Linoleic acid and α-linolenic acid inhibit conjugative transfer of an IncX4 plasmid carrying mcr-1.

AIMS: The aim of this study was to determine the effects of unsaturated fatty acids on clinical plasmids. METHODS AND RESULTS: Two unsaturated fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) at final concentration 0, 0·03, 0·3 and 3 mmol l-1 , respectively, were used to assess the effects on conjugative transfer of a mcr-1-harbouring plasmid pCSZ4 (IncX4) in conjugation experiment. The inhibitory mechanisms were analysed by molecular docking and the gene expression of virB11 was quantitated by qRT-PCR. Target plasmid diversity was carried out by TrwD/VirB11 homology protein sequence prediction analysis. Our results showed that LA and ALA inhibit plasmid pCSZ4 transfer by binding to the amino acid residues (Phe124 and Thr125) of VirB11 with dose-dependent effects. The expression levels of virB11 gene were also significantly inhibited by LA and ALA treatment. Protein homology analysis revealed a wide distribution of TrwD/VirB11-like genes among over 37 classes of plasmids originated from both Gram-negative and Gram-positive bacteria. CONCLUSIONS: This study demonstrates representing a diversity of plasmids that may be potentially inhibited by unsaturated fatty acids. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work reported here provides additional support for application of curbing the spread of multiple plasmids by unsaturated fatty acids.

The association and interaction analysis of hypertension and uric acid on cardiovascular autonomic neuropathy.

BACKGROUND: The purpose of this study was to evaluate associations among hypertension (HTN) and uric acid (UA) with cardiovascular autonomic neuropathy (CAN), and to estimate the extent to which synergistic effects of HTN and UA affect the outcome in a Chinese population. METHOD: We conducted a large-scale, population-based study to analyze the association and interaction of the two factors for CAN in a sample of 2092 Chinese people. Univariate and multiple linear regression (MLR) analysis were employed to detect these relationships. Interaction on an additive scale can be calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). RESULT: After adjusting for confounding factors, MLR showed that HTN was independently associated with CAN (P < 0.001). A significant interaction effect of UA and HTN on CAN was detected (P = 0.035; RETI = 1.483, 95 % CI 0.415-2.551; AP = 0.360, 95 % CI -0.043 to 0.76 and S = 1.908, 95 % CI 0.152-3.66). CONCLUSION: Our findings suggest that HTN is independently and significantly associated with CAN and offer evidence to support the hypothesis that HTN and UA have interaction effects to influence the progression of CAN.

Reduced tibial speed of sound in Chinese infants at birth compared with Caucasian peers: the effects of race, gender, and vitamin D on fetal bone development.

SUMMARY: This study compared bone status between Chinese and Caucasian infants at birth, showing that Chinese neonates have lower tibial speed of sound, which is influenced by gender, gestational age, season of birth, and maternal vitamin D status. The effects of these factors on fetal bone development were discussed. INTRODUCTION: We compared the differences of speed of sound (SOS) accessed by quantitative ultrasound between Chinese and Caucasian infants at birth and explored the relationship between the concentrations of serum 25-hydroxyvitamin D [25(OH)D] and bone SOS in maternal-infant pairs. METHODS: SOS for the tibial bone was measured at birth in 267 Chinese infants. We used the Z-scores for the direct comparisons which were available from the instrument based data of gender and age-matched Caucasian peers. The concentrations of serum 25(OH)D and bone SOS in 32 maternal-infant pairs were measured at birth in winters. RESULTS: the Chinese infants had lower SOS demonstrated by the Z-scores. Significant differences of SOS and Z-scores were found between genders, gestational ages, birth weight, and seasons of birth. The differences of Z-scores negatively decreased with gestational age, suggesting that the bone status of Chinese infants lags behind that of the Caucasian infants during the last trimester of pregnancy in utero. The tibial SOS of infants born in winters was 2.0% higher than those born in summers after adjustment. The infant SOS correlated with maternal serum 25(OH)D (r = 0.399, P = 0.024) and infant serum 25(OH)D (r = 0.394, P = 0.026). CONCLUSIONS: Chinese neonates have lower SOS which is influenced by gender, gestational age, season of birth, and maternal vitamin D status. It is inferred that, in pace with gestational age, race and gender effects on fetal bone development are modified by materno-fetal vitamin D status.

Methadone-induced desensitization of the delta-opioid receptor is mediated by uncoupling of receptor from G protein.

