Raised Activity of L-Type Calcium Channels Renders Neurons Prone to Form Paroxysmal Depolarization Shifts

Neuronal L-type voltage-gated calcium channels (LTCCs) are involved in several physiological functions, but increased activity of LTCCs has been linked to pathology. Due to the coupling of LTCC-mediated Ca²⁺ influx to Ca²⁺-dependent conductances, such as K_Ca or non-specific cation channels, LTCCs act as important regulators of neuronal excitability. Augmentation of after-hyperpolarizations may be one mechanism that shows how elevated LTCC activity can lead to neurological malfunctions. However, little is known about other impacts on electrical discharge activity. We used pharmacological up-regulation of LTCCs to address this issue on primary rat hippocampal neurons. Potentiation of LTCCs with Bay K8644 enhanced excitatory postsynaptic potentials to various degrees and eventually resulted in paroxysmal depolarization shifts (PDS). Under conditions of disturbed Ca²⁺ homeostasis, PDS were evoked frequently upon LTCC potentiation. Exposing the neurons to oxidative stress using hydrogen peroxide also induced LTCC-dependent PDS. Hence, raising LTCC activity had unidirectional effects on brief electrical signals and increased the likeliness of epileptiform events. However, long-lasting seizure-like activity induced by various pharmacological means was affected by Bay K8644 in a bimodal manner, with increases in one group of neurons and decreases in another group. In each group, isradipine exerted the opposite effect. This suggests that therapeutic reduction in LTCC activity may have little beneficial or even adverse effects on long-lasting abnormal discharge activities. However, our data identify enhanced activity of LTCCs as one precipitating cause of PDS. Because evidence is continuously accumulating that PDS represent important elements in neuropathogenesis, LTCCs may provide valuable targets for neuroprophylactic therapy.     

Acceptance of dental care following early extractions under rectal sedation with diazepam in preschool children

The aim of the study was to evaluate the effect of amnesia in preschool children on their later acceptance of dental care. Forty-six 4-6-year-old children, who between 2 and 4 years previously had had primary incisors extracted because of trauma, were reexamined for dental health and acceptance of dental care. The extractions had been performed under rectal sedation with diazepam (0.7 mg/kg body weight). Information about dental treatment and degree of cooperation during the intervening period was obtained from records at the referring clinic. The parents were interviewed about their child's experience of amnesia concerning the extractions, background variables, and experiences of dental care before the follow-up examination. Amnesia concerning the extractions was reported in 85% of the children. Twenty-nine percent had on some occasion exhibited behavior management problems (BMP) during the intervening period. Lack of amnesia was significantly associated with BMP (P < 0.002). Children without amnesia concerning the extractions tended to accept dental care less well at the reexamination. Parents were able to predict their child's acceptance of dental care at the follow-up with a significant degree of success (P = 0.02). In conclusion, amnesia in preschool children concerning extractions seems to be essential to facilitate positive acceptance of future dental care.     

The metabolic consequences of thyroxine replacement in adult hypopituitary patients

The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n?=?1595) with and without CH from KIMS (Pfizer International Metabolic Database) were studied before and after 2?years of GH replacement. CH patients (CH, n?=?1080) were compared with TSH sufficient patients (TSHsuff n?=?515) as one group and divided by thyroxine dose/kg/day into tertiles (CHlow-mid-high). Anthropometry, fasting glucose, glycosylated haemoglobin (HbA1c), blood pressure, lipids, IGF-I SDS, quality of life and morbidity were studied. Analyses were standardized for gender, age, number and types of pituitary insufficiencies, stimulated GH peak, age at GH deficiency onset, aetiologies and, when appropriate, for weight and GH dose. At baseline, TSHsuff patients did not differ from CH or CHmid in any outcome. CHlow (≤1.18?μg thyroxine/kg/day) had increased weight, BMI and larger waist circumference (WC), CHhigh (≥1.58?μg thyroxine/kg/day) had lower weight, BMI, WC and IGF-I than TSHsuff and compared to their predicted weights, BMIs and WCs. For every 0.1?μg/kg/day increase of thyroxine dose, body weight decreased 1.0?kg, BMI 0.3?kg/m(2), and WC 0.65?cm. The GH sensitivity of the CH group was higher (0.76?±?0.56 SDS/mg GH) than that of TSHsuff patients (0.58?±?0.64 SDS/mg GH), P?相似文献   

Ten-year natural course of habitual snoring and restless legs syndrome in a population aged 61–63?years at the baseline

Purpose

We investigated the prevalence, natural course, and associated risk factors of habitual snoring (HS) and restless legs syndrome (RLS) over a period of 10?years among an aging population from their early sixties to their seventies.

Methods

A population-based follow-up study among all persons born in 1935 and living in the city of Oulu in northern Finland was conducted. In this study, we examined subjects who had participated in two subsequent surveys conducted in 1996?C1998 and 2007?C2008. The data were gathered by questionnaires, as well as by laboratory and clinical measurements.

Results

Altogether 457 (55%) of the 838 eligible subjects participated in both surveys. The prevalence of both RLS and HS decreased during the 10?years from 21% to 15% and from 26% to 19%, respectively. Half of those who snored in 1996?C1998 stopped snoring in 10?years time, and half of those who suffered from restless legs at least three times per week in 1996?C1998 suffered from this syndrome never or less than once a week in 2007?C2008. The 10-year incidence of new cases of both HS and RLS was 7%. Male gender predicted best the incidence of new HS in 10?years, while the Zung sum score as a marker of depressive symptoms and waist circumference predicted RLS.

