摘要:

The effectiveness of the combined administration of 5-fluorouracil (5-FU) and Krestin (PSK) on experimentally induced liver cancer has not been established. This study was undertaken to elucidate the effect of the combined administration of these drugs on tumor growth and metastasis. Male inbred WKNH strain rats were used. The drugs used were 5-FU and PSK, each dissolved in water and fed orally. The drugs were administered separately or concurrently in standardized cycles to the tumor-bearing animals. KDH-8 ascitic liver cancer cells were subcutaneously transplanted into WKA rats. The tumor growth inhibition rates of S-FU and PSK were then determined. Eighteen days afer subcutaneous transplantation, tumor growth in the combined administration group was significantly inhibited, compared to the control group and the single treatment groups (p>. 05). In addition, a liver metastatic model was prepared by transplanting KDH-8 cells into the spleen. Then the metastatic inhibitory effects of S-FU and PSK were analyzed. At 14 days, the mean number of liver metastatic nodules was approximately 63 in the control group. However, the combined-medicated group showed a much lower number of nodules (40), indicating that metastasis was significantly inhibited (p>. 05).

ISSN:0894-1939    

DOI:10.3109/08941939509015386

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Because adenine nucleotide catabolites may be important during postischemic lung reperfusion, we examined the pathway of adenosine monophosphate (AMP) degradation in ischemic lung tissue. Once the pattern of degradation is known, pharmacological interventions can be considered, offering new methods of reducing lung reperfusion injury. For this purpose we used the isolated rabbit lung. Rabbit lungs were flushed in situ with a modified Krebs Henseleit solution (60 ml/kg). The lungs were removed and stored deflated, immersed in saline solution at 37°C. At regular times, biopsies were taken, and adenine nucleotides, nucleosides, and bases were measured in these biopsies using high performance liquid chromatography (HPLC). During lung ischemia, a very significant increase of inosine monophosphate (IMP) was found. Adenosine levels on the other hand did not increase. Hypoxanthine was the major end catabolite of ischemic lung tissue (constituting 92% of the nucleoside and purine base fraction at 4 hours ischemia). To further determine the pathway of AMP degradation, 400 mM of the adenosine deaminase inhibitor erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA) was added to the lung flush solution. During ischemia, adenosine triphosphate (ATP) breakdown was unaltered but adenosine became the major catabolite (2.8 times the concentration of hypoxanthine at 4 hours ischemia). These data suggest that: I) in rabbit lung tissue, de-phosphorylation of AMP to adenosine is more important than deamination to IMP; 2) hypoxanthine is the major end catabolite of ischemic lung tissue. By inhibiting the enzyme deaminase, reduced hypoxanthine levels and increased adenosine levels were obtained. Pharmacological interventions are now available to interfere with the formation of adenine nucleosides and bases in ischemic lung tissue. The importance of adenine nucleotide catabolites to postischemic lung reperfusion injury is discussed.

ISSN:0894-1939    

DOI:10.3109/08941939509015387

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Newborns suffering from severe respiratory difficulties and not responding to conventional methods have been successfully treated by extracorporeal circulation with a membrane oxygenator (ECMO). However, the technique needs a highly specialized staff, excellent laboratory support, and continuous surveillance of the procedure to prevent complications. In a series of experiments on newborn and preterm lambs, we have investigated a relatively simpler technique of respiratory support that involves a pumpless arteriovenous bypass by cannulating both umbilical arteries and the umbilical vein. A highly efficient microporous membrane oxygenator (MO) with very low resistance was selected. This type of perfusion that mimics the placental circulation, besides providing an additional amount of oxygen to the blood, has proven to be very effective for CO2extraction. Before its application in humans, however, improvements in the catheters to be inserted in the umbilical vessels, some modifications in the design of the MO, and improvements in the blood compatibility of all foreign surfaces in contact with blood are needed.

