Tizanidine (DS103-282), a centrally acting muscle relaxant, selectively depresses excitation of feline dorsal horn neurones to noxious peripheral stimuli by an action at alpha 2-adrenoceptors

The effects of microiontophoretic ejection of tizanidine were compared with those of adrenoceptor agonists on responses of single laminae IV and V neurones to noxious and innocuous cutaneous stimuli. Tizanidine, noradrenaline and clonidine depressed neuronal responses to noxious but not innocuous stimuli. Spontaneous activity was also depressed by these three substances. By contrast, beta- and alpha 1-adrenoceptor agonists had no consistent effect on neuronal responses to cutaneous stimuli. The selective actions of tizanidine, noradrenaline and clonidine were reversibly antagonized by the alpha 2-adrenoceptor antagonist RX781094 but not by WB4101 (alpha 1 antagonist). The binding of an alpha 2-adrenoceptor ligand to rat brain membranes was preferentially displaced by tizanidine. These results indicate an interaction of tizanidine with central alpha 2-adrenoceptors.     

Change in immune response to hepatitis B in boys with haemophilia

Eleven of 27 haemophilic boys who received a common batch of Factor VIII concentrate subsequently developed acute hepatitis B; although 9 were considered not to have been previously exposed to the virus, 2 other boys had been considered immune to hepatitis B. The amount of concentrate received by each child, together with their HIV-antibody status and T-lymphocyte subset distribution prior to exposure, did not influence their response to the hepatitis B virus (HBV). The two previously immune children who became infected, however, had evidence of the HIV-associated persistent generalized lymphadenopathy syndrome. Detailed investigation of the suspect batch of concentrate revealed hepatitis B surface antibody to a titre of 112 miu/ml, but surface antigen was not detectable, even after dissociation of antigen and antibody. As a result of this outbreak, 5 of the 11 boys remain carriers of the virus and 2 other family members have contracted acute hepatitis B. The possibility that the response of the haemophiliacs to HBV may be altered due to acquired alteration of their immune function is discussed. Regular screening of haemophiliacs, including those immune to hepatitis B, is recommended, since even with regular donor screening, HBV remains a major infective risk to haemophiliacs receiving Factor VIII replacement therapy, and the risk to an individual may change with time.     

Influence of cement layer thickness on the adhesive bond strength of polyalkenoate cements.

The fracture toughness and yield stress values of model zinc polycarboxylate and glass polyalkenoate cements have been used to calculate plastic zone sizes. The size of the plastic zone at the crack tip in these materials has been used to predict whether cement layer thickness is likely to influence the adhesive bond strength. In the model zinc polycarboxylate cement studied, the plastic zone size was comparable to the cement layer thickness and had a pronounced influence on the shear bond strengths obtained. In contrast, the plastic zone sizes obtained for the glass polyalkenoate cements were much smaller and the shear bond strengths were found to be much less dependent on cement layer thickness.     

Morphologic and biochemical changes in articular cartilages of immature beagle dogs dosed with difloxacin.

Quinolones are efficacious antibacterial compounds, but they have been associated with arthralgia in human patients; experimentally, they have caused lesions in articular cartilages of immature animals. The earliest morphologic and biochemical changes induced in articular-epiphyseal cartilage complexes by difloxacin, a fluoroquinolone, were investigated in 27 3-month-old Beagle dogs that were dosed orally with the drug at 300 mg/kg body weight per day. Paraffin-embedded sections of humeral and femoral heads that were stained with either hematoxylin and eosin or toluidine blue and fast green were evaluated histologically, and lesions were scored according to established criteria. Although morphologic changes were not observed in cartilages of the control dogs or of the treated dogs in the 24-hr group, the severity of lesions, as represented by mean scores for lesions, increased during the 36-48 hr after dosing. The initial morphologic change, observed in cartilages from the treated dogs of the 36- and the 48-hr groups, was necrosis of chondrocytes that was rapidly followed by disruption of extracellular matrix and formation of fissures. Although glycosaminoglycan was aggregated along the margins of fissures, its concentration was not reduced in cartilages of any group of treated dogs. Collagen, however, was depleted from the cartilages of the dogs that were euthanized 36 or 48 hr after the first dose of difloxacin. Because degenerative changes were observed ultrastructurally in chondrocytes by 24 hr in a previous study, it was concluded that collagen was lost from affected cartilages as an early sequel to the degeneration of chondrocytes.     

Demonstration of carcinoembryonic antigen in bone marrow from patients with carcinoma.

Primary and secondary tumour and bone marrow trephine biopsies from 20 patients with carcinomas were stained for carcinoembryonic antigen by the three stage immunoperoxidase method. Six marrow biopsies contained tumour deposits, five of which were positive for carcinoembryonic antigen. A further five marrow biopsies contained single carcinoembryonic antigen positive cells of uncertain origin. Carcinoembryonic antigen staining may be a useful adjunct to conventional histology in the diagnosis of marrow metastases.     

Muscle satellite (stem) cell activation during local tissue injury and repair

In post-mitotic tissues, damaged cells are not replaced by new cells and hence effective local tissue repair mechanisms are required. In skeletal muscle, which is a syncytium, additional nuclei are obtained from muscle satellite (stem) cells that multiply and then fuse with the damaged fibres. Although insulin-like growth factor-I (IGF-l) had been previously implicated, it is now clear that muscle expresses at least two splice variants of the IGF-I gene: a mechanosensitive, autocrine, growth factor (MGF) and one that is similar to the liver type (IGF-IEa). To investigate this activation mechanism, local damage was induced by stretch combined with electrical stimulation or injection of bupivacaine in the rat anterior tibialis muscle and the time course of regeneration followed morphologically. Satellite cell activation was studied by the distribution and levels of expression of M-cadherin (M-cad) and related to the expression of the two forms of IGF-I. It was found that the following local damage MGF expression preceded that of M-cad whereas IGF-IEa peaked later than M-cad. The evidence suggests therefore that an initial pulse of MGF expression following damage is what activates the satellite cells and that this is followed by the later expression of IGF-IEa to maintain protein synthesis to complete the repair.     

Functional and morphologic studies of the adrenal cortex and kidney in ovine toxaemia of pregnancy

Functional and morphologic studies of the adrenal cortex and kidney have been carried out in pregnant sheep with spontaneous or dietary restriction-induced ovine toxaemia. It was found that proteinuria was an inconstant feature and no animal showed glomerular lesions analogous to those found in human preeclampsia; thus ovine toxaemia cannot be regarded as a precise experimental model for human toxaemia of pregnancy. The elevation of blood cortisol levels and the morphologic appearance of the adrenal zona fasciculata found in such animals suggest an adrenal response comparable to that caused by adrenocorticotrophic hormone. In addition, animals with severe disease showed evidence of stimulation of the renin-angiotensin-aldosterone system as reflected by elevated blood renin and aldosterone concentrations and raised renal juxtaglomerular indices. Ultrastructural changes in the adrenal zona glomerulosa and renal juxtaglomerular myoepithelioid cells in toxaemic animals resembled those described in non-pregnant sodium-depleted sheep. The finding of juxtaglomerular peripolar cell mitoses and granule exocytosis, the latter only being previously observed in sodium depleted sheep, together with the ultrastructural changes in the adrenal zona glomerulosa and juxtaglomerular myoepithelioid cells, suggest that sodium depletion may play a role in this disease.