The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G>C and APOA5 −1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (P<0.05). Furthermore, the frequencies of the APOA5 c.56 G>C polymorphism and LPL c.27 G>A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 −1131 T>C, c.56 G>C and/or LPL c.27 G>A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval=1.8–7.5, P<0.0001). The HTG patients showed similar allele frequencies of the APOA5, APOC3 and LPL polymorphisms, whereas the NDCP showed similar allele frequencies as the normolipidemic APOE2/2. Patients with the APOC3 3238 G>C/APOA5 −1131 T>C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2.     

Histamine H1 receptor knockout mice exhibit impaired spatial memory in the eight-arm radial maze

Background and purpose:

In the mammalian brain, histaminergic neurotransmission is mediated by the postsynaptic histamine H₁ and H₂ receptors and the presynaptic H₃ autoreceptor, which also acts as a heteroreceptor. The H₁ receptor has been implicated in spatial learning and memory formation. However, pharmacological and lesion studies have revealed conflicting results. To examine the involvement of histamine H₁ receptor in spatial reference and working memory formation, H₁ receptor knockout mice (KO) were tested in the eight-arm radial maze. Previously, we found that the H₁ receptor-KO mice showed reduced emotionality when confronted with spatial novelty. As it is known that emotions can have an impact on spatial learning and memory performance, we also evaluated H₁ receptor-KO mice in terms of emotional behaviour in the light–dark box.

Experimental approach:

Mice lacking the H₁ receptor and wild-type mice (WT) were tested for spatial reference and working memory in an eight-arm radial maze with three arms baited and one trial per day. Emotional behaviour was measured using the light–dark test.

Key results:

The H₁ receptor-KO mice showed impaired spatial reference and working memory in the radial maze task. No significant differences between H₁ receptor-KO and WT mice were observed in the light–dark test.

Conclusions and implications:

The spatial memory deficits of the H₁ receptor-KO mice might be due to the reported changes in cholinergic neurochemical parameters in the frontal cortex and the CA1 subregion of the hippocampus, to impaired synaptic plasticity in the hippocampus, and/or to a dysfunctional brain reward/reinforcement system.     

Ondansetron compared with metoclopramide in the treatment of established postoperative nausea and vomiting

We have studied 746 males and females undergoing general anaesthesia for any type of surgical procedure in a double-blind, controlled, randomized study. After experiencing at least one nausea and/or one emetic episode in the 6 h after recovery from anaesthesia, patients received either ondansetron 4 mg i.v. or metoclopramide 10 mg i.v. Patients were observed for postoperative nausea and vomiting (PONV) for 24 h after drug administration. Complete control of PONV was achieved more frequently in the ondansetron-treated patients compared with the metoclopramide-treated patients during the 24-h period (59% vs 41% (P < 0.001) and 44% vs 34% (P = 0.006) for emetic episodes and nausea, respectively). Furthermore, ondansetron was associated with greater patient satisfaction than metoclopramide (P < 0.001) with 49% and 32% of patients, respectively, very satisfied. The overall incidence of adverse events was similar in the ondansetron (7%) and metoclopramide (8%) groups. Ondansetron was as well tolerated and more effective than metoclopramide for all assessment criteria in the treatment of established PONV.      

Efficacy and safety of a new single-dose terbinafine 1% formulation in patients with tinea pedis (athlete''s foot): a randomized, double-blind, placebo-controlled study

BACKGROUND: Tinea pedis is a common dermatophyte infection with frequent recurrences. Terbinafine (presently used as a 1-week topical treatment of tinea pedis) is now available in a novel topical solution (film-forming solution--FFS), developed to allow single application. OBJECTIVES: To demonstrate the efficacy and safety of terbinafine 1% FFS in a randomized, double-blind, placebo-controlled, phase III trial, and to determine relapse or re-infection rate of tinea pedis at 12 weeks. PATIENTS/METHODS: Fifty-four centres (27 in France; 27 in Germany) enrolled 273 evaluable patients (2 : 1 randomization). Patients applied terbinafine 1% FFS or placebo only once between, under and over the toes, soles and sides of both feet. Efficacy assessments included direct microscopy, mycological culture, and clinical signs and symptoms at baseline, and at weeks 1, 6 and 12 after the single drug application. RESULTS: Effective treatment (negative mycology plus absent/minimal symptoms) at week 6 in the terbinafine 1% FFS group was 63%; vehicle was 17% (P相似文献   

HLA-DRB1*04 subtypes are associated with increased inflammatory activity in early rheumatoid arthritis

The sequence polymorphism of HLA-DRB1 molecules in 84 rheumatoid arthritis (RA) patients with early RA has been analysed to evaluate whether particular HLA-DR alleles influence disease progression in the early stage of the disease. Clinical data were analysed by grouping the patients according to disease-associated haplotype combinations (DRB1*04,04/DRB1*04,01/DRB1*04,X/DRB1*01,X) in comparison to patients who did not carry these haplotypes (DRB1*X,X). Our results indicate that patients with early RA who are homozygous for DRB1*04 exhibit an elevated inflammatory activity and an increase of joint affections. In addition, the amino acid polymorphism (QR/KRAA) at position 70-74 seems to affect the production of rheumatoid factors. These results support the role of HLA-DRB1 alleles in the pathogenesis of RA and indicate that patients with particular HLA-DRB1*04 haplotype combinations may require intensified therapeutic interventions in the early stage of the disease to prevent disease progression.