Rainfall triggers more deep-seated landslides than Cascadia earthquakes in the Oregon Coast Range, USA.

The coastal Pacific Northwest USA hosts thousands of deep-seated landslides. Historic landslides have primarily been triggered by rainfall, but the region is also prone to large earthquakes on the 1100-km-long Cascadia Subduction Zone megathrust. Little is known about the number of landslides triggered by these earthquakes because the last magnitude 9 rupture occurred in 1700 CE. Here, we map 9938 deep-seated bedrock landslides in the Oregon Coast Range and use surface roughness dating to estimate that past earthquakes triggered fewer than half of the landslides in the past 1000 years. We find landslide frequency increases with mean annual precipitation but not with modeled peak ground acceleration or proximity to the megathrust. Our results agree with findings about other recent subduction zone earthquakes where relatively few deep-seated landslides were mapped and suggest that despite proximity to the megathrust, most deep-seated landslides in the Oregon Coast Range were triggered by rainfall.

Combined effects of exposure to engineered silver nanoparticles and the water-soluble fraction of crude oil in the marine copepod Calanus finmarchicus.

While it is likely that ENPs may occur together with other contaminants in nature, the combined effects of exposure to both ENPs and environmental contaminants are not studied sufficiently. In this study, we investigated the acute and sublethal toxicity of PVP coated silver nanoparticles (AgNP) and ionic silver (Ag+; administered as AgNO3) to the marine copepod Calanus finmarchicus. We further studied effects of single exposures to AgNPs (nominal concentrations: low 15 µg L-1 NPL, high 150 µg L-1 NPH) or Ag+ (60 µg L-1), and effects of co-exposure to AgNPs, Ag+ and the water-soluble fraction (WSF; 100 µg L-1) of a crude oil (AgNP + WSF; Ag++WSF). The gene expression and the activity of antioxidant defense enzymes SOD, CAT and GST, as well as the gene expression of HSP90 and CYP330A1 were determined as sublethal endpoints. Results show that Ag+ was more acutely toxic compared to AgNPs, with 96 h LC50 concentrations of 403 µg L-1 for AgNPs, and 147 µg L-1 for Ag+. Organismal uptake of Ag following exposure was similar for AgNP and Ag+, and was not significantly different when co-exposed to WSF. Exposure to AgNPs alone caused increases in gene expressions of GST and SOD, whereas WSF exposure caused an induction in SOD. Responses in enzyme activities were generally low, with significant effects observed only on SOD activity in NPL and WSF exposures and on GST activity in NPL and NPH exposures. Combined AgNP and WSF exposures caused slightly altered responses in expression of SOD, GST and CYP330A1 genes compared to the single exposures of either AgNPs or WSF. However, there was no clear pattern of cumulative effects caused by co-exposures of AgNPs and WSF. The present study indicates that the exposure to AgNPs, Ag+, and to a lesser degree WSF cause an oxidative stress response in C. finmarchicus, which was slightly, but mostly not significantly altered in combined exposures. This indicated that the combined effects between Ag and WSF are relatively limited, at least with regard to oxidative stress.

Use of intracoronary KCl in the beating and asystolic heart to determine the mechanism of initiation of the left ventricular mechanoreceptor reflex.

