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1
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Rapid normalization of severe hypercholesterolemia mediated by lipoprotein X after liver transplantation in a patient with cholestasis - a case report

100%
Jankowski K., Wyzgał A., Wierzbicka A., Tronina O., Durlik M., Pruszczyk P.
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2015
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vol. 62
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issue 3
621-623
EN
Hypercholesterolemia is a common disorder in adult population, but total cholesterol concentrations beyond 1000 mg/dl occur rarely, and are found in patients with homozygous familial hypercholesterolemia and familial lecithin-cholesterol acyltransferase deficiency, in chronic graft-versus-host disease of the liver, after intravenous infusion of fat emulsion (intralipid), in newborn infants with immature liver function, and in obstructive biliary cholestasis. Cholestasis induces a dramatic increase in plasma cholesterol and the appearance of an abnormal lipoprotein, lipoprotein X (LpX), in the plasma. We report a case of severe hypercholesterolemia mediated by LpX in a patient transplanted for primary biliary cirrhosis (PBC), who was qualified for liver re-transplantation (re-LTx) due to chronic cholestasis. Four months after re-LTx, the cholesterol concentration was normal. The problems in diagnosis and treatment are discussed.
2
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EDIBLE MUSHROOMS IN PROPHYLAXIS AND TREATMENT OF HUMAN DISEASES

88%
MUSZYNSKA B., SUŁKOWSKA-ZIAJA K., ŁOJEWSKI M., OPOKA W., ZAJĄC M., ROJOWSKI J.
Medicina Internacia Revuo
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2013
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vol. 25
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issue 101
170-183
EN
In recent years an increase in the consumption of edible mushrooms has been observed. In many countries mushrooms have been a popular delicacy, as they add flavor and texture to a meal. Mushrooms are able to accumulate both primary and secondary metabolites. Some of them may play an antioxidant role, e.g. phenolic and indole compounds, flavonoids, terpenoids, sterols, ascorbic acid, ergothioneine and carotenoids and are a source of elements, e.g. selenium. Indole compounds fulfill the role of neurotransmitters or their precursors, exhibit antioxidant, anticancer, anti-inflammatory and anti-aging actions, regulate the diurnal cycle in humans and take part in blood coagulation. Biologically and therapeutically active metabolites of fungi are used to treat such serious diseases as cardiovascular diseases, diabetes, atherosclerosis and cancer. The intake of mushrooms clearly has a cholesterol-lowering effect or hypocholesterolemic effect by different mechanisms such as decreasing VLDL, improving lipid metabolism, inhibiting of activity of HMG-CoA reductase, and consequently preventing the development of atherosclerosis. The antioxidant and anti-inflammatory compounds occurring in mushrooms also may contribute to reduce the atherosclerosis risk.
3
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PCSK9 – nowe perspektywy farmakoterapii hipolipemizującej u pacjentów z chorobą wieńcową

