Anti-arrhythmic activities of opioid agonists and antagonists and their stereoisomers.

1. A series of opioid agonists, antagonists and their (+)-stereoisomers were tested for antiarrhythmic activity in the rat coronary artery occlusion model. 2. Naloxone (0.01-2 mg kg-1) significantly reduced the incidence and severity of cardiac arrhythmias, in accordance with previous published studies. 3. The non-opioid stereoisomer, (+)-naloxone, was equipotent with naloxone against occlusion-induced arrhythmia. 4. Similar non-stereospecific antiarrhythmic effects were induced by another opioid antagonist, Win 44,441-3 and its stereoisomer Win 44,441-2. 5. The opioid agonists, morphine and levorphanol, protected against occlusion-induced arrhythmia as did the opioid antagonists, and the (+)-stereoisomer, dextrorphan, was equipotent to levorphanol. 6. It is concluded that the antiarrhythmic effects of opioid drugs are not mediated by opioid receptors. A direct effect on ionic currents in cardiac muscle is suggested as the mechanism of opioid antiarrhythmic activity.


Effects of antagonists on quisqualate and nicotinic receptor-mediated currents of midbrain neurones in culture.

1. The action of non-N-methyl-D-aspartate (non-NMDA) and nicotinic antagonists on excitatory postsynaptic currents (e.p.s.cs) and on quisqualate (Quis)- and nicotine-gated currents was studied by use of whole-cell recording in dissociated culture of the rat midbrain. 2. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX; 0.1 microM) and kynurenic acid (0.1 mM) attenuated network-generated and miniature e.p.s.cs while mecamylamine (100 microM) and hexamethonium (400 microM) had no effect. Acetylcholine (ACh) enhanced or suppressed e.p.s.cs. The suppressing effect of ACh was blocked by atropine (0.1-10 microM). 3. ACh (50-1000 microM) and quisqualate (Quis, 0.1-20 microM) induced inward currents with the same reversal potential as e.p.s.cs. 4. Application of Quis and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) in a low concentration (0.5 and 5 microM, respectively) evoked a maintained current which was attenuated by CNQX (1 microM) and kynurenic acid (0.5 mM) but not by mecamylamine (100 microM). 5. Higher concentrations of Quis (5-20 microM) and AMPA (50-100 microM) evoked a transient and a maintained current component. Kynurenic acid (1 mM) reduced the transient but not the maintained component. CNQX (5-10 microM) increased the maintained component without reducing the transient one; 20 microM CNQX reduced both components. 6. ACh-induced transient current was mimicked by nicotine and reversibly and dose-dependently blocked by mecamylamine. Atropine (10 microM), hexamethonium (400 microM) as well as CNQX (100 microM) and kynurenic acid (1 mM) did not affect the current. 7. Hexamethonium (50-400 microM) voltage-dependently depressed the maintained current elicited by both Quis and ACh. 8. In conclusion, although the antagonists examined here seem to discriminate between non-NMDA and nicotinic receptor-mediated e.p.s.cs, they vary considerably in respect of their mode of action when tested on Quis, AMPA and ACh-induced currents.


Pharmacological evidence for the possible involvement of repetitive action potentials in facilitation by GABA of catecholamine secretion in bovine adrenal chromaffin cells.

1. gamma-Aminobutyric acid (GABA) evokes catecholamine (CA) secretion and enhances the stimulation-evoked CA secretion via facilitation of Ca2+ entry in a Cl(-)-dependent manner. The present study was designed to investigate further the ionic mechanism of modulation by GABA of CA secretion from adrenal medulla, using a primary culture of bovine chromaffin cells. 2. Tetrodotoxin (TTX), a voltage-sensitive Na+ channel blocker, reduced GABA-evoked CA secretion. 3. Inhibition of the sodium pump by ouabain or removal of extracellular K+ enhanced GABA-evoked CA secretion in a TTX-sensitive manner. 4. Tetraethylammonium (TEA) and cesium, which are known to block some types of K+ channels, markedly enhanced GABA-evoked CA secretion in a concentration-related fashion. TEA-induced enhancement of the GABA-evoked CA secretion was attenuated by TTX or replacement of extracellular Na+ by choline. On the other hand, ouabain accelerated the effect of TEA. 5. TEA and ouabain also enhanced GABA-induced Ca2+ influx and accumulation of cytosolic Ca2+, assessed with 45Ca2+ uptake and quin2 fluorescence. 6. Veratridine increased accumulation of cytosolic Ca2+ in a TTX-sensitive manner. GABA facilitated the veratridine-induced elevation of cytosolic Ca2+ even when the GABA-induced rise of cytosolic Ca2+ levelled off. 7. These results suggest the involvement of repetitive action potentials in modulation of GABA by Ca2+ mobilization and, as a consequence, of the CA secretion in chromaffin cells.


Changes in neurotransmitter sensitivity in the mouse neocortical slice following propranolol and theophylline administration.

1. The mouse neocortical slice has been used to examine the sensitivity of neurones to isoprenaline, 5-hydroxytryptamine (5-HT) and adenosine acutely and following chronic treatment of animals with propranolol or theophylline. 2. While having little effect alone, all three agonists enhanced the d.c. depolarizing potential produced by N-methyl-D-aspartate (NMDA). The effect of (-)-isoprenaline (0.2 microM) was shared by (+)-isoprenaline at the much higher concentration of 10 microM. 3. Superfusion of slices with theophylline or 8-phenyltheophylline blocked responses to adenosine with evidence of selectivity. A single injection of theophylline 24 h before slice preparation did not alter agonist sensitivity, but when administered daily at 100 mg kg-1 for 14 days, the xanthine caused a loss of sensitivity to adenosine and (-)-isoprenaline but not 5-HT. The lower dose of theophylline, 10 mg kg-1 daily, also led to a loss of adenosine responses but no change of sensitivity to the amines. 4. Following the 14 day treatment with theophylline at 100 mg kg-1 daily in two groups of mice, responses to adenosine recovered to control levels after 20 days. 5. Propranolol superfusion blocked responses to both isomers of isoprenaline and 5-HT but did not affect sensitivity to adenosine. 6. Chronic treatment with propranolol at 25 mg kg-1 daily for 14 days induced a loss of sensitivity to (-)-isoprenaline and 5-HT but not adenosine. A lower dose of 5 mg kg-1 daily caused no change in responses to adenosine or 5-HT, but yielded an increased sensitivity to (-)-isoprenaline. 7. The results are discussed with respect to reports of receptor up-regulation in binding studies; caution is clearly required in extrapolating from such work to receptor activity in a functional system, especially in the case of theophylline and adenosine.


Alkylation with beta-funaltrexamine suggests differences between mu-opioid receptor systems in guinea-pig brain and myenteric-plexus.

1. The effects of pre-incubation with beta-funaltrexamine (beta-FNA) on the binding of [3H]-[D-Ala2, MePhe4, Gly-ol5]enkephalin ([3H]-DAMGO) to homogenates of guinea-pig brain and myenteric-plexus longitudinal muscle have been studied. 2. beta-FNA pretreatment of brain homogenates in Tris-HCl buffer reduced the amount of [3H]-DAMGO binding. This was principally due to a reduction in the maximal number of binding sites measurable. However, approximately 30% of sites labelled by 1 nM [3H]-DAMGO were insensitive to 1 microM beta-FNA. Similar findings were obtained when the alkylation was performed in brain homogenates prepared in Krebs solution buffered with HEPES. 3. beta-FNA pretreatment of whole myenteric-plexus longitudinal muscle strips caused an increase in the IC50 values of mu-agonists, but not of kappa-agonists. However, the binding of [3H]-DAMGO to homogenates of myenteric-plexus longitudinal muscle was not altered by pre-incubation with beta-FNA in Tris-HCl buffer. On the other hand when the pretreatment was carried out in whole tissue in Krebs solution, or in homogenates in the presence of NaCl and Gpp(NH)p, a marked reduction in [3H]-DAMGO binding was observed. 4. These results suggest that a low affinity form of the mu-opioid receptor is the physiologically relevant site for beta-FNA alkylation in the myenteric-plexus and that differences exist between mu-receptor systems in guinea-pig myenteric plexus and brain.


Dissociation of a ferric maltol complex and its subsequent metabolism during absorption across the small intestine of the rat.

1. The fate and disposition of [59Fe]-ferric [3H]-maltol after intravenous administration were investigated in anaesthetized rats. Immediate dissociation of ferric iron from maltol took place in the circulation even with high doses of ferric maltol (containing 1 mg elemental iron). In plasma samples withdrawn within 1 min of injection and subjected to gel filtration, 59Fe eluted with the high molecular weight proteins whilst the tritium was associated with low molecular weight material. 2. The rates of elimination of 59Fe and of tritium from the plasma and their ultimate fate were very different. The half life for 59Fe in the plasma was around 70 min and 59Fe appeared mainly in the bone marrow and liver. There was an initial rapid exit of tritium from the plasma with a half life of around 12 min. This was followed either by a plateau or by a rise in tritium levels, involving entry of maltol metabolites into the circulation. These metabolites could be recovered in the urine. 3. Entry of 59Fe and of tritium into the blood plasma after intraduodenal administration of [59Fe]-ferric [3H]-maltol was also very different. At low doses of ferric maltol (containing 100 micrograms elemental iron), the tritium appeared in the plasma in highest amounts within seconds and then decreased whilst there was a slow rise in 59Fe levels. At higher doses of ferric maltol (containing 7 mg elemental iron), levels of 59Fe in the plasma were highest at 5 min and then fell whereas tritium levels rose steadily. Mucosal processing of 59Fe prevented further entry of iron at high dose into the circulation. 4. Initial rates of uptake of [3H]-maltol into isolatcd intestinal fragments were measured over a range of concentrations and revealed that maltol alone could diffuse freely into the tissues whereas maltol complexed to iron showed saturable uptake kinetics similar to those seen with the iron itself. 5. After intestinal uptake, 59Fe and tritium were associated with different subcellular fractions, maltol itself being metabolized to the glucuronide conjugate within the intestinal mucosa. 6. It is concluded that dissociation of metal and ligand takes place before entry into the intestinal mucosa. Iron is then taken up on the endogenous carrier and processed in the normal way whilst maltol enters by diffusion, its rate of entry being limited by the degree of dissociation. It is subsequently metabolized by conjugation and eliminated rapidly from the body in the urine.


Peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) activates capsaicin-sensitive primary afferent nerves in guinea-pig atria and urinary bladder.

