Hyperphosphatemia is associated with cardiac valve calcification in chronic hypoparathyroidism.

PURPOSE: To evaluate the association between metabolic abnormalities and cardiovascular risk factors in patients with chronic hypoparathyroidism (HPP). PATIENTS AND METHODS: Patients 18 years and older, glomerular filtration > 30 mL/min/1.73 m2 and no documented coronary artery disease were selected. Serum calcium, phosphorus, glucose, lipids, PTH, 25(OH)D and FGF23 were measured. Cardiovascular risk was estimated by the European Society of Cardiology (ESC) calculator. Transthoracic echocardiogram and carotid ultrasound were performed to detect carotid plaques (CP), carotid intima-media thickness (IMT), cardiac valve calcification (CVC), and left ventricular hypertrophy (LVH). RESULTS: Thirty-seven patients (94.6% female), aged 56.0 ± 13.5 years and HPP duration 7.0 (4.0; 11.3) years, were included. Fifteen were classified as low cardiovascular risk, 9 as intermediate risk, 9 as high risk and none as very high risk. The prevalence of CP, CVC and LVH was 24.3%, 24.3% and 13.5%, respectively. IMT values were within normal ranges in all cohort. FGF23 were not associated with CP, IMT, CVC or LVH. After logistic regression, phosphorus was the only significant metabolic variable impacting CVC in univariate analysis (OR 2.795; 95% CI 1.132-6.905; p = 0.026), as well as in the multivariate analysis (OR 3.572; 95% CI 1.094-11.665; p = 0.035). Analysis by ROC curve showed serum phosphorus > 5.05 mg/dL (AUC 0.748; CI 0.584-0.877; p = 0.05) as the best cutoff point associated with valve heart calcification (sensitivity 78%; negative predictive value 91.3%). CONCLUSION: Hyperphosphatemia was associated with CVC in HPP patients. Further studies are needed to investigate whether the control of hyperphosphatemia may reduce cardiovascular risk in this population.

Effect of betaine and arginine in lysine-deficient diets on growth, carcass traits, and pork quality.

Forty entire male pigs from a commercial crossbreed (Duroc × Large White × Landrace) were used to investigate the individual or combined effects of betaine and Arg supplementation in Lys-deficient diets on growth performance, carcass traits, and pork quality. Pigs with 59.9 ± 1.65 kg BW were randomly assigned to 1 of 5 dietary treatments ( = 8). The 5 dietary treatments were normal Lys and CP diet (0.51% Lys and 16% CP; control), reduced Lys and CP diet (0.35% Lys and 13% CP), reduced Lys and CP diet with betaine supplementation (0.33%), reduced Lys and CP diet with Arg supplementation (1.5%), and reduced Lys and CP diet with betaine and Arg supplementation (0.33% betaine and 1.5% Arg). Pigs were slaughtered at 92.7 ± 2.54 kg BW. The Lys-deficient diets (-35% Lys) increased intramuscular fat (IMF) content by 25% ( = 0.041) and meat juiciness by 12% ( = 0.041) but had a negative effect on growth performance ( < 0.05) of pigs. In addition, Lys-deficient diets increased L* ( = 0.005) and b* ( = 0.010) muscle color parameters and perirenal fat deposition ( < 0.001) and decreased both HCW ( = 0.015) and loin weight ( = 0.023). Betaine and Arg supplementation of Lys-deficient diets had no effect on IMF content but increased ( < 0.05) overall pork acceptability. Arginine supplementation also increased ( = 0.003) meat tenderness. Differences in fatty acid composition of pork were not detected among dietary treatment groups. However, oleic acid was positively correlated ( < 0.05) with IMF content, juiciness, flavor, and overall acceptability of meat. Data confirm that dietary CP reduction enhances pork eating quality but negatively affects pigs' growth performance. Moreover, it is suggested that betaine and Arg supplementation of Lys-deficient diets does not further increase IMF content but improves some pork sensory traits, including overall acceptability.

Protective effects of the angiotensin type 1 receptor antagonist losartan in infection-induced and arthritis-associated alveolar bone loss.

