1-14C-Linoleic Acid distrubution in various tissue lipids of guinea pigs following an oral dose

A recent study on the metabolism of 1-¹⁴C-α-linolenic acid in the guinea pig revealed that the fur had the highest specific activity of all tissues examined, 48 h after dosing. The present study investigated the pattern of tissue lipid labeling following an oral dose of 1-¹⁴C-linoleic acid after the animals had been dosed for the same time as above. Guinea pigs were fed one of two diets with a constant linoleic acid content (18% total fatty acids) and a different content of α-linolenic acid (0.3 or 17.3%) from weaning for 3 wk and 1-¹⁴C-linoleic acid was given orally to each animal for 48 h prior to sacrifice. The most highly labeled tissues (dpm/mg of linoleic acid) were liver, followed by brain, lung and spleen, heart, kidney and adrenal and intestines, in both diet groups. The liver had almost a three-fold higher specific activity than skin and fur which was more extensively labeled than the adipose and carcass. Approximately two-thirds of the label in skin plus fur was found in the fur which, because of a low lipid mass, would indicate that the fur was highly labeled. All tissues derived from animals on the diet with the low α-linolenic acid level were significantly more labeled than the tissues from the animals on the high α-linolenic acid diet, by a factor of 1.5 to 3. The phospholipid fraction was the most highly labeled fraction in the liver, free fatty acids were the most labeled fraction in skin & fur, while triacyglycerols were the most labeled in the carcass and adipose tissue. In these tissues, more than 90% of the radioactivity was found in fatty acids with 2-double bonds in the tissue lipids. These data indicate that the majority of label found in guinea pig tissues 48 h after dosing was still associated with a fatty acid fraction with 2-double bonds, which suggests there was little metabolism of linoleic acid to more highly unsaturated fatty acids in this time frame. In this study, the labeling of guinea pig tissues with linoleic acid, 48 h after dosing, was quite different from the labeling with α-linolenic acid reported previously. The retention of the administered radioactivity from ¹⁴C-linoleic acid in the whole body lipids was 1.6 times higher in the group fed the low α-linolenic acid diet (diet contained a total of 1.8 g PUFA/100 g diet)compared with the group fed the high α-linolenic acid diet (diet contained 3.6 g PUFA/100 g diet). The lack of retention of ¹⁴C-labeled lipids in the whole body would be consistent with an increased rate of β-oxidation of the labeled fatty acid on the diet rich in PUFA, a result supported by other studies using direct measurement of labeled carbon dioxide.

Revisiting delta-6 desaturate regulation by C18 unsaturated fatty acids, depending on the nutritional status

Dietary polyunsaturated fatty acids (PUFA) play a key role in regulating delta-6 desaturase (D6D), the key enzyme for long-chain PUFA biosynthesis. Nevertheless, the extent of their effects on this enzyme remains controversial and difficult to assess. It has been generally admitted that C18 unsaturated fatty acids (UFAs) regulate negatively delta-6 desaturase (D6D). This inhibition has been evidenced in regard to a high glucose/fat free (HG/FF) diet used in reference. However, several nutritional investigations did not evidence any inhibition of desaturases when feeding fatty acids.

Because the choice of the basal diet appeared to be of primary importance in such experiments, our goal was to reconsider the specific role of dietary UFAs on D6D regulation, depending on nutritional conditions. For that, sixteen adult Wistar rats were fed purified linoleic acid, α-linolenic acid or oleic acid, included in one of two diets at 4% by weight: an HG/FF or a high starch base (HS) where the pure UFAs replaced a mixed vegetable oil. Our results showed first that D6D specific activity was significantly greater when measured in presence of an HG/FF than with an HS/4% vegetable oil diet. Secondly, we found that linoleic and alpha-linolenic acids added to HG/FF reduced the specific activity of D6D. In contrast, when pure UFAs were added to an HS base, D6D specific activities remained unchanged or increased. Concordant results were obtained on D6D mRNA expression.

Altogether, this study evidenced the importance of the nutritional status in D6D regulation by C18 UFAs: when used as control, HG/FF diet stimulates D6D compared with a standard control diet containing starch and 4% fats, leading to an overestimation of the D6D regulation by UFAs. Then, UFAs should be considered as repressors for unsaturated fatty acid biosynthesis only in very specific nutritional conditions.

