Supplementation of oleic acid, stearic acid, palmitic acid and ß-hydroxybutyrate increase H3K9me3 in endometrial epithelial cells of cattle cultured in vitro.

There is growing evidence that greater than homeostatic blood concentrations of nonesterified fatty acids (NEFAs) and ß-hydroxybutyrate (BHBA) have negative consequences on dairy cow's fertility, but effects on cell homeostasis in the reproductive system is not completely understood. In this study, lipids accumulation, reactive oxygen species (ROS) concentrations, abundance of gene transcripts, and immunofluorescence signal of H3K4me3 and H3K9me3 were evaluated in endometrial epithelial cells of cattle cultured with NEFAs (Oleic (OA), Stearic (SA) and Palmitic (PA) acids), BHBA, NEFAs + BHBA or each of the three NEFAs alone. The cellular lipids were in greater concentrations as a result of NEFAs + BHBA, NEFAs, SA or OA supplementation, but not by BHBA or PA. The ROS concentrations were greater when there were treatments with NEFAs + BHBA, NEFAs or BHBA. The relative mRNA abundance for genes involved in the regulation of apoptosis (XIAP), glucose transport (GLUT3), and DNA methylation (DNMT1) were greater when there were NEFAs + BHBA, but not NEFAs, BHBA, OA, SA or PA treatments. The immunofluorescence signal for H3K9me3 was greater when there were NEFAs + BHBA, NEFAs or PA, but not by BHBA, OA or SA treatments. These findings indicate that NEFAs and BHBA have an additive effect on endometrial cells of cattle by altering epigenetic markers and the expression of genes controlling important cellular pathways. Furthermore, there was cellular lipid accumulation and increased H3K9me3 in cultured bovine endometrial cells that was mainly induced by OA and PA treatments, respectively.

A TLR7/8 Agonist-Including DOEPC-Based Cationic Liposome Formulation Mediates Its Adjuvanticity Through the Sustained Recruitment of Highly Activated Monocytes in a Type I IFN-Independent but NF-κB-Dependent Manner.

Novel adjuvants, such as Toll-like receptors (TLRs) agonists, are needed for the development of new formulations able to circumvent limitations of current vaccines. Among TLRs, TLR7/8 agonists represent promising candidates, as they are well described to enhance antigen-specific antibody responses and skew immunity toward T helper (TH) 1 responses. We find here that the incorporation of the synthetic TLR7/8 ligand 3M-052 in a cationic DOEPC-based liposome formulation shifts immunity toward TH1 responses and elicits strong and long-lasting germinal center and follicular T helper cell responses in adult mice. This reflects the prolonged recruitment of innate cells toward the site of immunization and homing of activated antigen-loaded monocytes and monocyte-derived dendritic cells toward draining lymph nodes. We further show that this adjuvanticity is independent of type I IFN but NF-κB-dependent. Overall, our data identify TLR7/8 agonists incorporated in liposomes as promising and effective adjuvants to enhance TH1 and germinal center responses.

Effect of stearic or oleic acid on milk performance and energy partitioning when fed in diets with low and high rumen-active unsaturated fatty acids in early lactation.

This experiment was conducted to determine the effects of stearic acid (SA; C18:0) or rumen-protected oleic acid (OA; C18:1 cis-9) on milk performance and energy partitioning of early lactation cows when supplemented in diets with low and high level of rumen unsaturated fatty acids (RUFA). In low RUFA experiment (LRUFA), FA supplement rich in either SA or calcium salts OA was added to a basal diet with a low concentration of RUFA (0.75% vs. 1.4%, LRUFA-SA vs. LRUFA-OA). In high RUFA experiment (HRUFA), 2% soybean oil was added to the diet fed in the LRUFA experiment. In each experiment, 30 multiparous cows were blocked by parity and predicted transmitting ability for milk yield and were randomly fed 1 of 2 treatment diets from 2 to 13 wk postpartum. In the LRUFA experiment, LRUFA-SA had 2.4 kg/d more dry matter intake (DMI) (P < 0.01), 3.8 kg/d more energy-corrected milk (P < 0.01), and 0.3% units more milk fat percentage (P < 0.01) and 0.2 kg/d more milk fat yield (P < 0.01). Dietary treatments did not affect body weight, energy balance, and energy intake partitioning into milk, maintenance, and body tissues (P > 0.1). In the HRUFA experiment, HRUFA-SA had 1.4 kg/d more DMI (P = 0.03) but similar milk and milk components yields (P > 0.1). HRUFA-SA had a tendency to gain more body weight (P = 0.07) and had more positive energy balance (P = 0.01) and decreased gross feed efficiency (milk yield/DMI) (P = 0.01). Consistently, HRUFA-SA increased intake energy partitioning into body tissues (P = 0.02) and decreased energy partitioning into milk (P = 0.01). In summary, SA supplementation had more DMI relative to OA, but the effects on milk and milk fat production were different and affected by the level of RUFA in the basal diet. In application, SA supplementation was more effective to improve milk production when included in the basal diet with the low RUFA.

