The acylureido penicillin mezlocillin is active against gram-positive, gram-negative, and anaerobic bacteria. It easily penetrates the outer membrane of gram-negative bacteria, and it has a strong affinity for penicillin binding protein 3. Its stability to beta-lactamases is weak. Mezlocillin is synergistic when given in combination with aminoglycoside antibiotics. In pharmacokinetic studies mezlocillin conforms to a two compartment open model; its pharmacokinetic properties are dose-dependent. The half-life of the drug is about 1 hour after intravenous injection and 1.5 hours after intramuscular injection. Protein binding ranges from 16 to 42%, and 55% of a dose is excreted in the urine. Biliary excretion ranges from 0.5 to 25%. Clinical trial cure rates were as follows: bacteremia (78%), respiratory tract (62%), urinary tract (81%), gynecological (86%), bone and joint (55%), intraabdominal (67%) and skin and soft tissue (59%). The frequency of adverse reactions was 7.7%. Interstitial nephritis, CNS toxicity, and bleeding have not been reported.

Bacteria↗

PubMedDate not supplied

MR microscopy of chick embryo vasculature.

Six-day-old chick embryos were examined with magnetic resonance microscopy after vascular perfusion fixation and perfusion with gadolinium-doped gelatin to high-light the developing vascular anatomy. Gadolinium gelatin, with its short T1, provided a source of signal contrast within the vessels. The entire embryo was embedded in gelatin to minimize susceptibility artifacts that are prevalent at the high field strength (7.0 T) used. A series of single-section spin-echo images were acquired with various TRs to determine the optimal imaging sequence for a three-dimensional (3D) acquisition. The combination of gadolinium gelatin in the vascular spaces, gelatin embedding of the specimen, and optimal acquisition parameters yielded a 3D stack of high-resolution images that was readily reconstructed and rendered to effectively demonstrate the developing thoracic vessels in the embryo.

Animals↗

PubMedDate not supplied

Stimulation of iodine organification in porcine thyroid cells by thyroid stimulators.

Several Graves' sera were simultaneously assessed in a bioassay based on the ability of porcine thyroid cells to organify 125I and in a radioreceptor assay for TSH receptor binding activity. Both assay systems were sensitive to 1 mcU/ml (final concentration) of unlabelled bovine TSH. Six Graves' sera were studied in detail over a wide (0-1.0 mcl sera) dose response range in repeat determinations. Two sera exhibited parallel binding and stimulating. However, two sera revealed significant inhibition of 125I-TSH binding prior to the demonstration of stimulation and the other two sera showed stimulatory capabilities before significant binding was evident. IgG was prepared from one serum by ammonium sulphate precipitation and chromatography on Sepharose 6B and then subjected to preparative isoelectric focusing. The isoelectric distribution of the two activities were found to be identical with major peaks of activity at pl=9.5 and pl=8.5. In summary: 1) each Graves' sera exhibits different dose-response curves with respect to binding and stimulation, 2) at certain concentrations of sera, only binding or stimulation were evident, 3) neither assay was consistently more sensitive for the presence of Graves' immunoglobulins, 4) for one Graves' sera, binding and stimulation could not be separated by isoelectric focusing. These studies would suggest each Graves' immunoglobulin has inherently different characteristics in its interaction with the TSH receptor.

Animals↗

PubMedDate not supplied

Conditioned place preference induced by intraventricular infusions of acetaldehyde.

Multiple intracerebroventricular infusions of acetaldehyde were shown to induce conditioned place preference in laboratory rats. Those animals receiving acetaldehyde infusions displayed an increased preference for environmental cues previously paired with the drug administration. These results indicate that acetaldehyde, when present in the brain, may have reinforcing properties.

Acetaldehyde↗

PubMedDate not supplied

A multi-dimensional examination of the positive reinforcing properties of acetaldehyde.

The suggestion that acetaldehyde may be endowed with positive reinforcing properties and may in fact mediate some of the psychopharmacological actions of ethanol has been examined by us and other investigators using a variety of paradigms. We first reported that non-dependent animals would self-administer acetaldehyde through an intra-cerebroventricular route. In addition, we have demonstrated that central infusion induced a conditioned place preference. We have also shown that an animal's propensity to self-administer acetaldehyde directly into the brain was related to its subsequent voluntary intake of ethanol. Lastly, we have reported that inhibition of acetaldehyde metabolism resulted in an enhancement of alcohol-induced euphoria in man. The data collected to date from four different paradigms strongly support the notion that acetaldehyde is endowed with positive reinforcing properties which may play a critical role in the mediation of ethanol euphoria.

