Differences in corneal and anterior segment morphology between diabetic vs. healthy children and adolescents: a systematic review and meta-analysis.

OBJECTIVE: To compare corneal and anterior segment morphology among children and adolescents with and without diabetes. MATERIALS AND METHODS: PubMed, Embase and Scopus databases were systematically searched. Studies that were observational in design were considered. Included studies should have been done in young children and/or adolescents and compared relevant outcomes of interest based on the diabetic status. The outcomes of interest were related to corneal morphology, morphology of lens, as well as important characteristics of anterior segment such as depth, pupillary diameter, intra-ocular pressure and axial length. The pooled effect sizes were reported as weighted mean difference (WMD). STATA software was used for statistical analysis. RESULTS: The meta-analysis included 17 studies. Diabetic children had lower corneal endothelial cell density (cells/mm2) (WMD -215.7, 95% CI: -406.5, -24.9), higher central corneal thickness (µm) (WMD 12.66, 95% CI: 5.47, 19.84), higher lenticular thickness (mm) (WMD 0.25, 95% CI: 0.13, 0.36) and density (WMD 3.02, 95% CI: 2.23, 3.81) than non-diabetic children. The anterior chamber depth (mm) (WMD -0.17, 95% CI: -0.24, -0.09) and pupillary diameter (mm) (WMD -0.61, 95% CI: -1.12, -0.10) was significantly reduced in diabetic children, compared to non-diabetic children. No differences in the corneal curvature, corneal diameter, spherical equivalent, intra-ocular pressure, axial length, tear film breakup time and Schirmer test were noted among diabetic and non-diabetic children. CONCLUSIONS: Significant structural changes in cornea and lens along with reduction in anterior chamber depth and pupillary diameter were found. These morphological changes may be indication for early and prompt management and underscore the need for more advanced ophthalmological evaluation techniques, in addition to routine examination.

[A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection].

Objective: To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection. Methods: Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval. Results: 132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death. Conclusion: Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

[Influence of occupational aluminum exposure on cognitive function and glutamate receptor protein expression in workers].

Objective: To investigate the influence of occupational aluminum exposure on cognitive function and glutamate receptor protein expression in peripheral blood lymphocytes in workers and the possibility of glutamate receptor being used as a biomarker for cognitive impairment in aluminum workers. Methods: From October to December, 2014, cluster sampling was performed to select 121 workers in aluminum electrolysis workshop as exposure group and 231 workers in thermoelectric workshop and logistics department as control group. Mini-Mental State Examination, clock drawing test, digit span test (DST) , verbal fluency test (VFT) , and Fuld Object-Memory (FOM) Evaluation were used to analyze cognitive function. Graphite furnace atomic absorption spectrophotometry was used to measure plasma aluminum level as an exposure indicator. Enzyme-linked immunosorbent assay was used to measure the content of glutamate receptor proteins in peripheral blood lymphocytes, including the subunits of N-methyl-D-aspartate receptor NR1, NR2A, and NR2B and metabotropic glutamate receptor 1 (mGluR1) . The correlation between cognitive function indices and the content of glutamate receptor proteins was analyzed. Results: There was no significant difference in plasma aluminum level between the control group and the exposure group (132.52±80.40 µg/L vs 182.88±72.32 µg/L, P>0.05) . According to the plasma aluminum level, the study subjects were divided into control group and low-, medium-, and high-level plasma aluminum groups, and there were significant differences in plasma aluminum level between these groups (all P<0.01) . The high-level plasma aluminum group had a significantly lower memory ability score than the control group and the low- and medium-level plasma aluminum groups (all P<0.05) . The high-level plasma aluminum group had lower DST and digital span forward (DSF) scores than the control group and the low-and medium-level plasma aluminum groups. The low-, medium-, and high-level plasma aluminum groups had lower digital span backward (DSB) scores than the control group. The medium-and high-level plasma aluminum groups had lower VFT scores than the control group and the low-level plasma aluminum group. The high-level plasma aluminum group had significantly lower expression of NR1 and NR2A proteins than the control group and the low-and medium-level plasma aluminum groups, and the medium- and high-level plasma aluminum groups had significantly higher expression of mGluR1 protein than the control group and the low-level plasma aluminum group (all P<0.05) . The expression of NR1 and NR2A proteins was negatively correlated with plasma aluminum level (r=-0.475 and -0.692, both P<0.05) , andthe expression of mGluR1 protein was positively correlated with plasma aluminum level (r=0.756, P<0.05) . The expression of NR1 protein was positively correlated with DSF, DSB, DST, and VFT scores (r(s)=0.213, 0.249, 0.271, and 0.228, all P<0.05) , and the expression of NR2A protein was positively correlated with VFT score (r(s)=0.206, P<0.05) . Conclusion: Occupational aluminum exposure may affect workers' memory function, and the expression of NR1 and NR2A in peripheral blood lymphocytes is correlated with cognitive function indices and can be used as biomarkers for cognitive impairment in aluminum workers.

