The cuticular plate of the hair cell in relation to morphological gradients of the chicken basilar papilla

The aim of the present study was to provide details on the diversity and morphological gradients in the anatomy of the cuticular plate of hair cells in the chicken basilar papilla. The structure of the cuticular plate, which is mainly made up of a network of actin filaments, may be related to differences in the mechanical demands on the anchorage of the stereovillar bundle. We describe the morphological gradients in the cuticular plates as seen in transverse section for four positions along the basilar papilla. Three different shapes of cuticular plate could be distinguished. In general, cuticular plates in neurally-lying hair cells have their main mass on the neural side of the cells; for abneural cells, the converse is true. The shape of the plates changes gradually across the papilla; symmetrical forms exist. The hair-cell bundle orientation (and thus the preferred direction of stimulation of the bundle), as measured using scanning EM preparations, does not correlate with the shape of the plate in transverse section. The present data confirm the notion developed from other studies that (1) there are no distinct populations of hair cells, (2) there are no linear or monotonic morphological gradients, and (3) the gradients on the papilla are species- and position-specific.     

Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver

The metabolism of imipramine by human liver microsomes was examined using a combination of five strategies. Human hepatic microsomes produced N-desmethylimipramine (84%), 2-hydroxyimipramine (10%), and 10-hydroxyimipramine (6%). Preincubation of human hepatocytes in culture with beta-naphthoflavone and macrolides exclusively induced the formation of desmethylimpramine (552%, p < 0.05, and 234%, p < 0.003, respectively). Correlations were obtained between rates of imipramine demethylation and cytochrome P-450 (P-450) 1A2 (r = 0.88, p < 0.001) and P-450 3A (r = 0.80, p < 0.02) concentrations in human liver microsomal preparations from 13 different subjects. Anti-P-450 1A2 and anti-P-450 3A antibodies selectively inhibited N-demethylation (80% and 60%, respectively). N-Demethylation was completely inhibited when anti-1A2 and anti-3A were added simultaneously. Kinetic studies with human microsomes confirm the contribution of two different enzymes in the N-demethylation. The Km of 1A2 was similar to the high affinity Km in human liver microsomes, whereas the Km of 3A was similar to the low affinity Km in human liver microsomes. P-450 1A2 was apparently more efficient than 3A4 (lower Km and higher Vmax) but was expressed in much lower concentration. Human P-450s 1A2 and 3A4 expressed in yeast efficiently produced desmethylimipramine. These results suggest that P-450 1A2 and P-450 3A4 are the major enzymes involved in imipramine N-demethylation in human hepatic microsomes. Similar experiments were conducted using P-450 2D6, and they confirmed that P-450 2D6 catalyzes imipramine 2-hydroxylation. Interindividual variations in 3A4 hepatic content may explain the large variations in imipramine blood levels observed after uniform dosages and thus may explain the variations in clinical efficacy. Caution might be advised in the clinical use of tricyclic antidepressants when drugs are also administered that induce or inhibit P-450s 3A4 and 1A2.     

Control of smooth muscle cell proliferation by psoralen photochemotherapy

PURPOSE: Restenosis after balloon angioplasty or the intimal hyperplasia occurring at distal anastomoses of bypass grafts severely limits the long-term therapy for peripheral vascular disease. The aim of this study was to evaluate the application of psoralen photochemotherapy with ultraviolet A (UVA)-activated 8-methoxypsoralen (8-MOP) to suppress smooth muscle cell (SMC) proliferation in vitro by the formation of 8-MOP-DNA monoadducts and interstrand cross-links to inhibit DNA synthesis. METHODS: Bovine aorta SMC (2 x 10(4)/cm2) were treated with 8-MOP (0 to 1000 ng/ml) for 30 minutes, followed by UVA (2 joule/cm2) to determine the dose of 8-MOP and UVA that inhibits SMC proliferation. RESULTS: The results show that 8-MOP in the range 30 to 1000 ng/ml in combination with 2 joule/cm2 UVA inhibited SMC proliferation by 40% to 60% 3 days after treatment. In time course studies the growth of SMC treated with 100 ng/ml 8-MOP and 2 joule/cm2 UVA were monitored over 5 days, and this regimen was found to be cytostatic. SMC viability was confirmed by trypan blue exclusion. CONCLUSIONS: Our studies suggest that 8-MOP/UVA photochemotherapy may represent a novel approach to the control of localized SMC proliferation.     

Optimizing the detection of colorectal liver metastases within the Canadian health care system

BACKGROUND: Five to seven percent of patients with psoriasis suffer additionally from accompanying arthritis. AIM OF THE STUDY: In this article, we review the current knowledge on clinical, diagnostic and therapeutic aspects of the disease. PATIENTS AND RESULTS: Data are presented on the treatment of six patients with the immunosuppressant ciclosporin. Therapeutic results with this drug are superior to agents traditionally used for management of psoriatic arthritis. CONCLUSION: The therapeutic options have been enlarged by the introduction of new immunosuppressive drugs, particularly ciclosporin.     