1. We have investigated the ability of the N-formyl-methionyl-leucyl-phenylalanine (FMLP) a synthetic analogue of a chemotactic peptide derived from a variety of bacteria, to activate capsaicin-sensitive primary afferents in the guinea-pig atria and urinary bladder. 2. In the isolated, electrically-driven left atria from reserpine-pretreated guinea-pigs (atropine in the bath), FMLP (3 nM-1 microM) produced a biphasic positive inotropic response. The late component of this response was selectively abolished by in vitro capsaicin pretreatment while both the early and late responses were abolished by indomethacin. 3. The inotropic response to FMLP in the guinea-pig atria was unaffected by ruthenium red. The late but not the early response was strongly inhibited or abolished by tetrodotoxin (TTX), omega-conotoxin (CTX) or by the C-terminal fragment (8-37) of human alpha-calcitonin gene-related peptide (hCGRP). hCGRP-(8-37) acts as competitive antagonist at CGRP receptors. 4. In the guinea-pig isolated bladder, FMLP (10 nM-10 microM) produced a concentration-dependent contraction which was unchanged by previous in vitro capsaicin, TTX or CTX pretreatment. The response to low concentrations of FMLP was suppressed by indomethacin, irrespective of the capsaicin pretreatment. 5. FMLP (10 microM) produced a significant increase in the outflow of CGRP-like immunoreactivity (CGRP-LI) from superfused guinea-pig atria or urinary bladder. CGRP-LI outflow induced by FMLP was blocked by indomethacin or in vitro capsaicin pretreatment. 6. These findings indicate that FMLP activates the 'efferent' function of capsaicin-sensitive primary afferents via prostanoid generation. This action could provide a neurogenic contribution to the overall inflammatory response produced by bacteria-derived peptides in inflamed tissues. In addition the present data indicate that endogenous prostanoids generated during exposure to FMLP produce peptide secretion from sensory nerves via a TTX- and CTX-sensitive but ruthenium red-resistant mechanism.


Modification of the rat uterine response to oestrogen and tamoxifen by thromboxane antagonists.

1. The thromboxane receptor antagonists EP092, AH23848 and BM 13.505 were used to investigate the role of thromboxane in the uterotrophic response to oestradiol and tamoxifen. 2. The parameters examined were uterine blood flow (measured by the microsphere technique), uterine wet and dry weights and the concentrations of cytosolic and nuclear oestrogen receptors. 3. Only EP092 potentiated the hyperaemic response to oestrogen but all three thromboxane antagonists inhibited oestradiol-stimulated uterine growth. This inhibition was accompanied by a decrease in nuclear oestrogen receptor concentration. 4. The uterotrophic response to tamoxifen was unaffected by the thromboxane antagonists. 5. The mechanism by which the thromboxane antagonists may be exerting their growth inhibitory effect is discussed, although, whether this effect can be attributed to blockade of thromboxane receptors or to some other mechanism is not clear from this study.


Regional heterogeneity in the contractile and potentiating effects of neuropeptide Y in rat isolated coronary arteries: modulatory action of the endothelium.

1. Neuropeptide Y (NPY) induced a concentration-dependent contraction of isolated rings of proximal epicardial (PC) and distal intramural (DC) coronary arteries of the rat, with an EC50 of ca. 1 x 10(-7) M. The NPY-induced contraction at 3 x 10(-7) M was significantly smaller in PC than DC arteries: 34% vs. 55% of the 125 mM K(+)-induced response, respectively. 2. NPY (2 x 10(-8) M) increased the sensitivity to noradrenaline (NA) and 5-hydroxytryptamine (5-HT) more in PC (4.2 and 2.8 fold, respectively) than in DC arteries (2.2 and 1.4 fold, respectively). The maximal contractile response to NA and 5-HT was increased more in DC (43% and 29%, respectively) than in PC arteries (20% and 12%, respectively). 3. Removal of the endothelium increased the sensitivity and maximal response to NPY as well as the spontaneous myogenic tone in PC but not in DC arteries. NPY had no relaxing effect on PC and DC arteries submaximally contracted with 10(-6) M prostaglandin F2 alpha, suggesting that spontaneous rather than stimulated release of endothelium-derived relaxing factor (EDRF) depresses the contractile action of NPY in PC arteries. 4. The results indicate a heterogeneity in the contractile and potentiating action of NPY in rat coronary arteries depending on size or location in the coronary circulation.


The role of nitric oxide as an endogenous regulator of platelet and neutrophil activation within the pulmonary circulation of the rabbit.

1. Intravenous (i.v.) administration of adenosine diphosphate (ADP), platelet activating factor (PAF) and thrombin induced a dose-related accumulation of 111indium-labelled platelets within the thoracic region of anaesthetized rabbits. 2. I.v. administration of the inhibitor of NO biosynthesis, L-NG-nitro arginine methyl ester (L-NAME; 10 mg kg-1) significantly potentiated the peak platelet accumulation induced by ADP, PAF and thrombin. Additionally L-NAME prolonged the disaggregation of platelets in comparison to D-NAME (10 mg kg-1). Such changes were reversible by the administration of L-arginine (900 mg kg-1). 3. I.v. administration of PAF induced a small accumulation of 111indium-labelled neutrophils within the pulmonary circulation which could be greatly potentiated by pretreatment of the animals with L-NAME. In contrast, thrombin administration did not cause significant accumulation of 11indium-labelled erythrocytes in the pulmonary circulation of anaesthetized rabbits. 4. Intracarotid (i.c.) administration of thrombin induced a marked accumulation of radiolabelled platelets within the cranial vasculature which was not potentiated by the prior administration of L-NAME (at either 10 mg kg-1 or 100 mg kg-1). 5. These results suggest that endogenous NO may regulate platelet and polymorphonuclear leukocyte activation within the pulmonary but not the cerebral circulation of rabbits.


4-Aminopyridine-induced increase in basal and stimulation-evoked [3H]-NA release in slices from rat hippocampus: Ca2+ sensitivity and presynaptic control.

1. We have examined the mechanisms by which the K(+)-channel blocker 4-aminopyridine (4-AP) can dose-dependently increase both basal [3H]-noradrenaline ([3H]-NA) release and the [3H]-NA release evoked by electrical stimulation, but not the release of [3H]-acetylcholine ([3H]-ACh), from slices of rat hippocampus. 2. Both the electrically evoked and the 4-AP-induced release were blocked by tetrodotoxin (TTX) (3 microM). The Ca(2+)-dependence of the 4-AP-induced release (EC50 0.15 mM) was, however, different from that of the electrically evoked [3H]-NA release (EC50 0.76 mM). 3. The 4-AP-induced release could be inhibited by CdCl2(10 microM) and omega-conotoxin (30 nM), but not by nifedipine (1 microM). 4. Transmitter release evoked by 100 microM 4-AP could be blocked by the alpha 2-adrenoceptor agonist, UK 14,304 (0.1 microM) and by the A1-receptor agonist R-N6-phenylisopropyl adenosine (R-PIA, 1 microM) and increased by the alpha 2-adrenoceptor antagonist, yohimbine (1 microM), both in 0.25 and 1.3 mM Ca(2+)-containing medium. By contrast, the effect of alpha 2-adrenoceptor agonist and antagonists on transmitter release evoked by electrical stimulation was markedly reduced in the presence of 4-AP (100 microM). 5. The results suggest that 4-AP can depolarize some nerve endings in the central nervous system, leading to transmitter release that is dependent on nerve impulses and Ca2+. Furthermore, the fact that alpha 2-receptors and adenosine A1 receptor agonists can influence the release of NA evoked by 4-AP suggests that these drugs may have actions that are independent of blockade of aminopyridine-sensitive K(+)-channels.


Hoe 140 a new potent and long acting bradykinin-antagonist: in vitro studies.

1. Hoe 140 (D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]bradykinin) is a new bradykinin (BK)-antagonist. It was tested in several in vitro assays and compared with D-Arg-[Hyp2,Thi5,8,D-Phe7]BK. 2. In receptor binding studies in guinea-pig ileum preparations, Hoe 140 showed an IC50 of 1.07 x 10(-9) mol l-1 and a KI value of 7.98 x 10(-10) mol l-1. 3. In isolated organ preparations Hoe 140 and D-Arg-[Hyp2,Thi5,8, D-Phe7]BK inhibited bradykinin-induced contractions concentration dependently, with IC50-values in the guinea-pig ileum preparation of 1.1 x 10(-8) mol l-1 and 3 x 10(-5) mol l-1, respectively. pA2 values in this tissue were 8.42 and 6.18, respectively. In the rat uterus preparation the IC50 value was 4.9 x 10(-9) mol l-1 for Hoe 140. D-Arg-[Hyp2, Thi5,8, D-Phe7]BK showed an IC50 of 4.0 x 10(-6) mol l-1. The IC50 values in the guinea-pig isolated pulmonary artery were 5.4 x 10(-9) mol l-1 and 6.4 x 10(-6) mol l-1, respectively. In the rabbit aorta no inhibitory effects on Des-Arg9-BK induced contractions were observed. 4. In cultured bovine endothelial cells, Hoe 140 antagonized (IC50 = 10(-8) mol l-1) bradykinin-induced endothelium-derived relaxing factor (EDRF) release and the bradykinin-induced increase in cytosolic free calcium (IC50 = 10(-9) mol l-1). 5. Hoe 140 (10 -7mol I1) totally suppressed the bradykinin-induced (10 8 to 10- mol I') prostacyclin (PGI2) release from cultured endothelial cells of bovine aorta. D-Arg-[Hyp2, Thi5'8, D-Phe7]BK (10- 7 mol I1- ) showed a weaker antagonism. 6. Taken together these results show that Hoe 140 is a highly potent bradykinin antagonist. It was two to three orders of magnitude more potent than D-Arg-[Hyp2, Thi5 8, D-Phe7]BK.


Hoe 140 a new potent and long acting bradykinin-antagonist: in vivo studies.

1. The potency, duration of action and tolerability of Hoe 140, a novel and highly potent bradykinin (BK) antagonist in vitro, has been tested in different in vivo models and compared with the well-known BK antagonist D-Arg-[Hyp2, Thi5,8, D-Phe7]BK. 2. Hoe 140 is highly potent and long acting in inhibiting BK-induced hypotensive responses in the rat. Four hours after s.c. administration of 20 nmol kg-1, inhibition still amounted to 60% whereas the effect of 200 nmol kg-1 of D-Arg-[Hyp2, Thi5,8, D-Phe7]BK was not significant. 3. BK-induced bronchoconstriction in guinea-pigs was strongly inhibited by Hoe 140. The magnitude and duration of inhibition confirmed the findings obtained in the blood pressure experiments in the rat. 4. Carrageenin-induced inflammatory oedema of the rat paw was considerably inhibited at i.v. doses between 0.1 and 1 mg kg-1. 5. In conscious dogs, intravenous doses of 0.01 and 0.1 mg kg-1 of Hoe 140 and D-Arg-[Hyp2, Thi5,8, D-Phe7]BK were well tolerated. At doses of 1 mg kg-1 adverse effects occurred that were attributed to the residual BK agonistic activity of both compounds. 6. Hoe 140 has been shown to be a highly potent and long acting BK antagonist in vivo in different animal species and models. This makes it appropriate to investigate further the physiological and pathophysiological role of BK.


