bluuebunny/crossref_metadata_2025 huggingface dataset:
Vagal Influence on Compensatory Ovarian Growth is Important Only Briefly after Hemicastration
Authors: Trkulja Vladimir , Lackovic Zdravko
Published: July 2017

Hemicastration induces growth of the remnant ovary in the rat. As evidenced by the effects of total abdominal vagotomy, vagal innervation markedly influences this compensatory ovarian growth. In the present experiments, vagotomy inhibited compensatory ovarian growth when performed immediately after hemicastration, but not when delayed until 4.5 hr after hemicastration. Brief exposure of subdiaphragmal portion of the vagi nerves to 2% lidocaine shortly before hemicastration also inhibited compensatory growth. Fifteen minutes after hemicastration, markedly elevated tissue concentrations of cyclic adenosine monophosphate (cAMP) were recorded in the remnant ovaries This accumulation of cAMP was inhibited by vagotomy that preceded hemicastration, as well as by lidocaine pretreatment of the vagi nerves, and partly by vagotomy that followed 10 min after hemicastration. At 5 hr after hemicastration, tissue cAMP concentrations in the remnant ovaries were not elevated and were not affected by vagotomy. The present results suggest that vagal influence on the compensatory ovarian growth is important only during a short period of time after hemicastration (apparently shorter than 4.5 hr), and that it, at least briefly after hemicastration, includes neural input to the ovary.
Cancer Chemopreventive and Tumoricidal Properties of Saffron (Crocus sativus L.)
Authors: Abdullaev Fikart I.
Published: July 2017

Since cancer is the most common cause of death in the world population, the possibility that readily available natural substances from plants, vegetables, herbs, and spices may be beneficial in the prevention of cancer warrants closer examination. Saffron in filaments is the dried, dark red stigmata of Crocus sativus L. flowers and it is used as a spice, food colorant, and a drug in medicine. A growing body of research has demonstrated that saffron extract itself and its main constituents, the carotenoids, possess chemopreventive properties against cancer. This review discusses recent literature data and our results on the cancer chemopreventive activities of saffron and its main ingredients
Histidine Suppresses Food Intake through Its Conversion into Neuronal Histamine
Authors: Yoshimatsu Hironobu , Chiba Seiichi , Tajima Daisuke , Akehi Yuko , Sakata Toshiie
Published: July 2017

Hypothalamic neuronal histamine has been shown to regulate feeding behavior and energy metabolism as a target of leptin action in the brain. The present study aimed to examine the involvement of l-histidine, a precursor of neuronal histamine, in the regulation of feeding behavior in rats. Intraperitoneal (ip) injection of l-histidine at doses of 0.35 and 0.70 mmol/kg body weight significantly decreased the 24-hr cumulative food and water intakes compared to phosphate buffered saline injected controls (P < 0.05 for each). This suppression of feeding was mimicked dose-dependently by intracerebroventricular infusion of histidine at doses of 0.5, 1.0, and 2.0 μmol/rat (P < 0.05 for each). Pretreatment of the rats with an ip bolus injection of α-fluoromethylhistidine, a suicide inhibitor of a histidine decarboxylase (HDC), at a dosage of 224 μmol/kg blocked the conversion of histidine into histamine and attenuated the suppressive effect of histidine on food intake from 64.2% to 88.1% of the controls (P < 0.05). Administration of 0.35 mmol/kg histidine ip increased the concentration of hypothalamic neuronal histamine compared with the controls (P < 0.05). HDC activity was increased simultaneously by histidine administration compared with the controls (P < 0.05). The present findings indicate that l-histidine suppresses food intake through its conversion into histamine in the hypothalamus
Scrotal Cooling Increases Rectal Temperature in Man
Authors: Vash Peter D. , Engels Thomas M. , Kandeel Fouad R. , Greenway Frank
Published: July 2017

The aim of this study was to evaluate the effect of scrotal cooling on rectal temperature in man. Pilot studies suggested that immersing the scrotum in a 30°C water bath increased rectal temperature, but immersing the scrotum in a 0°C water bath did not. Six healthy young men immersed their scrotums in a 35°C water bath for 11 min followed by 21 min at 30°C. Rectal temperature rose by 0.38 ± 0.04°C (P < 0.01) in response to the 30°C water bath. Repetition of the study by immersing the hands instead of the scrotum in the water bath had no effect on rectal temperature. The scrotum appears to play a role in human temperature regulation.
Factors Involved in the Regulation of Type I Collagen Gene Expression: Implication in Fibrosis
Authors: Ghosh Asish K.
Published: July 2017

Type I collagen, the major component of extracellular matrix in skin and other tissues, is a heterotrimer of two α1 and one α2 collagen polypeptides. The synthesis of both chains is highly regulated by different cytokines at the transcriptional level. Excessive synthesis and deposition of collagen in the dermal region causes thick and hard skin, a clinical manifestation of scleroderma. To better understand the causes of scleroderma or other tissue fibrosis, it is very Important to investigate the molecular mechanisms that cause upregulation of the Type I collagen synthesis in these tissues. Several cis-acting regulatory elements and trans-acting protein factors, which are involved in basal as well as cytokine-modulated Type I collagen gene expression, have been identified and characterized. Hypertranscription of Type I collagen in scleroderma skin fibroblasts may be due to abnormal activities of different positive or negative transcription factors In response to different abnormally induced signaling pathways. In this review, I discuss the present day understanding about the involvement of different factors in the regulation of basal as well as cytokine-modulated Type I collagen gene expression and its implication in scleroderma research.
Sphingoid Bases and Ceramide Induce Apoptosis in HT-29 and HCT-116 Human Colon Cancer Cells
Authors: Ahn Eun Hyun , Schroeder Joseph J.
Published: July 2017

