Freshwater Cyanobacterial Blooms and Primary Liver Cancer Epidemiological Studies in Serbia

A large part of Central Serbia experiences continual shortage of sufficient ground water resources. For that reason, more than 20 reservoirs serve as drinking water suppliers. Significant and persistent cyanobacterial “blooms” have been recognized in nine of them. Samples for cyanotoxin analyses were taken during and after “blooms” in ?elije Reservoir and from Kru?evac town-supplied tap water from that reservoir two days later. Concentration of microcystin-LR was 650 μ gL^–1 in the reservoir, while the tap water contained 2.5 μ gL^–1.

In the two investigated periods, the high primary liver cancer (PLC) mortality of 11.6 from 1980–1990 and extremely high PLC incidence of 34.7 from 2000–2002 were observed in the regions affected by heavy cyanobacterial “blooms.” In contrast, PLC mortality and incidence rates were substantially lower in the regions not affected by cyanobacterial blooms: in 1980–1990 the rate of PLC mortality amounted to 2.7 in Kosovo, 7.6 in Vojvodina, and 8.3 in the non-affected regions of Central Serbia; while in 2000–2002 PLC incidence amounted to 4.1 in Kosovo, 5.2 in Vojvodina, and 13.6 in the non- or less-affected regions of Central Serbia. Keeping in mind that the most affected PLC regions in Central Serbia (Topli?ki, Ni?ki, and ?umadijski regions) have the water supply systems based on six reservoirs found regularly in bloom during summer months and that some of the regions are also connected with two boundary “blooming” reservoirs, representing a total of eight of nine blooming reservoirs, it is easy to presume that the PLC incidence could be related to drinking water quality.

The uneven geographic distribution of liver cancer in Serbia is conspicuous and hot spots could be related to drinking water supply. It is very clear that the high-risk regions for PLC occurrence correspond with drinking water reservoirs continually found with cyanobacterial blooms, and the low risk regions correspond with water supplies not affected by cyanobacteria.     

MODES OF INACTIVATION OF NEUROHYPOPHYSIAL HORMONES: SIGNIFICANCE OF PLASMA DISAPPEARANCE RATE FOR THEIR PHYSIOLOGICAL RESPONSES

Analogues of oxytocin and deaminooxytocin with 4-glutamine replaced by 4-glutamic acid methyl ester readily lose their uterotonic activity when incubated with rat serum, presumably by hydrolysis to the much less active 4-glutamic acid derivatives. On the other hand, inactivation of the deaminooxytocin analogue in the rat uterus, as demonstrated by the 'oil-bath'technique, is only slightly more rapid than that of deaminooxytocin and distinctly slower than that of oxytocin. Its in situ/in vitro ratio of uterotonic activity is less than 0.1 whereas that for deaminooxytocin is about 3 and also the persistence of the uterotonic effect in situ is slightly less than that of deaminooxytocin. The results with these 'rapidly inactivated'analogues can be used as proof of some predictions of the three-compartment model for tissue distribution of neurohypophysial hormones and its influence upon the time course of a biological response published earlier. The potential use of analogues of neurohypophysial hormones as probes for inactivation mechanisms and the results thus far obtained are discussed.     

Effects of Lidocaine on Shock-Induced Vulnerability

Introduction: Lidocaine is known to increase the defibrillation threshold (DFT) of monophasic shocks (MS) and have no effect on DFT of biphasic shocks (BS). The aim of this study was to enhance our understanding of the mechanisms of vulnerability and defibrillation through the investigation of this difference.
Methods and Results: We studied the effect of 15 μM lidocaine on shock-induced vulnerability using fluorescent imaging of Langendorff-perfused rabbit hearts. Vulnerability was assessed as vulnerable window with shock strengths of 15 to 150 V and vulnerable period (VP) with shock delivery phase of 0% to 100% of action potential duration (% APD). With MS, lidocaine caused a significant increase in both the upper limit of vulnerability (ULV, 71 ± 17 V vs 120 ± 1.5 V, P < 0.01) and upper limit of VP (91 ± 8.0% APD vs 110 ± 4.2% APD, P < 0.01). With BS, lidocaine had no effect on ULV (40 ± 3.4 V vs 45 ± 4.5 V) and did not increase the upper limit of VP (78 ± 8.9% APD vs 96 ± 12% APD, P < 0.01). Lidocaine caused reduction of the conduction velocity during pacing (0.58 ± 0.08 m/s vs 0.44 ± 0.05 m/s, P < 0.01), shock-induced break excitation (0.82 ± 0.17 m/s vs 0.30 ± 0.07 m/s, P < 0.01), and postshock reentry (0.34 ± 0.07 m/s vs 0.19 ± 0.08 m/s, P < 0.01). Lidocaine had no effect on shock-induced virtual electrode polarization.
Conclusion: Lidocaine increased MS ULV due to slowing of shock-induced break-excitation wavefronts, which resulted in enhanced probability of survival of virtual electrode induced phase singularity. Lidocaine had no effect on BS ULV because no break excitation was induced by BS. Reduction of conduction velocity by lidocaine resulted in increased dispersion of repolarization and led to upper limit of VP increase for both MS and BS. (J Cardiovasc Electrophysiol, Vol. 14, pp. S237-S248, October 2003, Suppl.)     

