Comparison of rat liver preservation with Eurocollins and a modified University of Wisconsin solution: transplantation and isolation of hepatocytes for culture

The efficiency of Eurocollins or modified University of Wisconsin (UW) solution (MUW) in preserving rat livers was compared. After cold storage with one of the solutions, the livers were transplanted or perfused by collagenase for isolation of hepatocytes. Five of the 6 rats receiving a graft preserved with MUW versus none of the 6 rat receiving a graft preserved with Eurocollins solution survived 24 h or more. A significantly greater number of hepatocytes were isolated from livers preserved with MUW than from livers preserved with Eurocollins solution. This suggests a better reperfusion of MUW-preserved livers by collagenase resulting from less endothelial injury. LDH release by cultured hepatocytes, ketone body production and stimulation by glucagon were not significantly different between the two groups. These results confirm the superiority of MUW solution over Eurocollins in preserving liver grafts. They suggest that the advantage of MUW solution results from better protection of vascular endothelium rather than of hepatocytes.     

No excess of DR*3/4 in Ashkenazi Jewish or Hispanic IDDM patients

The gene frequencies, haplotype relative risks, and zygotic assortments of HLA-DR in three ethnically defined samples of insulin-dependent diabetes mellitus (IDDM) patients were determined in a prospective family study. Although DR3 and DR4 were positively associated with IDDM in the probands of 123 northern European, 94 Ashkenazi Jewish, and 49 New York Hispanic families, significant excess of DR*3/4 heterozygotes was observed only among the probands from families of northern European ancestry. There was also a significant decrease in the frequency of Bw62,DR4 haplotypes derived by northern European patients from their mothers compared with their fathers. This difference, together with data reported in the literature, suggests that the expressivity of the susceptible genotype(s) in IDDM patients may be modified by protective maternal effects associated with Bw62,DR4 and probably other DR4 haplotypes. Samples of IDDM patients from populations with high frequencies of these modifiers should have different DR-gene frequencies contributed by fathers and mothers, capable of accounting for the observed Hardy-Weinberg disequilibrium. We postulate that, because the mechanism of action of these modifiers is distinct from that of the susceptibility gene, the difference must be considered in devising strategies for elucidation of the mode of inheritance of the disease and for understanding the molecular nature of the susceptibility.     

Comparative toxicity of ethylene dichloride in F344/N, Sprague-Dawley and Osborne-Mendel rats

Studies were conducted to compare the toxicity of ethylene dichloride (EDC) in F344/N rats, Sprague-Dawley rats, and Osborne-Mendel rats. Ten rats/sex/group were exposed to EDC in drinking-water at 0, 500, 1000, 2000, 4000 and 8000 ppm for 13 wk. The highest concentration was limited by the maximum solubility of EDC in water (about 9000 ppm). In addition, F344/N rats (10/sex/group) were administered EDC in corn oil by gavage to compare toxicity resulting from bolus administration with that of continuous exposure in drinking-water. Gavage doses of EDC were within the range of total daily doses (in mg/kg body weight/day) resulting from exposure in drinking-water. EDC administered by gavage resulted in greater toxicity to F344/N rats than did administration of similar doses in drinking-water. All males receiving 240 and 480 mg/kg body weight and 9/10 females receiving 300 mg/kg body weight by gavage died before the end of the study. Necrosis of the cerebellum was observed in the brains of 3 males receiving 240 mg/kg body weight and 3 females receiving 300 mg/kg body weight. Hyperplasia and inflammation of the forestomach mucosa were observed in 8 male and 3 female rats that died or were killed in moribund condition. EDC caused minimal toxicity to F344/N, Sprague-Dawley and Osborne-Mendel rats at the drinking-water concentrations used in these studies; only female F344/N rats had EDC-related renal lesions. Based on mortality and EDC-related lesions, the no-effect levels for EDC administered by gavage to F344/N rats were 120 mg/kg body weight for males and 150 mg/kg body weight for females.     

Uncertainty in Fitted Estimates of Apparent in Vivo Metabolic Constants for Chloroform

It has become common practice to rely on fitted estimates ofapparent in vivo metabolic constants (e.g., V_max and K_M) inparameterization of PBPK models. Yet, quantitative estimatesof precision in these fitted parameters are not routinely reported.Such information is needed to assess the reliability of modelpredictions. The purpose of this study was to assess the precisionin estimates of V_max and K_M for chloroform, accounting for boththe statistical uncertainties in parameter estimates from individualdata sets and any additional uncertainty due to differencesin the parameter estimates derived from various experiments.Joint confidence regions for V_max and K_M from each experiment,generated using maximum likelihood techniques, were used toevaluate these questions. Three previously published data setswere considered. Estimates of V_max and K_M obtained from thesedata sets differed more than could be explained as a consequenceof a limited number of observations, measurement error, or stochasticerror. Issues associated with the use of maximum likelihoodtechniques to estimate joint confidence regions, the estimationof metabolic constants from individual experiments within agas uptake study versus the full data set, the degree of overlapin the joint confidence regions for metabolic constants obtainedfrom separate data sets, and the implications for risk assessmentare discussed.     

Evaluation of cerebral perfusion from bypass arteries using selective intraarterial microsphere tracer after vascular reconstructive surgery.

BACKGROUND AND PURPOSETo detect areas of cerebral perfusion from bypass arteries after vascular reconstruction, we administered selective intraarterial microsphere tracer into the external carotid arteries and determined (via single-photon emission computed tomography [IA-SPECT]) whether the distribution of radiotracer matched the arteriographic distribution of contrast material as shown on external carotid angiograms.METHODSWe compared the extent of regional distribution of tracer after external carotid artery injection of 20 to 40 MBq of 99mTc-HMPAO or 99mTc-ECD with that of contrast medium on the external carotid angiograms in 582 cortical regions in 12 patients with atherosclerotic occlusive disease and in 18 patients with moyamoya disease.RESULTSMarked accumulation of tracer was found only in the expected, specific, newly developed areas of cerebral perfusion from bypass arteries. The regional distribution of tracer corresponded to that of contrast medium in 523 regions (90%) and did not correspond in 59 regions (10%). Significant overestimation of the distribution of contrast material relative to that of tracer was observed in the patients with moyamoya disease.CONCLUSIONSPECT showed slightly different distribution of tracer from that predicted by conventional angiography. IA-SPECT should enhance the analysis of newly developed areas of cerebral perfusion from the bypass arteries.     

Methaemoglobin formation in the koala and the possum

Measurements were made of glutathione (GSH) levels, catalase activity and the oxidant sensitivity of the erythrocytes from the koala (Phascolarctos cinereus) and the common brushtail possum (Trichosurus vulpecula). The oxidant sensitivity was tested by treating the haemolysates with either 0.55 him H₂O₂ or 1.4mm NaNO₂. The erythrocytes of the koala had greater levels of GSH and catalase and yet were found to be more susceptible to oxidation induced by both these oxidants.     

Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy

Osteoclastogenesis inhibitory factor (OCIF) is a novel secreted protein that inhibits osteoclastogenesis both in vitro and in vivo. In this study, we examined the effects of OCIF on serum calcium (Ca) concentrations in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy. In normal mice, a single intraperitoneal injection of OCIF reduced serum Ca levels in a dose-dependent manner. Significant decrease in serum Ca (by 1.6 ± 0.3 mg/dL, n = 5) was observed 2 h after the injection of OCIF at 20 mg/kg and the hypocalcemic effect continued for up to 12 h. Serum phosphate (Pi) concentrations also decreased in response to OCIF. Urinary excretion of Ca, Pi, and creatinine did not change significantly after injection of OCIF or vehicle. In hypercalcemic, tumor-bearing nude mice, a single intraperitoneal injection of OCIF at 20 mg/kg resulted in a dramatic decrease in serum Ca (maximal decrease 2.8 ± 0.37 mg/dL, n = 11), which continued for up to 24 h. The results suggest that OCIF decreased serum Ca through its inhibitory effect on bone resorption. Furthermore, it is suggested that OCIF has therapeutic potential for the treatment of hypercalcemic conditions such as malignancy-associated hypercalcemia.     

Diagnosis of ligament rupture of the ankle joint: Physical examination, arthrography, stress radiography and sonography compared in 160 patients after inversion trauma

We prospectively enrolled 160 consecutive patients with inversion trauma of the ankle in a diagnostic protocol that included physical examination within 2 days and at 5 days after trauma, arthrography, stress radiography, and ultrasonography. 135 patients had pathological lateral ligament laxity on the later physical examination or lateral ligament rupture diagnosed on arthrography and they were operated on. 122 of these patients had ligament ruptures.

At clinical follow-up after a minimum of half a year, all of the patients who were not operated on had stable joints without signs of previous ligament ruptures.

Delayed physical examination at 5 days after the injury led to the highest overall sensitivity (96%) and specificity (84%) for the detection of a ligament rupture. Additional diagnostic procedures, at a considerable cost, yielded little additional information.