Pre-electoral coalition agreement from the Black-Scholes point of view.

A political party can be considered as a company whose value depends on the voters support i.e. on the percentage of population supporting the party. Dynamics of the support is thus as a stochastic process with a deterministic growth rate perturbed by a white noise modeled through the Wiener process. This is in an analogy with the option modeling where the stock price behaves similarly as the voters' support. While in the option theory we have the question of fair price of an option, the question that we ask here is what is a reasonable level of support that the coalition of a "major" party (safely above the election threshold) and a "minor" party (under or around the election threshold) should achieve in order for the "minor" party to get one more representative. We shall elaborate some of the conclusions in the case of recent elections in Montenegro (June, 2023) which are particularly interesting due to lots of political subjects entering the race.

Docking-based analysis and modeling of the activity of bile acids and their synthetic analogues on large conductance Ca2+ activated K channels in smooth muscle cells.

OBJECTIVE: The objective of this study was to perform docking-based analysis of bile acid binding on the protein complex of channels and to derive neural network that predicts the influence of bile acids and their synthetic analogues on the activity of BK(Ca) channels in smooth muscle cells based on descriptors for bile acids and their synthetic analogues and on their already published activities using patch-clamp techniques. MATERIALS AND METHODS: Ligands for molecular docking were optimized using computer routine for minimization of energy by using the force field MMFF94 via Chem3D 15.0 and ligands and protein channel complex were prepared in AutoDockTools 1.5.6. AutoDock Vina 4.0 software was used for blind docking; processing and verification of the obtained results was performed via Discovery Studio 4.0. Neural network was derived using descriptors for bile acids and their synthetic analogues and their already published activities on calcium-activated K+ channels in smooth muscle cells (ChemDraw Professional 15.0, Dragon 6 software). RESULTS: Molecular docking was performed for: lithocholic acid, deoxycholic acid, 5ß-cholanoic acid, 3ß-hydroxi-5ß-cholanoic acid, henodeoxycholic acid, ursocholic acid and α-muricholic acid. Neural network model Multiple layer perceptron is derived, having 0.9259 training performances and 0.3673 test performances, training error 0.0073 and test error 0,1607. Model was tested for henodeoxycholic, ursocholic and α-muricholic acid, and internal validation of the model is performed. CONCLUSIONS: Molecular docking suggested that the pharmacophore for maximizing the activity of BK(Ca) channels in the steroid skeleton of bile acids is the C3 quasi-axial α-OH group and the C24 carboxyl function. Derived neural network model successfully predicted activities of tested bile acids on Ca2+ activated K+ channels in smooth muscle cells.

Contrasting physiological responses between invasive sea lamprey and non-target bluegill in response to acute lampricide exposure.

Control of invasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes of North America uses lampricides, which consist of 3-trifluoromethyl-4-nitrophenol (TFM) and niclosamide. Lampricides are thought to inhibit aerobic energy synthesis, with TFM having a relatively greater selective action against lampreys. While the toxicity and physiological effects of TFM are known, the impacts associated with exposure to niclosamide and TFM:niclosamide mixtures are poorly characterized in fishes. Therefore, focusing on energy metabolism, we quantified the physiological responses of larval sea lamprey and bluegill (Lepomis macrochirus), a non-target, native species. Exposures consisted of each lampricide alone (TFM at the species-specific 24 h LC10; niclosamide at 1.5% of the mixture's TFM concentration) or a mixture of the two (larval sea lamprey at TFM 24 h LC10 + 1.5% niclosamide; bluegill at sea lamprey's TFM 24 h LC99.9 + 1.5% niclosamide) for 24 h. Tissues (brain, skeletal muscle, and liver) were sampled at 6, 12, and 24 h of exposure and assayed for concentrations of ATP, phosphocreatine, glycogen, lactate, and glucose and tissue lampricide levels. In larval sea lamprey, TFM had little effect on brain and skeletal muscle, but niclosamide resulted in a depletion of high energy substrates in both tissues. Mixture-exposed lamprey showed depletion of high energy substrates, accumulation of lactate, and high mortality rates. Bluegill were largely unaffected by toxicant exposures. However, bluegill liver showed lower glycogen and lactate under all three toxicant exposures suggesting increased metabolic turnover. Bluegill also had lower concentrations of TFM and niclosamide in their tissues when compared to lamprey. Our results indicate that lampricide toxicity in sea lamprey larvae is mediated through a depletion of high energy substrates because of impaired aerobic ATP synthesis. We also confirmed that non-target bluegill showed high tolerance to lampricide exposure, an effect potentially mediated through a high detoxification capacity relative to lampreys.

