ABSTRACT
Double-J ureteral stents disposal is associated with the appearance of side effects in up to 90% of the patients. The main causes of these symptoms are related to stent's design and the materials they are manufactured from. Vesicoureteral reflux and bladder trigone irritation are the etiopathogenic causes of ureteral stents associated morbidity. Due to this, and in order to improve patients' quality of life, stents that avoid reflux have been developed. Among anti-reflux designs, the first was a double-J stent the bladder tip of which is provided with a polymeric membrane that prevents retrograde flow of urine through its internal drainage channel. This design showed satisfactory vesicaresults, although not statistically significant. Their use in renal transplantation has also been assessed not only to decrease morbidity and ascending infection but also to improve graft survival. Other designs try to thin the distal end and even change it to a surgical suture thread, with the aim of eliminating the internal drainage channel in order to cause the minimum interference with the UVJ. Recently, two prototypes were evaluated in animal models and have achieved reduction of VUR. The first consists of a valve attached to the distal end of a traditional double-J stent, acting as a backflow prevention device. The second design is an intra-ureteral stent that acts like a double-J stent, but without crossing the UVJ and therefore preventing reflux completely. Nowadays, the use of these devices is not implemented in hospitals due to the absence of scientific evidence supporting the superiority of these designs over conventional stents.
Subject(s)
Urinary Catheters , Vesico-Ureteral Reflux/prevention & control , Equipment Design , HumansABSTRACT
Induced pluripotent stem cells (iPSC) offer a unique opportunity for developmental studies, disease modeling and regenerative medicine approaches in humans. The aim of our study was to create an in vitro 'patient-specific cell-based system' that could facilitate the screening of new therapeutic molecules for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited form of fatal arrhythmia. Here, we report the development of a cardiac model of CPVT through the generation of iPSC from a CPVT patient carrying a heterozygous mutation in the cardiac ryanodine receptor gene (RyR2) and their subsequent differentiation into cardiomyocytes (CMs). Whole-cell patch-clamp and intracellular electrical recordings of spontaneously beating cells revealed the presence of delayed afterdepolarizations (DADs) in CPVT-CMs, both in resting conditions and after ß-adrenergic stimulation, resembling the cardiac phenotype of the patients. Furthermore, treatment with KN-93 (2-[N-(2-hydroxyethyl)]-N-(4methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), an antiarrhythmic drug that inhibits Ca(2+)/calmodulin-dependent serine-threonine protein kinase II (CaMKII), drastically reduced the presence of DADs in CVPT-CMs, rescuing the arrhythmic phenotype induced by catecholaminergic stress. In addition, intracellular calcium transient measurements on 3D beating clusters by fast resolution optical mapping showed that CPVT clusters developed multiple calcium transients, whereas in the wild-type clusters, only single initiations were detected. Such instability is aggravated in the presence of isoproterenol and is attenuated by KN-93. As seen in our RyR2 knock-in CPVT mice, the antiarrhythmic effect of KN-93 is confirmed in these human iPSC-derived cardiac cells, supporting the role of this in vitro system for drug screening and optimization of clinical treatment strategies.