Resistin-Like Molecule-α Causes Lung Injury in Rats with Acute Pancreatitis by Activating the PI-3K/Akt-NF-κB Pathway and Promoting Inflammatory Cytokine Release.

BACKGROUND: Resistin-like molecule-α (RELMα) has diverse regulatory functions in inflammation, but its role in severe acute pancreatitis (SAP) and acute pancreatitis associated lung injury (APALI) remains unclear. METHODS: SAP was induced in rats. RELMα protein expression was detected in lung tissue of rats to determine the relationship between APALI and RELMα. To investigate the effect of RELMα overexpression or knockdown on APALI, rats were given an intravenous injection of adenovirus vector before SAP induction. Lung and pancreatic samples were harvested 16 h after induction. After detection of RELMα protein levels, the severity of pancreatic and pulmonary injury was scored histologically, and serum and tissue levels of inflammatory mediators were measured. TUNEL assay and immunofluorescence were used to estimate pulmonary apoptosis and endothelial barrier integrity in lung tissue of SAP rats with RELMα knockdown. RESULTS: RELMα expression was significantly up-regulated in APALI and was related to the lung injury index. RELMα overexpression aggravated the release of inflammatory cytokines including interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor-α, and serum C-reaction protein; the expression of inflammatory mediators phosphorylated (p)-AKT, p-P65, p-P38 mitogen activated protein kinase, p-extracellular regulated kinase, and intracellular adhesion molecule-1; and lung injury. RELMα knockdown had opposite effects. In addition, RELMα knockdown improved expression of proliferative cellular nuclear antigen, Bcl-2, zonal occluding-1 and Claudin-1 in lung tissue of SAP rats. CONCLUSION: RELMα is associated with lung injury severity in SAP. RELMα augments inflammatory activity by increasing inflammatory cytokine release.

[Association between serum aluminium level and methylation of amyloid precursor protein gene in workers engaged in aluminium electrolysis].

OBJECTIVE: To investigate the association between serum aluminium level and methylation of the promoter region of amyloid precursor protein (APP)gene in workers engaged in aluminium electrolysis. METHODS: In 2012, 366 electrolysis workers in an aluminium factory were enrolled as exposure group (working years >10 and age >40 years)and divided into low-exposure group and high-exposure group based on the median serum aluminium level. Meanwhile, 102 workers in a cement plant not exposed to aluminium were enrolled as control group. Graphite furnace atomic absorption spectrometry was used to measure serum aluminium level, methylation specific PCR was used to measure the methylation rate of the promoter region of APP gene, and ELI-SA was used to measure the protein expression of APP in lymphocytes in peripheral blood. RESULTS: The exposure group had a significantly higher serum aluminium level than the control group (45.07 µg/L vs 30.51 µg/L, P< 0.01). The exposure group had a significantly lower methylation rate of the promoter region of APP gene than the control group (18.85% vs 25.49%, P=0.025), and the high-exposure group had a significantly lower methylation rate of the promoter region of APP gene than the low-exposure group (15.84% vs 21.85%, P<0.05). The exposure group had a significantly higher protein expression of APP in lymphocytes in peripheral blood than the control group (66.73 ng/ml vs 54.17 ng/ml, P<0.05); compared with the low-exposure group (65.39 ng/ml), the high-exposure group showed an increase in the protein expression of APP in lymphocytes in peripheral blood (67.22 ng/ml), but there was no significant difference between these two groups (P>0.05). The multivariate logistic regression analysis showed that with reference to the control group, low aluminium exposure (OR=1.86, 95% CI 1.67~3.52)and high aluminium exposure (OR=2.98, 95% CI 1.97~4.15)were risk factors for a reduced methylation rate of the promoter region of APP gene. CONCLUSION: Reduced methylation of the promoter region of APP gene may be associated with increased serum aluminium level, and downregulated methylation of the promoter region of APP gene may accelerate APP gene transcription.

