Characterization of nephropathy induced by immunization with high molecular weight dextran

Background. Injection of DEAE dextran into Lewis rats can produce proteinuria and has been reported as a model of IgA nephropathy. Methods. Cationic diethyl aminoethyl (DEAE) dextran of molecular weight 500 KDa was injected into male Lewis rats. After a pre-immunization period of 3 weeks, the animals were divided into two groups: group 1 (n=14) received daily i.v. injections of 3.5 mg of antigen, group 2 (n=14) was injected with 1.5 mg three times per week for a total period of 6 weeks. I.v. treatment was initiated with gradually increasing doses of DEAE dextran in both groups for 1 week, after which the maintenance dose was reached. Results. We observed the appearance of proteinuria in a nephrotic range after 5 weeks of i.v. injections in group 1 (urinary excretion: 332±83 mg/24 h, controls: 53±14 mg/24 h). In group 2, the proteinuria was almost equal to protein excretion of healthy rats of the same weight (67±20 mg/24 h). The serum and urine creatinine were normal. By light microscopy of kidney biopsies, the presence of focal and segmental proliferation of mesangial cells after 6 weeks of i.v. injections was identified. Immunohistochemistry revealed no deposition of IgA, IgM, IgG, or C3. Using anti-ED1 antibodies, there was no evidence of interstitial infiltration of monocytes/macrophages after 6 weeks of i.v. injections. Staining for proliferating cell nuclear antigen (PCNA) did not show the presence of proliferating cells either in glomeruli or in the interstitium. Staining with FITC-WGA lectin revealed focal and segmental loss of the negative charge in the capillary wall. By electron microscopy there was deposition of dextran in the basal membrane and segmental and focal damage of the podocyte foot processes. As the chemokine RANTES may be involved in glomerular injury, we examined the kidneys of proteinuric and non-proteinuric rats for the presence of RANTES. By indirect immunofluorescence only the proteinuric rats showed RANTES deposition in mesangium. Conclusions. Injection of rats with DEAE dextran leads to dose-dependent proteinuria without deposition of immune complexes but with podocyte damage. This is associated with local expression of the chemokine RANTES which may play a role in proteinuria of glomerular disease.     

Cost-effectiveness analysis of guidelines for antihypertensive care in Finland

Background  

Hypertension is one of the major causes of disease burden affecting the Finnish population. Over the last decade, evidence-based care has emerged to complement other approaches to antihypertensive care, often without health economic assessment of its costs and effects. This study looks at the extent to which changes proposed by the 2002 Finnish evidence-based Current Care Guidelines concerning the prevention, diagnosis, and treatment of hypertension (the ACCG scenario) can be considered cost-effective when compared to modelled prior clinical practice (the PCP scenario).     

Behavioral and enzymatic interactions between benzyl alcohol and ethanol.

Acute IP injection of benzyl alcohol but not benzaldehyde (0.5 g/kg) caused aversion to voluntary drinking of 5% ethanol solution by male rats with preference to ethanol. Benzyl alcohol noncompetitively inhibited hepatic alcohol dehydrogenase of rats maintained for a short term on 5% ethanol compared to control. The results suggest an adverse interaction between benzyl alcohol and ethanol underlying the observed aversion to ethanol.     

Serological evidence that dry heating of clotting factor concentrates prevents transmission of non-A, non-B hepatitis

A new test for antibodies specific for an agent causing non-A, non-B hepatitis (NANBH) was used to screen 45 children with coagulation disorders who received factor concentrates. It was found that the test results correlated with clinical evidence of NANBH and that heat treatment of concentrates (80 degrees C for 72 hours) appears to have prevented transmission of NANBH.     

Apolipoprotein B gene DNA polymorphisms are associated with macro- and microangiopathy in non-insulin-dependent diabetes mellitus

