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Biomedical subjects

A I Csapo

Publications and source records attributed to A I Csapo.

At least 37 records · Page 2Linked to original sources
PubMed1978

The effect of ibuprofen on the intrauterine pressure and menstrual pain of dysmenorrheic patients.

In 12 dysmenorrheic patients we examined the therapeutic action of the Prostaglandin-synthesis inhibitor: Ibuprofen, a non-steroidal analgesic agent. Ibuprofen highly significantly reduced the resting pressure (P less than 0.001), active pressure (P less than 0.001) and frequency (P less than 0.05) of cyclic activity of the uterus, as well as menstrual pain (P less than 0.001). Since these effects occurred after a single oral dose of 800 mg Ibuprofen, without side effects or complications, extensive field trials are recommended with this and other PG-synthesis inhibitors, to assess their therapeutic benefits.

Administration, Oral↗
PubMed1977

Prevention of the abortifacient action of antiprogesterone serum by progesterone.

Earlier studies1-4 showed that when rats of 10 days' gestation are passively immunized with antiprogesterone (A-P) globulins the biologically available progesterone (P) unbound by A-P (Pu) not only falls precipitously but also remains low for days, despite the rapid clearance of A-P. This finding suggested that the effective reduction of Pu affects P synthesis, probably through action on the fetoplacental unit. If so, pregnancy should be protected from the effect of A-P by P treatment to prevent the reduction of Pu. The present studies demonstrated that if P treatment was delayed for six hours after the administration of A-P, Pu did not return to physiologic levels, and pregnancy did not continue. However, if P was given three hours after A-P, at the same time, or three hours before A-P, the reduction of Pu was short-lived or prevented, and thus pregnancy was protected.

Abortifacient Agents↗
PubMed1977

The effect of naproxen-sodium on the intrauterine pressure and menstrual pain of dysmenorrheic patients.

The Prostaglandin-synthesis inhibitor: Naproxen-Sodium (NS) (an analgesic agent) very significantly (P less than 0.001) reduced the "resting" and "active" pressures and the frequency of cyclic uterine activity of 10 dysmenorrheic patients. It also highly significantly reduced (P less than 0.001) menstrual pain. Since these effects were observed after a single oral dose of 1100 mg NS, without side effects or complications, extensive field trials are recommended for assessing therapeutic benefits of this treatment.

Adult↗
PubMed1977

The effects of ovariectomy and stretch on the regulatory profile and activity of the uterus.

Following ovariectomy of five New Zealand white rabbits at day 25 of pregnancy, the intrauterine pressure (IUP) and uterine progesterone (P) and prostaglandin (PG) levels were measured sequentially at days 25, 26 and 27. At day 25, when the uterine P and PGE and PGF were high, massive intrauterine treatment with 500 microng PGF2alpha provoked only a sustained contracture on which only low level oscillation in IUP was superimposed. At day 26, when the P levels had decreased significantly (P less than 0.001) and the PG levels had not changed significantly, 50 microng PGF2alpha significantly increased cyclic IUP as compared with the day 25 value (P less than 0.001). At day 27, when the P levels decreased further, as little as 5 microng PGF2alpha provoked still higher cyclic IUP, in spite of a significant reduction in PG levels (P less than o.05). Stretching the uterus of six post partum and six 26 days pregnant rabbits (after removing the uterine contents) significantly increased the uterine PGF levels (P less than o.001). However, stretch increased only cyclic IUP of the post partum uterus and was without effect on the pregnant uterus, which still had high P levels. These results indicate that the myometrium is activated by exogenous PG or stretch, regardless of whether the uterine PG levels increase, remain unchanged or even moderately decrease, provided that the uterine P levels are reduced to a critical value.

Animals↗
PubMed1977

Inhibition of prostaglandin synthesis and contractility in the rabbit and rat uterus by ibuprofen.

