First observation of 28O.

Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10-21 s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called 'doubly magic' nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.

Observation of a correlated free four-neutron system.

A long-standing question in nuclear physics is whether chargeless nuclear systems can exist. To our knowledge, only neutron stars represent near-pure neutron systems, where neutrons are squeezed together by the gravitational force to very high densities. The experimental search for isolated multi-neutron systems has been an ongoing quest for several decades1, with a particular focus on the four-neutron system called the tetraneutron, resulting in only a few indications of its existence so far2-4, leaving the tetraneutron an elusive nuclear system for six decades. Here we report on the observation of a resonance-like structure near threshold in the four-neutron system that is consistent with a quasi-bound tetraneutron state existing for a very short time. The measured energy and width of this state provide a key benchmark for our understanding of the nuclear force. The use of an experimental approach based on a knockout reaction at large momentum transfer with a radioactive high-energy 8He beam was key.

NSGO-OV-UMB1/ENGOT-OV30: A phase II study of durvalumab in combination with the anti-CD73 monoclonal antibody Oleclumab in patients with relapsed ovarian cancer.

OBJECTIVES: In patients with epithelial ovarian cancer (EOC), the clinical efficacy of monotherapy with immune checkpoint inhibitors (ICIs) against PD-1/PD-L1 is modest. To enhance response rates to these immunotherapeutic agents and broaden the indications for their use, new approaches involving combinational therapy are needed. The immune regulator CD73 is a potential target, as it promotes tumor escape by producing immunosuppressive extracellular adenosine in the tumor microenvironment. Here, we present the results from the NSGO-OV-UMB1/ENGOT-OV-30 trial evaluating the activity of combining the anti-CD73 antibody oleclumab with the anti-PD-L1 checkpoint inhibitor durvalumab in patients with recurrent EOC. METHODS: In this phase II open-label non-randomized study, patients with CD73-positive relapsed EOC were intravenously administered oleclumab (3000 mg, Q2W) and durvalumab (1500 mg, Q4W). The primary endpoint was disease control rate (DCR) at 16 weeks. The expression of PD-L1 and CD8 was assessed by immunohistochemistry of archival tumors. RESULTS: This trial included 25 patients with a median age of 66 years (47-77 years). Twenty-two patients were evaluable for treatment activity analysis. The DCR was 27%, the median progression-free survival was 2.7 months (95% CI: 2.2-4.2) and the median overall survival was 8.4 months (95% CI: 5.0-13.4). Infiltration of CD8+ cells and PD-L1 expression on tumor cells were observed in partially overlapping sets of 74% of the tumor samples. Neither CD8- nor PD-L1-positivity were significantly associated with better DCR. CONCLUSIONS: Combined treatment with oleclumab and durvalumab was safe and demonstrated limited anti-tumor activity in patients with recurrent EOC.

Serratia sp. CP-13 augments the growth of cadmium (Cd)-stressed Linum usitatissimum L. by limited Cd uptake, enhanced nutrient acquisition and antioxidative potential.

AIMS: The current study was aimed to evaluate the beneficial effects and bioremediation potential of a Cd-tolerant bacterial strain, Serratia sp. CP-13, on the physiological and biochemical functions of Linum usitatissimum L., under Cd stress. METHODS AND RESULTS: The bacterial strain was isolated from the wastewater collection point of Chakera, Faisalabad, Pakistan, as this place contains industrial wastewater of the Faisalabad region. The Serratia sp. CP-13, identified through 16S rRNA gene sequence analysis, exhibited a significant phyto-beneficial potential in terms of in vitro inorganic phosphate solubilization, indole-3-acetic acid production and 1-aminocyclopropane-1-carboxylic acid deaminase activity. Effects of Serratia sp. CP-13 inoculation on L. usitatissimum were evaluated by growing the plants in CdCl2 (0, 5 or 10 mg kg-1 dry soil)-spiked soil. Without inoculation of Serratia sp. CP-13, Cd stress significantly reduced the plant biomass as well as the quantity of proteins and photosynthetic pigments due to enhanced H2 O2 , malondialdehyde (MDA) contents and impaired nutrient homeostasis. Subsequently, Serratia sp. CP-13 increased the plant fresh and dry biomass, plant antioxidation capacity, whereas it decreased the lipid peroxidation under Cd stress. In parallel, Serratia sp. inoculation assisted the Cd-stressed plants to maintain an optimum level of nutrients (K, Ca, P, Mg, Fe and Mn). CONCLUSIONS: The isolated bacterial strain (Serratia sp. CP-13) when applied to Cd-stressed L. usitatissimum inhibited the Cd uptake, reduced Cd-induced lipid peroxidation, maintained the optimum level of nutrients and thereby, enhanced L. usitatissimum growth. The analysis of bio-concentration and translocation factor revealed that L. usitatissimum with Serratia sp. CP-13 inoculation sequestered Cd in plant rhizospheric zone. SIGNIFICANCE AND IMPACT OF THE STUDY: Serratia sp. CP-13 inoculation is a potential candidate for the development of low Cd-accumulating linseed and could be used for phytostabilization of Cd-contaminated rhizosphere/soil colloids.

