[A clinical analysis of hepatic veno-occlusive disease after hematopoietic stem cell transplantation].

Objective: To analyze the outcome and the prognostic factors of hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT). Methods: A total of 797 patients receiving HSCT were analyzed retrospectively. The prophylaxis regimen of HVOD in the First Affiliated Hospital of Guangxi Medical University consisted of low molecular weight heparin and lipoprostaglandin E1 (PGE1). Results: Fifty-nine patients (7.4%) developed HVOD at 3-49 days after HSCT (median 12 days). Age younger than 15 years at transplant(HR= 6.47, P<0.001), busulphan conditioning (HR=6.40, P<0.001), thalassemia major (HR=6.35, P<0.001), allogeneic transplantation (HR=7.74, P=0.005) were univariate risk factors for HVOD. Multivariate analyses suggested that thalassemia major and busulphan conditioning were independently correlated with the development of HVOD. Conclusion: Thalassemia major and busulphan conditioning are independent risk factors for HVOD after HSCT.

Clinical and pathological features and treatment of AIDS-related cutaneous Kaposi's sarcoma in Chinese Han patients.

This retrospective study aimed to observe the clinicopathological features and immunological phenotypes, and explore effective treatment and prognosis for 12 Chinese Han patients with acquired immunodeficiency syndrome-related cutaneous Kaposi's sarcoma. All 12 patients were human immunodeficiency virus-positive, and underwent the standard highly active antiretroviral therapy (HAART). Skin lesions mainly presented as purple, or rufous papules, or plaques; skin biopsy showed diffuse or flaky infiltration of spindle cells, active proliferation of slit-like vasculature, erythrocyte exudation, hemosiderin deposition, and inflammatory cell infiltration. Immunohistochemical analysis showed the expression of Ubiquitin C-terminal hydrolase L1 (+), and CD31 (+) in T-cells; factor VIII (+) and HHF-35 (+) in the proliferating vascular endothelial cells; vimentin (+) and S-100 protein (-) in the vessel wall; and CD34 (+++) in the spindle cells of 6 cases, with 1 case of negative CD34 expression. Four patients with confined lesions underwent surgery and microwave therapy, and received a favorable prognosis. Two patients with limited lesions underwent microwave therapy, and the lesions subsided. Of six patients with widely distributed sarcomas, five underwent microwave therapy and one received combined chemotherapy; five attained significant efficacy, and one died. There were no significant differences in the clinicopathological features and immunological phenotypes between the Chinese Han patients and those from other populations. Along with basal HAART, patients in early stages, with sarcomas <2 cm in diameter should undergo surgery and microwave therapy, while patients with sarcomas >2 cm in diameter should undergo chemotherapy and microwave therapy.

Efficacy of Deferasirox for the treatment of iron overload in Chinese thalassaemia major patients: results from a prospective, open-label, multicentre clinical trial.

OBJECTIVE: To assess the efficacy and safety of deferasirox in Chinese thalassaemia major (TM) patients BACKGROUND: EPIC (Evaluation of Patients' Iron Chelation with Exjade(®)) was a large multi-national study and, notably, the first clinical trial of an iron chelator registered with the Chinese State Food and Drug Administration. METHODS: Efficacy and safety of deferasirox were compared in Chinese (n = 117) and non-Chinese (n = 998) TM patients. Deferasirox was initiated at 20 mg kg(-1) day(-1), with titration increments of 5-10 mg kg(-1) day(-1), based on serum ferritin trends and safety parameters. RESULTS: At baseline, Chinese patients were younger than non-Chinese (mean age 6·8 versus 19·5 years), with higher median serum ferritin (4519 vs 3058 ng mL(-1)). Over 1 year, mean actual deferasirox dose was similar for Chinese and non-Chinese patients (24·6 and 24·0 mg kg(-1) day(-1), respectively); median serum ferritin did not change significantly from baseline in Chinese patients (+340 ng mL(-1), P = 0·102) and significantly decreased in non-Chinese patients (-220 ng mL(-1); P < 0·001). In the 1-year extension in Chinese patients, (mean actual deferasirox dose 33·6 mg kg(-1) day(-1)), median serum ferritin decreased (-756 ng mL(-1); P = 0·0397), with a numerically higher reduction in patients aged ≥6 to < 12 than <6 years (-982 vs -457 ng mL(-1), respectively). The safety profile of deferasirox in Chinese patients was similar to the overall population with respect to clinically-relevant findings. CONCLUSION: Age and deferasirox exposure influenced study findings, supporting the need for longer-term treatment and dose escalation to ≥30 mg kg(-1) day(-1) to achieve neutral or negative iron balance in heavily iron overloaded and younger Chinese patients.