Sixty uterine strips were excised from 8 pregnant and 7 post partum rabbits and stimulated electrically in vitro until they developed maximum isometric tension. The non-steroidal anti-inflammatory agent, Ibuprofen, at concentrations of 125, 250 and 500 microng/ml, significantly reduced tension of the 55 experimental uteri (P less than 0.001) within 7.5 minutes, in comparison with the pretreatment value. Tension in 15 solvent-treated controls remained stable during the same observation period. The reduction in tension was greater in the post partum than the pregnant uteri (P greater than 0.05). Sixteen additional uterine strips, excised from 4 pregnant and 4 post partum rabbits were treated either with 500 microng Ibuprofen or solvent for 7.5 minutes. Radioimmunoassay showed that Ibuprofen significantly reduced the uterine levels of PGF (P less than 0.001) and PGE (P less than 0.001 post partum; P less than 0.05 pregnant) and again the effect was greater in the post partum uteri. These findings suggest that the suppression of uterine function by Ibuprofen is mediated by inhibition of PG-synthesis. In a subsequent study, 36 rats were treated with Ibuprofen on days 20 and 21 of pregnancy, at the ineffective dose level of 4 mg/day and the effective levels of 12, 20 and 30 mg/day. In comparison with the first group, spontaneous labor was significantly delayed in the other three groups (P less than 0.05, P less than 0.01 and P less than 0.001, respectively). In addition, 7 rats were treated with 30 mg/day Ibuprofen and 7 with solvent on days 19 and 20 of pregnancy. On day 21, the Ibuprofen-treated rats showed a significant (P less than 0.001) reduction in the uterine PGF and PGE concentrations, indicating that the prolongation of pregnancy is mediated by an inhibition of uterine PG-synthesis.

Animals↗
PubMed1976

The critical control of progesterone levels and pregnancy by antiprogesterone.

Circulating plasma progesterone (P) has been quantitatively controlled in the rat "model" through highly specific binding by treatment with anti-P (A-P). Knowing the constant, which characterizes the binding of P to A-P in plasma, sequential assays of circulating A-P and A-P bound total P (Pt) revealed the levels of the biologically active unbound P (Pu). The studies showed that at different stages of gestation the mechanisms through which A-P reduces Pu and terminates pregnancy are the same. However, the doses of AP which effectively reduce Pu and also the critical levels of Pu at which pregnancy terminates are different. The moderate and transient physiologic P-withdrawal (Pw) at midterm permits the continuation of normal gestation, but pregnancy is terminated by a drastic and sustained reduction in Pu. In contrast, when Pu is only slightly and briefly reduced below physiologic levels, pregnancy continues and only retarded conceptus growth signals that Pw occurred. Apparently Pw has to be controlled and measured with "razor's-edge" precision to fully expose and define the regulatory significance of this steroid in the maintenance and termination of pregnancy. Short of this precision, the key regulator of the pregnant uterus will remain buried, as it has been during 40 years, in controversial findings.

Abortion, Spontaneous↗
PubMed1976

Effects of progesterone, prostaglandin F2alpha and its analogue ICI 81008 on the excitability and threshold of the uterus.

Forty-eight uterine strips were excised from 24 New Zealand white rabbits and studied in vitro. Sixteen strips were examined when eight animals were 25 days pregnant, 24 strips when 12 animals were about 12 hours postpartum, and eight strips about 12 hours after four animals received a single dose of 5 mg. progesterone (P) at spontaneous delivery. When after repeated exposures to electric fields (60 cycles per second, alternating current, of optimum strength, four seconds' duration at intervals of 30 seconds) the approximately 0.5 Gm. strips developed approximately 40-50g wall tension (WT) in steady state, the field strength was reduced in graded steps from 12 v per 5 cm. to 10, 8, 6, 4 and 3 v per 5 cm. and WT recorded. By measuring the effect on WT of "decreasing electric field stimulation" (DEFS), myometrical excitably and threshold were characterized and quantitated. The technique is based on the relationship between the fraction of myometrial cells activated in the total cell population and WT. As the stimulus is decreased in graded steps from optimal to increasingly suboptimal, DEFS activates fewer and fewer cells reflected by the decrease in WT. Threshold is defined by the strength of the minimum electric field which provokes WT and subthreshold by the field strength which fails to excite. Thus fractional WT averages the excitability of cells in the tissue and thus DEFS characterizes this important parameter of uterine function and quantitates threshold under a variety of regulatory conditions. The comparative study of excised uteri in three different endocrine states showed that the regulatory conditions of normal pregnancy (P levels 9 ng. per milliliter) suppressed excitability and increased threshold (to 6 v per 5 cm.). Post partum (P levels 1 ng. per milliliter) excitability increased and threshold decreased (to 4 v per 5 cm.), unless P treatment prevented this characteristic change by suppressing excitability and increasing threshold (to 6 v per 5 cm.). Both regulatory agents, prostaglandin F2alpha (PGF2alpha) and its analogue ICI 81008, increased excitability and decreased threshold significantly in picogram per milliliter concentrations. However, this effect was observed only when the P levels were low. These compounds had little effect, even in manogram per milliliter concentrations, when the P levels were high. The studies also revealed a close relationship between threshold and spontaneous uterine activity. Low threshold promoted while high threshold suppressed spontaneous activity. In similar concentrations the oxytocic actions of PGF2alpha and ICI 81008 were similar but the effect of ICI 81008 was prolonged through strong binding at myometrical sites.

