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Biomedical subjects

A Forman

Publications and source records attributed to A Forman.

At least 91 records · Page 5Linked to original sources

Immunoreactive oxytocin and vasopressin in the non-pregnant human uterus and oviductal isthmus.

The regional distribution of immunoreactive OT and AVP in the human uterus was investigated. Specimens of non-pregnant human uterus and oviduct were homogenized and extracted. The tissue levels exceeded the plasma concentrations of the peptides. The largest quantities of both peptides were found in the cervix and oviductal isthmus. The amounts found in the uterine fundus and isthmus were, however, not significantly different. Only 23% of immunoreactive OT eluted in the position of standard peptide on high-performance liquid chromatography. All immunoreactive AVP eluted with standard AVP after additional ether extraction of octadecasilyl extracts. We conclude that the human uterus contains materials immunologically and chromatographically identical to oxytocin and vasopressin.

Adult↗

Effects of isradipine, a new calcium antagonist, on postpartum uterine activity.

The effects of a new calcium antagonist, isradipine (PN 200-110) on postpartum uterine activity and the maternal cardiovascular system were investigated. Uterine activity was recorded by a microtip transducer catheter inserted transcervically within 45 min of normal vaginal delivery. 0.5 mg of isradipine was given as a bolus injection during 5 min to 7 women with spontaneous uterine activity and 1 mg was given during a 15-min period to another 8 women with oxytocin-stimulated uterine activity. Matched controls with similar pre-injection activity (+/- 5%) but not given the drug were selected for comparison. The effects of the drug in 3 women (given 1 mg of isradipine) were compared with those in matched controls and in women given 0.25 mg of terbutalin i.v. as a bolus injection. Isradipine had a marked inhibitory effect on both spontaneous and oxytocin-stimulated uterine activity. The inhibitory effect of 1 mg of isradipine seemed comparable to that of 0.25 mg of terbutalin. The inhibition occurred within 1-2 min after the injection and was sustained throughout the study period (2 h). A transient reduction of the systolic (mean maximum decrease 10-15%) and diastolic blood pressure (mean maximum decrease 15-20%) was seen, particularly during the injection period. Hypotension (systolic blood pressure less than 80 mmHg) was not recorded. A moderate increase in pulse rate (mean maximum increase 22-27%) was seen in all cases. The results show that isradipine given as a bolus injection can inhibit early postpartum uterine activity, with minimal side effects.

Adult↗

Effects of some neurotransmitters and prostanoids on isolated human intracervical arteries.

Human cervical tissue specimens were excised after hysterectomy at various phases of the menstrual cycle (n = 12), and small intracervical arteries were dissected free by microtechnique. Ring preparations of the vessels were prepared and mounted in organ baths, and isometric circular tension was recorded. Norepinephrine, 3 X 10(-8) to 10(-5) mol/L, produced concentration-dependent contractions, whereas 3 X 10(-7) to 10(-6) mol/L prostaglandin F2 alpha inconsistently produced weak contractions and slightly increased tension induced by 10(-5) mol/L norepinephrine. Prostaglandin I2, 10(-9) to 10(-6) mol/L, prostaglandin E2, 3 X 10(-9) to 10(-6) mol/L, vasoactive intestinal polypeptide, 10(-9) to 10(-7) mol/L, and substance P, 10(-12) to 10(-9) mol/L, induced relaxation of vessels precontracted by 10(-5) mol/L norepinephrine. It is suggested that several mechanisms for the local release of vasoactive compounds may influence cervical blood flow. Thus, sympathetic control of cervical blood flow may be modulated by peptide neurotransmitters such as vasoactive intestinal polypeptide and substance P and by local synthesis of prostaglandins E2 and I2.

Arteries↗

Effects of human calcitonin gene-related peptide and substance P on human intracervical arteries.

The contractile effects of substance P and human calcitonin gene-related peptide (human CGRP) on isolated human intracervical arteries were studied. Human cervical tissue specimens were excised after hysterectomy at various phases of the menstrual cycle (n = 14) and small intracervical arteries were dissected free by microtechnique. Ring preparations of the vessels were prepared and mounted in organ baths, and isometric circular tension was recorded. Neither compound affected resting tension. Both peptides showed potent relaxing effects on vessels precontracted by noradrenaline 10(-5) M. Substance P exhibited the higher potency, while human CGRP showed the higher efficacy. The relaxing effects of the two compounds were unaffected by pretreatment with indomethacin 10(-6) M, propranolol 10(-6) M and atropine 10(-6) M. The results support a role for the two peptides in the regulation of cervical blood flow.

