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P H Larsen

Publications and source records attributed to P H Larsen.

9 recordsLinked to original sources

Interleukin-1 is a key regulator of matrix metalloproteinase-9 expression in human neurons in culture and following mouse brain trauma in vivo.

An acute trauma to the CNS rapidly results in the upregulation of inflammatory cytokines that include interleukin-1 (IL-1). We report here that the levels of several matrix metalloproteinases (MMPs) are also elevated following a corticectomy trauma injury to the mouse CNS. The delayed upregulation of MMPs compared to that for IL-1 suggests the possibility that inflammatory cytokines regulate MMP production in CNS trauma. To resolve this, we developed a method to isolate and maintain highly enriched human fetal neurons or astrocytes in culture and examined the regulation by cytokines of the activity of a subgroup of MMPs, the gelatinases (MMP-2 and -9). While both neuronal and astrocytic cultures displayed comparable MMP-2 activity, as evidenced by gelatin zymography, levels of MMP-9 were proportionately higher in neurons compared to astrocytes. Of a variety of cytokines and growth factors tested in vitro, only IL-1beta was effective in increasing the neuronal expression of MMP-9. Finally, an IL-1 receptor antagonist attenuated the increase of neuronal MMP-9 in culture and abolished the injury-induced increase of MMP-9 in the mouse brain. These results implicate IL-1beta as a key regulator of neuronal MMP-9 in culture and of the elevation of MMP-9 that occurs following mouse CNS trauma.

Animals↗

Matrix metalloproteinase-9/gelatinase B is required for process outgrowth by oligodendrocytes.

Oligodendrocytes (OLs) extend processes to contact axons as a prerequisite step in myelin formation. As the OL processes migrate toward their axonal targets, they modify adhesion to their substrate, an event that may be regulated by matrix metalloproteinases (MMPs). In the mouse optic nerve, MMP-9/gelatinase B increases during myelin formation. Although tissue inhibitor of metalloproteinase (TIMP)-3 also increases in parallel, the developing optic nerve has focally active MMPs demonstrable by in situ zymography. The distribution of proteolytic activity is similar to that of myelin basic protein, a marker of myelin formation. OLs in culture secrete MMP-9 and express active cell-associated metalloproteinases at the growing tips of their processes. TIMP-1 and a function-perturbing anti-MMP-9 antibody attenuate outgrowth of processes by OLs, indicating a requirement for MMP-9 in process outgrowth. Process reformation is retarded significantly in OLs cultured from MMP-9 null mice, as compared with controls, providing genetic evidence that MMP-9 is necessary for process outgrowth. These data show that MMP-9 facilitates process outgrowth by OLs in vivo and in culture.

Adult↗

[Varying prescriptions of benzodiazepines in general practice].

The aim of this study was to describe differences in patterns of benzodiazepine prescription in Svendborg. All benzodiazepine prescriptions filled by the two pharmacies in Svendborg between February and 31 March 1990 were registered. During the period, 3364 prescriptions were issued to 2262 persons (1837 tranquillizers and 1272 sedatives). General practitioners provide about 90% of benzodiazepine prescriptions. Practices with a high prescription level accounted for four times as many prescriptions as did practices with a low prescription level. By comparing the prescription level and the composition of the practice population we found that practices with a high prescription level had more women and elderly people enrolled than had the practices with a low prescription level. After standardization for age and sex the difference was reduced from 3.8 to 2.8, but practices with many elderly and female patients still provided more benzodiazepine prescriptions. Major benzodiazepine consumers (> 2 DDD/per day) constricted for 8.8% of the total amount of consumers and accounted for about 25% of the benzodiazepines prescribed during the investigation period. The number of major consumers enrolled in a practice varied between 2.8 to 13.0 per/1,000 patients. The difference in the prescription pattern could to a certain extent be explained by this difference, but there would still be a difference that can not be accounted for in our study. However, we anticipate that this variation could be due to differences in procedures and attitudes to the prescription of benzodiazepines.

Adult↗

[Prescription of benzodiazepines in general practice].

General practitioners are responsible for about 90% of all prescriptions for psychotropic drugs which benzodiazepines account for approximately 75%. In order to obtain a quantitative and qualitative assessment of the consumption in Svendborg, all benzodiazepine prescriptions were registered during a two-month period (February and March 1990). A total of 3364 prescriptions were issued to 6% (2262 persons) of the population. Of these, 1837 (54.6%) were prescriptions for tranquillizers, 1272 (37.8%) for hypnotics and 255 (7.6%) for both tranquillizers and hypnotics. The prevalence of benzodiazepine users increased with age and women were responsible for about 2/3 of the total consumption. Small but frequent prescriptions were issued to the younger users of benzodiazepines while older users generally received prescriptions for greater quantities at longer intervals. One in four persons over 80 years of age used sedatives. On account of the pharmaceutical, social and economic consequences of the widespread use of benzodiazepines in the elderly population, restrain should be observed in prescribing benzodiazepines.

Adult↗

[Traffic accidents load on the Danish hospital system].

During 1984, the police registered 14,383 injured persons resulting from traffic accidents. A total of 7,093 of these could be found again in the National Patient Register. The National Patient Register had further information about 8,095 persons who had been injured in traffic accidents. The total number of persons injured in traffic accidents in 1984 increases thus by 56% when these two registers are combined. Traffic accidents in 1984 were responsible for at least 204,020 bed-days. This corresponds to occupation of 716 of the beds in Danish hospitals throughout the year by the victims of traffic accidents. One third of these beds are occupied by the drivers/passengers of private cars, vans etc. The average number of bed-days is 13.4. Pedestrians have the longest periods of hospitalization with 24.1 per accident and cyclists have the shortest periods of hospitalization with 8.3 days per accident.

Accidents, Traffic↗