Kinyua, Esther Wairimu;Maina, Charles Irungu;Kaingu, Catherine Kaluwa;Wafula, David Kayaja
셀메드
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제10권1호
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pp.2.1-2.8
/
2020
Uterotonics have the ability to contract uterus. Such plants might be useful in augmenting or inducing labour, expelling retained afterbirth and for abortifacient purposes. Limitations associated with conventional treatments have made herbal medicines a feasible alternative for the management of these conditions. The aim of this study was to evaluate the contractile effects of Uvariodendron kirkii extracts on isolated uterine strips of female Wistar rats. Isolated strips of Wistar rats' uteri were treated with 20, 40, 80 and 160 mg/ml concentrations of Uvariodendron kirkii aqueous extract. The plant extract was also tested against prostaglandin and oxytocin induced uterine contractions. Uvariodendron kirkii extract concentrations (20, 40, 80 and 160 mg/ml) increased the frequency of uterine contraction (16.53, 25.12, 33.48 and 56.39 percentages respectively) compared to the control. The graded extract concentrations caused a significant increase in amplitude (force) of uterine contractions by 2.87, 9.22, 16.37 and 24.32 percentages respectively. The concentrations significantly increased the frequency of oxytocin induced uterine contractions by 6.92; 28.31; 47.06, 58.78 percentages respectively. The graded extract concentrations also significantly increased the amplitude of oxytocin induced uterine contractions by 6.07; 9.40; 15.19 and 23.56 percentages respectively. Uvariodendron kirkii extract concentrations significantly increased the frequency and amplitude of prostaglandin induced contractions. The percentage increase in frequency was 11.44, 8.92, 20.65 and 35.71 at 20, 40, 80 and 160 mg/ml respectively. The mean amplitude of prostaglandin induced uterine contractions also increased (4.75, 3.89, 8.29 and 15.91% at 20. 40, 80 and 160 mg/ml respectively). The extract caused a dose dependent increase in uterine frequency and amplitude of contraction. The findings of thisstudy are useful in generating a novel uterotonic agent that will be useful in augmenting labour or in expelling retained after birth in cattle. More studies at molecular level will further elucidate the plant mechanism of action.
Objectives: The aim of this study was to demonstrate the benefit of Traditional Korean Medicine as an adjuvant therapy in management of early uterine contractions and the prevention of Preterm Birth (PTB). Methods: It is a case report of a 38 year-old-woman hospitalized for irregular uterine contractions and cervical change at 33+3/7weeks of gestation. After 7 trials of IVF and artificial insemination, conception was successful via IVF with help of traditional Korean medicines. 2 TKMs were prescribed: Gami-danggui-san, and Antae-eum. 120 ml of Gami-danggui-san was given twice a day morning and evening along with same amount of Antae-eum once a day from 31 August 2013 to 28 November 2013. Tocolytics (Ritodrine) was administered as a first aid for maintenance of pregnancy. Information regarding progress until the delivery was collected during the patient’s visit. Results: As of 34+2/7 weeks of gestation, intermittent uterine contractions appeared (5-12 min) on cardiotocography and vaginal bleeding was also smeared at 34+3/7 weeks. However, enhanced tocolytics and continuous administration of herbal medicine sustained the pregnancy to term. At 37+2/7 weeks, no sign of labor with restored cervical length was confirmed. The woman gave a term birth to a healthy infant via vaginal delivery at 39+3/7 gestational weeks. Conclusions: Our report implies the potential of herbal medicine as a adjuvant therapy for preterm labor treatment. Further studies are needed to assess the safety and efficacy of TKM herbal medicine as a therapeutic alternative for curing preterm birth.