Arteries↗

Effects of VIP and PHM in human intracervical arteries.

The relaxing effects of vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) on human intracervical arteries were studied. Cervical tissue specimens were excised after hysterectomy at various phases of the menstrual cycle (n = 12) and small intracervical arteries were dissected free by microtechnique. Ring preparations of the vessels were prepared and mounted in organ baths, and isometric circular tension was recorded. None of the compounds showed any effects in unstimulated cervical arterial preparations. In vessels precontracted by noradrenalin 10(-5) M, VIP 10(-8) - 10(-6) M and PHM 10(-8) - 10(-6) M induced similar, concentration-dependent relaxation with a maximum effect of 73.2 +/- 12.7% relaxation for VIP 10(-6) M and 79.6 +/- 11.8% for PHM 10(-6) M, as compared to 10.7 +/- 3.1% decrease in tension for control preparations treated with solvent (mean +/- SE, n = 6). Simultaneous addition of VIP 5 x 10(-7) M and PHM 5 x 10(-7) M produced additive effects. Pretreatment with indometacin 10(-6) M, atropine 10(-6) M or propranolol 10(-6) M did not significantly influence these responses. Both peptides might be involved in regulation of blood flow in the human cervix.

Cervix Uteri↗

Effects of thiopentone or chlormethiazole on human placental stem villous arteries.

Small placental stem villous arteries were micro dissected from specimens obtained at normal term vaginal delivery (n = 25). Ring preparations of the vessels were mounted in organ baths and isometric tension was measured. Prostaglandin F2 alpha (PGF2 alpha) 10(-7)-10(-4) mol litre-1 produced concentration-dependent contractile responses that were inhibited by thiopentone 10(-4)-10(-3) mol litre-1 and by chlormethiazole 3 x 10(-4)-3 x 10(-3) mol litre-1. Thiopentone 10(-4)-10(-3) mol litre-1 and chlormethiazole 3 x 10(-4)-3 x 10(-3) mol litre-1 decreased the tension in vessels previously treated with PGF2 alpha 10(-5) mol litre-1. Chlormethiazole 3 x 10(-3) mol litre-1 inhibited, and thiopentone 10(-4)-10(-3) mol litre-1 abolished contractile responses to 5-hydroxytryptamine. Contractions induced by angiotensin II were inhibited by thiopentone 10(-3) mol litre-1 and chlormethiazole 3 x 10(-3) mol litre-1. The concentrations of the two drugs needed to affect contractile activation of isolated human stem villous arteries exceeded the free plasma concentrations reached during anaesthesia induced by the agents during Caesarean section, and the present results do not suggest any major effects of thiopentone or chlormethiazole on fetal placental vascular resistance during the clinical use of these drugs.

Angiotensin II↗

Adult onset Hallervorden-Spatz disease with neurofibrillary pathology. A discrete clinicopathological entity.

Three adults with progressive cognitive decline and extrapyramidal dysfunction were studied. They were all mentally retarded women without known chromosomal abnormalities, ranging in age at the time of onset from 31 to 42 yrs with an average duration of illness of 6 yrs. Neurological signs were stereotyped and consisted of a unilateral equinovarus foot posture followed by progressive dementia, rigidity and quadriparesis. Identical pathological findings were noted in all cases. There was marked deposition of iron-containing pigments in the globus pallidus and reticulate zone of the substantia nigra. Numerous axonal spheroids were noted in these areas and in the gracile and cuneate nuclei. In addition to these typical changes of Hallervorden-Spatz disease (HSD), abundant neurofibrillary tangles (NFTs) were found within the hippocampus, neocortex, nuclei of basal forebrain, subthalamic nucleus and brainstem reticular formation. Rare Hirano bodies and granulovacuolar degeneration were noted within the hippocampus; neuritic plaques and amyloid deposits were absent. Ultrastructurally the NFTs were mostly paired helical filaments (PHFs) with a diameter of 20 to 25 nm and a half-periodicity of 80 nm. Straight filaments and incompletely twisted forms were also seen. Immunocytochemistry with polyclonal antibodies to PHFs was positive in a distribution identical to that of Bodian-positive NFTs. Biochemical analysis of frozen frontal cortex from 1 case revealed a 94% depletion of the cholinergic marker enzyme choline acetyltransferase. Somatostatin-like immunoreactivity was within normal range. Study of 1 case with laser microprobe mass analysis revealed evidence of aluminium accumulation in tangle-bearing hippocampal neurons. Adjacent tangle-free neurons failed to show comparable accumulations. These findings indicate that adult onset HSD occurring in mentally retarded individuals may represent a distinct clinicopathological entity associated with neurofibrillary pathology without amyloid deposition.