Complex dietary sphingolipids such as sphingomyelin and glycosphingolipids have been reported to inhibit development of colon cancer. This protective role may be the result of turnover to bioactive metabolites including sphingoid bases (sphingosine and sphinganine) and ceramide, which inhibit proliferation and stimulate apoptosis. The purpose of the present study was to investigate the effects of sphingoid bases and ceramides on the growth, death, and cell cycle of HT-29 and HCT-116 human colon cancer cells. The importance of the 4,5-trans double bond present in both sphingosine and C2-ceramide (a short chain analog of ceramide) was evaluated by comparing the effects of these lipids with those of sphinganine and C2-dihydroceramide (a short chain analog of dihydroceramide), which lack this structural feature. Sphingosine, sphinganine, and C2-ceramide inhibited growth and caused death of colon cancer cells in time-and concentration-dependent manners, whereas C2-dihydroceramide had no effect. These findings suggest that the 4,5-trans double bond is necessary for the inhibitory effects of C2-ceramide, but not for sphingoid bases. Evaluation of cellular morphology via fluorescence microscopy and quantitation of fragmented low-molecular weight DNA using the diphenylamine assay demonstrated that sphingoid bases and C2-ceramide cause chromatin and nuclear condensation as well as fragmentation of DNA, suggesting these lipids kill colon cancer cells by Inducing apoptosis. Flow cytometric analyses confirmed that sphingoid bases and C2-ceramide increased the number of cells in the A0 peak indicative of apoptosis and demonstrated that sphingoid bases arrest the cell cycle at G2/M phase and cause accumulation in the S phase. These findings establish that sphingoid bases and ceramide induce apoptosis In colon cancer cells and implicate them as potential mediators of the protective role of more complex dietary sphingolipids in colon carcinogenesis.
Soluble T-Lymphocyte Antigen-Specific Immunoproteins: A Progress Report
Authors: Cone Robert E. , Georgiou George M. , Little Colin H.
Published: July 2017

T-cell-derived proteins that bind nominal (non-MHC-associated) antigen specifically (TABM) express V and C region epitopes of the T-cell receptor (TCR) for antigen and have a significant similarity in amino acid sequence to TCR α-chain V and C region. The presence of these immunoproteins in human serum and a specific increase in serum TABM in infectious disease, chemical sensitivity, and food intolerance suggest that TABM may impact on pathogenesis through the modulation of cell-mediated immunity, the antigen-specific concentration and delivery of immunoregulatory cytokines such as TGF-β and elastase, and the induction of the release of substance P by sensory neurons. In this Minireview update, we describe advances in the detection and quantitation of human TABM by monoclonal antibodies, and the association of increased human serum TABM titers in infectious disease, chemical sensitivity, and food intolerance. We suggest that the immunomodulatory mode of action of these immunoproteins may be the antigen-specific focusing of cytokines associated with TABM.
Anatomy of the Spinal Accessory Nerve Plexus: Relevance to Head and Neck Cancer and Atherosclerosis1
Authors: Brown Henry
Published: July 2017

The term spinal accessory nerve plexus may be defined as the spinal accessory nerve with all its intra- and extracranial connections to other nerves, principally cranial, cervical, and sympathetic. The term is not new. This review examines its applied anatomy in head and neck cancer and atherosclerosis. Over the centuries, general studies of neural and vascular anatomy and embryology formed a basis for the understanding upon which the plexus is described. During the past century, its anatomy and blood supply have come to be better understood. The importance of almost all of the plexus to head, neck, and upper extremity motor and sensory functions has come to be realized. Because of this understanding, surgical neck dissection has become progressively more conservative. This historical progression is traced. Even the most recent anatomic studies of the spinal accessory nerve plexus reveal configurations, new to many of us. They were probably known to classical anatomists, and not recorded in readily available literature, or not recorded at all. Human and comparative anatomic studies indicate that the composition of this plexus and its blood supply vary widely, even though within the same species their overall function is very nearly the same. Loss of any of these structures, then, may have very different consequences in different individuals. As a corollary to this statement, data are presented that the spinal accessory nerve itself need not be cut during surgical neck dissections for severe impairment to occur. In addition, data are presented supporting the theory that atherosclerosis by obstructing vessels to this plexus and its closely connected brachial plexus will very likely result in their ischemic dysfunction, often painful. Finally evidence, as well as theory, is stated concerning anatomic issues, methodology, outcome, and possible improvements in surgical procedures emphasizing conservatism.
TNF-α Sensitizes HT-29 Colonic Epithelial Cells to Intestinal Lactobacilli1
Authors: McCracken Vance J. , Chun Taehoon , Baldeón Manuel E. , Ahrné Siv , Molin Göran , Mackie Roderick I. , Gaskins H. Rex
Published: July 2017

