Silver is used widely in wound dressings and medical devices as a broad-spectrum antibiotic. Metallic silver and most inorganic silver compounds ionise in moisture, body fluids, and secretions to release biologically active <svg style="vertical-align:-2.7337pt;width:27.15px;" id="M1" height="15.95" version="1.1" viewBox="0 0 27.15 15.95" width="27.15"  xmlns="http://www.w3.org/2000/svg">
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</svg>. The ion is absorbed into the systemic circulation from the diet and drinking water, by inhalation and through intraparenteral administration. Percutaneous absorption of <svg style="vertical-align:-2.7337pt;width:27.15px;" id="M2" height="15.95" version="1.1" viewBox="0 0 27.15 15.95" width="27.15"  xmlns="http://www.w3.org/2000/svg">
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</svg> through intact or damaged skin is low. <svg style="vertical-align:-2.7337pt;width:27.15px;" id="M3" height="15.95" version="1.1" viewBox="0 0 27.15 15.95" width="27.15"  xmlns="http://www.w3.org/2000/svg">
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			<text transform="matrix(1,0,0,-1,-56.82,67.16)">
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</svg> binds strongly to metallothionein, albumins, and macroglobulins and is metabolised to all tissues other than the brain and the central nervous system. Silver sulphide or silver selenide precipitates, bound lysosomally in soft tissues, are inert and not associated with an irreversible toxic change. Argyria and argyrosis are the principle effects associated with heavy deposition of insoluble silver precipitates in the dermis and cornea/conjunctiva. Whilst these changes may be profoundly disfiguring and persistent, they are not associated with pathological damage in any tissue. The present paper discusses the mechanisms of absorption and metabolism of silver in the human body, presumed mechanisms of argyria and argyrosis, and the elimination of silver-protein complexes in the bile and urine. Minimum blood silver levels consistent with early signs of argyria or argyrosis are not known. Silver allergy does occur but the extent of the problem is not known. Reference values for silver exposure are discussed.

Alan B. G. Lansdown

A Pharmacological and Toxicological Profile of Silver as an Antimicrobial Agent in Medical Devices

Erectile dysfunction (ED) affects up to 50% of men between the ages of 40 and 70. Treatment with PDE-5 inhibitors is effective in the majority of men with ED. However, PDE-5 inhibitors are not effective when levels of nitric oxide (NO), the principle mediator of erection, are low. The pharmacologic actions of three new potential treatments for ED are discussed in this paper: (1) sGC stimulators/activators, (2) Rho-kinase inhibitors, and (3) sodium nitrite.

George F. Lasker

Jason H. Maley

Philip J. Kadowitz

A Review of the Pathophysiology and Novel Treatments for Erectile Dysfunction

Accumulating evidence indicates that ATP-binding cassette (ABC) transporter ABCG2 plays a key role in regulating the cellular accumulation of porphyrin derivatives in cancer cells and thereby affects the efficacy of photodynamic therapy and photodynamic diagnosis. The activity of porphyrin efflux can be affected by genetic polymorphisms in the <i>ABCG2</i> gene. On the other hand, Nrf2, an NF-E2-related transcription factor, has been shown to be involved in oxidative stress-mediated induction of the <i>ABCG2</i> gene.  Since patients have demonstrated individual differences in their response to photodynamic therapy, transcriptional activation and/or genetic polymorphisms of the <i>ABCG2</i> gene in cancer cells may affect patients' responses to photodynamic therapy.  Protein kinase inhibitors, including imatinib mesylate and gefitinib, are suggested to potentially enhance the efficacy of photodynamic therapy by blocking ABCG2-mediated porphyrin efflux from cancer cells. This review article provides an overview on the role of human ABC transporter ABCG2 in photodynamic therapy and photodynamic diagnosis.

