Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the s...Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the sn-2 position of the glycerol backbone(more than 70%)and in unsaturated fatty acids at the sn-1,3 position.The specific TAG structure in HMF plays a valuable function in infant growth.Sn-2 palmitate(mainly 1,3-dioleoyl-2-palmitoyl-glycerol)is one of the structured TAGs that is commonly supplemented into infant formula in order to enable it to present a similar structure to HMF.In this review,the development of the lipase-catalyzed synthesis of sn-2 palmitate over the last 25 years are summarized,with a focus on reaction schemes in a laboratory setting.Particular attention is also paid to the commercialized sn-1,3 regioselective lipases that are used in structured TAGs synthesis,to general methods of TAG analysis,and to successfully developed sn-2 palmitate products on the market.Prospects for the lipase-catalyzed synthesis of sn-2 palmitate are discussed.展开更多
The present study shows that double-stranded RNA-dependent protein kinase (PKR) regulates the protein expres- sion level and phosphorylation of Bcl-2 and plays an anti-apoptotic role in human hepatocellular carcinom...The present study shows that double-stranded RNA-dependent protein kinase (PKR) regulates the protein expres- sion level and phosphorylation of Bcl-2 and plays an anti-apoptotic role in human hepatocellular carcinoma ceils (HepG2). In various types of cells, saturated free fatty acids (FFAs), such as palmitate, have been shown to induce cellular apoptosis by several mechanisms. Palmitate down-regulates the activity of PKR and thereby decreases the level of Bcl-2 protein, mediated in part by reduced activation of the NF-KB transcription factor. In addition to the level of Bel-2 protein, the phosphorylation of Bcl-2 at different amino acid residues, such as Ser70 and Ser87, is also important in regulating cellular apoptosis. The decrease in the phosphorylatiou of Bcl-2 at Ser70 upon exposure to palmitate is mediated by inhibition of PKR and possibly by c-Jun N-terminal kinase (JNK), whereas the phosphory- lation of Bcl-2 at Ser87 is unaffected by palmitate or PKR. In summary, PKR mediates the regulation of the protein level and the phosphorylation status of Bel-2, providing a novel mechanism of palmitate-induced apoptosis in HepG2 cells.展开更多
Vitamin A palmitate (VAP) contains retinol and palmitic acid which is easily absorbed by body and widely used in skin care products. But, it is a hydrophobic and oxidation sensitive molecule which undergoes rapid degr...Vitamin A palmitate (VAP) contains retinol and palmitic acid which is easily absorbed by body and widely used in skin care products. But, it is a hydrophobic and oxidation sensitive molecule which undergoes rapid degradation especially in an aqueous environment. The purpose of this study was to prepare microcapsules of VAP using combination maltodextrin and modified starches. Emulsion of VAP was prepared using cremophore RH 40 with Tween 80 in a homogenizer and formed emulsion was spray-dried. The spray process was optimized using a central composite design for two variables to obtain microcapsules with desirable characteristics. Microcapsules containing 30% of VAP were produced using different concentration of wall materials. The prepared microcapsules were evaluated for their physical, morphological, in-vitro drug release and SEM study. The results showed that obtained microcapsules are nearly spherical in shape with a particle size ranged from 1 to 12 μm. The drug content and encapsulation efficiency (53% - 63%) of different batches were found within acceptable range. These stabilized drug loaded microcapsules were incorporated into silicone cream based formulation for convenient topical application and evaluated for its physicochemical parameters. The drug release study showed 80.18% to 83.43% of drug release from VAP microcapsules while topical formulations prepared by VAP microcapsules showed 67.09% to 71.45% drug release at the end of 24 hrs. The formulations were kept for 3 months stability study as per ICH guidelines and found to be stable.展开更多
In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was elimin...In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was eliminated by adjusting the stirring rate. The results showed that the two-step reaction followed a tetrahedral mechanism and conformed to second-order reaction kinetics. Nucleophilic attack on the carbonyl carbon afforded an intermediate, containing a tetrahedral carbon center. The intermediate ultimately decomposed by elimination of the leaving group, affording isopropyl palmitate. The experimental data were analyzed at different temperatures by the integral method. The kinetic equations of the each step were deduced, and the activation energy and frequency factor were obtained. Experiments were performed to verify the feasibility of kinetic equations, and the result showed that the kinetic equations were reliable. This study could be very signi ficant to both industrial application and determining the continuous production of isopropyl palmitate.展开更多
