3-hydroxy-3-methyl glutaryl coenzyme A reductase: an essential actor in the biosynthesis of cantharidin in the blister beetle Epicauta chinensis Laporte.

Cantharidin (C(10)H(12)O(4)) is a monoterpene defensive toxin in insects involved in chemical defence as well as in courtship and mating behaviours. It is relatively well known in the medical literature because of its high anticancer activity and as an effective therapy for molluscum contagiosum. However, little is known about its biosynthesis pathway in vivo, and no enzyme involved in cantharidin biosynthesis has been identified. The purpose of this study was to identify the crucial enzyme that is involved in the biosynthesis of cantharidin. Using the homology cloning method, a 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) gene, the rate-limiting enzyme in the mevalonate pathway, was cloned from the blister beetle Epicauta chinensis. Quantitative reverse transcription PCR and gas chromatography methods revealed that the HMGR transcripts had a positive correlation with cantharidin production in the beetles (R = 0.891). RNA interference (RNAi) knockdown of HMGR mRNA expression was achieved by microinjection of a specific double-stranded RNA with more than 90% RNAi efficiency, and an apparent decrease of cantharidin production was observed. Furthermore, the HMGR mRNA was greatly upregulated by exogenous juvenile hormone III (JH III), and cantharidin production was also raised in males; however, when injecting the JH III with RNAi of HMGR mRNA at the same time, cantharidin production did not rise. These results demonstrate that HMGR is an essential enzyme in cantharidin biosynthesis in the blister beetle E. chinensis, which further verifies previous research results demonstrating that cantharidin is synthesized de novo by the mevalonate pathway in blister beetles.

Serum immunoglobulin E level and its impact on the pregnancy outcome associated with fetal growth restriction: a prospective cohort study.

We evaluated the relationship between total serum immunoglobulin E (IgE) levels and pregnancy outcome in a prospective cohort study focusing on fetal growth restriction (FGR). Sixty women with FGR and twenty with normal singleton pregnancy were enrolled during their third trimester. Infants were followed up for 6 months. Blood samples were obtained from pregnant women during the third trimester; cord blood samples were also taken. Six months after birth, blood samples were obtained from infants. Demographic and baseline characteristics were compared between groups. Birth weight, length and head circumference of neonates in the FGR group were lower than those in the control group. Total serum IgE level was significantly increased in third-trimester pregnant women with FGR compared with normal group (P < 0.05). However, this trend was not observed in the cord blood at birth or peripheral blood of 6-month-old infants. The prevalence of atopic eczema between the 2 groups was similar. Linear regression analysis revealed that the IgE level in the third trimester was negatively correlated with birth weight (P < 0.05). Higher serum IgE level in the cord blood was significantly associated with an increased risk of being small for gestational age (P < 0.05). In conclusion, IgE levels in the third trimester of pregnancy and cord blood are strongly related to birth outcomes of FGR.

Epidemiological investigation of physique situation for birth high-risk children aged 9-15 years in Chengdu, Southwest China.

BACKGROUND: As the intrauterine environment can effect children's growth and development, this study aimed to explore the relationship between birth high-risk and physique situation of 9 to 15-year-old children by cross-sectional investigation, and to provide clues for the monitoring, prevention, and treatment of growth deviation in children. MATERIALS AND METHODS: This study recruited 7,194 students aged 9 to 15 years in primary and junior schools. Their parents were asked to complete the birth situation questionnaire. Measurements included height, weight, and body mass index (BMI). Birth high-risk infant was defined according to the gestational age and birth weight. Growth deviation was classified as underweight, short stature, overweight, and obesity. RESULTS: The prevalence of all kinds of growth deviations in preterm, full-term, and post-term birth groups were similar, the same as the physique situation at school age among both sexes. The incidence of small for gestational age (SGA) was 6.23%, when at school age, part of SGA had catch-up growth. However, the prevalence of underweight and short stature for SGA was highest in three groups. The weight and height at school age in SGA group was less than that in appropriate for gestational age (AGA) and large for gestational age (LGA) groups. The prevalence of overweight and obesity for LGA and macrosomia were highest in three groups. At school age, the weight in macrosomia and LGA groups was higher than that in the other groups. CONCLUSIONS: Longitudinal height and weight development and growth of children with birth high-risk are different from normal children. In order to improve healthy situation, more attention should be paid to height and weight development of those children with birth high-risk at school age, even in pre-school age. Prevention may already begin during pregnancy.

