Vasopressin analog influences the performance of males on a reaction time task

The effects of desmopressin acetate (DDAVP), a vasopressin analogue, were investigated using the Sternberg Item Recognition Task. This task requires a subject to memorize a target set of up to four digits and then quickly to decide whether or not a given probe was in the original memory set. Fifteen college aged males were used as subjects in this study. Subjects received, in a double blind procedure, 0.6 ml of DDAVP (60 micrograms) or an equal volume of vehicle solution during the first test session. One week later, during the second test session, the hormone-placebo treatments were reversed. The results indicated significant main effects for set size and decision type and an interaction between treatment and session. Treatment with DDAVP during the second but not the first session improved performance at each set size as compared to treatment with the vehicle. These results indicate that DDAVP, combined with experience on this task, improved attentional processes but did not influence memory, which would have been indicated by an interaction between treatment and size of memory set.     

模拟降水减少对帽儿山地区兴安落叶松径向生长的影响

以2004年在小兴安岭帽儿山地区栽植的兴安落叶松(Larix gmelinii)为研究对象,在2012年,经过100%减雨、50%减雨、冬季除雪和对照4种处理,在控雨的前期(6月)和后期(8月)用微生长锥取样利用石蜡切片方法测量扩大细胞的径向长度和数量。在10月末用生长锥取样,打磨后测量成熟管胞的径向长度和数量,进而分析降水减少对兴安落叶松径向生长的影响。结果表明:在帽儿山地区,生长季温度与兴安落叶松径向生长显著正相关,降水在生长季后期为负相关。大树芯成熟管胞测定表明,3块样地综合而言,除雪组成熟管胞数量最多,其次是对照组,50%减雨组和100%减雨组成熟管胞数量最少;管胞径向长度在各个处理组之间差异不显著。但是,在3块样地中,成熟管胞数量和径向长度在相同处理间测定结果有差别,样地1的100%减雨组、50%减雨组、除雪组和对照组中成熟管胞数量随土壤湿度增加而增加,径向管胞长度差异不明显;样地2的除雪组中成熟管胞径向长度显著小于其他3个实验组,而50%减雨组、100%减雨组和对照组的成熟管胞径向长度和数量均差异不显著;样地3中4个实验组的成熟管胞数量均差异不显著,成熟管胞径向长度100%减雨组略小于其他3个实验组,这与样地3遮阴较大、土壤湿度较高有关。石蜡切片的形成层扩大细胞分析表明:在减雨处理的初期(6月份),样地3在扩大细胞的数量上,随着不同处理间土壤湿度的减小而减少。在减雨处理的后期(8月份),样地1扩大细胞的数量随着不同处理间土壤湿度的减小而减少。研究结果表明降水减少会对兴安落叶松径向生长产生影响,其影响程度取决于微环境条件的差异,且不同时期降水减少的影响也有差异。     

Relaxation training as a treatment for chronic headaches in an individual having severe developmental disabilities

We have assessed effects of a simplified relaxation training on the frequency of headaches and consumption of analgesic headache medication in an adult male with severe developmental disabilities as well as chronic mixed headaches. The subject received Behavioral Relaxation Training (BRT) after a baseline period during which frequency of headache complaint, analgesic medication consumption, and independent relaxation behaviors were monitored. BRT consists of the utilization of modeling, prompting, feedback, and positive reinforcement in order to establish and maintain the subject's participation in 10 overt relaxed postures. The behaviors were learned to at least an 80% proficiency during a 10-minute alternating self-regulatory (1 min)/corrective feedback (1 min) relaxation phase across several sessions. Headache complaints were reduced by 48% and analgesic medication consumption by 51% as assessed during a 2-month posttreatment evaluation. These results should be considered not only as support of BRT as a viable method of relaxation training but also as a suggestion that BRT and other self-regulatory treatment should be considered for use with individuals having moderate to severe developmental disabilities.     

