Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
[26] l. : il. ; 31 cm
The role of epoxyeicotrienoic acids in the pathophysiology of ANG II-dependent form of hypertension will be studied.
Bude studován vliv zvýšených koncentrací epoxyeikosatrienových kyselin navozený farmakologickou blokádou jejich degradace, tj. inhibicí solubilní epoxid hydrolázy, na rozvoj ANG II-dependentní formy hypertenze.
- MeSH
- Epoxide Hydrolases pharmacology MeSH
- Hypertension drug therapy MeSH
- Clinical Medicine MeSH
- Hydroxyeicosatetraenoic Acids pharmacology MeSH
- Angiotensin II Type 2 Receptor Blockers therapeutic use MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Conspectus
- Farmacie. Farmakologie
- NML Fields
- kardiologie
- angiologie
- farmacie a farmakologie
- farmakoterapie
- NML Publication type
- závěrečné zprávy o řešení grantu IGA MZ ČR
Smyslem imunosupresivní léčby po transplantaci ledviny je nastolit takový stav organismu, který umožňuje akceptovat přítomnost štěpu (zamezit rejekci transplantátu) a současně zachovat obranyschopnost příjemce vůči infekcím. Imunosupresivní režimy lze rozdělit na induk-ční, udržovací a antirejekční. Indukční imunosupresivní režim je použit u nemocných ve vysokém imunologickém riziku a je tvořen kombinací základních imunosupresiv a polyklonální či monoklonální protilátky. Na něj pak navazuje udržovací režim, který v současnosti u většiny nemocných sestává z trojkombinace takrolimu, mykofenolát mofetilu a prednisonu. Antirejekční imunosupresivní režim je určen k léčbě rejekčních epizod. Snahou transplantologů je stanovit před transplantací imunologické riziko pacienta, vzít v úvahu kvalitu nabídnutého orgánu a poté zahájit imunosupresivní léčbu „šitou na míru“ konkrétní situaci.
The goal of immunosuppressive treatment after kidney transplantation is to make the patient's body accept the transplant (to prevent transplant rejection) while maintaining the body's natural defence against infection. The immunosuppressive regimens can be classified as induction, maintenance and anti-rejection. The induction immunosuppressive regimen is used in patients at high immunological risk and combines first-line immunosuppressants with polyclonal or monoclonal antibodies. It is followed by a triple maintenance regimen that currently consists of tacrolimus, mycophenolate mofetil and prednisone. The anti-rejection immunosuppressive regimen is needed to control rejection episodes. Based on the assessment of the pre-transplant immunological risk and donor organ quality, transplantologists tailor the immunosuppressive regimen to the patient's needs.
- Keywords
- imunosupresivní režim, rejekce, celulární rejekce, humorální rejekce,
- MeSH
- Azathioprine administration & dosage metabolism adverse effects MeSH
- Cyclosporine administration & dosage metabolism adverse effects MeSH
- Hydroxycorticosteroids administration & dosage metabolism adverse effects MeSH
- Immunosuppressive Agents administration & dosage pharmacokinetics pharmacology MeSH
- Immunoglobulins, Intravenous administration & dosage metabolism adverse effects MeSH
- Drug Therapy, Combination MeSH
- Mycophenolic Acid administration & dosage metabolism adverse effects MeSH
- Boronic Acids administration & dosage metabolism adverse effects MeSH
- Humans MeSH
- Intercellular Signaling Peptides and Proteins metabolism MeSH
- Antibodies, Monoclonal pharmacology adverse effects therapeutic use MeSH
- Graft Rejection drug therapy immunology MeSH
- Tacrolimus administration & dosage metabolism adverse effects MeSH
- TOR Serine-Threonine Kinases antagonists & inhibitors metabolism adverse effects MeSH
- Kidney Transplantation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- MeSH
- Immunosuppressive Agents MeSH
- Congresses as Topic MeSH
- Humans MeSH
- Organ Transplantation MeSH
- Transplantation Immunology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Newspaper Article MeSH
OBJECTIVE: Recent studies have shown that the heptapeptide angiotensin-(1-7) [Ang-(1-7)] exerts important vasoactive actions and can act as an endogenous physiological antagonist of angiotensin II (Ang II) within the renin-angiotensin system (RAS). The present study was performed to evaluate the effects, first, of chronic increases of Ang-(1-7) levels, second, of [7-D-Ala], an Ang-(1-7) receptor antagonist, and, third, of an angiotensin-converting enzyme 2 (ACE2) inhibitor on the course of hypertension and of renal function of the nonclipped kidney in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats. METHODS: Blood pressure (BP) was monitored by radiotelemetry. Elevation of the effect of circulating Ang-(1-7) levels was achieved either by chronic subcutaneous infusion of Ang-(1-7) through osmotic minipumps or by employing transgenic rats that express an Ang-(1-7)-producing fusion protein [Ang-(1-7)TGR+/+] (and its control Ang-(1-7)TGR-/-). [7-D-Ala] was also infused subcutaneously and the ACE2 inhibitor was administrated in drinking water. On day 25 after clipping, rats were anesthetized and renal function was evaluated. RESULTS: Chronic infusion of Ang-(1-7) did not modify the course of 2K1C hypertension and did not alter renal function as compared with saline vehicle-infused 2K1C rats. Chronic infusion of [7-D-Ala] or treatment with the ACE2 inhibitor worsened the course of hypertension and elicited decreases in renal hemodynamics. [Ang-(1-7)TGR+/+] and [Ang-(1-7)TGR-/-] rats exhibited a similar course of hypertension. CONCLUSION: The present data support the notion that Ang-(1-7) serves as an important endogenous vasodilator and natriuretic agent and its deficiency might contribute to the acceleration of 2K1C Goldblatt hypertension.
- MeSH
- Angiotensin I pharmacology genetics blood MeSH
- Angiotensin II analogs & derivatives pharmacology genetics blood metabolism MeSH
- Surgical Instruments MeSH
- Infusion Pumps, Implantable MeSH
- Cardiomegaly metabolism physiopathology MeSH
- Blood Pressure physiology drug effects MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Peptide Fragments pharmacology genetics blood MeSH
- Rats, Transgenic MeSH
- Disease Progression MeSH
- Hypertension, Renovascular chemically induced metabolism physiopathology MeSH
- Telemetry MeSH
- Vasodilator Agents pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Angioplasty utilization MeSH
- Humans MeSH
- Nephrology trends MeSH
- Renal Artery Obstruction therapy MeSH
- Hypertension, Renovascular diagnosis complications physiopathology MeSH
- Research trends MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Interview MeSH
- Comparative Study MeSH
