Schlaf bei neurodegenerativen Erkrankungen

Zusammenfassung Die neurodegenerativen Erkrankungen bestehen aus einer Gruppe heterogener, progredient verlaufender Erkrankungen unterschiedlicher Ätiologie, die ein oder mehrere Systeme beeinträchtigen. Sie treten überwiegend im höheren Lebensalter auf, in dem sich zusätzlich sowohl die Art wie auch das Ausmaß des Schlafes ändern. Die neurodegenerativen Prozesse verursachen strukturelle Veränderungen der Schlaf-Wach-Generatoren im Hirnstamm, die Schlafstörungen wie Tagesschläfrigkeit, Insomnie, nächtliche bewegungs- und schlafbezogene Atmungsstörungen sowie Störungen des zirkadianen Schlaf-Wach-Rhythmus zur Folge haben können. Bei manchen neurodegenerativen Erkrankungen sind im Vorfeld der Krankheitsmanifestation auftretende Schlafstörungen bereits Krankheitsprädiktoren. Polysomnographisch finden sich Schlaffragmentierung, tonische oder phasische Beinbewegungen, Störungen der Atemmuskulatur, verminderter Tiefschlaf, Abwesenheit von REM-Schlaf oder REM-Schlaf ohne Muskelatonie, vermehrte Arousal- und Weckreaktionen, epileptiforme EEG-Aktivität oder schlafbezogene Atmungsstörungen. Sehr häufig sind REM-Schlaf-Verhaltensstörungen assoziiert mit neurodegenerativen Erkrankungen. In dieser Übersichtsarbeit werden Symptomatik, Pathophysiologie und polysomnographische Befunde von Schlafstörungen häufiger neurodegenerativer Erkrankungen vorgestellt.     

Is substance P a primary afferent neurotransmitter for nociceptive input? III. Valproic acid and chlordiazepoxide decrease behaviors elicited by intrathecal injection of substance P and excitatory compounds

Intrathecal (i.t.) injections of substance P (SP) and kainic acid in rats produced rostrally directed scratches with the hindlimbs and caudally directed bites or licks. These behaviors, together with myoclonic twitches and vocalization, were also produced by I.T. morphine and strychnine. Intrathecal valproic acid (VA) significantly reduced all behaviors when these occurred spontaneously, and VA and chlordiazepoxide both reduced these behaviors when they were evoked by a light cotton swab tap to the lumbosacral region, in rats treated with the excitatory compounds. Since neither anticonvulsant affected the thermal or mechanical pain threshold at these doses, these results suggest that (a) the behaviors elicited by i.t. injection of the excitatory compounds are not responses to perceived pain, but rather the expression of a spinal convulsive-like state, and (b), since scratching and biting were the only behaviors produced by SP, this peptide is neither necessary nor sufficient for the elicitation of pain at the spinal level. Although our experiments do not rule out other roles for SP in pain processes such as that of a neuromodulator, it is unlikely that this compound is a traditional primary afferent neurotransmitter of pain.     

Reformulation and drop size of apraclonidine hydrochloride.

We performed a prospective, double-masked, placebo-controlled, six-period, cross-over study in which normal subjects were randomly assigned to treatment and compared three different formulations of apraclonidine hydrochloride (the present commercially available formulation, and formulations with hydroxypropylmethylcellulose or lysolecithin). We also evaluated the efficacy of a 16-microliters and 30-microliters drop size. The magnitude and duration of decrease in intraocular pressure was comparable for all formulations. Most subjects tolerated all formulations well with only a few reporting any side effects. The best-tolerated formulation was 0.5% apraclonidine hydrochloride delivered with a 16-microliters drop size. Dry mouth developed frequently with the commercially available 1% apraclonidine solution. Blurred vision complicated the use of the formulation containing hydroxypropylmethylcellulose. Both dry mouth (P less than .05) and blurred vision (P = .004) were statistically significant side effects.     

The Association of Different Measures of Insulinaemia with Vascular Risk Factors in Healthy Normoglycaemic Normotensive Non-obese Men and Women

