The effects of high-fat, high-sugar, and high-fat high-sugar diets on hippocampal-dependent spatial and contextual memory

Diets that are high in fat and sugar are associated with cognitive deficits in humans. Rodent models using these diets have shown that they produce deficits on tasks that assess hippocampal-dependent spatial learning and memory. However, less is known about the effect of such diets on other hippocampal-dependent forms of cognition. To examine the nature and specificity of diet-induced impairments in hippocampal function, rats were fed standard chow supplemented with sucrose solution, high-fat chow, or both high-fat chow and sucrose solution. These rats were then assessed on their memory for the location and identity of objects, and their formation and use of hippocampal-dependent representations of context. Chapter 2 showed that relatively short-term dietary intake of fat, sugar, or fat and sugar lasting two-months or less adversely affects performance on a number of hippocampal-dependent spatial memory tasks. This conclusion was based on a meta-analysis of the results from rodent studies using different diets (high in fat, high in sugar, or high in both fat and sugar) and different tasks to assess hippocampal-dependent spatial learning and memory (water maze, place recognition, radial arm maze, and spontaneous alternation). The analysis revealed that the largest effect was produced by exposure to a combined high-fat and high-sugar diet, with medium effects produced by high-fat diet or high-sugar diet. Of the different tasks used to assess spatial learning and memory, the largest effect was observed in the radial arm and radial water maze tasks, with medium effects in the place recognition, the spontaneous alternation, and the Morris water maze tasks. Chapter 3 demonstrated that rats fed chow and a sucrose solution performed just as well as control rats fed chow on a perirhinal-dependent object-recognition task, but demonstrated impaired performance, compared with controls, on a hippocampal-dependent place-recognition task. Rats exposed to high-sugar diet also performed comparably to controls in a context fear conditioning protocol, although there was some evidence that high-sugar rats generalised the context fear memory to a similar context more than control rats. The generalisation effect was only observed when context fear was assessed using a within-subject design and when rats were tested in the similar context before the conditioning context. Chapter 4 established that the selective impairment in place recognition memory observed in high-sugar rats extended to rats exposed to a diet high in fat, or high in both fat and sugar. There was no evidence that any one diet produced a more significant impairment than the other diets. There was also no evidence that the impairment worsened with longer exposure to the diet. Finally, rats exposed to any of these diets performed comparably to chow-fed rats in a context pre-exposure fear conditioning task that is critically dependent on hippocampal function. The findings from this thesis are discussed in relation to the insights gained from observing impairments that appear to be selective to spatial learning and memory, future directions of research for examining the effect of high-fat and/or high-sugar diets on hippocampal-dependent configural processing, the role of the hippocampus in diet-induced deficits, and the translational implications for dietary effects on human cognition and eating behaviours

Bioactivity of the Murex Homeopathic Remedy and of Extracts from an Australian Muricid Mollusc against Human Cancer Cells

Marine molluscs from the family Muricidae are the source of a homeopathic remedy Murex, which is used to treat a range of conditions, including cancer. The aim of this study was to evaluate the in vitro bioactivity of egg mass extracts of the Australian muricid Dicathais orbita, in comparison to the Murex remedy, against human carcinoma and lymphoma cells. Liquid chromatography coupled with mass spectrometry (LC-MS) was used to characterize the chemical composition of the extracts and homeopathic remedy, focusing on biologically active brominated indoles. The MTS (tetrazolium salt) colorimetric assay was used to determine effects on cell viability, while necrosis and apoptosis induction were investigated using flow cytometry (propidium iodide and Annexin-V staining, resp.). Cells were treated with varying concentrations (1–0.01 mg/mL) of crude and semi-purified extracts or preparations (dilute 1 M and concentrated 4 mg/mL) from the Murex remedy (4 h). The Murex remedy showed little biological activity against the majority of cell lines tested. In contrast, the D. orbita egg extracts significantly decreased cell viability in the majority of carcinoma cell lines. Flow cytometry revealed these extracts induce necrosis in HT29 colorectal cancer cells, whereas apoptosis was induced in Jurkat cells. These findings highlight the biomedical potential of Muricidae extracts in the development of a natural therapy for the treatment of neoplastic tumors and lymphomas

