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Lege Artis Medicinae

MARCH 20, 2016

[Clinical trials for evaluating cardiovascular safety of SGLT-2- inhibitor drugs in patients with type 2 diabetes]


[SGLT-2-inihibitors are considered as a new class among oral antidiabetic drugs. The first derivatives of this class became available in the last couple of years in Hungary. According to the requirements from regulatory bodies, randomized, controlled clinical trials have been initiated in order to evaluate the cardiovascular safety of nearly all new antidiabetic drugs in patients with type 2 diabetes. Among SGLT-2-inhibitors, only one trial with empagliflozine has been completed so far. Based on the endpoints of the EMPA-REG OUTCOME trial a significant decrease in different cardiovascular events and total mortality was observed in type 2 diabetic patients with elevated cardiovascular risk. The exact pathomechanism of this beneficial effect has not been clearly understood. Currently, the position statements and scientific guidelines clearly describe the place of SGLT-2-inhibitor drugs in the treatment algorithm; the beneficial effect of empagliflozine on cardiovascular events should seriously be considered when making therapeutic decision. Together with the results of ongoing studies with SGLT-2-inhibitors (dapagliflozine: DECLARE, canagliflozine: CANVAS), these data will provide a more robust evidence about the cardiovascular safety of this new class of oral antidiabetic drugs. ]

Hypertension and nephrology

SEPTEMBER 20, 2015

[The role of sodium-glucose cotransporters in diabetic nephropathy]

HODREA judit, BALOGH Dóra Bianka, LÉNÁRT Lilla, KŐSZEGI Sándor, HOSSZÚ Ádám, VANNAY Ádám, WAGNER J. László, REUSZ György, SZABÓ J. Attila, FEKETE Andrea

[Diabetic nephropathy is the main cause of chronic kidney disease affecting about one-third of type 2 diabetic patients. The exact pathomechanism is not known, therefore the treatment and the prevention is still unsolved. However appropriate glycemic control and lowering blood pressure significantly slow the progression of kidney damage these treatment options are still not enough to stop renal injury. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest drugs in the treatment of diabetes. By inhibiting the glucose reabsorption in the proximal tubules SGLT2 inhibitors lower blood glucose level and facilitate glucosuria. This paper summarizes the effect of SGLT2 inhibitors currently approved in Europe paying particular attention to their possible renoprotective effects.]

Hypertension and nephrology

DECEMBER 10, 2013

[Current diagnosis and treatment of membranous nephropathy]


[Primary membranous nephropathy is a common glomerular disorder characterized by subepithelial immune deposits. The pathomechanism underlying these lesions has only recently been elucidated: M-type phospholipase A2receptor (PLA2R) protein emerged as being the leading autoantigen. Antibodies to PLA2R, typically of IgG4 subclass are expressed in 70-80% of patients with primary membranous nephropathy. The level of autoantibody to PLA2R was shown to correlate with disease severity and to change parallel with disease activity in response to therapy. While mild forms of the disease are prone to spontaneous remission and carry excellent prognosis, severe forms often progress into end-stage renal disease without treatment and necessitate immunosuppression. The latest guidelines recommend the application of corticosteroids with alkylating agents or calcineurin inhibitors as first-line therapy. Promising new therapies that are currently being explored for this disease include rituximab, mycophenolate mofetil, and adrenocorticotropic hormone.]

Lege Artis Medicinae

DECEMBER 18, 2013

[The effects of angiotensin receptor blockers on the nervous system in hypertension and dementia]


[The renin-angiotensin system (RAS) is one of the most important mechanisms regarding the pathomechanism and treatment of hyprtension. The most of the elements of the RAS are found in the nervous system too. The effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ARBs) is based on the inhibition of the RAS. ARBs might have a special role in the central nervous system because they do not decrease the production of angiotensin but inhibit its harmful effects mediated through the AT1 receptor while allowing the stimulation of AT2 receptors with resulting pleiotrophic actions. Hypertension is the most important risk factor for stroke and has a negative effect on cognitive functions. Antihypertensive treatment has an effect on the nervous system; in addition to the consequences of the reduced blood pressure, ARBs might provide additional advantages in stroke and dementia prevention.]