A high-performance liquid chromatography (HPLC) method has been developed and validated for the determination of dexamethasone palmitate (DXP) in bronchoalveolar fluid lavage samples (BALF). DXP in rat BALFs containin...A high-performance liquid chromatography (HPLC) method has been developed and validated for the determination of dexamethasone palmitate (DXP) in bronchoalveolar fluid lavage samples (BALF). DXP in rat BALFs containing the internal standard (IS), testosterone decanoate (TD), was extracted using a mixture of chloroform and methanol (9:1, v/v). Extracts were then centrifuged, dried and dissolved in acetonitrile. A chromatographic separation based on an isocratic elution was done using acetonitrile and water (85:15, v/v) as a mobile phase at a flow rate of 1.2 mL/min. The graph of the developed method was linear within the tested calibration range of 0.5 - 40 μg/mL. The overall extraction recovery of DXP from BALF samples was 84.3% ± 1.6%. The accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of ≤15% at all concentrations. This methodology has been applied to determine levels of DXP in BALF samples collected from rats treated with DXP large porous particles. The measured concentrations were successfully evaluated using a non-compartment pharmacokinetic model. Since the developed method requires only a microvolume (100 μL) of BALF sample for analysis, it is therefore particularly suitable for the evaluation of drug biodistribution in lung.展开更多
AIM: To investigate the effects of methyl palmitate and lutein on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats and explore the possible mechanisms. METHODS: Male Sprague-Dawley rats were divided into...AIM: To investigate the effects of methyl palmitate and lutein on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats and explore the possible mechanisms. METHODS: Male Sprague-Dawley rats were divided into 4 groups:(1) control;(2) LPS;(3) Methyl palmitate; and(4) Lutein groups. Methyl palmitate(300 mg/kg, ip) was administered 3 times per week on alternating days while lutein(100 mg/kg, oral) was given once daily. After 1 wk of vehicle/methyl palmitate/lutein treatment, ALI was induced by a single dose of LPS(7.5 mg/kg, iv). After 24 h of LPS injection, animals were sacrificed then biochemical parameters and histopathology were assessed. RESULTS: Treatment with methyl palmitate attenuated ALI, as it significantly decreased the lung wet/dry weight(W/D) ratio, the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid(BALF) andhistopathological damage. However, methyl palmitate failed to decrease lactate dehydrogenase(LDH) activity in BALF. On the other hand, lutein treatment produced significant anti-inflammatory effects as revealed by significant decrease in accumulation of inflammatory cells in lung, LDH level in BALF and histopathological damage. Methyl palmitate and lutein significantly increased superoxide dismutase(SOD) and reduced glutathione(GSH) activities with significant decrease in the lung malondialdehyde(MDA) content. Importantly, methyl palmitate and lutein decreased the level of the inflammatory cytokine tumor necrosis factor-α(TNF-α) in the lung. Lutein also reduced LPS-mediated overproduction of pulmonary nitrite/nitrate(NO-2/NO-3), which was not affected by methyl palmitate pretreatment. CONCLUSION: These results demonstrate the potent protective effects of both methyl palmitate and lutein against LPS-induced ALI in rats. These effects can be attributed to potent antioxidant activities of these agents, which suppress inflammatory cell infiltration and regulated cytokine effects.展开更多
BACKGROUND Paliperidone palmitate is a once-monthly injectable,atypical antipsychotic.To our knowledge,there has been only one report of paliperidone palmitate-induced angioedema presenting with acute laryngeal edema ...BACKGROUND Paliperidone palmitate is a once-monthly injectable,atypical antipsychotic.To our knowledge,there has been only one report of paliperidone palmitate-induced angioedema presenting with acute laryngeal edema with subsequent respiratory arrest.Here,we present a case report of paliperidone palmitate-induced angioedema with a relatively mild clinical presentation compared with the previously reported case,and the patient's condition was not complicated by lifethreatening anaphylaxis.CASE SUMMARY A 79-year-old female,who had a major neurocognitive disorder due to Alzheimer's disease with behavioral disturbances.Paliperidone palmitate was offlabel used to control her aggression,irritability,and psychosis.After induction doses(150 mg and 100 mg intramuscularly,given 1 wk apart),she developed intermittent swelling of the face,eyelids,and lips on day 17 after the initial dose,and the edema was explicitly seen on day 20.The diagnosis was paliperidone palmitate-induced angioedema.The monthly injection dose was discontinued on day 33 after the initial dose.The angioedema was subsequently alleviated,and it had completely resolved by day 40 after the initial dose.CONCLUSION Paliperidone palmitate-induced angioedema is a rare condition and can present with a mild,intermittent facial edema,which may be overlooked in clinical practice.展开更多
