Inhibition of matrix metalloproteins 9 attenuated Candida albicans induced inflammation in mouse cornea.

Since the severe corneal ulceration of mouse cornea is known to occur with inflammation. As one of imperative matrix metalloproteinase, the potential roles of matrix metalloproteins 9 (MMP9) in corneal ulceration and keratitis are still unveiled caused by fungal invasion. In this study, Candida albicans (CA) inoculated wild-type KM mice cornea was used as a model pathogen in corneal inflammation.  CA invasion significantly stimulated the expression of collagen IV and MMP9 detected by RT-PCR, Real-time PCR and Immunofluorescent staining in mouse cornea as soon as 6 hours post infection, and relatively decreased at 1 day post infection. For examining the role of MMP9 in fungal keratitis, the mice corneas were subconjunctivally injected MMP9 antibody or recombinant MMP9 protein 6 hours prior to CA inoculation, using rabbit IgG as control. Subconjunctival injection of recombinant MMP9 protein prior to CA inoculation enhanced, whereas MMP9 antibody attenuated corneal ulceration and inflammation, examining basement membrane, fungal load, myeloperoxidase (MPO) and proinflammatory cytokines including Macrophage inflammatory protein 2 (MIP2), Interleukin-1ß (IL-1ß) and Tumor necrosis factor-α (TNF-α). Inhibition of MMP9 could potentially attenuate Candida albicans induced inflammation in mouse cornea.

Molecular and characterization of NnPPO cDNA from lotus (Nelumbo nucifera) in rhizome browning.

The complete cDNA (NnPPO) of polyphenol oxidase in Nelumbo nucifera was successfully isolated, using Rapid amplification cDNA end (RACE) assays. The full-length cDNA of NnPPO was 2069 bp in size, containing a 1791 bp open reading frame coding 597 amino acids. The putative NnPPO possessed the conserved active sites and domains for PPO function. Phylogenetic analysis revealed that NnPPO shared high homology with PPO of high plants, and the homology modeling proved that NnPPO had the typical structure of PPO family. In order to characterize the role of NnPPO, Real-time PCR assay demonstrated that NnPPO mRNA was expressed in different tissues of N. nucifera including young leave, rhizome, flower, root and leafstalk, with the highest expression in rhizome. Patterns of NnPPO expression in rhizome illustrated its mRNA level was significantly elevated, which was consistent with the change of NnPPO activity during rhizome browning. Therefore, transcriptional activation of NnPPO was probably the main reason causing rhizome browning.

The exceptional chelating ability of dimethylaluminum chloride and methylaluminum dichloride. The merged stereochemical impact of alpha- and beta-stereocenters in chelate-controlled carbonyl addition reactions with enolsilane and hydride nucleophiles.

A systematic investigation of the stereoselectivity in Lewis acid-promoted (Mukaiyama) aldol reactions of achiral unsubstituted enolsilanes and chiral beta-hydroxy aldehydes proceeding under conditions favoring chelation control is presented. Good stereocontrol can be realized for enolsilane aldol reactions of beta-alkoxy and beta-silyloxy aldehydes bearing only an alpha- or a beta-stereogenic center. Examination of the chelated intermediates for alpha,beta-disubstituted aldehydes concludes that the syn aldehyde diastereomer possesses the arrangement of stereocenters wherein the alpha- and beta-substituents impart a reinforcing facial bias upon the aldehyde carbonyl. Aldol reactions of syn aldehydes were thus observed to proceed with uniformly excellent diastereofacial selectivity. Aldol reactions of the corresponding anti aldehydes containing opposing stereocontrol elements at the alpha- and beta-positions exhibit variable and unpredictable selectivity.

A novel phosphotyrosine mimetic 4'-carboxymethyloxy-3'-phosphonophenylalanine (Cpp): exploitation in the design of nonpeptide inhibitors of pp60(Src) SH2 domain.

The novel phosphotyrosine (pTyr) mimetic 4'-carboxymethyloxy-3'-phosphonophenylalanine (Cpp) has been designed and incorporated into a series of nonpeptide inhibitors of the SH2 domain of pp60(c-Src) (Src) tyrosine kinase. A 2.2 A X-ray crystal structure of 1a bound to a mutant form of Lck SH2 domain provides insight regarding the structure-activity relationships and supports the design concept of this new pTyr mimetic.

Synthesis and antitumor activity of spin labeled derivatives of podophyllotoxin.