Subject(s)
Arrhythmias, Cardiac/drug therapy , Benzylamines/pharmacology , Benzylamines/therapeutic use , Calcium-Calmodulin-Dependent Protein Kinase Type 2/antagonists & inhibitors , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Tachycardia, Ventricular/drug therapy , Adolescent , Adult , Animals , Arrhythmias, Cardiac/complications , Arrhythmias, Cardiac/enzymology , Arrhythmias, Cardiac/pathology , Base Sequence , Calcium/metabolism , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Cell Differentiation/drug effects , Child , Child, Preschool , Female , HEK293 Cells , Humans , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Induced Pluripotent Stem Cells/metabolism , Male , Mice , Molecular Sequence Data , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Pedigree , Phenotype , Receptors, Adrenergic, beta/metabolism , Ryanodine Receptor Calcium Release Channel/genetics , Tachycardia, Ventricular/complications , Tachycardia, Ventricular/enzymology , Tachycardia, Ventricular/pathologyABSTRACT
The Pacific whiteleg shrimp Litopenaeus vannamei (Penaeidae) is one of the most important cultivated species in world aquaculture. In Brazil, the northeastern states are home to the main shrimp producers. As shrimp aquaculture has expanded and intensified, diseases have progressively become one of the most serious threats to this industry. Infectious hypodermal and hematopoietic necrosis virus (IHHNV) is an enzootic viral agent in Brazilian shrimp farms. Its is usually diagnosed by histological methods. However, to detect sub-clinical or acute IHHNV infection, more refined methods based on molecular techniques have been utilized. We found that by using "universal" primers and a single-step PCR diagnostic test, it was difficult to distinguish between non-infective forms of the virus and active IHHNV. Detection of IHHNV was more accurate when we used two alternative molecular strategies, namely 1) single-step PCR amplification based on gene choice and 2) reverse transcription coupled with PCR.
Subject(s)
Crustacea/virology , Transcription, Genetic , Virus Diseases/diagnosis , Viruses/isolation & purification , Animals , Base Sequence , DNA Primers , Diagnosis, Differential , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
PIP: Puerto Rican migration to the US has been a more or less continuous process since 1917. The perspective of viewing return migration as a circulation process suggests that there are entries, exits, and reintergration into the metropolitan labor market. This study explores the circulatory movements of Puerto Rican families, events that influence the adaptation process when returning to Puerto Rico, and cultural identity aspects. Data collected by means of 2 research instruments that were administered to the respondents simultaneously were used: 1) a life history matrix and 2) an open-ended questionnaire. These interviews outlined the principal problems of adaptation as mentioned by the circulating migrants. The most difficult problems to adjust to were economic and employment (58%), followed by social acceptance (23%), education (17%), and language (15%). Transportation, medical services, and recreational facilities were also problems mentioned as being significant. It is expected that a great majority of migrant laborers will go to live in immigrant residential locations in large US cities. It is also expected that these migrants will meet with certain value conflicts by living in urban ghettos. These families will have serious difficulties finding economic stability and will possibly consider migrating once again as an alternative to their social reality. This study illustrates that: 1) the migrants return in family groups; 2) they face discriminatory problems in employment agencies and schools; 3) they look forward to a formal education as a means of social mobility; 4) they identify themselves with values, habits, and Puerto Rican traditions; and 5) they value the quality of life in Puerto Rico.^ieng
Subject(s)
Acculturation , Emigration and Immigration , Social Change , Transients and Migrants , Americas , Caribbean Region , Demography , Developed Countries , Developing Countries , Educational Status , Employment , Latin America , North America , Population , Population Dynamics , Prejudice , Puerto Rico , Social Class , Social Problems , Socioeconomic Factors , United StatesABSTRACT
A rapid and sensitive high-performance liquid chromatographic assay was developed for triamterene and 6-p-hydroxytriamterene in plasma. Plasma (0.5 ml), after addition of the internal standard, was extracted with 10 ml of ether-isopropanol (95:5). After thorough mixing and separation of phases, the organic layer was evaporated to dryness under nitrogen. The residue was reconstituted with 500 microliters of mobile phase [acetonitrile-water-acetic acid (60:39.5:0.5)], and 100 microliters was injected into the chromatograph. Chromatographic separation was carried out on a C18 muBondapak column at a flow rate of 1 ml/min. Detection of compounds in the column eluent was by UV absorption at 365 nm. The retention times for 6-p-hydroxytriamterene, triamterene, and the internal standard were 7.5, 9.0, and 12.0 min, respectively. The lower limit of detection for each compound was 20 ng/ml. Recoveries of triamterene and 6-p-hydroxytriamterene were 91--99 and 828--95%, respectively, over a 40--240-ng/ml range.