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This study examined the temporal physiological and molecular events following the treatment of the liver with a tissue ablation modality that combined electroporation with electrolysis (E2). Rat liver was treated with an E2 waveform and the tissue examined, 1 h, 3 h, 6 h and 24 h with: H&E, Masson Trichrome, TUNEL stains and Western blot. H&E and TUNEL stains have shown that cell death began to be evident 3 h and hepatocyte regeneration was seen 24 h after treatment. H&E and Masson trichrome have shown that the extracellular matrix and the large lumens, appeared intact after E2. Western blot has shown the following molecular events after E2: cleaved caspase 3-downgraded at 1 h, upgraded at 24 h (apoptosis); cleaved Caspase 1 and cleaved GSDMD-upgraded at 6 h (pyroptosis), RIP3-upgraded at 1 h, MLKL-upgraded at 3 h (necroptosis). The mechanism of cell death was possible initiated by necroptosis pathway. Pyroptosis pathway was also activated. The observation that cell death from E2 was by programed necrosis and the details on the temporal molecular pathways, may have value for the recent attempt to combine electroporation mediated ablation with immunological treatment, by demonstrating that the cell death from E2 involves an inflammatory response and by providing data that could be used to design the optimal timing for the injection of immunological adjuvants., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The vagus nerve and several brainstem nuclei to which it projects have been closely associated with food intake. The aim of this study was to determine the degree to which the same or different information on food intake is processed by this nerve and by one of these nuclei, the external lateral parabrachial subnucleus (LPbNe). For this purpose, we analyzed the solid and liquid food intake of Wistar rats subjected to vagal deafferentation with capsaicin or lesions of the LPbNe. Vagotomized animals consumed significantly larger amounts of solid food during the first 24 h post‑surgery but not at 48, 72, or 96 h. Animals with LPbNe lesions also consumed larger amounts of liquid and solid foods but only during periods of 60 min on day 5 and 90 min on day 6 post‑surgery, respectively. According to these findings, both the vagus nerve and the LPbNe appear to be involved in short‑term regulation of food intake, although they participate over different time scales. These data are discussed in terms of the potential importance of the vagal‑parabrachial axis in the rapid processing of nutritional information from the upper gastrointestinal tract.

The pancreatic hormone amylin and its agonist salmon calcitonin (sCT) act via the area postrema (AP) and the lateral parabrachial nucleus (PBN) to reduce food intake. Investigations of amylin and sCT signaling in the ventral tegmental area (VTA) and nucleus accumbens (NAc) suggest that the eating inhibitory effect of amylin is, in part, mediated through the mesolimbic 'reward' pathway. Indeed, administration of the sCT directly to the VTA decreased phasic dopamine release (DA) in the NAc. However, it is not known if peripheral amylin modulates the mesolimbic system directly or whether this occurs via the AP and PBN. To determine whether and how peripheral amylin or sCT affect mesolimbic reward circuitry we utilized fast scan cyclic voltammetry under anesthesia to measure phasic DA release in the NAc evoked by electrical stimulation of the VTA in intact, AP lesioned and bilaterally PBN lesioned rats. Amylin (50μg/kg i.p.) did not change phasic DA responses compared to saline control rats. However, sCT (50μg/kg i.p.) decreased evoked DA release to VTA-stimulation over 1h compared to saline treated control rats. Further investigations determined that AP and bilateral PBN lesions abolished the ability of sCT to suppress evoked phasic DA responses to VTA-stimulation. These findings implicate the AP and the PBN as important sites for peripheral sCT to decrease evoked DA release in the NAc and suggest that these nuclei may influence hedonic and motivational processes to modulate food intake., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Deafening elicits a deterioration of learned vocalization, in both humans and songbirds. In songbirds, learned vocal plasticity has been shown to depend on the basal ganglia-cortical circuit, but the underlying cellular basis remains to be clarified. Using confocal imaging and electron microscopy, we examined the effect of deafening on dendritic spines in avian vocal motor cortex, the robust nucleus of the arcopallium (RA), and investigated the role of the basal ganglia circuit in motor cortex plasticity. We found rapid structural changes to RA dendritic spines in response to hearing loss, accompanied by learned song degradation. In particular, the morphological characters of RA spine synaptic contacts between 2 major pathways were altered differently. However, experimental disruption of the basal ganglia circuit, through lesions in song-specialized basal ganglia nucleus Area X, largely prevented both the observed changes to RA dendritic spines and the song deterioration after hearing loss. Our results provide cellular evidence to highlight a key role of the basal ganglia circuit in the motor cortical plasticity that underlies learned vocal plasticity., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The habenula is activated in response to stressful and aversive events, resulting in exploratory inhibition. Although possible mechanisms for habenula activation have been proposed, the effects of chronic stress on the habenular structure have never been studied. Herein, we assessed changes in volume, cell density and dendritic structure of habenular cells after chronic stress exposure using stereological and 3D morphological analysis. This study shows for the first time that there is a hemispherical asymmetry in the medial habenula (MHb) of the adult rat, with the right MHb containing more neurons than its left counterpart. Additionally, it shows that chronic stress induces a bilateral atrophy of both the MHb and the lateral habenula (LHb). This atrophy was accompanied by a reduction of the number of neurons in the right MHb and the number of glial cells in the bilateral LHb, but not by changes in the dendritic arbors of multipolar neurons. Importantly, these structural changes were correlated with elevated levels of serum corticosterone and increased anxious-like behavior in stressed animals. To further assess the role of the habenula in stress-related anxiety, bilateral lesions of the LHb were performed; interestingly, in lesioned animals the chronic stress protocol did not trigger increases in circulating corticosterone or anxious-like behavior. This study highlights the role of the habenula in the stress responses and how its sub-regions are structurally impacted by chronic stress with physiological and behavioral consequences., (Copyright © 2016. Published by Elsevier Inc.)

The authors estimated fluorine compounds content of workplace air in electrolysis workshops of aluminium production, for various electrolysis technologies. The data cover results of physical and chemical analysis and material constitution of produced toxic dust complexes, urinary excretion levels of fluorine ion and fluorides accumulation in hair of aluminium production workers.