Deamination of newly-formed dopamine in rat renal tissues.

1. The present study has examined the formation of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in slices of the rat renal cortex and the renal medulla loaded with exogenous L-beta-3,4-dihydroxyphenylalanine (L-DOPA). The effects of pargyline and of two selective inhibitors of monoamine oxidase (MAO) types A and B, respectively Ro 41-1049 and Ro 19-6327, on the deamination of newly-synthesized dopamine in kidney slices incubated with exogenous L-DOPA were also tested. The assay of L-DOPA, dopamine, noradrenaline and DOPAC was performed by means of h.p.l.c. with electrochemical detection. 2. Incubation of renal slices with exogenous L-DOPA resulted in a concentration-dependent accumulation of dopamine and DOPAC; the tissue levels of newly-formed dopamine and DOPAC in slices of the renal medulla were 6-8% of those in cortical slices. 3. Pargyline (0.1 mM) produced a marked decrease (84% reduction) in the formation of DOPAC in kidney slices loaded with 1.0 mM L-DOPA; this effect was accompanied by a 17% increase in the accumulation of dopamine. Similar effects were obtained at higher concentrations of pargyline (0.5 and 1.0 mM). At 5.0 and 10.0 mM pargyline, a marked decrease (46 and 76% reduction) in the accumulation of newly-formed dopamine was observed. 4. The accumulation of dopamine and DOPAC was found to be time-dependent in experiments in which tissues were incubated with 5 and 10 microM L-DOPA for 5, 10, 20 and 30 min. Pargyline (0.1 mM) produced an increase in the accumulation of dopamine at all incubation periods and decreased the formation of DOPAC. 6. It is concluded that deamination of newly-formed dopamine in kidney slices loaded with L-DOPA constitutes an important mechanism of amine inactivation. The results presented also suggest that most of the MAO, located inside the compartment where the synthesis of dopamine occurs, is of the A type.


The effect of artemether plus mefloquine on Myanmar patients with complicated falciparum malaria.

The effect of artemether plus mefloquine versus quinine on 35 patients with complicated falciparum malaria including 5 patients with cerebral malaria were studied. All patients treated with the artemether-mefloquine combination survived and all were free from toxic effects of the drugs. Three patients on quinine therapy died. The mortality rate was 8.5%. The mean parasite clearance time of patients treated with artemether plus mefloquine was significantly shorter than those treated with quinine but there was no significant difference in the mean fever clearance of the two groups of patients. There was no recrudescence with artemether and mefloquine; the recrudescence rate was 5.5% with quinine. The study showed that the artemether-mefloquine combination is superior to quinine for the treatment of patients with complicated falciparum malaria, including cerebral malaria.


The biological and epidemiological basis of drug resistance in malaria parasites.

Natural populations of Plasmodium falciparum without previous drug exposure are mixtures of individual parasites with different levels of response to a specific medicament. Exposure to sublethal drug concentrations will eliminate the highly and moderately sensitive individuals. The less sensitive part of the parasite population is being selected and given the opportunity of propagating. Underdosed mass drug administration and subcurative medication have this direct effect. An indirect effect with the same result is observed with drugs having a long half-life, where new infections invade the blood while subtherapeutic residual drug concentrations are still present. This militates against the use of drugs with long half-life in areas with intensive malaria transmission, and for a rational therapeutic use of alternative antimalarials based on reliable microscopic diagnosis, adequate dose regimens, post-treatment follow-up, further alternative treatment of recrudescences with the objective of radical cure.


Overview: epidemiology of malaria and its control in countries of the WHO South-East Asia region.

The malaria situation in the WHO South-East Asia Region is reviewed in terms of its epidemiological diversity, problems encountered and implications for control. Varying host-parasite-vector interrelationships are shown to be influenced significantly by prevailing environmental conditions (eg topographic, climatic) as well as behavioral and socio-economic determinants. Drug-resistant falciparum malaria and vector resistance to insecticides are the main biological deterrents to the success of control programs. Thus, the potential for malaria transmission remains high in many places. The malaria control strategy includes Primary Health Care and integration with basic health services. However, operational research is needed in many of the countries in the Region.


Dynamics of multi-drug resistance in Plasmodium falciparum in Thailand.

Since the initial report of resistance of Plasmodium falciparum to chloroquine in 1960 in the Thai-Cambodian border resistance to alternative drugs occurred early after their introduction. This development is considered to be the result of population migration and excessive drug pressure along with the presence of a multi-resistance gene within the parasite population. Multi-resistant strains as such have been disseminated throughout the country by returning migrant populations.


Current measures of containment of multi-drug resistant falciparum malaria in Thailand.

Resistance of P. falciparum to mefloquine emerged along the Thai-Cambodian border following the falciparum malaria outbreak in Bo Rai areas in late 1988. Efforts have been made since then to prevent or delay the spread of multi-drug resistant strains by restricting the use of mefloquine, limiting the distribution of the drug for presumptive treatment and chemoprophylaxis, encouraging personal protection, strengthening the case follow-up system, increasing physician awareness, and mass treatment with primaquine of gem miners crossing the borders.


In vitro sensitivity of Plasmodium falciparum to chloroquine and other antimalarials in east Timor and east Kalimantan, Indonesia.

In Indonesia resistance of Plasmodium falciparum to chloroquine has spread to all provinces except Yogyakarta since the first report in 1974. The proportion of resistant cases is relatively low except in Irian Jaya and East Timor. The results of in vitro tests performed in East Timor showed 81.0% resistance to chloroquine, 87.5% to amodiaquine, 20.0% to sulfadoxine-pyrimethamine (S-P), 4.8% to mefloquine, and 100% sensitivity to quinine. The percentage of failures was between 11.1% and 71.4% and highest with the S-P combination. Multidrug resistance was observed in 9 cases (or 11.1%). The results of in vitro tests in East Kalimantan were: 62.8% resistance to chloroquine, 100% to amodiaquine, 85.7% to S-P combination, 3.2% to quinine, and 2.5% to mefloquine. Failures rates ranged between 21.2% and 37.1% the highest being with mefloquine. Multidrug resistance was more prominent and observed in 59 cases (84.3%) of which one case was resistant to 5 antimalarials, while 4 cases (5.7%) were resistant to chloroquine only, compared to 72 cases (88.9%) in East Timor.


Overview: pathophysiology and management of cerebral malaria.

Cerebral malaria is still a major cause of death in patients suffering from malaria. Much of the research work in the past two decades has been done to clarify the pathophysiology of cerebral malaria which hopes to improve the management of the disease and concomitantly reduce mortality. However, the pathogenesis of cerebral malaria is still not clear. The pathophysiology of coma is believed to be brain anoxia from ischemia due to sequestration of erythrocytes containing mature parasites in cerebral capillaries and venules. Three possible mechanisms of sequestration (cytoadherence, rosette formation and decreased deformability of the infected erythrocytes) are postulated. The management of cerebral malaria includes early diagnosis and early treatment with potent antimalarial drugs, early detection and treatment of complications, correction of fluid and electrolyte imbalance and proper nursing care. In spite of these efforts, a high mortality rate (ranging 10-40%) is still encountered.


Malaria in Cambodia.

There are around half a million cases of malaria with 5-10,000 deaths per year in Cambodia. Incidence rates vary in different parts of the country. Malaria control is hampered by multiple drug resistance of Plasmodium falciparum, inaccessibility to the major vector, poor security in most malarious areas, and lack of resources. The control strategy emphasises improvement of clinical management and provision of prompt and accurate diagnosis in order to reduce morbidity and to prevent mortality. In addition health information and drug distribution systems are being improved. The use of pyrethroid-treated mosquito nets and health education are being promoted. Particular attention is given to returning refugees as they settle into the country.


Malaria control program in Indonesia.

The malaria situation in Indonesia is reviewed in the major island group of Java-Bali and the remainder of the archipelago called the Outer Islands. Based on their varying epidemiological patterns the areas for control have been stratified and efforts are directed towards the rational use of antimalarial drugs and the institution of integrated vector control ie chemical control in conjunction with biological control and environmental management. The targets of malaria control vary as well between island groups. Administrative, technical and operational constraints are identified. Drug-resistant malaria, forest-related malaria, lack of personnel, supervision and coordination, inadequate resources, and community participation are among the main issues confronting the national malaria control program. Research and training needs are emphasized in the recommendations.


The malaria situation and antimalaria program in Laos.

Malaria is endemic in all 17 provinces of Laos. Transmission is perennial with a "seasonal peak" coinciding with the rainy season. The vectors Anopheles minimus and An. balabacensis (=dirus) remain susceptible to DDT. Chloroquine-resistance of Plasmodium falciparum is at the RI-RII level. Multidrug resistance is not yet a problem. Major constraints of the antimalaria program involve logistics and operational problems solutions to which are specifically addressed in the recommendations.


Current status of malaria in Malaysia.

The Malaria Eradication Program was started in 1967 in Peninsular Malaysia. Since then and up to 1980, there was a reduction in the number of reported malaria cases from 160,385 in 1966 to 9,110 cases for Peninsular Malaysia. Although the concept of eradication has changed to one of control in the 1980, the anti-malaria activities have remained the same. However, additional supplementary activities such as the use of impregnated bednets, and the Primary Health Care approach, have been introduced in malarious and malaria-prone areas. Focal spraying activity is instituted in localities with outbreaks in both malaria-prone and non-malarious areas. Passive case detection has been maintained in all operational areas. In 1990, 50,500 cases of malaria were reported of which 69.7% (35,190) were from Sabah, 27.8% (14,066) from Peninsular Malaysia and 2.5% (1,244) from Sarawak. Until June 1991 a total of 18,306 cases were reported for the country. Plasmodium falciparum continues to be the predominant species, contributing to 69.6% of the parasites involved. The case fatality rate for 1990 was 0.09%. There were 43 deaths all of which were attributed to cerebral malaria. The problems faced in the prevention and control of malaria include problems associated with the opening of land for agriculture, mobility of the aborigines of Peninsular Malaysia (Orang Asli) and inaccessibility of malaria problem areas. There is need to ensure prompt investigation and complete treatment of cases especially in malarious areas. The promotion of community participation in control activities should be intensified. Primary Health Care should be continued and intensified in the malarious areas.(ABSTRACT TRUNCATED AT 250 WORDS)


Current status of malaria and control activities in the Philippines.