Microemulsions based on TPGS and isostearic acid for imiquimod formulation and skin delivery.

Imiquimod (IMQ) is an immunostimulant drug topically used for the treatment of actinic keratosis and basal cell carcinoma. IMQ formulation and skin delivery is difficult because of its very low solubility in the most of pharmaceutical excipients and very poor skin penetration properties. The purpose of this study was to develop a microemulsion to optimize imiquimod skin delivery using d­α­tocopherol polyethylene glycol-1000 succinate (TPGS) as surfactant (so as to take advantage of its thickening properties) and isostearic acid as oil phase. This fatty acid was selected since it has demonstrated a good solubilizing power for imiquimod and it has also shown to contribute to its therapeutic activity. We have built pseudo-ternary diagrams using two different co-surfactants (Transcutol® and propylene glycol - PG) in a 1:1 ratio with TPGS and then selected microemulsions in the clear and viscous regions of the diagrams. The systems were characterized in terms of rheology and X-ray scattering; additionally, the capability to promote IMQ skin uptake was evaluated ex-vivo on a porcine skin model. All the formulations selected in the gel-microemulsion regions behaved as viscoelastic solids; X-rays scattering experiments revealed in all cases the presence of an ordered lamellar structure, but with differences in terms of interlamellar distance and flexibility between Transcutol® and PG-containing systems. A higher flexibility and a greater hydrophobic volume, possibly interconnected at some point, was associated to the use of Transcutol® and had an impact on the microemulsion capacity to solubilize IMQ as well as on the capability to enhance drug uptake into the skin. The best performing gel-like microemulsion was composed of ≈26% of water, ≈21% of isostearic acid, ≈26% of TPGS and ≈27% of Transcutol® and accumulated, after 6 h of contact, 3.0 ±â€¯1.1 µg/cm2 of IMQ. This value is higher than the one reported in the literature for the commercial cream (1.9 ±â€¯0.8 µg/cm2), despite the 4-times lower concentration of the vehicle (13 mg/g for the microemulsion vs 50 mg/g for the commercial cream).

Interesterified Palm Olein (IEPalm) and Interesterified Stearic Acid-Rich Fat Blend (IEStear) Have No Adverse Effects on Insulin Resistance: A Randomized Control Trial.

Chemically-interesterified (CIE) fats are trans-fat free and are increasingly being used as an alternative to hydrogenated oils for food manufacturing industries to optimize their products' characteristics and nutrient compositions. The metabolic effects of CIE fats on insulin activity, lipids, and adiposity in humans are not well established. We investigated the effects of CIE fats rich in palmitic (C16:0, IEPalm) and stearic (C18:0, IEStear) acids on insulin resistance, serum lipids, apolipoprotein concentrations, and adiposity, using C16:0-rich natural palm olein (NatPO) as the control. We designed a parallel, double-blind clinical trial. Three test fats were used to prepare daily snacks for consumption with a standard background diet over a period of 8 weeks by three groups of a total of 85 healthy, overweight adult volunteers. We measured the outcome variables at weeks 0, 6, and at the endpoint of 8. After 8 weeks, there was no significant difference in surrogate biomarkers of insulin resistance in any of the IE fat diets (IEPalm and IEStear) compared to the NatPO diet. The change in serum triacylglycerol concentrations was significantly lower with the IEStear diet, and the changes in serum leptin and body fat percentages were significantly lower in the NatPO-diet compared to the IEPalm diet. We conclude that diets containing C16:0 and C18:0-rich CIE fats do not affect markers of insulin resistance compared to a natural C16:0-rich fat (NatPO) diet. Higher amounts of saturated fatty acids (SFAs) and longer chain SFAs situated at the sn-1,3 position of the triacylglycerol (TAG) backbones resulted in less weight gain and lower changes in body fat percentage and leptin concentration to those observed in NatPO and IEStear.

Effect of dietary palmitic and stearic acids on sucrose motivation and hypothalamic and striatal cell signals in the rat.