Toshihisa Ishikawa

Hiroshi Nakagawa

Yuichiro Hagiya

Naosuke Nonoguchi

Shin-ichi Miyatake

Toshihiko Kuroiwa

Key Role of Human ABC Transporter ABCG2 in Photodynamic Therapy and Photodynamic Diagnosis

Ghrelin, a peptide hormone, newly identified in oral mucosal tissues, has emerged recently as an important mediator of the processes of mucosal defense. Here, we report on the mechanism of ghrelin protection against ethanol cytotoxicity in rat sublingual salivary gland cells. The protective effect of ghrelin was associated with the increase in NO and PGE2, and upregulation in cytosolic phospholipase <svg style="vertical-align:-3.13504pt;width:17.5px;" id="M2" height="14.5625" version="1.1" viewBox="0 0 17.5 14.5625" width="17.5"  xmlns="http://www.w3.org/2000/svg">
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</svg> (<svg style="vertical-align:-3.13504pt;width:42.674999px;" id="M3" height="14.5625" version="1.1" viewBox="0 0 42.674999 14.5625" width="42.674999"  xmlns="http://www.w3.org/2000/svg">
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</svg>) activity and arachidonic acid (AA) release.  The loss in countering effect of ghrelin occurred with cNOS inhibitor, L-NAME, as well as indomethacin and  COX-1 inhibitor, SC-560, while COX-2 inhibitor, NS-398, and iNOS inhibitor, 1400W, had no effect. The effect of L-NAME was reflected in the inhibition of ghrelin-induced cell capacity for NO production, <svg style="vertical-align:-3.13504pt;width:42.674999px;" id="M4" height="14.5625" version="1.1" viewBox="0 0 42.674999 14.5625" width="42.674999"  xmlns="http://www.w3.org/2000/svg">
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</svg> activation and PGE2 generation, whereas indomethacin caused only the inhibition in PGE2.  Moreover, the ghrelin-induced up-regulation in AA release was reflected in the <svg style="vertical-align:-3.13504pt;width:42.674999px;" id="M5" height="14.5625" version="1.1" viewBox="0 0 42.674999 14.5625" width="42.674999"  xmlns="http://www.w3.org/2000/svg">
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</svg> phosphorylation and S-nitrosylation. Inhibition in ghrelin-induced S-nitrosylation was attained with L-NAME, whereas the ERK inhibitor, PD98059, caused the blockage in <svg style="vertical-align:-3.13504pt;width:42.674999px;" id="M6" height="14.5625" version="1.1" viewBox="0 0 42.674999 14.5625" width="42.674999"  xmlns="http://www.w3.org/2000/svg">
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</svg> protein phosphorylation as well as S-nitrosylation. Thus, ghrelin protection of salivary gland cells against ethanol  involves cNOS-derived NO induction of <svg style="vertical-align:-3.13504pt;width:42.674999px;" id="M7" height="14.5625" version="1.1" viewBox="0 0 42.674999 14.5625" width="42.674999"  xmlns="http://www.w3.org/2000/svg">
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</svg> activation through S-nitrosylation for the increase in AA release at the site of COX-1 action for PGE2 synthesis.

Bronislaw L. Slomiany

Amalia Slomiany

Mechanism of Cytosolic Phospholipase <svg style="vertical-align:-3.27605pt" height="15.5125" version="1.1" viewBox="0 0 18.200001 15.5125" width="18.200001" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg"><g transform="matrix(.017,-0,0,-.017,.062,11.363)"><path id="x41" d="M673 0h-245v28q47 6 58 16t1 39l-55 154h-213q-31 -87 -36 -129q-16 -47 -5 -61t68 -19v-28h-226v28q50 7 68.5 23.5t43.5 80.5l214 524l24 9l193 -536q23 -63 41.5 -79.5t68.5 -21.5v-28zM418 280l-81 255h-2q-74 -197 -101 -255h184z" /></g><g transform="matrix(.012,-0,0,-.012,11.813,15.45)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g></svg> Activation in Ghrelin Protection of Salivary Gland Acinar Cells against Ethanol Cytotoxicity

Reduced nitric oxide (NO) bioavailability and increased oxidative stress are major factors mediating ischemia/reperfusion  (I/R) injury.  Tetrahydrobiopterin (<svg     style="vertical-align:-3.27605pt;width:29.4125px;" id="M1" height="15.25" version="1.1" viewBox="0 0 29.4125 15.25" width="29.4125"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
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			<g transform="matrix(.012,-0,0,-.012,23.012,15.187)"><path id="x34" d="M456 178h-96v-72q0 -51 12.5 -62.5t72.5 -16.5v-27h-256v27q65 5 78 17t13 62v72h-260v28q182 271 300 426h40v-407h96v-47zM280 225v295h-2q-107 -148 -196 -295h198z" /></g>

		
	
