The role of hypoxia inducible factor-1α in the progression of chronic heart failure

Transkripční faktor hypoxií indukovaný faktor 1α (HIF-1α) je klíčový regulátor fyziologických a buněčných adaptačních procesů při nedostatku kyslíku. Za hypoxie (nebo ischemie) se hladina HIF-1α zvyšuje v důsledku inaktivace HIF-1α degradujících enzymů prolyl hydoxyláz. HIF-1α také hraje významnou roli při spouštění protektivních buněčných a metabolických dějů v srdci za různých patofyziologických podmínek. Zdá se, že stabilizace HIF-1α se může uplatňovat při omezení škodlivých remodelačních procesů spojených s rozvojem chronického srdečního selhání (CHF). Cílem bakalářské práce bude shrnout poznatky o úloze HIF-1α při rozvoji CHF.Transcription factor hypoxia inducible factor-1α (HIF-1α) is a key regulator of physiological and cellular mechanisms to adapt to deficiency of oxygen. In hypoxia (or ischemia) HIF-1α level increases as HIF-1α-degrading enzymes prolyl hydroxylases are inactive due to low oxygen level. HIF-1α plays also essential role in triggering cellular protection and metabolic alteration during pathophysiological conditions in the heart. It has been suggested that stabilization of HIF-1α in myocardium may prevent deleterious remodelling induced by various forms of chronic heart failure (CHF). The project aims to outline current knowledge about the role of HIF-1α in the progression of CHF.Department of PhysiologyKatedra fyziologieFaculty of SciencePřírodovědecká fakult

IMRT using simultaneous integrated boost (66 Gy in 6 weeks) with and without concurrent chemotherapy in head and neck cancer – toxicity evaluation

AimTo evaluate the toxicity of intensity-modulated radiotherapy with simultaneous integrated boost (SIB-IMRT) in head and neck cancer patients treated using a protocol comprising 66 Gy to the PTV1 (planning target volume; region of macroscopic tumour) and 60 Gy and 54 Gy to the regions with high risk (PTV2) and low risk (PTV3) of subclinical disease in 30 fractions in six weeks.Material and MethodsBetween December 2003 and February 2006, 48 patients (median age 55; range 25–83, performance status 0–1) with evaluable non-metastatic head and neck cancer of various localizations and stages (stages: I–1; II–8; III–12; IV–27 patients, resp.) were irradiated according to the protocol and followed (median follow-up 20 months; range 4–42). Ten patients underwent concurrent chemotherapy (CT) and in 15 patients the regimen was indicated postoperatively because of close or positive margins. In all cases the regimen was used as an alternative to conventional radiotherapy (70 Gy in 7 weeks). The acute and late toxicities were evaluated according to RTOG and RTOG/EORTC toxicity scales, respectively.ResultsAll patients finished the treatment without the need for interruption due to acute toxicity. No patient experienced grade 4 toxicity. More severe acute toxicity was observed in patients with CT, but the most severe toxicity was grade 3. Grade 3 toxicity was observed in the skin, mucous membrane, salivary glands, pharynx/oesophagus and larynx in 8.4%, 35.4%, 39.6% and 2.1%, in the CT subgroup in 10%, 100%, 90%, 10%, respectively. The trend of impairment of acute toxicity by concurrent chemotherapy was statistically confirmed by Fisher's exact test (for mucous membranes p=0.000002 and pharyngeal/oesophageal toxicity p=0.0004). The most severe late toxicity was grade 2 subcutaneous tissue (34.2%), mucous membrane (36.8%) and larynx (11.1%), grade 3 in salivary gland (2.6%) and grade 1 in skin (84.2%) and spinal cord (5.4%). The late toxicity was not increased by chemotherapy.ConclusionIn light of the toxicity profile we consider the presented regimen to be an alternative to conventional radiotherapy 70 Gy in 7 weeks. The addition of CT requires more intensive supportive care

The role of hypoxia inducible factor-1α in the progression of chronic heart failure

Transcription factor hypoxia inducible factor-1α (HIF-1α) is a key regulator of physiological and cellular mechanisms to adapt to deficiency of oxygen. In hypoxia (or ischemia) HIF-1α level increases as HIF-1α-degrading enzymes prolyl hydroxylases are inactive due to low oxygen level. HIF-1α plays also essential role in triggering cellular protection and metabolic alteration during pathophysiological conditions in the heart. It has been suggested that stabilization of HIF-1α in myocardium may prevent deleterious remodelling induced by various forms of chronic heart failure (CHF). The project aims to outline current knowledge about the role of HIF-1α in the progression of CHF