The presence of disinfection by-products (DBPs) releasing from ballast water management systems (BWMS) can cause a possible adverse effects on humans. The objectives of this study were to compute the Derived No Effect Levels (DNELs) for different exposure scenarios and to compare these levels with the exposure levels from the measured DBPs in treated ballast water. The risk assessment showed that when using animal toxicity data, all the DNELs values were approximately 10(3)-10(12) times higher than the exposure levels of occupational and general public exposure scenarios, indicating the level of risk was low (risk characterization ratios (RCRs) < 1). However, when using human data, the RCRs were higher than 1 for dichlorobromomethane and trichloromethane, indicating that the risk of adverse effects on human were significant. This implies that there are apparent discrepancies between risk characterization from animal and human data, which may affect the overall results. We therefore recommend that when appropriate, human data should be used in risk assessment as much as possible, although human data are very limited. Moreover, more appropriate assessment factors can be considered to be employed in estimating the DNELs for human when the animal data is selected as the dose descriptors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The memories that are formed between rewarding and drug-associated contextual cues have been suggested to contribute to drug addiction relapse. Recent evidence has indicated that the ventrolateral orbital cortex (VLO) plays important roles in reward-based learning and reversal learning. However, whether the VLO is required for methamphetamine-induced contextual memory formation is not well understood. In the present study, a three-phase methamphetamine-induced conditioned place preference (CPP) model was used to investigate the effects of VLO lesions on the formation of drug-associated contextual memories in rats. We found that the VLO lesions themselves elicited no observable effects on place preferences. However, the VLO lesions delayed the acquisition and extinction phases of CPP without affecting the expression level. Furthermore, the VLO lesions did not have an obvious influence on CPP reinstatement. These results indicate that electrolytic lesions of the bilateral ventrolateral orbital cortex can inhibit the formation of methamphetamine-induced contextual memories in rats. Moreover, VLO may not be critically involved in memory storage and retrieval., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Intracranial self-stimulation (SS) in the lateral hypothalamus, a rewarding deep-brain stimulation, is able to improve acquisition and retention of implicit and explicit memory tasks in rats. SS treatment is also able to reverse cognitive deficits associated with aging or with experimental brain injuries and evaluated in a two-way active avoidance (2wAA) task. The main objective of the present study was to explore the potential of the SS treatment to reverse the complete learning and memory impairment caused by bilateral lesion in the lateral amygdala (LA). The effects of post-training SS, administered after each acquisition session, were evaluated on distributed 2wAA acquisition and 10-day retention in rats with electrolytic bilateral LA lesions. SS effect in acetylcholinestaresase (AchE) activity was evaluated by immunohistochemistry in LA-preserved and Central nuclei (Ce) of the amygdala of LA-damaged rats. Results showed that LA lesion over 40% completely impeded 2wAA acquisition and retention. Post-training SS in the LA-lesioned rats improved conditioning and retention compared with both the lesioned but non-SS treated and the non-lesioned control rats. SS treatment also seemed to induce a decrease in AchE activity in the LA-preserved area of the lesioned rats, but no effects were observed in the Ce. This empirical evidence supports the idea that self-administered rewarding stimulation is able to completely counteract the 2wAA acquisition and retention deficits induced by LA lesion. Cholinergic mechanisms in preserved LA and the contribution of other brain memory-related areas activated by SS could mediate the compensatory effect observed., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Signaled active avoidance (AA) paradigms train subjects to prevent an aversive outcome by performing a learned behavior during the presentation of a conditioned cue. This complex form of conditioning involves pavlovian and instrumental components, which produce competing behavioral responses that must be reconciled for the subject to successfully avoid an aversive stimulus. In signaled AA paradigm for rat, we tested the hypothesis that the instrumental component of AA training recruits infralimbic prefrontal cortex (ilPFC) to inhibit central amygdala (CeA)-mediated Pavlovian reactions. Pretraining lesions of ilPFC increased conditioned freezing while causing a corresponding decrease in avoidance; lesions of CeA produced opposite effects, reducing freezing and facilitating avoidance behavior. Pharmacological inactivation experiments demonstrated that ilPFC is relevant to both acquisition and expression phases of AA learning. Inactivation experiments also revealed that AA produces an ilPFC-mediated diminution of pavlovian reactions that extends beyond the training context, even when the conditioned stimulus is presented in an environment that does not allow the avoidance response. Finally, injection of a protein synthesis inhibitor into either ilPFC or CeA impaired or facilitated AA, respectively, showing that avoidance training produces two opposing memory traces in these regions. These data support a model in which AA learning recruits ilPFC to inhibit CeA-mediated defense behaviors, leading to a robust suppression of freezing that generalizes across environments. Thus, ilPFC functions as an inhibitory interface, allowing instrumental control over an aversive outcome to attenuate the expression of freezing and other reactions to conditioned threat.

In humans recognition memory deficits, a typical feature of diencephalic amnesia, have been tentatively linked to mediodorsal thalamic nucleus (MD) damage. Animal studies have occasionally investigated the role of the MD in single-item recognition, but have not systematically analyzed its involvement in other recognition memory processes. In Experiment 1 rats with bilateral excitotoxic lesions in the MD or the medial prefrontal cortex (mPFC) were tested in tasks that assessed single-item recognition (novel object preference), associative recognition memory (object-in-place), and recency discrimination (recency memory task). Experiment 2 examined the functional importance of the interactions between the MD and mPFC using disconnection techniques. Unilateral excitotoxic lesions were placed in both the MD and the mPFC in either the same (MD + mPFC Ipsi) or opposite hemispheres (MD + mPFC Contra group). Bilateral lesions in the MD or mPFC impaired object-in-place and recency memory tasks, but had no effect on novel object preference. In Experiment 2 the MD + mPFC Contra group was significantly impaired in the object-in-place and recency memory tasks compared with the MD + mPFC Ipsi group, but novel object preference was intact. Thus, connections between the MD and mPFC are critical for recognition memory when the discriminations involve associative or recency information. However, the rodent MD is not necessary for single-item recognition memory.

