[Clinical and genetic analysis of cases of progressive familial intrahepatic cholestasis type 3].

Objective: To conduct clinical and genetic analysis in two cases of cholestatic liver disease to determine the specific etiology of cholestasis. Methods: Clinical data and the medical histories in family members of two cases were collected. The gene variation was detected by whole-exome sequencing technology. Sanger sequencing validation and bioinformatics analysis were performed on patients and their parents with suspected pathogenic mutations. Results: Whole-exome sequencing showed that the ABCB4 gene of case 1 (a male, 16 years old) had compound heterozygous mutations of c.646C > T from the father and c.927T > A from the mother, while the ABCB4 gene of case 2 (a female, 17 years old) had a compound heterozygous mutation of c.2784-1G > A from the father and c.646C > T from the mother. New mutation sites that had not been previously reported were c.646C > T, c.927T > A, and c.2784-1G > A. Conclusion: In this study, both cases had progressive familial intrahepatic cholestasis type 3 (PFIC-3) caused by ABCB4 gene mutations, and it also enriched the ABCB4 pathogenic variant spectrum. Whole-exome sequencing technology provides a reliable diagnostic tool for etiological analysis.

Application effect of multidisciplinary collaborative nursing process in emergency care of patients with hypertensive cerebral hemorrhage.

OBJECTIVE: The aim of the study was to analyze the effect of applying multidisciplinary collaborative nursing process (MCNP) in the emergency care of patients with hypertensive cerebral hemorrhage. PATIENTS AND METHODS: A total of 124 patients with hypertensive cerebral hemorrhage admitted to Qinghai University Affiliated Hospital from January 2020 to January 2021 was divided into control group (treated with regular emergency care, n=64) and study group (treated with MNCP, n=58). The effect of emergency treatment was compared between the two groups. RESULTS: Compared to the control group, initial treatment time, time of opening peripheral veins, first blood drawing time, time of imaging examination, emergency room treatment time, and hospital stay time were lower in MCNP group, the difference was significant (p<0.05). There were significant differences in Functional Independence Assessment (FIM) and National Institutes of Health Stroke Scale (NIHSS) scale scores between the control group and the MCNP group in treatment for 1 week in hospital (p<0.05). The level of total bile acid (TBA) and activated partial thromboplastin time (APTT) in the MCNP group were significantly lower than in the control group (p<0.05). The nursing satisfaction in MCNP was also improved compared to that in the control group (p<0.05). CONCLUSIONS: MCNP enhances the rational improvement of patients' awareness, improves the comprehensive quality of emergency treatments and optimizes prognosis; therefore, it is worthy of clinical promotion and application.

[Clinical features of children with post-primary tuberculosis].

Objective: The aim of this study was to summarize the clinical and imaging characteristics of post-primary tuberculosis in children, so as to improve the early identification and diagnosis of post-primary tuberculosis. Methods: This was a retrospective study which enrolled children who were admitted to the Department No.2 of Respiratory Medicine, Beijing Children's Hospital Affiliated to Capital Medical University between January 2015 to December 2020 and with a diagnosis of post-primary tuberculosis. Results: A total of 30 patients were enrolled, including 10 males and 20 females. The age on admission were 13.0 (12.0, 13.3) years. Their common symptoms were cough and fever, there were 26 cases (87%) with cough and 23 cases (77%) with fever, but only 4 cases (13%) had other toxic symptoms (night sweat, weakness or weight loss) of tuberculosis other than fever. Blood examination showed that the white blood cell count was (10±3)×109/L, accompanied by elevated proportion of neutrophils (0.69±0.11) and increased level of C-reactive protein (31 (15,81) mg/L). The common radiographic findings of CT were nodular or mass shadow with cavitation (19 cases (63%)), consolidation (13 cases (43%)), bronchogenic spread (12 cases (40%)), hilar or mediastinal lymphadenopathy (5 cases (17%)) in this cohort. The affected locations included the right upper lobe (21 cases (70%)), the left lower lobe (17 cases (57%)) and the right lower lobe (15 cases (50%)). Acid-fast bacillus smears and mycobacterial cultures were attempted for all cases, resulting in 33% (10/30) with smear positivity and 50% (15/30) with culture positivity. Conclusions: Post-primary tuberculosis in children has no specific clinical manifestations. Imaging of chest CT is mainly manifested as nodular shadow with cavitation, consolidation or bronchogenic spread. Accurate identification of post-primary tuberculosis is crucial for preventing the spread and early treatment of tuberculosis.

