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PubMed1996

Changes in T-lymphocyte subpopulations and serum lymphokine concentrations after partial hepatectomy in rats.

The relationship between liver regeneration and immunological response does exist. Extrathymic T cells and serum lymphokines are believed to be changed after partial hepatectomy, but there is still much controversy. This study evaluates the changes of peripheral blood T-lymphocyte subpopulations, natural killer (NK) cells, serum lymphokines, and NK cells in the remnant liver after partial hepatectomy. Male Wistar rats weighing around 200 g were used as subjects. Partial hepatectomies (67%) were done. Counting T-lymphocyte subpopulations (includes T3, T4, T8, T-IL2R, and NK cells) by using fluorescin isothiocyanate or phycoerythrin was performed preoperatively and on 1,2,3,5,7, and 10 d postoperatively. Serum gamma-interferon (gamma-IFN), interleukin-2 and interleukin-2 receptor concentrations were measured. Absolute number of NK cells in the remnant liver was also counted. Rats with right-side nephrectomy, sham operation, and no operation were used as control groups. Comparing the difference between all groups, we found that all T-lymphocyte subpopulations in peripheral blood, serum gamma-IFN, peripheral blood NK cells, and the absolute number of NK cells in the remnant liver of hepatectomized rats increased markedly, and were significantly higher than control groups rats, on the fifth and seventh post-hepatectomy day. It is suggested that gamma-IFN and NK cells were activated markedly and might play important roles in the regulation of liver regeneration after partial hepatectomy.

Animals↗
PubMed1997

Contrasting effects of identical nutrients given parenterally or enterally after 70% hepatectomy: bacterial translocation.

High mortality occurs in rats with 70% hepatectomy fed intravenous (IV) total parenteral nutrition (TPN; 13.9% glucose, 4.17% amino acids, 1.46% fat, electrolytes, trace minerals, and vitamins providing 216 kcal.kg-1.d-1) but not when the identical nutrients are given at the same rate enterally (gastrostomy). We hypothesized that a difference in bacterial translocation (BT) was a contributing factor to this phenomenon. Forty-five male Sprague-Dawley rats (300-360 g) were divided into five groups and underwent the following: control (no operation), sham (intraperitoneal [IP] pentobarbital anesthesia, central venous and gastrostomy catheters, laparotomy, sham hepatectomy), standard oral feeding (SOF), TPN (IV nutrients), and total enteral nutrition (TEN; gastrostomy). The SOF, TPN, and TEN groups had IP pentobarbital anesthesia, central venous and gastrostomy catheters, and 70% hepatectomy. Postoperatively, control and SOF (both catheters plugged) rats ate a commercial rat chow and drank tap water ad libitum pre- and postoperatively. The sham, TPN, and TEN groups were given the identical infusate composition as above, but the nutrient concentrations were cut in half (110 kcal/kg) and three-quarters (165 kcal/kg) on postoperative days 1 and 2, respectively. At the end of postoperative day 2, all rats were euthanized. BT to mesenteric lymph nodes (MLNs), liver, spleen, and lungs was significantly higher in the TPN rats compared with all other groups, except that BT to the MLNs was similar in the TPN and TEN groups. Bacteremia was found only in the TPN rats. BT in TPN rats with 70% hepatectomy was significantly greater 48 h after operation than in those fed the identical nutrients enterally at the same rate; this correlates with the previously reported significantly greater mortality in rats with 70% hepatectomy receiving TPN.

Animals↗
PubMed2001

Role of PAF in acute liver injury after extended hepatectomy: overexpression of PAF receptor mRNA in Kupffer cells.

