Pharmacokinetics and metabolic disposition of 14C-metronidazole-derived radioactivity in rat after intravenous and intravaginal administration

Urinary metabolites and the pharmacokinetics of radioactivity derived from 14C-metronidazole (14C-MTZ) were determined after intravenous (iv) or intravaginal (ivg) administration of 10 mg/kg to adult rats. Following iv or ivg administration, the disappearance of 14C from blood followed the kinetics of a two-compartment open-system model. The blood half-lives of 14C during the beta-phase were 10.9 +/- 1.6 and 13.6 +/- 4.2 hr, after iv and ivg administration, respectively. After ivg application, the MTZ-derived radioactivity was detected in tail blood at 5 min, peaked at 1 hr, declined rapidly to 6 hr and more slowly thereafter. The vaginal absorption half-life of 14C-MTZ was 0.28 +/- 0.09 hr. About 12% of the administered dose remained in the vagina after 1 hr and 1.5% after 24 hr. At 24 hr, the tissue distribution and concentration of 14C were similar in iv and ivg dosed rats, the highest 14C concentration being present in the kidneys and lowest in the fat. The percentages of the dose excreted in 24 hr in the urine and feces were 58 and 15 after iv administration, compared to 37 and 40 after the ivg route, respectively. Unchanged 14C-MTZ and five of its metabolites were detected in the urine irrespective of the route of administration. The results show that metronidazole is rapidly absorbed through the vaginal mucosa of the rat and the metabolism and excretion of this chemotherapeutic agent are influenced by the route of administration.     

Monoclonal anti thy 1.2 antibodies from hybridoma HO13-4 do not react with mouse natural killer cells

The susceptibility of NK cells and immune cytotoxic T-cells to treatment with (a) monoclonal anti thy 1.2 antibodies from hybridoma HO13-4, (b) rabbit anti-mouse T-cell antiserum and (c) gamma globulins prepared from AKR/J anti C3H/HeJ antiserum was studied in the presence of rabbit complement. Monoclonal anti thy 1.2 antibody treatment completely abolished the cytotoxic activity of immune T-cells derived from C57BL/6J mice (H-2b) immunized with (C57BL/6J x DBA/2)F1 spleen cells (H-2bd) against P815 (H-2d) target cells. The same treatment had no significant effect on the NK activity of spleen cells from unimmunized mice against YAC target cells. Rabbit anti-mouse T-cell and mouse anti theta antisera also abrogated completely the immune T cell activity of spleen cells. This treatment however also resulted in a partial loss of NK activity. These results indicate that conventional anti theta antisera contain antibodies which recognize antigenic specificities on T-cells as well as on a population of NK cells. The cross reactivity is not a result of thy 1.2 antigen expression on NK cells and T-cells as recognized by the monoclonal antibodies. The specificity recognized by the monoclonal antibody (HO13-4) is only expressed on T-cells.     

The production of Mullerian inhibiting substance by the fetal, neonatal and adult rat

The obligate aerobic yeast Rhodoturula gracilis was found to take up the alditols D-glucitol, D-mannitol, ribitol, xylitol, D-arabinitol, L-arabinitol and erythritol by means of a constitutive mobile membrane carrier. This uptake involved active transport, that is, it was dependent on the supply of metabolic energy, leading to the accumulation of alditols inside the cells. The accumulation ratio (intracellular concentration to extracellular concentration, Si/SO) was much lower for alditols than for monosaccharides. As for monosaccharides, this ratio decreased with increasing extracellular concentration, even to values below 1. The kinetic data showed that the carrier system for alditols was identical to that for monosaccharides, though it had a much lower affinity and maximum velocity for alditols. Hence the uptake of alditols was blocked in the presence of monosaccharides. Only ribitol and L-arabinitol were catabolized following enzyme induction. The other alditols were not broken down.     

H] Tryptamine and 3H-water as diffusible internal standards for measuring brain extraction of radio-labeled substances following carotid injection

Urinary amino acid excretion was determined in 31 leukemic patients and 29 normal individuals by rapid gas chromatographic analysis of 16 amino acids as their N-acetyl-n-propyl esters. The leukemic patients were concurrently undergoing, or had recently completed, chemotherapy. It was found that aspartic acid, threonine, and serine were of significance in distinguishing between patients "on" therapy and those "off" therapy. Patients with advanced disease have the greatest aminoaciduria, although both the normal and leukemic populations have wide individual ranges. Within both populations, men excrete a greater variety and quantity of amino acids than women. It is concluded that analysis of urinary amino acids represents a history of complex metabolic events, which is potentially useful for evaluating patient response to chemotherapy in leukemia.     