[Clinical features and early diagnostic clues of chronic granulomatous disease].

Objective: To explore the early clinical clues for diagnosis of chronic granulomatous disease (CGD). Methods: One hundred and thirty-nine children with CGD seen in Beijing Children's Hospital from January 2007 to October 2020 were included in this study. The clinical features including age of onset, first presentations, reason for being hospitalized, etiology, imaging features, clues for early diagnosis of all patients were evaluated retrospectively. According to the time of diagnosis, the patients were divided into two groups, cases diagnosed before 2015 and after 2015 and 2015. The time of diagnosis, the length of stay and the hospital charges were compared between the two groups. T test and χ2 test were used for statistical analyses. Results: One hundred and nineteen of the cases were males and 20 were females. The age of onset was 4 months (8 d to 14 years), and 103 cases (74.1%) had onset before 1 year of age. The age at diagnosis was 1.8 years (21 d to 14.7 years), and the time of diagnosis delay was 1 year (7 d to 13.7 years). One hundred and thirty-five cases (97.1%) had pulmonary infection as the main reason for hospitalization, of whom 76 cases (56.3%) had positive pulmonary etiology. One hundred and thirty-six patients (97.8%) were referred cases, of whom 5 were suspected of CGD before referral, and the misdiagnosis rate was as high as 96.3% (131/136). Eight early clues for diagnosis were found, the frequency from high to low, large bacillus Callmette-Guer scar in 99 cases (70.5%), left axillary lymphadenopathy or calcification in 73 cases (52.5%), skin or other lymph node infections in 58 cases (41.7%), skin scars in 50 cases (36.0%), multiple lung nodules in 42 cases (30.2%), perianal abscess in 35 cases (25.2%), pulmonary Aspergillus infection in 26 cases (18.7%) and pulmonary Burkholderia infection in 15 cases (10.8%). A total of 120 cases of CGD were diagnosed by respiratory burst test during hospitalization, including 55 cases diagnosed before 2015 and 65 cases diagnosed after 2015. After using these 8 early diagnosis clues, the cases diagnosed after 2015 had shorter time of diagnosis and the length of stay and lower hospitalization charge than cases diagnosed before 2014, and the difference was statistically significant ((25±7) vs. (10±5) d, (29±7) vs. (18±6) d, (3.7×104±1.2×104) vs. (3.2×104±1.2×104) Yuan, t=13.763, 9.262, 2.381, all P<0.05). Conclusions: Patients with CGD are younger at onset and the diagnosis is delayed. Pulmonary infections are the most common. Large BCG scar, left axillary lymphadenopathy or calcification, skin or other lymph node infections, skin scars, multiple lung nodules, perianal abscesses, pulmonary Aspergillus infection and Burkholderia infection can help early diagnosis of CGD.

[Clinical features of cystic fibrosis associated allergic bronchopulmonary aspergillosis in children].