Acetaldehyde↗

PubMedDate not supplied

Lack of effect of dopamine D2 blockade on ethanol intake in selected and unselected strains of rats.

Previous research has suggested that brain catecholamines may be involved in regulating ethanol intake. This study was designed to look more specifically at dopamine (DA) and whether DA D2 receptor blockade with the antagonist pimozide would alter ethanol consumption in rats. Subjects were male Maudsley Reactive and Wistar rats, the former previously shown to consume larger amounts of ethanol than the latter. Both strains were screened for ethanol intake by presentation of ethanol solutions (free choice with water) in increasing steps from 2% to 10% (v/v) on an alternate-day schedule. Following the screening period, animals were switched to a schedule of everyday presentation of the 10% (v/v) ethanol solution (free choice with water) for 10 baseline days. Animals were then divided into high and low drinking levels according to whether their mean baseline ethanol intake (g/kg) fell within +/- 0.5 SD of the mean intake of their group (Maudsley Reactives: mean = 2.55 g/kg, low drinkers < 1.63, high drinkers > 3.47; Wistars: mean = 2.17 g/kg, low drinkers < 1.53, high drinkers > 2.82). The animals were assigned to one of five treatment groups for 5 subsequent days where they received IP injections of pimozide (0.08, 0.24, or 0.48 mg/kg), tartaric acid, or saline. Following the treatment period, ethanol consumption was recorded for 5 posttreatment days. No significant differences due to treatment were observed for either intake or preference of ethanol across treatments, drinking groups, or strains. The results obtained in the present study suggested that interference in DA neurotransmission through administration of the D2 antagonist pimozide does not significantly alter ethanol consumption in either MR or Wistar animals.

Alcohol Drinking↗

PubMedDate not supplied

The regulation of alcohol consumption in rats: the role of alcohol-metabolizing enzymes-catalase and aldehyde dehydrogenase.

Aldehyde dehydrogenase (ALDH) and catalase enzymatic activities in brain were assayed and compared to measures of alcohol consumption in two groups of animals screened and maintained on free-choice alcohol access under different conditions. In the first group of Long-Evans rats screened and maintained in home cages, mean alcohol intake was 3.49 g/kg/day with a range of 1.69-5.33 g/kg/day. When alcohol intake (g/kg), total ALDH, low K(m) ALDH, and catalase activities were entered in a multiple regression, a significant correlation of r = 0.51 (p < 0.05) was obtained. In the second group of rats consisting of Long-Evans, P, and NP rats screened using a drinkometer procedure, a multiple correlation between ALDH and catalase enzyme activities and alcohol intake of r = 0.42 (p < 0.05) was obtained. There was a strong relationship between the frequency of alcohol drinking bouts and the activities of catalase and ALDH (r = 0.68, p < 0.0001). The P rats had significantly higher catalase activities than either the NP or Long-Evans rats. The results of the present study confirmed earlier reports on the role of alcohol-metabolizing enzymes in the regulation of alcohol intake. The results also highlighted the fact that the activity of these alcohol-metabolizing enzymes may play a mediating role in patterns of alcohol intake displayed by animals selected for high and low alcohol drinking and also unselected animals.

Alcohol Drinking↗

PubMedDate not supplied

Magnetic resonance microscopy of embryos.

We demonstrate that magnetic resonance (MR) microscopy provides a mechanism to investigate normal and abnormal developmental anatomy in a non-destructive and distortion-free manner. Techniques for the fixation, embedding, perfusion and image acquisition of embryos between 3 and 30 mm crown rump length are described. We describe the perfusion of a contrast agent to enhance images of the developing embryonic vasculature. Data are acquired as three-dimensional isotropic arrays which permit images to be reformatted retrospectively in any plane. The data are available for archiving, distributing and for post-acquisition manipulations. MR microscopy is a fast technique for producing three-dimensional reconstructions and is free from registration and sectioning artifacts.

Anatomy, Artistic↗

PubMedDate not supplied

Magnetic resonance imaging of embryos: an Internet resource for the study of embryonic development.

The recent amassing of gene expression data to study development in mammals has led to an increased demand for access to human embryological data. The difficulty of obtaining well-preserved human embryos presents an important challenge to studying human development. The Multidimensional Human Embryo project is generating an image data set based on magnetic resonance microscopy of specimens from the highly respected Carnegie Collection of Human Embryos. The data are available from a web site to facilitate the work of clinicians, investigators, and students of human development. A consequence of the project will be to preserve a highly respected, yet impermanent, collection of human embryos and minimize the need for collecting new specimens.

Embryo, Mammalian↗