Risk assessment of malignant transformation of oral leukoplakia in patients with previous oral squamous cell carcinoma.

The aim of this study was to identify the risk factors associated with developing oral squamous cell carcinoma (OSCC) from surgically excised oral leukoplakia (OL) in patients with previous oral cavity cancer. Clinicopathological data of 84 patients who were treated for OL between July 2002 and July 2020 and who had previously received treatment for OSCC were reviewed retrospectively. The follow-up time ranged from 0.69 to 17.99 years (mean 6.78 ± 4.25 years). The overall cumulative malignant transformation rate was 25% and the annual transformation rate was 5.73%. Kaplan-Meier survival analysis and the log-rank test showed that Candida infection (P = 0.010) was a risk factor associated with malignant transformation. In the multivariate Cox regression analysis, tongue and floor of the mouth as the location of the leukoplakia (P = 0.039), multifocal lesions of OL (P = 0.047), and Candida infection (P = 0.018) were the three independent prognostic factors related to the development of OSCC from the treated OL. A cautious approach to OL of the tongue with Candida infection or multifocal disease in this group of patients would be appropriate.

Course and prognosis of myasthenia gravis: a systematic review.

The clinical course of myasthenia gravis (MG) is variable, and spontaneous remission is still uncommon. Knowledge of the prognostic factors may help understand the course of MG and thus optimize its management. A systematic review search was conducted in MEDLINE and EMBASE for English language studies from 1985 through 2009. We identified additional studies by reviewing bibliographies of retrieved articles and hand search main journal of neurology. Studies evaluating variables associated with or predictive of remission in adult patients with MG were included. Because of methodological heterogeneity, we refrained from statistical pooling, instead, a best evidence synthesis was used for summarizing the results. From 1810 potentially relevant studies, 13 cohort studies met the inclusion criteria. The included studies were heterogeneous considerably in sample size, disease duration, follow-up years, definition of remission, and analysis. Study quality was limited by retrospective design in most studies and lack of multivariate analysis. Time of diagnosis from onset (<1 year) showed strong evidence of predicting a better remission. In studies using completely stable remission outcomes, there was strong evidence that age at onset (<40 years) was of prognostic importance. Furthermore, gender showed no association with remission. Time of diagnosis from onset and age at onset were found to be predictors of remission. Gender does not seem to predict the course of MG. Our findings should be interpreted with caution because of the clinical and methodological heterogeneity of included studies.

Overexpression of clusterin correlates with tumor progression, metastasis in gastric cancer: a study on tissue microarrays.

Clusterin (CLU) is expressed in a wide variety of human tissues and fluids. Overexpression of cytoplasmic clusterin (sCLU) has been implicated in cancer development and progression. The aim of the present study is to evaluate the association of sCLU overexpression with clinicopathological features of human gastric carcinomas (GC).We constructed a gastric cancer tissue microarray containing 173 primary gastric carcinomas and 70 paired non-neoplastic mucosa specimens. The expression of sCLU was studied by immunohistochemistry. The correlations between sCLU expression and clinicopathological features, p53 abnormality, as well as Ki67 activation were analyzed. Overexpressions of sCLU was detected in 28.5% (n=165) of primary GCs by immunohistochemical staining, but not in non-neoplastic mucosa. Clinical association study found that overexpression of sCLU was significantly correlated with lymph-node metastasis (p < 0.001), tumor invasion (p < 0.001) and TNM stage (p < 0.001). In Kaplan-Meier survival analysis, overexpression of sCLU was significantly correlated with unfavorable survival in advanced GCs (p < 0.03). Furthermore, the association of sCLU with abnormal expression of p53 was ascertained. These results suggested that overexpression of sCLU was involved in the progression of GC and it's oncogenic function might be associated with p53 abnormality. Overexpression of sCLU seems to be related with patient's shorter survival in late stage GC.

Correlation between kidney and peripheral nerve functions in Type 2 diabetes.

