Two regions in the isolated brainstem of the frog that modulate respiratory-related activity.

Using microinjection techniques, we have explored the isolated, complete midline sectioned brainstem of the frog (Rana catesbeiana) to identify regions that influence the endogenous respiratory-related motor activity. Ten-nanoliter injections of lidocaine (1%), GABA (100mM) and glutamate (10 and 100 mM) into discrete regions of the rostral and the caudal brainstem produced different effects on the phasic neural discharge. In the rostral site lidocaine, GABA and glutamate injections altered neural burst frequency with little or no effect on burst amplitude.

Respiratory motor output of the sectioned medulla of the neonatal rat.

The respiratory motor output of the isolated medulla-spinal cord of the neonatal rat was recorded after three types of sections: (1) Complete midsagittal section of the medulla abolished all rhythmic neural activity recorded from the hypoglossal C4 ventral rootlets. (2) Complete transection at the level of the root of cranial nerve X decreased the burst frequency of the respiratory related motor output; transection of the medulla caudal to the obex had no effect on burst frequency recorded from the hypoglossal roots. Combining these rostral and caudal transections resulted in a transverse slice preparation 1.

Novel fluorinated antiinflammatory steroid with reduced side effects: methyl 9 alpha-fluoroprednisolone-16-carboxylate.

In an effort to test the hypothesis that 9 alpha-fluorination of a steroidal antedrug would enhance receptor binding affinity and local antiinflammatory activity, without concomitantly increasing adverse systemic effects, a fluorinated analog, 10, of methyl 11 beta, 21-dihydroxy- 3,20-dioxo-1,4-pregnadiene-16 alpha-carboxylate (DP16CM, 1) was synthesized and evaluated. In the acute rat croton oil-induced ear edema bioassay, 10 was found to be twice as potent as 1. This increase in topical potency was consistent with enhanced binding affinity of 10, relative to 1.

Central retinal artery occlusion in a patient with Marfan's syndrome.

A case of central retinal artery occlusion in a patient with Marfan's syndrome secondary to possible thromboembolism from a prolapsed mitral valve is presented. Clinical investigations and treatment of this condition are discussed. The world literature on retinal occlusive events secondary to mitral valve prolapse is briefly summarised.

New anti-inflammatory antedrugs: steroid acid esters and amides.

Therapeutic use of anti-inflammatory steroids is limited, due primarily to their suppressive effects on pituitary function and the immune system. In an attempt to circumvent the untoward systemic effects of corticosteroids, a new approach, the antedrug concept, was formulated by Lee. The term "antedrug" describes a drug that is active upon local application but is easily biotransformed, on entry into the systemic circulation, to an inactive or much less active metabolite.

New potent topical anti-inflammatory steroids with reduced side effects: derivatives of steroid-16-carboxy esters.

Therapeutic use of anti-inflammatory steroids is limited due to their potential suppressive effects on pituitary-adrenal function and the immune system. Based on the antedrug concept, a new class of potent locally active compounds with reduced risk of side effects has been synthesized from prednisolone by introducing a metabolically labile methoxycarbonyl substituent at C-16. Results of topical application of the lead compound, methyl 11 beta,17 alpha,21-trihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate (P16CM;1), showed that it was 14 times more potent than prednisolone and that it had a greatly reduced tendency to cause systemic side effects.

Liquid chromatography of lanthanide chelates of 1-(p-nitrophenyl)ethylenediamine-N,N,N',N' -tetra-acetic acid.

Preparation of the chelating agent, 1-(p-nitrophenyl)ethylenediamine-N,N,N',N'-tetra-acetic acid (p-nitrophenylEDTA), is described in detail. Separation of p-nitrophenylEDTA chelates of ytterbium(III), erbium(III), dysprosium(III) and europium(III) has been achieved by reversed-phase ion-pair liquid chromatography. With spectrophotometric detection at 254 nm, linear responses over about four orders of magnitude were achieved with detection limits (S/N = 2) of about 0.

Synthesis and pharmacological evaluation of conjugates of prednisolone and non-steroidal anti-inflammatory agents.

Esters of prednisolone with ibuprofen and indomethacin were prepared by coupling the 21-hydroxy moiety of the glucocorticoid to the carboxylic group of the non-steroidal anti-inflammatory agents. The local and systemic anti-inflammatory activities of the conjugates were evaluated using the cotton pellet granuloma bioassay and their topical activity evaluated by the croton oil-induced ear edema assay, in male Sprague-Dawley rats. The results indicate that these conjugates possess greater local and topical anti-inflammatory activity than prednisolone.

Effects of prolonged inflation on pulmonary stretch receptor discharge in turtles.

The tonic and phasic discharge characteristics of single, slowly adapting pulmonary stretch receptors (SAR) were examined before and after 1 h periods of constant pressure inflation to normal resting (VLr, pressure = 0 cm H2O) and elevated (VLe, pressure = 10 cm H2O) lung volumes in turtles (Chrysemys sp.). Based on their discharge at VLr, SAR were classified as either low (n = 13) or high threshold (n = 4) receptors.

Clinical trial with levo-norgestrel and testosterone oenanthate for male fertility control.

Two groups of six men took levo-norgestrel (250 or 500 microgram daily) by mouth and testosterone oenanthate (200 mg monthly, intramuscurlarly) for six months. A three months placebo period preceded the medication which was followed by a recovery phase of 6-10 months. Two volunteers withdrew due to side effects.

The effects of low doses of cyproterone acetate on some functions of the reproductive system in normal men.

One daily dose of either 5 mg or 10 mg cyproterone acetate (CA) was administered to 2 groups of 4 fertile men for 6 months. The medication was preceded by a 3 months placebo period and followed by a recovery phase of 5 to 8 months. During CA-treatment the sperm count/ml decreased and the percentage of abnormal spermatozoa increased slightly (0.

Serum-testosterone during oral administration of testosterone in hypogonadal men and transsexual women.

Testosterone tablets of crystal size 2-5 micrometer were administered orally for 10 dags to 3 human subjects with low endogenous serum testosterone (se-T) levels. Fifty mg testosterone increased se-T slightly, while one daily dose of 200 mg maintained the se-T level within normal range for men for more than 12h. No cumulative effect was seen.

Absence of hCG-like activity in the blood of women fitted with intra-uterine contraceptive devices.

Blood was obtained at various stages of the menstrual cycle from 201 women fitted with intra-uterine contraceptive devices (IUDs), and plasma levels of hCG were determined by radioimmunoassay. Urine samples were obtained from 117 of these women and tested, before and after sephadex gel filtration, in a haemagglutination inhibition test for pregnancy (Pregnosticon). Plasma hCG was undetectable (less than 25 MLU/ml) in all but one of the 201 women and, in this instance, the hCG-assay appeared to be measuring a midcycle peak of LH, as evidenced by high plasma FSH levels.

Concentration of oestrogens and androgens in human ovarian venous plasma and follicular fluid throughout the menstrual cycle.

The concentrations of androstenedione, testosterone, oestrone and oestradiol-17beta were measured in peripheral and ovarian venous blood and follicular fluid of women at various stages of the menstrual cycle. The concentration of oestradiol was similar in small follicles (diameter less than 8 mm) at all stages of the menstrual cycle and in large follicles (diameter greater than or equal to 8 mm) except during the mid- and late follicular phase when the concentration reached a peak (approximately 1500 ng/ml). The concentration of androstenedione was lowest in large preovulatory follicles at midcycle at a time when the secretion into the ovarian vein was markedly increased.