75%
Pauli N., Rac M.
Farmacja Polska
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2020
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vol. 76
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issue 6
312-317
EN
Optimal hypolipemic therapy reduces the risk of cardiovascular death. The drugs used in Poland are: statins, ion exchange resins, cholesterol absorption inhibitors, fibrates and proprotein subtylsin/cexin type 9 converting enzyme inhibitors (PCSK9). The function of PCSK9 is to bind receptors for LDL (LDLR) and reduce their amount in cell membrane, mainly hepatocytes and in circulation. The gene encoding PCSK9 is located on chromosome 1p32.3. The mature transcript consists of 12 exons, 692 amino acids. PCSK9 is synthesised as a zymogen and consists of several domains. The N-domain is a catalytic site inhibitor causing the mature PCSK9 protein to be catalytically neutral. PCSK9 acts through the transcription factor SREBP-2 - a protein that binds steroid response sequences. It is a mechanism of regulation through feedback. The LDLR receptor contains a domain structurally similar to the epithelial growth factor EGF-A, which is essential for recirculating the receptor from the endosome to the cell membrane. PCSK9 binds to this fragment of LDLR. Binding of EGF-A fragment by PCSK9 leads to internalisation of LDLR and its retention in the cell followed by degradation in lysosomes. A slightly different mechanism of action of PCSK9 is also possible. It binds inside the LDLR cell which has been internalized after the LDL particle has been attached. Then such a complex is degraded in the lysosome. The expression of PCSK9 promotes apoB100 secretion in liver cells. Thus, PCSK9 provides homeostasis in intracellular cholesterol transport. The polymorphism of a single nucleotide of PCSK9 gene associated with overexpression of PCSK9 protein leads to increased LDLR degradation in lysosomes. Decreasing the amount of LDLR results in a decrease in the receptor capture of LDL particles and prolongation of their retention in plasma. In this situation, LDL particles may undergo chemical modification (oxidation, glycosylation) and damage endothelial cells. Inhibition of PCSK9 gene expression or inhibition of PCSK9 activity is the aim of therapy in the treatment of hypercholesterolemia and its complications. The drugs injected are interfering RNA and monoclonal antibodies. Studies confirm that by reducing the activity of SREBP-2, PCSK9 inhibitors are effective in reducing plasma LDL concentration, not only preventing LDLR degradation, but also reducing PCSK9 itself from liver. Thus, they reduce the risk of cardiovascular death or the need for hospitalization due to unstable coronary disease and coronary revascularization. The knowledge of molecular basis of PCSK9 and its inhibitors seems important in clinical practice due to the need of using these drugs in the treatment of lipid disorders, in accordance with the current cardiologic standards.
PL
Optymalna terapia hipolipemizująca zmniejsza ryzyko zgonu z przyczyn sercowo-naczyniowych. Lekami stosowanymi w Polsce są: statyny, żywice jonowymienne, inhibitory wchłaniania cholesterolu, fibraty i inhibitory proproteinowej konwertazy subtylizyny/keksyny typu 9 (PCSK9). Funkcją PCSK9 jest wiązanie receptorów dla LDL (LDLR) i zmniejszenie ich ilości w błonie komórkowej, głównie hepatocytów oraz w układzie krążenia. Gen kodujący PCSK9 jest zlokalizowany na chromosomie 1p32.3. Dojrzały transkrypt składa się z 12 eksonów, z 692 aminokwasów. PCSK9 syntetyzowany jest w postaci zymogenu i składa się z kilku domen. N-domena jest inhibitorem miejsca katalitycznego powodując, że dojrzałe białko PCSK9 jest katalitycznie obojętne. PCSK9 działa poprzez czynnik transkrypcyjny SREBP-2 – (sterol regulatory element-binding protein-2) białko wiążące sekwencje odpowiedzi na sterole. Jest to mechanizm regulacji poprzez sprzężenie zwrotne. Receptor LDLR (low density lipoprotein receptor) zawiera domenę EGF-A (epidermal growth factor). PCSK9 wiąże się z tym fragmentem LDLR, co prowadzi do jego internalizacji i zatrzymania w komórce, a następnie degradacji w lizosomach. PCSK9 może też wiązać LDLR wewnątrz komórki. Nadekspresja białka PCSK9 prowadzi do zwiększenia degradacji LDLR w lizosomach. Zahamowanie ekspresji genu PCSK9 lub zahamowanie aktywności białka PCSK9 jest celem terapii w leczeniu hipercholesterolemii i jej powikłań. Lekami podawanymi w iniekcjach są małe interferujące RNA (siRNA, small interfering RNA) i przeciwciała monoklonalne. Badania potwierdzają, że zmniejszając aktywność SREBP-2, inhibitory PCSK9 są skuteczne w redukcji stężenia LDL w osoczu, nie tylko zapobiegając degradacji LDLR, ale też zmniejszając wydzielanie samego PCSK9 z wątroby. Znajomość molekularnych podstaw mechanizmu działania PCSK9 i jego inhibitorów wydaje się ważna w praktyce klinicznej, z uwagi na konieczność stosowania tych leków w terapii zaburzeń lipidowych.
4
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Zaburzenia lipidowe u pacjentów z zawrotami głowy

