Enhancement of aflatoxin B1-induced enzyme altered hepatic foci in rats by treatment with carbon tetrachloride

Hysterectomy is the second most commonly performed major operation in the United States. Approximately one in three women will have this operation, resulting in 590,000 procedures per year. The most common indications for hysterectomy are leiomyomata uteri, abnormal uterine bleeding, endometriosis, pelvic pain, and pelvic organ prolapse. Although hysterectomy is an appropriate therapeutic option for some women with these conditions, in many instances less radical alternatives may be offered. Leiomyomata may be managed expectantly if symptoms are not bothersome; for women with troubling leiomyomata symptoms, alternatives to hysterectomy include: endoscopic removal or destruction of myomas, arterial embolization, or hormonal therapy to inhibit or modify bleeding. Endometriosis and abnormal uterine bleeding of leiomyomata are both amenable to hormonal therapy. Pelvic pain is most effectively approached with a thorough evaluation (particularly for nongynecologic illness), with specific therapy directed at the cause of the pain. Pelvic organ prolapse may respond symptomatically to pelvic floor exercises, or to the use of a pessary. After alternatives to removal of the uterus are discussed, the informed woman may decide that hysterectomy is the option best suited to her. It is unusual for hysterectomy to be her only option.     

Prolonged decrease in hepatic connexin32 in chronic liver injury induced by carbon tetrachloride in rats

The dynamics of intraventricular blood flow, i.e. its rapid evolution, implies the rise of intraventricular pressure gradients (IPGs) characteristic of the inertia-driven events as experimentally observed by Pasipoularides (1987, 1990) and by Falsetti et al. (1986). The IPG time course is determined by the wall contraction which, in turn, depends on the load applied, namely the intraventricular pressure which is the sum of the aortic pressure (i.e., the systemic net response) and the IPG. Hence the IPGs account, at least in part, for the wall movement. These considerations suggest the necessity of a comprehensive analysis of the ventricular mechanics involving both ventricular wall mechanics and intraventricular fluid dynamics as each domain determines the boundary conditions of the other. This paper presents a computational approach to ventricular ejection mechanics based on a fluid-structure interaction calculation for the evaluation of the IPG time course. An axisymmetric model of the left ventricle is utilized. The intraventricular fluid is assumed to be Newtonian. The ventricle wall is thin and is composed of two sets of counter-rotating fibres which behave according to the modified version of Wong's sarcomere model proposed by Montevecchi and Pietrabissa and Pietrabissa et al. (1987, 1991). The full Navier-Stokes equations describing the fluid domain are solved using Galerkin's weighted residual approach in conjunction with finite element approximation (FIDAP). The wall displacement is solved using the multiplane quasi-Newton method proposed by Buzzi Ferraris and Tronconi (1985). The interaction procedure is performed by means of an external macro which compares the flow fields and the wall displacement and appropriately modifies the boundary conditions to reach the simultaneous and congruous convergence of the two problems. The results refer to a simulation of the ventricular ejection with a heart rate of 72 bpm. In this phase the ventricle ejects 61 cm3 (ejection fraction equal to 54 percent) and the ventricular pressure varies from 78 mmHg to 140 mmHg. The IPG show an oscillating behaviour with two major peaks at the beginning (11.09 mmHg) and at the end (4.32 mmHg) of the ejection phase, when the flow rate hardly changes, according to the experimental data. Furthermore the wall displacement, the wall stress and strain, the pressure and velocity fields are calculated and reported.     