A cell line (SCABER) derived from squamous cell carcinoma of the human urinary bladder

An established cell line derived from a documented squamous cell carcinoma of human urinary bladder is described. The cultured cells retained the characteristic morphology of the tumor of origin for 40 in vitro passages. Numerous desmosomes were found between cultured cells. Chromosome analysis showed hypotetraploidy with no obvious modal number, while distinctive marker chromosomes and a male karyotype were present.     

Mean systemic pressure and mean pulmonary pressure: their effects on the total artificial heart

Mean systemic pressure (MSP) and mean pulmonary pressure (MPF), which are mean driving pressures for venous return in the natural heart, were studied in 11 calves in which the natural heart had been replaced with a total artificial heart (TAH). They were measured simply by stopping the artificial heart pumping. Although blood translocation from the arterial to the venous side was not performed, the eventual right and left atrial pressures reached six to eight seconds after stopping the TAH would represent MSP and MPP with reasonable accuracy. The MSP varied from nine to 3k mmHg (20+/-6 mmHg), whereas the MPP varied from nine to 39 mmHg (22+/-7 mmHg). The MSP varied in close relation to the right atrial pressure prior to cessation of the TAH (r=0.9124). Increases in RAP and MSP were mainly attributed to an increase in circulating blood volume. In the performance of the TAH, MSP (or MPP), proper diastolic duration and vacuum application during diastole was of prime importance in determining the end-diastolic ventricular volume.     

Family centered maternity care: its relationship to perinatal regionalization and neonatal intensive care

For several months prior to birth a major portion of a family's attention, conversation, thought, and often worry, is directed toward the idea of a new child. This prolonged attention and anticipation contribute to making childbirth an emotionally charged experience. In psychological terms, it is therefore a critical period of peak motivation for learning, and a time to peak susceptibility to reinforcement. Theory, reason, and scientific evidence indicate thng with childbirth and early postpartum experiences, can significantly affect subsequent parental behaviors, the child's central environment influence. Evidence strongly suggests that these parental attitudes and behaviors so crucial to the child's ultimate well-being are learned rather than derived instinctually, and therefore they are malleable and can be taught, directed, and corrected. Through education and reinforcement it is possible to encourage parental behaviors and child interactions which are products of feelings of control, competence, accomplishment, understanding, and caring. Similarly we can recognize and work toward replacing attitudes, feelings, and behaviors that express fear, worry, and insecurity about the child. Over the past 50 years major changes have occurred in the practice of obstetrics and newborn pediatrics. Other major changes will necessarily occur as we move toward perinatal regionalization. Changes instigated solely on physiologic data can have unrecognized collateral effects on the psychological component of the childbirth experience. All concerned health care personnel, especially obstetricians and pediatricians, can insist that the importance of desirable mother-father-child interactions be recognized and that practices fostering them be afforded a high priority. I would like to endorse a comment from a recent article by Richmond concerning the advent of behavioral pediatrics by adding that behavioral obstetrics is also "an idea whose time has arrived".     

The frequency of disfluencies during phonatory transitions in stuttered and nonstuttered speech

The AA. investigated the frequency of antibodies against Toxoplasma gondii in 426 women with repeated abortions, perinatal mortality and malformed newborns. They showed on the whole a low incidence even if they demonstrated a high incidence (77.7%) of antibodies in women with malformed newborns. The meaning of the observations are briefly discussed.     

The wick catheter technique for measurement of intramuscular pressure. A new research and clinical tool

The wick catheter technique was developed in 1968 for measurement of subcutaneous pressure and has been modified for easy intramuscular insertion and continuous recording of interstitial fluid pressure in animals and humans. Studies in dogs of the anterolateral compartment of the leg in simulation of the compartment syndrome showed the technique to be accurate and reproducible. The wick catheter technique is capable of important clinical applications in the diagnosis and treatment of acute and chronic compartment syndromes.