BACKGROUND: Although greater impairments in nerve functions parameters are most likely to occur with a lower kidney function, there is a paucity of information on the relationship between the kidney and peripheral nerve functions parameters in Type 2 diabetes. AIM: To address the impact of peripheral nerve functions in Type 2 diabetes patients in different stages of chronic kidney diseases (CKD). DESIGN: This prospective study enrolled 238 patients with Type 2 diabetes at a tertiary medical center. METHOD: We designed composite amplitude scores of nerve conductions (CAS) as a measure of severity of peripheral neuropathy (PN), and used estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) parameters to stage CKD in Type 2 diabetes patients. The intrapersonal mean, standard deviation and coefficient of variation of eGFR for 238 patients were obtained in the 3 years prior to the study. RESULTS: The patients who had lower eGFR and higher UACR were older, with longer diabetes duration, a greater percentage of retinopathy and PN and higher CAS. Multiple linear regression analysis revealed that diabetes duration and eGFR were independently associated with CAS, and a cut-off value of eGFR in the presence of PN was 65.3 ml/min/1.73 m2. CONCLUSION: We observed a close relationship between the severity of kidney and peripheral nerve function in patients with diabetes. If a patient's eGFR value is below 65.3 ml/min/1.73 m2 or the UACR value is above 98.6 mg/dl, caution is needed with the presence of PN even in diabetic patients who are asymptomatic.

The outcomes of statin therapy in patients with acute ischemic stroke in Taiwan: a nationwide epidemiologic study.

BACKGROUND: Acute stroke is the third leading cause of death in Taiwan. Although statin therapy is widely recommended for stroke prevention, little is known about the epidemiology of statin therapy after acute ischemic stroke (AIS) in Taiwan. To investigate the effects of statin therapy on recurrent stroke, intracranial hemorrhage (ICH), coronary artery disease (CAD), cost of hospitalization and mortality, we conducted a nationwide population-based epidemiologic study. METHODS: Cases of AIS were identified from the annual hospitalization discharge diagnoses of the National Health Insurance Research Database with the corresponding International Classification of Diseases, ninth revision codes from January 2001 to December 2010. We divided the AIS patients into three groups: non-statin, pre-stroke statin and post-stroke statin. RESULTS: A total of 422 671 patients with AIS (including 365 419 cases in the non-statin group, 22 716 cases in the pre-stroke statin group and 34 536 cases in the post-stroke statin group) were identified. When compared to the non-statin group, both statin groups had a lower recurrent stroke risk [pre-stroke statin: odds ratio (OR) = 0.84; 95% confidence interval (CI) = 0.82-0.87; P < 0.0001; post-stroke statin: OR = 0.89; 95% CI = 0.86-0.91; P < 0.0001], lower ICH risk (pre-statin: OR = 0.75; 95% CI = 0.69-0.82; P < 0.0001; post-stroke statin: OR = 0.75; 95% CI = 0.71-0.81; P < 0.0001), and a lower mortality rate (pre-stroke statin: OR = 0.56; 95% CI = 0.53-0.59; P < 0.0001; post-stroke statin: OR = 0.51; 95% CI = 0.48-0.53; P < 0.0001). In terms of CAD, only the post-statin group had a lower risk (OR = 0.81; 95% CI = 0.79-0.84; P < 0.0001) than the non-statin group. The post-statin group had the lowest 1-year medical costs after index discharge among the three groups. CONCLUSIONS: Statin therapy reduced the risks of recurrent stroke, CAD, ICH and the first year mortality in patients after AIS. Treatment with statin therapy after AIS is a cost-effective strategy in Taiwan.

Non-life-threatening leukopenia in a renal transplant recipient with acute overdose of mycophenolate mofetil.

Mycophenolate mofetil (MMF) is increasingly used as an immunosuppressant for organ transplantation and for treatment of autoimmune diseases. As yet, the experience with acute overdose of MMF in humans is limited. Herein we have reported a 40-year-old female kidney recipient with moderate leukopenia and lack of gastrointestinal toxicity following ingestion of 25 g MMF, which was confirmed by serum drug levels. We treated the patient with charcoal decontamination and oral cholestyramine. She recovered completely without sequelae.

[Clinical analysis of autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation in thalassemia major].