Excessive fat ectopically deposited in the non-adipose tissues is considered as one of the leading causes of myopathy.The aim of this study was to investigate the role of Dihydroartemisinin(DHA)in palmitate(PAL)-incub...Excessive fat ectopically deposited in the non-adipose tissues is considered as one of the leading causes of myopathy.The aim of this study was to investigate the role of Dihydroartemisinin(DHA)in palmitate(PAL)-incubated H9c2 cells(lipotoxicity-induced cell injury model).Cell viability of PAL-treated cells was determined by MTT assay,and apoptotic regulators were examined by qRT-PCR and western blot analysis,in the absence or in the presence of DHA,respectively.Expression levels of miR-133b and Sirt1 were also evaluated by qRT-PCR and western blotting examination.PAL decreased the viability of H9c2 cells and enhanced the expression of apoptotic genes.DHA reversed the effect of PAL on cell viability and lowed the level of Caspase3 and Bax.It also lowered the expression of miR-133b,while enhanced the expression of Bcl-2.Sirt1 was revealed as target of miR-133b through transcriptional regulation and the process was affected by DHA.DHA partially protected against the PAL-induced lipotoxicity by influencing the expression of miR-133b that hindered the activity of Sirt1.DHA may be used as a potential treatment in clinical management for lipotoxicity induced heart complications.展开更多
A simple efficient isocratic reversed-phase HPLC method was developed and validated for the determination of clindamycin palmitate hydrochloride (CPH) and its commercially available oral solution products. Separation ...A simple efficient isocratic reversed-phase HPLC method was developed and validated for the determination of clindamycin palmitate hydrochloride (CPH) and its commercially available oral solution products. Separation was achieved on a Phenomenex Zorbax (Luna) cyano column (150 × 4.6 mm, 5 μm) with a Phenomenex cyano guard cartridge (4 × 3.0 mm) on Agilent 1050 series HPLC system. CPH and its resolution standard lincomycin were eluted isocratically at a flow rate of 1 mL/min with a simplified mobile phase (potassium phosphate buffer (5 mM, pH 3.0)—acetonitrile—tetrahydrofuran (20:75:5, v/v/v)) and detected at 210 nm. The column was maintained at 25?C. The method was validated according to USP category I requirements. Robustness and forced degradation studies were also conducted. CPH marketed drug products were obtained from a drug distributor and assayed for potency using the validated method. Validation acceptance criteria were met in all cases. The analytical range for CPH was 15 - 500 μg/mL and the linearity was r2 > 0.999 over three days. The method was determined to be specific and robust. Both accuracy (92.0% - 103.8%) and precision (0.67% - 1.52%) were established across the analytical range for low, intermediate and high QC concentrations. Method applicability was demonstrated by analyzing two marketed products of CPH, in which results showed potency >98%. The method was determined to be an enhancement over the current USP methodology for assay as a result of increased efficiency, reduced organic solvents and the elimination of matrix modifiers. This method was successfully applied for the quality assessment of: 1) currently marketed drug products and 2) will in future assess the product quality of novel dosage forms of CPH for pediatric use.展开更多
High performance enzymatic synthesis of oleyl palmitate, a wax ester was carried out by lipase-catalyzed esterification of palmitic acid and oleyl alcohol. Response surface methodology (RSM) based on 5-level, 3-vari...High performance enzymatic synthesis of oleyl palmitate, a wax ester was carried out by lipase-catalyzed esterification of palmitic acid and oleyl alcohol. Response surface methodology (RSM) based on 5-level, 3-variable of centre composite rotatable design (CCRD) was used to evaluate the interactive effects of synthesis, of temperature (40-60 ℃); amount of enzyme (0.1-0.4 g) and substrate molar ratio of oleyl alcohol to palmitic acid (1:1-4:1) on the percentage yield of wax ester. All reactions were fixed at 1 hour of reaction time. The optimum condition obtained from RSM for the reactions were temperature of 57.9 ℃, enzyme amount of 0.26 g and molar ratio of substrates of 2.92. The actual experimental yield was 91.2% under the optimum condition, which compared well with the maximum predicted value of 92.0%. Comparison of predicted and experimental values reveal good correspondence between them, implying that empirical models derived from RSM can be used to adequately describe the relationship between the factors and response in the synthesis of oleyl palmitate.展开更多