We have reported that motivation for sucrose is increased in rats fed a moderate (31%) mixed-fat diet for 4-6 wk. In this study, rats were fed diets containing 32% stearic (STEAR) or palmitic (PALM) acid, and behavior, metabolic profile, and cell signals were compared with those of rats fed a matched low-fat diet (LF; 11% fat) diet. Rats fed STEAR or PALM increased sucrose motivation relative to LF rats (one-way ANOVA for lever presses; P = 0.03). Diet did not change fasting glucose, insulin, total cholesterol, triglycerides, intravenous glucose tolerance test glucose profile, percent body fat, or total kilocalories, although kilocalories as fat were increased (ANOVA, P < 0.05). Cell signals were assessed in rats ranked from high to low sucrose motivation. Diet did not alter Thr and Ser phosphorylation of Akt in the medial hypothalamus (HYP) and striatum (STR). However, Ser phosphorylation of GSK3Β was decreased in HYP and STR from both high- and low-performer tertiles of STEAR and PALM rats (ANOVA within each brain region, P < 0.05). Two histone 3 (H3) modifications were also assessed. Although there was no effect of diet on the transcription-repressive H3 modification, H3K27me3, the transcription-permissive H3 modification, H3K4me3, was significantly decreased in the HYP of high performers fed PALM or STEAR (ANOVA, P = 0.013). There was no effect of diet on H3K4me3 levels in HYP of low performers, or in STR. Our findings suggest signal-specific and brain region-specific effects of PALM or STEAR diets and may link downstream signaling effects of GSK3Β activity and H3 modifications with enhanced motivational behavior.

Protective efficacy of a hydroxy fatty acid against gastric Helicobacter infections.

BACKGROUND: We have previously revealed that omega-3 polyunsaturated fatty acids can prevent Helicobacter pylori infection by blocking the futalosine pathway, an alternative route for menaquinone (MK) biosynthesis. MATERIALS AND METHODS: 1, Different H. pylori strains were grown in liquid media supplemented with linoleic acid, an omega-6 fatty acid, or its 10-hydroxy derivative, 10-hydroxy-cis-12-octadecenoic acid (HYA), in the presence or absence of MK. The bacterial numbers in the media were estimated by plating; 2, C57BL/6NCrl mice received drinking water supplemented with different fatty acids starting from 1 week before infection with H. pylori or Helicobacter suis until the end of the experiment. The gastric colonization levels of H. pylori or H. suis were determined 2 weeks after infection by plating or quantitative PCR, respectively; 3, Mice were given HYA, starting 1 week before infection with H. suis and continuing until 6 months after infection, for analysis of the gastric conditions. RESULTS: 1, A low concentration (20 µmol/L) of HYA in culture broth suppressed the growth of H. pylori, and this inhibition was reduced by MK supplementation; 2, HYA treatment protected mice against H. pylori or H. suis infection; 3, HYA treatment suppressed the formation of lymphoid follicles in the gastric mucus layer after H. suis infection. CONCLUSIONS: HYA prevents gastric Helicobacter infections by blocking their futalosine pathways. Daily HYA supplementation is effective for the prevention of gastric mucosa-associated lymphoid tissue lymphoma induced by persistent infection with H. suis.

Stearic acid suppresses mammary gland development by inhibiting PI3K/Akt signaling pathway through GPR120 in pubertal mice.

It has been demonstrated that dietary high fat diet negatively affects the pubertal mammary gland development. The aim of the present study was to investigate the effects of stearic acid (SA), an 18-carbon chain saturated fatty acid, on mammary gland development in pubertal mice and to explore the underlying mechanism. Our results demonstrated that dietary supplementation of 2% SA suppressed mammary duct development, with significant reduction of terminal end bud (TEB) number and ductal branch. In accord, the expression of proliferative marker Cyclin D1 was markedly decreased by dietary SA. Furthermore, dietary SA led to increase of G protein-coupled receptor 120 (GPR120) expression and inhibition of PI3K/Akt signaling pathway in mammary gland of pubertal mice. In good agreement with the in vivo findings, the in vitro results showed that 40 µM SA significantly suppressed proliferation of mouse mammary epithelial cell HC11 by regulating mRNA and/or protein expression of proliferative markers such as Cyclin D1/3, p21, and PCNA. Meanwhile, SA activated GPR120 and inhibited PI3K/Akt signaling pathway in a GPR120-dependent manner. In addition, SA-induced inhibition of PI3K/Akt signaling pathway, suppression of HC11 proliferation, and alteration of proliferative markers expression were abolished by knockdown of GPR120 with siRNA. Collectively, these findings showed that SA suppressed mammary gland development of pubertal mice, which was coincident with the SA-inhibited HC11 proliferation, and was associated with inhibition of PI3K/Akt signaling pathway through activation of GPR120. These data provided new insights into the regulation of mammary gland development by dietary fatty acids.

Does supplemental 18:0 alleviate fish oil-induced milk fat depression in dairy ewes?