The ability of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) to influence epithelial interleukin (IL)-8 responses to the intestinal bacterium Lactobacillus plantarum 299v was analyzed in the human HT-29 colonic epithelial cell line. In the absence of TNF-α, IL-8 mRNA expression was not detectable by Northern blot analysis in HT-29 cells alone or in HT-29 cells co-cultured with L. plantarum 299v. However, TNF-α induced IL-8 mRNA expression, and co-culture of TNF-α-treated HT-29 cells with L. plantarum 299v significantly increased IL-8 mRNA expression above levels induced by TNF-α alone in an adhesion-dependent manner. The increase in IL-8 mRNA expression was not observed in TNF-α-treated HT-29/L. plantarum 299v co-cultures using heat-killed lactobacllli or when L. plantarum adhesion was prevented using mannoside or a trans-well membrane. Paradoxically, IL-8 secretion was decreased in TNF-α-treated HT-29 cells with L. plantarum 299v relative to cells treated with TNF-α alone. TNF-α-mediated responsiveness to L. plantarum 299v was further investigated by analyzing expression of a coreceptor for bacterial cell wall products CD14. HT-29 cells expressed CD14 mRNA and cell-surface CD14; however, TNF-α did not alter CD14 mRNA or cell-surface expression, and blockade of CD14 with monoclonal antibody MY4 did not alter the IL-8 response to L. plantarum 299v in TNF-α-treated HT-29 cells. These results indicate that although TNF-α sensitizes HT-29 epithelial cells to intestinal lactobacilli, the bacteria exert a protective effect by downregulating IL-8 secretion.
Oxidative Stress, Mitochondrial DNA Mutation, and Impairment of Antioxidant Enzymes in Aging
Authors: Wei Yau-Huei , Lee Hsin-Chen
Published: July 2017

Mitochondria do not only produce less ATP, but they also increase the production of reactive oxygen species (ROS) as byproducts of aerobic metabolism in the aging tissues of the human and animals. It is now generally accepted that aging-associated respiratory function decline can result in enhanced production of ROS in mitochondria. Moreover, the activities of free radical-scavenging enzymes are altered in the aging process. The concurrent age-related changes of these two systems result in the elevation of oxidative stress in aging tissues. Within a certain concentration range, ROS may induce stress response of the cells by altering expression of respiratory genes to uphold the energy metabolism to rescue the cell. However, beyond the threshold, ROS may cause a wide spectrum of oxidative damage to various cellular components to result in cell death or elicit apoptosis by induction of mitochondrial membrane permeability transition and release of apoptogenic factors such as cytochrome c. Moreover, oxidative damage and large-scale deletion and duplication of mitochondrial DNA (mtDNA) have been found to increase with age in various tissues of the human. Mitochondria act like a biosensor of oxidative stress and they enable cell to undergo changes in aging and age-related diseases. On the other hand, it has recently been demonstrated that impairment in mitochondrial respiration and oxidative phosphorylation elicits an increase in oxidative stress and causes a host of mtDNA rearrangements and deletions. Here, we review work done in the past few years to support our view that oxidative stress and oxidative damage are a result of concurrent accumulation of mtDNA mutations and defective antioxidant enzymes in human aging.
Differences of Subcutaneous Adipose Tissue Topography Between Type-2 Diabetic Men and Healthy Controls
Authors: Horejsi Renate , Möller Reinhard , Pieber Thomas R. , Wallner Sandra , Sudi Karl , Reibnegger Gilbert , Tafeit Erwin
Published: July 2017

Men with noninsulin-dependent diabetes mellitus (type 2 DM) provide a different subcutaneous body fat distribution and a concentration of fatness on the upper trunk compared with healthy subjects. However, subcutaneous fat distribution is always measured in an inaccurate and/or very simplified way (e.g., by caliper), and to date, there exists no study reporting on the exact and complete subcutaneous adipose tissue distribution of type 2 DM men. A new optical device, the LIPOMETER, enables the nonivasive, quick, and safe determination of the thickness of subcutaneous adipose tissue layers at any given site of the human body. The specification of 15 evenly distributed body sites allows the precise measurement of subcutaneous body fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). SAT-Tops of 21 men with clinically proven type 2 DM (mean age of 57.5 ± 6.7 years) and 111 healthy controls of similar age (mean age 59.0 ± 5.4 years) were measured. In this paper, we describe the precise SAT-Top differences of these two groups and we present the multidimensional SAT-Top information condensed in a two-dimensional factor value plot. In type 2 DM men, especially in the upper trunk, SAT-Top is significantly increased (up to +50.7% at the neck) compared with their healthy controls. One hundred eleven of the 132 individuals (84.1%) are correctly classified (healthy or type 2 DM) by their subcutaneous fat pattern by stepwise discriminant analysis.
Pulmonary Hypertension Syndrome in Young Chickens Challenged with Frozen and Autoclaved Cultures of Enterococcus faecalis
Authors: Tankson J. D. , Thaxton J. P. , Vizzier-Thaxton Y.
Published: July 2017

Enterococcus faecalis, when administered in a growth medium or sterile saline, will cause pulmonary hypertension syndrome (PHS) in chickens. The objective of this study was to determine if frozen and/or autoclaved cultures of E. faecalis retain ability to evoke PHS. In Trial 1, chicks were inoculated with 3.6 × 107 E. faecalis (IA) in tryptic soy broth (TSB) from either a live culture or one that had been autoclaved (120°C for 20 min). Controls received TSB. Autoclaved and live cultures produced the same degree of PHS in a majority of the birds. Trial 2 used the same protocol, except a frozen (–70°C for 60 min) culture of E. faecalis was compared with the control. The results agreed with those of Trial 1, i.e., the frozen culture also produced PHS. Trial 3 was conducted to determine if E. faecalis caused PHS by producing and releasing some unknown substance into the supernatant. Incidence of PHS was based on percentage of birds exhibiting ascites fluid at 24 hr after challenge. Controls received sterile, frozen, or autoclaved TSB. As compared with controls, those birds that received challenge with E. faecalis alone, supernatant alone, and E. faecalis plus supernatant from live cultures exhibited similar incidence of ascites, whereas birds that received E. faecalis plus supernatant and supernatant alone from cultures that had been either frozen or autoclaved exhibited elevated incidence of ascites as compared with controls. Also, with frozen and autoclaved cultures, those birds that received only pelleted E. faecalis exhibited incidence of ascites that did not differ from controls. Apparently, E. faecalis produces PHS in chicks by producing and releasing an unknown toxin.
Mechanism of Action of Progesterone Antagonists
Authors: Leonhardt Susan A. , Edwards Dean P.
Published: July 2017