The coordination of locomotion and respiration is widespread among mammals, although the underlying neural mechanisms are still only partially understood. It was previously found in neonatal rat that cyclic electrical stimulation of spinal cervical and lumbar dorsal roots (DRs) can fully entrain (1:1 coupling) spontaneous respiratory activity expressed by the isolated brainstem/spinal cord. Here, we used a variety of preparations to determine the type of spinal sensory inputs responsible for this respiratory rhythm entrainment, and to establish the extent to which limb movement-activated feedback influences the medullary respiratory networks via direct or relayed ascending pathways. During in vivo overground locomotion, respiratory rhythm slowed and became coupled 1:1 with locomotion. In hindlimb-attached semi-isolated preparations, passive flexion-extension movements applied to a single hindlimb led to entrainment of fictive respiratory rhythmicity recorded in phrenic motoneurons, indicating that the recruitment of limb proprioceptive afferents could participate in the locomotor-respiratory coupling. Furthermore, in correspondence with the regionalization of spinal locomotor rhythm-generating circuitry, the stimulation of DRs at different segmental levels in isolated preparations revealed that cervical and lumbosacral proprioceptive inputs are more effective in this entraining influence than thoracic afferent pathways. Finally, blocking spinal synaptic transmission and using a combination of electrophysiology, calcium imaging and specific brainstem lesioning indicated that the ascending entraining signals from the cervical or lumbar limb afferents are transmitted across first-order synapses, probably monosynaptic, in the spinal cord. They are then conveyed to the brainstem respiratory centers via a brainstem pontine relay located in the parabrachial/Kölliker-Fuse nuclear complex.

Birds and mammals exploit interaural time differences (ITDs) for sound localization. Subsequent to ITD detection by brainstem neurons, ITD processing continues in parallel midbrain and forebrain pathways. In the barn owl, both ITD detection and processing in the midbrain are specialized to extract ITDs independent of frequency, which amounts to a pure time delay representation. Recent results have elucidated different mechanisms of ITD detection in mammals, which lead to a representation of small ITDs in high-frequency channels and large ITDs in low-frequency channels, resembling a phase delay representation. However, the detection mechanism does not prevent a change in ITD representation at higher processing stages. Here we analyze ITD tuning across frequency channels with pure tone and noise stimuli in neurons of the barn owl's auditory arcopallium, a nucleus at the endpoint of the forebrain pathway. To extend the analysis of ITD representation across frequency bands to a large neural population, we employed Fourier analysis for the spectral decomposition of ITD curves recorded with noise stimuli. This method was validated using physiological as well as model data. We found that low frequencies convey sensitivity to large ITDs, whereas high frequencies convey sensitivity to small ITDs. Moreover, different linear phase frequency regimes in the high-frequency and low-frequency ranges suggested an independent convergence of inputs from these frequency channels. Our results are consistent with ITD being remodeled toward a phase delay representation along the forebrain pathway. This indicates that sensory representations may undergo substantial reorganization, presumably in relation to specific behavioral output.

The features of development of the skin vessels lesions in 550 aluminum production workers have been investigated. The high prevalence of these disorders have been revealed in anode-operators and cell-operators, 49, 3 and 26.0% of workers, respectively. The regularity and staging of the development of this abnormity have been established, etiology, pathogenesis and clinical significance of those remain unknown.

Multi-year follow-up of 358 workers of aluminum pot rooms, including 165 individuals suffering from fluorosis, has shown significant changes in the clinical picture of the chronic occupational fluorine intoxication, developed under modern conditions of production, at lower concentrations of fluorine compounds in the air of working area. In this connection, the pathology of the musculoskeletal system plays the dominating role in this clinical picture and has the large variability of combinations of the individual sections destructions of the bone tissue. The main criterion to establish the phase of the disease is still the number and severity of the signs of this destruction. The visceral pathology in contemporary production circumstances is registered with less frequency and loses a number of the previously described clinical manifestations, however, is still of some importance to identify the early signs of the disease and to prevent the dental fluorosis on time.

The aim of this research is to investigate the role of the occupational risks in the development of pain syndromes of the locomotor system in workers employed in basic workplaces at aluminum potrooms, basing on the periodic health screenings data. It has been determined that working under the conditions of toxical fluorides-related exposure and athletic overexertion increases the risk of the upper arm pain syndrome development 4.3 fold. The maximum relative risk (108.2) has been revealed in the workers of such kind of professions having the length of employment upper 20 years and suffering simultaneously from cervical osteochondrosis and pulmonary diseases.

Context-specific adaptation (Shelhamer M, Clendaniel R. Neurosci Lett 332: 200-204, 2002) explains that reflexive responses can be maintained with different "calibrations" for different situations (contexts). Which context cues are crucial and how they combine to evoke context-specific adaptation is not fully understood. Gaze stabilization in birds is a nice model with which to tackle that question. Previous data showed that when pigeons (Columba livia) were hung in a harness and subjected to a frontal airstream provoking a flying posture ("flying condition"), the working range of the optokinetic head response [optocollic reflex (OCR)] extended toward higher velocities compared with the "resting condition." The present study was aimed at identifying which context cues are instrumental in recalibrating the OCR. We investigated that question by using vibrating stimuli delivered during the OCR provoked by rotating the visual surroundings at different velocities. The OCR gain increase and the boost of the fast phase velocity observed during the "flying condition" were mimicked by body vibration. On the other hand, the newly emerged relationship between the fast-phase and slow-phase velocities in the "flying condition" was mimicked by head vibration. Spinal cord lesion at the lumbosacral level decreased the effects of body vibration, whereas lesions of the lumbosacral apparatus had no effect. Our data suggest a major role of muscular proprioception in the context-specific adaptation of the stabilizing behavior, while the vestibular system could contribute to the context-specific adaptation of the orienting behavior. Participation of an efferent copy of the motor command driving the flight cannot be excluded.

Rats with combined bilateral lesions of the retrosplenial cortex and the fornix or rats with unilateral lesions to the anterior thalamus and the hippocampus, made in opposite hemispheres (disconnection preparation), and combined with unilateral damage of the retrosplenial cortex in either hemisphere, were tested on a spatial-visual conditional learning task in which they learned arbitrary associations between stimuli and the scene in which they were embedded. All experimental groups were impaired in comparison with normal animals. The more severe deficits occurred when (1) both the fornix and the retrosplenial cortex were damaged bilaterally thus depriving the hippocampus both from subcortical interactions via the fornix and retrosplenial-mediated interactions and (2) when, in the crossed lesion preparation, the unilateral retrosplenial lesion was made in the hemisphere with the intact hippocampus, again because this lesion would be maximally disconnecting the hippocampus from functional interaction with the anterior thalamic nucleus and retrosplenial-mediated input.

