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Made available in DSpace on 2021-06-25T12:24:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-10-28 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundacao Universidade Federal de Mato Grosso do Sul - UFMS/MEC DS-CA scholarship The liver is an important metabolic organ in vertebrates. In anurans, the hepatosomatic index (HSI) reflects differences in energy storage and reproductive activities between males and females. The objective of this study was to describe the histological and histometric parameters of the livers of five species of Neotropical anurans, taking sex-related differences into account. We also tested how the relationship between quantitative histometric variables and HSI varied between males and females in different species. Five males and five females of Elachistocleis matogrosso, Leptodactylus podicipinus, Lysapsus limellum, Pseudis platensis, and Trachycephalus typhonius were captured in central Brazil during the rainy season. HSI did not vary according to sex, but it varied among species. Elachistocleis matogrosso had the highest HSI due to the large hepatocyte size. The percentage of melanomacrophage centers (MMCs) was higher in P. platensis and L. limellum. In T. thyphonius, hepatocyte area was negatively associated with HSI, while the MMC percentages were positively associated with HSI. The liver plays a key role in reproductive activities, especially for species with explosive reproduction. Additionally, histometric patterns and volumetric structural density varied between males and females due to energy utilization for reproduction. Not only are these results important for future studies on hepatic morphophysiology but they also provide tools for evolutionary and phylogenetic studies. Univ Fed Mato Grosso do Sul, Inst Biosci, Grad Program Anim Biol, Campo Grande, MS, Brazil Univ Fed Mato Grosso do Sul, Inst Biosci, Lab Expt Pathol, Campo Grande, MS, Brazil Univ Estadual Paulista, Dept Biol, Sao Jose Do Rio Preto, SP, Brazil Univ Estadual Paulista, Dept Biol, Sao Jose Do Rio Preto, SP, Brazil CNPq: 304552/2019-4 FAPESP: 2018/01078-7

Two cases of visceral leishmaniasis are presented; one patient was from an endemic region and visceral leishmaniasis was suspected clinically, while the other was from a non-endemic region and it was not suspected clinically. Bone marrow examination was negative in both cases and both showed different morphological pictures in the liver biopsies. These are discussed. Importance of travel history is also highlighted even if it is in distant past.

Amino acids tyrosine (Tyr) and tryptophan (Trp) play a significant role in the regulation of energy metabolism, locomotor activity, and eating behavior. We studied the possibility of modulating these processes in obesity by increasing the pool of Tyr and Trp in the experimental diet. As a model of obesity, we used Wistar rats fed a diet with an excess specific energy value (HFCD) for 64 days. Trp led to a normalization of the rats’ body weight almost to the control level, but increased anxiety-like behavior and decreased long-term memory. The consumption of amino acids resulted in increased grip strength and impairment of short-term memory. The locomotor activity of animals decreased with age as a result of Tyr consumption, while Trp, on the contrary, prevented this. The Tyr supplementation led to the normalization of triglycerides and LDL. In the spleen cell lysates, amino acids suppressed the production of proinflammatory cytokines. The liver tissue morphology showed that the consumption of Tyr noticeably weakened the signs of fatty degeneration. The addition of Trp, on the contrary, led to an unfavorable effect, consisting of the appearance of a high number of large rounded fatty vacuoles. The data obtained indicate a more pronounced anti-inflammatory effect of Tyr as compared to Trp.

We studied the effects of the addition of large neutral amino acids, such as tyrosine (Tyr) and tryptophan (Trp), in mice DBA/2J and tetrahybrid mice DBCB receiving a high-fat, high-carbohydrate diet (HFCD) for 65 days. The locomotor activity, anxiety, muscle tone, mass of internal organs, liver morphology, adipokines, cytokines, and biochemical indices of animals were assessed. The Tyr supplementation potentiated increased anxiety in EPM and contributed to a muscle tone increase, a decrease in the AST/ALT ratio, and an increase in protein anabolism in both mice strains. Tyr contributed to a decrease in liver fatty degeneration and ALT reduction only in DBCB that were sensitive to the development of obesity. The addition of Trp caused an increase in muscle tone and potentiated an increase in anxiety with age in animals of both genotypes. Trp had toxic effects on the livers of mice, which was manifested in increased fatty degeneration in DBCB, edema, and the appearance of micronuclei in DBA/2J. The main identified effects of Tyr on mice are considered in the light of its modulating effect on the dopamine neurotransmitter metabolism, while for the Trp supplement, effects were presumably associated with the synthesis of its toxic metabolites by representatives of the intestinal microflora.

