The health benefits of the (n-3) PUFA, EPA, and DHA have created a demand for fish and fish oil, the main sources of these PUFA. Production animals, such as poultry, are potential alternate and ...sustainable sources of EPA and DHA, provided these fatty acids can be synthesized from plant-derived α-linolenic acid ALA, 18:3(n-3). Because elongases are potential control points in the conversion of ALA to DHA in rats, we examined the chicken elongases, ELOVL2 and ELOVL5, which had not been characterized. ELOVL2 activity was limited to C20-22 PUFA substrates and the major product of ELOVL2 metabolism of EPA was 24:5(n-3). This indicates that ELOVL2 can sequentially elongate EPA to docosapentaenoic acid DPA, 22:5(n-3) and then onto 24:5(n-3). ELOVL5 selectivity was broader with elongation of C18-22 PUFA substrates. The ability of chicken ELOVL5 to efficiently synthesize 24:5(n-3) is unique compared with ELOVL5 enzymes from other species. The expression of ELOVL5 was higher than ELOVL2 in livers of broiler chickens and their expression did not change when dietary ALA was increased from 0.6 to 1.3% of dietary energy for 42 d. The expression of both genes was higher than previously seen in rats. The chicken elongase enzymes are unlike those of any species studied to date, because both ELOVL2 and ELOVL5 have the ability to efficiently elongate DPA. In addition, the relative abundance of ELOVL2 and ELOVL5 in the liver suggests that chickens may be able to metabolize more DPA through to 24:5(n-3), the precursor of DHA, compared with other species such as rats. PUBLICATION ABSTRACT
ABSTRACT
Club drug abuse is a growing problem in the United States. Beyond addiction and toxicity are endocrine effects which are not well characterized. Specifically, the changes in appetite ...following exposure to drugs of abuse are an interesting but poorly understood phenomenon. Serum hormones such as leptin, ghrelin, growth hormone (GH), and neuropeptide‐Y (NP‐Y) are known to affect appetite, but have not been studied extensively with drugs of abuse. In this work, we examine the effects of club drugs 3,4‐methylenedioxymethamphetamine (MDMA) (ecstasy) and methamphetamine (METH) (doses of 5, 20 and 40 mg/kg) on serum concentrations of these hormones in adult male Sprague‐Dawley rats 6, 12, 24 and 48 hours after drug administration. In a dose‐dependent manner, MDMA was shown to cause transient significant decreases in serum leptin and GH followed by a base line recovery after 24 hours. Conversely, serum ghrelin increased and normalized after 24 hours. Interestingly, serum NP‐Y showed a steady decrease in both treatment of MDMA and METH at different time points and dosages. In humans, abuse of these drugs reduces eating. As evident from these data, acute administration of METH and MDMA had significant effects on different serum hormone levels involved in appetite regulation. Future studies should be performed to see how chronic, low dose drug administration would affect hormone levels and try to answer questions about the physiological mechanisms involved in the anorexic paradigm observed in drug use.
New treatment strategies are required for the debilitating inflammatory bowel diseases (IBD), Crohn's Disease and Ulcerative Colitis. DP inhibitors can prolong the bioactivity of the potent ...intestinotrophic growth factor glucagon-like peptide-2 (GLP-2(1-33)). We investigated whether novel inhibitors of DP activity could modify the course of disease activity in the dextran sulfate sodium (DSS) model of colitis. C57BL/6 mice consumed 2 percent DSS in drinking water for 6 days. Mice were orally gavaged twice daily with 0.9% saline, 10 mg/kg isoleucyl-cyano-pyrrolidine (P59/99) or isoleucyl-thiazolidine (P32/98). Assessment of disease severity incorporated a disease activity index (DAI), together with histological assessment of crypt area and depth in the distal colon. DP activity was significantly inhibited at all time points. The DAI was significantly lower in the P59/99 and P32/98 treatment groups compared to saline treatment in all three time courses. Crypt hyperplasia (p<0.05) was observed in the saline group compared to P32/98 treatment at day 9. This preliminary study shows that novel inhibitors of DP activity may provide a new treatment strategy for IBD.
Emu oil possesses significant anti-inflammatory properties in vivo, primarily when applied topically. However, to date, the evidence supporting its therapeutic application has been largely anecdotal, ...and significant batch-to-batch variations in potency have been reported. Nevertheless, the anti-inflammatory properties of emu oil suggest therapeutic promise for the adjunctive treatment of a range of disparate gastrointestinal diseases and disorders characterised by inflammatory processes. These include the idiopathic condition inflammatory bowel disease, chemotherapy-induced mucositis, non-steroidal anti-inflammatory drug enteropathy and the various infective enteritides (i.e. fungal, bacterial and viral gastroenteritis). Although rigorous scientific investigations are in their infancy, the evidence for emu oil efficacy in extra-intestinal disorders, supported by limited in vivo investigations of other naturally sourced oils, identifies emu oil as a possible adjunct to conventional treatment approaches for inflammatory disorders affecting the gastrointestinal system.