To provide further evidence that the veratrum alkaloids' mechanical, positive inotropic effect and not their chemical depolarising action predominates in initiating the left ventricular mechanoreceptor (including the Bezold) reflex the effect of intracoronary KCl, a chemical depolarising agent like the veratrum alkaloids, but with a negative inotropic effect, was studied in beating and verapamil-asystolic hearts. Five dogs were placed on a total cardiac bypass, pneumonectomised and their coronary and systemic circulations isolated and perfused separately, at a constant rate, so that changes in systemic pressure reflected changes in systemic resistance. Injection of 5 mmol X litre-1 KCl into the isolated coronary circulation caused cardiac asystole and a resultant reflex rise in systemic pressure (resistance) of 26 +/- 9% (p less than 0.05) above the control of 10.5 +/- 0.7 kPa (79 +/- 5 mmHg). This pressure rise, which indicates predominance of KCl's mechanical, negative inotropic over its chemical depolarising effect, was abolished by vagotomy, indicating its reflex nature. Contrariwise, in five other pneumonectomised dogs, similarly perfused on total cardiac bypass but with cardiac asystole from intracoronary verapamil, a subsequent, similar intracoronary dose of KCl now produced a fall in systemic pressure (resistance) of 8 +/- 2% (p less than 0.005) below the control of 12.8 +/- 0.5 kPa (96 +/- 4 mmHg). This pressure fall, presumably due to chemical depolarisation of the left ventricular mechanoreceptors, was also abolished by vagotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Reflex hypotension due to regional activation of left ventricular mechanoreceptors to explain the hypotension noted in clinical myocardial ischaemia or reperfusion.

To determine if regional increases in myocardial contractility, as may occur clinically in angina pectoris, myocardial infarction, or coronary thrombolysis, can initiate the reflex hypotension that sometimes accompanies these conditions, regional injections of positive inotropic agents were made into 32(3)% of the left ventricular myocardium in seven pneumonectomised dogs on total cardiac bypass. The coronary and systemic circulations were isolated and perfused separately. The systemic circulation was perfused at a constant rate so that changes in systemic pressure reflected changes in resistance. Regional injections of doses from 0.001 to 1.0 micrograms noradrenaline in a 0.1 ml volume appreciably increased regional contractility, detected visually and by strain gauge arches, whereas global contractility (left ventricular peak dP/dt) was increased much less. This caused a fall in the systemic pressure (resistance) of 14(2)% below the control value of 78(5)mm Hg, at the largest dose. The decreases in resistance were abolished by bilateral vagotomy, proving their reflex nature. The smaller (0.0001-0.01 micrograms) doses of noradrenaline and the smallest (0.25 micrograms) dose of veratridine increased regional contractility almost without increasing global contractility, indicating that the increase in regional contractility was the major cause of the reflex decrease in systemic resistance. In one animal a decrease in contractility in a control myocardial region occurred simultaneously with the experimentally produced increase in regional left ventricular contractility. This decrease may be analogous to the increase in contractility in the non-ischaemic left ventricular myocardium that occurs simultaneously with the decrease in contractility in the ischaemic region in clinical or experimental myocardial infarction. Left ventricular mechanoreceptors in the region with increased contractility probably initiate the reflex hypotension that sometimes occurs in both circumstances. Thus in angina pectoris or acute myocardial infarction the reflex hypotension probably originates in the hyperactive non-ischaemic myocardial region, whereas in coronary arterial thrombolysis it probably originates in the newly reperfused, formerly ischaemic, region.

Cerebrovascular adaptation in chronic hydrocephalus.

This study characterizes the regional changes in vascularity, which accompanies chronic progressive hydrocephalus. Fifteen dogs underwent surgical induction of hydrocephalus and were used for histologic studies. Animals were divided into 4 groups: surgical control, short term (< or = 5 weeks), intermediate term (8 weeks), and long term (10 to 12 weeks). Vessel diameter, density, and luminal area were calculated by imaging quantification after manual vessel identification in the cortical gray, white matter, and caudate nucleus. Capillary vessel diameter decreased 23.5% to 30.2% (P < 0.01) in the caudate, but then returned to normal at 12 weeks. Capillary vessel density decreased 53.5% (P < 0.05) in the cortical gray, but then increased to 234.8% (P < 0.01) over surgical controls at 12 weeks. There was no initial decrease in capillary density in the caudate; however, the long-term group capillary density was significantly greater (172.8% to 210.5%, P < 0.01) than surgical controls. Overall, there was a short-term decrease in lumen area, with recovery in the longer term. Glial fibrillary acidic protein (GFAP) immunohistochemistry demonstrated the pattern of GFAP staining and reactive astrocytes differed in the caudate compared with the occipital cortex. This data suggest that an increase in capillary density and diameter may be an adaptive process allowing maintenance of adequate cerebral perfusion and metabolic support in the hypoxic environment of chronic hydrocephalus.