ISSN:0894-1939    

DOI:10.3109/08941939509015388

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Silicone prostheses, when implanted within the soft tissues of the breast, evoke an inflammatory reaction. In response to silicone exposure, inflammatory mediator production by individual cells has been observed in various experimental studies. In this study, inflammatory mediator production by periprosthetic tissues (whole organ) was measured. The mediator levels were correlated with both the tissue histopathology of the periprosthetic capsules and the clinical symptoms noted by each patient. Tissue surrounding breast implants removed at surgery from ten women (average age and implant duration 40 and 7 years respectively) was cultured in vitro for 24 hours. Control tissues consisting of (a) augmentation mammaplasty skin scars from eight additional patients and (b) knee synovium from seven orthopedic surgery patients with arthritis undergoing primary joint arthroplasty were similarly cultured. The mediators [interleukin-2 (IL-2), tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PCE)] liberated into the culture media were measured by an enzyme linked immunosorbent assay. When compared to controls, the mediator levels of IL-6 and TNF-αwere substantially greater, although IL-2 and PCE, were lower. Levels varied greatly from patient to patient: in pg/ml per 10 g tissue, IL-2 ranged from 10 to over 1,000; TNF-αfrom 100 to 1,000; IL-6 from 100 to 1,000,000; and PCE, from 100 to 10,000. The correlation between TNF-a and PCE, levels was. 5 between IL-6 and PCE, was. 6, and between IL-6 and TNF-αwas. 77. The correlation between TNF-αand IL-6 was statistically significant at a p-value less than. 01. Elevated levels of TNF-αproduction were associated with an increased number of macrophages and overall tissue cellularity (p>. 05). No significant relationship was observed between mediator production and clinical symptoms. We conclude that overall cellularity, specifically macrophages, in the periprosthetic capsule may lead to TNF-αproduction but that cytokine production by periprosthetic tissues alone is not a predictor of clinical symptomatology in patients with silicone breast prostheses.

ISSN:0894-1939    

DOI:10.3109/08941939509015389

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Hypercholesterolemia is associated with altered arterial endothelial and smooth muscle cell function. This study examines the influence of hypercholesterolemia on external jugular venous endothelial and smooth muscle cell vasoreactivity. Eighteen New Zealand White rabbits received a 1% cholesterol diet: in nine animals, this diet was continued until harvest at 8 weeks (hypercholesterolemic group), but in the other nine animals, the diet was changed to standard rabbit chow after 4 weeks and continued for a further 4 weeks (cholesterol reduction group). The change in the diet resulted in a 70% decrease in serum cholesterol concentration. Eight animals received standard rabbit chow for 8 weeks. Hypercholesterolemia induced hypersensitivity and increased maximal contractions to norepinephrine and endothelin-I. In addition, the maximal response to bradykinin increased, and a contraction to serotonin was induced in the veins from the hypercholesterolemic animals. Cholesterol reduction induced bradykinin hypersensitivity but had no effect on endothelin-I sensitivity. Norepinephrine hypersensitivity returned to normal and the serotonin response disappeared. A decrease in the maximal contractile responses to these agonists was also observed. Hypercholesterolemia interfered with dose-dependent, EDRF (endothelium derived relaxing factor)-mediated relaxation induced by acetylcholine but, following the reduction of serum cholesterol, normal acetylcholine-induced, endothelium-dependent relaxation returned. Non-endothelium-dependent relaxation to sodium nitroprusside of precontracted veins was unaffected by the presence of high cholesterol concentrations. There were no morphological changes apparent in the veins of either the hypercholesterolemic or the cholesterol reduction groups. In conclusion, this study suggests that hypercholesterolemia induces reversible functional abnormalities in venous tissue and this ability of the jugular veins to recover may be, in part. linked to the lack of morphological changes.

ISSN:0894-1939    

DOI:10.3109/08941939509015390

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

This study investigates the role of verapamil, a calcium channel blocker, combined with allopurinol, a xanthine-oxidase inhibitor, when given at reperfusion afer severe renal ischemia injury in the rat. Male Sprague-Dawley rats were subjected to 60 minutes of warm ischemia by cross clamping the whole left renal pedicle (artery and vein). At the end of ischemia, the clamps were removed and a contralateral nephrectomy was performed. The animals (n = 40 per group) were divided into five groups: Group 1, ischemic control (IC) receiving lactated Ringer's; Group 2, allopurinol (A) 100 mg/kg; Group 3, verapamil (V) 1.25 mg/kg; Group 4, receiving a combination of A + V at the same concentrations; and Group 5, sham group. Each drug was given intravenously at the end of the ischemic period at reperfusion. Survival was evaluated at 7 days. Renal damage was assessed by kidney function tests (serum creatinine and blood urea nitrogen, or BUN), light histology. Lipid peroxidation was measured in renal tissue using the TBA (thiobarbituric acid) assay. The best survival rate was seen in the combination group of A + V (70% at 7 days; p>. 01 vs. control). Single drugs were not as effective as the combination when compared to the IC. Serum creatinine at 24 and 48 hours showed a significant difference between the IC and treatment groups. At 72 hours there were no differences among the treated groups. Histological damage was more pronounced in the IC (Grade 4.0) than in the allopurinol (3.4±0.8), verapamil (3.0), or A + V (2.2±0.04). It was evident that the combination of A + V had the most significant beneficial effect in the survival and histological structure.