The present study aimed to assess the effect of Zn supplementation on trace element levels in the liver, serum, and hair of rats with dietary-induced non-alcoholic fatty liver disease (NAFLD). A total of 26 3-month-old female Wistar rats were divided into four groups: control, NAFLD, Zn-supplemented (227 mg/L zinc as Zn sulfate Zn(SO)4 dissolved in a drinking water), and NAFLD-Zn-supplemented. NAFLD was verified by histological assessment of liver samples. The serum was examined for routine biochemical parameters. Trace elements content was assessed using inductively coupled plasma mass spectrometry (ICP-MS). Zn treatment resulted in an improvement in liver weight and morphology. Dietary supplementation with Zn prevented NAFLD-induced decrease liver Co. The tendency to increase liver Fe in the Zn-treated group was observed. Zn treatment decreased hepatic Al and serum V levels. However, Zn administration did not affect NAFLD-induced I, Mn, and Se depletion in the liver. Hair Zn levels raised in Zn-supplemented groups. Conclusively, the results of the study indicate that Zn supplementation could have a beneficial effect in modulation of the altered trace element status and liver morphology. •Zn treatment improved liver weight and morphology in rats with NAFLD. •Zn supplementation decreased liver Al in NAFLD. •Treatment by Zn prevented depletion of liver Co. •Zn decreased serum V and increased hair Zn levels. •No effect of Zn on NAFLD-induced hepatic I, Mn and Se depletion was observed.

A wide range of endocrine disrupter chemicals can mimic steroid hormones causing adverse health effects. Nonylphenol (NP) and t-octhylphenol (t-OP) are man-made alkylphenolic environmental contaminants possessing controversial endocrine disruption properties. This study has investigated the effects of NP and t-OP enriched diets on hepatic tissue and biotransformation activities in the liver. To this aim, sea bream juveniles were fed with commercial diet enriched with three different doses of NP (NP1: 5mg/kg bw, NP2: 50mg/kg bw and NP3: 100mg/kg bw) or t-OP (t-OP1: 5mg/kg bw, t-OP2: 50mg/kg bw and t-OP3: 100mg/kg bw) for 21 days. A significant increase of the hepatosomatic index was observed in NP1 and t-OP1. Alteration of liver morphology was observed in both NP and t-OP exposed juveniles although the most altered endpoints were observed in t-OP2 with 100% of tissue degeneration. Ethoxyresorufin-O-deethylase activity was significantly inhibited by NP and t-OP (p0.05), while catalase activity was significantly induced, at both doses. A different pattern of protein expression of different isoforms of both vitellogenin and zona radiata protein was evidenced within the treatments. In addition, a significant increase in the abundance of the stress induced heat shock protein 70 gene in the liver of t-OP2 fish and a significant increase in the abundance of the estrogen induced cathepsin D gene in the liver of NP1 and t-OP2 fish, were observed. Finally, estradiol-17β (E2) and testosterone (T) plasma levels and E2/T showed significantly different patterns in NP and t-OP exposed against control fish.

Cimicifuga racemosa (black cohosh) is a herbaceous perennial plant, that has been traditionally used for a variety of ailments (dyspepsia, climacteric complaints, muscular rheumatisms, menstrual cramps). From laboratory and clinical studies, black cohosh seems to have a relatively good safety profile, even if a number of case reports of hepatotoxicity were a matter of recent concern. Aim A number of case reports indicated that C. racemosa could induce hepatotoxicity. We evaluated the effects of black cohosh extract on liver morphology, and on levels of various hepatic function indices in rats. Methods Wistar rats received 300 mg/kg/day of C. racemosa extract by gavage, for 30 days. Biochemical analysis of serum was conducted by an automated, random-access clinical chemistry analyzer. Liver samples were used for hystomorphological and immunohistochemical examination, for the detection of apoptosis (TUNEL assay), and for the determination of GSH level (spectrophotometrical analysis). Results C. racemosa extract does not affect liver morphology and hepatic function indices, in rats. Conclusions On the basis of experimental data, the use of 300 mg/kg/day of black cohosh appears quite safe in rats. Nevertheless, in humans the safety of C. racemosa should be further monitored, in terms of patient-related factors.