The location and morphology of preganglionic neurons and the distribution of visceral afferents from the rat pelvic nerve: a horseradish peroxidase study.

Preganglionic neurons of the sacral parasympathetic nucleus (SPN) were located almost exclusively (98%) within the L6-S1 spinal cord segments. The SPN contained approximately 550 neurons of medium size (10 X 20 micron). These were mainly located in the intermediolateral gray matter and had dendrites that extended into the dorsolateral funiculus, along the lateral marginal zone of the dorsal horn, and medially into the dorsal gray commissure. Labeled dorsal root ganglion cells were almost all located (95%) in the L6 and S1 ganglia. An average of approximately 1,500 sensory neurons were found. These were small cells (17 X 25 micron) whose central processes entered Lissauer's tract from which two groups of collaterals emerged: 1) a prominent lateral pathway along the lateral margin of the dorsal horn that extended into the region of the SPN and also into the dorsal gray commissure, 2) a less prominent medial pathway extending around the dorsal margin of the dorsal horn to terminate in the dorsal gray commissure. These two collateral groups formed fiber bundles that were spaced by approximately 100 micron between centers when observed in the horizontal plane. A third afferent bundle, composed of rostrocaudally oriented fibers, was located in the sagittal plane immediately ventral to the central canal. Comparisons are made between the results in rats and the results of similar experiments performed in cats and monkeys.

The effects of naloxone on the neural control of the urinary bladder of the cat.

Naloxone in doses ranging from 0.5 to 512 micrograms/kg i.v., enhanced reflex contractions of the urinary bladder of the cat. At the lowest doses (threshold, 0.5-5 micrograms/kg) the drug increased the frequency of spontaneous bladder contractions. In large doses (10-100 micrograms/kg) the drug produced an initial tonic contraction of bladder lasting 15-40 min followed by a period of high frequency rhythmic activity. Multiunit firing in parasympathetic postganglionic nerves on the surface of the urinary bladder was also enhanced. Bursts of firing which in untreated animals occurred during large bladder contractions occurred continuously during the entire sustained contraction of the bladder following large doses of naloxone. Various evidence indicates that the site of action of naloxone is in the central nervous system. These findings suggest that the parasympathetic reflex pathway to the urinary bladder may be subject to tonic enkephalinergic inhibitory control.

Morphological and electrophysiological properties of pelvic ganglion cells in the rat.

Intracellular recording and dye injection were used to study the morphological and electrophysiological properties of rat pelvic ganglion cells. The dye-injected cells measured on the average 37 micron by 22.5 micron and had a mean number of 1.5 primary processes (axon and dendrites). The cells received unmyelinated preganglionic inputs from either the pelvic (parasympathetic) or the hypogastric (sympathetic) nerves, but no cells received inputs from both nerves. The number of synaptic inputs to each cell varied between 1 and 5 with a mean of 2. Each cell had at least one large amplitude suprathreshold EPSP which always initiated an action potential. These properties, namely, morphological simplicity, small number of inputs, security of synaptic transmission and lack of convergence between sympathetic and parasympathetic inputs, suggest that the capacity for synaptic modulation and integration in this ganglion is minimal. Such a structure should therefore relay preganglionic information to target organs with little or no alteration.

Colon and anal sphincter contractions evoked by microstimulation of the sacral spinal cord in cats.

The colon and anal sphincter contractions induced by microstimulation of the S2 spinal cord were investigated by measuring the intraluminal pressure change via saline filled balloons in alpha-chlorolose anesthetized cats. Stimulation of sacral ventral roots (S1-S3) revealed that the S2 efferent outflow usually produces the largest colon response. Stimulation of the S2 ventral root or the spinal cord both indicated that 15 Hz stimulation was the optimal frequency for evoking colon contractions. Colon and anal sphincter contractions were also influenced by stimulation intensity and pulsewidth. Locations in S2 spinal cord, where microstimulation evoked a distal/proximal colon pressure response that was greater than the anal sphincter response, included the area of sacral parasympathetic nucleus (SPN), the area medial to the SPN extending to the dorsal commissure, and areas deep in the ventral horn. Anal sphincter relaxation was evoked by microstimulation in more restricted locations in S2 spinal cord, which appeared to overlap with those evoking anal sphincter contractions. These results suggest a possible method to evoke colon contraction and defecation by microstimulation of the S2 spinal cord with multiple microelectrodes.