To clarify the pathophysiology of acute liver injury after extended hepatectomy, we investigated the relationship between the site and levels of expression of platelet activating factor (PAF) receptor mRNA, and the blood levels of endotoxin, cytokines, and prostaglandin E2 (PGE2), using a rat model of 70% hepatectomy. After hepatectomy, a significant rise in serum tumor necrosis factor-alpha (TNF-alpha) was observed at 1 hr, the interleukin-6 (IL-6) levels had increased at 3 hr, and PGE2 levels had increased at 6 hr, but there were no significant increases in endotoxin levels in portal vein blood. Overexpression of PAF receptor mRNA in liver tissue was observed as early as 1 hr after hepatectomy, with peak expression occurring at 6 hr, and PAF receptor mRNA was significantly overexpressed in Kupffer cells. The PAF produced in the vicinity of Kupffer cells appears to play a very important role as one of the initial mediators of the acute liver injury that occurs after major hepatectomy.

Acute Disease↗
PubMed2002

Liver pathology and cell proliferation after octreotide administration following partial hepatectomy in rats: an experimental study.

Octreotide is a somatostatin analog introduced for clinical use that inhibits the growth of various tumors in rats. This study investigates liver pathology after octreotide treatment following partial (2/3) hepatectomy in rats. Thirty rats, weighing 250-300 g underwent partial hepatectomy and were divided in to two groups. Group A (N = 25) received octreotide subcutaneously [2 microg Sandostatin (Sandoz) in 1 ml normal saline every 12 hr for 15 days]. Group B (N = 5) was injected with 1 ml normal saline subcutaneously every 12 hr for the same time period; animals in this group were used as controls. At the end of the experiment rats were sacrificed and liver tissue was obtained for pathologic examination. Liver sections from group A (octreotide administration) showed extensive cholangiolar and fibrous tissue proliferation in the hepatectomy area, and hypertrophy and swelling of Kupffer cells in the liver parenchyma. Sections from the hepatectomy surface from group B (controls) displayed signs of liver regeneration. Proliferation activity (Ki-67+ cells) was higher in the cholangiolar epithelium in group A and in hepatocytes in group B. In conclusion, the results of this study show that octreotide inhibits liver regeneration, which occurs after partial hepatectomy in rats and enhances hyperplasia of cholangiolar and fibrous tissue.

Animals↗
PubMed1975

Partial hepatectomy and toxicity of dimethyl-nitrosamine and carbon tetrachloride, in relation to the carcinogenic action of dimethylnitrosamine.

The yield of tumours in the liver of rats was increased when dimethylnitrosamine was given 1, 6 or 12 h after partial hepatectomy and still further increased if it was given after an interval of 24-72 h. The increase was greater after two-thirds than after one-third hepatectomy. An increase in the number of kidney tumours was also found. Microsomal DMN-demethylase activity was depressed after partial hepatectomy for up to 6 days in mice and rats. The LD50 of DMN on the other hand was decreased for 3 days, after which it returned to normal. The extent of liver necrosis produced by DMN was increased at 6 and 24 h after partial hepatectomy but was within the usual range at longer intervals. These results suggest that prolonged exposure of the tissues to DMN after partial hepatectomy played a significant role in the development of liver tumours as well as those in the kidney, in addition to the role of regeneration of the liver, and that the relative roles were still to be elucidated.

Animals↗
PubMed2001

Ras adenoviruses modulate cyclin E protein expression and DNA synthesis after partial hepatectomy.

Ras-genes encode for proteins important for transmitting extracellular signals from the cytoplasm to the nucleus. In this study we investigated the impact of Ras on cell cycle progression after hepatectomy by using adenoviral vectors (adv) expressing beta-galactosidase (beta-gal), a dominant-negative (Ras N17) or a dominant-active (Ras 61L) form of H-Ras. Partial hepatectomy was performed in mice treated with the different adenoviruses and cell cycle progression was studied by analysing factors involved in cell cycle control during liver regeneration. After hepatectomy, adv Ras 61L increases DNA synthesis significantly in comparison to the other treatment groups. Higher Ras activity results in an early increase of transcriptional active E2F-3, which is associated with higher cyclin E, but almost unchanged cyclin D protein expression. However, Northern blot analysis and cyclin E promoter experiments indicate that, besides transcriptional mechanisms also post-transcriptional mechanisms are involved in regulating cyclin E protein expression after partial hepatectomy in mice treated with adv Ras 61L. Cyclin E phosphorylation studies demonstrate that adv Ras 61L results in hypophosphorylation of cyclin E compared to the control group at early time points after hepatectomy, when cyclin E protein expression strongly increases and there is only a minor effect on cyclin E mRNA levels. Our experiments indicate adv Ras 61L in vivo increases Cyclin E expression by higher transcription via E2F and a post-transcriptional mechanism. These mechanisms result in an earlier activation of an active CDK2/Cyclin E complex which, in turn, triggers DNA synthesis.

