Altered dimerization of metabotropic glutamate receptor 3 in schizophrenia.

BACKGROUND: Metabotropic glutamate receptors (mGlus) may be involved in the pathophysiology of schizophrenia. Group II mGlus (mGlu2 and mGlu3) have attracted considerable interest since the development of potent specific agonists that exhibit atypical antipsychotic-like activity and reports of a genetic association between the mGlu3 gene and schizophrenia. METHODS: In this postmortem study, mGlu3 protein levels in Brodmann area 10 of prefrontal cortex from schizophrenic (n = 20) and control (n = 35) subjects were analyzed by western immunoblotting using a novel specific mGlu3 antibody and an antibody for the vesicular glutamate transporter 1 (VGluT1). RESULTS: We report a significant decrease in the dimeric/oligomeric forms of mGlu3 in schizophrenic patients compared with control subjects, whereas total mGlu3 and VGluT1 levels were not altered significantly. CONCLUSIONS: This is the first experimental evidence that mGlu3 receptor levels are altered in schizophrenia and supports the hypothesis that neurotransmission involving this particular excitatory amino acid receptor is impaired in schizophrenia.     

Stronger association of drug-induced progressive multifocal leukoencephalopathy (PML) with biological immunomodulating agents

Aim  

The aim of the present study was to collect and compare cases of drug-induced PML in order to contribute to the debate about the role of the underlying diseases and/or drug immunosuppression in PML occurrence.     

Macular electroretinogram as a function of age of subjects

Macular and paramacular electroretinograms in response to two adjacent checks (6 deg/side), alternating at constant mean luminance, were recorded in 34 normal subjects ranging in age from 16 to 74 years. The macular electroretinogram declines progressively in amplitude with age (R = –0.42; P = 0.013). The amplitude ratio between macular and paramacular responses tends to be independent of age (R = -0.21; P = 0.22).Age-related changes in the macular electroretinogram shown in our study are consistent with previous anatomical and functional studies, which indicate a deterioration of photoreceptors beyond 20 years of age. These results suggest a possible use of this technique for future studies on macular degeneration.     

Spontaneous reporting of adverse drug reactions in an Italian region: Six years of analysis and observations

Pharmacovigilance started in Italy in 1965, and from 1987 reporting of ADRs has been mandatory. Doctors have to send the filled forms on suspected ADRs to the Local Health Districts which transmit biannually all the reports to the Health Department. In a Northern Italian Region (Veneto) spontaneous reporting of adverse drug reactions (ADRs) has been studied during the period 1988–1993. This Region contributes a substantial percentage of the total Italian reports. The total number of reports was 3700, most of these (54 per cent) coming from GPs. A great variability in the reporting rate among the 36 districts of Veneto Region (range: 0–8.8 per 10,000 inhabitants per year) and an important under-reporting have been evident. Underreporting is also emphasized by the fact that in 1993 the Veneto doctors who sent at least one report were only 2.7 per cent. On the whole about 35 per cent of reports concerned minor reactions caused by drugs which have a well known toxicological profile. Comparison between reports coming from Veneto and the UK in some cases show a similar safety profile (omeprazole and simvastatin), whereas in other cases (e.g. terfenadine, glafenine, fluoxetine) no correspondence can be found. This article reveals the limits of the actual spontaneous reporting in Italy and suggests some possible measures for improving it.     

Pattern electroretinogram as a function of spatial frequency in ocular hypertension and early glaucoma

Pattern electroretinograms (PERGs) in response to 8.3 Hz alternating gratings (16.6 rev/sec) of different spatial frequencies were recorded in normal subjects as well as in patients affected by early glaucoma and ocular hypertension. In normal subjects the PERG response is spatially tuned, with a maximum at about 1.5 cycles/deg and attenuation at higher and lower spatial frequencies. In all cases of early glaucoma and in the great majority of cases of ocular hypertension the PERG was reduced, as compared with that of normal subjects, mainly in the medium range of spatial frequencies (at which the PERG has its maximal amplitude).     

Testicular regression syndrome. A case report

Testicular regression syndrome occurred in a 20-year-old, white, phenotypic female with a 46,XY karyotype. The basal levels of serum gonadotropins were elevated, while the testosterone was in the normal range. Estrogens were undetectable. At laparotomy no gonadal rudiments or müllerian or wolffian derivatives were found. The logical diagnosis was late embryonic testicular regression with a specific testicular insult 62-63 days after fertilization.     

Assessment of enamel hypoplasia in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

The features of enamel hypoplasia in a small group of patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) are described. Using a recently developed method, the authors evaluated quantitatively the amount of defect in each tooth by measuring the width of the hypoplastic lesions and dividing the value by the crown height. They then assessed the degree of damage in each tooth type (from central incisors to second premolars) and patient. Canines were the most severely affected among maxillary and mandibular teeth, but all tooth types were involved. Analysing both the differences between patients and their age at the beginning of the defect, the authors observe that hypoparathyroidism is not responsible for the onset of enamel hypoplasia in APECED, although it may contribute to the damage.     

A fatal postpartum Clostridium sordellii associated toxic shock syndrome.

Clostridium sordellii is an infrequent human pathogen. It has been demonstrated to be occasionally responsible for myonecrosis or gas gangrene. Interestingly, in the obstetric literature, some cases of postpartum maternal deaths have been associated with C sordellii infection causing a rapidly lethal toxin mediated syndrome. This is the first reported case of postpartum death in a 29 year old woman, in which a toxigenic C sordellii was isolated from the patient's blood antemortem during the fatal toxic shock, strongly indicating its role in this rare syndrome.     

Nasal response of rhinitic and non-rhinitic subjects to histamine and methacholine: a comparative study.

The nasal responses to provocation with histamine and methacholine were compared in 20 subjects with and 20 without rhinitis. Two variables were measured: nasal airways resistance and the development of rhinorrhoea. Histamine had a greater effect than methacholine in increasing nasal airways resistance while the converse was true for rhinorrhoea. Rhinitic subjects had a significantly greater response to histamine induced changes in nasal airways resistance (p less than 0.05), rhinorrhoea (p less than 0.05) and methacholine induced rhinorrhoea (p less than 0.01) than those without rhinitis. No significant differences were found between the two groups in methacholine induced changes in nasal airways resistance. The findings show that, like the lower airways of patients with asthma, the nasal mucosa of rhinitic subjects shows a greater responsiveness to non-specific agonists than that of non-rhinitic subjects.