The mode of action of lipid-soluble antioxidants in biological membranes. Relationship between the effects of ubiquinol and vitamin E as inhibitors of lipid peroxidation in submitochondrial particles. The effects of ubiquinol and vitamin E on ascorbate- and ADP-Fe(3+)-induced lipid peroxidation were investigated in beef heart submitochondrial particles before and after extraction of ubiquinone and vitamin E, and after reincorporation of either or both of these components. It is concluded that ubiquinol is capable of inhibiting lipid peroxidation without the mediation of vitamin E, but may also amplify the antioxidant effect of the latter. It is pointed out that ubiquinol is the only known lipid-soluble antioxidant that can be synthesized de novo in animal cells, and for which there exists an enzymic mechanism--the mitochondrial electron-transport system--that can regenerate the antioxidant from its oxidized form resulting from its inhibitory effect on lipid peroxidation. These features, together with its high degree of hydrophobicity and its general occurrence in biological membrane and in low-density lipoprotein, suggest a highly important role of ubiquinol in cellular defense against oxidative damage.


Antioxidant function of coenzyme Q.

Antioxidant function of coenzyme Q. Evidence for in vivo antioxidative activity of reduced CoQ homologs has been presented. This came from studies with experimental endotoxemia in mice, reoxygenation of rat liver following ischemia, and reoxygenation of canine heart following 24-hour cold preservation. In radical-induced injury of hepatocytes, it has been first shown that reduced CoQ9 acts as a potential antioxidant regardless of its cellular concentration, whereas reduced CoQ10 acts in cells containing CoQ10 as the predominant homolog. The antioxidant activity of reduced CoQ homologs appears to be independent of that of alpha-tocopherol under the conditions employed.


beta-Carotene and disease prevention.

beta-Carotene and disease prevention. Cancer and cardiovascular disease are still the number one and two killer diseases in most developed countries. There is justified hope that beta-carotene will be proven efficacious in the prevention and/or delaying of the onset of these chronic diseases. Chronic disease prevention through better nutrition, judicious use of supplements and better lifestyles will assume added importance in the coming years as the proportion of the population over 65 years increases.


Brain histamine: psychoneuroimmune regulator in physiological and pathological conditions. HA is a biogenic amine widely distributed in the CNS, with neurons located in the posterior hypothalamus. HA acts as a neurotransmitter and/or neuromodulator regulating neuroendocrine and neuroimmune functions, circadian rhythms, sleep-wakefulness cycle, body temperature, centrally-mediated neurovegetative functions, cerebrovascular control, and behavior and learning. Changes in brain HA are observed in aging. High levels of HA in CSF and CNS of AD patients might reflect a reactive response to neuroimmune activation and tissue damage.


Diurnal monoamine variation in young and old rats: a microdialysis study. The levels of striatal extracellular DA, DOPAC, HVA and 5-HIAA significantly decreased in aged rats compared to young adults. The magnitude of age-related reduction was greater in dopaminergic than serotonergic substances. The levels of striatal extracellular monoamines in young adult rats showed significant diurnal variations. On the other hand, these substances of aged rats, except for HVA, did not exhibit significant diurnal variations. Enriched environment housing increased levels of striatal extracellular DOPAC in aged rats, but did not influence on the age-related changes of diurnal variations in the striatal extracellular monoamines.


Thiamine responsive pyruvate dehydrogenase deficiency. We studied a PDH deficient patient who is clinically responsive to thiamine. High Km and low Vmax values for the TPP were identified in the patient's cultured cells. Immunoblot analysis detected trace amount of mutant E1 alpha polypeptide which was 3.5 KD larger than normal in size. Four-nucleotide deletion in the E1 alpha gene causes a reading frame shift, producing an abnormal polypeptide with additional 31 amino acids at C-terminus of the E1 alpha subunit. The tryptophan (codon 383) and lysine (385) residues near the C-terminus might play a crucial role in the binding of TPP to the E1.


The family of protein kinase C in transmembrane signalling for cellular regulation. Signal-induced hydrolysis of inositol phospholipid produces two second messengers, diacylglycerol and inositol trisphosphate. Diacylglycerol activates protein kinase C, whereas inositol trisphosphate mobilizes Ca2+ from its internal store. Analogously, signal-induced hydrolysis of choline phospholipid generates two second messengers, unsaturated free fatty acid and lysophosphatidylcholine. The free fatty acid synergizes with diacylglycerol to activate protein kinase C and causes full activation of the enzyme even at the basal level of Ca2+. On the other hand, lysophosphatidylcholine dramatically enhances cellular responses such as cell proliferation and differentiation under the conditions where diacylglycerol and Ca2+ are available. It is likely that all of the immediate products of signal-induced degradation of inositol and choline phospholipids are involved directly in concert in the transmembrane control of cellular functions.


Further metabolism of 1 alpha,25-dihydroxyvitamin D3 in target cells. Calcitriol-inducible C-24 oxidation in target cells gives rise to calcitroic acid in a variety of cells. The pathway probably involves a transient C23-aldehyde intermediate. The pathway appears to play a crucial role in the duration of the 1,25-(OH)2D3 signal in target cells. New analogs can be designed to render the molecule more susceptible or more resistant to target cell catabolism. However, these changes do not guarantee survival of the drug due to alternative degradatory pathways.


Evolutionary biology and pathology of vitamin D. There is mounting evidence that essentially all fungi, plants and animals living on earth produce provitamin D. It is likely that once exposed to sunlight, these provitamins are converted to previtamin D. It is unclear why fungi, phytoplankton, zooplankton and plants have the capacity to produce such large quantities of provitamin D. It is likely, however, that provitamin D and possibly vitamin D play an important biologic role in these organisms. Buchala and Schmid found, for example, that vitamin D3 promoted adventitious root development. It may be that provitamin D has a more fundamental function in lower life forms. Provitamin D and its photoproducts have UV absorption spectra that overlap with the ultraviolet absorption spectra from ultraviolet radiation-sensitive macromolecules including DNA, RNA and proteins. Thus, provitamin D and photoisomers could serve as a photon sink, and therefore, act as a natural sunscreen to protect lower life forms from the damaging effects of the high energy ultraviolet radiation that they are exposed to. It is more clear, however, that amphibians, reptiles, birds, mammals and humans all require vitamin D and that the vitamin D must be metabolized to 1,25(OH)2D3 before it can carry-out its physiologic functions on calcium and bone metabolism. The intense research activities during the past decade on the antiproliferative and differentiation activities of 1,25(OH)2D3 has opened a new chapter for this vitamin/hormone. 1,25(OH)2D3 and its analogs are being developed for the treatment of psoriasis, breast cancer, and leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Tissue-specific production of the third component of complement(C3) by vitamin D in bone. The third component of complement (C3) is a protein produced by osteoblastic cells in response to 1 alpha,25(OH)2D3. The bone C3 appears to be involved in differentiation of bone marrow cells into osteoclasts in concert with other vitamin D-dependent factors. Further studies are needed to understand the precise role of C3 in bone.


Mechanism of action of oxytocin in rat vagal neurones: induction of a sustained sodium-dependent current. 1. The mechanism of action of oxytocin on vagal neurones of the rat was studied using single-electrode voltage-clamp recordings from brainstem slices. The ionic basis of the oxytocin-induced current was examined by changing the composition of the perfusion solution and by making use of channel blockers. 2. In neurones clamped at or near their resting potential, oxytocin generated a sustained, TTX-insensitive inward current whose peak amplitude was concentration related. This current was detectable at 10 nM, was half-maximal at about 100 nM and was maximal at micromolar concentrations of peptide. 3. The oxytocin current was inward over membrane potentials ranging from -110 to -20 mV and was voltage dependent, since it increased in magnitude as the membrane was depolarized from the resting potential toward less negative potentials. 4. Partial replacement of extracellular sodium by equimolar N-methyl-D-glucamine reversibly attenuated or suppressed the oxytocin current. By contrast, substituting part of extracellular chloride or blocking calcium currents did not modify it. Increasing the transmembrane potassium gradient was also without effect and none of the potassium channel blockers TEA, 4-amino pyridine (4-AP), apamin, caesium or barium affected the oxytocin current. This current is thus at least in part carried by sodium. 5. The activation of the oxytocin current as a function of the membrane potential could be quantitatively simulated using a Boltzmann equation, suggesting that oxytocin acts by inducing the opening of a voltage-dependent channel which can exist in either of two states, open or closed. 6. Lowering the extracellular calcium concentration from 2 to 0.1 mM, while keeping the magnesium concentration constant at 1 mM, enhanced the response to oxytocin. This low calcium-induced potentiation of the oxytocin current was 1.4-3-fold and was reversible. 7. We conclude that oxytocin increases the excitability of vagal neurones by generating a persistent, voltage-gated current which is sodium dependent, is insensitive to TTX and is modulated by divalent cations.


Dynamic changes in human diaphragm length: maximal inspiratory and expulsive efforts studied with sequential radiography. 1. The maximal voluntary pressure generated by the diaphragm (transdiaphragmatic pressure, Pdi) is about 50% greater during maximal expulsive efforts than during maximal inspiratory efforts against a closed airway. However, these pressures cannot be increased by interpolated phrenic stimuli in trained subjects. This suggests that variable neural drive is not responsible for the difference in voluntary pressure. To investigate whether dynamic changes in diaphragm length during inspiratory and expulsive efforts could account for this difference, we used digital sequential radiography at 6 frames per second. 2. During the development of peak Pdi in inspiratory efforts, total diaphragm length decreased by about 20% in the antero-posterior and lateral projections. During maximal expulsive efforts (with glottis open), the diaphragm shortened slightly in the early stage of pressure development but then lengthened due to contraction of abdominal muscles before peak pressure was achieved. 3. Given that force increases when a contracting muscle is lengthened (expulsive effort) and decreases during shortening (inspiratory effort), this study provides a definitive explanation for the difference in maximal voluntary pressure between pure inspiratory and expulsive efforts.