Accumulating evidence supports an important role for nerve growth factor (NGF) in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid ...Accumulating evidence supports an important role for nerve growth factor (NGF) in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid (PA), a metabolic factor implicated in the development of dia- betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF significantly attenuated the levels of reactive oxygen species (ROS) and malondialde- hyde (MDA) in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 (PI3K inhibitor), Akt VIII inhibitor, and PD98059 (ERK1/2 inhibitor). Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 signaling pathways.展开更多
Candida antarctica lipase B (CAL-B) was used as a catalyst in the synthesis of palmitolyglucose ester in the ionic liquids, 1-butyl-3-methylimidazolium triflu- oromethanesulfonate ([Bmim][TfO]), with glucose as a subs...Candida antarctica lipase B (CAL-B) was used as a catalyst in the synthesis of palmitolyglucose ester in the ionic liquids, 1-butyl-3-methylimidazolium triflu- oromethanesulfonate ([Bmim][TfO]), with glucose as a substrates and palmitic acid vinyl ester as the acyl donor. The effect of substrate ratio, lipase content, and temperature on the activity and stability of lipase was studied. The reaction conditions in [Bmim][TfO] re- sulting in the highest yield of the sugar ester were a temperature of 50?C, enzyme concentration of 50 mg/ mL, and a molar ratio of glucose/vinyl palmitate of 1:3. The major reaction product was purified and char- acterized by FT-IR, HPLC, MS and NMR, as being 6-O-palmitolyglucose ester. The advantages of ionic liquid vs. organic solvent were noted.展开更多
Objective: To examine the wound healing properties of eicosane, pentadecane and palmitic acid by evaluating in term of anti-microbial, anti-inflammatory, proliferation, migration and collagen synthesis. Methods: Anti-...Objective: To examine the wound healing properties of eicosane, pentadecane and palmitic acid by evaluating in term of anti-microbial, anti-inflammatory, proliferation, migration and collagen synthesis. Methods: Anti-microbial activities of Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa were evaluated by carrying out disk diffusion and agar well diffusion methods. Growth rate of tested bacteria was also evaluated for 8 h in conjunction with the sample drugs. Besides, U937 cell lines were used as model study for realtime mRNA genes expression studies of TNF-毩 and IL-12 under the treatment. Proliferation, migration and collagen content synthesis were carried out on human dermal fibroblast. Results: None of the sample drugs possessed significant inhibition of bacteria tested in this study both in disk diffusion and agar well diffusion methods. In contrary, significantly low expressed mRNA gene expression levels of TNF-毩 and IL-12 were found under the treatment of respective drugs. Meanwhile in proliferation, migration and hydroxyproline content analysis, all the sample drugs showed no significant positive stimulation. Conclusions: This study therefore explains that apart from their potential in downregulating pro-inflammatory cytokines, these three compounds which were examined individually may not be good candidates in promoting wound healing.展开更多
Exposure of macrophages and microglia cells to the saturated palmitic acid (PA) leads to reduction in the mitochondrial membrane potential (), shrinkage of the cells and apoptosis. Here we show that the Cannabis compo...Exposure of macrophages and microglia cells to the saturated palmitic acid (PA) leads to reduction in the mitochondrial membrane potential (), shrinkage of the cells and apoptosis. Here we show that the Cannabis component Cannabidiol (CBD) rescues both macrophages and microglia cells from the detrimental effects of PA. CBD prevents the shrinkage in cell size and the reduction incaused by PA. The protective effect of CBD on the macrophage mitochondria is important for sustaining the macrophage population even under the immunosuppressed conditions caused by this drug. To a similar extent, the antagonistic effect of CBD on PA-mediated microglia cytotoxicity is important for its role in neuroprotection.展开更多
目的:评估精神分裂症患者接受棕榈酸帕利哌酮注射液1个月剂型(once-monthly paliperidone palmitate,PP1M)治疗后内分泌、代谢情况。方法:对51例口服利培酮治疗有效的精神分裂症患者换用PP1M治疗后,于基线及治疗后1个月、3个月、6个月...目的:评估精神分裂症患者接受棕榈酸帕利哌酮注射液1个月剂型(once-monthly paliperidone palmitate,PP1M)治疗后内分泌、代谢情况。方法:对51例口服利培酮治疗有效的精神分裂症患者换用PP1M治疗后,于基线及治疗后1个月、3个月、6个月、12个月监测内分泌、代谢等相关指标,于基线及治疗后12个月对患者进行个体和社会功能量表(personal and social performance scale,PSP)评估。结果:治疗12个月时PSP因子分对社会有益的活动、扰乱及攻击行为两项与基线相比,差异具有统计学意义(t=-2.07、3.71,P均<0.05);重复测量方差分析显示,不同时间点,患者体质量指数、腰围、血糖、血脂等指标差异均无统计学意义(P>0.05);而在血清泌乳素(prolactin,PRL)上,差异具有统计学意义(F=3.021,P<0.05),且各个时间点血清泌乳素浓度均高于基线(P均<0.05)。结论:PP1M对代谢影响较小,且能改善患者社会功能,但会导致血清PRL水平增高,需引起关注。展开更多
基金supported by a National Natural Science Foundation of China grant(31701558)the Young Elite Scientists Sponsorship Program by CAST(2017QNRC001)+1 种基金the Overseas Expertise Introduction Project for Discipline Innovation(111 Project,B90719028)the national first-class discipline program of Food Science and Technology(JUFSTR20180202).