BACKGROUND AND OBJECTIVE: The angiotensin type 1 (AT1) receptor has been implicated in the pathogenesis of inflammatory bone disorders. This study aimed to investigate the effect of an AT1 receptor antagonist in infection-induced and arthritis-associated alveolar bone loss in mice. MATERIAL AND METHODS: Mice were subjected to Aggregatibacter actinomycetemcomitans oral infection or antigen-induced arthritis and treated daily with 10 mg/kg of the prototype AT1 antagonist, losartan. Treatment was conducted for 30 d in the infectious condition and for 17 d and 11 d in the preventive or therapeutic regimens in the arthritic model, respectively. The mice were then killed, and the maxillae, serum and knee joints were collected for histomorphometric and immunoenzymatic assays. In vitro osteoclast assays were performed using RAW 264.7 cells stimulated with A. actinomycetemcomitans lipopolysacharide (LPS). RESULTS: Arthritis and A. actinomycetemcomitans infection triggered significant alveolar bone loss in mice and increased the levels of myeloperoxidase and of TRAP(+) osteoclasts in periodontal tissues. Losartan abolished such a phenotype, as well as the arthritis joint inflammation. Both arthritis and A. actinomycetemcomitans conditions were associated with the release of tumor necrosis factor alpha (TNF-α), interferon-gamma, interleukin-17 and chemokine (C-X-C motif) ligand 1 and an increased RANKL/osteoprotegerin ratio in periodontal tissues, but such expression decreased after losartan treatment, except for TNF-α. The therapeutic approach was as beneficial as the preventive one. In vitro, losartan prevented LPS-induced osteoclast differentiation and activity. CONCLUSION: The blockade of AT1 receptor exerts anti-inflammatory and anti-osteoclastic effects, thus protecting periodontal tissues in distinct pathophysiological conditions of alveolar bone loss.

Estrogen receptors α and ß have different roles in the induction and trafficking of progesterone receptors in hypothalamic ventromedial neurons.

Progesterone receptor (PR) activation in the ventrolateral division of the hypothalamic ventromedial nucleus (VMNvl) is essential for promoting female sexual behavior. Estrogen receptor (ER) α, in contrast to ERß, has been implicated in the induction of PRs. The simultaneous activation of ERα and ERß, although not increasing the number of PR-immunoreactive neurons in the VMNvl, facilitates lordosis, which suggests that ERß and/or the ERα-ERß interaction might play a role in PR dynamics and/or PR expression by individual neurons. To address this question, we used western blot and immunohistochemical studies to determine the amounts and subcellular distributions of both PR isoforms in VMNvl neurons of ovariectomized rats injected with estradiol benzoate or with specific agonists of ERα and ERß, alone or in association. The present data show that ERα activation does not change PR expression in individual neurons, but increases the number of PRs in the VMNvl, because it increases the number of neurons expressing PRs. Conversely, ERß activation does not change the total number of PRs in the VMNvl, but increases the labeling intensity of the perikaryal cytoplasm, which suggests that it promotes the transport of PRs from neurites into cell bodies. In addition, the simultaneous activation of ERα and ERß increases the expression of PRs by individual neurons and, consequently, increases the total number of PRs in the VMNvl. Our findings reveal that individual and simultaneous activation of ERα and ERß have different effects on the levels and subcellular location of PRs in VMNvl neurons.

The combination of arginine and leucine supplementation of reduced crude protein diets for boars increases eating quality of pork.

