Mitogen-activated protein kinases in normal and (pre)neoplastic ovarian surface epithelium

Mitogen-activated protein kinases (MAPKs) are a group of serine/threonine kinases which are activated in response to a diverse array of extracellular stimuli and mediate signal transduction from the cell surface to the nucleus. It has been demonstrated that MAPKs are activated by external stimuli including chemotherapeutic agents, growth factors and reproductive hormones in ovarian surface epithelial cells. Thus, the MAPK signaling pathway may play an important role in the regulation of proliferation, survival and apoptosis in response to these external stimuli in ovarian cancer. In this article, an activation of the MAPK signaling cascade by several key reproductive hormones and growth factors in epithelial ovarian cancer is reviewed.     

Creatine kinase isoenzyme activity during and after an ultra-distance (200 km) run

It is commonly assumed that creatine kinase (CK) activity in plasma is related to the state of an inflammatory response at 24-48 h, and also it has shown biphasic patterns after a marathon run. No information is available on CK isoenzymes after an ultra-marathon run. The purpose of the present study is to examine the CK isoenzymes after a 200 km ultra-marathon run and during the subsequent recovery. Blood samples were obtained during registration 1 2 h before the 200-km race and during the race at 100 km, 150 km and at the end of 200 km, as well as after a 24 h period of recovery. Thirty-two male ultra-distance runners participated in the study. Serum CPK showed a marked increase throughout the race and 24 h recovery period (p < 0.001). Serum CK during the race occurs mostly in the CK-MM isoform and only minutely in the CK-MB isoform and is unchanged in the CK-BB isoform. High-sensitivity C-reactive protein (hs-CRP), oestradiol, AST and ALT increased significantly from the pre-race value at 100 km and a further increase took place by the end of the 200 km run. The results of our study demonstrate a different release pattern of creatine kinase after an ultra-distance (200 km) run compared to the studies of marathon running and intense eccentric exercise, and changes in several biomarkers, indicative of muscle damage during the race, were much more pronounced during the latter half (100–200 km) of the race. However, the increases in plasma concentration of muscle enzymes may reflect not only structural damage, but also their rate of clearance.     

Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases

Artificial endonucleases consisting of a FokI cleavage domain tethered to engineered zinc-finger DNA-binding proteins have proven useful for stimulating homologous recombination in a variety of cell types. Because the catalytic domain of zinc-finger nucleases (ZFNs) must dimerize to become active, two subunits are typically assembled as heterodimers at the cleavage site. The use of ZFNs is often associated with significant cytotoxicity, presumably due to cleavage at off-target sites. Here we describe a structure-based approach to reducing off-target cleavage. Using in silico protein modeling and energy calculations, we increased the specificity of target site cleavage by preventing homodimerization and lowering the dimerization energy. Cell-based recombination assays confirmed that the modified ZFNs were as active as the original ZFNs but elicit significantly less genotoxicity. The improved safety profile may facilitate therapeutic application of the ZFN technology.     

Biology and physiology of Calbindin-D9k in female reproductive tissues: Involvement of steroids and endocrine disruptors

Although Calbindin-D9k (CaBP-9k), a cytosolic calcium binding protein which has calcium binding sites, is expressed in various tissues, i.e., intestine, uterus, and placenta, potential roles of this gene and its protein are not clearly understood. Uterine CaBP-9k may be involved in controlling myometrial activity related with intracellular calcium level and is not under the control of vitamin D despite the presence of vitamin D receptors. But, it is under the control of the sex steroid hormones, estrogen (E2) and progesterone (P4), in female reproductive systems including the uterus and placenta. Thus, in this review, we summarize recent research literature in regards to the expression and regulation of CaBP-9k in mammals and introduce the research data of recent studies by us and others.     

Genotoxic activity of 3-[3-phenyl-1,2,4-oxadiazol-5-yl] propionic acid and its peptidyl derivatives determined by Ames and SOS response tests

Compounds derived from 1,2,4-oxadiazole have being reported for their anti-inflammatory activity. However, those compounds should be devoid of any genotoxic side effect. In this work, the genotoxic activity of peptidomimetic moiety-containing 1,2,4-oxadiazoles derivatives was tested based on the Ames and SOS Chromotest. The results showed no mutagenic activity on the Ames test for 3-[3-phenyl-1,2,4-oxadiazol-5-yl] propionic acid (POPA) parental drug, but a weak SOS response induction on Chromotest. The chemical modifications reduced that response to a non-significative level, with l-phenylalanine peptidomimetic derivative being showing the lowest induction response. The results pointed out for the effectiveness of promoting chemical modifications of biological active compounds to increase its mode of action, showed in previous work, without increasing and even decreasing its DNA damage effect.     

Undergraduate geriatric education through community service learning

doi: 10.1111/j.1741‐2358.2010.00444.x Undergraduate geriatric education through community service learning Introduction: Despite the exponential growth of the elderly population worldwide, geriatric education has been a formal component of only a few dental schools’ curricula. Objective: To describe the geriatric community service learning (CSL) component of the professionalism and community service (PACS) module, and to explore a CSL project carried out by a group of first year dental students at a long‐term care facility. Methods: A literature review was performed to present and describe the CSL component of the PACS module. Students’ personal reflections were used to illustrate some of the joys and challenges of experiencing a long‐term care facility environment. Results: The newly developed PACS module combines community service learning with the long‐term care experience. Students develop, apply and evaluate an educational health promotion activity in a long‐term care facility. Conclusions: The PACS module has encouraged students to acquire comprehensive knowledge and awareness of the needs and dynamics of a long‐term care as they collaboratively interacted with personnel from the facility to develop their projects. The authors would like to engage other schools in discussing the need to integrate community‐based geriatric education into their dental curricula.