[Correlation of carbon dioxide derived parameters during cardiopulmonary bypass with acute kidney injury after pediatric cardiac surgery].

Objective: To explore the correlation of the ratio of venous-arterial carbon dioxide (CO2) tension difference to arterial-venous O2 content difference (Pv-aCO2/Ca-vO2) and venous-arterial CO2 gradient (Pv-aCO2) during cardiopulmonary bypass (CPB) with acute kidney injury (AKI) after pediatric cardiac surgery. Methods: The clinical data of children (1 month ≤ age ≤ 3 years old) who underwent open heart surgery under CPB in West China Hospital of Sichuan University from March 2021 to August 2022 were retrospectively analyzed. All paired blood gases of the children during CPB (the sampling time interval of arterial and venous blood was within 10 minutes) were collected. According to the Failure, Loss, End-Stage Renal Disease (pRIFLE) diagnostic criteria, the children were divided into AKI group and non-AKI group. Multivariate logistic regression analysis was performed to identify the risk factors of postoperative AKI in pediatric cardiac surgery. Results: A total of 213 children were enrolled (101 males and 112 females), aged 12(6, 24) months, and 84 of them (39.4%) developed AKI. Three children died in AKI group, with a mortality of 3.6%. There were no deaths in non-AKI group. The incidence of postoperative low cardiac output syndrome (LCOS) was higher in AKI group [29.8% (25/84) vs 7.0% (9/129), P<0.001]. In addition, compared with the non-AKI group, children in AKI group had longer recovery time [15 (6, 78) h vs 6 (3, 19) h, P<0.001], mechanical ventilation time [17 (7, 97) h vs 6 (4, 20) h, P<0.001], intensive care unit (ICU) stay [6 (4, 11) d vs 3 (2, 5) d, P<0.001], and hospital stay [12 (9, 18) d vs 9 (8, 11) d, P<0.001]. A total of 317 arterial and venous blood gas pairs from 30 (n=207), 60 (n=75) and 90 min (n=35) after aortic clamping were included in the analysis. Univariate analysis showed that Pv-aCO2/Ca-vO2 (P=0.015) at 30 min after aortic clamping, Pv-aCO2 (P=0.041) and Pv-aCO2/Ca-vO2 (P=0.014) at 60 min after aortic clamping, peak Pv-aCO2 (P=0.009), peak Pv-aCO2/Ca-vO2 (P<0.001) and the average value of Pv-aCO2/Ca-vO2 (P=0.001) were higher in AKI group. Multivariate logistic regression analysis showed that longer duration of CPB (OR=1.013, 95%CI: 1.003-1.023, P=0.012), higher peak Pv-aCO2/Ca-vO2 (OR=1.337, 95%CI: 1.037-1.723, P=0.025) were risk factors for AKI. Conclusion: The occurrence of AKI after pediatric cardiac surgery is related to the short-term adverse clinical prognosis, and longer duration of CPB and higher peak Pv-aCO2/Ca-vO2 are independent risk factors for AKI.

Author Correction: An investigation into the mechanism of nobiletin's inhibition of papillary thyroid cancer using network pharmacology analysis and experimental pharmacology.

Correction to: European Review for Medical and Pharmacological Sciences 2023; 27 (4): 1553-1564. DOI: 10.26355/eurrev_202302_31398-PMID: 36876711-published online on February 15, 2023. After publication, the authors applied some corrections to the galley proof: -       The order of Table I and II has been inverted. -       The scale bar of Figure 9A has been inserted in the Legend. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/31398.

An investigation into the mechanism of nobiletin's inhibition of papillary thyroid cancer using network pharmacology analysis and experimental pharmacology.