Fifty-four entire male pigs (Duroc × Pietrain × Large White × Landrace) from a commercial crossbred operation were used to investigate the effect of dietary Arg supplementation, protein reduction (PR), and Leu supplementation on performance, carcass traits, and meat quality. Pigs weighing 58.9 ± 1.6 kg BW were randomly assigned to 1 of 6 treatments (n = 9). The 6 dietary treatments were normal CP diet (16% CP, NPD), reduced CP diet (13% CP, RPD), reduced CP diet with Leu addition to 2.0% (RPDL), normal CP diet supplemented with 1% Arg (16% CP, Arg-NPD), reduced CP diet supplemented with 1% Arg (13% CP, Arg-RPD), and reduced CP diet with Leu addition to 2.0% and supplemented with 1% Arg (13% CP, Arg-RPDL). Pigs were slaughtered at 91.7 ± 1.6 kg BW. Dietary Arg supplementation had no effect on intramuscular fat (IMF) content but produced meat off-flavor and increased meat tenderness and overall acceptability. The PR increased (P < 0.001) IMF content (45% to 48%) but negatively affected the growth performance of pigs. In addition, PR increased (P < 0.05) back fat thickness and decreased loin weight. Leucine addition did not affect IMF content, back fat thickness, or loin weight. There was an increase of juiciness with PR and Leu addition, which accompanied the increase of IMF content with the low-CP diet. The PR increased meat deposition of 18:1c9, SFA, MUFA, and PUFA, which were not correlated with any pork sensory trait. The main combined effect of Arg was an increased tenderness and overall acceptability of pork. In conclusion, it was confirmed that dietary CP reduction enhances pork eating quality but negatively affects growth performance and carcass characteristics of pigs.

Ethylazinphos interaction with membrane lipid organization induces increase of proton permeability and impairment of mitochondrial bioenergetic functions.

Ethylazinphos increases the passive proton permeability of lipid bilayers reconstituted with dipalmitoylphosphatidylcholine (DPPC) and mitochondrial lipids. A sharp increase of proton permeability is detected at insecticide/lipid molar ratios identical to those inducing phase separation in the plane of DPPC bilayers, as revealed by differential scanning calorimetry (DSC). Ethylazinphos progressively depresses the transmembrane potential (DeltaPsi) of mitochondria supported by piruvate/malate, succinate, or ascorbate/TMPD. Additionally, a decreased depolarization induced by ADP depends on ethylazinphos concentration, reflecting a phosphorylation depression. This loss of phosphorylation is a consequence of a decreased DeltaPsi. A decreased respiratory control ratio is also observed, since ethylazinphos stimulates state 4 respiration and inhibits ADP-stimulated respiration (state 3). Ethylazinphos concentrations up to 100 nmol/mg mitochondrial protein increase the rate of state 4 together with a decrease in DeltaPsi, without significant perturbation of state 3 and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled respiration. For increased insecticide concentrations, the state 3 and FCCP-uncoupled respiration are inhibited to approximately the same extent. The perturbations are more pronounced when the energization is supported by pyruvate/malate and less effective when succinate is used as substrate. The present data, in association with previous DSC studies, indicate that ethylazinphos, at concentrations up to 100 nmol/mg mitochondrial protein, interacts with the lipid bilayer of mitochondrial membrane, changing the lipid organization and increasing the proton permeability of the inner membrane. The increased proton permeability explains the decreased oxidative phosphorylation coupling. Resulting disturbed ATP synthesis may significantly underlie the mechanisms of ethylazinphos toxicity, since most of cell energy in eukaryotes is provided by mitochondria.

Effects of alcohol on the synthesis and expression of hypothalamic peptides.

Studies aimed at analyzing the deleterious effects of excess alcohol in the brain have revealed structural alterations that are often associated with functional and behavioral disturbances. Among the neuronal damage related to prolonged alcohol exposure, alterations in the synthesizing capabilities and levels of expression of neuroactive peptides have been increasingly reported. Actually, such changes frequently represent the sole repercussion of acute and short-term exposure to ethanol. This review gathers the existing data on the effects of ethanol exposure on the synthesis and expression of hypothalamic peptides. Amid those that can act both as neurotransmitters and neurohormones, we allude to vasopressin, corticotropin-releasing hormone, thyrotropin-releasing hormone and pro-opiomelanocortin and related peptides produced by paraventricular, supraoptic and arcuate neurons. With respect to peptides that act exclusively as neurotransmitters, we address the effects of alcohol on vasoactive intestinal polypeptide, gastrin-releasing peptide, somatostatin and vasopressin synthesized by suprachiasmatic neurons. Hypothalamic neurons that produce peptides that act as neurotransmitters are supposed to be modulated primarily by influences exerted by neuronal afferents, whereas those producing peptides that additionally act as neurohormones are also regulated by peripheral stimuli (e.g., plasma levels of circulating hormones, osmotic challenges). These peculiar features endue the hypothalamus with characteristics that are particularly propitious to enlighten the still cryptic mechanisms underlying the ethanol effects on protein synthesis.