Alteration of ventilatory activity by intralaryngeal CO2 in the cat. 1. We investigated the responses of phrenic and hypoglossal nerve activities to the addition of 3, 5 and 10% CO2 to a constant flow of warm, humidified air through the isolated upper airway in decerebrate, paralysed, artificially ventilated cats. 2. In bilaterally vagotomized animals, intralaryngeal CO2 caused a dose-related decrease in peak integrated phrenic activity. This response became attenuated with time, but was still discernible after 3 min of continuous intralaryngeal CO2. In the same experiments, intralaryngeal CO2 caused a gradual increase in peak integrated hypoglossal nerve activity. 3. Intermittent pulsing of intralaryngeal CO2 during neural inspiration or expiration resulted in similar, but smaller decreases in the phrenic activity of some animals. Hypoglossal activity was not influenced appreciably by this procedure. 4. Systemic hypercapnia attenuated the phrenic responses to intralaryngeal CO2. The hypoglossal responses were greatly reduced or abolished. 5. In vagally intact cats, ventilated by a servo-respirator in accordance with phrenic nerve activity, intralaryngeal CO2 resulted in only a trace of reduction in phrenic discharge. After bilateral vagotomy, the same animals showed typical responses, as described above. 6. All responses to intralaryngeal CO2 were abolished after bilateral section of the superior laryngeal nerves (SLNs). 7. We conclude that intralaryngeal CO2 acts by way of receptors with afferents in the SLNs to decrease phrenic and increase hypoglossal nerve activities. The responses are not importantly gated during neural inspiration or expiration. The responses to intralaryngeal CO2 are most clearly demonstrable after bilateral vagotomy, suggesting that vagal mechanisms serve to stabilize respiratory motor neural activity in intact animals.


Responses of laryngeal receptors to intralaryngeal CO2 in the cat. 1. We recorded afferent activities of single fibres in the superior laryngeal nerves of decerebrate or anaesthetized, paralysed cats while 3, 5 and 10% CO2 was added to a constant flow of warm, humidified air through the isolated upper airway. 2. Fifty-three receptors with discharge frequencies modulated by intralaryngeal CO2 were studied. Of these, forty-eight showed CO2-induced attenuation of their firing rates. Pulses of 3, 5 or 10% CO2, alternating with air at intervals ranging from 1.5 to 60 s, also diminished the discharge frequencies. This diminution was greater with higher CO2 concentrations and longer pulse durations. 3. Five of the fifty-three receptors were stimulated by intralaryngeal CO2. The discharge frequencies of these units increased slowly and by only a few impulses per second during CO2 exposure. 4. Thirty-four of the CO2-sensitive receptors were tested with other stimuli, including water, saline, positive and negative intralaryngeal pressures and cold air. The responses to these stimuli varied among receptors, but many of the units that reduced their frequencies with intralaryngeal CO2 were consistently stimulated by positive and/or negative intralaryngeal pressures. 5. Thirty-six of the receptors were anatomically located by probing the upper airway. Twenty-six were in the larynx, and ten were in the rostral trachea, within 5 mm of the cricoid cartilage. 6. The results, which are directly applicable to the investigation of reflex responses reported in the preceding paper, indicate that the predominant initial response to intralaryngeal CO2 under the conditions of these studies is attenuation of laryngeal receptor activity.


A role for low-frequency, rhythmic synaptic potentials in the synchronization of cat thalamocortical cells. 1. Low-frequency, rhythmic synaptic potentials and their ability to evoke and modulate membrane potential oscillations in thalamocortical (TC) cells of the cat dorsal lateral geniculate nucleus (dLGN) were investigated using intracellular recordings in a brain slice preparation. Three types of rhythmic synaptic potentials were distinguished: EPSPs, IPSPs and 'complex synaptic potentials' consisting of an IPSP followed by an EPSP. 2. The frequency of all three types of synaptic potentials was insensitive to changes in the membrane potential. At potentials positive to -50 mV, the EPSPs and the complex potentials gave rise to action potentials, while between -65 and -80 mV all three types of synaptic potential evoked low-threshold Ca2+ potentials. TC cells which displayed rhythmic synaptic potentials were either cells that showed spontaneous pacemaker oscillation or cells that were brought to oscillate by the rhythmic EPSPs or depolarizing (i.e. reversed IPSPs. 3. The low-frequency (1.9 +/- 0.2 Hz), rhythmic EPSPs were observed in 23 (out of 192) cells, were abolished by tetrodotoxin (TTX; n = 4) and by the combined application of DL-2-amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione (n = 3), and were insensitive to bicuculline (n = 4). Paired intracellular recordings (n = 32) demonstrated the presence of simultaneously occurring EPSPs in a pair of cells situated 75 microns apart. 4. The low-frequency (2.2 +/- 0.3 Hz), rhythmic IPSPs were observed in 5 (out of 192) cells, were blocked by bicuculline (n = 3), and reversed in polarity at -65 mV. The low-frequency (1.3 +/- 0.3 Hz), rhythmic 'complex potentials' were observed in 5 (out of 192) cells and were abolished by TTX (n = 2). 5. Intracellular depolarizing current pulses delivered at different phases of the pacemaker oscillations revealed the existence of two different types of phase resetting. Furthermore, a current pulse of critical amplitude and duration applied at a specific phase of the cycle abolished the pacemaker oscillations. 6. These results indicate that the low-frequency, rhythmic synaptic potentials recorded in TC cells of the dLGN (i) originate from other TC cells that are in the pacemaker oscillating mode, (ii) are capable of driving other TC cells to oscillate rhythmically, or of modulating the frequency of pacemaker oscillations, and (iii) provide a means by which oscillatory activities of TC cells can be synchronized in the absence of sensory, cortical and reticular thalamic inputs.


Histochemical arguments for muscular non-shivering thermogenesis in muscovy ducklings. 1. The histochemical characteristics of gastrocnemius muscle were investigated in 6-week-old cold-acclimated (5 weeks, 4 degrees C) and glucagon-treated (5 weeks, 25 degrees C, 103 nmol/kg I.P. twice daily) muscovy ducklings, two groups able to develop non-shivering thermogenesis in vivo. A comparison was made with thermoneutral controls (25 degrees C) of the same age. All animals were fed ad libitum. Fibre type, fibre area and capillary supply have been studied. Further, a quantitative histochemical method for mitochondrial Mg(2+)-ATPase activity was developed to characterize the mitochondrial coupling state in situ. 2. White gastrocnemius was composed of fast glycolytic (FG) and fast oxidative glycolytic (FOG) fibres, while red gastrocnemius contained FOG and slow oxidative (SO) fibres. In white gastrocnemius, the proportion of FG fibres was higher in glucagon-treated than in control or cold-acclimated ducklings. In red gastrocnemius, the proportion of SO fibres was higher in both cold-acclimated and glucagon-treated ducklings than in controls. The area of all fibres was generally lower in glucagon-treated than in other ducklings. 3. The capillary density was higher in both red and white components of the gastrocnemius muscle in cold-acclimated and glucagon-treated than in control ducklings, as a result of an increased number of capillaries around each fibre. 4. In all fibres, except the FG type in cold-acclimated ducklings, the staining intensity of the Mg(2+)-ATPase reaction was higher in cold-acclimated and glucagon-treated than in control ducklings whereas the staining intensity with maximal decoupling of oxidative phosphorylation by dinitrophenol was unchanged. This indicated a more loose-coupled state of mitochondria in situ in all fibres of cold-acclimated ducklings, and in FOG fibres of white gastrocnemius and SO fibres of red gastrocnemius in glucagon-treated ducklings. 5. These results indicated a higher oxidative metabolism of skeletal muscle in both cold-acclimated and glucagon-treated than in control ducklings, and for most of the parameters studied, a similarity between cold acclimation and glucagon treatment. Because of the higher loose-coupled state of muscle mitochondria in cold-acclimated and glucagon-treated than in control ducklings, the higher oxidative capacity of skeletal muscle in these ducklings could be used for heat production rather than ATP synthesis and account for muscular non-shivering thermogenesis.


Respiratory-related activity patterns in preganglionic neurones projecting into the cat cervical sympathetic trunk. 1. Activity in 233 single sympathetic preganglionic neurones that project to the superior cervical ganglion was analysed with respect to central components of respiration (phrenic nerve discharge) and to the afferent feedback generated by mechanical events occurring with ventilation in anaesthetized and artificially ventilated cats. 2. The activity in ninety-one neurones was modulated during the respiratory cycle in two ways: directly by the central inspiratory drive, and indirectly by ventilation-related blood pressure changes, acting via the systemic baroreceptors. The direct influence was prominent in vagotomized animals or those with a raised respiratory drive, and consisted of an inspiratory increase in activity and decreases of activity in early inspiration and postinspiration. The indirect influence (excitation due to baroreceptor unloading) usually dominated in normocapnic cats with intact vagus nerves. This population of neurones showed both similar reflex responses and a similar respiratory modulation of activity as postganglionic neurones supplying hindlimb skeletal muscle. 3. Sixty-one neurones discharged exclusively, or almost exclusively, during central inspiration. This discharge pattern neither depended on the integrity of vagal nor baroreceptor afferents. The activity of these neurones was abolished during hyperventilation and enhanced during hypercapnia. In the latter state, a small activation was often seen in stage II expiration. 4. In normocapnia the remainder of neurones (n = 81) exhibited no, or no pronounced, respiratory modulation of activity, except three neurones which showed a prominent expiratory pattern being of central and not of reflex origin. They were not a homogeneous population and included neurones exhibiting reflex responses similar to those of postganglionic neurones supplying hindlimb skin (n = 36), neurones responding to light (n = 4), and others (n = 41). 5. It is concluded that distinct types of thoracic preganglionic neurone differ with respect to respiratory modulation of their activity stemming from both central and reflex sources. Thus, the temporal profile of activity in these neurones in relation to respiration is another functional characteristic which can be used to distinguish between populations of sympathetic neurones.