The effects of progesterone on target tissues are mediated by progesterone receptors (PRs), which belong to a family of nuclear receptors and function as Iigand-activated transcription factors to regulate the expression of specific sets of target genes. Progesterone antagonists repress the biological actions of progesterone by “actively” inhibiting PR activation. This work discusses the first clinically used progesterone antagonist RU486 and closely related compounds in terms of how these compounds inhibit progesterone action through heterodimerization and competition for DNA binding and by the recruitment of corepressors to promoters of target genes to repress transcription. We discuss cellular factors that may influence the activity of these compounds, such as the availability of coactivators and corepressors and the context of specific target promoters in any given cell type. We also discuss steroidal and nonsteroidal antagonist selectivity for PR versus other steroid hormone receptors and suggest that it may be possible to develop tissue/cell specific modulators of PR.
Neonatal Nutrition: Metabolic Programming of Pancreatic Islets and Obesity1
Authors: Srinivasan Malathi , Laychock Suzanne G. , Hill David J. , Patel Mulchand S.
Published: July 2017

Obese individuals are more likely to suffer from diseases termed the “metabolic syndrome,” which includes type 2 diabetes. It is now recognized that early life dietary experiences play an important role in the etiology of such diseases. In this context, the consequences of a high carbohydrate (HC) dietary intervention in neonatal rats is being studied in our laboratory. Artificial rearing of 4-day-old rat pups on a HC milk formula up to Day 24 results in the immediate onset of hyperinsulinemia, which persists throughout the period of dietary intervention. Several adaptations at the biochemical, cellular, and molecular levels in the islets of these HC rats support the onset and persistence of the hyperinsulinemic condition during this period. Some of these adaptations include a distinct leftward shift in the insulin secretory capacity, increased hexokinase activity, increased gene expression of preproinsulin and related transcription factors and specific kinases in 12-day-old HC islets, and alterations in the number and size of islets. These adaptations are programmed and expressed in adulthood thereby sustain the hyperinsulinemic condition in the postweaning period and form the basis for adult-onset obesity. HC females spontaneously transmit the HC phenotype (chronic hyperinsulinemia and adult-onset obesity) to their progeny. Collectively, our results indicate that even a mere switch in the nature of the source of calories (from fat rich in rat milk to carbohydrate rich in the HC milk formula) during critical phases of early development in the rat results in metabolic programming of islet functions leading to chronic hyperinsulinemia (throughout life) and adult-onset obesity. This metabolic programming, once established, forms a vicious cycle because HC female rats spontaneously transmit the HC phenotype to their progeny. The results from our laboratory in the context of metabolic programming due to neonatal nutritional experiences are discussed in this review.
Species Comparison of Methemoglobin Reductase
Authors: Rockwood Gary A. , Armstrong Kevin R. , Baskin Steven I.
Published: July 2017

Methemoglobin (MHb) formation is effective in treating cyanide (CN) poisoning. Endogenous activity of the enzyme MHb reductase (MR) reflects the capacity to reduce MHb and thus represents a key factor for evaluating anti-CN efficacy of MHb formers. MR activity was measured in whole blood of nine animal species and was compared with human MR activity. The animals in this comparative study included seven nonhuman primate (NHP) species, the beagle dog, and the ferret. Although exhibiting higher MR activity than in humans, the rhesus and aotus NHPs' average MR activity was the closest to humans', with raw data from each NHP showing overlap with human raw data. The beagle dog, used extensively to study anti-CN characteristics of MHb formers, was the sole species that displayed MR activity lower than in humans, with no data overlap. Based on MR activity, the rhesus and aotus NHPs may each represent a more accurate model for predicting human responses to MHb formers. The data from this study provides a unique interspecies enzyme comparison, which should facilitate future rational development of anti-CN MHb formers.
Expression of the Prodynorphin Gene after Experimental Brain Injury and Its Role in Behavioral Dysfunction
Authors: Redell John B. , Moore Anthony N. , Dash Pramod K.
Published: July 2017

Traumatic brain injury (TBI) causes excess release of neurotransmitters, such as glutamate, and increases intracellular calcium levels. Elevated levels of calcium, and perhaps other intracellular second messengers, as a result of TBI can alter the expression of many genes. The protein products of some of these genes may be signals for TBI-associated memory dysfunction. Therefore, identification of genes whose expression is altered after TBI in the hippocampus, a structure in the medial temporal lobe that plays a critical role in memory formation and storage, and elucidation of the role(s) of their protein products may shed light on the molecular mechanisms underlying TBI-elicited memory dysfunction. The prodynorphin gene is expressed in hippocampal granule cells, and its expression has been reported to be enhanced as a result of elevated intracellular calcium. The prodynorphin protein is proteolytically cleaved to generate multiple dynorphin peptides, which can modulate neurotransmitter release through the activation of presynaptic κ opioid receptors. In this study, we report that 1) TBI transiently increases prodynorphin mRNA in the hippocampus, 2) dynorphin peptide immunoreactivity is enhanced for up to 24 hr after TBI and 3) intracerebroventricular infusion of the κ receptor antagonist nor-binaltorphimine (nor-BNI) impairs subsequent performance in a spatial memory task. These results suggest that dynorphin action may serve a beneficial role after TBI.
Tumor-Derived Cytokines Dysregulate Macrophage Interferon-γ Responsiveness and Interferon Regulatory Factor-8 Expression
Authors: Mullins David W. , Martins Ryan S. , Elgert Klaus D.
Published: July 2017