Isolation of a Paracoccidioides brasiliensis strain from the soil of a coffee plantation in Ibiá, State of Minas Gerais, Brazil.

Paracoccidioides brasiliensis has rarely been isolated from its habitat in rural areas. In order to investigate the hypothesis that human infection with this fungus is linked to coffee plantations (Coffea arabica), material was collected monthly over a period of 1 year from farms in the town of Ibiá, State of Minas Gerais, Brazil. A total of 760 samples of soil, coffee leaves and fruits was cultured and inoculated into mice. A fungus isolated from the liver of a mouse inoculated with soil showed temperature-dependent dimorphism and in vitro mycelium and yeast phases characteristic of P. brasiliensis. Yeast cells of this fungus caused disseminated infection after intraperitoneal inoculation in Wistar rats from which the fungus was re-isolated. An antigen reacting with sera from patients with paracoccidioidomycosis was obtained from this P. brasiliensis strain; antigenic identity with strain 339 and with four other P. brasiliensis strains was detected by gel immunodiffusion. However, when the exo-antigen was submitted to SDS-PAGE, we observed low gp43 expression in this new strain, which we called Ibiá. The isolation of P. brasiliensis from the soil at a coffee plantation suggests that this is one of its habitats and supports the hypothesis of acquisition of paracoccidioidomycosis during agricultural activity in these areas.

Effects of a lipophilic environmental pollutant (DDT) on the phospholipid and fatty acid contents of Bacillus stearothermophilus.

Cultures of Bacillus stearothermophilus grown in a complex medium containing 1 microM DDT, exhibited longer lag adapting periods, decreased specific growth rates, and lower growth yield as compared to control cultures. The membrane lipid composition from cells grown in the presence of the insecticide was significantly different from that of control cells. The effects of DDT (2,2-bis(p-chlorophenyl)-1, 1,1-trichloroethane) on growth and lipid composition of bacterial cells were also determined in cultures grown in a medium supplemented with Ca2+ (membrane stabilizer) to further clarify the influence of growth conditions on bacterial responses to the toxicant. The main membrane-lipid changes induced by DDT relate to a very significant increase (74%) of the relative concentration of a phosphoglycolipid, an increase of the phosphatidylethanolamine content, with a parallel decrease of phosphatidylglycerol and an unidentified phospholipid X0. The changes of the phospholipid acyl chains relate to an increase of straight chains and a parallel decrease of branched chains. The effects of DDT-induced lipid composition alterations on membrane physical properties were monitored by fluorescence polarization studies with bacterial polar lipid dispersions. Changes in the membrane lipids upon growing the bacteria in a DDT-containing medium promoted, as expected, more ordered membranes with a shift of the phase transition temperature to higher values. Data are interpreted in the frame of an adaptation mechanism to counteract the membrane perturbation resulting from the accumulation of the insecticide molecules in the lipid bilayer.

Comparative study of the lipid composition of rabbit and lobster sarcoplasmic reticulum.

Sarcoplasmic reticulum (SR) membranes isolated from rabbit and lobster muscles have similar phospholipid classes, but they differ in plasmalogen content. The plasmalogenic species are mostly distributed among phosphatidylethanolamines (PE's) and make up about 62% of the total in rabbit SR and about 46% in lobster membranes. Lobster SR phospholipids contain large amounts of polyunsaturated fatty acids which are present in low amounts in rabbit membranes. The total unsaturated fatty acids of phosphatidylcholines (PC's) represent about 53% and 73% of the total fatty chains for rabbit and lobster SR, respectively. The values found for PE's were about 56% and 64%, respectively. Furthermore, lobster membranes contain significant amounts of PC and PE molecular species with unsaturated fatty acids in positions 1 and 2, whereas rabbit SR contain low amounts.