Characteristic features of noradrenaline-induced Ca2+ mobilization and tension in arterial smooth muscle of the rabbit. 1. Effects of noradrenaline (NAd) on changes in cellular Ca2+ concentration ([Ca2+]i) and tension were investigated, and these effects were compared with those evoked by 128 mM K+ or caffeine in intact smooth muscle strips or by inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) or caffeine in beta-escin-treated chemically skinned smooth muscle strips of the rabbit mesenteric artery. 2. In physiological solution containing 2.6 mM Ca2+, application of 128 mM K+ or 10 microM NAd produced a phasic, followed by a tonic increase in [Ca2+]i and tension. NAd (10 microM) produced a larger tonic tension than did 128 mM K+ but a smaller increase in [Ca2+]i. When the [Ca2+]i-tension relationship was observed in ionomycin- and 128 mM K(+)-treated muscle strips, 10 microM NAs shifted the relationship to the left and enhanced the maximum amplitude of contraction. These results suggest that NAd increases the sensitivity of contractile proteins to Ca2+ in smooth muscle of the rabbit mesenteric artery. 3. Noradrenaline (10 microM) or caffeine (10 mM), but not 128 mM K+, produced a phasic increase in both [Ca2+]i and tension in Ca(2+)-free solution containing 2 mM EGTA. When 10 mM caffeine had been applied in Ca(2+)-free solution, subsequent application of 10 microM NAd did not increase [Ca2+]i. By contrast, when 10 microM NAd had been applied in Ca(2+)-free solution, subsequent application of 10 mM caffeine still increased [Ca2+]i. Ryanodine (50 microM) abolished the increase in [Ca2+]i induced by 10 mM caffeine or 10 microM NAd in intact and in skinned smooth muscle strips. These results suggest that NAd releases Ca2+ from the ryanodine-sensitive Ca2+ storage sites. 4. Noradrenaline (10 microM) synthesized Ins(1,4,5)P3 in Ca(2+)-free solution in intact smooth muscle strips. Following application of 10 microM NAd, a relatively long time lag (around 1 s) was always observed before the initiation of the increase in [Ca2+]i whether in the presence or absence of Ca2+. The maximum rate of rise of [Ca2+]i induced by 10 mM caffeine was much larger than that induced by 10 microM NAd in Ca(2+)-containing or Ca(2+)-free solution (containing 2 mM EGTA). Both [Ca2+]i and tension reached their peak in a shorter time with caffeine (10 mM) than with 10 microM NAd. In Beta-escin-treated skinned smooth muscle strips, 20 microM Ins(1,4,5)P3 10 mM caffeine or 10 microM NAd increased Ca2+ in Ca(2+)-free solution following brief application of 0.3 microM Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)


Stellate cell inhibition of Purkinje cells in the turtle cerebellum in vitro. 1. The stellate cell-mediated inhibition of Purkinje cells was studied by intracellular recordings in an in vitro slice preparation of the turtle cerebellar cortex. A graded inhibitory postsynaptic potential (IPSP) was recorded in Purkinje cells upon stimulation of the parallel fibre-stellate cell pathway. 2. The IPSP was abolished by bicuculline, and had a reversal potential around -75 mV, consistent with a GABAA receptor-operated Cl- conductance dominating the response investigated here. 3. Paired recordings from synaptically coupled stellate cells and Purkinje cells demonstrated that the inhibitory input from a single stellate cell is sufficient to reduce the firing in a Purkinje cell. 4. The extracellular-evoked IPSP interacted with the active postsynaptic membrane properties in the Purkinje cell. Interaction with both the Na+ plateau and the IA prolonged the responses to an IPSP, making the net effect of the inhibitory response dependent on the membrane potential in each postsynaptic neurone. 5. A precisely timed IPSP was particularly efficient in reducing dendritic Ca2+ influx. 6. The voltage-dependent Ca2+ component of a climbing fibre response (CFR) as well as of a parallel fibre (PF) input was reduced by the IPSP. 7. It is suggested that Ca2+ spike-mediated reduction in Purkinje cell excitability may be prevented by the stellate cell IPSP-mediated reduction in Ca2+ influx.


Studies of transepithelial Cl- transport in cultured cauda epididymal cells of rats by the short-circuit current method. 1. Monolayer cultures of cauda epididymides from male Sprague-Dawley rats (210-230 g) were studied by the short-circuit current (ISC) technique to characterize the properties of the transepithelial chloride transport. In HCO(3-)-free, HEPES-buffered solution, adrenaline (0.23 microM) added to the basolateral side led to an increase in ISC and transepithelial conductance (gt). 2. Decreasing apical chloride concentration ([Cl-]a) progressively from 126.7 to 0 mM by substituting chloride with gluconate increased the ISC response to adrenaline (delta ISC) in a linear fashion with a slope of -1.6 x 10(-3) mu equiv h-1 cm-2 per millimolar change in [Cl-]a. Pretreating the tissue with a chloride channel blocker diphenylamine-2-carboxylate (DPC) on the apical side significantly reduced the slope to -4.9 x 10(-4) mu equiv h-1 cm-2 per millimolar change in [Cl-]a. 3. By substituting apical chloride with various anions and measuring the change in ISC upon adrenaline stimulation, the selectivity sequence of the apical anion conductance was found to be NO3- approximately Br- > Cl- > I- > gluconate > isethionate. 4. When the monolayers were bathed with Krebs-Henseleit solution containing 25 mM HCO3- and 5% CO2, the delta ISC at each [Cl-]a as well as the dependence of delta ISC on [Cl-]a (slope = -3.3 x 10(-3) mu equiv h-1 cm-2 per millimolar change in [Cl-]a) were significantly greater than the HCO(3-)-free counterpart. Addition of 0.1 mM acetazolamide or 0.5 mM SITS (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid) to the basolateral side significantly reduced the effects of HCO3- and CO2. 5. When the tissues were bathed on both sides with HCO(3-)-free, HEPES-buffered solution and were clamped at various transepithelial potential differences (PDt) from +30 mV (lumen positive) to -30 mV (lumen negative), the relationship between the clamping current response to adrenaline (delta ICL) and the PDt applied was linear. Zero clamping current response was found at -6 mV. Decreasing [Cl-]a to 0 mM reduced the dependence of delta ICL on PDt and delta ICL was positive at all PDt tested. The response of the transepithelial conductance to adrenaline (delta gt) did not depend on the PDt applied but was reduced with decreasing apical chloride concentration.(ABSTRACT TRUNCATED AT 400 WORDS)


Abnormality of superior mesenteric artery blood flow responses in human sympathetic failure. 1. Systemic and regional haemodynamic responses, including superior mesenteric artery blood flow, were measured during stimuli which increase sympatho-neural activity in age-matched normal subjects (controls) and in two groups of patients with sympathetic failure (pure autonomic failure and multiple system atrophy). The stimuli included the pressor tests (mental arithmetic, cutaneous cold and isometric exercise) and head-up tilt. 2. In the controls, the blood pressure did not rise in some during mental arithmetic, but rose in all subjects during cutaneous cold and isometric exercise and was maintained during head-up tilt. In sympathetic failure patients, blood pressure was unchanged during each pressor test and fell during head-up tilt. 3. In the controls, superior mesenteric artery blood flow did not fall significantly during mental arithmetic but fell (with a corresponding rise in calculated superior mesenteric artery vascular resistance), during cutaneous cold, isometric exercise and head-up tilt. In sympathetic failure patients, there were no changes in superior mesenteric artery blood flow and vascular resistance during the pressor tests and head-up tilt. 4. There were no changes in cardiac index or forearm blood flow during each pressor test in both controls and patients. Cardiac index fell and forearm vascular resistance rose during head-up tilt in the controls only. 5. In conclusion, active constriction of the superior mesenteric artery occurs in normal subjects during sympatho-neural activation induced by stimuli such as cutaneous cold, isometric exercise and head-up tilt. This does not occur in patients with sympathetic failure and probably contributes to postural hypotension, emphasizing the role of the splanchnic vascular bed in overall blood pressure control. This study confirms the necessity of integrity of sympathetic pathways in the neural control of the splanchnic vascular bed.


Activation of protein kinase C suppresses responses to NMDA in rat CA1 hippocampal neurones. 1. The effects of 1-oleoyl-2-acetylglycerol (OAG), an activator of protein kinase C (PKC), on NMDA receptor-mediated responses were investigated in CA1 neurones of hippocampal slices using current- and voltage-clamp techniques. 2. Topical application of OAG caused a suppression of the slow, voltage-sensitive, NMDA receptor-mediated component of excitatory postsynaptic potentials (EPSPs) evoked by stimulating the schaffer-collateral commissural afferents and had no effect on the fast, voltage-insensitive, quisqualate/kainate component. 3. OAG suppressed the amplitude of inward current responses to NMDA down to about one-third of control responses. OAG could also increase the duration of the responses to NMDA by up to twofold. The effect of OAG on the duration but not on the amplitude of the response to NMDA was blocked by pre-loading cells with the K+ channel blocker, Cs+. Topical application of OAG had no significant effect on current responses to quisqualate. 4. An OAG isomer, which does not activate PKC, had no effect on responses to NMDA. Intracellular application of the kinase inhibitor, H-7, completely blocked the effect of OAG on the amplitude and duration of responses to NMDA, as well as on the slow EPSP. Finally, topical application of another activator of PKC, phorbol 12-myristate 13-acetate (PMA), also suppressed responses to NMDA. PMA reduced the slow component of synaptic responses in about half of the cells tested. 5. We propose that activation of PKC in CA1 hippocampal neurones suppresses NMDA receptor-mediated responses.


Detection of slow movements imposed at the elbow during active flexion in man. 1. Subjects' ability to detect movements imposed at the elbow during active flexion was measured. Movements of three different angular velocities (0.04, 0.4 and 4.4 deg/s) were applied to the arm while subjects maintained one of two force levels of active flexion. The threshold magnitudes for detection of the direction of imposed movement were found. 2. All thresholds were very small. At the lowest velocity of movement the average threshold was 0.13 deg and no subject had a threshold of greater than 0.3 deg. This contrasts with thresholds of over 2 deg measured in a previous study when the muscles about the joint were relaxed. Thresholds decreased further with increasing velocity of movement. 3. No difference was found between the two levels of contraction of the elbow flexors. However, extension (stretch of the contracting muscle) and flexion thresholds were calculated separately, and smaller extensions than flexions could be detected. 4. These findings indicate that conscious detection of imposed movements is greatly enhanced during active muscle contraction. Movements which cause unloading of the contracting agonist, as well as movements which result in stretch, are more easily detected than when the muscle is contracting. The discussion focuses on possible mechanisms for this enhancement.