Adenoviridae↗
PubMed2000

Preoperative portal vein embolization improves prognosis after right hepatectomy for hepatocellular carcinoma in patients with impaired hepatic function.

BACKGROUND: Percutaneous transhepatic portal vein embolization (PTPE) increases the safety of subsequent major hepatectomy. The aim of this study was to determine the effect of PTPE on long-term prognosis after hepatectomy in patients with hepatocellular carcinoma (HCC). METHODS: Seventy-one patients with HCC underwent right hepatectomy between 1984 and 1998. Preoperative PTPE was performed in 33 patients (group 1) and was not used in 38 patients (group 2). Outcome after operation was compared between the groups. The patients were further divided according to the median tumour diameter (cut-off 6 cm) and indocyanine green retention rate at 15 min (ICGR15) (cut-off 13 per cent). RESULTS: The cumulative survival rate was significantly higher in group 1 than in group 2 in patients with an ICGR15 of at least 13 per cent. Tumour-free survival rates were similar in both groups. Of patients with tumour recurrence after right hepatectomy, those in group 1 were more frequently subjected to further treatment. CONCLUSION: Preoperative PTPE improves the prognosis after right hepatectomy for HCC in patients with impaired hepatic function, although it does not prevent tumour recurrence.

Adult↗
PubMed1996

Selective portal vein embolization with absolute ethanol induces hepatic hypertrophy and makes more extensive hepatectomy possible.

Portal vein embolization has been used recently to decrease the amount of the liver to be resected and to enhance the function of the remaining hypertrophied lobes. We have observed a strong contact destructivity of absolute ethanol and used it for portal vein embolization. The present study was performed to produce hepatic hypertrophy and to show histopathologic changes that follow ethanol embolization of rat liver. Hepatic proliferation and histopathology were studied in rats receiving low and high doses of absolute ethanol via portal vein and rats undergoing 70% hepatectomy alone. The liver weight of the unresected and unembolized lobes increased rapidly after embolization and hepatectomy. Although the increase was more rapid in the high-dose group than the low-dose group in early days, the final results were not different from each other and were almost equal to those after hepatectomy. Complete obstruction of portal venous branches and massive necrosis were the main histopathologic observations after portal vein embolization with all doses of ethanol. Because the mortality rate in the low-dose group was lower than in the high-dose group and extensive necrosis of the liver parenchyma and subsequent regeneration was sufficient, using minimum dose of ethanol was much safer. Based on the biochemical and hematologic parameters, portal vein embolization with low-dose ethanol did not impair liver function more than hepatectomy alone during the initial 14 days. Portal vein embolization with absolute ethanol makes more extensive hepatectomy possible by reducing the volume necessary to resect and preserves the function of the remaining liver.

Animals↗
PubMed1996

Role of Kupffer cells and the spleen in modulation of endotoxin-induced liver injury after partial hepatectomy.

