Value of dobutamine stress tissue Doppler in evaluation of LV functional improvement after elective PCI

Aim: To clarify the value of dobutamine stress tissue Doppler in the evaluation of LV functional improvement after elective PCI.Methods: The study included 60 patients with hibernating viable myocardium proved by DSE referred for an evaluation of myocardial viability prior to revascularization. Hemodynamic and echocardiographic variables (LVEF, WMSI and TDI Sm) were assessed at rest and during stress. 1 month after PCI follow up echocardiography and TDI were done. Patients were divided into 2 groups: (Group I): 18 patients (30%) with no global functional recovery and (Group II): 42 patients (70%) with global functional recovery.Results: SBP, DPB, HR, EF, WMSI and (Sm) increased significantly at stress P = 0.001. After 1 month patients were divided into 2 groups according to functional recovery. There were no statistically  significant differences between two groups neither as regards age, sex, risk factors (P >0.05) nor as  regards SBP, DBP, HR, rate/pressure product, EF and WMSI during stress but Sm increased during stress and after1 month follow up in Group II (P = 0.001). Univariate regression showed that (Sm) is the only predictor for global functional recovery. ROC curve statistical analysis shows that (Sm) is more sensitive and accurate than (WMSI) in the detection of viable myocardium which predicts improvement after revascularization (sensitivity 100%, 50% and accuracy 93.3%, 83.3% respectively).Conclusion: Stress TDI provides a feasible and quantitative technique that improves reproducibility of DSE. Sm during stress showed better accuracy than WMSI for the prediction of functional recovery following revascularization and was simple, sensitive and accurate for the detection of subtle myocardial systolic velocity changes

Common variants in FOXP1 are associated with generalized vitiligo

In a recent genome-wide association study of generalized vitiligo, we identified ten confirmed susceptibility loci. By testing additional loci that showed suggestive association in the genome-wide study, using two replication cohorts of European descent, we observed replicated association of generalized vitiligo with variants at 3p13 encompassing FOXP1 (rs17008723, combined P = 1.04 × 10−8) and with variants at 6q27 encompassing CCR6 (rs6902119, combined P = 3.94 × 10−7)

The puzzle of self-reported weight gain in a month of fasting (Ramadan) among a cohort of Saudi families in Jeddah, Western Saudi Arabia

<p>Abstract</p> <p>Background</p> <p>During Ramadan fast, approximately one billion Muslims abstain from food and fluid between the hours of sunrise to sunset, and usually eat a large meal after sunset and another meal before sunrise. Many studies reported good health-related outcomes of fasting including weight loss. The objective of this study is to identify the local pattern of expenditure on food consumption, dietary habits during Ramadan and correlate that to self-reported weight gain after Ramadan in a group of families in Jeddah, Western Saudi Arabia.</p> <p>Methods</p> <p>A Cross-section study using a pre-designed questionnaire to identify the local pattern of expenditure on food consumption, dietary habits during Ramadan and correlate that to self-reported weight gain after Ramadan in a representative cohort of Saudis living in Jeddah. It was piloted on 173 nutrition students and administered by them to their families.</p> <p>Results</p> <p>A total of 173 Saudi families were interviewed. One out of 5 indicated that their expenditure increases during Ramadan. Approximately two thirds of the respondents (59.5%) reported weight gain after Ramadan. When asked about their perspective explanations for that: 40% attributed that to types of foods being rich in fat and carbohydrates particularly date in (Sunset meal) 97.7% and rice in (Dawn meal) 80.9%. One third (31.2%) indicated that it was due to relative lack of physical exercise in Ramadan and 14.5% referred that to increase in food consumption. Two thirds (65.2%) of those with increased expenditure reported weight gain.</p> <p>Conclusion</p> <p>Surprisingly weight gain and not weight loss was reported after Ramadan by Saudis which indicates timely needed life-style and dietary modification programs for a population which reports one of the highest prevalence rates of diabetes.</p

Emergence of 3D Printed Dosage Forms: Opportunities and Challenges

The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such as extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, including design flexibility and control and manufacture which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry

Jet dispensing of multi-layered films for the co-delivery of three antihypertensive agents

Three-layer thin films comprising of two polymers as substrate (ethyl cellulose and, copovidone K28) and three antihypertensive agents (hydrochlorothiazide, amiloride HCl, and carvedilol) were printed using jet dispensing technology. Two film formulations with different ethyl cellulose to copovidone K28 ratio (i.e., 90/10 and 50/50 w/w) were prepared using a three-course dispensing. The films were characterized regarding surface morphology, solid-state properties, polymer-drug interactions, drug distribution in each layer, and in vitro drug release. All the components of the films were found to be in the amorphous state apart from hydrochlorothiazide which retained its crystallinity. FT-IR spectroscopy revealed hydrogen bond interactions between carvedilol and copovidone K28. Combinations of ethyl cellulose and copovidone K28 provide suitable polymeric film substrates with the ability to modify drug release. Particularly, decreased ethyl cellulose to copovidone K28 weight ratio was found to suppress the crystallization of hydrochlorothiazide and to increase the release rate of the dispensed drugs. Jet dispensing was found to be a rapid technology for the preparation of multi-layered films that can be used as personalized formulations for the delivery of combinations of drugs