[Overexpression, homology modeling and coenzyme docking studies of the cytochrome P450nor2 from Cylindrocarpon tonkinense].

Cytochrome P450nor catalyzes an unusual reaction that transfers electrons from NADP/NADPH to bound heme directly. To improve the expression level of P450nor2 from Cylindrocarpon tonkinense (C.P450nor2), Escherichia coli system was utilized to substitute the yeast system we constructed for expression of the P450nor2 gene, and the protein was purified in soluble form using Ni(+)-NTA affinity chromatography. In contrast to P450nor from Fusarium oxysporum (F.P450nor) and P450nor1 from Cylindrocarpon tonkinense (C.P450nor1), C.P450nor2 shows a dual specificity for using NADH or NADPH as electron donors. The present study developed a computational approach in order to illustrate the coenzyme specificity of C.P450nor2 for NADH and NADPH. This study involved homology modeling of C.P450nor2 and docking analyses of NADH and NADPH into the crystal structure of F.P450nor and the predictive model of C.P450nor2, respectively. The results suggested that C.P450nor2 and F.P450nor have different coenzyme specificity for NADH and NADPH; whilst the space around the B'-helix of the C.P450nor2, especially the Ser79 and Gly81, play a crucial role for the specificity of C.P450nor2. In the absence of the experimental structure of C.P450nor2, we hope that our model will be useful to provide rational explanation on coenzyme specificity of C.P450nor2.

Genome sequencing and systems biology analysis of a lipase-producing bacterial strain.

Lipase-producing bacteria are naturally-occurring, industrially-relevant microorganisms that produce lipases, which can be used to synthesize biodiesel from waste oils. The efficiency of lipase expression varies between various microbial strains. Therefore, strains that can produce lipases with high efficiency must be screened, and the conditions of lipase metabolism and optimization of the production process in a given environment must be thoroughly studied. A high efficiency lipase-producing strain was isolated from the sediments of Jinsha River, identified by 16S rRNA sequence analysis as Serratia marcescens, and designated as HS-L5. A schematic diagram of the genome sequence was constructed by high-throughput genome sequencing. A series of genes related to lipid degradation were identified by functional gene annotation through sequence homology analysis. A genome-scale metabolic model of HS-ML5 was constructed using systems biology techniques. The model consisted of 1722 genes and 1567 metabolic reactions. The topological graph of the genome-scale metabolic model was compared to that of conventional metabolic pathways using a visualization software and KEGG database. The basic components and boundaries of the tributyrin degradation subnetwork were determined, and its flux balance analyzed using Matlab and COBRA Toolbox to simulate the effects of different conditions on the catalytic efficiency of lipases produced by HS-ML5. We proved that the catalytic activity of microbial lipases was closely related to the carbon metabolic pathway. As production and catalytic efficiency of lipases varied greatly with the environment, the catalytic efficiency and environmental adaptability of microbial lipases can be improved by proper control of the production conditions.

[Impact of improvement of diabetes on survival after radical pancreatic resection in patients with pancreatic cancer and diabetes].

OBJECTIVE: To explorer the effect of improvement of diabetes on survival after radical pancreatic resection in patients with pancreatic cancer and diabetes. METHODS: Seventy-three patients who underwent radical resection for pancreatic cancer at Ruijin Hospital (Shanghai, China) between July 2007 and December 2011 and had preoperative diabetes were retrospectively analyzed. Clinical characteristics and overall postoperative survival were compared between patients with controlled/uncontrolled diabetes. Among patients with uncontrolled diabetes, comparison was made in clinical characteristics and overall postoperative survival between patients with long-term (≥2 years) diabetes and those with new-onset (<2 years) diabetes. RESULTS: Controlled diabetes after radical pancreatic resection was observed in 38.4% (28/73) in the patients with pancreatic cancer and diabetes. The median follow-up time was 44.5 months (95CI: 31.7-57.2 months). Patients in whom diabetes was controlled had well-differentiated tumors and longer overall survival compared to patients with uncontrolled diabetes [median overall survival (95%CI) 41.0 (34.2-47.7) months vs 17.0 (14.8-19.2) months, P<0.001]. Among the 45 patients with uncontrolled diabetes, there was no differences in clinic characteristic and overall survival between new-onset (n=21) and long-term diabetes (n=24) [median overall survival (95%CI): 17.8 (15.7-20.1) months vs 15.8 (10.5-21.1) months, P=0.198]. CONCLUSION: Good postoperative control of diabetes after radical pancreatic resection in patients with pancreatic cancer and diabetes may predict favorable survival.