The paper attempts to present the current malaria situation in the Philippines which includes its distribution, morbidity and mortality rates, parasitology, the appearance of drug-resistant parasites, and entomological aspects. Under the current malaria control program, the objective is to reduce the incidence of malaria to one per one thousand population by year 2000 and to prevent its reintroduction to malaria-freed areas. Following the tactical variants of malaria control advocated by WHO, the program successfully reduced the incidence from 14.5/1,000 population in 1987 to 7.3/1,000 in 1990 but leveled off in 1991. Malaria is still among the 10 leading causes of morbidity. Problems encountered and research priorities are included in the report.


Vaccine strategies for malaria: applicability in areas of seasonal or epidemic malaria.

The likely effects of different vaccine strategies was tested using computer simulation of malaria transmission. In areas of seasonal or epidemic malaria, vaccines directed against all stages (pre-erythrocytic, erythrocytic and sexual) gave similar reductions in disease transmission. These models indicate that such vaccines may be much more effective that commonly predicted. The major effect will be to slow the spread of, rather than totally prevent malaria. As such, the use of such vaccines will be heavily dependent on integrated control programs involving other forms of control.


Overview: clinical pharmacology of antimalarials.

The effectiveness of antimalarials depends on its pharmacodynamics ie inhibitory effect on the parasites and unwanted effects on the host. It also depends on the pharmacokinetics of the drugs. The ideal antimalarials are drugs that show curative activity in the absence of toxicity to the host. Recommendation for antimalarial dosage regimens should be based on pharmacokinetic and pharmacodynamic studies in appropriate populations ie ethnic groups, adults children, and in pregnancy. Chloroquine remains the drug of choice for treating malaria caused by Plasmodium species other than P. falciparum. Even in the presence of chloroquine resistance the drug may still be quite useful, especially in areas with high communal immunity. In general sulfadoxine/pyrimethamine (S/P) should be used as an alternative antimalarial when chloroquine fails. The decision to change to S/P from chloroquine depends on many factors. Quinine still remains the drug of choice for severe chloroquine-resistant falciparum malaria. Resistance to mefloquine has appeared the exact mechanism being unknown. In general, before the use of any combination of antimalarial drugs the superiority (efficacy and side-effects) over each of the individual drugs should be clearly demonstrated. The combination of mefloquine with sulfadoxine/pyrimethamine was made on the grounds that the combination would delay the resistance to mefloquine. Desferrioxamine will hardly be an agent to be used on its own for treating malaria due to the high recrudescent rate. However, a recent report indicated that its association with antimalarial drugs in the management of severe and complicated falciparum malaria shortens fever and parasite clearance time and resolves complications faster than the standard antimalarial drug alone. Clinical trials with halofantrine has been done in several countries in the region from 1988 to the present with diverse results. Further studies on a larger scale should be carried out to ascertain whether these are due to variation in drug absorption or drug resistance. An improved formulation of halofantrine must be developed to ensure adequate absorption and bioavailability. The artermisinin group of antimalarials is known to be highly effective and independent, in its mode of action, from standard malaria drugs but associated with high recrudescent rate. Phase II studies are needed for determining/optimizing therapeutic dose regimens and to ensure safer and more effective use of these compounds.


[The missing inflammatory syndrome].

An inflammatory disease is sometimes suspected despite a normal erythrocyte sedimentation rate (ESR). When this dissociation is present, the reasons for the lack of ESR elevation, which concern the red cells, the plasma and the laboratory techniques, must be excluded, the reality of the inflammatory syndrome being then confirmed by assay of the inflammatory proteins. However, an inflammatory syndrome is missing in 5 to 10 percent of inflammatory diseases, more frequently in cases of polymyositis or scleroderma, less frequently in those of giant cell arteritis. Little information can be found in the literature, concerning the missing inflammatory syndrome. Does it confer peculiar semeiological or prognostic features? Is the dissociation related to the patient, as would appear in some special cases, or to the disease, as suggested by the small rise of the C-reactive protein in acute episodes of lupus erythematosus? The absence of inflammatory syndrome is a source of diagnostic problems when the symptoms are atypical or when there are no specific signs of the suspected disease. Differential diagnoses, especially non-inflammatory diseases, must then be carefully discussed. Improving our knowledge of the missing inflammatory syndrome would require the creation of this key-word.


The outcome of arthritis: measures of function, X-rays damage, pain and patients' satisfaction.

The outcome of arthritis has several dimensions. These include mortality, morbidity, radiological measures of joint destruction, pain, and patients' satisfaction with therapy. Functional disability measured by health status questionnaires, is directly associated with long-term outcome and mortality. Long term clinical trials should incorporate functional indices as outcome measures. Studies measuring the outcome of arthritis should define clear end-points involving the determination of functional classes and this will allow standardised and sensitive end points. An example would be the time taken to reach a given functional class or increase from baseline by one functional class. Patients' satisfaction with treatment is a different dimension of response. There are considerable advantages in using an index of patients' satisfaction when determining the therapeutic efficacy in short term clinical trials. It gives a different indication of the response to treatment than conventional clinical and laboratory measures of disease activity. Alleviating pain and preservation of function remain the major therapeutic goals, and both reflect the outcome of arthritis. Outcome measures have shifted from laboratory markers and radiographic techniques to measures of health status, pain, and patients' satisfaction. These should become a routine part of patient assessment.


Enteric coated naproxen; a double blind trial comparing the tolerance of enteric coated and standard formulations.

Enteric coated naproxen (Nycopren) was compared with standard naproxen in a double blind comparative trial of 348 patients with either rheumatoid or osteoarthritis. There were slightly fewer gastric side effects and slightly fewer withdrawals because of side effects in the enteric coated naproxen group but the differences did not reach statistical significance. There was no significant difference in the efficacy of the two formulations. A satisfaction index was used to assess the therapeutic ratio with visual analogue scales assigned to both efficacy and side effects. The scale performed as intended and is worthy of further exploration.


Enteric-coated and plain naproxen tablets in osteoarthritis; tolerability and efficacy.

The aim of this 8 week study, was to compare the tolerability and efficacy of enteric-coated (ECT) and plain naproxen tablets (PT). Ninety eight patients (mean age 66 years) with osteoarthritis were included in a randomized, multi-centre, double-blind, cross-over study. Response variables were monitored at 2 week intervals for the duration of the study. Sixteen patients withdrew from the study, eight because of gastrointestinal (GI) adverse events (ECT 5, PT3). There was no significant difference in patients preference. Eighteen patients reported GI adverse events only on PT compared to 9 on ECT (n.s.). In the first treatment period the severity of adverse events was significantly less on ECT (P = 0.015). Both enteric-coated and plain naproxen tablets were effective and well tolerated. In conclusion, the study did not show any clinical significant difference in tolerability or efficacy between the formulations in osteoarthritis of the knee and/or the hip, although some of the variables did show statistical significant difference or tendency in favour of the enteric coated tablets.


Morning stiffness and nightime pain in ankylosing spondylitis. A comparison between enteric-coated and plain naproxen tablets.

Thirty-nine patients with ankylosing spondylitis participated in a randomized, double-blind, double-dummy, multi-cross-over study with enteric-coated (ECT) and plain (PT) naproxen tablets. The duration of the study was 24 days with 6 treatment periods of 4 days. The majority of the patients were taking 750 mg naproxen daily. The mean plasma concentration of naproxen in the morning was 36% higher with ECT (p < 0.001). No significant differences regarding duration of morning stiffness and night time pain were found in this patient category. The mean duration of morning stiffness was 116 minutes (ECT) and 125 minutes (PT). We were not able to show correlation between plasma concentration of naproxen and duration of morning stiffness.


Enteric coated naproxen tablets.

It is postulated that the gastroduodenal mucosal side effects of naproxen are partly based on topical toxicity. With enteric coated aspirin tablets as a model product, enteric coated naproxen formulations have been developed. The extent of absorption is the same for enteric coated and plain tablets. The onset of absorption is delayed as a result of retention of larger particles in the stomach and more so when taken along with food. The gastric emptying of enteric coated naproxen granules is less influenced by food intake, but so far without any verified reduction of gastroscopic findings. The gastro-intestinal transmit has been studied by use of gamma scintigraphy.


Naproxen-associated gastroduodenal toxicity: enteric coated granules versus plain tablets.

Two naproxen formulations were compared with regard to gastroduodenal endoscopic findings. Using a dose of 500 mg bid for one week, plain tablets were compared to enteric coated granules in a gelatine capsule in a randomized, cross over, double-blind, double dummy study in 16 healthy, male volunteers. Endoscopic evaluation revealed no difference between the two formulations. Since previous studies with enteric coated naproxen tablets indicated a favourable side effect profile compared to plain tablets, the present data indicates that enteric coated formulations are not all alike, and should be studied individually.


NSAID-associated gastrointestinal damage: methodological considerations and a review of the experience with enteric coated naproxen.

Various methods are available for investigating gastrointestinal adverse effects of NSAIDs. Upper endoscopy is regarded a gold standard for controlled studies, but the grading and categorization of the visual impression of mucosal changes is complicated. Faecal blood loss represents another aspect of the toxicity, but quantitative measurements require the cumbersome procedure of 51Cr-labelling of red blood cells. For monitoring distal gut effects, permeability tests can be applied, and combination of tracer substances may further enhance the method. Measurements of electrical potential differences over the gastric mucosa are also available to monitor functional aspects of the gastric mucosal integrity. Controlled endoscopic trials have indicated an advantage of enteric coated naproxen tablets over plain tablets. Distal transfer of the toxicity by small bowel release of the active substance, has not been confirmed by permeability tests.


Retraction of Ross and LoLordo findings concerning blocking in serial feature-positive discriminations.

Findings concerning the effectiveness of stimuli from various conditioning procedures in blocking conditioned excitation and occasion-setting functions of an added stimulus in a serial feature-postive discrimination training procedure (LoLordo & Ross, 1987; Ross & LoLordo, 1986, 1987) are retracted. Videotapes on which the published data were based were rescored by 2-5 people, most of whom were uninformed about group memberships of the subjects. In no case did the rescoring confirm any of the orginal findings of blocking. Possible factors contributing to the discrepancies are discussed. The experiments should be repeated with feature stimuli that are less similar to each other and with several scorers, at least one of whom is unaware of the group assignment of the subjects.


Expert computer program for the management of laser surgery.

Since 1960 when the first laser was produced, different types of lasers were developed and over one hundred of them are actually used in medicine. These facts makes very difficult for a surgeon to optimally utilize different types of laser in varying surgical circumstances, unless a laser expert is actually participating in the procedure. As this presence is impractical, if not impossible in every case, we are offering a computer program which presents information in a flexible and friendly way; it is self perfecting and greatly expandable.


[Anthropometric study of students of Palo Blanco, Department of Tinogasta, Province of Catamarca, Argentina].

An anthropometric cross-sectional research was carried out in 211 students from Palo Blanco, in Tinogasta, Catamarca province. They were 110 boys and 101 girls aged 6-12 years, and they attended classes at the local school. Palo Blanco is a rural place, in a "very unfavorable" area, located on the west of Catamarca province, at 1.700 meters above sea level. Its climate is continental and half-deserted with a large diurnal thermometrical range. Measurements of body weight and standing height were obtained; then their averages and percentiles were compared with measurements of two samples obtained from urban areas. One of them was taken from students attending classes in Tinogasta (a city that belongs to the district having the sa-name), and the other from Catamarca city (the Capital of the province). Its aim was to determine the existence of some differences in the variables that were investigated, and that could de due to the rural situation of Palo Blanco's students. The anthropometrical variables in Palo Blanco's students resulted in values similar to those obtained in Tinogasta city, while both of them showed a significant difference, not only in body weight but also in standing height, in comparison to the students from the head city of Catamarca, especially in males. It may be concluded that conditions that differ from those derived of the rural situation, have incidence upon the behavior of these anthropometrical variables.


[Pancreatic ascites and pleural effusion].

Pancreatic ascites consists in the presence of pancreatic juice into the peritoneal cavity, coming from pseudocysts or pancreatic ducts breaches, that produce the accumulation of an exudate rich in proteins and amylase; these findings certify the diagnosis. We report a case of pancreatic ascites with pleural effusion: alcoholic patient, without previous episodes of acute pancreatitis, with ascites, weight loss, abdominal pain, right pleural effusion, insidious onset, blood level of amylase: more than 1024 UD; CT: ascites, right pleural effusion, pseudocyst in the head (24 mm) and in the tail (77 mm) of the pancreas. a transgastric cystogastrostomy in the cyst of 8 cm and a transduodenal punction in the cyst of 3 cm were performed, with an excellent postoperative result.


[Compact disk-read only memory].

The new technology has made possible the new information methods development. Isn't erasable, it is compatible with personal computers, and without additional online charge. The CD-ROM, Compact Disc Read Only Memory. These electronic media, used in the information digital storage, come from the compact audio disc. One CD-ROM covers over 250,000 text's pages, or 300,000 book's cards or 1,500 diskettes of 360 kbytes. In a compact disc there could be words, sounds, charts and images. MEDLINE database on compact disc, allows to search the current year on one CD-ROM, covering over 300,000 citations from 3,200 publications, material drawn from both English and foreign language publications.


Cytochemical localization of sorbitol dehydrogenase in kidney and liver from Myiopsitta m. monachus (Boddaert, 1783), during embryonic development.

A histochemical study to determine the localization of sorbitol dehydrogenase (SDH) in kidney and liver from embryionic, young and adult Myiopsitta m. monachus was performed. The enzyme activity increased with age in both organs. In the kidney, the enzyme appeared at the proximal convoluted tubules, and increased in the basal cytoplasm of the tubular cells. In the liver the localization was diffuse in the lobule but more intense in the cytoplasm of hepatocytes, especially in the perinuclear areas. These studies indicate that the cytochemical enzyme localization differs in this species, which is more evolutioned than Gallus gallus, and would be related to ontogenetic and phylogenetic differentiation.


[Profile of spermatic morphology in normospermic and dyspermic patients].

The evaluation of spermatic morphology is of importance due to its prognostic value in potential male fertility, both in natural and in assisted reproduction. In the present work, the morphologic profile of samples of semen from normal and dispermic patients was determined, in order to establish a correlation between structure and function. Samples were obtained from male partners of infertile couples who attended andrologic consultation. The smears were stained by the Papanicolaou technique, and the criteria of the OMS and the recent modification of Kruger were followed to evaluate spermatic morphology. Of all the patients studied (n = 46), 35% were normospermics (A), 39% asthenospermics, 7% oligospermics, 2% terastospermics and 17% presented combined alterations. The average percentage of normal spermatozoa was of 23.7 +/- 1.23 in the whole population. When group A patients were compared with asthenospermics, significant differences were found in the percentage of spermatozoa with middle piece and tail alterations, in the last group (p < 0.02). Similarly, when samples were analysed according to the presence of alterations: none (A), one (B) two or more (C), it was observed that the percentage of normal forms decreased in the groups in that order (A < B < C); (A or B vs C p < 0.05). The percentage of tapering spermatozoa was significantly higher in group C (p < 0.01 vs A or B). From the above results, it appears that 1) the larger number of functional alterations is related to a higher percentage of structural anomalies, and 2) the deficient motility in the asthenospermic group, is associated to the middle piece and tail alterations.(ABSTRACT TRUNCATED AT 250 WORDS)


Rubeosis iridis and neovascular glaucoma: I. Etiopathogenesis and treatment--the present state of the problem.

Rubeosis iridis is one of the severest complications of the occlusive diseases of retinal vessels associated with retinal hypoxia. In the pathogenesis of rubeosis, the author emphasizes the chronicity of retinal hypoxia which leads to the production of the vasoproliferative substance. This so-called vasoproliferative factor then induces the new formation of vessels on the retina, the optic disc, the iris and the anterior chamber angle. Neovascularization of the anterior chamber angle then very often results in the development of the prognostically very unfavourable neovascular glaucoma. It shows that the most effective methods of treatment of rubeosis iridis are the so-called coagulation techniques-panretinal photocoagulation or cryocoagulation. By application of these techniques, we achieve the destruction of the anatomical substrate which is responsible for the production of the vasoproliferative substance, and the result is involution of rubeosis on the iris and in the anterior chamber angle.


Rubeosis iridis and neovascular glaucoma: II. Our own experiences with the treatment by cryocoagulation.

The author evaluates the effect of two cryosurgical methods on the development of rubeosis iridis in neovascular glaucoma. In 12 eyes, cyclo-cryocoagulation was used as a single method, in 26 eyes, trans-scleral panretinal cryocoagulation was used in combination with cyclo-cryocoagulation in one session. Markedly better results were achieved by using the combined cryosurgical method. When trans-scleral panretinal cryocoagulation was applied in combination with cyclo-cryocoagulation, all the patients showed, 6 weeks postoperatively, a marked involution of rubeosis iridis. Complete regression of rubeosis iridis after cyclo-cryocoagulation was achieved only in one eye. The insufficient regression of rubeosis iridis in neovascular glaucoma, after the performance of single cyclo-cryocoagulation, the author explains in that way that by this surgical method only one component in the pathogenesis of rubeosis iridis is resolved. The author assumes that in the pathogenesis of rubeosis iridis in neovascular glaucoma, two components play their role: not only the underlying disease which conditions the development of proliferative retinopathy but also the high intraocular pressure which reduces the blood-flow in the retinal bed and thus increases retinal hypoxia.


Painful eye in neovascular glaucoma and its treatment with cryocoagulation.

The author summarizes the present knowledge concerning the treatment of pain in neovascular glaucoma. The treatment of the pain is very closely connected with a good compensation of the intraocular pressure. The author did not find a correlation between the degree of the elevated intraocular pressure and the ocular pain. He compares the results of the treatment of ocular pain in neovascular glaucoma with cyclo-cryocoagulation as a single method with those of the method of trans-scleral panretinal cryocoagulation in combination with cyclo-cryocoagulation performed in one session. In the treatment of ocular pain, markedly better results were achieved by using trans-scleral panretinal cryocoagulation in combination with cyclo-cryocoagulation. Complete relief from pain was achieved the fifth postoperative day in 54.5% when only cyclo-cryocoagulation was performed, in 100% when trans-scleral panretinal cryocoagulation was carried out in combination with cyclo-cryocoagulation. According to the author, this stands in connection with the better compensation of the intraocular pressure after the combined cryosurgical intervention and, in all probability, also with the assumed analgesic effect of panretinal cryocoagulation, which is obviously due to damage to the sensitive nerves of the bulb during freezing of the sclera an the choroid.


The nucleus raphe magnus of the cat. I. Quantitative analysis of neurons.

According to the shape of the perikarya six different types of the neurons in the nucleus raphe magnus of the cat were classified: spherical, oval, fusiform, pyramidal, piriform and stellate. According to size small, medium, large and giant cells were described. The spherical neurons are small and the most uniform in the shape and the stellate perikarya are the most variable in the shape and size.


The visual outcome in neovascular glaucoma patients treated with cryocoagulation.

The outcome of visual acuity in neovascular glaucoma is generally speaking very poor and frequently the result is a blind and painful eye. The author summarizes the outcome of visual acuity in neovascular glaucoma after the treatment with two cryosurgical methods--cyclo-cryocoagulation as a single surgical method and trans-scleral panretinal cryocoagulation in combination with cyclo-cryocoagulation at one session. In 38 eyes with acute neovascular glaucoma, cyclo-cryocoagulation as a single method was applied to 12 eyes and the combined cryosurgical method to 26 eyes. The author has shown that the impairment of the visual acuity after acute elevation of intraocular pressure in neovascular glaucoma is very rapid. He estimates that the loss of visual acuity is reversible within one week after the acute elevation of the intraocular pressure. In eyes where the initial visual acuity is poor--fingers in front of the eye and worse--the hope to maintain the visual acuity for a longer period is small, and that despite the good compensation of the intraocular pressure. In 6 eyes where the visual acuity was relatively good (6/24-3/60) up to one week prior the operation, it was possible in 5 eyes to maintain the visual acuity (6/24-2/60) for at least 6 months by application of the combined cryosurgical method.


Single fiber EMG in multiple sclerosis.

A group of 25 patients with sclerosis multiplex (SM) was examined by means of single fiber (SF) EMG. This group had the mean value of jitter 55.0 +/- 4.5 microseconds and fiber density (FD) 2.15 +/- 0.12. The findings of the patients with the first attack of illness and the findings of the patients with twenty-year duration are the same. A hypothesis is suggested that not only the peripheral neuron but also the CNS structures take part in the increase of jitter. The different results of stimulated single fiber (SSF) and SF EMG are discussed; the former reflects only the peripheral part of the nervous system due to peripheral stimulation. The higher levels of CNS cannot take part in it.


