Anti-tuberculosis drug-induced acute liver failure requiring transplantation in the second trimester of pregnancy: a case report.

BACKGROUND: Treatment of tuberculosis (TB) during pregnancy can reduce maternal and foetal complications. However, it may also induce fatal liver injury. CASE PRESENTATION: We present a case of a 26-year-old pregnant woman who underwent orthotopic liver transplantation for anti-TB drug-induced fulminant hepatic failure (FHF). Her tuberculous pleurisy was treated with rifampin, isoniazid and pyrazinamide. An artificial liver support system (ALSS) was unable to reverse the liver injury while serving as a bridge to liver transplantation. She had a successful liver transplantation operation at 17 3/7 weeks of gestation. The foetal ultrasound scan showed mild foetal bilateral ventriculomegaly at 21 5/7 weeks of gestation, and labour was induced via double-balloon catheter as soon as the allograft function was stable. Despite immunosuppression, the TB was well controlled with linezolid, levofloxacin and pyridoxine at the 8 months follow-up. CONCLUSIONS: Anti-TB drug-induced liver failure during pregnancy is rare. We present a case of successful treatment of FHF in which an artificial liver support system combined with liver transplantation. The FHF was caused by anti-TB drugs with difficulties due to pregnancy status and post-transplant anti-TB treatment. Mild foetal ventriculomegaly was found in our case. Further research is still needed to identify the risks of TB treatment and liver transplantation in pregnant women. A multidisciplinary team coordinated properly to optimize patient outcomes.

Roles of ion channels in regulation of acetylcholine-mediated vasoconstrictions in umbilical cords of rabbit/rats.

We recently demonstrated that acetylcholine (ACh) produced reliable vasoconstrictions in the umbilical cords. This study investigated the possible mechanisms with different antagonists. ACh-mediated vasoconstrictions were decreased by voltage-operated calcium (Ca2+) channels antagonist nifedipine or inositol-1,4,5-trisphosphate-mediated Ca2+ release antagonist 2-aminoethyl diphenylborinate, indicating that both extracellular and intracellular calcium modulated the ACh-stimulated umbilical contraction. Intracellular Ca2+ concentrations were increased simultaneously with vasoconstrictions by ACh in the umbilical vessels. Inhibiting large-conductance calcium-dependent potassium (BK) channels enhanced ACh-mediated contraction, whereas inhibiting voltage dependent potassium (K+), inward rectifier K+ and ATP-sensitive K+ channels had no effects. Incubation with specific K+ channel inhibitors showed that ACh suppressed BK currents rather than 4-aminopyridine-sensitive K+ channels currents. The results suggested that blood vessels in umbilical cords had special characteristics in response to cholinergic signals. ACh-stimulated umbilical vasoconstrictions were mediated via muscarinic receptor subtype 1/3-protein kinase C/cyclooxygenase-BK channel pathways.

Chronic hypoxia in pregnancy affected vascular tone of renal interlobar arteries in the offspring.

Hypoxia during pregnancy could affect development of fetuses as well as cardiovascular systems in the offspring. This study was the first to demonstrate the influence and related mechanisms of prenatal hypoxia (PH) on renal interlobar arteries (RIA) in the 5-month-old male rat offspring. Following chronic hypoxia during pregnancy, phenylephrine induced significantly higher pressor responses and greater vasoconstrictions in the offspring. Nitric oxide mediated vessel relaxation was altered in the RIA. Phenylephrine-stimulated free intracellular calcium was significantly higher in the RIA of the PH group. The activity and expression of L-type calcium channel (Cav1.2), not T-type calcium channel (Cav3.2), was up-regulated. The whole-cell currents of calcium channels and the currents of Cav1.2 were increased compared with the control. In addition, the whole-cell K(+) currents were decreased in the offspring exposed to prenatal hypoxia. Activity of large-conductance Ca(2+)-activated K(+) channels and the expression of MaxiKα was decreased in the PH group. The results provide new information regarding the influence of prenatal hypoxia on the development of the renal vascular system, and possible underlying cellular and ion channel mechanisms involved.

Maternal high-salt diets affected pressor responses and microvasoconstriction via PKC/BK channel signaling pathways in rat offspring.