Ukkola O, Savolainen MJ, Salmela PI, von Dickhoff K, Kesäniemi YA. Apolipoprotein B gene DNA polymorphisms are associated with macro-and microangiopathy in non-insulin-dependent diabetes mellitus. Clin Genet 1993: 44: 177–184. © Munksgaard, 1993 The relationship between diabetic macroangiopathy or microangiopathy and apolipoprotein B (apoB) polymorphism was studied in 139 male and 129 female patients with non-insulin-dependent diabetes (NIDDM) mellitus, comprising consecutive patients with poor diabetic control (HBA1 13.2%\pm2.7 (SD)) referred to our hospital. Plasma cholesterol and triglyceride concentrations were higher in the patients who were homozygous for the X2 allele (presence of Xba I cleavage site). Patients with the X1 allele (absence of Xba I cleavage site) tended to have a higher frequency of macroangiopathy, although the differences were not statistically significant. There was no difference in the prevalence of microangiopathy between the groups. In subjects with only an R1 allele (= R +; homozygous for the presence of EcoR I cleavage site) the prevalence of coronary heart disease (CHD) was observed to be high (61.9%) as compared to the subjects possessing an R2 allele (= R —; homozygous or heterozygous for the absence of the EcoR I cleavage site) (46.7%; p<0.02). When the polymorphisms Xba I (subjects homozygous for the absence of the cutting site = X +; subjects homozygous or heterozygous for the presence of the cutting site = X —) and EcoR I were combined, the prevalence of macroangiopathy was observed to be high in X + R + (80.0%) as compared with X + R- (44.2%), X-R+ (56.8%) and X-R- (50.0%) (p<0.03). The prevalence of macroangiopathy tended to be particularly high in patients with the apoprotein E4 allele (phenotype E4\4 or E4/3), combined with either X+ or R +. Our findings suggest that variation at the apoB locus is one of the factors involved in predisposing diabetic patients to the development of arterial disease. As in previous studies the effect of the variation at the apoB gene on circulating lipid levels was observed. The data also support a role for the e4 allele of the apolipoprotein E gene as an important determinant of macroangiopathy in NIDDM.     

The Effect of Small Variation of the Frequent Auditory Stimulus on the Event-Related Brain Potential to the Infrequent Stimulus

We investigated whether the mismatch process between a rare stimulus and the trace of frequent stimulus, which generates the mismatch-negativity component of the event-related potential, can tolerate a small variation in the intensity of the frequent stimulus. Series of short tone pips were presented to 10 subjects while they were reading a book and ignoring the auditory stimuli. The intensity (mean 80dB) of the frequent stimulus (600 Hz) varied within a range that was different in different blocks. The probability of the infrequent stimuli which were, in different blocks, either intensity deviants (600 Hz/70dB) or frequency deviants (650 Hz/80dB) was 10%. Both deviant stimuli elicited mismatch negativity even when the intensity of the frequent stimulus varied, although the amplitude of this component decreased with the increasing variability of the frequent stimulus. These results show that the generator process of mismatch negativity tolerates some variation in the repetitive stimulus, thus indicating that this process is also activated in ecologically more valid conditions. This is crucial to the interpretation of the generator process of mismatch negativity as a biologically vital warning mechanism.     

Beta-endorphin in the brainstem and the cerebellum of the human infant: regional levels' profile assessed with immunoaffinity chromatography and solid phase radioimmunoassay

The regional levels' profile of human beta-endorphin (beta h-EP) was studied in the brainstem and the cerebellum of 16 infant victims of "Sudden Infant Death Syndrome" and other death causes. An immunoaffinity chromatography procedure based on a monoclonal antibody directed specifically against the N-terminus of beta-EP was used to extract this peptide from the tissue samples. Beta-EP was then assessed quantitatively by means of a very sensitive solid phase radioimmunoassay (using a polyclonal antibody specific for the C-terminus of beta-EP) developed especially for the study presented here.     

Control of mesenteric arterial tone in vitro in humans and rats

The majority of the findings concerning arterial physiology and pathophysiology originate from studies with experimental animals, while only limited information exists about the functional characteristics of human arteries. Therefore, the aim of the present work was to compare the control of vascular tone in vitro in mesenteric arterial rings of corresponding size (outer diameter 0.75–1 mm) from humans and Wistar-Kyoto rats. The relaxations to acetylcholine (ACh) were clearly less marked in the mesenteric arteries of humans when compared with rats. How-ever, when calcium ionophore A23187 was used as the vasodilator, the endothelium-mediated relaxations did not significantly differ between these species. The NO synthase inhibitor N ^G-nitro-l-arginine methyl ester (l-NAME) attenuated the relaxations to ACh and A23187 in both groups. The endothelium-independent relaxations to the β-adrenoceptor agonist isoprenaline and the nitric oxide (NO)-donor nitroprusside were somewhat lower in human arteries, while vasodilation induced by the K⁺ channel opener cromakalim was similar between humans and rats. Arterial contractile sensitivity to noradrenaline and serotonin was slightly lower in human vessels, whereas contractile sensitivity to KCl was similar between these species. The contractions induced by cumulative addition of Ca²⁺ with noradrenaline as the agonist were effectively inhibited in both groups by the calcium channel blocker nifedipine, the effect of which was clearly more pronounced in human arteries. In conclusion, the control of vascular tone of isolated arteries of corresponding size from humans and rats appeared to be rather similar. The most marked differences between these species were the impaired endothelium-mediated dilation to ACh and the more pronounced effect of nifedipine on the Ca²⁺-induced contractions in human arteries. Received: 1 October 1998 / Accepted: 4 January 1999