Pentobarbital-induced drinking does not rely on a renal dipsogen

Injections of pentobarbital have been shown to produce drinking in both deprived and nondeprived rats and a number of other studies have shown that pentobarbital is a potent renin releasor. Since renin has been shown to be involved in thirst regulatory mechanisms and since the dipsogenic actions of other renin-releasing agents have been blocked by nephrectomy, we sought to determine whether or not pentobarbital-induced drinking relies on a renal dipsogen. Rats were either "sham" operated or nephrectomized under ether anesthesia. Five to six hours later, animals in each group were injected with either 9.5 mg/kg pentobarbital sodium or vehicle, and intakes were measured 60 minutes later. Statistical analysis of water intakes indicated that pentobarbital produced significant drinking in both control operated and in nephrectomized rats, and that the intakes in these two groups did not differ. These results indicate that pentobarbital-induced drinking is not secondary to increased plasma renin activity and may suggest the involvement of central mechanisms in the drinking response.     

NANC transmitters in the female pig urethra–localization and modulation of release via α2-adrenoceptors and potassium channels

1. To investigate further the release, localization and identity of a non-nitrergic mediator of smooth muscle relaxation in the female pig urethra, we studied the effects of drugs acting at α₂-adrenoceptors or K⁺ channels, the effects of capsaicin and chemical sympathectomy, and the actions of several transmitter candidates.
2. Electrical field stimulation (EFS; frequencies above 12 Hz) of spontaneously contracted smooth muscle strips from the female pig urethra evoked long-lasting, frequency-dependent relaxations in the presence of prazosin, scopolamine, and N^G-nitro-L-arginine. Treatment with the selective α₂-adrenoceptor agonist UK-14 304 markedly reduced the relaxations evoked by EFS at all frequencies tested (16–30 Hz). The inhibitory effect of UK-14 304 was completely antagonized by the α₂-adrenoceptor antagonist rauwolscine. The muscarinic M₁ receptor antagonist, pirenzepine, or exogenously administered carbachol, did not have any effects on the electrically evoked relaxations.
3. Inhibition of high conductance Ca²⁺ activated K⁺ channels by iberiotoxin or charybdotoxin significantly enhanced the relaxations evoked by EFS at all frequencies. However, inhibition of voltage-sensitive K⁺ channels with 4-aminopyridine or dendrotoxin-1, treatment with the ATP-sensitive K⁺ channel blocker, glibenclamide, or treatment with the high and low conductance Ca²⁺ activated K⁺ channel blockers, tetraethylammonium chloride and apamin, had no effect on the relaxations evoked by EFS.
4. Electrically evoked relaxations were not affected by adrenergic denervation with 6-hydroxydopamine (6-OHDA) at any frequency. However, treatment with 6-OHDA abolished prazosin-sensitive electrically induced contractions, and a long-lasting relaxation was revealed. Treatment with capsaicin, believed to damage selectively a subpopulation of primary afferent fibres, did not affect basal tone or relaxations evoked by EFS.
5. Exogenously applied vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating peptide (PACAP)-27, PACAP-38, adenosine, ATP and 5-hydroxy-tryptamine caused relaxations of the urethral preparations, whereas prostaglandin E₂ and calcitonin gene-related peptide had no effects. VIP 10-28, α, β-methylene-ATP, reactive blue-2, suramin or indomethacin did not reduce the electrically-evoked relaxations at any frequency. However, the relaxations were slightly reduced by trypsin or α-chymotrypsin.
6. The present results suggest that the release of the unknown mediator in the female pig urethra can be modulated via α₂-adrenoceptors and high conductance Ca²⁺ activated K⁺ channels. Furthermore, the mediator does not appear to be localized to or released from adrenergic or capsaicin-sensitive sensory nerve-endings. The identity of the transmitter remains to be established.