Spontaneous conversion of first onset atrial fibrillation.

BACKGROUND/AIM: We studied all patients admitted to hospital with first onset atrial fibrillation (AF) to determine the probability of spontaneous conversion to sinus rhythm and to identify factors predictive of such a conversion. METHODS: We retrospectively reviewed charts of 438 consecutive patients admitted to hospital with first onset AF from 1 January 2006 to 31 December 2009. The patients were divided into two groups, recent onset AF defined as AF < 48 h or longer lasting AF, defined as AF > 48 h. RESULTS: Spontaneous conversion occurred in 54% (n = 203; 95% confidence interval: 49-59%). In the group with first onset AF < 48 h, spontaneous conversion occurred in 77%, compared with 36% in the group with first onset AF > 48 h. Logistic regression analysis identified duration of AF as a highly significant predictor of spontaneous conversion to sinus rhythm (odds ratio 5.9; 95% confidence interval: 4.0-8.6, P < 0.001). CONCLUSIONS: Spontaneous conversion occurred in 54%, increasing to 77% when AF had persisted less than 48 h.

Non-invasive diagnostics of the maxillary and frontal sinuses based on diode laser gas spectroscopy.

PROBLEM: Suspected, but objectively absent, rhinosinusitis constitutes a major cause of visits to the doctor, high health care costs, and the over-prescription of antibiotics, contributing to the serious problem of resistant bacteria. This situation is largely due to a lack of reliable and widely applicable diagnostic methods. METHOD: A novel method for the diagnosis of rhinosinusitis based on non-intrusive diode laser gas spectroscopy is presented. The technique is based on light absorption by free gas (oxygen and water vapour) inside the sinuses, and has the potential to be a complementary diagnostic tool in primary health care. The method was evaluated on 40 patients with suspected sinus problems, referred to the diagnostic radiology clinic for low-dose computed tomography (CT), which was used as the reference technique. MAIN RESULTS: The data obtained with the new laser-based method correlated well with the grading of opacification and ventilation using CT. The sensitivity and specificity were estimated to be 93% and 61%, respectively, for the maxillary sinuses, and 94% and 86%, respectively, for the frontal sinuses. Good reproducibility was shown. PRINCIPAL CONCLUSION: The laser-based technique presents real-time clinical data that correlate well to CT findings, while being non-intrusive and avoiding the use of ionizing radiation.

Mercury distribution across 14 U.S. Forests. Part I: spatial patterns of concentrations in biomass, litter, and soils.

Results from a systematic investigation of mercury (Hg) concentrations across 14 forest sites in the United States show highest concentrations in litter layers, strongly enriched in Hg compared to aboveground tissues and indicative of substantial postdepositional sorption of Hg. Soil Hg concentrations were lower than in litter, with highest concentrations in surface soils. Aboveground tissues showed no detectable spatial patterns, likely due to 17 different tree species present across sites. Litter and soil Hg concentrations positively correlated with carbon (C), latitude, precipitation, and clay (in soil), which together explained up to 94% of concentration variability. We observed strong latitudinal increases in Hg in soils and litter, in contrast to inverse latitudinal gradients of atmospheric deposition measures. Soil and litter Hg concentrations were closely linked to C contents, consistent with well-known associations between organic matter and Hg, and we propose that C also shapes distribution of Hg in forests at continental scales. The consistent link between C and Hg distribution may reflect a long-term legacy whereby old, C-rich soil and litter layers sequester atmospheric Hg depositions over long time periods. Based on a multiregression model, we present a distribution map of Hg concentrations in surface soils of the United States.

Vestibular PREHAB and gentamicin before schwannoma surgery may improve long-term postural function.

