Heart norepinephrine concentration after chronic alcohol ingestion in the rat

Summary The effect of long-term alcohol ingestion on the norepinephrine concentration of the heart was investigated in rats. The alcoholic animals showed a highly significant increase in cardiac norepinephrine concentration as compared with the corresponding controls. It is further suggested that continued exposure to high levels of norepinephrine may play a role in the development of cardiomyopathy in chronic alcoholism.     

Stimulation of the respiration of polymorphonuclear leucocytes by antileucocyte antibodies

Riassunto Gli anticorpi antileucociti provocano una marcata stimolazione della respirazione, rotenone, Antimicina A e cianuro insensibile, ed una aumentata attività del ciclo degli esosomonofosfati nei leucociti di cavia.     

Effect of menadione on the phagocytic activity of guinea-pig polymorphonuclear leucocytes

Riassunto Menadione in vitro inibisce l'attività fagocitaria di leucociti polinucleati in aerobiosi e in anaerobiosi. Vengono riportate prove sperimentali dalle quali risulta che l'effetto del menadione non è in rapporto con l'inibizione della glicolisi o con l'attività di trasporto di elettroni nella ossidazione dei piridinnucleotidi ridotti tramite una DT diaforasi.     

Palaeontology: early Neolithic tradition of dentistry

Prehistoric evidence for the drilling of human teeth in vivo has so far been limited to isolated cases from less than six millennia ago. Here we describe eleven drilled molar crowns from nine adults discovered in a Neolithic graveyard in Pakistan that dates from 7,500-9,000 years ago. These findings provide evidence for a long tradition of a type of proto-dentistry in an early farming culture.     

NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses

Clinical studies consistently demonstrate that a single sub-psychomimetic dose of ketamine, an ionotropic glutamatergic NMDAR (N-methyl-D-aspartate receptor) antagonist, produces fast-acting antidepressant responses in patients suffering from major depressive disorder, although the underlying mechanism is unclear. Depressed patients report the alleviation of major depressive disorder symptoms within two hours of a single, low-dose intravenous infusion of ketamine, with effects lasting up to two weeks, unlike traditional antidepressants (serotonin re-uptake inhibitors), which take weeks to reach efficacy. This delay is a major drawback to current therapies for major depressive disorder and faster-acting antidepressants are needed, particularly for suicide-risk patients. The ability of ketamine to produce rapidly acting, long-lasting antidepressant responses in depressed patients provides a unique opportunity to investigate underlying cellular mechanisms. Here we show that ketamine and other NMDAR antagonists produce fast-acting behavioural antidepressant-like effects in mouse models, and that these effects depend on the rapid synthesis of brain-derived neurotrophic factor. We find that the ketamine-mediated blockade of NMDAR at rest deactivates eukaryotic elongation factor 2 (eEF2) kinase (also called CaMKIII), resulting in reduced eEF2 phosphorylation and de-suppression of translation of brain-derived neurotrophic factor. Furthermore, we find that inhibitors of eEF2 kinase induce fast-acting behavioural antidepressant-like effects. Our findings indicate that the regulation of protein synthesis by spontaneous neurotransmission may serve as a viable therapeutic target for the development of fast-acting antidepressants.     

Dual-component NMDA receptor currents at a single central synapse

Present thinking about the way that the NMDA (N-methyl-D-aspartate) class of glutamate receptor operates at central synapses relies mainly on information obtained from single-channel and whole-cell recordings from cultured neurons stimulated by exogenous NMDA receptor agonists. The mechanisms that operate in the postsynaptic membrane of a normal neuron following release of the natural transmitter are far less clear. An important problem is that most normal neurons receive many excitatory synapses (10(3)-10(5) per cell) and these synapses are located on slender dendritic elements far away from the somatic recording site, making the study of discrete synaptic events difficult. Typically, when populations of synapses are activated, NMDA receptor-mediated synaptic potentials appear as slowly rising, long-lasting waves superimposed on faster, non-NMDA-receptor potentials. Although believed to be critical for NMDA receptor function, this slow time-course would not be predicted from single-channel kinetics and its origin remains puzzling. We have now analysed the events occurring at the level of a single excitatory synapse using a simple, small, neuron--the cerebellar granule cell--which has an unusually simple glutamatergic input. By applying high-resolution whole-cell recording techniques to these cells in situ, we were able to study the nature of elementary NMDA receptor-mediated synaptic currents. Contrary to expectations, the prominent currents are fast but are followed by slow ones. Both types of current are strongly voltage-dependent but differ subtly in this respect. Furthermore, the currents are absent unless glycine is provided.     

Activation of amino acids in the liver in CCl4 intoxication

Riassunto La reazione di attivazione degli aminoacidi è significativamente diminuita nel fegato di ratti nelle prime ore dopo la somministrazione di CCl₄. Questa alterazione si accorda con la dimostrata diminuzione delle sintesi proteiche e può rappresentare uno dei fattori primitivi e principali nella genesi delle modificazioni biochimiche e morfologiche che si osservano in questa condizione patologica.     

Interaction of smooth muscle relaxant drugs with calmodulin and cyclic nucleotide phosphodiesterase

Some smooth muscle relaxant drugs with an unknown mechanism of action have been tested for their interaction with calmodulin and with calmodulin-induced cyclic nucleotide phosphodiesterase (PDE) activity. The affinity of these drugs for calmodulin does not parallel their inhibitory effect on the calmodulin activation of PDE. The lack of parallelism could be due to a binding of the drugs to different sites on calmodulin; furthermore a binding of papaverine, octylonium bromide and felodipine to PDE molecule might also be considered to explain their inhibitory effect on PDE basal activity. The myolytic effect of octylonium bromide and pinaverium bromide may be due to their interaction with calmodulin-dependent systems.