In vitro production of parathyroid hormone-related protein by cholesteatoma and normal skin

Severe inflammation and infection of the middle ear occasionally results in clinical evidence of bone resorption but with the addition of the cholesteatoma epithelium it becomes inevitable. This study examined production by the cholesteatoma epithelium of a bone resorbing factor, namely parathyroid hormone-related protein (PTH-rP), which would not be expected in inflammatory states alone. PTH-rP was detected in the conditioned medium of primary and secondary cell cultures derived from 12 cholesteatoma biopsies. The levels of PTH-rP were significantly greater than in control cultures of cells derived from normal scalp tissue. Production by the cholesteatoma epithelium may explain the increased incidence of bone resorption in this disease, particularly in cases where inflammation is minimal.     

Differences in the shedding of soluble TNF receptors between endotoxin-sensitive and endotoxin-resistant mice in response to lipopolysaccharide or live bacterial challenge

TNF-alpha plays a pivotal role in the pathogenesis of septic shock. It exerts its effects by binding two cell surface receptors, designated TNF-R I and II, also referred to as the p55 and p75 receptors, respectively. TNF-Rs are transmembrane proteins, which on cleavage of their extracellular domains, result in the release of soluble fragments (sTNF-R). sTNF-R levels increase markedly during infection, and may serve to modulate TNF-alpha bioactivity. The mechanisms regulating this process are uncertain. To investigate this, we measured sTNF-R release in endotoxin-sensitive C3H/HeN and endotoxin-resistant C3H/HeJ mice given LPS or live Gram-negative bacteria. In C3H/HeN mice, there was a rapid early response during the first 4 h, and a second peak at 8 h, particularly noticeable in the case of the p75 receptor. Prior administration of neutralizing Abs to TNF-alpha or IFN-gamma had no effect on receptor shedding. Surprisingly, C3H/HeJ mice also responded to both bacterial challenge and to LPS by shedding sTNF-R; the magnitude and duration of the early response was not substantially different from C3H/HeN mice, although the second peak was absent. Peritoneal macrophages from C3H/HeN mice responded promptly (5 h) when stimulated with LPS in vitro, and by 22 h levels had increased five- to 10-fold. In contrast, cells from C3H/HeJ mice demonstrated only a very modest response at 22 h following maximal stimulation. The data suggest that there may be at least two separately regulated pathways that control sTNF-R shedding in these mice.     

Potential for oxytetracycline administration by three routes to cause milk residues in lactating cows, as detected by radioimmunoassay (Charm II) and high-performance liquid chromatography test methods

Milk antimicrobial residues are a serious concern for the dairy industry. Residues of the tetracycline family of antimicrobials have been reported in market milk by investigators, using radioimmunoassay and microbial receptor technology (hereafter referred to as the Charm II test). In response to these reports, an investigation was conducted to determine the potential of 3 extra-label routes of oxytetracycline (OTC) administration to cause milk residues above the Food and Drug Administration safe value of 30 parts per billion (ppb). Lactating Holstein cows were administered OTC once by use of 1 of 3 routes: IV at 16.5 mg/kg of body weight (n = 6); IM at 11 mg/kg (n = 6); and intrauterine (IU) at 2 g in 500 ml of saline solution/cow (n = 6). Duplicate milk samples were collected at the milking prior to drug administration and for the next 13 milkings at 12-hour intervals. Concentrations of OTC in milk samples were analyzed by use of the Charm II tes for tetracyclines (limit of OTC detection, approx 5 ppb) and were compared with concentrations determined by use of a high-performance liquid chromatography (HPLC) method (lower limit of OTC quantitation, approx 2 ppb). The potential for milk OTC residues above the Food and Drug Administration safe value of 30 ppb after treatment was considerably greater for the IV and IM routes, compared with the IU route.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synthesis and Electronic Spectra of some Disperse Dyes Derived from 8–Phenylazolilolidine

Absorption spectra of 8–phenylazolilolidine and eleven para–substituted derivatives have been determined for solutions in ethanol and ethanolic hydrogen chloride. The pronounced bathochromic shifts and increases in intensity of the first band observed for the corresponding julolidine analogues, relative to the appropriate derivatives of 4–dimethylaminoazobenzene, are somewhat reduced with the lilolidine compounds. The difference in frequency between the absorption maxima of the dyes and their azonium salts correlates well (r=0. 993) with the unmodified Hammett values of the substituents. The lilolidine dyes are suitable for transfer printing, but show poor light–fastness properties on synthetic–polymer fibres.     

Steroids after birth-puberty

The production of gonadal steroids in the perinatal period may have an important influence on the later development of the hypothalamo-pituitary-gonadal axis. In the prepubertal period there is an increased output of gonadal steroids and of androgens from the adrenal cortex, with a further increase as the secondary sex characters develop. The precise role of individual steroids in the maturation of the reproductive system and of the neuroendocrine regulating mechanisms will probably remain unclear unless conclusions are based on longitudinal studies in which hormone production is related precisely to different parameters of sexual development and somatic growth.