CADASIL in Arabs: clinical and genetic findings

<p>Abstract</p> <p>Background</p> <p>Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is increasingly recognized as an inherited arterial disease leading to a step-wise decline and eventually to dementia. CADASIL is caused by mutations in <it>NOTCH3 </it>epidermal growth factor-like repeat that maps to chromosome 19. CADASIL cases have been identified in most countries of Western and Central Europe, the Americas, Japan, Australia, the Caribbean, South America, Tanzania, Turkey, South Africa and Southeast Asia, but not in Arabs.</p> <p>Methods</p> <p>We studied three families from Saudi Arabia (Family A), Kuwait (Family B) and Yemen (Family C) with 19 individuals affected by CADASIL.</p> <p>Results</p> <p>The mean age of onset was 31 ± 6 and the clinical presentation included stroke in 68%, subcortical dementia in 17% and asymptomatic leukoariosis detected by MRI in 15%. Migraine and depression were frequently associated, 38% and 68% respectively. The mean age of death was 56 ± 11. All <it>NOTCH3 </it>exons were screened for mutations, which revealed the presence of previously reported mutations c.406C>T (p.Arg110>Cys) in two families (family A&B) and c.475C>T (p.Arg133>Cys) mutation in family C.</p> <p>Conclusion</p> <p>CADASIL occurs in Arabs, with clinical phenotype and genotype similar to that in other ethnic groups.</p

Changes in liver mitochondrial plasticity induced by brain tumor

BACKGROUND: Accumulating data suggest that liver is a major target organ of systemic effects observed in the presence of a cancer. In this study, we investigated the consequences of the presence of chemically induced brain tumors in rats on biophysical parameters accounting for the dynamics of water in liver mitochondria. METHODS: Tumors of the central nervous system were induced by intraveinous administration of ethylnitrosourea (ENU) to pregnant females on the 19th day of gestation. The mitochondrial crude fraction was isolated from the liver of each animal and the dynamic parameters of total water and its macromolecule-associated fraction (structured water, H(2)Ost) were calculated from Nuclear Magnetic Resonance (NMR) measurements. RESULTS: The presence of a malignant brain tumor induced a loss of water structural order that implicated changes in the physical properties of the hydration shells of liver mitochondria macromolecules. This feature was linked to an increase in the membrane cholesterol content, a way to limit water penetration into the bilayer and then to reduce membrane permeability. As expected, these alterations in mitochondrial plasticity affected ionic exchanges and led to abnormal features of mitochondrial biogenesis and caspase activation. CONCLUSION: This study enlightens the sensitivity of the structured water phase in the liver mitochondria machinery to external conditions such as tumor development at a distant site. The profound metabolic and functional changes led to abnormal features of ion transport, mitochondrial biogenesis and caspase activation

Expression of RFC/SLC19A1 is Associated with Tumor Type in Bladder Cancer Patients

Urinary bladder cancer (UBC) ranks ninth in worldwide cancer. In Egypt, the pattern of bladder cancer is unique in that both the transitional and squamous cell types prevail. Despite much research on the topic, it is still difficult to predict tumor progression, optimal therapy and clinical outcome. The reduced folate carrier (RFC/SLC19A1) is the major transport system for folates in mammalian cells and tissues. RFC is also the primary means of cellular uptake for antifolate cancer chemotherapeutic drugs, however, membrane transport of antifolates by RFC is considered as limiting to antitumor activity. The purpose of this study was to compare the mRNA expression level of RFC/SLC19A1 in urothelial and non-urothelial variants of bladder carcinomas. Quantification of RFC mRNA in the mucosa of 41 untreated bladder cancer patients was performed using RT-qPCR. RFC mRNA steady-state levels were ∼9-fold higher (N = 39; P<0.0001) in bladder tumor specimens relative to normal bladder mRNA. RFC upregulation was strongly correlated with tumor type (urothelial vs. non-urothelial; p<0.05) where median RFC mRNA expression was significantly (p<0.05) higher in the urothelial (∼14-fold) compared to the non-urothelial (∼4-fold) variant. This may account for the variation in response to antifolate-containing regimens used in the treatment of either type. RFC mRNA levels were not associated with tumor grade (I, II and III) or stage (muscle-invasive vs. non-muscle invasive) implying that RFC cannot be used for prognostic purposes in bladder carcinomas and its increased expression is an early event in human bladder tumors pathogenesis. Further, RFC can be considered as a potential marker for predicting response to antifolate chemotherapy in urothelial carcinomas

The taper of cast post preparation measured using innovative image processing technique

<p>Abstract</p> <p>Background</p> <p>No documentation in the literature about taper of cast posts. This study was conducted to measure the degree of cast posts taper, and to evaluate its suitability based on the anatomy aspects of the common candidate teeth for post reconstruction.</p> <p>Methods</p> <p>Working casts for cast posts, prepared using Gates Glidden drills, were collected. Impressions of post spaces were made using polyvinyl siloxan putty/wash technique. Digital camera with a 10' high quality lens was used for capturing two digital images for each impression; one in the Facio-Lingual (FL) and the other in the Mesio-Distal (MD) directions. Automated image processing program was developed to measure the degree of canal taper. Data were analyzed using Statistical Package for Social Sciences software and One way Analysis of Variance.</p> <p>Results</p> <p>Eighty four dies for cast posts were collected: 16 for each maxillary anterior teeth subgroup, and 18 for each maxillary and mandibular premolar subgroup. Mean of total taper for all preparations was 10.7 degree. There were no statistical differences among the total taper of all groups (P = .256) or between the MD and FL taper for each subgroup. Mean FL taper for the maxillary first premolars was lower significantly (P = .003) than the maxillary FL taper of the second premolars. FL taper was higher than the MD taper in all teeth except the maxillary first premolars.</p> <p>Conclusions</p> <p>Taper produced did not reflect the differences among the anatomy of teeth. While this technique deemed satisfactory in the maxillary anterior teeth, the same could not be said for the maxillary first premolars. Careful attention to the root anatomy is mandatory.</p