Single fiber EMG in cerebrovascular stroke (CVS).

This paper gives previously unpublished data about fiber density (FD) and jitter in patients with CVS. The cluster of these values is very similar to that found in sclerosis multiplex (SM). There is a problem whether both clusters represents the same disorder of CNS compared with amyotrophic lateral sclerosis (ALS) or spinal muscular atrophy which have different values. Another problem is the participation of presumed central lesion on the increased jitter, the mechanism of which is still unknown.


Tetanic syndrome and its examination.

The article presents a new electromyographic method; it describes the non-invasive examination of tetany with surface electrodes. This method is more sensitive than the classical needle technique and, moreover, the necessity to use expensive disposable needle electrodes is avoided.


The nucleus raphe magnus of the cat. II. Quantitative analysis of axosomatic synapses.

Quantitative analysis of axosomatic synapses in the nucleus raphe magnus of the cat showed great variations in their number, shape and size. There exist some relations between the size of perikarya and the number and size of the synaptic knobs. In the small neurons the number and size of synapses was smaller than in the large neurons, but there exist some exception from this rule. The observed morphological differences can be ascribed to different functional significance of various neurons.


Enzymatic equipment of the developing human eye.

The activities of a number of enzymes seen in adults and in animal material were found in the anlage of the developing eye in relatively early stages. Using standardized methods according to Lojda, activities of the following enzymes were proved in cryostat sections of the 9 and 10-week eye: ALP, ACP, ATP, TPP, alpha-GPDH and G6PDH. In 19-week eye moreover, positive reaction for DPP IV, ANE, CHE, ACHE was also detected, while G6PDH activity disappeared. In neither of the age categories SDH activity could be seen.


Early prenatal development of the brush border enzymes in the embryonal intestine.

Standard methods were used for the study of the activity of brush border enzymes in the epithelium of the intestine of 45 human embryos aged from 4 to 22 weeks of the intrauterine life. Enzymes of the peptidase group (DPP IV, APM, APA, GGT, BBEP), of the phosphatase group (ALP, ACP, AMP, ATP), and of the disaccharidase group (saccharose, lactase, trehalase) were studied. In the embryonal developmental period (to week 8), the activity of proteases was mainly detected on the luminal surface of the primitive pseudostratified columnar epithelium of the intestine anlage. The highest activity was displayed by DPP IV. In the period from the 8th week, villi are formed from the duodenum up to the ileum. After week 9, differentiation of Lieberkühn crypts was observed. The activity of proteases was very high (DPP IV especially) in the differentiating microvillous zone of primitive enterocytes. Gradient of apex-base activity of the villus was maximal on the apex of villi. After week 12 of the intrauterine life, the activity of disaccharidases ALP and AMP occurs in the differentiating brush border, and a low activity of BBEP of the protease group is present.


[Activity of gamma-glutamyl-transpeptidase in embryonic human organs].

The histochemical distribution of gamma-glutamyltranspeptidase (GGT) in organs of human embryos and fetuses was studied. In youngest embryos (4-7 weeks), a high GGT activity in the epithelium of the proximal part of embryonic intestine was recorded. Maximum of the activity was localised on membranes of luminal surface of primitive epithelium. High GGT activity in differentiating hepatocytes was also observed. In older fetuses (8-20 weeks) the activity of GGT gradually increases. In the epithelium of intestinal villi apex-basis gradient of the activity was recorded. The highest GGT activity in differentiating brusch border of the epithelium of proximale tubuli of fetal kidney was observed as well.


[Quantitative evaluation of capillaries in the myocardium of human embryos].

On cryostat sections of hearts of human embryos and fetuses aged 7 to 20 weeks, the length, density and internal surface (area) of capillaries were studied in surface unit of the ventricular myocardium using a semi-automatic apparatus MOP AM 03. The DPP IV and ALP-positive capillary segments were evaluated separately.


The effect of morphine on lymphocyte viability in vitro.

The effect of morphine on viability of the lymphocytes in peripheral blood, thymus and spleen of laboratory rats of the inbred Wistar strain was studied. Blood mononuclear cells for lymphocyte separation were obtained from the interface after Ficoll-Verografin gradient centrifugation. Lymphocyte suspension from the thymus and spleen was acquired by means of the Potter-Elvehjem homogenizer in icy Tyrod solution. Cell viability was studied by a simple method according to Hanks and Wallace after 6 hours incubation in normal oxygen atmosphere at 37 degrees C. Morphine reduced viability of the blood lymphocytes by 34%, of the spleen lymphocytes by 14% and the viability of the thymus lymphocytes was reduced by 18% in contrast to viability of the control group.


Effect of morphine on phagocytic activity of the polymorphonuclears and monocytes.

The effect of morphine on the phagocytic activity of the polymorphonuclears (PMN), and monocytes in peripheral blood of laboratory rats of inbred Wistar strain was studied in vitro. Phagocytic activity of both types of the white blood cells was examined by the classical method using microspherical hydrophilic particles (Hema-particles), phagocytosis of the Hema-particles was determined by light microscopy. For evaluation of the leukocyte adherence, the method of MacGregor was used. Morphine was proved to influence phagocytic activity of individual types of the leukocytes in different way. Phagocytic activity of the PMNs was suppressed (by 14.0%), and that of monocytes was potentiated (by 17.1%).


"Nude rabbit" with aplasia of B-lymphoid structures.

An original observation of the randombred nude rabbit with aplasia of B-lymphoid structures (absence of the follicles in lymph nodes and spleen, no Peyer's plaques). The thymus gland and the T-dependent structures in the spleen and lymph nodes were-on the contrary-well preserved. The nude skin of this genetic rabbit mutant contained large numbers of hair follicles showing almost intrafollicular retention of hairs with their subsequent dysplasia at the subepidermal and ostiopilar level.


Lymphocyte proliferation and T-lymphocyte subsets during experimental immunomodulation of Balb/C mice by Olimunostim.

To objectivize possible immunomodulatory effects of polybacterial lysate Olimunostim (P. acnes, K. pneumoniae, S. aureus), splenic lymphocyte proliferation and T-lymphocyte subsets were followed-up in Balb/c mice administered perorally the lysate or saline (controls). The enhanced spontaneous lymphocyte proliferation observed at the beginning of Olimunostim application preceded a gradual increase of lymphocyte reactivity to T-mitogens reaching the maximum five days after the administration of the last dose and returning back to the control levels ten days afterwards. This stimulation of lymphocyte proliferation was accompanied by Olimunostim induced increase of CD4+ splenic lymphocytes being most pronounced five days after the end of immunomodulation and later returning to the initial values. The last experiment revealed an enhanced response of the in vivo primed lymphocytes after the re-exposure to Olimunostim in vitro. It is concluded that mostly nonspecific activation mechanisms, plausibly also parallelly induced specific immunity, are involved in Olimunostim modulatory effects on the cellular immune response.


Study of modulatory effects of Olimunostim on cellular immunity in healthy humans.

To objectivize potential modulatory effects of polybacterial lysate Olimunostim on cellular immunity, the T-lymphocyte subpopulations and lymphocyte reactivity to mitogens were followed up in 10 healthy volunteers subjected to Olimunostim application and parallelly in 6 healthy individuals receiving placebo. The preparation, which was applied perorally in seven consecutive daily doses, had no effects on T-lymphocytes and their subpopulations and exerted only a limited influence on lymphocyte reactivity to mitogens. Both the moderate suppression of proliferative response to Con A and PWM, observed after the application of the three doses of Olimunostim, and the insignificantly enhanced response to PHA and Con A, revealed shortly after the last dose was given, were only of transient character and in comparison with the control group were not proved to be statistically significant. To explain the discordance of these results with the recently reported modulatory effects of Olimunostim on murine lymphocytes it is suggested, that the performed tests using the peripheral blood lymphocytes cannot mirror the processes developing in the diseased tissues. With respect to this presumption and also to the observations of enhanced immunomodulatory effect of Olimunostim on terrain altered by infection, it is proposed to investigate cellular immune parameters in specific disease sites of Olimunostim treated patients suffering from recurrent infections.


Immunological profile of patients with recurrent respiratory infections.

The authors present an analysis of the results of laboratory immunological examination of 52 patients suffering from recurrent respiratory infections. Besides the typical laboratory correlates of chronic inflammation, several findings indicated the depressed function of cellular and partially humoral immunity. The immunological parameters, most frequently decreased in comparison with normal values, were as follows: the response to the recall antigens of Imunoskintest (lower in 54% of patients), the relative number of CD3+ lymphocytes (35%), the CD4/CD8 ratio (37%), phagocytic activity (37%) and also serum IgA (12%). This means that more than two thirds of patients displayed at the time of examination a substantial alteration of one or more immunological parameters, the depression of cellular immunity was much more pronounced. It is concluded that the laboratory immunological examination of patients with recurrent respiratory infections is very important for revealing of an underlying cause of the disease and for indicating the adequate immunomodulatory treatment.


The preheparin and postheparin lipids of high density lipoprotein subfractions: relation to the serum insulin and postheparin plasma lipase activities in normal human.

The preheparin and postheparin lipoprotein lipids (cholesterol C and triacylglycerols TAG) were related to the serum insulin and to the postheparin plasma activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in normolipemic human. The positive correlation, although not statistically significant, of insulin level of the LPL activity was found, while no correlation to the HL activity was seen. Under preheparin conditions: 1) both insulin level and LPL activity were negatively related to the VLDL-C/TAG ratio indicating an enrichment of VLDL with TAG, 2) moreover, the LPL activity was positively related to the HDL-C and HDL3-C, 3) the HL activity predominated in relation to the HDL, and particularly to the HDL3, as indicated by negative correlations to the both lipids and to the lipid/apoA-I ratios of HDL and HDL3. This lipid depletion of HDL3 was more expressive due to the TAG, while HDL2 appeared to be relatively enriched with TAG, as suggested by correlations of C/TAG ratios with HL activity. The in vivo acceleration of lipoprotein metabolism by heparin resulted in: 1) the reduction of VLDL-TAG and HDL2-TAG, and in the increase of HDL3-TAG, 2) the appearance of positive relation of HDL2-C to the LPL activity and of opposite relation to the HL activity, 3) the lack of HL correlation to the TAG of HDL and HDL3. Even under these conditions no relation of insulin level to any HDL lipid was revealed. The results suggest that in normal human the HL affects more considerably than LPL the lipid metabolism of HDL subfractions and it does not seem to be under insulin control.


