[Associations between plasma n-3 polyunsaturated fatty acids and gestational diabetes mellitus in the second trimester].

Objective: To examine the associations between plasma n-3 polyunsaturated fatty acids (PUFAs) in the second trimester and gestational diabetes mellitus (GDM) among Chinese pregnant women. Methods: Based on data from the Tongji-Shuangliu Birth Cohort enrolled from 2017 to 2019 in the Shuangliu Maternal and Child Health Hospital, it conducted a case-control study among 269 GDM cases who were diagnosed by 75 g oral glucose tolerance test, and 538 non-GDM controls matched at a 1∶2 ratio on maternal age and gestational weeks. The age range of the 807 women was 18-40 years. Fasting plasma n-3 PUFAs were determined by gas chromatography-mass spectrometry in the second trimester (24-28 weeks). Participants were categorized into quartiles (Q1-Q4) of plasma n-3 PUFAs based on distributions in the control group. Conditional logistic regression models were applied to estimate the associations between plasma n-3 PUFAs and GDM. Results: The median (interquartile) relative concentrations of plasma n-3 PUFA C22∶5n-3 was significantly lower in women with GDM 0.87 (0.72, 1.07) compared with women without GDM 0.94 (0.75, 1.19)(P=0.001). Plasma n-3 PUFA C22∶5n-3 was inversely associated with GDM, with an OR (95%CI) of 0.75 (0.62-0.90) for each SD increase of relative concentration. Compared with the Q1 group, the OR values and 95%CIs of Q2, Q3, and Q4 groups were 0.97 (0.62-1.51), 0.72 (0.45-1.15), and 0.54 (0.32-0.90), respectively (Ptrend<0.05). However, there were no significant associations of C18∶3n-3, C20∶5n-3, C22∶6n-3, and total n-3 PUFAs with GDM. Conclusion: Plasma n-3 PUFA C22∶5n-3 was inversely associated with GDM during the second trimester.

[Association between serum uric acid to creatinine ratio and metabolic syndrome based on community residents in Chashan town, Dongguan city].

Objective: To analyze the association between serum uric acid to creatinine ratio (SUA/Cr) and metabolic syndrome among community residents in Chashan town, Dongguan city. Methods: Participants were from the prospective cohort study of chronic diseases in natural populations in South China conducted in Chashan town, Dongguan city from 2018 to 2019. A total of 11 334 participants with complete data were included by using convenient sampling method. Demographic characteristics, lifestyle and health status were collected through questionnaire and physical examination. The venous blood of the subjects was collected to detect the levels of serum uric acid, creatinine and blood lipid. All participants were divided into four groups (Q1-Q4) according to the quartile of SUA/Cr level. The relationship between SUA/Cr and metabolic syndrome and its components (abdominal obesity, high triglyceride, low level of high density lipoprotein cholesterol, hypertension and abnormal glucose metabolism) were analyzed by using logistic regression model. Results: The mean age of 11 334 participants was (49.52±10.02) years. Male participants accounted for 44.2% (5 015/11 334). The prevalence of metabolic syndrome was 31.2% (3 532/11 334), and the level of SUA/Cr was 5.17±1.53. The prevalence of metabolic syndrome in group Q1-Q4 was 22.3% (631/2 834), 26.5% (752/2 833), 34.9% (988/2 833) and 41.0% (1 161/2 834), respectively. After adjusting for relevant confounding factors, the result of logistic regression model showed that compared with group Q1, the risk of metabolic syndrome in group Q2-Q4 was significantly higher, with OR (95%CI) values about 1.41 (1.23-1.60), 2.19 (1.93-2.49) and 3.01 (2.65-3.42) respectively. The risk of each component of metabolic syndrome in group Q2-Q4 was higher (Ptrend<0.001). The SUA/Cr level of participants with normal uric acid level was significantly positively correlated with metabolic syndrome. The risk of metabolic syndrome increased with the increase of SUA/Cr level, but there was the same trend without significant differences in patients with hyperuricemia (Pinteraction=0.008). Conclusion: There is a positive correlation between SUA/Cr level and the risk of metabolic syndrome among community residents in Chashan town, Dongguan city.

[Relationship of quality and duration of sleep with hypertension among adults in Guangzhou].

