Spike-timing relationship of neurochemically-identified dorsal raphe neurons during cortical slow oscillations.

The firing activity of dorsal raphe neurons is related to arousal state. However, it is unclear how this firing activity is precisely related to cortical activity, in particular oscillations occurring during sleep rhythms. Here we conducted single-cell extracellular recordings and juxtacellular labelling while monitoring electrocorticogram (ECoG) activity in urethane anaesthetised rats, to relate activity in neurochemically identified groups of neurons to cortical slow-wave activity (SWA). We observed that electrophysiological heterogeneity in dorsal raphe neurons revealed different neurochemical groups of DRN neurons and was mirrored by significant differences in the phase and strength of coupling to the cortical slow oscillations. Spike firing relationship of clock-like neurons, identified as 5-HT (5-hydroxytryptamine) or serotonin neurons, was higher during the inactive component of the oscillations. In contrast, half of the identified bursting 5-HT neurons did not exhibit strong cortical entrainment; those that did fired most during the inactive component of the SWA. Two groups of putatively non-5-HT neurons (irregular slow-firing and fast-firing) exhibited significant coherence and fired most during the active component of the SWA. These findings indicate that within the DRN electrophysiologically and neurochemically discrete neuronal groups exhibit distinct relations to cortical activity.

[Tissue diffusion of amoxicillin-clavulanic acid for antibiotic prophylaxis in colorectal surgery]. / Diffusion tissulaire de l'amoxicilline-acide clavulanique pour une antibioprophylaxie en chirurgie colorectale.

Tissue penetration of amoxicillin and clavulanic acid given for antibiotic prophylaxis was studied in 15 patients. On induction of anesthesia patients were given 2 g amoxicillin and 200 mg clavulanic acid. The same dose was given two hours later. At time of surgical incision amoxicillin and clavulanate levels were 15.9 +/- 7.7 micrograms/g and 2.23 +/- 2.69 micrograms/g in abdominal wall fat and 16.6 +/- 10.5 and 1.72 +/- 1.35 micrograms/g in epiploic fat, respectively. Similar levels were measured at time of closure of the abdomen. In colonic wall, amoxicillin et clavulanate levels were 22.7 +/- 13.4 micrograms/g and 2.65 +/- 2.35 micrograms/g. By comparison with blood levels, tissue penetration of both drugs was 20 to 30 p. cent into fatty tissues and 60 to 70 p. cent into colonic wall.

Enzymatic control of estrogen production in human breast cancer: relative significance of aromatase versus sulfatase pathways.

One-third of the cases of breast cancer in postmenopausal women are hormone-dependent and the lesions regress upon treatment with antiestrogens or inhibition of estrogen biosynthesis. In these patients, estrogens are synthesized in extraglandular tissues from adrenal precursors and re-enter plasma to produce estrone levels of 52 +/- 6.5 pg/ml (mean +/- SEM) and estradiol concentrations of 13.1 +/- 0.7 pg/ml. However, the fact that the levels of estrogen in breast tumor tissue are an order of magnitude higher than plasma levels suggested the possibility of in situ estrogen production. To address this possibility, we measured several enzymes involved in estradiol biosynthesis in human tumors. Forty-eight of 61 tumors contained aromatase (estrogen synthetase) activity ranging from 5-80 pg/gm protein per hour. By comparison, the levels of estrone sulfatase were 10(6) higher, ranging from 0.8-125 micrograms/gm protein per hour. Because the sulfatase enzyme was of lower affinity (i.e., Km = 27 microM) than that of aromatase (i.e., 0.027 microM), the amount of estrogen formed under conditions of similar substrate concentrations was compared and found to be 10-fold higher via the sulfatase enzyme. In 41 additional tumors, the 17 beta-hydroxysteroid dehydrogenase enzyme, catalyzing the conversion of estrone to estradiol, was uniformly present. To test the biologic relevance of the estrone sulfate to estrone to estradiol pathway, estrogen-dependent nitrosomethylurea rat mammary tumors were grown in soft agar in the presence of estrone sulfate. Concentrations of estrone sulfate of 10(-6) microM significantly (p less than 0.01) stimulated colony formation in this system in which 75.5-98.6% of estrone sulfate was converted to estrone and 0.2 to 6% to estradiol. These data support the hypothesis that mammary carcinomas can synthesize estradiol in situ from circulating estrogen precursor and that local conversion is biologically important. On the basis of comparative data, the estrone sulfate to estrone to estradiol pathway is quantitatively more important than that involving androstenedione to estrone to estradiol.