The cardiovascular, endocrine and renal response of tetraplegic and paraplegic subjects to dietary sodium restriction. 1. The effects of change from a high to low sodium diet upon renal sodium and water excretion and hormone responses were studied in patients with dissociated sympathetic control (DS, tetraplegic) and controls with sympathetic control largely intact (IS, paraplegic). 2. Total and fractional urinary sodium excretion fell in response to sodium restriction in both groups, but the fall in fractional sodium excretion was greater in the DS group compared with the IS group (DS, 1.34 +/- 0.12 to 0.42 +/- 0.05%; IS, 0.96 +/- 0.08 to 0.52 +/- 0.06%). 3. Supine mean arterial pressure fell during the low salt period in the DS group (80.2 +/- 2.7 to 74.4 +/- 2.3 mmHg) but was unaffected by salt restriction in the IS group (101 +/- 2.3 to 98.8 +/- 2.7 mmHg). In the DS group, creatinine clearance remained constant throughout the low salt period (103.7 +/- 7.9 to 98.3 +/- 9.7 ml min-1), but fell during salt restriction in the IS group (101.4 +/- 8.5 to 83.2 +/- 5 ml min-1). 4. Plasma renin activity was lower during salt loading in DS subjects but increased more rapidly and to higher levels in response to salt restriction (DS, 1021 +/- 142 to 4439 +/- 355; IS, 1765 +/- 269 to 3683 +/- 465 pg angiotensin I ml-1 h-1). Plasma atrial natriuretic peptide concentration was higher in the DS group during salt loading and salt restriction (DS, 37.6 +/- 5.6 to 22 +/- 3.8; IS, 20.2 +/- 2.3 to 11 +/- 1.6 pg ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)


Differential effects of tetracaine on two kinetic components of calcium release in frog skeletal muscle fibres. 1. Intramembrane charge movements and changes in intracellular calcium concentration were recorded simultaneously in voltage clamped cut skeletal muscle fibres of the frog in the presence and absence of tetracaine. 2. Extracellular application of 20 microM tetracaine reduced the increase in myoplasmic [Ca2+]. The effect on the underlying calcium release flux from the sarcoplasmic reticulum was to suppress the peak of the release while sparing the steady level attained at the end of 100 ms clamp depolarizations. 3. While the peak of the release flux at corresponding voltages was reduced by 62% after the addition of tetracaine, the rate of inactivation was the same when the pulses elicited release fluxes of similar amplitude. 4. Higher concentrations of tetracaine, 0.2 mM, abolished the calcium signal in stretched fibres whereas in slack fibres this concentration left a non-inactivating calcium release flux. 5. Lowering the extracellular pH antagonized the effect of the drug both on charge movements and on calcium signals. The permanently charged analogue tetracaine methobromide lacked effects on excitation-contraction coupling. 6. These results imply that the two kinetic components of calcium release flux have very different tetracaine sensitivities. They are also consistent with an intracellular site of action of the drug at low concentration. Taken together they strongly suggest that the inactivating and non-inactivating components of calcium release correspond to different pathways: one that inactivates, is sensitive to tetracaine and is controlled by calcium, and another that does not inactivate, is much less sensitive to tetracaine and is directly controlled by voltage.


Dynamics of the ventilatory response in man to step changes of end-tidal carbon dioxide and of hypoxia during exercise. 1. Four human subjects exercised in hypoxia (end-tidal partial pressure of O2 (P(ET),O2) ca 55 Torr; heart rate ca 100-130 beats min-1), and the contribution to the respiratory drive of the peripheral and central chemoreflex pathways have been separated on the basis of the latencies and the time courses of the responses to sudden changes of stimulus. 2. The subjects were exposed to repeated end-tidal step changes in PCO2 of ca 3-3.5 Torr (at nearly constant P(ET),O2) and PO2 (between ca 55 and 230 Torr) at three regions along the expiratory ventilation VE-P(ET),CO2 response line (hypocapnia, eucapnia, hypercapnia). The dynamics of the ventilatory responses were calculated using a two-compartment non-linear least-squares optimization method. 3. The component of the response attributable to the peripheral chemoreflex loop may in some subjects contribute up to 75% of the ventilatory drive during mild hypocapnic hypoxic exercise and ca 72% of the total gain following steps of P(ET),CO2 during hypoxic exercise. These data support the notion that the effectiveness of the peripheral chemoreceptor pathway is enhanced in moderate exercise. 4. During hypoxic exercise, the time delays and time constants attributed to the peripheral chemoreflex pathways (ca 3.5 and 9 s respectively) and to the central chemoreflex pathways (ca 9.5 and 47 s respectively) are some of the shortest reported. 5. The dynamics of the peripheral and central chemoreflex pathways appeared to be largely independent of each other. 6. There was a notable absence of systematic change of inspiratory and expiratory durations during the step-induced transients.


Control of an external force in leg extensions in humans. 1. We investigated the hypothesis that mono- and bi-articular muscles perform different functions: the former are chiefly dependent on their mechanical advantage, while the latter are considered to be mainly concerned with controlling the direction of an external force. 2. Seven subjects were asked to exert a constant external force in various directions from three different positions. Feedback was given on the amplitude (300 and 600 N) and direction of the force vector. 3. During each trial the position of the subject was registered. Ground reaction force and muscle activity (EMG) from the main mono- and bi-articular upper leg muscles were recorded. Link segment modelling was used to obtain net moments about the knee and hip joints. For each muscle the mechanical advantage was calculated in each force direction. 4. The task of controlling the ground reaction force was performed with little interindividual variation as reflected by the variability of the different force and EMG variables. 5. A linear relationship between the difference in activity of rectus femoris and hamstrings and the difference in net moment around the knee and hip was found. This relationship showed very high correlation coefficients of 0.96 (300 N) and 0.97 (600 N) and was independent of position. Mean correlations between this activity difference and the angle of the force vector were also high: -0.95 (300 N) and -0.94 (600 N). 6. The mono- as well as the bi-articular muscles increased in activity when a larger mechanical advantage could be obtained from them, except for the biceps femoris (short head). 7. The results support the hypothesis that bi-articular muscles have a unique role in controlling the distribution of net moments about the joints, and as a consequence, in controlling the direction of the external force exerted on the environment.


Myofibrillar fatigue versus failure of activation during repetitive stimulation of frog muscle fibres. 1. Single fibres isolated from the anterior tibialis muscle of Rana temporaria (temperature, 2-5 degrees C; sarcomere length, 2.10 microns) were fatigued using two separate protocols that led to different degrees of depression of tetanic force. Under control conditions the fibre was stimulated to produce a 1 s fused isometric tetanus at 300 s intervals. A moderate degree of fatigue (tetanic force reduced to 70-80% of the control value) was produced by decreasing the intervals between tetani to 15 s ('fatiguing protocol 1'). A more pronounced depression of tetanic force (to 40-50% of the control value) was produced by evoking a single twitch at 1-2 s intervals ('fatiguing protocol 2'). 2. Fatiguing protocol 1 reduced the contracture response to submaximal and supramaximal concentrations of caffeine (3-15 mM) in proportion to the decrease in tetanic force. These results support the view that fatiguing stimulation according to protocol 1 leads to a true 'myofibrillar fatigue' with no failure of activation of the muscle fibre. 3. Fatiguing protocol 2 reduced the amplitudes of isometric twitch and tetanus to below 10 and 50% of the control values, respectively. By contrast, the maximal contracture response to caffeine (15 mM) was depressed by merely 2-3% of its prefatigue value. 4. Force and instantaneous fibre stiffness were recorded simultaneously during twitch and tetanus as fatigue was induced by protocol 2. During the initial part of fatigue (tetanic force reduced by 25% of control) stiffness was reduced by merely 9% in accordance with previous measurements during fatigue induced by protocol 1. However, with further depression of twitch and tetanus by protocol 2 there was a marked reduction of fibre stiffness. These results, together with the findings reported under point 3, strongly suggest that at an advanced state of fatigue induced by protocol 2 the decrease in active force is largely due to failure of activation of the contractile system. 5. Muscle fibres were quickly frozen for electron microscopical examination after shortening below slack length (to approximately 1.6 microns sarcomere spacing) during tetanic stimulation. In non-fatigued fibres, and in fibres fatigued according to protocol 1, the myofibrils exhibited a straight appearance throughout the preparation suggesting that the entire volume of the fibre was properly activated. In fibres fatigued by protocol 2, on the other hand, only the most peripheral layers of myofibrils remained straight after shortening, whereas the centre of the fibre showed marked waviness indicating failure of the inward spread of activation in this case.


Different firing patterns generated in dendrites and somata of CA1 pyramidal neurones in guinea-pig hippocampus. 1. Intracellular recordings, taken from CA1 pyramidal cells in guinea-pig hippocampal slices, were used to examine the origins of repetitive and burst firing in these cells. Single action potentials were elicited by depolarizing current injection at somatic recording sites. In contrast, current injection during intradendritic recordings initiated burst firing in the dendrites. Burst firing could be elicited in the soma by direct depolarization of distal apical dendrites (> 150 microns from the cell body layer) with large extracellular polarizing electrodes. 2. Intracellular recordings were taken simultaneously from the apical dendrites and pyramidal cell somata with the intention of impaling the same neurone with both electrodes. Paired dendrite-soma recordings confirmed that rhythmic single action potentials were generated at the cell soma, whereas bursts of action potentials were initiated in the distal apical dendrites (> 150 microns from the cell body layer). Fast spikes in the dendrite often triggered fast spikes in the soma, but not all fast spikes in the dendritic burst were 'relayed' to the soma. 3. In paired recordings, when a dendritic action potential failed to elicit a full somatic action potential, a 'd-spike' was commonly recorded in the soma. Somatic d-spikes were uniform all-or-none responses that could be shown, in some cases, to trigger the full somatic action potentials. 4. Attenuated spikes could be recorded in the dendrites, triggered by action potentials initiated at the cell soma. Dendritic responses to somatic stimulation sometimes varied in amplitude, but always showed a direct correspondence with somatic action potentials. 5. Dendritic recordings taken closer to the pyramidal cell bodies (< 150 microns from the cell body layer) showed a 'transitional' region where single action potentials rather than burst discharges could be evoked. After-potentials of these single spikes differed from those associated with somatic spikes in that proximal dendritic spikes had depolarizing after-potentials. The observed shift from after-hyperpolarization to depolarizing after-potentials in intradendritic recordings taken progressively further from the cell body corresponds to the change from repetitive to burst firing. 6. The results indicate that activity of the CA1 pyramidal cell soma, presumably a reflection of its output, can be either burst or repetitive firing. Somatic 'bursts,' unlike the burst discharges seen in the apical dendrites or the burst discharges reported in CA3 cells, are not initiated locally. Rather, they appear to be simply a rapid spike-for-spike response by the soma to the fast spikes that form part of the apical dendritic burst.(ABSTRACT TRUNCATED AT 400 WORDS)


The effects of ventricular end-diastolic and systolic pressures on action potential and duration in anaesthetized dogs. 1. Although it is known that mechanical events in the heart influence the duration of the cardiac action potential, there is no quantitative information on the effects of independent changes in ventricular end-diastolic and systolic pressures. 2. Experiments were carried out on open-chest anaesthetized dogs in which the autonomic nervous influences on the heart were prevented and monophasic action potentials were recorded form the epicardial surface of the left ventricle. The duration of these action potentials was taken as the interval from the upstroke to the point of 90% repolarization. 3. Elevation of left ventricular peak systolic pressure, at constant end-diastolic pressure, significantly shortened the monophasic action potential. 4. Elevation of end-diastolic pressure at constant peak systolic pressure significantly lengthened the monophasic action potential. 5. Responses were not dependent on release of noradrenaline from sympathetic nerve terminals because they persisted after administration of bretylium tosylate. They were also not due to myocardial ischaemia because they persisted when coronary perfusion pressure was maintained at a constant high level. 6. Simultaneous recordings of changes in myocardial segment length showed the expected responses to changes in ventricular pressures: increases in shortening in response to increases in diastolic pressure and no consistent effect from changes in systolic pressure. 7. These investigations demonstrate the independent effects of changes in systolic and end-diastolic pressures on cardiac action potential duration. This effect is likely to be an effect of the mechanical events, i.e. contraction-excitation feedback. This response may be mediated through changes in myocardial fibre tension, the consequent changes in fibre shortening, or both.