The influences of extracellular $Ca^{2+}\;and\;K^+$ upon the spike action potentials were studied in isolated uterine strips of rat. Regular, rhythmic uterine contractions were induced by the administration of oxytocin$(0.2{\sim}0.5\;I.U.)$, and recorded with force transducer. Spike action potentials were extracellularly measured by use of suction electrode, and compared with those recorded intracellularly by glass microelectrode. The results obtained were as follows : 1) The frequency and duration of spike bursts, and the number of spikes in a burst could be analyzed by use of both methods. But the absolute values of membrane potential were not measurable with the suction electrode. 2) The duration of contraction$(CD_{90};\;the\;duration\;of\;90%\;relaxation)$ was lengthened from the control 17.0 sec to 20.6 sec, in parallel with the increase of spike number from the control 21 to 26, as the increase in $Ca^{2+}$ concentration from 2 to 4 mM. 3) The amplitude and frequency of contractions were gradually decreased, simultaneously with the decrease in the number of spikes in a burst, when the $Ca^{2+}-antagonist$, verapamil was administered cumulatively. 4) The number of spikes was changed from the control 15 to 7, in cabs of the administration of ver)'low dose of verapamil$(10^{-6}\;g/l)$. 5) Increase in the numbers of spike bursts was well matched to the increase in frequency of contractions when extracellular $K^+$ was increased.
In obstetrics, cardiotocography is a procedure to record the fetal heartbeat and the uterine contractions usually during the last trimester of pregnancy. It helps to monitor patterns associated with the fetal activity and to detect the pathologies. In this paper, random forest classifier is used to classify normal, suspicious and pathological patterns based on the features extracted from the cardiotocograms. The results showed that random forest classifier can detect these classes successfully with overall classification accuracy of 93.6%. Moreover, important features are identified to reduce the feature space. It is found that using seven important features, similar classification accuracy can be achieved by random forest classifier (93.3%).
This study was undertaken to illustrate the uterotonic effect of Leonurus sibiricus. It was dissolved in sterile water and several different dosages were administered both in vitro and in vivo study. Rat uterine tissue for in vitro bioassay was obtained from estrous rat. From the low to high dosages of Leonurus sibiricus were tried and each uterine contraction was recorded and integrated. Anesthetized estrous rat for in vivo study was cannulated into the jugular vein for infusion of the compound. Another cannula with a balloon tipped and water filled was inserted into the uterus to measure uterine activity. While the uterine tissue did not respond to low dosage of compound, high dosage of compound stimulated the tissue to contract less than 1 minute with low amplitude. In vivo rat uterus showed a certain, consistent pattern of contractions which was initial relaxation and followed by prolonged and increased amplitude of contractions. It also caused a short breathing stop which might be due to acute acidosis.
The aim of this study was to determine the roles of ET-1 and NO on uterine blood flow in pregnancy. Uterine arteries were isolated from 17 nonpregnant and 12 pregnant women. Nonpregnant group included patients with median age of $48.6{\pm}2.3$ years who underwent hysterectomy, because of myoma. Pregnant group included patients with median age of $31.3{\pm}1.4$ years undergoing cesarean delivery. ET-1 and ET-2 induced concentration-dependent contraction in isolated nonpregnant and pregnant uterine arteries. The contractile response and maximal contraction were increased in pregnant uterine arteries. In nonpregnant uterine arteries, there was no contraction in response to ET-3, whereas pregnancy induced concentration-dependent contraction by ET-3. Tissue nitrite/nitrate level and immunohistochemical staining of eNOS and iNOS were increased in pregnant uterine arteries, compared with nonpregnant uterine arteries. In addition, the expressions of eNOS and iNOS mRNA were significantly increased in pregnancy. Moreover, contractions by ET isopeptides, including ET-1, were enhanced, and immunohistochemical staining of ET-1 and ET-1 mRNA expression was increased in pregnant uterine arteries. These results suggest that NO production by increased NOS activity, especially eNOS activity, is related to placental and uterine blood flow. Furthermore, ET-1 appears to play a pathophysiological role in pregnant complications such as hypertension.
Munoz-Perez, Victor Manuel;Fernandez-Martinez, Eduardo;Ponce-Monter, Hector;Ortiz, Mario I.
