Is sarcopenia a better predictor of complications than body mass index? Sarcopenia and surgical outcomes in patients with rectal cancer.

AIM: Sarcopenia, or a reduction of lean muscle mass, is associated with poorer outcomes in cancer patients. Few previous studies have examined this potentially correctable risk factor in patients with locally advanced rectal cancer. METHOD: Skeletal muscle mass index was measured retrospectively on initial staging CT scans of patients undergoing chemoradiation followed by radical resection for rectal cancer for the period 2007-2013. Patients were categorized as sarcopenic or nonsarcopenic and differences in terms of demographics, pre-, peri- and postoperative outcomes were examined. RESULTS: Forty-seven patients were included; their mean age was 59.3 (36-82) years and 61.7% were men. We considered that 55.2% of men and 44.4% of women were sarcopenic; the overall prevalence of sarcopenia was 51.1%. Age, preoperative haemoglobin and albumin were significantly related to sarcopenia. Body mass index (BMI) and obesity (BMI > 30 kg/m2 ) were not associated with sarcopenia. Blood transfusions were more frequent in sarcopenic patients (P = 0.001). Although readmissions and length of stay were not increased, overall postoperative complications were significantly higher in sarcopenic patients (P = 0.03). Neither BMI nor obesity was associated with postoperative complications. CONCLUSION: Sarcopenia was present in over 50% of patients with locally advanced rectal cancer at diagnosis. It was associated with a higher incidence of both blood transfusion and postoperative complications. BMI did not correlate with these negative outcomes. Sarcopenia may be a better predictor of surgical outcomes than BMI or obesity.

Classification of Cannabis Strains Based on their Chemical Fingerprint-A Broad Analysis of Chemovars in the German Market.

Introduction: Cannabis cultivars were usually categorized based on their genetic profile as sativa, indica, or hybrid types. However, these three criteria do not allow sufficient differentiation between the numerous varieties of cannabis strains. Furthermore, this classification is based on morphological and bio-geographical properties of the plants and does not represent the chemical composition of different cultivars. The concentration of cannabinoids and terpenes are crucial for the pharmacological effect, not only because of the known entourage effect, and therefore needs to be considered by categorization. Materials and Methods: A total of 140 medicinal cannabis flowers available on the German market were analyzed regarding their individual terpene profile using GC-MS analysis. Statistical evaluation was performed to investigate correlations and data relations as well as for clustering. Results: Multivariate analysis showed correlations between individual terpenes. However, there was no statistical correlation between terpene profiles and their respective genetic profile. Terpene profiles of sativa, indica, and hybrid strains are quite heterogenous and clearly showed that there is no relation between terpenes and the estimated pharmacological effect. As a result, we suggest a new classification system based on individual terpene profiles to faster a comprehensive understanding of the expected medical effect. Discussion: Considering main terpenes, we established a concept of six clusters with various terpene profiles being attributed to different medicinal applications. We excluded tetrahydrocannabinol (THC) and cannabidiol (CBD) content from clustering as most of the strains were THC dominant and therefore distort the results. Our pattern of strains with similar terpene profiles might refine the existing classes of chemotypes with different THC:CBD content. Conclusion: The categorization of cannabis strains based on their terpene profiles allows a clearer, finer and, above all, more meaningful classification than the existing sativa/indica classification. Due to the entourage effect and the interactions between cannabinoids and terpenes, this group of substances is also given the necessary consideration when selecting the right medicine for the individual. Within the next steps, further studies are needed with the aim of mapping clinical validated effects to our chemovars. If it is possible to correlate therapy of symptoms to specific chemical profiles personalized cannabinoid therapy will be possible.

[An interesting case: recovery of a transmurally penetrated abdominal pad by the means of laparoscopy]. / Der interessante Fall: Laparoskopisch unterstützte Bergung eines transmural penetrierten Bauchtuches.