Effects of static magnetic field on some pathogenic microorganisms.

A high power superconductive magnetostatic system MAGNEX was used by the authors for two microbial strains Escherichia Coli and Staphylococcus Aureus, the magnetic induction values were 0.5-4 T and the exposure time was 30-120 minutes. In this paper morphological traits, standard biochemical tests, sensitivity and effects influence of some chosen sorts of antibiotics are considered and evaluated here. All the above given criteria and facts were analysed and the authors have come to the conclusion that magnetic DC field has no significant influence on the growth, the biochemical activity as well as on the antibiotics effects on the strains examined.


Fatty acids in lipids of nasoethmoidal polyps.

In 29 samples of recurrent nasoethmoidal polyps removed from 11 patients, the relative fatty acids composition was established by means of gas chromatography. Four samples of nasal mucosa of patients without polyps were subjected to the same procedure. A significant increase in the content of linoleic acid (18:2, n-6) as well as in the index "linoleic acid/oleic acid" was found. Proportion of arachidonic acid was high both in polyps and in control samples of nasal mucosa. An orientation examination of fatty acids in individual fractions of lipids, compared to serum values, showed that the main source of arachidonic acid appears to be phospholipids.


Quantitative indices in paternity cases.

The study discusses the basic quantitative indices used as a standard method in foreign professional literature dealing with paternity cases. They are as follows: 1. mean probability of exclusion (PE) which characterizes the informative value of the experts opinions and is the same in all the disputes evaluated by this expert. 2. relative frequency of men chosen at random from the population and excluded at given phenotype of mother and child (RME). 3. probability of paternity (PP) for particular trio: mother-child-the accused man. Hereinafter the results of our studies in the HLA laboratory in Olomouc from 1976-1991 are introduced.


HLA antibodies in renal transplant candidates.

The level of anti-HLA antibodies was followed in 155 patients of the chronic dialyzed program: against antigens HLA Class I and antigens HLA-DR representing HLA Class II. Correlation between the titre of these antibodies and additional factors were analyzed. The effect of pregnancy and consequently of sex was proved. Of significance were the number of dialyses undergone and the time of inclusion into the dialyses program. Positive correlation between the titre of both types of anti-HLA antibodies is so significant that it makes possible to concentrate on the more simple anti HLA I antibodies determination. The result of crossmatch test is of crucial importance when making decisions on suitable recipient of the kidney from the set of patients of dialyzed program (DP). The presence of anti-HLA alloantibodies can cause hyperacute rejection. The anti-HLA alloantibodies titre is regularly followed in DP patients. Several significant hypotheses can be verified in a large enough set of patients (hypotheses marked with ordinal numbers 1-5): 1. Only the titre of anti-HLA Class I antibodies is usually followed in DP patients. Some workplaces abroad consider it useful to follow even the anti-HLA Class II antibodies. Is anti-HLA I and HLA II antibodies titre in such a significant correlation that it is sufficient to follow only anti-HLA Class I? 2. Mechanisms of HLA antigen sensitization in DP patients are well known. We can verify the influence of transfusion number, allograft rejections and number of previous pregnancies on the anti-HLA antibodies titre.(ABSTRACT TRUNCATED AT 250 WORDS)


HLA-A and HLA-B typing: classification of errors.

The authors followed the frequency of errors in serologic identification of HLA-A and HLA-B antigens. They analyzed 205 paternity cases evaluated independently by two judicial experts (a revision of expert opinions). The specification of revealed discrepancies is demonstrated in the study and possible causes of their origin are analyzed. In the conclusions the authors recommend useful steps leading to the decrease of error frequency in HLA antigen typing. The HLA system--the major histocompatibility system of a man, has a broad utilization in the field of practical medicine. HLA compatibility should be respected in the choice of the couple donor-recipient for transplant therapy. HLA, as a highly polymorphic system, is successfully applied in forensic medicine. A strong association with some diseases makes it possible to utilize HLA as a supporting diagnostic sign. The commission for nomenclature of WHO at XI. International Histocompatibility Workshop (1991) recognized the following numbers of HLA specificities: 25 A, 55 B, 10 C, 21 DR, 9 PQ, 6 DP. At present HLA laboratories used mostly serological methods. The need to mutually differentiate HLA antigens which are similar due to their molecular structure puts an extraordinary demand on HLA laboratories. On one hand, a great number of HLA phenotypes exist in the population, which ensures the identification of every individual and the distinguishing of self-nonself components. On the other hand there appear the limited possibilities of HLA laboratories with relatively low numbers of diagnostic sera. We inquired how often errors occurred in HLA antigens determination. We chose a set of 205 auditing experts opinions of paternity cases for analyzing the problem.(ABSTRACT TRUNCATED AT 250 WORDS)


Prescription of psychopharmaca in common psychiatric diagnoses (discussion on the results of an anonymous survey).

The authors have made an anonymous survey among Czechoslovak psychiatrists on the prescription of psychopharmaca in select psychiatric diagnoses. The first place is occupied by haloperidol, perfenazin and chlorpromazine in hallucinatory paranoid syndromes, amitriptyline and clomipramine in depressions. The authors also wanted to find out which drugs were regarded as unsuitable by each psychiatrist. The replies varied considerably. In comparison with a similar survey made ten years ago, the methods of treatment relatively persist and novelties are rather wished for than really administered.


Vitamin E and A and periodontium in pregnant diabetics.

The authors followed physiological levels of vitamin E and A in four-week intervals in the course of physiological pregnancy in 11 insulin dependent diabetics. The highest mean levels of both vitamins were found in the IIIrd trimester. Simultaneously, the periodontal condition and the standard of oral hygiene were evaluated by means of epidemiological indexes in two-week intervals. The most marked inflammatory changes of periodontium occurred in the 8th month and were followed by an improvement before delivery, though the standard of oral hygiene was unchanged. The possibility of the eventual contribution of both vitamins in the improvement of periodontal condition in the final stage of pregnancy seems evident.


Luminol-dependent chemiluminescence and the clinical course of multiple sclerosis.

The luminol-dependent chemiluminescence activity before and after the ACTH (Synacthen) treatment was investigated in multiple sclerosis patients and the dependence of the changes of chemiluminescence upon the disease course was evaluated. The tests were performed with granulocytes and monocytes in the presence or in the absence of autologous thrombocytes and, further, the activity of whole blood was tested. All the test were performed both without additional stimuli (spontaneous activity) and with opsonized zymosan. Of the parameters tested, only the spontaneous chemiluminescence activity of whole blood displayed an evidence of dependence on clinical course of the disease. In clinically improved patients a decrease of the whole blood chemiluminescence was found. Similar trend was observed in chemiluminescence of whole blood stimulated by zymosan and in spontaneous granulocyte activity in the presence of autologous thrombocytes. The results show that the whole blood chemiluminescence is decreased in improved patients and suggest that this decrease might be related to the leukocyte-thrombocyte interaction.


[Si vis pacem, para pacem instead of si vis pacem, para bellum].

In the article the danger of the nuclear war and its possible medical, biological as well as environmental consequences for the population of the whole world have been presented. War is determined by political, social and economic problems, but it need not be the only way of solving complex world conflicts. War is generated in human mind and it is only human mind which can prevent it. The world-wide organization called "International Physicians for the Prevention of Nuclear War" (IPPNW) was set up in 1981 to prove that it is better for the mankind to live in peace than to confront the nuclear peril. In case of the nuclear war health service would not be effective at all and the world's population should have no doubts about it. There is no doubt that the radiologists and other physicians, physicists working on radiation and other technical personnel are particularly responsible for popularizing in the society the knowledge of the basic physical facts and of the medical consequences of nuclear danger.


The influence of selenium on the reproduction of rats.

Selenium is a vestigial element indispensable for man and animal, having adverse effects when in bigger quantities. Among the diseases resulting from selenium deficiency in animals the most important are nutritional muscular dystrophy, exudative disthesis (most common in poultry), and nutritional hepatic dystrophy. In the man chronic intoxication occurs most of all, which is observed in selenium bearing regions. Taking into consideration geographic distribution on some of the diseases beneficial influence of selenium is observed in cardiac and vascular diseases, and hypertension. The correlation between selenium deficiency and mortality caused by neoplasm is also notable. It is unquestionable that selenium inhibits the activity of enzymes, especially those containing sulfohydryl groups. The stabilization of lysosomal membranes leads to the presumption that selenium prevents peroxidation processes in tissues and cell membranes. The influence of selenium on reproduction is also worth noticing. Its supply turns out to be effective in cases of infertility of sheep, and partly in rats, pigs, and poultry. The embryo dies in pigs fed on fodder poor in selenium and vitamin E. The degeneration of the ovaries and placenta accretion occur in cows in cases of selenium deficiency. The excess of selenium can affect negatively the reproductive system. The element is thought to be a teratogenic agent. Since it permeates through the placenta and lactic gland easily, the symptoms of selenosis appear in new-born animals; many of them have developmental anomalies occurring at the same time. In birds the decrease in laying eggs and their incubation occur in case of selenium deficiency.


[Evaluation of the healing value of Iwonicz mineral water in balneo-climatic therapy of chronic hyperplastic laryngitis with wide pachydermic changes of laryngeal mucous membrane after microsurgery by the Kleinsasser method].

The paper comprises clinical estimation of using Iwonicz mineral water Elin 7 in balneotherapy of chronic hyperplastic laryngitis after its microsurgical therapy by Kleinsasser method. Investigation in the group of 246 people showed that combined treatment, i.e. microsurgery and balneotherapy, is an effective method of healing some hyperplastic inflammatory diseases of mucous membrane of the larynx.


[Diagnosis of dental caries based on intra-oral roentgenograms].

On 238 intra-oral roentgenograms there were assessed carious process, shape, size, extent and depth of defects as well as the possibility of complications in teeth which were not treated. There were assessed 277 defects, out of which 194 in upper teeth and 83 in lower ones. In all the teeth of the maxilla and of the mandible there was found the greatest number of amorphic defects and semilunar contact surfaces. There were also observed a lot of defects in radiciform cementum, thus, often under the gingivae. These are sites difficult for access for clinical examination. That is why radiologic examination is often conclusive in localizing carious process and in accurate diagnosing in the case of pulpitis going on.


Influence of Metizol ("polfa") on the liver of pregnant rats.