Adult↗

Acute effects of nitrendipine in pregnancy-induced hypertension.

The acute effects of a single, 20 mg oral dose of nitrendipine were studied in 10 women at between 32 and 42 weeks gestation with stable pregnancy-induced hypertension (PIH). Blood pressure (BP), maternal heart rate and fetal heart rate (FHR) were assessed for 8 h after nitrendipine intake together with the plasma levels of nitrendipine, noradrenaline, adrenaline, plasma renin activity (PRA) and vasopressin. The mean initial systolic/diastolic BP was 158 (SEM 3.7)/108 (SEM 2.7) mmHg. Within 1 h stable, reduced mean BP-levels of 141-145/90-95 mmHg were reached and maintained for 4 h after medication. This antihypertensive effect was closely related to the maternal plasma concentration of nitrendipine, which reached a maximum of 9.1 (SEM 2.6) ng/ml 3 h after tablet intake. After 4 h, systolic and diastolic BPs slowly increased in parallel to a successive decrease in plasma concentrations of nitrendipine. Maternal heart rate increased by less than 10%, while FHR remained unchanged. No hypotensive incidents occurred. The initial mean plasma concentrations of noradrenaline, adrenaline, vasopressin and PRA did not change during the treatment. No major maternal and no fetal side-effects were observed. Three of 10 patients experienced mild, transient facial flushing.

Adult↗

Combined intracervical PGE2 and intra-amniotic PGF2 alpha for induction of 2nd trimester abortion.

Fourteen consecutive patients (mean gestational age 18.1 weeks, range 15-23 weeks) referred for therapeutic termination of pregnancy were induced into abortion by intra-amniotic PGF2 alpha 40 mg followed by oxytocin stimulation. 14 other patients (mean gestational age 17.9 weeks, range 15-23 weeks) were pretreated with intracervical PGE2 1.0 mg in gel for 4 h prior to induction of abortion with intra-amniotic PGF2 alpha 40 mg without further stimulation. The induction-abortion interval for patients treated with intra-amniotic PGF2 alpha and oxytocin, was 19.1 +/- 2.94 h (+/- SE, n = 14) with a success rate of 80% after 24 h. After pretreatment with intracervical PGE2 1.0 mg in viscous gel, intra-amniotic PGF2 alpha 40 mg induced abortion after 11.2 +/- 1.12 h (+/- SE, n = 14) with a 100% success rate after 24 h. No systemic side effects of the PGE2 pretreatment were noted. No cervical laceration was observed. The results need further confirmation, but still suggest cervical priming with intracervical PGE2 1.0 mg in gel and subsequent induction of abortion by intra-amniotic PGF2 alpha 40 mg as an attractive principle for 2nd trimester abortion.

Abortion, Induced↗

Oxytocin- or low-dose prostaglandin F2 alpha-infusion for stimulation of labor after primary rupture of membranes. A prospective, randomized trial.

One hundred consecutive women with singleton pregnancies and primary rupture of membranes (PROM) after 36 weeks of gestation were included in a prospective, randomized trial of intravenous infusion of oxytocin (up to 30 mIU/min) versus low-dose prostaglandin F2 alpha(PGF2 alpha, up to 6.0 micrograms/min). Cesarean section was performed in 12 patients because of suspected disproportion or intra-uterine asphyxia. Effective contractions or labor progress failed to become established within 8 hours in another 4 women stimulated with PGF2 alpha and 2 stimulated by oxytocin. The stimulation delivery time (hours) for the remaining 82 women treated with PGF2 alpha or oxytocin, respectively was 8.7 against 12.1 for initial Bishop score less than 5 (p less than 0.01), (Mann-Whitney test), 7.2 vs. 7.1 for Bishop score 5-8 and 5.7 vs. 4.2 for Bishop score greater than 8. Patients with initial Bishop score less than 5 seemed to need analgetics less often when treated with PGF2 alpha than with oxytocin. Frequencies of side effects and instrumental deliveries as well as the fetal outcome were similar for the two treatment schedules. The results of the study suggest that low-dose PGF2 alpha infusion may be the more appropriate treatment for women with an unfavorable initial Bishop score.

Adolescent↗

Inhibitory effects of nitrendipine on myometrial and vascular smooth muscle in human pregnant uterus and placenta.