Tumors can evade immune responses through suppressor signals that dysregulate host effector cell function. In this study we demonstrate that tumor-derived suppressor molecules impede host antitumor immune activity through dysregulation of multiple macrophage (MΦ) pathways, including suppressed production of cytotoxic and immunostimulatory agents and impaired expression of the interferon regulatory factor-8 (IRF-8) protein, a critical transducer of interferon-γ-mediated activation pathways. The tumor-derived immunosuppressive cytokines interieukin-10 and transforming growth factor-β, constrain IRF-8 production by normal MΦs, regardless of priming, and IRF-8 is also dysregulated in primary MΦs from tumorburdened hosts. Collectively, these data describe a new mechanism by which tumors disrupt immune function and suggest that abrogation of tumor-derived immunoregulatory factors in situ can restore immune function and enhance antitumor efficacy.
Gastrointestinal and Microbial Responses to Sulfate-Supplemented Drinking Water in Mice
Authors: Deplancke Bart , Finster Kai , Graham W Vallen , Collier Chad T. , Thurmond Joel E. , Gaskins H. Rex
Published: July 2017

There is increasing evidence that hydrogen sulfide (H2S), produced by intestinal sulfate-reducing bacteria (SRB), may be involved in the etiopathogenesis of chronic diseases such as ulcerative colitis and colorectal cancer. The activity of SRB, and thus H2S production, is likely determined by the availability of sulfur-containing compounds in the intestine. However, little is known about the impact of dietary or inorganic sulfate on intestinal sulfate and SRB-derived H2S concentrations. In this study, the effects of short-term (7 day) and long-term (1 year) inorganic sulfate supplementation of the drinking water on gastrointestinal (GI) sulfate and H2S concentrations (and thus activity of resident SRBs), and the density of large intestinal sulfomucin-containing goblet cells, were examined in C3H/HeJBir mice. Additionally, a PCR-denaturing gradient gel electrophoresis (DGGE)-based molecular ecology technique was used to examine the impact of sulfate-amended drinking water on microbial community structure throughout the GI tract. Average H2S concentrations ranged from 0.1 m M (stomach) to 1 m M (cecum). A sulfate reduction assay demonstrated in situ production of H2S throughout the GI tract, confirming the presence of SRB. However, H2S generation and concentrations were greatest in the cecum and colon. Sulfate supplementation of drinking water did not significantly increase intestinal sulfate or H2S concentrations, suggesting that inorganic sulfate is not an important modulator of intestinal H2S concentrations, although it altered the bacterial profiles of the stomach and distal colon of 1-year-old mice. This change in colonic bacterial profiles may reflect a corresponding increase in the density of sulfomucin-containing goblet cells in sulfate-supplemented compared with control mice.
The Effect of Fructooligosaccharides with Various Degrees of Polymerization on Calcium Bioavailability in the Growing Rat
Authors: Kruger Marlena C. , Brown Katherine E. , Collett Gabrielle , Layton Lee , Schollum Linda M.
Published: July 2017

Maximizing peak bone mass during adolescence may be the key to postponing and perhaps preventing bone fractures due to osteoporosis in later life. One mechanism to maximize peak bone mass is to maximize calcium absorption, and it has been suggested that inulin and oligofructose might be one of the ways of doing so. In this study, fructooligosaccharides with various degrees of polymerization have been compared in terms of impact on calcium absorption, bone density, and excretion of collagen cross-links in the young adult male rat. The various oligosaccharides were oligofructose (DP2-8), inulin (DP>23), and a mixture of 92% inulin and 8% short-chain oligofructose (DP2-8). Measuring ex vivo bone mineral density (BMD) and bone mineral content (BMC) showed that BMD was significantly higher in the group fed inulin (DP>23) in both femurs, whereas BMC was significantly higher in the spine. The excretion of fragments of Type 1 collagen decreased in all groups over the 4 weeks of feeding, but the decrease was most significant in the group fed inulin (DP>23). Several hypotheses have been offered to explain the effect of the fructooligosaccharides on calcium absorption and retention. These include the production of organic acids that would acidify the luminal contents and enhance solubility and hence absorption, or possibly a mechanism via calbindinD9k. This study is unique in that it compares the different fructooligosaccharides in the same model, and it clearly shows that the various fructans do not have the same effect. In our model, inulin (DP>23) had the most significant effect on calcium bioavailability.
Myostatin Gene Expression is Reduced in Humans with Heavy-Resistance Strength Training: A Brief Communication
Authors: Roth Stephen M. , Martel Gregory F. , Ferrell Robert E. , Metter E. Jeffrey , Hurley Ben F. , Rogers Marc A.
Published: July 2017

