聚焦女人心

女人的情感,的确难以揣测。也许。身为男人你不了解女人的复杂；也许,作为女人你无法看透自己的内心。但电影聚焦了女性的心理与独特气质,电影中刻画的女人,也许就是你的某个隐形部分。     

The use of a stereological method to estimate the volume of Schistosoma mansoni granulomas: the effect of zinc deficiency

Kidney xenotransplantation is not yet a realistic clinical treatment modality. However, during the last decades more than 30 kidneys from other species have been transplanted into humans; some of the kidneys sustained some function up to 60 days. Recent progress in genetic engineering has raised the possibility to create large transgenic animals which express human complement regulatory proteins (CRP). Since early complement activation is believed to be the main triggering event for xenograft destruction, complement regulation by species-specific CRP should avoid hyperacute rejection in transspecies transplantation. The perfusion of hDAF-transgenic pig kidneys with human blood was not associated with the morphological signs of hyperacute rejection when compared to non-transgenic control organs. Specific immunohistology could demonstrate that the transgene was sufficient to regulate complement activation beyond C3 despite the endothelial deposition of xenoantibodies. In the future, these organs could be further optimized and ultimately tested in a clinical pilot protocol under appropriate immunosuppression.     

Subunit structure of rod cGMP-phosphodiesterase

The rod cGMP phosphodiesterase (PDE) is the G-protein-activated effector enzyme that regulates the level of cGMP in vertebrate photoreceptor cells. Rod cGMP PDE is generally viewed as a heterotrimeric protein composed of catalytic alpha and beta subunits ( approximately90 kDa each) and two copies of the inhibitory subunit gamma ( approximately 10 kDa). However, the possibility that rod PDE could exist as distinct isoforms, such as alphaalphagamma2 and betabetagamma2 has not been ruled out. We have studied this question using cross-linking of PDE subunits with maleimidobenzoyl-N-hydroxysuccinimide ester and para-phenyldimaleimide. The cross-linking resulted in major products with molecular mass of 100 and 150 kDa, a doublet at approximately 180-190 kDa, and a doublet at approximately 210-220 kDa. Cross-linked products were analyzed using polyclonal-specific anti-PDEalphabeta, anti-PDEalpha, anti-PDEbeta, or anti-PDEgamma antibodies. The anti-PDEalpha and anti-PDEalphabeta antibodies recognized all the cross-linked products, whereas anti-PDEbeta and anti-PDEgamma antibodies did not interact with the 150-kDa band, indicating that the composition of this band is most likely alphaalpha. Similar analysis of cross-linked products of trypsin-treated PDE preparations revealed bands that are likely formed by PDEbeta subunit. The molecular size of holo-PDE and trypsin-activated PDE were studied using analytical ultracentrifugation in order to determine if oligomerization of PDE could account for the cross-linking of identical PDE subunits. The sedimentation analysis of both holo-PDE and ta-PDE revealed homogeneous samples with molecular masses of approximately220 and approximately150 kDa, respectively. These results indicate that PDE is likely a mixture of the major species alphabetagamma2, minor species alphaalphagamma2, and possibly betabetagamma2. Our data are consistent with the detection of low PDE activity in the rd mouse, which lacks any functional PDEbeta subunit.     

Effects of antioxidants on streptonigrin-induced DNA damage and clastogenesis in CHO cells

This study evaluates the comparative efficacy of antioxidant vitamins (ascorbic acid and alpha-tocopherol) and non-vitamin antioxidants (glutathione, cysteine and L-2-oxothiazolidine-4-carboxylate (OTZ)) in modulating the detoxification pathway of lactating dams and suckling murine pups. In dams, 100 mg/kg b.w./day treatment of each of the vitamin and non-vitamin antioxidants induced a significant increase in the hepatic level of acid soluble sulfhydryl (-SH) compared to the modulating efficiency of OTZ, glutathione and alpha-tocopherol in the kidney tissue. In the liver and kidney tissues of suckling pups OTZ and alpha-tocopherol were effective in modulating the -SH level. A statistically significant increase in the hepatic glutathione-S-transferase (GST) level was observed by OTZ, glutathione and alpha-tocopherol, while only OTZ was effective in the kidney tissue of dams and pups. In the murine system, the modulation of cellular GST/GSH status, specifically by OTZ, alpha-tocopherol and interacting antioxidant pool, may potentially ameliorate the pathophysiology of oxidative stress.     