63%
Zielińska-Bliźniewska H., Urbaniak J., Jałocha-Kaczka A., Michalska J., Olszewski J.
Aktualności Neurologiczne
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2012
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vol. 12
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issue 3
143-148
EN
Introduction: The aim of this work was to evaluate lipid disorders in patients with vertigo. Material and methods: Study population included a group of 918 patients, thereof 598 women and 320 men, aged 18–83 (mean age 55±0.5 years), treated for vertigo at the Department of Otolaryngology and Laryngological Oncology, Military Medical Academy, University Teaching Hospital in Lodz since 2009 thru 2011. Each patient underwent a detailed interview with otolaryngological, otoneurological, neurological and ophthalmological examination as well as transcranial ultrasound and computed tomography of cervical spine and head to exclude organic diseases of central nervous system. Laboratory tests included serum total cholesterol, serum triglyceride, serum HDL and LDL, and serum glucose levels. Results: Among 918 vertigo patients,539 cases (58.71%) had central vertigo whereas 379 (41.28%) – mixed vertigo, thereof 366 women (67.90%) with central vertigo and 232 (61.21%) with mixed vertigo. Among 320 men (34.78%), 173 (32.09%) had central vertigo and 147 (38.78%) – mixed vertigo. Lipid fraction analysis in patients with vertigo revealed elevated total cholesterol levels in 67.03% of patients studied, thereof 71.34% men and 64.76% women. Higher LDL cholesterol levels were found in 51.57% of the patients, thereof 54.83% men and 49.83% women. HDL cholesterol levels were normal in most of the patients (61.99%). Triglyceride (69.45%) and glucose (59.25% men and 67.78% women) levels were within normal limits. Conclusions: Lipid disorders, particularly those expressed by elevated total cholesterol and LDL fraction, can be considered as risk factors in vertigo.
PL
Wprowadzenie: Celem pracy była ocena zaburzeń lipidowych u pacjentów z zawrotami głowy. Materiał i metody: Badania przeprowadzono na grupie 918 chorych, w tym 598 kobiet i 320 mężczyzn, w wieku 18–83 lat (średnia wieku 55±0,5), leczonych w latach 2009–2011 w Klinice Otolaryngologii i Onkologii Laryngologicznej z Zespołem Pracowni Audiologicznych i Foniatrycznych Uniwersyteckiego Szpitala Klinicznego im. WAM w Łodzi z powodu zawrotów głowy. U wszystkich chorych przeprowadzono szczegółowy wywiad, badanie przedmiotowe otolaryngologiczne, otoneurologiczne. Każdy pacjent był konsultowany neurologicznie, okulistycznie i internistycznie oraz miał wykonywane USG naczyń doczaszkowych, tomografię komputerową odcinka szyjnego kręgosłupa i głowy w celu wykluczenia schorzeń organicznych ośrodkowego układu nerwowego. Przeprowadzono także badania laboratoryjne, takie jak stężenie cholesterolu całkowitego, triglicerydy, frakcję cholesterolu LDL i HDL oraz stężenie glukozy w surowicy krwi. Wyniki: W grupie 18 pacjentów z zawrotami głowy u 539 (58,71%) miały one pochodzenie ośrodkowe, a u 379 chorych (41,28%) charakter mieszany, w tym u 366 kobiet (67,90%) rozpoznano zawroty pochodzenia ośrodkowego, a u 232 (61,21%) typu mieszanego. Spośród 320 mężczyzn (34,78%) z zawrotami głowy u 173 (32,09%) stwierdzono zawroty pochodzenia ośrodkowego, a u 147 (38,78%) typu mieszanego. Analizując stężenia frakcji lipidów u badanych, odnotowano podwyższone wartości cholesterolu całkowitego u 67,03% z nich, w tym u 71,34% mężczyzn i 64,76% kobiet. Podwyższone stężenia frakcji cholesterolu LDL zaobserwowano u 51,57% pacjentów, w tym u 54,83% mężczyzn i 49,83% kobiet. Frakcja HDL cholesterolu u większości chorych (61,99%) była w normie. Również stężenie triglicerydów u większości badanych (u 69,45%) nie odbiegało od normy, podobnie jak stężenie glukozy (u 59,25% mężczyzn oraz 67,78% kobiet). Wnioski: Zaburzenia lipidowe, zwłaszcza cholesterolu całkowitego i frakcji LDL w surowicy krwi, mogą być jedną z przyczyn zawrotów głowy.
5
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Wpływ melatoniny na czynność układu sercowo-naczyniowego

63%
Sewerynek E.
Folia Medica Lodziensia
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2010
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vol. 37
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issue 1
69-87
EN
The ageing process is associated with an increasing number of cardiovascular incidents, both acute and chronic. Also the concentrations of certain hormones undergo a gradual decrease with age, including: oestrogens, androgens, dehydroepiandrosterone, dehydroapiandrosterone sulphate or melatonin. The association between melatonin and circulation has been the subject of interest for the last few years. It has also been demonstrated that the vasospastic or vasodilative effects of melatonin depend on the activation of certain receptors by the hormone. Cardioprotective effects of melatonin have been demonstrated in both experimental and clinical studies. In cardiac ischemia-reperfusion models or in the course of oxidative process induction, following the administration of medical agents with cardiotoxic effects, protective effects of melatonin have been demonstrated. In patients with ischaemic heart disease, lower nocturnal melatonin concentrations were found vs. those in a group of healthy persons; the more severe cardiac disease and the higher risk for sudden cardiac death, the lower melatonin concentrations are observed. Lower melatonin concentrations have also been confirmed in patients with hypercholesteronaemia and increased LDL-cholesterol fraction levels, as well as in patients with arterial hypertension. Melatonin administration normalised blood pressure in patients with arterial hypertension. The presented paper aims at summarising the up-to-date knowledge of the role of melatonin in circulation control.
PL
melatonin. The association between melatonin and circulation has been the subject of interest for the last few years. It has also been demonstrated that the vasospastic or vasodilative effects of melatonin depend on the activation of certain receptors by the hormone. Cardioprotective effects of melatonin have been demonstrated in both experimental and clinical studies. In cardiac ischemia-reperfusion models or in the course of oxidative process induction, following the administration of medical agents with cardiotoxic effects, protective effects of melatonin have been demonstrated. In patients with ischaemic heart disease, lower nocturnal melatonin concentrations were found vs. those in a group of healthy persons; the more severe cardiac disease and the higher risk for sudden cardiac death, the lower melatonin concentrations are observed. Lower melatonin concentrations have also been confirmed in patients with hypercholesteronaemia and increased LDL-cholesterol fraction levels, as well as in patients with arterial hypertension. Melatonin administration normalised blood pressure in patients with arterial hypertension. The presented paper aims at summarising the up-to-date knowledge of the role of melatonin in circulation control.
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