The effect of N-3 fatty acids on plasma myeloperoxidase levels in healthy adults.

OBJECTIVE: To examine the effect of marine n-3 polyunsaturated fatty acids (PUFA) supplementation in a low to moderate and a high dose on plasma levels of myeloperoxidase (MPO) in healthy individuals. BACKGROUND: Atherosclerosis is a chronic inflammatory disease and MPO, which is secreted primarily from activated neutrophils and monocytes, has pro-inflammatory properties and has been linked with both initiation and propagation of atherosclerosis. Marine n-3 PUFA have anti-inflammatory properties, but whether n-3 PUFA affect plasma levels of MPO is largely unknown. METHODS: Sixty healthy adults were randomized to three groups receiving either 6.6 g PUFA/day, 2.0 g PUFA/day or a control oil (olive oil) for 12 weeks. Blood samples were drawn at baseline and after exposure. Plasma levels of MPO were measured using a MPO ELISA-kit (from Mercodia, Uppsala, Sweden) with specific mouse monoclonal antibodies. RESULTS: Plasma MPO concentrations (microg/L) at baseline were 36.9 +/- 9.4; 36.2 +/- 7.1 and 35.4 +/- 11.3 (for high dose-, low dose- and control-group, respectively). After 12 weeks of supplementation we found no significant changes in plasma MPO in any of the groups nor between groups, with values after intervention of 36.1 +/- 8.6; 37.0 +/- 8.2 and 34.4 +/- 11.1, respectively. CONCLUSION: Supplementation with n-3 PUFA has no effect on plasma levels of MPO in healthy adults with low baseline levels of MPO.

Serum concentrations of matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1 and alpha2-macroglobulin in healthy subjects after supplementation with different doses of marine n-3 fatty acids.

OBJECTIVE: Extracellular matrix modification by matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) and alpha2-macroglobulin may affect the stability of atherosclerotic plaques. Marine n-3 polyunsaturated fatty acids (n-3 PUFA) may protect against plaque rupture. The aim was to investigate the effect of marine n-3 PUFA supplementation on serum levels of MMP-9, TIMP-1, and alpha2-macroglobulin. METHODS: Healthy volunteers were randomized to receive capsules contributing either 6.6 g marine n-3 PUFA/day, 2.0 g marine n-3 PUFA/day or 6.6 g of olive oil (control). Serum MMP-9, TIMP-1 and alpha2-macroglobulin was measured at baseline and after 12 weeks of supplementation. One way ANOVA or Kruskal-Wallis test was used to compare groups. RESULTS: 60 healthy volunteers were enrolled and no subjects dropped out of the 12 week study. There were no statistically significant changes in serum levels of MMP-9, TIMP-1, and alpha2-macroglobulin in any of the three treatment groups (P=0.85, P=0.23 and P=0.87, respectively). CONCLUSION: Supplementation with marine n-3 PUFA had no effect on serum levels of MMP-9, TIMP-1 and alpha2-macroglobulin in healthy subjects. The possible protection offered by marine n-3 PUFA against plaque rupture is therefore unlikely to be mediated through a change in serum levels of MMP-9, TIMP-1 and alpha2-macroglobulin.

Ineffectiveness of Nickel in augmenting the hepatotoxicity in protein deficient rats / Eficacia del níquel en aumentar la hepatotoxicidad en ratas con deficiencia en proteínas

This study was designed to determine the toxic effects of nickel sulfate on the biochemical and elemental profile of liver in protein deficient rats. Nickel sulfate in the dose of 800mg/l in drinking water was administrated to Sprauge Dawley (S.D) normal control as well as protein deficient rats for a total duration of eight weeks. The effects of nickel treatment and protein deficiency when given separately and in combination were studied on rat liver marker enzymes like Alkaline phosphatase (ALP),Glutamate oxaloacetate transaminase (GOT), Glutamate pyruvate transaminase (GPT) and also on the status of essential elements in rat liver. Protein deficient,Ni treated as well as combined protein deficient and nickel treated rats showed significant reductions in the body weight and hepatic protein contents as compared to normal control rats. Hepatic alkaline phosphatase activity and alanine aminotransferase showed a significant elevation in rats subjected to protein deficiency, nickel treatment and combined protein deficiency and nickel treatment.As regards to hepatic levels of aspartate aminotransferase a significant elevation was observed in protein deficient and nickel treated protein deficient animals. Nickel administration to normal and protein deficient rats has resulted in a significant increase in concentrations of nickel, phosphorus and sulfur in liver tissue. The concentration of zinc and copper in liver tissue decreased significantly in protein deficient, nickel treated and nickel treated protein deficient animals. Tissue iron concentrations were found to be decreased in protein deficient animals, but the concentrations of iron got elevated significantly in nickel treated and nickel treated protein deficient animals. It has been observed that selenium got decreased significantly in protein deficient, nickel treated and nickel treated protein deficient animals when compared to normal animals. The elevation of selenium in nickel treated protein deficient animals was also significantly higher when compared to protein deficient animals (AU)