     

Presynaptic inhibition of synaptic transmission in the rat hippocampus by activation of muscarinic receptors: involvement of presynaptic calcium influx

1. Modulation of presynaptic voltage-dependent calcium channels (VDCCs) by muscarinic receptors at the CA3–CA1 synapse of rat hippocampal slices was investigated by using the calcium indicator fura-2. Stimulation-evoked presynaptic calcium transients ([Ca_pre]_t) and field excitatory postsynaptic potentials (fe.p.s.ps) were simultaneously recorded. The relationship between presynaptic calcium influx and synaptic transmission was studied.
2. Activation of muscarinic receptors inhibited [Ca_pre]_t, thereby reducing synaptic transmission. Carbachol (CCh, 10 μM) inhibited [Ca_pre]_t by 35% and reduced fe.p.s.p. by 85%. The inhibition was completely antagonized by 1 μM atropine. An approximate 4^th power relationship was found between presynaptic calcium influx and postsynaptic responses.
3. Application of the N-type VDCC-blocking peptide toxin ω-conotoxin GVIA (ω-CTx GVIA, 1 μM) inhibited [Ca_pre]_t and fe.p.s.ps by 21% and 49%, respectively, while the P/Q-type VDCC blocker ω-agatoxin IVA (ω-Aga IVA, 1 μM) reduced [Ca_pre]_t and fe.p.s.ps by 35% and 85%, respectively.
4. Muscarinic receptor activation differentially inhibited distinct presynaptic VDCCs. ω-CTx GVIA-sensitive calcium channels were inhibited by muscarinic receptors, while ω-Aga IVA-sensitive channels were not. The percentage inhibition of ω-CTx GVIA-sensitive [Ca_pre]_t was about 63%.
5. Muscarinic receptors inhibited presynaptic VDCCs in a way similar to adenosine (Ad) receptors. The percentage inhibition of ω-CTx GVIA-sensitive [Ca_pre]_t by Ad (100 μM) was about 59%. There was no significant inhibition of ω-Aga IVA-sensitive channels by Ad. The inhibitions of [Ca_pre]_t by CCh and Ad were mutually occlusive.
6. These results indicate that inhibition of synaptic transmission by muscarinic receptors is mainly the consequence of a reduction of the [Ca_pre]_t due to inhibition of presynaptic VDCCs.

     

Hard tissue laser ablation mechanisms

The aim of this work is the experimental and theoretical investigation of the influence of variable laser parameters (wavelength, fluence, pulse repetition rate) and of the optical and thermophysical properties of bone tissue (absorption coefficient, tissue inhomogeneity) as well as of the sample thickness on ablation thresholds and ablation rate. Ablation and perforation experiments were conducted using a semiconductively pre-ionized transverse excitation atmospheric pressure (TEA) carbon dioxide (CO₂) laser (10.6m and a sliding discharge TEA [hydrogen fluoride (HF)] laser (2.9m). The experimental data are discussed with respect to the following ablation mechanisms: thermal melting and vaporization process, pressure oscillation of gases released by the thermal decomposition of collagen and/or apatite, stresses due to the expansion of superheated water.     

飞行员不成熟防御机制与心理健康、 个性、生活事件、社会支持的相关性研究

目的　探讨飞行员心理防御机制与心理社会因素的相关性。方法　对312 例飞行员进行防御方式问卷,卡特尔16 种个性因素问卷,症状自评量表,紧张性生活事件量表,社会支持评定量表测评。结果　揭示飞行员不成熟防御机制与心理健康水平,生活事件,社会支持显著相关,个性因素明显的影响不成熟防御机制;患病飞行员采用不成熟防御机制明显的多。结论　在飞行员心理卫生保健工作中,揭示并修正飞行员不成熟防御机制是十分必要的。     

波特竞争战略与现代医院战略管理

通过对现代企业战略界所所推崇的波特竞争战略的探讨,简单波特的三种竞争战略,分析了随着我国市场经济的建立,开放改革的不断深入,医院战略管理所面临的困惑,根据我国现代医院管理的实际,提供了波特竞争战略对医院战略的一些启示。     

Locomotor activity and catecholamine receptor binding in adult normotensive and spontaneously hypertensive rats

Summary The binding of³H-WB 4101, an ₁-adrenoceptor antagonist, to membranes of the cerebral cortex, the hypothalamus, and the lower brainstem was examined in adult spontaneously hypertensive (SH) rats and in normotensive Wistar Kyoto (WK) controls. The specific binding of³H-WB 4101 (0.33 nM) was significantly higher in homogenates from the cerebral cortex of SH rats as compared to WK rats. No differences were detected between SH and WK rats in the specific binding of³H-spiroperidol (0.25 nM), a dopamine receptor antagonist, to membranes from the corpus striatum and the limbic forebrain. The locomotor activity was significantly higher in SH rats as compared to WK controls, in all probability due to a lack of habituation to environmental change. It is suggested that the high reactivity of SH rats is related to a dysfunction in the noradrenergic neurons in the central nervous system.     