Objective: To explore the diagnosis, treatment and prognosis of autoimmune hemolytic anemia (AIHA) after allo-HSCT in patients with thalassemia major (TM). Methods: A retrospective analysis of AIHA status after allo-HSCT in 291 TM patients from July 2007 to December 2017 was conducted. Results: Five of the 291 TM patients (1.72%) were diagnosed with post-transplant AIHA. The median time of AIHA was 7 (5-12) months after HSCT. All post-transplant AIHA patients were positive in direct and indirect Coombs test, the main clinical manifestations were dizziness, fatigue, pale complexion, skin and sclera yellow, and soy sauce urine. The incidence of AIHA was higher after unrelated donor transplantation (6.36%, 4/63) compared with that of sibling donor transplantation (0.43%, 1/228). One patient who received only prednison was dead. Four patients who received rituximab combined with prednisolone were alive, Coombs test in two of them were negative. Conclusions: AIHA after allo-HSCT developed in 1.72% patients with TM. Monitoring of Coombs test was important for diagnosis of post-transplant AIHA. The incidence of post-transplant AIHA was higher in unrelated donors compared with that of sibling donors transplantation. Treatment of rituximab combined glucocorticoid was effective strategy for post-transplant AIHA.

A review of hematopoietic cell transplantation in China: data and trends during 2008-2016.

Hematopoietic cell transplantation (HCT) activity in China was surveyed to assess its current status. A record number of HCTs (21 884: 16 631 allogeneic (76%) and 5253 autologous (24%)) were reported by 76 centers in China between 1 January 2008 and 30 June 2016. HCT trends included continued growth in transplant activity, a continued rapid increase in haploidentical donors (HID), and slower growth for unrelated donors, matched-related donors (MRD) and cord blood transplantation (CBT). The proportion of HID HCT among allogeneic HCTs increased from 29.6% (313/1062) in 2008 to 48.8% (1939/3975) in 2015, even 51.7% (1157/2237) in the first half of 2016. During this time frame, the proportion of MRD HCTs among allogeneic HCTs decreased from 48.1% (511/1062) to 33.0% (332/3975). The proportion of unrelated donor HCTs among allogeneic HCTs decreased from 20.4 (216/1062) to 13.6% (540/3975). The proportion of CBTs among allogeneic HCTs was increased from 2.1% (22/1062) to 4.2% (184/3975). HCTs have been increasing continuously for all indications except chronic myelogenous leukemia. Severe aplastic anemia is a common HCT indication among non-malignant diseases in China. The number of cases of allogeneic HCT for this disorder has increased annually, from 59 (5.6%) in 2008 to 569 (14.3%) in 2015, even 334 (14.9%) in the first half year in 2016. This survey clearly shows recent trends for HCTs in China.

Haploidentical transplant for myelodysplastic syndrome: registry-based comparison with identical sibling transplant.

Encouraging results from a small sample of patients with myelodysplastic syndrome (MDS) undergoing haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) must be extended. Furthermore, an algorithm derived from a comparison of the outcomes of HID and identical-sibling donor (ISD) HSCT must be established. Therefore, the outcomes of 454 MDS patients who underwent HSCT from HIDs (n=226) or ISDs (n=228) between 2003 and 2013 that were reported to the Chinese Bone Marrow Transplantation Registry were analyzed. Among the 3/6 HID (n=136), 4-5/6 HID (n=90) and ISD patient groups, the 4-year adjusted cumulative incidences of non-relapse mortality were 34, 29 and 16%, respectively (overall P=0.004), and of relapse were 6, 7 and 10%, respectively (overall P=0.36). The 4-year adjusted probabilities of overall survival were 58, 63 and 73%, respectively (overall P=0.07), and of relapse-free-survival were 58, 63 and 71%, respectively (overall P=0.14); pairwise comparison showed that the difference was only statistically significant in the 3/6 HID vs ISD pair. The data suggest that ISDs remain the best donor source for MDS patients while HIDs (perhaps 4-5/6 HID in particular) could be a valid alternative when an ISD is not available; human leukocyte antigen disparity had no effect on survival among the HID patients.

Outputs of hepatic copper and cadmium stimulated by tetrathiomolybdate (TTM) injection in Long-Evans Cinnamon (LEC) rats pretreated with cadmium, and in Fischer rats pretreated with copper and cadmium.