Parasympathetic ganglia: naloxone antagonizes inhibition by leucine-enkephalin and GABA.

Synaptic transmission in parasympathetic ganglia of the cat urinary bladder was depressed by low doses (0.1-10 micrograms i.a.) of Leu- or Met-enkephalin but only by larger doses (10 micrograms-1 mg i.a.) of morphine. Naloxone blocked the depressant effects of the opiates as well as the depression produced by GABA, but did not block the depressant effects of norepinephrine. Intracellular recording revealed that Leu-enkephalin reduced EPSP-amplitude and lowered the probability of synaptically evoked firing without altering postsynaptic membrane potential or resistance. These findings suggest that enkephalinergic inhibition in bladder ganglia is mediated at least in part by a presynaptic site of action on delta opiate receptors.

The presence of leucine-enkephalin in the sacral preganglionic pathway to the urinary bladder of the cat.

Leucine-enkephalin (L-ENK) nerve terminals which surround the cholinergic neurons in ganglia of the cat urinary bladder are eliminated after transection of the sacral ventral roots or the pelvic nerve. These findings, coupled with other anatomical and physiological data, suggest that L-ENK may be a cotransmitter with acetylcholine in the sacral preganglionic pathways to the urinary bladder.

Mechanism of action of local anesthetics on synaptic transmission in the rat.

The mechanism of action of local anesthetics on synaptic transmission and their effects on synaptic components and on electrophysiologic properties of the nerve cell body are not clear. Therefore, the effects of lidocaine and bupivacaine on pre- and postsynaptic mechanisms underlying synaptic transmission in sympathetic ganglia were studied utilizing the techniques of intracellular recording and stimulation on isolated superfused superior cervical ganglia of rats. Lidocaine and bupivacaine either depressed or completely blocked synaptic transmission in sympathetic ganglia in a dose-dependent manner. Blockade of axonal conduction in presynaptic fibers was preceded by increased latency (the latency increased from 11.2 +/- 0.9 to 16.5 +/- 1.4 ms, mean +/- SEM, P less than 0.01) when the drugs were applied to the presynaptic nerves. Application of the drugs directly to the ganglion produced alterations in postsynaptic membrane properties consisting of decreased membrane resistance (from 40 +/- 3 to 32 +/- 3 M omega, P less than 0.01), increased firing threshold (from 14 +/- 0.5 to 18 +/- 0.5 mV, P less than 0.01), and decreased action potential amplitude (P less than 0.01) and/or blockade of action potential generation. Resting postsynaptic membrane potential did not change significantly. These changes were reversible. However, even after the excitatory postsynaptic potential resulting from presynaptic nerve stimulation had fully recovered during washout of the local anesthetic, the threshold for evoking the spike potential (firing level) still remained elevated for both presynaptic and intracellular stimulation of the ganglion cell, suggesting prolonged cell depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiology of male sexual function.

The male sexual response cycle consists of excitement, plateau, orgasm, and resolution. The initial event, penile erection, is produced by arteriolar dilatation and increased blood flow to the erectile tissue of the penis. Erection is a reflex response initiated by visual, olfactory, or imaginative stimuli impinging upon supraspinal centers or by genital stimulation that in turn activates spinal reflex mechanisms. Sacral parasympathetic and thoracolumbar sympathetic nerves provide the efferent vasodilator input to the penis. Parasympathetic nerves also stimulate secretion from the seminal vesicles and prostate and Cowper's glands during the plateau phase. The orgasmic phase is characterized by seminal emission and ejaculation and the accompanying sensations. Emission of semen into the urethra depends on sympathetic nerves that elicit contractions of smooth muscles in the vas deferens, seminal vesicles, and prostate. Rhythmic contractions of striated muscle (bulbocavernosus and ischiocavernosus) generated by efferent pathways in the pudendal nerve eject semen from the urethra.