Lymphangiomas are rare benign tumors. In most cases, resection is necessary to obtain a precise histopathological analysis. There are capillary, caverous and cystic lymphangiomas. The therapy of choice is a complete excision. Recurrence has been reported after incomplete resection. We present the case of a 45-year-old man with a lymphangioma of the omentum minus and -review the literature.

Dementia in a retired world boxing champion: case report and literature review.

OBJECTIVE: Dementia in retired boxers, also referred to as "dementia pugilistica" (DP), is usually attributed to repeated concussive and subconcussive blows to the head. We report the case of a former world boxing champion whose progressive cognitive decline could be ascribed to DP, cerebral infarcts and Wernicke-Korsakoff syndrome. This case demonstrates that dementia in retired boxers may be caused and/or exacerbated by etiologic factors other than DP. MATERIALS AND METHODS: We correlated the clinical features with the histochemical and immunohistochemical changes observed on autopsy brain material from a retired boxer, reviewed the literature on boxing-related dementia, and compared our findings with previous reports on DP. RESULTS: Neuropathologic examination revealed numerous neurofibrillary tangles (NFTs), rare neuritic plaques (NPs), multiple cerebral infarcts, fenestrated septum pellucidum, atrophic and gliotic mamillary bodies, and pale substantia nigra and locus ceruleus. CONCLUSIONS: Our neuropathologic data confirmed the notion that dementia in retired boxers could be due to several factors such as DP, multiple cerebral infarcts and Wernicke-Korsakoff syndrome. Our findings illustrate the need to comprehensively examine former boxers with dementia as well as carefully evaluate the neuropathologic changes that may cause or contribute to the patient's cognitive and behavioral symptoms. Such an approach is crucial in order to provide prompt and more definitive therapies.

Duration of surgery affects the risk of complications following total hip arthroplasty.

AIMS: The aim of this study was to assess the influence of operating time on 30-day complications following total hip arthroplasty (THA). PATIENTS AND METHODS: We identified patients aged 18 years and older who underwent THA between 2006 and 2016 from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. We identified 131 361 patients, with a mean age of 65 years (sd 12), who underwent THA. We used multivariable regression to determine if the rate of complications and re-admissions was related to the operating time, while adjusting for relevant covariables. RESULTS: The mean operating time decreased from 118.3 minutes (29.0 to 217.0) in 2006, to 89.6 minutes (20.0 to 240.0) in 2016. After adjustment for covariables, operating times of between 90 and 119 minutes increased the risk of minor complications by 1.2 (95% confidence interval (CI) 1.1 to 1.3), while operating times of between 120 and 179 minutes increased the risk of major complications by 1.4 (95% CI 1.3 to 1.6) and minor complications by 1.4 (95% CI 1.2 to 1.5), and operating times of 180 minutes or more increased the risk of major complications by 2.1 (95% CI 1.8 to 2.6) and minor complications by 1.9 (95% CI 1.6 to 2.3). There was no difference in the overall risk of complications for operating times of between 20 and 39, 40 and 59, or 60 and 89 minutes (p > 0.05). Operating times of between 40 and 59 minutes decreased the risk of re-admission by 0.88 (95% CI 0.79 to 0.97), while operating times of between 120 and 179 minutes, and of 180 minutes or more, increased the risk of re-admission by 1.2 (95% CI 1.1 to 1.3) and 1.6 (95% CI 1.3 to 1.8), respectively. CONCLUSION: These findings suggest that an operating time of more than 90 minutes may be an independent predictor of major and minor complications, as well as re-admission, following THA, and that an operating time of between 40 and 90 minutes may be ideal. Prospective studies are required to confirm these findings. Cite this article: Bone Joint J 2019;101-B(6 Supple B):51-56.

Same-day and delayed hospital discharge are associated with worse outcomes following total knee arthroplasty.