Structural and Biochemical Characterization of Peroxiredoxin Q beta from Xylella fastidiosa CATALYTIC MECHANISM and HIGH REACTIVITY

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A new approach to the granulation of beta-cyclodextrin inclusion complexes

Cyclodextrins (CDs) are annular oligosaccharides containing 6-12 glucose unities joined together by alpha-1,4 bonds. They have a conical-truncated shape with a lipophilic cavity in which different molecules can be included resulting in a stable inclusion complex. The cyclodextrins have been widely applied in pharmaceutical technology with the objective of increasing the solubility, stability and bioavailability of drugs in different pharmaceutical dosage forms, such as tablets. In order to obtain beta-CD tablets, liquid dispersions of drug/beta-CD are usually submitted to different drying processes, like spray-drying, freeze-drying or slow evaporation, being this dry material added to a number of excipients. However, such drying processes can generate particulate materials showing problems of flow and compressibility, needing their conversion into granulates by means of wetting with granulation liquid followed by additional drying. In this work, the main objective was to evaluate the preparation of tablets without the need of this additional drying step. For this purpose an aqueous dispersion containing acetaminophen/beta-CD complex and cornstarch was dried using a spouted bed and the obtained granules were compressed in tablets. Acetaminophen was used as model drug due to its low water solubility and the inexpensive and widely available cornstarch was chosen as excipient. Acetaminophen powder was added into a beta-cyclodextrin solution prepared in distilled water at 70 degrees C. Stirring was kept until this dispersion cooled to room temperature. Then cornstarch was added and the resulting dispersion was dried in spouted bed equipment. This material was compressed into tablets using an Erweka Korsh EKO tablet machine. This innovative approach allowed the tablets preparation process to be carried out with fewer steps and represents a technological reliable strategy to produce beta-cyclodextrin inclusion complexes tablets. (C) 2010 Elsevier By. All rights reserved.

Lateral septal area alpha(1)-and alpha(2)-adrenoceptors differently modulate baroreflex activity in unanaesthetized rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Bed nucleus of the stria terminalis alpha(1) and alpha(2) adrenoceptors differentially modulate the cardiovascular responses to exercise in rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Low protein diet confers resistance to the inhibitory effects of interleukin1 beta on insulin secretion in pancreatic islets

High protein content in the diet during childhood and adolescence has been associated to the onset insulin-dependent diabetes mellitus. We investigated the effect of interleukin-1 beta (IL-I beta) on insulin secretion, glucose metabolism, and nitrite formation by islets isolated from rats fed with normal protein (NP, 17%) or low protein (LP, 6%) after weaning. Pretreatment of islets with IL-1 beta for 1 h or 34 h inhibited the insulin secretion induced by glucose in both groups, but it was less marked in LP than in NP group. Islets from LP rats exhibited a decreased IL-1 beta -induced nitric oxide (NO) production, lower inhibition of D-[(UC)-C-14]-glucose oxidation to (CO2)-C-14, and less pronounced effect of IL-1 beta on alpha -ketoisocaproic acid-induced insulin secretion than NP islets. However, when the islets were stimulated by high concentrations of K+ the inhibitory effect of IL-1 beta on insulin secretion was not different between groups. In conclusion, protein restriction protects beta -cells of the deleterious effect of IL-1 beta, apparently, by decreasing NO production. The lower NO generation in islets from protein deprived rats may be due to increased free fatty acids oxidation and consequent alteration in Ca2+ homeostasis. (C) 2001 Elsevier B.V. All rights reserved.

Tamoxifen inhibits transforming growth factor-alpha gene expression in human breast carcinoma samples treated with triiodothyronine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Amniotic Fluid Interleukin-1 Beta and Interleukin-6, but not Interleukin-8 Correlate with Microbial Invasion of the Amniotic Cavity in Preterm Labor

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Relationship of IL-1 and TNF-alpha polymorphisms with Helicobacter pylori in gastric diseases in a Brazilian population

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Elevated progesterone concentrations enhance prostaglandin F-2 alpha synthesis in dairy cows

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Biological Response to Wollastonite Doped alpha-Tricalcium Phosphate Implants in Hard and Soft Tissues in Rats

The biological response following subcutaneous and bone implantation of beta-wollastonite(beta-W)-doped alpha-tricalcium phosphate bioceramics in rats was evaluated. Tested materials were: tricalciurn phosphate (TCP), consisting of a mixture of alpha- and beta-polymorphs; TCP doped with 5 wt. % of beta-W (TCP5W), composed of alpha-TCP as only crystalline phase; and TCP doped with 15 wt. % of beta-W (TCP15), containing crystalline alpha-TCP and beta-W. Cylinders of 2x1 mm were implanted in tibiae and backs of adult male Rattus norvegicus, Holtzman rats. After 7, 30 and 120 days, animals were sacrificed and the tissue blocks containing the implants were excised, fixed and processed for histological examination. TCP, TCP5W and TCP15W implants were biocompatible but neither bioactive nor biodegradable in rat subcutaneous tissue. They were not osteoinductive in connective tissue either. However, in rat bone tissue beta-W-doped alpha-TCP implants (TCP5W and TCP15W) were bioactive, biodegradable and osteoconductive. The rates of biodegradation and new bone formation observed for TCP5W and TCP15W implants in rat bone tissue were greater than for non-doped TCP.

Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Structural Basis of Importin-alpha-Mediated Nuclear Transport for Ku70 and Ku80

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Interleukin-10 but not Transforming Growth Factor beta inhibits murine activated macrophages Paracoccidioides brasiliensis killing: Effect on H2O2 and NO production

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)