New Books Received

Almost every case of eclampsia is preventable. Prevention depends on prenatal care. The earliest possible detection of preeclampsia and of a rise in blood pressure is essential. Edema is the first warning sign; suggested treatment includes rest, minimum salt diet, and acetazolamide. Notification of eclampsia would be an effective weapon in reducing the incidence of the disease.     

Imaging and retention measurements of selenium 75 homocholic acid conjugated with taurine,and the carbon 14 glycochol breath test to document ileal dysfunction due to late radiation damage

In order to assess ileal dysfunction in patients with complaints after pelvic radiation therapy, retention measurements and scintigraphic imaging with selenium 75 homocholic acid conjugated with taurine (⁷⁵Se-HCAT), combined with the carbon 14 glycochol breath test, were evaluated in 39 patients. In 22 patients without ileal resection the results of the⁷⁵Se-HCAT test and the breath test differentiated between a normal functioning ileum (both tests negative) and ileal dysfunction as a cause of complaints (one or both tests positive). Among the patients with ileal dysfunction, the combination of both tests permitted those with bacterial overgrowth (breath test positive,⁷⁵Se-HCAT negative) to be separated from patients with evidence of bile acid malabsorption (⁷⁵Se-HCAT positive, breath test positive or negative). In 17 patients with small-bowel resection, the⁷⁵Se-HCAT test helped to estimate the severity of bile acid malabsorption with implications for therapy. In this group the breath test was false-negative in 7 cases with abnormal⁷⁵Se-HCAT. Additional systematically performed scintigraphic imaging improved the accuracy of the⁷⁵Se-HCAT test, revealing cases with prolonged colonic accumulation of the radiopharmaceutical, causing spurious retention values. In conclusion, assessment of ileal dysfunction by nuclear medicine techniques in post-irradiation conditions provides information about the aetiology and therefore the possibility of adjustment in the clinical management. Offprint requests to: R.A. Valdes Olmos     

Further evidence of lipid peroxidation in post-enteropathic haemolytic-uraemic syndrome

Lipid peroxidation may play a role in the pathogenesis of the haemolytic-uraemic syndrome (HUS). Thirteen children with the post-enteropathic form of HUS were studied using conjugated diene lipids as markers of in vivo lipid peroxidation. Levels of total conjugated diene lipids and 9,11-linoleic acid, the principal conjugated diene in human plasma, were greater in the acute phase of this disorder than in controls. The ratio of plasma vitamin E to lipid was lower than that in children with other renal diseases, and the expected positive correlation between vitamin E and lipids did not hold for HUS patients. These data provide further evidence of lipid peroxidation in HUS and a disturbance in the metabolism of the principal lipid-bound anti-oxidant vitamin E.     

Quantification of glycine and taurine conjugated bile acids in human bile using 1H NMR spectroscopy.

A simple method for quantification of conjugated bile acids in human bile using (1)H NMR spectroscopy is presented. Bile acids in human bile are essentially conjugated with either glycine or taurine. The amide NH resonances from the conjugated bile acids are invariably devoid of interfering signals in (1)H NMR spectra. Under physiologic conditions of human bile (pH approximately 7.0 to 7.7), amide signal intensities are attenuated due to the chemical exchange and hence quantitative estimation is precluded. In the present study, the quantity of total glycine and taurine conjugated bile acids could be obtained accurately by suppressing the amide exchange by reducing the pH slightly lower than physiologic value (6.0 +/- 0.5). Further, the quantity of glycine conjugated bile acids can be calculated accurately by subtracting the quantity of taurine conjugated bile acids from the total conjugated bile acids as determined from the present method.     

共轭亚油酸对正常动物细胞和人体肿瘤细胞间通讯功能的影响

为探讨c9,t11-共轭亚油酸 (CLA)的抑癌作用可能机制 ,在促癌物 (TPA)存在下 ,对正常细胞(CHL)以及人体肿瘤细胞 (SGC 790 1细胞和MCF 7细胞 )的细胞间隙连接通讯功能 (GJIC)的影响 ,采用划痕标记染料示踪技术 (SLDT) ;c9,t11 CLA剂量为 2 5 (mol L ,5 0 (mol L ,10 0 (mol L和 2 0 0 (mol L ,阴性对照为乙醇。结果显示 ,c9,t11 CLA可明显地提高TPA对CHL细胞的GJIC的抑制效应 ,当c9,t11 CLA浓度为 2 0 0 (mol L作用 48h时 ,细胞间隙通讯功能基本上与阴性对照组相近 ;当用c9,t11 CLA作用SGC 790 1细胞和MCF 7细胞2 4h和 48h时 ,可见 (2 4h 10 0 μmol L的MCF 7细胞 ) 2 4h 2 0 0 μmol L和 48h 10 0、2 0 0 μmol L剂量组的肿瘤细胞有一定的细胞间隙通讯功能。提示c9,t11 CLA可提高SGC 790 1细胞和MCF 7细胞的GJIC的功能 ,并且不同程度的拮抗TPA对CHL细胞GJIC的抑制效应     

