BACKGROUND: This study was designed to determine the relationship of propranolol pharmacokinetic parameters with portosystemic shunt in CCl4-induced cirrhotic rats. METHODS: Cirrhotic rats(n=6) were induced by intramuscular injection of CCl4 in olive oil(two time per weeks) for 12 weeks. Controls (n=6) were injected intramuscularly with the same dose of olive oil for 12 weeks. We evaluated the amount of portosystemic shunt by thallium-201 per rectal scintigraphy. After intravenous bolus injection of propranolol (2mg/kg) to rats, the serum propranolol concentrations were analyzed by a HPLC-fluorimetric detector system. Pharmacokinetic parameters such as C0, AUC, t(1/2(beta)), and CLp were determined in each group. Then, a small amount of heptic tissue was obtained and subjected to determination of the hepatic collagen content by quantitating 4-hydroxyproline and were inspected by microscope after hematoxylin and eosin stain. RESULTS: In liver biopsy, liver fibrosis progressed in CCl4-induced cirrhotic rats. The serum concentrations of propranolol were significantly (p < 0.01) elevated in CCl4-induced cirrhotic rats. Mean amount of 4-hydroxyproline, mean H/L ratio, and mean AUC in CCl4-induced cirrhotic rats was significantly (p < 0.01) higher than that in control rats. There was a relationship between AUC, H/L ratio, and amount of 4-hydroxyproline. CONCLUSION: H/L ratio may help in the selection of drug dosage (especially blood flow dependent drug) in pre-clinical studies for chronic liver disease during the drug development process.
Animals ; Carbon Tetrachloride Poisoning/*complications ; Chromatography, High Pressure Liquid ; English Abstract ; Liver Cirrhosis, Experimental/*metabolism/physiopathology ; Portal System/physiopathology ; Propranolol/*pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Thallium Radioisotopes/diagnostic use

The aim of the present study was to evaluate the ability of Tl-201 abdominal SPECT to differentiate between chronic focal pancreatitis and pancreatic malignancy. Seventeen patients (12 men, 5 women; mean age, 56 years; 9 pancreatic cancer, 8 chronic pancreatitis) with pancreatic mass were prospectively investigated with Tl-201 abdominal SPECT. In all patients, CT and/or US could not clarify the nature of the pancreatic mass. Focal hot uptake was present in 8 of 9 patients with pancreatic cancer, while it was present in 2 of 8 patients with chronic pancreatitis. Therefore, the sensitivity and specificity of the present study were 89% and 75%, respectively. A significant difference of Tl-201 uptakes was noted between benign and malignant masses (p& 0.05). Therefore, we concluded that Tl-201 abdominal SPECT was a useful test in differentiation of malignant from benign pancreatic mass, especially when the differentiation could not be made by other imaging modalities
Abdomen/*radionuclide imaging ; Chronic Disease ; Diagnosis, Differential ; Evaluation Studies ; Female ; Follow-Up Studies ; Human ; Male ; Middle Age ; Pancreatic Neoplasms/*radionuclide imaging ; Pancreatitis/*radionuclide imaging ; Prospective Studies ; Reproducibility of Results ; Sensitivity and Specificity ; Support, Non-U.S. Gov't ; Thallium Radioisotopes/*diagnostic use ; Tomography, Emission-Computed, Single-Photon/methods

In a patient receiving 5-fluorouracil and levamisole, neurologic deficits suggest the cerebral demyelinating syndrome as a differential diagnosis. The authors report a patient diagnosed as multifocal inflammatory leukoencephalopathy for which thallium-201 ((201)Tl) single photon emission computed tomography (SPECT) and proton magnetic resonance spectroscopy (MRS) were employed as noninvasive diagnostic tools. (201)Tl SPECT study was negative and proton MRS showed an increase of choline and lactate and well preserved N-acetylaspartate. These findings support histopathologic findings of multifocal inflammatory leukoencephalopathy revealing demyelination with relative axonal sparing in the patient.
Adjuvants, Immunologic/adverse effects/therapeutic use ; Antimetabolites, Antineoplastic/adverse effects/therapeutic use ; Aspartic Acid/*analogs & derivatives/metabolism ; Axons/pathology ; Biopsy ; Brain/pathology ; Brain Neoplasms/secondary ; Choline/metabolism ; Colorectal Neoplasms/drug therapy/pathology ; Diagnosis, Differential ; Fluorouracil/adverse effects/therapeutic use ; Human ; Lactic Acid/metabolism ; Leukoencephalopathy, Progressive Multifocal/*diagnosis/etiology ; Levamisole/adverse effects/therapeutic use ; Magnetic Resonance Spectroscopy/*methods ; Male ; Middle Aged ; Neoplasm Metastasis ; Thallium Radioisotopes/*diagnostic use ; Tomography, Emission-Computed, Single-Photon/*methods