The role of nigral and thalamic output pathways in the expression of oral stereotypies induced by amphetamine injections into the striatum

Microinjections of amphetamine into the ventrolateral striatum (VLS) elicit a striking behavioral syndrome characterized by compulsive oral and forelimb motor stereotypies. The neural pathways that mediate these behavioral responses downstream from the striatum have not yet been identified. In a series of experiments, we investigated the involvement of the substantia nigra pars reticulata (SNr) and the ventromedial nucleus of the thalamus (VMT) in the mediation of this behavioral syndrome. We demonstrated that lidocaine-induced reversible inactivation of the SNr reduced amphetamine-induced stereotyped biting and gnawing behaviors, suggesting that the nigral output pathway plays a significant role in the expression of these behavioral responses. In turn, injections of lidocaine into the VMT only transiently reduced amphetamine-stimulated biting and increased stereotyped gnawing and paw nibbling, suggesting that the expression of oral stereotypies induced by amphetamine injections into the VLS is not dependent on thalamocortical feedback.     

Cellular expression of ionotropic glutamate receptor subunits in subpopulations of neurons in the rat substantia nigra pars reticulata

In order to characterize the expression of ionotropic glutamate receptor immunoreactivity in subpopulations of neurons in the rat substantia nigra pars reticulata (SNr), double labeling experiments were performed. Neurons in the reticulata were found to display GluR1, GluR2, GluR2/3, GluR4, N-methyl-D-aspartate receptor 1 (NMDAR1) and NMDAR2B immunoreactivity. Some of the reticulata neurons were shown to display GluR1 and GluR2 immunoreactivity or GluR2 and GluR4 immunoreactivity at the single cell level. In addition, subpopulations of reticulata neurons were characterized on the basis of the strong expression of parvalbumin (PV) and GABA transaminase immunoreactivity. All of the reticulata neurons that displayed strong immunoreactivity for PV or GABA transaminase also displayed immunoreactivity for GluR1, GluR2/3, GluR4, NMDAR1 and NMDAR2B. A tiny portion (around 15%) of reticulata neurons that display NMDAR1 immunoreactivity was found to be PV- or GABA-transaminase-negative. The present results indicate that native alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)-type receptors and NMDA-type receptors in the rat substantia nigra are composed of heteromeric receptor subunits. The present findings further demonstrate that most of the AMPA-type and NMDA-type glutamate receptor subunits are primarily expressed by subpopulations of neurons in the rat SNr.     

端粒酶的调节基因TRAP在皮肤基底细胞癌中的表达及意义

目的:探讨端粒酶的调节基因TRAP在皮肤基底细胞癌中的表达情况。方法:用免疫组化S-P法检测TRAP在38例皮肤基底细胞癌、15例正常皮肤中的表达。结果:TRAP在皮肤基底细胞癌的表达高于正常皮肤(P<0.01);在未分化型与分化型基底细胞癌表达的差异无统计学意义。结论:TRAP的异常高表达可能与皮肤基底细胞癌的发病有关。TRAP的表达与基底细胞癌的病理分型无关。     

小儿腔隙性脑梗死的病因与CT分析

目的探讨小儿腔隙性脑梗死的病因与CT表现。方法对43例腔隙性脑梗死的临床资料进行分析。结果(1)病因:头轻微外伤21例,上呼吸道感染8例,水痘2例,线粒体脑肌病(MELAS),烟雾病1例,系统性红斑狼疮1例,原因不明9例。(2)临床表现:偏瘫41例,失语5例,癫疒间10例,突发性耳聋2例。(3)CT:43例患儿发现51处病灶,其中15例患儿发现一侧或双侧基底节区点状或片状钙化,其附近存在类圆形点或片状低密度灶。(4)预后:40例患儿在12周内症状消失。结论小儿与成人引起腔隙性脑梗死病因不同,预后好。基底节钙化与外伤后急性偏瘫的发生有一定关系。     

Cortical cholinergic inputs mediate processing capacity: effects of 192 IgG-saporin-induced lesions on olfactory span performance

An olfactory span task that required rats to discriminate an olfactory stimulus added to an increasing list of such stimuli (nonmatching-to-sample; NMTS) was employed to assess the role of the basal forebrain cholinergic system in the animals' olfactory working memory capacity. A separate group of animals was trained in a matching-to-sample (MTS) version of this task that did not tax span performance. NMTS animals required significantly more sessions to reach an olfactory span of 18 stimuli than MTS rats. Infusions of the cholino-immunotoxin 192 IgG-saporin into the basal forebrain resulted in decreases of cortical acetylcholinesterase (AChE)-positive fibre density ranging from 80% in frontodorsal and frontoparietal regions to 35% in the pyriform cortex and 24% in the olfactory bulb. Postsurgery span performance was significantly reduced in lesioned NMTS but not MTS animals. Span performance in lesioned NMTS animals recovered following 4 weeks of postoperative training; however, these animals' span remained vulnerable to the effects of increased intertrial intervals. The distribution of errors in lesioned animals indicated a recency effect. In NMTS animals, olfactory span performance during the initial two postoperative weeks correlated significantly with AChE-positive fibre density in neocortical but not olfactory areas. The privileged, automatic processing of olfactory stimuli in rats may have contributed to the transience of the lesion effect. The results support the crucial role of cortical cholinergic input in the mediation of aspects of processing capacity.     