This study examined changes in myostatin gene expression in response to strength training (ST). Fifteen young and older men ( n = 7) and women ( n = 8) completed a 9-week heavy-resistance unilateral knee extension ST program. Muscle biopsies were obtained from the dominant vastus lateralis before and after ST. In addition to myostatin mRNA levels, muscle volume and strength were measured. Total RNA was reverse transcribed into cDNA, and myostatin mRNA was quantified using quantitative PCR by standard fluorescent chemistries and was normalized to 18S rRNA levels. A 37% decrease in myostatin expression was observed in response to ST in all subjects combined (2.70 ± 0.36 vs 1.69 ± 0.18 U, arbitrary units; P < 0.05). Though the decline in myostatin expression was similar regardless of age or gender, the small number of subjects in these subgroups suggests that this observation needs to be confirmed. No significant correlations were observed between myostatin expression and any muscle strength or volume measure. Although further work is necessary to clarify the findings, these data demonstrate that myostatin mRNA levels are reduced in response to heavy-resistance ST in humans.
Influence of Nitric Oxide on the Secretory Function of the Bovine Corpus Luteum: Dependence on Cell Composition and Cell-to-Cell Communication
Authors: Jaroszewski Jerzy J. , Skarzynski Dariusz J. , Blair Robert M. , Hansel William
Published: July 2017

The objective of the present study was to investigate the role of cell-to-cell contact in the influence of nitric oxide (NO) on the secretory function of the bovine corpus luteum (CL). In Experiment 1, separate small luteal cells (SLC) or large (LLC) luteal cells were perfused with 100 μ M spermineNONOate, a NO donor, or with 100 μ M Nω-nitro-L-arginine methyl ester (L-NAME), a NO synthase (NOS) inhibitor; in Experiment 2, a mixture of LLC and SLC and endothelial cells was cultured and incubated with spermineNONOate or L-NAME; in Experiment 3, spermineNONOate was perfused into the CL (100 mg/4 hr) by a microdialysis system in vivo. Perfusion of isolated SLC and LLC with the NO donor or NOS inhibitor (Experiment 1) did not affect ( P > 0.05) secretion of progesterone (P4) or oxytocin (OT). L-NAME perfusion increased ( P < 0.05) leukotriene C4 (LTC4) secretion by both SLC and LLC cells. Treatment of mixtures of luteal cells with an NO donor (Experiment 2) significantly decreased ( P < 0.001) secretion of P4 and OT and increased ( P < 0.001) production of prostaglandin F2α (PGF2α) and LTC4. L-NAME stimulated ( P < 0.001) P4 secretion, but did not influence ( P > 0.05) OT, PGF2α or LTC4 production. Intraluteal administration (Experiment 3) of spermineNONOate increased ( P < 0.001) LTC4 and PGF2α, decreased OT, but did not change P4 levels in perfusate samples. These data indicate that cell-to-cell contact and cell composition play important roles in the response of bovine CL to treatment with NO donors or NOS inhibitors, and that paracrine mechanisms are required for the full secretory response of the CL in NO action. Endothelial cells appear to be required for the full secretory response of the CL to NO.
Effect of Chronic Hypoxia on Inducible Nitric Oxide Synthase Expression in Rat Myocardial Tissue
Authors: Grilli Alfredo , Lutiis Maria Anna De , Patruno Antonia , Speranza Lorenza , Cataldi Amelia , Centurione Lucia , Taccardi Alfonso A. , Napoli Pericle Di , Caterina Raffaele De , Barbacane Renato , Conti Pio , Felaco Mario
Published: July 2017

The purpose of our study was to evaluate the effect of chronic exposure to low cellular oxygen tension (90% N2and 10% O2for 14 days) in Inducing apoptosis and activation of transcription and translation of inducible nitric oxide (NO) synthase (INOS) in rat hearts tissue. Rats were divided into four groups: normoxic, hypoxic, rats maintained in normoxic condition for 7 days and subjected to hypoxic conditions for another 7 days, and rats maintained in hypoxic condition for 7 days and subjected to normoxic conditions for another 7 days. At the 7th and 14th days, five rats from each group were sacrificed. Immunohistochemical and Western blot analysis were performed on myocardial tissue to reveal the presence of INOS. Expression of INOS was determined by RT-PCR. Apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and by detection of internucleosomal DNA fragmentation by electrophoresis. Electrophoretic analysis of DNA showed oligonucleosomal fragmentation in the hypoxic groups, but no ladder was observed in the other groups. This data was confirmed through end labeling with streptavidin-biotin (biotin d-UTP). INOS expression was evaluated through immunohistochemical techniques (Ab anti-INOS) and Western blotting, and the results were quantified with a computerized imaging analysis. The expression of INOS protein was greater in the hypoxic groups; in the normoxic groups, only a nonspecific background was detected. This data was supported with results obtained through RT-PCR, which showed the specific transcription of mRNA for INOS in the same experimental conditions. In addition, the INOS activity was also evaluated and was found to be more active in the hypoxic groups (0.1 ± 0.01 vs 0.02 ± 0.003). The present study shows that exposure to low oxygen tension is capable of inducing programmed cell death and activating INOS.
Short-Term Food Restriction and Refeeding Alter Expression of Genes Likely Involved in Brain Glucosensing
Authors: Zhou Jun , Roane David S. , Xi Xiaochun , Bogacka Iwona , Li Bing , Ryan Donna H. , Martin Roy J.
Published: July 2017