Vegetables,fruit, and cancer. II. Mechanisms

The epidemiologic literature on the relationship between vegetable and fruit consumption and human cancer at a variety of sites was reviewed systematically in Part I.¹ It was concluded that consumption of higher levels of vegetables and fruit is associated consistently, although not universally, with a reduced risk of cancer at most sites, and particularly with epithelial cancers of the alimentary and respiratory tracts. Possible mechanisms by which vegetable and fruit intake might alter risk of cancer are addressed here. A large number of potentially anticarcinogenic agents are found in these food sources, including carotenoids, vitamins C and E, selenium, dietary fiber, dithiolthiones, glucosinolates and indoles, isothiocyanates, flavonoids, phenols, protease inhibitors, plant sterols, allium compounds, and limonene. These agents have both complementary and overlapping mechanisms of action, including the induction of detoxification enzymes, inhibition of nitrosamine formation, provision of substrate for formation of antineoplastic agents, dilution and binding of carcinogens in the digestive tract, alteration of hormone metabolism, antioxidant effects, and others. It appears extremely unlikely that any one substance is responsible for all the associations seen. Possible adverse effects of vegetable and fruit consumption are also examined. One way to consider the relationships reviewed here is to hypothesize that humans are adapted to a high intake of plant foods that supply substances crucial to the maintenance of the organism, but only some of which are currently called essential nutrients. Cancer may be the result of reducing the level of intake of foods that are metabolically necessary—it may be a disease of maladaptation.Authors are with the Division of Epidemiology, School of Public Health, University of Minnesota, 1-210 Moos Tower, 515 Delaware Street SE, Minneapolis, MN 55455, USA. Address correspondence to Dr Potter. This work was supported by NIH Grants CA 50305, CA 46618, and CA 09607.     

GABA-Mediated Presynaptic Inhibition in Crayfish Primary Afferents by Non-A,Non-B GABA Receptors

GABAergic presynaptic inhibition has been investigated in primary afferents using an in vitro preparation of the crayfish, Procambarus clarkii. Presynaptic terminals of a leg proprioceptor, the coxo-basal (CB) chordotonal organ, were impaled in the neuorpil of the 5th thoracic ganglion. Pressure ejection of small volumes of the GABAA or GABAB receptor agonists, muscimol and 3-aminopropylphosphinic acid (3-APA), both induce depolarizing responses in the impaled CB sensory terminal. These depolarizations are not blocked by the specific GABAA and GABAB receptor antagonists, SR-95531 and phaclofen, but they are abolished by picrotoxin. Both muscimol- and 3-APA-induced depolarizations are carried by an increase in conductance to Cl-. The presynaptic increase in conductance to Cl- by GABA receptor activation leads to a depression of sensory synaptic transmission through a shunting of the incoming spikes. Monosynaptic EPSPs elicited in motor neurons by CB sensory nerve stimulation are depressed by muscimol and 3-APA. GABA-mediated presynaptic modulation occurs in crayfish primary afferents which can adjust the gain of reflexes. These results show that GABA-activated Cl- channels can induce a modulation of synaptic transmission, but also that the distinction between GABAA and GABAB receptors, as in vertebrates, is not applicable to the crustacean primary afferents.     

Monoaminergic-cholinergic relationships and the chemical communication matrix of the substantia nigra and neostriatum

The historical development of histochemical methods for monoamines and chemicals involved with cholinergic function is reviewed. The use of these methods to elucidate neurochemical interactions in the substantia nigra and caudate-putamen complex is then discussed. Three hypotheses accounting for the localization of acetylcholinesterase within and/or on substantia nigra, pars compacta neurons are presented and evaluated:

1. (a) to catabolize acetylcholine released from afferent cholinergic fibers,

2. (b) to catabolize substance P released from some neostriato-nigral axon terminals, and/or

3. (c) to serve as a communication link with nigral vasculature.

Despite experimental evidence in favor of each of these possibilities, none have met with unqualified acceptance. Possible mechanisms and morphologic substrates accounting for dopaminergic-cholinergic, serotonergic-cholinergic, GABAergic-cholinergic, enkephalinergic-cholinergic, and cholinergic-cholinergic interactions in the caudate-putamen complex are discussed. These include synaptic and non-synaptic relationships, dendroaxonic information flow, and mutual regulatory processes.