Supplementation of dairy ewe diet with marine lipids may be an effective strategy for modulating milk fatty acid composition but induces milk fat depression (MFD). This syndrome has been associated with a shortage of 18:0 for uptake and Δ(9)-desaturation that may impair the capacity of the mammary gland to achieve an adequate fluidity for milk fat secretion. On this basis, it was suggested that supplemental 18:0 may contribute to alleviate marine lipid-induced MFD in sheep. To test this hypothesis, 12 lactating ewes were allocated to 1 of 3 lots and used in a 3×3 Latin square design with 3 periods of 28 d each and 3 experimental treatments: a total mixed ration without lipid supplementation (control) or supplemented with 20 g/kg of DM of fish oil alone (FO) or in combination with 20 g/kg of DM of 18:0 (FOSA). Diets were offered ad libitum, and animal performance and rumen and milk fatty acid composition were studied at the end of each period. After completing the Latin square trial and following a change-over design, the in vivo digestibility of supplemental 18:0 was estimated using 6 lactating sheep. As expected, diet supplementation with fish oil increased the milk content of some potentially health-promoting fatty acids (e.g., cis-9,trans-11 18:2, trans-11 18:1, 20:5n-3, 22:5n-3, and 22:6n-3), but reduced milk fat concentration and yield (-20% in both FO and FOSA treatments). Thus, although reductions in milk 18:0 and cis-9 18:1 output caused by FO (-81 and -51%, respectively) were partially reversed with FOSA diet (-49 and -27%, respectively), the addition of 18:0 to the diet did not prove useful to alleviate MFD. This response, which could not be fully accounted for by the low digestibility coefficient of supplemental 18:0, may challenge the theory of a shortage of this fatty acid as a mechanism to explain fish oil-induced MFD in sheep. Effects of FO and FOSA on rumen and milk fatty acid composition would support that increases in the concentration of some candidate milk fat inhibitors (e.g., cis-9 16:1 or 10-oxo-18:0) might play a relevant role in this type of MFD.

Milk production responses to dietary stearic acid vary by production level in dairy cattle.

Effects of stearic acid supplementation on feed intake and metabolic and production responses of dairy cows with a wide range of milk production (32.2 to 64.4 kg/d) were evaluated in a crossover design experiment with a covariate period. Thirty-two multiparous Holstein cows (142±55 d in milk) were assigned randomly within level of milk yield to treatment sequence. Treatments were diets supplemented (2% of diet dry matter) with stearic acid (SA; 98% C18:0) or control (soyhulls). The diets were based on corn silage and alfalfa and contained 24.5% forage neutral detergent fiber, 25.1% starch, and 17.3% crude protein. Treatment periods were 21 d with the final 4 d used for data and sample collection. Compared with the control, SA increased dry matter intake (DMI; 26.1 vs. 25.2 kg/d) and milk yield (40.2 vs. 38.5 kg/d). Stearic acid had no effect on the concentration of milk components but increased yields of fat (1.42 vs. 1.35 kg/d), protein (1.19 vs. 1.14 kg/d), and lactose (1.96 vs. 1.87 kg/d). The SA treatment increased 3.5% fat-corrected milk (3.5% FCM; 40.5 vs. 38.6 kg/d) but did not affect feed efficiency (3.5% FCM/DMI, 1.55 vs. 1.53), body weight, or body condition score compared with the control. Linear interactions between treatment and level of milk yield during the covariate period were detected for DMI and yields of milk, fat, protein, lactose, and 3.5% FCM; responses to SA were positively related to milk yield of cows. The SA treatment increased crude protein digestibility (67.4 vs. 65.5%), tended to increase neutral detergent fiber digestibility (43.6 vs. 42.3%), decreased fatty acid (FA) digestibility (56.6 vs. 76.1%), and did not affect organic matter digestibility. Fatty acid yield response, calculated as the additional FA yield secreted in milk per unit of additional FA intake, was only 13.3% for total FA and 8.2% for C18:0 plus cis-9 C18:1. Low estimated digestibility of the SA supplement was at least partly responsible for the low FA yield response. Treatment did not affect plasma insulin, glucagon, glucose, and nonesterified FA concentrations. Results show that stearic acid has the potential to increase DMI and yields of milk and milk components, without affecting conversion of feed to milk, body condition score, or body weight. Moreover, effects on DMI and yields of milk and milk components were more pronounced for higher-yielding cows than for lower-yielding cows.

Clinical evaluation of a dioic acid-based formulation on facial skin in an Indian population.

