In-vitro antiplatelet effect of melatonin in healthy individuals and patients with type 2 diabetes mellitus.

PURPOSE: The incidence of acute myocardial infarctions (AMI) shows circadian variation typically peaking during morning hours with a decline at night. However, this variation does not occur in patients with diabetes mellitus (DM). The night's decline of AMI may be partially explained by melatonin-related platelet inhibition. Whether this effect is absent in diabetic patients is unknown. The aim was to study the effect of melatonin on in-vitro platelet aggregation in healthy individuals and patients with type 2 DM. METHODS: Platelet aggregation was measured in blood samples from healthy individuals (n = 15) and type 2 DM patients (n = 15) using multiple electrode aggregometry. Adenosine diphosphate (ADP), arachidonic acid (ASPI) and thrombin (TRAP) were used as agonists. Aggregability for each subject was tested after adding melatonin in two concentrations. RESULTS: In healthy individuals, melatonin inhibited platelet aggregation in both higher (10-5 M) and lower concentrations (10-9 M) induced by ADP, ASPI, and TRAP (p < 0.001, p = 0.002, p = 0.029, respectively). In DM patients, melatonin did not affect platelet aggregation in both concentrations induced by ADP, ASPI, and TRAP. Melatonin decreased platelet aggregation induced by ADP, ASPI, and TRAP significantly more in healthy individuals compared to patients with DM. (p = 0.005, p = 0.045 and p = 0.048, respectively). CONCLUSION: Platelet aggregation was inhibited by melatonin in healthy individuals. In-vitro antiplatelet effect of melatonin in type 2 DM patients is significantly attenuated.

Lysosomal sequestration of weak base drugs, lysosomal biogenesis, and cell cycle alteration.

Lysosomes, now known to take part in multiple cellular functions, also respond to various stress stimuli. These include biogenesis in response to nanomolar concentrations of hydrophobic weak-base anticancer drugs. However, since lysosomal stress mediated by accumulation of weak-base drugs at such concentrations has never been proven and these drugs have diverse effects on malignant cells, we investigated whether the interpretation of the data was true. We found that lysosomal accumulation of the drugs daunorubicin, doxorubicin, mitoxantrone, symadex, chloroquine, clomipramine and sunitinib alone, was insufficient to induce lysosomal alkalization i.e., lysosomal stress-mediated biogenesis at nanomolar concentrations. Instead, we found that some of the drugs used induced G2 phase arrest and lysosomal biogenesis that is associated with activation of transcription factor EB (TFEB). Similarly, cantharidin, a control compound that does not belong to the weak base drugs, induced cell cycle arrest in the G2 phase associated with TFEB-driven lysosomal biogenesis. Overall none of the tested drugs caused stress-induced lysosomal biogenesis at nanomolar concentrations. However, daunorubicin, doxorubicin, mitoxantrone, symadex and cantharidin induced a massive block in the G2 phase of the cell cycle which is naturally associated with TFEB-driven lysosomal biogenesis.

Fistuloclysis as a method of nutritional management in a patient with high output enteroatmospheric fistula - a case report.

Enteric fistula is a pathological communication between the small intestine and surrounding tissue. In case of communication with body surface it is called an enterocutaneous or enteroatmospheric fistula. There are many causes of enterocutaneous/enteroatmospheric fistula occurrence. A common result is malnutrition and organ dysfunction which leads to increased morbidity and mortality of the patients. Adequate nutritional support is a very important element in the management of patients with enterocutaneous/enteroatmospheric fistulas. One of the options of nutritional support is fistuloclysis which means administration of enteral nutrition formula to the distal fistula. We present the case of 76-year-old patient with a high-localized and high output enteroatmospheric fistula in whom we were able to reach adequate nutritional status using fistuloclysis, followed by closure of the fistula.

Complementary therapy in diabetic patients with chronic complications: a pilot study.

BACKGROUND: Oxidative stress and dysregulation of antioxidant function play a pivotal role in the diabetic complications. METHODS: Fifty-nine patients with diabetes were randomly assigned into three groups. 1) PL group (n = 19): Polarized light (PL) was applied to neuropathic ulcers of diabetic foot twice daily for ten minutes in pulse regimen during three months. 2) QALA group (n = 20): Antioxidants (60 mg hydrosoluble CoQ10, 100 mg alpha-lipoic acid (ALA) and 200 mg vitamin E) were used in two daily doses for three months. 3) QALAPL group (n = 20): Patients used antioxidants along with PL applications. To test for differences in means, paired Student's t-test (before and after three months) was used. RESULTS: Three months application of PL significantly increased plasma concentrations of coenzyme Q10, alpha-tocopherol, tau-tocopherol and beta-carotene, and decreased lactate dehydrogenase (LDH) activity. Supplementation with antioxidants decreased plasma lipid peroxides, increased concentration of CoQ10 and improved echocardiographic parameters. Simultaneous application of PL and antioxidants significantly stimulated plasma CoQ10 and alpha-tocopherol concentrations, decreased LDH activity and contributed to improvement in heart left ventricular function in diabetics. CONCLUSION: Thus the data show that supportive therapy with PL along with the antioxidants hydrosoluble CoQ10, alpha-lipoic acid and vitamin E is an effective way of controlling the complications of type 2 diabetes (Tab. 7, Fig. 2, Ref. 44).

