at different applied energies ranging between 500 and 50,000kJ/kg TS. Batch anaerobic digestion tests were performed on samples prepared by mixing sonicated and untreated substrate at two different ratios (25:75 and 75:25 w/w). The results showed that when applied as a post-treatment of digestate, ultrasonication can positively affect the yield of anaerobic digestion, mainly due to the dissolution effect of complex organic molecules that have not been hydrolyzed by biological degradation. A good correlation was found between the CH4 production yield and the amount of soluble organic matter at the start of digestion tests. The maximum gain in biogas production was 30% compared to that attained with the unsonicated substrate, which was tentatively related to the type and concentration of the metabolic products.


Subject(s)
Biofuels , Refuse Disposal/methods , Solid Waste , Ultrasonics/methods , Anaerobiosis , Biodegradation, Environmental , Food , Hydrolysis , Lignin/chemistry , Methane/biosynthesis , Sewage/chemistry
6.
Environ Technol ; 35(9-12): 1462-9, 2014.
Article in English | MEDLINE | ID: mdl-24701944

ABSTRACT

Activated sludge process is the most widely diffused system to treat wastewater to control the discharge of pollutants into the environment. Microorganisms are responsible for the removal of organic matter, nitrogen, phosphorous and other emerging contaminants. The environmental conditions of biological reactors significantly affects the ecology of the microbial community and, therefore, the performance of the treatment process. In the last years, ozone has been used to reduce excess sludge production by wastewater treatment plants (WWTPs), whose disposal represents one of the most relevant operational costs. The ozonation process has demonstrated to be a viable method to allow a consistent reduction in excess sludge. This study was carried out in a full-scale plant treating municipal wastewater in two parallel lines, one ozonated in the digestion tank and another used as a control. Bacterial communities of samples collected from both lines of digestion thanks were then compared to assess differences related to the ozonation treatment. Data were then analysed with terminal restriction fragment length polymorphism (T-RFLP) analysis on 16S rRNA gene. Differences between bacterial communities of both treated and untreated line appeared 2 weeks after the beginning of the treatment. Results demonstrated that ozonation treatment significantly affected the activated sludge in WWTP.


Subject(s)
Microbial Consortia , Ozone , Sewage , Waste Management , Polymorphism, Restriction Fragment Length
7.
Biomed Res Int ; 2013: 935351, 2013.
Article in English | MEDLINE | ID: mdl-23865075

ABSTRACT

Kidney dosimetry in (177)Lu and (90)Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with (177)Lu DOTATATE and 30 with (177)Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6 h and the 3 d points. We found that data should be collected until 100 h for (177)Lu therapy and 70 h for (90)Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (t-test, P < 0.10), with DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05).


Subject(s)
Kidney/diagnostic imaging , Octreotide/analogs & derivatives , Organometallic Compounds/pharmacokinetics , Radiometry , Receptors, Peptide/metabolism , Aged , Aged, 80 and over , Calibration , Cohort Studies , Humans , Kinetics , Middle Aged , Octreotide/pharmacokinetics , Risk Factors , Time Factors , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed
8.
Ann Oncol ; 24(3): 693-701, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23131390

ABSTRACT

BACKGROUND: To obtain a prognostic stratification model for resected gastric cancer patients. PATIENTS AND METHODS: Clinicopathological and molecular data (expression of Cdx2, Apc, ß-catenin, E-cadherin, Fhit, p53, and human epidermal growth factor receptor-2 (Her2); HER2 and TOPO2A gene copy number; PIK3CA mutations; microsatellite instability) were correlated to cancer-specific/overall survival (CSS/OS) using a Cox model. Individual patient probability (IPP) was estimated by logistic equation. A continuous score to identify risk-classes was derived according to the model ratios. RESULTS: Two-hundred eight patients were studied (median follow-up 20 months). At multivariate analysis, sex, stage, margins, location, nodes, Apc, and Fhit were independent predictors for CSS; the same factors (and age and Her2, except Fhit) predicted OS. Multivariate model predicted IPP with high prognostic accuracy (0.90 for CSS; 0.91 for OS). A two-class model significantly separated low- and high-risk patients for CSS (23.4% and 85.6%, P < 0.0001) and OS (21.4% and 82.0%, P < 0.0001). A three-class model differentiated low-, intermediate-, and high-risk patients for CSS (6.3%, 35.3%, and 88.0%, P < 0.0001) and OS (6.1%, 34.6%, and 86.5%, P < 0.0001). CONCLUSIONS: A risk classification system comprising the immunohistochemical expression of three proteins (Apc, Fhit, and Her2) and five clinicopathological parameters (stage, resected nodes, margins, location, and sex) accurately separates the resected gastric cancer patients into three classes of risk.