The hypothesis that both activated Kupffer cells and the spleen may be responsible for endotoxin-induced liver injury following partial hepatectomy was investigated. Male rats were divided into a sham group receiving laparotomy alone and three groups receiving a two-thirds hepatectomy; one group was given normal saline (NS) solution as a vehicle control, one group received intravenous gadolinium chloride (GC group) (7 mg/kg body weight) for 2 days before intravenous injection of endotoxin to inhibit Kupffer cell phagocytosis, and the third group simultaneously underwent splenectomy and partial hepatectomy (SH group). As endotoxin, lipopolysaccharide (LPS) (1 mg/kg body weight) was administered intravenously 2 days after surgery. In the GC and SH groups, phagocytic activity was reduced to approximately 40% of that in the sham group. The highest plasma tumor necrosis factor alpha (TNF-alpha) level (8,544 +/- 1,223 pg/mL) was observed in the NS group at 1 hour after LPS administration, and the level was significantly reduced by GdCl3 or splenectomy (P < 0.05). Inhibition of Kupffer cell function and splenectomy attenuated functional and structural liver damage associated with the decreased hepatic infiltration of polymorphonuclear leukocytes (PMNs) and reduced priming of circulating PMNs in the early stage of endotoxemia following partial hepatectomy. Consequently, the 24-hour survival rate of the SH and GC groups was significantly improved to 50% and 80%, respectively (P < .05), while that of the NS group was 12.5%. These findings indicate that the modification of inflammatory mediator generation by splenectomy or inhibition of Kupffer cell function may be beneficial for the prevention of endotoxin-induced liver injury after partial hepatectomy.

Animals↗
PubMed2001

Estimating the prognosis of hepatic resection in patients with metastatic liver tumors from colorectal cancer with special concern for the timing of hepatectomy.

BACKGROUND: The effect of the time interval between colorectal and liver resection for metastatic lesions on the patient's survival remains controversial. Pretreatment classification for predicting the prognosis of this disease has not yet been reported. METHODS: Nine clinical factors revealed by preoperative examinations, intraoperative screening before liver resection, and resection margin were examined in 304 patients who underwent hepatic resections for metastatic colorectal carcinoma. The patients were divided according to the timing of hepatectomy and both tumor number and maximum diameter to devise a staging system. RESULTS: Tumor number and maximum tumor size were significant prognostic factors in the metachronous hepatectomy group, and resection margin was significant in the synchronous group. The following staging system was proposed: stage I, n < or = 3 and diameter < 5 cm in the metachronous hepatectomy group (n = 86); stage II, n < or = 3 and diameter > or = 5 cm in the metachronous hepatectomy group (n = 46); and stage III, n > or = 4 and diameter > 5 cm in the metachronous group and the synchronous hepatectomy group (n = 144). CONCLUSIONS: The current study revealed that the factors that influenced the patient's prognosis were different between the synchronous and metachronous groups. It may be useful to develop a staging system that considers this difference.

Adult↗
PubMed2001

Effectiveness of systematized hepatectomy with Glisson's pedicle transection at the hepatic hilus for small nodular hepatocellular carcinoma: retrospective analysis.

BACKGROUND: The effectiveness of systematized hepatectomy with transection of Glisson's pedicle at the hepatic hilus in patients with small nodular hepatocellular carcinoma (HCC) has not been confirmed. METHODS: Surgical outcomes were reviewed in 204 patients with single nodular HCCs less than 5 cm in greatest diameter, including 68 patients with tumors that showed extranodular growth and 136 patients with tumors that did not, who had undergone curative hepatectomy (partial hepatic resection, n = 114; systematized hepatectomy, n = 90) from 1990 through 1994. RESULTS: The rates of microscopic vascular invasion and intrahepatic metastasis were significantly higher in patients who had single nodular HCCs with extranodular growth (34% and 49%) than in patients who had single nodular HCCs without extranodular growth (13%, P =.001, and 4%, P <.001). The 5-year survival rate in patients who had single nodular HCCs with extranodular growth was significantly greater after systematized hepatectomy (67%) than after partial hepatic resection (21%, P =.0002). Multivariate analysis showed that the type of operation was an independent prognostic factor in patients with single nodular HCCs with extranodular growth (P =.0008). CONCLUSIONS: Systematized hepatectomy with Glisson's pedicle transection at the hepatic hilus should be performed in patients who have single small nodular HCCs with extranodular growth because these tumors often invade within the liver sector containing the tumor.