Deficits of masticatory movements caused by lesions in the orofacial somatosensory cortex of the awake cat

The purpose of this study was to determine the role of somatosensory cortex (SI) in the control of orofacial movements during eating.We identified perioral and tongue projection regions of the cat SI and destroyed cells in one region by injecting kainic acid. The effects on orofacial behavior were then studied over a period of 4-6 weeks. Cats with unilateral lesions in the perioral region (PL-cats) dropped food from the contralateral side of the mouth in the early phase. Failure in erection of the contralateral whisker hairs during masticatory movements and delay of the masticatory start were observed throughout the experimental period. Furthermore, in the late phase, PL-cats showed prolongations of the masticatory and food intake periods, which were accompanied by the increase in the number of swallows and chewing cycles. Cats with unilateral lesions in the tongue region (TL-cats) showed the prolongation of the masticatory period in the early phase, which was accompanied by the increase in the number of swallows and chewing cycles. TL-cats did not show the prolongation of the food intake period and failure in erection of the contralateral whisker hairs. In both PL- and TL-cats, masticatory and swallowing rhythms were normal.     

Deficits of masticatory movements caused by lesions in the orofacial somatosensory cortex of the awake cat

The purpose of this study was to determine the role of somatosensory cortex (SI) in the control of orofacial movements during eating. We identified perioral and tongue projection regions of the cat SI and destroyed cells in one region by injecting kainic acid. The effects on orofacial behavior were then studied over a period of 4-6 weeks. Cats with unilateral lesions in the perioral region (PL-cats) dropped food from the contralateral side of the mouth in the early phase. Failure in erection of the contralateral whisker hairs during masticatory movements and delay of the masticatory start were observed throughout the experimental period. Furthermore, in the late phase, PL-cats showed prolongations of the masticatory and food intake periods, which were accompanied by the increase in the number of swallows and chewing cycles. Cats with unilateral lesions in the tongue region (TL-cats) showed the prolongation of the masticatory period in the early phase, which was accompanied by the increase in the number of swallows and chewing cycles. TL-cats did not show the prolongation of the food intake period and failure in erection of the contralateral whisker hairs. In both PL- and TL-cats, masticatory and swallowing rhythms were normal.     

Biosensor reporting of root exudation from Hordeum vulgare in relation to shoot nitrate concentration

The aim of this study was to determine the relationship between shoot nitrate concentration, mediated by nitrate supply to roots, and root exudation from Hordeum vulgare. Plants were grown for 14 d in C-free sand microcosms, supplied with nutrient solution containing 2 mM nitrate. After this period, three treatments were applied for a further 14 d: (A) continued supply with 2 mM nitrate (zero boost), (B) supply with 10 mM nitrate (low boost), and (C) supply with 20 mM nitrate (high boost). At the end of the treatment period, a bacterial biosensor (Pseudomonas fluorescens 10586 pUCD607, marked with the lux CDABE genes for bioluminescence) was applied to the microcosms to report on C-substrate availability, as a consequence of root exudation. The nitrate boost treatments significantly affected shoot nitrate concentrations, in the order C>B>A. In treatments receiving a nitrate boost (B, C), increased shoot nitrate concentration was correlated with increased plant biomass, reduced root length, reduced number of root tips, and increased mean root diameter, relative to the no boost treatment (A). Imaging of biosensor bioluminescence (proportional to metabolic activity in response to availability of root exudates) indicated that root exudation increased with decreasing shoot nitrate concentration. Biosensor reporting of root C-flow indicated that exudation was greater from root tip regions than from the whole root, but that specific exudation rates for all sites were unaffected by treatments. Total root exudation across treatments was found to be closely correlated with total root length, indicating that increased root exudation, per unit root biomass, with decreasing nitrate supply was associated with altered root morphology, as a consequence of systemic plant responses to internal N-status.     

Relaxation training as a treatment for chronic headaches in an individual having severe developmental disabilities

We have assessed effects of a simplified relaxation training on the frequency of headaches and consumption of analgesic headache medication in an adult male with severe developmental disabilities as well as chronic mixed headaches. The subject received Behavioral Relaxation Training (BRT) after a baseline period during which frequency of headache complaint, analgesic medication consumption, and independent relaxation behaviors were monitored. BRT consists of the utilization of modeling, prompting, feedback, and positive reinforcement in order to establish and maintain the subject's participation in 10 overt relaxed postures. The behaviors were learned to at least an 80% proficiency during a 10-minute alternating self-regulatory (1 min)/corrective feedback (1 min) relaxation phase across several sessions. Headache complaints were reduced by 48% and analgesic medication consumption by 51% as assessed during a 2-month posttreatment evaluation. These results should be considered not only as support of BRT as a viable method of relaxation training but also as a suggestion that BRT and other self-regulatory treatment should be considered for use with individuals having moderate to severe developmental disabilities.This research was supported in part by grants from NIMH, MH-41341, and NINCDS, NS-23440.     

