Adenosine negatively regulates duodenal motility in mice: role of A1 and A2a receptors .

BACKGROUND AND PURPOSE: Adenosine is considered to be an important modulator of intestinal motility. This study was undertaken to investigate the role of adenosine in the modulation of contractility in the mouse duodenum and to characterize the adenosine receptor subtypes involved. EXPERIMENTAL APPROACH: RT-PCR was used to investigate the expression of mRNA encoding for A(1), A(2A), A(2B) and A(3) receptors. Contractile activity was examined in vitro as changes in isometric tension. KEY RESULTS: In mouse duodenum, all four classes of adenosine receptors were expressed, with the A(2B) receptor subtype being confined to the mucosal layer. Adenosine caused relaxation of mouse longitudinal duodenal muscle; this was antagonized by the A(1) receptor antagonist and mimicked by N(6)-cyclopentyladenosine (CPA), selective A(1) agonist. The relaxation induced by A(1) receptor activation was insensitive to tetrodotoxin (TTX) or N(ω)-nitro-l-arginine methyl ester (l-NAME). Adenosine also inhibited cholinergic contractions evoked by neural stimulation, effect reversed by the A(1) receptor antagonist, but not myogenic contractions induced by carbachol. CPA and 2-p-(2-carboxyethyl) phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride hydrate (CGS-21680), A(2A) receptor agonist, both inhibited the nerve-evoked cholinergic contractions. l-NAME prevented only the CGS-21680-induced effects. S-(4-Nitrobenzyl)-6-thioinosine, a nucleoside uptake inhibitor, reduced the amplitude of nerve-evoked cholinergic contractions, an effect reversed by an A(2A) receptor antagonist or l-NAME. CONCLUSIONS AND IMPLICATIONS: Adenosine can negatively regulate mouse duodenal motility either by activating A(1) inhibitory receptors located post-junctionally or controlling neurotransmitter release via A(1) or A(2A) receptors. Both receptors are available for pharmacological recruitment, even if only A(2A) receptors appear to be preferentially stimulated by endogenous adenosine. LINKED ARTICLE: This article is commented on by Antonioli et al., pp. 1577–1579 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01529.

INCIDENCE OF PSYCHOTIC DISORDERS IN PALERMO: PRELIMINARY DATA

Background: The incidence of psychotic disorders varies in different geographical areas (McGrath 2004). Recent data suggest that the incidence is higher in males, migrant minorities and in urban areas. There aren\u2019t many available epidemiological data on the incidence of psychotic disorders in Italy. This is the first incidence study on psychotic disorders carried out in Palermo, the capital of Sicily. Methods: we screened all patients presenting with their first episode of psychosis to the mental health services of our catchment area (5 inpatient, 5 outpatient units and 3 private psychiatric hospitals) over a period of three years (2008-2011). The diagnosis of psychosis was defined using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN Wing, J. K., et al., 1990).The main socio-demographic data were collected using the MRC Social Data Schedule. When subjects were not available (did not consent) for interview, information was collected from clinical notes. The population at risk referred to the people aged from 18-65 who were resident in the same catchment area (Palermo Municipality) in the period considered, according to the data of the Statistic Office of Palermo Municipality). Results: we identified 216 patients affected by a first episode of psychosis (FEP): 135 M (62.5%) and 81 F (37.5%), mean age 31.42 years (SD: 11.44). 77.1% of FEP had a diagnosis of non affective psychosis, 12.8% of affective psychosis and 10.1% received a diagnosis of other psychosis. 204 subjects were Caucasian, 12 non Caucasian belonging to various ethnicities and they were all first generation migrants (4 Indian, 3 African, 2 Bangladeshi, and 3 Mixed). Population at risk is 425.194 people. The mean age of onset was lower in men than women M: 29.98 years (SD: 10.41) vs. F: 34.28 (SD:12.64) (p=0.013)The incidence of psychotic disorders in our catchment area is 16,9 per 100.000 person years. It was higher in men 21,9 per 100.000 than women 12,2 per 100.000. Discussion: Our study is the first epidemiological study in Sicily investigating the incidence of psychotic disorders. In our population men have a higher incidence of psychotic disorders than women and an earlier age of onset