[Research advances on the application of rehabilitation exercise training in pediatric burn rehabilitation].

The sequelae of pediatric burn seriously affect the physical function and quality of life of children with burns. Rehabilitation exercise training mainly based on aerobic and resistance exercise can effectively alleviate the negative effects. This article reviews the effects of rehabilitation exercise training on cardiopulmonary function, muscle function, and quality of life of children with burns, and introduces the latest rehabilitation exercise training prescription for children with burns based on type, mode, intensity, frequency, and time of exercise, so as to improve the level of rehabilitation treatment for children with burns.

[Prospective study on the effects of resistance training with elastic band at home on muscle function and walking ability of severely burned children].

Objective: To explore the effects of resistance training with elastic band at home on muscle function and walking ability of severely burned children. Methods: A prospective non-randomized controlled study was conducted. From January 2022 to April 2023, 40 children with severe burns who met the inclusion criteria were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital. According to the willingness of the children or their families, the children were assigned to conventional rehabilitation group and combined rehabilitation group. During the study, 8 children dropped out of the study, 17 children were finally included in the conventional rehabilitation group with 6 males and 11 females, aged (8.5±2.4) years, and 15 children were included in the combined rehabilitation group with 5 males and 10 females, aged (9.6±2.5) years. The children in the 2 groups received conventional burn rehabilitation treatment in the hospital, including active and passive activity training, scar massage, and pressure therapy. The children in combined rehabilitation group received resistance training with elastic band of 3 to 5 times per week after discharge, and the children in conventional rehabilitation group received daily activity ability training after discharge. Before home rehabilitation training (1 week before discharge) and 12 weeks after home rehabilitation training, the grip strength was measured using a handheld grip dynamometer, the muscle strengths of the upper and lower limbs were measured using a portable dynamometer for muscle strength, lean body mass was measured by bioelectrical impedance measuring instrument, and the 6-min walking distance was measured. Data were statistically analyzed with independent sample t test, paired sample t test, Mann-Whitney U test, or Fisher's exact probability test. Results: After 12 weeks of home rehabilitation training, the grip strengths of children in combined rehabilitation group and conventional rehabilitation group were (15±4) and (11±4) kg, respectively, which were significantly higher than (10±4) and (9±4) kg before home rehabilitation training (with t values of -9.99 and -11.89, respectively, P values all <0.05); the grip strength of children in combined rehabilitation group was significantly higher than that in conventional rehabilitation group (t=3.24, P<0.05). After 12 weeks of home rehabilitation training, the muscle strengths of upper and lower limbs of children in combined rehabilitation group (with t values of -11.39 and -3.40, respectively, P<0.05) and the muscle strengths of upper and lower limbs of children in conventional rehabilitation group (with t values of -7.59 and -6.69, respectively, P<0.05) were significantly higher than those before home rehabilitation training, and the muscle strengths of upper and lower limbs of children in combined rehabilitation group were significantly higher than those in conventional rehabilitation group (with t values of 3.80 and 7.87, respectively, P<0.05). After 12 weeks of home rehabilitation training, the lean body mass of children in combined rehabilitation group was significantly higher than that before home rehabilitation training (t=0.21, P<0.05). After 12 weeks of home rehabilitation training, the 6-min walking distances of children in conventional rehabilitation group and combined rehabilitation group were significantly longer than those before home rehabilitation training (with t values of -5.33 and -3.40, respectively, P<0.05), and the 6-min walking distance of children in combined rehabilitation group was significantly longer than that in conventional rehabilitation group (t=3.81, P<0.05). Conclusions: Conventional burn rehabilitation treatment in hospital and home resistance training with elastic band for 12 weeks after discharge can significantly improve the muscle function and walking ability of severely burned children.

Serum alpha-fetoprotein response can predict prognosis in hepatocellular carcinoma patients undergoing radiofrequency ablation therapy.