Recent studies have shown that the hippocampus is critical for the context-dependent expression of extinguished fear memories. Here we used Pavlovian fear conditioning in rats to explore whether the entorhinal cortex and fornix, which are the major cortical and subcortical interfaces of the hippocampus, are also involved in the context-dependence of extinction. After pairing an auditory conditional stimulus (CS) with an aversive footshock (unconditional stimulus or US) in one context, rats received an extinction session in which the CS was presented without the US in another context. Conditional fear to the CS was then tested in either the extinction context or a third familiar context; freezing behavior served as the index of fear. Sham-operated rats exhibited little conditional freezing to the CS in the extinction context, but showed a robust renewal of fear when tested outside of the extinction context. In contrast, rats with neurotoxic lesions in the entorhinal cortex or electrolytic lesions in the fornix did not exhibit a renewal of fear when tested outside the extinction context. Impairments in freezing behavior to the auditory CS were not able to account for the observed results, insofar as rats with either entorhinal cortex or fornix lesions exhibited normal freezing behavior during the conditioning session. Thus, contextual memory retrieval requires not only the hippocampus proper, but also its cortical and subcortical interfaces.

In previous studies we have suggested that the dorsal hippocampus is involved in spatial consolidation by showing that rats with electrolytic hippocampal lesions exhibit a profound deficit in the retention of an allocentric task 24 days after the acquisition. However, in various hippocampal-dependent tasks, several studies have shown an overestimation of the behavioral deficit when electrolytic versus axon-sparing cytotoxic lesions has been used. For this reason, in this report we compare the effects on spatial retention of electrolytic and neurotoxic lesions to the dorsal hippocampus. Results showed a similar deficit in spatial retention in both groups 24 days after acquisition. Thus, the hippocampus proper and not fibers of passage or extrahippocampal damage is directly responsible for the deficit in spatial retention seen in rats with electrolytic lesions.

The entorhinal cortex lesion paradigm is a widely accepted and efficient method to provoke reactive synaptogenesis and terminal remodeling in the adult CNS. This approach has been used successfully to contrast the profile of reactivity from various proteins associated with Alzheimer's disease pathophysiology in wild-type and apolipoprotein E (apoE)-deficient (APOE ko) mice. Results indicate that the production of the beta-amyloid 1-40 peptide (A beta 40) is increased in response to neuronal injury, with a timing that is different between wild-type and APOE ko animals. Moreover, we report that baseline levels of the A beta 40 peptide are significantly higher in the APOE ko mice. The expression of the apolipoprotein E receptor type 2 (apoER2) is also modulated by the deafferentation process in the hippocampus, but only in APOE ko mice. These results provide novel insights as to the molecular mechanisms responsible for the poor plastic response reported in apoE4-expressing and apoE deficient mice in response to hippocampal injury.

Across different behavioural tasks, nucleus accumbens (n.acc) lesions have generated conflicting effects on locomotor activity and in particular, the relative roles of the n.acc shell and core subfields in this have been controversial. To date there is only one study examining effects of lesions to the medial n.acc on elevated plus-maze (EPM) behaviour; these lesions were shown to increase both locomotor and exploratory activity. Given the well-documented distinction between shell and core, the present study sought to extend previous research by testing lesions selective to each n.acc subfield in the EPM. Results showed no statistical differences between core lesioned and sham-operated animals on any measure. In contrast, shell lesions consistently reduced locomotion and exploratory activity. This direction of effects is opposite to that previously observed after medial n.acc. lesions. In conclusion, locomotion and exploratory activity were clearly reduced by shell but not core lesions, consistent with other evidence for the functional heterogeneity of n.acc shell and core.

We investigated the roles of the auditory cortex in discrimination learning of vowel-like sounds consisting of multiple formants. Rats were trained to discriminate between synthetic sounds with four formants. Bilateral electrolytic lesions including the primary auditory cortex and the dorsal auditory association cortex impaired multiformant discrimination, whereas they did not significantly affect discrimination between sounds with a single formant or between pure tones. Local lesions restricted to the dorsal/rostral auditory association cortex were sufficient to attenuate multiformant discrimination learning, and lesions restricted to the primary auditory cortex had no significant effects. These findings indicate that the dorsal/rostral auditory association cortex but not the primary auditory cortex is required for discrimination learning of vowel-like sounds with multiple formants in rats.

The habenula complex modulates the activity of dopamine and serotonin systems in the brain. An important question remains whether there is a link between habenula dysfunction and monoamine-related disorders, such as schizophrenia. In this study, we describe an interaction between habenula lesions and stress that produces long-lasting effects on behavior. Mice received control lesions or bilateral electrolytic lesions of the habenula and were tested for fear-potentiated startle and freezing measures of conditioned fear. They were also tested for prepulse inhibition (PPI) and locomotor activity in the presence or absence of a dopaminergic agonist (apomorphine) or an atypical antipsychotic with mixed dopamine/serotonin antagonist properties (clozapine). There were no detectable effects of habenula lesions on fear conditioning and no effects on PPI in the absence of stress. However, following conditioned fear stress, habenula-lesioned animals showed decreased PPI which normalized with clozapine. Lesioned animals also showed diminished activity at baseline, with hyperlocomotion following apomorphine. These data support the hypothesis that the habenula may be normally involved in stress-dependent regulation of monoamine systems.

In models of global brain injury, such as stroke or epilepsy, a large increase in neurogenesis occurs in the dentate gyrus (DG) days after the damage is induced. In contrast, more focal damage in the DG produces an increase in neurogenesis within 24 hr. To determine how cell proliferation and differentiation differs in the DG after acute injury in the DG, focal electrolytic lesions were made and mitotic activity was assessed at early (1 day) and late (5 day) time points. At the early time point, bromodeoxyuridine (BrdU)-positive cells were diffusely spread throughout the extent of the hippocampus that was ipsilateral to the lesion. No significant increase in the subgranular zone (SGZ) of the DG was observed. When BrdU was administered at the later time point, the number of BrdU+ cells in the SGZ of the DG was significantly increased. This fourfold increase in BrdU+ cells also resulted in a significant increase in neurogenesis, as measured 6 weeks following BrdU administration. This increase in neurogenesis was not observed when BrdU was administered at the early time point. These results indicate that focal injury in the DG activates two temporally specific proliferation events and that enhanced neurogenesis is observed only following a latent period after the lesion is made., (Copyright 2005 Wiley-Liss, Inc.)