Physiology of the urinary bladder and urethra.

Activation of the parasympathetic pathways to the detrusor muscle and inhibition of somatic input to the external urethral sphincter are the essential neuronal events initiating release of urine. The former occurs via a spinobulbospinal pathway, whereas the latter is produced by inhibitory mechanisms in the sacral spinal cord. The sympathetic outflow to the urinary tract promotes urine storage by increasing urethral resistance and depressing detrusor contractions. Sympathetic activity is generated at least in part by a spinal vesicosympathetic reflex pathway. Evidence indicates that the integration of sympathetic and parasympathetic inputs to the bladder can occur at the level of the peripheral autonomic ganglion as well as at levels of the effector organ. The existence of facilitatory and adrenergic inhibitory mechanisms in ganglia and the identification of spontaneously active ganglion cells raise the possibility that vesical ganglia may have a role in modulating or "filtering" the efferent neural input to the bladder.

Effects of lidocaine on the excitability and membrane properties of the nerve cell soma.

The effects of lidocaine, an amide local anesthetic, on the electrophysiologic properties of the nerve cell soma were studied on isolated superfused superior cervical ganglia of rats. Administration of 400 nmol of lidocaine to the preparation evoked significant reversible changes in the membrane properties of the nerve cell soma. The firing threshold, the action potential duration and the intracellular current threshold for firing the cells increased significantly (p less than 0.01), while the action potential amplitude decreased significantly (p less than 0.01). The resting membrane potential change was not significant. The membrane resistance decreased by 20% (p less than 0.01). The change in membrane resistance, and the spike potential evoked by excitatory postsynaptic potential or intracellular current injection were the last to recover after application of lidocaine. The results show that the postsynaptic cell body is a major site of action of the local anesthetic lidocaine, and that it is more sensitive to the action of lidocaine than the presynaptic nerve fibers. The implication of the results is that when local anesthetics are injected to areas where cell bodies and processes (axons and dendrites) are present together, such as during stellate ganglion block, lumbar sympathetic block, celiac plexus block and intrathecal administration for spinal anesthesia, the cell bodies and the processes are all affected, and their excitability and function suppressed. Further, the duration of the block will be determined by the duration of lidocaine-induced cell block rather than the duration of lidocaine-induced nerve fiber block.

Effects of bupivacaine on the membrane properties of nerve cell soma.

While the effects of local anaesthetics on axonal conduction and axonal membrane have been extensively studied, there is little information about the actions of these agents on nerve cell soma. Therefore, the effects of the amide local anaesthetic bupivacaine on the electrophysiologic properties of the nerve cell soma were studied on isolated superfused superior cervical ganglia of rats. Administration of 100-200 nM of bupivacaine to the preparation produced marked changes in membrane properties of the cell soma. The resting membrane potential did not change, but the membrane resistance decreased 20% (P less than 0.01). The firing threshold, the action potential duration at 50% of maximal amplitude, and the intracellular current threshold for firing the cells increased significantly (P less than 0.01), while the action potential amplitude decreased significantly (P less than 0.01), before its complete blockade. The results show that the cell soma is a major site of action of local anaesthetics. The implication of the results is that when local anaesthetics are applied to areas where cell bodies and processes (axons and dendrites) are present together, such as during celiac plexus block, lumbar sympathetic block, stellate ganglion block, etc., they will all be effectively depressed and/or blocked.

Inhibition and facilitation in parasympathetic ganglia of the urinary bladder.