Human myometrial visceral and vascular preparations and placental chorionic and stem villous vessels were dissected from myometrial and placental specimens obtained at term Caesarean section and after vaginal delivery. Vascular ring preparations and myometrial strips were mounted in organ bath and isometric tension recorded. Only myometrial preparations developed spontaneous contractile activity, which was effectively blocked by the calcium channel blocker nitrendipine (NTD) 10(-7) M. Pretreatment with calcium-depleted medium for 30 min. almost abolished myometrial responses to high K+ (124 mmol), oxytocin (OX) and prostaglandin F2 alpha (PGF2 alpha). Vascular responses to high K+ (124 mmol) were also nearly abolished by such treatment. However, noradrenaline (NA), vasopressin (VP) and PGF2 alpha in myometrial arteries and PGF2 alpha in chorionic vessels and stem villous arteries induced significant, but reduced contractions after calcium depletion. In all vascular preparations, exposed to calcium-depleted medium, NTD (10(-8) M) almost abolished contractions induced by calcium (0.1-4.0 mM) in the presence of K+ (124 mmol) and depressed responses to calcium in the presence of the other agonists tested. NTD (10(-10)-10(-7) M) depressed myometrial contractions induced by K+, OX and PGF2 alpha more effective than vascular responses to K+, NA, VP and PGF2 alpha in the myometrial arteries and K+ and PGF2 alpha in the placental arteries. It is concluded that activation of contraction in vessels from the human utero-placental unit implies multiple cellular sources of calcium, while in myometrial smooth muscle, influx of superficially bound calcium may be an important initial step in contractile activation. Treatment with calcium channel blockers during late human pregnancy might involve relaxation of the myometrium together with vasodilatation of the myometrial and foetal placental vascular beds.

Calcium↗

Effects of calcium channel blockers on the female genital tract.

Contractile activity and vascular resistance in the female genital tract are influenced by several smooth muscle tissues with individual mechanisms for control of mechanical activation. Calcium channel blockers have potent relaxant effects on preparations of human myometrium. The myometrial arteries utilize multiple sources of calcium for contractile activation, and excitation-contraction coupling in isolated vessels from non-pregnant uteri seems comparatively less sensitive to nifedipine than in corresponding myometrial preparations. Contractile activation of myometrial and placental arteries at term is inhibited by nitrendipine and nifedipine. Human oviductal smooth muscle depends on superficially bound calcium for mechanical activation, but only phasic contractions can be abolished by nifedipine, while tonic contractions induced by various agents are more resistant to the calcium channel blocker. Menstrual uterine contractions and pain are effectively counteracted by nifedipine in normal and dysmenorrhoeic women. Such therapy may represent an alternative principle in the treatment of dysmenorrhea. Nifedipine has potent relaxant effects on the mid-term pregnant and the post-partum uterus and calcium channel blockers may prove useful in the treatment of premature labor. Nifedipine and related compounds may further show effective in the treatment of pregnancy-associated hypertension. Whether such treatment in late pregnancy involves maintained or even improved placental perfusion could be assumed from in vitro data but needs further studies.

Animals↗

Effects of calcium channel blockers on urinary tract smooth muscle.

Influx of calcium from the extracellular medium seems to be important for spontaneous as well as agonist-induced contractile activity in urinary tract smooth muscle. To a various extent this calcium influx occurs through pathways which can be blocked by calcium channel blockers. These drugs effectively suppress spontaneous ureteral activity in vitro. Whether they affect ureteral motility in vivo or whether they can counteract ureteral spasm associated with ureteral stones have not been established. Calcium channel blockers partially block electrically as well as agonist-induced detrusor contractions. Some of these drugs abolish even atropine-resistant contractile responses induced by electrical stimulation in detrusor muscle. Drugs with combined antimuscarinic and calcium channel blocking effect therefore have an attractive effect profile. Experiences with calcium channel blockers in the treatment of patients with 'unstable bladder' are limited, but results obtained with terodiline seem promising. Even if calcium channel blockers reduce agonist-induced contraction in isolated urethral muscle, their clinical effect on urethral function seems to be small. The effects of calcium blockers on urinary tract smooth muscle may be clinically useful and deserve further study.

Animals↗

Differential effects of angiotensin, vasopressin and oxytocin on various smooth muscle tissues within the human uteroplacental unit.