Animals↗
PubMed1976

Termination of pregnancy with double prostaglandin impact.

With the "double PG impact" (DPGI) technique in 100 sedated first- and second-trimester volunteers, pregnancy was terminated successfully in 99 with a total extraovular PGF2alpha dose of 19.0 +/- 1.5 mg. in 16.9 +/- 0.9 hours. Two thirds of the patients received only the initial dose of 11.6 +/- 0.5 mg. of PG and aborted in 12.9 +/- 0.7 hours without requiring supplemental treatment. Only mild and transient side effects and 14 indicated curettages were recorded. Excepting one gravida (who failed to abort), plasma progesterone in 99 patients decreased at 3 hours after DPGI from 32.5 +/- 1.7 to 22.7 +/- 1.2 ng. per milliliter (P less than 0.001). The rate of progesterone withdrawal and IAT showed a close relationship and the first-trimester patients aborted at a lower progesterone level than the second-trimester patients (P less than 0.001).

Abortion, Induced↗
PubMed1976

Menstrual induction by the vaginal application of ICI 81008 gel.

After approximately 2 weeks menstrual delay (positive Pregnosticon Tests) "menstrual induction" was attempted in 75 gravidas by repeated vaginal application of a gel, containing 200 or 400 mug/ml ICI 81008. After approximately 10 minutes, following the 1st vaginal delivery of 400 mug ICI 81008, the uterus responded to this PGF2alpha analogue with sustained contracture. The highest success rate in induced bleeding (93%) and pregnancy termination (79%), without supportive therapy, was achieved when 400 mug ICI 81008 was administered 2 to 5 times at 4 hour intervals. Those gravidas (21%), who failed in induced menstruation, or stopped bleeding within 24 hour- after treatment, had positive Pregnosticon Tests on day 14 and were curetted. The side effects, mostly vomiting and increased blood pressure, were transient and subjectively and medically acceptable. While the vaginal application of the drug is apparently less effective than the intrauterine (1), it has the advantage of simple delivery and the potential of self-administration.

Abortion, Induced↗
PubMed1976

The effects of progesterone, prostaglandin F2alpha and oxytocin on the calcium-activation of the uterus.

The relationship between "activator-calcium" (A-Ca), progesterone (P), prostaglandin F2alpha (PGF2alpha) and oxytocin (Oxy) has been examined in 100 uterine strips of 34 pregnant and 100 strips of 34 post partum rabbits. At the 25th day of gestation, uterine P was 13.9+/-1.3 ng/g, while within 3-12 hours post partum 3.3+/-0.3 ng/g tissue (P less than 0.001). Uterine strips, mounted isometrically in Krebs' solution, sustained maximum excitability in a steady state when exposed every 30 seconds for 4 seconds to an electric field of 12 V/5 cm (a.c.). The maximally contracting muscles were then rinsed at intervals of 6 minutes with Ca-free Krebs. In Ca-free Krebs, the post partum uterus lost 31% of its Ca and 96% of its excitability in a short 25 minutes, while the pregnant uterus lost 30% of its Ca and 93% of its excitability in 50 minutes (P less than 0.001). Since the extracellular space is approximately 30% in the uterus, this approximately 30% Ca, lost by both muscles, most probably was extracellular Ca and the small A-Ca fraction which is presumably "bound" more strongly at the membrane systems of the P-dominated pregnant, than the non-dominated post partum uterus. The significantly faster and more complete recovery from Ca-deficiency and inexcitability of the pregnant than the post partum uterus (P less than 0.001), at different levels of external Ca, further substantiates this premise. So does the demonstration that exposure to Ca-free Krebs increases 45Ca-efflux 400% in the post partum and only 110% in the pregnant uterus (P less than 0.001). Exposure to 100 ng/ml PGF2alpha in normal Krebs has a similar effect on the 45Ca-efflux of the post partum uterus, while the response of the pregnant uterus is indistinct (P less than 0.001). These highly significant differences between the post partum and the pregnant uteri in their Ca-efflux explain the higher threshold (P less than 0.001) and lower "sensitivity" to PGF2alpha and Oxy (P less than 0.001) of the pregnant than the post partum uterus. The already very highly significant differences between the two muscles, in threshold and sensitivity to these two most potent oxytocics, were increased still further by rendering the uterine strips Ca-deficient. All together, these findings substantiate the early contention (1-7, 18, 19) that uterine function at the cellular level is regulated by opposing actions of the suppressor P and the intrinsic stimulant PG or other oxytocic agents on threshold, excitability and the Ca-activation of the contractile process.

Animals↗