Subject(s)
Acid Anhydride Hydrolases/metabolism , Adenomatous Polyposis Coli Protein/metabolism , Carcinoma/metabolism , Neoplasm Proteins/metabolism , Receptor, ErbB-2/metabolism , Stomach Neoplasms/metabolism , Adenomatous Polyposis Coli Protein/genetics , Adult , Aged , Aged, 80 and over , Area Under Curve , Carcinoma/mortality , Carcinoma/secondary , Carcinoma/surgery , DNA Mutational Analysis , Female , Gene Expression , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , ROC Curve , Receptor, ErbB-2/genetics , Retrospective Studies , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
9.
Metab Brain Dis ; 27(4): 567-72, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22791269

ABSTRACT

Awareness of previous hepatic encephalopathy (HE) and compliance with treatment can probably reduce HE recurrence. The aim of this study was to assess the degree of awareness of previous HE and its treatment in a group of cirrhotic patients and their caregivers. Thirty-five cirrhotic patients with a history of HE and their caregivers (n = 31) were enrolled. Patients underwent evaluation of HE (clinical, psychometry and electroencephalography), quality of life (SF36 questionnaire), and awareness of HE/treatment on an ad hoc questionnaire (QAE). Caregivers underwent the QAE plus the Caregiver Burden Inventory. On the day of study, 7 patients were unimpaired, 8 had minimal and 20 low-grade overt HE. Of the patients, 37 % were aware of previous HE, 6 % of being on treatment and 6 % understood treatment effects. Of the caregivers, 48 % were aware of previous HE, 6 % of their relative being on treatment and 6 % understood treatment effects. Significant correlations were observed between neuropsychiatric status/linear HE indices and both the patients' quality of life and the caregivers' burden. In conclusion, HE awareness was poor in both patients and caregivers, most likely in relation to insufficient/inadequate provision of information.


Subject(s)
Caregivers/psychology , Hepatic Encephalopathy/psychology , Aged , Cost of Illness , Educational Status , Electroencephalography , Female , Health Knowledge, Attitudes, Practice , Hepatic Encephalopathy/therapy , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/psychology , Male , Mental Disorders/etiology , Mental Disorders/psychology , Mental Disorders/therapy , Middle Aged , Neuropsychological Tests , Psychometrics , Quality of Life , Surveys and Questionnaires
10.
Q J Nucl Med Mol Imaging ; 55(5): 560-6, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21242948

ABSTRACT

AIM: Patients candidate to radioiodine treatment of autonomous functioning thyroid nodule (AFTN) are characterized by a wide range of nodule volumes with different shapes. To optimize the treatment, pretherapeutic dosimetry should account also for the dependence of deposited energy on the nodule geometry. METHODS: We developed a Monte Carlo code in Geant4 to simulate the interaction of beta and gamma radiations emitted by Na-131I into ellipsoidal volumes of soft tissue homogeneously uptaking the radionuclide, surrounded by a simplified antropomorphic phantom. We simulated 9 volumes between 0.1 and 50 cm3, each one with 8 different ellipsoidal shapes. We considered the data of 10 patients affected by AFTN, whose nodule volumes were in the range 1-40 cm3, who underwent radioiodine therapy following the traditional dosimetric approach. The patients underwent ultrasonographic (US) study, in order to determine the nodule volume, and radioiodine thyroid uptake measurements between 3 and 168 hours after radioiodine tracer dose administration. RESULTS: We found an analytical relationship between the average deposited energy and the ellipsoid's semiaxes and we included it in the formula for the calculation of activity to be administered, A0. For the 10 patients studied, A0 calculated with our approach ranges from +9% to -2% with respect to the one calculated with the traditional formula. CONCLUSION: The proposed model, accounting for the dependence of beta and gamma absorbed fractions from nodule volume and shape, can lead to a more accurate estimation of A0 during AFTN therapy. Since the measurement of nodule axes is routinely obtained from pretherapeutic US, our approach can be introduced in the clinical practice without changing the diagnostic pre-therapeutic protocol.