AIMS: To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). MATERIALS AND METHODS: Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of ≥100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. RESULTS: After a median follow-up of 26.7 ± 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and ≥100 ng/ml, respectively (p = 0.003). In the 58 patients with a baseline AFP of ≥100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively (p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 (p = 0.009), non-optimal AFP response (p = 0.023), and creatinine >1.5 mg/dl (p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively (p < 0.001). Multivariate analysis demonstrated platelet count ≤10(5)/mm(3) (p = 0.048), tumour size >2 cm (p = 0.027), and non-optimal AFP response (p < 0.001) were independent risk factors associated with tumour recurrence after RFA. CONCLUSIONS: Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.

Associations of IL-1ß and IL-6 gene polymorphisms with Parkinson's disease.

OBJECTIVE: The aim of this study was to explore the associations of interleukin-1ß (IL-1ß) and IL-6 gene polymorphisms with the pathogenesis of Parkinson's disease. PATIENTS AND METHODS: A total of 200 patients with Parkinson's disease in our hospital were collected as the disease group. Meanwhile, 200 healthy subjects were taken as the control group. Peripheral blood samples were drawn from all research subjects. The polymorphic regions of IL-1ß and IL-6 were amplified via polymerase chain reaction (PCR). Moreover, the polymorphisms were detected and analyzed, followed by further analysis based on the changes in gene expressions and Hoehn-Yahr grade of patients. RESULTS: The allele distributions at IL-1ß rs571556428 (p=0.015) and IL-6 rs543214973 (p=0.012) were statistically different between control group and disease group. In disease group, the G allele frequency at IL-1ß rs571556428 and T allele frequency at IL-6 rs543214973 were significantly higher (p<0.05). Genotype distributions at IL-1ß rs572292175 (p=0.017) and rs571556428 (p=0.000), and IL-6 rs543214973 (p=0.002) in disease group were also different from those in control group. In addition, the frequencies of CT genotype at IL-1ß rs572292175, AA genotype at IL-1ß rs571556428 and AA genotype at IL-6 rs543214973 in disease group were significantly lower (p<0.05). After modeling and analysis, it was found that the distribution of recessive model at IL-1ß rs571556428 (p=0.012) and IL-6 rs543214973 (p=0.014) in disease group exhibited significant differences from those in control group. The frequencies of TA haplotype at IL-1ß rs572292175 and rs571556428 (p=0.038) and GA haplotype at IL-6 rs1474348 and rs543214973 (p=0.047) in disease group were lower than those in control group (p<0.05). The polymorphisms at IL-1ß rs571556428 and IL-6 rs1474348 were significantly associated with gene expression (p<0.05). Moreover, the expressions of IL-1ß and IL-6 rose significantly in patients with GG genotype at rs571556428 and CG genotype at rs1474348, respectively (p<0.05). Furthermore, the polymorphism at IL-1ß rs571556428 was significantly correlated with the grade of Parkinson's disease (p=0.000). Parkinson's disease was in a higher grade (grade 4-5) in patients with AA genotype, whereas in a lower grade (grade 1-2) in patients with GG and AG genotypes. CONCLUSIONS: IL-1ß and IL-6 gene polymorphisms are significantly associated with the pathogenesis of Parkinson's disease.

MiR-20a lowers chemosensitivity of liver cancer Huh-7 cells via regulating NF-кB expression.