Objective: To analyze the clinical features of cystic fibrosis (CF) associated allergic bronchopulmonary aspergillosis (ABPA) in children. Methods: A retrospective study was performed in 22 children who were diagnosed with CF associated ABPA in Beijing Children's Hospital affiliated to Capital Medical University from March 2010 to March 2020. The clinical features, imaging characteristics, laboratory results and the prognosis were reviewed. Results: A total of 22 cases met the diagnostic criterion, including 12 males and 10 females. The age of diagnosis was (10.4±2.8) years and the age of onset was (5.5±4.4) years. Clinical manifestations included cough and expectoration (22 cases), recurrent wheezing (15 cases), hemoptysis (7 cases), failure to thrive (12 cases), pancreatitis (10 cases), hepatomegaly (7 cases), splenomegaly (4 cases) and steatorrhea (4 cases). CT scans of all the patients showed pulmonary infiltrates and central bronchiectasis, combined with mucoid impaction in 17 cases and high density mucus plug in 12 cases. Eosinophilia was found in 18 patients. Total IgE and serum levels of A. fumigatus-specific IgE were elevated in all 22 patients. Positive culture of sputum or bronchoalvedar lauage fluid for fungus were in 15 cases, with single Aspergillus infection in 8 cases and mixed Aspergillus infection in 3 cases. The predominant bacteria found in the airways were Pseudomonas aeruginosa (17 cases), followed by staphylococcas. aureus (6 cases) and stenotrophomonas. maltophilia (5 cases). Pulmonary function revealed obstructive ventilation dysfunction in 4 cases, mixed dysfunction in 11 cases, and small airway dysfunction in 4 cases. Regarding the treatment, 3 were treated only with systemic corticosteroid, while the remaining 19 cases also received antifungal agents.The follow up continued for 1-7 years, and 6 maintained remission, 10 had recurrent episodes, 1 died, and 5 lost to follow up. Conclusions: CF associated ABPA is extremely rare in China. The overlapping clinical, radiographic, and immunologic features of these two diseases make the diagnosis challenging. Systemic corticosteroids are considered the first-line therapy for these patients, and adjuvant antifungal agents may be helpful. Recurrence rate in our center is high.

[Value of sweat conductivity testing in the diagnosis of cystic fibrosis in children].

Objective: To assess the diagnostic value of sweat conductivity testing in Chinese children with cystic fibrosis (CF). Methods: This is a retrospective study. Sweat conductivity tests were conducted in 45 CF children (CF group) and 200 non-CF children (non-CF group) diagnosed with other chronic pulmonary diseases at the No. 2 Department of Respiratory Medicine, Beijing Children's Hospital from May 2014 to June 2018. Pearson's chi-square test was used to assess the differences between CF and non-CF groups. A receiver operating characteristic curve was constructed to calculate the best cut-off value to diagnose or rule out CF. The pulmonary function parameters (forced expiratory volume in the first second, forced vital capacity,forced expiratory flows at 75% of exhaled vital capacity) of CF children over 6 years old were analyzed. The relationship between sweat conductivity and pulmonary function was compared between the two groups (80-120mmol/L vs.>120mmol/L). Results: The age of CF group was 9 (7,12) years old, 19 males (42%) and 26 females(58%); the age of non-CF group was 8 (5,11) years old, 106 males (53%) and 94 females(47%). The results of sweat conductivity test showed that sweat conductivity in CF group 108(99, 122) mmol/L was significantly higher than that in non-CF group 43(36, 52) mmol/L (χ(2)=207, P<0.01). A cut-off value of 80 mmol/L for CF diagnosis showed a sensitivity of 93.3% and a specificity of 98.5%. The receiver operating characteristic curve analysis suggested the best conductivity cut-off value for the diagnosis of CF was at 83.5 mmol/L,with a sensitivity of 93.3% and a specificity of 100%,and an area under the curve of 0.993 (95% confidence interval 0.985-1.000). The best conductivity cut-off value to rule out CF diagnosis was at 63.5 mmol/L,with a sensitivity of 97.8% and a specificity of 90.5%. There was no correlation between the level of sweat conductivity and the extent of pulmonary function decline. Conclusions: Sweat conductivity testing can be used for the screening of CF in Chinese children. A diagnosis of CF should be considered if the value is greater than 80 mmol/L.

[Analysis on efficacy and safety of total neoadjuvant therapy in patients with locally advanced rectal cancer with high risk factors].