Este estudio fue diseñado para determinar los efectos tóxicos del sulfato de níquel sobre el perfil bioquímico y de oligoelementos del hígado en ratas con deficiencia de proteínas.Se administró sulfato de níquel, a la dosis de 800 mg/l, en el agua de bebida de ratas Sprauge Dawley (S-D) normales control y con deficiencia de proteínas, durante 8 semanas. Se estudiaron los efectos del tratamiento con níquel y de la deficiencia de proteínas, por separado y en combinación,sobre marcadores enzimáticos hepáticos de la rata como la fosfatasa alcalina (FA), la glutamato oxalacetato transaminasa (GOT), la glutamato piruvato transaminasa (GPT) y también el estado de oligoelementos en el hígado de la rata. Las ratas con deficiencia de proteínas, las ratas tratadas con níquel, así cómo aquéllas con la combinación de deficiencia de proteínas y tratamiento con níquel mostraron reducciones significativas en el peso corporal y en el contenido hepático de proteína, en comparación con las ratas normales control. La actividad hepática fosfatasa alcalina y alanina aminotransferasa mostró una elevación significativa en las ratas sometidas a deficiencia de proteínas, a tratamiento con níquel, y a la combinación de deficiencia de proteínas y tratamiento con níquel. Con respecto de las concentraciones hepáticas de aspartato aminotransferasa, se observó una elevación significativa en los animales con deficiencia de proteínas y en aquellos tratado con níquel y con deficiencia de proteínas. La administración de níquel a ratas normales y con deficiencia de proteínas ha producido un aumento significativo de las concentraciones de níquel, fósforo y azufre en el tejido hepático. La concentración de cinc y cobre en el tejido hepático disminuyó significativamente los animales con deficiencia de proteínas, los tratados con níquel, y aquellos con deficiencia de proteínas tratados con níquel. Se halló que las concentraciones tisulares de hierro estaban disminuidas en los animales con deficiencia de proteínas, pero aumentaron significativamente en los animales tratados níquel y aquellos con deficiencia de proteínas tratados con níquel. Se observó que el selenio disminuyó significativamente en los animales con deficiencia de proteínas, los tratados con níquel, y aquellos con deficiencia de proteínas tratados con níquel, en comparación con los animales normales. La elevación de selenio en los animales con deficiencia de proteínas tratados con níquel también fue significativamente superior en comparación con los animales con deficiencia de proteínas (AU)

Role of zinc in regulating the levels of hepatic elements following nickel toxicity in rats.

This study was designed to determine the protective effects of zinc on the hepatotoxicity induced by nickel in rats. Female Sprague-Dawley (SD) rats received either nickel sulfate alone in the dose of 800 mg/L nickel in drinking water, zinc sulfate alone in the dose of 227 mg/L zinc in drinking water, and nickel plus zinc or drinking water alone for a total duration of 8 wk. The effects of different treatments were studied on activities of rat liver marker enzymes like alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferases (AST) and on the status of essential elements in rat liver. The study revealed a significant increase in the activities of enzymes ALP and ALT in rats subjected to nickel treatment. Interestingly, zinc supplementation to rats treated with nickel brought back the raised activities of these enzymes to within normal limits. Further, the levels of elements in liver that include zinc, copper, selenium, and potassium were found to be significantly suppressed following nickel treatment, whereas the levels of iron and sulfur were elevated. However, zinc treatment alone did not cause any appreciable change in the concentration of these elements. To the contrary, when zinc was given to nickel-treated rats, the concentrations of zinc, copper, potassium, and phosphorus were not significantly different from that of normal controls, whereas the levels of iron, selenium, and sulfur were improved in comparison to nickel-treated rats but were not within the normal limits. The present study concludes that zinc has the ability to maintain the levels of hepatic elements and has bearing in regulating the liver functions by maintaining the activities of marker enzymes in conditions of nickel toxicity.

Hepatic oxygen exchange and energy metabolism in hyperdynamic porcine endotoxemia: effects of the combined thromboxane receptor antagonist and synthase inhibitor DTTX30.