A vanishing dynamic capillarity limit equation with discontinuous flux.

We prove existence and uniqueness of a solution to the Cauchy problem corresponding to the dynamics capillarity equation ∂ t u ε , δ + div f ε , δ ( x , u ε , δ ) = ε Δ u ε , δ + δ ( ε ) ∂ t Δ u ε , δ , x ∈ M , t ≥ 0 u | t = 0 = u 0 ( x ) . Here, f ε , δ and u 0 are smooth functions while ε and δ = δ ( ε ) are fixed constants. Assuming f ε , δ → f ∈ L p ( R d × R ; R d ) for some 1 < p < ∞ , strongly as ε → 0 , we prove that, under an appropriate relationship between ε and δ ( ε ) depending on the regularity of the flux f , the sequence of solutions ( u ε , δ ) strongly converges in L loc 1 ( R + × R d ) toward a solution to the conservation law ∂ t u + div f ( x , u ) = 0 . The main tools employed in the proof are the Leray-Schauder fixed point theorem for the first part and reduction to the kinetic formulation combined with recent results in the velocity averaging theory for the second. These results have the potential to generate a stable semigroup of solutions to the underlying scalar conservation laws different from the Kruzhkov entropy solutions concept.

The role of oxidative stress as a risk factor for rupture of posterior inferior cerebellar artery aneurysms.

Cerebral aneurysm affects 2-5% of the population and posterior inferior cerebellar artery (PICA) aneurysms account for 1-3% of all intracranial aneurysms. Oxidative stress is known to contribute to the progression of cerebrovascular disease and it may be increased by inflammation, a key contributor to cerebral aneurysm development and rupture. The aim of this study was to examine the role of overall oxidative stress as a risk factor for rupture of PICA aneurysms. This study included 29 patients with PICA aneurysms: 18 ruptured and 11 unruptured. We determined catalase, malondialdehyde, myeloperoxidase and carbonyl groups in homogenates of excised aneurysm tissue after surgery and plasma levels of C reactive protein and fibrinogen. The patient's age and sex, size of aneurysms, multiplicity, history of previous subarachnoidal hemorrhage (SAH) and risk factors for oxidative stress such as hypertension and smoking were compared between unruptured and ruptured aneurysms. Maximal diameter and SAH history were independent predictors for aneurysm rupture. Activity of catalase was decreased while activity of myeloperoxidase, levels of malondialdehyde, carbonyl groups in aneurismal tissue and plasma levels of C reactive protein and fibrinogen were increased in patients with ruptured aneurysms. Plasma levels of C reactive protein and fibrinogen showed positive correlation with myeloperoxidase, malondialdehyde, carbonyl groups and PHASES score and negative correlation with catalase. These findings suggest that oxidative stress may contribute importantly to rupture of PICA aneurysms and plasma levels of C reactive protein and fibrinogen correlate with oxidative stress markers in tissue.

Subchronic methionine load induces oxidative stress and provokes biochemical and histological changes in the rat liver tissue.

The aim of this study was to assess the effects of L-cysteine (Cys) (7 mg/kg) and N-acetyl-L-cysteine (NAC) (50 mg/kg) in the rat liver caused by subchronic i.p. application of methionine (Met) (0.8 mmol/kg) during 21 days. Malondialdehyde (MDA) concentration, glutathione content (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and acetylcholinesterase (AchE) activities were determined in the liver tissue and activities of liver enzymes (AST, ALT, ALP, and GGT) and concentrations of total proteins and albumin were determinated in plasma/serum. Catalase, superoxide dismutase, and acetylcholinesterase activities were increased by Cys and NAC. Met caused periportal mononuclear infiltration and rare focal necrosis of hepatocytes. In Cys- and NAC-supplemented groups, intracellular edema and microvesicular fatty changes without necrosis were noticed. We observed decrease of AST, ALT, and ALP activity in the methionine-treated group. Our results indicate that Cys and NAC application can increase activity of antioxidative enzymes and prevent intensive histological changes in liver in condition of subchronic methionine exposure.