The effect of teratogens on maternal corticosterone levels and cleft incidence in A/J mice.

It is unknown whether orofacial clefting, one consequence of teratogenic exposure, results from a direct interaction between the teratogen and the embryonic palate, or indirectly from maternal alterations caused by the teratogen. In the current study pregnant A/J mice were exposed to one of three cleft-inducing agents in order to examine the relationship between drug-induced clefting and the response of maternal plasma corticosterone to drug administration. The agents used, haloperidol (HAL), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), or phenytoin (PHT), were administered in teratogenic doses between 0800 and 0930 on gestational day 10 (GD 10). For corticosterone determinations, mice were dosed on GD 10, and blood was collected at 1, 4, 24, or 48 hr after dosing. For fetal evaluation of cleft lip and/or cleft palate, mice were dosed on GD 10 and killed on GD 18. Phenytoin was the most potent inducer of cleft lip and palate and induced a sustained elevation of plasma corticosterone in maternal animals. The other treatments, in order of decreasing potency to induce clefting and/or cause an elevation of corticosterone in plasma were 2,4,5-T > HAL > controls. Correlations between maternal corticosterone levels and clefting incidence were very high at all time points examined; total exposure (area under the curve) was also highly correlated. A linear relationship between drug-induced increases in maternal corticosterone levels and the incidence of clefting in A/J mice was evident. Based on these findings, we believe that increased maternal corticosterone levels may play a role in orofacial clefting in A/J mice.     

Stress reduction treatment of severe recurrent genital herpes virus

Four individuals with high-frequency recurrences of genital herpes virus of at least 2 years' duration were treated with two behavioral stress-reduction treatments. Subjects were given 10 weekly sessions of frontalis EMG biofeedback (2 subjects) or progressive muscle relaxation treatment (2 subjects). Presession and postsession frontalis EMG measures were recorded for all subjects across treatment. Outcome was measured by daily and weekly symptom charting mailed in weekly over 6 months, or by telephone interview after 6 months. Results demonstrated substantial improvement in reported symptoms with both treatments. Relaxation treatment resulted in a 66% and 100% reduction in frequency of recurrences. Frontalis EMG biofeedback resulted in a 72% and 7% reduction in frequency of recurrences. Follow-up at 1-year posttreatment showed that treatment effects were maintained by one subject, partially maintained by two, and reversed in one subject. The need for controlled investigation is emphasized.The authors thank Stephen Ritz for his contribution to this study.     

Protective effect of nebivolol on reserpine-induced neurobehavioral and biochemical alterations in rats

Reserpine-induced orofacial dyskinesia is a model that shares some mechanists’ aspects with tardive dyskinesia whose pathophysiology has been related to oxidative stress. The present study was aimed to explore neuroprotective effects of nebivolol, an antihypertensive agent, on reserpine-induced neurobehavioral and biochemical alterations in rats. Reserpine (1 mg/kg, s.c.) was used to induce neurotoxicity. Administration of reserpine for 3 days every other day significantly increased the vacuous chewing movements (VCMs), tongue protrusions (TPs) and reduced the locomotor activity in rats. Pre-treatment with nebivolol (5 and 10 mg/kg, p.o. for 5 days) showed dose dependant decrease in VCMs and TP induced by reserpine. Nebivolol also showed significant improvement in locomotor activity. Reserpine significantly increased lipid peroxidation and reduced the levels of defensive antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) in rat brain. Nebivolol reversed these effects of reserpine on oxidative stress indices; indicating amelioration of oxidative stress in rat brains. The results of the present study indicated that nebivolol has a protective role against reserpine-induced orofacial dyskinesia. Thus, the use of nebivolol as a therapeutic agent for the treatment of tardive dyskinesia may be considered.     