Developmental biology of the common marmoset: proposal for a "postnatal staging". The published knowledge on neurobiological, psychological, and ethological aspects of development in Callithrix jacchus is still limited. We have collected published and unpublished data from several Callithrix colonies and pooled information on criteria for developmental progress and maturation using a questionnaire sent to numerous experts in the field. The data suggest that developmental stages can be defined not only for the embryonic and fetal but also for the postnatal period. Based on multifactorial definitions, using criteria selected from maturational changes in the motor and visual systems and behavioral features, we propose to subdivide postnatal development of the common marmoset into seven periods ("stages").


Transmission of SIVMne from female to male Macaca nemestrina. Three SIVMne-infected female pigtailed macaques (Macaca nemestrina) were mated with two SIV-negative males. The females exhibited signs of SAIDS and SIVMne was readily isolated from peripheral blood mononuclear cells (PBMC). Both males became infected with SIVMne, developed SAIDS, and died. This is the first documented case of the transmission of SIVMne between adult macaques housed together. Although transmission through scratching or biting cannot be ruled out, heterosexual transmission appears the most likely mode of SIVMne transmission in this study.


Measurement of serum IgE antibodies against Japanese cedar pollen (Cryptomeria japonica) in Japanese monkeys (Macaca fuscata) with pollinosis. IgE antibodies against allergens of Japanese cedar (Cryptomeria japonica, CJ) pollen in the serum of seven Japanese monkeys (Macaca fuscata) with pollinosis were measured by fluorometric indirect enzyme-linked immunosorbent assay (ELISA). All of the monkeys were found to have specific IgE to the crude pollen antigen. The specific IgE levels were well correlated with those determined by the Pharmacia CAP system. IgE antibodies were then assayed with two kinds of purified allergens (Cry j I and Cry j II) by the ELISA. We found that five monkeys had specific IgE to both allergens, although the other two had IgE only to Cry j I or Cry j II; there is different immune responsiveness to the two major allergens in the monkeys.


Dependence of biphasic heart rate response to sustained hypoxia on magnitude of ventilation in man. We studied the dynamic profile of respiratory and circulatory activities during sustained isocapnic hypoxia in healthy males. In response to end-tidal PO2 depression to about 55 Torr, minute ventilation first increased briskly and then depressed. Such biphasic response to hypoxia was also observed in the heart rate. A significantly positive correlation was found between the magnitudes of ventilatory and heart rate responses. No significant increases were found in arterial noradrenaline and potassium, but adrenaline significantly increased gradually with time. Furthermore, when VT and f were intentionally maintained constant so as to prevent the biphasic ventilatory change, the biphasic heart rate response previously seen in spontaneous hypoxic breathing disappeared. We suggest that the heart rate is mainly determined by the pulmonary vagal inflation reflex. Putative neurochemicals to elicit hypoxic ventilatory depression, and arterial catecholamine and potassium concentrations may not be directly related to the specific profile of the biphasic heart rate response during moderate hypoxia.


Peripheral vascular response to local cold stress of tropical men during sojourn in the Arctic cold region. Peripheral vascular response to local cold stress was studied on 4 groups of volunteers by eliciting cold-induced vasodilatation (CIVD) response during immersion of right hand in cold water (4 degrees C) for 30 min, to examine whether tropical men can get acclimatized to local cold compared to temperate zone people, during Arctic cold exposure. Group A and B (10 each) were drawn from tropical region of India, while Group C and D (6 each) from temperate zone of Russia and natives of Arctic, respectively. Initial study was conducted on control Group A at Delhi. Group B was airlifted to the Arctic (70 degrees N, 38 degrees E), where measurements were done on them during the seventh week of acclimatization, then they were flown back to Delhi and retested. For comparison, study was done at the Arctic on six migrants (Group C) from temperate zone of Russia and 6 natives (Group D) of the Arctic. There was a significant improvement of CIVD response and peripheral blood flow of tropical men due to acclimatization to Arctic environment, which was similar to that of the migrants but lower than the natives. Thus local cold acclimatization is possible even in tropical men as in those of the temperate zone people.


Possible role of red cell deformability and microvasculature in microcirculation. The roles of the deformability of red blood cells (RBC) and the microvasculature in the maintenance of blood flow were investigated in terms of the pressure (P)-flow rate (Q) relationships in human RBC suspension perfusions of bullfrog hind limb. Although isotonicity for the bullfrog is approximately 215 mOsm/kgH2O, perfusions in intact hind limbs showed no change in the P-Q relationship at test solution osmolalities ranging from approximately 150 to approximately 300 mOsm/kgH2O. The deformability of RBC was examined in glutaraldehyde-fixed hind limbs. Perfusion of fixed limbs with RBC suspension revealed minimum resistance to flow at osmolalities of approximately 250 to approximately 420 mOsm/kgH2O, whereas the same experiment in intact limbs revealed minimum flow resistance at osmolalities of approximately 200 to approximately 300 mOsm/kgH2O. It was noteworthy that the reduction of RBC deformability was not observed in intact limbs at osmolalities of approximately 250 to approximately 200 mOsm/kgH2O. Heinz body-forming RBC from a patient with unstable hemoglobin (Hb) disease (Hb Yokohama) exhibited a marked reduction in deformability as compared with normal RBC in fixed limbs, while there was no discernible difference between the two types of RBC in intact limbs, thereby suggesting that the microvascular bed can compensate, to an appreciable extent, for the impaired deformability of RBC, probably via its distensibility and/or a wall effect. The present study has considerable implications concerning the link between in vitro experiments and the in vivo situation, including the hemodynamic characteristics of RBC suspensions such as the effective viscosity.


Expiratory activity of the inspiratory muscles during cough. To investigate the neural mechanism of the expiratory activity of the inspiratory muscles during a cough, EMG of the respiratory muscles were recorded in anesthetized and tracheostomized dogs. A laparoscope was used to minimize injury to the abdominal muscles for implantation of the electrodes into the costal diaphragm. During the expulsive phase of a cough, the diaphragm was active in 7 of 12 dogs and the external intercostal muscle was active in 3 of 6 dogs. During a cough, the expiratory activity of the diaphragm, after the termination of its inspiratory activity, started at 52.9 +/- 24.6 ms, and that of external intercostal muscle started at 51.1 +/- 20.5 ms. The expiratory activity of the internal intercostal muscle and of the transversus abdominis started at 34.3 +/- 13.0 and 27.8 +/- 15.2 ms, respectively. The onset of expiratory activity of the inspiratory muscles is significantly later than that of expiratory muscles. Continuous activity in the expiratory muscles evoked by airway occlusion, i.e., Hering-Breuer reflex, was suppressed during the inspiratory phase of a cough, but not suppressed during the expulsive phase even when the expiratory activity of the diaphragm was observed. We concluded that the expiratory activity of inspiratory muscles is controlled independently of both expiratory activity of the expiratory muscles and inspiratory activity of the inspiratory muscles.


An analysis of post-contracture potentiation in frog twitch skeletal muscle. Post-tetanic potentiation (PTP) was mimicked by post-contracture potentiation (PCP) in the twitch muscle of frog. A marked PCP was observed in small bundles of semitendinosus muscle in tetrodotoxin (TTX)-containing solution under current clamp condition. Contractures were induced by a constant depolarizing current pulse of 1 s every 5 min. Each contracture (C) was preceded and followed by a twitch-corresponding short contracture, T1 and T2, with an interval of 2 s. The ratio of twitch height, T2/T1, was measured and compared under various conditions. In TTX-containing Ringer solution, T2/T1 depended on magnitude of both T and C. When T2/T1 was plotted against C/T1 a quasi-linear relationship was found. The slope of the curve was 0.076 and was found to decrease when the duration of T was increased to 1 s. In TTX-containing solution, addition of 2 mM Ba2+ or 1 mM caffeine potentiated T as well as C but decreased T2/T1 markedly. Similar effects were observed when Na+ was replaced with TEA+ or when bath temperature was lowered from 20 to 8 degrees C. In all cases T2/T1 vs. C/T1 curve was shifted to the left and downwards. It was considered that these results could be attributable to an elevation of the resting Ca2+ concentration in the sarcoplasm. Thus the phenomenon of PCP probably reflects the time course of Ca2+ transients in the conditioning contracture C.


Effects of time-varying electromagnetic fields on K+ (Rb+) fluxes and surface charge of HeLa cells. The magnetic flux density was varied intermittently from 0.35 to 1.77T and from 0.07 to 1.54 or 1.77T by manual and automatic switchings, respectively, of the power source of an electromagnet. The durations of the "switching-on time" and "-off time" were varied but kept equal. An electric eddy current induced in the culture medium by changes in the magnetic flux density was simulated. When the durations were shorter than 10s, ouabain-sensitive Rb+ influx (active K+ influx) into cultured HeLa cells was significantly inhibited, but the ouabain-insensitive Rb+ influx (passive K+ influx) was not influenced significantly. Inhibition of active Rb+ influx increased with time during exposure for 2 h. Conversely, K+ efflux from the cells was significantly stimulated by the exposure. Microfluorometric examinations of cells loaded with the fluorescent pH indicator 4-heptadecyl-7-hydroxycoumarin (6 microM) and the membrane potential indicator diS-C3-(5) (1 microM) suggested increase in the negative charge on the cell surface during exposure. The observed changes in the K+ (Rb+) fluxes would be related to change in the electric properties of the cell surface caused by exposure to intermittent electromagnetic fields.