Objective: To explore the relationship of sleep quality and sleep duration with hypertension among adults aged 30-79 years old in Guangzhou. Methods: According to multi-stage stratified cluster sampling, 12 747 residents aged 30-79 years old were sampled and surveyed in Guangzhou from January 2018 to March 2019. Data on general demographic characteristics, sleep quality, sleep duration and hypertension were collected through questionnaire survey, the Pittsburgh sleep quality index (PSQI) and physical examination. Multivariate logistic regression models were used to analyze the putative association between sleep quality, sleep duration and hypertension. Restrictive cubic spline curve was used to draw the dose-response relationship curve between sleep quality, sleep time and hypertension. Results: The mean age of the subjects was (52.68±12.17) years, the prevalence of hypertension was 36.6% (4 664/12 747), the average score of PSQI was (4.70±2.88), and the average sleep time was (7.00±1.32) hours. The prevalence of hypertension was positively associated with the PSQI score. Compared to the subjects with a score less than 3, OR (95%CI) of hypertension with a PSQI score of 3-5, 5-8, ≥9 were 1.14 (1.02-1.27), 1.17 (1.03-1.34), 1.41 (1.21-1.64), respectively. The relationship between sleep duration and hypertension appeared U-shaped. Compared with 6 to 8 hours sleep duration, both sleep duration<6 hours with OR(95%CI) of 1.27(1.12-1.43) or >8 hours with OR(95%CI) of 1.20(1.05-1.38) was associated with hypertension. Conclusion: Both poor sleep quality, longer or shorter sleep duration were responsible for increased risk of cognitive impairment in older Chinese.

Amelogenin domain-containing NlChP38 is necessary for normal ovulation in the brown planthopper.

The brown planthopper (BPH), Nilaparvata lugens, is a major threat to rice production. The eggshell plays an important role in insect reproduction. The constituents and formation process of BPH eggshells remains largely unknown. Here, we report a novel eggshell-associated protein, NlChP38, containing an amelogenin domain, that is essential for normal ovulation in the BPH. NlChP38 is specifically expressed in the follicular cells from egg chambers at both RNA and protein levels. RNA interference of NlChP38 resulted in oocytes with loose and thin eggshell structure and caused ovulation difficulties. Immunofluorescence localization showed NlChP38 is deposited between follicular cells and oocytes during late choriogenesis. These results indicate that NlChP38 plays an important role in eggshell formation and could be a potential target for RNA interference control of the BPH.

[The value of Clermont score in detection intestinal mucosal ulcer of Crohn's disease].

Objective: To explore the value of Clermont score in the detection of intestinal mucosal ulcer in Crohn's disease (CD). Methods: From May 2015 to August 2017, 45 patients (28 males and 17 females; median age was 25 years) were confirmed to have ileocolic CD by endoscopic and pathological examinations at Nanjing General Hospital. All patients underwent MRE and DWI examinations. Based on the appearance of intestinal mucosa endoscopically, intestine segments from 45 patients were divided into three groups, namely, no ulceration group (NU), superficial ulceration group (SU), and deep ulceration group (DU). Several factors contribute to Clermont score calculation. These included the measurement of intestinal wall thickness using MRE, evaluation of intestinal wall edema and ulceration by MRE, DWI performance and ADC value of each segment. One-way ANOVA was utilized to compare the Clermont scores and ADC values of the intestine segments among the three groups. The efficacy of the Clermont scores and ADC values in evaluating intestinal mucosal ulcer in CD was verified using ROC analysis. Results: A total of 137 intestine segments were included in the study with 30 cases in NU, 37 cases in SU, and 70 cases in DU.DU had the highest Clermont score (22.5±4.5),following were SU(15.8±3.5) and NU(10.2±1.3)(F=179.935,P<0.01).The ADC values of DU ((1.34±0.17)×10(-3)mm(2)/s) was lower than NU ((2.07±0.52)×10(-3)mm(2)/s) and SU ((1.52±0.23)×10(-3) mm(2)/s) (F=83.822,P<0.01).The AUCs of using Clermont score and ADC value in differentiating deep ulcerations were 0.887 and 0.733, respectively. Conclusions: Either Clermont score or ADC value can be used to evaluate mucosal ulcer in CD. Clermont score demonstrates a better efficacy than ADC value in detecting deep ulcerations.

Identification and functional analysis of a novel chorion protein essential for egg maturation in the brown planthopper.