Objective: To evaluate the safety and preliminary efficacy of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer (LARC) with high risk factors. Methods: Data of 101 patients who were diagnosed with stage II-III rectal cancer with high risk factors and received TNT between March 2015 and January 2018 at West China Hospital of Sichuan University were analyzed retrospectively. Inclusion criteria: (1) patients were diagnosed with stage II-III rectal cancer by high-resolution MRI combined with CT and endorectal ultrasound; (2) at least one high risk factor: cT4a, cT4b, cN2, EMVI+, CRM+ and lateral lymph node+; (3) distance from tumor to anal verge was within 15 cm; (4) Eastern Collaborative Oncology Group (ECOG) performance status score was 0-1; bone marrow function, liver function and kidney function were suitable for chemoradiotherapy; (5) patients were treated with TNT strategy; (6) the follow-up data and postoperative pathological data were complete. Patients with previous rectal cancer surgery (except prophylactic colostomy), pelvic radiotherapy, and systemic chemotherapy, those with distant metastases, those without neoadjuvant radiotherapy, those receiving less than 4 cycles of neoadjuvant chemotherapy were excluded. The regimen of TNT: 3 cycles of induction CAPOX (oxaliplatin plus capecitabine) were followed by pelvic radiotherapy and concurrent CAPOX, then 3 cycles of consolidation CAPOX were delivered after radiotherapy. Total mesorectal resection (TME) or watch-and-wait strategy was selected according to the therapeutic effect and patients' wishes. Short-term efficacy, including tumor regression grade (TRG), pathological complete response (pCR), clinical complete response (cCR), postoperative complications within 30 days of surgery, and adverse events (AE) to radiotherapy and chemotherapy (measured using CTCAE 4.0) was analyzed. Results: The 101 patients included 68 males (67.3%) and 33 females (32.7%) with a median age of 54 years. The proportion of patients with cT4a, cT4b, cN2 and enlarged lateral lymph node was 13.9%, 29.7%, 56.4% and 43.6%, respectively. The mean cycle of neoadjuvant chemotherapy was 6.0±1.3. Seventy-five patients (74.3%) received at least 6 cycles of neoadjuvant chemotherapy and 100 (99.0%) completed radiotherapy. The mean cycle of induction and consolidation chemotherapy was 2.0±0.9 and 2.8±1.0 respectively. Most common grade 3 AE was leucopenia (n=13, 12.9%) and thrombocytopenia (n=7, 6.9%). Grade 3 diarrhea and radiation dermatitis were observed in 5 cases (5.0%) respectively. Grade 3 anemia and rectal pain were observed in 4 cases (4.0%) respectively. And rectal mucositis was observed in 2 cases (2.0%). Most of the AE was observed during concurrent chemoradiotherapy. No grade 4 or higher AE was observed. After TNT, 32 patients (31.7%) achieved pCR or cCR, and 62 patients (60.4%) achieved partial response (PR). Only 2 patients (2.0%) developed distant metastasis after chemoradiotherapy, while the other patients did not show disease progression. Seven patients (6.9%) with cCR refused surgery and selected watch-and-wait, while 7 patients without cCR still refused surgery. The other 87 patients (86.1%) underwent TME successfully. The mean interval from the completion of chemoradiotherapy to surgery was (20.1±8.5) weeks. The R0 resection rate was 97.7% (85/87).The morbidity of surgical complication was 16.1% (14/87), including pelvic infection or abscess in 6 cases (6.9%), anastomotic leakage in 3 (3.4%), hemorrhage in 2 (2.3%), and gastrointestinal dysfunction in 3 (3.4%). Pathological findings revealed that 24 cases (27.6%) had TRG 0, 20 (23.0%) had TRG 1, 30 (34.5%) TRG 2, and 13 (14.9%) TRG 3. Conclusion: TNT is safe and has good short-term efficacy for locally advanced rectal cancer patients with high risk factors.

Establishment of TBS reference plots and correlation between TBS and BMD in healthy mainland Chinese women.

UNLABELLED: The trabecular bone score (TBS) was obtained from the gray levels of a dual X-ray absorptiometry (DXA) image to evaluate bone microarchitecture. Here, we established the reference plots of TBS in healthy Chinese women of Nanjing area. The TBS references are similar with French and US Caucasian women but higher than Japanese women. PURPOSE: The aim of the study was to establish the reference plots of the TBS in healthy Chinese women of the Nanjing area. METHODS: A total of 537 healthy Chinese women of the Nanjing area were recruited, and the study was approved by the Ethics Committee of the First Affiliated Hospital with Nanjing Medical University. The TBS of the lumbar spine and the bone mineral density (BMD) of the lumbar spine and femur were measured using dual X-ray absorptiometry. The mean ± standard deviation (SD) of the TBS in women with different age groups was calculated. The correlation of TBS and age and BMD was calculated using regression analysis. RESULTS: The reference plots of the TBS were established in healthy Chinese women of the Nanjing area between the ages of 20 and 89 years. The average TBS for total subjects was 1.32 ± 0.11 and reached the peak at the age of 20-29 years and then decreased with age thereafter. The determinant coefficient between TBS and age was 0.5065 while between TBS and BMD was 0.5191. After adjusting for lumbar total BMD, the TBS significantly correlated with age in whole subjects and only in the subgroup of ages 50-59 years. CONCLUSIONS: This study suggested that TBS decreased with age and correlated positively with BMD. The TBS reference of Chinese women is similar with those of French and US Caucasian women but higher than that of Japanese women. Furthermore, the TBS may be more significantly applied in women in menopause for less than 10 years.