Subject(s)
Iodine Radioisotopes/therapeutic use , Thyroid Nodule/radiotherapy , Aged , Female , Humans , Male , Middle Aged , Models, Theoretical , Monte Carlo Method , Phantoms, Imaging , Radiotherapy Dosage , Thyroid Nodule/pathology
11.
Phys Med Biol ; 56(2): 357-65, 2011 Jan 21.
Article in English | MEDLINE | ID: mdl-21160113

ABSTRACT

We applied a Monte Carlo simulation in Geant4 in order to calculate the absorbed fractions for monoenergetic electrons in the energy interval between 10 keV and 2 MeV, uniformly distributed in ellipsoids made from soft tissue. For each volume, we simulated a spherical shape, four oblate and four prolate ellipsoids, and one scalene shape. For each energy and for every geometrical configuration, an analytical relationship between the absorbed fraction and a 'generalized radius' was found, and the dependence of the fit parameters from electron energy is discussed and fitted by proper parametric functions. With the proposed formulation, the absorbed fraction for electrons in the 10-2000 keV energy range can be calculated for all volumes and for every ellipsoidal shape of practical interest. This method can be directly applied to evaluation of the absorbed fraction from the radionuclide emission of monoenergetic electrons, such as Auger or conversion electrons. The average deposited energy per disintegration in the case of extended beta spectra can be evaluated through integration. Two examples of application to a pure beta emitter such as (90)Y and to (131)I, whose emission include monoenergetic and beta electrons plus gamma photons, are presented. This approach represent a generalization of our previous studies, allowing a comprehensive treatment of absorbed fractions from electron and photon sources uniformly distributed in ellipsoidal volumes of any ellipticity and volume, in the whole range of practical interest for internal dosimetry in nuclear medicine applications, as well as in radiological protection estimations of doses from an internal contamination.


Subject(s)
Monte Carlo Method , Radiometry/methods , Radiotherapy/methods , Absorption , Algorithms , Computer Simulation , Electrons , Photons , Radioisotopes/chemistry
12.
Diabet Med ; 27(10): 1195-200, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20854389

ABSTRACT

AIMS: Permanent neonatal diabetes is a rare condition affecting 1 in 300,000-400,000 live births; only in 60% of cases it is possible to identify the genetic defect. The condition of pancreatic agenesis is rarer still. Only two genes are known to determine this phenotype: PDX-1 and PTF1A. Congenital heart defects are among the most common developmental anomalies, affecting 1% of newborns, and the GATA4 gene is less frequently involved in these disorders. An Italian child with pancreatic agenesis and an atrial septal defect was genetically investigated to elucidate whether the association of the two pathologies was casual, or represented a new pancreatic/cardiac syndrome. METHODS: A panel of pancreas development genes, including GCK, Kir6.2, PTF1A, PDX-1, HNF-1A, NgN3, SOX17, SOX7, SOX9, INS, HNF1-B and SUR1 plus the GATA4 gene, were screened for characterization of pancreatic agenesis and cardiac defect. RESULTS: Screening for genes causing permanent neonatal diabetes was negative. A novel mutation in GATA4 (c1512C>T) was detected and functional characterization confirmed a reduced activity of the protein. In the family members, the GATA4 mutation co-segregates with a cardiac phenotype, but not with pancreatic agenesis. CONCLUSIONS: We describe the first report of pancretic agenesis with an associated cardiac defect and a mutation in the GATA4 gene. We could not establish that the GATA4 mutation was causative for pancreatic agenesis and further genetic investigation to detect the genetic cause of the pancreas agenesis was unsuccessful. We conclude that, the two pathologies are attributable to two independent events.


