Astroglial alterations in rat hippocampus during chronic lead exposure.

The present study was performed in order to follow the response of astroglial cells in the rat hippocampus to chronic low-level lead exposure. The experiments combined immunohistochemistry using anti-glial fibrillary acidic protein (GFAP) antibody and conventional transmission electron microscopy (EM). Chronic administration with drinking water [1 g% w/v (subclinical dose) of lead acetate dissolved in distilled water] was started through the mother's milk when pups were 7 days old. Following weaning, experimental offspring were treated for 3 months with the same concentration of adulterated water. The group of intoxicated animals and their controls were sacrificed by perfusion-fixation at 30, 60, and 90 days of exposure. After 60 days of lead treatment, staining of GFAP-positive cells demonstrated an astroglial transformation from the quiescent to the reactive state, characterized by an increase in GFAP. In control rats no changes in GFAP immunostaining were observed. The intensity of the astroglial response was enhanced after 90 days of lead intoxication, showing an increment of GFAP immunoreactivity. Quantification of these changes was made by computerized image analysis, confirming that the sectional areas of the astroglia in lead-exposed animals were larger than those in controls. These results are consistent with the ultrastructural alterations. Simultaneously with the increment in gliofilaments, intranuclear inclusions were seen in some astrocytes. The mechanisms by which lead affects astrocytes are unknown. Probably the astroglial changes induced by lead intoxication produce microenvironmental modifications that may disturb the neuronal function.     

Circulating adipocytokines in non-diabetic and Type 1 diabetic children: relationship to insulin therapy, glycaemic control and pubertal development.

AIM: To determine the influence of Type 1 diabetes mellitus on circulating adipocytokines in children. METHODS: The circulating concentrations of leptin, adiponectin, resistin and tumour necrosis factor (TNF)-alpha were measured in 91 children, aged 11.1 +/- 2.7 years, with Type 1 diabetes mellitus (T1DM). Ninety-one healthy children were selected as control subjects. RESULTS: Body mass index-adjusted leptin concentrations were higher in the pubertal diabetic children compared with the control children. There was a significant positive correlation between leptin and daily insulin dose in the diabetic group. Circulating adiponectin concentrations were higher in the prepubertal diabetic children and were positively associated with HbA(1c). Resistin concentrations were lower in the prepubertal non-diabetic subjects compared with the pubertal non-diabetic children, whose values were higher than those of the diabetic children. TNF-alpha concentrations were similar in non-diabetic and diabetic children. CONCLUSIONS: Circulating concentrations of adipocytokines are abnormal in Type 1 diabetic children, although the direction of change differs by cytokine. Pubertal development, in addition to insulin treatment and glycaemic control, also influences the concentrations.     

P6 Complaints of halitosis related to the oral cavity. A preliminary report of 700 consecutive patients

Patients with complaints of halitosis do seek treatment from physicians and dental practitioners, because of the fear that their halitosis may interfere with their social activities. Although the prevalence of halitosis has been reported to be as high as 50%, most physicians and dental practitioners are poorly informed about the causes and treatments of halitosis. In order to care for patients with complaints of halitosis a multidisciplinary team was established at the Erasmus Medical Centre, Rotterdam, The Netherlands. The team included a dental hygienist, an otorhinolaryngologist, and a dentist, who developed a special halitosis programme. One short press release regarding the establishment of the team, was provided to the national press-centre. In the out-patient clinic more than 700 patients were seen by the team. Using a structured questionnaire fed to a PC, patients answered questions regarding complaints about the oral cavity, the upper respiratory tract, the throat, their general health, their cleansing habits of the oral cavity, and prior experiences with general physicians, dental practitioners, and medical specialists. They underwent examinations of the extent of their halitosis, of the perioral and neck region, the oral cavity, the upper respiratory tract, and the upper digestive tract. Finally, the members of the team came to a joint diagnosis and a joint treatment plan for every individual patient. Of the first 700 consecutive patients around 90% had a natural dentition without removable partial dentures. More than 60% were diagnosed as having periodontal disease with pockets of 4 mm or more in the maxilla. This figure was more than 50% in the mandible. Around 95% had tongue coating.     