International audience; BACKGROUND: Transient elastography (TE) is widely used for non-invasive assessment of liver fibrosis in HIV-HCV co-infected patients. TE, however, cannot determine liver morphology. Acoustic radiation force impulse (ARFI) imaging is a novel procedure enabling assessment of liver fibrosis during a conventional ultrasonographic examination. This study evaluated the correlation between liver fibrosis measurements by TE and ARFI. METHODS: Each of 46 HIV-HCV patients underwent both ARFI and TE within 6 months. Patients were evaluated by the "equivalent METAVIR" scoring system, using previously established cut-off values. Agreements between the ARFI and TE scores were estimated by Kappa coefficients, with Kappa values ≥0.40, ≥0.60, and ≥0.80 defined as moderate, good and very good agreement, respectively. RESULTS: ARFI and TE yielded "Equivalent Metavir" fibrosis scores of F1 in 26 and 31 patients, respectively; F2 in nine and seven, respectively; F3 in three and two, respectively; and F4 in eight and six, respectively. The two methods showed very good agreement in predicting overall stages [Kappa = 0.82] and for F ≥3 [Kappa = 0.80] and moderate agreement in predicting significant fibrosis F ≥2 [Kappa = 0.50]. Morphologic ultrasound analysis concomitant to ARFI detected two hepatocarcinomas. CONCLUSIONS: ARFI showed promising results in the non-invasive assessment of liver fibrosis in HIV-HCV patients, with liver fibrosis staging similar to that of TE. Moreover, ARFI can assess morphology and fibrosis during the same session.

The purpose of this study was to evaluate the spectrum of MR imaging features of primary sclerosing cholangitis.A retrospective review was performed of MR imaging findings including MR cholangiography and multiphasic contrast-enhanced dynamic sequences in 22 patients with primary sclerosing cholangitis. MR imaging analysis included abnormalities of intra- and extrahepatic bile ducts, abnormalities of liver parenchyma, changes in liver morphology, and lymphadenopathy.Abnormal findings of bile ducts were seen in all 22 patients; the most common finding was intrahepatic bile duct dilatation (77%), followed by intrahepatic bile duct stenosis (64%), extrahepatic bile duct wall enhancement (67%), extrahepatic bile duct wall thickening (50%), extrahepatic bile duct stenosis (50%), and intrahepatic bile duct beading (36%). Increased enhancement of the liver parenchyma on dynamic arterial-phase images, predominantly in the peripheral areas of the liver, was identified in 56% of patients. Other findings included periportal lymphadenopathy (77%), periportal high signal intensity on T2-weighted images (68%), hypertrophy of the caudate lobe (68%), and abnormal hyperintensity of the liver parenchyma on T1-weighted images (23%).On MR imaging, primary sclerosing cholangitis showed several characteristic features, including bile duct abnormalities and increased enhancement of the liver parenchyma. MR cholangiography and contrast-enhanced dynamic MR techniques are useful for revealing intra- and extrahepatic signs of primary sclerosing cholangitis.

Sucrose acetate isobutyrate (SAIB), a mixture of esters of sucrose with a composition approximating the name sucrose diacetate hexaisobutyrate, has been used for over 30 yr in many countries as a 'weighting' or 'density-adjusting' agent in non-alcoholic carbonated and non-carbonated beverages. As part of the demonstration of safety of SAIB as a direct food additive in human diets, a program of toxicity testing was started in the late 1950s that culminated in extensive studies of SAIB in rodents, monkeys and humans over the last decade. This review summarizes the toxicity data, accrued up until 1988, that precede the safety studies published elsewhere in this issue. SAIB has been shown to have very low acute and chronic toxicities in rats, monkeys, and, except for effects on the liver, in dogs at feeding levels of up to 10% in the diet. Slight effects seen in rats and monkeys at levels of 10% in the diet are unlikely to be directly caused by exposure to SAIB. In dogs, however, SAIB causes decreases in bromosulfophthalein (BSP) and indocyanine green (ICG) elimination from the serum immediately following a single dose, indicative of interference with biliary excretion. On repeated feeding in dogs, SAIB caused increases in serum alkaline phosphatase levels, but enzymes indicative of toxic effects on the liver were unaffected. On prolonged feeding to dogs, SAIB caused changes in liver morphology revealed by electron microscopy. All of these effects were reversed when SAIB was withdrawn from the diet. The no-effect level for these effects in dogs was near 5 mg/kg body weight, but these effects were not seen in rats fed up to 4 g/kg body weight/day, monkeys fed up to 10 g/kg body weight/day, or humans fed up to 20 mg/kg body weight/day. The toxicity and pharmacological studies in dogs, rats and monkeys suggest that the effect of SAIB on biliary excretion and liver morphology in dogs is essentially pharmacological rather than toxicological in nature and that the difference between the effects in dogs at levels as low as 5 mg/kg body weight/day, and the lack of effects in rats or monkeys at levels up to 10 g/kg/day is not merely a quantitative difference between species, but an absolute qualitative difference.