Several genes involved in glucosensing of the endocrine pancreas have been proposed to serve a similar function in the brain. These genes include the glucose transporter-2 (Glut-2) and glucokinase (GK). In addition, the glucagon-like peptide 1 receptor, which serves as a downstream signal modulator in pancreatic glucosensing and centrally alters feeding, is also of interest. We used quantitative real-time RT-PCR to measure changes in hypothalamic and brainstem Glut-2, GK, and Glp-1R expression of these genes induced by food restriction and refeeding. Sprague-Dawley rats were 50% food restricted for 1 day; one-half of the food-restricted rats were refed with chow for 1 hr before sacrifice. In both hypothalamus and brainstem, gene expression of Glut-2, GK, and Glp-1R was significantly lower in refed rats compared with food-restricted rats. The measures of gene expression in two feeding control groups (ad libitum and voluntarily overfed animals) were Intermediate between the food-restricted and refed groups, but were not significantly different from each other. The results indicate that putative glucosensing (GK, Glut-2, and Glp-1R) gene expression in the hypothalamus and brainstem is reduced in response to food Intake, depending on prior nutritional status.
Negative Regulation of Interleukin-12 Production by a Rapamycin-Sensitive Signaling Pathway: A Brief Communication
Authors: Uthaisangsook Suwannee , Day Noorbibi K. , Hitchcock Remi , Lerner Aaron , James-Yarish Michelle , Good Robert A. , Haraguchi Soichi
Published: July 2017

Interleukin-12 (IL-12), an important cytokine in host defense against microbial pathogens, regulates natural killer and T-cell function(s) including the induction of γ-interferon production. The major cellular sources of IL-12 are monocytes/macrophages. Bacteria, bacterial products, and intracellular parasites are the most efficient inducers of IL-12 production. In the present study we show that a signal transduction pathway sensitive to rapamycin may have an important role in the regulation/suppression of Staphylococcus aureus–induced IL-12 production in vitro. Human peripheral blood mononuclear cells, monocytes, or a human monocytic cell line THP-1 were stimulated with S. aureus Cowan strain 1 (SAC) in the presence or absence of rapamycin and investigated for production of IL-12 protein by enzyme-linked immunosorbent assay and IL-12 p40 mRNA accumulation by RNase protection assay or real-time quantitative polymerase chain reaction. The results show that rapamycin significantly enhances SAC-induced IL-12 p70 protein production and IL-12 p40 mRNA accumulation. Further the results demonstrate that wortmannin enhances SAC-induced IL-12 p40 mRNA accumulation, whereas Ly294002 does not. These data indicate that a rapamycin-sensitive signaling pathway may act as a negative feedback cascade in the regulatory mechanisms of IL-12 production.
Ingestion of Proanthocyanidins Derived from Cacao Inhibits Diabetes-Induced Cataract Formation in Rats
Authors: Osakabe Naomi , Yamagishi Megumi , Natsume Midori , Yasuda Akiko , Osawa Toshihiko
Published: July 2017

Proanthocyanidins derived from cacao (CLP) have various antipathophysiological functions. We have tested whether dietary supplementation with CLP prevents cataract formation in rats with diabetes induced by streptozotocin (STZ), using histological, histochemical, and biochemical analyses. Starting at 7 days after the streptozotocin challenge, the animals were fed either a normal diet or a diet containing 0.5% w/w CLP over 10 weeks. There were no significant differences in plasma and urine glucose concentrations, plasma fructose amines, and plasma thiobarbituric reactive substances (TBARS) between the two dietary groups. Antioxidant status as assessed by measuring lipid peroxide production in plasma in response to azocompounds was lower in the STZ-rats fed control diet than in animals fed CLP. Opacity was first detected in the lenses of the control dietary group 5 weeks after STZ injection and cataracts had developed in the majority of these animals by 10 weeks. These changes were rarely seen in the STZ/CLP diet group. Histological examinations of the eyes of the STZ-treated normal diet group revealed focal hyperplasia of the lens epithelium and liquefaction of cortical fibers. There were similar but considerably less severe changes in the animals fed CLP. Hydroxynonenal (HNE), a marker of oxidative stress, was detected immunohistochemically in the lenses of the STZ-treated normal diet group, but not of those receiving CLP. Our findings suggest that CLP inhibits diabetes-induced cataract formation possibly by virtue of its antioxidative activity.
Calcium Bioavailability and Kinetics of Calcium Ascorbate and Calcium Acetate in Rats
Authors: Cai Jianwei , Zhang Qinmin , Wastney Meryl E. , Weaver Connie M.
Published: July 2017

The objective was to investigate the bioavailability and mechanism of calcium absorption of calcium ascorbate (ASC) and calcium acetate (AC). A series of studies was performed in adult Sprague-Dawley male rats. In the first study, each group of rats (n = 10/group) was assigned to one of the five test meals labeled with 45Ca: (i) 25 mg calcium as heated ASC or (ii) unheated ASC, (iii) 25 mg calcium as unheated AC, (iv) 3.6 mg Ca as unheated ASC, or (v) unheated AC. Femur uptake indicated better calcium bioavailability from ASC than AC t both calcium loads. A 5-min heat treatment partly reduced bioavailability of ASC. Kinetic studies were performed to further investigate the mechanism of superior calcium bioavailability from ASC. Two groups of rats (n = 10/group) received oral doses of 25 mg Ca as ASC or AC. Each dose contained 20 μCi 45Ca. Two additional groups of rats (n = 10/group) received an intravenous injection (iv) of 10 μCi 45Ca after receiving an unlabeled oral dose of 25 mg calcium as ASC or AC. Sequential blood samples were collected over 48 hrs. Urine and fecal samples were collected every 12 hrs for 48 hrs and were analyzed for total calcium and 45Ca content. Total calcium and 45Ca from serum, urine, and feces were fitted by a compartment kinetics model with saturable and nonsaturable absorption pathways by WinSAAM (Windows-based Simulation Analysis and Modeling). The difference in calcium bioavailability between the two salts was due to differences in saturable rather than passive intestinal absorption and not to endogenous secretion or calcium deposition rate. The higher bioavailability of calcium ascorbate was due to a longer transit time in the small intestine compared with ASC.
Insulin-Mediated Increase in Sympathetic Nerve Activity is Attenuated by C-Peptide in Diabetic Rats
Authors: Rizk Natalie , Dunbar Joseph C.
Published: July 2017