In insect eggs, the chorion has the essential function of protecting the embryo from external agents during development while allowing gas exchange for respiration. In this study, we found a novel gene, Nilaparvata lugens chorion protein (NlChP), that is involved in chorion formation in the brown planthopper, Nilaparvata lugens. NlChP was highly expressed in the follicular cells of female adult brown planthoppers. Knockdown of NlChP resulted in oocyte malformation and the inability to perform oviposition, and electron microscopy showed that the malformed oocytes had thin and rough endochorion layers compared to the control group. Liquid chromatography with tandem mass spectrometry analysis of the eggshell components revealed four unique peptides that were matched to NlChP. Our results demonstrate that NlChP is a novel chorion protein essential for egg maturation in N. lugens, a hemipteran insect with telotrophic meroistic ovaries. NlChP may be a potential target in RNA interference-based insect pest management.

Thermal-noise-limited higher-order mode locking of a reference cavity.

Higher-order mode locking has been proposed to reduce the thermal noise limit of reference cavities. By locking a laser to the HG02 mode of a 10-cm long all ultra-low expansion (ULE) cavity and measuring its performance with the three-cornered-hat method among three independently stabilized lasers, we demonstrate a thermal-noise-limited performance of a fractional frequency instability of 4.9×10-16. The results match the theoretical models with higher-order optical modes. The achieved laser instability improves the all ULE short cavity results to a new low level.

[Diagnostic and therapeutic values of interphase fluorescence in situ hybridization in B-cell lymphomas: a clinicopathologic analysis of 604 cases].

Objective: To investigate the feasibility and value of interphase fluorescence in situ hybridization (FISH) in the pathological diagnosis, differential diagnosis and therapeutic assessment of B-cell lymphomas. Methods: The cohort included 604 cases of B-cell lymphoma which were collected at West China Hospital from May 2010 to December 2016.And all were subjected to interphase FISH using 11 break apart or fusion probes (MYC, bcl-2, bcl-6, IRF4, MYC/IgH, bcl-2/IgH, CCND1/IgH, IgH, API2/MALT1, p53/ATM, and D13S319/CEP12). Results: The median age of the 604 B-cell lymphoma patients was 47.7 (aged 2-90) years including 372 men and 232 women. All the cases was divided into 463 large B cell lymphomas(LBL) and 141 small B cell lymphomas, and the total interphase FISH positive rate was 59.8% (361/604). Among the 463 LBL, 12.5% (58/463), 9.5% (44/463) and 2.2% (10/463) of cases showed MYC, bcl-6 and bcl-2 gene rearrangements respectively; and 363 diffuse large B cell lymphoma (DLBCLs) were reclassified as germinal center B-cell (GCB) subtype (38.6%, 140/363) and non-GCB subtype (61.4%, 223/363) by Hans algorithm. The rearrangement rates in GCB and non-GCB DLBCL were 45.7%(64/140)and 21.5%(48/223; P=0.001), respectively. Compared to the non-GCB DLBCL, GCB DLBCL showed higher MYC and bcl-2 gene rearrangements (P=0.001). Eleven (2.4%, 11/463) cases had MYC and bcl-6 or bcl-2 gene rearrangement (double-hit lymphoma); one (0.2%, 1/463) case had MYC, bcl-6 and bcl-2 gene rearrangements (triple-hit lymphoma); two (0.4%, 2/463) cases had bcl-2 and bcl-6 gene rearrangements. MYC translocation and MYC/IgH fusion were detected in 94.2%(81/86) and 83.7%(72/86) cases of Burkitt lymphomas. IRF4 rearrangement was detected in two cases of IRF4+ LBCL. Genetic abnormalities were detected in 9/19, 100%(29/29), 30.8%(12/39) and 68.5%(37/54) cases of follicular lymphoma, mantle cell lymphoma, MALT lymphoma and chronic lymphocytic leukemia, respectively. Conclusions: Interphase FISH can rapidly and accurately detect the genetic changes in B-cell lymphomas. Different genetic changes are specifically valuable to the diagnosis, differential diagnosis, prognosis evaluation and treatment guidance of various B-cell lymphomas.

[Diagnostic significance of lymph node core needle biopsy for lymphoproliferative disease: a clinicopathologic study of 1 013 cases].