AIMS: To evaluate the influence of discharge timing on 30-day complications following total knee arthroplasty (TKA). PATIENTS AND METHODS: We identified patients aged 18 years or older who underwent TKA between 2005 and 2016 from the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) database. We propensity score-matched length-of-stay (LOS) groups using all relevant covariables. We used multivariable regression to determine if the rate of complications and re-admissions differed depending on LOS. RESULTS: Our matched cohort consisted of 76 246 TKA patients (mean age 67 years (sd 9)). Patients whose LOS was zero and four days had an increased risk of major complications by an odds ratio (OR) of 1.8 (95% confidence interval (CI) 1.0 to 3.2) and 1.5 (95% CI 1.2 to 1.7), respectively, compared with patients whose LOS was two days. Patients whose LOS was zero, three, and four days had an increased risk of minor complications (OR 1.8 (95% CI 1.3 to 2.7), 1.2 (95% CI 1.0 to 1.4), and 1.6 (95% CI 1.4 to 1.9), respectively), compared with patients whose LOS was two days. In addition, a LOS of three days increased the risk of re-admission by an OR of 1.2 (95% CI 1.0 to 1.3), and a LOS of four days increased the risk of re-admission by an OR of 1.5 (95% CI 1.3 to 1.6), compared with a LOS of two days. CONCLUSION: Patients discharged on days one to two postoperatively following TKA appear to have reduced major and minor complications compared with discharge on the day of surgery, or on days three to four. Prospective clinical data are required to confirm these findings. Cite this article: Bone Joint J 2019;101-B(7 Supple C):70-76.

Breast cancer surgery decreases serum brain-derived neurotrophic factor concentrations in middle aged women: relationship to the serum C-reactive protein concentration.

The aim of this study was to establish the effect of breast cancer surgery in middle aged women on the serum (s) and plasma (p) brain-derived neurotrophic factor concentrations [BDNF]s and [BDNF]p, respectively, in relation to the serum C-reactive protein [CRP]s concentration measured before and at 24 hours after surgery. Eighteen patients with recently diagnosed breast cancer (mean ± SE): age 49.1 ± 1.6 years, body mass 69.8 ± 2.2 kg, BMI 25.8 ± 0.8 kg m-2, participated in this study. The [BDNF]s before the surgery amounted to 25 523 ± 1 416 pg ml-1. At 24 h after the surgery it decreased to 21 551 ± 998 pg ml-1 (P = 0.004). This decrease was accompanied by a significant (P = 0.001) decrease in the platelet count (PLT) from 254.7 ± 12.2 k µl-1 before, to 228.8 ± 9.7 k µl-1 after the surgery. The [CRP]s increased from 3.59 ± 0.79 mg l-1 before to 25.04 ± 4.65 mg l-1 after the surgery (P = 0.002). A significant positive correlation was found between the [BDNF]s and the PLT both before (P = 0.003) as well as after the surgery (P = 0.027). Moreover, a significant positive correlation (P = 0.046) was found between [BDNF]s and the [CRP] s before the surgery. At 24 h after the surgery the [BDNF]s and the [CRP]s still correlated positively (P = 0.044), despite the fact that the surgery significantlly decresed the [BDNF]s and increased [CRP]s. No significant effect of the surgery on the [BDNF]p was found. We have concluded that serum BDNF concentration in breast cancer patients positively correlates with serum CRP both before and at 24 h after the surgery. Moreover, breast cancer surgery decreases serum BDNF concentration at 24 h after operation and increases [CRP]s.

Surgical repair versus conservative treatment and subacromial decompression for the treatment of rotator cuff tears: a meta-analysis of randomized trials.

