Conventionally, the architecture of arteries is based around the close-packed smooth muscle cells and extracellular matrix. However, the adventitia and endothelium are now viewed as key players in vascular growth and repair. A new dynamic picture has emerged of blood vessels in a constant state of self-maintenance. Recent work raises fundamental questions about the cellular heterogeneity of arteries and the time course and triggering of normal and pathological remodelling. A common denominator emerging in hypertensive remodelling is an early increase in adventitial cell density suggesting that adventitial cells drive remodelling and may initiate subsequent changes such as re-arrangement of smooth muscle cells and extracellular matrix. The organization of vascular smooth muscle cells follows regular arrangements that can be modelled mathematically. In hypertension, new patterns can be quantified in these terms and give insights to how structure affects function. As with smooth muscle, little is known about the organization of the vascular endothelium, or its role in vascular remodelling. Current observations suggest that there may be a close relationship between the helical organization of smooth muscle cells and the underlying pattern of endothelial cells. The function of myoendothelial connections is a topic of great current interest and may relate to the structure of the internal elastic lamina through which the connections must pass. In hypertensive remodelling this must present an organizational challenge. The objective of this paper is to show how the functions of blood vessels depend on their architecture and a continuous interaction of different cell types and extracellular proteins.

UK-14,304 [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine]-mediated vasodilator responses were studied on wire myograph-mounted mouse aorta to determine the cells involved, mechanisms of action, and subtypes of ␣ 2 -adrenoceptors. In the presence of induced tone, UK-14,304 produced concentration-related vasodilatation that was abolished by rauwolscine, N -nitro-L-arginine methyl ester (L-NAME), or endothelium removal, indicating that endothelial ␣ 2 -adrenoceptors can release nitric oxide. In the ␣ 2A -adrenoceptor knockout mouse and the D79N mouse, a functional knockout of the ␣ 2A -adrenoceptor, these relaxant effects of UK-14,304 were lost, indicating the involvement of the ␣ 2A -adrenoceptor. UK-14,304 could also contract aorta: a small contraction occurred at high concentrations, was enhanced by L-NAME, and was absent in the ␣ 1D -adrenoceptor knockout mouse, indicating activation of the ␣ 1D -adrenoceptor. There was no evidence for a contractile ␣ 2 -adrenoceptor-mediated response. A fluorescent ligand, quinazoline piperazine bodipy, antagonized the relaxant action of UK-14,304. This compound could be visualized on aortic endothelial cells, and its binding could be prevented by rauwolscine, providing direct evidence for the presence of ␣ 2 -adrenoceptors on the endothelium. Norepinephrine reduced tone in the ␣ 1D -adrenoceptor knockout and controls, an effect blocked by rauwolscine and L-NAME but not by prazosin. This suggests that norepinephrine activates endothelial ␣ 2 -adrenoceptors. In conclusion, the endothelium of mouse aorta has an ␣ 2A -adrenoceptor that responds to norepinephrine; promotes the release of nitric oxide, causing smooth muscle relaxation; and that can be directly visualized. Knockout or genetic malfunction of this receptor should increase arterial stiffness, exacerbated by raised catecholamines, and contribute to heart failure.All three ␣ 2 -adrenoceptors have distinct, yet poorly defined, roles in the control of the vascular system. The limited selectivity of agonists and antagonists has therefore prompted the use of transgenic mouse models. The subtypes are ␣ 2A , ␣ 2B , and ␣ 2C : the mouse ortholog of the human ␣ 2A -adrenoceptor is sometimes called the ␣ 2D -or ␣ 2A/D -adrenoceptor; we use the generic term ␣ 2A -adrenoceptor (Alexander et al., 2004). They have two direct pharmacological effects on blood vessels that can modify vascular tone: a direct vasopressor action (for review, see Wilson et al., 1991;Guimaraes and Moura, 2001) and vasodilatation via endothelium-derived relaxant factors (Cocks and Angus, 1983;Vanhoutte, 2001). They also reduce sympathetic traffic centrally and inhibit transmitter release from sympathetic postganglionic nerves (Starke, 2001), although this is not well established as a physiological phenomenon in blood vessels. Available pharmacological data and knockout studies, although not definitive, present evidence for, at least, ␣ 2A -, ␣ 2B -, and ␣ 2C -adrenoceptors for vasoconstriction, ␣ 2A -and ␣ 2C -adrenoceptors for sympatho-...

Background: Cyclophosphamide (CP) has been known as an anticancer drug with several side effects on various organs such as a male reproductive system that can cause infertility. Objective: To evaluate the possible combined effects of zinc oxide nanoparticles (nZno) and melatonin (Mel) on sperm parameters and histopathological changes of the testis in CP-treated rats. Materials and Methods: 42 adult male Wistar rats were divided into six groups. GI: control, GII: 60 mg/kg/wk CP, GIII and GIV, 10 mg/kg/wk Mel and 5mg/kg/wk nZno and GV: 5 mg/kg/wk nZno and 10 mg/kg/wk Mel were given 2 hr prior to CP injection, respectively,GVI: 5mg/kg/wk nZno and 10 mg/kg/wk Mel simultaneously. After 8 wk of treatment, rats were sacrificed and testis and epididymis were harvested for further evaluation. Results: The CP-treated group showed significant decreases in the body, testes and epididymis weights and sperm parameters (sperm count, viability, motility) with an increase abnormal sperms when compared with the control (p<0.001), as well as many histological alterations included decreased diameters of seminiferous tubules and Johnsen's Testicular Score (with degeneration, desquamation, multi-nucleated giant cell formation), whereas combined treatment (GV), showed more protective effects on CP-induced reproductive system damage compared with groups III or IV (p<0.001). Conclusion: These results suggest simultaneous administration of Mel and nZno have more effectively protections against CP-induced reproductive damage than Mel or nZno alone.

Cockroaches are considered to be important reservoirs for protozoan and helminth parasites ,particularly an emerging Lophomonas spp., protozoan parasite. German cockroaches, Blattella germanica (B. germanica), are domestic pest distributed worldwide. However, little information is available regarding the burden of Lophomonas spp. infestation among domestic cockroach population worldwide. The present study investigated parasitic agents, emphasizing Lophomonas spp. infestation among B. germanica in northern Iran. During spring and summer 2018, a total of 496 adults B. germanica (265 males and 231 females) were trapped by hand and glass traps from the teaching hospitals in Mazandaran, Sari, northern Iran. All cockroaches were identi ed using taxonomic keys. Each cockroaches was anesthetized with chloroform and the alimentary tract removed. Each section was smeared onto a glass slide. All the smears were examined under light microscopy to determine the presence of the parasites. Ten genera of parasites were identi ed from the trapped B. germanica; overall, 233 (47%) were found to be positive for helminths (n=135) and protozoa (n=98). The helminths included Aspiculuris tetraptera egg ( 67/233, 28.7%), Oxiuros sp. (39/233; 16.7%), Dentostomella translucida (17/233; 7.3%), and nematodes Ova (12/233; 5.2%). The protozoan parasites identi ed Gregarina sp. (61/233; 26.2%), Entamoeba sp. (19/233; 8.2%), Blastocystis sp. (5/233; 2.1%), Lophomonas (4/233; 1.7%), Nyctotherus sp. (4/233; 1.7%), unclassi ed agella (5/233; 2.1%). Lophomonas spp. was detected within the gut of B. germanica, for the rst time, in Iran. It has previously been identi ed in the gut of cockroaches a long time ago, however, thisis the rst attempt to detect Lophomonas in cockroaches housing in hospitals. Thereby, it possibly presenting pose a serious respiratory infection risk for patients and health care personnel.

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