Objective: To study the clinicopathologic features of lymphoproliferative disease by lymph node core needle biopsy(CNB)and to evaluate the diagnostic significance of CNB for lymphoproliferative disease. Methods: The annual distribution, entity constitute, clinical finding, gross feature, morphologic change, affiliate study and repeat biopsy diagnosis of 1 013 cases of lymph node CNB diagnosed at West China Hospital of Sichuan University from January 2009 to December 2015 were investigated. Results: (1) Proportion of lymph node CNB in total amount of biopsy specimens increased from 0.2% in 2009 to 0.8% in 2015.(2) The study cohort included 471 lymphomas, 12 atypical lymphoid hyperplasia (ALH), 136 suspected lymphomas, 372 benign lesions, and 22 cases of descriptive diagnoses. The most common types were diffuse large B cell lymphoma and T-lymphoblastic lymphoma. (3) Majority of patients were adolescents and children younger than 20 years or the elderly older than 60 years. 53.1% CNB tumor specimen consisted of ≥4 tissue cores and 40.5% were >2 cm in length. (4) 104 CNB cases with previous history of excision biopsy was included 45 carcinomas(no metastatic carcinoma was found), 32 lymphomas for treatment observation.1/14 suspicious lymphomas, 1/1 ALH and 3/22 cases benign lesions were diagnosed as lymphoma by repeat biopsy respectively. (5) 217 CNB cases were diagnosed as lymphoma by subsequent CNB (70), or subsequent excision biopsy (147) including 78.5%(73/93) suspected lymphomas, 5/7 ALH and 32.3%(20/62)benign lesions. Conclusions: Lymph node CNB has certain clinical indications, although limited for the diagnosis of lymphoproliferative disorders. Suspected lymphomas and ALH diagnosed by CNB should be followed by repeat tissue biopsy. For the benign lesions by CNB it does not rule out additional biopsy to further investigate the lesion.

Chitinase-like gene family in the brown planthopper, Nilaparvata lugens.

Chitinases are important enzymes required for chitin degradation and reconstruction in insects. Based on a bioinformatics investigation, we identified 12 genes encoding putative chitinase-like proteins, including 10 chitinases (Cht), one imaginal disc growth factor (IDGF) and one endo-ß-N-acetylglucosaminidase (ENGase) in the genome of the brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae). These 12 genes were clustered into nine different groups, with 11 in glycoside hydrolase family 18 groups (groups I-VIII) and one in the ENGase group. Developmental and tissue-specific expression pattern analysis revealed that the transcript levels of eight genes peaked periodically during moulting and were mainly expressed in the integument, except NlCht2, NlCht4, NlIDGF and NlENGase. NlCht2, NlIDGF and NlENGase were expressed at all stages with slight periodical changes and mainly expressed in the female reproductive organs in adults, whereas NlCht4 was highly expressed only at the adult stage in the male reproductive organs. Lethal phenotypes were observed in insects challenged by double-stranded RNAs for NlCht1, NlCht5, NlCht7, NlCht9 and NlCht10 during moulting, suggesting their significant roles in old cuticle degradation. NlCht1 was the most sensitive gene, inducing 50% mortality even at 0.01 ng per insect. Our results illustrate the structural and functional differences of chitinase-like family genes and provide potential targets for RNA interference-based rice planthopper management.

Chitin deacetylase family genes in the brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae).

Chitin deacetylases (CDAs) are enzymes required for one of the pathways of chitin degradation, in which chitosan is produced by the deacetylation of chitin. Bioinformatic investigations with genomic and transcriptomic databases identified four genes encoding CDAs in Nilaparvata lugens (NlCDAs). Phylogenetic analysis showed that insect CDAs were clustered into five major groups. Group I, III and IV CDAs are found in all insect species, whereas the pupa-specific group II and gut-specific group V CDAs are not found in the plant-sap/blood-sucking hemimetabolous species from Hemiptera and Anoplura. The developmental and tissue-specific expression patterns of four NlCDAs revealed that NlCDA3 was a gut-specific CDA, with high expression at all developmental stages; NlCDA1, NlCDA2 and NlCDA4 were highly expressed in the integument and peaked periodically during every moulting, which suggests their roles in chitin turnover of the insect old cuticle. Lethal phenotypes of cuticle shedding failure and high mortality after the injection of double-stranded RNAs (dsRNAs) for NlCDA1, NlCDA2 and NlCDA4 provide further evidence for their functions associated with moulting. No observable morphological and internal structural abnormality was obtained in insects treated with dsRNA for gut-specific NlCDA3.

