A coated implantable medical device 10 includes a structure 12 adapted for introduction into the vascular system, esophagus, trachea, colon, biliary tract, or urinary tract; at least one layer 18 of a bioactive material positioned over the structure 12; and at least one porous layer 20 positioned over the bioactive material layer 18. Preferably, the structure 12 is a coronary stent, and the bioactive material is at least one of heparin, dexamethasone or a dexamethasone derivative. The device 10 includes layers 18 and 22 of heparin and dexamethasone, the layer 22 of dexamethasone being positioned above the layer 18 of heparin. The layers of bioactive material also can be individual materials or a combination of different materials. Unexpectedly, the more soluble heparin markedly promotes the release of the less soluble dexamethasone above it. The porous layer 20 is composed of a polymer applied by vapor or plasma deposition and provides a controlled release of the bioactive material. It is particularly preferred that the polymer is a polyimide, parylene or a parylene derivative, which is deposited without solvents, heat or catalysts, merely by condensation of a monomer vapor.

Coated implantable medical device

3 The sertoli cell

Hirsutism: Implications, etiology, and management☆

THE ability of cells to interact and communicate is a biological phenomenon that developed with the evolution of multicellular organisms. The cell-cell interactions that have evolved are essential for the survival of both simple organisms such as dictyostelium and complex organisms such as mammals. These cellular associations allow an organism to develop capacities that are greater than the simple sum of their individual parts. As early as 1878, Claude Bernard proposed that the “milieu interieur” (i.e. internally produced fluid environment) and a cybernetic-like control system (i.e. cell-cell interactions and communication) in multicellular organisms are needed to adaptively regulate the growth, development, and maintenance of normal tissue function (1, 2). The experimental analysis of cellular interactions was initiated with the investigation of cell aggregation in simple organisms such as sponges (3, 4) and progressed into the areas of embryology (5) and cell biology (6, 7). Analysis of cell biology on ...

Cell-Cell Interactions in the Testis

Two cell lines have been isolated from testis of immature BALB/c mice. These lines have each been cloned several times and have been established in culture for over 2 years. The cells are epithelial in appearance and do not form tumors when injected into BALB/c - nu/nu mice. l’hc cell lines can be said to be two distinct cell types on the basis of their morphology, hormone response, responses to gonadotropins, and metabolism of steroids. One line (TM4) has been tentatively identified as being of Sertoli cell origin, since it shows a growth response to purified ovFSH and an increase in cAMP in the presence of FSII but not LII. The other line (TM3), believed to be Leydig cells, is not growth-stimulated by either LII or FSII, shows an increase in cAMP in the presence of LII, and a change in the metabolism of Itm4 Cl cholesterol in the presence of LI-I.

Establishment and characterization of two distinct mouse testicular epithelial cell lines.

Direct measurement of androgen receptors in cultured sertoli cells

The present invention relates generally to indwelling medical devices. In particular, there is provided a device constructed from permeable or impermeable material having a pharmacologically active agent (7) or ingredient layer (3, 10) surrounding the device, and a sheath (2, 11) which is permeable to the pharmacologically active agent or ingredient. This construction provides a device that allows the pharmacologically active agent or ingredient located between the catheter tube (1) and the sheath (2) to slowly diffuse through the sheath and/or inner tube (4), thus inhibiting microbial infection on the outer surface and lumen of the catheter (5, 13).

A multipurpose anti-microbial silastic sheath system for the prevention of device-related infections

Concentrations of high affinity (Ka equals 5.5 plus or minus 0.83 times 10-8M-1) androgen binding activity in carbonextracted rat testicular supernatants have been determined by Scatchard plot analysis under a variety of hormonal situations: (a) 0-90 days following hypophysectomy; (b) 0-60 days of daily injection of NIH-FSH-P1 (150 mug) beginning 1 day after hypophysectomy; and (c) 0-60 days of daily FSH treatment beginning 30 days after hypophysectomy. The high affinity binding component declined from 0.32 pmoles/mg protein intact adults to 0.28, 0.17, and less than 0.08 (limit of detectability) pmoles/mg protein at 11, 16 and 31 days, respectively. FSH treatment beginning immediately after surgery slowed this decline, giving values of 0.30, 0.17, and 0.12 pmoles/mg protein after 11, 29, and 54 days of treatment, respectively. Expressed as pmoles per testis this represented 96, 61, and 40% of the intact control level. Similar effects on the level of androgen binding protein (Rf 0.54) were measured by steady-state polyacrylamide gel electrophoresis (PAGE). The concentration in both testis and epididymis declined gradually to nondetectable levels by 30 days after surgery. FSH treatment for 11, 29, and 54 days, respectively, resulted in 0.37, 0.38, and 0.03 pmoles of sites/mg protein in testis compared to 0.34 in intact controls and 5.7, 2.6, and 0.2 pmoles/mg protein in epididymis compared to 2.8 in intact controls. Doses of 80, 150, and 300 mug FSH/rat/day for 3 days beginning 30 days after hypophysectomy when postmeiotic elements of the germinal epithelium had degenerated caused graded increases in both testicular and epididymal levels of androgen binding protein. Prolonged FSH treatment (150 mug) under these conditions resulted in an increase in binding activity to a level of 0.12, 0.19, 0.17, and 0.20 pmoles/mg protein after 3, 11, 25, and 56 days of treatment. On a per testis basis this represented less than 20% of intact control levels. PAGE estimates were comparable except at the long treatment intervals. These results indicate that FSH treatment influences the level of androgen binding protein in adult testis and epididymis. This may reflect a direct influence on synthesis, degradation, and transport and/or indirect effects on general maintenance and responsiveness of the pertinent cell types.

Hormonal Influences on the Level of Testicular Androgen Binding Activity: Effect of FSH Following Hypophysectomy

The in vivo pattern of circulating testosterone (T) was investigated in unrestrained, conscious, individual male rats during 24 and 48 h. Each rat exhibited its own characteristic in vivo diurnal rhythm. When these individual patterns of T were grouped, the mean values also showed a diurnal rhythm. Although T concentrations peaked during the dark and light periods, the most pronounced elevations were observed during the dark periods (2200-2330 h). Lowest T concentrations were noted during the late dark and early light hours (0400-0700 h). The pattern of T was further investigated by extending the experimental period to 48 h. The pattern of T observed during the first 24 h repeated itself on the second day, thus demonstrating the authenticity of this diurnal rhythm. Rats were exposed to a reversed light/dark regimen which resulted in an inversion of the rhythm of circulating T. These data indicate that the pattern of circulating T is not intrinsically regulated.

In Vivo Patterns of Circulating Steroids in Adult Male Rats. I. Variations in Testosterone during 24- and 48-Hour Standard and Reverse Light/Dark Cycles*

Robert K. Tcholakian

Papers

Direct measurement of androgen receptors in cultured sertoli cells

A multipurpose anti-microbial silastic sheath system for the prevention of device-related infections

Hormonal Influences on the Level of Testicular Androgen Binding Activity: Effect of FSH Following Hypophysectomy

In Vivo Patterns of Circulating Steroids in Adult Male Rats. I. Variations in Testosterone during 24- and 48-Hour Standard and Reverse Light/Dark Cycles*

Rapid oscillations in plasma levels of testosterone luteinizing hormone and follicle-stimulating hormone in men.