Chemically modified tetracycline (CMT-8) and estrogen promote wound healing in ovariectomized rats: Effects on matrix metalloproteinase-2, membrane type 1 matrix metalloproteinase, and laminin-5 γ2-chain

Estrogen deficiency is associated with impaired cutaneous wound healing. Remodeling of the extracellular matrix in wound healing involves the action of matrix metalloproteinases on basement membrane zone components, especially laminin-5. We studied the effects of estrogen and a potent matrix metalloproteinase inhibitor, chemically modified non-antimicrobial tetracycline, CMT-8, on wound healing in ovariectomized rats. At the tissue level, laminin-5 gamma2-chain expression was decreased and the migration-inductive 80 kDa form of laminin-5 gamma2-chain was absent in ovariectomized rats when compared with sham and CMT-8- or estrogen-treated ovariectomized animals as detected by Western blotting. The highest levels of gelatinolytic activity (matrix metalloproteinase-2 and -9) were found in sham animals. Levels were reduced in ovariectomized rats and were lowest after treating ovariectomized rats with CMT-8 or estrogen as analyzed by functional activity assay and zymography. The total amount of membrane type 1-matrix metalloproteinase was unchanged in all groups. We conclude that CMT-8 and estrogen can promote wound healing in ovariectomized rats, not only by normalizing wound bed total collagen content and structure, but also by recovering the expression and processing of key molecules in wound healing, i.e., laminin-5 gamma2-chain. This study shows, for the first time, the role of estrogen and CMT-8 in laminin-5 gamma2-chain modulation in vivo.     

Effect of lactate and bicarbonate on human peritoneal mesothelial cells, fibroblasts and vascular endothelial cells, and the role of basic fibroblast growth factor.

BACKGROUND: In patients on long-term continuous ambulatory peritoneal dialysis (CAPD), peritoneal dysfunction may occur due to loss of peritoneal mesothelial cells, peritoneal fibrosis and neovascularization. Lactate, long used as a buffer in peritoneal dialysates, has been substituted by bicarbonate in recent years. However, their effects on the peritoneum of CAPD patients are unknown. This study investigated the influence of lactate and bicarbonate on peritoneal dysfunction in CAPD patients. METHODS: The mitochondrial activity of human peritoneal mesothelial cells (HPMCs) and their expression of basic fibroblast growth factor (bFGF) were studied after culture under various conditions. We also assessed the mitochondrial-activating effect of the supernatant of those cultures on human peritoneal fibroblasts (HPFBs) and human umbilical vein endothelial cells (HUVECs) and the effect of recombinant human bFGF on the mitochondrial activity of HPFBs and HUVECs. We used the WST-1 assay to determine mitochondrial activity in HPMC. RESULTS: At pH 7.4, the mitochondrial activity of HPMCs was lowest in a medium containing 40 mM (Lac), intermediate in a lactate (15 mM) plus bicarbonate (25 mM) medium (Lac/Bic), and highest in a 40 mM bicarbonate medium (Bic). In culture supernatant, the increase of bFGF was: Lac > Lac/Bic > Bic. Mitochondrial activation of HPFBs and HUVECs was stimulated by HPMC culture supernatants in the following decreasing order: Lac > Lac/Bic > Bic. The effects of these supernatants were suppressed by a bFGF-neutralizing antibody, while recombinant bFGF caused concentration-dependent mitochondrial activation in HPFBs and HUVECs. CONCLUSIONS: The role of bFGF in peritoneal fibrosis and neovascularization may be important. A bicarbonate-containing medium is better than a lactate-containing medium for preserving cell viability in HPMCs and preventing bFGF expression by these cells.     

Trends of youth suicide in Europe during the 1980s and 1990s – gender differences and implications for prevention

Youth suicide constitutes a considerable public health problem in many European countries. Suicide mortality in adolescents and young adults has increased during the 1980s and 1990s in several European countries and predominantly in young males. This paper summarises the international discussion on potential reasons for these trends, including changes in ascertainment practices, in the prevalence of psychopathology (mainly depression and substance abuse), in psychosocial and socio-economic conditions and in the methods chosen for suicidal behaviour. Potential reasons for the gender differences in trends are scrutinised.     

Group coping skills training for anxiety and depression: its application with chronic patients

The literature on group coping skills training is reviewed and a model involving the use of a wide range of coping strategies with patients heterogeneous in terms of presenting problem is advocated. This study evaluates the effect of such an approach with a chronic inpatient and day-hospital patient population (n = 36) presenting with problems of anxiety and depression. Results suggest that the use of such groups can facilitate the transition from hospital to community. Further they are associated with symptomatic improvement that is of clinical significance in up to 50% of cases, which is largely maintained at 1 year follow-up and which is associated with a positive change in social functioning. In the light of this experience suggestions are made regarding the screening of patients and ways of enhancing group cohesion.     

Patient teaching or patient counselling?

Careless or confused use of terms such as information giving, teaching and counselling may lead to inadequate understanding and practice. In view of the progress made in this area, designed to help patients cope with illness and treatment, this paper aims to clarify and identify similarities and differences between these activities and discuss their relevance for those in most need of these types of care. Having recognised the complexity and persistence of such needs, patients, their relatives and nurses should perhaps decide their respective roles and work towards improving the quality of and opportunities for such interventions.     

Biliary excretion of radioactivity after intravenous administration of [3H]25-hydroxyvitamin D3 in man

The biliary excretion of radioactivity after intravenous [3H]25-hydroxyvitamin D3 was studied in nine patients with T-tube bile drainage. The mean +/- SD 24-hr radioactivity excretion in T-tube bile expressed as a percentage of the administered dose was 6.7 +/- 2.9%; after correction for incomplete bile collection, the value obtained was 16.0 +/- 11.1%. Chloroform solubility of biliary radioactivity increased from 27.4 +/- 8.9% to 72.9 +/- 10.1% following incubation with beta-glucuronidase. High-performance liquid chromatographic analysis of chloroform extracts of bile revealed that most of the eluted radioactivity was more polar than [3H]25-hydroxyvitamin D3. No free [3H]25-hydroxyvitamin D3 was demonstrated. Thus in man, most of the biliary radioactivity excreted following [3H]25-hydroxyvitamin D3 is in the form of water-soluble compounds, mainly glucuronides. However, our results suggest that glucuronides of metabolites other than 25-OHD3 are predominantly formed.     

Arrhythmogenic right ventricular dysplasia/cardiomyopathy assessed with 64-slice computed tomography

A 69-year-old man was admitted to hospital because of sustainedventricular tachycardia with right bundle branch block morphology.After abolition of ventricular tachycardia, an electrocardiogramshowed atrial fibrillation, complete right bundle