Photoperiodic control of the time of parturition in alpacas (Lama pacos)

Twenty-three mature female alpacas in late gestation in October (spring group) and in January (summer group), were randomly allocated to two treatments. In each season, one group was placed indoors under natural light and the other group was placed in a treatment room which could be totally blacked out to external light and had artificial lights controlled by an automatic time switch. Lights in the treatment room were switched on at 12:00 h and switched off at 02:30 h. Video cameras were used to record the times of parturition. The mean time of parturition for alpaces in the treatment room (16:43 h ± 69 min) was 6 h 23 min later (P < 0.001) than the alpacas in the control room (10:20 h ± 67 min). The mean intervals from sunrise or lights-on to parturition and from sunset or lights-off to parturition were similar for both treatment groups, and there were no effects of treatments on gestation length. The mean interval from the start of the treatments to parturition was shorter (P < 0.001) in the spring group(18 ± 2 days) than in the summer group (36 ± 2 days). In conclusion, the results showed that the time of parturition in alpacas is under photoperiodic control.     

Repeated superovulation using a simplified FSH/eCG treatment for in vivo embryo production in sheep

This study investigated the efficacy of a simplified repeated superovulation treatment (eCG plus FSH in a single dose, rather than the usual protocol of six decreasing doses of FSH) in the in vivo embryo production in Ojalada donor ewes during the breeding season. In vitro viability after vitrification and warming of embryos recovered from both treatments was also assessed. In addition, the study examined the effects of the concentration of anti-eCG antibodies before each eCG/FSH treatment on in vivo embryo production. Thirty-eight females at the end of their reproductive lives were given the decreasing (n = 19) or simplified (n = 19) superovulatory treatment up to three times at intervals of ≥ 50 d. The onset of estrus was 5 h earlier (P < 0.05) among ewes that received the eCG/FSH protocol (25.2 ± 0.80 h) than it was among those that received the decreasing superovulatory treatment (30.1 ± 1.0 h), but the two treatments did not differ significantly in ovulation rates or the number and viability of embryos recovered. Both of the superovulatory protocols were significantly (P < 0.05 to P < 0.01) less effective after the first application. After three superovulatory treatments, the average number of viable embryos per ewe was 14.1 ± 2.3 and 13.7 ± 2.5 in the decreasing and simplified protocols, respectively. High anti-eCG antibody concentrations just before the superovulatory treatment with eCG/FSH were associated with a significant decrease (P < 0.05) in the rates of fertilization, viability, and freezability, especially in the second and third recoveries. Repeated superovulatory treatments with eCG/FSH can provide an efficient means of producing high quality embryos in the ewes of endangered breeds at the end of their reproductive lives, although further studies are needed to characterize the response associated with high concentrations of anti-eCG antibodies.     

Nonparametric Methods in Crossover Trials

The crossover design is often used in biomedical trials since it eliminates between subject variability. This paper is concerned with the statistical analysis of data arising from such trials when assumptions like normality do not necessarily apply. Nonparametric analysis of the two-period, two-treatment design was first described by Koch in a paper 1972. The purpose of this paper is to study nonparametric methods in crossover designs with three or more treatments and an equal number of periods. The proposed test for direct treatment effects is based on within subject comparisons after removing a possible period effect. With only two treatments this test reduces to the twosided Wilcoxon signed rank test. By simulation experiments the validity of the significance level of the test when using the asymptotic distribution of the test statistic are manifested and the power against different alternatives illustrated. A test for first order carryover effects can be constructed by a straightforward generalization of the test proposed by Koch in 1972. However, since this test is based on between subject comparisons its power will be low. Our recommendation is to consider the crossover design rather than the parallel group design if the carryover effects are assumed to be neglible or positive and smaller then the direct treatment effects.     

