Silver(I)-imidazole cyclophane gem-diol complex, 3 [Ag2C36 N10(O)4](2+)2(x)-, where x = OH- or CO3(2-), was synthesized and well characterized. The minimum inhibition concentration tests showed that the aqueous form of 3 is 2 times less effective as an antibiotic than 0.5% AgNO3, with about the same amount of silver. The antimicrobial activity of 3 was enhanced when encapsulated into Tecophilic polymer by electrospinning to obtain mats made of nano-fibers. The fiber mats released nanosilver particles, which in turn sustained the antimicrobial activity of the mats over a long period of time. The rate of bactericidal activity of 3 was greatly improved by encapsulation, and the amount of silver used was much reduced. The amount of silver contained in the fiber mat of 3, with 75% of 3 and 25% Tecophilic, was 8 times less than that in 0.5% AgNO3 and 5 times lower than that in silver sulfadiazine cream 1%. The fiber mat was found to kill S. aureus at the same rate as 0.5% AgNO3, with zero colonies on an agar plate, and about 6 times faster than silver sulfadiazine cream. The silver mats were found effective against E. coli, P. aeruginosa, S. aureus, C. albicans, A. niger, and S. cerevisiae. Transmission electron microscopy and scanning electron microscopy were used to characterize the fiber mats. The acute toxicity of the ligand (imidazolium cyclophane gem-diol dichloride) was assessed by intravenous administration to rats, with an LD 50 of 100 mg/kg of rat.

The bis(N-heterocyclic carbene) (NHC) silver complex, 3, with a methyl carbonate anion was formed from the reaction of the iodide salt of methylated caffeine, 1, with silver (I) oxide in methanol. Attempts to crystallize this complex from a mixture of common alcohols and ethyl acetate led to the formation of an NHC-silver acetate complex, 4. The more direct synthesis of 4 was accomplished by the in-situ deprotonation of 1 by silver acetate in methanol. Complex 4 demonstrated antimicrobial activity against numerous resistant respiratory pathogens from the lungs of cystic fibrosis (CF) patients including members of the Burkholderia cepacia complex that cause a high rate of mortality in patients with cystic fibrosis (CF). Application of this NHC silver complex to primary cultures of murine respiratory epithelial cells followed by microarray analysis showed minimal gene expression changes at the concentrations effective against respiratory pathogens. Furthermore, methylated caffeine without silver showed some antibacterial and antifungal activity.

The objective of our study was to determine the genetic influence on blood pressure in spontaneously hypertensive rats (SHR), and normotensive Wistar-Kyoto (WKY) rats using genetic crosses. Blood pressure was measured by tail sphygmomanometry from 8 to 20 weeks of age. Blood pressure was significantly higher from 12 to 20 weeks in the male offspring derived from WKY mothers x SHR fathers as compared with male offspring derived from SHR mothersxWKY fathers (180±4 versus 160±5 well-studied animal model of human essential hypertension. This inbred strain was developed by selective breeding of the Wistar-Kyoto (WKY) stock for higher blood pressure.1 The response to this selection was rapid, with almost 100% hypertension by generation three.2 This quick selective response indicates that only a few genetic loci were involved. This genetically selected SHR strain spontaneously and consistently develops moderate-to-severe hypertension between 7 and 15 weeks of age and has served as one model of genetic hypertension in humans. 34 Several studies have shown that, although the SHR is stress responsive, it is actually quite resistant to elevated dietary sodium unless coupled with high stress.5 -7 However, the genetic mechanism of hypertension in the SHR model is not yet understood, and comparative studies of various genetic hypertensive rat strains suggest several different pathogenic mechanisms.8 A few studies have used crosses of closely related strains and subsequent backcrosses that further support the idea that very few loci (from one to four) appear to be Received October 2,1989; accepted in revised form April 19,1990. involved in the development of SHR hypertension. -12Also, a few studies have examined genetic markers of hypertension using different animal models. 13-19 However, no consistent trends have emerged across rat models and specifically in the SHR as to the specific genes responsible for hypertension.One of the more studied rat models with regard to the genetics of hypertension is the Dahl salt-sensitive (DS) and salt-resistant (DR) rat. In the DS rat there is no reported evidence for sex-linked loci controlling blood pressure.20 Sex steroids do, however, exert effects as female DS rats show slower sodiuminduced rises in blood pressure than males and castration of females altered their blood pressure to respond like that of males to salt. 21 Endocrine studies have shown that the adrenals are necessary for the development of hypertension in DS rats, 22 and genetic studies have shown that the characteristic steroid patterns of DS and DR rats are controlled by a single genetic locus (HYP-1) with two codominant alleles.14 However, there are other loci involved as the HYP-1 locus accounted for a 16 mm Hg blood pressure difference between DS and DR rats and the remaining difference was due to other unidentified genetic loci (see Reference 23 for a comprehensive review on DS and DR rats).Also, in the psychosocial stress hypertension mouse model, 24 the rat model, 2 -25 and in human hypertension, there is highe...

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We report on five 6-month experiments during which five colonies of four male and four female rats were exposed to psychosocial stress. Monthly blood pressure measurements by a tail-cuff method showed a modest (10 mm Hg) increase in two studies using Sprague-Dawley rats. In two further studies using the more aggressive Long-Evans strain, terminal direct carotid arterial pressures were taken as well, and in one study the differences exceeded 20 mm Hg. A fifth study used the Wistar-Kyoto, hyperactive (WKHA) strain developed by Hendley, and no differences were observed. Heart and adrenal weights; adrenal catecholamine synthetic enzymes; and heart, aortic, and kidney histology were measured and showed significant changes, which for the most part paralleled blood pressure changes. Social instability and the associated blood pressure changes were made more severe by periodic mixing of males from different colonies. This had no effect on the peaceable WKHA rats, some effect on the Sprague-Dawley rats, and a severe effect on the Long-Evans rats. The WKHA rats failed to show blood pressure changes despite stress-induced increases in heart and adrenal weights. Thus, different types of psychosocial stress and different genetics combine to induce a variety of neuroendocrine changes, not all of which necessarily lead to increased blood pressure.