AIMS: The purpose of this study was to compare the effectiveness of surgical repair to conservative treatment and subacromial decompression for the treatment of chronic/degenerative tears of the rotator cuff. MATERIALS AND METHODS: PubMed, Cochrane database, and Medline were searched for randomized controlled trials published until March 2018. Included studies were assessed for methodological quality, and data were extracted for statistical analysis. The systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: Six studies were included. Surgical repair resulted in a statistically significantly better Constant-Murley Score (CMS) at one year compared with conservative treatment (mean difference 6.15; p = 0.002) and subacromial decompression alone (mean difference 5.81; p = 0.0004). In the conservatively treated group, 11.9% of patients eventually crossed over to surgical repair. CONCLUSION: The results of this review show that surgical repair results in significantly improved outcomes when compared with either conservative treatment or subacromial decompression alone for degenerative rotator cuff tears in older patients. However, the magnitude of the difference in outcomes between surgery and conservative treatment may be small and the 'success rate' of conservative treatment may be high, allowing surgeons to be judicious in choosing those patients who are most likely to benefit from surgery. Cite this article: Bone Joint J 2019;101-B:1100-1106.

Slow voltage-dependent changes in channel open-state probability underlie hysteresis of NMDA responses in Mg(2+)-free solutions.

Many single-channel studies rely on the assumption that the channels are functioning under steady-state conditions. In examining the basis for nonlinear whole-cell current-voltage curves in Mg(2+)-free solutions we discovered that N-methyl-D-aspartate (NMDA) channels in excised patches reversibly shifted their open-state probability (Po) in a voltage-dependent way, exhibiting approximately 3- to 4-fold greater Po at positive potentials than at rest. Changes in Po were mainly attributable to shifts in frequency of channel opening. Po changed remarkably slowly (2-15 min), explaining the hysteresis of whole-cell current-voltage curves obtained in nonequilibrium conditions. The slow increase in Po provides a mechanism by which NMDA channels can substantially increase Ca2+ influx in cells depolarized for prolonged periods of time and may play a role in excitotoxicity.

Influence of Polypharmacy on the Quality of Life in Stable Kidney Transplant Recipients.

BACKGROUND: Kidney transplant recipients are frequently treated for other medical conditions and experience polypharmacy. The aim of our study was to evaluate quality of life in relation to medicines' burden in these patients. METHODS: We studied 136 unselected patients with mean post-transplant time of 7.2 ± 4.6 years. Quality of life was evaluated using a validated Polish version of the Kidney Disease Quality of Life-Short Form questionnaire. Data concerning the type (generic name) and number of currently prescribed medications were collected by interview survey. The participants were divided into 3 groups: group 1, patients with a maximum of 4 different medications (n = 37); group 2, patients with 4 to 9 medications (n = 76); and group 3, patients receiving at least 10 different medications (n = 23). RESULTS: The number of medicines taken regularly ranged from 2 to 16. Patients with ≥10 drugs had the highest body mass index and lowest estimated glomerular filtration rate. Patients treated with ≥10 drugs, compared to patients from the 2 other groups, had presented lower subscales results concerning the physical functioning (65.9 vs 84.5 in group 1 and 83.4 in group 2, P < .001 for both comparisons), pain (57.2 vs 82.7 and 76.5, respectively, P < .001 for both), social function (66.8 vs 82.1 and 80.4, respectively, P = .04 for both), and energy/fatigue (54.8 vs 67.7, P = .03 and 65.4, P < .05). Multivariate regression analysis revealed that the number of drugs independently influenced physical functioning, pain, and social function subscales. CONCLUSIONS: Polypharmacy is associated with lower quality of life in patients after successful kidney transplantation. The negative impact of polypharmacy is particularly seen regarding physical functioning and pain severity.

Melatonin and serotonin effects on gastrointestinal motility.