Effects of mechanical stretch on membrane currents of single ventricular myocytes of guinea-pig heart. A technique to record whole cell membrane current during stretching single cardiac myocytes was developed. Ventricular myocytes were dissociated by treating guinea-pig hearts with collagenase. One end of the cell was fixed either to a microglasstool tip or to a glass plate, while the other end was attached either to a microglasstool tip or to a suction pipette, which was mounted on a micromanipulator. A time-independent current showing a reversal potential of -15 +/- 4 mV (n = 7) was activated when the myocytes were stretched more than 20% of the length between two fixed point. The current gradually relaxed during the maintained stretch, and disappeared on releasing the stretch. We failed to detect any consistent change in either the L-type Ca2+ current or the inward rectifier K+ current. For comparison, current changes induced by inflating the cell using a hypo-osmotic solution were recorded. The inflation was not accompanied by any change in the time-independent current. Instead, the delayed rectifier K+ current was increased to 170 +/- 48% control by the 70% hypo-osmotic solution. Thus, the effect of mechanical stretch on the time-independent current is different from those of hypo-osmotic cell inflation. The stretch-induced time-independent current is compared with reported current changes induced by the intracellular microinjection of Ca2+.


The effects of leg-cooling on blood lactate disappearance following supramaximal exercise. In order to clarify whether leg-cooling after supramaximal treadmill exercise will change lactate disappearance rate from venous blood, blood lactate, calf blood flow, and skin temperature were determined in cold application and non-cold application recovery. In the cooling experiments, both legs were cooled with ice packs for 23 min during recovery. The skin temperature was significantly lower in the cold application as compared with the non-cold application. However, no significant difference was found in the blood lactate and/or calf blood flow between cold and non-cold conditions. In addition, there was no significant difference in the slope of regression line (blood lactate/blood flow) between cold and non-cold applications. These results suggest that no significant difference in the blood lactate between cold and non-cold applications could be explained by the lack of difference in the blood flow between cold and non-cold applications.


Osmotically inactive space during hyperosmotic stress in the perfused submandibular gland of the rat. Cell volume changes were measured by an impedance method during hyperosmotic stress in the perfused rat submandibular gland. When the perfusate osmolarity was raised to 484 mosmol, the cell volume decreased and remained at a plateau level (79%). The decrease was smaller than expected from the extracellular fluid osmolarity change. Furthermore, the potassium content of the gland increased by 7% during the hyperosmotic stress. These results suggest that the cell volume changes observed during hyperosmotic stress are affected by the existence of an osmotically inactive space and by an increase in the intracellular solute content.


Stretch-induced force development in Mytilus smooth muscle during submaximal activation. When the anterior byssal retractor muscle of Mytilus edulis is stretched by 5-20% during submaximal activation with 100 mM K+ or 10(-5) M acetylcholine, it exhibited a delayed force development after the completion of stretch. The effect of ions and drugs on the stretch-induced activation suggests the stretch-induced release of Ca2+ from the inner surface of the plasma membrane.


An improved method for measurement of sweat expulsions during profuse sweating. We present an improved ventilated-capsule method of recording for clear sweat expulsion patterns using nitrogen gas as a carrier gas heated to promote sweat evaporation. With this method, sweat expulsion patterns were more clearly recorded than with the conventional ventilated-capsule method. Taking the derivatives of these recordings of sweating expulsions could eliminate slow fluctuation components in the patterns of sweating. The results indicate that this method is useful in providing more-accurate measurements of sweat expulsion frequencies during profuse sweating.


[Function of the serotoninergic system of blood platelets in patients with hypertension]. To investigate if there can be alterations in the 5-hydroxytryptamine (5-HT) uptake system in the sensitivity of platelets in patients with essential hypertension, 38 hypertensive patients and 37 normotensive healthy subjects were compared. In patients, the maximal 5-HT uptake velocity was reduced. The density of binding sites for 3H-imipramine was elevated in hypertensive females, but unchanged in males. The sensitivity of 5-HT uptake to trazodone was unchanged in patients. Half-maximal concentrations of 5-HT for inducing a shape change reaction of platelets were positively correlated with diastolic blood pressure in male patients and were reduced in female mild hypertensives. It is suggested that these changes are likely to be involved in the pathogenesis of hypertension.


[Baroreflex control and circadian variability of arterial blood pressure in patients with "mild" hypertension and hemodynamically insignificant atherosclerotic lesions of the carotid arteries]. Sinocarotid baroreflex control by means of the neck chamber technique (-40 mm Hg, 4 min) and blood pressure monitoring with a SpaceLabs 90207 system were performed in 45 patients with mild essential hypertension who were divided into 2 groups: (1) those with hemodynamically insignificant carotid atherosclerotic lesions (n = 19) and (2) those without them (n = 26). Group 1 patients showed a decreased cardiochronotropic component of baroreflex control, higher blood pressure variability and less pronounced nocturnal blood pressure fall. The above facts are likely to contribute to progression of essential hypertension and aggravation of target organ lesions.


[Testing of arterial hypertension with physical exercise PWCx ]. The relation of physical fitness (PF) to blood pressure (BP) and arterial hypertension risk factors was studied in a representative sample by PWCX exercise testing. The relations were studied at the initial stage, during exercise and recovery by using the multivariance stepwise regression analysis. This complex approach allowed the independent relation of PF to BP to be found. In normotensive males, systolic BP determined 4% PF variability after the first exercise, while in hypertensive males, the second exercise heart rate and age determined 27 and 9% PF variability, respectively. In normotensive females, the first exercise heart rate determined 62% PF variability, in hypertensive females, the second exercise systolic BP and age determined 4 and 2% PF variability, respectively. The value x shows the relation of PF to heart rate and BP in the restorative period and is an additional significant parameter of PF and the functional status of the cardiovascular system.


[Application of biomechanical stimulation of lower extremity muscles in the treatment of patients with hypertension]. The impact of biomechanical stimulation of lower extremity muscles was studied in patients with essential hypertension on systemic blood pressure and its hemodynamic components. A short-term (10-15-minute) antihypertensive effect was found in a 2-minute stimulation session. Inclusion of biomechanical stimulation into the multimodality treatment of patients with Stage II hypertensive disease will enhance its efficiency. The mechanism responsible for the depressive effects of biomechanical stimulation and the role of the hemodynamic pump function of skeletal muscles in this process are discussed in the paper.


[Transesophageal electrostimulation of the atrium in patients with ischemic heart disease combined with arterial hypertension in disability evaluation ]. The author studied 78 patients (60 males and 18 females) aged 36 to 60 years (mean age 50 +/- 6 years). They all were diagnosed as having coronary heart disease (CHD) concurrent with arterial hypertension. Transesophageal atrial pacing test (TEACT) was positive in 68 (87.2%), and negative in 4 (5.1%) patients. It failed to reach diagnostic ECG criteria in 6 (7.7%) patients. A close relationship was found between the number of diseased coronary arteries and the sensitivity of TEACT. The TEACT parameters were found to be related to bicycle ergometric ones. The findings showed that the threshold rate of induced rhythm decreased when the patients increased their functional class of exercise-induced angina pectoris, the appearance of ST-segment depression being delayed and its disappearance increased. Thus, transesophageal atrial pacing allows the functional class to be defined in patients with CHD concurrent with arterial hypertension from the threshold rate of imposed rhythm and the time of ST-segment depression appearance and disappearance and can be useful both in the diagnosis and appraisal of the working capacity in patients with coronary heart disease concurrent with arterial hypertension.


[Antianginal activity of cardil and cordafen in patients with non-Q wave myocardial infarction]. The antianginal activity of Cardil, 240-360 mg/day, and Cordafen, 30-60 mg/day, was evaluated in 74 patients with non-Q wave acute myocardial infarction. Repeated 24-hour ECG monitoring was used as an objective tool for the evaluation of their therapeutical efficiency in two randomized groups. Unlike Cordafen, Cardil significantly reduced the average heart rate from 4.7 to 1.5 and the average duration from 20.5 to 11.5 min and the average total duration of myocardial ischemic episodes from 95.1 min/day to 16.7 min/day. Both Cardil and Cordafen considerably reduced the total duration of painful ischemic attacks, but only did Cardil reduce silent episodes (p < 0.001). Both Cardil and Cordafen substantially reduced resting ischemia, but Cardil also decreased the rate of exercise-induced ischemic episodes (p < 0.05).


[Impact of exercise test on signal-averaged ECG in patients with myocardial infarction]. To examine the impact of exercise test (bicycle ergometry) and exercise-induced transient ischemic changes in ST segment on signal-averaged ECG parameters, the authors studied a homogeneous group including 65 patients (62 males and 3 females) with a 2-3-week history of primary myocardial infarction. The findings showed that induced myocardial ischemia caused no significant changes in signal-averaged ECG and late potentials, exercise might induce late potentials without clear-cut ECG signs of myocardial ischemia. It was also indicated that exercise-labile late potentials were significantly more frequently associated with the development of ventricular arrhythmias than steady late potentials.


[Possibilities for the rehabilitation of patients with myocardial infarction without application of coronary drugs during hospital treatment ]. When restorative treatment was performed in 51 patients with myocardial infarction, 3 groups were identified, each including 17 persons. The main group comprised those whose rehabilitation had been achieved by early physical trainings with coronary active agents; the first control consisted of those who had gone in for physical exercises and received antianginal drugs, the second control group included those whose rehabilitation had been conducted by the well-known procedures (therapeutical exercises, graded walking, nitrates, beta-blockers, calcium antagonists). The treatment resulted in improvement in the functional status of patients from the main and the first control groups as compared to those from the second control group. It is concluded that in patients with myocardial infarction without pain syndrome in the subacute period of the disease the efficiency of restorative treatment may be enhanced by using early individualized physical trainings without application of coronary active drugs.


[X syndrome: does left ventricular myocardial perfusion suffer during exercise?]. Sixteen patients with the X syndrome underwent thallium-201 myocardial scintigraphy. Eleven patients with one-coronary artery disease served as a control group. During bicycle ergometry all the 16 patients showed various degrees of local myocardial perfusion impairments. The foci were located in the basins of various coronary vessels. Impaired myocardial perfusion in patients with the X syndrome was similar to that in patients with moderate, but hemodynamically significant stenosis of a coronary artery. At the same time the impairments were significantly less pronounced than in those with critical stenosis of a coronary artery. Thus, patients with the X syndrome have not only clinical signs of coronary heart disease (anginal episodes), but they also have marked myocardial perfusion impairments during exercise.


[Responses of peripheral blood circulation in treadmill exercise test as a criterium for evaluation of central hemodynamics and anaerobic threshold]. The study was undertaken to examine whether the linear arterial blood velocity in the lower extremities is related to impaired cardiac pump function and anaerobic threshold. A stepwise treadmill test was performed in 40 healthy individuals and 39 patients with cardiac malformations. The changes in maximal diastolic blood velocity and resistive index which had been determined by Doppler echoflowmetry after each step of the treadmill test were compared with those in the oxygen restoration coefficient, ventilation equivalent by oxygen and carbon dioxide levels in the expired air. It was found that the blood velocity in the lower extremities may be used as noninvasive criteria for impaired cardiac pump function and anaerobic threshold.