Drugs are the largest group of substances inactivated by the liver. They may have a stimulatory or inhibitory effect on the system of hepatic enzymes. Metizol is a thyrostatic belonging to the group of trimidazole derivatives. Its mechanism of action consists in inhibition of triiodothyronine++ and thyroxin secretion by the thyroid, owing to inactivation of the enzymes causing iodination of the thyrosine groups of thyroglobulin. This relatively little toxic drug when used for a prolonged period may lead to hyperaemia of the thyroid, and in pregnant women (by passing through the placenta) its side effects may threaten the foetus. The future mother affected with hyperthyroidism should receive full Metizol doses to avoid the danger of a thyroid crisis. A radical improvement of her health should be reached before childbirth.


[Ultrastructure of epithelial cells of rat seminal vesicles in the period of functional transformation and puberty].

It was found that the ultrastructure of the epithelial cells of the rat seminal vesicles changes during the period of puberty. The changes consist in formation of the cell organelles that participate in the production of secretion and in differentiation of the epithelial cells into the secretory and basal cells. The complementary biochemical studies indicate the close relationship between the formation of the typical ultrastructure of the secretory glandular cells of seminal vesicles and the presence of fructose in the secretion of these glandular cells.


[Histoenzymatic picture of rat gastric mucosa under the influence of dexamethasone].

White male [correction of female] rats were given Dexamethasone in a single dose 0.35 mg/24 hrs. Group I was given the drug once, group II--received it for 2 days, and group III--for 7 days. 24 hrs after the medicine had been given the mucous membrane of the stomach corpus was collected for examinations. There were performed: H+E staining, PAS reaction and histochemical reaction to the activity of ATP-ase, acid phosphatase and alkaline phosphatase. The results obtained were compared with those obtained in a group of control animals which were given distilled water. The administration of Dexamethasone did not affect significantly the activity of the examined hydrolases, however, it damaged the mucous barrier of the stomach, specially in the animals after 7 days of application of the drug.


[Histochemical picture of kidneys from pregnant female rats subjected to the action of vibramycin].

Female rats were given intragastrically, by means of a probe, Vibramycine in suspension, in a dose 4 mg/kg body weight, in different stages of pregnancy. On kidney sections there were performed: H+E staining, PAS reaction, histochemical determination of enzymes activity: alkaline phosphatase, ATP-ase, SDH and LDH. In non-pregnant females receiving the drug there was observed an intensification of alkaline phosphatase activity in brush border of main tubules of the kidney and a slight broadening of the light of the tubules. In pregnant females receiving the drug, most clearly in the second half of pregnancy a slight intensification of the activity of the examined enzymes was observed.


[Morphometric investigations of rat parotid gland after experimental encortone treatment].

The influence of Encortone treatment in the dose of 1 mg/kg of body mass on the secretory segments of male rat parotid gland was investigated. The changes of section area of cell nuclei, secretory cells, serous acini and changes of the number of cells in the acini were statistically analyzed. The observed changes depended upon the period of Encortone treatment. Seven-day Encortone treatment caused a statistically significant increase of the cell nuclei size and decrease of the cell and acini sizes. Changes of these parameters were result of cell hyperplasia and formation of new acini. Thirty-day Encortone treatment caused hypertrophy of cell nuclei, cells and acini of rat parotid.


[A case of hydatidiform mole with an unclear clinical picture].

The authors presented the case of hydatidiform mole with unclear clinical picture. They discussed clinical difficulties in the diagnosing of that lesion, and stressed the role of US method in establishing the specific final diagnosis.


Relation between somatic development and some environmental factors in the male population of vocational mining schools in the Lublin Coal Basin.

Somatic development of a child, although genetically determined, depends also on the influence of biogeographic and socio-economic factors of the environment. The effects of these factors popular in the literature are seen in the differences of somatic development of children brought up in urban and rural environments. In comparison with urban population, country children are characterized by lower growth and body mass, delayed manifestation of sexual maturity, greater amount of incorrect posture features, worse state of nutrition and lower index of mental development. The differences in somatic development of children were also found while comparing the size of agglomeration and socio-professional factors determining parents' level of education and financial situation of the family. One could also observe the improvement of somatic development of children living in regions of quick and intensive urbanization and industrialization.


Cardiovascular diseases risk factors in male population from mining vocational schools of the Lublin Coal Basin.

Contrary to certain industrial countries which secure an impressive decrease in coronary heart mortality, Poland has had, especially in the last decade, the significant increase of morbidity and mortality caused by cardiovascular diseases. Although this phenomenon concerns mainly the middle-age mean groups, special care for the whole population should be undertaken. The successful way to decrease the death rate and morbidity attributed to coronary heart disease (CHD) are the long-term prevention programs as for example Multiple Risk Factor Intervention Trial, Belgian Heart Disease Prevention Project, Lipid Research Clinics Coronary Primary Prevention Trial and others. Because there is some evidence that certain risk factors occur also among children, it seems that the effectiveness and efficacy of such prevention programs may be increased when started in the young population.


Evaluation of lung function in male population from vocational mining schools of the Lublin Coal Basin.

Occupational exposure to dust and other environmental factors in coal miners may impair the lung function of workers. Besides the coal workers' pneumoconiosis, the inhaled dust may cause decreased ventilatory capacity as a due to chronic bronchitis (9, 13). The same diseases, especially chronic bronchitis, are common in general population and may arise not only from occupational reasons (11, 12). The involvement of the genetic factors, environmental pollutions and cigarette smoking should be considered.


Evaluation of nutritional status of male population from mining vocational schools in the Lublin coal basin.

The basic nutritional mistake in Polish population at considerably rare deficiency of proteins and calories is incorrect composition of diet with the excess of animal fat and carbohydrates. Social and economic changes which influence living conditions result in the change of diet whose trends are not always correct. The problem is the quality of food products, contamination of pollution due to industrialization and the use of chemicals in agriculture, and inadequate proportion in the essential food components or supply of the indispensable trace elements. The other problem is overnutrition leading to obesity which is one of risk factors in civilization diseases (8, 11). The nutritional status depends on the level of education and economic situation of different social groups. It is expected that among the pupils of vocational mining schools who usually come from numerous peasant and working class families nutritional mistakes may occur very often. It denotes both malnutrition and incorrect proportion in consumption of proteins, animal fats and carbohydrates. On the other hand, the expected changes in social and economic status due to a good job create new conditions for proper nutrition. An additional factor which should be taken into account are nutritional requirements resulting from specific character of underground work.


[Analysis of caries dynamics in permanent teeth of children 6-9 years old from Lublin].

The stomatological examination was carried out in 443 children aged 6-9 years including 203 boys and 240 girls. It was ascertained that the prevalence of caries of permanent teeth in children aged 6 was 3.64%, aged 7-50.88%, aged 8-73.53% and aged 9-76.81%. The DMF index in children aged 6 was 0.05, aged 7-1.375, aged 8-1.852 and in those aged 9 it was 2.308. There was noticed some more advancement in caries process in girls than in boys.


[Histochemical and histologic examination of kidney from white rats after experimental administration of dexamethasone].

Kidneys of the rats which had been intragastrically administered Dexamethasone (10 mg/kg), were examined. Observations were carried out after a single and twice repeated application of the preparation, as well as after 7 days of everyday administration. It was found, on the basis of histological and histochemical observations (reaction to alkaline phosphatase activity, reaction to acid phosphatase activity, PAS-method staining), that both single and twice administration of Dexamethasone do not cause the damage of the kidney parenchyma, whereas after 7 days of everyday application of the preparation irreversible changes can be observed.


[Histopathologic and histochemical examination of rat liver after prolonged experimental application of potassium bichromate].

The rats were given potassium bichromate (K2Cr2O7) in dose of 2 and 5 mg/kg of body weight and magnesium chloride (MgCl2) in dose of 500 mg/kg for a period of 30 days. The two compounds were also given conjointly (K2Cr2O7-5 mg+MgCl2-500 mg). There were carried out histopathological as well as histochemical examinations of acid phosphatase activity, alkaline phosphatase activity and adenosine triphosphatase activity in the liver. With small doses (2 mg) of potassium bichromate no changes have been stated. With larger doses (5 mg) of potassium bichromate an increase of histochemical reaction to acid phosphatase as well as forming of histopathological changes such as parenchymatous degeneration, steatosis of hepatocytes and their necrobiosis have been observed. There has not been found any protective action of magnesium chloride on the cytotoxic activity of potassium bichromate on the liver cell.


[Effect of potassium dichromate on histopathologic changes in testicles of white rats and results of atomic pilograms on fur].

Male rats were administered, for the period of 30 days, potassium dichromate (K2Cr2O7) in a dose of 2 and 5 mg/kg of body weight and magnesium chloride (Mg Cl2) in a dose of 500 mg/kg of body weight. These two substances were also administered jointly (K2C2O7-5 mg/kg and MgCl2-500 mg/kg of body weight). In the testicles of animals receiving K2Cr2O7 in a dose of 5 mg/kg of body weight in groups III and IV there were observed changes of significant degree, mainly degenerative and multifocal, which consisted in degenerative changes of various degrees and changes of necrotic epithelium cells which, in turn, consist in cell hyper- or hypochromasia of chromatolysis or pycnosis and, too, in lesions of testicle epithelium of the spermatic epithelium cells. The cells of the Leydig intraparenchymatous gland did not reveal any histopathological changes as well as changes in the increase of hyatochemical tests. The highest concentration of chrome was in the hair of the animals receiving K2Cr2O7 in a dose of 5 mg/kg of body weight.


[Effect of pharmacologic blocking of the antigen-antibody reaction in adult respiratory distress syndrome (ARDS)].

In the experimental model of ARDS in rats there was investigated the influence of Intal (Fisons, GB) on the changes in the rat's lungs. Intal was inhaled through the respiratory system. Morphological examinations were carried out by hematoxylin and eosin staining. The results of experiment show that Intal seems to be a protective remedy in ARDS.


Search behavior in various breeds of adult dogs (Canis familiaris): object permanence and olfactory cues.

Human analog tests of object permanence were administered to various breeds of adult dogs (Canis familiaris). Experiment 1 showed that the performance of terriers, sporting, and working dogs did not differ. Dogs succeeded in solving invisible displacement problems, but performance was lower than in visible displacement tests. Familiarity with the task had some influence because invisible displacement tests were more successful if they were preceded by visible displacement tests. In Experiment 2, odor cues from the target object and the hiding screens were available or were masked. Results confirmed that success was lower in invisible than in visible displacement tests and that these problems were solved on the basis of representation of visual information rather than on the basis of olfactory cues or of local rule learning. Dogs are compared with other species that display Stage 6 object permanence.