Trait anxiety affects the orofacial nociceptive response in rats

The aims of the present study were to assess the influence of: a) trait anxiety on orofacial pain; and b) orofacial pain on state anxiety. Forty-four rats were initially exposed to the free-exploratory paradigm for the evaluation of their anxiety profiles. In accordance to the parameter "Percentage of time in the novel side", the animals were considered as presenting high or low levels of trait anxiety when presenting values below the 1st quartile, or above the 3rd quartile, respectively. A week later, formalin-1.5% was injected into the upper lip of each animal. The behavioural nociceptive response, characterized by increased orofacial rubbing (OR), was quantified for 30 minutes, as follows: Total time OR (0-30 minutes: total pain), 1st phase OR (0-6 minutes: neurogenic pain), and 2nd phase OR (12-30 minutes: inflammatory pain). Immediately after this test, but still under the effect of formalin, the rats were submitted to the Elevated Plus-maze test (EPM). The results showed that the high trait anxiety individuals presented higher frequency of OR than the low trait anxiety ones, except during the neurogenic pain period. However, no correlation was found between OR frequency and levels of state anxiety presented on the EPM. In conclusion, the animals presenting higher anxiety profiles were the most susceptible to orofacial pain, nevertheless, orofacial pain did not influence state anxiety.     

Acidification effects on vesicular-arbuscular mycorrhizal (VAM) infection, growth and nutrient uptake of established heathland herb species

A greenhouse experiment was carried out to determine whether the decline of Arnica montana L. in heathland vegetation in the Netherlands could be caused by a detrimental effect of soil acidification on vesicular-arbuscular mycorrhiza of this species. Arnica montana and two non-declining species from the same habitat, Hieracium pilosella L. and Deschampsia flexuosa (L.) Trin., were grown with and without the vesicular-arbuscular mycorrhizal (VAM) fungus Glomus fasciculatum (Thaxter sensu Gerdemann) Gerd. and Trappe in pots with an extremely nutrient-poor, sandy soil. They were percolated weekly with nutrient solution with different pH values, viz. 5.5, 4.5, 3.5 and 2.5. At intervals of three weeks and up to 12 weeks, measurements were made on growth, nutrient uptake and VAM infection.In the most acid treatments growth and nutrient uptake were reduced in all species. VAM infection decreased only slightly with decreasing pH of the treatments. Without VAM, Arnica montana died and Hieracium pilosella hardly grew at the most acid treatments. Therefore it is concluded that VAM decreased the stress caused by the most acid treatments. Leachate from the most acid treatment had a pH of approximately 4, and contained considerable amounts of aluminium, dissolved from the solid phase of the soil. This might have played a role in the detrimental effects on the plants in the case of the most acid treatment. No evidence was found in this experiment that the decline of Arnica montana was due to detrimental effects of soil acidification on VAM of this species.     

南亚热带两种优势树种叶凋落物分解对模拟酸雨的响应

通过对模拟酸雨处理下鼎湖山季风常绿阔叶林优势树种锥栗(Castanopsis chinensis)和木荷(Schima superba)叶凋落物分解的研究,试图探讨南亚热带区域日益严重的酸雨对森林凋落物分解的影响规律以及可能的机制。试验应用分解袋法进行,并设计4个模拟酸雨强度处理:CK(p H值4.5左右的天然湖水)、T1(p H值4.0)、T2(p H值3.5)和T3(p H值3.0)。21个月的分解结果表明,模拟酸雨抑制了两种优势树种叶凋落物的分解。CK、T1、T2和T3 4个处理下的分解速率常数k值分别为:锥栗(1.18、0.93、0.94和0.86)和木荷(1.10、0.97、0.88和0.94),与CK相比,k值在T1、T2和T3均有下降的趋势。同时,模拟酸雨下两种优势树种叶凋落物的质量残留率均为:T3T2T1CK。酸雨对凋落物分解的抑制作用可能与酸雨胁迫下土壤酸化从而导致土壤微生物活性下降有关。     

Neuropathic orofacial pain: Cannabinoids as a therapeutic avenue

Neuropathic orofacial pain (NOP) exists in several forms including pathologies such as burning mouth syndrome (BMS), persistent idiopathic facial pain (PIFP), trigeminal neuralgia (TN) and postherpetic neuralgia (PHN). BMS and PIFP are classically diagnosed by excluding other facial pain syndromes. TN and PHN are most often diagnosed based on a typical history and presenting pain characteristics. The pathophysiology of some of these conditions is still unclear and hence treatment options tend to vary and include a wide variety of treatments including cognitive behaviour therapy, anti-depressants, anti-convulsants and opioids; however such treatments often have limited efficacy with a great amount of inter-patient variability and poorly tolerated side effects. Analgesia is one the principal therapeutic targets of the cannabinoid system and many studies have demonstrated the efficacy of cannabinoid compounds in the treatment of neuropathic pain. This review will investigate the potential use of cannabinoids in the treatment of symptoms associated with NOP.     

