Possible explanation for interictal-ictal transition: Evolution of epileptiform activity,in hippocampal slice by chloride depletion

Summary In thin hippocampal slices, paroxysmal epileptiform discharge was generated in high potassium medium. Removal of chloride from the high potassium medium caused explosive potentiation of the paroxysmal discharge and emergence of clonic relapsing discharges. Evolution of the paroxysm to regenerative seizure was attributed to the reduction of inhibitory postsynaptic potentials.     

Early foetal thrombosis induced by Thalidomide in mouse: Possible explanation for teratogenicity

Summary Mouse foetuses were treated by Thalidomide on days 11–12 in order to verify whether the drug would induce blood abnormalities leading to circulatory troubles. About 18% of the treated foetuses showed both severe limb haemorrhages on day 14, and obvious alterations of the nucleated red blood cells of vitelline origin. These blood abnormalities, occurring suddenly during the well-known critical stage of foetal development, could be responsible for circulatory blocks leading to necrosis.     

Possible role of intestinal alkaline phosphatase activity in thiamine transport.

Thiamine deficiency caused a marked decrease of intestinal alkaline phosphatase (al-Pase) activity, but had no effect on the Ca++-ATPase activity and Ca++-absorption in rats. The al-Pase activity was significantly decreased 1 h after oral administration of ethanol at 0.5 and 2.5 g/kg. In contrast, Mg++-, Ca++-and (Na+ + K+)-ATPase activities did not change after the administration of ethanol. These findings show that the al-Pase activity, unlike the Ca++-ATPase activity, is not related to Ca++-absorption. A possible role of al-Pase activity in the active transport of thiamine in the intestine was discussed.     

Role of proline in the imprinting developed by dipeptides — in Tetrahymena Possible role in hormone evolution

The effects of proline and serine dipeptides containing phenylalanine, alanine and leucine on the behaviour of receptors of Tetrahymena were investigated. Only proline-containing dipeptides were able to develop positive imprinting, and the activity depended on which other amino acid was present in the dipeptide. In contrast to the positive imprinting effect of the dipeptides Pro-Phe and Pro-Ala, the dipeptide Pro-Pro and Pro-Leu caused negative imprinting. Serine dipeptides produced negative imprinting in all cases. The possible importance of proline in the evolution of hormone specificity is discussed.     

4-Aminopyridine and barium chloride attenuate the anti-epileptic effect of carbamazepine in hippocampal slices

Summary The exact mode of action of the anti-epileptic agent carbamazepine is unknown. In hippocampal slices in which epileptiform discharges were induced by addition of penicillin to the perfusion medium, the depressant effect of carbamazepine was attenuated by the potassium-channel blockers barium chloride (0.1 mM) and 4-aminopyridine (200 M), which suggested that potassium fluxes might be involved in the mechanism of action of carbamazepine.     

Reexamination of vertical activity in rats treated with lithium chloride

Summary Injection of hypertonic LiCl i.p. has several nonspecific adverse effects in rats. No evidence was obtained forJohnson's hypothesis that the effect of LiCl on rearing is mediated by environmental stimuli.Acknowledgments. The author thanks Aarhus University, The Danish Medical Research Council, andMarianne Jensen for assistance.     

Phasic hippocampal activity during paradoxical sleep in the rat: selective suppression after diazepam administration

Summary The effects of diazepam on tonic (T) and phasic (P) components of the paradoxical-sleep hippocampal theta rhythm were studied in the rat. Results show that diazepam, a benzodiazepine analogue known to interfere with the putative neurotransmitter -aminobutyric acid (GABA) in the mammalian central nervous system, selectively abolishes P. They confirm previous data according to which sedative/anaesthetic drugs cause, an apparent dissociation of T and P of the paradoxical-sleep hippocampal theta rhythm. Moreover, they suggest a possible involvement of GABA in the neurochemical mechanisms underlying P in the rat.     

Hypothermia induced in mice by enzyme-mediated depletion of serotonin

Summary Injection of a purified serotonin (and tryptophan)-degrading enzyme into mice produced a pronounced hypothermia when the mice were maintained at 22°C, but not at 30°C. Brain levels of serotonin and tryptophan were strikingly depleted, but concentrations of norepinephrine and dopamine remained unchanged.This investigation was supported by grants CA-18844 and CA-08748 awarded by the National Cancer Institute, DHEW. We thank Barbara Morelli and Margaret Costello for their technical assistance.     

Hypothermia induced in mice by enzyme-mediated depletion of serotonin

Injection of a purified serotonin (and tryptophan)-degrading enzyme into mice produced a pronounced hypothermia when the mice were maintained at 22 degrees C, but not at 30 degrees C. Brain levels of serotonin and tryptophan were strikingly depleted, but concentrations of norepinephrine and dopamine remained unchanged.     

Radiation-released histamine in the rhesus monkey as modified by mast-cell depletion and antihistamine.

4000 rads of mixed gamma neutron radiation administered to rhesus monkeys released a significant amount of histamine into their circulation. When the monkeys were treated with a mast-cell histamine depleter (compound 48/80) for 4 days and then irradiated, no increase in circulating histamine was seen. When 48/80 was give 20 min after irradiation, only a slight increase in histamine was seen, indicating that 4000 rads had released most of the mast-cell histamine.     