OBJECTIVE: Surgery and radioactive iodine therapy are the main treatments for papillary thyroid carcinoma (PTC), and effective drugs are lacking. As a promising natural product, nobiletin (NOB) has a wealth of pharmacological activities like anti-tumor, antivirus, and other effects. In this research, bioinformatics methods and cellular assays were combined to explore how NOB inhibited PTC. MATERIALS AND METHODS: Our NOB targets were derived from three databases, including the SwissTargetPrediction database, Traditional Chinese Medicine System Pharmacology Database, and the TargetNet server. Four databases were used to identify disease-related targets: GeneCards, PharmGkb, Online Mendelian Inheritance in Man, and DisGeNET. Finally, cross-targets of disease and drug were deemed as pharmacological targets, and they were used for GO and KEGG enrichment analysis. STRING and Cytoscape were applied for PPI Network and core Targets Ranking. Molecular docking analysis validated binding affinity values for NOB and core targets. By using cell proliferation and migration assays, NOB was assessed for its effects on PTC proliferation and migration phenotype. Western blot validated the downregulation of the PI3K/Akt pathway. RESULTS: (1) Preliminarily, 85 NOB targets were predicted for NOB intervention in PTC. (2) Our core target screening identified TNF, TP53, and EGFR, and our molecular docking results confirmed good binding between NOB and protein receptors. (3) NOB inhibited proliferation and migration of PTC cells. PI3K/AKT pathway target proteins were downregulated. CONCLUSIONS: (1) Bioinformatics analyses revealed that NOB may inhibit PTC by regulating TNF, TP53, EGFR and PI3K/AKT signalling pathway. (2) As evidenced by cell experiments, there was an inhibition of proliferating and migrating PTCs by NOB via the PI3K/AKT signalling pathway.

[Effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis].

OBJECTIVE: To evaluate the effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis. METHODS: A "admission-hospitalization-discharge" whole-process health education model was created, 101 inpatients with ascites type of advanced schistosomiasis were given the whole-process health education. The scores of schistosomiasis control knowledge, attitudes towards schistosomiasis control and healthy behaviors, and awareness of schistosomiasis control knowledge, correct rate of attitudes towards schistosomiasis control and correct rate of healthy behaviors were compared among inpatients with ascites type of advanced schistosomiasis before and after implementation of the whole-process health education. RESULTS: The scores of schistosomiasis control knowledge, schistosomiasis control attitudes and healthy behaviors were all significantly higher among inpatients with ascites type of advanced schistosomiasis after implementation of the whole-process health education than before implementation (Z = -7.688, -3.576 and -4.328, all P values < 0.01). In addition, the awareness of schistosomiasis control knowledge increased from 54.3% to 82.7% (χ2 = 188.886, P < 0.01), and the correct rate of attitudes towards schistosomiasis control increased from 88.4% to 98.0% (χ2 = 22.001, P < 0.01), while the correct rate of healthy behaviors increased from 48.2% to 59.7% (χ2 = 11.767, P < 0.01). CONCLUSIONS: The whole-process health education model may remarkably improve the awareness of schistosomiasis control knowledge and promote the formation of positive attitudes towards schistosomiasis control and correct behaviors among inpatients with ascites type of advanced schistosomiasis, which is of great significance to facilitate patients' cure.

[Analysis of clinical and psychological characteristics in 250 patients with fibromyalgia].

To analyze the clinical and psychological characteristics of fibromyalgia (FM), so as to further understand and improve the capability of identifying FM. The clinical data of 250 FM patients diagnosed in the outpatient clinic of the Department of Rheumatology, the First Medical Center, Chinese PLA General Hospital, from December 2019 to September 2021, were collected and analyzed. The patients aged 40 (31.0, 52.3) years, including 188 female patients (75.2%) and 62 male patients (24.8%). There was a statistically significant difference in age comparison between female [42.5 (33.0,54.0) years] and male patients [32.5 (27.8,43.5) years] (P<0.001). The score of pain degree was 6 (4, 8), and [7 (5, 8)] of female patients was higher than [6 (4, 7)] of the male patients (P=0.040). The widespread pain index (WPI) was 13 (10,15). The regions with high pain incidence were left shoulder girdle (87.2%, 218/250), right shoulder girdle (86.8%, 217/250), upper back (86.4%, 216/250), neck (79.6%, 199/250) and lower back (77.6%, 194/250) and etc. The incidence of chest pain in female patients (55.3%, 104/188) was lower than that in male patients (75.8%, 47/62) (P=0.004). The symptom severity scale (SSS) score was 8 (7-10). 74.6% (185/248) suffered from anxiety and 77.5% (193/249) suffered from depression in 249 patients. Female patients were more common in FM patients than male patients, the median age of female patients was older than that of male patients, and the median score of pain severity of female patients was higher than male patients. Shoulders girdle, upper back, neck and lower back were the most frequently reported pain regions, and the incidence of chest pain in female patients was lower than that in male patients. The incidence of major non-painful symptoms was high and the proportion with anxiety or depression was high. The above clinical features are very helpful for early diagnosis of FM.

[Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors].

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

[Effect of rational emotive therapy on negative emotion in advanced schistosomiasis patients with repeated hospitalization].

OBJECTIVE: To examine the effect of rational emotive therapy on negative emotions among advanced schistosomiasis patients with repeated hospitalizations. METHODS: A total of 97 advanced schistosomiasis patients with anxiety and depressive emotions that were hospitalized in Xiangyue Hospital of Hunan Institute of Schistosomiasis Control for three times or more were enrolled, and given rational emotive therapy for 4 weeks in addition to routine nursing care. The scores for anxiety, depression and quality of life were estimated in patients before and after the rational emotive therapy using the Self-Rating Anxiety Scale (SRS), the Self-Rating Depression Scale (SDS) and WHOQOL-BREF Form. RESULTS: The SAS and SDS scores were significantly lower 4 weeks following rational emotive therapy than before the intervention (SAS score, 45.40 ± 7.77 vs. 59.25 ± 9.29, t = 14.021, P < 0.01; 51.48 ± 8.01 vs. 63.93 ± 9.59, t = 12.991, P < 0.01). The percentages of patients with moderate and severe anxiety and depression were significantly lower 4 weeks following rational emotive therapy than before the intervention (P < 0.01), and the scores for each item in the quality of life were all significantly greater 4 weeks following rational emotive therapy than before the intervention (P < 0.01). CONCLUSIONS: Rational emotive therapy may improve the negative emotions and the quality of life of advanced schistosomiasis patients with repeated hospitalizations.

Application of miniSTR Loci and Its Detection System for Degraded Materials in Forensic Medicine.

OBJECTIVES: To establish multiplex system of 16 miniSTR loci, and explore its application value for the degraded materials in forensic medicine. METHODS: The multiplex system of 16 miniSTR loci was established using a six-dye fluorescence labeling technology and its application value in forensic medicine was assessed. RESULTS: A six-dye fluorescence labeling miniSTR amplification kit was developed, which enabled 15 autosomal STR loci, Amelogenin locus and DYS391 to be typed simultaneously. This method showed good specificity and could provide stable and accurate typing results with a sensitivity of 50 pg. This system also provided a good test result for the normal biological sample of actual cases. CONCLUSIONS: The multiplex system of 16 miniSTR loci has application value for degraded and trace materials with the advantages of high sensitivity and database compatibility, which can be used for forensic casework.

Epigallocatechin-3-gallate local pre-exposure application prevents SHIV rectal infection of macaques.

Epigallocatechin-3-gallate (EGCG), a natural and major ingredient of green tea, has been shown to have anti-inflammation and anti-HIV-1 properties. We demonstrated that the intrarectal administration of EGCG could protect rhesus macaques from repetitive, intrarectal challenges with low-dose SHIVSF162P3N. This protection has a per-exposure risk reduction of 91.5% (P = 0.0009; log-rank test) and a complete protection of 87.5% (P < 0.001; Fisher's exact test). All protected animals showed no evidence of systemic and mucosal SHIV infection as demonstrated by the absence of viral RNA, DNA and antibodies. In contrast, all controls became infected after repeated SHIV challenges (a median of 2.5 times, range of 1-8 times). Mechanistically, EGCG could block the binding of HIV-1 gp120 to CD4 receptor and suppress the macrophage infiltration/activation in the rectal mucosa of macaques. These data support further clinical evaluation and development of EGCG as a novel, safe and cost-effective microbicide for preventing sexual transmission of HIV-1.

Inhibition of the Na+/H+ exchanger protects the immature rabbit myocardium from ischemia and reperfusion injury.