Effect of parenteral and enteral nutrition on hepatic albumin synthesis in rats

It is well known that surgery significantly decreases immune responses. Laparoscopic cholecystectomy (LC) is a "miniinvasive" surgical procedure; and on the basis of this consideration we have investigated if and how the immune response is modified in patients after laparoscopic cholecystectomy compared to patients who underwent open cholecystectomy. Immune activity [neutrophils, total lymphocytes count, lymphocytes subpopulations, human leukocyte antigen-DR (HLA-DR)] was evaluated in 53 patients 1 day before surgery and respectively, 1, 3, and 6 days after surgery; 26 patients underwent "open" cholecystectomy and 27 LC. A day after surgery, patients with open cholecystectomy showed a significant increase (p < 0.05) in plasma neutrophils, while they were almost unchanged in LC patients. Monocyte antigen HLA-DR was reduced in patients with "open" cholecystectomy. We recorded two cases (7.6%) of respiratory tract infection in the "open" group. In conclusion, LC strongly reduces postoperative (p.o.) pain and hospitalization, and it promotes earlier recovery and return to normal activity, avoiding p.o. immunosuppression, mostly due to conservation of HLA-DR activity, with less p.o. morbidity compared to that seen with open surgery.     

Effect of pretreatment of rats with an urinary preparation on liver injuries induced by carbon tetrachloride and alpha-naphthylisothiocyanate

The effect of oral administration of a preparation of human urine (PHU) on the progression of acute liver injury was examined in rats intoxicated with carbon tetrachloride (CCl4) and alpha-naphthylisothiocyanate (ANIT) PHU protected the liver from CCl4-induced injury as judged by morphological and biochemical observations. In contrast, PHU aggravated ANIT-induced injury as judged also by morphological and biochemical observation. PHU prevented the increase in hepatic glutathione (GSH) and lipid peroxidation induced by CCl4. But PHU enhanced the increase in hepatic GSH caused by ANIT. These results indicate that the effect of PHU on hepatic GSH concentrations is through an indirect pathway. Clinical application of PHU on hepatitis should be explored further.     

Alteration of hepatic DNA synthesis in rats treated with N-nitrosodimethylamine during early stages of copper deficiency

The main aim of this research was to clarify that nutritional dietary copper may participate in the protective action against hepatocarcinogenesis in rats by N-nitrosodimethylamine (NDMA). The copper concentrations in serum and liver from 2 to 8d after rats were first fed a copper deficient diet (copper, 0.6 ppm) decreased significantly compared to those of pair-fed rats (copper in a control diet, 7 ppm). The subcellular distribution of copper in the liver at 5d after feeding of a copper deficient diet began was measured and the copper concentrations in soluble and nuclear fractions decreased at a similar rate in copper deficient rats treated with or without NDMA, compared to those of pair-fed rats. The incorporation of [3H]thymidine into rat liver DNA at 48 h after treatment with NDMA markedly increased under the experimental conditions used. By giving rats a copper deficient diet for a few days the increased incorporation of [3H]thymidine into liver DNA of rats treated with NDMA was enhanced compared to that of pair-fed rats treated with NDMA. The activity of thymidine kinase in liver of copper deficient rats treated with NDMA was also found to increase significantly compared to that of pair-fed rats treated with NDMA.     

A comparison of parameters used to assess liver damage in sheep treated with carbon tetrachloride

Changes in serum enzyme levels, liver histology and liver function tests have been correlated to determine the usefulness of these tests in assessing liver status. The effects of carbon tetrachloride administration on these parameters has been determined in a group of 20 sheep. Normal levels, elevated levels after injury and the effect of elapsed time after injury are reported for serum glutamic dehydrogenase, sorbitol dehydrogenase, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactate dehydrogenase, fructose-1-phosphate adlolase, alkaline phosphatase, cholesterol and proteins. Variation in the time of elevation of enzyme activities may be useful in determining the elapsed time between acute injury and serum sampling. In comparison to sheep fed an adequate diet, a diet with a restricted protein intake was associated with increased severity of histological lesions and decreased liver function.     