ISSN:0894-1939    

DOI:10.3109/08941939509015391

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Bacterial infection and bacteremia are common complications in patients with acute liver failure. Bacterial translocation from the gut has been suggested to be a major cause of bacterial infections in experimental acute liver failure. In the present study, a water-soluble ethylhydroxyethyl cellulose (EHEC) was administrated orally 1 and 24 hours prior to 90% hepatectomy in the rat in order to prevent bacterial translocation in experimental acute liver failure induced by subtotal liver resection in the rat. Ninety percent hepatectomy alone resulted in 80 to 100% translocation to mesenteric lymph nodes or blood 2 and 4 hours after operation, There was no translocation in rats undergoing sham operation or 90% hepatectomy with EHEC administration prior to operation (p>. 01). Bacterial overgrowth. increased bacterial adherence onto the intestinal surface, and diminished intestinal and mucosal mass were also observed in animals with subtotal liver resection, but not in those administered EHEC. A delayed 2-hour intestinal transit time occurred in both groups receiving subtotal liver resection, with or without oral EHEC. EHEC inhibited bacterial growth and DNA synthesis and altered bacterial surface properties after 1-hour incubation with bacteria in vitro, an interaction that was not further influenced by time. These results imply that EHEC may alter enterobacterial capacities of metabolism, proliferation, and invasion by effects on the bacterial surface. Furthermore, EHEC seems to possess a trophic action on the intestine, though without enhancing the intestinal motility.

ISSN:0894-1939    

DOI:10.3109/08941939509015392

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

A chronic cerebrospinal fluid access system is described for use in the conscious sling-restrained dog. In a pilot study of ten dogs, a fenestrated barium-impregnated silastic catheter was surgically implanted in the subarachnoid space of the second cervical vertebra through a dorsal laminectomy. This fenestrated catheter was coupled to a subcutaneous access port. Following surgery, cerebrospinal fluid was sampled weekly and evaluated for protein content and cytology. The cerebrospinal fluid albumin to serum albumin ratio was calculated for each sample to evaluate blood-brain barrier integrity. The instrumentation was successfully implanted in five of the first eight dogs using a midbody dorsal laminectomy. Cerebrospinal fluid access was maintained in these dogs for 21±10 days. Using a slight modification of the original technique, the final two dogs were instrumented through a caudodorsal laminectotny of the second cervical vertebra. The cerebrospinal fluid access system remains patent after 444 days of study in these two dogs. Necropsy evaluation suggested that catheter failure in the immediate postoperative period was due to gross malposition of the catheter. Chronic catheter failure occurred secondary to obstruction by local fibrous tissue reaction. Using this instrumentation, a pharmacokinetic evaluation of the plasma and cerebrospinal fluid deposition of an intravenous bolus of acyclovir was successfully performed twice in a single dog without complications. This instrumentation could provide chronic cerebrospinal fluid access for multiple pharmacokinetic studies in the conscious dog.

ISSN:0894-1939    

DOI:10.3109/08941939509015393

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

We investigated the effects of liver denervation on hemodynamic circulation in seven anesthetized pigs. Simultaneous measurements of the hepatic artery and portal vein were performed with an ultrasound Doppler flow meter before and after liver denervation. Neither resting systemic nor hepatic hemodynamics changed following liver denervation. However, temporary occlusion of the portal vein resulted in a significant increase in hepatic artery flow in the innervated liver (from 123±15 ml/min to 177±17 mu/min, p. 05). Thus, the reciprocity between the hepatic artery and portal vein in the innervated liver disappeared in the denervated liver. The absence of an increase in the hepatic artery flow during portal vein occlusion might intensify symptoms of portal vein thrombosis in liver transplantation. In the denervated liver, a significant decrease also occurred in systolic blood pressure and central venous pressure from 1 to 3 min after portal vein occlusion. Since the liver plays a crucial role in the maintenance of cardiovascular homeostasis during blood loss, it is likely that denervation at the porta hepatis induced a lack of vasoconstriction in the portal territory. Liver denervation might further exacerbate this response to hypotension. The current study confirms that the hepatic nerves play an important role in hepatic arterial and portal venous interactions aimed at maintaining a constant blood flow through the liver. We also suggest that the hepatic nerves are important for cardiovascular homeostasis.

ISSN:0894-1939    

DOI:10.3109/08941939509015394

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

ISSN:0894-1939    

DOI:10.3109/08941939509015395

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor