Phalloidin-induced morphological and functional changes of rat liver

The hepatotoxic effect of phalloidin, a mushroom poison, was examined in whole liver and in isolated liver cell plasma membranes. By electron microscopy, a thickening of the pericanalicular microfilamentous network was noted. Bile canalicular enriched plasma membrane fractions of livers from phalloidin-treated animals contained increased amounts of microfilaments. Analysis of the peptides in these fractions, by sodium dodecyl sulfate polyacrylamide gel electrophoresis, indicated that although the actin peptide bands were prominent, a band apparently corresponding to myosin was drastically reduced. The morphological change was accompanied by a reduced bile flow and biliary excretion of bile acids, proteins and the exogenous organic anion dibromosulphthalein. These changes may result from a modification of the microfilaments, suggesting a role of the microfilaments in the liver membrane structure and function.     

The digestive apparatus during hibernation: morphological and functional changes

During hibernation feeding is suspended and the digestive apparatus is in a condition of functional rest. This paper is a review of data published in the period from 1966 to 1999 on the structure/function relationship in the digestive apparatus of hibernating animals. The available information is partial, due to differences in methodology and species used; however, it is apparent from the data that the digestive apparatus undergoes an important rearrangement during hibernation, inclusive of mass loss and reduced/arrested mitotic activity, in the presence of a generally preserved morphology of the organs. All changes are reversible upon arousal. Recent findings show that, during hibernation, protein expression may be enhanced in the intestine as well as transport activities in the mucosa. Therefore, the hibernation condition is finely regulated, representing a potentially useful model for studies aimed at improving organ preservation procedures (e.g. for transplantation).     

The influence of dosage regimen on experimental gentamicin nephrotoxicity: dissociation of peak serum levels from renal failure

Peak serum levels of gentamicin were varied in rats by administering a standard nephrotoxic dosage of 40 mg/kg per day in one (QD), two, or three (TID) daily doses. The QD animals had the highest peak serum levels but showed no appreciable increase of serum creatinine concentrations over a 10-day treatment period. The TID rats had the lowest peak serum levels, but, after 10 days of drug administration, the serum creatinine concentration (2.8 +/- 0.2 mg/100 ml, mean +/- SE) was significantly higher than in control rats (0.6 +/- 0.01 mg/100 ml) (P less than 0.001). After two days of gentamicin treatment, the renal concentration of gentamicin was 269 +/- 77 micrograms/g in the QD rats and 820 +/- 29 micrograms/g in the TID rats (P less than 0.001). In this rat model, the frequency of doses was a more important factor in the development of nephrotoxicity than the peak serum concentration of gentamicin. The results suggest that dose frequency should be considered when data from different laboratories are compared.     

Relationship between morphological and functional changes in the stomach with aging]

The authors investigated the relationship between morphological changes and functional changes of the stomach with ageing, especially in term of change of gastric emptying in 92 healthy subjects. We checked the difference in chronological age and the stomach age in these subjects (in order to assess these subjects). The morphological change was evaluated by extent of atrophic gastritis in endoscopical atrophic border and histological findings of biopsy specimens, and the functional change was evaluated by maximal acid output in gastric secretion. Atrophic gastritis was expanded and maximal acid output was significantly reduced with ageing. From these results we confirmed that there was no difference between the chronological age and the stomach age and the quality of these subjects was very good. Gastric emptying was investigated by the acetaminophen method. In spite of ageing, gastric emptying was almost constant in these healthy subjects.     

Myocardial bridges: morphological and functional aspects.

OBJECTIVE--To assess the arrangement of myocardial bridges. DESIGN--A necropsy study of 90 consecutive hearts (56 male, 34 female). RESULTS--Myocardial bridges, either single or multiple, were seen in 50 (55.6%) of the 90 hearts. The left anterior descending artery was the most commonly affected artery. Thirty five of the 50 hearts which contained in total 41 muscle bridges were dissected further with a magnifying glass. Two different types of muscle bridges could be identified. Thirty one of these 41 myocardial bridges were superficial, crossing the artery transversely towards the apex of the heart at an acute angle or perpendicularly. The remaining 10 myocardial bridges crossed the left anterior descending coronary artery and surrounded it by a muscle bundle that arose from the right ventricular apical trabeculae and crossed the artery transversely, obliquely, or helically before terminating in the interventricular septum. CONCLUSIONS--The superficial type of myocardial bridge does not seem to constrict the artery during systole but the deep muscle bridges, by virtue of their relation with the left anterior descending coronary artery, could twist the vessel and thus compromise its diastolic flow. This may result in ischaemia.     

Myocardial bridges: morphological and functional aspects.

OBJECTIVE--To assess the arrangement of myocardial bridges. DESIGN--A necropsy study of 90 consecutive hearts (56 male, 34 female). RESULTS--Myocardial bridges, either single or multiple, were seen in 50 (55.6%) of the 90 hearts. The left anterior descending artery was the most commonly affected artery. Thirty five of the 50 hearts which contained in total 41 muscle bridges were dissected further with a magnifying glass. Two different types of muscle bridges could be identified. Thirty one of these 41 myocardial bridges were superficial, crossing the artery transversely towards the apex of the heart at an acute angle or perpendicularly. The remaining 10 myocardial bridges crossed the left anterior descending coronary artery and surrounded it by a muscle bundle that arose from the right ventricular apical trabeculae and crossed the artery transversely, obliquely, or helically before terminating in the interventricular septum. CONCLUSIONS--The superficial type of myocardial bridge does not seem to constrict the artery during systole but the deep muscle bridges, by virtue of their relation with the left anterior descending coronary artery, could twist the vessel and thus compromise its diastolic flow. This may result in ischaemia.     

Aging cochleas in the F344 rat: morphological and functional changes

The Fischer 344 rat strain has been frequently used as an animal model of rapid aging. The present study was aimed at evaluating the incidence of apoptotic cells in the inner ear of 20-24-month-old F344 rats and to correlate it with cochlear function using otoacoustic emissions. Staining with cresyl violet and the enzymatic labeling (terminal deoxynucleotidyl transferase, TdT) of fragmented DNA revealed large numbers of apoptotic cells in the marginal and basal layers of the stria vascularis and in adjacent cells of the spiral ligament. The amplitudes of distortion products otoacoustic emissions (DPOAEs), which reflect functional state of the outer hair cells, were significantly reduced or totally absent in these animals. In contrast to old F344 rats, no marked DPOAE amplitude reduction and smaller numbers of apoptotic cells were found in young 4-month-old F344 rats or in aged 24-28-month-old Long Evans rats. The accumulation of apoptotic cells, mainly in the basal layer of the stria vascularis and in adjacent cells of the spiral ligament, leads to a detachment of the stria vascularis from the spiral ligament and results in the impairment of outer hair cell function. This specific type of strial deterioration suggests that aged F344 rats can serve as an animal model of strial presbycusis.     

Effects of urinary trypsin inhibitor on pancreatic enzymes and experimental acute pancreatitis

Therapeutic effect and the mechanism of the action of human urinary trypsin inhibitor (MTI) on experimental acute pancreatitis were studied. MTI significantly increased survival rate of animals with experimental acute pancreatitis induced by the infusion of trypsin or phospholipase A₂ into pancreas or by a closed duodenal loop. The efficacy of MTI on these types of pancreatitis were higher than those of aprotinin. Pancreatic enzymes were released from pancreatic slice by trypsin or phospholipase A₂, and this release was inhibited by MTI. Further, these pancreatic enzymes caused a secondary release of enzymes from other pancreatic slice, suggesting that these enzymes injured pancreatic tissue and that a chain reaction of pancreatic enzyme activation may play an important role in the pathogenesis of acute pancreatitis. MTI suppressed the secondary enzyme-induced pancreatic injury more strongly than aprotinin. These results suggest that MTI may suppress pathogenesis and development of pancreatitis by inhibiting the chain reaction of pancreatic enzyme activation.     

Preparation of porcine thyroid follicles with preserved polarity: functional and morphological properties in comparison to inside-out follicles

One of the main problems in establishing isolated thyroid follicles in vitro is their tendency to form inside-out follicles. The reason for this change in polarity is unknown. We describe here a method for the preparation of stable thyroid follicles with preserved polarity for at least 6 days. Isolated follicles were obtained by infusion of collagenase (1.5 mg/ml) dissolved in minimal essential medium into the artery of intact thyroid glands. The morphological and functional properties of these follicles were compared to inside-out follicles. These inside-out follicles were obtained by digestion of minced thyroid tissue in a collagenase (1 mg/ml) solution. The polarity of follicles was proved by morphological criteria. Follicles with preserved polarity did not change polarity for at least 6 days in the presence of 1% or 5% fetal calf serum. As the culture conditions for both preparation methods were identical, we conclude that the preparation method rather than the culture condition is responsible for the preservation of cell polarity of isolated thyroid follicles in our system. Increases in cyclic AMP levels induced either by bovine thyrotropin (10(-3) U/ml) or by isoproterenol (10(-6) M) as well as iodide uptake and organification were rapid and significant in right-side-right follicles but not in inside-out follicles. Therefore the TSH receptor and the beta-adrenergic receptor appear to be exclusively located at the basal membrane of follicular cells. In addition, iodide uptake apparently is unidirectional.     

Intravascular thermography: Immediate functional and morphological vascular findings.

AIMS: To investigate safety, feasibility, and injurious effect on endothelial cells of a thermography catheter as well as effect of flow on measured temperature in non-obstructive arteries. METHODS AND RESULTS: Safety and feasibility were tested in both rabbit aortas and pig coronary arteries. Evaluation of endothelial damage by the catheter (acute, 7 and 14 days) was performed in pig coronaries using Evans Blue, scanning electron microscopy (SEM) and Factor-VIII antibody and compared with normal arteries and arteries that underwent intravascular ultrasound (IVUS). The effect of flow on temperature heterogeneity was analysed both in vitro and in vivo conditions. All procedures were successful without any adverse events; intra- and inter-operator variability was low. Intracoronary use of the catheter was associated with acute but reversible de-endothelialization, paralleling the findings associated with IVUS use. Changes in flow velocities under physiologic flow conditions did not significantly influence the temperature differences measured both in vitro and in vivo; temperature heterogeneity was more pronounced in absence of flow. CONCLUSIONS: Intracoronary thermography using a dedicated catheter is safe and feasible with a similar degree of de-endothelialization as IVUS. Temperature heterogeneity remained unchanged under normal physiologic flow conditions allowing clinical use of thermography.     

Cocaine-induced liver cell injury: comparison of morphological features in man and in experimental models

Although investigative research of animal models in cocaine metabolism and associated liver cell injury has been fairly extensive during the past 10 yr, little evidence of hepatotoxicity has been documented in man. We report a case of fulminant hepatic failure and acute rhabdomyolysis resulting from cocaine use. Coagulative-type perivenular and midzonal necrosis and periportal microvesicular fatty change were the predominant morphological features throughout all lobules of the liver, in contrast to periportal necrosis described in the only previous case report with biopsy. Differences in zonal necrosis caused by the same drug are not typically seen in man experiencing direct or indirect intrinsic hepatotoxicity. However, experimental models have shown cocaine to have this ability, dependent on enzyme induction or inhibition, sex and dose. Therapeutic approaches for prevention of possible liver cell injury by cocaine toxicity are discussed.     

Early morphological and functional changes in pancreas following necrosectomy for acute severe necrotizing pancreatitis.

INTRODUCTION: Morphological and functional changes in the pancreas after surgical pancreatic necrosectomy have not been studied extensively. AIMS: To study morphological changes in the pancreas, and exocrine and endocrine pancreatic function following pancreatic necrosectomy. METHODS: Eighteen adult patients surviving at least one month after pancreatic necrosectomy for acute necrotizing pancreatitis were followed up. Contrast-enhanced computed tomography was done every six months. Stool fat was estimated at 3-month intervals, and need for and response to enzyme supplements were recorded. Blood sugar was measured every fortnight; in patients with hyperglycemia, need for oral hypoglycemic agents or insulin was recorded. Additional pancreatic imaging was done in some cases. RESULTS: Six weeks after surgery, nine of 18 patients had exocrine insufficiency. Thirteen patients developed endocrine insufficiency, including 5 who also had exocrine insufficiency. At the end of the study, 13 patients had endocrine insufficiency and 2 had exocrine insufficiency. Pancreatic size was subnormal in all patients at the end of six months. Pancreatography in three cases did not reveal any ductal abnormality. CONCLUSIONS: Necrotizing pancreatitis affects pancreatic exocrine or endocrine function in more than half the patients.     

脂多糖致肺血管内巨噬细胞形态和功能的改变

目的探讨肺血管内巨噬细胞（ＰＩＭ）在感染性急性肺损伤（ＡＬＩ）发病中的作用。方法仿Ｍｏｒｔｏｎ法灌洗肺血管床，贴壁法分离猪ＰＩＭ，并用光镜、电镜观察鉴定；胸腺细胞增殖法测脂多糖（ＬＰＳ）刺激前后ＰＩＭ培养上清白细胞介素１β（ＩＬ－１β）活性，酶联免疫吸附试验（ＥＬＩＳＡ）法测肿瘤坏死因子α（ＴＮＦ－α）、白细胞介素６（ＩＬ－６）、白细胞介素８（ＩＬ－８）含量。结果刺激后的ＰＩＭ伪足增长、增多，溶酶体和吞噬体亦增多；释放ＴＮＦα、ＩＬ－１β、ＩＬ－６、ＩＬ－８增多，峰值分别出现在刺激后的１ｈ、２ｈ、４ｈ和６ｈ。与刺激前相比，Ｐ＜０．０１。结论改良的Ｍｏｒｔｏｎ法能成功分离猪ＰＩＭ；ＬＰＳ刺激后的ＰＩＭ吞噬分泌功能活跃，其中ＴＮＦα、ＩＬ－１β升高最早，提示其在ＡＬＩ发病早期起重要作用；而ＩＬ－６、ＩＬ－８升高较晚，可能在ＡＬＩ发病后期起重要作用