Neurons in vesical parasympathetic ganglia receive excitatory and inhibitory inputs from both divisions of the autonomic nervous system. Sacral parasympathetic pathways (cholinergic) provide the major excitatory input to these ganglia via activation of nicotinic receptors. Parasympathetic pathways also activate muscarinic inhibitory and excitatory receptors, which may exert a modulatory influence on transmission. Cholinergic transmission is relatively inefficient when preganglionic nerves are stimulated at low frequencies (< 1 Hz). However, excitatory postsynaptic potentials (EPSPs) and postganglionic firing markedly increase during repetitive stimulation at frequencies of 1-10 Hz. It is concluded that enhanced transmitter release accounts for the temporal facilitation and that vesical ganglia function as "high pass filters" that amplify the parasympathetic excitatory input to the detrusor muscle during micturition. Transmission in vesical ganglia is also sensitive to adrenergic inhibitory and facilitatory synaptic mechanisms elicited by efferent pathways in the hypogastric nerves. The effects of exogenous norepinephrine indicate that adrenergic inhibition is mediated by alpha receptors and reflects primarily a presynaptic depression of transmitter release although postsynaptic adrenergic hyperpolarizing and depolarizing effects have also been noted. Adrenergic facilitation is mediated by beta receptors as well as unidentified receptors. Norepinephrine also can inhibit or excite spontaneously active neurons in vesical ganglia. The existence of inhibitory and facilitatory synaptic mechanisms in vesical ganglia provides the basis for a complex ganglionic modulation of the central autonomic outflow to the bladder.

Excitatory effect of substance P in parasympathetic ganglia of cat urinary bladder.

Intra-arterial administration of substance P (0.1-50 micrograms/kg) to the urinary bladder of the cat produced slow-onset and sustained bladder contractions, asynchronous firing of bladder postganglionic nerves, and facilitation of nicotinic transmission in bladder ganglia. Intracellular recording from bladder ganglia in vitro revealed that substance P depolarized ganglion cells and initiated burst of action potentials (maximal frequency 6-7 Hz). The ganglionic excitatory effect of substance P in situ was blocked by gamma-aminobutyric acid (2-20 micrograms/kg) and the substance P antagonist [D-Arg1,D-Pro2,D-Trp7.9,Leu11]substance P (0.5-20 micrograms/kg) but was not altered by atropine (10-100 micrograms/kg), hexamethonium (0.5-2 mg/kg), norepinephrine (2-20 micrograms/kg), or leucine enkephalin (0.5-20 micrograms/kg). The bladder contractions elicited by substance P were not blocked by atropine, hexamethonium, or [D-Arg1,D-Pro2,D-Trp7.9,Leu11]substance P (0.1-10 micrograms/kg) but were blocked by another substance P antagonist, [D-Pro2,D-Phe7,D-Trp9]substance P. These data indicate that substance P has a direct postsynaptic excitatory effect on neurons in the vesical parasympathetic ganglia and on bladder smooth muscle cells. The differential effects of substance P antagonists on the excitatory responses at these two sites indicate the responses were mediated by different types of tachykinin receptors.

Regulation of urinary bladder capacity by endogenous opioid peptides.

Naloxone administered to chloralose or ketamine anesthetized cats reduced urinary bladder capacity. Successive cystometrograms revealed that naloxone in doses of 0.5 microgram./kg. to 15 micrograms./kg. i.v. reduced the volume necessary to evoke micturition by 10 to 50 per cent, respectively. The effect was maximal within a few minutes, remained constant for about 1/2 hour and returned to control values over the next 2 to 3 hours. Following return to control, subsequent doses of naloxone produced no further effect on capacity. In chloralose anesthetized animals naloxone also increased the frequency and amplitude of low amplitude pressure waves on the tonus limb of the cystometrogram. Intrathecal administration of naloxone to the sacral spinal cord did not significantly reduce the volume necessary to evoke micturition even at large doses, but did increase the amplitude of micturition contractions. These data, along with previous reports, suggest that mu receptors in the brainstem alter urinary bladder capacity, while delta receptors in the spinal cord modulate the magnitude of bladder contractions. Pharmacological manipulation of these receptor systems could provide a tool for the management of neurogenic bladder dysfunction.