Pericardium of the frog, Rana esculenta, is morphologically designed as a lymphatic space

The importance of the pericardium and the pericardial fluid (PF) in the control of cardiac function has emerged over the past few years. Despite the acknowledgment that amphibians are exposed to both dehydration and excessive water accumulation, nothing is known about their pericardial structure and the morphological basis of the PF formation. We have studied the parietal pericardium (PP) morphology in Rana esculenta by electron microscopy. SEM images of the inner surface, which lines the pericardial cavity, revealed the presence of large vesicles and many small circular openings. TEM observations showed that the PP is made up of an inner mesothelial lining, often constituted by two layers of very flat cells lying on a basal membrane and of regularly oriented collagen bundles. The PP outer surface is lined by a layer of flat cells, without a basal membrane. The mesothelial cells had overlapping boundaries with complex intercellular connections and a rich pool of caveolae opened in the direction of both the pericardial cavity and intercellular spaces. These cells indicate an intense intracellular and/or intercellular transfer of fluids and substances. The intraperitoneal injection of the idromineral hormone, Val5-ANG II, induced PP modifications, particularly evident at the level of the structures involved in the transmesothelial traffic. These lymphatic-like traits suggest that the frog PP represents a large lymphatic sac, subject to paracrine-endocrine remodeling, which can actively adjust the PF, influencing the composition and volume of the myocardial interstitial fluid. © 2003 Wiley-Liss, Inc

The involvement of MMP-2 and MMP-9 in heart exercise-related angiogenesis.

Little is known about the involvement of matrix metalloproteinases (MMPs) in cardiac vascular remodelling induced by exercise. Our aim was to evaluate and localize MMP-2 and MMP-9's activities in relation to capillary proliferation in mouse hearts trained for 15, 30 and 45 days. METHODS: Sixty-three mice were randomly assigned to 7 groups: four control sedentary groups (C0, C15, C30 and C45) and three groups trained by an endurance protocol (T15, T30 and T45). MMP-2 and MMP-9 were examined with zymography and immunostaining analyses. Capillary proliferation was evaluated counting the number of CD31-positive cells. RESULTS: Different activity patterns of the latent form of both MMPs were found. Pro-MMP-9 increased after 15 days of training; whereas pro-MMP-2 gradually decreased after 30 and 45 days of training below the control groups. The latter was inversely correlated with capillary growth. MMP-9 was mainly localized in myocardiocytes and less evident in capillaries. Conversely, MMP-2 was more intense in capillary endothelial cells and slightly in myocardiocytes. CONCLUSIONS: A different spatiotemporal modulation of pro-MMP-2 and pro-MMP-9 activities has been detected in the myocardium during angiogenesis related to the aerobic training. These results can be useful to draw up training protocols for improving the performance of healthy and diseased human hearts

High blood levels of IL-6 nicely correlate with animal survival in trained C26 bearing mice

Exercise is a beneficial adjunct therapy to maintain or enhance quality of life in cancer patients. Recently, few studies demonstrated a correlation between high concentrations of IL-6 and a poor survival. This depends on the equilibrium between the concentrations of IL-6 and sIL-6R. Exercise induces a beneficial increase in circulating IL-6 (1). Fresh fragments of solid C26 tumor were inoculated in healthy 3 months-old mice (n=230, M=115 and F=115). The experimental procedure were 12 weeks long. During the first 6 weeks, mice were randomly assigned to one of the experimental conditions: sedentary (SED) or progressive training (TRP). After the first 6 weeks, all mice were inoculated with a fresh fragment of tumor. All trained adult mice after the tumor inoculation were randomly assigned to a different training program: low intensity training (TRL), moderate intensity training (TRM) and high intensity training (TRH). Mice run 5 days per week on a Rota-Rod following one of the specific training program (TRP ,TRL, TRM and TRH) (2). After tumor inoculation the mice were daily weighted and tumor size monitored until death. Moreover, 8 mice for each group were sacrificed when cachexia occurred (>9% body weight loss), and blood samples were stored for CBA Enhanced flex set flow-cytometric assays (IL-6 and TNF-alpha). The TRM and TRH training protocol performed by trained adult male mice extend the median survival compared to the sedentary adult mice and trained female mice. Interesting the beneficial effect of exercise seemed to be mediated extending the survival days. Significant high blood levels of IL-6 were recorded among the male trained mice (TRM and TRH) groups in comparison with sedentary adult mice and trained female mice (TRM and TRH). The results suggest that endurance exercise as adjuvant therapy is gender and physical training level specific. This effect seems to be mediated by IL-6 blood levels