BACKGROUND: Unilateral vestibular deafferentation (uVD), as performed in vestibular schwannoma surgery, results in a chronic vestibular deficit, though most of the insufficiency can be compensated by other sensory input. By vestibular training (prehabituation) performed before surgery, motor adaptation processes can be instigated before the actual lesion. The adaptation processes of the altered sensory input could be affected if the vestibular ablation and surgery were separated in time, by pretreating patients who have remaining vestibular function with gentamicin. OBJECTIVE: To determine whether presurgical deafferentation would affect postsurgery postural control also in a long-term perspective (6 months). METHOD: 41 patients subjected to trans-labyrinthine schwannoma surgery were divided into four groups depending on the vestibular activity before surgery (with no clinical significant remaining function n = 17; with remaining function n = 8), whether signs of central lesions were present (n = 10), and if patients with remaining vestibular activity were treated with gentamicin with the aim to produce uVD before surgery (n = 6). The vibratory posturography recordings before surgery and at the follow-up 6 months after surgery were compared. RESULTS: The subjects pretreated with gentamicin had significantly less postural sway at the follow-up, both compared with the preoperative recordings and compared with the other groups. CONCLUSION: The results indicate that by both careful sensory training and separating the surgical trauma and the effects of uVD in time, adaptive processes can develop more efficiently to resolve sensory conflicts, resulting in a reduction of symptoms not only directly after surgery but also perhaps up to 6 months afterwards.

Atmospheric deposition of metals to forest vegetation.

Atmospheric deposition during the growing season contributes one-third or more of the estimated total flux of lead, zinc, and cadium from the forest canopy to soils beneath an oak stand in the Tennessee Valley but less than 10 percent of the flux of manganese. The ratio of the wet to dry deposition flux to the vegetation during this period ranges from 0.1 for manganese to 0.8 for lead to approximately 3 to 4 for cadmium and zinc. Interactions between metal particles deposited on dry leaf surfaces and subsequent acid precipitation can result in metal concentrations on leaves that are considerably higher than those in rain alone.

Atmospheric deposition and canopy interactions of major ions in a forest.

Airborne particles and vapors contributed significantly to the nutrient requirements and the pollutant load of a mixed hardwood forest in the eastern United States. Dry deposition was an important mechanism of atmospheric input to the foliar canopy, occurring primarily by vapor uptake for sulfur, nitrogen, and free acidity and by particle deposition for calcium and potassium. The canopy retained 50 to 70 percent of the deposited free acidity and nitrogen, but released calcium and potassium. Atmospheric deposition supplied 40 and 100 percent of the nitrogen and sulfur requirements, respectively, for the annual woody increment. This contribution was underestimated significantly by standard bulk deposition collectors.

Potassium-induced decrease in cytosolic Na+ alleviates deleterious effects of salt stress on wheat (Triticum aestivum L.).

Accumulation of NaCl in soil causes osmotic stress in plants, and sodium (Na+ ) and chloride (Cl- ) cause ion toxicity, but also reduce the potassium (K+ ) uptake by plant roots and stimulate the K+ efflux through the cell membrane. Thus, decreased K+ /Na+ ratio in plant tissue lead us to hypothesise that elevated levels of K+ in nutrient medium enhance this ratio in plant tissue and cytosol to improve enzyme activation, osmoregulation and charge balance. In this study, wheat was cultivated at different concentrations of K+ (2.2, 4.4 or 8.8 mm) with or without salinity (1, 60 or 120 mm NaCl) and the effects on growth, root and shoot Na+ and K+ distribution and grain yield were determined. Also, the cytosolic Na+ concentration was investigated, as well as photosynthesis rate and water potential. Salinity reduced fresh weight of both shoots and roots and dry weight of roots. The grain yield was significantly reduced under Na+ stress and improved with elevated K+ fertilisation. Elevated K+ level during cultivation prevented the accumulation of Na+ into the cytosol of both shoot and root protoplasts. Wheat growth at vegetative stage was transiently reduced at the highest K+ concentration, perhaps due to plants' efforts to overcome a high solute concentration in the plant tissue, nevertheless grain yield was increased at both K+ levels. In conclusion, a moderately elevated K+ application to wheat seedlings reduces tissue as well as cytosolic Na+ concentration and enhances wheat growth and grain yield by mitigating the deleterious effects of Na+ toxicity.

RSDL decontamination of human skin contaminated with the nerve agent VX.