Hyperinsulinaemia is said to be a risk factor for cardiovasculardisease, but the extent to which different insulinaemic measuresare associated with vascular risk factors in ostensibly healthyindividuals, and whether they operate independently in men andwomen, remains uncertain. The association between risk factors and various insulinaemicmeasures was examined in 148 men and 118 women who were normoglycaemic,normotensive, and non-obese (body mass index in men <27,in women <25). A 75 g glucose tolerance test was administeredafter blood sampling for fibrinogen, lipids, lipoproteins andinsulin. Insulin was also measured after 1 and 2 hours. Significantunivariate correlations (p<0.01) were most consistently recordedbetween insulinaemic measures and fasting serum triglyceridesin men and women, whilst systolic blood pressure only correlatedwith insulinaemia in women, and diastolic blood pressure correlatedwith fasting and 2 hour insulinaemic measures in men and women.Inconsistent associations were noted with total serum cholesterolin men and women, with high density lipoprotein cholesterol,body mass index, apoprotein B and A1 in men, and with fibrinogenin women. Age was not correlated with any insulinaemic measurein men or women. Differences in vascular risk factors between quintiles of theinsulinaemic measures were examined, after correction for bodymass index. The dominant association with fasting and post-glucoseload insulinaemic measures was with triglycerides, especiallyin women, with less frequent graded differences between quintilesobserved for total cholesterol, and diastolic and systolic bloodpressures in men and women. The incidence of other risk factors often only differed in thelowest or highest quintile in comparison to other quintiles,suggesting a threshold rather than a graded effect. Furthermore,differences in HDL cholesterol and apoprotein B were only recordedfor top quintiles of post-glucose challenge/integrated insulinaemicmeasures in men, whilst serum fibrinogen concentrations onlydiffered significantly in women in the top insulinaemic areaunder the curve quintile. In the absence of additional risk factors such as diabetes,hypertension and obesity, insulinaemic measures are not consistentlyrelated to blood pressure and measures of lipid metabolism andcoagulation, and are thus a weak predictor of other cardiovascularrisk factors. The vascular risk profile associated with insulinappears somewhat different in apparently healthy men and women.     

Methodological issues associated with using different cut-off points to categorize outcome variables.

Knowledge of the factors that contribute to delay in seeking medical treatment for acute myocardial infarction (AMI) provides the basis for interventions that are intended to facilitate prompt care-seeking behaviour. However, operational definitions of delay time vary across research studies. The use of inconsistent cut-off times to distinguish between delayers and non-delayers is likely to compromise comparability and generalizability of the findings across studies. The purpose of this paper is to examine the impact of inconsistent operationalization of delay, in terms of cut-off times, on the validity of research findings pertaining to identifying its predictors. Secondary data analysis was performed using a sample of 73 patients who had recently experienced out-of-hospital AMI and concluded that their symptoms were related to the heart. Several regression models were built to examine the influence of using different cut-off times (1, 2, 3, 6, and 12 hours, median delay) on the number and nature of predictors ofAMI care-seeking delay.The impact of varying cut-off times on the explained variance, sensitivity, specificity, and predictive values associated with each regression model was examined. The use of different cut-off times produced different sets of independent predictors, which varied in number and nature.The variance explained by the different regression models as well as their classification indices varied. Use of different cut-off times for the definition of delay time led to inconsistent results. Thus, it is recommended that criteria be established among clinicians and researchers with regard to operationally defining care-seeking delay for AMI.     

Effect of two preventive programs on oral health knowledge and habits among Brazilian schoolchildren

Abstract – The effect upon dental health knowledge and dental health behavior of a comprehensive and a less comprehensive preventive program was compared in a 3-yr follow up study. The comprehensive program included active participation of the students and parental involvement. The study group consisted of 186 Brazilian schoolchildren 13 yr of age at the start of the program. A reference group from another school of similar socioeconomic level was included in the analyses. The data were collected from questionnaires filled in by the children under surveillance after the completion of the program. Significant differences in knowledge as well as in reported behavior were observed. The children enrolled in the comprehensive program in general scored higher in dental health knowledge than did those in the less comprehensive program. However, the latter group of children seemed to have acquired more correct knowledge during the period than had the control and reference children. Similar results were obtained concerning reported dental health behavior.     

Time course of vascular prostanoid production in the fructose‐hypertensive rat

1 There is a relationship between hypertension, insulin resistance and an altered plasmatic lipid profile known as ‘metabolic syndrome’. Fructose (F) overload induces in the rat a mild hypertension associated with metabolic alterations such as hyperglycemia, hypertriglyceridemia and insulin resistance, resembling such syndrome. 2 Prostanoids (PR), metabolites of arachidonic acid, include vasoactive substances synthesized and released by the vessel wall. An altered pattern of PR release has been previously found in mesenteric vessels of experimental diabetic rats. 3 This study analyzed the effects of F‐overload during different periods (4, 9, 15 and 22 weeks) on PR release in aorta (A) and mesenteric vascular beds (MVB). Animals received tap water (control) or F solution (10% w/v) to drink. 4 Rats with F overload showed significantly higher systolic blood pressure, glycemia and triglyceridemia than controls; but no differences in this parameters were found among periods of treatment either in controls or experimental animals. 5 In A, prostacyclin was decreased at 9, 15 and 22 weeks of treatment when compared to 4 weeks and controls. In MVB, prostacyclin showed different patterns of release in the studied periods of F overload. Prostaglandin (PG) E₂ diminish in MVB at the same extent in all periods. No changes were observed in A. The vasoconstrictor thromboxane was elevated in the MVB at 9 weeks. PGF₂α, also a vasoconstrictor, remains unchanged. 6 In conclusion, F overload provokes in the rat a decrease in the vascular production of vasodilator PR and, in one of the studied periods, an increase in the release of the vasoconstrictor thromboxane, leading to a negative imbalance in the prostacylin/thromboxane ratio. This could be involved in the blood pressure alterations found in this experimental model of metabolic syndrome.