The aim of this work was to investigate the effects of 1,18-octadecen-9-dioic acid (dioic acid) and a Rumex occidentalis extract complex for their skin-lightening action in an Indian population. Prior to the clinical study, the efficacy of dioic as an inhibitor of melanogenesis was confirmed on dark-pigmented human melanocytes. As part of a 12-week vehicle-controlled clinical study, the skin-lightening effect of a test product containing 1% dioic acid, 2% of a Rumex occidentalis extract and sunscreens (SPF 15) was assessed on the facial skin of 71 Indian female volunteers. Change in skin colour was monitored by (A) Chroma Meter® measurement (L*, a*, b*) and Individual Typology Angle (ITA˚) calculation and (B) Visual grading of standardized photographs by a dermatologist. Colorimetric measurements on volunteers' cheeks showed a significant increase of L* and ITA˚ compared to baseline after 4, 8 and 12 weeks of test product application. For both L* and ITA˚ measurements, changes were significantly different than the SPF 15-containing vehicle at weeks 4 and 12. These results were confirmed by the dermatological visual grading. The overall skin-lightening action of the test product was beyond the one observed with the SPF 15 vehicle. These findings show that a dioic acid and Rumex occidentalis complex deliver a significant skin-lightening effect on facial skin in an Indian population.

A propofol microemulsion with low free propofol in the aqueous phase: formulation, physicochemical characterization, stability and pharmacokinetics.

The purpose of this study was to develop a propofol microemulsion with a low concentration of free propofol in the aqueous phase. Propofol microemulsions were prepared based on single-factor experiments and orthogonal design. The optimal microemulsion was evaluated for pH, osmolarity, particle size, zeta potential, morphology, free propofol in the aqueous phase, stability, and pharmacokinetics in beagle dogs, and comparisons made with the commercial emulsion, Diprivan(®). The pH and osmolarity of the microemulsion were similar to those of Diprivan(®). The average particle size was 22.6±0.2 nm, and TEM imaging indicated that the microemulsion particles were spherical in appearance. The concentration of free propofol in the microemulsion was 21.3% lower than that of Diprivan(®). Storage stability tests suggested that the microemulsion was stable long-term under room temperature conditions. The pharmacokinetic profile for the microemulsion showed rapid distribution and elimination compared to Diprivan(®). We conclude that the prepared microemulsion may be clinically useful as a potential carrier for propofol delivery.

A comparative study of non-lipid nanoemulsion of propofol with solutol and propofol emulsion with lecithin.

BACKGROUND AND OBJECTIVES: Some formulations have been proposed to reduce the adverse reactions due to the lipid emulsion containing soybean oil used as propofol carrier. This study for endoscopy sedation was aimed at evaluating and comparing the safety, effectiveness and adverse effects of the use of propofol nanoemulsion compared to propofol currently commercialized. METHOD: In this prospective study, 150 patients were submitted to upper digestive endoscopy. These patients were allocated into two groups: the control group (CONT Group; n=75) and the nanoemulsion group (NE Group; n=75). HR, SBP, DBP, SpO(2) and BIS (which is considered to be appropriate between 65 and 75 during procedure) were monitored. Gender, age, weight, height, BMI, ASA physical status, times and doses were analyzed, as well as adverse effects (phlogistic signs and pain on injection, apnea, nausea/vomiting) and alterations in monitoring variables. A p-value < 0.05 was considered significant. RESULTS: The groups had similar results concerning anthropometric data and physical status. None of the patients developed apnea or presented phlogistic signs in the injection site. The incidence of pain on injection in the CONT Group was 82.7% and 53.3% in the NE Group (p<0.001), and the incidence of nausea and vomiting was 10.7% in the CONT Group and 2.7% in the NE Group (p>0.05). The times, induction doses and the SBP and DBP values at the end of examination and at the moment of discharge from the PACU were lower in the NE Group (p<0.05). CONCLUSIONS: Lipid propofol and propofol nanoemulsion were equivalent concerning effectiveness, safety and adverse effects in the doses used. There was a lower incidence of pain on injection in the nanoemulsion formulation.

Estudo comparativo entre propofol em nanoemulsão não lipídica com solutol e em emulsão com lecitina / A comparative study of non-lipid nanoemulsion of propofol with solutol and propofol emulsion with lecithin / Estudio comparativo entre el propofol en la nanoemulsión no lipídica con solutol y en la emulsión con lecitina