Quantify steatosis, fibrosis, and focuses of extramedullary erythropoiesis (ER) in the liver and report it to the causes of death in the perinatal. Morphologic analysis of steatosis', percentage of fibrosis, and ER of 467 perinatal autopsies. Cases with hypoxia/perinatal anoxia and ascending infection showed higher percentage of fibrosis. The number of ER was significantly higher among premature infants and in cases with infection. Our results contribute to a better quality of perinatal care through clinical demonstration of which injuries are associated with them, what may help in early diagnosis of these alterations in children who survive.

Although the general liver morphology is similar in all mammals, there are some structural features in apparently healthy laboratory rodents. These peculiarities are known to be influenced by a great variety of endogenous and exogenous factors. Incidence, intensity, development and disappearance of such elements as extramedullary haemopoiesis, polyploidy, intranuclear and intracytoplasmic inclusions depend markedly upon genetics, age, hygienic condition, hormonal regulation and nutrition of the animals. It is concluded from this short review that the term "normal histology" should only be understood as being relative and that it may only be applied to a given, well defined animal population held under well defined conditions.

With modern imaging technologies, including helical CT and MR imaging, the evaluation of liver morphology, blood flow and detection and characterization of liver neoplasms is possible in a noninvasive manner. Experiences in numerous institutions have established that both imaging methods are highly accurate in diagnosing hepatic pathology. Three-dimensional evaluation is feasible with fast imaging techniques such as multislice CT. With tissue-specific MR contrast agents such as SPIO, our capability is enhanced not only with respect to lesion detection but also lesion characterization.

Although it has been known for many years that the liver receives a nerve supply, it is only with the advent of immunohistochemistry that this innervation has been analysed in depth. It is now appreciated not only that many different nerve types are present, but also that there are significant differences between species, especially in the degree of parenchymal innervation. This has stimulated more detailed investigation of the innervation of the human liver in both health and disease. At the same time, functional studies have been underlining the important roles that these nerves play in processes as diverse as osmoreception and liver regeneration. This article briefly reviews current understanding of the morphology and functions of the hepatic nerve supply.

Ethanol was administered to female and male Wistar rats by mixing it with their drinking water. Ethanol concentrations were gradually increased up to either 8% or 15%. Female rats receiving 8% ethanol in their drinking water consumed 5-13 g, males 4-10 g daily. The ethanol/total food caloric intake percentages were 13 to 20% and 9 to 15% for female and male rats, respectively. There was no difference in body weight and relative liver weight between treated rats and their controls. Female and male rats receiving 15% of ethanol in their drinking water consumed 8-14 g ethanol per kg body weight per day. The percentages of ethanol/total food caloric intake were stabilized at about 25% for both sexes. Growth of the rats differed only slightly from controls; a tendency for a higher increase of body weight of the control rats was found. No difference in relative liver weight between ethanol-treated and control rats was observed. Microscopic examinations revealed that the ethanol treatment resulted in fat accumulation in the liver cells. A proliferation of the Smooth Endoplasmic Reticulum (SER) was more marked in the 15% dosed rats than in the 8% dosed rats and more distinct in female rats than in male rats in both dosage groups.

The effects of 2 recently developed trypanocidal agents, Diamidinophenylindol (DAPI) and Diimidazolinophenylindol (DIPI) at doses of 10-30 micrograms/g intraperitoneally (i.p.) on serum GOT, GPT and sorbitol dehydrogenase (SDH) levels and on liver morphology have been investigated in mice. Pentamidine served as reference drug. Both agents caused dose-dependent increases in serum transaminases and SDH, and discrete morphological changes of the liver, e.g., fatty degenerations, azinoperipheral vacuolisation and alterations of the nuclei, at least at the higher dosage.

Biliary excretion of xenobiotics is a complex process involving uptake into liver, intracellular sequestration and/or biotransformation, and transport into bile. A description of liver morphology is included to aid in the understanding of how chemical and physiological factors affect hepatic uptake and biliary excretion. Data will be presented with morphine and nalorphine that illustrate how efficient the intestinal and hepatobiliary system is in clearing drugs from the body. However, enterohepatic circulation can interfere with these processes.