The Long-Evans Cinnamon (LEC) rat, an inbred mutant rat derived from the Long-Evans strain, is characterized by spontaneous hepatitis due to gross accumulation of hepatic Cu. The accumulation, accompanied by marked induction of metallothionein (MT), is believed to be due to the inherent lack of output of Cu into the bile duct and blood vessels. In this study, the acute effect of tetrathiomolybdate (TTM), a chelator for output of hepatic Cu and Cd in LEC rats treated with Cd, was investigated. Female LEC rats were injected subcutaneously with Cd (Cd; 1.0 mg/kg) to induce Cd, Cu-MT. Fischer rats were treated with Cd (Cd; 1.0 mg/kg) and Cu (Cu; 3.0 mg/kg). Forty-eight hours after the injections of metals, TTM (5 mg/kg bw) was injected intravenously under anesthesia. The TTM injection rapidly stimulated biliary excretions of Cu (at a microgram/ml level) and Cd (at a ng/ml level). Furthermore, Cu and Cd concentrations were increased in serum sampled 60 min after the TTM injection. The increase of biliary Cu excretion was not accompanied by increased biliary excretion of MT. The TTM injection caused the hepatic Cu concentrations to decrease from 306 +/- 2 to 262 +/- 12 and from 43 +/- 6 to 20 +/- 5 micrograms/g in LEC and Fischer rats, respectively. The hepatic Cd concentration was not decreased by TTM treatment. Hepatic MT and Cu, but not Cd, concentrations in the MT fraction were also reduced by TTM injection. Our results showed that TTM can rapidly remove Cu from MT to increase bile and blood Cu levels. The output of Cd stimulated by TTM injection may be related to MT reduction resulting from removal of MT-bound Cu. Our results indicate that to avoid the toxic effect of Cu, TTM injection is an effective initial treatment, although it remains to be established how metals, including Cu, are finally metabolized.

Accumulation of orally given cadmium in Long-Evans Cinnamon (LEC) rats with an inherently abnormal copper metabolism.

An inherent defect of biliary Cu excretion and subsequent Cu deposition in the liver have been found in Long-Evans Cinnamon (LEC) rats, which are promising models of Wilson disease. LEC and Fischer rats were given water containing Cd (CdCl2) at a level of 5 ppm for 30 days. Regardless of drinking Cd water, LEC rats showed a very high concentration of Cu (200 to 250 microgram/g) and Cu-metallothionein (Cu-MT) (18 mg/g) in the liver. There was no difference of Cd accumulation in the liver between the two strains exposed to Cd (2.6 and 2.7 microgram/g in the Fischer and LEC groups, respectively). However, the renal Cd concentration was slightly but significantly higher in LEC rats (3.5 microgram/g) than in Fischer rats (2.0 microgram/g). The ratio of renal Cd contents to the sum of renal and hepatic Cd contents was significantly higher in LEC rats (0.25) than in Fischer rats (0.15). The serum Cd concentration in Cd-treated LEC rats increased threefold compared to Cd-treated Fischer rats. It seems likely that Cd from the liver is transported into the kidney in the form of Cd, Cu-MT. There was no difference in uptake of Cd in the hepatic MT fraction between the two strains. Although biliary Cu excretion in LEC rats was significantly lower than that in Fischer rats, reduced excretion of Cd into bile was not found in LEC rats. The gross amounts of Cu and Cu-MT influenced the accumulation of Cd in the kidney rather than in the liver when Cd was given orally at a low level to LEC rats. Our results suggest tht Cu and Cd do not share the same sites of hepatobiliary excretion in rats, although the main route of their excretion is via bile.

Decreased hepatobiliary secretion of inorganic mercury, its deposition and toxicity in the Eisai hyperbilirubinemic rat with no hepatic canalicular organic anion transporter.

Eisai hyperbilirubinemic (EHB) rats, a new mutant strain inbred from Sprague-Dawley (SD) rats, show no inherent expression of the canalicular multidrug resistance protein (cMrp) and lack canalicular multispecific organic anion transporter (cMOAT) activity. A sample of 203Hg (40 microCi with 40 microg Hg/kg) was injected intravenously (i.v.) into four male SD and EHB rats. Biliary excretion of reduced-glutathione (GSH) was 426 and 2 microg/bile for 15 min in the SD and EHB rats, respectively. Biliary excretion of 203Hg for 45 min in EHB rats significantly decreased to 1/4 of that of the SD rats. However, there was no difference in the hepatic uptake of 203Hg between the two strains. Other rats were injected subcutaneously (s.c.) with HgCl2 solution (at 0.2 and 1.6 mg/kg) containing 203Hg. Some 4 days after the injection of 0.2 mg/kg, about 3 and 13% of the total dose was found in the liver in SD and EHB rats, respectively. The hepatic supernatant Hg was recovered mainly in the void volume of a Sephadex column. Some 2 days after the injection of 1.6 mg/kg, these values were 3 and 23% in SD and EHB rats, respectively. The increased retention stimulated hepatic metallothionein (MT) induction and increased the proportion of Hg in the MT region on the Sephadex column. On the other hand, biliary excretion of 203Hg for 15 min in EHB rats was about 1/6-1/4 of that in SD rats. With the injection of 1.6 mg/kg, hepatic and renal functions worsened in EHB rats. In particular, severe necrosis was found in the renal tubules. Our results suggest that biliary secretion of inorganic Hg may be partly regulated by the ATP-dependent transport system, the glutathione S-conjugate export pump (GS-X pump) composed of Mrp and MOAT. Significantly decreased excretion stimulates hepatic retention of inorganic Hg. However, the hepatic lesions are less predictive. The MT induction may reduce the toxicity of metal to the liver cells.