JUSTIFICATIVA E OBJETIVOS: Formulações têm sido propostas com o objetivo de reduzir as reações adversas decorrentes da emulsão lipídica de óleo de soja utilizada como veículo do propofol. O objetivo deste estudo foi avaliar comparativamente, em sedação para endoscopia, a segurança, eficácia e efeitos adversos do uso do propofol em nanoemulsão em relação ao propofol comercializado atualmente. MÉTODO: Foram incluídos neste estudo prospectivo 150 pacientes submetidos a procedimentos endoscópicos digestivos altos, divididos em grupo-controle (Grupo CONT; n = 75) e grupo nanoemulsão (Grupo NE; n = 75). Foram monitorados FC, PAS, PAD, SpO2 e BIS (considerado apropriado entre 65 e 75, durante o procedimento). Foram analisados: gênero, idade, peso, altura, IMC, estado físico ASA; tempos e doses utilizadas; efeitos adversos (sinais flogísticos e dor à injeção, apneia, náuseas/vômitos) e alterações nas variáveis de monitoramento. Considerou-se significativo p < 0,05. RESULTADOS: Os grupos foram homogêneos quanto aos dados antropométricos e estado físico. Nenhum paciente apresentou apneia nem sinais flogísticos no local da injeção. A incidência de dor à injeção no grupo CONT foi 82,7% e 53,3% no grupo NE (p < 0,001) e de náuseas e vômitos foi 10,7% no grupo CONT e 2,7% no grupo NE (p > 0,05). Os tempos, as doses de indução e os valores das PAS e PAD ao final do exame e no momento da alta da SRPA foram menores no grupo NE (p < 0,05). CONCLUSÕES: O propofol lipídico e o propofol em nanoemulsão, nas doses utilizadas, foram equivalentes em relação a eficácia, segurança e efeitos adversos, ressaltando-se a menor incidência de dor à injeção da formulação em nanoemulsão.

BACKGROUND AND OBJECTIVES: Some formulations have been proposed to reduce the adverse reactions due to the lipid emulsion containing soybean oil used as propofol carrier. This study for endoscopy sedation was aimed at evaluating and comparing the safety, effectiveness and adverse effects of the use of propofol nanoemulsion compared to propofol currently commercialized. METHOD: In this prospective study, 150 patients were submitted to upper digestive endoscopy. These patients were allocated into two groups: the control group (CONT Group; n = 75) and the nanoemulsion group (NE Group; n = 75). HR, SBP, DBP, SpO2 and BIS (which is considered to be appropriate between 65 and 75 during procedure) were monitored. Gender, age, weight, height, BMI, ASA physical status, times and doses were analyzed, as well as adverse effects (phlogistic signs and pain on injection, apnea, nausea/vomiting) and alterations in monitoring variables. A p-value < 0.05 was considered significant. RESULTS: The groups had similar results concerning anthropometric data and physical status. None of the patients developed apnea or presented phlogistic signs in the injection site. The incidence of pain on injection in the CONT Group was 82.7% and 53.3% in the NE Group (p < 0.001), and the incidence of nausea and vomiting was 10.7% in the CONT Group and 2.7% in the NE Group (p > 0.05). The times, induction doses and the SBP and DBP values at the end of examination and at the moment of discharge from the PACU were lower in the NE Group (p < 0.05). CONCLUSIONS: Lipid propofol and propofol nanoemulsion were equivalent concerning effectiveness, safety and adverse effects in the doses used. There was a lower incidence of pain on injection in the nanoemulsion formulation.

JUSTIFICATIVA Y OBJETIVOS: Las formulaciones han sido propuestas con el objetivo de reducir las reacciones adversas provenientes de la emulsión lipídica de aceite de soja utilizada como vehículo del propofol. El objetivo de este estudio, fue la evaluación comparativa en la sedación para la endoscopia, la seguridad, la eficacia y los efectos adversos del uso del propofol en la nanoemulsión con relación al propofol actualmente comercializado. MÉTODO: En este estudio prospectivo se incluyeron 150 pacientes sometidos a procedimientos endoscópicos digestivos altos, divididos en grupo control (Grupo CONT; n = 75) y grupo nanoemulsión (Grupo NE; n = 75). Se monitorizaron FC, PAS, PAD, SpO2 y BIS (considerado apropiado entre 65 y 75, durante el procedimiento). Fueron analizados el sexo, la edad, el peso, la altura, el IMC, el estado físico ASA; tiempos y dosis utilizados; efectos adversos (signos flogísticos y dolor a la inyección, apnea, náuseas/vómitos) y las alteraciones en las variables de monitorización. Se consideró como significativo p < 0,05. RESULTADOS: Los grupos fueron homogéneos en cuanto a los datos antropométricos y al estado físico. Ningún paciente presentó apnea ni signos flogísticos en la región de la inyección. La incidencia de dolor a la inyección en el grupo CONT fue de 82,7% y 53,3% en el grupo NE (p < 0,001) y de náuseas y vómitos fue 10,7% en el grupo CONT y 2,7% en el grupo NE (p > 0,05). Los tiempos, las dosis de inducción y los valores de las PAS y PAD al final del examen y en el momento del alta de la SRPA fueron menores en el grupo NE (p < 0,05). CONCLUSIONES: El propofol lipídico y el propofol en nanoemulsión en las dosis utilizadas, fueron equivalentes con relación a la eficacia, seguridad y efectos adversos, destacando la menor incidencia de dolor a la inyección de la formulación en nanoemulsión.

