The effects of antihistamines with varying anticholinergic properties on voluntary and involuntary movement

ObjectiveRecent evidence indicates that antihistamines can affect movement, which is most likely due to altered neurotransmission in cholinergic and histaminergic pathways. The purpose of this study was to determine if antihistamines with varying anticholinergic properties differentially affect voluntary and involuntary movement control.MethodsEleven healthy subjects were enlisted into a human double blind, placebo-controlled, five-way crossover study. Drowsiness, reaction time, and physiological tremor were examined 1-, 2-, and 3-hr post-ingestion of antihistamines with known anticholinergic profiles. These were the first-generation promethazine, and second-generation loratadine, desloratadine, and fexofenadine. Hyoscine butylbromide was used in an additional experiment to determine how a peripheral antimuscarinic drug influenced neuromotor function.ResultsPromethazine, desloratadine and fexofenadine increased drowsiness. Promethazine increased simple and choice reaction time and reduced tremor. Desloratadine increased choice reaction time and tremor, while loratadine slowed simple and choice reaction time.ConclusionCentral anticholinergic and antihistaminergic properties of antihistamines potentially contribute to movement dysfunction.SignificanceSecond-generation antihistamines have provided the consumer with a safer alternative to the first-generation sedating antihistamine. However, the results of this study suggest that loratadine and desloratadine have the potential to affect movement control, and further research is warranted to understand the clinical relevance of these findings.     

Platelet reactivity in type 2 diabetes mellitus: a comparative analysis with survivors of myocardial infarction and the role of glycaemic control

Patients with type 2 diabetes mellitus exhibit considerable platelet dysfunction, though this is poorly characterized in patients with diabetes taking aspirin for the primary prevention of cardiovascular events. We sought to compare platelet function in this patient population with that of a high-risk group of non-diabetic subjects with a history of previous myocardial infarction (MI), and to assess whether glycaemic control impacts on platelet function. Methods: Platelet aggregation was measured in response to incremental concentrations of five platelet agonists using light transmission aggregometry. All patients were taking aspirin, and aspirin insensitivity was defined as ≥ 20% arachidonic acid (AA) mediated aggregation. Patients with diabetes were divided according to glycaemic control (HbA(1c)): optimal ≤ 6.5, good 6.6-7.4 and suboptimal ≥ 7.5%. Results: In total, 85 patients with type 2 diabetes and 35 non-diabetic patients with previous MI were recruited. Compared to MI patients, diabetes patients had increased aggregation in response to multiple concentrations of epinephrine, collagen, adenosine diphosphate and AA. Aspirin insensitivity was more common in type 2 diabetes (15% vs. 0%, p=0.037). Platelet aggregation was increased in response to several agonists patients with suboptimal glycaemic control compared to patients with optimal control. Aspirin insensitivity was also more common in patients with suboptimal glycaemic control compared to those with good or optimal control (26.0% vs. 8.3% vs. 4%, p=0.04). Conclusion: Patients with type 2 diabetes mellitus, without proven vascular disease, exhibit platelet dysfunction and have increased platelet aggregation and aspirin insensitivity compared to non-diabetic patients with previous MI. Platelet dysfunction in diabetes is more severe in patients with suboptimal glycaemic control.     

How actual motor competence and perceived motor competence influence motor‐skill engagement of a novel cycling task

In early childhood, factors that contribute to motor‐skill engagement (MSE) are unknown. Our aim was to explore the relationships between actual and perceived motor competence and their influences on MSE on a balance bike (bike with no pedals). A secondary aim was to investigate whether MSE had an effect on ability on a balance bike. This study comprised of 45 children (29% female) aged 4.5 ± 0.5 years. MSE was assessed using distance travelled on a balance bike over an 8‐week period. Actual motor competence was assessed using the Movement Assessment Battery for Children, second edition. Perceived motor competence was assessed using the Pictorial Scale of Perceived Movement Skill Competence. Ability on a balance bike was measured using timed trials on a specifically designed track. Pearson product‐moment correlations were used to assess relationships between actual and perceived motor competence and ability on a balance bike. Linear regressions were used to examine whether actual or perceived motor competence or ability on a balance bike predicted MSE. Repeated measures ANOVA was used to examine whether there was a difference in ability on a balance bike between three MSE groups over 8 weeks. No relationships were found, and none of the variables predicted MSE. There was a significant difference between the MSE groups on ability on a balance bike over time (P = 0.019). Investigating the contributors to MSE on a novel cycling task during early childhood provides knowledge to ensure children are given the best opportunities for practice and acquisition of skills.     

Implications of the initial mutations in membrane cofactor protein (MCP; CD46) leading to atypical hemolytic uremic syndrome

The hemolytic uremic syndrome is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. There are two general types. One occurs in epidemic form and is diarrheal associated (D+HUS). It has a good prognosis. The second is a rare form known as atypical (aHUS), which may be familial or sporadic, and has a poor prognosis. aHUS is increasingly recognized to be a disease of defective complement regulation, particularly cofactor activity. Mutations in membrane cofactor protein (MCP; CD46) that predispose to the development of aHUS were first identified in 2003. MCP is a membrane-bound complement regulator that acts as a cofactor for the factor I-mediated cleavage of C3b and C4b deposited on host cells. More than 20 different mutations in MCP have now been identified in patients with aHUS. Many of these mutants have been functionally characterized and have helped to define the pathogenic mechanisms leading to aHUS development. Over 75% of the reported mutations cause a reduction in MCP expression, due to homozygous, compound heterozygous or heterozygous mutations. This deficiency of MCP leads to inadequate control of complement activation on endothelial cells after an initiating injury. The remaining MCP mutants are expressed, but demonstrate reduced ligand (C3b/C4b) binding capacity and cofactor activity of MCP. MCP mutations in aHUS demonstrate incomplete penetrance, indicating that additional genetic and environmental factors are required to manifest disease. MCP mutants as a cause of aHUS have a favorable clinical outcome in comparison to patients with factor H (CFH) or factor I (IF) mutations. In 90% of the renal transplants performed in patients with MCP-HUS, there has been no recurrence of the primary disease, whilst >50% of factor I or factor H deficient patients have had a prompt recurrence. This highlights the importance of defining and characterizing the underlying genetic defects in patients with aHUS.     

An Examination of Gender Differences in the Association of Adolescent Substance use with Eating and Weight Loss Attitudes

Objective: To assess gender differences in the relationship between eating and weight loss attitudes (EWAs), and 30-day tobacco and alcohol use among adolescents, while controlling for potential confounds (age, country of birth, psychological distress, pubertal development, peer alcohol and tobacco use, and sexual activity). Methods: School students aged between 11 and 17 years (N = 10,273) from high schools in the State of Victoria (Australia) completed surveys in class under conditions of anonymity and confidentiality. Results: The interaction between EWAs and gender was significant for tobacco use but not for alcohol use, indicating that the effect of EWAs on tobacco use, but not alcohol use, vary by gender. Conclusions: Tobacco use was related to EWAs in adolescent females but not males, and this is consistent with the possibility that females use tobacco in an instrumental fashion to control weight. Implications and Contribution: Female adolescents high in eating and weight loss attitudes were more likely to engage in tobacco use. In contrast, eating and weight loss attitudes were not related to male tobacco use. These results point to the potential importance of developing gender-specific approaches towards addressing problematic behaviors in adolescent populations.