Inhibitory effects of crude soybean trypsin inhibitor on pancreatic ductal carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine.

The effects of soybean trypsin inhibitor (SBTI) administration during the promotion phase of pancreatic carcinogenesis were investigated. Female Syrian golden hamsters were given three weekly s.c. injections of N-nitrosobis(2-oxopropyl)amine (BOP) each at a dose of 10 mg/kg and then administered 5% SBTI diet for the following 37 weeks. Additional groups of animals received the BOP injection alone or the 5% SBTI diet alone as controls. At week 40 of the experiment, all surviving animals were killed and development of pancreatic lesions was assessed histopathologically. The results showed that the incidence of dysplastic lesions in hamsters of the BOP/SBTI group was significantly decreased as compared to that of the BOP group (P < 0.01). A similar but not significant tendency was also found for pancreatic adenocarcinomas. In addition, the number of dysplastic lesions in the pancreas head portion in the BOP/SBTI group were significantly decreased as compared to the BOP group value (P < 0.05). Furthermore, atrophic changes of the pancreatic exocrine tissue were more severe in the BOP group than in the BOP/SBTI group (P < 0.01), indicating that SBTI treatment gave effective protection against the replacement process of acinar cell induced by BOP. Thus, the present experiment demonstrated that SBTI can inhibit hamster pancreatic ductal carcinogenesis when given in the promotion phase, in clear contrast to the enhancing effects reported for preneoplastic acinar lesion development in rats.     

Reactivity of monoclonal anti-human skin basal cell antibody to cultured keratinocytes in serum-free medium

The reactivity of the monoclonal anti-human skin basal cell antibody (3B4-6) to cultured keratinocytes was examined by immunofluorescence techniques in order to verify the change in distribution of basal cell antigens during the in vitro differentiation of keratinocytes cultured in serum-free medium. The basal cells' antigen(s) determinants recognized by 3B4-6 were present in the cytoplasm of the cells at low concentration of Ca2+ (0.03 mM). High concentrations of Ca2+ (0.1 mM approximately 0.3 mM) induced the reactivity on the cell surface. This result was confirmed by flow cytometry analysis. The staining pattern was different from that of anti-involucrin antibody in 0.3 mM Ca2+ culture medium. This MoAb might be a useful tool for monitoring the degree of differentiation of cultured keratinocytes.     

A case report of entrapment of PTCA balloon catheter caused by its rupture

This is a report of a rare case in which an angioplasty balloon catheter became entrapped within the lumen of the coronary artery after the balloon ruptured during percutaneous transluminal coronary angioplasty (PTCA). The patient was a 69-year-old man who underwent elective PTCA of the circumflex coronary artery (Cx) with USCI 2.5 mm new Probe. The inflation failed to dilate the lesion up to 18 bar; at this pressure, balloon rupture was observed. Any attempt to withdraw the balloon catheter across the lesion was not successful, and then the patient was transferred to the operating room for removal of the balloon catheter. After establishing cardiopulmonary bypass, an arteriotomy in the Cx confirmed that the balloon fragment had become entrapped at a sharp edge of calcific stenosis after balloon rupture. The entrapped catheter was successfully removed from the arteriotomy of the Cx, and coronary bypass grafting was performed to the left anterior descending artery which had restenosis after PTCA 3 months ago. The patient had an uneventful postoperative course and was discharged in excellent condition 30 days after surgery. The balloon rupture of PTCA had been considered a minor problem, however, as this case demonstrated, this seemingly benign complication may lead to potentially disastrous consequences.     

Inhibition of cyclin-dependent kinases improves CA1 neuronal survival and behavioral performance after global ischemia in the rat.