The cholinergic agonist pilocarpine injected intraperitoneally (ip) increases mean arterial pressure (MAP) and superior mesenteric (SM) vascular resistance and reduces submandibular/sublingual gland (SSG) vascular resistance. In the present study, we investigated the effects of electrolytic lesions of the anteroventral third ventricle (AV3V) region on the changes in MAP, SM, and SSG vascular resistances induced by ip pilocarpine. Male Holtzman rats anesthetized with urethane (1.0 g/kg) and chloralose (60 mg/kg) were submitted to sham or electrolytic AV3V lesions and had pulsed Doppler flow probes implanted around the arteries. Contrary to sham rats, in 1-h and 2-day AV3V-lesioned rats, pilocarpine (4 micromol/kg) ip decreased MAP (-41 +/- 4 and -26 +/- 4 mm Hg, respectively, vs. sham: 19 +/- 4 mm Hg) and SM (-48 +/- 11 and -45 +/- 10%, respectively, vs. sham: 41 +/- 10%) and hindlimb vascular resistances (-65 +/- 32 and -113 +/- 29%, respectively, vs. sham: 19 +/- 29%). In 7-day AV3V-lesioned rats, pilocarpine produced no changes on MAP and SM and hindlimb vascular resistances. Similar to sham rats, pilocarpine reduced SSG vascular resistance 1 h after AV3V lesions (-46 +/- 6%, vs. sham: -40 +/- 6%), but it produced no effect 2 days after AV3V lesions and increased SSG vascular resistance (37 +/- 6%) in 7-day AV3V-lesioned rats. The responses to ip pilocarpine were similar in 15-day sham and AV3V-lesioned rats. The cholinergic antagonist atropine methyl bromide (10 nmol) iv slightly increased the pressor response to ip pilocarpine in sham rats and abolished for 40 min the fall in MAP induced by ip pilocarpine in 1-h AV3V-lesioned rats. The results suggest that central mechanisms dependent on the AV3V region are involved in the pressor responses to ip pilocarpine. Although it was impaired 2 and 7 days after AV3V lesions, pilocarpine-induced salivary gland vasodilation was not altered 1 h after AV3V lesions which suggests that this vasodilation is not directly dependent on the AV3V region.

Background: Palliation of pancreatic cancer remains the only option for the majority of patients. Palliative techniques such as surgical bypass and endoscopic retrograde cholangiopancreatography (ERCP) with stenting are not ideal. The 'ideal' palliative technique would combine the efficacy of surgery with the minimal complications of an endoscopic procedure. Endoscopically delivered perductal electrolytic ablation of pancreatic lesions has the potential to meet these criteria., Methods: Fifteen pigs were used. The pancreatic duct was cannulated with an electrolysis catheter. Animals were randomised to either: controls, treatment 2-week survivor or treatment 8-week survivor. An electrolytic dose was administered to the treatment animals. Post-operatively, serum amylase and leucocyte count were assessed. Pancreata were histologically examined to detect evidence of acute pancreatitis., Results: Electrolysis was well tolerated. There was no difference in post-operative hyperamylasaemia and leucocyte count between the groups. Histological examination showed inflammation at the ablation site at 2 weeks, by 8 weeks this was replaced by scarring., Conclusion: The results of this study suggest that endoscopic perductal electrolytic ablation of the pancreas is feasible and safe. Biochemical and histological findings indicate self-limiting localised inflammation of the pancreas. This technique may have a role in the palliation of pancreatic cancer and warrants further investigation., (2005 S. Karger AG, Basel)

In a rat model of unilateral hindpaw inflammation, it is unclear whether the coeruleospinal modulation system is active at spinal segments distant from the inflamed plantar region, such as the cervical segments. To clarify this query, in the present study we measured paw withdrawal latency (PWL) to thermal stimuli on four paws (both forepaws and both hindpaws) following induction of inflammation and compared PWLs between rats with bilateral lesions of the locus coeruleus/subcoeruleus (LC/SC) and rats with sham operation. Unilateral hindpaw inflammation was produced by a subcutaneous injection of carrageenan (2 mg in 0.15 ml saline). Prior to carrageenan injection, in all four paws, PWLs did not differ between the LC/SC-lesioned and the sham-operated rats. Four hours after carrageenan injection, PWLs in the inflamed left hindpaw decreased significantly in both the LC/SC-lesioned and the sham-operated rats. The decreased PWLs of the LC/SC-lesioned group were significantly shorter than those of the sham-operated group. These phenomena which were observed in the inflamed left hindpaw were also observed in the non-inflamed left forepaws. In the right forepaws and the right hindpaws, no significant change in PWL was observed between before and 4 h after injection in both the sham-operated and the LC/SC-lesioned rats. These results suggest that unilateral hindpaw inflammation activates the coeruleospinal modulation system and that this modulation system is active not only at the lumbar segments but also at the cervical level where spinal segments are distant from the inflamed plantar region.

The role of the claustrum in Pavlovian heart rate (HR) conditioning was studied in the rabbit (Oryctolagus cuniculus) by (a) mapping claustral projections to the prefrontal cortex (PFC), (b) recording claustral single-unit discharge to sensory stimulation and conditioning stimuli during HR conditioning, and (c) assessing the effects of claustral damage on HR conditioning. Contralateral and ipsilateral claustral projections to the PFC were found. Claustral cells responded to nonsignal stimulation with increased discharge and also showed conditioned stimulus-evoked increases in discharge during Pavlovian HR conditioning. Moreover, claustral lesions diminished the magnitude of the HR-conditioned response without affecting the cardiac-orienting response to the conditioned stimulus or the cardiac-unconditioning response to the unconditioned stimulus, suggesting a role for the claustrum in associative learning., (((c) 2004 APA, all rights reserved))