Further studies on renal nerve stimulation induced release of noradrenaline and dopamine from the canine kidney in situ

The renal venous outflow of dopamine and noradrenaline were studied in the canine kidney in situ in connection with renal nerve stimulation (RNS). RNS (0.5-4 Hz) caused frequency-dependent increases in the outflow of both catecholamines, which could be detected already at 0.5 Hz. The ratio dopamine/noradrenaline in renal venous plasma (approximately 0.15) was not influenced by varying the RNS parameters but was significantly enhanced (to about 0.25) by pretreatment with guanethidine according to a procedure previously used to demonstrate renal dopaminergic vasodilatation. The unstimulated kidney removed conjugated dopamine (which represents 98–99% of the total dopamine in plasma). During RNS the conjugated dopamine outflow to renal venous blood increased, but measurements of conjugated dopamine were less reliable than measurements of free dopamine to assess dopamine release from the kidney. When studying the renal nerve contributions to the renal venous outflow of dopamine and noradrenaline more accurate estimates may be obtained by correcting for the removal of catecholamines delivered to the kidney in arterial plasma. Such corrections were performed with endogenous adrenaline or radiolabelled noradrenaline. The two methods of correction yielded similar results and showed that RNS reduced catecholamine extraction in the kidney. The high ratio of dopamine/noradrenaline in kidney tissue (with a preferential distribution of dopamine to the cortex) and the dopamine outflow to renal venous plasma during RNS support the existence of specific dopaminergic nerves in the dog kidney.     

Conjugated linoleic acid inhibits peritoneal metastasis in human gastrointestinal cancer cells

The effect of conjugated linoleic acid (CLA) on peritoneal metastasis was examined by in vitro treatment of cancer cells and mouse peritoneal metastasis models. First, cell growth of MKN28 human gastric cancer cells and Colo320 human colon cancer cells was suppressed by CLA in a dose-dependent manner with an increment in apoptosis. CLA significantly inhibited invasion into type IV collagen-coated membrane of MKN28 and Colo320 cells (p < 0.05). CLA-induced growth inhibition was recovered by the exposure to antisense S-oligodeoxynucleotide for peroxisome proliferator-activated receptor (PPAR)-gamma in both cell lines. BALB/c nu-nu mice were inoculated with MKN28 and Colo320 cells into their peritoneal cavity, and administrated with CLA intraperitoneally (weekly, 4 times). CLA treatment did not affect food intake or weight gain of mice. CLA treatment significantly decreased metastatic foci of both cells in the peritoneal cavity (p < 0.005). Survival rate in mice inoculated with MKN28 or Colo320 cells was significantly recovered by CLA treatment (p = 0.0025 and 0.0052, respectively). Protein production in MKN28 and Colo320 cells treated with CLA showed a decrease in epidermal growth factor receptor and transforming growth factor-alpha and an increase in Bax. These findings suggest that CLA inhibits metastasis of human gastric and colon cancer cells.     

Antisense inhibition of gene expression and growth in gram-negative bacteria by cell-penetrating peptide conjugates of peptide nucleic acids targeted to rpoD gene

Gram-negative bacteria (GNB) cause common and severe hospital- and community-acquired infections with a high incidence of multidrug resistance (MDR) and mortality. The emergence and spread of MDR-GNB strains limit therapeutic options and highlight the need to develop new therapeutic strategies. In this study, the peptide (RXR)₄XB- and (KFF)₃K-conjugated peptide nucleic acids (PPNAs) were developed to target rpoD, which encodes an RNA polymerase primary σ⁷⁰ that is thought to be essential for bacterial growth. Their antimicrobial activities were tested against different clinical isolates of MDR-GNB in vitro and in infection models. The (RXR)₄XB- and (KFF)₃K- conjugated PNAs were bactericidal against different strains of MDR-GNB in concentration-dependent and sequence-selective manner, whereas a PPNA with a scrambled base sequence had no effect on growth. Among tested PPNAs, (RXR)₄XB conjugate PPNA06 showed more potent and broad spectrum inhibition in multidrug-resistant Escherichia coli, Salmonella enterica, Klebsiella pneumoniae, and Shigella flexneri in vitro and in vivo. The results were associated with suppression of rpoD mRNA and σ⁷⁰ expression, as well as σ⁷⁰ downstream regulated genes including ftsZ, mazF, prfB, rpoS, seqA, turfB and ygjD. The treatment of PPNA06 on mono- or multiple MDR-GBN infected human gastric mucosal epithelial cells demonstrated the complete inhibition on bacterial growth and no influence on morphology and growth of human cells. Also, PPNA06 did not show the induction of antibiotic resistance as compared with classical antibiotics in GNB. These findings firstly demonstrate that rpoD is potential target for developing antisense antibiotics, and indicate that peptide conjugates of anti-rpoD PNA are active against GNBs in vitro and in vivo. Our results offer a feasible strategy for treating MDR-GNB infections.