The study of outcomes for CAPD versus hemodialysis patients

Tacrine [1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate (THA), Cognex] is a potent acetylcholinesterase inhibitor recently approved for treatment of mild-to-moderate Alzheimer's disease. The potential for THA and/or a metabolite of THA to accumulate in brain tissue was investigated by autoradiographic and metabolic profiling techniques in rats given single and multiple doses of [14C]THA. In addition, the brain-to-plasma distribution time course of orally administered 1-hydroxy-THA (1-OH-THA, 24 mg/kg), a primary rat metabolite with anticholinesterase activity, was also examined. Results from a 16 mg/kg single-dose study showed THA to cross the blood-brain barrier readily and concentrate in brain tissue, approximately 5-fold compared with plasma. The metabolite 1-OH-THA was found in much lower amounts relative to THA and when given separately at a similar dose the levels in brain tissue were comparable with plasma concentrations. After multiple-dose administration, THA concentrations in brain tissue were approximately 3-fold higher than those achieved after a single oral dose. However, concentration of 1-OH-THA metabolite increased only 50%. These data suggest a marked difference between the ability of THA and 1-OH-THA to accumulate in brain tissue and may reflect differences in lipophilicity as estimated by calculated log p values. The relevance of THA accumulation in brain tissue to delays observed in THA clinical management of Alzheimer's disease remains to be established.     

Secondary alveolar bone grafting--five-year periodontal and radiographic evaluation in 100 consecutive cases

A prospective study of secondary alveolar bone grafting based on the Norwegian (Oslo) team approach has been conducted by the CLP Unit at the Princess Margaret Hospital for Children in Perth, Australia, since 1982. The 5-year results of 100 consecutive cases of uni- and bilateral cases are presented according to periodontal and radiographic parameters of tooth support. The vast majority of cases grafted (98%) resulted in the eventual eruption of the cleft side cuspid/lateral incisor within acceptable parameters of tooth support. The results confirm the predictability of this safe procedure when utilized within a strict clinical protocol involving the whole CLP team.     

Role of vanadium in nutrition: metabolism, essentiality and dietary considerations

Vanadium is a pervasive element of biological systems, being widely distributed across the food supply. Food refining and processing appear to increase vanadium content. At higher intakes, it accumulates in body tissues such as liver, kidney and bone. Essentiality of the nutrient has been established in lower life forms but the significance and extent of vanadium's role in humans has been overshadowed by the absence of deficiency symptoms in man. While the pharmacological properties of vanadium have stimulated much interest, knowledge of basic metabolic processes regulating vanadium remains incomplete. Ultimate determination of essentiality for humans will depend on greater understanding of the fundamental biochemical roles of vanadium.     

Training hygienists for an auxiliary role in orthodontics

This article describes the procedures that dental hygienists may undertake in the United Kingdom at the present time and compares these with the 'expanded duties' function of auxiliary personnel abroad. An 'expanded duties' training programme in orthodontic procedures taught to Canadian Hygienists at Birmingham Dental Hospital is described in detail.     

Expression cloning of a rat liver Na(+)-independent organic anion transporter

The interactions between platelets and plasma proteins previously shown to adhere to biomaterials were evaluated, using monoclonal antibodies (mAbs) against specific platelet surface glycoprotein (GP) receptors. Purified 51Cr-labeled human platelets in plasma-free medium were incubated with each of the following antibodies: mAb 10E5 [anti-GP IIb/IIIa; fibrinogen, von Willebrand factor (vWF), and fibronectin receptor]; mAb 6D1 (anti-GP Ib-IX; vWF receptor); mAb IV.3 (anti-Fc gamma RII; IgG receptor); polyclonal antiserum A108 or mAb BIIG4 (anti-GP Ic-IIa; fibronectin receptor). Antibody-treated platelets were added to microtiter wells coated with fibronectin, fibrinogen, vWF, IgG, vitronectin, albumin, or platelet-poor plasma (PPP). 51Cr-labeled platelet adhesion to matrix proteins was expressed as a percentage of that measured on PPP-coated surface. Platelets adhered to fibrinogen, fibronectin, vWF, or IgG immobilized on polystyrene. Limited binding to either vitronectin or albumin was detected. Binding to fibrinogen and IgG was blocked by mAb 10E5. Binding to IgG was also blocked by mAb IV.3. Binding to fibronectin, reduced in the presence of mAb 10E5, mAb BIIG4, or the polyclonal antiserum A108 alone, was further reduced by combined 10E5 and BIIG4 or 10E5 and A108. Neither mAb 10E5 nor 6D1 alone blocked adhesion to vWF; however, the combination of 10E5 and 6D1 significantly reduced platelet adhesion to this matrix. Finally, platelet adhesion to the plasma-coated surface was reduced by mAbs 10E5 and BIIG4. These results indicate that multiple adhesion receptors can mediate platelet adhesion to matrix proteins immobilized on surfaces.     