A delayed matching-to-sample task was designed to assess memory for direction information in rats. During the study phase, rats traversed a maze arm oriented in 1 of 3 directions. After a delay period, a test phase was presented that required a choice between the study phase direction and a foil direction. Once rats reached a learning criterion, probe trials suggested that normal rats favor the use of direction, rather than turning response, information and use vestibular feedback. Rats were then given hippocampus, medial caudate nucleus (MCN), or cortical control lesions. Unlike control rats, those with hippocampus and MCN lesions exhibited marked impairments when retested. However, all rats were able to learn a direction discrimination task. These results suggest that the hippocampus and MCN support processes associated with short-term memory for direction information., (((c) 2004 APA, all rights reserved))

The purpose of our study is to determine the alteration of neurobehavioral parameters, autonomic nervous function and lymphocyte subsets in aluminum electrolytic workers of long-term aluminum exposure. 33 men who were 35.16 +/- 2.95 (mean +/- S.D) years old occupationally exposed to aluminum for 14.91 +/- 6.31 (mean +/- S.D) years. Air Al level and urinary aluminum concentration was measured by means of graphite furnace atomic absorption spectrophotometer. Normal reference group were selected from a flour plant. Neurobehavioral core test battery (NCTB) recommended by WHO was utilized. Autonomic nervous function test battery recommended by Ewing DJ was conducted on subjects. FAC SCAN was used to measure the lymphocyte subsets of peripheral blood. The mean air aluminum level in the workshop was 6.36 mg/m3, ranged from 2.90 to 11.38 mg/m3. Urinary aluminum of the Al electrolytic workers (40.08 +/- 9.36 microgram/mg.cre) was obviously higher than that of control group (26.84 +/- 8.93 m/mg.cre). Neurobehavioral results showed that the scores of DSY, PAC and PA in Al electrolytic workers were significantly lower than those of control group, The score of POMSC, POMSF and SRT among Al exposed workers were significantly augmented in relation to those of control group. Autonomic nervous function test results showed that R-R interval variability of maximum ratio of immediately standing up in Al electrolytic workers were decreased compare with the control group, while the BP-IS, HR-V, HR-DB, R30:15 had no significant change. Peripheral blood lymphocyte subsets test showed that CD4-CD8+ T lymphocyte in Al electrolytic workers increased. This study suggests that Al exposure exerts adverse effects on neurobehavioral performance, especially movement coordination and negative mood, and parasympathetic nervous function; moreover it increase CD4-CD8+ T lymphocyte subsets.

Background and Purpose: Recent reports describe a high rate of thromboembolic events related to Guglielmi detachable coil (GDC) use in the treatment of cerebral aneurysms. The purpose of this study was to investigate electrolysis-related changes of blood as a potential cause of thromboembolic complications associated with GDC use., Methods: For in vitro observations, 15 GDCs (10 conventional coils and five insulated coils) were experimentally detached under microscopic observation. Three coils were detached in normal saline, five in human serum, and seven in heparinized human blood. For animal experiments, two coils were detached in two canine normal common carotid arteries with systemic heparinization. Immediately after detachment, the arteries were exposed, and clot formations were observed., Results: Significant amounts of gas bubbles were observed in all in vitro observations; more were seen in conventional coils, which required longer detachment times, than in insulated coils. Gas generation started with the growth of tiny bubbles into larger ones. In insulated coils, gas was generated only at the detachment zone, and no difference between saline, serum, and blood environments was observed. During detachment within heparinized blood, clot formations of 2-3-mm diameter were observed at the detachment zones of insulated coils. Animal experiments showed clot formation at the detachment zone, and bubble entrapments around the clots were also found., Conclusion: The electrolytic detachment mechanism of the platinum coil can generate gas bubbles during the application of electric current. In association with electrothrombosis, this phenomenon may be a potential cause of thromboembolic complications during the treatment of cerebral aneurysms by use of GDCs.

Background: Electrolytic ablation is a relatively new method for the local destruction of colorectal liver metastases. Experimental work in animal models has shown this method to be safe and efficacious. However, before proceeding to clinical trials it was necessary to confirm these findings in a pilot study of five patients., Methods: Five patients with colorectal liver metastases were studied prospectively. Each patient underwent a potentially curative liver resection. One of the metastases to be removed was treated using electrolysis before resection. Each patient was monitored closely during and after electrolysis to determine any morbidity associated with the treatment. Once resected, the metastases were examined histologically for completeness of ablation., Results: All patients tolerated the electrolysis well; there were no deaths or complications related to the treatment. Histological examination of the resected metastases which had been treated electrolytically showed complete tissue destruction with no viable malignant cells remaining at the site of treatment., Discussion: This pilot study of electrolytic ablation of liver metastases in five patients showed the treatment to be well tolerated and safe. Additionally, it demonstrated total destruction of the malignant tissue at the site of electrolysis. Based on these encouraging results, clinical trials can now begin.