Chronic exposure of neuroblastoma x glioma (NG108-15) hybrid cells and rat mu-receptor-transfected Chinese hamster ovary (CHO) cells to 10 microM morphine resulted in a compensatory and antagonist-precipitated increase in cAMP accumulation. However, incubation of these cells with 10 microM methadone during chronic exposure to morphine substantially prevented the actions of morphine. Chronic methadone treatment caused a pronounced reduction in agonist-stimulated binding of [35S]GTPgammaS to G proteins, but it did not produce significant down-regulation of delta-opioid receptors, whereas chronic morphine treatment failed to induce either uncoupling of delta-opioid receptors from G proteins or down-regulation of delta-opioid receptors. In contrast to chronic treatment with morphine alone, treatment of cells with morphine and methadone simultaneously resulted in a significant decrease in agonist-stimulated binding of [35S]GTPgammaS to G proteins. The action of methadone-mediated uncoupling of the receptor from the G protein was blocked by the nonselective protein kinase inhibitor [1-(5-isoqinolinesulfony)-2-methylpiprazine](H7), but not by the specific protein kinase C inhibitor, chelerythrine. The data demonstrate that methadone desensitizes the delta-opioid receptor by uncoupling the receptor from the G protein. In this way, methadone antagonizes the morphine-mediated adaptive sensitization and overshoot of adenylate cyclase. The functional desensitization of opioid receptors by methadone may explain why methadone is effective in the treatment of morphine dependence.

The difference between methadone and morphine in regulation of delta-opioid receptors underlies the antagonistic effect of methadone on morphine-mediated cellular actions.

To investigate the cellular and molecular basis for using methadone in substitution therapy for morphine addiction, the difference between methadone and morphine in causing desensitization of delta-opioid receptors was examined, and the effects of methadone pretreatment on opiate-induced inhibition of forskolin-stimulated cAMP accumulation was studied. Methadone substantially attenuated the ability of [D-Ala2,D-Leu5]enkephalin (DADLE), morphine and methadone to inhibit forskolin-stimulated cAMP accumulation. Methadone was able to block the morphine-induced compensatory increase in intracellular cAMP levels and naloxone-precipitated cAMP overshoot after chronic exposure to morphine. The protein kinase inhibitor (1-5-isoquinolinesulfony)-2-methylpiperazine) (H7) could significantly block the chronic methadone treatment-induced loss of the ability of DADLE to inhibit adenylate cyclase. The protein kinase inhibitor chelerythrine was able to block the acute methadone treatment-induced loss of the ability of DADLE to inhibit adenylate cyclase. In contrast, morphine did not cause a substantial desensitization of the delta-opioid receptor. These results indicate that methadone is different from morphine in its regulation of the delta-opioid receptor. In addition, these results also indicate that the mechanisms of delta-opioid receptor desensitization induced by acute and chronic methadone treatment are different.

Changes in body fluid markers in intestinal ischemia.

New Zealand rabbits were assigned randomly to three groups: sham operation, intestinal simple obstruction, and strangulation obstruction. To relate possible changes in the body fluid content of biochemical markers to the strangulation process, subsequent samples of blood and peritoneal fluid, for the determination of levels of creatine kinase (CK), lactic acid (LA), xanthine oxidase (XO), and inorganic phosphate (IP), were obtained at 1-, 2-, 4-, and 6-hour intervals, and intestinal histological specimens were graded blindly. Significant increases in plasma LA (3.93 +/- 0.26 v 2.99 +/- 0.37; P < .05), peritoneal LA (5.03 +/- 1.14 V 3.33 +/- 0.86; P < .05), and CK (940 +/- 146 v 772 +/- 165, P < .05) occurred after 1 hour of ischemic injury. Except for serum CK, all parameters in the blood and peritoneal fluid in group 3 were markedly elevated within 4 hours. The serum CK remained almost unchanged throughout the 6-hour study period. The results suggest that plasma LA, peritoneal LA, and CK are sensitive indicators in the early diagnosis of bowel ischemia; the determination of both serum and peritoneal XO and IP was also helpful for early diagnosis; in contrast, serum CK was not a useful indicator. The value of any biochemical marker as an early diagnostic tool for intestinal ischemia depends not only on its quantity but also on its location and mechanism of release.

[Carcinoma of the extrahepatic bile duct in young child--a case report].

A child, 2 years old, male suffering from severe jaundice, melena, severe anemia and right upper abdominal mass was admitted into our hospital. Diagnosis of obstructive jaundice was made before operation. On exploration, a tumor mass was found in the pancreatic head, which involved the duodenum and distal common bile duct. Pancreaticoduodenectomy with one stage pancreaticojejunostomy, choledochojejunostomy and gastrojejunostomy was carried out. Postoperative pathology showed adenocarcinoma of the distal common bile duct invading the periampullary tissues of the duodenum and infiltrating, to a lesser extent, into the pancreatic head. Carcinoma arising from the distal common bile duct is rare in infancy and childhood. Radical resection should be attempted if possible. In general, the prognosis is poor in this tumor. No complication after operation occurred on this patient but close follow-up is necessary. Pathology related to this tumor is discussed with a review of literature.