Age-related cataract

Cataract, opacification of the lens, is one of the commonest causes of loss of useful vision, with an estimated 16 million people worldwide affected. Several risk factors have been identified in addition to increasing age--genetic composition, exposure to ultraviolet light, and diabetes. However, no method to halt the formation of a cataractous lens has been shown to be effective. Nevertheless, advances in surgical removal of cataracts, including small-incision surgery, use of viscoelastics, and the development of intraocular lenses, have made treatment very effective and visual recovery rapid in most cases. Despite these advances, cataract continues to be a leading public-health issue that will grow in importance as the population increases and life expectancy is extended worldwide.     

Dual‐Dye Optical Mapping after Myocardial Infarction: Does the Site of Ventricular Stimulation Alter the Properties of Electrical Propagation?

Introduction: Myocardial infarction (MI) disrupts electrical conduction in affected ventricular areas. We investigated the effect of MI on the regional voltage and calcium (Ca) signals and their propagation properties, with special attention to the effect of the site of ventricular pacing on these properties.
Methods: New Zealand White rabbits were divided into four study groups: sham-operated (C, n = 6), MI with no pacing (MI, n = 7), MI with right ventricular pacing (MI + RV, n = 6), and MI with BIV pacing (MI + BIV, n = 7). At 4 weeks, hearts were excised, perfused, and optically mapped. As previously shown, systolic and diastolic dilation of the LV were prevented by BIV pacing, as was the reduction in LV fractional shortening.
Results: Four weeks after MI, optical mapping revealed markedly reduced action potential amplitudes and conduction velocities (CV) in MI zones, and these increased gradually in the border zone and normal myocardial areas. Also, Ca transients were absent in the infarcted areas and increased gradually 3–5 mm from the border of the normal zone. Neither BIV nor RV pacing affected these findings in any of the MI, border, or normal zones.
Conclusions: MI has profound effects on the regional electrical and Ca signals and on their propagation properties in this rabbit model. The absence of differences in these parameters by study group suggests that altering the properties of myocardial electrical conduction and Ca signaling are unlikely mechanisms by which BIV pacing confers its benefits. Further studies into the regional, cellular, and molecular benefits of BIV pacing are therefore warranted.     

Acute leukemia associated with valproic acid treatment: A novel mechanism for leukemogenesis?

Valproic acid has been previously associated with hematologic toxicity, including a reversible myelodysplasia-like syndrome without chromosomal abnormalities. We now report three cases of acute leukemia with features of secondary leukemia associated with valproic acid therapy: two cases of acute myelogenous leukemia with multilineage dysplasia, one with trisomy 8 and one with monosomy 7, and one case of secondary acute lymphoblastic leukemia with del (7) (q22q34), del (9) (q21.11q22), del (11) (q12q23). One patient had a previous myelodysplastic syndrome while on valproic acid. Valproic acid has been previously shown to be a histone deacetylase inhibitor. Inhibition of histone deacetylase causes a relaxation of chromatin structure and thus increases susceptibility to DNA damage and sensitizes cells to radiation. We propose that valproic acid therapy may lead to secondary leukemia by increasing DNA damage through chronic inhibition of histone deacetylase.     

Liver dysfunction in Pennsylvania's multitransfused hemophiliacs

Transaminase values [alanine amino transferase (ALT) and aspartate amino transferase (AST)] and markers for hepatitis B were serially determined in 558 hemophiliacs exposed to blood products. Hepatitis B surface antigen (HB_sAg) persistent for over 12 months was present in 6% of the patients. Antibody to hepatitis B surface antigen (anti-HBs) was noted in 90% of the 259 patients treated with factor VIII or IX concentrates but in only 49% of the 43 patients treated with fresh frozen plasma (FFP) or cryoprecipitate. Persistently abnormal transaminase values were noted in 31% of the patients treated with commercial concentrates but in only one (2%) of the patients exposed to cryoprecipitate or FFP. This difference continued even when the two groups of patients were matched for the amount of blood products, up to 50, 000 units, which they had received in the study period. In the concentrate-treated patients, no correlation could be found between transaminase values and the number of units of factor VIII or IX they had received during the six years of the study (1973–1978).Supported in part by the Pennsylvania Hemophilia Centers and the Pennsylvania State-Wide Hemophilia Program.     

Acetaminophen toxicity up-regulates MRP2 expression in the liver of cats: an old story with new vision

This study was conducted to clarify the role of efflux transporter MRP₂ in acetaminophen-induced hepatotoxicity in cats. Sixteen mixed bred male cats and four liver samples from mixed breed male dogs were used. The cats were assigned into four groups (n?=?4), received saline and 2, 10 and 50?mg/kg doses of acetaminophen orally for 14 days. Unlike the intact dogs, the MRP₂ was not detectable in control cats. MRP₂ at mRNA level was expressed in the liver of cats, which received the medium and high doses. Data suggest that the MRP₂ expression may involve in the acetaminophen-induced hepatotoxicity in cats.