文摘Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the sn-2 position of the glycerol backbone(more than 70%)and in unsaturated fatty acids at the sn-1,3 position.The specific TAG structure in HMF plays a valuable function in infant growth.Sn-2 palmitate(mainly 1,3-dioleoyl-2-palmitoyl-glycerol)is one of the structured TAGs that is commonly supplemented into infant formula in order to enable it to present a similar structure to HMF.In this review,the development of the lipase-catalyzed synthesis of sn-2 palmitate over the last 25 years are summarized,with a focus on reaction schemes in a laboratory setting.Particular attention is also paid to the commercialized sn-1,3 regioselective lipases that are used in structured TAGs synthesis,to general methods of TAG analysis,and to successfully developed sn-2 palmitate products on the market.Prospects for the lipase-catalyzed synthesis of sn-2 palmitate are discussed.
文摘The present study shows that double-stranded RNA-dependent protein kinase (PKR) regulates the protein expres- sion level and phosphorylation of Bcl-2 and plays an anti-apoptotic role in human hepatocellular carcinoma ceils (HepG2). In various types of cells, saturated free fatty acids (FFAs), such as palmitate, have been shown to induce cellular apoptosis by several mechanisms. Palmitate down-regulates the activity of PKR and thereby decreases the level of Bcl-2 protein, mediated in part by reduced activation of the NF-KB transcription factor. In addition to the level of Bel-2 protein, the phosphorylation of Bcl-2 at different amino acid residues, such as Ser70 and Ser87, is also important in regulating cellular apoptosis. The decrease in the phosphorylatiou of Bcl-2 at Ser70 upon exposure to palmitate is mediated by inhibition of PKR and possibly by c-Jun N-terminal kinase (JNK), whereas the phosphory- lation of Bcl-2 at Ser87 is unaffected by palmitate or PKR. In summary, PKR mediates the regulation of the protein level and the phosphorylation status of Bel-2, providing a novel mechanism of palmitate-induced apoptosis in HepG2 cells.
文摘Vitamin A palmitate (VAP) contains retinol and palmitic acid which is easily absorbed by body and widely used in skin care products. But, it is a hydrophobic and oxidation sensitive molecule which undergoes rapid degradation especially in an aqueous environment. The purpose of this study was to prepare microcapsules of VAP using combination maltodextrin and modified starches. Emulsion of VAP was prepared using cremophore RH 40 with Tween 80 in a homogenizer and formed emulsion was spray-dried. The spray process was optimized using a central composite design for two variables to obtain microcapsules with desirable characteristics. Microcapsules containing 30% of VAP were produced using different concentration of wall materials. The prepared microcapsules were evaluated for their physical, morphological, in-vitro drug release and SEM study. The results showed that obtained microcapsules are nearly spherical in shape with a particle size ranged from 1 to 12 μm. The drug content and encapsulation efficiency (53% - 63%) of different batches were found within acceptable range. These stabilized drug loaded microcapsules were incorporated into silicone cream based formulation for convenient topical application and evaluated for its physicochemical parameters. The drug release study showed 80.18% to 83.43% of drug release from VAP microcapsules while topical formulations prepared by VAP microcapsules showed 67.09% to 71.45% drug release at the end of 24 hrs. The formulations were kept for 3 months stability study as per ICH guidelines and found to be stable.
