Reelin-immunoreactivity in the hippocampal formation of 9-month-old wildtype mouse: effects of APP/PS1 genotype and ovariectomy

Reelin, an extracellular matrix protein has an important role in the migration, correct positioning and maturation of neurons during development. Though it is generally down-regulated in the postnatal period, expression of this large glycoprotein continues in the adult brain in some cell populations. In the present study, we examined the distribution of reelin-immunoreactivity (-ir) in the hippocampal formation of 9-month-old wildtype mice (WT). Then, reelin-ir in normal mice was compared to that of transgenic mice (APP/PS1) carrying mutated human APP and PS1 genes, which are linked to the familial form of Alzheimer's disease (AD). The APP/PS1 mice were additionally burdened with a second risk factor for AD, namely depletion of circulating gonadal hormones by ovariectomy (APP/PS1 + OVX). The analyses revealed that in adult WT reelin-ir is expressed by Cajal-Retzius cells and a subgroup of interneurons throughout the hippocampal formation. In addition, layer II projection neurons in the lateral entorhinal subfields are reelin-ir. Interestingly, ovariectomy decreases the number of reelin-ir cells in the hilus in WT mice, whereas AD-related genotype alone induces only a non-significant reduction. Unexpectedly, additional stress, e.g., depletion of gonadal hormones, does not aggravate the slight reduction in the reelin cell number in the APP/PS1 mice. We propose that the changes in normal reelin-ir are linked to disturbances in repair mechanisms in which APP/PS1 and gonadal hormones are involved and which are perturbed in neurodegenerative conditions, namely AD.     

Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action,Efficacy and Safety

Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine.     

Drug safety and tolerability in prophylactic migraine treatment

Introduction: Migraine is a frequent, disabling primary headache disorder, whose pathomechanism is not yet fully understood. Prophylactic treatment is advisable for migraineurs with severe or highly frequent attacks, which impair the quality of life.

Areas covered: The different types of prophylactic migraine drugs are discussed, with particular regard to potential adverse effects and safety issues. β-Adrenergic blockers, antiepileptic drugs and calcium-channel blockers are drugs widely used for migraine prevention, whereas complementary medicine and onabotulinumtoxin A can be used in selected cases.

Expert opinion: The background of the recurrence and chronification of migraine attacks has not been fully clarified, and causative preventive therapy is therefore not currently available. The tolerability and adverse effects of the currently used medications often limit their use. β-Adrenergic receptor blockers may induce adverse cardiovascular events, whereas flunarizine is frequently associated with a weight gain and depression. As most migraine sufferers are young women of child-bearing age, the use of valproate is limited. Topiramate is associated with central nervous system-related side effects. There is a need for future development of pathomechanism-based preventive drugs, and personalized therapy tailored to the patient.     

Repetitive jumping and sprinting until exhaustion alters hamstring reflex responses and tibial translation in males and females

The incidence of anterior cruciate ligament injuries is considerably higher in females than in males and the underlying mechanisms are still under debate. Research indicates that the neuromuscular system of females and males might respond differently to the same fatigue protocol due to differences in muscle activation during movement tasks. This study analyzed sex differences in hamstring reflex responses and posterior‐anterior tibial translation (TT) before and after fatiguing exercise. We measured the isolated movement of the tibia relative to the femur as a consequence of mechanically induced TT in standing subjects as well as muscle activity of the hamstrings before and after repetitive jumping and sprinting until exhaustion. Muscle fatigue delayed reflex onset latencies in females and males. A reduction in reflex responses associated with an increased TT was observed after fatiguing exercise for both sexes. Data indicate that the used fatigue protocol altered the latency and magnitude of reflex responses as well as TT in females and males. Based on the results of previous research and the outcome of this study, it might be that sex‐specific effects of fatigue on reflex activity and mechanical stability of the knee depend on the kind of fatiguing exercise. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1687–1692, 2015.     

Dental fear and anxiety scores of a Hungarian population living in the Hungarian-Slovakian border region. A pilot study

The aim of the authors was to investigate whether living as a minority has an influence on the dental fear and anxiety values. In this study 201 volunteers (n = 201, inside border Hungarians 144, outside border Hungarians 57, male 90, female 111; age 8 to 83 years, mean 44 +/- 16 yrs.) were investigated. Our methods included collection of demographic data (gender, age, marital status, profession), and administration of the Hungarian versions of dental fear and anxiety related scales namely: DAS, DAQ, DASQ, DFS, DBS, STAI-S, STAI-T and Expectation Scale. Mean values of the scales were: DAS: 10,34 +/- 3,54; DAQ: 2,3 +/- 1,15; DASQ: 12,58 +/- 4,55; DFS: 40,37 +/- 15,67; DBS: 32,89 +/- 12,94; Expectation Scale: 2,87 +/- 3,56, STAI-S: 39,51 +/- 10,68; STAI-T 41,65 +/- 9,08. The mean scores of all the scales were higher in the case of Hungarians living inside the borders of Hungary. The differences were significant in the case of DAS, DAQ, DASQ and DFS scales (p < 0,05). Data of our study indicate that living as a minority not necessarily leads to the increase of dental fear and anxiety.     

Influence of patient characteristics on preventive service delivery and general practitioners’ preventive performance indicators: A study in patients with hypertension or diabetes mellitus from Hungary

Background: Regular primary healthcare (PHC) performance monitoring to produce a set of performance indicators for provider effectiveness is a fundamental method for improving guideline adherence but there are potential negative impacts of the inadequate application of this approach. Since performance indicators can reflect patient characteristics and working environments, as well as PHC team contributions, inadequate monitoring practices can reduce their effectiveness in the prevention of cardiometabolic disorders.

Objectives: To describe the influence of patients’ characteristics on performance indicators of PHC preventive practices in patients with hypertension or diabetes mellitus.

Methods: This cross-sectional analysis was based on a network of 165 collaborating GPs. A random sample of 4320 adults was selected from GP’s patient lists. The response rate was 97.3% in this survey. Sociodemographic status, lifestyle, health attitudes and the use of recommended preventive PHC services were surveyed by questionnaire. The relationship between the use of preventive services and patient characteristics were analysed using hierarchical regression models in a subsample of 1659 survey participants with a known diagnosis of hypertension or diabetes mellitus.

Results: Rates of PHC service utilization varied from 18.0% to 97.9%, and less than half (median: 44.4%; IQR: 30.8–62.5) of necessary services were used by patients. Patient attitude was as strong of an influencing factor as demographic properties but was remarkably weaker than patient socioeconomic status.

Conclusion: These findings emphasize that PHC performance indicators have to be evaluated concerning patient characteristics.