Human exposure to 3-carene by inhalation: toxicokinetics, effects on pulmonary function and occurrence of irritative and CNS symptoms

Terpenes, especially 3-carene, may irritate the skin and mucous membranes and prolonged exposure may result in allergic contact dermatitis or chronic lung function impairment. The toxicokinetics of 3-carene were studied in human volunteers exposed by inhalation (2 hr 50 W) in an exposure chamber on three occasions. The exposure concentrations were approximately 10, 225, and 450 mg/m3 3-carene. The relative pulmonary uptake was high, approximately 70% for the higher exposure levels. Total uptake increased linearly with increasing exposure. The blood clearance of 3-carene observed in this study, 0.9 liter.kg-1.hr-1, indicates that 3-carene is fairly readily metabolized. About 3% of the total uptake was eliminated unchanged via the lungs while less than 0.001% was eliminated in the urine after the end of exposure. A long half time in blood was observed in the terminal phase which indicates a high affinity to adipose tissues. A statistically significant divergence between ratings of irritation during the high exposure level and during the medium and control levels was observed. The difference in airway resistance after exposure to a high concentration of 3-carene compared to control level was not significant (P = 0.02).     

Development of brain damage after neonatal hypoxia-ischemia: Excitatory amino acids and cysteine

The aim of this study was to investigate the possible role of excitatory amino acids (EAAs) and cysteine in the development of brain damage after hypoxia-ischemia (HI) in neonates. In a rat model of neonatal HI, changes in extracellular (ec) amino acids in cerebral cortex were measured with microdialysis and correlated with the extent of brain damage at the site of probe placement. Extracellular concentrations of glutamate, aspartate and cysteine increased during HI and remained elevated during reperfusion. During HI the pattern of EAA changes was the same in the infarcted, undamaged and border zone regions. During reperfusion, however, the ec concentrations of glutamate, aspartate and cysteine were higher in infarcted and border zone areas compared to undamaged tissue. HI also produced a slight increase of tissue concentration of cysteine and decrease of tissue concentration of glutamate in parietal cortex of the HI hemisphere. The effect of cysteine on brain damage induced by HI and glutamate was also investigated. A subtoxic dose of cysteine potentiated glutamate toxicity in the arcuate nucleus and enhanced brain infarction after HI in neonatal rats. The results show that in neonatal HI the extracellular levels of EAAs during HI are not directly related to brain injury but the EAA levels during reflow predict the extent of infarction. Cysteine increases HI-induced brain injury and potentiates glutamate toxicity in neonatal rats. Speculatively, elevated level of cysteine during reperfusion may participate in the excitotoxic cascade leading to brain injury.     

In vivo anti-melanoma activities of the Melan-A/MART-1101–115 T CD4+ cell peptide

Malignant melanoma causes significant health problems. The identification of tumour-associated antigens has led to novel approaches to increase T cell mediated anti-tumour immune response. Melan-A/MART-1 has been use as target antigen for several T cell based immunotherapeutic treatments. More recently, the critical role of CD4+ T cells in inducing and maintaining anti-tumour immunity has been increasingly recognized. In order to optimize tumour immunotherapy, greater efforts have been concentrated on the identification of tumour antigens presented by MHC class II molecules to CD4+ T cells. In a publication, Tiwari et al. (2004) [1] have identified by a computational approach the 15-mer amino-acid sequence 101–115 (PPAYEKLSAEQSPPP) of the Melan-A/MART-1 as a good target for a vigorous and safe immunotherapy. Therefore, we have investigated the in vivo anti-tumour activity of this peptide in a murine melanoma model. For the prophylactic treatment, 20 μg or 50 μg peptide was subcutaneously injected in mice once a week during 3 weeks before tumour induction. Treatment with 50 μg peptide significantly affected tumour development. Thus, our preliminary data demonstrate potential in vivo prophylactic activity of the 101–115 peptide-based vaccine to control melanoma growth.     

Breast milk donors in France: a portrait of the typical donor and the utility of milk banking in the French breastfeeding context.

Although information regarding attitudes and characteristics of human blood donors has been researched, little is known about the motivations and demographic and personality characteristics of women who choose to donate their breast milk. Eight milk banks in France participated in a study examining donor characteristics, providing data on 103 women. The results showed that the donors were women of average childbearing age with strong support at home. Almost half did not work outside of the home, compared to the national average of 80% of women in this age group; similarly, a large number (currently working or not) were from the health and social services fields. Reasons for donation were largely altruistic, and a general optimistic attitude prevailed within the participants. The results of this study provide useful information for the recruitment of potential donors as well as information on how to facilitate and provide optimal service through milk donation.     