文摘In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was eliminated by adjusting the stirring rate. The results showed that the two-step reaction followed a tetrahedral mechanism and conformed to second-order reaction kinetics. Nucleophilic attack on the carbonyl carbon afforded an intermediate, containing a tetrahedral carbon center. The intermediate ultimately decomposed by elimination of the leaving group, affording isopropyl palmitate. The experimental data were analyzed at different temperatures by the integral method. The kinetic equations of the each step were deduced, and the activation energy and frequency factor were obtained. Experiments were performed to verify the feasibility of kinetic equations, and the result showed that the kinetic equations were reliable. This study could be very signi ficant to both industrial application and determining the continuous production of isopropyl palmitate.
文摘A high-performance liquid chromatography (HPLC) method has been developed and validated for the determination of dexamethasone palmitate (DXP) in bronchoalveolar fluid lavage samples (BALF). DXP in rat BALFs containing the internal standard (IS), testosterone decanoate (TD), was extracted using a mixture of chloroform and methanol (9:1, v/v). Extracts were then centrifuged, dried and dissolved in acetonitrile. A chromatographic separation based on an isocratic elution was done using acetonitrile and water (85:15, v/v) as a mobile phase at a flow rate of 1.2 mL/min. The graph of the developed method was linear within the tested calibration range of 0.5 - 40 μg/mL. The overall extraction recovery of DXP from BALF samples was 84.3% ± 1.6%. The accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of ≤15% at all concentrations. This methodology has been applied to determine levels of DXP in BALF samples collected from rats treated with DXP large porous particles. The measured concentrations were successfully evaluated using a non-compartment pharmacokinetic model. Since the developed method requires only a microvolume (100 μL) of BALF sample for analysis, it is therefore particularly suitable for the evaluation of drug biodistribution in lung.
文摘AIM: To investigate the effects of methyl palmitate and lutein on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats and explore the possible mechanisms. METHODS: Male Sprague-Dawley rats were divided into 4 groups:(1) control;(2) LPS;(3) Methyl palmitate; and(4) Lutein groups. Methyl palmitate(300 mg/kg, ip) was administered 3 times per week on alternating days while lutein(100 mg/kg, oral) was given once daily. After 1 wk of vehicle/methyl palmitate/lutein treatment, ALI was induced by a single dose of LPS(7.5 mg/kg, iv). After 24 h of LPS injection, animals were sacrificed then biochemical parameters and histopathology were assessed. RESULTS: Treatment with methyl palmitate attenuated ALI, as it significantly decreased the lung wet/dry weight(W/D) ratio, the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid(BALF) andhistopathological damage. However, methyl palmitate failed to decrease lactate dehydrogenase(LDH) activity in BALF. On the other hand, lutein treatment produced significant anti-inflammatory effects as revealed by significant decrease in accumulation of inflammatory cells in lung, LDH level in BALF and histopathological damage. Methyl palmitate and lutein significantly increased superoxide dismutase(SOD) and reduced glutathione(GSH) activities with significant decrease in the lung malondialdehyde(MDA) content. Importantly, methyl palmitate and lutein decreased the level of the inflammatory cytokine tumor necrosis factor-α(TNF-α) in the lung. Lutein also reduced LPS-mediated overproduction of pulmonary nitrite/nitrate(NO-2/NO-3), which was not affected by methyl palmitate pretreatment. CONCLUSION: These results demonstrate the potent protective effects of both methyl palmitate and lutein against LPS-induced ALI in rats. These effects can be attributed to potent antioxidant activities of these agents, which suppress inflammatory cell infiltration and regulated cytokine effects.
文摘BACKGROUND Paliperidone palmitate is a once-monthly injectable,atypical antipsychotic.To our knowledge,there has been only one report of paliperidone palmitate-induced angioedema presenting with acute laryngeal edema with subsequent respiratory arrest.Here,we present a case report of paliperidone palmitate-induced angioedema with a relatively mild clinical presentation compared with the previously reported case,and the patient's condition was not complicated by lifethreatening anaphylaxis.CASE SUMMARY A 79-year-old female,who had a major neurocognitive disorder due to Alzheimer's disease with behavioral disturbances.Paliperidone palmitate was offlabel used to control her aggression,irritability,and psychosis.After induction doses(150 mg and 100 mg intramuscularly,given 1 wk apart),she developed intermittent swelling of the face,eyelids,and lips on day 17 after the initial dose,and the edema was explicitly seen on day 20.The diagnosis was paliperidone palmitate-induced angioedema.The monthly injection dose was discontinued on day 33 after the initial dose.The angioedema was subsequently alleviated,and it had completely resolved by day 40 after the initial dose.CONCLUSION Paliperidone palmitate-induced angioedema is a rare condition and can present with a mild,intermittent facial edema,which may be overlooked in clinical practice.
