Autosomal Recessive Nonsyndromic Arrhythmogenic Right Ventricular Cardiomyopathy without Cutaneous Involvements: A Novel Mutation

The arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic disease frequently associated with desmosomal mutations, mainly attributed to dominant mutations in the Plakophilin‐2 (PKP2) gene. Naxos and Carvajal are the syndromic forms of ARVD/C due to recessive mutations. Herein, we report an autosomal recessive form of nonsyndromic ARVD/C caused by a mutation in the PKP2 gene. After examination and implementation of diagnostic modalities, the definite diagnosis of ARVD/C was confirmed by detection of ventricular tachycardia with a left bundle branch configuration and a superior axis, T‐wave inversion in right precordial leads (i.e., V1‐V3) in a 12‐lead electrocardiogram, and a right ventricle outflow tract dilatation. Neither cutaneous involvement nor other abnormalities were observed. Genetic testing was performed during which an intronic mutation of c.2577+1G>T in the PKP2 gene was observed homozygously. The c.2577+1G>T disrupts PKP2 mRNA splicing and causes a nonsyndromic form of ARVD/C.     

Nonenzymatic glucose sensor based on disposable pencil graphite electrode modified by copper nanoparticles

A nonenzymatic glucose sensor based on a disposable pencil graphite electrode (PGE) modified by copper nanoparticles [Cu(NP)] was prepared for the first time. The prepared Cu(NP) exhibited an absorption peak centered at ~562 nm using UV-visible spectrophotometry and an almost homogenous spherical shape by scanning electron microscopy. Cyclic voltammetry of Cu(NP)-PGE showed an adsorption controlled charge transfer process up to 90.0 mVs⁻¹. The sensor was applied for the determination of glucose using an amperometry technique with a detection limit of [0.44 (±0.01) μM] and concentration sensitivity of [1467.5 (±1.3) μA/mMcm⁻²]. The preparation of the Cu(NP)-PGE sensor was reproducible (relative standard deviation = 2.10%, n = 10), very simple, fast, and inexpensive, and the Cu(NP)-PGE is suitable to be used as a disposable glucose sensor.     

Teratogenic effects of retinoic acid on neurulation in mice embryos.

Retinoic acids (RA) are natural chemicals that exert a hormone-like activity and a variety of biological effects on early development of mouse. In this study, the probable teratogenic effects of RA on CNS have been investigated in pregnant mice (n = 20) divided into four groups: (1) untreated controls, (2) controls which received a single dose of DMSO, (3) a group that received 40 mg/kg, and (4) a group that received 60 mg/kg of all-trans RA in DMSO, respectively on the eighth day of gestation. Embryos whose dams had received 40 and 60 mg/kg doses of RA, showed malformations and decreased size. At 40 mg/kg dosage level, 50% of the embryos had closed neural tubes while at 60 mg/kg dosage level the neural tube failed to close. The neuroblast mantle layers were disorganized in the 40 mg/kg and even more in the 60 mg/kg exposed group compared to the controls. In mitosis, the density of chromatin was increased in the 60 mg/kg dose group. Compared to controls the 40 and 60 mg/kg dose groups of RA treated dams decreases in the luminal longitudinal and internal measures were observed. Also the thickness of ventricular, mantle and marginal layers was smaller. Wide intercellular spaces due to the degenerated cells at high doses of RA as well as an accumulation of intercellular fluid were observed. Therefore, the wedge shape of neuroepithelium was abolished, preventing the elevation of the neural wall.     

Certain vitamin D metabolites potentiate the expression of parathyroid hormone bioactivity

With the development of a sensitive bioassay for the skeletal effects of parathyroid hormone (PTH), it has become possible to investigate the possible interaction between PTH and vitamin D3 metabolites. This assay is based on the stimulation of glucose-6-phosphate dehydrogenase (G6PD) activity in either the hypertrophic chondrocytes of the growth plate or the osteoblasts lining the metaphyseal trabeculae of rat metatarsals. The response to PTH is paralleled by the activity of dibutyryl cAMP. None of the vitamin D3 metabolites tested had any effect on enzyme activity when tested by themselves. However, both 1,25(OH)2D3 and 25(OH)D3 caused a dose-related potentiation of the response to PTH. Neither 1,24,25(OH)3D3 nor 1,25(OH)2D3 26,23-lactone potentiated the response to PTH. Because this potentiation of the response to PTH occurs after only 8 minutes, it is suggested that it represents a nongenomic response to the vitamin D3 metabolites.     

Evaluation of craniosynostosis with three-dimensional CT imaging

Technological advances in computer image analysis have made possible three-dimensional (3D) surface reformations of anatomic structures from contiguous axial CT slices. We have recently utilized this new imaging technique in six patients with primary, isolated craniosynostosis. In each case 3D CT demonstrated the exact extent of synostosis, and in five cases 3D CT images facilitated surgical planning by precisely localizing the proper site for craniectomy. Three-dimensional CT may be a useful adjunct to imaging and surgical planning in this condition.     

Effects of pressure sensitive adhesives and chemical permeation enhancers on the permeability of fentanyl through excised rat skin

Drug-in-adhesive patches (DIAPs) of fentanyl were formulated using various pressure sensitive adhesives (PSAs) and various chemical permeation enhancers (CPEs). The effects of PSAs and CPEs on skin permeation of fentanyl from DIAPs were evaluated using modified jacketed Franz diffusion cells fitted with excised rat abdominal skin. It was demonstrated that the permeation rate or steady state flux (J(ss)) of the drug through the excised rat skin was dependent on the viscosity and type of acrylic PSA as well as the type of CPE. Among different acrylic PSAs, Duro-Tak 2054 and Duro-Tak 2516 showed the highest J(ss) of 1.95 microg cm(-2) h(-1) and the lowest J(ss) of 1.43 microg cm(-2) h(-1), respectively. Among the various CPEs used, propylene glycol and polyethylene glycol 400 showed 1.61 and 1.18, the highest and the lowest enhancement ratios (ER) of the skin permeation of fentanyl, respectively. Oleic acid and cetyl alcohol moderately increased the skin permeation of fentanyl. It was also shown that increasing the concentration of CPE led to reduction in the adhesion property of PSA as measured by the 180 degrees peeling strength test. Moreover, it was found that the permeation rate increased as the fentanyl loading increased from 1 to 3%. The skin permeation rate of fentanyl did not increase significantly beyond 3% drug loading. It was concluded that propylene glycol as a CPE and cosolvent in 10% (m/m) with 3% fentanyl loading in Duro-Tak 2054 showed an effective monolithic DIAP for the development of a transdermal therapeutic system for fentanyl.     

Long-term results of renal transplantation: A single-center analysis of 1200 transplants

The present study is a report of long-term results of the first 1200 operations from December 1988 to December 2003. Graft and patient survival rates in eligible cases were computed with Kaplan-Meier analysis. Recipients were 808 men, 392 women of mean age 33.6 +/- 12.5 years. Eighty six percent of cases used organs from living donors (40% related, 41% unrelated, and 5% spouses) and 14% from cadaveric source. The most common causes of end-stage renal disease were chronic glomerulonephritis (18.2%); reflux nephropathy (13.4%); and diabetic nephropathy (10.1%). Among 215 (17.9%) patients, 156 patients (13%) died in the posttransplant period. Most common causes of death were cardiovascular (28.3%), graft loss (20.7%), and infections (19.6%). The 1- and 3-year patient survival rates were 94% and 91.5%, and graft survival rates were 88% and 84%. Although the success rate of operations was not satisfactory at the beginning, the current data reflect a >90% survival rate comparable to the major centers in the world.