Plasma fibronectin concentrations and liver morphology were investigated in 45 morbidly obese subjects (median overweight 88%) and in 42 normal weight controls, matched for sex and age. A significantly (P less than 0.01) raised plasma fibronectin concentration (median 464 mg/l, range 276-862 mg/l) was found in the obese subjects when compared with concentrations in the controls (median 348 mg/l, range 164-536 mg/l). Plasma fibronectin concentrations of the obese patients correlated significantly to their degree of overweight (r = 0.33, P less than 0.05) as well as to the degree of fatty change found in their liver biopsies (r = 0.33, P less than 0.05). Significantly (P less than 0.05) elevated plasma fibronectin concentrations even in obese subjects without hepatic fatty change indicate that liver fat accumulation is no prerequisite of the obesity-related elevation of plasma fibronectin. Raised plasma fibronectin concentration in obesity may more readily be explained by an increased fibronectin formation by lipocytes.

Summary In liver biopsy specimens from patients with normal liver morphology (n = 11), fatty liver (n = 9), chronic hepatitis (n = 12) or cirrhosis (n = 3) the total glutathione and GSH-S-transferase activities towards an aryl and an epoxide substrate were measured. As compared to livers without pathomorphological changes there was a tendency to higher values for glutathione in the groups with definite liver diseases. Lower activities were seen in these pathological groups for the aryl transferase whereas epoxide transferase activity was only detectable in 7 out of 35 specimens. In post-mortem specimens (n = 58) of human livers with and without histopathological alterations no clearcut differences were found for glutathione and GSH-S-transferases except that there was a tendency to lower aryl transferase activities in livers with tumour metastases, whereas the epoxide transferase activities seemed to be higher.

Four types of liver functional images were obtained by calculating for each point on an image matrix the local uptake rate, the local uptake transit time, the point's own maximum and the time necessary to attain the maximum. The study was based on 52 cases: 21 controls and 31 cases of hepatic disease. The controls showed a homogeneous spread of colloidal substance on the images of local uptake rate and local transit time, despite variations in liver tissue thickness. In the cases of parenchymal lesions revealed by deficient uptake on standard images, local variations of uptake rate were almost always shown even in instances where the standard images showed minimal variation. This technique therefore would seem to bring additional diagnostic assistance by permitting a better appreciation of liver morphology and function and the processing time required (approx. 1.5 min.) does not necessitate an increase in overall examination time.

1. 1. Morphological changes were found in livers of rats and chicks after acute poisoning with ethylene dibromide (EDB). 2. 2. In rats, EDB induced sinusoidal dilations and centrilobular necrosis, beginning from 8 hr after poisoning. 3. 3. In chicks the central areas were almost unchanged and portal areas were found to be affected by EDB; the concentration of eosinophilic granulocytes was much greater in EDB-treated livers than in controls.

Ten patients were treated for obesity with jejunoileal shunt operation. Liver biopsies were performed in seven both during and 10 to 27 months after operation. The degree of fatty infiltration showed no distinct trend. Steatosis increased in three, decreased in three and remained unchanged in one. Two liver specimens were entirely normal at follow-up examination. Serum aspartate transaminase and sulfobromophthalein retention tests showed a transient deterioration after surgery, but later improved as compared with preoperative values. Prothrombin values decreased, but remained within normal limits. All other liver-function tests were unchanged. The present investigation does not support the contention that jejunoileal shunt for obesity should be abandoned for fear of severe liver damage.

Male New Zealand rabbits were fed diets containing either 0.27% cyclopropenoid fatty acids (CPFA) or 0.5% cholesterol or both in combination. Compared with control animals, those receiving CPFA tended to have higher plasma- and liver-cholesterol levels and a higher incidence of aortic atherosclerosis. A similar pattern was seen when animals fed cholesterol and CPFA were compared with animals fed cholesterol alone. The observed increases in liver cholesterol, plasma cholesterol and plasma triglycerides indicated a wide range of sensitivity to CPFA. Some animals had plasma-cholesterol levels eight to ten times as high as normal after feeding had continued for 3 wk, while others showed only slight changes after 5 wk. Liver cells from all CPFA-fed animals had altered morphology and often showed extensive damage.

