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Biomedical subjects

K Folkers

Publications and source records attributed to K Folkers.

At least 163 records · Page 9Linked to original sources
PubMed1980

Inhibition of preovulatory gonadotropin secretion in the rhesus monkey by [(<Glu-Pro)1,D-Phe2,D-Trp3,6]-LHRH.

We report the first example of a complete inhibition of preovulatory gonadotropin secretion resulting from administration of a luteinizing hormone releasing hormone antagonist during a spontaneous menstrual cycle. The antagonist, [(<Glu-Pro)1,D-Phe2,D-Trp3,6]-LHRH, was administered to a rhesus monkey beginning on Day 9 of the menstrual cycle; ovulation did not occur and preovulatory peaks of LH and FSH were not observed despite elevations in serum estradiol-17 beta of sufficient strength and duration to elicit gonadotropin surges. Midcycle gonadotropin surges had already commenced in another monkey, however the antagonist did partially inhibit LH and FSH secretion although ovulation and luteinization were not prevented. Normal hormone secretion patterns and luteal function were observed in another monkey when the antagonist was given after the midcycle FSH and LH peaks had already occurred. These data emphasize the importance of beginning treatment with LHRH antagonists early in the follicular phase of the menstrual cycle.

Animals↗
PubMed1980

Plasma concentration of neurotensin-like immunoreactivity (NTLI) and lower esophageal sphincter (LES) pressure in man following infusion of (Gln4)-neurotensin.

(Gln4)-neurotensin was infused i.v. for 5 to 70 min at 3 different infusion rates (6, 12 and 18 pmol X kg-1 X min-1, respectively) in 19 male volunteers, aged 26-47. The plasma concentration of neurotensin-like immunoreactivity (NTLI), the lower esophageal sphincter (LES) pressure, blood pressure, heart rate. ECG and blood glucose concentration were measured. The volunteers did not report any subjective effects during the infusion. Following infusion periods of 30 min or more the volunteers often reported bowel movements starting 5 min or more after cessation of the infusion. Neither blood pressure nor heart rate changed significantly. No changes were noted in the continuous ECG or in the blood glucose concentration. Apparent steady state levels of about 300 pM NTLI were reached at about 40 min during infusion of 12 pmol X kg-1 X min-1 (Gln4)-neurotensin. In all volunteers the LES pressure was significantly reduced within 5 min of starting the infusion. In 6 volunteers 12 pmol X kg-1 X min-1 (Gln4)-neurotensin was infused i.v. for 5 min. The LES pressure decreased significantly (P less than 0.01) from 13.7 +/- 1.3 mmHg to 5.3 +/- 0.8 mmHg. The decrease in the LES pressure occurred at plasma NTLI concentrations of approximately 50 pM, i.e. at levels below those obtained in man after a meal or the ingestion of fat. The present data further support the hypothesis that in man plasma neurotensin, or a neurotensin metabolite is an endocrine hormone involved in the postprandial regulation of the motor functions of the gastrointestinal tract.

Adult↗
PubMed1980

On the inhibitory effects of luteinizing hormone-releasing hormone analogs.

A detailed study of the activity of LHRH analog antagonists has been made in four assay systems which measure inhibition of the action of LHRH on isolated rat pituitaries in vitro, inhibition of the release of the LH induced by LHRH in vivo in adult male rats and adult male chimpanzees, and inhibition of spontaneous ovulation in cycling female rats. Only a partial correlation was observed between the in vitro and in vivo assays. Currently, the most potent LHRH analog antagonists in the present study were based on a 1,2,3,6-tetra-substituted LHRH sequence. The analogs [D less than Glu1,DPhe2,DTrp3,DTrp6]-LHRH, Ac-[Pro1,DPhe2,DTrp3,DTrp6]LHRH and [(Glu-Pro)1, dphe2,DTrp3,DTrp6]LHRH completely inhibited spontaneous ovulation in cycling rats at a dosage of 200 microgram/rat, sc. The most potent inhibitors of ovulation were always very potent in vitro, but other analogs having identical in vitro activities had little or no antiovulatory activity even at substantially higher dosages. The analogs inhibited the action of LHRH in the rat more easily than in the chimpanzee. Twelve of 13 analogs at the analog to LHRH ratio of 100:1 significantly inhibited the LH response, while only 5 of 9 of these same analogs inhibited the LH response in the chimpanzee at the analog to LHRH ratio of 333:1. Only 1 of 8 analogs at a high dosage inhibited the binding of labeled LH to the gonadal LH receptor in vitro. The inability of the less polar (cyclopentane carboxylic acid) analogs to inhibit ovulation could be explained, at least partially, in terms of impaired absorption sc. Although the cyclopentane carboxylic acid analogs effectively inhibited the action of LHRH in vitro and, when given iv in vivo, they were not effective in blocking the LHRH-stimulated LH response in adult male rats when given sc, which is the mode of administration of the antiovulatory assay, suggesting the importance of the route of administration.