Association between STAT3 gene polymorphisms and ulcerative colitis susceptibility: a case-control study in the Chinese Han population.

Ulcerative colitis (UC) is a chronic inflammation of the large intestine. The aim of this study was to investigate the association of two polymorphisms in STAT3 with the risk of UC development in the Chinese Han population. This is a hospital-based case-control study involving 56 UC patients and 274 controls. Genotyping was performed using the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. Statistical analyses were conducted using logistic regression and genotype risk score. Overall, there was a significant difference between patients and controls in the genotype distribution of rs2293152 (P = 0.044). The risk for UC associated with the rs2293152-G mutant allele was increased (odds ratio = 2.76; 95% confidence interval = 1.06- 7.24) under the dominant model. However, we failed to find any obvious differences in the rs4796793 genotype or allele distributions between the UC patients and controls, and did not detect any significant association of the rs4796793 polymorphism with UC across different genetic models of inheritance. Our study implies that the STAT3 rs2293152 polymorphism may be associated with the occurrence of UC and might be used as a predictive factor for UC in the Chinese Han population.

Treatment of pancreatic carcinoma by adenoviral mediated gene transfer of vasostatin in mice.

BACKGROUND: Tumour growth is angiogenesis dependent and antiangiogenesis therapy may represent a promising therapeutic option. AIMS: To evaluate the inhibitory effect of vasostatin gene mediated by a replication deficient recombinant adenovirus (Ad) on human pancreatic cancer in vivo and to investigate the mechanism of action of vasostatin. METHODS: Human umbilical vein endothelium derived ECV304 cells were infected with Ad-vasostatin and Ad-lacZ, and compared with phosphate buffered saline (PBS). MTT (3,-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay was used to estimate the proliferation of ECV304 cells; tube formation assay and choriallantoic membrane assay were used to evaluate angiogenesis in vivo and in vitro. Xenografted nude mice with pancreatic cancer were established to observe in vivo tumour growth suppression. Microvessel density revealed by CD31 immunohistochemical staining was measured. RESULTS: Growth and tube formation of ECV304 cells infected with Ad-vasostatin were suppressed significantly compared with cells infected with Ad-lacZ or cells treated with PBS. Neovascularisation in the Ad-vasostatin group was less than that in the PBS and Ad-lacZ groups, based on chorioallantoic membrane results. Volumes of pancreatic tumours in the Ad-vasostatin group were significantly smaller than those in the PBS and Ad-lacZ groups at the end of the treatment period. Microvessel density in the Ad-vasostatin group was significantly lower than that in the Ad-lacZ and PBS groups. CONCLUSION: The vasostatin gene mediated by adenovirus is efficient for gene therapy for pancreatic carcinoma. Suppression of vasostatin on proliferation of vascular endothelium cells and angiogenesis may account for its effect.

[Study on effect of emodin on TGF beta 1 expression in pancreatic tissue of rats suffering from acute pancreatitis].

OBJECTIVE: To investigate the effect and mechanism of emodin on pancreatic repairing and remodeling in treating acute pancreatitis by analyzing the change of cytokine transforming growth factor beta 1(TGF beta 1) gene expression, DNA synthesis and protein content in pancreatic tissue. METHODS: Acute pancreatitis was induced in rats by intraperitoneal infusion of caerulein, treated or untreated by emodin. The animals were sacrificed at 6, 24, 48, 72 or 96 hrs after treatment separately. The mRNA expression of TGF beta 1, DNA synthesis and total protein content in pancreatic tissue were tested by reverse transcription-polymerase chain reaction (RT-PCR), 3H-thymidin method and Lowry's method respectively. RESULTS: Serum amylase level was decreased significantly after emodin treatment. TGF beta 1 mRNA expression was undetectable in the intact pancreas or in 6 hrs after pancreatitis induction in the non-treated group, but revealed at 24 hrs after and reached the peak at 72 hrs later. However, in the emodin treated group, TGF beta 1 mRNA expression was detected at 6 hrs after treatment, with a higher level in 24 hrs and 48 hrs as compared with the non-treated group, and reaching the peak at 48 hrs after treatment. Moreover, the DNA synthesis and total protein content in pancreatic tissue decreased significantly at 72 hrs and 48 hrs after induction respectively, but both parameters increased significantly in the emodin treated group 96 hrs after treatment. CONCLUSION: The mechanism of emodin in treating acute pancreatitis might be by way of enhancing cytokine TGF beta 1 gene expression, regulating cell growth and differentiation, stimulating the formation of extracellular matrix components, increasing DNA synthesis and protein content, and to take part in pancreatic repairing and remodeling.