</svg>) is an essential cofactor of endothelial NO synthase (eNOS) to produce NO, whereas dihydrobiopterin (<svg     style="vertical-align:-3.27605pt;width:29.4125px;" id="M2" height="15.25" version="1.1" viewBox="0 0 29.4125 15.25" width="29.4125"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x42"/></g><g transform="matrix(.017,-0,0,-.017,9.99,11.112)"><use xlink:href="#x48"/></g>

			<g transform="matrix(.012,-0,0,-.012,23.012,15.187)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g>

		
	
</svg>)
 can shift the eNOS product profile from NO to superoxide, which is further converted to hydrogen peroxide (<svg     style="vertical-align:-3.27605pt;width:19.475px;" id="M3" height="15.25" version="1.1" viewBox="0 0 19.475 15.25" width="19.475"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x48"/></g>

			<g transform="matrix(.012,-0,0,-.012,13.087,15.187)"><use xlink:href="#x32"/></g>

		
	
</svg> <svg     style="vertical-align:-3.27605pt;width:19.1625px;" id="M4" height="15.5125" version="1.1" viewBox="0 0 19.1625 15.5125" width="19.1625"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.363)"><path id="x4F" d="M381 665q131 0 226.5 -93t95.5 -239q0 -158 -96 -253t-238 -95q-137 0 -231 95t-94 238q0 142 92.5 244.5t244.5 102.5zM359 629q-89 0 -151 -74.5t-62 -208.5q0 -141 69 -233t175 -92q90 0 150.5 74t60.5 211q0 152 -69 237.5t-173 85.5z" /></g>

			<g transform="matrix(.012,-0,0,-.012,12.763,15.45)"><use xlink:href="#x32"/></g>

		
	
</svg>) and cause I/R injury.  The effects of <svg     style="vertical-align:-3.27605pt;width:29.4125px;" id="M5" height="15.25" version="1.1" viewBox="0 0 29.4125 15.25" width="29.4125"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x42"/></g><g transform="matrix(.017,-0,0,-.017,9.99,11.112)"><use xlink:href="#x48"/></g>

			<g transform="matrix(.012,-0,0,-.012,23.012,15.187)"><use xlink:href="#x34"/></g>

		
	
</svg> and <svg     style="vertical-align:-3.27605pt;width:29.4125px;" id="M6" height="15.25" version="1.1" viewBox="0 0 29.4125 15.25" width="29.4125"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x42"/></g><g transform="matrix(.017,-0,0,-.017,9.99,11.112)"><use xlink:href="#x48"/></g>

			<g transform="matrix(.012,-0,0,-.012,23.012,15.187)"><use xlink:href="#x32"/></g>

		
	
</svg>
 on oxidative stress and postreperfused cardiac functions were examined in ex vivo myocardial and in vivo femoral I (20&#x2009;min)/R (45&#x2009;min) models.  In femoral I/R, <svg     style="vertical-align:-3.27605pt;width:29.4125px;" id="M7" height="15.25" version="1.1" viewBox="0 0 29.4125 15.25" width="29.4125"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x42"/></g><g transform="matrix(.017,-0,0,-.017,9.99,11.112)"><use xlink:href="#x48"/></g>

			<g transform="matrix(.012,-0,0,-.012,23.012,15.187)"><use xlink:href="#x34"/></g>

		
	
</svg>
 increased NO and decreased <svg     style="vertical-align:-3.27605pt;width:19.475px;" id="M8" height="15.25" version="1.1" viewBox="0 0 19.475 15.25" width="19.475"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x48"/></g>

			<g transform="matrix(.012,-0,0,-.012,13.087,15.187)"><use xlink:href="#x32"/></g>

		
	
</svg> <svg     style="vertical-align:-3.27605pt;width:19.1625px;" id="M9" height="15.5125" version="1.1" viewBox="0 0 19.1625 15.5125" width="19.1625"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.363)"><use xlink:href="#x4F"/></g>

			<g transform="matrix(.012,-0,0,-.012,12.763,15.45)"><use xlink:href="#x32"/></g>

		
	
</svg> releases relative to saline control, and these effects correlated with improved postreperfused cardiac function.  By contrast, <svg     style="vertical-align:-3.27605pt;width:29.4125px;" id="M10" height="15.25" version="1.1" viewBox="0 0 29.4125 15.25" width="29.4125"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x42"/></g><g transform="matrix(.017,-0,0,-.017,9.99,11.112)"><use xlink:href="#x48"/></g>