Prevalence of exon 11 internal tandem duplications in the C-KIT proto-oncogene in Australian canine mast cell tumours.

OBJECTIVE: To measure the prevalence of internal tandem duplications (ITDs) in exon 11 of the proto-oncogene C-KIT in a sample of Australian cutaneous canine mast cell tumours (MCTs) drawn from general practice and to evaluate relationships between tumour mutation status and prognostic factors including signalment, tumour histological grade, tumour anatomical location and tumour size. METHODS: C-KIT exon 11 ITDs were detected by PCR in DNA extracted from formalin-fixed, paraffin-embedded canine MCTs sourced from three veterinary diagnostic laboratories in Adelaide and Melbourne. Tumours were graded according to two different systems (Patnaik and Kiupel systems) by board-certified anatomical pathologists blinded to the PCR results. Relationships between tumour mutation status and prognostic factors were evaluated using a generalised binary logistic regression analysis. RESULTS: ITDs were identified in 13 of 74 cutaneous canine MCT samples, giving an overall prevalence of 17.6% (95% confidence interval: 8.9-26.2%). ITDs were detected in 10 of 18 Patnaik grade III MCTs (55.6%) and 11 of 22 Kiupel high-grade MCTs (50%). Wald chi-square analysis revealed that detection of tumour ITDs was significantly associated with both Patnaik's and Kiupel's histologic grading systems (each: P < 0.001). The presence of the ITDs in MCTs was not associated with signalment, tumour anatomical location or tumour size. CONCLUSION: The prevalence of C-KIT exon 11 ITDs in Australian canine MCTs is similar to the prevalence in overseas canine populations (overall prevalence in Australia approximately 18%). ITDs were more frequently identified in higher grade MCTs.

Vascularisation of the geniculate ganglion.

BACKGROUND: Lack of the relevant data in the literature and possible clinical significance of the geniculate ganglion vasculature inspired us to examine the vessels of this ganglion. MATERIALS AND METHODS: Twelve temporal bones were taken during autopsy and microdissected. Four geniculate ganglions were taken as well, serially sectioned and used for haematoxylin-eosin and trichrome staining, and for CD34 immunostaining. RESULTS: The geniculate ganglion was supplied by the petrosal artery, which averaged 1.1 in number, 0.44 mm in the outer diameter, 0.24 mm in the luminal diameter, and 17.1 mm in length. The artery approached the greater petrosal nerve, giving off 1-3 twigs to it with a mean diameter of 24 µm, and entered the nerve hiatus or a small bone opening close to the ganglion. Before the artery continued to the tympanic segment of the facial nerve, it gave rise to 1 (8.33%), 2 (75.00%) or 3 (16.67%) branches to the geniculate ganglion, which ranged in diameter between 18 µm and 56 µm (mean 29 µm). From the formed superficial network, several twigs penetrated the ganglion and built an intraganglionic plexus. The counting, performed in microscopic fields, each measuring 341.7 µm × 250.0 µm in size, contained between 20 and 38 (mean 28.1) ganglion cells, as well as from 87 to 143 microvessels (mean 99.8), so that the neuron/vessel ratio was 1:3.6. CONCLUSIONS: This is the first detailed examination of the geniculate ganglion vasculature. The obtained data could be of clinical importance, especially in relation to the Bell's palsy, ganglionitis, geniculate neuralgia, petrous bone imaging, and operations in the same region.

Brain and art: illustrations of the cerebral convolutions. A review.

BACKGROUND: Aesthetics and functional significance of the cerebral cortical relief gave us the idea to find out how often the convolutions are presented in fine art, and in which techniques, conceptual meaning and pathophysiological aspect. MATERIALS AND METHODS: We examined 27,614 art works created by 2,856 authors and presented in art literature, and in Google images search. RESULTS: The cerebral gyri were shown in 0.85% of the art works created by 2.35% of the authors. The concept of the brain was first mentioned in ancient Egypt some 3,700 years ago. The first artistic drawing of the convolutions was made by Leonardo da Vinci, and the first colour picture by an unknown Italian author. Rembrandt van Rijn was the first to paint the gyri. Dozens of modern authors, who are professional artists, medical experts or designers, presented the cerebralc onvolutions in drawings, paintings, digital works or sculptures, with various aesthetic, symbolic and metaphorical connotation. Some artistic compositions and natural forms show a gyral pattern. The convolutions, whose cortical layers enable the cognitive functions, can be affected by various disorders. Some artists suffered from those disorders, and some others presented them in their artworks. CONCLUSIONS: The cerebral convolutions or gyri, thanks to their extensive cortical mantle, are the specific morphological basis for the human mind, but also the structures with their own aesthetics. Contemporary authors relatively often depictor model the cerebral convolutions, either from the aesthetic or conceptual aspect. In this way, they make a connection between the neuroscience and fineart.