Identification of a 94-kilodalton antigen on Leishmania promastigote forms and its specific recognition in human and canine visceral leishmaniasis

We have analysed by immunoblotting sera from humans and dogs with visceral leishmaniasis, from the Old World as well as the New. When lysates of promastigotes are used as antigens, antibodies against a 94 kDa Leishmania component are detected, regardless of the age and geographical origin of the patient, the serum antibody titre as measured by indirect immunofluorescence, and the number of arcs in counterimmunoelectrophoresis. Low dilutions of sera from patients with Old and New World cutaneous leishmaniasis did not react with the 94-kDa antigen, whatever the species of Leishmania used as antigens. Sera from patients with other infections than leishmaniases, or without infection, are negative, even at low dilution. Anti-94 kDa antibodies were detected in the sera of Leishmania-infected dogs from both the Old and the New World. When lysates of Leishmania mexicana axenic amastigotes are used as antigens, the 94-kDa antigen was little or none identified by sera from humans and dogs with visceral leishmaniasis, and never recognized by control sera. Thus, the specific recognition of the 94-kDa promastigote antigen in human and canine visceral leishmaniasis suggests that this antigen could be a potential candidate in the differential immunodiagnosis of the disease.     

Stability of 11S globulin from Vicia faba seeds

Heat denaturation of 11S globulin, a dodecameric globular protein isolated from Vicia faba seeds was studied using scanning microcalorimetry at pH 7.6 and NaCl concentrations from 0 to 1 M. The specific enthalpy of denaturation was shown to be a linear function of temperature. The ratio of the calorimetric enthalpy to the effective one (Van't-Hoff's) per protomer of 11 S globulin was 0.9 ± 0.06. It is concluded that at first approximation 11 S globulin protomers denaturated independently in conformity with the two-state model. The plotted temperature-dependent specific free energy of 11 S globulin denaturation at different NaCl concentrations demonstrated that an increase in the salt content brought about the rise in protein stability. The maximum 11 S globulin stability is reached at about 300°K. The molar free energy of denaturation at 300°K in 1 M NaCl is 918 kJ/mol.     

Structural requirements of the oxytocin receptor in rat uterus

Published and newly calculated pA₂-values of 147 neurohypophyseal hormone analogues (7 positions varied) acting as inhibitors of oxytocin on isolated rat uterus in vitro have been subjected to fractionation according to the method by Free and Wilson which was slightly modified for this purpose. The computation was carried out in several steps. After each step, substances with outlying pA₂ -values were el minated. The reduced group containing 73–79% of the original substances displayed a high degree of additivity of side chain contributions (SCC). This group seems to follow the “participation” rule as formulated by Free and Wilson. Analysis of the group of eliminated substances and of the resulting SCC-spectrum (level diagram) enabled us to draw some conclusions concerning the structural requirements of receptor binding: i) The intact ring structure is necessary for the peptide-receptor interaction: linear peptides or peptides with an extended ring are always outliers; ii) Carba analogues (substitution with CH₂ in the disulfide ring) display better affinities than peptides with an S-S ring; d -Arg⁸ substitution decreases the binding affinity; iii) Considerably better additivity is achieved when peptides are divided into subgroups with vasopressin-like and oxytocin-like features; populations of receptors more specific for vasopressin and for oxytocin, respectively, can be assumed. Estimates of the “true” receptor-peptide dissociation constants can be obtained by summation of the corresponding SCC's in each investigated position. The value obtained for oxytocin is identical with the medium affinity binding site on myometrial cells, and not with the high affinity site. A nonlinear relationship exists between SCC's computed from pA₂-values for magnesium-free and magnesium-containing (0.5 mm ) media but no evidence speaks in favor of a Mg-potentiating effect on receptor binding.     

Effects of Postmyocardial Infarction Scar Size, Cardiac Function, and Severity of Coronary Artery Disease on QT Interval Dispersion as a Risk Factor for Complex Ventricular Arrhythmia

The aim of the study was to determine the relation between QT dispersion and ventricular arrhythmia after myocardial infarction, as well as the effects of postinfarction scar size, cardiac function, and severity of coronary artery disease on QT dispersion. Three hundred three patients, 3 months after myocardial infarction, and a group of 21 healthy subjects were evaluated. QT dispersion was the difference between maximal and minimal QT interval in 12-ECG leads. Postinfarction scar size was determined by Selvester's QRS scoring system. Cardiac function was evaluated by echocardiography and exercise stress test, and the severity of coronary artery disease by the number and degree of coronary artery stenoses. QT dispersion increased significantly in relation to the severity of arrhythmia (< 50 premature ventricular complexes vs ventricular tachycardia; 61.6 [± 12.3] vs 84.8 [± 16.4] ms, P < 0. 001). QT dispersion > 80 ms was associated with ventricular tachycardia with the sensitivity of 68% and specificity of 88%. QT dispersion also increased significantly, dependent on the postinfarction scar size (0% vs ± 33% of left ventricular myocardium; 61.8 [± 16.4] vs 74.7 [± 16] ms, P < 0. 001), as well as in the case of significantly impaired cardiac function. Although QT dispersion increased with the number of diseased vessels and the degree of stenoses, the differences were not significant (P > 0. 05). In conclusion, QT dispersion is a risk marker of complex ventricular arrhythmia in the chronic stage of myocardial infarction. Multiple regression analysis indicates that only the postinfarction scar size has an independent effect on QT dispersion (R²= 0. 39, P < 0. 05).     

Structure and correlates of alcohol dependence in clinical samples in the United States and Russia

Using items from the Composite International Diagnostic Interview, dimensionality of the alcohol dependence syndrome was assessed in clinical samples in the United States and Russia. In both groups, a single-factor model provided a high degree of goodness of fit thus demonstrating cross-cultural coherence of the construct. The item dealing with narrowing of the drinking repertoire is most disparate in each sample. Seventy of alcohol consequences was moderately related to alcohol dependence in both samples. Demographic variables, however, correlated less with severity of consequences. After the effects of severity of dependence and demographics were removed, quantity/frequency of recent alcohol consumption did not contribute to severity of consequences. Country, however, remained a significant, but small, predictor of severity of alcohol consequences.