Three new nitroxyl labeled derivatives of podophyllotoxin 4-6 have been synthesized and evaluated for their antitumor activity in vitro. Compounds 4-6 showed significant inhibitory activity against human nasopharyngeal carcinoma KB,lung cancer A549 and stomach carcinoma SGC-7901 cells, as well as mouse leukemia L1210 and P388 cells. Compounds 4 and 5 exhibited comparable or superior activity to clinically used etoposide (VP-16,2) in their inhibition of these cell lines.

[Plasma endothelin level in patients with pregnancy induced hypertension and its correlation with atrial natriuretic peptide].

Plasma levels of endothelin (ET) and atrial natriuretic peptide (ANP) were measured in 32 normal pregnant women and 26 patients with pregnancy induced hypertension (PIH). The correlation between ET and ANP were examined. This study indicated that the levels of ET and ANP in hypertensive pregnancy were higher than those of the normal pregnancy (P < 0.01). There was no correlation between ET and ANP in normal pregnancy (r = 0.18, P > 0.05), but significant inverse correlation in the patient with PIH (r = -0.57, P < 0.05). There findings suggested that ET may play an important role in the pathogenesis of PIH. An imbalance of increased amount of ET relative to deficient ANP may lead to PIH.

[Clinical analysis of 36 repeat cesarean sections performed extraperitoneally].

Extraperitoneal repeat cesarean section (CS) performed in 36 women with previous intraperitoneal CS (group A) was compared with another 36 cases of intraperitoneal repeat CS (group B). The average blood loss was 146ml in group A and 230ml in group B (P < 0.01). Operation time in group A lasted 40 minutes including 9 cases of tubal ligation coincidentally and 66 minutes in B with 12 tubal ligation (P < 0.05). There were 2 cases of peritoneal damage and 1 transient hematuria in group A. Postoperative morbidity in group A was 16.7% and 38.9% in group B (P < 0.01). The average time for bowel function recurrence was 26.2 hours in A and 52.6 in B respectively. No evident complication occurred in either group. It indicated that extraperitoneal route might be superior to intraperitoneal one for repeat cesarean section.

[Motilin and gastrin in human milk].

The concentrations of motilin and gastrin were determined in the blood and milk of 45 women 3-5 days postpartum, and in the blood of 20 healthy non-pregnant women as control. Plasma motilin concentration (443.05 +/- 140.79 ng/L) and serum gastrin level (301.32 +/- 100.98 ng/L) were significantly higher in postpartum women than those in the control (366.12 +/- 96.23 ng/L and 76.13 +/- 13.11 ng/L, respectively) (P < 0.01). The concentrations of both motilin and gastrin in the milk were approximately one half of those in the blood and they were not present in the boiled milk. The results indicated that both hormones in the human milk may be important for development and maturation of gastro-intestinal function in neonates, especially for immature babies.

[Changes of plasma motilin concentration in pregnancy and early postpartum period].

Plasma motilin concentration were determined by radioimmunoaction from 180 women during pregnancy and early postpartum period as compared with 20 healthy non-pregnant women. The results showed that mean plasma motilin concentration (384.40 +/- 110.30 ng/L) was higher in the first trimester of pregnancy than that of healthy non-pregnant women (366.12 +/- 96.23 ng/L), however, this difference did not reach statistical significance (P > 0.05). The mean plasma motilin concentration (323.90 +/- 125.10 ng/L) was lower in the second trimester of pregnancy than in the first trimester of pregnancy (P < 0.05), while the mean plasma motilin concentration in the third trimester of pregnancy (121.04 +/- 27.00 ng/L) was significantly lower than in second (P < 0.01) and the mean plasma motilin concentration in 3-5 d after delivery (443.05 +/- 140.79 ng/L) reached an even higher value (P < 0.01). Our results suggests that pregnancy appears to have a profound inhibitory effect on plasma motilin and this may in part be responsible for the gastrointestinal hypomotility during pregnancy.

[The use of synthetic haANP III in the treatment of heart failure in pregnancy induced hypertension].

Highly active atrial natriuretic peptide III (haANP III) was administered for the treatment of heart failure due to pregnancy induced hypertension (PIH) in 7 patients with success. The heart failure was rapidly controlled within 24-48 hours with lowering of the blood pressure, disappearance of edema and urinary protein and alleviation of subjective symptoms. The plasma level of renin, angiotensin, aldosterone (RAA) and SOD all decreased. The results suggested that haANP III had the ability to facilitate the excretion of sodium and water, dilate the blood vessels and inhibit the action of RAA, and it could effectively reduce heart load and improve the cardiac function. Therefore, haANP III seemed to be an ideal new drug in treating heart failure in PIH, and it would have a wide scope for future development.