SCOPE: High-salt (HS) intake is linked to hypertension, and prenatal exposure to maternal HS diets may have long-term impact on cardiovascular systems. The relationship between HS diets and cardiovascular disease has received extensive attention. This study determined pressor responses and microvessel functions in the adult offspring rats exposed to prenatal HS. METHODS AND RESULTS: The offspring of 5-month old as young adults in rats were used. Blood pressure, vascular tone, intracellular Ca(2+), and BK channels in mesenteric arteries were measured in the offspring. Phenylephrine (Phe)-induced pressor responses were significantly higher in the prenatal HS offspring. Vessel tension and intracellular Ca(2+) concentrations associated with Phe-induced pressor responses were increased in the mesenteric arteries of the HS offspring. PKC α- and δ-isoforms were upregulated in mesenteric arteries of the HS offspring. The enhanced Phe-mediated vascular activity was linked to the altered PKC-modulated BK channel functions. CONCLUSION: The results suggested that prenatal exposure to HS altered microvascular activity probably via changes in PKC/BK signaling pathways, which may lead to increased risks of hypertension in the offspring.

High-sucrose diets in pregnancy alter angiotensin II-mediated pressor response and microvessel tone via the PKC/Cav1.2 pathway in rat offspring.

This study determines the influence of a prenatal high-sucrose (HS) diet on angiotensin II (Ang II)-mediated pressor response and determine the underlying mechanism. Pregnant rats were provided with a 20% sucrose solution diet throughout gestation. Blood pressure and vascular response to Ang II were measured in 5-month-old adult offspring. Currents of L-type Ca(2+) channels (Cav1.2) were measured in smooth muscle cells of small mesenteric arteries from the offspring. Ang II-mediated pressor response was higher in the offspring exposed to prenatal high sugar compared with the control. In mesenteric arteries from the HS offspring, AT1 receptors (AT1R), not AT2 receptors, mediated the increased vasoconstriction; protein kinase C (PKC) antagonist GF109203X suppressed the Ang II-increased vasoconstriction; PKC agonist phorbol 12,13-dibutyrate produced a greater contractile response that was reversed by the Cav1.2 antagonist nifedipine. The expression of PKCα was increased, whereas PKCδ was unchanged; KCl-induced vasoconstriction was stronger and was suppressed by nifedipine; nifedipine also reduced the enhanced vasoconstriction by Ang II. In addition, the Cav1.2 of smooth muscle cells in mesenteric arteries from the HS offspring showed larger current density, although its expression was unchanged. The data suggest that a HS diet during pregnancy alters Ang II-mediated pressor response and microvessel tone acting through the PKC/Cav1.2 pathway in the offspring that may in part be because of alterations in AT1Rs, PKCα and Cav1.2.

Angiotensin II-mediated vascular changes in aged offspring rats exposed to perinatal nicotine.

This study determined the long-term influence of prenatal nicotine exposure (PN) on blood pressure and vascular functions in the aged offspring rats. PN did not affect body weight and plasma adrenocorticotropic hormone level; however, it significantly reduced plasma angiotensin I and angiotensin II in both sexes. Systolic pressure in the male aged PN offspring was significantly higher. Angiotensin II-increased mean arterial pressure was higher in the aged PN offspring than that in the control regardless of sex. AT1 receptor blocker losartan, not AT2 receptor antagonist PD123319, reduced blood pressure in the aged PN rats more than that in the control. In the aged PN offspring, angiotensin II-increased vessel contraction and intracellular calcium level were higher in small mesenteric arteries. Acetylcholine-mediated vascular relaxation was weaker, and nitric oxide-related endothelial functions were damaged in aortic rings of PN offspring. Thickness of the wall of mesenteric arteries was increased in the male aged PN offspring. Ratio of AT1/AT2 receptors was significantly increased in the vessel of the PN group regardless of sex. These data provide new information on the very long term influence of PN on vascular structures and functions in the aged offspring, demonstrate that the aged PN female rats were not free of vascular risks after menopause, and suggest that multiple pathways may be involved in the detrimental alterations of the cardiovascular system of the PN rats.