The gastrointestinal tract represents the most important extra pineal source of melatonin. Presence of melatonin (M) suggests that this hormone is somehow involved in digestive pathophysiology. Release of GI melatonin from serotonin-rich enterochromaffin EC cells of the GI mucosa suggest close antagonistic relationship with serotonin (S) and seem to be related to periodicity of food intake. Food deprivation resulted in an increase of tissue and plasma concentrations of M. Its also act as an autocrine and paracrine hormone affecting not only epithelium and immune system but also smooth muscle of the digestive tract. Low doses M improve gastrointestinal transit and affect MMC. M reinforce MMCs cyclic pattern but inhibits spiking bowel activity. Pharmacological doses of M delay gastric emptying via mechanisms that involve CCK2 and 5HT3 receptors. M released in response to lipid infusion exerts a modulatory influence that decreases the inhibitory effects of the ileal brake on gastric emptying. On isolated bowel S induces dose dependent increase in tone and reduction in amplitude of contraction which is affected by M. M reduced the tone but not amplitude or frequency of contraction. M is a promising therapeutic agent for IBS with activities independent of its effects on sleep, anxiety or depression. Since of its unique properties M could be considered for prevention or treatment of colorectal cancer, ulcerative colitis, gastric ulcers and irritable bowel syndrome.

Parallel versus serial processing: new vistas on the distributed organization of the visual system.

Recent functional studies question the validity of the hierarchical model of organization for processing visual information in cortical areas. The results of these studies suggest that beyond the primary visual cortex (V1), information is not serially processed through successive cortical areas, but that it is simultaneously processed in several areas. The idea that visual information is functionally segregated into different, parallel channels as it circulates through V1 and V2 towards V4 and the middle temporal visual area is also challenged by recent studies that report a smaller degree of functional specialization within the visual areas than previously thought.

Crossmodal audio-visual interactions in the primary visual cortex of the visually deprived cat: a physiological and anatomical study.

Blind individuals often demonstrate enhanced non-visual perceptual abilities. Neuroimaging and transcranial magnetic stimulation experiments have suggested that computations carried out in the occipital cortex may underlie these enhanced somatosensory or auditory performances. Thus, cortical areas that are dedicated to the analysis of the visual scene may, in the blind, acquire the capacity to participate in other sensory processing. However, the neural substrate that underlies this transfer of function is not fully characterized. Here we studied the synaptic and anatomical basis of this phenomenon in cats that were visually deprived by dark rearing, either early visually deprived after birth (EVD), or late visually deprived after the end of the critical period (LVD); data were compared with those obtained in normally reared cats (controls). The presence of synaptic and spike responses to auditory stimulation was examined by means of intracellular recordings in area 17 and the border between areas 17 and 18. While none of the cells recorded in control and LVD cats showed responses to sound, 14% of the cells recorded in EVD cats showed both subthreshold synaptic responses and suprathreshold spike responses to auditory stimuli. Synaptic responses were of small amplitude, but well time-locked to the stimuli and had an average latency of 30+/-12ms. In an attempt to identify the origin of the inputs carrying auditory information to the visual cortex, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected in the visual cortex and retrograde labeling examined in the cortex and thalamus. No significant retrograde labeling was found in auditory cortical areas. However, the proportion of neurons projecting from supragranular layers of the posteromedial and posterolateral parts of the lateral suprasylvian region to V1 was higher than that in control cats. Retrograde labeling in the lateral geniculate nucleus showed no difference in the total number of neurons between control and visually deprived cats, but there was a higher proportion of labeling in C-laminae in deprived cats. Labeled cells were not found in the medial geniculate nucleus, a thalamic relay for auditory information, in either control or visually deprived cats. Finally, immunohistochemistry of the visual cortex of deprived cats revealed a striking decrease in pavalbumin- and calretinin-positive neurons, the functional implications of which we discuss.

Ionic mechanisms underlying repetitive high-frequency burst firing in supragranular cortical neurons.