[Effect of N-stearoylethanolamine(NSE) on activity of angiotensine-converting enzyme in the brain structures and blood plasma of rats with streptozotocine-induced diabetes].

The influence of saturated N-acylethanolamine--N-stearoylethanolamine (NSE) on the activity of angiotensine-converting enzyme (ACE) in the brain structures of rats with streptozotocine-induced diabetes was studied. It was shown that decreased activity of ACE was observed in the hypothalamus, increased--in the anterior pituitary. The NSE suspension administration to rats with experimental diabetes in a dose 50 mg/kg of body weight during 10 days caused a decrease in ACE activity in the anterior pituitary, whereas in the hypothalamus and hippocampus ACE activity did not change significantly. At the same time, introduction of NSE to intact animals led to the reduction of activity of ACE in the hippocampus, anterior pituitary and blood plasma. It is known that the highest amount of ACE in the brain structures is located in the membrane-bound state. Thus, the changes we have found in the activity of ACE in the control rats and in animals with induced diabetes may be related to the ability of NSE to the modulation of cell membranes lipid profile. Changes in the activity of ACE under the action of N-acylethanolamines may be one of the mechanisms for implementation of anti-hypertensive and anti-inflammatory action of these compounds.

Design and in vitro evaluation of effervescent gastric floating drug delivery systems of propanolol HCl.

Abstract. The purpose of this research was to develop and evaluate effervescent gastric floating tablets of propranolol HCl. The oral delivery of antihypertensive propranolol HCl was facilitated by preparing an effervescent floating dosage form which could increase its absorption in the stomach by increasing the drug's gastric residence time. In the present work, effervescent floating tablets were prepared with a hydrophilic carrier such as polyethylene oxide (PEO WSR N 60K and PEO WSR 303) as a release retarding agent and sodium bicarbonate as a gas generating agent. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, drug release and rate order kinetics. From the results, P9 was selected as an optimized formulation based on their 12 h drug release, minimal floating lag time and maximum total floating time. The optimized formulation followed first order rate kinetics with erosion mechanism. The optimized formulation was characterized with FTIR studies and no interaction between the drug and the polymers were observed.

Design and in vitro evaluation of effervescent gastric floating drug delivery systems of propanolol HCl / Diseño y evaluación in vitro de sistemas de administración de tabletas flotantes gástricas everfescentes de HCl propanolol

The purpose of this research was to develop and evaluate effervescent gastric floating tablets of propranolol HCl. The oral delivery of antihypertensive propranolol HCl was facilitated by preparing an effervescent floating dosage form which could increase its absorption in the stomach by increasing the drug’s gastric residence time. In the present work, effervescent floating tablets were prepared with a hydrophilic carrier such as polyethylene oxide (PEO WSR N 60K and PEO WSR 303) as a release retarding agent and sodium bicarbonate as a gas generating agent. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, drug release and rate order kinetics. From the results, P9 was selected as an optimized formulation based on their 12 h drug release, minimal floating lag time and maximum total floating time. The optimized formulation followed first order rate kinetics with erosion mechanism. The optimized formulation was characterized with FTIR studies and no interaction between the drug and the polymers were observed.

El propósito de la presente investigación fue desarrollar y evaluar tabletas flotantes, efervescentes de HCL propranolol. La administración oral del antihipertensivo HCL propranolol se facilitó mediante la preparación de una forma de dosificación flotante y efervescente que permitiría su absorción en el estómago, mediante el aumento del tiempo de residencia gástrico de la droga. En el presente trabajo, las tabletas flotantes efervescentes fueron preparadas con un portador hidrofílico, tal como el óxido de polietileno (PEO WSR N 60K and PEO WSR 303), como agente retardador y bicarbonato de sodio como un agente generador de gas. Se evaluaron todas las propiedades fisicoquímicas de las tabletas preparadas, su flotación in vitro y su tasa de orden cinético. Se seleccionó el P9 a partir de los resultados obtenidos, como una fórmula óptima, basados en la liberación de la droga a las 12 h, tiempo mínimo de retraso para flotación y máximo tiempo total de flotación. La formulación optimizada siguió una tasa cinética de primer orden con mecanismo de erosión. Esta fórmula óptima se caracterizó mediante estudios FITR y no se observó ninguna interacción entre la droga y los polímeros utilizados.

The chain length of dietary saturated fatty acids affects human postprandial lipemia.

