Effect of ursodeoxycholic acid treatment on the altered progesterone and bile acid homeostasis in the mother-placenta-foetus trio during cholestasis of pregnancy

Aim

Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and elevated bile acid concentrations in maternal serum. This is accompanied by an enhanced risk of intra-uterine and perinatal complications. High concentrations of sulphated progesterone metabolites (PMS) have been suggested to be involved in the multifactorial aetiopathogenesis of ICP. The aim of this study was to investigate further the mechanism accounting for the beneficial effect of oral administration of ursodeoxycholic acid (UDCA), which is the standard treatment, regarding bile acid and PMS homeostasis in the mother-placenta-foetus trio.

Method

Using HPLC-MS/MS bile acids and PMS were determined in maternal and foetal serum and placenta. The expression of ABC proteins in placenta was determined by real time quantitative PCR (RT-QPCR) and immunofluorescence.

Results

In ICP, markedly increased concentrations of bile acids (tauroconjugates > glycoconjugates >> unconjugated), progesterone and PMS in placenta and maternal serum were accompanied by enhanced concentrations in foetal serum of bile acids, but not of PMS. UDCA treatment reduced bile acid accumulation in the mother-placenta-foetus trio, but had no significant effect on progesterone and PMS concentrations. ABCG2 mRNA abundance was increased in placentas from ICP patients vs. controls and remained stable following UDCA treatment, despite an apparent further increase in ABCG2.

Conclusion

UDCA administration partially reduces ICP-induced bile acid accumulation in mothers and foetuses despite the lack of effect on concentrations of progesterone and PMS in maternal serum. Up-regulation of placental ABCG2 may play an important role in protecting the foetus from high concentrations of bile acids and PMS during ICP.     

Analysis of mononuclear cell infiltrate and cytokine production in murine autoimmune gastritis

BACKGROUND & AIMS: Murine autoimmune gastritis, induced by day-3 thymectomy, is characterized by cellular infiltrates and circulating autoantibodies to gastric hydrogen/potassium adenosine triphosphatase. The aim of this study was to analyze the cellular infiltrates and cytokines in autoimmune gastritis. METHODS: Stomachs and blood samples from day-3 thymectomized BALB/c mice were obtained from 2 to 12 weeks after thymectomy for analysis. RESULTS: At 4 weeks, the gastritic infiltrates were composed of macrophages and CD4+ T cells, accompanied by major histocompatibility complex class II expression on gastric epithelial cells. Mucosal B cells, scant at 4 weeks, were abundant at 8 weeks, coincident with the peaking of autoantibodies to gastric hydrogen/potassium adenosine triphosphatase. CD8+ T cells increased marginally during the 12 weeks. Mononuclear cells from diseased stomachs transferred gastritis to nu/nu recipients. At 4 weeks, interleukins 2, 3, 5, 6, and 10; interferon gamma; tumor necrosis factor alpha; and granulocyte-macrophage colony-stimulating factor were detected in gastritic mucosa, but interleukin 4 was not. CONCLUSIONS: The early lesion of autoimmune gastritis is composed of macrophages and CD4+ T cells with major histocompatibility complex class II expression in gastric epithelial cells. Autoantibody production is a late event. Our results are consistent with a lesion mediated by CD4+ T cells producing a mix of Th1- and Th2-type cytokines. (Gastroenterology 1996 Jun;110(6):1791-802)     

Claudins: unlocking the code to tight junction function during embryogenesis and in disease

Gupta IR, Ryan AK. Claudins: unlocking the code to tight junction function during embryogenesis and in disease. Claudins are the structural and molecular building blocks of tight junctions. Individual cells express more than one claudin family member, which suggests that a combinatorial claudin code that imparts flexibility and dynamic regulation of tight junction function could exist. Although we have learned much from manipulating claudin expression and function in cell lines, loss‐of‐function and gain‐of‐function experiments in animal model systems are essential for understanding how claudin‐based boundaries function in the context of a living embryo and/or tissue. These in vivo manipulations have pointed to roles for claudins in maintaining the epithelial integrity of cell layers, establishing micro‐environments and contributing to the overall shape of an embryo or tissue. In addition, loss‐of‐function mutations in combination with the characterization of mutations in human disease have demonstrated the importance of claudins in regulating paracellular transport of solutes and water during normal physiological states. In this review, we will discuss specific examples of in vivo studies that illustrate the function of claudin family members during development and in disease.     

Needle cricothyroidotomy revisited.

