Aging influences development and progression of early aortic atherosclerotic lesions in cholesterol-fed rabbits

The arterial wall in aged animals shows an increased susceptibility to develop atherosclerotic lesions, although the mechanisms by which aging acts are still unclear. We investigated early aortic lesions in aged rabbits (5 to 6 years old, AH group) and young rabbits (2 months old, YH group) after 2 months of 0.2% cholesterol feeding. Fatty streaks or spots mainly in the proximal segments occupied a relative surface area that was greater in AH than in YH rabbits, although plasma cholesterol and lipoprotein levels did not differ. YH lesions showed an irregular endothelial profile mainly from accumulations of large, rounded, RAM 11-positive macrophagic foam cells. There was a higher percentage of myocytic, CD-5-positive, proliferating, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and larger accumulation of glycosaminoglycans in AH fatty streaks than in YH lesions. Ligation-mediated polymerase chain reaction confirmed differences in apoptosis. Early fibromuscular coats and subendothelial plasma-like insudate were also observed in AH lesions. Aged-matched normocholesterolemic rabbits showed a diffuse aortic intimal thickening composed of myocytic cells with a synthetic phenotype and extracellular matrix rich in glycosaminoglycans. In addition, in aged rabbits, we observed a spontaneous increase of monocytes adhering to the endothelial surface and a reduced expression of endothelial nitric oxide synthase in areas distant from the branches. These plasma cholesterol-independent spontaneous changes in the aortic wall of aged rabbits seem to act as a multiple atherogenic risk factor. Moreover, age-related differences in the distribution, composition, and proliferative and apoptotic rates represent crucial events during the progression of early fatty streaks to advanced plaques.     

Effect of chenodeoxycholic acid on liver structure and function in man: a stereological and biochemical study

Chenodeoxycholic acid (CDCA) is an effective treatment for dissolving gallstones but experimental studies have suggested that it might be hepatotoxic. The present study is concerned with a group of patients undergoing medical therapy for gallstones for periods of 30 days up to 14 months with CDCA (15 mg/kg/day). Routine functional tests, determination of some liver microsomal enzymes and stereological studies of the liver tissue have been performed and the data have been compared with those obtained before treatment. No significant changes were observed in the functional tests throughout the study. Also the microsomal mixed function oxidase system seemed unaffected by CDCA therapy. The histological features of the liver biopsies were not appreciably different from those observed prior to treatment. Although there were large interindividual variations, the volume density of parenchymal steatosis and of the lipocytes remained comparable in the ssme individual. The ultrastructural features noted in untreated subjects such as curled mitochondrial cristae, slight intracellular bile retention, increased surface density of the rough endoplasmic reticulum were still evident after 14 months of treatment. No additional changes were noted. These results show that no evidence of hepatotoxicity seems to develop in man under therapy with CDCA at the dose considered. But the structural abnormalities observed before treatment appear to persist even in subjects under long-term therapy.     

Feasibility of simultaneous Tc99m sestamibi and 2D-echo cardiac imaging during dobutamine pharmacologic stress

Feasibility of simultaneous 2D-Echo and SPECT Tc99m Sestamibi imaging during dobutamine infusion was evaluated in a female population with suspected coronary artery disease and scheduled for diagnostic coronary angiography. A total of 49 consecutive subjects were studied. Patients under continuous ECG and 2D-Echo monitoring underwent standard dobutamine infusion at increasing doses to a diagnostic end-point. Tc99m Sestamibi was administered at the peak of the dobutamine effect. With this approach, 35 patients were identified correctly by 2D-Echo (Sensitivity = 60.1%; Specificity = 83.3%; Agreement = 71.4%; k = 0.43). Perfusion imaging with Tc99m Sestamibi resulted in correctly identifying 41 patients (Sensitivity = 83%; Specificity = 84%; Agreement = 83.6%; k=0.67). Combining information obtained from the two tests resulted in increased specificity (92%) and decreased sensitivity (64%). Simultaneous assessment of perfusion and function with Tc99m Sestamibi and 2D-Echo imaging during dobutamine administration is easily performed without added risk or discomfort to the patient. Tc99m Sestamibi appeared to be slightly superior to 2D-Echo for the detection of CAD in this population, but the difference does not reach conventional statistical significance. The combined use of the two independent tests did not substantially improve the diagnostic accuracy of each method.     

The fate of electron opaque tracers (horseradish peroxidase and lanthanum chloride) during valproic acid-induced choleresis