Effect of a thyroid hormone treatment on brain protein synthesis in rats

The effect of the thyroid hormone on the rate of brain protein synthesis in rats was studied. Experiments were conducted on three groups of rats given 6-propyl-2-thiouracil (PTU, a thyroid inhibitor) without a triiodothyronine (T3) treatment, those treated with PTU + T3, and those treated with neither PTU nor T3 (control). The fractional rates of protein synthesis in the brain, liver, and kidney of rats given PTU + T3 were significantly greater than those in rats given PTU alone. In the brain and kidney, the RNA activity [g of protein synthesized/(g of RNA.d)] were significantly correlated with the fractional rates of protein synthesis. In the liver and kidney, the RNA concentration (mg of RNA/g of protein) was related to the fractional rate of protein synthesis. These results suggest that the thyroid hormone treatment would be likely to increase the rate of protein synthesis in the brain of rats, and that the RNA activity is, at least partly, related to the fractional rate of brain protein synthesis.     

Ultrastructural changes in liver damage induced by carbon tetrachloride in spontaneously hypertensive rats and Wistar-Kyoto rats

The establishment of a better local area medical centre containing hospitals and clinics is thought to be a very important issue. The medical information system, which should be accepted by both hospitals and clinics, has been studied using graphic user interface (GUI) and a three dimensional structure. Our system files medical records and blood examination data as well as diagnostic images, which may be the first attempt in the world. It has been favourably evaluated by physicians through clinical evaluation.     

Influence of pretreatment with carbon tetrachloride on paracetamol-induced hepatotoxicity

The influence of preventive treatment with a low dose of carbon tetrachloride on paracetamol-induced hepatotoxicity was evaluated in the rat. The haloalkane was given intraperitoneally (200 microliter/kg) 48 hours prior to paracetamol (PRCT; 2000 mg/kg, os). In parallel groups of rats were treated with CCl4 or PRCT alone. Twelve hours after paracetamol all the animals were killed. Liver damage was determined by evaluating total lipid and triglyceride accumulation in hepatic tissue and the serum activity of alanine-amino transferase (S.GPT). In addition, both the hepatic concentration of reduced glutathione (GSH) and the production "in vitro" of TBA-reacting compounds by liver homogenate were assayed. The results obtained indicate CCl4 "per se" induces a significant triglyceride accumulation but does not influence either the hepatic GSH level or the leakage of GPT into the blood stream. In addition, the haloalkane does not stimulate the production of TBA-reacting substances by hepatic tissue. Paracetamol, alone, produces a slight increase of hepatic triglycerides while induces a significant (+ 108%) enhancement of S.GPT activity. The drug is also able to stimulate the lipid peroxidation "in vitro", whereas provokes a marked decrease of GSH in liver tissue. Combined treatment with the two poisons results in a minor alteration of hepatocyte function as shown by the lack of GPT in serum and by the reduced fall of hepatic GSH as well as by a decreased production of TBA-reacting compounds. In our opinion, CCl4 partially protects against paracetamol-induced liver injury by interacting with enzymes which are responsible for the biotransformation of PRCT to a reactive arylating species that bind to cell molecules.     

Effect of 1,3-dithia-2-thioxo-cyclopent-4-ene and its derivatives on liver injury induced by carbon tetrachloride and orotic acid in rats

The protective effect of 1,3-dithia-2-thioxo-cyclopent-4-ene (DT827A) and its two derivatives of 4-phenyl-1,3-dithia-2-thioxo-cyclopent-4-ene (DT827B) and 4-(4-fluorophenyl)-1,3-dithia-2-thioxo-cyclopent-4-ene (DT827C) on liver injury induced by carbon tetrachloride (CCl4) and orotic acid was studied using male rats. The approximate lethal doses were about 100 mg/kg for DT827A-treated animals and more than 800 mg/kg for the other two compounds-treated groups. Single oral administration of the three test compounds at the dose levels of 2 and 10 mg/kg 1 hour before CCl4 exposure revealed a protective effect on the findings of centrolobular necrosis, balloon cells and macrophage infiltration in histopathological findings in livers in the order of DT827B-treated rats > DT827A-treated rats > DT827C-treated rats. Repeated oral administration of the compounds at the dose levels of 2 and 10 mg/kg/day for 10 consecutive days revealed a protective effect against liver injury on the findings of centrolobular necrosis, balloon cells and macrophage infiltration in the order of DT827B-treated rats > DT827A-treated rats [symbol: see text] DT827C-treated rats. Simultaneous administration of the compounds at the dose level of 10 mg/kg/day together with a high sucrose diet containing orotic acid for 12 days revealed an inhibitory effect on fatty liver formation in the order of DT827B-treated rats > DT827C-treated rats > DT827A-treated rats. A hepatoprotective potential of the DT827 series compounds was suggested under the conditions of these studies, and DT827B was considered to be the most effective.     