BACKGROUND: This study investigated the cardioprotective effects of pharmacologic pretreatment with HOE642, a selective Na(+)/H(+ )exchanger (NHE) isoform-1 inhibitor, in immature rabbit hearts, as compared with ischemic preconditioning (IPC). METHODS: For this study, 36 isolated immature New Zealand white rabbit hearts were equilibrated on the Langendorff apparatus. They were randomly divided into three groups: control group, IPC group, and HOE642 group. The hearts in each group were subjected to 60 min of ischemia plus 60 min of reperfusion (I/R). In the IPC group, the hearts were preconditioned by 5 min of ischemia followed by 10 min of reperfusion before I/R. In the HOE642 group, the hearts were pretreated with HOE642 (5 mumol/l) for 15 min before I/R. Left ventricular performance (LVDP, +dp/dt(max), -dp/dt(max)), coronory artery flow (CF), myocardial water content, adenosine triphosphate (ATP), cardiac-specific enzymes (creatine kinase [CK], CK fraction MB [CK-MB], and lacate dehydrogenase [LDH]), and intracellular calcium content were measured. Myocardial ultrastructure was observed under transmission electron microscopy. RESULTS: The recovery rates for left ventricular performance and CF in both the HOE642 and the IPC groups increased compared with those for the control subjects (p < 0.05). Moreover, the recovery rates for LVDP, +dp/dt(max), -dp/dt(max), and CF in the HOE642 group were markedly higher than in the IPC group at most time points of reperfusion (p < 0.05). Compared with the control group, CK, CK-MB, and LDH in the HOE642 group were decreased significantly (p < 0.05), whereas only LDH was reduced in the IPC group (p < 0.05). Water content was significantly reduced and ATP reserve was significantly increased in both the IPC and HOE642 groups (p < 0.05). However, compared with the IPC group, water content in the HOE642 group was significantly lower (81.26% +/- 1.26% vs 83.58% +/- 1.27%; p < 0.05) and ATP was significantly higher (21.46 +/- 2.40 vs 17.66 +/- 1.50 mug/g; p < 0.05). The HOE642 pretreatment exerted a better effect of reducing calcium overload than IPC (265.8 +/- 41.1 vs 408.5 +/- 56.8 mg/kg dry weight; p < 0.05). The blinded ultrastructural assessment under transmission electron microscopy showed that HOE642 brought about more myocyte salvage than IPC. CONCLUSION: This study demonstrated that HOE642 pretreatment is superior to IPC against ischemia and reperfusion injury in isolated immature rabbit myocardium.

Microsatellite mapping of a Triticum urartu Tum. derived powdery mildew resistance gene transferred to common wheat (Triticum aestivum L.).

A powdery mildew resistance gene from Triticum urartu Tum. accession UR206 was successfully transferred into hexaploid wheat (Triticum aestivum L.) through crossing and backcrossing. The F1 plants, which had 28 chromosomes and an average of 5.32 bivalents and 17.36 univalents in meiotic pollen mother cells (PMC), were obtained through embryos rescued owing to shriveling of endosperm in hybrid seed of cross Chinese Spring (CS) x UR206. Hybrid seeds were produced through backcrossing F1 with common wheat parents. The derivative lines had normal chromosome numbers and powdery mildew resistance similar to the donor UR206, indicating that the powdery mildew resistance gene originating from T. urartu accession UR206 was successfully transferred and expressed in a hexaploid wheat background. Genetic analysis indicated that a single dominant gene controlled the powdery mildew resistance at the seedling stage. To map and tag the powdery mildew resistance gene, 143 F2 individuals derived from a cross UR206 x UR203 were used to construct a linkage map. The resistant gene was mapped on the chromosome 7AL based on the mapped microsatellite makers. The map spanned 52.1 cM and the order of these microsatellite loci agreed well with the established microsatellite map of chromosome arm 7AL. The resistance gene was flanked by the microsatellite loci Xwmc273 and Xpsp3003, with the genetic distances of 2.2 cM and 3.8 cM, respectively. On the basis of the origin and chromosomal location of the gene, it was temporarily designated PmU.

One hundred and one new microsatellite loci derived from ESTs (EST-SSRs) in bread wheat.