The role of succinic acid in cardiac ischemic tolerance in rats

Succinate is one of the intermediate in the Krebs cycle, which in recent years has been shown to interfere with other cellular events, some of which may affect cardiac ischemic tolerance. The aim of this project was to clarify its cardioprotective role in rat hearts subjected to acute ischemia-reperfusion. The myocardial resistance to acute ischemia (infarct size and incidence and severity of ischemic and reperfusion arrhythmias) was analyzed using the Langendorff method of isolated perfused heart at a constant flow with acute succinate administration. Local ischemia was induced by ligation of left anterior descending coronary artery. Acute administration of 1 mM succinate before 60 minutes of ischemia or before reperfusion only had a beneficial effect on reducing the infarct size by 25-30 % compared to the control group. At the same time, it had an adverse effect on the incidence and severity of ischemic and reperfusion arrhythmias. Key words: Succinate, heart, rat, heart-attack, ventricular arrhythmia

LOW-GRADE MYOFIBROBLASTIC SARCOMA OF THE LARYNX: CASE REPORT AND REVIEW OF LITERATURE

Low-grade myofibroblastic sarcoma (LGMS) is a very rare, atypical myofibroblastic tumor with fibromatosis-like features with predilection mostly in head and neck region. LGMS occurs primarily in adult patients with a slight male predominance. Only few cases of LGMS affecting the larynx have been reported in literature to this date. We describe a case of low-grade myofibroblastic sarcoma of the larynx in a 40-year-old male patient. The clinicopathological characteristics, immunohistochemical findings and treatment are discussed

IMRT with the Use of Simultaneous Integrated Boost in Treatment of Head and Neck Cancer: Acute Toxicity Evaluation

Acute toxicity has been evaluated in head and neck cancer patients treated with intensity-modulated radiotherapy using simultaneous integrated boost (SIB-IMRT). The basis of the treatment protocol is an irradiation in 30 fractions with a total dose: 66 Gy to the region of macroscopic tumor, 60 Gy to the region of high-risk subclinical disease and 54 Gy to the region of low-risk subclinical disease. Between December 2003 and September 2005, 38 patients with carcinoma of different locations in the head and neck region were irradiated. Five patients underwent concurrent chemotherapy (weekly cisplatin). Acute toxicity was evaluated according to Radiation Therapy Oncology Group toxicity scale for skin, mucous membrane, salivary glands, pharynx and esophagus and larynx. All 38 patients completed the therapy without urgency of interruption due to acute toxicity of radiotherapy. No patient experienced grade 4 toxicity. More severe toxicity was observed in patients with concurrent chemotherapy. The results confirm that the irradiation according to our SIB-IMRT protocol is a therapy with acceptable toxicity and there is a space for radiobiological enhancement of this regimen by concurrent chemotherapy, e.g. weekly cisplatin

Respiratory Epithelial Adenomatoid Hamartoma.

Respirační epiteliální adenomatoidní hamartom (REAH) patří do skupiny benigních sinonazálních lézí; projevuje se jako izolovaná afekce v nosní dutině a vedlejších nosních dutinách či v souvislosti s chronickou rinosinusitidou s polypy, výskyt může být oboustranný.Respiratory epithelial adenomatoid hamartoma (REAH) belongs to the group of benign sinonasal lesions, manifesting as an isolated lesion or in coincidence with chronic rhinosinusitis with polyps. Objective: Herein, we present clinical data of our REAH patients and provide an overview of the literature on the subject. Materials and Methods: Retrospective analysis of age, sex, symptoms, imaging examination, operation methods, and recurrence. Results: During the period 2013--2018, six REAH patients aged 48--76 (median 61.5 years) were diagnosed at the Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital Hradec Kralové. Before the diagnosis of REAH, the smell disorder was detected in five cases, nasal obstruction and secretion in five patients as well. In isolated form, REAH was found once at the posterior edge of the septum, twice in the olfactory cleft. In association with chronic rhinosinusitis with polyps, REAH was detected twice in olfactory cleft and once in ethmoids. Five patients have been operated by endonasal endoscopic surgery, four patients under general anesthesia and one patient under local anesthesia. Five patients are followed-up without recurrence (range 5 months -- 5 years, median 48 months). One patient refused surgery and is not followed-up. Conclusion: Respiratory epithelial adenomatoid hamartoma is a benign sinonasal lesion. Histological examination is essential for the differential diagnosis of lesions needing other treatment strategies. After complete surgical removal, recurrence is rar