Dermal exposure to low volatile organophosphorus compounds (OPC) may lead to penetration through the skin and uptake in the blood circulation. Skin decontamination of toxic OPCs, such as pesticides and chemical warfare nerve agents, might therefore be crucial for mitigating the systemic toxicity following dermal exposure. Reactive skin decontamination lotion (RSDL) has been shown to reduce toxic effects in animals dermally exposed to the nerve agent VX. In the present study, an in vitro flow-through diffusion cell was utilized to evaluate the efficacy of RSDL for decontamination of VX exposed to human epidermis. In particular, the impact of timing in the initiation of decontamination and agent dilution in water was studied. The impact of the lipophilic properties of VX in the RSDL decontamination was additionally addressed by comparing chemical degradation in RSDL and decontamination efficacy between the VX and the hydrophilic OPC triethyl phosphonoacetate (TEPA). The epidermal membrane was exposed to 20, 75 or 90% OPC diluted in deionized water and the decontamination was initiated 5, 10, 30, 60 or 120min post-exposure. Early decontamination of VX with RSDL, initiated 5-10min after skin exposure, was very effective. Delayed decontamination initiated 30-60min post-exposure was less effective but still the amount of penetrated agent was significantly reduced, while further delayed start of decontamination to 120min resulted in very low efficacy. Comparing RSDL decontamination of VX with that of TEPA showed that the decontamination efficacy at high agent concentrations was higher for VX. The degradation mechanism of VX and TEPA during decontamination was dissected by 31P NMR spectroscopy of the OPCs following reactions with RSDL and its three nucleophile components. The degradation rate was clearly associated with the high pH of the specific solution investigated; i.e. increased pH resulted in a more rapid degradation. In addition, the solubility of the OPC in RSDL also influenced the degradation rate since the degradation of VX was significantly faster when the NMR analysis was performed in the organic solvent acetonitrile compared to water. In conclusion, we have applied the in vitro flow-through diffusion cell for evaluation of skin decontamination procedures of human epidermis exposed to OPCs. It was demonstrated that early decontamination is crucial for efficient mitigation of epidermal penetration of VX and that almost complete removal of the nerve agent from the skin surface is possible. Our data also indicate that the pH of RSDL together with the solubility of OPC in RSDL are of primary importance for the decontamination efficacy.

Low adiponectin levels at baseline and decreasing adiponectin levels over 10 years of follow-up predict risk of the metabolic syndrome.

AIM: Adiponectin is the most abundant adipokine and may play a key role in the interplay between obesity, inflammation, insulin resistance and the metabolic syndrome (MetS). Thus, this large population-based cohort investigated whether adiponectin at baseline and/or a decrease in adiponectin during follow-up is associated prospectively with the risk of incident MetS. METHODS: Using a prospective study design, the development of MetS was examined in 1134 healthy participants from the community. Plasma adiponectin was measured at study entry and again after a median follow-up of 9.4 years (IQR: 9.2-9.7). During follow-up, 187 participants developed MetS, and 439 presented with at least two components of MetS. RESULTS: During follow-up, adiponectin decreased in participants who developed MetS, whereas adiponectin was increased in those who did not develop MetS (P<0.001). Those with low adiponectin levels (quartile 1) at baseline had an increased risk of developing MetS (OR: 2.92, 2.08-6.97; P<0.001) compared with those with high levels (quartile 4). After adjusting for confounding variables, low adiponectin levels at baseline remained independently associated with MetS (OR: 2.24, 1.11-4.52; P=0.017). Similarly, participants with a decrease in adiponectin during follow-up also had an increased risk of MetS (OR: 2.96, 2.09-4.18; P<0.001). This association persisted after multivariable adjustments, including for baseline adiponectin (OR: 4.37, 2.77-6.97; P<0.001). Finally, adiponectin levels at follow-up were inversely associated with an increase in the number of components of MetS (P<0.001); geometric mean adiponectin levels were 9.5mg/L (95% CI: 9.0-10.0) for participants with no components vs 7.0mg/L (95% CI: 6.3-7.9) for those with four to five components. CONCLUSIONS/INTERPRETATION: Low plasma adiponectin levels at baseline and decreasing adiponectin levels during follow-up are both associated with an increased risk of MetS.

Methodology and dosimetry in adrenal medullary imaging with iodine-131 MIBG.

Iodine-131 MIBG scans were performed in 59 patients in order to localize intra- or extra-adrenal pheochromocytomas (pheos), or to visualize hyperplastic adrenal medulla. Images were obtained from the pelvis to the base of the skull on Days 1, 4, and 7 after tracer injection. The 15 patients with histopathologic confirmation of adrenal medullary disease had positive scans. In three of these, the pheos were visible only on images obtained on Day 7. One scan was false negative. After excluding patients with a predisposition to adrenal medullary disease, nine subjects (28%) without verification of pheo displayed adrenal uptake of the radionuclide. Late images produce a low rate of false-negative scans; the background activity diminishes and even small pheos can be detected. In order to increase the quality of late images, 40 MBq [131I]MIBG was used instead of 20 MBq. The dosimetric considerations are discussed.