OBJECTIVE: The aim of this study was to explore the regulatory effect of micro ribonucleic acid (miR)-20a on nuclear factor-κB (NF-кB) in liver cancer Huh-7 cells, and to elucidate its influence on the chemosensitivity of Huh-7 cells. MATERIALS AND METHODS: Huh-7 cells with overexpression of miR-20a or knockout of miR-20a were first constructed. Quantitative polymerase chain reaction (qPCR) was adopted to detect the expression level of miR-20a in each group of cells. The sensitivity of cells to cisplatin and doxorubicin in each group was measured using methyl thiazolyl tetrazolium (MTT) assay, and the 50% inhibitory concentration (IC50) was calculated. Hoechst 33258 staining was performed to detect the apoptosis of cells in each group. Furthermore, the expression levels of apoptosis-associated proteins and the NF-кB signaling pathway-related proteins in each group of cells were determined via Western blotting. RESULTS: The expression level of miR-20a in blank control group was considerably higher than that in knockout group (p<0.01). Meanwhile, cells in overexpression group exhibited a notably higher expression level of miR-20a than blank control group (p<0.01). Cells in knockout group had dramatically enhanced sensitivity to doxorubicin and cisplatin (p<0.01), with a prominently decreased IC50 value (p<0.01). However, cells in overexpression group exhibited remarkably weakened sensitivity (p<0.01) and increased IC50 value (p<0.01). After treatment with doxorubicin and cisplatin, the apoptosis level of cells rose substantially in knockout group (p<0.01), whereas declined significantly in overexpression group (p<0.01). Moreover, knockout group exhibited a notably elevated expression level of Caspase-3 (p<0.01), and a considerably decreased ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein (Bax) (p<0.01). The expression level of Caspase-3 declined remarkably (p<0.01), however, the ratio of Bcl2/Bax increased substantially (p<0.01) in overexpression group. The expression level of NF-кB inhibitor beta (NF-кBIB) was markedly up-regulated (p<0.01), while the expression levels of Livin and Survivin declined remarkably (p<0.01) in knockout group. Furthermore, overexpression group had a considerably decreased expression level of NF-кBIB (p<0.01), but notably increased expression levels of Livin and Survivin (p<0.01). CONCLUSIONS: MiR-20a up-regulates the expressions of the downstream proteins Livin and Survivin, decreases the expressions of apoptosis-associated proteins, weakens the sensitivity of cells to chemotherapy drugs and lowers the apoptosis level of cells by activating the NF-кB signaling pathway in liver cancer Huh-7 cells.

Taq1a polymorphism (rs1800497) is associated with obesity-related outcomes and dietary intake in a multi-ethnic sample of children.

BACKGROUND: In adults, the Taq1a polymorphism (rs1800497) near the D2 receptor (DRD2) gene is associated with body mass index and binge eating and is more prevalent among non-Hispanic Blacks (NHB) and Hispanic-Americans (HA) relative to non-Hispanic Whites (NHW). We hypothesize Taq1a polymorphism (rs1800497) risk alleles contribute to paediatric racial/ethnic differences in obesity phenotypes. OBJECTIVES: This study aims to characterize the relationship between the Taq1a polymorphism (rs1800497), diet and adiposity in a multi-ethnic cohort of 286 children (98 NHB, 76 HA and 112 NHW), ages 7-12. METHODS: Dual-energy X-ray absorptiometry, computed tomography scans and two 24-h dietary recalls assessed body composition, fat distribution and dietary intakes, respectively. RESULTS: Children with two Taq1a risk alleles (NHB = 50.0%, HA = 43.3%, NHW = 6.7%) reported a 20% increase in total energy intake (P = 0.0034) and per cent of calories from sugar consumed (P = 0.0077) than did children with less than two risk alleles. Children with two Taq1a risk alleles demonstrated significantly higher total body fat (P = 0.0145), body fat percentage (P = 0.0377), intra-abdominal adiposity (P = 0.0459), subcutaneous abdominal adiposity (P = 0.0213) and total abdominal adiposity (P = 0.0209) than did children with one or no Taq1a risk alleles. CONCLUSIONS: Our results suggest that having two Taq1a risk alleles is associated with an increase in reported calorie and sugar consumption and is a potential risk factor for early development of excess adiposity in multi-ethnic children. These results need to be confirmed in a larger sample.

Evaluation of interleukin-6, interleukin-10 and human hepatocyte growth factor as tumor markers for hepatocellular carcinoma.

AIM: Serum alpha-fetoprotein (AFP) is the most important tumor marker for hepatocellular carcinoma (HCC). Previous reports indicated that HCC was also associated with increased levels of interleukin (IL)-6, IL-10 and hepatocyte growth factor (HGF). This study investigated the role of these cytokines as tumor markers for HCC. METHOD: A total of 128 adults were prospectively enrolled and categorized into four groups: normal subjects (n=29), chronic hepatitis B or C (n=50), non-HCC tumors (n=23) and HCC (n=26). Serum AFP, IL-6, IL-10 and HGF levels were determined in all subjects. RESULTS: The expression of IL-6 or IL-10 (> or =3 pg/ml), or high level of HGF (>1000 pg/ml) or AFP (>20 ng/ml) was observed in only 0-3% of normal subjects. Patients with HCC more frequently had higher IL-6 and IL-10 levels (p<0.05), whereas HGF levels in HCC patients were not significantly elevated compared to patients with chronic hepatitis or non-HCC tumors. Among patients with low (<20 ng/ml) AFP level, IL-6 or IL-10 expression was significantly associated with the existence of HCC (p<0.05). Patients with large (>5 cm) HCC more often had increased IL-6, IL-10 or AFP levels (p values all <0.05). CONCLUSIONS: Serum levels of IL-6 and IL-10 are frequently elevated in patients with HCC but not in benign liver disease or non-HCC tumors. IL-6 and IL-10 may help identify a subset of HCC patients with low AFP level, and may serve as complementary tumor markers in these patients.