Elevated BDNF mRNA expression in the medial prefrontal cortex after d-amphetamine reinstated conditioned place preference in rats.

Drug addiction behavior that is established and maintained by psychostimulants has been shown to be associated with the expression of brain-derived neurotrophic factor (BDNF) in the mesolimbic dopamine (DA) system. Cocaine has been used for most prior studies testing this effect of psychostimulants and therefore relatively little is known about its counterpart amphetamine (AMP). To fill this gap, the present study was designed to test whether BDNF mRNA expression levels in the DA terminal regions were changed specifically by d-AMP-induced conditioned place preference (CPP) followed by drug-primed reinstatement. The dose of d-AMP, 1mg/kg, was confirmed to significantly induce CPP. Using this dose, a group of rats was initially subjected to d-AMP CPP, which was followed by entry into an extinction protocol with an additional 3-day withdrawal before a drug-primed reinstatement test was carried out. Following extinction of d-AMP CPP, a lower dose of d-AMP, namely 0.75mg/kg, was able to significantly reinstate CPP. The BDNF mRNA levels in the selected brain areas were determined by real-time polymerase chain reaction (PCR) after the CPP and reinstatement. The BDNF mRNA level in the medial prefrontal cortex (mPFC) was significantly increased after the reinstatement, but not the CPP test. And, none of the other four assessed brain areas showed any change in BDNF mRNA level after d-AMP CPP or reinstatement. These findings support the notion that BDNF is involved in drug-seeking behavior and indicate that d-AMP reinstatement after extinction may be linked to an increase in BDNF mRNA expression in the mPFC.

Decreased thrombospondin-I (TSP-I) expression in the hippocampus of streptozotocin-induced diabetic rats.

Diabetes mellitus (DM) may give rise to cognitive impairment, but the pathological mechanism involved was still unknown. We investigated the thrombospondin-I (TSP-I) expression level in hippocampus of streptozotocin-induced diabetic rats, which, as a matricellular, calcium-binding protein that participates in cellular responses to growth factors, cytokines and injury, has been indicated as important synaptogenic components recently. We employed 20 streptozotocin (STZ)-induced diabetic rats. The weight, blood sugar and urine sugar were measured before and after model induction in diabetes and normal groups. We did immunohistochemical localization of TSP-I and RT-PCR was applied to determine TSP-I mRNA level in the hippocampus of both groups. Moreover, transmission electron microscope (TEM) was used to study the ultrastuctural changes of the hippocampus. All data were analyzed by the independent samples t-test. We found that the expression of TSP-I markedly decreased in the hippocampal neuronal cells. Moreover, TEM results showed the ultrastructures of diabetic hippocampus, including area CA1 and DG, neurons were characterized by mitochondria swelling, increased heterochromatin accumulation and reduced synaptic contacts. The present study provides experimental evidences that decreased TSP-I expression may help to explain the reduced synaptogenesis and altered hippocampal ultrastucture, both of which may contribute to the pathogenesis of diabetic dementia.

Inhibition of quorum sensing in Serratia marcescens H30 by molecular regulation.

Quorum sensing in Serratia marcescens, which uses two types of signaling molecules-N-acyl homoserine lactones and furanosyl borate diester-play important regulatory roles in the synthesis of 2,3-butanediol and prodigiosin. In the hope of understanding the effect of quorum sensing on physiologic metabolism, we established two molecular strategies, one to express acyl-homoserine lactone hydrolase to inactivate AI-1 signaling molecule using an expression vector with lactose as the inducer and the other to mutate luxS gene with a suicide plasmid pUTKm2 to inhibit the synthesis of AI-2 signaling molecule.