The Korean Journal of Physiology and Pharmacology
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제21권4호
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pp.429-437
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2017
The aim of this study was to evaluate the relaxant and anti-inflammatory effects of two thalidomide analogs as phosphodiesterase-4 (PDE-4) inhibitors in pregnant rat uterus. Uteri from Wistar female rats were isolated at 19 day of pregnancy. Uterine samples were used in functional studies to evaluate the inhibitory effects of the thalidomide analogs, methyl 3-(4-nitrophthalimido)-3-(3,4- dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl 3-(4-aminophthalimido)- 3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe), on prostaglandin-$F2{\alpha}$ ($PGF2{\alpha}$)-induced phasic, $K^+$-induced tonic, and $Ca^{2+}$-induced contractions. Accumulation of cAMP was quantified in uterine homogenates by ELISA. Anti-inflammatory effect was assessed by using ELISA for determination of the pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ ($TNF{\alpha}$) and interleukin (IL)-$1{\beta}$, and anti-inflammatory IL-10, from uterine explants stimulated with lipopolysaccharide (LPS). Nifedipine, forskolin and rolipram were used as positive controls where required. Both thalidomide analogs induced a significant inhibition of the uterine contractions induced by the pharmaco- and electro-mechanic stimuli. Nifedipine and forskolin were more potent than the analogs to inhibit the uterine contractility, but these were more potent than rolipram, and 4APDPMe was equieffective to nifedipine. Thalidomide analogs increased uterine cAMP-levels in a concentration-dependent manner. The LPS-induced $TNF{\alpha}$ and $IL-1{\beta}$ uterine secretion was diminished in a concentration-dependent fashion by both analogs, whereas IL-10 secretion was increased significantly. The thalidomide analogs induced utero-relaxant and anti-inflammatory effects, which were associated with the increased cAMP levels as PDE-4 inhibitors in the pregnant rat uterus. Such properties place these thalidomide analogs as potentially safe and effective tocolytic agents in a field that urgently needs improved pharmacological treatments, as in cases of preterm labor.
Although extracellular $Ca^{2+}$ entry through the voltage-dependent $Ca^{2+}$ channels plays an important role in the spontaneous phasic contractions of the pregnant rat myometrium, the role of the T-type $Ca^{2+}$ channels has yet to be fully identified. The aim of this study was to investigate the role of the T-type $Ca^{2+}$ channel in the spontaneous phasic contractions of the rat myometrium. Spontaneous phasic contractions and $[Ca^{2+}]_i$ were measured simultaneously in the longitudinal strips of female Sprague-Dawley rats late in their pregnancy (on day 18 ${\sim}$ 20 of gestation: term=22 days). The expression of T-type $Ca^{2+}$ channel mRNAs or protein levels was measured. Cumulative addition of low concentrations (< 1 ${\mu}M$) of nifedipine, a L-type $Ca^{2+}$ channel blocker, produced a decrease in the amplitude of the spontaneous $Ca^{2+}$ transients and contractions with no significant change in frequency. The mRNAs and proteins encoding two subunits (${\alpha}$ 1G, ${\alpha}$ 1H) of the T-type $Ca^{2+}$ channels were expressed in longitudinal muscle layer of rat myometrium. Cumulative addition of mibefradil, NNC 55-0396 or nickel induced a concentration-dependent inhibition of the amplitude and frequency of the spontaneous $Ca^{2+}$ transients and contractions. Mibefradil, NNC 55-0396 or nickel also attenuated the slope of rising phase of spontaneous $Ca^{2+}$ transients consistent with the reduction of the frequency. It is concluded that T-type $Ca^{2+}$ channels are expressed in the pregnant rat myometrium and may play a key role for the regulation of the frequency of spontaneous phasic contractions.