Involvement of caspase-3 and GD3 ganglioside in ceramide-induced apoptosis in Farber disease

Farber's disease (FD) is a rare genetic disorder caused by ceramidase deficiency, which results in ceramide accumulation in lung, liver, colon, skeletal muscle, cartilage, and bone. Although this disease has been symptomatically characterized, little is known about its molecular pathogenetic process. Because recent studies reported that ceramide accumulation induces GD3 ganglioside formation and apoptosis, we investigated, in tissue obtained via colonoscopy from seriously involved patients, the possible involvement of ceramide in FD colonocyte destruction. Histochemical and TUNEL analyses of paraffin-embedded sections revealed that 45 ± 4.3% of FD colonocytes showed morphological signs of apoptosis compared with the 8 ± 2.3% of constitutive epithelial cell death. Importantly, immunohistochemical study for pro-apoptotic factors showed that GD3 accumulation colocalized with active caspase-3 and cleaved K18 in FD colon tissue. These findings provide evidence for a role of the apoptotic ceramide pathway in the pathogenesis of FD

Research of cardiomyocyte precursors in adult rat heart

Recent reports supported the existence of stem cells in adult hearts. However, phenotype and localization of these cells have not been completely described and it is unknown if cardiac regenerative potential differs from one subject to another. The aims of our work were to identify different populations of cardiac stem cells by the analysis of specific markers and to evaluate the expression variability of these markers in 12 adult rat hearts. The expression of CD9, taube nuss and nanog suggests the presence of stem cells from the earliest stages of embryogenesis in adult myocardium. Their different expression could be associated to the degree of stem cell differentiation. CD34 and c-Kit antibodies were used to detect stem cells committed to one or more specific tissue lineages and we found a strong immunoreactivity for CD34 exclusively in the endothelial cells and a low positivity for c-Kit in the interstitium and next to the vessels. Moreover, as c-Kit expression highly differed within all examined hearts, we suggest that cardiomyogenic potential is different among the various subjects. Undifferentiated cells with myogenic-committed phenotype expressing GATA-4 and nestin were found, respectively, in the interstitial and myocardial cells and in few interstitial cells. Therefore, the physiologic turn over of cardiomyocytes may occur in adult hearts as it has been shown in many others organs. The study of myogenic potential could be important to identify markers specific of stem cells in in vivo adult myocardium that may be used to purify these cells and evaluate their regenerative ability

ROLE OF CHAPERONES IN HEALTHY BOWEL AND IBD.

The chaperoning system is the wole complement of chaperones, co-chaperones and chaperone cofactors of the body that preserves cell and tissue homeostasis. Its structural and/or functional defects can cause pathologic conditions, nemed chaperonopathies. Large bowel homeostasis includes a healthy status of the mucosal tissues and the microbiota. An alteration of one of them may determine, in turn, modifications of the other. Molecular chaperones of bacteria and human origin have been implicated in inflammatory bowel disease (IBD). In IBD chaperone levels usually increase and their cellular and subcellular loclization change. This is considered a physiological stress-response of mucosal cells to inflammation. However, chaperones also play active roles in IBD pathogenesis, e.g. perpetuate inflammation. Therefore, IBD can be classified among the chaperonopathies. This classification opens the door to the design and application of new forms of treatment targeting the chaperones, namely chaperonopathy