Risks and complications of total parenteral nutrition. Personal experience

Total parenteral nutrition is now a broadly used method whose efficacy is confirmed, even if it is still not free from risk of complications. The Authors report their own clinical experience on 130 cases in the period 1981-1988. Complications were registered in 4.6% of the observed cases. They underline the problems relating to this subject.     

Trend surface models in the representation and analysis of time factors in cancer mortality

A method of graphic representation of time factors in cancer mortality is presented, based on different tonalities of grey applied to the surface of the matrix defined by various age-specific rates. It is illustrated using mortality data from cancers of the mouth or pharynx, oesophagus, larynx and lung in Italian and Swiss males. Progressively more complex regression surface equations are defined, on the basis of two independent variables (age and cohort) and a dependent one (each age-specific rate). General patterns of trends were thus identified, showing important similarities in cohort and period effects, but also noticeable differences in time-related factors in mortality from various neoplasms of the upper digestive and respiratory tract. For instance, there were declines in mortality from cancers of the mouth or pharynx in the oldest age groups, whereas rates were appreciably upwards at younger and middle age, particularly in Italy. Likewise, cancers of the oesophagus and, chiefly, of the larynx were substantially increasing, on a cohort basis, in oldest Italian males. Temporal pattern for laryngeal cancer in Italy was similar to that of lung cancer, thus suggesting that (cigarette) smoking has a greater impact on this cancer site as compared with alcohol. However, it is difficult to explain, on this basis alone, the totally diverging pattern for cancer of the larynx (downwards) and of the lung (upwards) observed among older Swiss males. These examples indicate that trend surface models are a useful summary guide to illustrate and understand the general patterns of age, period and cohort effects in cancer mortality.     

Inherited Neurodegenerative Disorders Caused by CAG/Polyglutamine Tract Expansions: Symposium Introduction

At the beginning of this decade, the American Association of Neurology decided that the 1990's should be labelled "the decade of the brain" for expected advances in our understanding of neurological disorders and neuroscience. By the end of this decade, clinicians and researchers who work in the field of inherited neurological disorders might well remember the 1990's as "the decade of the trinucleotide repeat". At the time of writing this introduction, eleven inherited neurological disorders have been found to be caused by expansions of trinucleotide repeats, and a twelfth trinucleotide repeat expansion mutation has been identified (6), although the gene containing this mutant triplet repeat has not been cloned to our knowledge (Table 1).     

Muscarinic modulation of endogenous noradrenaline release from adrenergic terminals in the guinea-pig colon

1 The present study examined the role of muscarinic receptors in the modulation of noradrenaline (NA) release in the guinea-pig isolated distal colon. The spontaneous endogenous NA overflow assayed by HPLC-ED was taken as an index of NA release from enteric noradrenergic nerve terminals. 2 Physostigmine (10 μm ) significantly enhanced spontaneous endogenous NA overflow. Hyoscine (muscarinic antagonist), (R)-(-)-trihexyphenidyl and telenzepine (M₁-selective antagonists), and 11[[2-[(diethylamino)methyl]-1-piperydil]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116, M₂-selective antagonist) inhibited NA overflow in a concentration dependent manner, with the following EC₅₀ values: 131.74 (18.19–953.96), 101.62 (58.83–175.60), 150 (60–330), 30 (5–170) nm , respectively. 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M₁- and M₃- selective antagonist) had no significant effect up to 100 μm . 3 The muscarinic agonist oxotremorine inhibited NA overflow in a concentration dependent manner, with an EC₅₀ value of 0.67 (0.30–1.51) μm . The response to oxotremorine was inhibited by muscarinic antagonists with the following order of potency: hyoscine = (R)-(-)-trihexyphenidyl = telenzepine > 4-DAMP >> AF-DX 116. 4 In the presence of 3 μm tetrodotoxin (TTX), the effect of oxotremorine and 4-DAMP was unchanged, while hyoscine, (R)-(-)-trihexyphenidyl, telenzepine and AF-DX 116, instead of inhibiting, significantly enhanced NA overflow. 5 The present results indicate that, in the guinea-pig colon, endogenous acetylcholine sustains spontaneous NA release by activating muscarinic receptors possibly located on interneurones. In addition, inhibitory muscarinic receptors may exist on adrenergic terminals.