Synthesis and antibacterial activity of O-methyl derivatives of azalide antibiotics: II. 6-OME derivatives via clarithromycin

Direct O-methylation of various derivatives of 9-deoxo-8a- and 9a-aza-8a-homo-erythromycin (2',3'-bis-Cbz protected) gives 6-OMe derivatives only in a small number of special cases. The 6-OMe-azalides can, however, be synthesized beginning from clarithromycin.     

Economic assessment of low flow anesthesia with analysis of the break-even point. Experience at an underutilized operating room

BACKGROUND: Many authors indicate the importance of economic saving obtained with the use of the inhalation rebreathing anaesthesia instead of non rebreathing anaesthesia, always referring to parameters which are the duration of anesthesia (1 hour) and the use of the operating theatre each year. It is presumed that the utilization of rebreathing system is at least a 1.000 hours/year. However it is not necessary that all the operating theatres employ 1.000 hours/year in rebreathing anesthesia. This method requires annual depreciation costs of the capital invested for the purchase of new adequate ventilators, to modificative those already existing and guarantee adequate monitoring and the maintenance of these equipment. The importance is stressed of individuating a method of economical evaluation comparing the effective savings obtained with the real utilization of rebreathing anesthesia for each operating theatre and the costs of purchasing and maintaining the equipment. From our point of view the break-even point analysis has demonstrated to be a consistent instrument for the evaluation of the real economic advantage of rebreathing system in each hospital. METHODS: It is suggested to utilize a conventional formula for the determination of the break even point, which means the minimal number of hours for year that justifies economically the adoption of rebreathing anaesthesia. RESULTS AND CONCLUSIONS: An example of this analysis has been applied for an operating theatre in the hospital of Morbegno, where the major utilization of regional anaesthesia leads to a reduced number hours/year of rebreathing anesthesia which remains anyhow economically advantageous.     

In vitro induction of F1 hybrid anti-parent cell-mediated cytotoxicity

Spleen cells from normal (C57BL/6 X DBA/2)F1 mice were sensitized in vitro for 5 days with irradiated C57BL/6 or DBA/2 parental stimulating cells. Effector cells were generated which specifically lysed 51Cr-labeled targets (leukemia or mitogen-stimulated lymphoid cells) H-2-matched with the parental genotype used for sensitization. The response of F1 spleen cells to the C57BL/6 parent was stronger and more reproducible than that to the DBA/2 parent. The kinetics of generation of effector cells were similar for the F1 anti-parent and an F1 anti-allogeneic response. However, the magnitude of the F1 anti-C57BL/6 cytotoxic response was considerably lower than the F1 response to allogeneic cells. The ratio of responder to stimulator cells in the cultures was more critical for the former than for the latter response. Several lots of fetal bovine serum were found to be adequate for supplementing the medium in the induction of J1 hybrid anti-parent and anti-allogeneic cytotoxic effector cells. Based on these and other studies, it would appear that the F1 hybrid anti-parent cytotoxic response provides an in vitro model of murine hemopoietic graft rejection in vivo. This response may be elicited by a mechanism distinct from T cell-mediated cytotoxicity and involve different subpopulations of spleen cells.     

Reversal by naloxone of the effects of morphine on the unanesthetized dog]

In unasthetized dogs naloxone induced effects opposed to those of morphine (tachycardia, agitation, hyperthermia, tachypnea) and mydriasis. These effects were moderate and transient; some of them were elicited with low doses being border-line after 0.03 mg.kg-1 s.c., statistically significant after 0.1 mg.kg-1 s.c.; they increased slightly with the dose. After repeated administrations, acute tolerance developed and some moderate morphine-like effects (miosis, sedation) were observed. The stimulatory effects described here may result from antagonism of a morphinomimetic natural ligand,and represent thus indirect arguments in favour of normal functions of this ligand; these functions would be to temper not only algesic but also other stimulant reactions. The limitation of the effects might result from the limited release of this ligand in normal dogs and (or) from interfering morphinomimetic properties of naloxone, which are apparently unmasked when administrations are repeated. Both, stimulatory and inhibitory effects of naloxone are not liable to represent noticeable side-effects of this drug, but they both might play some role in the mechanisms of precipitated abstinence.     

Psychotic exacerbations produced by neuroleptics

Thirteen schizophrenic patients who developed abnormal psychotic behavior as an adverse reaction to a neuroleptic are described. A. Three patients showed a marked increase in the psychopathology during neuroleptic treatment. These episodes were treated by decreasing or discontinuing the neuroleptics. They did not respond to anticholinergic durgs nor did they respond to an increase in dosage, (another side effect previously reported and referred to here) indeed this treatment worsened the situation. B. Ten patients showed a mixed picture of catatonic excitement or inhibition on neuroleptics and several developed hallucinatory episodes. All of these exacerbations were terminated by anticholinergic injections. Other more familiar CNS abnormalities produced by neuroleptics are briefly discussed.     

Morphometric study of trout gills: a light-microscopic method suitable for the evaluation of pollutant action

1. Methods are described for the morphometric estimation of parameters of the gill system of trout which are relevant to its function in gas exchange. The methods have been used with 1 mum sections viewed under the light microscope. 2. In particular the diffusion distances between water and blood are measured, which together with determinations of gill area, provide figures for the morphometrically estimated diffusing capacity. 3. The methods have been used to compare the diffusing capacity of gills from control fish and those treated in polluted waters. The concept of relative diffusing capacity (Drel) is introduced which enables comparisons to be made without the need to determine the absolute diffusing capacity. 4. Quantitative estimation of changes in relative volumes and surface areas of components of the secondary lamellae were determined, and employed to explain the possible anatomical causes of changes in Drel. 5. It is suggested that these methods can be of value in the comparison of the gills of fish treated in different waters.