Aged↗
PubMed1988

Differential effects of partial hepatectomy on hepatic and renal heme and cytochrome P450 metabolism.

Partial hepatectomy has been suggested to affect hepatic and renal cytochrome P450 content and the related drug metabolizing enzyme system. In addition, cytochrome P450 and its dependent activities have been shown to be regulated by the availability of cellular heme. We, therefore, studied cytochrome P450 in addition to the level of heme oxygenase, the rate-limiting enzyme of heme catabolism, and delta-aminolevulinic acid (ALA) synthase, the rate-limiting enzyme of heme synthesis, in the remnant liver and intact kidneys of rats after two-thirds hepatectomy. The level of hepatic heme oxygenase was elevated threefold in partially hepatectomized rats as compared to sham-operated rats, while ALA synthase was decreased by 40%. This was reflected in decreased hepatic cytochrome P450 content, ie, from 0.689 +/- 0.175 nmole/mg to 0.505 +/- 0.089 nmole/mg protein and associated decreased drug metabolizing enzymes: aryl hydrocarbon hydroxylase, 7-ethoxycoumarin-O-deethylase, and benzphetamine N-demethylase, by 40%, 40%, and 47%, respectively. In contrast, renal heme oxygenase was not changed after hepatectomy, whereas renal ALA synthase was increased by fourfold. Renal cytochrome P450, aryl hydrocarbon hydroxylase, 7-ethoxycoumarin-O-deethylase, and benzphetamine N-demethylase were increased after partial hepatectomy by 84%, 360%, 165% and 406%, respectively. These data indicate that partial hepatectomy decreases liver cytochrome P450 levels by inducing heme oxygenase and inhibiting ALA synthase activities. In this situation the kidney plays a substitutive role in metabolizing endogenous substrates oxygenated by cytochrome P450 isozymes.

Animals↗
PubMed1993

Total hepatectomy and liver transplantation as two-stage procedure.

OBJECTIVE: This article describes the experience with a bridging procedure for a prolonged anhepatic period during clinical liver transplantation in case of special emergency situations. SUMMARY BACKGROUND DATA: Hepatic necrosis due to fulminant hepatitis or acute graft failure, as well as severe liver trauma are well-known and accepted indications for urgent liver transplantation. Prerequisite is the allocation of a suitable donor organ. If no allograft is available in time, patients with "toxic liver syndrome" or exsanguinating hemorrhage have been shown to benefit from advanced total hepatectomy. METHODS: As a modification of the standard one-stage procedure, recipient hepatectomy and subsequent liver transplantation are performed in two separate operations. To bridge the prolonged anhepatic period and to allow decompression and return of venous blood, an end-to-side portocaval shunt is constructed temporarily. RESULTS: Thirteen of thirty-two patients underwent hepatectomy but not transplantation subsequently, and died within 34 hours after progressive deterioration. In 19 of 32 patients, transplantation was realized 6-41 hours after hepatectomy; 9 of 19 patients died, mostly from sepsis. Ten of nineteen liver recipients survived the procedure including three unrelated late deaths; presently, seven patients are alive with a follow-up of 3 to 46 months. CONCLUSIONS: Two-stage total hepatectomy with temporary portocaval shunt, and subsequent liver transplantation can be a life-saving approach in patients most likely to die of the sequelae of advanced liver or graft necrosis or exsanguination that cannot be controlled by conventional treatment or immediate liver transplantation.

Adolescent↗
PubMed2000

Minimal blood loss living donor hepatectomy.

