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.

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.  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.  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.  Keywords: - 3D printing technology, recent trend, Opportunities, personalize medicine, challenges, future

Epigenetics: Pharmacology and Modification Mechanisms Involved in Cardiac, Hepatic and Renal Disease

For a long time scientists have tried to describe disorders are due to genetic as well as environmental factors. In the past few years, revolution in technology that has made it possible to decipher the human genome. Epigenetics explains the capability gene expression regulation without modifying the genetic sequence. Epigenetic mechanisms are rooted changes in molecules, or nuclear characteristics that can alter gene expression without altering the sequences of DNA, i.e. DNA methylation, histone modification, and non-coding RNAs. Learning of the fundamental epigenetic modification allowing gene expression as well as cellular phenotype are advanced that novel insights into the epigenetic control of cardiovascular disease, hepatic disease, as well as chronic kidney disease are now emerging. From a half of century ago, in human disease the role of epigenetics has been considered. This subject has attracted many interests in the past decade, especially in complicated diseases like cardiovascular disease, hepatic disease as well as chronic kidney disease. This review first illustrates the history and classification of epigenetic modifications and the factors (i.e. genetic, environment, dietary, thought process and lifestyle) affecting to the epigenetics mechanisms. Likewise, the epigenetics role in human diseases is think out by targeting on some diseases and at the end, we have given the future perspective of this field. This review article provides concepts with some examples to describe a broad view of distinct aspects of epigenetics in biology and human diseases. Keywords: - Epigenetics, DNA methylation, Histone modifications, microRNAs and Gene expression and Disease

A Review on Life Cycle Management Approach on Asset Qualification

All equipment’s used in the production of products shall be properly Validated, Qualified and Calibrated to demonstrate that it is suitable for its intended purpose. Qualification is an important aspect of the pharmaceutical quality system. When the equipment is properly qualified, verified and maintained, there is the possibility of Consistent performance of the equipment. A well designed qualification program saves valuable time and cost. Qualification is called a cyclic process because it is a never ending process. Appropriate documentation of the qualification program is very important as lack of the documented evidence does not give any meaning to qualification (Not documented it means not done).  The current programs and procedures of equipment qualification used within any pharmaceutical and bioscience industry are based on ‘regulatory requirements’, ‘voluntary standards’, ‘vendor practices’, and ‘industry practices’. The output is considerable variation in the way any pharmaceutical and biotechnological companies approach for the laboratory equipment. The lifecycle management approach of equipment qualification covers entire life cycle for the specification, design, manufacturing, installation, commissioning, qualification (4Qs Model DQ, IQ, OQ, PQ), operation & maintenance of equipment in a risk based life cycle management approach. The goal of any regulated pharmaceutical and bioscience company is to provide reliable and valid data suitable for its intended purpose. Main goal of equipment qualification is to form the basis for written procedures for production and process control which are designed to assure that the drug products have the SISPQ (Safety, Identity, Strength, Purity and Quality) Keywords: Validation, Calibration, Life cycle management approach, Qualification (4Qs Model- DQ, IQ, OQ & PQ), SISPQ (Safety, Identity, Strength, Purity and Quality

The Development of Lightweight Electronics Enclosures for Space Applications

This paper outlines the end to end effort to produce lightweight electronics enclosures for NASA GSFC electronics applications with the end goal of presenting an array of lightweight box options for a flight opportunity. Topics including the development of requirements, design of three different boxes, utilization of advanced materials and processes, and analysis and test will be discussed. Three different boxes were developed independently and in parallel. A lightweight machined Aluminum box, a cast Aluminum box and a composite box were designed, fabricated, and tested both mechanically and thermally. There were many challenges encountered in meeting the requirements with a non-metallic enclosure and the development of the composite box employed several innovative techniques

Preliminary Evidence of the Efficacy of Time-Resolved Broad-Spectrum Optical Mammography in Monitoring Neoadjuvant Chemotherapy

We present initial results of a clinical trial involving breast cancer patients under neoadjuvant chemotherapy, monitored through our time-resolved optical mammograph. Besides hemoglobin, water and lipids, we assess collagen concentration systematically for the first time

Monitoring Neoadjuvant Chemotherapy Through Time Domain Diffuse Optical Spectroscopy in Breast Cancer Patients: Preliminary Clinical Results

The purpose of this clinical study is to monitor NeoAdjuvant Chemotherapy through time domain Diffuse Optical Spectroscopy, correlate the optical results with conventional imaging techniques and pathological response and eventually predict the efficacy of NAC in breast cancer patients. Our seven wavelength (635 -1060 nm) optical mammograph is used to perform non-invasive measurements on patients undergoing NAC in this study. The broad spectral range helps us to fully analyze tissue composition, that includes hemoglobin, water lipids and collagen concentration, to track the tumor response during the course of the therapy. In this paper, we present the preliminary results of five patients

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

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

SUBCLINICAL RENAL DAMAGE IS ASSOCIATED WITH A REDUCED CHOROIDAL THICKNESS IN PATIENTS WITH PRIMARY HYPERTENSION

Objective: The retina is considered the easiest accessible window to study the state of the systemic microcirculation, even if the choroid is the most important vascular layer of the eye. Our understanding of the choroid has been greatly increased in last years since the introduction of advanced techniques of optical coherence tomography (OCT). Our study was aimed to assess choroidal thickness by using Swept-Source OCT (SS-OCT) in essential hypertensive patients (EHs) with and without subclinical renal damage (SRD). Design and method: We enrolled 100 EHs of which 65 without kidney damage and 35 with SRD. In all the participants SS-OCT and a routine biochemical work-up were performed. Glomerular filtration rate (GFR) was estimated by the CKD-EPI equation (eGFR). SRD was defined, by the presence of microalbuminuria or eGFR between 30 and 60\u200amL/min/1.73 m2. OCT measurements were performed according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, that divides the macula into 9 subfields. The circular grid consists of 3 concentric rings. The inner and outer rings are further divided into quadrants: temporal, nasal, superior, and inferior. Design and method: Furthermore, we calculated the average of the individuals values of the four quadrants separately for the inner and the outer ring. The average of all the 9 regions of the ETRDS grid (including the inner, the outer and the central rings) was also calculated. Results: EHs with SRD showed thinner choroidal thicknesses than those without kidney damage (all p\u200a<\u200a0.05), even after adjustment for age (figure). Overall choroidal thickness correlated significantly and directly with eGFR (r\u200a=\u200a0.36) and negatively with urinary albumin excretion (r\u200a=\u200a- 0.39). The association of choroidal thickness with SRD was confirmed in multiple logistic regression analyses once the effect of age, anti-hypertensive therapy and triglycerides was accounted for. The odds ratio of having SRD associated with a standard deviation increase of overall choroidal thickness was 0.43 (0.24\u20130.75, 95% confidence interval; p\u200a=\u200a0.007). Conclusions: Our study confirms the close relationships between changes in ocular microcirculation and renal dysfunction