IT 9302, a synthetic interleukin-10 agonist, diminishes acute lung injury in rabbits with acute necrotizing pancreatitis

BACKGROUND: Proinflammatory cytokines (eg, tumor necrosis factor [TNF]-alpha, interleukin [IL]-1 and Il- 8) are believed to play an important role in the pathogenesis of acute necrotizing pancreatitis (ANP) and its systemic complications. Recently, IL-10 has emerged as a major anti-inflammatory cytokine, inhibiting the secretion and activities of inflammatory cytokines. Further, a protective effect of IL-10 has recently been shown in experimental acute pancreatitis. The purpose of this study was to test the potential role of a newly developed IL-10 agonist, IT 9302, in a model of ANP in rabbits. METHODS: ANP was induced in 18 rabbits by retrograde injection of 5% chenodeoxycholic acid in the pancreatic duct, followed by duct ligation. The rabbits were allocated to pretreatment with intravenous physiologic saline solution or IT 9302 (200 micrograms/kg) 30 minutes before the induction of ANP. RESULTS: Injection of IT 9302 resulted in a significant reduction in the blood levels of TNF-alpha and IL-8 from 3 to 6 hours. IT 9302 also reduced the amount of ascitic fluid and significantly inhibited neutrophil infiltration and margination, as well as the number of CD11b- and CD18-positive cells in the lung tissues. By contrast, the local pancreatic necrosis, as well as the biochemical changes such as serum amylase, lipase, and calcium, was sever and similar in both groups. Survival was improved significantly after treatment with IT 9302. CONCLUSIONS: As expected, IT 9302 cannot change the degree of ANP induced by 5% bile acid but does reduce mortality rates and the development of acute lung injury, probably through the inhibition of circulating levels of TNF-alpha, IL-8, and the expression of the adhesion molecule complex CD11b/CD18.     

Survival in ovarian cancer treated in a gynecological department of a central hospital

The characteristics of 73 patients with all stages of epithelial ovarian cancer were retrospectively analysed with emphasis on prognostic factors and survival. The patients underwent total hysterectomy, bilateral oophorectomy and infracolic omentectomy. Efforts were made to reduce the tumor burden as much as possible without endangering the general health status of the patient. Postoperative treatment was cisplatin 60 mg/m2 body surface and cyclophosphamide 50 mg/m2 every four weeks (CP). Patients with low general health status were offered either treosulphane 1 g daily for four weeks alternating with four weeks without treatment, or no treatment. Patients in FIGO stage IA and B generally received no postoperative chemotherapy treatment. Fifteen percent were in FIGO stage I, 7% in stage II, 5% in stage III and 23% in stage IV. Fifteen patients could be radically operated, however, only three patients who were in stage III. Fifty-four patients were treated with CP, 11 with treosulphane and eight patients did not receive postoperative treatment. In 28 patients second look laparotomy was performed. Only six patients had a complete pathological response, two of these in stage III. Stage and tumour grade could be identified as prognostic factors. Three-year survival was 70% in stage I, 67% in stage II, 28% in stage III and 0% in stage IV. Survival in 43 patients in stage III and IV was statistically compared to 265 patients from a prospective, randomized study by the Danish Ovarian Cancer Group (DACOVA), comparing cyclophosamide and cisplatin with and without doxorubicin. We found no statistical difference in survival between patients in our material and the DACOVA-material except in patients with low grade tumours whose survival in the CAP-arm of the DACOVA-study was superior. The rate of complete pathological response was significantly better in the DACOVA-study.     