Influence of metabolic syndrome on hypertension-related target organ damage

OBJECTIVES: The aim of our study was to analyse, in a wide group of essential hypertensive patients without diabetes mellitus, the influence of metabolic syndrome (MS) (defined according to the criteria laid down in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults) on markers of preclinical cardiac, renal and retinal damage. DESIGN: Cross-sectional study. SETTING: Outpatient hypertension clinic. SUBJECTS AND METHODS: A total of 353 young and middle-aged hypertensives, free from cardiovascular and renal diseases (and 37% of whom had MS), underwent echocardiographic examination, microalbuminuria determination and non-mydriatic retinography. RESULTS: When compared with subjects without MS, hypertensive patients with MS exhibited more elevated left ventricular (LV) mass (either normalized by body surface area or by height elevated by a power of 2.7), higher myocardial relative wall thickness, albumin excretion rate (AER) and a greater prevalence of LV hypertrophy (57.7% vs. 25.1%; P < 0.00001), of microalbuminuria (36.2% vs. 19.3%; P = 0.002) and of hypertensive retinopathy (87.7% vs. 48.4%; P < 0.00001). These results held even after correction for age, 24-h blood pressures, duration of hypertension, previous antihypertensive therapy, and gender distribution. The independent relationships between LV mass and MS, and between AER and MS, were confirmed in multivariate regression models including MS together with its individual components. CONCLUSIONS: MS may amplify hypertension-related cardiac and renal changes, over and above the potential contribution of each single component of this syndrome. As these markers of target organ damage are well-known predictors of cardiovascular events, our results may partly explain the enhanced cardiovascular risk associated with MS

CONTROLLO GLICOMETABOLICO E ABITUDINI ALIMENTARI IN ADOLESCENTI CON DIABETE MELLITO TIPO 1

Background: Gli studi che hanno valutato le abitudini alimentari dei bambini e adolescenti con diabete, hanno riportato una percentuale di assunzione di carboidrati più bassa di quella minima raccomandata spesso associata ad un maggiore consumo di grassi e ad una ridotta assunzione di fibre . Alcuni studi che hanno valutato il rapporto tra composizione della dieta e controllo glicometabolico in soggetti con diabete tipo 1, hanno evidenziato che una dieta ricca di grassi e povera di fibre è associata ad un peggior controllo glicometabolico. Obiettivo: Valutare in adolescenti affetti da diabete mellito tipo 1, con diverso grado di controllo metabolico, la frequenza di consumo settimanale dei vari gruppi di alimenti e l’eventuale correlazione di questa con i valori di emoglobina glicosilata ( HbA1c). Metodo: In 43 soggetti (M/F :22/21; età 11-14 anni) suddivisi in due gruppi in rapporto al valore mediano di HbA1c ( 8,45%), sono stati raccolti i dati relativi ai consumi alimentari degli ultimi tre mesi attraverso un questionario di frequenza di consumo ed è stata considerata la frequenza di scelte alimentari settimanali per gruppo di alimenti. Risultati I soggetti con miglior controllo glicometabolico (HbA1c< 8,45%) presentavano una maggiore frequenza di consumo settimanale dei seguenti gruppi di alimenti: frutta( p<0,0001) , ortaggi (p=0,017) e legumi ( p=0,03). I soggetti con peggior controllo glicometabolico ( HbA1c > 8,45%) consumavano con maggiore frequenza alimenti appartenenti al gruppo di salumi (p=0,007), formaggi (p=0,02) e dolci /bevande zuccherate (p=0,0065). I valori di HbA1c erano inversamente correlati alla frequenza di consumo settimanale di frutta ((r – 0,65 p< 0,0001) e a quello di ortaggi( r – 0,32 p < 0,017) e direttamente correlati alla frequenza settimanale di consumo di alimenti appartenenti ai gruppi di salumi ( r 0,37 p< 0,007). Conclusioni: Il controllo glicometabolico in adolescenti con diabete tipo 1 è influenzato dalla frequenza di consumo settimanale di alimenti ricchi di fibre e di grassi animali. I principi di una san

Enniatin and Beauvericin Biosynthesis in Fusarium Species: Production Profiles and Structural Determinant Prediction

Citation: Liuzzi, V. C., Mirabelli, V., Cimmarusti, M. T., Haidukowski, M., Leslie, J. F., Logrieco, A. F., . . . Mule, G. (2017). Enniatin and Beauvericin Biosynthesis in Fusarium Species: Production Profiles and Structural Determinant Prediction. Toxins, 9(2), 17. doi:10.3390/toxins9020045Members of the fungal genus Fusarium can produce numerous secondary metabolites, including the nonribosomal mycotoxins beauvericin (BEA) and enniatins (ENNs). Both mycotoxins are synthesized by the multifunctional enzyme enniatin synthetase (ESYN1) that contains both peptide synthetase and S-adenosyl-L-methionine-dependent N-methyltransferase activities. Several Fusarium species can produce ENNs, BEA or both, but the mechanism(s) enabling these differential metabolic profiles is unknown. In this study, we analyzed the primary structure of ESYN1 by sequencing esyn1 transcripts from different Fusarium species. We measured ENNs and BEA production by ultra-performance liquid chromatography coupled with photodiode array and Acquity QDa mass detector (UPLC-PDA-QDa) analyses. We predicted protein structures, compared the predictions by multivariate analysis methods and found a striking correlation between BEA/ENN-producing profiles and ESYN1 three-dimensional structures. Structural differences in the beta strand's Asn789-Ala793 and His797-Asp802 portions of the amino acid adenylation domain can be used to distinguish BEA/ENN-producing Fusarium isolates from those that produce only ENN