Biliary excretion of exogenous cadmium, and endogenous copper and zinc in the Eisai hyperbilirubinuric (EHB) rat with a near absence of biliary glutathione.

Mutant Eisai hyperbilirubinuric (EHB) rats derived from an inbred strain of Sprague-Dawley (SD) rats are characterized by a near absence of biliary excretion of glutathione (GSH) due to inherently impaired ATP-driven organic anion transport. Cd (0.1 mg/kg bw from CdCl2) was injected intravenously into EHB rats and control SD rats. Output of biliary excretion of Cd was followed over 15-min intervals up to 60 min. Cd was excreted rapidly and reached the maximum level (73.2 ng/15 min) in the period from 15 to 30 min in SD rats. Its excretion in EHB rats, however was one-fortieth (only 1.8 ng/15 min) of that in SD rats. Biliary concentrations of two endogenous metals, Cu and Zn were also measured. The output of Cu in EHB rat bile (50 ng/15 min before Cd injection) was about one-fifth of that in SD rat bile (270 ng/15 min). The output was not influenced by the Cd injection in the two groups. There was a slight difference of Zn output between the two groups. The biliary excretion of GSH was 500 to 700 micrograms/15 min and only 1 to 2 micrograms/15 min in SD and EHB rats, respectively. Sixty min after Cd injection, the Cd concentrations in the serum, liver and kidney were slightly higher in EHB rats than in SD rats. There was no difference in the hepatic metallothionein (MT-I and-II) concentration between SD (34 micrograms/g liver) and EHB (33 micrograms/g liver) rats. The renal Cu concentration was about four times in the higher in the EHB rat than in the SD rat. These results suggest that reduced biliary excretion of Cd is mainly, but that of Cu is only partly, based in reduced canalicular transport of GSH due to lack of an ATP-driven organic anion transport system, not MT induction in EHB rats. It seems likely that biliary excretion of Cd is regulated mainly by the canalicular anion transport in rats.

Iron depletion prevents adenine nucleotide decomposition and an increase of xanthine oxidase activity in the liver of the Long Evans Cinnamon (LEC) rat, an animal model of Wilson's disease.

The Long Evans Cinnamon (LEC) rat, which accumulates excess Cu in the liver as in patients with Wilson's disease, is a mutant strain displaying spontaneous hepatitis. It was reported that Fe, like Cu, increases in the liver and that the severity of hepatitis is modified by Fe in the diet. In this experiment, oxidative stress increased by Fe was investigated before the onset of hepatitis. To examine the effect of Fe on the progress into hepatitis, LEC female rats were fed an Fe-regular (Fe 214 microg/g; Fe(+) group) or an Fe-restricted (Fe 14 microg/g; Fe(-) group) diet from 53 days of age for 35 days. Fischer rats were also fed as control animals. Adenine nucleotide decomposition was determined as an index of oxidative stress based on xanthine oxidase activity. The size of the hepatic pool of adenine nucleotides (ATP+ADP+AMP) was significantly smaller in LEC rats than Fischer rats. The energy charge (ATP+0.5ADP)/(ATP+ADP+AMP) was smaller in Fe(+) groups than in Fe(-) groups. In the LEC rat liver, the Fe concentration in the Fe(+) group was 160% of that in Fe(-) group and the correlation coefficient between the hepatic Fe concentration and the energy charge was significant. In this strain, an increase of xanthine oxidase activity resulted in an increase of xanthine, an oxidized metabolite of hypoxanthine in the liver. The results suggest the involvement of the Fe in the progression into hepatitis in the LEC rat, even if the dietary Fe concentration is similar to that of commercial diet.