OBJECTIVE: We compared the effects of thromboxane receptor antagonist and synthase inhibitor DTTX30 on systemic and liver blood flow, oxygen (O2) exchange and energy metabolism during 24 h of hyperdynamic endotoxemia with untreated endotoxemia. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-seven domestic pigs: 16 during endotoxemia with volume resuscitation alone; 11 with endotoxemia, volume resuscitation and treatment with DTTX30. INTERVENTIONS: Continuous infusion of Escherichia coli lipopolysaccharide (LPS) for 24 h together with volume resuscitation. After 12 h of endotoxemia, DTTX30 was administered as a bolus of 0.12 mg kg-1 followed by 12 h continuous infusion of 0.29 mg kg-1 per h. MEASUREMENTS AND RESULTS: DTTX30 effectively counteracted the endotoxin-associated increase in TXB2 levels and increased 6-keto-PGF1 alpha with a significant shift of the thromboxane/prostacyclin ratio towards predominance of prostacyclin. DTTX30 prevented the significant progressive endotoxin-induced decrease of mean arterial pressure (MAP) below baseline while maintaining cardiac output (CO), and increased the fractional contribution of liver blood flow to CO without an effect on either hepatic O2 delivery or O2 uptake. The mean capillary hemoglobin O2 saturation (HbO2) on the liver surface and HbO2 frequency distributions remained unchanged as well. CONCLUSIONS: DTTX30 significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased the endogenous glucose production (EGP) rate, EGP returned towards baseline levels in the DTTX30-treated group. Thus, in our model DTTX30 resulted in hemodynamic stabilization concomitant with improved hepatic metabolic performance.

Hepatic O2 exchange and liver energy metabolism in hyperdynamic porcine endotoxemia: effects of iloprost.

OBJECTIVE: To compare the effects of a 12 h continuous infusion of iloprost, a stable prostacyclin analogue, on hepatic blood flow (Qliv), O2 exchange, and energy metabolism during a 24 h hyperdynamic, porcine endotoxemia with volume resuscitation alone. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-eight domestic pigs: 16 animals during endotoxemia with volume resuscitation alone (ETX), 12 with endotoxemia, volume resuscitation, and treatment with iloprost (ILO). INTERVENTIONS: Endotoxemia was initiated by continuous infusion of E. coli lipopolysaccharide. Animals were resuscitated with hetastarch, aimed at maintaining a MAP of > 60 mmHg. After 12 h of endotoxemia, iloprost was administered for 12 h in the treatment group, titrated to avoid pharmacologically induced hypotension (MAP < 60 mmHg). MEASUREMENTS AND RESULTS: Iloprost significantly increased Qliv, with no effect on hepatic O2 delivery. Mean capillary hemoglobin O2 saturation (HbScO2) on the liver surface, as well as HbScO2 frequency distributions--a measure of microcirculatory O2 availability--remained unchanged. Treatment with iloprost, however, significantly attenuated the endotoxin-induced derangements of cellular energy metabolism as reflected by the diminished progressive decrease in hepatic lactate uptake rate and a blunted increase in hepatic venous lactate/pyruvate ratios. While endotoxin significantly increased endogenous glucose production (EGP) rate, iloprost restored EGP to normal at the end of the experiment. CONCLUSIONS: Thus, in a clinically relevant model of human sepsis, iloprost did not produce potential adverse effects but rather ameliorated hepatic metabolic disturbances and, thereby, hepatic energy balance.

Utilization of myristic and palmitic acid in humans fed different dietary fats.

To assess the influence of dietary fat composition on the contribution of dietary myristic and palmitic acid to total fat oxidation and energy production, eight healthy men consumed diets containing 40% of total energy as fat, largely as either butter, tallow or corn oil, for 11 days. On days 8 and 11 of each diet, [1-13C]-myristic or [1-13C]-palmitic acid (20 mg kg-1 body weight) was ingested mixed with the test breakfast meal. Respiratory gas exchange was measured before, and for 9h after, consumption of the meal. Breath 13CO2 enrichments were determined hourly by isotope ratio mass spectrometry. Cumulative 9-h percentage oxidation of dietary myristic acid exceeded that of palmitic acid (P < 0.01), but neither was influenced by fat treatment [n = 8, 7.1% (1.0) (SEM), 8.6% (0.9) and 8.9% (0.6) of dietary myristic acid and 3.3% (0.7), 3.0% (0.9), and 2.5% (0.6) of dietary palmitic acid from butter, tallow and corn oil meals respectively]. Net dietary myristic acid oxidation was greater (P < 0.05) after consumption of the meal high in butter than after consumption of other fats. Net dietary palmitic acid oxidation was similar after consumption of all test meals. Precedent fat treatment had no measurable effect on net fat or carbohydrate oxidation or energy expenditure. The overall contribution of dietary myristic or palmitic acid to total fat oxidation did not exceed 1% over 9 h for any dietary fat. These results suggest that, although dietary fatty acid content is the principal determinant of net dietary fatty acid oxidation, dietary fat sources with moderate differences in fat composition do not measurably alter total energy or substrate utilization after a meal.

