Biological Sciences

The present study was designed to test the hypothesis that melatonin inhibits nitrate tolerance in coronary arteries.Rings of porcine coronary arteries were suspended in organ chambers for isometric tension recording. Nitrate tolerance was induced by incubating the tissues with nitroglycerin (10−4M) for 90 min, followed by repeated rinsing for 1 h. Control rings that had not been exposed previously to nitroglycerin, but were otherwise treated identically, were studied simultaneously. The rings were contracted with U46619 (1–3 × 10−9M) and concentration–response curves to nitroglycerin (10−9–10−4M) were obtained.Nitrate tolerance was evident by a 15- to 20-fold rightward shift in the concentration–response curve to nitroglycerin in rings with and without endothelium exposed previously to the drug for 90 min. Addition of melatonin (10−9–10−7M) to the organ chamber during the 90-min incubation period with nitroglycerin partially inhibited nitrate tolerance in coronary arteries with intact endothelium; however, melatonin had no effect on nitrate tolerance in coronary arteries without endothelium.The effect of melatonin on nitrate tolerance in coronary arteries with endothelium was abolished by the melatonin receptor antagonist, S20928 (10−6M). In contrast to melatonin, the selective MT3-melatonin receptor agonist, 5-MCA-NAT (10−8–10−7M), had no effect on nitrate tolerance in coronary arteries.The results demonstrate that melatonin, acting via specific melatonin receptors, inhibits nitrate tolerance in coronary arteries and that this effect is dependent on the presence of the vascular endothelium.The present study was designed to test the hypothesis that melatonin inhibits nitrate tolerance in coronary arteries.Rings of porcine coronary arteries were suspended in organ chambers for isometric tension recording. Nitrate tolerance was induced by incubating the tissues with nitroglycerin (10−4M) for 90 min, followed by repeated rinsing for 1 h. Control rings that had not been exposed previously to nitroglycerin, but were otherwise treated identically, were studied simultaneously. The rings were contracted with U46619 (1–3 × 10−9M) and concentration–response curves to nitroglycerin (10−9–10−4M) were obtained.Nitrate tolerance was evident by a 15- to 20-fold rightward shift in the concentration–response curve to nitroglycerin in rings with and without endothelium exposed previously to the drug for 90 min. Addition of melatonin (10−9–10−7M) to the organ chamber during the 90-min incubation period with nitroglycerin partially inhibited nitrate tolerance in coronary arteries with intact endothelium; however, melatonin had no effect on nitrate tolerance in coronary arteries without endothelium.The effect of melatonin on nitrate tolerance in coronary arteries with endothelium was abolished by the melatonin receptor antagonist, S20928 (10−6M). In contrast to melatonin, the selective MT3-melatonin receptor agonist, 5-MCA-NAT (10−8–10−7M), had no effect on nitrate tolerance in coronary arteries.The results demonstrate that melatonin, acting via specific melatonin receptors, inhibits nitrate tolerance in coronary arteries and that this effect is dependent on the presence of the vascular endothelium.British Journal of Pharmacology (2003) 139, 1326–1332. doi:10.1038/sj.bjp.0705383

1. Eleven selected flavonoids were studied to evaluate their effects on the rat isolated ileum and to determine their structure-activity relationships. 2. The flavonoids rutin and 3',5,7-trihydroxy-4' methoxyflavone-7-rutinoside, which have a sugar moiety (O-rha-glu), had no significant effect on the ileum, indicating that the presence of sugar substitution reduces the biological activity of the flavonoids. 3. Nine other flavonoids caused inhibition of tonic and phasic contractions of the ileum with the following order of potency from highest to lowest: galangin, quercetin, chrysin, xanthomicrol, flavone, naringenin, fisetin, morin, and flavanone. 4. Flavones were more potent than flavanones, indicating that the double bond at carbon 2-3 increases the potency of the flavonoid. 5. Galangin, quercetin, chrysin, and xanthomicrol, which have hydroxyl substituents on carbon 3 and/or 5, showed higher potency than flavone, indicating that such hydroxyl groups are essential for the activity. 6. Galangin was more potent than quercetin, morin, and fisetin, suggesting that the hydroxyl substituents on ring B attenuate the potency. 7. Quercetin caused more potent relaxation of the ileum than morin, suggesting that the presence of a hydroxyl group at C-2' of ring B attenuates the myolytic activity.