Neocortical neurons in awake, behaving animals can generate high-frequency (>300 Hz) bursts of action potentials, either in single bursts or in a repetitive manner. Intracellular recordings of layer II/III pyramidal neurons were obtained from adult ferret visual cortical slices maintained in vitro to investigate the ionic mechanisms by which a subgroup of these cells generates repetitive, high-frequency burst discharges, a pattern referred to as "chattering." The generation of each but the first action potential in a burst was dependent on the critical interplay between the afterhyperpolarizations (AHPs) and afterdepolarizations (ADPs) that followed each action potential. The spike-afterdepolarization and the generation of action potential bursts were dependent on Na(+), but not Ca(2+), currents. Neither blocking of the transmembrane flow of Ca(2+) nor the intracellular chelation of free Ca(2+) with BAPTA inhibited the generation of intrinsic bursts. In contrast, decreasing the extracellular Na(+) concentration or pharmacologically blocking Na(+) currents with tetrodotoxin, QX-314, or phenytoin inhibited bursting before inhibiting action potential generation. Additionally, a subset of layer II/III pyramidal neurons could be induced to switch from repetitive single spiking to a burst-firing mode by constant depolarizing current injection, by raising extracellular K(+) concentrations, or by potentiation of the persistent Na(+) current with the Na(+) channel toxin ATX II. These results indicate that cortical neurons may dynamically regulate their pattern of action potential generation through control of Na(+) and K(+) currents. The generation of high-frequency burst discharges may strongly influence the response of postsynaptic neurons and the operation of local cortical networks.

Membrane mechanisms underlying contrast adaptation in cat area 17 in vivo.

Contrast adaptation is a psychophysical phenomenon, the neuronal bases of which reside largely in the primary visual cortex. The cellular mechanisms of contrast adaptation were investigated in the cat primary visual cortex in vivo through intracellular recording and current injections. Visual cortex cells, and to a much less extent, dorsal lateral geniculate nucleus (dLGN) neurons, exhibited a reduction in firing rate during prolonged presentations of a high-contrast visual stimulus, a process we termed high-contrast adaptation. In a majority of cortical and dLGN cells, the period of adaptation to high contrast was followed by a prolonged (5-80 sec) period of reduced responsiveness to a low-contrast stimulus (postadaptation suppression), an effect that was associated, and positively correlated, with a hyperpolarization of the membrane potential and an increase in apparent membrane conductance. In simple cells, the period of postadaptation suppression was not consistently associated with a decrease in the grating modulated component of the evoked synaptic barrages (the F1 component). The generation of the hyperpolarization appears to be at least partially intrinsic to the recorded cells, because the induction of neuronal activity with the intracellular injection of current resulted in both a hyperpolarization of the membrane potential and a decrease in the spike response to either current injections or visual stimuli. Conversely, high-contrast visual stimulation could suppress the response to low-intensity sinusoidal current injection. We conclude that control of the membrane potential by intrinsic neuronal mechanisms contributes importantly to the adaptation of neuronal responsiveness to varying levels of contrast. This feedback mechanism, internal to cortical neurons, provides them with the ability to continually adjust their responsiveness as a function of their history of synaptic and action potential activity.

Cellular mechanisms of long-lasting adaptation in visual cortical neurons in vitro.

The cellular mechanisms of spike-frequency adaptation during prolonged discharges and of the slow afterhyperpolarization (AHP) that follows, as occur in vivo with contrast adaptation, were investigated with intracellular recordings of cortical neurons in slices of ferret primary visual cortex. Intracellular injection of 2 Hz sinusoidal or constant currents for 20 sec resulted in a slow (tau = 1-10 sec) spike-frequency adaptation, the degree of which varied widely among neurons. Reducing either [Ca(2+)](o) or [Na(+)](o) reduced the rate of spike-frequency adaptation. After the prolonged discharge was a slow (12-75 sec) AHP that was associated with an increase in membrane conductance and a rightward shift in the discharge frequency versus injected current relationship. The reversal potential of the slow AHP was sensitive to changes in [K(+)](o), indicating that it was mediated by a K(+) current. Blockade of transmembrane Ca(2+) conductances did not reduce the slow AHP. In contrast, reductions of [Na(+)](o) reduced the slow AHP, even in the presence of pronounced Ca(2+) spikes. We suggest that the activation of Na(+)-activated and Ca(2+)-activated K(+) currents plays an important role in prolonged spike-frequency adaptation and therefore may contribute to contrast adaptation and other forms of adaptation in the visual system in vivo.