BACKGROUND: Donor hepatectomy with maximal safety while preserving graft viability is of principal concern in living donor liver transplantation. There are compelling reasons for avoiding blood transfusion, even with autologous blood, to avoid the potential risks it imposes on healthy donors. This study aims to describe the surgical technique and clinical outcomes of living donor hepatectomy with minimal blood loss requiring no blood transfusion. METHODS: Donor hepatectomy was performed in 30 living donors according to a detailed preoperative imaging study of the vascular and biliary anatomy. Liver parenchymal transection was carried out with strict adherence to a meticulous surgical technique without vascular inflow occlusion to either side of the liver. Pre-, intra-, and postoperative data were gathered, and factors related to blood loss were analyzed retrospectively. RESULTS: The intraoperative blood loss ranged from 20 to 300 ml with a mean of 72.0+/-58.9 ml (median, 55 ml), and neither homologous nor autologous blood transfusion was required in any of the donors intra- and postoperatively. All 30 donors were discharged with minimal complications, and remain well at a mean follow-up of 24 months after donation. Excellent graft viability was verified by the fact that all 30 recipients are alive and well with a few manageable complications. The actual graft and patient survival are both 100% at the time of writing. CONCLUSIONS: Regardless of the extent of donor hepatectomy, blood loss can and should be kept to a minimum, and living donor hepatectomy without blood transfusion is a realistic objective.

Adolescent↗
PubMed2003

Portal vein embolization before right hepatectomy: prospective clinical trial.

OBJECTIVE: To assess the impact of liver hypertrophy of the future liver remnant volume (FLR) induced by preoperative portal vein embolization (PVE) on the immediate postoperative complications after a standardized major liver resection. SUMMARY BACKGROUND DATA: PVE is usually indicated when FLR is estimated to be too small for major liver resection. However, few data exist regarding the exact quantification of sufficient minimal functional hepatic volume required to avoid postoperative complications in both patients with or without chronic liver disease. METHODS: All consecutive patients in whom an elective right hepatectomy was feasible and who fulfilled the inclusion and exclusion criteria between 1998 and 2000 were assigned to have alternatively either immediate surgery or surgery after PVE. Among 55 patients (25 liver metastases, 2 cholangiocarcinoma, and 28 hepatocellular carcinoma), 28 underwent right hepatectomy after PVE and 27 underwent immediate surgery. Twenty-eight patients had chronic liver disease. FLR and estimated rate of functional future liver remnant (%FFLR) volumes were assessed by computed tomography. RESULTS: The mean increase of FLR and %FFLR 4 to 8 weeks after PVE were respectively 44 +/- 19% and 16 +/- 7% for patients with normal liver and 35 +/- 28% and 9 +/- 3% for those with chronic liver disease. All patients with normal liver and 86% with chronic liver disease experienced hypertrophy after PVE. The postoperative course of patients with normal liver who underwent PVE before right hepatectomy was similar to those with immediate surgery. In contrast, PVE in patients with chronic liver disease significantly decreased the incidence of postoperative complications as well as the intensive care unit stay and total hospital stay after right hepatectomy. CONCLUSIONS: Before elective right hepatectomy, the hypertrophy of FLR induced by PVE had no beneficial effect on the postoperative course in patients with normal liver. In contrast, in patients with chronic liver disease, the hypertrophy of the FLR induced by PVE decreased significantly the rate of postoperative complications.

Adult↗
PubMed2006

Adoptive transfer of TRAIL-expressing natural killer cells prevents recurrence of hepatocellular carcinoma after partial hepatectomy.