Subject(s)
Diabetes Mellitus, Type 1/genetics , GATA4 Transcription Factor/genetics , Heart Septal Defects, Atrial/genetics , Child, Preschool , Congenital Abnormalities/genetics , DNA Mutational Analysis , Diabetes Mellitus, Type 1/diagnosis , Heart Septal Defects, Atrial/diagnosis , Humans , Magnetic Resonance Imaging , Male , Mutation , Pancreas/abnormalities
13.
Phys Med Biol ; 54(20): N479-87, 2009 Oct 21.
Article in English | MEDLINE | ID: mdl-19779222

ABSTRACT

We studied through Monte Carlo simulation in Geant4 the absorbed fractions for photons, characterized by energies ranging from 10 keV to 1000 keV, which can be emitted by gamma radionuclides uniformly distributed in ellipsoidal volumes of soft tissue. The same analytical relationship between absorbed fraction and the 'generalized radius' as introduced in a previous paper was found, and the dependence of its parameters rho(0) and s on photon energy is discussed and fitted by suitably chosen parametric functions. As a consequence, the absorbed fraction for photons in the 10-1000 keV energy range can be calculated for all volumes and for every ellipsoidal shape of practical interest. Such results can be a useful complement for the dosimetry of beta- and gamma-emitting radionuclides during internal radiotherapy or gamma emitters employed in diagnostic nuclear medicine.


Subject(s)
Radiometry/methods , Adsorption , Algorithms , Computer Simulation , Humans , Monte Carlo Method , Photons , Radioisotopes/chemistry , Radiotherapy/methods , Radiotherapy Dosage
14.
Phys Med Biol ; 54(13): 4171-80, 2009 Jul 07.
Article in English | MEDLINE | ID: mdl-19521004

ABSTRACT

We developed a Monte Carlo simulation in Geant4 to calculate the absorbed fractions for electrons emitted by (199)Au, (177)Lu, (131)I, (153)Sm, (186)Re and (90)Y, characterized by average energies ranging from 86 keV to 949 keV, uniformly distributed in ellipsoidal volumes of soft tissue. Code validation results with respect to reference data for doses, ranges and absorbed fractions in spheres are presented. An analytical relationship between the absorbed fraction and a 'generalized radius' is introduced in analogy with the transfer function of a first-order high-pass filter, and the dependence of its parameters rho(0) and s from the average electron energy and range is discussed. A generalization for the estimation of absorbed fractions for other radionuclides is also proposed. Such results can be useful to improve accuracy and easiness of calculation in dosimetry during internal radiotherapy.


Subject(s)
Models, Biological , Neoplasms/physiopathology , Neoplasms/radiotherapy , Radioisotopes/therapeutic use , Radiometry/methods , Radiotherapy, Computer-Assisted/methods , Beta Particles/therapeutic use , Computer Simulation , Humans , Radiopharmaceuticals/therapeutic use , Radiotherapy Dosage
16.
J Radiol Prot ; 29(2): 239-50, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19454797

ABSTRACT

We have developed a Monte Carlo simulation in Geant4 to compare the attenuation properties and the bremsstrahlung radiation yield of different types of plastic materials employed as shields for beta- radioactive sources. Code validation results against Sandia and NIST data are presented. For polypropylene (C3H6), polystyrene (C2H3), polyamide nylon-6 (C6H11ON), poly-methyl methacrylate (C5H8O2), polycarbonate (C16H6O3), polyethylene terephthalate (C10H8O4), polyvinyl chloride (C2H3Cl) and polytetrafluoroethylene (C2F4) we evaluated the mean and maximum ranges for electrons originating from 90Sr and 90Y, as well as the number and spectrum of the bremsstrahlung x-rays produced. Significant differences appear between the various materials, and the choice of the best one also depends on the physical properties requested for each specific application.