Endothelial cell morphology in areas of in vivo Evans blue uptake in the aorta of young pigs. II. Ultrastructure of the intima in areas of differing permeability to proteins

The fine structure of the intima of the pig aortic arch is described for areas of spontaneously differing in vivo endothelial permeability, as demarcated by uptake of the protein-binding azo dye Evans blue. Areas of enhanced permeability (blue areas) consistently show a variety of features not observed in areas devoid of dye accumulation (white areas). The subendothelial space of blue areas is markedly thickened and edematous, containing collagen, elastic tissue elements, and undifferentiated cells dispersed in an amorphous floccular matrix of low electron density. Endothelial cells in blue areas are generally cuboidal, with relatively short, frequently vacuolated junctions. In contrast, endothelial cells from white areas are flat and elongate, with long intercellular junctions exhibiting many interdigitations. Cytoplasmic differences include a well-developed rough endoplasmic reticulum and more frequent lysosomal bodies in blue areas and a prominent Golgi apparatus in the endothelium of white areas. Additionally, endothelial cell injury or death with and without denudation occurs with a significantly greater frequency in blue relative to white areas. An endothelial glycocalyx is some threefold thicker over the surface of white relative to blue areas. It is concluded that neither endothelial structure nor function are homogeneous within the aortic arch of the young pig and that areas of spontaneously differing permeability to proteins are associated with a spectrum of alterations in endothelial and intimal morphology.     

Acetylation of hydroxytyrosol enhances its transport across differentiated Caco-2 cell monolayers

Hydroxytyrosol and hydroxytyrosyl acetate are two well-known phenolic compounds with antioxidant properties that are present in virgin olive oil. Since the in vivo biological activity of polyphenols is dependent on their intestinal absorption and metabolism, the absorption of hydroxytyrosol and hydroxytyrosyl acetate and the extent to which they are conjugated and metabolised during transfer across intestinal Caco-2/TC7 cell monolayers, was investigated. LC-DAD and LC-MS were used for the quantification and identification of metabolites. Further evidence was obtained by observing metabolite susceptibility to β-glucuronidase treatment and by comparison of products of in vitro conjugation reactions of authentic phenolics with those produced by the CaCo-2 cells. Homovanillyl alcohol was the only conjugate detected as a result of hydroxytyrosol metabolism, and accounted for 20% of the total metabolites detected in the basolateral compartment after 2 h of incubation. Hydroxytyrosyl acetate was largely converted into free hydroxytyrosol (38.4%) and subsequently metabolised into homovanillyl alcohol (6.7%). In addition, hydroxytyrosyl acetate glucuronide (17.4%) together with non-metabolised hydroxytyrosyl acetate (37.5%) were also detected. Both hydroxytyrosyl acetate and hydroxytyrosol were transferred across human Caco-2/TC7 cell monolayers, but the acetylated compound exhibited an apparent permeability (Papp_AP→BL/Papp _BL→AP) 2.1-fold higher than free hydroxytyrosol. For both compounds, all conjugates were preferentially transported to the basolateral side. These results show that the acetylation of hydroxytyrosol significantly increases its transport across the small intestinal epithelial cell barrier, and supports further research into hydroxytyrosyl acetate as a hydroxytyrosol prodrug offering enhanced bioavailability.     

Natural history of myocardial hypertrophy and its association with hyperinsulinism in infants of diabetic mothers

This work is devoted to the study of polarographic reduction of three antibiotic compounds including adriamycin, chloramphenicol and erythromycin and of a synthetic antibacterial chemotherapeutic compound--5-nitrofurantoin. The polarographic reduction was performed in the strictly anhydrous N,N-dimethylformamide with or without alpha-lipoic acid (LA) by the means of DC polarography. The values of half-wave potentials E1/2 and parameter of potential carcinogenicity were determined for the all compounds. Adriamycin was reduced during the five-step process, other compounds were reduced in two steps. The presence of LA in a polarographic solution resulted in a new polarographic one-electron wave in the range of -1.120 V to -1.790 V vs. SCE possessing a diffuse and reversible character. Its height is linearly dependent on the LA concentration in solution. The highest parameter of potential carcinogenicity tg alpha was determined for adriamycin (0.575) which belongs among compounds classified by WHO as "probably carcinogenic to humans". The lowest determined value of parameter tg alpha belonged to 5-nitrofurantoin (0.290) which has not yet been included into the IARC classification.     

Intelligent Sensing for Citizen Science

Interest in Citizen Science has grown significantly over the last decade. Much of this interest can be traced to the provision of sophisticated platforms that enable seamless collaboration, cooperation and coordination between professional and amateur scientists. In terms of field research, smart-phones have been widely adopted, automating data collection and enriching observations with photographs, sound recordings and GPS coordinates using embedded sensors hosted on the device itself. Interaction with external sensor platforms such as those normally used in the environmental monitoring domain is practically null-existent. Remedying this deficiency would have positive ramifications for both the professional and citizen science communities. To illustrate the relevant issues, this paper considers a common problem, that of data collection in sparse sensor networks, and proposes a practical solution that would enable citizen scientists act as Human Relays thus facilitating the collection of data from such networks. Broader issues necessary for enabling intelligent sensing using common smart-phones and embedded sensing technologies are then discussed.     

Phase IIa safety and immunogenicity of a therapeutic vaccine, TA-GW, in persons with genital warts

A fusion protein vaccine consisting of human papillomavirus 6 L2E7 with Alhydrogel was developed for the treatment of genital warts. Twenty-seven subjects with genital warts received 3 immunizations over 4 weeks in an open-label study. The vaccine was well-tolerated, and all subjects made serum IgG antibodies, predominantly IgG1, against L2E7. Nineteen of 25 tested persons made antigen-specific T cell proliferative responses to L2E7, and peripheral blood mononuclear cells when cultured with L2E7 in vitro produced both interferon-gamma and interleukin (IL)-5, although IL-5 predominated after the final vaccination. Five subjects completely cleared warts within 8 weeks. Subjects whose warts were not cleared by 8 weeks were offered conventional therapy. Recurrence of warts was not seen in any of the 13 persons whose warts cleared by vaccine alone or with conventional therapy. While these preliminary results of the use of this therapeutic immunogen are encouraging, proof of efficacy will require randomized double-blind trials.