Radioiodine treatment of hyperthyroidism in a pregnant women.

UNLABELLED: We describe the effects of radioiodine treatment of a pregnant thyrotoxic woman. METHODS: The woman received 500 MBq of (131)I in her 20th gestational week. The pregnancy was discovered 10 days after radioiodine administration. A gamma camera examination of the abdomen at that time showed a distinct focus of activity, which was interpreted as the fetal thyroid. Gamma camera examinations of the mother and fetus were performed at 10, 11, 12, 13 and 18 days after administration of the therapeutic activity and were the basis of dose calculations. The child was examined by hormone tests and mental performance tests, up to 8 yr after birth. RESULTS: The uptake at 24 hr postadministration was calculated to be 10 MBq (2%) in the fetal thyroid gland. The effective half-life was 2.5 days, giving a calculated absorbed dose to the fetal thyroid gland of 600 Gy, which is considered to be an ablative dose. The calculated absorbed dose to the fetal body, including brain, was about 100 mGy, and 40 mGy to the fetal gonads. Doses were estimated taking contributions from radioiodine in the mother, the fetal body and the fetal thyroid into consideration. The woman was encouraged to continue her pregnancy and received levothyroxine in a dose to render her slightly thyrotoxic. At full term, an apparently healthy boy, having markedly raised cord blood serum thyroid-stimulating hormone concentration and subnormal thyroxine (T4) and low-normal triiodothyronine (T3) concentrations, was born. Treatment with thyroxine was initiated from the age of 14 days, when the somatosensoric evoked potential latency time increased to a pathological value and hormonal laboratory tests repeatedly confirmed the hypothyroid state. At 8 yr of age, the child attends regular school. A neuropsychological pediatric examination showed that the mental performance was within normal limits, but with an uneven profile. He has a low attention score and displays evidently subnormal capacity regarding figurative memory. CONCLUSION: Radioiodine treatment in pregnancy in the 20th gestational week does not give a total absorbed dose to the fetal body that justifies termination of pregnancy. A high absorbed dose to the fetal thyroid, however, should be the basis of the management of the pregnancy and offspring.

Mass balance of trace elements in Walker branch watershed: relation to coal-fired steam plants.

A mass balance study of trace element flows at the TVA Allen Steam Plant at Memphis showed that most of the released Hg, some Se, and probably most Cl and Br are discharged to the atmosphere as gases. The elements As, Cd, Cu, Ga, Mo, Pb, Sb, Se, and Zn were concentrated in fly ash compared to slag and were more concentrated in the ash discharged through the stack than in that collected by the precipitator, while Al, Ba, Ca, Ce, Co, Eu, Fe, Hf, K, La, Mg, Mn, Rb, Sm, Sr, Ta, Th, and Ti showed little preferential partitioning between the slag and the collected or discharged fly ash. The elements Cr, Cs, Na, Ni, U, and V exhibited behavior intermediate between the latter two groups. This information about stack emissions of trace elements from the Allen Plant was used to estimate the likely range of air concentrations and input (dry and wet deposition) to the Walker Branch Watershed. The watershed, which is on the ERDA reservation at Oak Ridge, is within 20 km of three coal-fired steam plants, two in the TVA system and one belonging to ERDA. The estimated input values are compared to measurements of Cd, Cr, Cu, Hg, Mn, Ni, Pb, and Zn in wet precipitation falling on the watershed during 1973 and 1974. Dry deposition of these elements could not be measured directly but estimates indicated that this could be of the same order of magnitude as the rainwater input. A six-month mass balance indicated that the watershed efficiently retains Pb (97-98% of the atmospheric input,) Cu (82-84%), while Cr (69%), Mn (57%), Zn (73%), and Hg (69%) are less well retained.

Early diagnosis of and surgical strategy for adrenal medullary disease in MEN II gene carriers.