Factor Xa is a serine protease positioned at the convergence point of the intrinsic and extrinsic coagulation pathways and is therefore an attractive target in the development of novel anticoagulant drugs. The objective of this study was to evaluate the efficacy of CI-1031 (N-[2-[5-amidino-2-hydroxyphenoxy]-6-[3-(1-methyl-1H-imidazolin-2-yl)-phenoxy]-3,5-difluoropyrid), a potent and selective inhibitor of Factor Xa, in a canine electrolytic injury model of arterial and venous thrombosis. Enoxaparin (enoxaparin sodium), a low molecular weight heparin currently approved for treatment and prevention of deep vein thrombosis and unstable angina, was also tested for efficacy in this model. CI-1031 was administered intravenously to anesthetized dogs at three doses: 1.25, 2.5 and 5 microg/kg/min (n=5 for each group) as a continuous infusion for 5.5 h. The control group (n=5) received a continuous infusion of vehicle (3.69 mmol citric acid and 0.9% sodium chloride solution) at a rate of 1 ml/kg/h. Ninety minutes after administration of CI-1031 prothrombin times increased 1.2-, 1.6- and 2.0-fold over baseline values in the 1.25, 2.5 and 5 microg/kg/min groups, respectively. The time to formation of an occlusive thrombus in the femoral arteries averaged 69+/-5 min in the control group compared to 127+/-19, 192+/-33 and 219+/-15 min in the low-, mid- and high-dose CI-1031 groups. In the femoral veins, occlusion time in the controls averaged 56+/-11 min compared to 153+/-22, 137+/-30 and 214+/-26 min in the three treatment groups. Thrombus weights in the control arteries averaged 51+/-4 mg compared to 45+/-5, 28+/-10 and 15+/-3 mg in the CI-1031 treated groups. On the venous side, control thrombus weights averaged 96+/-18 mg compared to 75+/-16, 51+/-16 and 25+/-4 mg in the low-, mid- and high-dose CI-1031 groups. A plasma CI-1031 concentration of approximately 400 ng/ml was associated with a 50% reduction in thrombus weight relative to control animals. Enoxaparin was administered intravenously at a loading dose of 50, 100 or 200 IU/kg for 1 h followed by a maintenance infusion of 25, 50 or 100 IU/kg/h for 4.5 h. The most dramatic changes in coagulation parameters were observed in thrombin time with virtually no changes in prothrombin time. Enoxaparin elicited a dose-dependent increase in time to thrombotic occlusion and a dose-dependent decrease in thrombus weight similar to that observed with CI-1031. Time to occlusion in the enoxaparin-treated groups averaged 117+/-33, 188+/-32 and 217+/-22 min in the low-, mid- and high-dose groups in the femoral arteries and 84+/-22, 171+/-31 and 133+/-33 min in the femoral veins. Thrombus weights averaged 33+/-10, 12+/-5 and 10+/-4 mg in the arteries and 32+/-9, 13+/-2 and 21+/-6 mg in the veins in the low-, mid- and high-dose groups. Blood loss with CI-1031 tended to be less than enoxaparin at doses that provided comparable efficacy. These results demonstrate that CI-1031, like enoxaparin, is an effective antithrombotic agent in an established canine model of arterial and venous thrombosis. CI-1031 provided dose-dependent efficacy with minimal changes in ex vivo coagulation parameters, suggesting it may be a safe and effective antithrombotic agent for both arterial and venous indications.

Background: The treatment of patients with unresectable liver tumours remains an unsolved clinical problem. Several methods of locoregional treatment have been developed. These methods rely mainly on direct thermal or chemical insults and consequently have their own inherent limitations in clinical usage. The 'ideal' treatment would combine the direct cytotoxic effects of chemical treatments with the relative predictability of thermal insults, without the associated complications. This study aims to investigate whether the direct chemical effect of electrolytic hepatic necrosis is associated with any heating effect, and if so, whether the temperature change is dose-dependent., Methods: An electrolytic 'dose' sufficient to induce a localized zone of hepatic necrosis was delivered to the livers of rats and pigs via implanted platinum electrodes., Results: The results showed that there was no significant temperature increase at low current levels (2-4 mA) in the rat liver. In the pig, there was a significant (P < 0.01) increase in temperature of 4.2 degrees C during electrolysis, when delivered at between 20 and 50 mA. However, such a small increase in temperature would have been insufficient to cause appreciable thermal necrosis., Conclusions: This study demonstrates that electrolysis-induced hepatic necrosis is produced without an increase in temperature; clearly cell death results from the direct effects of cytotoxic electrode products and an alteration of intracellular pH. Consequently, it is likely that as a method for ablating liver tumours, electrolysis should be associated with fewer complications than other forms of locoregional treatment.

The effect of endothelin-1 (ET-1) on thrombus formation in vivo was evaluated in two well-established canine models of coronary artery thrombosis. First, the possible antithrombotic effect of ET-1 was examined using the cyclic flow reduction (CFR) model of coronary artery stenosis, vascular endothelial cell and intimal smooth muscle cell injury, and periodic acute platelet thrombus formation. Using a rating system of 0 (no inhibition) to 3 (complete inhibition), ET-1 administration at 0.1, 0.5, and 1.0 microgram/kg, i.v. bolus, produced scores of 1.0 +/- 0.2 (n = 10), 1.8 +/- 0.4 (n = 8), and 2.1 +/- 0.3 (n = 7), respectively. ET-1 injection inhibited ex vivo platelet aggregation induced by ADP and U-46619 by 30-60%. When aspirin was administered at 5 mg/kg prior to ET-1 administration at 0.5 microgramoff, ET-1 produced a CFR rating of 2.7 +/- 0.2 (n = 6). However, higher dose aspirin (30 mg/kg, i.v.) significantly inhibited the antithrombotic effect of ET-1 (0.5 +/- 0.5, n = 4). The antithrombotic effect of ET-1 was also examined using an electrolytic injury model of arterial thrombosis. The time required to produce an occlusive thrombus during the experiments in which ET-1 was administered at 10 and 20 ng.kg-1.min-1 was 77 +/- 15 (p < 0.08) and 105 +/- 16 min (p < 0.05), respectively, compared to 44 +/- 5 min when vehicle was infused. Cardiovascular changes following occlusion were not significantly different between dogs given ET-1 and those given vehicle, suggesting that elevated plasma levels of ET-1 did not exacerbate the adverse effects of coronary occlusion. In addition, plasma ET-1 levels were elevated significantly after occlusion in the dogs given vehicle (from 7.4 to 12.4 pg/ml). Taken together, these date provide further evidence to support the notion that ET-1 release during ischemia may be involved in a protective mechanism that impeded thrombus formation in the stenosed coronary artery.

Fourteen healthy adult Japanese females were selected to participate in a comparative study of hair plucking (a temporary hair removal technique) and the blend method (a permanent hair removal technique). The effectiveness of permanent hair removal and the safety of the blend method were examined in this study. If hairs of the left axilla were removed by the blend method, then hairs of the right axilla were removed by plucking, and vice versa. Every hair was removed and the number of hairs was counted each time. Sessions were conducted every three weeks, and the experiment continued until no new hair growth was seen using the same experimental standard. Electrologists with more than 1000 hours of experience were selected to perform electrolysis. Examinations of the axilla, before and after each test, were conducted by the authors. The results showed that the number of hairs decreased in the axilla with each session using the blend method: permanent hair removal was achieved in an average of 26.8 weeks or 9.9 sessions. However, the number of hairs did not decrease in the axilla after plucking. Also, there were no reports of hair removal related side-effects in this study. It was thus demonstrated that the blend method is a safe and effective way of achieving permanent hair removal.