Minimal and maximal incidence rates of skin cancer in Caucasians estimated by use of sigmoidal UV dose–incidence curves

BackgroundSigmoidal (S-shaped) dose–cancer incidence relationships are often observed in animal bioassays for carcinogenicity. Ultraviolet (UV) radiation is an established skin carcinogen. The aim of this study is to examine if S-shaped curves describe the relationship between solar UV doses and skin cancer incidences, and if such relationships can be used to estimate threshold levels of non-carcinogenic UV exposure, as well as maximal incidence rates.MethodsWe studied the incidence rate–annual erythema-effective UV dose relationship for squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and cutaneous melanoma (CM) among different Caucasian populations in Europe, Australia and New Zealand.ResultsOur analysis indicates that S-shaped associations describe the data well (P < 0.0001). The age-adjusted incidence rates for cases expected to be due to other causes than solar UV exposure (at zero UV dose) were found to be around 0.6, 9.7 and 4.0 per 100,000 for women in 1997–2007 for SCC, BCC and CM, respectively, and around 1.2, 14.3 and 2.6 per 100,000 for men. The analysis indicates that SCC, BCC and CM have maximal incidence of 361 ± 24, 1544 ± 49 and 36 ± 4 per 100,000 for women, and 592 ± 35, 2204 ± 109 and 50 ± 4 per 100,000 for men.ConclusionsBetween 89 and 95% of the annual CM cases, around 99.8% SCC and 99.4% BCC cases are caused by solar UV exposure. The analysis did not identify any “safe” UV dose below which the risk for skin cancer was absent. Avoidance of UV radiation has a potential to reduce the incidence of skin cancer in fair-skinned population.     

Abnormal motor surround inhibition associated with cortical and deep grey matter involvement in multiple sclerosis

ObjectiveMotor surround inhibition (mSI) is a physiological mechanism that contributes to hand movement control by focusing voluntary movement. Growing evidence suggests that hand movement control is impaired in multiple sclerosis. The aim of the study was to evaluate mSI in MS and to investigate the brain structures involved in mSI in multiple sclerosis.MethodsWe recruited 33 patients and 23 controls. To investigate mSI, we delivered transcranial magnetic single pulses during index finger flexion. Motor evoked potentials were recorded and first dorsal interosseous (“active muscle”) and from the abductor digiti minimi (“surround muscle”). mSI was expressed as the ratio between Motor evoked potentials recorded from the surround muscle during movement and at rest. Participants underwent a magnetic resonance study.ResultsPatients had impaired mSI as compared with controls. Magnetic resonance showed that basal ganglia had smaller volumes and higher mean diffusivity than controls. Impaired mSI correlated with primary motor cortex and basal ganglia involvement in multiple sclerosis.ConclusionAltered mSI in multiple sclerosis is related to cortical and subcortical grey matter involvement.SignificanceOur study provides the first demonstration of a pathophysiological mechanism underlying hand movement control dysfunction in multiple sclerosis. mSI represents a new therapeutic target of multiple sclerosis rehabilitative approaches.     

Starch digestibility modulation significantly improves glycemic variability in type 2 diabetic subjects: A pilot study

Background and aimsIn type 2 diabetes (T2D) patients, the reduction of glycemic variability and postprandial glucose excursions is essential to limit diabetes complications, beyond HbA1c level. This study aimed at determining whether increasing the content of Slowly Digestible Starch (SDS) in T2D patients’ diet could reduce postprandial hyperglycemia and glycemic variability compared with a conventional low-SDS diet.Methods and resultsFor this randomized cross-over pilot study, 8 subjects with T2D consumed a controlled diet for one week, containing starchy products high or low in SDS. Glycemic variability parameters were evaluated using a Continuous Glucose Monitoring System.Glycemic variability was significantly lower during High-SDS diet compared to Low-SDS diet for MAGE (Mean Amplitude of Glycemic Excursions, p < 0.01), SD (Standard Deviation, p < 0.05), and CV (Coefficient of Variation, p < 0.01). The TIR (Time In Range) [140–180 mg/dL[ was significantly higher during High-SDS diet (p < 0.0001) whereas TIRs ≥180 mg/dL were significantly lower during High-SDS diet. Post-meals tAUC (total Area Under the Curve) were significantly lower during High-SDS diet.ConclusionOne week of High-SDS Diet in T2D patients significantly improves glycemic variability and reduces postprandial glycemic excursions. Modulation of starch digestibility in the diet could be used as a simple nutritional tool in T2D patients to improve daily glycemic control.Registration numberin clinicaltrials.gov: NCT 03289494.     

Photodynamic therapy effective for the treatment of actinic keratosis and basal cell carcinoma in bullous pemphigoid patients

Treating skin cancers and extensive actinic keratosis in patients with bullous pemphigoid (BP) can be challenging. Treatment options pose unique risks in these patients as surgical wounds can have delayed wound healing and photodynamic therapy (PDT) may exacerbate their blistering disease. We report the successful use of PDT to treat actinic keratosis and skin cancers in two patients with BP, both of whom had excellent response to PDT and tolerated treatment without any bullous disease flares. Carefully selected patients with skin cancers and stable, well controlled BP can be safely considered for treatment using PDT.