Animals↗
PubMed1980

Inhibition of acid secretion from vagally innervated and denervated gastric pouches by (Gln4)-neurotensin.

In dogs with innervated fundic pouches an intravenous infusion of (Gln4)-neurotensin, 60 pmol X kg-1 X min-1, reduced the pentagastrin-stimulated acid secretion to 40% of the control secretory rate. After vagal denervation of the fundic pouches the same dose of (Gln4)-neurotensin did not significantly change the secretion. These findings suggest that (Gln4)-neurotensin does not act directly on parietal cells but inhibits acid secretion at a presynaptic level.

Animals↗
PubMed1979

Structural requirements in positions 1, 2, 3, and 6 of the luteinizing hormone-releasing hormone (LH-RH) for antiovulatory activity.

Sixteen analogues of the luteinizing hormone-releasing hormone (LH-RH) were synthesized by the solid-phase method. In new and surprising relationships, it was found that the substitution of D-Trp into position 3 of [D- less than Glu1,D-Phe2,amino acid3,D-Phe6]-LH-RH significantly enhanced the antiovulatory potency, but substitution by Pro, N-Me-Phe,N-Me-Leu, or L-Trp reduced antiovulatory activity. The substitution of L- less than Glu in position 1 of [D-Phe2,Pro3,D-Phe6]-LH-RH by cyclohexylcarbonyl (Chc), benzoyl (Bz), Ac, Hyp, Ac-Met, hydrogen, Pro, and D- less than Glu residues, and the substitution of D-Phe in position 2 by D-Trp, D-His, D-Phg, and L-Phe residues resulted in analogues with no antiovulatory activity at 750 microgram/rat. Structural requirements for the design of inhibitors of higher potency have been discussed.

Amino Acid Sequence↗
PubMed1979

Clinical results of a cross-over treatment with pyridoxine and placebo of the carpal tunnel syndrome.

Clinical evaluation was made of cross-over treatments by pyridoxine and a placebo of patient 22 having the carpal tunnel syndrome. Extraordinary monitoring of the specific activities of the erythrocyte glutamic oxaloacetic transaminase proved a severe vitamin B6 deficiency, which was partially corrected by the Recommended Dietary Allowance of 2 mg, and completely corrected by 100 mg. The severity of the syndrome diminished on the Recommended Dietary Allowances and the patient was asymptomatic at the higher dosage. On placebo, both the vitamin B6 deficiency and syndrome reappeared. Retreatment with 100 mg again corrected both the deficiency and syndrome. Measurements (total n = 19) of flexion of proximal interphalangeal joints of the index fingers by a goniometer, and of pinch by the Preston gauge revealed objective normalization. Scores of 17 symptoms revealed reductions at both the 2- (P less than 0.01) and 100-mg (P less than 0.001) dosages. Conduction through the carpal tunnels had improved by electromyography. These and previous data on a total of 22 patients showed the concomitant presence of a deficiency of vitamin B6 and the carpal tunnel syndrome; a causal relationship is apparent.

Adult↗
PubMed1979

Synthesis of substance P analogs and agonistic and antagonistic activities.

Fourteen analogs of substances P (SP), six previously synthesized by a solution method and eight newly synthesized by a solid-phase technique, have been tested for agonistic and antagonistic activities utilizing the isolated guinea pig ileum. The primary objective is to achieve effective inhibitors of SP. These analogs had agonistic activities ranging from negligible to that equivalent to SP. Six of the fourteen analogs had some degree of antagonistic activity [D-Leu8, D-Phe9]-SP is an analog which constitutes a lead to new substitutions, because it had antagonistic activity, but only negligible agonistic activity. One concept for effective antagonistic activity requires negligible or no agonistic activity.

Animals↗
PubMed1979

Prevention by coenzyme Q10 of the electrocardiographic changes induced by adriamycin in rats.

The administration of adriamycin (ADM) to rats has consistently caused a widening of the QRS complex of the electrocardiogram. When coenzyme Q10 was also administered, beginning two days before ADM, this widening of the QRS complex and the elongation of the Q-T interval were reduced or totally prevented, depending upon conditions. ADM alone or with coenzyme Q10 did not alter the P-R interval. Some control by coenzyme Q10 of the cardiotoxicity of adriamycin in cancer patients is promising.

Animals↗