Four hundred and seventy-eight microsatellite markers derived from expressed sequence tags (EST-SSRs) were screened among three mapping populations (W-7984xOpata 85, WOpop; LumaixHanxuan, LHpop; WenmaixShanhongmai, WSpop). The number of polymorphic EST-SSR primer pairs found in WOpop, LHpop and WSpop was 92, 58 and 29 respectively. A total of 101 EST-SSR loci amplified from 88 primer sets were distributed over the 20 chromosomes of the reference maps (no markers were located on chromosome 4B). These 101 mapped EST-SSR markers add to the existing 450 microsatellite loci previously mapped in bread wheat. Seventy-four of the 101 loci showed significant similarities to known genes, including 24 genes involved in metabolism, 4 in cellular structures, 9 in stress resistance, 12 in transcription, 2 in development, 2 transporters and 21 storage proteins. Besides gliadin and glutenin, most of the 53 genes with putative functions were mapped for the first time by EST-SSR markers in bread wheat. Sequence alignment of the mapped wheat EST-SSR loci allowed tentative assignment of functionality to the other members of grasses family. Colinearity combined with homology information offers an attractive approach to comparative genomics.

Changes in serum interleukin-8 and interleukin-12 levels in patients with ischemic heart disease in a Chinese population.

Increasing evidence has indicated the important roles of inflammation and immune response in the development of atherosclerosis and ischemic heart disease (IHD). We measured the serum interleukin (IL)-8 and IL-12 levels of patients with unstable angina pectoris (UAP) and patients with acute myocardial infarction (AMI), and compared findings with those of normal subjects. The results showed that the serum level of IL-8 was significantly higher in patients with UAP and patients with AMI than in healthy control subjects. To our knowledge, this is the first report that serum IL-12 level was elevated in patients with AMI but not in patients with UAP. These findings suggest that IL-8 and IL-12 are involved in the process of IHD, and serum IL-12 may be a marker for differentiating AMI from UAP.

Characterization of the human NDRG gene family: a newly identified member, NDRG4, is specifically expressed in brain and heart.

RTP/Drg1/Cap43/rit42/TDD5/Ndr1/NDRG1 (referred to as NDRG1 hereafter) is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation. Recently, the mutation of this gene was reported to be causative for hereditary motor and sensory neuropathy-Lom. Here, we cloned two human cDNAs encoding NDRG3 and NDRG4, which are homologous to NDRG1. These two genes, together with NDRG1 and a previously deposited cDNA (designated NDRG2), constitute the NDRG gene family. The four members share 57-65% amino acid identity. NDRG4 was further characterized because its mRNA expression was quite specific in brain and heart, in contrast to the relatively ubiquitous expression of the other three members. NDRG4 mRNA consists of three isoforms, NDRG4-B, NDRG4-B(var), and NDRG4-H. Northern and Western blot analyses showed that NDRG4-B was expressed only in the brain, whereas NDRG4-H was expressed in both brain and heart. NDRG4-B(var) was a minor product. NDRG4 expression was more abundant in adult than fetal brain and heart and was markedly decreased in the Alzheimer's diseased brain. In situ hybridization showed that NDRG4 was localized in neurons of the brain and spinal cord. The NDRG4 gene contains 17 exons. mRNA expression of the three NDRG4 isoforms is regulated by alternative splicing and possibly by alternative promoter usage. The finely tuned expression of the NDRG gene family members suggests that they have different specific functions.

Effects of storage and cooking on the iodine content in iodized salt and study on monitoring iodine content in iodized salt.

In order to ensure that the intake of iodine from iodized salt is adequate, the effects of cooking, storage and iodination on iodine content in iodized salt have been studied. For monitoring the analytical performance, a quality control examination was also undertaken. The loss of iodine was greater when salt was stored in plastic bag than in glass bottle. The loss was greater in fortified salt stored at 37 degrees C and under 76% humidity than in that at 20-25 degrees C and under lower humidity. The retention of iodine varied with the kind of foods and also was influenced by the water content of cooked food. In general, the retention of iodine during cooking varied considerably (from 36.6% to 86.1%). The iodine concentration in salts varied greater from 3.0 to 100.3 mg/kg in salt for markets, and from 0 to 90.0 mg/kg in salts for households. 48.3% of samples from markets were found to be in compliance with national standards (30-50 mg/kg), and 72.0% of samples from households were in compliance with national standard (20-50 mg/kg). Analytical data collected from 8 of the cooperative laboratories for an analytical reference material showed a 95% confidence interval of the population mean for both precision and accuracy, falling within X +/- 2SD and passing quality control examination.