This hypothesis-testing study evaluated the relationship between fetal alcohol syndrome (FAS) and neurodevelopmental disorder (ND) diagnoses within the Independent Healthcare Research Database ...(IHRD).
De-identified eligibility and claim healthcare records prospectively generated from the 1990–2012 Florida Medicaid system were analyzed using SAS software. There were 89,766 children continuously eligible with ≥10 outpatient office visits during the 120 month period following birth in the cohort examined. A total of 321 children were diagnosed with FAS. Autism spectrum disorder (ASD) (n = 922), tics (n = 551), attention deficit disorder/attention deficit-hyperactivity disorder (ADD/ADHD) (n = 20,260), mental retardation (MR) (n = 915), and specific delays in development (SDD) (n = 24,630) incidence rates were examined using frequency risk ratio (RR) and logistic regression models.
The incidence rate of tics (RR = 5.68), ADD/ADHD (RR = 2.30), MR (RR = 7.83), SDD (RR = 2.88), and ASD (RR = 6.74) were significantly increased among FAS diagnosed children as compared to undiagnosed children. Adjusted (for gender, race, residency, and date of birth) odds ratios (ORs) were significantly increased for tics (OR = 4.87), ADD/ADHD (OR = 3.40), MR (OR = 7.91), SDD (OR = 9.56), and ASD (OR = 6.87) when comparing the FAS diagnosed children to undiagnosed children.
Tens of thousands of American children with lifetime costs in the billions of US dollars were estimated to be impacted by FAS-associated NDs. These impacts are particularly tragic because FAS is dependent upon lifestyle.
Complete IgHC gene rearrangement occurs only in B cells in a stage-specific and ordered manner. We used gene targeting to reposition a distal V sub(H) gene segment to a region just 5' of the D sub(H) ...gene cluster and found its activation to be highly dependent on the chromosomal domain within which it resides. The targeted V sub(H) gene segment rearranged at a higher frequency than its endogenous counterpart, its rearrangement was no longer ordered, and its ability to be silenced by allelic exclusion was lost. Additionally, the targeted V sub(H) gene segment lost lineage specificity, as VDJ sub(H) rearrangement was observed in thymocytes. These data suggest that locus contraction, mimicked by proximal targeting, can override any regulation imposed by DNA sequences immediately surrounding V sub(H) gene segments.
A novel virus named 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) causes symptoms that are classified as coronavirus disease (COVID-19). Respiratory conditions are extensively described among more ...serious cases of COVID-19, and the onset of acute respiratory distress syndrome (ARDS) is one of the hallmark features of critical COVID-19 cases. ARDS can be directly life-threatening because it is associated with low blood oxygenation levels and can result in organ failure. There are no generally recognized effective treatments for COVID-19, but treatments are urgently needed. Anti-viral medications and vaccines are in the early developmental stages and may take many months or even years to fully develop. At present, management of COVID-19 with respiratory and ventilator support are standard therapeutic treatments, but unfortunately such treatments are associated with high mortality rates. Therefore, it is imperative to consider novel new therapeutic interventions to treat/ameliorate respiratory conditions associated with COVID-19. Alternate treatment strategies utilizing clinically available treatments such as hyperbaric oxygen therapy (HBOT), packed red blood cell (pRBC) transfusions, or erthropoiesis-stimulating agent (ESA) therapy were hypothesized to increase oxygenation of tissues by alternative means than standard respiratory and ventilator treatments. It was also revealed that alternative treatments currently being considered for COVID-19 such as chloroquine and hydroxychloroquine by increasing hemoglobin production and increasing hemoglobin availability for oxygen binding and acetazolamine (for the treatment of altitude sickness) by causing hyperventilation with associated increasing levels of oxygen and decreasing levels of carbon dioxide in the blood may significantly ameliorate COVID-19 respiratory symptoms. In conclusion, is recommend, given HBOT, pRBC, and ESA therapies are currently available and routinely utilized in the treatment of other conditions, that such therapies be tried among COVID-19 patients with serious respiratory conditions and that future controlled-clinical trials explore the potential usefulness of such treatments among COVID-19 patients with respiratory conditions.
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