Phosphate transport by plasma membranes of enterocytes during development: role of 1,25-dihydroxycholecalciferol.

The present studies were designed to investigate phosphate transport across the brush border and basolateral membranes of enterocytes and to determine the effect of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] on these processes in suckling and adolescent rats. Vitamin D deficiency was induced in suckling rats by feeding pregnant dams a vitamin D-deficient diet 48 h after insemination; they were then kept in the dark. Vitamin D deficiency in the adolescent rats was induced by feeding the vitamin D-deficient diet to weanling rats for 4 wk. V max values for Na(+)-dependent phosphate uptake in the brush border membranes of vitamin D-deficient and 1,25(OH)2D3-injected suckling rats was 0.7 +/- 0.1 and 1.5 +/- 0.2 nmol.mg protein-1.10 s-1 (P less than 0.01), respectively; V max values in adolescent rats were 0.2 +/- 0.05 and 0.36 +/- 0.04 nmol.mg protein-1.10 s-1 (P less than 0.05), respectively. Vmax values for Na(+)-dependent phosphate uptake in basolateral membranes of vitamin D-deficient and 1,25(OH)2D3-treated suckling rats were 0.006 +/- 0.001 and 0.047 +/- 0.006 nmol.mg protein-1.10 s-1 (P less than 0.01).     

The role of platelets in peripheral vascular disease.

Platelets play a major role in acute ischaemic syndromes and peripheral vascular disease. They are involved in the development and progression of atherosclerosis, native vessel and graft thrombosis. They have a central role in the development of restenosis and reocclusion after peripheral percutaneous transluminal angioplasty. Antiplatelet therapy has been shown to be beneficial in patients undergoing peripheral vascular surgery or radiological intervention. Yet current routine therapy, namely aspirin and dipyridamole are limited in their mode of action and efficacy. Recent developments in the understanding of platelet function has led to the development of new more potent drugs such as clopidogrel. Combination of drugs and more specific investigation of individual platelet function may well result in improved bypass and angioplasty patency rates. The results of proposed large randomised controlled trials on the role and safety of aspirin and clopidogrel are awaited with interest. Given the importance of platelets in peripheral vascular disease highlighted in this review, achieving an optimal safe anti-platelet effect for each patient with peripheral vascular disease should be the target of future research.     

Examination of potential mechanism(s) of metallothionein induction by diethyl maleate.

Diethyl maleate (DEM) is a glutathione-depleting agent that can increase the levels of the sulfhydryl-rich protein metallothionein (MT) in liver. The purpose of the present study was to examine the mechanism(s) by which DEM increases mouse hepatic MT levels. DEM appears to be an indirect MT inducer as suggested by the lack of increase in MT levels when cultured mouse hepatocytes were exposed to DEM. Four possible mechanisms by which indirect MT inducers may cause an elevation in MT concentrations in liver were examined. Zn levels did not increase prior to the increase in hepatic MT, thus, a Zn redistribution to the liver is not the cause of the liver MT induction by DEM. The adrenal gland products were not required for MT induction in liver, as adrenalectomy did not abolish the increase in hepatic MT caused by DEM. The elevation in liver MT does not appear to be due solely to the decrease in liver glutathione (60%) in the initial hour after DEM, because phorone, which decreases liver glutathione (80%), produced only a fourfold increase in hepatic MT. Activation of macrophages does not seem to account for the rise in liver MT levels, as there was no increase in abundance of cytokine mRNAs for TNF-alpha, IL-1 beta, or IL-6 in the liver. These data suggest that the induction of hepatic MT by DEM does not occur in response to (1) an increase in liver Zn that precedes the increase in liver MT, (2) release of adrenal gland products, (3) decrease in liver glutathione, or (4) increased cytokine gene expression.     

Hyperalgesic change over the craniofacial area following urate crystal injection into the rabbit's temporomandibular joint

The aim of this investigation was to study the characteristics of hyperalgesia and inflammatory change in the craniofacial area following the production of an acute arthritis of the temporomandibular joint (TMJ) in the rabbit. Unilateral arthritis was produced by the injection of monosodium urate (MSU) into the TMJ of the rabbits. Hyperalgesia was evaluated by the reduction in the threshold of the head-withdrawal response to pressure stimulation, and inflammatory change was determined by the quantitative Evans-blue test and light-microscopic examination of histological sections. Several hours after an injection of MSU (0.15, 0.5, 1.5 mg), hyperalgesic changes were observed over not only the MSU-administered condyle, but also over the ipsilateral masseter muscle and temporal muscle in a dose dependent manner, and lasted for more than 24 h before gradual recovery. The other craniofacial region showed no significant threshold-reduction. Although a very intense inflammatory sign was found in the region of the MSU-treated TMJ, a decreased or negative sign was found in the masseter muscle with a very low threshold. Local block of the TMJ using Bupivacaine® suggested that the hyperalgesic change in the masseteric region was partly due to prolonged excitation of TMJ afferents.     