Subject(s)
Models, Statistical , Plastics/chemistry , Radiation Protection/instrumentation , Radiation Protection/methods , Radiometry , Beta Particles , Computer Simulation , Materials Testing , Monte Carlo Method , Radiation Dosage , Scattering, Radiation
17.
Diabet Med ; 25(6): 651-6, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18544102

ABSTRACT

AIMS: Heterozygous activating mutations in KCNJ11, which encodes the Kir6.2 subunit of the pancreatic ATP-sensitive potassium (K(ATP)) channel, cause both permanent and transient neonatal diabetes. Identification of KCNJ11 mutations has important therapeutic implications, as many patients can replace insulin injections with sulphonylurea tablets. The aim was to determine if a KCNJ11 mutation was responsible for a dominantly inherited form of diabetes mellitus, showing variability in age at diagnosis, in an Italian family. METHODS: We sequenced KCNJ11 in members of a three-generation family with variable phenotypes of dominantly inherited diabetes mellitus. One had transient early-onset diabetes, one had impaired glucose tolerance during the second pregnancy, and two had young-onset diabetes. None of the subjects showed permanent neonatal diabetes or neurological symptoms. RESULTS: A novel heterozygous mutation (c. 679C-->G and c. 680A-->T) was identified, resulting in a GAG-->CTG (E227L) substitution in KCNJ11. Functional studies of recombinant heterozygous K(ATP) channels revealed a small reduction in channel inhibition by ATP (IC(50) of 15 micromol/l and 38 micromol/l for wild-type and heterozygous channels, respectively) and an increase in the resting K(ATP) current. This would be expected to impair insulin secretion. The results are in agreement with the mild phenotype of the patients. CONCLUSIONS: Our results broaden the spectrum of diabetes phenotypes resulting from KCNJ11 mutations. They indicate testing for KCNJ11 mutations should be considered not only for neonatal diabetes but also for other forms of dominantly inherited diabetes with later onset, especially where these are associated with a low body mass index and low birth weight.


Subject(s)
Diabetes Mellitus/genetics , Mutation/genetics , Potassium Channels, Inwardly Rectifying/genetics , Adult , Female , Heterozygote , Humans , Male , Pedigree , Phenotype , Pregnancy
18.
Cell Biol Toxicol ; 24(6): 541-52, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18228151

ABSTRACT

The aim of the present study was to investigate on the suitability of the sea urchin as a sentinel organism for the assessment of the macro-zoobenthos health state in bio-monitoring programmes. A field study was carried out during two oceanographic campaigns using immuno-competent cells, the coelomocytes, from sea urchins living in a marine protected area. In particular, coelomocytes subpopulations ratio and heat shock protein 70 (HSC70) levels were measured in specimens of Paracentrotus lividus (Lamark, 1816) collected in two sampling sites, namely Pianosa and Caprara Islands, both belonging to the Tremiti Island Marine Protected Area (MPA) in the Southern Adriatic Sea, Italy. By density gradients separation performed on board the Astrea boat, we found an evident increase in red amoebocytes, a subpopulation increasing upon stress, in those specimens collected around Pianosa (strictly protected area with no human activities allowed), unlike those collected around Caprara (low restrictions for human activities). Likewise, we found higher HSC70 protein levels in the low impacted site (Pianosa) by Western blots on total coelomocyte lysates. The apparent paradox could be explained by the presence in the Pianosa sampling area of contaminating remains from Second World War conventional ammunitions and a merchant boat wreck. Metal determination performed using sea urchin gonads by inductively coupled plasma atomic emission spectrometry (ICP-AES) revealed higher Fe and lower Zn levels around Pianosa with respect to Caprara, in accordance with the persistent contaminating metal sources, and thus calling for remediation measures. Taken all together, our results confirm the feasibility of using sea urchin coelomocytes as biosensors of environmental stress.