基金supported by Nantong Science and Technology Project(MS12018020,MS12018041)Jiangsu Government Scholarship for Overseas Studies(JS-2017-200)+1 种基金the Doctoral Scientific Research Foundation of Nantong University(135420505015)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(11KJB180010).
文摘Excessive fat ectopically deposited in the non-adipose tissues is considered as one of the leading causes of myopathy.The aim of this study was to investigate the role of Dihydroartemisinin(DHA)in palmitate(PAL)-incubated H9c2 cells(lipotoxicity-induced cell injury model).Cell viability of PAL-treated cells was determined by MTT assay,and apoptotic regulators were examined by qRT-PCR and western blot analysis,in the absence or in the presence of DHA,respectively.Expression levels of miR-133b and Sirt1 were also evaluated by qRT-PCR and western blotting examination.PAL decreased the viability of H9c2 cells and enhanced the expression of apoptotic genes.DHA reversed the effect of PAL on cell viability and lowed the level of Caspase3 and Bax.It also lowered the expression of miR-133b,while enhanced the expression of Bcl-2.Sirt1 was revealed as target of miR-133b through transcriptional regulation and the process was affected by DHA.DHA partially protected against the PAL-induced lipotoxicity by influencing the expression of miR-133b that hindered the activity of Sirt1.DHA may be used as a potential treatment in clinical management for lipotoxicity induced heart complications.
文摘A simple efficient isocratic reversed-phase HPLC method was developed and validated for the determination of clindamycin palmitate hydrochloride (CPH) and its commercially available oral solution products. Separation was achieved on a Phenomenex Zorbax (Luna) cyano column (150 × 4.6 mm, 5 μm) with a Phenomenex cyano guard cartridge (4 × 3.0 mm) on Agilent 1050 series HPLC system. CPH and its resolution standard lincomycin were eluted isocratically at a flow rate of 1 mL/min with a simplified mobile phase (potassium phosphate buffer (5 mM, pH 3.0)—acetonitrile—tetrahydrofuran (20:75:5, v/v/v)) and detected at 210 nm. The column was maintained at 25?C. The method was validated according to USP category I requirements. Robustness and forced degradation studies were also conducted. CPH marketed drug products were obtained from a drug distributor and assayed for potency using the validated method. Validation acceptance criteria were met in all cases. The analytical range for CPH was 15 - 500 μg/mL and the linearity was r2 > 0.999 over three days. The method was determined to be specific and robust. Both accuracy (92.0% - 103.8%) and precision (0.67% - 1.52%) were established across the analytical range for low, intermediate and high QC concentrations. Method applicability was demonstrated by analyzing two marketed products of CPH, in which results showed potency >98%. The method was determined to be an enhancement over the current USP methodology for assay as a result of increased efficiency, reduced organic solvents and the elimination of matrix modifiers. This method was successfully applied for the quality assessment of: 1) currently marketed drug products and 2) will in future assess the product quality of novel dosage forms of CPH for pediatric use.
文摘High performance enzymatic synthesis of oleyl palmitate, a wax ester was carried out by lipase-catalyzed esterification of palmitic acid and oleyl alcohol. Response surface methodology (RSM) based on 5-level, 3-variable of centre composite rotatable design (CCRD) was used to evaluate the interactive effects of synthesis, of temperature (40-60 ℃); amount of enzyme (0.1-0.4 g) and substrate molar ratio of oleyl alcohol to palmitic acid (1:1-4:1) on the percentage yield of wax ester. All reactions were fixed at 1 hour of reaction time. The optimum condition obtained from RSM for the reactions were temperature of 57.9 ℃, enzyme amount of 0.26 g and molar ratio of substrates of 2.92. The actual experimental yield was 91.2% under the optimum condition, which compared well with the maximum predicted value of 92.0%. Comparison of predicted and experimental values reveal good correspondence between them, implying that empirical models derived from RSM can be used to adequately describe the relationship between the factors and response in the synthesis of oleyl palmitate.