[A study of a mutant of thermostable alkaline phosphatase].

To reveal the mechanism of protein thermostability, we used in vivo random mutagenesis to generate variants of pTAP503F which contained thermostable alkaline phosphatase (FD-TAP). After screening about 5,000 clones, we obtained 4 temperature-sensitive mutants. The study of enzymatic properties of one mutant (TAPM3) showed that the thermostability of the mutant enzyme descended a lot, compared to the wild type, while the thermoactivity remained stable. DNA sequencing showed that the G-A transition in position 1,239 resulted in the substitution from glysine to serine in position 427. This mutation conspicuously affected thermostability, Michaelis constant and energy of activation. This suggests that only one substitution of amino acid will make great changes in thermostability and other properties, meanwhile, side-chain size, charge of residues and so on, which loosen the structure of protein, will result in the descent of thermostability.

[Studies on the recurrent attacks of acute adenolymphangitis due to Malayan filariasis].

OBJECTIVE: To explore the role of filarial and bacterial infections in the recurrent attacks of acute adenolymphangitis due to malayan fialriasis. METHODS: 1. To observe the seasonal fluctuation of acute attacks by performing monthly follow-up on patients with history of acute attacks in recent years. 2. To study the relationship between bacterial infection and filarial adenolymphangitis by performing bacteria culture and anti-streptolysin O test. 3. To investigate the variation of acute attacks by controlling filariasis transmission or by treating patients with a history of recurrent acute attacks. RESULTS: 1. The peak of acute attacks in patients coincided with the peak of vector transmission season. 2. Of the 97 cases examined by bacteria culture, 90 cases were negative; of the 255 cases examined by anti-streptolysin O test, the titres in 94.1% (143/152) of the cases with first attack and simple adenolymphangitis were within normal limits, however, the titres in 27.2% (28/103) of the cases complicated with elephantiasis were increased. 3. The acute attack rate of adenolymphangitis per year reduced significantly in cases with first attack and simple adenolymphangitis after effective control of filariasis transmission. 4. There was no evidence of the reduction of acute attacks by treating patients with DEC alone. CONCLUSION: In malayan filariasis endemic areas, the main causes of recurrent attacks of acute adenolymphangitis might be the repeated filarial infections due to the persistence of filariasis transmission.

[Correlation analysis of (G + C)% of coding sequence and thermostability of xylose isomerase of thermophiles].

Statistical analysis about amino acids and coding sequence of xylose isomerase were performed in a number of thermophiles and mesophiles. It was found that there are correlations between the (G + C)% of the coding sequence and that of 1st, 2nd and 3rd position of the code of amino acids. There were also positive (for hydrophobic amino acids) and negative (for hydrophilic amino acids) correlation between the content of individual amino acids in the enzyme protein and the (G + C)% of their respective coding sequence. It speaks for the notion that high content of (G + C) in the coding sequence tends to increase the thermostability of the corresponding protein. The results in the statistical analysis of amino acid substitutions leading to change in thermostability of the protein may also be interpreted in the same way. An increase in the (G + C)% of DNA of a bacterium can therefore not only increase the thermostability of DNA itself but its proteins as well. Evolutionary consequence concerning thermophily and coding system are discussed.

A rare variant translocation t(3;8)(q29;q22) without AML1/ETO fusion transcript in a case of oligoblastic leukemia.

A 43-year-old man with oligoblastic leukemia and t(3;8) variant translocation is reported. At first he was classified as refractory anemia with excess of blasts in transformation according to the FAB criteria for myelodysplastic syndrome. Remission was obtained after intensive chemotherapy. After 8 months, a relapse occurred as overt M2 AML. At presentation chromosome study of bone marrow cells using R- and G-bandings revealed 45,X, -Y,t(3;8)(q29;q22) in 35 of the 42 metaphases analyzed and 46,XY,t(3;8) in one metaphase in addition to normal karyotype in the other six metaphases. However, RT-PCR assay showed no AML1/ETO fusion transcript. At relapse, a karyotype of 46, XY,t(3;8), deletion(4)(p14), add(7)(q32) was observed in all abnormal cells indicating a clonal karyotypic evolution. We believed that this case should be diagnosed as an early form of M2 AML initially. It may be the first case of oligoblastic leukemia with t(3;8) variant translocation. Further study is needed to elucidate its molecular entity.