Pathological study of corticospinal-tract degeneration in Friedreich''s ataxia

The pattern of fibre degeneration in the lateral corticospinal tract (LCST) was studied in a case of Friedreich's ataxia (FA). There was preferential involvement of the lateral area of the LCST in the cervical spinal cord. More caudally, the degeneration involved the entire area of the LCST and did not reveal a medial to lateral gradient of involvement. We suggest that this distinctive pattern of tract degeneration is a consequence of the somatotopic organization of the LCST, with the dying-back degeneration preferentially affecting those LCST fibers that extend to the lumbo-sacral spinal cord. This pattern of tract degeneration may be a useful morphological marker of dying-back degeneration in corticospinal tracts.     

Polyethylene wear in unicondylar knee prostheses. 106 retrieved Marmor, PCA, and St Georg tibial components compared.

106 unicondylar knee replacement tibial components were retrieved and analyzed for the amount and type of polyethylene wear. Three different designs were retrieved which had essentially the same femorotibial conformity. Each design showed a characteristic failure pattern. The polyethylene of PCA tibial components showed serious delamination after only short durations, as a result of heat pressing. St Georg sledge prostheses showed some delamination after 4 years' duration due to sub-surface cracks which were initiated by fusion defects in the polyethylene; metal backing of the components did not affect delamination of this prosthesis. The Marmor designs showed the least wear, with shiny depressions and surface pitting; no delamination was observed in the Marmor prosthesis. Molecular weight determination by gel permeation chromatography and analysis of crystallinity using Fourier transformation infra-red spectroscopy demonstrated that St George polyethylene had higher molecular weight and crystallinity than Marmor polyethylene. In some of the components investigated, crystallinity and molecular weight of the polyethylene were reduced under the wear track when compared with the unworn polyethylene. Since fusion defects may cause delamination of polyethylene we urge manufacturers to reduce the number of such defects.     

Balance of prostacyclin and thromboxane in offspring of parents with premature coronary arterial disease.

6-keto-prostaglandin F1a and thromboxane B2 were determined in order to obtain more information about the prostacyclin synthesis and thromboxane A2 release in 3- to 18-year-old healthy children and in offspring of parents who have had an acute myocardial infarction before the age of 45. The authors demonstrated a reduction of plasma prostacyclin synthesis in children with a positive family history of premature coronary arterial disease. Thromboxane levels in the affected adolescent boys were significantly lower compared with the controls. The ratio of thromboxane:prostacyclin in endangered children did not show a significant difference from that of healthy controls. These data indicate that prostaglandins are a definitive marker for identifying cardiovascular risk children. It must be supposed that in adolescence, only in boys, with a positive family history of premature coronary arterial disease, a compensatory mechanism exists to protect them from developing an imbalance in the regulation of prostaglandins.     

Spectral and color Doppler artifacts.

Artifacts in spectral and color Doppler imaging can be confusing and lead to misinterpretation of flow information. The authors review these artifacts by considering three main causes: inappropriate equipment settings, anatomic factors, and physical and technical limitations of the modality. Incorrect gain, wall-filter, or velocity scale settings can cause loss of clinically important information or distortion of the tracing. Reflection of the Doppler signal from highly reflective surfaces can create a color Doppler mirror image. Vascular motion can introduce artifactual variation in velocity as the sample volume passes through different velocities in a laminar flow state. Unintentional motion can cause a generalized Doppler shift. Increasing the angle of Doppler interrogation degrades the quality of the tracing and gives the impression of spectral broadening. As angulation approaches 90 degrees, directional ambiguity can occur, suggesting bidirectional flow. Grating and side lobes can interrogate areas unrelated to the sample volume and introduce extraneous Doppler information to the apparent area of interrogation. Recognition of these artifacts is essential to proper interpretation of Doppler information and rendering a correct diagnosis.