Methylamine accumulation in cultured cells as a measure of the aqueous storage compartment in the laboratory diagnosis of genetic lysosomal diseases

Intracellular accumulation of the lysosomotropic compound [¹⁴C]methylamine was used to estimate the size of the lysosomal compartment in fibroblasts cultured from patients with a variety of lysosomal storage diseases. In previous work from our laboratory, it was shown that methylamine accumulation was significantly increased in diseases with infantile or juvenile onset and storage of predominantly water-soluble material such as in the mucopolysaccharidoses, mucolipidoses, and oligosaccharidoses. In the present study, methylamine incorporation was abnormally increased in cells from patients with glycogenosis type II and with Niemann-Pick type C disease, whereas it was normal in other sphingolipidoses and in the late-infantile and juvenile forms of neuronal ceroid lipofuscinoses. The methylamine test was also checked regarding its potential use for prenatal diagnostic testing. In model systems with cultured amniotic or chorionic villus cells, lysosomal storage was experimentally induced by the cathepsin inhibitor leupeptin and was readily detected when compared to untreated controls. Cultured amniotic cells from a fetus with mucopolysaccharidosis II were found to incorporate significantly higher amounts of [¹⁴C]methylamine than the normal controls. The results indicate that the methylamine accumulation method is an additional tool in the diagnosis and prenatal diagnosis of lysosomal diseases with abnormal storage of water-soluble material. © 1996 Wiley-Liss, Inc.     

Mechanisms of drug-induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo

Objective. T cells treated with DNA methylation inhibitors overexpress lymphocyte function-associated antigen 1 (LFA-1), which results in autoreactivity, and the autoreactive cells cause a lupus-like disease in vivo, suggesting a mechanism by which some agents may cause drug-induced lupus. This study compared the effects of procainamide (Pca) and hydralazine (Hyd) with those of structural analogs, to determine if the degree of LFA-1 overexpression and T cell autoreactivity correlated with the ability of the agents to induce autoimmunity. Methods. Cloned murine T helper 2 cells were treated with Pca, N-acetylprocainamide, Hyd, Phthalazine, or hydroxyurea (HU). The treated cells were then compared for LFA-1 overexpression, autoreactivity, and the ability to induce autoimmunity in vivo. Results. Pca and Hyd were more potent than their analogs or HU in all 3 assays. Conclusion. The results support a relationship between LFA-1 overexpression, T cell autoreactivity, and autoimmunity, and suggest a mechanism by which Pca and Hyd, but not the analogs, may cause drug-induced lupus.     

Therapeutic potential of silymarin as a natural iron‐chelating agent in β‐thalassemia intermedia

Abnormal iron accumulation in vital organs is one of the major complications of β‐thalassemia intermedia (β‐TI). Silymarin, a flavonolignan isolated from Silybum marianum, significantly decreases the serum ferritin levels of β‐TI patients. This finding suggests silymarin as a safe and effective natural iron‐chelating agent for the treatment of iron‐overloaded conditions.     

Influence of Sequential Liquid Ammonia and Caustic Mercerization Pre-Treatment on Dyeing Performance of Knit Cotton Fabric

A two-stage sequential pretreatment including caustic mercerization (CM) and liquid ammonia (LA) treatment was applied to investigate the influence on dyeing performance and handle of knit cotton fabric, and the relationship between dye size and dyeing properties. Various techniques were applied to characterize all the treated fabrics. X-ray diffraction (XRD) and Fourier-transform infrared (FTIR) analyses of the treated fabrics confirmed that both sequential treatments decreased the crystallinity of cotton fabric more than only the CM or LA treatment. The pattern of cellulose I was transferred to a mixed configuration of cellulose II and cellulose III after the CM/LA or LA/CM treatment. Thermal performances measured by thermogravimetric analysis (TGA) and differential thermogravimetry (DTG) techniques showed that the thermal stability of the treated cotton only marginally decreased. The wicking height increased after the sequential CM/LA treatment, indicating that the hydrophilicity of the fabric increased. The dye absorption and color uniformity were better for the reactive dye with a smaller molecular weight (Reactive Red 2) compared with the one with a larger molecular weight (Reactive Red 195). The total dye fixation efficiency (T%) increased to 72.93% and 73.24% for Reactive Red 2 dyeings of CM/LA- and LA/CM-cotton fabric from 46.75% of the untreated fabric, respectively; the T% increased to 65.33% and 72.27% for Reactive Red 195 dyeings of CM/LA- and LA/CM-cotton fabric from 35.17% of the untreated fabric, respectively. The colorfastness and dye exhaustion and fixation percentages of the samples were enhanced after the treatments. Furthermore, compared to the single CM or LA treatment, the softness handle properties were further improved after the fabrics were sequentially treated by CM/LA. The developed pre-treatment of CM/LA can be used in the textile industry to promote the dyeability, handle, and mechanical properties of knit cotton fabrics.     

Safety and predictors of adherence of a new rehabilitation program for older women with congestive heart failure

Objectives To assess the safety of a cardiac rehabilitation program for older women with Congestive Heart Failure (CHF) and determine if certain factors influence adherence. Methods Women over the age of 65 with CHF attended an exercise program supervised by a physiotherapist. Quality of life was measured by the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and severity of disease by the New York Heart Association (NYHA) Class. Subjects were classified into those who attended 90% or more of the sessions and those who attended less than 90% of the sessions. Results Fifty-one subjects were studied. Eight subjects did not attend any sessions. Of the 43 attendees, the average percentage of sessions attended was 87%. There were no significant differences between the two groups in age, MLHFQ or NYHA Class. There was only one adverse event out of 280 participant attendances. Conclusions The program had a high level of adherence in this population. Age, MLHFQ or NYHA Class did not impact on session attendance. Our data suggests this program is safe for this population. Further research is needed to determine other predictors of attendance and the examination of safety issues and long-term adherence to exercise in this population.     

Management of chronic heart failure in the older population

Chronic heart failure （CHF） is the leading cause of hospitalization for those over the age of 65 and represents a significant clinical and economic burden. About half of hospital re-admissions are related to co-morbidities, polypharmacy and disabilities associated with CHF. Moreover, CHF also has an enormous cost in terms of poor prognosis with an average one year mortality of 33%–35%. While more than half of patients with CHF are over 75 years, most clinical trials have included younger patients with a mean age of 61 years. Inadequate data makes treatment decisions challenging for the providers. Older CHF patients are more often female, have less cardiovascular diseases and associated risk factors, but higher rates of non-cardiovascular conditions and diastolic dysfunction. The prevalence of CHF with reduced ejection fraction, ischemic heart disease, and its risk factors declines with age, whereas the prevalence of non-cardiac co-morbidities, such as chronic renal failure, dementia, anemia and malignancy increases with age. Diabetes and hypertension are among the strongest risk factors as predictors of CHF particularly among women with coronary heart disease. This review paper will focus on the specific consideration for CHF assessment in the older population. Management strategies will be reviewed, including non-pharmacologic, pharmacologic, quality care indicators, quality improvement in care transition and lastly, end-of-life issues. Palliative care should be an integral part of an interdiscipli-nary team approach for a comprehensive care plan over the whole disease trajectory. In addition, frailty contributes valuable prognostic in-sight incremental to existing risk models and assists clinicians in defining optimal care pathways for their patients.