Oxindole, a sedative tryptophan metabolite, accumulates in blood and brain of rats with acute hepatic failure

Rats treated with oxindole (10-100 mg/kg i.p.), a putative tryptophan metabolite, showed decreased spontaneous locomotor activity, loss of the righting reflex, hypotension, and reversible coma. Brain oxindole levels were 0.05 +/- 0.01 nmol/g in controls and increased to 8.1 +/- 1.7 or 103 +/- 15 nmol/g after its administration at doses of 10 or 100 mg/kg i.p., respectively. To study the role that oxindole plays in the neurological symptoms associated with acute liver failure, we measured the changes of its concentration in the brain after massive liver damage, and we investigated the possible metabolic pathways leading to its synthesis. Rats treated with either thioacetamide (0.2 and 0.4 g/kg i.p., twice) or galactosamine (1 and 2 g/kg i.p.) showed acute liver failure and a large increase in blood or brain oxindole concentrations (from 0.05 +/- 0.01 nmol/g in brains of controls to 1.8 +/- 0.3 nmol/g in brains of thioacetamide-treated animals). Administration of tryptophan (300-1,000 mg/kg p.o.) caused a twofold increase, whereas administration of indole (10-100 mg/kg p.o.) caused a 200-fold increase, of oxindole content in liver, blood, and brain, thus suggesting that indole formation from tryptophan is a limiting step in oxindole synthesis. Oral administration of neomycin, a broad-spectrum, locally acting antibiotic agent able to reduce intestinal flora, significantly decreased brain oxindole content. Taken together, our data show that oxindole is a neurodepressant tryptophan metabolite and suggest that it may play a significant role in the neurological symptoms associated with acute liver impairment.     

Effects of long-term treatment of rats with ethanol, carbon tetrachloride and high fat-low protein diet on the Kupffer cell distribution with reference to chemical composition of the liver

Rats were treated for 3-4 months with ethanol or carbon tetrachloride or kept on a high fat-low protein diet. The cell distribution of the liver was investigated with special emphasis on the Kupffer cells with reference to lipids and collagen. Lipids were increased both histologically and chemically in all groups treated. All three treatments caused an increase of Kupffer cells, especially in the high fat-low protein group. The number of Kupffer cells and the content of liver lipids were strongly correlated. Collagen rose in the CCl4- and high fat-low protein groups. Cirrhosis was observed in CCl4--treated rats only.     

Simultaneous protective effect of a new chelating agent and zinc, on the carbon tetrachloride induced hepatic injury in squirrels

X-ray test of the osteo-articular system of upper limbs was carried out on 1231 saweyers and 272 controls as well as 50 intellectuals. Three x-ray tests were carried out on 207 sawyers and on a control group of 95 workers, to assess the progression of osseous changes. The same types od changes were found in sawyers and control group workers; besides similar frequency in the examined parts of the upper limb was found in them. The most frequent changes are: osseous cyst, osteoporosis degenerative-deformative changes and calcar of the ulnar. The greatest amounts of changes were observed in the bones and joints of the hand and next in elbow joint and acromioclavicular joint. It was observed that amoungst the sawyers and the control group workers, the greatest amounts of changes occur after 2 years of work. Progression of osseous changes after 3-4 years of work was observed in 30,9% sawyers and 12,6% control group workers.     