ABSTRACT— Horseradish peroxidase (HRP) and lanthanum chloride (LaCl₃) are useful tools for, respectively, the study of vesicular transport through the hepatocyte and the study of the permeability of junctional complexes. These tracers have been used to detect the changes associated with the choleresis independent of bile acids induced by valproic acid (VPA) in rats. The animals were given a single dose of VPA (600 mg/kg, ip). HRP (100 mg/kg) or 5 mM LaCl₃ were given intraportally after 1 h, when bile flow had increased twofold. The excretion of HRP in bile was measured colorimetrically up to 2 h after HRP. Ultrastructural morphometry was conducted on liver of intact rats taken from 1 to 40 min after HRP. The volume density (VD) of HRP-containing vesicles and of HRP-containing multivesicular bodies (MVB) was counted. In VPA-treated rats, HRP appeared in bile with a peak showing at 5 min against 20 min in controls, but the total amount of HRP excreted was less than in controls. The intrahepatocytic vesicular transport of HRP was also modified, showing a peak at 3 min in VPA-treated rats compared to 10 min in controls, together with a decreased VD of pericanalicular vesicles. This was accompanied by an increase of HRP-containing MVB, already evident at 5 min. VPA-induced changes in HRP transport through the hepatocytes appeared twofold: 1) during VPA-induced stimulation of bile flow, there was an early and short-lived increase of transcellular transport and biliary elimination of HRP: 2) a diversion of HRP towards the indirect, lysosomal pathway apparently occurred, in agreement with previous findings concerning the formation of numerous cytolysomes induced by VPA (Hepatology 1984: 4 : 1159–1166). The decreased amount of HRP excreted in bile could be accounted for by a diversion of HRP towards the degradation pathway. The pattern of distribution of LaCl₃ was similar in VPA-treated animals and in controls, suggesting that gross structural alterations of the junctional complexes are unlikely to occur during VPA-induced choleresis.     

Neuronal Ceroid Lipofuscinosis: An Ultrastructural,Genetic, and Clinical Study Report

The term "neuronal ceroid lipofuscinosis" (NCL) describes a complex of inherited neurodegenerative conditions associated with storage of lipopigments in brain tissue. In 1989 Dyken proposed a classification of NCL based on the age, clinical symptoms, and ultrastructural aspects of the lipopigments. At the ultrastructural level it is possible to distinguish 5 different patterns of osmiophilic lipopigments: usual lipofuscin, fingerprint deposits, granular profiles, curvilinear bodies, and microtubular aggregates. The concept that each ultrastructural pattern was the counterpart of a specific clinical type has been proved not to be true. Advances in molecular genetic techniques have allowed the identification of defective genes and their protein products in several NCL clinical forms. Ceroid lipofuscin deposits may be ultrastructurally observed not only in neuronal cells, but also in several other sites, such as trophoblastic cells, thus permitting prenatal diagnosis. In spite of recent advances in immunohistochemical identification of biochemical markers, the ultrastructural identification of lipofuscinic pigments remains the gold standard to identify NCL, together with clinical aspects and respective gene defects. This study describes the ultrastructural aspects observed in 8 cases of NCL syndromes (3 juvenile, 3 infantile, 1 late infantile, and 1 congenital clinical form). In these patients, genetic analysis was also performed.     

The role of ultrasonography in the assessment of peri-prosthetic hip complications

Purpose

Total hip arthroplasty (THA) is a widespread option for treating hip osteoarthritis. Peri-prosthetic complications after THA represent a common event influencing patient outcome and costs. The purpose of this paper is to report the use of ultrasonography (US) to detect peri-prosthetic complications in symptomatic patients who underwent THA.

Methods

We retrospectively reviewed the records of patients with THA who underwent imaging evaluation between January 2009 and December 2012 at two different institutions. We evaluated the presence/absence of superficial and/or deep peri-prosthetic collections as well as the presence/absence of a cutaneous sinus tract. For patients who underwent both MRI and US, a concordance correlation analysis between US and MR findings was performed.

Results

In the reference period, 532 symptomatic patients (mean age ± standard deviation 74 ± 12 years) underwent X-ray and MRI examinations for suspected peri-prosthetic complications. Among them, 111 (20.9 %) underwent also US. Overall, 108 patients underwent both US and MRI. US findings included 67 superficial collections, 48 subcutaneous fistulas, 74 deep peri-prosthetic collections. Twenty-four patients had solid, mass-like peri-prosthetic collections. In 11 patients, no peri-prosthetic complications were seen. MRI findings included 68 superficial collections, 49 subcutaneous fistulas, 79 deep peri-prosthetic collections. Twenty-four patients had solid, mass-like peri-prosthetic collections. In four patients, no peri-prosthetic complications were seen. Concordance analysis between US and MRI findings showed almost perfect agreement (k ≥ 0.89).

Conclusion

US is an efficient and practical imaging modality to evaluate peri-prosthetic complications in patients with THA, being almost comparable to MRI in detecting and characterizing these complications.     

Metabolomics Approach in Allergic and Rheumatic Diseases

Metabolomics is the analysis of the concentration profiles of low molecular weight compounds present in biological fluids. Metabolites are nonpeptide molecules representing the end products of cellular activity. Therefore, changes in metabolite concentrations reveal the range of biochemical effects induced by a disease or its therapeutic intervention. Metabolomics has recently become feasible with the accessibility of new technologies, including mass spectrometry and high-resolution proton nuclear magnetic resonance, and has already been applied to several disorders. Indeed, it has the advantage of being a nontargeted approach for identifying potential biomarkers, which means that it does not require a preliminary knowledge of the substances to be studied. In this review, we summarize the main studies in which metabolomic approach was used in some allergic (asthma, atopic dermatitis) and rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus) to explore the feasibility of this technique as a novel diagnostic tool in these complex disorders.