Regulation of expression of a cDNA from barley roots encoding a high affinity sulphate transporter

A cDNA encoding a high-affinity sulphate transporter has been isolated from barley by complementation of a yeast mutant. The cDNA, designated HVST1, encodes a polypeptide of 660 amino acids (M(r) = 72,550), which is predicted to have 12 membrane-spanning domains and has extensive sequence homology with other identified eukaryotic sulphate transporters. The K(m) for sulphate was 6.9 microM when the HVST1 cDNA was expressed in a yeast mutant deficient in the gene encoding for the yeast SUL1 sulphate transporter. The strong pH-dependency of sulphate uptake when HVST1 was expressed heterologously in yeast suggests that the HVST1 polypeptide is a proton/sulphate co-transporter. The gene encoding HVST1 is expressed specifically in root tissues and the abundance of the mRNA is strongly influenced by sulphur nutrition. During sulphur-starvation of barley, the abundance of mRNA corresponding to HVST1, and the capacity of the roots to take up sulphate, both increase. Upon re-supply of sulphate, the abundance of the mRNA corresponding to HVST1, and the capacity of the roots to take up sulphate, decrease rapidly, concomitant with rises in tissue sulphate, cysteine and glutathione contents. Addition of the cysteine precursor, O-acetylserine, to plants grown with adequate sulphur supply, leads to increases in sulphate transporter mRNA, sulphate uptake rates and tissue contents of glutathione and cysteine. It is suggested, that whilst sulphate, cysteine and glutathione may be candidates for negative metabolic regulators of sulphate transporter gene expression, this regulation may be overridden by O-acetylserine acting as a positive regulator.     

Dynamic structural and functional relationships in recombinant plasminogen activator inhibitor-1 (rPAI-1)

The conformational characteristics of active, latent, and denatured recombinant plasminogen activator inhibitor-1 (rPAI-1) were compared using UV spectroscopy, spectrofluorimetry and circular dichroism (CD) techniques. The UV absorbance wavelength maxima in all preparations approximated 280 nm, while the extinction coefficients of active and latent rPAI-1 differed by up to 60%. When incubated at 37 degrees C, the A280 of latent rPAI-1 was quite stable while the A280 of active rPAI-1 spontaneously increased, eventually approximating that of latent rPAI-1. Alkali difference spectroscopy yielded markedly divergent titration patterns for active and latent rPAI-1, suggesting that the tyrosine residues present in active and latent rPAI-1 differ in terms of solvent exposure. At an excitation wavelength of 280 nm, active rPAI-1 exhibited the greatest relative fluorescence quantum yield. The relative fluorescence of latent and denatured rPAI-1 were less than that of active PAI-1, and the emission maxima of both species were slightly red-shifted in comparison to that of active rPAI-1, suggesting that at least one of the four tryptophan residues present in rPAI-1 is less exposed to the aqueous environment in the active form of the molecule. In contrast, the derived secondary structures based on CD of active and latent rPAI-1 were nearly identical, with both moieties exhibiting approx. 40% alpha-helix and 15% beta-sheet. Taken together, these spectroscopic data provide evidence supporting the hypothesis that active and latent PAI-1 differ in terms of their tertiary conformation and aromatic residue exposure, while their secondary structures appear generally comparable. Furthermore, denaturant-induced reactivation of latent rPAI-1 produces a partially active rPAI-1 with spectroscopic properties similar to that of latent rPAI-1, suggesting that denatured rPAI-1 more closely resembles the latent rPAI-1 conformation after refolding. The spontaneous spectroscopic changes observed in rPAI-1 may reflect conformational transitions that are critical to the regulation of endogenous PAI-1 activity.