Kalipatnapu N. Rao

Acute hemorrhagic pancreatic necrosis in mice. Alterations of pancreatic lipase activity, pancreas lipids, and serum lipoproteins.

Acute hemorrhagic pancreatic necrosis (AHPN) with fat necrosis was induced in female mice by feeding a choline-deficient diet containing 0.5% DL-ethionine. Pancreatic lipase increases significantly prior to the onset of AHPN and is not accompanied by gross alterations in the lipid composition of the organs. In the same animals significant activities of pancreatic lipase were detected in serum and peritoneal cavity after 3 days of dietary regimen. Analysis of serum lipids and lipoproteins indicated no hyperlipemia prior to or after onset of AHPN.

Cerulein-Induced Pancreatitis in Rats: Increased Lysosomal Enzyme Activity and Autophagocytosis

The involvement of lysosomes in the normal secretory process of the exocrine pancreas and in the onset of acute, hormone-induced pancreatitis was studied. The enzymatic activities of cathepsin B and beta-galactosidase were determined in the pancreas of rats that had been stimulated by either maximal (0.25 microgram X kg-1 h-1) or supramaximal (5 micrograms X kg-1 h-1) concentrations of cerulein. Maximal stimulation led to a moderate increase in cathepsin B activity and the ultrastructural appearance of multivesicular bodies. Supramaximal stimulation resulted in formation of large cytoplasmic vacuoles and progressive destruction of acinar cells which was paralleled by a marked increase of lysosomal enzyme activity.

Acute hemorrhagic pancreatitis in mice: improved survival after indomethacin administration.

This study was designed to test whether indomethacin given in drinking water attenuates the severity of the acute hemorrhagic pancreatitis induced in mice fed a choline-deficient ethionine diet (CDE), and improves their survival. Three doses of indomethacin were tested, 20, 10 and 5 mg of indomethacin/l of drinking water, and their effects on the histopathology of the pancreas and liver, serum amylase activity levels, and mortality were determined. Even though 20 and 10 mg/l suppressed pancreatic injury, and the accompanying shock-like state, the mice died due to indomethacin hepatotoxicity. Hepatotoxicity was minimal at a dose of 5 mg/l, which resulted in preservation of significant amounts of normal pancreatic parenchyma, subsequent regeneration of acinar cells, and an increased survival of the mice. The results suggest that prostaglandins may play an important role in the pathogenesis of acute hemorrhagic pancreatitis, and that indomethacin attenuates the severity of the induced disease.

Acinar Cell Carcinoma of Rat Pancreas: Mechanism of Deregulation of Cholesterol Metabolism

The mechanism of deregulation of choleserol metabolism was studied in fast and slow growing nude mouse tumors and cancer cells in culture derived from azaserine-induced rat pancreatic acinar cell carcinoma. The tumors showed a loss of feedback control of the de novo synthesis of cholesterol, probably due to a loss of low density lipoprotein (LDL) receptors on plasma membranes or to a defect in the binding and internalization of LDL in the cancer cells. The hexosemonophosphate shunt pathway is stimulated in the cancer cells, presumably because of an increased demand for NADPH in cholesterol synthesis and for ribose phospate in DNA synthesis. The uncontrolled de novo synthesis of cholesterol is one of the factors responsible for the high rate of cell proliferation in the tumors.

Changes in serum and hepatic cholesterol in lead-induced liver hyperplasia.

Lead nitrate when injected intravenously as a single dose to male Wistar rats causes a strong hepatic proliferative response followed by reabsorption of excess tissue within 10-14 days. The rate of cell proliferation in this hyperplastic model was positively correlated with hepatic de novo synthesis of cholesterol, stimulation of the hexose monophosphate shunt pathway of glucose metabolism and with alterations in serum lipoproteins.