Clinical Neuroscience

NOVEMBER 30, 2013

[Assessment of the role of multidrug resistance-associated proteins in MPTP neurotoxicity in mice]


[Goals - The available scientific data indicate that the pathomechanism of Parkinson's disease (PD) involves the accumulation of endogenous and exogenous toxic substances. The disruption of the proper functioning of certain transporters in the blood-brain barrier and in the blood-cerebrospinal fluid barrier in PD would accompany to that accumulation. Although there is an emerging role of the dysfunction of multidrug resistance-associated proteins (MRPs), members of ATP-binding cassette (ABC) transporter superfamily, in neurodegenerative disorders, there is only a few available data as regards PD. So the aim of our study was the assessment of the role of certain MRPs (1,2,4 and 5) in neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods - Following the intraperitoneal administration of silymarin (with MRP1, 2, 4 and 5 inhibitory effects), naringenin (with MRP1, 2 and 4 stimulatory effects), sulfinpyrazone (with MRP1, 4 and 5 inhibitory and MRP2 stimulatory effects) and allopurinol (with MRP4 stimulatory effect) in doses of 100 mg/kg, 100 mg/kg, 100 mg/kg and 60 mg/kg, respectively, for one week before and after the administration of MPTP in C57B/6 mice in acute dosing regimen, the striatal concentrations of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid has been measured using high-performance liquid chromatography. Results - Although the results of these experiments showed that neither of these substances exerted significant influence on MPTP-induced striatal depletion of dopamine and its metabolites, naringenin exerted a slight prevention of dopamine decrease, while allopurinol considerably enhanced the MPTP-induced lethality in mice. The explanation of these findings would be that the stimulation of MRP1- and MRP2-mediated transport of glutathione conjugates of toxic substances may have slight beneficial effects, while stimulation of MRP4-mediated efflux of brain urate, which has an important antioxidant potency, may worsen the effects of oxidative stress.]

Clinical Neuroscience

OCTOBER 05, 2013

[The impact of the vitamin D in neurological diseases and neurorehabilitation: from demencia to multiple sclerosis. Part I: The role of the vitamin D in the prevetion and treatment of multiple sclerosis]


[The world-wide incidence of vitamin D deficiency is high, independently of age. Multiple sclerosis is a chronic disorder, occuring in those who possess or are exposed to a combination of genetic and environmental risk factors. One of the environmental factors associated with the development is vitamin D. Vitamin D is an immunomodulatory agent, its role is verified in many of autoimmune diseases. Vitamin D inhibits IL-6, IL-17 and IL-23 secretions which are crucial in Th1 and Th17 differentiation and also decreases proinflammatorical cytokine production. Moreover it enhances the immunosuppressive IL-10 cytokine secretion and inhibits the T-reg cell development. These cytokines and cells are essential for the pathomechanism of multiple sclerosis. Data have shown, that the vitamin D levels above 100 nmol/l (40 ng/ml) is essential for the prevention of multiple sclerosis. Below this level the vitamin D supplementation is reasonable. In pregnancy, the vitamin D deficiency at the last two semester increases the risk for the multiple sclerosis of the infant. The optimal vitamin D level for multiple sclerosis patients is 100-150 nmol/l (40-60 ng/ml). There is no consensus for the role of vitamin D in multiple sclerosis yet, but until the achieving this, the diagnosis and the treatment of the vitamin D deficiency is crucial for scelrosis multiplex patients and in cases of elevated risk. Data shows, that in patient with multiple sclerosis the normal vitamin D level is suboptimal, however the exact role of vitamin D and doses must be clarified by interventional studies.]

Journal of Nursing Theory and Practice

FEBRUARY 28, 2013

[Complications of diabetes on the foot, the treatment of diabetic foot ulcers]

RÉDLING Marianna

[Diabetic foot syndrome is an array of symptoms with a complex pathomechanism, the complications of which (if treated late) can make it necessary to amputate the limb. Approximately 15% of diabetes patients can expect foot sores to develop in the course of their illness. The author presents the vascular complications of diabetic that underpin the development of diabetic foot syndrome, the tests serving to diagnose them, and the typical clinical manifestations and complications of diabetic foot ulcers. The most important factors in the successful treatment of diabetic foot sores are summarised: normalisation of the general medical condition; alleviation of chronic pressure points; ensuring arterial circulation; infection control; regular and appropriate mechanical debridement; wound treatment in keeping with the given phase of healing; patient education; prevention of relapse. The author places particular emphasis on the screening tests, treatment methods and patient education tasks that can be performed by specialist nurses. ]

Clinical Neuroscience

JULY 30, 2013

[Shunt insufficiency due to knot formation in the peritoneal catheter]