			<g transform="matrix(.012,-0,0,-.012,23.012,15.187)"><use xlink:href="#x32"/></g>

		
	
</svg>
 decreased NO release relative to the saline control, but increased <svg     style="vertical-align:-3.27605pt;width:19.475px;" id="M11" height="15.25" version="1.1" viewBox="0 0 19.475 15.25" width="19.475"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x48"/></g>

			<g transform="matrix(.012,-0,0,-.012,13.087,15.187)"><use xlink:href="#x32"/></g>

		
	
</svg> <svg     style="vertical-align:-3.27605pt;width:19.1625px;" id="M12" height="15.5125" version="1.1" viewBox="0 0 19.1625 15.5125" width="19.1625"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.363)"><use xlink:href="#x4F"/></g>

			<g transform="matrix(.012,-0,0,-.012,12.763,15.45)"><use xlink:href="#x32"/></g>

		
	
</svg> release similar to the saline control, and these effects correlated with compromised postreperfused  cardiac function.  In conclusion, these results suggest that promoting eNOS coupling to produce NO and decrease <svg     style="vertical-align:-3.27605pt;width:19.475px;" id="M13" height="15.25" version="1.1" viewBox="0 0 19.475 15.25" width="19.475"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x48"/></g>

			<g transform="matrix(.012,-0,0,-.012,13.087,15.187)"><use xlink:href="#x32"/></g>

		
	
</svg> <svg     style="vertical-align:-3.27605pt;width:19.1625px;" id="M14" height="15.5125" version="1.1" viewBox="0 0 19.1625 15.5125" width="19.1625"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.363)"><use xlink:href="#x4F"/></g>

			<g transform="matrix(.012,-0,0,-.012,12.763,15.45)"><use xlink:href="#x32"/></g>

		
	
</svg> may be a key mechanism to restore postreperfused  organ function during early reperfusion.

Qian Chen

Elizabeth Eun Jung Kim

Katrina Elio

Christopher Zambrano

Samuel Krass

Jane Chun-wen Teng

Helen Kay

Kerry-Anne Perkins

Sailesh Pershad

Sloane McGraw

Jeffrey Emrich

Jovan S. Adams

Lindon H. Young

The Role of Tetrahydrobiopterin and Dihydrobiopterin in Ischemia/Reperfusion Injury When Given at Reperfusion

Testosterone has rapid nongenomic vasodilator effects which could be involved in protective cardiovascular actions. Several authors suggested specific mechanisms to explain this effect, but this matter was not clarified yet. We studied the actions of testosterone and cholesterol on endothelium-denuded rat aorta and their effects on the L-type <svg     style="vertical-align:-0.20473pt;width:32.362499px;" id="M1" height="16.1" version="1.1" viewBox="0 0 32.362499 16.1" width="32.362499"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,15.775)"><path id="x43" d="M614 175l29 -10q-33 -109 -57 -154q-121 -26 -184 -26q-90 0 -160.5 29t-112.5 77t-63.5 105.5t-21.5 119.5q0 157 108 253t277 96q36 0 71.5 -5t69 -13.5t36.5 -8.5q15 -102 20 -150l-29 -8q-20 79 -66.5 114t-128.5 35q-119 0 -187.5 -86t-68.5 -207&#xA;q0 -140 73.5 -227.5t188.5 -87.5q73 0 119.5 37.5t86.5 116.5z" /></g><g transform="matrix(.017,-0,0,-.017,11.503,15.775)"><path id="x61" d="M433 39l-85 -51q-27 0 -47 20q-16 16 -24 44q-5 -3 -24 -16.5t-27 -18.5t-23 -13.5t-25 -12t-19 -3.5q-52 0 -86 36.5t-34 85.5q0 71 81 99q128 43 155 65v17q0 54 -23 83.5t-62 29.5q-28 0 -45 -19t-29 -66q-7 -23 -29 -23q-15 0 -29 13t-14 30t31 40q25 19 68.5 40.5&#xA;t81.5 29.5q49 0 82 -27q45 -39 45 -123v-185q0 -60 35 -60q18 0 36 11zM275 84v156q-12 -6 -49 -23t-41 -19q-31 -14 -46 -31t-15 -43q0 -35 22.5 -55.5t48.5 -20.5q19 0 42 10.5t38 25.5z" /></g>

