Effects of Hypericum extract on the acetylcholine release: a loose patch clamp approach.

The St. John's Wort (Hypericum perforatum) extract (Hp) represents one of the most useful natural therapeutic agents in the treatment of moderate and mild depression. The antidepressant effects of Hp are different, by a molecular mechanism point of view, when compared to those of other antidepressant drugs and, we think, a further pharmacological characterization is needed. It is suggested that the neurochemical effects of Hp could be bind either to its activity on the uptake of some mediators in the central nervous system or to the inhibition of some enzymatic activity at the receptor level. The present study carried out with the loose patch clamp (LPC) in the mouse neuromuscular junction, indicates a potentiation of the acetylcholine (ACh) action at the mouse neuromuscular junction. The spontaneous release of ACh was unaffected by Hp indicating that neither presynaptic nor postsynaptic function are modified by Hp. Indeed, both the frequency and the amplitude of the miniature end-plate currents (mepcs) were unmodified by Hp. Furthermore, the mepcs decay time (tau), i.e. the apparent cholinergic channel life time, was significantly increased after Hp treatment. The other parameter affected was the amplitude of the evoked end-plate currents (epcs) which was constantly and in a dose dependent manner increased by Hp. These findings suggest a possible action of Hp on the acetylcholinesterase (AChE) in terms of a reduction of the degradation rate of ACh.     

CTLA-4 exon 1 polymorphism in patients with autoimmune blood disorders

CTLA-4 is a CD28 homologue that plays an important role in negative regulation of T-cell responses. Its transient expression on the surface of activated T cells antagonizes the activating signals and terminates the T-cell response. An A to G polymorphism at position 49 of the CTLA-4 first exon has recently been associated with several autoimmune disorders. In the present study we have examined the prevalence of the A and G alleles of the CTLA-4 gene in 50 patients with autoimmune hemolytic anemia (AIHA), of which 20 had idiopathic AIHA and 30 had AIHA and chronic lymphocytic leukemia (CLL), and in 60 patients with immune thrombocytopenic purpura (ITP). Control subjects were 100 healthy individuals and 100 CLL patients without clinical evidence for an autoimmune disease. The G allele was present at a significantly higher frequency among the patients with AIHA (P = 0.003), whereas no difference was observed between patients with ITP and controls. The G allele frequency was highest among CLL patients who had developed AIHA. The obtained data indicate that the G allele of CTLA-4 predisposes to the development of AIHA, particularly among patients with CLL.     

Risk analysis in tibial plateau fractures: association between severity, treatment and clinical outcome

Our retrospective study analyzes efficacy of treatment techniques we used for the reduction of tibial plateau fracture. A sample of 67 individuals is evaluated, 50 males and 17 females, and treated for a tibial plateau fracture from December 2003 to June 2008. The mean age is 46 (range 22–72). 35 patients were treated with cannulated screws alone, 21 were treated with plates alone, and 11 were treated with both plates and bone substitutes. All patients were clinically and radiographically followed up for an average time of 36.4 months (SD = 17.4; range 24–72). Data about patients sourced from the analysis of SF36, WOMAC and the Rasmussen score. Patients were divided into 4 groups and 2 subgroups, according to the synthesis method used and the severity of the fracture. The control group includes the patients diagnosed with a low-energy fracture treated with screws alone. The median of the total score of Rasmussen functional grading system resulted to be equal to 26; compared with the control group, there is strong relationship between the use of plates alone and the risk of obtaining a clinically less effective result (O.R. = 5.48; p = 0.003) even more when comparing Schatzker type IV, V, and VI (O.R. = 13; p = 0.0073). Radiographic evaluation shows less efficacy of bone substitute to reduce articular step-off. With regard to the SF36, patients treated with plate alone have been awarded the lowest score. The treatment of the most severe fractures of tibial plateau by means of internal fixation with plates can be improved with the use of bone substitutes.     

Quality assurance in drug demand reduction in European countries: an overview

Background: The EMCDDA, through its network of National Focal Points, collects information on the quality assurance systems for drugs-related interventions across European countries. European National Drug Strategies include recommendations for systems and approaches for the assurance of the quality of interventions.

Methods: We searched National Drug Strategies for elements related to quality assurance in drug demand reduction and summarised information through questionnaires administered to the EMCDDA Network of National Focal Points.

Results: In total, 15 National Drug Strategies and 60 questionnaires were analysed. Almost all the strategies include quality-related topics. Frequently, the Ministry of Health leads quality assurance although sometimes jointly with the Ministries of Education, Labour, Family and Social Welfare. Accreditation systems are common, but implemented in different ways. Training and education are widely provided, for the vast majority of countries, consisting of short-term training to keep professionals updated. Guidelines and Standards are gathering momentum as the major tools for the implementation of evidence-based recommendations and are usually available across countries.

Conclusions: Although the evidence base for interventions in drug demand reduction is becoming available and accepted, attention needs to be given to implementation issues. The European countries are rapidly moving towards paying greater attention to the quality of interventions.     

Detection of Genotype-Specific Antibody Responses to Glycoproteins B and H in Primary and Non-Primary Human Cytomegalovirus Infections by Peptide-Based ELISA

Background: Strain-specific antibodies to human cytomegalovirus (HCMV) glycoproteins B and H (gB and gH) have been proposed as a potential diagnostic tool for identifying reinfection. We investigated genotype-specific IgG antibody responses in parallel with defining the gB and gH genotypes of the infecting viral strains. Methods: Subjects with primary (n = 20) or non-primary (n = 25) HCMV infection were studied. The seven gB (gB1-7) and two gH (gH1-2) genotypes were determined by real-time PCR and whole viral genome sequencing, and genotype-specific IgG antibodies were measured by a peptide-based enzyme-linked immunosorbent assay (ELISA). Results: Among subjects with primary infection, 73% (n = 8) infected by gB1-HCMV and 63% (n = 5) infected by gB2/3-HCMV had genotype-specific IgG antibodies to gB (gB2 and gB3 are similar in the region tested). Peptides from the rarer gB4-gB7 genotypes had nonspecific antibody responses. All subjects infected by gH1-HCMV and 86% (n = 6) infected by gH2-HCMV developed genotype-specific responses. Among women with non-primary infection, gB and gH genotype-specific IgG antibodies were detected in 40% (n = 10) and 80% (n = 20) of subjects, respectively. Conclusions: Peptide-based ELISA is capable of detecting primary genotype-specific IgG responses to HCMV gB and gH, and could be adopted for identifying reinfections. However, about half of the subjects did not have genotype-specific IgG antibodies to gB.