Facial EMG responses to auditory stimuli.

Three studies were performed to investigate the effects of auditory stimuli (pure tones and environmental noise) of different intensities on surface EMG activity recorded over five facial muscle regions (M. frontalis lateralis, M. corrugator supercilii, M. orbicularis oculi, M. zygomaticus major, M. depressor anguli oris). The results show that with presentation of tones and noises of high intensity (> 85 dB) strong facial EMG reactions over muscles of the upper face (M. frontalis lateralis, M. corrugator supercilii, M. orbicularis oculi) were evoked. Among environmental noises of different valence but the same intensity, baby's crying evoked EMG reactions over facial muscles in the mouth region, possibly indicating that the subjects demonstrated expressions of dislike during this particular stimulation. It is also discussed whether facial EMG reactions to auditory stimulation of different intensities could be connected to changes in muscle tone of the middle ear muscles. The contraction of these muscles modulates sensitivity to auditory stimulation. Thus, facial EMG activity of the muscles of the upper face could serve as an indicator of sensitivity to external auditory stimuli. However, the evaluation of pleasant and unpleasant emotional reactions in response to auditory stimulation seems to be impossible.

[Organization and results of delayed autotransfusion in private practice. Apropos of 64 initial cases]. / Organisation et résultats de l'autotransfusion différée en pratique libérale. A propos des 64 premiers cas.

The authors have reviewed 64 cases of preoperative autotransfusion in 60 patients in private practice of orthopaedic surgery. In 78 per cent of the cases no homologous blood was necessary. They state that this method is safe, effective and easy to organize.

Fluoride and mineral redeposition in outermost layers of bovine enamel during surface softening.

Mineral and fluoride concentration changes in the outermost layers of bovine enamel (depth less than 1 micron) were measured after demineralization in unbuffered hydroxyethylcellulose gels of pH = 5.4 with an intrinsic fluoride concentration of about 0.02 ppm. A combination of two nuclear analytical techniques, Rutherford backscattering spectrometry (RBS) and proton-induced gamma ray emission spectrometry (PIGE) was applied to determine the Ca/P molar ratios and F depth profiles, respectively. When compared to deeper layers, a reduced loss of mineral content is observed for the depth range of about 0-0.1 micron corresponding well with a F concentration increase from about 500 to about 5,000 ppm in the same range. These findings are interpreted as a fluoride-induced partial remineralization of the superficial surface layer during an overall demineralization process.

[Severe light dermatosis following photo therapy in a newborn infant with congenital erythropoietic urophyria]. / Schwere Lichtdermatose nach Phototherapie bei einem Neugeborenen mit kongenitaler erythropoietischer Uroporphyrie

A newborn infant with hemolytic anemia and hepatosplenomegaly was treated by phototherapy for early jaundice. After 18 h, a dark brown pigmentation of the skin was noticed, leading to the assumption of a bronze baby syndrome. Indeed, the child was suffering from a severe disturbance of liver function. 4 days later, a severe bullous dermatosis with blody imbibition developed, covering all exposed parts of the body surface and reoccurring in many bursts over several weeks despite protection against light. A severe hemolytic anemia was constantly present. The baby died on the 50th day. The diagnosis of erythropoietic porphyria was suggested immediately after the onset of the bullous exanthema and proved by laboratory data as follows: uro- and coproporphyrin in the urine were extremely high, uroporphyrin being mainly of type-I isomer. In red cells, increased amounts of uro-, copro- and protoporphyrins were detected. Massive red fluorescence of erythroblasts (so-called porphyroblasts) in the bone marrow and in the blood could be observed. At autopsy, the liver showed multiple blood-forming areas and severe diffuse hemosiderosis, which is to be explained by a long existing, i.e. fetal hemolysis. Erythropoietic porphyria is such a rare disease that there is no reason to consider it as a general contraindication for phototherapy.