Some psychological characteristics of adolescents hospitalized following a suicide attempt.

BACKGROUND: In most countries, suicide is second or third leading cause of death in youth. Suicidal tendencies among youth have been the subject of extensive research. Reports of increased rate of suicide attempts in the past few decades indicate that this phenomenon has not been fully understood. AIM: The aim of this study was to better understand the phenomenon of adolescent suicide behavior by defining some specific psychological characteristics of adolescents who were hospitalized at the psychiatric ward because of the suicide attempt. METHODS: 62 participants were assigned to two groups: clinical (adolescents who were hospitalized after a suicide attempt) and non-clinical (adolescents without psychiatric symptoms). They filled in a series of instruments: a questionnaire examining adolescents' demographic characteristics, Rosenberg's Self-Esteem Scale, Youth Self Report. RESULTS: Compared to the non-clinical populaton adolescents attempting suicide had significantly more frequent suicidal thoughts (χ2 = 18.627, df = 1, p < .01), higher incidence of earlier attempts (χ2 = 10.008, df = 1, p < .01), they abused substances more often (χ2 = 7.398, df=1, p < .01), had higher incidence of fathers' psychopathology (χ2 = 11.77, df = 1, p < .01), lower level of self-esteem (t = 4.23, p < .01), and more significant expression of internalized (F/1.60/ = 19.02; p < .01) as well as externalized problems (F/1.60/ = 4.41; p < .05). CONCLUSIONS: This study point to some of the characteristics of adolescents who were hospitalized after a suicide attempt.  

Disorder verbal memory in alcoholics after delirium tremens.

AIMS: Alcohol delirium tremens suggests dysfunction of numerous brain regions. Several Authors suggest that alcohol and withdrawal from alcohol could cause neurotoxic lesions in the frontal lobe and thereby affect cognitive function. However, it is not that well known whether the consequences of the damage following delirium are only quantitative or qualitative. PATIENTS AND METHODS: Thirty alcohol-dependent patients after alcohol delirium (ADT-n1 = 30), and 30 alcohol-dependent patients without alcohol delirium (ALC-n2=30) were compared with neuropsychological test-battery. [(Wechsler Bellevue Intelligence Scale - WB form I, Wechsler memory scale and Rey Auditory Verbal Learning Test (RAVLT)]. Examinees were selected as equivalent pairs, in such a manner that they were of approximately same age, i.e. age difference was 0-5 years, they were of the same education level, and difference in the duration of drinking was not more than 3 years. RESULTS: In the group of ADT patients, IQ was 97.53, while it is 109.53 for ALC patients. Mental deterioration of the examined group is 40, and in the control group 13. Group of ADT patients had significantly lower achievements on subtests: arithmetic, block design and digit symbol. ADT patients' average memory quotient (MQ) is 81.8, which is three standard deviations lower compared to ALC patients (MQ 102.2) and standard values, according to Wechsler. In the first repetition of the series of 15 words RAVLT, is no difference (t-test=1.88; p > 0.05), while the difference in other repetitions is significant. Difference is also statistically significant regarding recollection after 30 minutes (t-test=3.66; p < 0.05). CONCLUSION: There is qualitative difference in cognitive deficiencies in alcoholics with delirium tremens and those with no alcohol delirium, while the predominant pathology of the cognitive-amnestic deficiency is in compliance with the dysfunction of the prefrontal lobe. Following alcohol delirium, verbal memory disorders occur within the intellectual decrease and attention disorder in general.

Clozapine-induced pericarditis.

