Introduction. Nonsteroidal antiinflammatory drugs (NSAIDs) remain the most widely prescribed medications worldwide. Despite generally accepted strategies to reduce the side effects of these drugs towards stomach mucosa, there is increasing evidence that enteric mucosa is also susceptible to NSAIDs toxicity. However, uptodate medicine provides limited options for small intestine protection in chronic NSAIDs users. Short peptides were repeatedly reported to be promising agents for gastroprotective purposes [1,2].Aim of research was to assess the effect of H-Glu-Asp-Gly-OH and H-Lys-Glu-Asp-OH on NO-synthases (NOS) activity and lipid peroxidation processes in small intestinal mucosa (SIM).

 Material and methods. Studies were conducted on white male rats, devided into 4 groups (n=6 per group): 1) control; 2) intragastrically (ig) administered indomethacin (IND), 10 mg/kg; 3-4) ig pretreated with H-Glu-Asp-Gly-OH and H-Lys-Glu-Asp-OH (10µg) ig 30 min before IND introduction. 24h later rats were sacrificed, small intestine was isolated, washed with saline, exposed to gross inspection and in SIM homogenates NOS activity and MDA content were determined. In blood plasma L-arginine concentration was measured.

Results. Gross inspection of SIM did not reveal any visible lesions in experimental animals. However, biochemical investigations of SIM homogenates revealed that nonselective cyclooxygenase (COX)-1/COX-2 blockage with IND caused the development of nitrosooxidative stress. In SIM of IND-treated rats the increase of activities of NOS (28%, p<0.05) and iNOS (35%, p<0.05) was revealed, cNOS activity had tendency to decrease and L-arginine concentration in plasma decreased by 40% (p<0.05) compared to control group. MDA content increased by 35% (p<0.05) compared to control animals. In H-Lys-Glu-Asp-OH-pretreated rats iNOS activity decreased by 26% (p<0.05) in SIM and L-arginine concentartion in plasma increased by 27% (p<0.05) compared to the effect of IND. Pretreatment with H-Glu-Asp-Gly-OH did not cause any statistically significant difference in nitrosooxidative stress indices in SIM and blood plasma, however a tendency to decrease of iNOS activity in SIM, compared to isolated effect of IND, was noted.

Conclusions. Nonselectice COX-1/-2 blockage with IND causes nitrosooxidative stress in SIM. Tripeptide H-Lys-Glu-Asp-OH  reversed pathobiochemical changes in SIM, induced by COX-1/COX-2 blockage and its molecular mechanism of action needs further elucidation.

Face index and penetrative sex is not the only path to orgasm. Even non-genital stimulation, like kissing, petting, or nipple play can do the trick. Whether you have in a new relationship, on your honeymoon or approaching the 10-year mark of marriage, having a good sex life takes a deep intimacy that goes beyond the physical. Having good sex means knowing how your partner's body works and what he needs. It means knowing your own needs, and owning your sexuality and pleasure! What better way to do this than by discovering new, interesting facts about female orgasms, right? These interesting facts about female orgasms will make sex with your partner feel new again. 70 per cent of female orgasms are clitoral in origin. Because the clitoris has over 8,000 nerve endings, it's no wonder that clitoral stimulation is responsible for most female orgasms. While clitoral orgasms happen more than vaginal orgasms for most women, it is possible to have both. This is what is known as a blended orgasm. This climax combo can be achieved through certain positions, such as lying on your back with feet dangling over the edge of the bed. Then, raise your pelvis during sex, as your partner reaches in to stimulate your clitoris.

Maintrac® is a laboratory based method to quantify in a reproducible manner living circulating tumor cells. This way it is possible to do further analytic with these cells. Be it molecular genetic testing of certain tumor characteristics or surface protein determination for real pharmaceutical target identification. Since these CTCs are alive it is possible to check all different chemotherapeutics and their killing rate on these CTCs. Best working medications can be selected before starting aggressive chemotherapies. Furthermore it is possible to monitor treatment success “just” by quantifying CTC over the cause of the therapy. Even during and after endocrine therapy it is possible to show how long to give i.e. Tamoxifen or when to switch to other, more efficient medication in case the cell number is increasing. This method was developed over the last decade and works on all tumors deriving from epithelial origin (almost all solid tumors). We showed in several clinical trials with > 650 patients and > 100,000 measurement significant improvement for patients and the overall relapse free survival while being monitored and treated based on this method. Maintrac is nowadays already used in clinical routine in ~30 countries worldwide.

Hyperpolarized (HP) agents have the potential to vastly improve MRI sensitivity for the diagnosis and management of many diseases. The hyperpolarization of xenon (129Xe) can result in an enhanced signal by a factor of up to 100,000, which enables direct detection of the HP agent with no background signal. HP 129Xe is a potentially valuable MR tracer for functional imaging due to its high solubility in the blood and brain, and its large chemical shift range. HP 129Xe can also be used withbiosensors for molecular MR imaging using the hyperpolarized xenon chemical exchange saturation transfer (HyperCEST) technique which allows the detection of probes at as low as femtomolar concentrations. HP 129Xe can be delivered to a target by means of dedicated molecular cage systems that can encapsulate xenon and bind to biological sites of interest using a targeting moiety, such as an antibody or a ligand, which enables detection of a specific biomarker. We have obtained the worlds first in vivo HyperCEST image via intravenous injection in a rat, which clearly illustrates the kidneys.

Human biology, or at least the understanding of the complexity of human biology, has exponentiated since the turn of the century. Previously it was thought that the human Genome, or at least its Transcriptome subset, expressed around 20,000 proteins. Yet the Human Proteome is currently estimated to be between 250,000 and 1 million proteins. Add to that the 42,000 components of the human Metabolome which have already been identified, and the process of identifying clinically useful biomarkers is becoming very difficult indeed. Our focus has been on yet another level of complexity, the Microbiome, understanding its biomarker contribution by both transcriptional and post-translational mechanisms. While studying the action of microbiome components on the VDR Nuclear Receptor we came to realize that the biomarkers loosely called “Vitamin D” were actually steroid transcriptional-factors, rather than “vitamins.” When we published this it seemed as though the whole world had descended on our shoulders. Clinical Medicine just didn’t want to know that what it thought was a biomarker for health was actually a biomarker for disease. Even today, now that the prosective studies are coming in, few appreciate the complexity of properly interpreting the “Vitamin D” biomarkers. Here we propose that TNF-alpha is also a compromized biomarker. The discovery that TNF-alpha release in the spleen is controlled primarily by the brain, and that brain immune activity is affected by the electrosmog which nowadays surrounds us, necessarily changes the way that this biomarker needs to be studied and interpreted.

Aurora-A serine threonine kinase is a key player in cell cycle controls and essential for the progression through mitosis. It was found over-expressed in many human cancers. A gain of activity was proved to favour chromosome instability and carcinogenesis in mice. More importantly its over-expression was also reported to lead to resistance to drugs such as microtubule poisons used in chemotherapy. Additionally a loss of Aurora-A activity leads to uncontrolled stem cells proliferation at the origin of cancers in Drosophila and presumably in mice too. Aurora-A kinase has been a priority target for the development of inhibitors to be used in cancer treatment. Using a chemical-genetic approach, we investigated the effects of a specific inhibition of Aurora-A kinase during cell cycle progression, in particular during mitosis, in normal conditions but also in the presence of taxol or nocodazole. At the contrary to previous reports, we found that Aurora-A kinase activity was essential to arrest the cells in mitosis in response to taxol or nocodazol. An inhibition of Aurora-A in the presence of these drugs clearly leads to abortive mitosis and formation of polyploidy cells.