Even though pregnancy is rare with cirrhosis and advanced liver disease, but it may co-exist in the setting of noncirrhotic portal hypertension as liver function is preserved but whenever encountered together is a complex clinical dilemma. Pregnancy in a patient with portal hypertension presents a special challenge to the obstetrician as so-called physiological hemodynamic changes associated with pregnancy, needed for meeting demands of the growing fetus, worsen the portal hypertension thereby putting mother at risk of potentially life-threatening complications like variceal hemorrhage. Risks of variceal bleed and hepatic decompensation increase many fold during pregnancy. Optimal management revolves round managing the portal hypertension and its complications. Thus management of such cases requires multi-speciality approach involving obstetricians experienced in dealing with high risk cases, hepatologists, anesthetists and neonatologists. With advancement in medical field, pregnancy is not contra-indicated in these women, as was previously believed. This article focuses on the different aspects of pregnancy with portal hypertension with special emphasis on specific cause wise treatment options to decrease the variceal bleed and hepatic decompensation. Based on extensive review of literature, management from pre-conceptional period to postpartum is outlined in order to have optimal maternal and perinatal outcomes. ( J CLIN EXP HEPATOL 2014;4:163-171) P regnancy associated with liver diseases is an infrequent situation, but when seen together, presents a complicated clinical situation. Portal hypertension develops as a result of number of etiologies. In the west, cirrhosis is the commonest cause of portal hypertension. In the setting of cirrhotic portal hypertension, pregnancy is very rare due to hepatocellular damage leading to amenorrhea and infertility, the incidence of cirrhosis in pregnancy has been reported as 1 in 5950 pregnancies. 1 Cirrhosis may get exacerbated during pregnancy and has significant adverse effects on the mother and the baby. [2][3][4] In the developing countries, other causes like extrahepatic portal vein obstruction contribute significantly to noncirrhotic portal hypertension (NCPH). Mostly liver function is much better preserved in women with NCPH and pregnancy is spontaneous in these women. Portal hypertension associated with pregnancy is a high risk situation as both pregnancy and portal hypertension share some of the hemodynamic changes. The physiological changes, in adaptation to the pregnancy and fetal needs, worsen the portal hypertension resulting in potentially life-threatening variceal bleed and other complications. Pregnancy is a potential hazard for occurrence of recurrent variceal bleed due to its hyperdynamic state causing increase in flow to the collaterals. 5-7 Therefore management in pregnancy requires knowledge of both the effects of changes during pregnancy on portal hemodynamics and the effects of portal hypertension and its cause on both mother and fetus, hepatotoxic...
The immunomodulatory potential of mesenchymal stromal cells (MSCs) and regulatory T cells (T-reg) is well recognized by translational scientists in the field of regenerative medicine and cellular therapies. A wide range of preclinical studies as well as a limited number of human clinical trials of MSC therapies have not only shown promising safety and efficacy profiles but have also revealed changes in T-reg frequency and function.However, the mechanisms underlying this potentially important observation are not well understood and, consequently, the optimal strategies for harnessing MSC/T-reg cross-talk remain elusive. Cell-to-cell contact, production of soluble factors, reprogramming of antigen presenting cells to tolerogenic phenotypes, and induction of extracellular vesicles ("exosomes") have emerged as possible mechanisms by which MSCs produce an immune-modulatory milieu for T-reg expansion. Additionally, these two cell types have the potential to complement each other's immunoregulatory functions, and a combinatorial approach may exert synergistic effects for the treatment of immunological diseases. In this review, we critically assess recent translational research related to the outcomes and mechanistic basis of MSC effects on T-reg and provide a perspective on the potential for this knowledge base to be further exploited for the treatment of autoimmune disorders and transplants.
The cardinal dogma of central nervous system (CNS) immunology believed brain is an immune privileged site, but scientific evidences gathered so far have overturned this notion proving that CNS is no longer an immune privileged site, but rather an actively regulated site of immune surveillance. Landmark discovery of lymphatic system surrounding the duramater of the brain, made possible by high resolution live imaging technology has given new dimension to neuro-immunology. Here, we discuss the immune privilege status of CNS in light of the previous and current findings, taking into account the differences between a healthy state and changes that occur during an inflammatory response. Cerebrospinal fluid (CSF) along with interstitial fluid (ISF) drain activated T cells, natural killer cells, macrophages and dendritic cells from brain to regional lymph nodes present in the head and neck region. To keep an eye on inflammation, this system hosts an army of regulatory T cells (CD25+ FoxP3+) that regulate T cell hyper activation, proliferation and cytokine production. This review is an attempt to fill the gaps in our understanding of neuroimmune interactions, role of innate and adaptive immune system in maintaining homeostasis, interplay of different immune cells, immune tolerance, knowledge of communication pathways between the CNS and the peripheral immune system and lastly how interruption of immune surveillance leads to neurodegenerative diseases. We envisage that discoveries should be made not only to decipher underlying cellular and molecular mechanisms of immune trafficking, but should aid in identifying targeted cell populations for therapeutic intervention in neurodegenerative and autoimmune disorders.
Estrogen treatment was not found to prevent intrauterine adhesions or improve reproductive outcome after hysteroscopic septal resection.
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