Survival benefit of transcatheter arterial chemoembolization in patients with hepatocellular carcinoma larger than 10 cm in diameter.

BACKGROUND: The safety and survival benefit of transcatheter arterial chemoembolization for patients with huge hepatocellular carcinoma is uncertain. AIM: To evaluate the role of embolization in unresectable hepatocellular carcinomas larger than 10 cm. METHODS: Twenty-six consecutive patients who had an unresectable hepatocellular carcinoma larger than 10 cm and refused aggressive treatment, were enrolled as the control group. Another 31 patients matching with the control cases and undergoing embolization for huge unresectable hepatocellular carcinoma served as the embolization group. Survival between the two groups was compared. RESULTS: Two patients (7%) died from embolization-related complications. Patients in embolization group had longer survival than those in control group (median survival: 9.13 vs. 2.1 months). The 1-, 3- and 5-year survival rates in embolization group were 42%, 13% and 7% respectively. The 1- and 3-year survival rates for patients in control group were 8% and 0% respectively. In multivariate analysis, embolization and prothrombin ratio < or =1.2 were two independent factors associated with a better survival. CONCLUSIONS: Embolization-related mortality is low for huge hepatocellular carcinoma, and the technique provides survival benefit in patients with unresectable hepatocellular carcinomas larger than 10 cm in diameter.

The effects of experimentally manipulated social status on acute eating behavior: A randomized, crossover pilot study.

Both subjective and objectively measured social status has been associated with multiple health outcomes, including weight status, but the mechanism for this relationship remains unclear. Experimental studies may help identify the causal mechanisms underlying low social standing as a pathway for obesity. Our objective was to investigate the effects of experimentally manipulated social status on ad libitum acute dietary intakes and stress-related outcomes as potential mechanisms relating social status and weight. This was a pilot feasibility, randomized, crossover study in Hispanic young adults (n=9; age 19-25; 67% female; BMI ≥18.5 and ≤30kg/m(2)). At visit 1, participants consumed a standardized breakfast and were randomized to a high social status position (HIGH) or low social status position (LOW) in a rigged game of Monopoly™. The rules for the game differed substantially in terms of degree of 'privilege' depending on randomization to HIGH or LOW. Following Monopoly™, participants were given an ad libitum buffet meal and energy intakes (kcal) were estimated by pre- and post-weighing foods consumed. Stress-related markers were measured at baseline, after the game of Monopoly™, and after lunch. Visit 2 used the same standardized protocol; however, participants were exposed to the opposite social status condition. When compared to HIGH, participants in LOW consumed 130 more calories (p=0.07) and a significantly higher proportion of their daily calorie needs in the ad libitum buffet meal (39% in LOW versus 31% in HIGH; p=0.04). In LOW, participants reported decreased feelings of pride and powerfulness following Monopoly™ (p=0.05) and after their lunch meal (p=0.08). Relative to HIGH, participants in LOW demonstrated higher heart rates following Monopoly™ (p=0.06), but this relationship was not significant once lunch was consumed (p=0.31). Our pilot data suggest a possible causal relationship between experimentally manipulated low social status and increased acute energy intakes in Hispanic young adults, potentially influenced by decreased feelings of pride and powerfulness. Increased energy intake over time, resulting in positive energy balance, could contribute to increased risk for obesity, which could partially explain the observed relationship between low social standing and higher weight. Larger and longitudinal studies in a diverse sample need to be conducted to confirm findings, increase generalizability, and assess whether this relationship persists over time.

Hepatitis B virus X mutants derived from human hepatocellular carcinoma retain the ability to abrogate p53-induced apoptosis.