[Use of immunosorption for selective decrease of lipoprotein (A) levels in patients with coronary atherosclerosis]. Lipoprotein (a) [L(a)] is an atherogenic lipoprotein, its human plasma concentration correlates with the occurrence of coronary heart disease. The procedure for selectively removing L(a) with an anti-L(a) immunosorbent was performed to treat 3 patients who had high L(a), normal total cholesterol and other lipoprotein levels. All the patients had coronary stenosis as documented by angiography. After L(a)-apheresis, the level of L(a) decreased by 72%, while that of other plasma components, including low density lipoproteins virtually unchanged. Thus, the procedure of L(a)-apheresis is an effective and safe method for lowering human blood L(a) concentrations. In addition, this in vivo model allows information on L(a) metabolism to be obtained.


[Impact of exercise on alimentary hyperlipoproteinemia in patients with ischemic heart disease]. The impact of graded exercises of various intensity and duration on serum lipoprotein values was examined in 20 patients with coronary heart disease (CHD) and 10 healthy individuals after a single dietary fat load (FL). FL resulted in hypertriglyceridemia which was accompanied by elevated apo-AI levels and reduced apo-B/apo-AI ratio in the healthy persons, whereas it was accompanied by lower apo-AI levels and increased apo-B/apo-AI ratio in the patients. The short-term maximum exercise in the presence of FL caused negative shifts in the lipid transport system both in the healthy persons and the patients, by elevating the level of apo-B-containing lipoproteins. Yet, the healthy individuals showed a further increase in apo-AI concentrations. The long-term exercise in the training mode corrected changes in lipid values, which had been induced by FL in the two groups of the examinees. There was a decrease in the levels of triglycerides, low density lipoprotein, cholesterol and an increase in the level of high density lipoprotein cholesterol.


[Correlation of antianginal effect of corinfar and diastolic function in patients with ischemic heart disease]. The study was undertaken to examine 45 patients with coronary heart disease and 14 healthy subjects by using radionuclide ventriculography, apex- and echocardiographies, bicycle ergometry, transesophageal electrocardiostimulation before therapy and at the action peak of corinfar in a dose of 30 mg. It was shown that corinfar failed to affect the unaltered diastolic function of the left ventricle. The normalizing effect of corinfar on left ventricular stiffness was found to result in higher coronary reserve, significantly enhanced exercise tolerance and to be an important mechanism of antianginal effect of the drug. Impaired left ventricular stiffness may be an additional criterion for using corinfar in patients with coronary heart disease.


[Effect of various antianginal agents on the frequency and duration of myocardial ischemic episodes in patients with stable angina pectoris]. The effects of verapamil, nifedipine, propranolol, and combinations of nifedipine+propranolol and nifedipine+verapamil were studied in 60 patients with stable angina pectoris. Verapamil was found to have a pronounced antianginal activity against all types of myocardial ischemia, whereas nifedipine relieved mainly painful ischemic episodes. By the end of 12-week therapy with propranolol, the agent lost its antiischemic effect in a third of patients, which was accompanied by an increase in the number and severity of silent ischemic episodes.


[ Combined therapy with isosorbide dinitrate, propranolol and nifedipine in patients with chronic ischemic heart disease]. Forty six patients with stable effort angina were treated with a combination of propranolol, nifedipine, and isosorbide dinitrate which produced a more profound anti-antianginal effect than each of them given alone. The combination also exerted more marked antihypertensive and antiarrhythmic effects. The combined therapy with the three drugs caused a moderate reduction in heart rate and peripheral resistance, but failed to result in clear-cut disturbances in the orthostatic regulation of the circulatory system. There was a more infrequent and less pronounced ST-segment depression, less marked pressor responses and higher heart rate with the combined therapy during exercise; the cardiac index also increased as before therapy. Physical fitness increased to a greater extent than with monotherapy. The combined therapy with three drugs is indicated when monotherapy fails and that with two agents is indicated when patients have concurrent essential hypertension and cardiac arrhythmias.


[Comprehensive evaluation of the severity of illness in patients with ventricular arrhythmias by using a mathematical method]. A comprehensive method for objectivization of the condition in patients with ventricular arrhythmias has been first developed and tested. Equations for determining the severity indices for ventricular arrhythmias, coronary dysfunction, heart failure, and arterial hypertension have been derived on the basis of isolation and mathematical formalization of clinical and instrumental signs of the above abnormalities. With the derived indices it is possible to make a valid comprehensive assessment of the severity of ventricular arrhythmias, to identify the syndrome predominant in the clinical course of the syndrome, and to quantify the efficiency of inpatient and long-term outpatient therapy.


[Reversal of withdrawal injuries of the heart and liver by adaptation to intermittent hypoxia when discontinuing ethanol in chronically alcoholized animals]. Adaptation to intermittent hypoxia in the hypobaric altitude chamber showed a two-fold decrease in ethanol consumption in chronically alcoholized rats and attenuated or arrested the withdrawal syndrome. The impact of adaptation to the withdrawal syndrome was that it prevented the development of withdrawal analgesia, higher alcohol consumption after its withdrawal, withdrawal hepatic activation of lipid oxidation products and blood release of the hepatic specific enzymes fructose monophosphataldolase and gamma-glutamyl transpeptidase. Concurrently, the adaptation prevented the withdrawal fall of the cardiac fibrillation threshold and marked disorders of ventricular contraction and relaxation. The paper discusses whether adaptation to intermittent hypoxia can be used in the management of the types of alcoholism in whose development the withdrawal plays the key role.


Effect of amphotericin B alone or in combination with rifampicin on phagocytosis of Candida species by human polymorphonuclear leukocytes. The influence of amphotericin B and rifampicin alone and in combination on the killing of Candida albicans, Candida tropicalis and Cryptococcus neoformans by human polymorphonuclear leukocytes was investigated in vitro. Granulocytes were harvested from the blood of healthy volunteers and resuspended with the above mentioned fungi. After 6 hours, 81.5% of C. albicans, 97% of C. tropicalis but only 34% of C. neoformans were killed. The activity of amphotericin B against C. albicans and C. tropicalis was better in granulocyte-free medium. A synergism between amphotericin B and rifampicin towards Candida could be detected. It was also demonstrated in the presence of polymorphonuclear leukocytes with a factor > 1 log in reduction of colony count. However, whether granulocytes were present or not, rifampicin (4 mcg/mL) alone did not exert any influence on growth of Candida.


Radiolabelled calmodulin ligands: their low affinity and high lipophilicity may lead to artefacts in binding studies. In order to characterize the interaction site of a series of putative calmodulin antagonists of the diphenylalkylamine type with calmodulin (CaM), a representative member of this chemical class was radiolabelled. The binding of the selected compound, [3H]-VUF 4576, to calmodulin was studied according to a recently described technique using CaM agarose. However, some peculiar results were obtained: the tight binding of [3H]-VUF 4576 increased in presence of cold VUF 4576, resulting in a high non-specific binding. The unexpected results could readily be explained by a high binding capacity of the labelled compound and the cold ligands to the walls of the test tubes used. Such results were also found when [3H]-chlorpromazine ([3H]-CPZ) was applied. In literature comparable findings have been published. To explain such results the influence of positive cooperativity or irreversible binding has been suggested. We suppose that not only in our study, but also in other published investigations, binding to glass of the radioligand and/or the cold compounds may have had a strong influence. We suggest, therefore, that care should be taken in interpreting non-classical displacement data obtained with ligands which combine a rather low affinity and a high degree of lipophilicity, not only for binding to calmodulin, but for other systems as well.


The anxiogenic-like effects of pentylenetetrazole in mice treated chronically with carbamazepine or valproate. The chronic effects of carbamazepine administration (5, 10, 20 mg/kg i.p. daily for 14 days) on the anxiogenic response to pentylenetetrazole were studied in the light/dark aversion test. In mice, these effects were compared with those of sodium valproate (100, 200 and 300 mg/kg i.p.), a putative anxiolytic drug, and lorazepam (0.025, 0.05 and 0.10 mg/kg i.p.), a well-established anxiolytic drug. The results showed that the anxiogenic-like behavior induced by subconvulsant doses of pentylenetetrazole (15 mg/kg i.p.) was antagonized by the chronic administration of lorazepam as well as sodium valproate, a GABA agonist. In fact, the increased aversion of mice for the light compartment of the light/dark box was reduced. Carbamazepine failed to significantly alter the anxiogenic-like behavior of mice. These findings provide further evidence for the absence of anxiolytic properties of carbamazepine and for a behavioral anxiolytic profile of valproate similar to that of benzodiazepines.


Further metabolic studies of codeine and morphine in mice pretreated with sympathomimetics. The effects of ephedrine and phenylpropanolamine (PPA) on the 24 h urinary excretion of morphine, codeine and their metabolites, and on the plasma and brain disposition of morphine and codeine at steady state in mice were studied. Morphine-3-glucuronide was the major urinary metabolite in morphine treated animals, while for codeine treated animals norcodeine and morphine-3-glucuronide were the major metabolites. In all cases percentage of drug excreted unchanged was 10-15% of the administered dose. Ephedrine or PPA pretreatment had no apparent effect on these parameters. The metabolic ratios for the different pathways were comparable in all treatment groups. Steady-state plasma and brain concentration-time profiles of codeine and morphine also showed marked similarity in all treatment groups. Apparently, ephedrine or PPA pretreatment has no effect on the disposition of morphine and codeine in mice. The results are discussed from the perspective of our earlier findings of dependence on cough mixtures containing opioids and sympathomimetics.


Histamine leukocytosis. II. Source of histamine leukocytosis. Leukocytes were labelled by intravenous injection of tritiated thymidine (3H-thymidine) in dogs to discover the source of the increased number of neutrophils in the circulating blood after injection of histamine in beeswax. Dogs with normal hemograms were given 1.0 mCi/kg of 3H-thymidine alone, and in different sequences, with histamine in beeswax. When 3H-thymidine was given during maintained histamine leukocytosis, labelled granulocytes appeared in and disappeared from the blood earlier than in control tests and the number of labelled cells was greater in the histamine-treated animals. Administration of histamine in beeswax 3 days after injection of 3H-thymidine also induced the premature appearance and disappearance of labelled neutrophils in the circulating blood. It was concluded that leukocytosis induced by the chronic action of histamine is due to 1) stimulated proliferation and differentiation of neutrophil precursor cells in the bone marrow and 2) the release of mature leukocytes from the bone marrow.