OBJECTIVE: To report a case of a patient treated with clozapine who developed pericarditis with pericardial effusion that resolved when the drug was discontinued. METHOD: Case report of a 21-year-old man with psychotic disorder that had been stable on clozapine therapy for five months (after failure of atypical antipsyhotic agents) presented to the emergency department complaining of chest pain and progressive shortness of breath that had lasted for a few days. Echocardiography showed a pericardial effusion suggestive of a cardiac tamponade, and the fluid was removed by pericardiocentesis. All other possible causes of the pericardial effusion were ruled out and clozapine was suspected as the most likely explanation. Clozapine was discontinued and the patient's symptoms improved markedly. DISCUSSION: According to the Naranjo probability scale, clozapine is a probable cause of pericarditis. Although clozapine is a known cause of myocarditis and cardiomyopathy, there are only several reports in the literature describing clozapine-induced pericarditis and pericardial effusion. In our patient, the pericardial effusion cleared within several days following clozapine discontinuation. CONCLUSION: There have been only a few cases of clozapine-induced pericarditis reported in the literature, however this adverse effect of clozapine can occur, as this case report clearly demonstrates. Cardiac adverse effects of clozapine are potentially life threatening, hence early recognition is essential to prevent serious outcomes.

The impact of heroin on visual memory.

INTRODUCTION AND AIM: Heroin abuse can lead to organic damage of cerebral structures, including sequels in cognitive and affective sphere, which are in positive relation with the duration of substance usage. Memory is one of the cognitive functions which is highly sensitive to opiate toxic effects. The aim of this research was determination of heroin impact on the visual memory of addicts, as well as the existence of specific relation of potential deficiencies in visual memory with the duration of substance use. METHODS: The research included 90 examinees, divided into three groups, depending on the duration of heroin intake. We used questionnaire for basic socio-demographic and addictological traits of examinees; Wechsler's scale for the assessment of the intelligence and Visual Memory Test (TVP), for the assessment of the visual memory. RESULTS: The achievements of heroin addicts with different duration of the substance abuse differ significantly (F = 1.83; df = 12; p < 0.05). Total number of errors examinees make in the first series of TVP (immediate visual memory) grows, almost linearly in the function of the duration of heroin abuse (p < 0.05), but in neither of groups meets criteria for the visual memory impairment. Deficiency of the delayed visual memory occurs in examinees who use heroin for one (total number of errors = 6.46; participation of typical organic errors = 31.7%) and longer than five years (total number of errors = 7.66; participation of typical organic errors = 26.7%). Univariate covariance analysis separates the average daily dosage of heroin as the most significant variable that contributes to the expression of the aforementioned deficiencies (F = 4.21; df = 2; p < 0.05). CONCLUSION: Heroin abuse leads to damage of delayed visual memory, whereby for the observed effect intake of the substance for a period longer than one year is necessary.

Serum and synovial fluid concentrations of CCL2 (MCP-1) chemokine in patients suffering rheumatoid arthritis and osteoarthritis reflect disease activity.

OBJECTIVE: To determine serum and synovial fluid (SF) concentrations of monocyte chemoattractant protein-1 (MCP-1) or CCL2 chemokine, in patients suffering (RA) and osteoarthritis (OA) and to correlate the values to disease activity, and other patient- and disease-related parameters. METHODS: The CCL-2/MCP-1 chemokine (CK) was measured in serum and SF of 30 RA and 15 OA patients using specific and very sensitive ELISA assay. RESULTS: The CCL2/MCP-1 CK was found in increased amounts in SF compared to serum (p < 0.001) and in RA compared to OA patients (p < 0.001). The values were significantly greater in RA patients with more active disease. Greater mean SF concentrations were observed in older RA patients, in patients with longer duration of RA disease and in those who had been treated with methotrexate. Also positive correlation was found between RA SF concentrations and SF leukocyte numbers (r = 0.497, p < 0.05). CONCLUSIONS: The SF and serum CCL2/MCP-1 concentrations are significantly greater in RA than in OA and in hda-RA than in mda-RA; increased SF over serum concentrations suggest that CCL2/MCP-1 is mainly produced locally by activated cells where it may exacerbate and sustain inflammation by attracting proinflammatory leukocytes, predominantly monocytes (Tab. 1, Fig. 2, Ref. 50). Full Text (Free, PDF) www.bmj.sk.

The effects of thermally induced gill remodeling on ionocyte distribution and branchial chloride fluxes in goldfish (Carassius auratus).