Connecting peptide (C-peptide) is secreted along with insulin in equimolar amounts into portal circulation in response to beta cell stimulation. The biological function of C-peptide had been mostly limited to establishing the secondary and tertiary structure of proinsulin. Recent studies have suggested that C-peptide can impact several functions, such as autonomic and sensory nerve function, insulin secretion, and microvascular blood flow. In this study we examined the effects of C-peptide in the presence or absence of insulin on cardiovascular and sympathetic nerve activity in both normal and streptozotocin (STZ)-induced diabetic Wistar rats. Animals were made diabetic by a single intravenous injection of STZ (50 mg/kg) and maintained for 6 weeks. The diabetic animals had higher plasma glucose, lower plasma insulin, and C-peptide, compared with the normal animals. To characterize cardiovascular and autonomic nervous responses, the animals were anesthetized with urethane/α-chloralose and instrumented for the recording of mean arterial pressure (MAP), heart rate (HR), and lumbar sympathetic nerve activity (LSNA). A bolus administration of C-peptide alone did not alter MAP, HR, or LSNA in normal or diabetic animals. The bolus administration of insulin alone increased HR and LSNA in normal and diabetic animals. However, the administration of insulin plus C-peptide attenuated the increase in HR in normals and the increase in LSNA in diabetic rats. We concluded that the C-peptides play a role in modulating the insulin-stimulated sympathetic nerve response.
Nutritional Significance and Metabolism of Very Long Chain Fatty Alcohols and Acids from Dietary Waxes
Authors: Hargrove James L. , Greenspan Phillip , Hartle Diane K.
Published: July 2017

Very long chain fatty alcohols obtained from plant waxes and beeswax have been reported to lower plasma cholesterol in humans. This review discusses nutritional or regulatory effects produced by wax esters or aliphatic acids and alcohols found in unrefined cereal grains, beeswax, and many plant-derived foods. Reports suggest that 5–20 mg per day of mixed C24–C34 alcohols, including octacosanol and triacontanol, lower low-density lipoprotein (LDL) cholesterol by 21%–29% and raise high-density lipoprotein cholesterol by 8%–15%. Wax esters are hydrolyzed by a bile salt–dependent pancreatic carboxyl esterase, releasing long chain alcohols and fatty acids that are absorbed in the gastrointestinal tract. Studies of fatty alcohol metabolism in fibroblasts suggest that very long chain fatty alcohols, fatty aldehydes, and fatty acids are reversibly inter-converted in a fatty alcohol cycle. The metabolism of these compounds is impaired in several inherited human peroxisomal disorders, including adrenoleukodystrophy and Sjögren-Larsson syndrome. Reports on dietary management of these diseases confirm that very long chain fatty acids (VLCFA) are normal constituents of the human diet and are synthesized endogenously. Concentrations of VLCFA in blood plasma increase during fasting and when children are placed on ketogenic diets to suppress seizures. Existing data support the hypothesis that VLCFA exert regulatory roles in cholesterol metabolism in the peroxisome and also alter LDL uptake and metabolism.
Zinc-Deficient Rats Have More Limited Bone Recovery During Repletion Than Diet-Restricted Rats
Authors: Hosea Heather J. , Taylor Carla G. , Wood Trisha , Mollard Rebecca , Weiler Hope A.
Published: July 2017

The objective of this study was to investigate the effects of dietary zinc deficiency and diet restriction on bone development in growing rats, and to determine whether any adverse effects could be reversed by dietary repletion. Weanling rats were fed either a zinc-deficient diet ad libitum (ZD; <1 mg zinc/kg) or nutritionally complete diet (30 mg zinc/kg) either ad libitum (CTL) or pair-fed to the intake of the ZD group (DR; diet-restricted) for 3 weeks (deficiency phase) and then all groups were fed the zincadequate diet ad libitum for 3, 7, or 23 days (repletion phase). Excised femurs were analyzed for bone mineral density (BMD) using dual-energy x-ray absorptiometry, and plasma was analyzed for markers of bone formation (osteocalcin) and resorption (Ratlaps). After the deficiency phase, ZD had lower body weight and reduced femur BMD, zinc, and phosphorus concentrations compared with DR; and these parameters were lower in DR compared with CTL. Femur calcium concentrations were unchanged among the groups. Reduced plasma osteocalcin in ZD and elevated plasma Ratlaps in DR suggested that zinc deficiency limits bone formation while diet restriction accelerates bone resorption activity. After 23 days of repletion, femur size, BMD, and zinc concentrations remained lower in ZD compared with DR and CTL. Body weight and femur phosphorus concentrations remained lower in both ZD and DR compared with CTL after repletion. There were no differences in plasma osteocalcin concentrations after the repletion phase, but the plasma Ratlaps concentrations remained elevated in DR compared with CTL. In summary, both ZD and DR lead to osteopenia during rapid growth, but the mechanisms appear to be due to reduced modeling in ZD and higher turnover in DR. Zinc deficiency was associated with a greater impairment in bone development than diet restriction, and both deficiencies limited bone recovery during repletion in growing rats.