Bioactivity of the Murex Homeopathic Remedy and of Extracts from an Australian Muricid Mollusc against Human Cancer Cells

Copyright © 2011 Kirsten Benkendorff et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Marine molluscs from the family Muricidae are the source of a homeopathic remedy Murex, which is used to treat a range of conditions, including cancer. The aim of this study was to evaluate the in vitro bioactivity of egg mass extracts of the Australian muricid Dicathais orbita, in comparison to the Murex remedy, against human carcinoma and lymphoma cells. Liquid chromatography coupled with mass spectrometry (LC-MS) was used to characterize the chemical composition of the extracts and homeopathic remedy, focusing on biologically active brominated indoles. The MTS (tetrazolium salt) colorimetric assay was used to determine effects on cell viability, while necrosis and apoptosis induction were investigated using flow cytometry (propidium iodide and Annexin-V staining, resp.). Cells were treated with varying concentrations (1–0.01 mg/mL) of crude and semi-purified extracts or preparations (dilute 1 M and concentrated 4 mg/mL) from the Murex remedy (4 h). The Murex remedy showed little biological activity against the majority of cell lines tested. In contrast, the D. orbita egg extracts significantly decreased cell viability in the majority of carcinoma cell lines. Flow cytometry revealed these extracts induce necrosis in HT29 colorectal cancer cells, whereas apoptosis was induced in Jurkat cells. These findings highlight the biomedical potential of Muricidae extracts in the development of a natural therapy for the treatment of neoplastic tumors and lymphomas

Mapping early environment using communication deviance: a longitudinal study of maternal sensitivity toward 6-month-old children

Communication deviance (CD) reflects features of the content or manner of a person's speech that may confuse the listener and inhibit the establishment of a shared focus of attention. The construct was developed in the context of the study of familial risks for psychosis based on hypotheses regarding its effects during childhood. It is not known whether parental CD is associated with nonverbal parental behaviors that may be important in early development. This study explored the association between CD in a cohort of mothers (n = 287) at 32 weeks gestation and maternal sensitivity with infants at 29 weeks in a standard play procedure. Maternal CD predicted lower overall maternal sensitivity (B = -.385; p < .001), and the effect was somewhat greater for sensitivity to infant distress (B = -.514; p < .001) than for sensitivity to nondistress (B = -.311; p < .01). After controlling for maternal age, IQ and depression, and for socioeconomic deprivation, the associations with overall sensitivity and sensitivity to distress remained significant. The findings provide new pointers to intergenerational transmission of vulnerability involving processes implicated in both verbal and nonverbal parental behaviors

Simultaneous Assessment of the Efficacy and Toxicity of Marine Mollusc–Derived Brominated Indoles in an In Vivo Model for Early Stage Colon Cancer

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution- NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).The acute apoptotic response to genotoxic carcinogens animal model has been extensively used to assess the ability of drugs and natural products like dietary components to promote apoptosis in the colon and protect against colorectal cancer (CRC). This work aimed to use this model to identify the main chemopreventative agent in extracts from an Australian mollusc Dicathais orbita, while simultaneously providing information on their potential in vivo toxicity. After 2 weeks of daily oral gavage with bioactive extracts and purified brominated indoles, mice were injected with the chemical carcinogen azoxymethane (AOM; 10 mg/kg) and then killed 6 hours later. Efficacy was evaluated using immunohistochemical and hematoxylin staining, and toxicity was assessed via hematology, blood biochemistry, and liver histopathology. Comparison of saline- and AOM-injected controls revealed that potential toxic side effects can be interpreted from blood biochemistry and hematology using this short-term model, although AOM negatively affected the ability to detect histopathological effects in the liver. Purified 6-bromoisatin was identified as the main cancer preventive agent in the Muricidae extract, significantly enhancing apoptosis and reducing cell proliferation in the colonic crypts at 0.05 mg/g. There was no evidence of liver toxicity associated with 6-bromoisatin, whereas 0.1 mg/g of the brominated indole tyrindoleninone led to elevated aspartate aminotransferase levels and a reduction in red blood cells. As tyrindoleninone is converted to 6-bromoisatin by oxidation, this information will assist in the optimization and quality control of a chemopreventative nutraceutical from Muricidae. In conclusion, preliminary data on in vivo safety can be simultaneously collected when testing the efficacy of new natural products, such as 6-bromoisatin from Muricidae molluscs for early stage prevention of colon cancer

Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study.

BackgroundEnrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors.MethodsIn a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies.Measurements and main resultsAn admission sTNFR1 concentration &gt; 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration &gt; 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level &gt; 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor.ConclusionsThresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials

Gastrointestinal and Hepatotoxicity Assessment of an Anticancer Extract from Muricid Molluscs

Copyright © 2013 Chantel B. Westley et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Marine molluscs from the family Muricidae are under development as a potential medicinal food for the prevention of colon cancer and treatment of gynaecological cancers. Here we report the outcome of the first in vivo toxicity assessment on an anticancer extract from a muricid mollusc containing brominated indole derivatives. Mice received the concentrated lipophilic extract by daily oral gavage over a two-week period. Mortality or clinical toxicity symptoms resulting from the extract were not detected during the trial, and there was no difference in the body weight of treated and control mice at the end of the trial. Histological analysis revealed some evidence for mild, idiosyncratic effects on the gastrointestinal tract and liver, including necrosis, fatty change, and inflammation in a small proportion (ud_less_than40%) of mice. This is likely to result from first-pass hepatic metabolism of tyrindoxyl sulphate combined with second-pass metabolism of indoles. Overall however, oral administration of muricid extract containing brominated indoles does not result in severe clinical toxicity

The Effect of Intrahippocampal Insulin Infusion on Spatial Cognitive Function and Markers of Neuroinflammation in Diet-induced Obesity

Obesity and high fat diet consumption contribute to the development of metabolic disorders, insulin resistance, neuroinflammation, and cognitive impairments. CNS administration of insulin into the brain can attenuate these cognitive impairments. The present study investigated whether hippocampal-dependent spatial memory impairments in a dietary induced mouse model of obesity could be improved by the direct administration of insulin into the hippocampus and whether this was associated with markers of hippocampal inflammation. C57Bl/6J mice consumed a low fat or high fat diet for 16 weeks and continuous intrahippocampal saline or insulin infusion for the final 4 weeks, during a period of behavioral testing, before gene expression analysis was performed. The high fat diet group demonstrated poorer spatial memory performance in the Morris water maze and Y-maze, supporting the hypothesis that high fat diet leads to hippocampal dependent cognitive impairment. Insulin infusion into the hippocampus reversed the deficit of high fat diet consumption on both of the tasks. Increased expression of inflammatory markers was detected in the hippocampus in the high fat diet group and expression of these markers was ameliorated in insulin infused mice. This demonstrates that CNS insulin can improve hippocampal-dependent memory and that hippocampal inflammation may be a factor in the development of cognitive deficits associated with diet-induced obesity. Furthermore, these data suggest that insulin may act to attenuate high fat diet induced cognitive deficits by reducing neuroinflammation

Calculus Volume 2

Calculus is designed for the typical two- or three-semester general calculus course, incorporating innovative features to enhance student learning. The book guides students through the core concepts of calculus and helps them understand how those concepts apply to their lives and the world around them. Due to the comprehensive nature of the material, we are offering the book in three volumes for flexibility and efficiency. Volume 2 covers integration, differential equations, sequences and series, and parametric equations and polar coordinates.https://commons.erau.edu/oer-textbook/1001/thumbnail.jp