Subject(s)
Biosensing Techniques , Environment , Geography , Sea Urchins/cytology , Seawater , Stress, Physiological , Animals , Biomarkers/metabolism , Gonads/chemistry , Gonads/drug effects , HSC70 Heat-Shock Proteins/metabolism , Italy , Metals/analysis , Phenotype , Sea Urchins/drug effects , Sea Urchins/immunology , Stress, Physiological/drug effects , Trace Elements/analysis , Water Pollutants, Chemical/toxicity
19.
Biochem Soc Trans ; 34(Pt 6): 1228-30, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17073791

ABSTRACT

TNT (2,4,6-trinitrotoluene) was the most common nitro aromatic explosive available in World War II ammunitions. The presence of ordnance dumped at sea might represent a great concern for marine species living close to dumping sites and the toxicological properties of the chemicals released into the marine environments need to be evaluated. The aim of the present study is to investigate the involvement of CYP (cytochrome P450) system in the metabolism of TNT in marine organisms by using the European eel [Anguilla anguilla (Linnaeus, 1758)] as model species. In vivo exposure to sublethal concentration of TNT (0.5, 1 and 2.5 mg/l) leads to a significant decrease in the phase I CYP1A catalytic activities such as EROD (7-ethoxyresorufin-O-de-ethylase) and MROD (7-methoxyresorufin-O-de-ethylase). On the opposite, a significant increase in NADPH cytochrome c reductase activity as well as phase II UDP-glucuronosyltransferase activity is observed. An inhibition at enzyme level is hypothesized for both CYP1A enzymes, also confirmed by a similar decrease observed after in vitro exposure. An active role of NADPH cytochrome c reductase and phase II enzymes in the TNT metabolism may also be hypothesized.


Subject(s)
Anguilla/metabolism , Cytochrome P-450 Enzyme System/metabolism , Trinitrotoluene/metabolism , Animals , Catalysis , Cytochrome P-450 CYP1A1/metabolism , Kinetics
20.
Inhal Toxicol ; 13(11): 1033-45, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11696872

ABSTRACT

The subchronic inhalation toxicity of ammonium persulfate was characterized using Sprague-Dawley rats (20/sex/group) at respirable dust concentrations of 0, 5.0, 10.3, and 25 mg/m(3). Whole-body exposures were conducted 6 h/day, 5 days/wk for 13 wk. Gravimetric airborne test material samples were taken daily and particle size samples were taken weekly from each exposure chamber for analysis. Ten animals/sex/group were necropsied after 13 wk of exposure, and 5 animals/sex/group were held for 6- and 13-wk recovery periods. Animals were observed for clinical signs. Effects on body weight, food consumption, clinical chemistry and hematology, ophthalmologic parameters, organ weights, gross lesions, and histopathology were evaluated. There were no exposure-related deaths during the study. Rales and increased respiration rate were noted in both males and females in the 25 mg/m(3) group, and in a few animals in the 10.3 mg/m(3) group. The incidence of these clinical signs decreased to zero during the first few weeks of the recovery period. Body weights for both males and females in the 25 mg/m(3) group were significantly depressed during most of the exposure period compared to the control group. By the end of the recovery period, body weights for the exposed animals were similar to the control group values. Lung weights were elevated in the 25 mg/m(3) group after 13 wk of exposure, but were similar to controls at 6 wk postexposure. Irritation of the trachea and bronchi/bronchiole was noted microscopically after 13 wk of exposure to 25 mg/m(3). These lesions had recovered by 6 wk postexposure. Based on the results of this study, the no-observed-adverse-effect level (NOAEL) was 10.3 mg/m(3), while the no-observed-effect level (NOEL) for exposure of rats to a dust aerosol of ammonium persulfate was 5.0 mg/m(3).


Subject(s)
Ammonium Sulfate/toxicity , Respiratory System/pathology , Ammonium Sulfate/administration & dosage , Animals , Body Weight , Dose-Response Relationship, Drug , Dust , Eating , Female , Inhalation Exposure , Male , No-Observed-Adverse-Effect Level , Rats , Rats, Sprague-Dawley , Respiratory System/drug effects
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