Pharmacokinetics and relative bioavailability of a new chewable, buffered acetylsalicylic acid tablet formulation in comparison to a conventional plain tablet. The pharmacokinetics of acetylsalicylic acid (ASA) and its main metabolite salicylic acid (SA) following single dose administration of a new chewable, buffered ASA tablet formulation and a conventional plain ASA tablet formulation were investigated in 12 healthy male subjects. The volunteers received in a randomized, crossover design two pharmaceutical units of both formulations containing 500 mg ASA each after an overnight fast on an empty stomach. ASA and SA in the collected plasma and urine samples were determined using an internally standardized validated HPLC method. Regarding the normalized extent parameters for ASA, an increase of about 114% for the maximum concentration (Cmax,norm) and about 16% for the area under the curve (AUC0----infinity,norm) was found for the new chewable, buffered tablet formulation as compared to the plain tablet. Comparing the corresponding parameters for the main metabolite, both formulations were statistically equivalent. The quotient of normalized areas (QAUC0-20min, norm/AUC0----infinity,norm) for ASA was higher by about 124% for the new formulation, indicating an increased and faster absorption during the first 20 min after administration. The time of the concentration maximum did not differ statistically. These data indicate that the new chewable, buffered ASA tablet formulation shows a significant benefit as compared to the plain ASA tablet. The new tablet produced higher plasma ASA concentrations in a shorter time, which is clinically important since higher ASA concentrations are assumed to be related to an improved analgesic efficacy.


AIDS and promiscuity: muddles in the models of HIV prevention. AIDS has been blamed on promiscuity and the promiscuous, and a major goal of many HIV-prevention programs has been to induce people to reduce the number of their sexual partners. Despite the salience of this concept in the AIDS discourse of scientists, policymakers, the media, religious leaders, and the gay community, critical analysis of the role of promiscuity in this epidemic has been lacking. Following a review of promiscuity in various genres of AIDS discourse, this article discusses promiscuity in American society and in HIV-prevention campaigns. The relative risks associated with monogamy, abstinence and promiscuity are examined, and the author concludes that the partner-reduction strategy, instead of contributing to a reduction in HIV transmission has been an impediment to AIDS prevention efforts, exacerbating the problem by undermining the sex-positive approaches to risk reduction that have proven effective. Responsibility for this misguided strategy is attributed to a moralistic approach to AIDS and to the misapplication of epidemiological concepts and inappropriate social science models to the task of promoting healthy forms of sexuality.


AIDS, sex and condoms: African healers and the reinvention of tradition in Zaire. Condoms offer considerable protection against sexual transmission of AIDS. Yet many Africans who are at risk of infection reject condoms as "unnatural." Data from Zaire have been used to examine this culturally constructed category in relation to sexuality, procreation, gender roles, class formation and international health and development policy. Much more than a simple transfer of biomedical technology is involved. Condom use with regular partners raises issues of cultural politics at many levels. "Traditional" African healers represent important social networks with considerable authority in poor urban communities. They are able to reinterpret cultural categories and endow behavior with new meanings. Action-research in Kinshasa was used to explore roles that healers might play in promoting change to safer sex practices.


HIV prevention: a dramaturgical analysis and practical guide to creating safer sex interventions. Safer sex is currently a major strategy for preventing HIV transmission. We examine safer sex interventions using an interactionist form of dramaturgical analysis. This approach yields a dynamic model with which to generate novel safer sex interventions highly sensitive to changing individual, cultural, and social variables. Our goal is to help medical anthropologists, applied social scientists, health educators, community outreach specialists, and those who are sexually active apply safer sex strategies more effectively.


Sex, drugs and videotape: the prevention of AIDS in a New York City shelter for homeless men. This paper documents a process of social change through participant observation. During the course of research a group response was facilitated by a team of residents, staff and researchers. The social context, a shelter for homeless men in New York City, will be presented first, emphasizing those aspects of resident living that are germane to HIV transmission. Next, we describe the group response, the creation of a video. This activity gave numerous insights to the investigators into how the men perceived the homeless state and something of their relationships to others within and outside the institutions. In particular, their views on women and sex were expressed in the video. The insights gained by the men and the investigators are analyzed in terms of a self-help strategy which was effective in conveying information about HIV transmission and prevention.


Alcohol and risky sex: in search of an elusive connection. Since the publication of the 1986 article by Stall, McKusick, Wiley, Coates and Ostrow, the conclusion that drinking alcohol prior to or during erotic encounters increases the probability of engaging in high-risk sexual behavior has been widely accepted, despite some contradictory findings from research on this hypothesis. This paper presents the results of tests of the alcohol/risky-sex hypothesis in a cohort of gay men in Flanders, Belgium. Failing to find evidence to support the hypothesis of a general effect of alcohol on sexual risk taking, we argue that previous conclusions on this matter must be viewed with extreme caution, especially in light of the implications that this failure to replicate has for AIDS prevention programs. Cultural, social, and methodological factors that could account for this failure to replicate are discussed in the context of a review of the literature on this hypothesis.


[The fragile X chromosome and psychiatry]. The importance of X fragile chromosome in mental retardation is outlined. Two male patients with a low IQ are studied. They were brothers and their mother too was non mental retarded cytogenetically X fragile positive.


[Pathology of adaptation according to Sami-Ali and index of conformity to the Rorschach test in ulcerative rectocolitis]. According to Sami-Ali's theoretical model the psychosomatic personality is characterised by an adaptation pathology whose main elements are the repression of imaginative thought and conformity to socio-cultural standards. This study examines adaptation pathology using the Rorschach test. The Authors have formulated a conformity index by relating kinestheses (M) and banal perceptions (BAN). The study was carried out on a sample of 41 patients suffering from ulcerous rectocolitis comprising 24 males and 17 women with a mean age of 32 years. As expected in the hypothesis 97.6% of the sample showed M values below the norm, and 68.3% had Ban values higher than normal, whereas the conformity index was positive and tendentially positive in 65.9% of cases. These findings confirm Sami-Ali's theory. Subjects with ulcerous rectocolitis form part of the adaptation pathology which characterised the psychosomatic personality, with an inverse proportionality between imaginative activity (kinesthesia below normal) and conformism (banal perceptions above the norm).


[The prophylaxis of benzodiazepine withdrawal syndrome in the elderly: the effectiveness of carbamazepine. Double-blind study vs. placebo]. A double-blind study was performed to evaluate carbamazepine for the prophylaxis of benzodiazepine withdrawal syndrome in elderly patients--a controversial subject despite the extensive use of such drugs in old age. Thirty-six outpatients aged > or = 60 yrs suffering from general anxiety disorders and benzodiazepine abuse underwent gradual discontinuation of benzodiazepine therapy in two groups, one treated with carbamazepine and one with placebo. The carbamazepine-treated group demonstrated a lower incidence of withdrawal symptoms rated according to the Physician Withdrawal Check List (p < 0.01), better results with the Hopkins Symptom Check List (Covi cluster, p < 0.01) and a more markedly reduced score with the Hamilton Rating Scale for Anxiety (p < 0.05). Only 3 out of 18 patients in said group complained of side effects attributable to carbamazepine, which disappeared at lower dosages.


[Bipolar disorder: clinical trials with fluoxetine]. Sixty patients (39 females and 21 males) aged between 20 and 65 (average 48.5) with bipolar disorder in the depressive phase, according to the DSM III-R diagnostic criteria, were treated with fluoxetine (20-60 mg/die) for 8 weeks. Evaluation of therapeutical efficacy was performed at 0 time and after 14, 28, 42, and 56 days, using the following psychometric tests; HAM-D, SCL-90, CGI. At the end of treatment 42 patients (70%) showed a reduction of the HAM-D score over 50%. Clinical results suggest that fluoxetine is affective in bipolar disorder. Tolerability was judged good and very good in 76% of patients. Side effects were very mild and in any case of rapid regression.


[Psychological reactions of medical staff to the patients infected with HIV-1]. This paper describes the relationship between medical staff and HIV-1 patients. Important mechanisms can be used by individuals with HIV-1 infection in order to accept their seropositivity to HIV-1. Among them, regression and negation are well-known. These mechanisms are related to countertransference lived by the medical staff. They are various as well as rejected by medical staff to avoid anxious reactions. On the contrary, the medical staff has to accept the experiences of the patients and to be ready to listen to the problems of HIV-1 infected people.


[Psychiatric emergency and first level intervention. Analysis of a series of attempted suicides at a Turin First Aid station]. The present study was carried out in a Turin Hospital and considers interventions for attempted suicide in the period March-May 1988, examining psychopathological and social characteristics. No epidemiological evaluation was made of the problem but rather an analysis of the specialist and general assistance given to these patients in First Aid structures, the therapeutic protocols that preceded the attempted suicide, motivations and modalities involved. In addition, a three-month follow-up looked at the therapeutic destiny of the cases. In the last analysis, an attempt was made to evaluate the therapeutic interaction between local psychiatric services and the First Aid facility of a general hospital: in fact, according to the health service reform law and the application of Law 180, the DEA, as a hospital structure, forms part of the structures delegated to the treatment of mental disturbances.


[Survey of hospitalization in a mental health service during the ten- year period 1981-1990]. The paper reports the findings of a 10-year statistical survey of the users and activities of the Mental Health Service Of S. Giovanni in Fiore (Cosenza). The incidence of booth voluntary and TSO hospitalisation is reported in relation to users and with reference to the Centre's activity during other periods.


Analysis of pneumococcal PspA microheterogeneity in SDS polyacrylamide gels and the association of PspA with the cell membrane. Pneumococcal surface protein A (PspA) is a protection-eliciting surface protein found on all pneumococci. Although highly cross-reactive, it displays interstrain variation in its size and in the expression of individual antibody reactive epitopes. PspA was not released in significant amounts from pneumococcal membranes treated with sodium carbonate, but was solubilized with SDS. Thus, PspA is either an integral membrane protein or is attached to an integral membrane component. By SDS-PAGE and immunoblot analysis, we found two predominant molecular sizes of PspA in each strain examined. The smaller band was about the size expected from the inferred amino acid sequence of PspA and the larger band appeared to be a dimer of the monomer PspA. When higher concentrations of lysate were run on SDS gels, it was also possible to detect many additional high molecular weight components that reacted with antibodies to PspA. These multiple high molecular weight PspA bands were not due to the attachment of PspA to peptidoglycan or teichoic acids, did not appear to be composed of degraded PspA and most likely resulted from non-covalent polymerization or aggregation of PspA.