FEKETE Gábor, NAGY Andrea, PATAKI István, BOGNÁR László, NOVÁK László

[The authors report a rare case of the peripheral obstruction of a ventriculoperitoneal shunt. Premature baby was operated on hydrocephalus due to germinal matrix bleeding. After two months of implantation of venticuloperitoneal shunt peripheral insufficiency of the system was emerged. During the shunt revision extensive knot formation became visible. We simply cut the catheter above the knot and the working shunt was replaced into the abdominal cavity. The postoperative course was uneventful and the baby was free of complaints for more than one year. The pathomechanism of knot formation is not clear thus the discovery of the problem during the operation is an unexpected event. In our opinion tight knot cannot be spontaneously formed intraabdominally. Loose knots can be developed and can reduce the capacity of liquor flow. We think that the knot tightens during pulling out. Longer peritoneal catheters can precipitate multiple looping and/or axial torquations and increase the peripheral resistance of the shunt. In such cases when the pulling out is challenged conversion to laparotomy is suggested.]

Clinical Neuroscience

MARCH 30, 2013

[Inclusion body myositis - a rarely recognized disorder]


[Inclusion body myositis is the most common disabling inflammatory myopathy in the elderly. It is more frequent in men and after the age of 50 years. Inflammatory and degenerative features coexist. There is a T-cell mediated autoimmunity driven by in situ clonally expanded cytotoxic CD8-positive T-cells invading non-necrotic muscle fibres expressing MHC-I antigen. The hallmarks of degeneration are the deposition of protein aggregates and the formation of vesicles. The course of the disease is slow and the diagnosis is usually set after several years. The muscle weakness and wasting is assymetric, affecting predominantly distal muscles of the upper extremity and proximal muscles of the legs. The signs and clinical course can be characteristic, but the diagnosis is established by muscle biopsy. There is currently no evidence based effective treatment for sIBM. Prednisone, azathioprine, methotrexate, cyclosporine and IFN-β failed. Oxandrolon did not improve symptoms. Treatment with intravenous immunglobuline (IVIG) induced in some patients a transient improvement of swallowing and of muscle strenght, but the overall study results were negative. A T-cell depleting monoclonal antibody (alemtuzumab), in a small uncontrolled study slowed down disease progression for a six-month period. Repeated muscle biopsies showed the reduction of T-cells in the muscle and the suppression of some degeneration associated molecules. An effective therapeutic mean should act on both aspects of the pathomechanism, on the inflammatory and the degenerative processes as well.]

Clinical Neuroscience

JULY 30, 2012

[Selective ultrastructural vulnerability in the cuprizone-induced experimental demyelination]

ÁCS Péter, KOMOLY Sámuel

[Background and purpose - It has been reported that multiple sclerosis has four different neuropathological subtypes, and two of them (type III and IV) are characterized by primary oligodendrocyte loss. However, the exact pathomechanism that lead to oligodendrocyte apoptosis in human demyelinating diseases is still elusive. The copper chelator cuprizone induces primary oligodendrocyte apoptosis and consequent demyelination in well defined areas of the mouse brain. Nevertheless, the precise subcellular events that result in oligodendrocyte cell death in the cuprizone model are still unknown. We aimed to study the ultrastructural alterations that might induce oligodendrocyte apoptosis in the cuprizone experimental demyelination model. Methods - C57BL/6 mice were given cuprizone for two, 21 and 35 days to induce demyelination to investigate early pathological events, and different stages of demyelination. In addition, mice were given cuprizone for 35 days and were allowed to recover for two or 14 days to study early and late remyelination. After the cuprizone treatment, mice were sacrificed and the corpus callosum, the superior cerebellar peduncle, the optic nerve and the sciatic nerve were studied by electron microscopy. Results - The ultrastructural analysis revealed that cuprizone induced oligodendrocyte apoptosis is accompanied by the formation of giant mitochondria in the affected cells in the corpus callosum and in the superior cerebellar peduncle. Apoptosis of the myelin producing cells was present through the whole cuprizone challenge. Severe demyelination occurred after three weeks of cuprizone administration associated with massive macrophage infiltration and astrocytosis of the demyelinated areas. Axons and neurons remained unaffected. Conclusion - The formation of giant mitochondria in myelin producing oligodendrocytes is the first pathological sign in the cuprizone experimental demyelination. Mitochondrium pathology in the cuprizone challenge might serve as a useful model to study the pathomechanism of multiple sclerosis subtypes (III and IV) characterized by primary oligodendrocyte degeneration.]