5 research outputs found
The Effect of Cyclophilin D Depletion on Liver Regeneration Following Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy
AIM: Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a modification of two-stage hepatectomy profitable for patients with inoperable hepatic tumors by standard techniques. Unfortunately, initially poor postoperative outcome was associated with ALPPS, in which mitochondrial dysfunction played an essential role. Inhibition of cyclophilins has been already proposed to be efficient as a mitochondrial therapy in liver diseases. To investigate the effect of Cyclophilin D (CypD) depletion on mitochondrial function, biogenesis and liver regeneration following ALPPS a CypD knockout (KO) mice model was created. METHODS: Male wild type (WT) (n = 30) and CypD KO (n = 30) mice underwent ALPPS procedure. Animals were terminated pre-operatively and 24, 48, 72 or 168 h after the operation. Mitochondrial functional studies and proteomic analysis were performed. Regeneration rate and mitotic activity were assessed. RESULTS: The CypD KO group displayed improved mitochondrial function, as both ATP production (P < 0.001) and oxygen consumption (P < 0.05) were increased compared to the WT group. The level of mitochondrial biogenesis coordinator peroxisome proliferator-activated receptor γ co-activator 1-α (PGC1-α) was also elevated in the CypD KO group (P < 0.001), which resulted in the induction of the mitochondrial oxidative phosphorylation system. Liver growth increased in the CypD KO group compared to the WT group (P < 0.001). CONCLUSIONS: Our study demonstrates the beneficial effect of CypD depletion on the mitochondrial vulnerability following ALPPS. Based on our results we propose that CypD inhibition should be further investigated as a possible mitochondrial therapy following ALPPS
Heart failure pharmacotherapy and cancer:pathways and pre-clinical/clinical evidence
Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.</p
Heart failure pharmacotherapy and cancer:pathways and pre-clinical/clinical evidence
Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.</p
A truncus coeliacus kompressziós szindróma – a hasi angina „mostohagyermeke”? = Celiac artery compression syndrome – stepchild of abdominal angina?
A krónikus, étkezéssel összefüggést nem mutató epigastrialis fájdalmak hátterében az esetek néhány százalékában a truncus coeliacus külső kompressziója áll.
Esetismertetés:
A szerzők egy 58 éves nőbeteg kórtörténetét ismertetik, akinél a hasi szervek ischaemiája, a felhasi fájdalom hátterében a preoperatív kivizsgálás a truncus coeliacuson rövid szakaszú stenosist okozó, a rekeszizom-hiátus aorticusát övező inas-izmos ívet igazolt. Előkészítést követően műtétet végeztünk, a trifurcatio eredésétől számított 8–10 mm-re levő heges, gyűrűszerű leszorítást felhasítottuk, a ganglion coeliacum egy részét eltávolítottuk. A beteg a posztoperatív 6. napon gyógyultan, panaszmentesen otthonába távozott.
Megbeszélés:
A klasszikus értelemben vett angina abdominalis a hasi szervek relatív ischaemiájának következménye. Ennek oka legtöbbször az érintett ér betegsége. Az artéria külső kompressziója csupán az esetek pár százalékát jelenti. A truncus coeliacus esetében ezt betegünknél a rekeszizom-hiátus aorticusát övező inas megerősödés okozta. A kivizsgálás során az erre utaló első jel az ér felett hallható „surranás” volt, a poststenoticus turbulens áramlás miatt. Az erre alapozott részletes radiológiai vizsgálatok igazolták a tényleges kórokot. Ennek ismeretében a felszabadító műtét teljes tünet- és panaszmentességet eredményezett.
Következtetés:
Bizonytalan hasi panaszok esetén gondolnunk kell az arteria coeliaca stenosisának lehetőségére is. Esetismertetésünkkel kívánjuk felhívni a figyelmet a hasi auscultatio jelentőségére, amely elengedhetetlen része a gasztroenterológiai vizsgálatoknak. A diagnózis felállításában a Doppler-duplexvizsgálat mellett komoly segítséget jelentettek az érfestési eljárások. A műtét lényegét képező érfelszabadítást célszerű mielőbb elvégezni, még mielőtt a tartós külső kompresszió degeneratív érfalelváltozást okoz.
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Background:
Celiac trunk compression in few percentages of the cases can cause chronic abdominal pain that shows no connection with eating.
Case report:
Detailed preoperative examinations showed significant, segmental stenosis of the celiac trunk, caused by outer compression of a tendonous arc of diaphragm, in the background of abdominal pain and mesenteric ischemia of a 58-year-old woman. After preparation we have executed the surgery by removing a tight ring, located at around 8–10 mm from the origin of trifurcation, and a part of the celiac ganglion. The patient was dismissed from our hospital 6 days after surgery in good general condition.
Discussion:
The abdominal pain can normally be the consequence of mesenteric ischemia. The rootcasue in most of the cases is the alteration of the particular artery. The outer compression is normally responsible only for a few percentages of the cases. In our case the problem was caused by a stronger tendonous part of the hiatus aorticus. The first sign of this during the examination was a recognisable noise over the artery, which was caused by the poststenotic turbulent flow. Detailed radiological examinations executed based on this indeed proved this malfunction.
Conclusion:
In case of unidentified abdominal pain we have to consider the possibility of the stenosis of the celiac trunk. By our case study we would like to call the attention to the importance of the auscultation over the abdomen, which is a relevant part of the basic physical examinations. When getting to the final diagnosis, apart from the duplex doppler sonography, we also used the results of angiography. The essence of the surgery was to get rid of the outer compression of the artery, which has to be done as soon as possible in order to avoid that compression causes degeneration of the artery itself