			<g transform="matrix(.012,-0,0,-.012,18.987,7.613)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g><g transform="matrix(.012,-0,0,-.012,24.699,7.613)"><path id="x2B" d="M535 230h-212v-233h-58v233h-213v50h213v210h58v-210h212v-50z" /></g>

		
	
</svg> current (<svg     style="vertical-align:-4.39397pt;width:28.9px;" id="M2" height="16.65" version="1.1" viewBox="0 0 28.9 16.65" width="28.9"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x49" d="M303 0h-265v28q62 5 76 19.5t14 77.5v400q0 63 -14 77.5t-76 19.5v28h265v-28q-62 -5 -76 -19.5t-14 -77.5v-400q0 -64 14 -78t76 -19v-28z" /></g>

			<g transform="matrix(.012,-0,0,-.012,5.862,15.187)"><use xlink:href="#x43"/></g><g transform="matrix(.012,-0,0,-.012,13.87,15.187)"><use xlink:href="#x61"/></g><g transform="matrix(.012,-0,0,-.012,19.094,15.187)"><path id="x2C" d="M95 130q31 0 61 -30t30 -78q0 -53 -38 -87.5t-93 -51.5l-11 29q77 31 77 85q0 26 -17.5 43t-44.5 24q-4 0 -8.5 6.5t-4.5 17.5q0 18 15 30t34 12z" /></g><g transform="matrix(.012,-0,0,-.012,21.807,15.187)"><path id="x4C" d="M495 163l30 -6q-19 -99 -36 -157h-453v28q63 5 77.5 20t14.5 78v400q0 63 -13 77t-75 19v28h261v-28q-61 -5 -74.5 -19t-13.5 -77v-395q0 -41 5 -59t18 -25q24 -13 96 -13q85 0 112 31q30 33 51 98z" /></g>

		
	
</svg>) and potassium current (<svg     style="vertical-align:-3.27605pt;width:14.55px;" id="M3" height="15.25" version="1.1" viewBox="0 0 14.55 15.25" width="14.55"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x49"/></g>

			<g transform="matrix(.012,-0,0,-.012,5.862,15.187)"><path id="x4B" d="M667 0h-153l-248 291q-28 32 -54 27v-190q0 -65 14.5 -80t77.5 -20v-28h-260v28q58 5 71 20t13 80v392q0 48 -6 66.5t-22 25.5t-59 10v28h258v-28q-59 -5 -73 -20.5t-14 -81.5v-175q29 6 70 45q101 97 167 178q23 27 20 37t-36 14l-23 3v28h240v-28q-57 -5 -86 -18.5&#xA;t-76 -56.5q-40 -35 -177 -175q97 -124 235 -272q39 -41 61.5 -54t59.5 -18v-28z" /></g>

		
	
</svg>). Testosterone (1&#x2013;100&#x2009;<svg     style="vertical-align:-3.56265pt;width:9.5625px;" id="M4" height="12.175" version="1.1" viewBox="0 0 9.5625 12.175" width="9.5625"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,7.675)"><path id="x1D707" d="M538 96q-38 -45 -84 -76.5t-71 -31.5q-44 0 -15 117q12 49 18 89h-2q-99 -128 -163 -178q-36 -28 -70 -28q-26 0 -44 38h-2q-16 -69 -16 -129q0 -43 11 -75.5t24 -42.5l1 -6q-7 -12 -24.5 -23t-37.5 -11q-40 0 -40 76q0 52 35 202l94 407l78 24l5 -5q-32 -122 -72 -310&#xA;q-7 -33 0 -55t25 -22q36 0 105.5 75t107.5 145l32 146l75 26h10q-50 -197 -78 -347q-7 -38 6 -38q7 0 31 17t47 39z" /></g>

		
	
</svg>M) totally relaxed, in a rapid and concentration-dependent way, the aortic rings contracted by KCl or by (<svg     style="vertical-align:-0.0pt;width:10.1px;" id="M5" height="4.8874998" version="1.1" viewBox="0 0 10.1 4.8874998" width="10.1"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,4.825)"><path id="x2212" d="M535 230h-483v50h483v-50z" /></g>

		
	