Increasing evidence suggests that cyclin-dependent kinases participate in neuronal death induced by multiple stresses in vitro. However, their role in cell death paradigms in vivo is not well characterized. Accordingly, the authors examined whether cyclin-dependent kinase inhibition resulted in functionally relevant and sustained neuroprotection in a model of global ischemia. Intracerebroventricular administration of the cyclin-dependent kinase inhibitor flavopiridol, immediately or at 4 hours postreperfusion after a global insult, reduced injury in the CA1 of the hippocampus when examined 7 days after reperfusion. No significant protection was observed when flavopiridol was administered 8 hours after reperfusion. The tumor-suppressor retinoblastoma protein, a substrate of cyclin-dependent kinase, was phosphorylated on a cyclin-dependent kinase consensus site after the global insult; this phosphorylation was inhibited by flavopiridol administration. Importantly, flavopiridol had no effect on core body temperature, suggesting that the mechanism of neuroprotection was through cyclin-dependent kinase inhibition but not through hypothermia. Furthermore, inhibition of cyclin-dependent kinases improved spatial learning behavior as assessed by the Morris water maze 7 to 9 days after reperfusion. However, the histologic protection observed at day 7 was absent 28 days after reperfusion. These results indicate that cyclin-dependent kinase inhibition provides an extended period of morphologic and functional neuroprotection that may allow time for other neuroprotective modalities to be introduced.     

Pharmacologic analysis of ketamine-induced cardiac actions in isolated, blood-perfused canine atria

Effects of ketamine were investigated on atrial rate and contractile force in the isolated, blood-perfused canine atrium. When a relatively small dose (3 micrograms) of ketamine was injected into the sinus node artery, positive chronotropic and inotropic responses were consistently observed. With doses of 10-300 micrograms i.a., biphasic (i.e., negative followed by positive) chronotropic and inotropic responses were induced. An extremely large dose of ketamine frequently produced biphasic chronotropic and only negative inotropic responses. The negative effects of ketamine were not affected by atropine pretreatment. After treatment with propranolol or imipramine, the positive effects were significantly suppressed. The effects were not influenced by tetrodotoxin. These results suggest that ketamine has (a) indirect cardioexcitatory properties mediated by a release of catecholamines which is due to a tyramine-like action, and (b) direct cardioinhibitory properties by which high doses depress the contractility rather than the pacemaker activity.     

Effect of circulatory assist devices on stunned myocardium

We studied the effects of mechanical circulatory assist devices on left ventricular oxygen consumption, the integrals of systolic left ventricular wall stress (SSI), and end-systolic elastance (Ees) in 8 sheep after 25 minutes of global ischemia. Extracorporeal membrane oxygenation at 35 mL/kg/min, intraaortic balloon counterpulsation, and an intraaortic double-balloon pump were studied alone or in combination. Left ventricular oxygen consumption, SSI, and Ees were measured before and during mechanical circulatory assistance. Left ventricular oxygen consumption was calculated from transit-time measurements of left main coronary artery blood flow and fiberoptic measurements of coronary sinus blood oxygen saturation. Three pairs of sonomicrometry crystals placed across three orthogonal ventricular axes were used to calculate instantaneous ventricular volumes and pressure-volume loops from which the SSI data were derived. The Ees was measured using a new single-beat aortic occlusive method. Extracorporeal membrane oxygenation alone increased SSI and did not change Ees in postischemic poorly contracting hearts. Intraaortic balloon counterpulsation alone significantly reduced SSI and increased Ees. The combination of extracorporeal membrane oxygenation and either the intraaortic balloon pump or the intraaortic double-balloon pump reduced SSI, increased Ees, and reduced left ventricular oxygen consumption. In postischemic dilated, poorly contracting hearts, the combination of extracorporeal membrane oxygenation and intraaortic balloon counterpulsation has important advantages over extracorporeal membrane oxygenation alone.     

Disposition and metabolism of [14C]sparfloxacin in the rat.