Regulatory Aspects of Cholesterol Metabolism in Cells with Different Degrees of Replication

This study explored cholesterol biosynthesis and its possible involvement in cell proliferation and cancer development. Normal proliferating cells and cancer cells were used to study the regulation of the cholesterol biosynthetic pathway. Evidence is presented that shows a positive correlation between the activity of the HMP pathway, DNA synthesis, and cholesterol biosynthesis; this evidence also shows a negative correlation between circulating cholesterol levels and/or cholesterol influx from serum to rates of cell proliferation. It is suggested that since cell proliferation is a prerequisite for the development of cancer, altering the HMP pathway, circulating cholesterol levels, and cholesterol influx from serum alters rates of cell proliferation and development of cancer.

Lipid composition and 3-hydroxy-3-methylglutaryl-CoA reductase acivity of acinar cell carcinoma of rat pancreas

The lipid composition and 3-hydroxy-3-methylglutaryl-CoA reductase activity of subcutaneous transplantable pancreatic acinar cell tumors on nude mice were compared with those of normal, regenerating, fetal and newborn rat pancreata. The tumors and also the fetal tissues showed decreased concentration in total lipids, increased concentration in sphingomyelin and an increase in cholesterol when compared to normal rat pancreas. The regenerating pancreas showed an intermediate elevation in these lipid parameters. Specifically, only tumor showed an increase in phosphatidylethanolamine/phosphatidylcholine ratio. The tumors and also the fetal tissues showed an increase in hydroxymethylglutaryl-CoA reductase activities, suggesting that the de novo synthesis of cholesterol is a requirement for cell proliferation. The cholesterol metabolism in normal tissues is under metabolic regulation as indicated by decreased hydroxymethylglutaryl-CoA reductase activities and decreased cholesterol concentration in postnatal tissues when compared with the fetal tissues. The fast growing AT3A tumor showed higher hydroxymethylglutaryl-CoA reductase activity when compared to the slow growing AT3B tumor, indicating that the differences in growth rate of the tumors may be related at least in part to differences in their cholesterol metabolism.

Lash’s: A bitter medicine: Biochemical analysis of an historical proprietary medicine

Patent medicines were widely used during the late 1800s and early 1900s. Bitters were one important subtype of patent medicines that were typically made from extracts of bitter tasting herbs. Lash’s Bitters was a popular patent medicine that was advertised as an extract of the bark of the buckthorn tree, Rhamnus purshiana, and was sold as a laxative. Analysis of the contents of an undisturbed bottle of Lashs Bitters, ca. 1918, revealed an ethanol content of 19.2% by volume as well as trace amounts of methanol. Potentially toxic concentrations of lead, 295 mg/dl, were also found. Interestingly, the medicine contained none of the active ingredient found in Rhamnus purshiana.

Acute Hemorrhagic Pancreatic Necrosis in Mice: Alterations of Serum Complement

Induction of acute hemorrhagic pancreatic necrosis by dietary means in mice produces alterations in the serum complement system. Total hemolytic complement, i.e., CH50, and native C3 levels fall during the development of pancreatitis while, at the same time, what could be immunoreactive C3 degradation products are demonstrable both in the circulation and in the urine. No evidence of renal deposition of C3 was obtained by immunofluorescence analysis, although marked alterations in proteinuria were observed, suggesting that renal dysfunction(s) is a feature of acute hemorrhagic pancreatic necrosis. Lack of renal complement deposition, together with our earlier negative findings with respect to pancreatic localization, suggests that serum complement alterations are side effects of the pancreatitis, attributable to intravascular, pancreatic enzyme-mediated degradation of serum complement components.

Acute Ethanol Intoxication in a 7-Month-old Infant

7-Month-old Infant KUDAKWASHE CHIKWAVA, DARLA R. LOWER, SUSAN H. FRANGISKAKIS, JORGE L. SEPULVEDA, MOHAMED A. VIRJI, AND KALIPATNAPU N. RAO* Department of Pathology, Division of Clinical Chemistry, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15261, USA Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15261, USA