Mechanisms of blockade of excitatory amino acid receptor channels.

Ion channels coupled to NMDA, kainate and AMPA receptors are the target of pharmacological regulation by a variety of drugs and ions. While these channels are all nonselectively permeated by Na+ and K+ ions, the NMDA receptor-channel complex contains a number of pharmacological sites distinct from those found on the others. For example, Mg2+ ions rapidly and reversibly block open NMDA channels in a highly voltage-dependent manner. Its extreme voltage dependence suggests that the Mg2+ binding site lies deep within the ion channel pore. By contrast the voltage-dependent block of activated channels by the dissociative anesthetic 'slow channel blockers' has unusual characteristics. In the fourth article in our series on excitatory amino acids, John MacDonald and Linda Nowak analyse the characteristics of these two types of block and describe the hypotheses that have been put forward to explain the mechanisms involved.

Parylene-based flexible neural probes with PEDOT coated surface for brain stimulation and recording.

Implantable neural prosthetics devices offer a promising opportunity for the restoration of lost functions in patients affected by brain or spinal cord injury, by providing the brain with a non-muscular channel able to link machines to the nervous system. Nevertheless current neural microelectrodes suffer from high initial impedance and low charge-transfer capacity because of their small-feature geometry (Abidian et al., 2010; Cui and Zhou, 2007). In this work we have developed PEDOT-modified neural probes based on flexible substrate capable to answer to the three critical requirements for neuroprosthetic device: efficiency, lifetime and biocompatibility. We propose a simple procedure for the fabrication of neural electrodes fully made of Parylene-C, followed by an electropolymerization of the active area with the conductive polymer PEDOT that is shown to greatly enhance the electrical performances of the device. In addition, the biocompatibility and the very high SNR exhibited during signal recording make our device suitable for long-term implantation.

Bicuculline: a convulsant with synaptic and nonsynaptic actions.

The convulsant bicuculline (BICUC) had both synaptic and nonsynaptic actions on mouse spinal cord neurons in primary dissociated cell culture. BICUC antagonized postsynaptic responses to the inhibitory neurotransmitter GABA (a synaptic action) and produced direct membrane depolarization by blocking a membrane potassium conductance and directly prolonging calcium-dependent action potentials (nonsynaptic actions). In cultured spinal cord neurons, BICUC also produced paroxysmal depolarizing events (PDE), which might be equivalent to in vivo convulsant-induced bursting in spinal cord neurons or paroxysmal depolarizing shifts (PDS) in cortical neurons. Thus, the concentrations of BICUC producing both synaptic and nonsynaptic actions overlapped those producing paroxysmal activity. The results suggest that in addition to antagonism of GABA-mediated synaptic inhibition, direct nonsynaptic actions of BICUC may be required for some neurons to develop PDS.

Spread of stimulating current in the cortical grey matter of rat visual cortex studied on a new in vitro slice preparation.

Extracellular electrical stimulation of the cortical grey matter is very often used in electrophysiological studies, but the parameters of the stimulation itself have received only little attention. This study addresses the issue of the spread of stimulating current in rat visual areas 17 and 18a maintained in vitro. The preparation of the slices relied on a protocol making use of several of the means known to limit the effects of ischaemia: Halothane anaesthesia was used during the surgery and intracardiac perfusion was employed to reduce the brain temperature, to increase the intracerebral concentration of glucose and magnesium and to decrease that of calcium. The spread of stimulating current has been determined from strength-distance relationships established for the activation of axons. The strength-distance curves could be fitted by a quadratic relationship, indicating that the threshold current for the activation of an axon increases as the square of the distance separating it from the tip of the stimulating electrode. The slope of the regression line between threshold intensity and squared distance (k coefficient) is highly variable from one axon to another (range 2100-27 500 microA/mm2, median 8850 microA/mm2). Part of this variability is related to differences in conduction velocity. The theoretical number of axonal branches and axon initial segments activated by a given current intensity has been extrapolated from these experimental results.