Effect of tumour necrosis factor-alpha on proliferation, activation and protein synthesis of rat hepatic stellate cells

BACKGROUND/AIMS: Hepatic stellate cells represent the principal matrix-synthesising cells of damaged liver and are targets of a number of cytokines currently under investigation. The study analyses the effects of tumour necrosis factor-alpha and interferon-gamma on proliferation, "activation" and protein synthesis of hepatic stellate cells. METHODS: Primary cultures of hepatic stellate cells were exposed to tumour necrosis factor-alpha and interferon-gamma. Cell proliferation was studied by 3H-thymidine and bromo-deoxy-uridine incorporation. Protein synthesis was analysed using immunoprecipitation, Western- and Northern blotting techniques. RESULTS: Proliferation of hepatic stellate cells was reduced by tumor necrosis factor-alpha and interferon-gamma, while "activation" of hepatic stellate cells as assessed by expression of smooth muscle alpha-actin and of TGF-beta/activin type I receptor was induced by tumour necrosis factor-alpha but downregulated by interferon-gamma. Tumour necrosis factor-alpha increased the synthesis of distinct extracellular matrix proteins, particularly of fibronectin and tenascin, but decreased collagen type III expression. In contrast, interferon-gamma reduced the synthesis of all connective tissue proteins tested. Among the protease inhibitors, interferon-gamma induced C1-esterase inhibitor synthesis, while tumour necrosis factor-alpha stimulated plasminogen activator inhibitor type 1 production. CONCLUSIONS: Tumour necrosis factor-alpha and interferon-gamma decrease proliferation of hepatic stellate cells, while "activation" of hepatic stellate cells and synthesis of proteins involved in matrix metabolism are regulated in a differential, cytokine-specific manner, suggesting that both cytokines play an important role in liver repair.     

Enhancement of hepatic and renal tumorigenesis with thyroidectomized NZR/Gd rats treated with dimethylnitrosamine

Endocrine modulation of DMN carcinogenesis was studied in NZR/Gd rats preconditioned by starving 48 hr and then injected i.p. once with 20 mg DMN/kg. Intact rats developed kidney tumors (44% TBA), most of tubular epithelial type resembling human tumors rather than mesenchymal. Thyroidectomy (Tx) 45 days before DMN significantly enhanced DMN carcinogenesis, renal carcinoma incidence increasing to 69%. Renal carcinomas showed more signs of malignancy in Tx rats. Other neoplastic responses useful for further studies including tumors in nasal epithelium (13%), liver (18%, increased to 59% in Tx rats), and lung (40%): these tumors were rare or not previously reported in single-dose experiments in other rat strains. A sex difference in lung tumor incidence (male 70%, female 16%) was statistically significant and thyroidectomy reduced the sex-differential (to 54% and 39% respectively). The increased incidence of kidney and liver tumors could be due to altered metabolism of DMN in tissues of Tx rats.     

Hepatoprotective effect of C-phycocyanin: protection for carbon tetrachloride and R-(+)-pulegone-mediated hepatotoxicty in rats

Effect of C-phycocyanin (from Spirulina platensis) pretreatment on carbontetrachloride and R-(+)-pulegone-induced hepatotoxicity in rats was studied. Intraperitoneal (i.p.) administration (200 mg/kg) of a single dose of phycocyanin to rats, one or three hours prior to R-(+)-pulegone (250 mg/kg) or carbontetrachloride (0.6 ml/kg) challenge, significantly reduced the hepatotoxicity caused by these chemicals. For instance, serum glutamate pyruvate transaminase (SGPT) activity was almost equal to control values. The losses of microsomal cytochrome P450, glucose-6-phosphatase and aminopyrine-N-demethylase were significantly reduced, suggesting that phycocyanin provides protection to liver enzymes. It was noticed that the level of menthofuran, the proximate toxin of R-(+)-pulegone was nearly 70% more in the urine samples collected from rats treated with R-(+)-pulegone alone than rats treated with the combination of phycocyanin and R-(+)-pulegone. The possible mechanism involved in the hepatoprotection is discussed.