Possible regulation of membrane-associated cyclic AMP phosphodiesterase in rat cerebral cortex by lipids.

Cyclic AMP phosphodiesterase (PDE) in membrane fraction from rat cerebral cortex was activated by Triton X-100, and treatment at alkaline pH and with phospholipase C. These results suggest that membrane PDE exists in a latent form and is influenced by microenvironmental changes within the membrane. Furthermore, the PDE, unlike soluble enzyme, is not influenced by a protein activator and Ca++.     

Antitumor activity of the Isodon diterpenoids: structural requirements for the activity.

A significant antitumor activity of oridonin (1) and lasiokaurin (2), the kaurene-type diterpenoids of Isodon species, was shown by their i.p. injection to the test mice inoculated by Ehrlich ascites carcinoma. Enmein (8), compounds 9 and 3 were also active under larger dose. Subsequently, the relationship between their chemical structure and antitumor activity was investigated, and the activity of oridonin (1) and lasiokaurin (2) was rationalized in terms of their structural feature.     

Reticulate evolution and cladism: Tests for the direction of evolution

Summary Reticulate evolution between ancestral-descendant lineages can be critically tested for by investigating the relationship between out-group and mid-point roots on numerically derived cladograms. The western grass-snake provides a worked example for the theoretical test.     

Adult hippocampal neurogenesis: regulation by HIV and drugs of abuse

New dentate granule cells are continuously generated from neural progenitor cells and integrated into the existing hippocampal circuitry in the adult mammalian brain through an orchestrated process termed adult neurogenesis. While the exact function remains elusive, adult neurogenesis has been suggested to play important roles in specific cognitive functions. Adult hippocampal neurogenesis is regulated by a variety of physiological and pathological stimulations. Here we review emerging evidence showing that HIV infection and several drugs of abuse result in molecular changes that may affect different aspects of adult hippocampal neurogenesis. These new findings raise the possibility that cognitive dysfunction in the setting of HIV infection or drug abuse may, in part, be related to alterations in hippocampal neurogenesis. A better understanding of how HIV and drugs of abuse affect both molecular and cellular aspects of adult neurogenesis may lead to development of more effective therapeutic interventions for these interlinked epidemics. Received 6 February 2007; received after revision 26 March 2007; accepted 25 April 2007     

Influence of reactive oxygen species production by monoamine oxidase activity on aluminum-induced mitochondrial permeability transition

Treatment of Ca2+-loaded mitochondria with both aluminum and tyramine results in a swelling of higher amplitude than with aluminum alone, while tyramine alone is ineffective. The phenomenon is accompanied by H2O2 production and thiol and pyridine nucleotide oxidation. Cyclosporin A, N-ethylmaleimide or dithioerythritol completely prevent these effects, while catalase exhibits a lower inhibition, pointing to the induction of the permeability transition (MPT) by an oxidative stress. Reactive oxygen species are generated by the interaction of aluminum with the inner membrane and the oxidation of tyramine by monoamine oxidase on the outer membrane. This different localization determines the oxidation of critical thiol groups located on both internal and external sides of pore-forming structures, resulting in MPT induction. The reduced effect by aluminum or the inefficacy by tyramine, when implied alone, can be attributable to the oxidation of thiol groups located only on the internal or external side, respectively. Ultrastructural observations show that aluminum plus tyramine induce the typical configuration of mitochondria that have undergone the MPT. Instead, with aluminum alone, the sensitive subpopulation, although swollen, preserves the outer membrane and shows an apparently orthodox configuration.     

Possible mechanism of rubidium-induced hyperactivity in the rat.

This study suggests that replacement of intracellular potassium by rubidium ions might lower the resting membrane potential. Thus rubidium-treated rats were more responsive to depolarizing influences and generated more cyclic AMP in the brainstem and consequently the behavioral changes.     

The stimulation of rat brain monoamine oxidase by dietary lithium chloride.

Lithium chloride administered to rats in drinking water for 30 days caused an increase of whole brain monoamine oxidase specific activity to approximately 140% of control. Carboxylesterase and formyltetrahydrofolate synthetase activities were not affected by Li+ either in vivo or in vitro.     

Secondary metabolism: an explanation in terms of induced enzyme mechanisms

Zusammenfassung Ist das Wachstum vonPenicillium urticae und anderer Pilze im Gleichgewicht gestört, so kommt es zu plötzlicher Akkumulierung wichtiger metabolischer Zwischenprodukte. Diese induzieren die Bildung neuer sekundärer Metabolite synthetisierender Enzyme, was Anlass zu weiterer Enzymentstehung ist und die Diversität der Stoffwechselendprodukte bestimmt.     

Possible effect of caerulein on calcitonin secretion in man.

Caerulein, infused in normal subjects, significantly reduces serum Calcium levels; in addition, when infused 60 or 90 min after radioactive calcium, it increases the specific plasma radioactivity, in a manner similar to calcitonin. These results suggest that in man caerulein stimulates calcitonin release.