Circadian and septadian variation in the occurrence of acute myocardial infarction in a Chinese population.

To investigate whether circadian or any other temporal pattern(s) exist in the occurrence of acute myocardial infarction (AMI) in a Chinese population, we analyzed 428 patients with confirmed AMI for temporal patterns of AMI occurrence. The patients admitted to the Affiliated Hospital of Shandong Medical University during 1991-95 were from Jinan, the capital city of Shandong Province of China, which has a population of 2.5 million. The chi-square test for goodness of fit was used to test the difference among the frequencies of AMI occurrence in 4 equal intervals (01.00-07.00 h, 07.00-13.00 h, 13.00-19.00 h, 19.00-01.00 h) during the day and among those on 7 days during the week. The results showed that AMI occurrence exhibited significant circadian (p<0.001) and septadian (day of the week) (p=0.046) periodicity, with a peak at 01.00-07.00 h and a trough at 13.00-19.00 h during the day, and a peak on Saturday and a trough on Wednesday during the week. The peak to trough ratio of risk was 2.7 during the day and 2.1 during the week. It is concluded that there were circadian and septadian biorhythms in AMI occurrence in the Chinese population and that these were different from those observed in Western populations. Further investigation of the underlying mechanisms may shed further light on the trigger mechanisms of AMI and thus be helpful in the prevention and treatment of AMI.

A precise interchromosomal reciprocal exchange between hot spots for cleavable complex formation by topoisomerase II in amsacrine-treated Chinese hamster ovary cells.

Among the aprt mutations induced in confluence-arrested Chinese hamster ovary D422 cells by the topoisomerase II poison amsacrine, there was a reciprocal exchange between the aprt gene and an unrelated sequence, accompanied by a chromosomal translocation at the aprt locus. The breakpoints in both parental sequences were hot spots for amsacrine-stimulated DNA cleavage in vitro, and the novel junctions formed were precisely as expected for a mechanism involving reciprocal exchange of topoisomerase II subunits followed by resealing of the breaks and correction of mismatches in the cohesive ends. The results are consistent with a role for direct subunit exchange in the production of chromosomal translocations by topoisomerase poisons, although more complex models involving double-strand breakage and repair could produce reciprocal exchanges of similar specificity.

Highly conservative reciprocal translocations formed by apparent joining of exchanged DNA double-strand break ends.

Chromosomal translocations induced by ionizing radiation and radiomimetic drugs are thought to arise by incorrect joining of DNA double-strand breaks. To dissect such misrepair events at a molecular level, large-scale, bleomycin-induced rearrangements in the aprt gene of Chinese hamster ovary D422 cells were mapped, the breakpoints were sequenced, and the original non-aprt parental sequences involved in each rearrangement were recovered from nonmutant cells. Of seven rearrangements characterized, six were reciprocal exchanges between aprt and unrelated sequences. Consistent with a mechanism involving joining of exchanged double-strand break ends, there was, in most cases, no homology between the two parental sequences, no overlap in sequences retained at the two newly formed junctions, and little or no loss of parental sequences (usually

Effects of isolation housing and timing of drug administration on amikacin kinetics in mice.

AIM: To study the influences of social condition and drug administration time on amikacin metabolism in mice. METHODS: Forty Male ICR mice were randomly assigned into 4 groups according to 1) housing condition: individual housing (I, one mouse in a cage) or aggregated housing (A, 10 mice in a cage) and 2) drug administration time: at midday (D) or at midnight (N), i.e. I-D, I-N, A-D, and A-N groups. Amikacin was injected s.c. 15 mg.kg-1 after 4 wk of raising at D or N. Blood samples were taken at 5, 10, 15, 20, 30, and 60 min after medication in each mouse. Plasma amikacin was measured by enzyme immunoassay. The concentration-time data were fitted with one-compartment open model in each mouse and data were analyzed with group t test. RESULTS: The clearance (Cl) of amikacin was larger and the half-life (T1/2) was shorter in A-N group than in A-D or I-N groups respectively. AUC(0-1) in A-N group was less than in I-N group. No differences of kinetic parameters between 2 isolated housing (I-D and I-N) groups were found. CONCLUSION: Aggregated housing and midnight drug administration increased the disposition of amikacin.