The role of potassium channels in the effects of resveratrol and naringenin on isolated human and rat venous blood vessels

Polifenoli su sloţena biljna, polusintetska i sintetska organska jedinjenja. Hrana sadrţi smešu različitih polifenola, a posebno voće i povrće, zeleni i crni čaj, crveno vino i dr. Nedavna istraţivanja govore u prilog značajne uloge polifenola u prevenciji kardiovaskularnih oboljenja, karcinoma, osteoporoze, neurodegenerativnih oboljenja i diabetes mellitusa. Najveći broj dokaza za to potiče iz in vitro i studija na ţivotinjama. Rezveratrol, polifenol iz crvenog groţđa i crvenog vina, je najviše proučavan polifenol. Za razliku od njega, naringenin, citrusni polifenol, pripada manje proučavanoj grupi polifenola, flavonoidima. Međutim, mehanizam vazodilatatornog i antivazokonstriktornog dejstva ovih polifenola na venskim krvnim sudovima još uvek nije proučen. Postoje dokazi da polifenoli mogu da aktiviraju kalijumove kanale (K-kanale) u glatkim mišićima arterijskih krvnih sudova i da na taj način dovedu do vazodilatacije. Ciljevi našeg istraţivanja bili su: a) da proučimo moguće antivazokonstriktorno i vazodilatatorno dejstvo rezveratrola i naringenina na izolovanoj portnoj veni pacova i humanoj pupčanoj veni, koje su prethodno kontrahovane na različite načine; b) da identifikujemo različite K-kanale vaskularnog glatkog mišića portne vene pacova i humane pupčane vene; c) da ispitamo da li K-kanali imaju značajnu ulogu u antivazokonstriktornom i vazodilatatornom dejstvu rezveratrola i naringenina; d) da proučimo postojanje dodatnog mehanizma dejstva rezveratrola i naringenina, koji je nezavisan od K-kanala, na izolovanim venskim krvnim sudovima. Kontrakcije portne vene pacova bez endotela izazivali smo pomoću električne stimulacije (ES), noradrenalina (NA), adenozin 5-trifosfata (ATP), rastvorom koji sadrţi visoku koncentraciju jona K+, kao i pomoću CaCl2...Polyphenols are complex plant-derived, semisynthetic or synthetic organic compounds. Foods contain complex mixtures of polyphenols, especially fruit and vegetables, green tea, black tea, red wine, etc. Recent studies strongly supports a role for polyphenols in the prevention of cardiovascular diseases, cancers, osteoporosis, neurodegenerative diseases, diabetes mellitus etc. Much of the evidence on the prevention of diseases by polyphenols is derived from in vitro or animal experiments. Resveratrol, polyphenol from grapes and red wine, is the most studied polyphenol, while naringenin, citrus polyphenol, belongs to the most studied group of polyphenols, flavonoids. However, the mechanisms of vasodilator and antivasoconctrictor effects of these polyphenols on venous blood vessels are not established. There are suggestions that polyphenols could activate potassium channels (K-channels) in the vascular smooth muscle cells and to induce relaxation of blood vessels. The aims of our research were: a) to analyze potential antivasoconstrictor and vasodilator effects of resveratrol and naringenin in the isolated rat portal vein and human umbilical vein, previously contracted in different ways; b) to identify K-channels in the vascular smooth muscle of human umbilical vein and rat portal vein; c) to examine whether K- channels play an important role in the antivasoconstictor and vasodilator effects of resveratrol and naringenin; d) to analyze additional potassium channel-independent effects of resveratrol and naringenin in the isolated venous blood vessels. Contractions of rat portal vein without endothelium were produced by electrical field stimulation of perivascular nerves (EFS), norepinephrine (NE), adenosine 5′-triphosphate (ATP), high K+ solution and by CaCl2 in Ca2+-free and high K+, Ca2+- free solution. In order to test whether resveratrol opens big calcium-sensitive (BKCa) channels, its effects were compared with those of NS 1619, a selective opener of BKCa channels..

Bioetička pitanja u vezi sa sigurnošću lijekova kod vulnerabilnih skupina

U cilju procjene stavova studenata medicine u odnosu na sudjelovanje vulnerabilnih subjekata u kliničkim ispitivanjima, proveli smo studiju presjeka (N = 174, studenti dodiplomskih studija Medicinskog fakulteta, Univerziteta u Beogradu). Studija presjeka provedena je tijekom jednog dana, na slučajno odabranim uzorcima studenata 3. godine (95/493 studenata) i 6. godine (79/510 studenata). Ukupno je odgovoreno na 83 % postavljenih pitanja. Rezultati studije pokazali su da studenti našeg fakulteta uglavnom nisu voljni sudjelovati kao dobrovoljci u kliničkim ispitivanjima, niti raditi u nehigijenskim romskim naseljima. Studenti su naglasili važnost dobivanja pristanka i djeteta i roditelja za sudjelovanje u kliničkom ispitivanju. Kada su u pitanju ispitivanja novih lijekova na populaciji starijih dementnih bolesnika, većina ispitanika smatra da informirani pristanak treba biti sličan pristanku za bilo koju drugu populaciju. U zaključku, tekući medicinski kurikulum treba biti više usmjeren na procjenu sigurnosti lijekova u vulnerabilnim skupinama. Posebno je potrebno unaprijediti rad s pripadnicima marginaliziranih skupina (npr. dodatna edukacija, posjeti nehigijenskim romskim naseljima i zajednički projekti)

Patient autonomy and informed consent in critically lll

Patient autonomy has been a cornerstone of contemporary clinical ethics since the Nuremberg trial, especially in American school of bioethics. Topic: Patient autonomy has been defined in the Nuremberg Code, and re-defined in the Declaration of Helsinki, Belmont Report and Barcelona Declaration. Founders and followers of the rights-oriented bioethics (for example, Hellegers, Beauchamp and Childers) have established and promoted the patient autonomy as the main principle of bio(medical) ethics since 1970s. However, there is a lot of controversy surrounding such a principle, especially in vulnerable patients. We aimed at evaluating the real meaning and value of patient autonomy in critical care settings regarding the communication between health workers and their patients and families. Conclusion: Protection of patients autonomy in critically ill is a complex issue. Careful benefit-risk assessment is needed in order to find the most appropriate way of obtaining the informed consent, proxy consent or to omit or delay it