Disposition and metabolism of [carbonyl-14C]sparfloxacin SPFX, 5-amino-1-cyclopropyl-7-(cis-3,5-dimethyl-1-piperazinyl)-6,8-difluoro- 1,4-dihydro-4-oxoquinoline-3-carboxylic acid, AT-4140; CAS 110871-86-8), a novel antimicrobial quinolone, were studied in rats mainly after oral administration at 10 mg/kg. SPFX was absorbed from the whole area of small intestine as shown by the loop method. The extent of absorption was around 70% when estimated by AUC, urinary excretion and biliary excretion. Plasma level of radioactivity reached Cmax of 1.32 micrograms eq/ml within 1 h after oral administration and decreased with a half-life of about 4 h. Higher levels of radioactivity than that in plasma were seen in kidney, liver, submaxillary gland, lung, trachea and many other tissues and lower levels, in eye ball, brain and some others. Most tissue levels decreased with time essentially in parallel with plasma level. In pregnant rats, levels of fetal radioactivity amounted to about 60% of maternal plasma level. In lactating rats, milk was found to contain radioactivity several times as high as plasma level, which decreased with a similar half-life. SPFX was bound to plasma protein, mainly to albumin, at about 40%. Unchanged SPFX and its glucuronide were found in the plasma, milk, bile and urine. Within 48 h, about half of the dosed radioactivity was excreted in the bile, and part of which was re-absorbed. Within 96 h, about 20 and 80% of dose were found in the urine and feces, respectively.     

A case of squamous cell carcinoma of the lung treated by right sleeve upper lobectomy after photodynamic therapy]

This patient, a 62-year-old female, with squamous cell carcinoma of the lung was inoperable because of poor pulmonary function due to severe bronchial stenosis by a tumor at the orifice of the right main bronchus. As the tumor decreased in size after photodynamic therapy (PDT), the bronchial stenosis decreased and her pulmonary function improved sufficiency to permit surgery. When right upper sleeve lobectomy was performed, only limited peribronchial inflammation related to PDT procedure was detected indicating only slight extrabronchial influence of PDT. This suggests that PDT is a viable adjunct modality in case in which surgery might possible be performed. The patient has a good postoperative course and is alive 18 months after surgery without any evidence of recurrence.     

The effect of dietary safflower phospholipid on steroids in gastrointestinal tract of rats fed a hypercholesterolemic diet.

The effect of dietary safflower phospholipid (Saf-PL) on the postprandial changes of steroids in the small intestinal and cecal contents was examined in rats fed a hypercholesterolemic diet. The triglyceride mixture (SP-Oil) containing a comparable amount of linoleic acid to Saf-PL was used as a reference fat source. Saf-PL suppressed the elevation of plasma cholesterol levels at all times after meal intake, when compared to SP-Oil. The reduction of plasma cholesterol in rats fed the Saf-PL diet was exclusively observed both in chylomicron plus very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions. The rate of gastric emptying was not modified by the Saf-PL diet. The level of neutral steroids in the small intestinal contents was almost comparable in both groups, but in the cecal contents and feces it was significantly higher in rats fed the Saf-PL diet. On the other hand, the level of acidic steroids in the small intestinal contents tended to be higher in rats fed the Saf-PL diet than in those fed the SP-Oil diet, whereas in the cecal contents and feces it was comparable in the two diets. These results suggest that Saf-PL causes the accumulation of neutral steroids in the cecum due to the rapid transit through the small intestine.     

Inhibitory effect of dibutyltin dichloride on pancreatic adenocarcinoma development by N-nitrosobis(2-oxopropyl)amine in the Syrian hamster

The effects of a single intragastric application of dibutyltin dichloride (DT), at a dose of 30 mg/kg body weight, on N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinogenesis were studied in female Syrian golden hamsters. DT, which has been shown to selectively induce bile duct injury, was administered either 1 week before or after BOP initiation. BOP was injected subcutaneously once a week for 5 weeks at a dose of 10 mg/kg body weight. Controls were injected with BOP alone or given DT without carcinogen. Animals sacrificed at the end of the 25-week experimental period showed a significant inhibitory effect of DT on pancreatic carcinoma induction when DT was given before BOP treatment, although no such influence was evident with DT treatment following BOP exposure. These results indicate that the bile duct and more especially common bile-duct injury induced by DT may be relevant to the inhibition of the initiation stage of BOP-induced pancreatic carcinoma development in Syrian hamsters.