Experiments were performed to evaluate the effects of temperature-induced changes in functional gill lamellar surface area on the distribution of ionocytes and branchial chloride fluxes in goldfish (Carassius auratus). In fish acclimated to warm water (25 degrees C), the ionocytes were scattered along the lamellae and within the interlamellar regions of the filament. In cold water (7 degrees C), the ionocytes were largely absent from the lamellae and filaments but instead were mostly confined to the outer regions of an interlamellar cell mass (ILCM) that formed within the interlamellar channels. Using a ;time-differential double fluorescent staining' technique, it was determined that in fish transferred from 25 degrees to 7 degrees C, the ionocytes on the outer edge of (and within) the ILCM originated predominantly from the migration of pre-existing ionocytes and to a lesser extent from the differentiation of progenitor cells. Despite the greater functional lamellar surface area in the warm-water-acclimated fish, there was no associated statistically significant increase in passive branchial Cl(-) efflux. Because the paracellular efflux of polyethylene glycol was increased 2.5-fold at the warmer temperature, it would suggest that goldfish specifically regulate (minimize) Cl(-) loss that otherwise would accompany the increasing functional lamellar surface area. In contrast to predictions, the numbers and sizes of individual ionocytes was inversely related to functional lamellar surface area resulting in a markedly greater ionocyte surface area in fish acclimated to cold water (5219+/-438 compared with 2103+/-180 microm(2) mm(-1) of filament). Paradoxically, the activity of Na(+)/K(+)-ATPase (as measured at room temperature) also was lower in the cold-water fish (0.43+/-0.06 compared with 1.28+/-0.15 micromol mg(-1) protein h(-1)) despite the greater numbers of ionocytes. There were no statistically significant differences in the rates of Cl(-) uptake in the two groups of fish despite the differences in ionocyte abundance. It is possible that to maintain normal rates of Cl(-) uptake, a greater ionocyte surface area is required in the cold-water fish that possess an ILCM because of the unfavorable positioning of the ionocytes on and within the ILCM, a structure lacking any obvious blood supply.

Pulsatile drug delivery to ileo-colonic segments by structured incorporation of disintegrants in pH-responsive polymer coatings.

Conventional pH-responsive coatings used for oral drug delivery to the lower parts of the gastro-intestinal tract often show a poor performance. A new system for site-specific pulsatile delivery in the ileo-colonic regions is described. The system is based on the non-percolating incorporation of disintegrants in a coating which consists further of a continuous matrix of pH-responsive polymer (Eudragit S). Extensive in vitro release studies were performed in which coatings with different concentrations and disintegrants were studied and compared to non-disintegrant containing coatings. In vitro data show that the incorporation of swelling agents in an Eudragit S-coating still allows delayed release in the simulated terminal ileum. The pulse time and the robustness could be improved compared to conventional Eudragit S-coatings. The augmented pH-responsiveness of the new coating was related to the swelling index of the applied disintegrant. Based on the in vitro data comparing different swelling agents, Ac-di-sol appears to be the best performing swelling agent. A proof-of-concept study in human subjects was performed to investigate the performance of the new system in vivo. Coated capsules containing the stable isotope (13)C(6)-glucose as the test compound were administered and the occurrence of (13)CO(2) in the breath of the subjects was measured. It could be shown that the coating is able to resist the environmental conditions in the stomach and duodenum and delay release until deeper parts of the intestines are reached. Furthermore, the capsule is able to maintain a pulsatile release profile. It is concluded that the structured incorporation of swelling agents in pH-responsive polymers improves the delayed, pulsatile release kinetics of coated capsules. In a proof-of-concept in vivo study it was shown that the newly developed coating enables pulsatile delivery of the content to the lower parts of the intestines.

Ryanodine receptors, voltage-gated calcium channels and their relationship with protein kinase A in the myocardium.

We present a review about the relationship between ryanodine receptors and voltage-gated calcium channels in myocardium, and also how both of them are related to protein kinase A. Ryanodine receptors, which have three subtypes (RyR1-3), are located on the membrane of sarcoplasmic reticulum. Different subtypes of voltage-gated calcium channels interact with ryanodine receptors in skeletal and cardiac muscle tissue. The mechanism of excitation-contraction coupling is therefore different in the skeletal and cardiac muscle. However, in both tissues ryanodine receptors and voltage-gated calcium channels seem to be physically connected. FK-506 binding proteins (FKBPs) are bound to ryanodine receptors, thus allowing their concerted activity, called coupled gating. The activity of both ryanodine receptors and voltage-gated calcium channels is positively regulated by protein kinase A. These effects are, therefore, components of the mechanism of sympathetic stimulation of myocytes. The specificity of this enzyme's targeting is achieved by using different A kinase adapting proteins. Different diseases are related to inborn or acquired changes in ryanodine receptor activity in cardiac myocytes. Mutations in the cardiac ryanodine receptor gene can cause catecholamine-provoked ventricular tachycardia. Changes in phosphorylation state of ryanodine receptors can provide a credible explanation for the development of heart failure. The restoration of their normal level of phosphorylation could explain the positive effect of beta-blockers in the treatment of this disease. In conclusion, molecular interactions of ryanodine receptors and voltage-gated calcium channels with PKA have a significant physiological role. However, their defects and alterations can result in serious disturbances.