Morphological study of neocortical areas in Rett syndrome

Various neocortical areas from four females aged 16–24 years with Rett syndrome (RS) were investigated and compared with brains of therapy-resistant partial epilepsy (TRPE) patients (18–25 years), infantile autism (IA), and control brains (24 and 58 years). The cytoarchitecture of area 10 (frontal), area 21 (temporal), area 4 (primary motor cortex), and area 17 (primary visual cortex) was studied by the combined Klüver-Barrera (luxol fast blue and cresyl violet) standard procedure. Autofluorescence of lipofuscin, immunofluorescence of synaptic vesicle proteins [synaptophysin (p38)] and lectin-stained (Wisteria floribunda agglutinin) perineuronal nets (PNs) were studied in the cortices using dual-channel confocal laser scanning microscopy. The brains of RS females show various types of morphological/cytoarchitectonical abnormalities of single pyramidal neurons in layers II–III, and V–VII of different cortical areas. The abnormalities include mild losses of pyramidal neurons, more pronounced in layers II and III than in layers V and VII, and more evident in frontal and temporal areas than in the visual cortex. Microdysgenesis, including abnormalities due to neuronal migration disorders, was not found in RS, in contrast to the observations in TRPE patients, strongly indicating that RS is not a neuronal migration disorder. Lipofuscin distribution was normal but amounts were lower in RS cases than in control and TRPE brains. PNs were less expressed in cortices of the IA case, but were clearly overexpressed in the motor cortex of RS. Quantitative analysis of p38 showed a decrease in the area occupied by p38 immunoreactivity by 20–40% in RS compared with controls. It is concluded that RS could best be explained by a postnatal synaptogenic developmental deficiency; the basic defect, however, is still completely unknown. Received: 26 February 1996 / Revised, accepted: 11 July 1996     

Effect of propentofylline (HWA 285) on extracellular purines and excitatory amino acids in CA1 of rat hippocampus during transient ischaemia.

1. The adenosine uptake blocker propentofylline (HWA 285) has previously been shown to protect hippocampal CA1 pyramidal cells from ischaemia-induced delayed neuronal death. The influence of propentofylline, on the extracellular concentrations of purines, aspartate and glutamate in the CA1 of the rat hippocampus during transient forebrain ischaemia was investigated. 2. Twenty min of ischaemia was induced by four-vessel occlusion in Wistar rats, extracellular compounds were sampled by use of microdialysis and EEG was recorded by a tungsten electrode attached to the dialysis probe. 3. Propentofylline (10 mg kg-1 i.p.) did not influence the basal levels of any of the compounds in the hippocampal dialysates. 4. The EEG became isoelectric within 20 s after induction of ischaemia. 5. Extracellular adenosine, inosine, hypoxanthine, aspartate and glutamate increased several fold during ischaemia and remained elevated during early reflow. Within 2 h of reperfusion the concentration of all compounds was normalized. Xanthine increased upon reperfusion and remained elevated after 2 h. 6. Propentofylline (10 mg kg-1 i.p.) administered 15 min before ischaemia significantly enhanced the ischaemia-evoked increase of adenosine but attenuated the increases of the other purine catabolites and of glutamate. 7. In separate in vitro experiments, propentofylline did not inhibit adenosine deaminase activity. 8. The present data show that propentofylline enhances extracellular adenosine and lowers extracellular glutamate in vivo during ischaemia. These findings may be important in relation to the neuroprotective properties of propentofylline.     

Impact of occupations and job tasks on the prevalence of carpal tunnel syndrome.

In this investigation reported epidemiologic studies on carpal tunnel syndrome (CTS) (15 cross-sectional studies involving 32 occupational or exposure groups and six case-referent studies) were reviewed. The prevalence of CTS in the different occupational groups varied between 0.6 and 61%. The highest prevalence was noted for grinders, butchers, grocery store workers, frozen food factory workers, platers, and workers with high-force, high-repetitive manual movements. Odds ratios greater than 10 were reported for exposed groups in three studies. On the basis of epidemiologic and other evidence, it was concluded that exposure to physical work load factors, such as repetitive and forceful gripping, is probably a major risk factor for CTS in several types of worker populations. At least 50%, and as much as 90%, of all of the CTS cases in these exposed populations appeared to be attributable to physical work load.