BACKGROUND: Antitumor activity of the liver natural killer (NK) cells reportedly decreases after partial hepatectomy, suggesting that patients with such depressed immune status are susceptible to the recurrence of hepatocellular carcinoma (HCC). We hypothesize that adoptive immunotherapy using activated NK cells can be a novel strategy to improve the depressed immune status in patients with HCC after hepatectomy or partial liver transplantation. In the present study, we have tested this hypothesis by using a mouse model. METHODS: Intraportal injection of 1-5 x 10(6) Hepa1-6 cells (hepatoma cell line) did not result in liver metastases in untreated B6 mice, but led to the growth of liver metastases after extensive partial hepatectomy. Utilizing this murine HCC metastasis model, we investigated the antitumor activity of both remnant liver and exogenously transferred NK cells. RESULTS: The anti-HCC activity of liver NK cells significantly decreased after partial hepatectomy. The expression of CD69 and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on liver NK cells was temporarily downregulated. The adoptive transfer of NK cells, including a TRAIL-expressing fraction, extracted from the liver perfusates of poly I:C-stimulated B6 mice inhibited the growth of liver metastasis in B6 or (B6xBALB/c) F1 (B6CF1) mice that underwent hepatectomy and received intraportal Hepa1-6 injection. CONCLUSIONS: These findings indicate that adoptive immunotherapy using activated NK cells extracted from normal liver perfusates may be a novel technique for reconstituting the depressed immune status in cases of living donor liver transplantation involving HCC patients, recipients of a partial liver graft.

Adoptive Transfer↗
PubMed1995

Inhibitory effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on rat hepatocyte proliferation induced by 2/3 partial hepatectomy.

To better understand the mode of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced alterations in hepatic cell proliferation and the potential link to tumour-promoting activity, we investigated the effects of TCDD on the expression of certain key genes involved in liver cell growth and the effects of TCDD on induced hepatocyte cell proliferation. Gene expression analysis was conducted, by Northern blot hybridization, using RNA isolated from female Sprague-Dawley rat livers collected at various times during a 14-day dosing period with TCDD known to produce alterations in cell proliferation. No major changes were observed in the expression of the transforming growth factors TGF-alpha and TGF-beta or in oncogenes ras, src and myc. However, the expression of the transcription factors C/EBP, HNF-1 alpha and HNF-4 decreased after 14 days of TCDD treatment. To investigate how TCDD affects hepatic growth, cell proliferation analysis was conducted in rats stimulated to undergo hepatocyte proliferation following either 2/3 partial hepatectomy or lead nitrate treatment. Cell proliferation was quantified by means of immunocytochemical detection of Proliferating Cell Nuclear Antigen (PCNA). Fourteen days of pretreatment with TCDD caused an overall inhibition of hepatocytes in the growth fraction (G1, S, G2 and M) from 61 +/- 3% in the control-partial hepatectomy group to 41 +/- 3% in the TCDD-partial hepatectomy group. A periportal pattern of cell proliferation was observed in the TCDD-partial hepatectomy group as compared to the panlobular pattern of cell proliferation in the control-partial hepatectomy group. TCDD pretreatment also produced an inhibition of cell proliferation induced by the liver mitogen lead nitrate. TCDD-induced inhibition of hepatocyte proliferation could play a role in TCDD tumour promotion and hepatocarcinogenesis through the creation of a environment whereby preneoplastic cells continue to expand while normal hepatocyte proliferation is inhibited.

Animals↗
PubMed1983

The influence of total hepatectomy on cerebral energy state, ammonia-related amino acids of the brain and plasma amino acids in the rat.

The influence of total hepatectomy on cerebral energy state, ammonia-related amino acids of the brain tissue and plasma amino acids was studied in anaesthetized rats after total hepatectomy. The hepatectomy was performed with the aid of a microsurgical three-stage procedure. In the first stage, division of the inferior vena cava was performed. In the second stage 4 weeks later a porta-caval anastomosis was constructed, followed after 1 week by a total hepatectomy. The brain energy state, defined as the concentrations of phosphocreatine, ATP, ADP and AMP, was unchanged 4 h after the hepatectomy. Plasma amino acids did not differ significantly between hepatectomized and shunted control rats. On the other hand, clear-cut increases in the concentrations of glutamine, and decreases in the concentrations of glutamate and aspartate, were observed in the fronto-parietal part of the cerebral cortex and the brain stem. These changes might explain the minor manifestations of cerebral dysfunction in the early phase of the hepatectomized state.

Alanine↗