A novel diketopiperazine improves functional recovery given after the onset of 6-OHDA-induced motor deficit in rats

Background and purpose:

Cyclo-L-glycyl-L-2-allylproline (NNZ-2591), a modified diketopiperazine, is neuroprotective and improves long-term function after hypoxic-ischaemic brain injury in rats. The present studies were designed to examine both the neuroprotective and neurotrophic actions of NNZ-2591 on neurochemical and behavioural changes in a rat model of Parkinson''s disease.

Experimental approach:

To examine its protective effect, either NNZ-2591 (20 ng·day⁻¹) or saline was given intracerebroventricularly for 3 days starting 2 h after 6-hydroxydopamine (6-OHDA) induced unilateral striatal lesion. In a subsequent experiment either NNZ-2591 (0.2, 1 and 5 mg·day⁻¹, s.c.) or saline was administered daily for 14 days starting 2 weeks after the lesion. Behavioural and neurochemical outcomes were examined using the adjusting step test and immunohistochemical staining.

Key results:

Cyclo-L-glycyl-L-2-allylproline given 2 h after the lesion reduced the degree of motor deficit compared with the saline-treated group. Delayed treatment with NNZ-2591, initiated after the onset of motor deficit, significantly improved motor function from week 7 onwards compared with the saline-treated group. Neither treatment regime altered nigrostriatal dopamine depletion. NNZ-2591 significantly enhanced the expression of doublecortin-positive neuroblasts in the sub-ventricular zone.

Conclusions and implications:

These studies reveal that early treatment with NNZ-2591 protects against the motor deficit induced by 6-OHDA and that treatment initiated after the establishment of motor impairment significantly improves long-term motor function. These effects of NNZ-2591 on functional recovery were independent of dopamine depletion and also appeared not to be symptomatic as the improved motor function was long-lasting. NNZ-2591 has potential as a therapeutic agent for neurodegenerative disorders.     

Offense related characteristics and psychosexual development of juvenile sex offenders

Objective:  

This article reports on offense related characteristics and the psychosexual development in subgroups of juvenile sex offenders as measured by the Global Assessment Instrument for Juvenile Sex Offenders (GAIJSO). The predictive validity of these characteristics for persistent (sexual) offensive behavior in subgroups of juvenile sex offenders was investigated.     

Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome

Radonic T, de Witte P, Groenink M, de Bruin‐Bon RACM, Timmermans J, Scholte AJH, van den Berg MP, Baars MJH, van Tintelen JP, Kempers M, Zwinderman AH, Mulder BJM. Critical appraisal of the revised Ghent criteria for diagnosis of Marfan syndrome. Marfan syndrome (MFS) is a connective tissue disorder with major features in cardiovascular, ocular and skeletal systems. Recently, diagnostic criteria were revised where more weight was given to the aortic root dilatation. We applied the revised Marfan nosology in an established adult Marfan population to define practical repercussions of novel criteria for clinical practice and individual patients. Out of 180 MFS patients, in 91% (n = 164) the diagnosis of MFS remained. Out of 16 patients with rejected diagnosis, four patients were diagnosed as MASS (myopia, mitral valve prolapse, borderline non‐progressive aortic root dilatation, skeletal findings and striae) phenotype, three as ectopia lentis syndrome and in nine patients no alternative diagnosis was established. In 13 patients, the diagnosis was rejected because the Z‐score of the aortic root was <2, although the aortic diameter was larger than 40 mm in six of them. In three other patients, the diagnosis of MFS was rejected because dural ectasia was given less weight in the revised nosology. Following the revised Marfan nosology, the diagnosis of MFS was rejected in 9% of patients, mostly because of the absence of aortic root dilatation defined as Z‐score ≥2. Currently used Z‐scores seem to underestimate aortic root dilatation, especially in patients with large body surface area (BSA). We recommend re‐evaluation of criteria for aortic root involvement in adult patients with a suspected diagnosis of MFS.     

Peak expiratory flow rate in healthy children aged 6–17 years

Peak expiratory flow rate (PEFR) was measured in a cross-sectional study in 861 healthy Danish schoolchildren aged 6–17 years using a Mini Wright peak flowmeter. We found a strong correlation between PEFR and height, age and sex. The results were comparable with those from previous studies using a Wright peak flowmeter. The equation for prediction of PEFR in boys was calculated as (3.8 × height) + (10.6 × age) - 313.2 ( p < 0.0001, r = 0.8), and for girls, PEFR = (2.2 × height) + (14.2 × age) - 143.9 ( p < 0.0001, r = 0.64). Our results appear to be reliable, as evidenced by the high correlation coefficient in this large sample. Among healthy children without previous asthma, earlier episodes of recurrent wheezing were reported in 8.8% and a significantly lower PEFR was found in this group.