Sixteen multiple endocrine neoplasia type II (MEN II) gene carriers--12 who had undergone thyroidectomy because of medullary carcinoma of the thyroid and 4 whose thyroid glands had been removed because of C cell hyperplasia--were examined for the presence of pheochromocytomas. No patient had sought medical advice for pheochromocytoma symptoms. Fourteen patients had MEN IIa syndromes, one patient had a MEN IIb and another patient had a mixed syndrome of von Recklinghausen's neurofibromatosis and MEN II. Eight patients had undergone unilateral adrenalectomy for pheochromocytoma 11 +/- 4 years before. The patients underwent clinical examination, determination of the urinary excretion of catecholamines and metabolites, and 131I-metaiodobenzylguanidine (131I-MIBG) and CAT scans. 131I-MIBG scanning was performed with images 1, 4, and 7 days after the radionuclide injection. In seven of eight patients who had undergone unilateral adrenalectomies, the 131I-MIBG scans showed accumulation of the radionuclide in the remaining adrenal gland. Bilateral adrenal accumulation of the radionuclide was demonstrated in seven of eight MEN IIa gene carriers who had not undergone adrenalectomy. Five patients, two of whom had undergone adrenalectomy, were found to have unilateral pheochromocytomas less than 2 cm in diameter. Only one of these five patients had an elevated excretion of urinary catecholamines. Between day 4 and day 7 after 131I-MIBG injection, adrenal glands with pheochromocytomas increased their relative accumulation of the radionuclide significantly more (p less than 0.02) than did adrenal glands without any demonstrable pheochromocytomas. All the pheochromocytomas were viewed by means of CAT scans. Only one MEN IIa patient had bilateral pheochromocytomas, but our findings indicate that there is a tendency to bilateral adrenal medullary hyperfunction in most MEN II gene carriers. As 131I-MIBG and CAT scans can facilitate the early diagnosis of pheochromocytomas, unilateral adrenalectomy can safely be performed in most MEN IIa patients. Bilateral pheochromocytomas develop in a majority of patients with MEN IIb syndromes. Bilateral adrenalectomy should therefore be performed in these patients.

Effects of neurokinin A and calcitonin gene-related peptide on mucociliary activity in rabbit maxillary sinus.

Substance P (SP) released from sensory C-fibers in the airways increases the mucociliary (m.c.) activity in the rabbit maxillary sinus. The purpose of the present study was to investigate the m.c. effects of two other neuropeptides, coexisting with SP in sensory neurones, neurokinin A (NKA) and calcitonin gene-related peptide (CGRP). NKA increased the m.c. activity dose-dependently (dose range 0.1-10.0 micrograms/kg, 88 pmol to 8.8 nmol/kg), the maximum increase being 41.9 +/- 2.6%. The effect was inhibited by pretreatment with the tachykinin antagonist (D-Pro2,D-Trp7,9)SP, but not with atropine or hexamethonium. Thus NKA released from sensory C-fibers may contribute to the non-cholinergic increase of m.c. activity observed after C-fiber stimulation. In contrast CGRP did not influence the m.c. activity. Neither did it influence the responses to NKA or SP. It is concluded that CGRP is unlikely to be involved in the control of m.c. function.

Ethanol inhibition of NMDA currents in acutely dissociated medial septum/diagonal band neurons from ethanol dependent rats.

The effect of acutely applied ethanol and the impact of chronic ethanol treatment, sufficient to induce tolerance and physical dependence, on N-methyl-D-aspartate (NMDA) receptor function were studied in acutely isolated neurons from the medial septum/diagonal band (MS/DB) of adult rats using whole cell, patch-clamp electrophysiology. There was a small positive correlation for capacitance and current amplitude activated by 100 microM NMDA for all groups. Also, cell membrane capacitance was significantly smaller for Ethanol Dependent (approximately 80-84%) than either Naive or Control cells. Therefore NMDA-activated responses were normalized for capacitance (current density, pA/pF) across all three groups. NMDA-activated (30-1000 microM) responses were significantly larger in cells from Control and Ethanol Dependent rats relative to those from Naives. In addition, estimated maximal responses were significantly larger for Ethanol Dependent cells, compared to either Control or Naive, respectively, while EC50s and slopes were not significantly different. Acute 60 mM ethanol significantly inhibited responses to 100 microM NMDA in all three groups, however, mean ethanol inhibition was 12-25% smaller after ethanol dependence. There was no evidence of acute tolerance to ethanol inhibition for any group, but examination of patterns of inhibition for individual neurons showed a few cells were resistant to ethanol or exhibited progressive loss of ethanol inhibition. These results suggest that NMDA receptor function in acutely isolated MS/DB neurons is increased following in vivo chronic ethanol treatment, and shows resistance to acute ethanol inhibition suggesting NMDA receptor-mediated cellular tolerance.