Molecular characterization of Serratia marcescens strains by RFLP and sequencing of PCR-amplified 16S rDNA and 16S-23S rDNA intergenic spacer.

AIMS: To establish the specific DNA patterns in 16S rDNA and 16S-23S rDNA intergenic spacer (IGS) regions from different kinds of Serratia marcescens strains using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and sequences analysis. METHODS AND RESULTS: Two pairs of primers based on the 16S rDNA and 16S-23S rDNA IGS were applied to amplify the rrn operons of two kinds of S. marcescens strains. About 1500 bp for 16S rDNA and four fragments of different sizes for 16S-23S rDNA IGS were obtained. PCR-amplified fragments were analysed by RFLP and sequence analysis. Two distinct restriction patterns revealing three to five bands between two kinds of strains were detected with each specific enzyme. According to the sequence analysis, two kinds of strains showed approximately 97% sequence homology of 16S rDNA. However, there was much difference in the sequences of IGS between the two kinds of strains. Intercistronic tRNA of strains H3010 and A3 demonstrated an order of tRNA of 5'-16S-tRNA(Ala)-tRNA(Ile)-23S-3', but strain B17 harboured the tRNA of 5'-16S-tRNA(Glu)-tRNA(Ile)-23S-3'. CONCLUSIONS: The method was specific, sensitive and accurate, providing a new technique for differentiating different strains from the same species. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper provided the first molecular characterization of 16S rDNA and 16S-23S rDNA IGS from S. marcescens strains.

Influence of interleukin-2 on Ca2+ handling in rat ventricular myocytes.

In the present study, we examined the effect of interleukin-2 (IL-2) on cardiomyocyte Ca(2+) handling. The effects of steady-state and transient changes in stimulation frequency on the intracellular Ca(2+) transient were investigated in isolated ventricular myocytes by spectrofluorometry. In the steady state (0.2 Hz) IL-2 (200 U/ml) decreased the amplitude of Ca(2+) transients induced by electrical stimulation and caffeine. At 1.25 mM extracellular Ca(2+) concentration ([Ca(2+)](o)), when the stimulation frequency increased from 0.2 to 1.0 Hz, diastolic Ca(2+) level and peak intracellular Ca(2+) concentration ([Ca(2+)](i)), as well as the amplitude of the transient, increased. The positive frequency relationships of the peak and amplitude of [Ca(2+)](i) transients were blunted in the IL-2-treated myocytes. The effect of IL-2 on the electrically induced [Ca(2+)](i) transient was not normalized by increasing [Ca(2+)](o) to 2.5 mM. IL-2 inhibited the frequency relationship of caffeine-induced Ca(2+) release. Blockade of sarcoplasmic reticulum (SR) Ca(2+)-ATPase with thapsigargin resulted in a significant reduction of the amplitude-frequency relationship of the transient similar to that induced by IL-2. The restitutions were not different between control and IL-2 groups at 1.25 mM [Ca(2+)](o), which was slowed in IL-2-treated myocytes when [Ca(2+)](o) was increased to 2.5 mM. There was no difference in the recirculation fraction (RF) between control and IL-2-treated myocytes at both 1.25 and 2.5 mM [Ca(2+)](o). The effects of IL-2 on frequency relationship, restitution, and RF may be due to depressed SR functions and an increased Na(+)-Ca(2+) exchange activity, but not to any change in L-type Ca(2+) channels.

[Hydrogen peroxide augments the injury effect of iron on the isolated rat heart and cardiomyocytes].

By using Langendorff perfused rat heart and enzymatically isolated cardiomyocytes, we investigated the augmented injury effect of iron on the myocardium by hydrogen peroxide and the underlying mechanisms. Cell-permeable iron (Fe-HQ) decreased the contractile amplitude, velocity and end-diastolic cell length of the cardiomyocyte but increased the contents of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and the myocardial malondialdehyde (MDA) while the left ventricular developed pressure (LVDP), +/-dp/dt(max), heart rate and coronary flow showed biphasic alterations. Hydrogen peroxide augmented the injury effect of iron accompanied by increases of coronary LDH, CK release and myocardial MDA content and decreases of LVDP, +/-dp/dt(max), and heart rate. Reduced glutathione could antagonize the injury effect of iron and hydrogen peroxide on the myocardium while dimethyl sulfoxide had no injury effect on the isolated heart. It is suggested that the functional injury of sulfhydryl group containing proteins may be involved in the augmentation of myocardial injury due to the increase of intracellular iron by hydrogen peroxide, but hydroxyl radicals may not.

