Biomedical subjects
Publications and source records attributed to V I Mel'nik.
A total of 869 patients with epilepsy having committed unlawful acts were examined. Several distinguishing features were noted in the above contingent of patients: unfavourable course of the illness, polymorphism of clinical manifestations, low level of social adaptation. Female subjects tended to display more profound psychopathological manifestations and lower level of social adaptation.
237 patients with epilepsy having committed 248 socially dangerous acts (SDA) during the period of nonconvulsive paroxysmal states (dysphorias, twilight sleep states of consciousness, schizophrenia-like psychoses) were studied by clinical-psychopathological routines. During the above psychopathological periods epileptic patients committed their SDAs on relatively rare occasions. But a high specific weight of aggressive acts having been committed during these very periods including grave ones (against life, health, and dignity of the personality), the incidence of the above states encountered in the clinical practice of dealing with epilepsy patients together with a high probability of their committing SDAs during the periods concerned determine the above contingent of patients in periods of nonconvulsive paroxysmal states as being of high social danger. In all cases the character of SDA was determined from the psychopathological context of psychotic episodes.
The effects of local anesthetics and barbiturates on the ATP-dependent H+ transport in synaptic vesicle membranes from rat brain were studied using a fluorescent probe, acridine orange. Local anesthetics depressed the active H+ transport with the following order of potencies: tetracaine trimecaine lidocaine procaine. Respective IC50 values were 0.07, 0.28, 0.46 and 0.60 mM. The local anesthetics also disrupted the endogenous pH gradient seen in the absence of ATP. Barbiturates inhibited the active H+ transport showing IC50 values in the range of 2-5 mM except for benzobarbital and barbital characterized by IC50 values of 0.5 and 20 mM, respectively. The order of potencies was benzobarbital hexobarbital amobarbital pentobarbital phenobarbital barbital. The endogenous pH gradient was not affected by the barbiturates. The results show that local anesthetics disrupt the H+ transport by acting as permeable weak bases (uncouplers) whereas barbiturates are likely to block and anion channel which maintains electroneutrality of the H+ transport in the membrane of synaptic vesicles.
The dependence of active transport of H+ on the presence of anions in synaptic vesicle membranes from rat brain was studied. The H+ transport was measured by monitoring the acidification of the vesicles with a permeant weak base-acridine orange. The fluorescence changes in the latter were proportional to the magnitude of artificially imposed pH gradients (delta pH). The ATP-dependent generation of delta pH was completely dependent on the presence of a permeant anion, was maximal at 150 mM Cl- and was inhibited, when the medium osmolarity was further increased by sucrose or KCl. At 150 mM only Br-, similar to Cl-, behaved as permeant anions, whereas I- was effective only at low (5-20 mM) concentrations. The anions--SCN-, ClO4-, HSO3- and I-(10-20 mM) as well as 4-acetamido-4'-isothiocyanatostilbene-2.2'-disulfonate (K0.5 = 14 microM) blocked the ATP-dependent generation of delta pH observed in the presence of Cl-, while other anions tested (F-, phosphate, bicarbonate, some organic anions) were virtually without effect and did not support the H+ transport. The dependence of the rate and extent of H+ accumulation on Cl- concentration was sigmoidal with a Hill coefficient of 2.8 and a Km value of 85-90 mM. The effects of anions point to the presence in the membrane of synaptic vesicles of an anion (chloride) channel whose conductance can regulate the H+ transport by switching it from an electrogenic to an electroneutral (coupled entry of H+ and Cl-) mode of operation.
The effects of trifluoperazine (TFP) on some membrane processes were studied in the isolated rat brain synaptic vesicles (SV). TFP (10(-5)-10(-4) M) was found to cause a sharp rise in the intensity of light scattering by SV suspension which was due both to an increased vesicle aggregation and to changes in the refraction index of the membrane. In addition, TFP blocked the ATP-dependent proton transport into the vesicles (K0.5 = 10(-6) M) with the concomitant stimulation of the ATPase activity which suggests an uncoupling effect caused by the permeation of this weak base through the membrane and subsequent protonation in an acid interior medium resulting in the elimination of a proton gradient. Thus, the neuroleptic drug--TFP has various effects on membrane processes which are apparently unrelated to its recognized role as a calmodulin antagonist.
Changes in pH in rat brain synaptic vesicles (SV) were studied with the use of the fluorescent slightly basic dye acridine orange. The pH value in isolated SV was found to be acidic, which was confirmed by the ionophore sensitive accumulation of the dye. Addition of ATP provoked further acidification of the intravesicular medium. The acidification rate reached a maximum after dissipation of the existing H+ gradient seen during preincubation in the absence of ATP. The ATP-dependent acidification was eliminated by the protonophore carbonylcyanide m-chlorophenylhydrazone, H4Cl or the detergent triton X-199 (0.025%). Valinomycin inhibited the ATP-dependent translocation of H+ whatever the incubation medium (with KCl or NaCl). Dicyclohexylcarbodiimide, a known inhibitor of proton ATPases (100 microM) as well as ethylmaleimide (100 microM) completely blocked H+ translocation whereas oligomycin, a specific blocker of mitochondrial H+-ATPase, and ouabain did not influence that process. ATP induced H+ translocation only in the presence of Mn2+ or Mg2+ but not in the presence of Ca2+. The translocation of H+ was not affected by the replacement of univalent cations (KCl, NaCl or Cl), however, it was prevented completely upon replacement of the penetrating anion Cl- by the non-penetrating anion O2-4 or upon replacement of the salts by sucrose. It is concluded that the ATP-dependent translocation of H+ in SV is mediated via H+-ATPase which maintains the low pH value in SV.