Needle cricothyroidotomy may provide a life-saving airway when tracheal intubation is not possible. Indications for needle cricothyroidotomy are discussed. Methods of needle/angiocatheter insertion and proposed means to connect to an oxygen source for intermittent insufflation are reviewed. A new technique for administering effective oxygenation and ventilation through a trans-tracheal catheter using materials commonly available in an emergency department is presented. Potential complications are discussed. Complete upper airway obstruction is a contraindication to needle cricothyroidotomy because of the risks of barotrauma. In a crisis situation, the emergency practitioner needs a simple, reliable, effective, and preplanned technique to deal with the "nightmare airway."     

Diagnosis and treatment of persistent dysphonia after laryngeal surgery: A retrospective analysis of 62 patients

Sixty-two patients with persistent or recurrent dysphonia after laryngeal surgery underwent interdisciplinary voice evaluation, laryngostroboscopy, and objective measurements of vocal function. The causes of persistent dysphonia were attributed to vocal fold scarring (n = 22), residual mass lesion (n = 8), residual inflammation (n = 13), recurrent mass (n = 4), and hyperfunctional voice disorder (n = 7). Laryngoscopy often showed excessive ventricular compression and anterior-to-posterior laryngeal compression. Ventricular dysphonia was often a compensatory gesture in response to poorly mobile vocal fold membranes. Stroboscopy was able to document a number of abnormalities which included abnormalities of laryngeal configuration, vibratory asymmetry, reduction of amplitude, and mucosal wave. Using a diversified approach consisting of medical therapy, voice therapy, and repeat surgery, better vocal function was able to be restored in the majority of patients. An interdisciplinary approach to the dysphonic patient after laryngeal surgery was most useful in defining the pathology and refining a treatment rehabilitation program.     

Design and synthesis of alpha,beta-unsaturated carbonyl compounds as potential ACE inhibitors

The alpha,beta-unsaturated amide that is incorporated into the basic structural frame of a simple substrate molecule of angiotensin converting enzyme was found to serve as a Michael acceptor for the catalytic carboxylate of Glu-127, inhibiting the enzyme irreversibly.     

Management of childhood constipation: parents' experiences

BACKGROUND: Constipation in childhood is common and places a burden on child health services. Whilst constipation can have a variety of causes, for most children it is usually non-organic and requires limited intervention. It has been suggested that health professionals can resent consultations for such a common problem, believing them to be inappropriate. However, they can underestimate the impact of this condition, leading to adverse clinical effects, as well as parental dissatisfaction. Little research has explored parents' experiences of consulting health professionals about the management of childhood constipation. AIM: To explore parents' experiences of consulting health professionals about management of childhood constipation and to use the findings to inform more effective therapeutic encounters when responding to parental concerns. METHODS: A phenomenological approach was adopted, using in-depth interviews with parents of 14 children receiving health interventions for constipation. FINDINGS: Six themes emerged from analysis including: 'enduring and extreme constipation', which reflected the substantial and sustained impact of the child's constipation; 'dismissed and fobbed off', which captured parents' feelings that their concerns were frequently dismissed by health professionals; 'asserting the need for action', a perception that they had reached a point at which they had to demand some intervention; and 'validation and acknowledgement', which reflected acknowledgment that, finally, their concerns for their child had been taken seriously and acted on. DISCUSSION: The findings indicate a failure by some health professionals to appreciate fully the significance of childhood constipation, thereby appearing to be unconcerned and insensitive to the needs of child and family. The impact of this is a potential loss of trust in health professionals by parents, which can then have implications for how they perceive and access health services for management of this common childhood problem. The findings offer an insight into parental experiences and indicate the need for a more sensitive approach during health consultations.     

Does community context influence reproductive outcomes of Mexican origin women in San Diego, California?

An increasing body of literature documenting what has become known as the Epidemiological Paradox has shown that some immigrant groups to the United States tend to have healthier birth outcomes than would be expected given their sociodemographic profiles. Furthermore, the children of these immigrants do not seem to enjoy the same advantage in reproductive health that their parents did. This phenomenon, though amply documented in the literature, has not been sufficiently explained. We investigate the role of assimilation in this paradox, and we do so within a spatial framework. We examine the effect of residence in a Mexican enclave in the attenuation of risk of low birth weight (LBW) for Mexican-origin mothers in San Diego County, California. We find that Mexican-origin women do seem to enjoy a reduced risk of giving birth to an LBW baby when they live in a Mexican enclave.