Curative effects of highly active atrial natriuretic peptide on severe pregnancy-induced hypertension.

A new highly active atrial natriuretic peptide (haANP), synthesized by a solid phase technique, was given by intravenous infusion to 20 patients with severe pregnancy-induced hypertension (PIH) and the curative result of haANP was observed. Compared with basal values, supine systolic and diastolic BP was lowered significantly (P < 0.01), which may be related to the specific receptor of hANP and inhibition of renin-angiotensin-aldosterone system (RAAS). The haANP was found to possess significant effects of antispasm, detumescence and reducing proteinuria, probably by repairing mildly injured glomerulae, strong effects of diuresis and improving heart function with no side effects. Auto-antibody of hANP was found in patients with severe PIH, which affected the function of target cells of highly concentrated endogenous hANP. This auto-antibody might be one of the causes for PIH.

[Antigenic localities in the tissues of Metagonimus yokogawai in the period of growth].

In order to observe the antigenic localization in the tissues of Metagonimus yokogawai in growth stages, immunogoldlabeling method was applied to using serum of the cat which infected with isolated metacercariae from Plecoglossus altivelis. The sectioned worm tissues from each growth stages were embedded in Lowicryl HM 20 medium, stained with infected serum IgG and protein A gold complex (particle size: 12 nm) and observed by electron microscopy. In the worm tissues of all experimental groups, the gold particles were specifically concentrated on the tegumental syncytium and cytoplasm of the tegumental cell as well as the secretory granules in the parenchymal tissue. In the 16th and 20th week grown worm tissues, the gold particles were specifically concentrated on the vesicles in the tegumental syncytium and cytoplasm of the tegumental cell. The gold particles were specifically concentrated on the caecal epithelia of the 4th, 8th and 12th week growth groups but slightly concentrated on those of the 16th and 20th week.

Distribution and characteristics of placental ANP receptors in normal and hypertensive pregnancy.

The ANP (atrial natriuretic peptide) receptor binding site was studied in human placentas of normal and hypertensive pregnancy. The results showed there were specific high affinity ANP receptors in the nonbrush border (fetal side), and their affinity to ANP was higher than that in the microvillous membrane (meternal side). The ANP receptor affinity in the nonbrush border and microvillous membrane of normal pregnancy was higher than that of hypertensive pregnancy. Though the weight of placentas of hypertensive pregnancy was lower than that of normal pregnancy, high ANP concentrations in the placental tissues, umbilical and maternal blood were found in hypertensive pregnancy. It is believed that the distribution of ANP receptors in the placentas is related to hemodynamics, maternal exchange and fluid and electrolyte balance. The decrease of ANP receptors and lowering of affinity in hypertensive pregnancy may influence the the target cell effect of ANP, especially in the fetal side. This may be related to the pathogenesis of hypertensive pregnancy.

Significance of changes in serum superoxide dismutase level in hypertensive syndrome of pregnancy.

The concentration of human serum superoxide dismutase-1 (hSOD-1) containing copper and zinc ions were measured by radioimmunoassay healthy nonpregnant women, 15 normal pregnant women, 15 patients with mild to moderate hypertension (MMHSP) and 15 with severe hypertensive syndrome of pregnancy (SHSP). The mean serum hSOD-1 concentration in nonpregnant women was 148.84 +/- 60.53 (x +/- s) micrograms/L; while in the other 3 groups it was 394.19 +/- 122.21 micrograms/L, 377.12 +/- 173.45 micrograms/L and 581.15 +/- 118.50 micrograms/L. The results suggest that harmful free radicals increase gradually and a strong body defence system against oxidation damage of tissue cells is produced in the course of normal pregnancy and MMHSP. With cardionatrin treatment serum hSOD-1 concentrations of patients ameliorated returned to the level of normal pregnancy. The results indicate that there is a positive correlation between cardionatrin and hSOD-1 levels (r = 0.569, P less than 0.05), and a physiological regulation of the defence system exists, which may be related to the white blood cells. Hence, hSOD-1 probably plays a significant role in defence during normal pregnancy and hypertensive syndrome of pregnancy (HSP).