Renal epithelia in long term gradient culture for biomaterial testing and tissue engineering

In the organism epithelia perform perfect barrier functions. Strong rheological and mechanical influences constitute the normal environment of this tissue throughout life. Most epithelia are exposed to different fluids at the luminal and basal sides. To obtain realistic information about tissue development in modern biomaterial testing and tissue engineering it is necessary to mimick the natural environment of epithelia. Cultured cells are brought in contact with an artificial extracellular matrix to determine whether proper development into a functional epithelium occurs. As under natural conditions the cultures have to withstand mechanical and fluid stress over a prolonged period of time in close contact to a selected biomaterial. However, development of tissue-specific features such as polarization, tightness and transport under in vitro conditions will only occur, if the biomaterial and the culture conditions support tissue development. Leakage, edge damage and pressure differences during culture have to be avoided so that the natural functions of the growing epithelium can develop. Our aim is to generate functional epithelia derived from renal explants containing stem cells, which are microsurgically isolated and placed into specific O-ring carriers for optimal handling. The cells develop in combination with a collagenous matrix from an embryonic into a functional collecting duct (rCD) epithelium. To achieve optimal culture conditions the tissue is placed in a gradient culture container. A typical environment can be simulated by superfusing different culture media at the luminal and basal sides. Within days epithelia growing inside the gradient container build up a physiological barrier, which is maintained during the whole culture period. The described method allows to investigate the influence of new biomaterials over prolonged periods of time.     

TMT-induced autonomic and behavioral changes and the neural basis of its processing

One of the main interests in the field of neuroscience is the investigation of the neural basis of fear. During recent years, an increasing number of studies have used trimethylthiazoline (TMT), a component of red fox feces, as a stimulus to induce fear in predator naive rats, mice, and voles. The aim of the present review is to summarize these studies. We present an overview to the autonomic and behavioral changes that are induced by TMT exposure. Then, we summarize the small number of studies that have examined the neural processing of the TMT stimulus. Finally, we compare these studies with those using a natural predator or predator odor to induce fear and discuss the possible use of TMT exposure in rodents as an animal model of unconditioned fear in humans.     

KATP channel openers: structure-activity relationships and therapeutic potential

ATP-sensitive potassium channels (K(ATP) channels) are heteromeric complexes of pore-forming inwardly rectifying potassium channel subunits and regulatory sulfonylurea receptor subunits. K(ATP) channels were identified in a variety of tissues including muscle cells, pancreatic beta-cells, and various neurons. They are regulated by the intracellular ATP/ADP ratio; ATP induces channel inhibition and MgADP induces channel opening. Functionally, K(ATP) channels provide a means of linking the electrical activity of a cell to its metabolic state. Shortening of the cardiac action potential, smooth muscle relaxation, inhibition of both insulin secretion, and neurotransmitter release are mediated via K(ATP) channels. Given their many physiological functions, K(ATP) channels represent promising drug targets. Sulfonylureas like glibenclamide block K(ATP) channels; they are used in the therapy of type 2 diabetes. Openers of K(ATP) channels (KCOs), for example, relax smooth muscle and induce hypotension. KCOs are chemically heterogeneous and include as different classes as the benzopyrans, cyanoguanidines, thioformamides, thiadiazines, and pyridyl nitrates. Examples for new chemical entities more recently developed as KCOs include cyclobutenediones, dihydropyridine related structures, and tertiary carbinols.     

Survival after surgical treatment of breast cancer

Background The principle objective of locoregional treatment in breast cancer is to eradicate local disease in the breast and local lymph nodes. Surgery in breast cancer provides locoregional control of the disease by resection appropriate to oncological principles, i.e. complete resection with tumour-free margins. Type and extent of breast surgery is dependent on tumour stage; beyond that and even more importantly, prognosis of an individual patient depends upon its stage at diagnosis.Method We reviewed the current literature, working out stage-specific survival and disease-free survival (DFS). The reported data were considered, according to stage and type of surgery, and a clear survey up to 20 years after surgery was depicted. Additionally, we assessed quality of life after breast cancer surgery.Results Overall survival (OS) rates after 5 years range from 93–84% in women diagnosed with stage I disease to 18% in women diagnosed with stage IV disease. In the management of stages I and II breast cancer, breast conservation with lumpectomy and radiation is a preferable alternative to mastectomy, with equivalent patient outcome. In stages III and IV breast cancer, surgery allows local control of the disease, but prognosis depends predominantly on the response to systemic treatment, as does prognosis in all breast cancer patients.Conclusion The reported data distributing patients outcome according to stage and surgical treatment provide a clear summary in order to estimate an individual patients risk.     

Catestatin--a novel neuropeptide in carcinoid tumors of the appendix

BACKGROUND: The aim of the study was to investigate the immunohistochemical distribution of the novel neuropeptide catestatin in carcinoid tumors. Catestatin, a novel 21 amino acid neuropeptide derived from chromogranin A, was determined immunohistochemically in 30 carcinoid tumors of the appendix and various carcinoid tumors of other localities. MATERIALS AND METHODS: Paraffin-embedded tissues from 30 carcinoid tumors of the appendix and 16 other carcinoid tumors (5 bronchus-, 5 stomach-, 2 small bowel-, 4 large bowel carcinoid tumors) were incubated with antibodies specific for catestatin, chromogranin A and chromogranin B. Immunohistochemical staining of catestatin was compared to staining with chromogranin A and B. Western blot analysis was performed in one patient with ileal carcinoid. RESULTS: Thirty patients (20 women, 10 men) with carcinoid tumors of the appendix and 16 patients with other localized carcinoid tumors were investigated. Twenty-six of the appendiceal tumors were localized in the apex of the appendix and 4 tumors in the midportion; none of the tumors was localized at the base of the appendix. Median tumor diameter was 10.7 mm (range 4-18 mm). Immunoreactivity to catesatatin was positive in 28 patients (negative in 2, 0-10% in 11 patients, 11-50% in 14 patients, 51-100% in 3 patients). In 16 patients with carcinoid tumors in various other localizations, catestatin was also expressed. Western blot analysis of ileal carcinoid showed abundant catestatin reactivity with accelerated processing of chromogranin A in the tumor tissue. CONCLUSION: Catestatin derived from chromogranin A, which is the most widely distributed marker of neuroendocrine tumors, is expressed in high frequency in carcinoid tumors of the appendix (93.3%).     

Postextrasystolic potentiation of vessel compression in myocardial bridging: detection by intravascular sonography

We present the case of 67-year-old man with exertional chest pain. Coronary angiography revealed myocardial bridging of the left anterior descending coronary artery (LAD) with mild systolic vessel compression. An intracoronary Doppler sonographic examination of the LAD showed a fingertip-shaped antegrade flow pattern with a steep acceleration of coronary flow velocity during early diastole, followed by a steep deceleration and then a plateau in the coronary flow velocity during mid and late diastole. An intravascular sonographic examination using a 30-MHz transducer catheter showed eccentric vessel compression during systole and substantial augmentation of vessel compression after an incidental extrasystole. Both intracoronary Doppler sonography and intravascular sonography provided important information that helped us to identify myocardial bridging in this patient.