Factor V Leiden in patients with venous thrombosis in Slovak population.

Resistance to activated protein C determined by factor V Leiden (FVL) is the most frequent inherited risk factor of venous thrombosis. The purpose of our work was to reveal the frequency of FVL in Slovak patients with venous thromboses, to characterise the nature of venous thromboses in this inherited thrombophilia, and to consider the screening approach to investigation of FVL in patients with venous thromboses. 350 patients with a diagnosis of venous thromboembolic disease from various regions of Slovakia were investigated. FVL, detected by polymerase chain reaction, was found in 128/350 (37%) patients with venous thromboses. 118/128 (92%) patients were heterozygous and 10/128 (8%) were homozygous carriers. In 108/128 (84%) patients with FVL the thromboembolic disease occurred spontaneously. Phlebothrombosis occurred predominantly in the lower limbs--117/128 (91%) patients, atypical localisations were rare. The first thromboembolic event was manifested before 40 years of age in 69% of patients. The family history was positive in 60/128 (47%) FVL carriers with thromboembolic disease. Recurrent thrombosis occurred in 30% of patients with FVL. In agreement with findings in other European countries, the prevalence of FVL was high in Slovak patients with thromboembolic disease. The investigation of FVL seems to be justified in patients before 40 years of age with venous thrombosis of lower limbs, in the absence of triggering factors and with a family history of venous thromboembolic disease.

[Importance of reelin in the development of the central nervous system. II. Cyclin-dependent kinase 5 as an important element in the reelin signalling cascade]. / Význam reelinu pri vývoji centrálního nervového systému. II. Cyklin-dependentní kináza 5 jako významný clánek reelinové signalizacní kaskády.

Expression of cyclin-dependent kinase 5 (Cdk5) gradually increases during embryonal development until it reaches maximal levels that persist in the adult brain. Cdk5 represents a key component in the reelin signalling cascade. Activity of p35/Cdk5 is critical for the development of normal, six-layered structure of the mammalian brain cortex. Although it is not required for splitting of the cortical pre-plate into the marginal zone and sub-plate, a process that is affected in absence of the reelin and/or Dab1, it is substantial for the later-born neurons to bypass sub-plate neurons and to enter into the embryonal cortical plate. The defect of p35/Cdk5 disrupts the classical inside-out histogenetic pattern of neocortex. Neurons that fail to migrate past older layers of cells accumulate beneath the sub-plate thus forming an abnormal, inverted outside-in configuration in p35/Cdk5 defective animals. Exploration of neuronal migration disturbancies can shed new light on some diseases of human brain development including different heterotopias and lissencephaly. From an evolutionary point of view, the involvement of Cdk5 in the reelin signalling cascade could define a new step in the brain gray matter development.

Effect of alpha-tocopherol, pyridoxine and dexpanthenol on the stress in crease of nonesterified fatty acids levels in the brain.

The supposed antistress effect of vitamins-alpha-tocopherol, pyridoxine and dexpanthenol (pantothenic acid precursor)--was followed on the model of nociceptive stress in laboratory rats. The decrease of the stress enhancement of nonesterified fatty acids (NEFA), estimated in the brain cortex, hypothalamus and the brain stem, was taken for the indicator of the antistress effect. Nonesterified fatty acids were determined with the help of gas chromatography following the separation performed by thin layer chromatographic method. Five-day application of alpha-tocopherol acetate (per os, 300 mg.kg-1) led to a decrease of the stress enhancement of arachidonic acid level in the brain stem.

[Use of 35-lead mapping of the precordium in the evaluation of left ventricular function in patients after myocardial infarct]. / Pouzitie 35-zvodového mapovania prekordia v hodnotení funkcie l'avej komory u pacientov po infarkte myokardu.

The aim of the investigation was to assess the ejection fraction and regional wall dyssynergy from 35-lead precordial or trunk back ECG taken from 18 consecutive patients after anterior and/or posterior myocardial infarction two months after the acute episode. The percentages of Q waves (% Q) and scores of Q and/or QS waves obtained from 35-lead ECG were compared with the ejection fraction and regional wall dyssynergy recorded by 2D echocardiography. A very good correlation (r = 0.82, SEE = 14.4, p = 0.01) was found between Q% and regional wall dyssynergy in patients with anterior myocardial infarction. There was also a good inverse correlation between ejection fraction and Q% (r = -0.71, SEE = 11.2, p = 0.05) in patients with anterior myocardial infarction. In patients with posterior myocardial infarction no significant correlation was observed by 35-precordial-lead ECG.