Tissue specimens from various parts of the uteroplacental unit were obtained from women undergoing caesarean section, and placental tissue from women with normal deliveries. Strips of myometrial tissue, and segments of intramyometrial arteries were dissected together with segments of chorionic plate arteries and veins, and stem villous arteries. The preparations were mounted in organ baths, isometric tension recorded, and the responses to angiotensin II, vasopressin, and oxytocin were studied. In myometrial preparations, angiotensin caused a slight, transient increase in the frequency of spontaneous contractions, but no changes in amplitude. In all vascular preparations angiotensin produced concentration-related contractions. The responsiveness of the preparations was myometrial artery greater than villous artery greater than chorionic plate artery = chorionic plate vein. All responses were transient and tachyphylaxis was pronounced in all tissues. Tachyphylaxis was not influenced by pretreatment with indomethacin. Vasopressin increased transiently frequency and amplitude of contractions in myometrial strips. Myometrial arteries responded with a sustained contraction, as did chorionic plate arteries and veins but the latter vessels were less responsive. Villous arteries did not respond to vasopressin. Oxytocin preferentially stimulated myometrial strips, but also had a weak concentration-related contractant effect on chorionic plate arteries and veins. Villous arteries did not respond to oxytocin. At a higher concentration, causing a pronounced increase in the frequency and amplitude of contractions of myometrial strips, oxytocin abruptly caused a marked contraction of myometrial arteries. Lower concentrations of the peptide had almost no effects. The results suggest that various smooth muscle tissues of the human uterus and placenta are highly differentiated as regards responses to angiotensin II, vasopressin, and oxytocin. The physiological and possible clinical importance of the present findings deserve further investigation.

Adult↗

Relaxant and contractile effects of some amines and prostanoids in myometrial and vascular smooth muscle within the human uteroplacental unit.

Tissue specimens of human myometrium and placenta were obtained at caesarean section and normal vaginal deliveries. Strips of myometrial tissue, and segments of intramyometrial arteries, chorionic plate arteries and veins, and stem villous arteries were dissected. The preparations were mounted in organ baths, and isometric tension was recorded. In myometrial preparations, prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), noradrenaline (NA) and serotonin (5-HT) all caused concentration-related contractions. In vascular preparations, the maximum contractant or relaxant effect, Emax or Imax, and the drug concentrations causing half maximum responses, EC50 or IC50 were determined. In intramyometrial arteries no significant differences between Emax or EC50 values were found for NA, 5-HT and PGF2 alpha. The Imax values (relaxation of vessels contracted by vasopressin) ranged prostacyclin (PGI2) greater than PGF2 alpha = PGE2, and the IC50 values PGF2 alpha = PGE2 = PGI2 (PGF2 alpha less than PGI2). Thus, PGF2 alpha showed dual effects. Only PGI2 relaxed placental vessels contracted by PGF2 alpha. In chorionic arteries, Emax values ranged PGE2 = PGF2 alpha greater than 5-HT greater than NA, and IC50 values 5-HT less than NA = PGF2 alpha = PGE2. In stem villous arteries, Emax ranged PGE2 = PGF2 alpha greater than 5-HT = NA, and EC50 5-HT = NA = PGE2 = PGF2 alpha. In chorionic veins the order of Emax values was PGF2 alpha = PGE2 greater than 5-HT greater than NA, and that of the EC50 values 5-HT less than NA = PGF2 alpha = PGE2. Smooth muscle tissues from the human uteroplacental unit show individual responses to prostanoids and amines, probably reflecting individual mechanisms for control of contractile activity and blood flow.

Adult↗

Different responses to prostaglandin F2 alpha and E2 in human extra- and intramyometrial arteries.

Tubal segments of the ascending uterine arteries and of intramyometrial arteries were obtained from 18 women who underwent hysterectomy at various phases of the menstrual cycle. Ring preparations of the vessels were mounted in organ baths and isometric tension was recorded. In extramyometrial arteries (outer diameter 2-3 mm) prostaglandin (PG) F2 alpha most potently, but also PGE2 caused concentration-related contractions. In contrast, the contractant effects of both PGs on intramyometrial arteries (outer diameter 0.5-0.6 mm) were negligible. Both extra- and intramyometrial vessels were relaxed to a moderate degree (10-25%) by low concentrations of PGF2 alpha and PGE2. No significant differences between the responses to vasopressin and noradrenaline were found between the vessel preparations. Thus human uterine arteries seem to change their responses to PGF2 alpha and PGE2 as they enter the myometrium and decrease in diameter, and the results raise doubt about the view that direct vasoconstrictor effects of these PGs contribute to the regulation of myometrial blood flow. Such effects of vasopressin and noradrenaline cannot be excluded.

Adolescent↗