Hypothalamic insulin and glucagon-like peptide-1 levels in an animal model of depression and their effect on corticotropin-releasing hormone promoter gene activity in a hypothalamic cell line

Background

In depression, excessive glucocorticoid action may cause maladaptive brain changes, including in the pathways controlling energy metabolism. Insulin and glucagon-like peptide-1 (GLP-1), besides regulation of glucose homeostasis, also possess neurotrophic properties. Current study was aimed at investigating the influence of prenatal stress (PS) on insulin, GLP-1 and their receptor (IR and GLP-1R) levels in the hypothalamus. GLP-1 and GLP-1R were assayed also in the hippocampus and frontal cortex – brain regions mainly affected in depression. The second objective was to determine the influence of exendin-4 and insulin on CRH promoter gene activity in in vitro conditions.

Characterization of pigmented dermo‐epidermal skin substitutes in a long‐term in vivo assay

In our laboratory, we have been using human pigmented dermo‐epidermal skin substitutes for short‐term experiments since several years. Little is known, however, about the long‐term biology of such constructs after transplantation. We constructed human, melanocyte‐containing dermo‐epidermal skin substitutes of different (light and dark) pigmentation types and studied them in a long‐term animal experiment. Developmental and maturational stages of the epidermal and dermal compartment as well as signs of homoeostasis were analysed 15 weeks after transplantation. Keratinocytes, melanocytes and fibroblasts from human skin biopsies were isolated and assembled into dermo‐epidermal skin substitutes. These were transplanted onto immuno‐incompetent rats and investigated 15 weeks after transplantation. Chromameter evaluation showed a consistent skin colour between 3 and 4 months after transplantation. Melanocytes resided in the epidermal basal layer in physiological numbers and melanin accumulated in keratinocytes in a supranuclear position. Skin substitutes showed a mature epidermis in a homoeostatic state and the presence of dermal components such as Fibrillin and Tropoelastin suggested advanced maturation. Overall, pigmented dermo‐epidermal skin substitutes show a promising development towards achieving near‐normal skin characteristics and epidermal and dermal tissue homoeostasis. In particular, melanocytes function correctly over several months whilst remaining in a physiological, epidermal position and yield a pigmentation resembling original donor skin colour.     

Seemingly healthy skin in atopic dermatitis: observations with the use of high‐frequency ultrasonography,preliminary study

Background: Atopic dermatitis (AD) is a chronic, relapsing skin disorder which is strictly determined by the epidermal barrier function. In previous studies, there is conclusive evidence that normal‐looking, nonlesional skin presents meaningful barrier function defect and a sub‐clinical eczematous skin reaction. Aim: The authors intended to visualize nonlesional AD skin with the use of high frequency ultrasonography to show that the normal‐looking, nonlesional skin may present significant abnormalities in USG examination. Methods: We have performed analysis with the use of high‐frequency 20 MHz skin sonography in the cases of 15 AD patients of the Department of Dermatology, Medical University, Poznań, Poland. The clinical score has been evaluated on the basis of W‐AZS index and EASI. The results were presented in the form of ultrasonographic images. Results: High frequency ultrasonography revealed an echopoor band within nonlesional skin of six (40%) examined AD patients and in all cases within skin lesions. Conclusion: Our results indicate the significant role of skin ultrasonography in the complete clinical evaluation of patients with AD, which may serve as an element in selection of the most appropriate topical treatment. An echopoor band beneath the echo entry within nonlesional skin of some AD patients may reflect subclinical eczematous reaction and the readiness for the development of typical skin lesions. For this purpose, we suggest to name an intact skin in AD as seemingly healthy skin.     

Impact of cardiac resynchronisation therapy on adaptation of circulatory and respiratory systems to exercise assessed by cardiopulmonary exercise test in patients with chronic heart failure