Na, K-ATPase activity of heart tissue homogenates was found to be depressed 6 and 24 h after the last injection of isoproterenol to rats (100 mg/kg s. c. daily for 2 consecutive days) whereas after 1 h it was essentially unchanged. The extent of the reduction in the enzyme activity was virtually the same both 6 and 24 h after myocardial necrosis induction (18 and 19%, respectively). The time-course of changes in the activity of the sarcolemmal marker enzyme was compared to the reported data on the increased sarcolemmal permeability in isoproterenol-induced myocardial necrosis.
Mg-ATPase of rat brain synaptic vesicles (SV) is considerably (by 85%) inhibited by dicyclohexyl carbodiimide (200 microM), a blocker of proton pumps, whereas orthovanadate (100 microM) does not produce any influence on the enzyme. Oligomycin (5 micrograms/ml) does not alter Mg-ATPase activity of the SV, whereas N-ethylmaleimide (300 microM) reduces it to a moderate degree, namely by 35%. This indicates that Mg-ATPase of the SV differs from mitochondrial ATPase. The protonophore p-trichloromethoxycarbonyl cyanide phenylhydrazone (20 microM) and bicarbonate anions (20 mM) stimulate slightly (by 12 to 25%) Mg-ATPase of the SV. Bicarbonate (20 mM) raises 1.8-2.1-fold Mg-ATPase activity of the mitochondria isolated from rat brain. It is assumed that the membrane of brain SV contains proton ATPase (H+-ATPase) differing from mitochondrial H+-ATPase in some of the properties.
Thirty-day hypokinesia in Wistar rats did not affect the rate of Ca2+ transport and the activity of Ca-ATPase in light and heavy fractions of sarcoplasmic reticulum of primarily white muscles. As hypokinesia was raised up to 90 days, these indicators increased. The intensity of lipid peroxidation in sarcoplasmic reticulum was lower in hypokinetic animals.
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A clinical and psychopathological investigation was carried out in 688 epilepsy patients who had committed in the interparoxysmal period illegal actions. It has been ascertained that criminal actions were committed by the above patients in the presence of the following syndromes: cerebroasthenic emotional lability, psychopathy-like, epileptic, organic, mixed type personality changes, and mental deficiency. Delinquencies were noted to be committed by predominantly mentally deficient patients and by those in the stages of psychopathy-like and epileptic type personality changes.
As many as 49 epileptic patients having performed socially dangerous actions during the period of psychotic level dysphorias were examined. The clinical pattern of dysphorias included explosive, dysthymoexplosive, dysthymic and paranoiac variants. A definition of dysphorias is given, with diagnostic criteria presented, for those developing at the psychotic level included.
The individual sensitivity of the male Wistar rats to acute pentylenetetrazole injection was studied, the density and the affinity of benzodiazepine receptors in the cerebellar cortex for 3H-diazepam was measured. It was demonstrated that the reactivity of benzodiazepine receptors underlies the individual sensitivity to pentylenetetrazole. The animals with higher sensitivity were characterized by more intensive reaction than the control and resistant animals, i.e., by an decrease in the receptors density (the initial receptors density being equal in the sensitive, resistant, and control animals). Daily injections of a subconvulsive dose of pentylenetetrazole during 24 days increase the animal sensitivity to this substance, and this was accompanied by an increase in the reactivity of benzodiasepine receptors. Later on, the produced high sensitivity became somewhat lower but persisted for 6 months. The receptors density in this period reduced almost by half. In sensitive rats, a single low dose of pentylenetetrazole injected 6 months after treatment increased the density of benzodiazepine receptors. The age-matched controls, the same acute dose of pentylenetetrazole decreased both the receptor density and affinity of their binding. It is suggested that the increase in reactivity of benzodiazepine receptors is actualized via the intracellular metabotropic feedback mechanism.
Extracellular ATP was used to test the involvement of purinergic P2 receptors in the modulation of GAB Aergic giant depolarizing potentials (GDPs) in rat neonatal hippocampus. Bath application of ATP reduced the GDP frequency in a concentration-dependent manner. The inhibitory effect of ATP persisted in the presence of adenosine P1 receptor antagonist DPCPX indicating the action of ATP on GDPs. It was suggested that, during development, ATP can modulate network-driven activity in the neonatal hippocampus through the activation of purinergic P2 receptors.