Conclusions

Overall, the prevalence of both HS and RLS seems to diminish during aging. The causes behind this still remain unknown and should be investigated with more sophisticated methods.     

Diet and risk of inflammatory bowel disease

BackgroundA better understanding of the environmental factors leading to inflammatory bowel disease should help to prevent occurrence of the disease and its relapses.AimTo review current knowledge on dietary risk factors for inflammatory bowel disease.MethodsThe PubMed, Medline and Cochrane Library were searched for studies on diet and risk of inflammatory bowel disease.ResultsEstablished non-diet risk factors include family predisposition, smoking, appendectomy, and antibiotics. Retrospective case–control studies are encumbered with methodological problems. Prospective studies on European cohorts, mainly including middle-aged adults, suggest that a diet high in protein from meat and fish is associated with a higher risk of inflammatory bowel disease. Intake of the n-6 polyunsaturated fatty acid linoleic acid may confer risk of ulcerative colitis, whereas n-3 polyunsaturated fatty acids may be protective. No effect was found of intake of dietary fibres, sugar, macronutrients, total energy, vitamin C, D, E, Carotene, or Retinol (vitamin A) on risk of ulcerative colitis. No prospective data was found on risk related to intake of fruits, vegetables or food microparticles (titanium dioxide and aluminium silicate).ConclusionsA diet high in protein, particular animal protein, may be associated with increased risk of inflammatory bowel disease and relapses. N-6 polyunsaturated fatty acids may predispose to ulcerative colitis whilst n-3 polyunsaturated fatty acid may protect. These results should be confirmed in other countries and in younger subjects before dietary counselling is recommended in high risk subjects.     

A SIX-CENTRE INTERNATIONAL STUDY OF THE OUTCOME OF TREATMENT IN PATIENTS WITH CLEFTS OF THE LIP AND PALATE: THE RESULTS OF A CROSS-LINGUISTIC INVESTIGATION OF CLEFT PALATE SPEECH

During the period 1964–73, 286 patients were treated for mandibular fractures. 229 patients (80%) attended the follow-up examination. The length of observation was from 1 to 9 years. The treatment and the follow-up evaluations in the 229 patients are described. Early fracture treatment has been the objective, also in patients who have undergone severe cerebral traumas. Antibiotic prophylaxis was implemented in cases of compound fractures. Preservation of teeth and tooth buds in the line of fracture was attempted. Clinical infection occurred in 0.4% of the patients. At the follow-up examination 1 patient presented with a fracture displacement outside the condylar process. Neither malocclusion nor pseudarthrosis following fracture or after treatment were seen. Permanent sensory disturbances in the innervation area of the mental nerve following fracture occurred in 8%. Radiological examination of the teeth in the line of fracture revealed unnoticed apical bone lesions in 17% of 118 patients. In a further 23% there was a negative response to the vitality test. Follow-up control of mandibular fractures is advised at 12 to 18 months after treatment.     

Effects of transcranial direct current stimulation on risky decision making are mediated by ‘hot’ and ‘cold’ decisions,personality, and hemisphere

Previous results point towards a lateralization of dorsolateral prefrontal cortex (DLPFC) function in risky decision making. While the right hemisphere seems involved in inhibitory cognitive control of affective impulses, the left DLPFC is crucial in the deliberative processing of information relevant for the decision. However, a lack of empirical evidence precludes definitive conclusions. The aim of our study was to determine whether anodal transcranial direct current stimulation (tDCS) over the right DLPFC with cathodal tDCS over the lDLPFC (anodal right/cathodal left) or vice versa (anodal left/cathodal right) differentially modulates risk‐taking in a task [the Columbia Card Task (CCT)] specifically engaging affect‐charged (Hot CCT) vs. deliberative (Cold CCT) decision making. The facilitating effect of the anodal stimulation on neuronal activity was emphasized by the use of a small anode and a big cathode. To investigate the role of individual differences in risk‐taking, participants were either smokers or non‐smokers. Anodal left/cathodal right stimulation decreased risk‐taking in the ‘cold’ cognition version of the task, in both groups, probably by modulating deliberative processing. In the ‘hot’ version, anodal right/cathodal left stimulation led to opposite effects in smokers and non‐smokers, which might be explained by the engagement of the same inhibitory control mechanism: in smokers, improved controllability of risk‐seeking impulsivity led to more conservative decisions, while inhibition of risk‐aversion in non‐smokers resulted in riskier choices. These results provide evidence for a hemispheric asymmetry and personality‐dependent tDCS effects in risky decision making, and may be important for clinical research on addiction and depression.     

How facial expressions in a Rett syndrome population are recognised and interpreted by those around them as conveying emotions

Rett syndrome (RTT) is a neurodevelopmental disorder, including autonomic nervous system dysfunctions and severe communication impairment with an extremely limited ability to use verbal language. These individuals are therefore dependent on the capacity of caregivers to observe and interpret communicative signals, including emotional expressions. People in general, including therapists tend to focus on changes in facial expressions to interpret a person's emotional state or choices, but with this population it is difficult to know if the interpretations are correct. The aims of this study were to investigate if the Facial Action Coding System (FACS) could be used to identify facial expressions, and differentiate between those that expressed emotions and those that were elicited by abnormal brainstem activation in RTT. The sample comprised 29 participants with RTT and 11 children with a normal developmental pattern, exposed to six different musical stimuli during non-invasive registration of autonomic brainstem functions. The results indicate that FACS makes it possible both to identify facial expressions and to differentiate between those that stem from emotions and those caused by abnormal brainstem activation. This knowledge may be a great help to an uninitiated observer, who otherwise might incorrectly interpret the latter as an expression of emotion.