Diminished Kv4.2/3 but not KChIP2 levels reduce the cardiac transient outward K+ current in spontaneously hypertensive rats

OBJECTIVE: A reduction of the Ca(2+)-independent transient outward potassium current (I(to)) in epicardial but not in endocardial myocytes of the left ventricle has been observed in cardiac hypertrophy and is thought to contribute to the electrical vulnerability associated with this pathology. METHODS: In the present study we investigated the molecular mechanisms underlying regional alterations in I(to) in hypertrophied hearts of spontaneously hypertensive rats (SHR) using the whole-cell patch-clamp technique, quantitative RT-PCR and heterologous expression of underlying ion channel subunits. RESULTS: I(to) was significantly smaller in epicardial myocytes of SHR than in Wistar-Kyoto (WKY) controls (11.1+/-0.9 pA/pF, n=20 vs. 16.8+/-1.7 pA/pF, n=20, p<0.01), but not different in endocardial myocytes from both groups. Quantitative RT-PCR analysis of the genes encoding I(to) revealed significantly lower levels of Kv4.2 and Kv4.3 mRNA in the epicardial region of SHR rats compared to WKY rats. In contrast, mRNA expression levels of all three splice variants of the beta-subunit KChIP2 were significantly higher in both endo- and epicardial myocytes from SHR than from WKY rats. In parallel, inactivation of I(to), which is negatively modulated by KChIP2, was slowed down in SHR while recovery from inactivation remained unchanged. Heterologous co-expression of increasing amounts of KChIP2b together with a fixed amount of Kv4.2 in Xenopus laevis oocytes revealed a hyperbolic relation of recovery from inactivation and inactivation time constant, demonstrating that KChIP2 preferentially affects inactivation, if its expression level is high. CONCLUSION: These results suggest that downregulation of I(to) in the left ventricle of SHR is mediated by a reduced expression of Kv4.2 and Kv4.3 (but not of KChIP2), whereas the slower inactivation of I(to) can be explained by increased expression levels of KChIP2 in SHR.     

Polyorchidism: a case report and classification

Polyorchidism is an uncommon congenital anomaly, defined as the presence of more than 2—histologically proven—testes. Approximately 90 cases are reported in the literature. It is found predominantly on the left side. We report a right-sided polyorchidism found during orchidopexy in a 6-year-old boy. The supernumerary testis had its own tunica vaginalis, epididymis, and deferent duct, but shared the blood supply with the ipsilateral distal testis. The diagnosis was confirmed histologically. Because of the shortness of its vessels, the supernumerary testis could not undergo orchidopexy and was removed.We review the classification systems proposed for polyorchidism. Most are based on embryologic considerations, but none is capable of including all cases described in the literature. Thus, we present an anatomical system for a more comprehensive taxonomy of polyorchidism according to its reproductive function.     

Patterns of interpersonal problems and their improvement in depressive and anxious patients treated with psychoanalytic therapy

Interpersonal problems were studied in 121 patients treated with psychoanalytic therapy using the Inventory of Interpersonal Problems. Four characteristic subtypes were identified, which differed in the quality and flexibility of their interpersonal behavior. Independent of the predominant type of interpersonal problems, the psychotherapy treatment led to strong decreases in interpersonal distress and increases in interpersonal differentiation. Psychoanalytic therapy was highly effective for all identified interpersonal subtypes and seems to help patients achieve more satisfactory relationships.     

Effects of a three-session skin rejuvenation treatment using stabilized hyaluronic acid-based gel of non-animal origin on skin elasticity: a pilot study

The purpose of this study was to evaluate in vivo the effects of micropuncture injections of stabilized hyaluronic acid-based gel of non-animal origin (NASHA™, Restylane Vital™) on skin elasticity, a major aspect of skin ageing. Patients (n = 19) underwent a series of three treatment sessions, spaced 4 weeks apart, with NASHA injected into the lower facial cheeks. Using the suction principle, 12 parameters describing the viscoelastic properties of the skin were assessed, before each treatment session and at follow-up visits 4 and 16 weeks after the last treatment. Treatment with NASHA significantly increased skin firmness and improved its viscoelastic recovery capacities. The most significant differences from baseline were noted at the end of the study. The changes observed in this study may underlie some of the cosmetic improvements noted after treatment with NASHA.     

