Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion.

Genetic variants that result in truncation in desmoplakin (DSP) are a known cause of arrhythmogenic cardiomyopathy (AC). In homozygous carriers, the combined involvement of skin and heart muscle is well defined, however, this is not the case in heterozygous carriers. The aim of this work is to describe cutaneous findings and analyze the molecular and ultrastructural cutaneous changes in this group of patients. Four women and eight men with a mean age of 48 ± 14 years were included. Eight met definitive criteria for AC, one was borderline and three were silent carriers. No relevant macroscopic changes in skin and hair were detected. However, significantly lower skin temperature (29.56 vs. 30.97 °C, p = 0.036) and higher transepidermal water loss (TEWL) (37.62 vs. 23.95 g m 2 h 1, p = 0.028) were observed compared to sex- and age-matched controls. Histopathology of the skin biopsy showed widening of intercellular spaces and acantholysis of keratinocytes in the spinous layer. Immunohistochemistry showed a strongly reduced expression of DSP in all samples. Trichogram showed regular nodules (thickening) compatible with pseudomonilethrix. Therefore, regardless of cardiac involvement, heterozygous patients with truncation-type variants in DSP have lower skin temperature and higher TEWL, constant microscopic skin involvement with specific patterns and pseudomonilethrix in the trichogram.

Effect of coenzyme A on outer hair cells in cisplatin ototoxicity: functional and ultrastructural study.

The aim of this study was to use functional and morphological analyses to evaluate the protective effect of coenzyme A (CoA) in cisplatin-induced toxicity in outer hair cells (OHC). Three groups of 8 guinea pigs were used: control (group I), cisplatin-treated (group II) and cisplatin + CoA-treated (group III). In groups II and III, a single ototoxic dose of cisplatin (10 mg/kg) was injected intraperitoneally. Group III was co-treated with CoA (900 µg/kg per day for 7 consecutive days). Electrocochleography (ECoG) recordings were made before and after the 7-day treatment period in all groups. After ECoG on day 7, all animals were anesthetized and the cochleae were removed and fixed for ultrastructural analysis. Cell damage in OHC was observed with transmission electron microscopy. Cisplatin induced a significant increase in auditory thresholds (p<0.001) compared to group I (control). In contrast, group III (cisplatin + CoA) had significantly reduced thresholds (p<0.001) compared to the group treated with cisplatin alone (group II).We found no significant differences between the control group and animals co-treated with cisplatin and CoA. The electron microscopy findings in OHC were consistent with these results. Ultrastructural analysis of OHC in group II showed morphological indications of necrosis, i.e. cytoplasmic swelling and vacuolation, and mitochondrial swelling. In group III the cell morphology of OHC was preserved, with ultrastructural characteristics similar to the control group. In conclusion, co-treatment with cisplatin with CoA inhibited antineoplastic-induced cytotoxicity in OHC in a guinea pig model.

[Bile duct reconstruction using 3-dimensional collagen tubes]. / Reconstrucción del conducto biliar mediante tubos tridimensionales de colágeno.

INTRODUCTION: In recent years, with widespread laparoscopic cholecystectomy and liver transplantation, complications involving the biliary system are increasing. All current techniques have a high risk of recurrence or high-morbidity. MATERIAL AND METHODS: A 3-dimensional collagen bile duct modified with agarose hydrogel was developed to substitute the affected extrahepatic bile duct. It was used in 40 guinea pigs and the histology and physiology was studied at 4 weeks, 3 and 6 months after transplantation. CONCLUSIONS: The graft shows to have a high potential in applications to treat hepatobiliary diseases which require surgery.

Tissue-engineering repair of extrahepatic bile ducts.

BACKGROUND: In recent years, with the widespread use of laparoscopic cholecystectomy and liver transplantation, complications involving the biliary system are increasing. All techniques available have a high risk of recurrence or high-morbidity problems. We developed a three-dimensional collagen duct modified with agarose hydrogel, to substitute the affected extrahepatic bile duct. MATERIALS AND METHODS: We used it in 40 guinea pigs and studied the histology and physiology at 4 wk, 3, and 6 mo after transplantation. Blood test, histologic techniques, and cholangiography were performed in all of them. RESULTS: All experimental animals survived up to their sacrifices. Our graft showed highly potential applications to treat hepatobiliary diseases that require surgery.