Extramedullary plasmacytoma of the tonsil: A new management

Introduction: Extramedullary plasmacytoma (EMP) is a rare tumor of all plasma cell neoplasms. The tumor is mainly localized in the head and neck region, but rarely involving the tonsil. Case presentation: The authors report the 5th case of EMP of the tonsil in the literature occurred in a 57-year-old Caucasian male. Conclusions: Through a review of the relevant literature, we consider adjuvant radiotherapy not necessary for EMP of tonsil because of an adequate resection achieved by surgery

Relationship between albumin excretion rate and aortic stiffness in untreated essential hypertensive patients

OBJECTIVES: To evaluate, in a group of nondiabetic essential hypertensive patients with normal renal function, the relationship between albumin excretion rate (AER) and carotid-femoral pulse wave velocity (PWV), as an index of aortic stiffness. DESIGN: Cross-sectional study. SETTING: Outpatient hypertension clinic. SUBJECTS: Seventy patients with mild-to-moderate essential hypertension, aged 42 +/- 8 years, never pharmacologically treated. All subjects underwent routine laboratory tests, 24-h ambulatory blood pressure (BP) monitoring, measurement of carotid-femoral PWV, by means of a computerized method, and AER. RESULTS: Microalbuminuric patients (AER > or = 20 microg min(-1); n = 19), when compared with normoalbuminuric subjects, showed more elevated 24-h BP (136/88 +/- 10/10 vs. 128/83 +/- 7/6 mmHg; P < 0.001 and P = 0.013, for systolic and diastolic BP respectively) and higher values of carotid-femoral PWV (10.4 +/- 2 m s(-1) vs. 9.2 +/- 1.3; P = 0.006). This latter difference remained statistically significant, even after correction by ancova for 24-h systolic and diastolic BP, and body mass index (BMI, P = 0.016). Univariate regression analysis disclosed a tight correlation between AER and carotid-femoral PWV (r = 0.42; P = 0.0003). This association was confirmed in a multiple regression model (beta = 0.35; P = 0.009) in which, as independent variables, besides PWV, 24-h BP, age, serum glucose values, smoking status, gender and BMI, were added. CONCLUSIONS: Our results seem to confirm that microalbuminuria may represent the early renal manifestation of a widespread vascular dysfunction, and therefore it is an integrated marker of cardiovascular risk

Association between sleep-disordered breathing and hearing disorders: Clinical observation in Sicilian patients

Introduction: To examine the putative association between Sleep-Disordered breathing and hearing disorders Material and methods: 120 Sicilian subjects ranging from 14 to 85 years of age who were divided in 46 cases suffering from tinnitus (G1 group) and 74 controls (G2 group) were evaluated through STOP BANG screening questionnaire and Four-Variable Screening Tool; after Data collecting each subject underwent Audiological assessment by multi-frequency audiometry (PTA) and Transient-evoked otoacoustic emissions (TEOAE-diagnostic) for each ear. Results: Cases showed: PTA significantly severe than the control group (58.70% vs. 16.89% hearing loss; P&lt;0.001), such as a lower signal-to-noise ratio (SNRs) (P&lt;0.05). Moreover Tinnitus subjects had a higher risk to develop Sleep-Disordered breathing respect to controls (P&lt;0.001). OSA risk population - subjects positive to both screening questionnaires - had tinnitus, wore hearing threshold mean values and, lower SNRs values than total cohort (P&lt;0.01). The relative risk of Sleep-Disordered breathing and tinnitus was 4.83 (P&lt;0.0001). Conclusions: Our results stress a probable association between tinnitus, hearing loss and Sleep-Disordered breathing even if further studies will be needed to confirm our findings

Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi

Recent Trends, Opportunities and Challenges in 3D Printing Technology for Personalize Medicine

The scrutiny of medical devices industry as well as pharmaceutical industry for its application in health care industry on different platform is captured the 3D printing technique.&nbsp; 3D printing technology withstand for a very long duration only because of the approval of medical devices, 3D printed tablets and also with the advent of USFDA guideline on technical consideration. This technology is specific to devices utilizing preservative manufacturing. Many thoughts are triggered by 3D printing this technology and for successful delivery of intended product which is necessarily take into a consideration. In this review paper expectation limitations of some regulatory companies, Advantages, disadvantages, what type problems are arises while establishing this setups for drug product production, method, application, and manufacturing risk are represented. It also gives information about the current status of 3D printing technology in research and development of drug products.&nbsp; For the fabrication of novel solid dosage form a number of 3D printing technology have been developed. This review is mainly focused on describing different technology used for the application of 3D printing in pharmaceutical industry.&nbsp; Keywords: - 3D printing technology, recent trend, Opportunities, personalize medicine, challenges, future