Chronic hepatitis B virus (HBV) infection and the integration of its X gene (HBx) are closely associated with the development of hepatocellular carcinoma (HCC). The integrated HBx frequently is truncated or contains point mutations. Previous studies indicated that these HBx mutants have a diminished co-transactivational activity. We have compared the effects of wild-type (wt) HBx and its naturally occurring mutants derived from human HCCs on transcriptional co-transactivation, apoptosis and interactive effects with p53. We demonstrated that overexpression of mutant, but not wt HBx, is defective in transcriptional co-transactivation of the NF-kappaB-driven luciferase reporter. By using a microinjection technique, the HBx mutants were shown to have an attenuated pro-apoptotic activity. This deficiency may be attributed to multiple mutations in the co-transactivation domain of HBx, that leads to decreased stability of the translated product. However, wt or mutant HBx bind to p53 in vitro and retain their ability to block p53-mediated apoptosis in vivo, which has been implicated as its major tumor suppressor function. The abrogation of p53-mediated apoptosis by integrated HBx mutants may provide a selective clonal advantage for preneoplastic or neoplastic hepatocytes and contribute to hepatocellular carcinogenesis.

The role of transcatheter arterial embolization for patients with unresectable hepatocellular carcinoma: a nationwide, multicentre study evaluated by cancer stage.

BACKGROUND: Transcatheter arterial embolization is a major palliative treatment for unresectable hepatocellular carcinoma, but the survival benefit of transcatheter arterial embolization is controversial. AIM: To evaluate the role of transcatheter arterial embolization in different stage of unresectable hepatocellular carcinoma and to select patients who can get the best benefit from the treatment. METHODS: From 1991 to 1995, 476 patients who had unresectable hepatocellular carcinoma from four medical centres in Taiwan were enrolled. Among them, 425 underwent transcatheter arterial embolization, and 51 received supportive treatment alone. The survivals between the two groups were compared. RESULTS: Among the 476 patients, transcatheter arterial embolization can significantly prolong survival. The 1-, 2-, and 5-year survival rates for patients who underwent transcatheter arterial embolization were 60.2%, 39.3%, and 11.5%; and the rates for patients who underwent supportive treatment were 37.3%, 17.6%, and 2%, respectively (P = 0.0002). The survival benefit of transcatheter arterial embolization was observed in patients between Cancer and the Liver Italian Program 0 and Cancer and the Liver Italian Program 4. In multivariate analysis, transcatheter arterial embolization, tumour size <5 cm and earlier Cancer and the Liver Italian Program stage were independent factors associated with a better survival. CONCLUSIONS: For patients who fulfilled the criteria of transcatheter arterial embolization, embolization can serve as a primary treatment for patients with unresectable hepatocellular carcinoma. The survival benefit of transcatheter arterial embolization is regardless of tumour stages.

Effect of calbindin D 28K on sodium transport by the luminal membrane of the rabbit nephron.

We previously reported that in the rabbit, the vitamin D-dependent calcium binding protein 28K (CaBP 28K) increases calcium (Ca2+) transport in the distal tubule by opening a high affinity Ca2+ channel in the luminal membrane. Since Na+ and Ca2+ transports are interdependent in this membrane, we questioned whether the calbindin has any influence on Na+ transport. Luminal membranes from rabbit proximal and distal tubules were purified and 22Na uptake by the membrane vesicles was measured using the rapid filtration technique. The vesicles were loaded with 280 mM mannitol and 20 mM Tris-Hepes pH 7.4, with either 3 microM CaBP or the carrier. Incubation medium contained 1 mM 22NaCl, 278 mM mannitol, and 20 mM Tris-Hepes pH 7.4. The presence of 3 microM CaBP 28K in the distal luminal membrane vesicles increased the 0.5 mM Ca2+ uptake from 0.91 +/- 0.21 to 1.84 +/- 0.33 pmol/microg/10 s (P < 0.01) and decreased 1 mM Na+ uptake from 0.62 +/- 0.15 to 0.27 +/- 0.08 pmol/microg/10 s (P < 0.05). A similar decrease of Na+ uptake was observed in proximal luminal membrane experiments. The effect on Na+ uptake by the distal membrane was dose-dependent with a IC50 of 4.5 microM. Addition of 2 mM Ca2+ to the incubation medium decreased 1 mM Na + uptake from 0.62 +/- 0.15 to 0.49 +/- 0.12 pmol/microg/10 s (P < 0.05), but did not influence the effect of CaBP 28K on Na+ uptake. Experiments performed in the presence and absence of ethyl isopropyl amiloride (EIPA) suggest that the effect of calbindin involves the Na+/H+ exchanger activity.