BACKGROUND: Cardiac resynchronisation therapy (CRT) has become a valuable therapeutic tool in patients with advanced chronic heart failure (CHF). The search for optimal methods for the assessment of CRT efficacy is still underway. AIM: To evaluate the impact of implantation of CRT devices in patients with CHF on adaptation of circulatory and respiratory systems to maximal exercise assessed by cardiopulmonary exercise tests (CPX) and 6-minute walking tests (6MWT). METHODS: We investigated 27 patients (22 males, 5 females, 61.2+/-9.1 years) with a CRT device implanted due to advanced CHF, which resulted from ischaemic or dilated cardiomyopathy. All patients before implantation underwent echocardiography, CPX with expired gas analysis and 6MWT. Investigations were repeated at 3-6 months after CRT implantation. In CPX we evaluated peak oxygen uptake (peak VO2), oxygen pulse, maximal minute ventilation-carbon dioxide production (VE/VCO2 (max)), and its slope (VE/VCO2 slope) and VE/VO2 slope, VO2 in anaerobic threshold (AT), and cardiac and respiratory reserve. In 6MWT we evaluated walking distance and heart rate and blood pressure response to exercise. RESULTS: We noted statistically higher mean peak VO2 after CRT implantation in the studied group: 11.34+/-3.38 vs. 14.56+/-3.99 ml/kg/min (p<0.0001) and 1.01 +/-0.44 vs. 1.4+/-0.55 l/min (p=0.003) and higher values of expired CO2: 1.00+/-0.43 vs. 1.43+/-0.67 l/min (p=0.004). The O2 pulse rose from 9.65+/-3.39 to 13.23+/-5.43 ml/beat (p=0.015). We also observed a significant reduction of VE/VCO2 slope from 42.34+/-13.35 before CRT to 34.77+/-6.04 after CRT (p=0.0196) and a significant decrease of VE/VO2 slope from 41.32 +/-15.46 to 34.01+/-6.27 (p=0.037). VE/VCO2 (max) fell from 58.02+/-15.86 to 50.1+/-13.14 (p=0.009). Patients estimated their dyspnoea on the Borg scale at peak exercise at 4.75+/-0.75 points before CRT and at 3.67+/-1.15 points (p=0.002) after CRT. Patients could walk a longer distance during 6MWT than before CRT (367+/-154.9 vs. 231.1+/-170.3 m, p<0.001). CONCLUSIONS: Cardiac resynchronisation therapy improves exercise tolerance measured by means of CPX and 6MWT, improves respiratory system efficiency and restores its adaptive mechanisms during exercise in patients with advanced CHF. Better exercise adaptation after CRT may be objectively measured with CPX parameters, and correlates with improvement of clinical symptoms. CPX seems to be a very helpful tool in assessing the results of CRT.     

Pharmacological versus invasive treatment in patients with atrial fibrillation

Aim of this prospective study was to assess quality of life (QoL), left ventricular (LV) function and exercise performance in two groups of patients (pts) with atrial fibrillation (Af) treated with: radiofrequency catheter ablation (RFA) and antiarrhythmic drugs (AA). Between 1996 and 2000 - 74 patients, 28 women, with drug refractory Af were enrolled by clinical indications for two modes of therapy: RFA and AA. RFA group consisted of 38 pts, 63.7 +/- 11.5 years old: 28 pts with RF AV Node ablation and pacemaker implantation (PI) and 10 pts with AV Node modification or right atrial isthmus RF ablation due to Af conversion to atrial flutter (Aflu) during medical therapy. AA group consisted of 36 pts, aged 59.7 +/- 13.8 years. Patients from RFA group suffered significantly more serious diseases than pts from AA group. No significant (sign.) differences between two groups were found in age, gender, arrhythmia history and number of AA taken. Pts were analyzed before entry, after 3 and 12 months of follow-up (3 mo. FU, 12 mo. FU) with following indices: LV function (Echo: EF & FS), exercise performance (treadmill test), QoL questionnaires, number of hospital admissions connected to arrhythmia or procedures (RFA & PI), number of AA drugs taken in RFA group. RFA group: Two deaths occurred due to end stage respiratory insufficiency (COPD), one pt required reposition of pacemaker lead. AA group: 3 pts required RFA due to uncontrolled Af/Aflu (AV Node ablation with PI - 1 pt, right atrial isthmus ablation - 2 pts). Analysis of two patients groups: LV function: Sign. improvement (EF & FS) in both groups in 12 mo. FU; Exercise performance: no sign. changes in 3 and 12 mo. FU. QoL: Arrhythmia scale: 3 mo. FU sign. reduction in both groups; 12 mo. FU reduction in RFA group only; Anxiety scale: 3 and 12 mo. FU sign. reduction of anxiety level in RFA group; Exercise and activity scales: 3 and 12 mo. FU sign. improvement in RFA group. During 3 and 12 mo. FU sign. less pts from RFA group required hospital admission versus pts from AA group. Sign. reduction in AA was noted in RFA group. Patients with symptomatic Af treated with RFA benefit from this kind of therapy more than patients treated with AA. Quality of life improvement visible in short term observation in patients from RFA group is still present after one year observation. Improvement in LV function is observed after one year in both groups of pts with Af.