Long-term benzimidazole treatment of alveolar echinococcosis with hematogenic subcutaneous and bone dissemination

We report a case of advanced alveolar echinococcosis (AE) that presented like a malignant tumor. It was diagnosed histologically from a subcutaneous nodule with skin inflammation on the right leg. Additionally, the patient showed bone metastases in the lower thoracic spine and the left third toe. This is the first case with proven hematogenic spread of AE to a subcutaneous site. The patient was treated with albendazole and remained stable for 6 years. When progression of AE occurred the therapy was changed to mebendazole, resulting in a stable condition for further 4 years.     

Tissue responses to nacreous implants in rat femur: an in situ hybridization and histochemical study

The interface of bone and aragonite nacre (Margaritifera, fresh water pearl mussel) was studied by in situ hybridization and a tartrate-resistant acid phosphatase (TRAP) histochemical assay. Columnar implants were inserted into rat femora for 4, 7, 14, 28 and 56 days. In medullary region, a burst of transient bone formation was observed, which propagated from the periphery towards the nacre implant. A fused interface of bone and nacre was observed at 14 days. Later, the new medullary bone was resorbed and bone marrow was re-established while a thin layer of bone tissue remained covering the implant surface. Expressions of collagen alpha1(I), osteocalcin, osteopontin mRNAs and TRAP in the surrounding tissue were monitored. Correlated with the histology events, a strong transient induction of collagen alpha1(I) and osteocalcin mRNAs as well as TRAP expression, exhibiting a peak signal intensity on day 7 and subsequent down-regulation after day 14 was observed. Osteopontin mRNA, in contrast, was expressed continuously. The degrading nacre surface appeared in direct contact with macrophages and multinucleated giant cells at both days 14 and 28. These cells expressed osteopontin mRNA intensively and some TRAP enzyme activity occasionally.     

Rhythmical slow wave electroencephalographic activity elicited by hippocampal injection of muscarinic agents in the rat

In freely moving male Wistar rats the hippocampal EEG was recorded by using chemitrodes (combinations of guide cannulas with bipolar recording electrodes) chronically implanted into the dorsal hippocampus (CA1).The muscarinic agents oxotremorine and arecoline applied intrahippocampally caused a long-lasting increase in the amount of rhythmical slow wave activity (RSA) of the hippocampal EEG accompanied by a decrease of the dominating frequency. At the same time, the well-known relationship between defined behavioral states and EEG patterns was abolished. The effect of oxotremorine could be blocked by subsequent application of the muscarinic antagonist scopolamine.The results support the hypothesis that a non-rhythmic activation of hippocampal muscarinic receptors may result in the generation of RSA within the hippocampal formation.     

Tacrolimus ointment causes inflammatory dendritic epidermal cell depletion but no Langerhans cell apoptosis in patients with atopic dermatitis

BACKGROUND: The topical immunomodulators tacrolimus and pimecrolimus are novel therapeutic options for atopic dermatitis (AD). The inhibition of nuclear factor of activated T cell-dependent proinflammatory cytokine production in cutaneous lymphocytes is an established effect of topical immunomodulators, which additionally influence mast cells, eosinophils, and dendritic cells (DCs). The latter include a reduced expression of the high-affinity IgE receptor FcepsilonRI, a reduced stimulatory capacity of lesional DCs, and a selective depletion of the inflammatory dendritic epidermal cells (IDECs) but not of Langerhans cells (LCs) from the lesional skin. OBJECTIVE: Because induction of apoptosis in lymphocytes is a reported tacrolimus effect, we asked whether tacrolimus ointment induces apoptosis of LCs or IDECs in AD lesions. METHODS: Epidermal single-cell suspensions were prepared from AD lesions of 9 tacrolimus-treated and 5 hydrocortisone butyrate-treated patients with AD before and after 1 week of treatment. Cell numbers, apoptosis rate, and immunophenotype were assessed by using the standardized FACS technique with terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, Annexin V, and 3-color immunophenotyping. Freshly isolated LCs and monocyte-derived DCs served as in vitro controls. RESULTS: Tacrolimus and steroid ointment induced a selective depletion of IDECs from the epidermis and reduced the expression of the costimulatory molecules CD80 and CD86. Tacrolimus ointment did not increase the rate of apoptotic DCs, whereas steroid ointment did so. The isolation-induced high apoptosis rate of freshly isolated LCs was unaffected by both drugs. CONCLUSION: Tacrolimus ointment selectively depletes IDECs and alters the immunophenotype of epidermal DCs in AD lesions, but there is no evidence for tacrolimus-induced DC apoptosis in this phenomenon.