In vitro effects of citral on the human myometrium: Potential adjunct therapy to prevent preterm births.

BACKGROUND: Premature infants contribute to infant morbidity and mortality especially in low resource settings. Information on tocolytic and/or anti-inflammatory effects of several plant extracts, such as citral, could help prevent preterm birth cases and reduce the number of preterm infants. The aim of this study was to evaluate the in vitro tocolytic and anti-inflammatory effect of citral on myometrial tissues of the human uterus. METHODS: Myometrial samples from uteri obtained after hysterectomy were used in functional tests to evaluate the inhibitory effect of citral on PGF-2α induced contractions. The intracellular cyclic adenosine monophosphate (cAMP) levels generated in response to citral in human myometrial homogenates were measured by ELISAs. Forskolin was used as a positive control. The anti-inflammatory effect of citral was determined through the measurement of two pro-inflammatory cytokines, tumor necrosis factor-α (TNFα) and interleukin (IL)-1ß, and the anti-inflammatory cytokine IL-10, in human myometrial explants stimulated with lipopolysaccharide (LPS). RESULTS: Citral was able to induce a significant inhibition of PGF-2α induced contractions at the highest concentration level (p < .05). Citral caused a concentration-dependent increase in myometrial cAMP levels (p < .05) and a concentration-dependent decrease in LPS-induced TNFα and IL-1ß production, while IL-10 production increased significantly (p < .05). The anti-inflammatory and tocolytic effects induced by citral could be associated with an increase in cAMP levels in human myometrial samples. CONCLUSION: These properties place citral as a potentially safe and effective adjuvant agent in preterm birth cases, an obstetric and gynecological problem that requires urgent attention.

Anti-inflammatory and utero-relaxant effect of α-bisabolol on the pregnant human uterus.

The aim of this study was to evaluate the in vitro anti-inflammatory and utero-relaxant effect of α-bisabolol on the pregnant human myometrium. Samples from the pregnant human myometrium were used in functional tests to evaluate the inhibitory effect of α-bisabolol (560, 860, 1,200 and 1,860 µM) on spontaneous myometrial contractions. The intracellular cyclic adenosine monophosphate (cAMP) levels generated in response to α-bisabolol in human myometrial homogenates were measured by ELISA. The anti-inflammatory effect of α-bisabolol was determined through the measurement of two pro-inflammatory cytokines, tumor necrosis factor-α (TNFα) and interleukin (IL)-1ß, and the anti-inflammatory cytokine IL-10, in pregnant human myometrial explants stimulated with lipopolysaccharide (LPS). Forskolin was used as a positive control to evaluate the cAMP and cytokine levels. α-Bisabolol was found to induce a significant inhibition of spontaneous myometrial contractions at the highest concentration level (p<0.05). α-Bisabolol caused a concentration-dependent decrease in myometrial cAMP levels (p<0.05) and a concentration-dependent decrease in LPS-induced TNFα and IL-1ß production, while IL-10 production did not increase significantly (p>0.05). The anti-inflammatory and utero-relaxant effects induced by α-bisabolol were not associated with an increase in cAMP levels in pregnant human myometrial samples. These properties place α-bisabolol as a potentially safe and effective adjuvant agent in cases of preterm birth, an area of pharmacological treatment that requires urgent improvement.

Inhibition of Uterine Contractility by Thalidomide Analogs via Phosphodiesterase-4 Inhibition and Calcium Entry Blockade.

Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4) inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl 3-(4-nitrophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl 3-(4-aminophthalimido)-3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe) and were compared to rolipram in functional studies of spontaneous phasic, K⁺-induced tonic, and Ca2+-induced contractions in isolated pregnant human myometrial tissues. The accumulation of cAMP was quantified in HeLa cells. The presence of PDE-4B2 and phosphorylated myosin light-chain (pMLC), in addition to the effect of thalidomide analogs on oxytocin-induced pMLC, were assessed in human uterine myometrial cells (UtSMCs). Thalidomide analogs had concentration-dependent inhibitory effects on spontaneous and tonic contractions and inhibited Ca2+-induced responses. Tonic contraction was equipotently inhibited by 4APDPMe and rolipram (IC50 = 125 ± 13.72 and 98.45 ± 8.86 µM, respectively). Rolipram and the thalidomide analogs inhibited spontaneous and tonic contractions equieffectively. Both analogs increased cAMP accumulation in a concentration-dependent manner (p < 0.05) and induced changes in the subcellular localization of oxytocin-induced pMLC in UtSMCs. The inhibitory effects of thalidomide analogs on the contractions of pregnant human myometrium tissue may be due to their PDE-4 inhibitory effect and novel mechanism as calcium-channel blockers.

[Fetus compressus and fetus papyraceous. Clinical differences (report of three cases)]. / Feto compreso y feto papiráceo. Diferencias clínicas, tres casos.

The items papyraceus fetus and fetus compressus are used like synonymous. The low incidence and the lack of reporting of these cases leads to confusion. Clinical evidence shows significant differences between them and sustain a proper diagnosis. We report 3 cases of patients with multiple pregnancy (2 twins and 1 triplets) observed in the death of one of the products of each patient, obtaining 2 fetus compressus and 1 fetus papyraceous, respectively.

Synergistic relaxing effect of the paracetamol and pyrilamine combination in isolated human myometrium.

OBJECTIVE: To evaluate the interaction type of the human uterine relaxant effect of the paracetamol-pyrilamine combination (PPC) in vitro. STUDY DESIGN: Uterine strips were contracted with KCl (60 mM) and treated with vehicle or increasing concentrations of paracetamol (100-3200 µM), pyrilamine (3.2-100 µM) or the PPC. The relaxing effects of the drugs alone and in combination were measured. Isobolographic analysis was used to determine the pharmacologic interaction type. RESULTS: Paracetamol, pyrilamine and the PPC produced a significant relaxing effect on non-pregnant human uterine strips pre-contracted with KCl (60 mM). The EC30 values for paracetamol and pyrilamine on the uterine contraction were 2391.3±595.3 µM and 14.7±1.7 µM, respectively. The derived experimental EC30 for the PPC was 401.8±129.8 µM. This value was significantly lower (p<0.05) than the theoretical EC30 expected for a purely additive interaction, which was 1203.0±297.7 µM for the PPC. The interaction index (γ) was 0.33±0.14 for PPC, being statistically different from unity. CONCLUSION: Data suggest that low doses of the PPC can interact synergistically and therefore this drug association may represent a therapeutic advantage for the clinical treatment of dysmenorreic pain.