Stress reduction treatment of severe recurrent genital herpes virus

Four individuals with high-frequency recurrences of genital herpes virus of at least 2 years' duration were treated with two behavioral stress-reduction treatments. Subjects were given 10 weekly sessions of frontalis EMG biofeedback (2 subjects) or progressive muscle relaxation treatment (2 subjects). Presession and postsession frontalis EMG measures were recorded for all subjects across treatment. Outcome was measured by daily and weekly symptom charting mailed in weekly over 6 months, or by telephone interview after 6 months. Results demonstrated substantial improvement in reported symptoms with both treatments. Relaxation treatment resulted in a 66% and 100% reduction in frequency of recurrences. Frontalis EMG biofeedback resulted in a 72% and 7% reduction in frequency of recurrences. Follow-up at 1-year posttreatment showed that treatment effects were maintained by one subject, partially maintained by two, and reversed in one subject. The need for controlled investigation is emphasized.     

Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats

The endocannabinoid system (ECS) plays an important role in pain processing and modulation. Since the specific effects of endocannabinoids within the orofacial area are largely unknown, we aimed to determine whether an increase in the endocannabinoid concentration in the cerebrospinal fluid (CSF) caused by the peripheral administration of the FAAH inhibitor URB597 and tooth pulp stimulation would affect the transmission of impulses between the sensory and motor centers localized in the vicinity of the third and fourth cerebral ventricles. The study objectives were evaluated on rats using a method that allowed the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation and URB597 treatment. The amplitude of ETJ was a measure of the effect of endocannabinoids on the neural structures. The concentrations of the endocannabinoids tested (AEA and 2-AG) were determined in the CSF, along with the expression of the cannabinoid receptors (CB1 and CB2) in the tissues of the mesencephalon, thalamus, and hypothalamus. We demonstrated that anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), was significantly increased in the CSF after treatment with a FAAH inhibitor, while tooth pulp stimulation had no effect on the AEA and 2-AG concentrations in the CSF. We also found positive correlations between the CSF AEA concentration and cannabinoid receptor type 1 (CB1R) expression in the brain, and between 2-AG and cannabinoid receptor type 2 (CB2R), and negative correlations between the CSF concentration of AEA and brain CB2R expression, and between 2-AG and CB1R. Our study shows that endogenous AEA, which diffuses through the cerebroventricular ependyma into CSF and exerts a modulatory effect mediated by CB1Rs, alters the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve. In addition, our findings may be consistent with the emerging concept that AEA and 2-AG have different regulatory mechanisms because they are involved differently in orofacial pain. We also suggest that FAAH inhibition may offer a therapeutic approach to the treatment of orofacial pain.     

Design and analysis of group sequential clinical trials with multiple primary endpoints

In many phase III clinical trials, it is desirable to separately assess the treatment effect on two or more primary endpoints. Consider the MERIT-HF study, where two endpoints of primary interest were time to death and the earliest of time to first hospitalization or death (The International Steering Committee on Behalf of the MERIT-HF Study Group, 1997, American Journal of Cardiology 80[9B], 54J-58J). It is possible that treatment has no effect on death but a beneficial effect on first hospitalization time, or it has a detrimental effect on death but no effect on hospitalization. A good clinical trial design should permit early stopping as soon as the treatment effect on both endpoints becomes clear. Previous work in this area has not resolved how to stop the study early when one or more endpoints have no treatment effect or how to assess and control the many possible error rates for concluding wrong hypotheses. In this article, we develop a general methodology for group sequential clinical trials with multiple primary endpoints. This method uses a global alpha-spending function to control the overall type I error and a multiple decision rule to control error rates for concluding wrong alternative hypotheses. The method is demonstrated with two simulated examples based on the MERIT-HF study.