Managing Pregnancy and Nursing Affecting African American Women with Inflammatory Bowel Disease: Clinical Outcomes and Parenthood.

Inflammatory bowel disease (IBD) is a term for two autoimmune diseases encompassing Crohn's disease (CD) and ulcerative colitis (UC) which are lifelong diseases affecting more than 3 million adults (1.3%) in the United States. IBD is characterized by chronic inflammation of the whole digestive system which results in damage to the gastrointestinal (GI) tract. IBD often emerges during adolescence and young adulthood. Maternal morbidity includes physical and psychological conditions that result from or are aggravated by pregnancy and have an adverse effect on a woman's health, the baby's health or both. Some women have health challenges that arise before or during pregnancy that could lead to complications. It is recommended for women to receive health care counseling before and during pregnancy. Compared to other developed countries, the United States has the highest rate of women dying of pregnancy related complications. During the past 25 years maternal mortality has been getting worse. African American women (AAW) with and/or without IBD are dying at significantly higher rates than other groups. This is linked to several factors, i.e., systemic, institutionalized, and structural racism in health-care delivery and subsequent toxic stress from people's lived experiences of racism, limited knowledge about healthcare system function, lack of access to healthcare, (inclusiveness and insurance policies) all of which negatively impact these patients. African Americans (AAs) are also up to three times as likely to experience severe maternal morbidity: unexpected outcomes of labor and delivery, deficient or lacking prenatal care and social determinants of health like lack of transportation, adequate employment, limited literacy, and limited healthcare access contribute to poor health outcomes. Studies on IBD patients indicate Medicaid expansion is associated with reduced rates of maternal morbidity, particularly for African American Women (AAW) and increased access to preconception and prenatal services that make pregnancy and childbirth safer for parent and baby. Herein we examine the physiological changes of pregnancy in patients diagnosed with inflammatory bowel disease and their relationship perinatal outcomes and parenthood.

Mitochondrial Fus1/Tusc2 and cellular Ca2+ homeostasis: tumor suppressor, anti-inflammatory and anti-aging implications.

FUS1/TUSC2 (FUSion1/TUmor Suppressor Candidate 2) is a tumor suppressor gene (TSG) originally described as a member of the TSG cluster from human 3p21.3 chromosomal region frequently deleted in lung cancer. Its role as a TSG in lung, breast, bone, and other cancers was demonstrated by several groups, but molecular mechanisms of its activities are starting to unveil lately. They suggest that Fus1-dependent mechanisms are relevant in etiologies of diseases beyond cancer, such as chronic inflammation, bacterial and viral infections, premature aging, and geriatric diseases. Here, we revisit the discovery of FUS1 gene in the context of tumor initiation and progression, and review 20 years of research into FUS1 functions and its molecular, structural, and biological aspects that have led to its use in clinical trials and gene therapy. We present a data-driven view on how interactions of Fus1 with the mitochondrial Ca2+ (mitoCa2+) transport machinery maintain cellular Ca2+ homeostasis and control cell apoptosis and senescence. This Fus1-mediated cellular homeostasis is at the crux of tumor suppressor, anti-inflammatory and anti-aging activities.

Functional expression of brain neuronal CB2 cannabinoid receptors are involved in the effects of drugs of abuse and in depression.

Major depression and addiction are mental health problems associated with stressful events in life with high relapse and recurrence even after treatment. Many laboratories were not able to detect the presence of CB2 cannabinoid receptors (CB2-Rs) in healthy brains, but CB2-R expression has been demonstrated in rat microglial cells and other brain-associated cells during inflammation. Thus, neuronal expression of CB2-Rs has been ambiguous and controversial, and its role in depression and substance abuse is unknown. In this study we tested the hypothesis that genetic variants of the CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances, including opiates, cocaine, and ethanol, in rodents. Here we demonstrate that a high incidence of Q63R but not H316Y polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated after exposure to stressors and administration of abused drugs. Mice that developed an alcohol preference had reduced CB2 gene expression, and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 antisense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. Using electron microscopy we report the subcellular localization of CB2-Rs that are mainly on postsynaptic elements in rodent brain. Our data demonstrate the functional expression of CB2-Rs in the brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuroimmunocannabinoid activity.

Ibogaine signals addiction genes and methamphetamine alteration of long-term potentiation.

The mapping of the human genetic code will enable us to identify potential gene products involved in human addictions and diseases that have hereditary components. Thus, large-scale, parallel gene-expression studies, made possible by advances in microarray technologies, have shown insights into the connection between specific genes, or sets of genes, and human diseases. The compulsive use of addictive substances despite adverse consequences continues to affect society, and the science underlying these addictions in general is intensively studied. Pharmacological treatment of drug and alcohol addiction has largely been disappointing, and new therapeutic targets and hypotheses are needed. As the usefulness of the pharmacotherapy of addiction has been limited, an emerging potential, yet controversial, therapeutic agent is the natural alkaloid ibogaine. We have continued to investigate programs of gene expression and the putative signaling molecules used by psychostimulants such as amphetamine in in vivo and in vitro models. Our work and that of others reveal that complex but defined signal transduction pathways are associated with psychostimulant administration and that there is broad-spectrum regulation of these signals by ibogaine. We report that the actions of methamphetamine were similar to those of cocaine, including the propensity to alter long-term potentiation (LTP) in the hippocampus of the rat brain. This action suggests that there may be a "threshold" beyond which the excessive brain stimulation that probably occurs with compulsive psychostimulant use results in the occlusion of LTP. The influence of ibogaine on immediate early genes (IEGs) and other candidate genes possibly regulated by psychostimulants and other abused substances requires further evaluation in compulsive use, reward, relapse, tolerance, craving and withdrawal reactions. It is therefore tempting to suggest that ibogaine signals addiction gene products.