It has been well known that estrogens stimulate the uterine contractility and progestins inhibit it. Then, one may expect that the uterine contractility and sensitivities to oxytocin (OT) and prostaglandin $F_{2{\alpha}}\;(PGF_{2{\alpha}})$ would be different among the estrus cycle. These hypotheses were tested using the mature female rat. Spontaneous isometric contractions of isolated uterine strips $(1{\times}0.3\;cm)$ from cyclic rats in various stages of the estrus cycle, bilateral ovarectomized rats and hypophysectomized rats were recorded in absence or presence with $estradiol-17{\beta}\;(E_2)$, progesterone $(P_4)$, OT and $PGF_{2{\alpha}}$. The results were summarized as follows: 1) The spontaneous uterine contractile force was the highest in the estrus rat and the lowest in the ovarectomized or the hypophysectomized rat. In the proestrus rat, the contractile frequency was the lowest (2.7 beats/10 min) and the contractile duration was the longest (70 sec). In the other groups, there were no any differencies in frequency (9 beats/10 min) and in duration (30 sec). 2) OT and $PGF_{2{\alpha}}$ stimulated the uterine contractility in all groups tested except in the hypophysectomized rat in which OT failed to stimulate the uterine contraction. $PGF_{2{\alpha}}$ was more effective in stimulating the uterine contraction than OT in all groups tested except in the estrus rat. OT-induced contraction was the highest in the estrus rat and $PGF_{2{\alpha}}-induced$ contraction was the lowest in the hypophysectomized rat. 3) Uterine contractilities were not changed by the in vitro treatments of $E_2$ or $P_4$ under the influence of endogenous steroids, however, $E_2$ and $P_4$ stimulated the uterine contraction in the ovarectomized rat in which endogenous steroids were almost abolished. 4) Increased uterine contraction by the treatment of OT was suppressed by in vitro $E_2$ or $P_4$ in the estrus rat, while it was potentiated by the $P_4$ in the proestrus rat. In other groups, exogenous $E_2$ or $P_4$ did not affect the OT-induced uterine contraction. 5) $PGF_{2{\alpha}}-induced$ uterine contraction was suppressed in the ovarectomized rat by $E_2$ and $P_4$, in the diestrus and proestrus rats by $P_4$ and in the hypophysectomized rat by $E_2$. In other groups, exogenous $E_2$ or $P_4$ was ineffective in altering the $PGF_{2{\alpha}}-induced$ uterine contraction. According to the above results, it may conclude that the mechanisms of the different uterine contractility and the different uterine sensitivity to OT or $PGF_{2{\alpha}}$ according to the estrus cycle are not explicable with only the serum concentrations of steroids, OT and $PGF_{2{\alpha}}$ but also other unknown factors.
Kim, Cheul-Hong;Lee, Sang-Hoon;Kim, Eun-Jung;Ahn, Ji-Hye;Choi, Eun-Ji;Yoon, Ji-Uk;Choi, In-Seok
Journal of Dental Anesthesia and Pain Medicine
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제19권6호
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pp.343-351
/
2019
Background: Preterm labor and miscarriage may occur in stressful situations, such as a surgical operation or infection during pregnancy. Pharyngeal and buccal abscess and facial bone fractures are inevitable dental surgeries in pregnant patients. Remifentanil is an opioid analgesic that is commonly used for general anesthesia and sedation. Nonetheless, no study has investigated the effects of remifentanil on amniotic epithelial cells. This study evaluated the effects of remifentanil on the factors related to uterine contraction and its mechanism of action on amniotic epithelial cells. Methods: Amniotic epithelial cells were preconditioned at various concentrations of remifentanil for 1 h, followed by 24-h lipopolysaccharide (LPS) exposure. MTT assays were performed to assess the cell viability in each group. The effects of remifentanil on factors related to uterine contractions in amniotic epithelial cells were assessed using a nitric oxide (NO) assay, western blot examinations of the expression of nuclear factor-kappa B (NF-κB), cyclooxygenase 2 (COX2), and prostaglandin E2 (PGE2), and RT-PCR examinations of the expression of the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α). Results: Remifentanil did not affect viability and nitric oxide production of amniotic epithelial cells. Western blot analysis revealed that remifentanil preconditioning resulted in decreased expressions of NF-κB and PGE2 in the cells in LPS-induced inflammation, and a tendency of decreased COX2 expression. The results were statistically significant only at high concentration. RT-PCR revealed reduced expressions of IL-1β and TNF-α. Conclusions: Preconditioning with remifentanil does not affect the viability of amniotic epithelial cells but reduces the expression of factors related to uterine contractions in situations where cell inflammation is induced by LPS, which is an important inducer of preterm labor. These findings provide evidence that remifentanil may inhibit preterm labor in clinical settings.
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