[Effects of interleukin-2 on the isolated rat heart and the mechanism].

The purpose of the present study was to explore the biological effects and mechanism of interleukin-2 (IL-2) on the isolated rat heart. The results showed that hrIL-2 increased the number of premature ventricular contraction, heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure and coronary flow in the isolated perfused rat heart. Heat inactivated hrIL-2 had no effect on the heart. Pretreatment with ryanodine canceled the positive effects of hrIL-2 on left ventricular developed pressure, left ventricular end-diastolic pressure and coronary flow but had no effects on arrhythmogenesis and tachycardia by hrIL-2. Pretreatment with nifedipine or low extracellular calcium abolished the arrhythmogenic effect of hrIL-2 and attenuated partially the augment of heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure and coronary flow. It suggests that the cardiac activity of hrIL-2 depended on the integrity of its spatial structure and transmembrane influx Ca2+ and intracellularly stored Ca2+ were involved in the cardiac activity of hrIL-2.

Operant performance following tail-pinch in the rat: effects of d-amphetamine.

To extend the investigation of tail-pinch induced behavioral changes, rats performing on a differential reinforcement of low rates of 10 sec (DRL10), a fixed-interval of 60 sec (F160), and a fixed-ratio of 20 (FR20) schedules were exposed to a paper clip applied to the tail. While a 10 min tail-pinch conducted 1 hr before operant sessions significantly altered the DRL10 behavior, this stressor had little effect on either F160 or FR20 responding. Marked DRL10 behavior performance changes following tail-pinch included increases in the number of lever presses, decreases in the number of the reinforcers, and disruption in the frequency distribution of inter-response times (IRT). These DRL10 operant deficits were diminished when the subject received a tail-pinch pretreatment followed by d-amphetamine treatment (0.2 and 2.0 mg/kg). In combination with biochemical data from others, the present results suggest that catecholamine systems are involved in modulation of DRL10 behavior following tail-pinch.

Arsenic trioxide-induced apoptosis and differentiation are associated respectively with mitochondrial transmembrane potential collapse and retinoic acid signaling pathways in acute promyelocytic leukemia.

Recent studies showed that arsenic trioxide (As2O3) could induce apoptosis and partial differentiation of leukemic promyelocytes. Here, we addressed the possible mechanisms underlying these two different effects. 1.0 microM As2O3-induced apoptosis was associated with condensation of the mitochondrial matrix, disruption of mitochondrial transmembrane potentials (DeltaPsim) and activation of caspase-3 in acute promyelocytic leukemia (APL) cells regardless of their sensitivity to all-trans retinoic acid (ATRA). All these effects were inhibited by dithiothreitol (DTT) and enhanced by buthionine sulfoximine (BSO). Furthermore, BSO could also render HL60 and U937 cells, which had the higher cellular catalase activity, sensitive to As2O3-induced apoptosis. Surprisingly, 1.0 microM As2O3 did not induce the DeltaPsim collapse and apoptosis, while 0.1 microM As2O3 induced partial differentiation of fresh BM cells from a de novo APL patient. In this study, we also showed that 0.2 mM DTT did not block low-dose As2O3-induced NB4 cell differentiation, and 0. 10.5 microM As2O3 did not induce differentiation of ATRA-resistant NB4-derived sublines, which were confirmed by cytomorphology, expression of CD11b, CD33 and CD14 as well as NBT reduction. Another interesting finding was that 0.10.5 microM As2O3 could also induce differentiation-related changes in ATRA-sensitive HL60 cells. However, the differentiation-inducing effect could not be seen in ATRA-resistant HL60 sublines with RARalpha mutation. Moreover, low-dose As2O3 and ATRA yielded similar gene expression profiles in APL cells. These results encouraged us to hypothesize that As2O3 induces APL cell differentiation through direct or indirect activation of retinoic acid receptor-related signaling pathway(s), while DeltaPsim collapse is the common mechanism of As2O3-induced apoptosis.