Induction of differentiation of human promyelocytic leukemia cell line HL-60 by retinoyl glucuronide, a biologically active metabolite of vitamin A.

We examined the differentiation activity of retinoyl beta-D-glucuronide, a biologically active physiological metabolite of vitamin A, using the human promyelocytic leukemic cell line HL-60, which can be induced to differentiate with retinoic acid. Retinoyl beta-D-glucuronide (1 microM) inhibited HL-60 cell proliferation by 55-75%, inhibited tritiated thymidine incorporation into DNA by 63-80%, and induced 38-50% of the cells to differentiate into mature granulocytes. The potency of growth inhibition and induction of differentiation by retinoyl beta-D-glucuronide was similar to that of all-trans-retinoic acid. The continuous presence of either retinoyl beta-D-glucuronide or all-trans-retinoic acid was not required to obtain maximum growth arrest and differentiation: a 1-hr exposure of HL-60 cells to the retinoids gave the same response (measured after a total incubation time of 48 hr) as a 24-hr or 48-hr continuous treatment. Retinoyl beta-D-glucuronide (0.1-0.2 mM) was 50% less cytotoxic to HL-60 cells than all-trans-retinoic acid at an equimolar concentration. Retinoyl beta-D-glucuronide was not significantly metabolized to other retinoids; retinoic acid was not formed during incubation. We conclude that retinoyl beta-D-glucuronide can arrest HL-60 cell proliferation and induce their differentiation into mature granulocytes; it may act by itself or by being hydrolyzed to retinoic acid, which could be immediately utilized and metabolized. The therapeutic use of this retinoid as an antineoplastic agent is suggested.     

Elevated Liver Enzymes along with Comorbidity Is a High Risk Factor for COVID-19 Mortality: A South Indian Study on 1,512 Patients

Background and Aims: Liver enzyme abnormalities in coronavirus 2019 (COVID-19) are being addressed in the literature. The predictive risk of elevated liver enzy...     

Successful treatment of acute inferior vena cava and unilateral renal vein thrombosis by local infusion of recombinant tissue plasminogen activator

Renal vein thrombosis can occur as a complication of nephrotic syndrome. We present the case of a young man with nephrotic syndrome caused by minimal change disease who developed acute inferior vena cava and left renal vein thrombosis. He was treated initially with intravenous heparin. Because of the persistence of severe left flank pain and gross hematuria, local infusion of recombinant tissue plasminogen activator was tried, with resolution of thrombi and subsidence of symptoms. Functional preservation of the involved kidney is good, as indicated by Tc-99m DMSA scan (involved kidney, 47.4%; uninvolved kidney, 52.6%). Anticoagulation is usually recommended as the treatment of choice in renal vein thrombosis. We believe that in cases with critical presentations, such as bilateral involvement, extension into inferior vena cava, acute renal failure, pulmonary embolism or severe flank pain, thrombolytic therapy should be considered as a second-line treatment if good response is not obtained with heparin.     

Forgotten foreign body in the larynx (A case report)

An interesting and unsual case of foreign body of larynx in adult is presented here, where the foreign body is a fish bone, quite large in size and has multiple projections by which it was impacted firmly in the subglottic region of larynx for about 3 months. Large irregular fish bone impacted for about 3 months in an adult larynx is very rare, and as such is reported.     

Heavy and light cigarette smokers have similar dysfunction of endothelial vasoregulatory activity: an in vivo and in vitro correlation

OBJECTIVES: The goal of this study was to investigate the dose-dependent effects of active cigarette smoking on endothelial nitric oxide (NO) and endothelin-1 (ET-1) biosynthesis. BACKGROUND: Limited studies have suggested that active cigarette smoking may be associated with a dose-dependent reduction of endothelium-dependent vasodilation (EDV). The underlying biochemical changes that cause this dose-specific effect, such as changes in the endothelial NO biosynthetic pathway and ET-1 production, have not been examined. METHODS: Flow- and nitroglycerin-mediated reactivity of the brachial artery were measured in eight nonsmokers, seven light smokers (< or =1 pack/week) and eight heavy smokers (> or =1 pack/day), and their sera were added to confluent ( approximately 85%) monolayers of human umbilical endothelial cells (HUVECs) for 12 h. Basal and substance P-stimulated NO and basal ET-1 production were measured. The HUVECs used for measuring basal NO production were lysed, and both endothelial NO synthase (eNOS) protein expression and eNOS activity were determined. RESULTS: Serum cotinine level and pack-years of smoking were significantly lower in light smokers compared with heavy smokers (p < 0.006 and p < 0.004, respectively). There were no significant differences between heavy smokers and light smokers in EDV (p = 0.52), basal- (p = 0.70) and stimulated-NO production (p = 0.95), eNOS protein (p = 0.40) and eNOS activity (p = 0.63). Compared with nonsmokers, all the parameters were significantly altered in both of the smokers' groups. No differences were found in nitroglycerin-mediated vasodilation and in vitro ET-1 production among the three groups. CONCLUSIONS: These results indicate light smoking may have similar detrimental effects on EDV and NO biosynthetic pathway as does heavy smoking. These data may have important implications concerning the amount of active cigarette exposure that imparts cardiovascular risk.     

Thymic cysts in mediastinal Hodgkin disease

Three cases of proved thymic cysts associated with mediastinal Hodgkin disease are presented. Two illustrate regression of lymphoma with chemotherapy but persistence of thymic cysts. The third case demonstrates a thymic cyst in untreated Hodgkin disease. These cases suggest that such cysts are probably neither coincidental with nor a consequence of therapy but are probably related to initial thymic involvement by Hodgkin disease.