</svg>)-Bay K8644 (BAY). Cholesterol also fully relaxed the contractions induced by KCl. None of the potassium channel antagonists tested (glibenclamide, tetraethylammonium and 4-aminopyridine) modified significantly the relaxant effect of testosterone. The antagonist of classic testosterone receptors, flutamide, did not modify the vasorelaxant effect of testosterone. Furthermore, testosterone and cholesterol inhibited either basal and BAY-stimulated <svg     style="vertical-align:-4.39397pt;width:28.9px;" id="M6" height="16.65" version="1.1" viewBox="0 0 28.9 16.65" width="28.9"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x49"/></g>

			<g transform="matrix(.012,-0,0,-.012,5.862,15.187)"><use xlink:href="#x43"/></g><g transform="matrix(.012,-0,0,-.012,13.87,15.187)"><use xlink:href="#x61"/></g><g transform="matrix(.012,-0,0,-.012,19.094,15.187)"><use xlink:href="#x2C"/></g><g transform="matrix(.012,-0,0,-.012,21.807,15.187)"><use xlink:href="#x4C"/></g>

		
	
</svg> in A7r5 cells and they have no effects on <svg     style="vertical-align:-3.27605pt;width:14.55px;" id="M7" height="15.25" version="1.1" viewBox="0 0 14.55 15.25" width="14.55"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x49"/></g>

			<g transform="matrix(.012,-0,0,-.012,5.862,15.187)"><use xlink:href="#x4B"/></g>

		
	
</svg>. In summary, our results demonstrate that cholesterol and testosterone relax rat aorta by inhibiting LTCC. This effect of testosterone is not mediated by the classic hormone receptor or by potassium channel activation. These results suggest that the vasodilator mechanism of cholesterol and testosterone is the same.

E. &#xc1;lvarez

E. Cairr&#xe3;o

M. Morgado

C. Morais

I. Verde

Testosterone and Cholesterol Vasodilation of Rat Aorta Involves L-Type Calcium Channel Inhibition

<i>Background</i>. <i>Teucrium polium</i> is used in Arab traditional medicine to treat liver diseases. Glutathione is an important intracellular antioxidant, and intrahepatic glutathione levels are depleted in liver diseases.
 <i>Hypothesis and Aim</i>. This investigation tested the hypothesis that aqueous extracts of <i>T. polium</i> maintains intracellular glutathione levels by augmenting glutathione peroxidase and glutathione reductase activity in cultured hepatocytes.
<i>Methods</i>.
The effects of increasing concentrations (0.01&#x2013;1&#x2009;mg/mL) of aqueous extract of <i>T. polium</i> were assessed in cultured HepG2 cells following 24 hours incubation on (1) cellular integrity using (a) the Trypan blue exclusion assay, (b) the [di-methylthiazol-2yl]-2,5-diphenyl-tetrazoliumbromide (MTT) assay, and (c) the lactate dehydrogenase (LDH) assay; (2) glutathione redox state; and (3) glutathione peroxidase and glutathione reductase activities using a repeated measures experimental design. 
<i>Results</i>. At concentrations of 0.375&#x2009;mg/mL and 0.5&#x2009;mg/mL, the extract increased the intracellular levels of total and reduced glutathione and had no effect on the intracellular amounts of oxidized glutathione. The extract had no effect on glutathione peroxidase and glutathione reductase activities. 
<i>Conclusion</i>.
These data indicate that the mechanism of the hepatoprotective action of aqueous extracts of <i>T. polium</i> may be, in part, due to augmenting intracellular glutathione levels.

Stella Shtukmaster

Predrag Ljubuncic

Arieh Bomzon

The Effect of an Aqueous Extract of <i>Teucrium polium</i> on Glutathione Homeostasis In Vitro: A Possible Mechanism of Its Hepatoprotectant Action

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<p><em>Advances in Pharmacological and Pharmaceutical Sciences</em> publishes original research articles and&nbsp;review articles in all areas of experimental and clinical pharmacology, pharmaceutics, medicinal chemistry and drug delivery.</p>


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Advances in Pharmacological and Pharmaceutical Sciences publishes original research articles and review articles in all areas of experimental and clinical pharmacology, pharmaceutics, medicinal chemistry and drug delivery.

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Advances in Pharmacological and Pharmaceutical Sciences

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Advances in Pharmacological and Pharmaceutical Sciences