Mechanism of 3-deazaguanine transport in the rat heart.

The aim of this study was to determine the mechanism of transport of 3-deazaguanine in the rat heart. We used single-pass, paired-tracer dilution method on isolated and retrogradely perfused rat hearts. The maximal cellular uptake (Umax) and total cellular uptake (Utot) of 3-deazaguanine were determined under control conditions and under influence of possible modifiers. Both Umax and Utot were significantly reduced in the presence of unlabeled 3-deazaguanine (from 19.57 +/- 2.02% to 8.14 +/- 1.19% and from 16.49 +/- 3.65% to 4.70 +/- 1.96%, n=6, respectively). The presence of pyrimidine nucleoside thymidine caused the reduction of both Umax and Utot (from 20.03 +/- 3.76% to 13.58 +/- 3.16% and from 16.43 +/- 3.58% to 11.94 +/- 3.13%, n=6, respectively). Also, we tested the effect of the absence of sodium ions in perfusion solution (both Umax and Utot, significantly reduced from 17.95 +/- 2.73% to 16.67 +/- 2.16% and from 16.68 +/- 2.97% to 14.81 +/- 3.04%, n=6, respectively) and the effect of dinitrophenol (both Umax and Utot significantly reduced from 19.09 +/- 3.68% to 10.58 +/- 3.14% and from 16.86 +/- 3.84% to 7.10 +/- 3.11%, n=6, respectively). The results of self- and cross-inhibition studies show that the transport of 3-deazaguanine is saturable, energy- and sodium-dependent and that 3-deazaguanine uses endogenous transport systems for thymidine and adenosine for its own transport.

Regulation of selectivity and translocation of aquaporins: an update.

All living beings need to solve the problem of controlled transport of water. To this purpose, a special group of integral membrane proteins called aquaporins has evolved. There are 13 known members of this family that act as channels for water and small solutes, such as glycerol and urea. Although they allow large flux of water, they successfully prevent passage of protons. Here, we present the review of the data from the literature on the selectivity mechanism of aquaporins. The regulation of aquaporin activity occurs through regulation of expression of their genes, changing the localization of the already existing proteins in the cells and direct regulation of the activity in situ. We present the review of new data on the mechanisms of direct regulation. Special emphasis is on the advances in comprehension of aquaporin-2 translocation in collecting tubule cells of the kidney. Four elements of this process are described: 1) the role of protein kinase A and phosphorylation of serine 256 on aquaporin-2, 2) the transport of vesicles along the microtubules toward the apical membrane, 3), the removal of cytoskeletal subapical obstruction and the role of Rho GTPase and ezrin-radixin-moesin proteins in this, and 4) elevation of the cytosolic Ca2+ concentration, the fusion of the vesicle with the apical membrane and the role of SNARE proteins in exocytosis.

Standardization of transrectal ultrasound-guided biopsy.

Ultrasound-guided biopsy is more sensitive to biopsy performed under the digital control, because 29% of prostatic cancers are not palpable. On the other hand, at least 30% of cancers are isoechogenic, so they cannot be viewed by transrectal ultrasound examination. It means that target biopsy is not sufficient for diagnosis of localized prostatic cancer, i.e., randomized samples are needed as well. More than ten years ago, the technique of sampling the six specimens became a standard procedure to which previously harvested target specimens from suspected growths were added. Today, the expansion of biopsy protocol is recommended, by obtaining the additional specimens from peripheral lateral area, four plus two samples if the prostate has volume over 50 ml. Larger number of biopsies requires anesthesia. In order to reduce complication, the cleaning of rectal ampulla and prophylactic use of quinolone are suggested.