Blood from 394 unselected autopsy cases was examined for HB Ag, HB Ab and AFP. Liver morphology of 71 cases of cirrhosis with hepatoma and 32 cases of cirrhosis without hepatoma was studied in detail and correlated to HB Ag, HB Ab, and AFP. Significantly lowered humoral immunity to HB Ag exposure was established for the cirrhosis with hepatoma cases. The exposure rate for both cirrhosis cases with hepatoma and cirrhosis cases without hepatoma was the same (48%), but about 80% of each exposed group were either HB Ag or HB Ab positive. The cirrhosis with hepatoma group tended to be HB Ag positive and the cirrhosis without hepatoma group tended to be HB Ab positive. The lowered immune response seems to be specific to the hepatoma association, because the group with neoplasms other than the hepatoma reacted exactly the same as the group of the cirrhosis without hepatoma. Twenty-five per cent of the cirrhosis with hepatoma were associated with inactive cirrhosis and 75% were associated with active cirrhosis. Seventy-two per cent of the inactive cirrhosis cases with hepatoma were exposed to HB Ag, but only 42% of the active cirrhosis cases with hepatoma were exposed to HB Ag. On the morphological basis, the inactive cirrhosis was interpreted as an impaired cellular immunity and the active cirrhosis as a delayed hypersensitivity reaction. The possibility was discussed that both are important factors in the development of hepatoma preceded by cirrhosis. AFP tends to be positive in the inactive cirrhosis with hepatoma as well as HB Ag, but the relationship between AFP and HB Ag for hepatocarcinogenesis needs further investigation.

SummaryLong-term administration of DEN to adult Swiss mice for periods of up to 24 weeks resulted in intense bile duct proliferation, formation of hepatic nodules, some of which appeared to be hyperplastic, and foci of lymphocytic infiltration. No hep-atocellular carcinomas or well-defined hepa-tomas were found in these DEN-treated mice. The only tumors observed were one hemangioma, and in 2 sections, tissue suggestive of cholangiocarcinoma. The significant increases in hexobarbital sleeping times and the striking resistance to the hepa-totoxic effects of CC14 in DEN-treated mice indicated that long-term exposure to DEN resulted in a progressive inhibition of liver DMES activity. Phenobarbital administration concurrent with DEN prevented the decreases in hexobarbital sleeping times but did not alter the morphologic changes in the liver produced by DEN, at least at the light microscopic level.

Summary Light and electron microscopical findings in a case of citrullinemia are reported. Light microscopy revealed in the liver fatty degeneration and groups of lytic liver cell necrosis as well as giant mitochondria. The predominant electron microscopical findings were RER membranes in concentric, circular and zig-zag arrangement. Some mitochondria showed marked increase in matrix density and widened intracristal spaces. The morphological changes are interpreted on the basis of animal experiments as the possible result of ATP deficiency due to ammonia intoxication in citrullinemia.

Twelve patients with proved Budd-Chiari syndrome (eight acute and four chronic cases) were examined, using real-time ultrasonography (US). In all acute cases, US study showed at least one hepatic vein with findings suggestive of the syndrome, such as stenosis, dilatation, thick wall echoes, thrombosis, abnormal course, or extrahepatic anastomosis. In chronic cases, hepatic veins were usually not visible. Modifications of liver morphology were present in all patients except those with recent onset of the disease. Caudate lobe hypertrophy was present in only six cases. US study is therefore the procedure of choice for initial diagnosis of acute Budd-Chiari syndrome. Pitfalls were the failure to detect two caval thromboses and one hepatic vein web. Cavography should still be performed systematically, but hepatic phlebography is useful in selected cases only.

The pentobarbital sleeping time of male and female Fischer strain rats was lengthened by single or multiple doses of the carcinogen N-hydroxy-N-2-fluorenylacetamide. The increase was greater in males than in females, and greater after three doses than after one dose. It was less when the compound was fed in the diet for one month than it was in acute experiments. The sleeping time was increased by a similar percentage at 24, 48, 96, and 168 hours after a single dose of the compound to males. Morphologic examination showed that damage to the liver was maximal after a 48-hour period, but that the liver was almost normal 7 days later. The histologic criteria of liver damage at these time intervals are presented.

Five markedly obese patients were subjected to complete starvation of several weeks, for the purpose of weight reduction, for periods of 10–28 days. Studies of liver function and structure were conducted prior to, during, and after the period of starvation.

The effect of ethionine on the ultrastructure of developing liver parenchymal cells of rat has been studied. Despite reports from other studies that ethionine does not alter fetal liver morphology, the present studies show clearly that changes in structure do occur. Mitochondrial dense granules increase, endoplasmic reticulum is disrupted, lipid droplets accumulate, and glycogen deposition is delayed. There is no evidence to date of ductule cell proliferation such as occurs with ethionine poisoning in adult rat.