基金supported by the National Natural Science Foundation of China,No.U1304815a grant from Key Project of Science and Technology Research of Henan Province of China,No.132102310097
文摘Accumulating evidence supports an important role for nerve growth factor (NGF) in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid (PA), a metabolic factor implicated in the development of dia- betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF significantly attenuated the levels of reactive oxygen species (ROS) and malondialde- hyde (MDA) in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 (PI3K inhibitor), Akt VIII inhibitor, and PD98059 (ERK1/2 inhibitor). Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 signaling pathways.
文摘Candida antarctica lipase B (CAL-B) was used as a catalyst in the synthesis of palmitolyglucose ester in the ionic liquids, 1-butyl-3-methylimidazolium triflu- oromethanesulfonate ([Bmim][TfO]), with glucose as a substrates and palmitic acid vinyl ester as the acyl donor. The effect of substrate ratio, lipase content, and temperature on the activity and stability of lipase was studied. The reaction conditions in [Bmim][TfO] re- sulting in the highest yield of the sugar ester were a temperature of 50?C, enzyme concentration of 50 mg/ mL, and a molar ratio of glucose/vinyl palmitate of 1:3. The major reaction product was purified and char- acterized by FT-IR, HPLC, MS and NMR, as being 6-O-palmitolyglucose ester. The advantages of ionic liquid vs. organic solvent were noted.
基金supported by the Centre of Excellence for Research,Value,Innovation and Entrepreneurship Research Grant Scheme UCSI University(UCSI-CERVIE-RGS Proj-in-FAS 039)
文摘Objective: To examine the wound healing properties of eicosane, pentadecane and palmitic acid by evaluating in term of anti-microbial, anti-inflammatory, proliferation, migration and collagen synthesis. Methods: Anti-microbial activities of Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa were evaluated by carrying out disk diffusion and agar well diffusion methods. Growth rate of tested bacteria was also evaluated for 8 h in conjunction with the sample drugs. Besides, U937 cell lines were used as model study for realtime mRNA genes expression studies of TNF-毩 and IL-12 under the treatment. Proliferation, migration and collagen content synthesis were carried out on human dermal fibroblast. Results: None of the sample drugs possessed significant inhibition of bacteria tested in this study both in disk diffusion and agar well diffusion methods. In contrary, significantly low expressed mRNA gene expression levels of TNF-毩 and IL-12 were found under the treatment of respective drugs. Meanwhile in proliferation, migration and hydroxyproline content analysis, all the sample drugs showed no significant positive stimulation. Conclusions: This study therefore explains that apart from their potential in downregulating pro-inflammatory cytokines, these three compounds which were examined individually may not be good candidates in promoting wound healing.
文摘Exposure of macrophages and microglia cells to the saturated palmitic acid (PA) leads to reduction in the mitochondrial membrane potential (), shrinkage of the cells and apoptosis. Here we show that the Cannabis component Cannabidiol (CBD) rescues both macrophages and microglia cells from the detrimental effects of PA. CBD prevents the shrinkage in cell size and the reduction incaused by PA. The protective effect of CBD on the macrophage mitochondria is important for sustaining the macrophage population even under the immunosuppressed conditions caused by this drug. To a similar extent, the antagonistic effect of CBD on PA-mediated microglia cytotoxicity is important for its role in neuroprotection.
文摘目的:评估精神分裂症患者接受棕榈酸帕利哌酮注射液1个月剂型(once-monthly paliperidone palmitate,PP1M)治疗后内分泌、代谢情况。方法:对51例口服利培酮治疗有效的精神分裂症患者换用PP1M治疗后,于基线及治疗后1个月、3个月、6个月、12个月监测内分泌、代谢等相关指标,于基线及治疗后12个月对患者进行个体和社会功能量表(personal and social performance scale,PSP)评估。结果:治疗12个月时PSP因子分对社会有益的活动、扰乱及攻击行为两项与基线相比,差异具有统计学意义(t=-2.07、3.71,P均<0.05);重复测量方差分析显示,不同时间点,患者体质量指数、腰围、血糖、血脂等指标差异均无统计学意义(P>0.05);而在血清泌乳素(prolactin,PRL)上,差异具有统计学意义(F=3.021,P<0.05),且各个时间点血清泌乳素浓度均高于基线(P均<0.05)。结论:PP1M对代谢影响较小,且能改善患者社会功能,但会导致血清PRL水平增高,需引起关注。