Abstract
The prevalence of adhesion (icaA and icaD) and toxin (tst, eta, and etb) genes was studied in 100 clinical Staphylococcus aureus isolates. The icaA, icaD, eta, etb and tst genes were detected by PCR in 91%, 91%, 2%, 1% and 43% of the isolates, respectively. Various gene combinations with the previously reported enterotoxin genes (sea, sec, sei, seg and seh) were detected in 47 of 100 isolates. These combinations fall into 3 groups: group I which includes one eta+sea containing isolate, group II which includes 25 (53.2%) isolates lacking tst gene but harboring icaA+icaD genes in 11 combinations with the enterotoxin genes and group III which includes 21 (44.7%) isolates harboring icaA+icaD+tst in 7 different combinations with the enterotoxin genes. The predominant gene combinations in group II and III isolates include seg + sei or seg of the enterotoxin gene cluster (egc). Furthermore, 20 isolates of group III have the corresponding gene combination profiles of 20 isolates of group II in addition to the tst gene. This could be attributed to loss or acquisition of SaPI1 and/or SaPI2 islands which carry the tst gene.
The dominancy of SaPI1/SaPI2 and egc associated toxin genes in the slimy isolates of S. aureus may be understood in the context of pathogenicity functioning genes. This data would contribute to the control of colonization and spread of these isolates in hospitals and community at large.

One hundred clinical Staphylococcus aureus including 57 methicillin-resistant (MRSA) and 43 methicllin-sensitive (MSSA) isolates were analyzed for susceptibility to three aminoglycosides and for the presence of genes encoding aminoglycoside modifying enzymes (AMEs). 52% of these isolates were resistant to 1-3 aminoglycosides, which included 65% MRSA and 35% MSSA isolates. The aminoglycoside resistance genes were more frequently identified in MRSA than in MSSA isolates. The most frequent gene was aac(6')/aph(2") and it was detected in 45% S. aureus isolates which included 52.6% MRSA and 34.8% MSSA isolates. The second prevalent gene was ant(4',4") and it was detected in 31% S. aureus which included 40.3% MRSA and 18.6% MSSA isolates. 21% of S. aureus isolates including 29.8% MRSA and 9.3% MSSA isolates, carried the aph(3')III gene. The most frequent combination of genes was aac(6
′
)/aph(2
′ ′ ) with ant(4',4") in 22.8% MRSA and in 16.2% MSSA isolates. The second dominant gene combination was aac(6')/aph(2") with aph(3')III in 17.5% MRSA and in 6.9% MSSA isolates. The ant(4',4") and aph(3′)III combination existed only in 7% MRSA isolates. The 3 genes coexisted in 5.3% MRSA and in 2.3% MSSA isolates. The concordance between the presence of genes and aminoglycoside resistance phenotype was observed in most MRSA and MSSA isolates. Emerging of isolates harboring these genes must not be ignored because it limits the choices in the number of antibiotics available to clinicians to treat staphylococcal infections in risk patients.

Torque teno virus (TTV) is the most common component of the human blood virobiota. Little is known, however, about the prevalence of TTV in humans and the most common farm domesticates in Jordan, or the history and modality of TTV transmission across species lines. We therefore tested sera from 396 Jordanians and 171 farm animals for the presence of TTV DNA using nested 5′-UTR-PCR. We then performed phylogenetic, ordination and evolutionary diversity analyses on detected DNA sequences. We detected a very high prevalence of TTV in Jordanians (~96%); much higher than in farm animal domesticates (~29% pooled over species). TTV prevalence in the human participants is not associated with geography, demography or physical attributes. Phylogenetic, ordination and evolutionary diversity analyses indicated that TTV is transmitted readily between humans across the geography of the country and between various species of animal domesticates. However, the majority of animal TTV isolates seem to derive from a single human-to-animal transmission event in the past, and current human-animal transmission in either direction is relatively rare. In conclusion, animal TTV in Jordan is historically derived from human variants; however, ongoing human-animal TTV exchange is minimal and zoonotic infection seems to be of limited importance.