OBJECTIVE: Saturated fats increase total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) and are linked to coronary artery disease risk. The effect of variance in chain length of saturated fatty acids (SFA) on coronary artery disease in human postprandial lipemia is not well elucidated. METHODS: A total of 20 healthy volunteers were challenged with 3 test meals, similar in fat content (~31% en) but varying in saturated SFA content and polyunsaturated/saturated fatty acid ratios (P/S). The 3 meals were lauric + myristic acid-rich (LM), P/S 0.19; palmitic acid-rich (POL), P/S 0.31; and stearic acid-rich (STE), P/S 0.22. Blood was sampled at fasted baseline and 2, 4, 5, 6, and 8 hours. Plasma lipids (triacylglycerol [TAG]) and lipoproteins (TC, LDL-C, high density lipoprotein-cholesterol [HDL-C]) were evaluated. RESULTS: Varying SFA in the test meal significantly impacted postprandial TAG response (p < 0.05). Plasma TAG peaked at 5 hours for STE, 4 hours for POL, and 2 hours for LM test meals. Area-under-the-curve (AUC) for plasma TAG was increased significantly after STE treatment (STE > LM by 32.2%, p = 0.003; STE > POL by 27.9%, p = 0.023) but was not significantly different between POL and LM (POL > LM by 6.0%, p > 0.05). At 2 hours, plasma HDL-C increased significantly after the LM and POL test meals compared with STE (p < 0.05). In comparison to the STE test meal, HDL-C AUC was elevated 14.0% (p = 0.005) and 7.6% (p = 0.023) by the LM and POL test meals, respectively. The TC response was also increased significantly by LM compared with both POL and STE test meals (p < 0.05). CONCLUSIONS: Chain length of saturates clearly mediated postmeal plasma TAG and HDL-C changes.

Fortification of sorghum (Sorghum vulgare) and pearl millet (Pennisetum glaucum) flour with zinc.

Deficiency of zinc is believed to be as widespread as that of iron, with equally serious consequences. Fortification of staple foods with this mineral is a cost-effective method that can be used to combat this deficiency. In the present study, flours of pearl millet and sorghum were evaluated as vehicles for fortification with zinc. Zinc stearate was used as the fortificant, and added at a level that provided 5mg Zn/100g flour. The metal chelator EDTA was used as a co-fortificant, the molar ratio of exogenous Zn:EDTA being 1:1. Bioaccessibility of zinc from the fortified flours, both raw and cooked, was determined by an in vitro simulated gastrointestinal digestion procedure. The results of the study revealed that there were differences among these two flours with respect to the feasibility of fortification with zinc. Although fortified pearl millet flour provided a higher amount of bioaccessible zinc, this was attributable to the presence of EDTA, rather than to the fortified zinc. The benefit of fortification with zinc was more evident in sorghum flour, compared to that in pearl millet flour, the increase in bioaccessible zinc content being more than 1.5 times higher as a result of fortification. Fortified sorghum and pearl millet flours were stable during storage for a period of up to 60 days. Thus, millet flours seem to be satisfactory candidates for fortification with zinc, and can be exploited to address zinc deficiency.

Postprandial effects of a lipid-rich meal in the rat are modulated by the degree of unsaturation of 18C fatty acids.

The fatty acid composition of high-fat diets is known to influence the magnitude of postprandial events that increase the risk of metabolic syndrome. These variations in magnitude may be directly ascribed to differences in the channeling of lipids toward oxidation or storage. A study was designed to compare the effects of 4 dietary fats on postprandial energy expenditure and on some risk factors of the metabolic syndrome. To avoid usual confounding factors due to simultaneous variations in chain length and double-bounds number of fatty acids, dietary fats were chosen to provide mainly 18-carbon fatty acids with 0 (stearic acid [SA]), 1 (oleic acid [OA]), 2 (linoleic acid [LA]), or 3 (alpha-linolenic acid [ALA]) double bounds. They were given as single high-fat test meals to 4 different groups of male rats. The resting metabolic rate and the lipid and carbohydrate oxidation were measured from oxygen consumption and carbon dioxide production using indirect calorimetry 2 hours before and 6.5 hours after the test meal. Plasma glucose, triglyceride, and chylomicron concentrations were determined at 0, 1.5, and 4 hours after the test meal. Postprandial concentration of glucose and triglyceride did not vary with the nature of the test meals, whereas that of chylomicrons was the highest after the LA test meal and the lowest after the SA test meal. Postprandial increase in resting metabolic rate was the highest after the LA and OA test meals, and the lowest after the SA and ALA test meals. Compared with the 3 other diets, the ALA test meal enhanced lipid oxidation and decreased glucose oxidation during the early postprandial period (0.25-3.25 hours). This suggests that stearic acid may not induce all the adverse effects classically described for other saturated fatty acids and that alpha-linolenic acid may beneficially influence energy partitioning, especially during the early postprandial state.