Molecular dynamics simulations of B-DNA: an analysis of the role of initial molecular configuration, randomly assigned velocity distribution, long integration times, and nonconstrained termini

Molecular dynamics simulations of three DNA sequences using the AMBER 3.0 force field were performed with implicit inclusion of water through a distance-dependent dielectric constant and solvated counterions. Simulations of the self-complementary DNA dodecamer d(CGCGAATTCGCG) were started from a regular B-DNA structure and the x-ray single crystal B-DNA structure. Although mean convergence during the 89-ps calculation was confirmed, localized differences in backbone torsionals and base-pair helicoidals were observed. A nanosecond simulation of the nonself-complementary 14 base-pair DNA d(GGCGGAATTGGCGG) indicates that most structural parameters stabilize within the first 100-200 ps, while isolated features show low-frequency oscillations throughout the calculation. The lack of harmonic constraints on the ends of the molecules was shown not to perturb the structural dynamics of the internal oligonucleotide beyond the external 2 base pairs. Comparison of three simulations of the nonself-complementary 14 base-pair DNA d(GGCGAAATTCGCGG), identical in all respects other than the assignment of initial Maxwellian atomic velocity distributions, revealed the inherent systematic variability. The three calculations result in nearly superimposable global structures, with localized variations in torsionals and helicoidals. Our results provide a basis for performing a comparative analysis of the effect of DNA sequence on localized structure.     

Intestinal metabolism of estrogens

Estrogen metabolism in the human intestine was studied in two ways. Firstly, by measuring the excretion of 12 estrogens in pooled human late pregnancy feces before and during the administration of ampicillin (2 g/day). Secondly, by administering 5.4 and 20 mg of 16alpha-hydroxyestrone orally to two postmenopausal women and analyzing the estrogens in simultaneously drawn portal and peripheral venous blood samples at time intervals from 0 to 150 min after steroid administration. The majority of the estrogens in normal pregnancy feces were unconjugated. The amounts of estradiol, estreon and 16-epiestriol excreted, relative to the principal estrogen estriol, were greater than in pregnancy bile or urine and 16alpha-hydroxyestrone, an important biliary estrogen, was only present in trace amounts. Considerable quantities of 15alpha-hydroxyestradiol-17beta were also found. Ampicillin administration, which decreases intestinal bacterial steroid metabolism, caused a huge increase in the fecal excretion of conjugated estrogens. In particular it caused very striking increases in the excretion of both unconjugated and conjugated, estriol, 15alpha-hydroxyestrone, 15alpha-hydroxyestradiol and 2-methoxyestrone. These findings emphasize the active role played by the intestinal microflora in estrogen metabolism under normal conditions. Administration of 16alpha-hydroxyestrone resulted in increases in portal venous unconjugated and conjugated 16alpha-hydroxyestrone, 16-oxoestradiol-17beta, 15alpha-hydroxyestrone, 16-epiestriol and conjugated estriol levels. The most significant finding in both subjects was the large increase in portal venous unconjugated 15alpha-hydroxyestrone. This would suggest that the human intestine (or intestinal contents) has the ability to carry out the transformation, 16alpha-hydroxyestrone leads to 15alpha-hydroxyestrone. Increases in the same estrogens were found in peripheral plasma, with the increase in conjugated estriol occurring in peripheral blood before it was seen in portal blood. The largest elevations in peripheral plasma values were seen in unconjugated estriol and conjugated 16alpha-hydroxyestrone in the subject who received the 20 mg dose and in unconjugated 16alpha-hydroxyestrone and 16-oxoestradiol-17beta in the subject who had the 5.4 mg dose. The intestinal and enterohepatic metabolism of estrogens is discussed in relation to these findings.