The antithrombotic efficacies of the coagulation factor Xa inhibitor recombinant tick anticoagulant peptide (rTAP) and heparin were compared in a canine model of left circumflex (LCX) coronary artery electrolytic lesion. Intravenous infusions of saline (controls), rTAP (50 micrograms/kg/min continuous infusion) or heparin (200 U/kg bolus followed by 2 U/kg/min continuous infusion) were started 60 min prior to the initiation of LCX coronary artery electrolytic injury (150 microA continuous anodal current). All 6/6 saline-treated control animals developed occlusive thrombi at 49.8 +/- 13.6 min after the initiation of vessel injury, and possessed a residual thrombus mass of 20.7 +/- 3.3 mg. In the rTAP treatment group, 4/6 preparations developed occlusive thrombi, but with times to thrombosis delayed significantly compared to both the saline control as well as to the heparin treatment group (202.7 +/- 28.9 min; p < 0.01 to both saline and heparin groups). The remaining 2 rTAP-treated preparations remained patent despite the continued electrical stimulation of the coronary vessel for 5 h. Residual thrombus mass in the rTAP treatment group was reduced markedly compared to the saline control group (4.4 +/- 1.0 mg; p < 0.01). Heparin infusion resulted in a modest but statistically insignificant delay in occlusive LCX coronary artery thrombosis compared to saline controls, with all 6/6 heparin-treated preparations occluding at 79.7 +/- 16.5 min after the initiation of vessel injury. Residual thrombus mass in heparin-treated animals, however, was reduced compared to saline controls (9.4 +/- 1.4 mg; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

The role of ear-piercing, tattooing, attendance at chiropodist or manicurist and barber shop shaving in transmitting hepatitis B and hepatitis non-A, non-B was evaluated. Data reported here were collected from 1985 to 1993 by the National Viral Hepatitis Surveillance System. The association between parenterally transmitted hepatitis and the considered risk factors was estimated, comparing 6,395 hepatitis B and 2,558 hepatitis non-A, non-B cases with 4,789 hepatitis A cases, using the case-control method. Of the non-A, non-B cases tested from 1991 to 1993, 56.6% were anti-HCV positive. The incidence of parenterally transmitted hepatitis cases reporting specific beauty treatments was also evaluated. Tattooing, ear-piercing and barber shop shaving were associated with both parenterally transmitted hepatitides, while attendance at a chiropodist or manicurist was associated only with hepatitis B. During the study period the incidence of acute hepatitis B and non-A, non-B cases reporting beauty treatments declined by 49%. In spite of this decline, considering that a large part of the general population is exposed to the considered risk factors, the role of beauty treatments in transmitting hepatitis B and hepatitis non-A, non-B should not be underestimated.

Sodium chloride intake was studied in male Holtzman rats weighing 250-300 g submitted to electrolytic and chemical lesion of the cell bodies, not fibers of the amygdaloid complex. Sodium chloride (1.5%) intake increased in animals with electrolytic lesion of the corticomedial nucleus of the amygdala. Sodium chloride (1.5%) intake increased after ibotenic acid injection into the corticomedial nucleus of the amygdala to a larger extent (26.6 +/- 9.2 to 147.6 +/- 34.6 ml/5 days). The results indicate that sodium intake response can be induced by lesions, which involved only cell bodies. The fibers of passage of the corticomedial nucleus of the amygdala produce a water intake less consistent than that induced by ibotenic acid, which is more acute. The results show that cell bodies of this region of the amygdala are involved in the control of sodium chloride intake.

The objective of this study was to define further the role of the trigeminal motor nucleus (TMNu) in the postnatal ontogeny of the mammalian craniofacial skeleton. To that end, 42 male Sprague-Dawley rats underwent stereotaxic surgery at 40 days of age; 21 received small electrolytic lesions to their left-side TMNu (lesioned group) while 21 had TMNu stimulation with no actual electrolytic lesion produced (sham group). Seven rats from each group were killed at 28, 56, and 84 days postoperative to analyze trigeminal motoneuron (TMNe) count, masticatory muscle weight, and osteological growth vector data. At all three time periods, lesioned animals showed significant differences 1) between the surgery and nonsurgery sides, and 2) from sham animals. However, sham animals also demonstrated significant between-side differences for medial pterygoid muscle weight (56 days), mandibular height (28 and 56 days), and mandibular length data (84 days); these data suggested that even relatively slight damage to TMNe can create morphological changes within the craniofacial complex. Snout deviation in a lesioned rat towards the opposite side from all other lesioned animals was correlated with unique damage to its pontine reticular formation; this suggested that the observed morphological alterations of the craniofacial complex may have been due not only to TMNu damage, but also to changed expressions of the masticatory central pattern generator (CPG). Morphological alterations of the craniofacial skeleton resulting from lesions to the TMNu were likely due to changed neuromuscular activity patterns of the masticatory muscles and their biomechanical effects upon bone.

Physical methods for the management of unwanted hair are critically reviewed. Electrolysis and thermolysis are popular and medically proven electrochemical and electrosurgical techniques for permanent hair removal. Many patients seek consultation with their physician prior to having this elective procedure performed. Clinical guidelines are presented for a successful consultation with such patients. Many years ago the unregulated practice of x-ray therapy by unlicensed and poorly trained personnel resulted in tragic morbidity and mortality. Some historical parallels exist between this disturbing period and present day electrolysis and thermolysis practice: only twenty-seven states currently require licensing for permanent hair removal, which is a procedure with rare but potentially serious complications.

Two cases of contact dermatitis from electroplating solutions were attributed to irritation from cyanide salts. Both demonstrated similar clinical features. In neither could concomitant contact allergy to other constituents of the plating solutions be demonstrated. In one case, irritation could not be attributed to the alkalinity of the plating solution. Contact dermatitis from cyanide plating solutions may be associated with systemic symptoms, since cyanide is rapidly absorbed through the skin. Poor handling and hygiene techniques in the workplace should be corrected immediately.

The purpose of this study was to investigate mortality patterns of aluminum reduction plant workers. A cohort was formed of 21,829 workers with five or more years employment in 14 reduction plants. Progress of the study was reported quarterly to a Tripartite Committee consisting of representatives from labor, management and government. Although the results of other studies relative to an excess of lung cancer in aluminum workers were not confirmed, there were indications of a higher than expected mortality in pancreatic cancer, lymphohematopoietic cancers, genitourinary cancer, nonmalignant respiratory disease and benign and unspecified neoplasms.