Acute renal failure after transarterial chemoembolization for hepatocellular carcinoma: a retrospective study of the incidence, risk factors, clinical course and long-term outcome.

BACKGROUND: Transarterial chemoembolization is effective for hepatocellular carcinoma. Acute renal failure may occur after transarterial chemoembolization because of radiocontrast agent, but its clinical aspects are unknown. AIM: To investigate the incidence, risk factors and outcome of acute renal failure, defined as increase of serum creatinine > 1.5 mg/dL, after transarterial chemoembolization. METHODS: A total of 235 hepatocellular carcinoma patients with 843 transarterial chemoembolization treatment sessions were analysed. RESULTS: Acute renal failure developed in 56 (23.8%) patients and the estimated risk of developing acute renal failure was 6.6% in each treatment session. Comparison between the episodes of transarterial chemoembolization with and without acute renal failure by using the generalized estimating equation disclosed that Child-Pugh class B (odds ratio: 2.6, P = 0.007) and treatment session (odds ratio: 1.3; P < 0.0001) were independent risk factors of acute renal failure. Twenty-seven patients had prolonged renal function impairment. Multivariate analysis by generalized estimating equation showed that Child-Pugh class B (odds ratio: 4.3, P = 0.0004) and diabetes mellitus (odds ratio: 5.2, P < 0.0001) were linked with prolonged acute renal failure, which independently predicted a decreased survival (relative risk: 2.3, P = 0.002). CONCLUSIONS: Acute renal failure after transarterial chemoembolization appears to be dose-related and is associated with the severity of cirrhosis. Patients with diabetes mellitus or Child-Pugh class B more frequently develop prolonged acute renal failure, which in turn is a poor prognostic predictor.

Comparison of transarterial chemoembolization and percutaneous acetic acid injection as the primary loco-regional therapy for unresectable hepatocellular carcinoma: a prospective survey.

BACKGROUND: Transarterial chemoembolization (TACE) and percutaneous acetic acid injection (PAI) are effective loco-regional therapies for hepatocellular carcinoma (HCC). AIM: To compare the therapeutic efficacy of TACE vs. PAI for unresectable HCC. METHODS: A total of 310 patients with unresectable HCCs (size

Factors predictive of liver cirrhosis in patients with chronic hepatitis B: a multivariate analysis in a longitudinal study.

OBJECTIVE AND DESIGN: Chronic hepatitis B virus (HBV) infection may lead to liver cirrhosis; however, factors associated with the development of cirrhosis have been incompletely studied. A total of 516 patients with chronic hepatitis B were followed up longitudinally to determine their outcome. METHODS: The clinical and pathological features were compared between those with and without cirrhosis occurrence. The risk factors were analysed, and the probability of the development of cirrhosis was estimated. RESULTS: During a mean follow-up period of 5.7 +/- 3.4 years (range 1-17 years), cirrhosis occurred in 71 patients, with a calculated annual incidence of 2.4%. Older age (> 45 years) at entry, male gender, persistent hepatitis (> 1.5-fold rise of serum alanine aminotransferase levels for at least one year) and diabetes mellitus were identified as independent risk factors of cirrhosis in a multivariate analysis (odds ratios 8.0, 19.3, 2.0 and 5.2, respectively; P values all < 0.05). A logistic regression equation was used to predict the probability of cirrhosis occurrence, which was as high as 76.6% when all risk factors were present. Acute exacerbation or super-infection by hepatitis C or D viruses were not significant predictors. Patients with subsequent cirrhosis had higher initial hepatic histological necro-inflammatory activities when compared to age- and sex-matched non-cirrhotic controls (Knodell's scores: 8.2 +/- 2.4 versus 6.0 +/- 4.1, P< 0.05). CONCLUSIONS: Patients who were elderly, male, diabetic or had a history of persistent and histologically severe hepatitis were at increased risks of liver cirrhosis. Aggressive anti-viral therapy may be needed for these patients and they should be closely monitored for HBV-related late complications.