[Thermostable alkaline phosphatase from Thermus sp. FD3041: cloning of the gene and expression in Escherichia coli].

A genomic library of Thermus sp. FD3041 which produces thermostable alkaline phosphatase (FD-TAP) was constructed with the vector pUC118 and the host E. coli TG1. 3-10kb inserted fragments of foreign DNA were identified in 90 percent of the 12,000 clones thus obtained. Five positive clones were detected after screening the plated library by the method of colony coloration for TAP in situ. Preliminary analysis of the enzyme expressed from one recombinant plasmid pTAP362 showed that the properties of the recombinant enzyme, such as the thermal stability and optimal temperature of reaction, were identical to those of the native enzyme. The gene of FD-TAP was located on the 2.0kb BamHI-HindIII fragment of the pTAP362, determined by its physical map and the change of enzyme activity in different partially deleted plasmids. Results of thermostability experiment in PCR thermal cycle showed that the FD-TAP would be suitable for labelling of primers and detection of PCR amplified products.

[Effects and mechanism of emodin and sandostatin on pancreatic ischemia in acute haemorrhagic necrotizing pancreatitis].

OBJECTIVE: To investigate pancreatic ischemia and abnormal metabolism of eicosanoids in acute haemorrhagic-necrotizing pancreatits (AHNP) and the effects of emodin or sandostatin on them. METHODS: Rats with AHNP were triggered with sodium taurocholate; the pancreatic blood flow (PBF) was detected with computerized tissue blood flowmeter, and plasma prostaglandin E2 (PGE2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane (TXB2) were determined with radioimmunoassay. RESULTS: There was a significant decrease of PBF in the early stage of AHNP. Compared with that in the untreated group, significant improvement of PBF was demonstrated in emodin as well as in sandostatin group which showed reduced PBF following infusion of sandostatin before triggering AHNP. In untreated group plasma TXB was significantly higher, with an increase of 4.5 times, than that in sham-operated group while 6-keto-PGF1 alpha or PGE2 tended to decrease. The above mentioned abnormal synthesis of eicosanoids was blocked either in emodin or in sandostatin group in which lessened damage of acini cells was shown by pathologic scoring or transmission electron microscope. Both of the two groups shared significantly lower mortalities than the untreated group. CONCLUSION: Either emodion or sandostatin could partly reverse the decrease of PBF in the early stage of AHNP, which may be ascribed at least in part to inhibition of abnormal synthesis of eicosanoids and improvement of cytoprotection of acini cells, and combined application of the two drugs might promise positively synergetic action as well.

[Therapeutic effects and mechanisms of tetramethylpyrazine on lung injury in acute haemorrhagic necrotizing pancreatitis in rats].

To evaluate the therapeutic effects and mechanisms of tetramethylpyrazine (TMP), a Chinese herbal medicine, on the lung injury in bile-induced acute haemorrhagic necrotizing pancreatitis (AHNP) in the SD rats, the rats were randomly divided into three groups: sham-operative, untreated and TMP treated. AHNP model were induced by ligation with 5% taurocholate. The changes of lung index, serum lipid peroxide (LPO), TXB2, 6-keto-PGF1 alpha, and lung pathology at light and electron microscope were all investigated at 1, 6, 12 hours after induction of AHNP model. Survival rate of AHNP in rats were recorded also. Results of the study showed that in untreated group, the time-related progressive pancreatic haemorrhage and necrosis, accompanied by pancreatitis-associated lung injury, such as pronounced pulmonary congestion, alveolar and interstitial edema, polymorphonuclear granulocytes infiltration, transparent membrane formation, the density of layer body in type II endothelial cells decreasing, with some vacuole formation, mitochondria, endoplasmic reticulum swollen, basal membrane of endothelial cells rupture were observed. The level of LPO elevated at 1 hour after induction of AHNP and peaked at 12 hours. TXB2 and 6-keto-PGF1 alpha was increased. Using TMP treatment, survival rate increased, and lung at light and electron microscope were much improved and lung index, value of LPO, TXB2 decreased significantly, 6-keto-PGF1 alpha increased slightly, the ratio of TXB2/6-keto-PGF1 alpha was stabilized. It was suggested that TMP has definite therapeutic effects on AHNP-related lung injury in rats, and exerted by scavenging oxygen free radical, inhibiting synthesis of TXA2, augmenting production of PGI2 and maintaining balance between TXA2 and PGI2.