[Free anterolateral thigh flap with superficial temporal vessels as recipient vessels for reconstruction of defect after maxillectomy in malignant tumor].

Objective: To study the effects of superficial temporal artery and vein as recipient vessels for the free anterolateral thigh flap on the appearance and functions after maxillectomy. Methods: Clinical data of 21 patients with malignant maxillary tumors in Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital of Central South University from January 2014 to November 2019, who were treated by free anterolateral thigh flap with temporal superficial vessels as the recipient vessels were analyzed retrospectively. There were 18 males and 3 females, with the age ranging from 29 to 73 years old, including 19 cases of squamous carcinoma, 1 case of adenoid cystic carcinoma and 1 case of osteosarcoma. Of those 7 patients underwent primary surgery, 14 patients received resurgery, and 6 patients had a history of postoperative radiotherapy and chemotherapy. Among 14 patients with resurgery, 13 had recurrent ipsilateral second site tumor and 1 had recurrent tumor, and all of them received the maxillectomy and reconstructive surgery with the free anterolateral thigh flap. Patients were evaluated with water swallow test and speech intelligibility score in 1, 3 and 6 months after operation. The data were statistically analyzed with SPSS 22.0 statistical software. Water swallow test results before and after operation were compared using the Wilcoxon rank sum test. The mean speech intelligibility scores before and after operation were compared by the paired t test. Results: Patients were followed up for 10-60 months. All free flaps survived after operation. No diplopia occurred. Breathing, swallowing and speaking functions were normal. No movement disorders caused by the donor of thigh flap. Water swallow test showed no phenomenon of water flowing into the nasal cavity or oral and nasal leakage with level Ⅰ for 4 cases, level Ⅱ for 13 cases, level Ⅲ for 3 cases and level Ⅳ for 1 case. The mean speech intelligibility scores before surgery and 1, 3 and 6 months after surgery were 4.31±0.13, 1.46±0.21, 2.15±0.45 and 2.87±0.76 respectively. There was statistically significant difference in the mean speech intelligibility scores between 1 and 6 months after surgery (F=78.456, P<0.05). Conclusion: It is safe and reliable to use the superficial temporal vessels as recipient vessels for free anterolateral thigh flap in the reconstruction of defect after maxillectomy in malignant tumors, with good outcomes of functions and a satisfactory restoration of outward appearance.

MiRNA-92a promotes cell proliferation and invasion through binding to KLF4 in glioma.

OBJECTIVE: Glioma is one of the most frequent brain tumors in adults, and it has a low 5-year survival rate. MicroRNA-92a (miR-92a) has been reported to be upregulated and acted as an oncogene in many cancers. The purpose of this study was to explore the molecular mechanisms of miR-92a and kruppel-like factor 4 (KLF4) in glioma. PATIENTS AND METHODS: Western blotting assay and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) were applied to calculate the relative expression of interest proteins and mRNAs. Luciferase ability assay was conducted to evaluate whether miR-92a was targeting to KLF4. RESULTS: A higher expression of miR-92a was observed in glioma tissues compared with the corresponding adjacent non-tumor tissues. The upregulation of miR-92a predicted poor prognostic characteristics of glioma. The overexpression miR-92a significantly promoted cell proliferation an invasion, while the knockdown of miR-92a presented the opposite results. MiR-92a bound to KLF4 and mediated the expression of KLF4 in glioma cells. The knockdown of miR-92a inhibited cell invasion-mediated EMT. Furthermore, the knockdown of miR-92a suppressed cell proliferation through the KLF4/AKT/mTOR signal pathway. CONCLUSIONS: MiR-92a promoted the proliferation through the KLF4/AKT/mTOR signal pathway in glioma. The newly identified miR-92a/KLF4/AKT/mTOR axis provides novel insight into the pathogenesis of glioma.

[An interlaboratory comparison study on the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels].

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People's Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories' results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion: The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

Direct actions of gossypol on cardiac muscle.

Gossypol, an orally active male contraceptive, has been reported to produce cardiotoxicity. In the present study, direct actions of gossypol on the heart muscle were examined using atrial muscle preparations isolated from guinea-pig heart. Gossypol (20-30 microM) produced a transient positive chronotropic effect in spontaneously beating right atrial muscle preparations and a transient positive inotropic effect which reached a peak at about 5 min followed by a marked negative inotropic effect in paced left atrial muscle. These effects of gossypol were not affected by blocking concentrations of phentolamine, nadolol or propranolol, cimetidine and atropine. Gossypol inhibited Na+,K+-ATPase isolated from guinea-pig brain, Na+ pump activity in electrically stimulated left atrial muscle preparations of guinea-pig heart and Na+/Ca2+ exchange in Na+-loaded sarcolemmal vesicles obtained from dog heart. Inhibition of Na+/Ca2+ exchange required high concentrations of gossypol and was rapidly reversible whereas Na+,K+-ATPase inhibition was apparently irreversible. These results indicate that micromolar concentrations of gossypol have direct actions on cardiac muscle.

Cardiodepressant actions of the orally active male contraceptive, gossypol, in guinea-pig heart muscle.

We have previously shown that gossypol has direct actions on isolated atrial muscle preparations. The possible mechanisms responsible for the transient positive and sustained negative inotropic effects of gossypol were examined under conditions that modify Ca2+ pools involved in contractile activation. In Langendorff preparations obtained from guinea-pig or rat heart, gossypol produced marked negative inotropic and arrhythmogenic effects but failed to produce a positive inotropic effect. Langendorff preparations were significantly more sensitive than atrial muscle preparations. In atrial muscle preparations, the negative inotropic effect of gossypol was not specific to utilization of superficial or intracellular Ca2+ pools; force-staircase phenomenon observed between 0.5 and 3 Hz, contractions elicited by slow action potentials in partially depolarized muscle, the inotropic effect of extracellular Ca2+ and potentiated post-rest contractions were all suppressed by gossypol to the similar extent. Low external Na+ concentrations abolished the positive inotropic effect of gossypol without affecting the negative inotropic effect. A low extracellular Ca2+ concentration enhanced the transient positive inotropic effect and delayed development of the negative inotropic effect. Simultaneous reduction of extracellular Na+ and Ca2+ concentrations abolished the positive inotropic effect and enhanced the negative inotropic effect. Gossypol inhibited ATP-dependent Ca2+ uptake by sarcolemmal vesicles obtained from dog heart. These results indicate that the actions of gossypol on cardiac muscle is not specific to utilization of either the superficial or intracellular Ca2+ pools involved in contractile activation.

Modification of the positive inotropic effects of catecholamines, cardiac glycosides and Ca2+ by the orally active male contraceptive, gossypol, in isolated guinea-pig heart.

Gossypol is an orally active male contraceptive with cardio-depressant side effects. To understand the mechanism of its cardiac actions, the interaction of gossypol with positive inotropic drugs was examined in isolated atrial muscle preparations obtained from guinea-pig heart. Gossypol delayed the onset of arrhythmias caused by digoxin. In the presence of gossypol, the positive inotropic effect of isoproterenol declined rapidly, and the effect of isoproterenol to increase tissue cyclic AMP concentrations was smaller. Pretreatment of atrial muscle with the combination of gossypol and isoproterenol markedly reduced effects of isoproterenol on developed tension and cyclic AMP concentrations when these effects were tested after the washout of the first dose of isoproterenol. These effects, however, were not specific to isoproterenol. The gossypol-isoproterenol pretreatment reduced the positive inotropic effect of ouabain or extracellular Ca2+. These results indicate that gossypol has pharmacodynamic interactions with several positive inotropic agents that are known to enhance developed tension by increasing intracellular Ca2+ transients.

[Toxicity study of epidermal growth factor eye medicine liquid].

OBJECTIVE: To apply for a new medicine certificate, the experiments of acute, long toxicity and side effects of EGF eye medicine liquid were investigated in animals. METHODS: All of examinations were done according to the instructions of "Requirements of the Toxicity Study of New Medicine" RESULTS: No toxicity or side-effect of EGF eye medicine liquid given by i.v., i.p., s.c. or eye-drop were been found. CONCLUSION: For the results of whole experiments are in complete accord with "the requirements of the toxicity study of new medicine", EGF eye medicine liquid will be safety in clinical application.