Biological,pathological,and multifaceted therapeutic functions of exosomes to target cancer

Exosomes,small tiny vesicle contains a large number of intracellular particles that employ to cause various diseases and prevent several pathological events as well in the human body.It is considered a“double-edged sword”,and depending on its biological source,the action of exosomes varies under physiological conditions.Also,the isolation and characterization of the exosomes should be performed accurately and the methodology also will vary depending on the exosome source.Moreover,the uptake of exosomes from the recipients’cells is a vital and initial step for all the physiological actions.There are different mechanisms present in the exosomes’cellular uptake to deliver their cargo to acceptor cells.Once the exosomal uptake takes place,it releases the intracellular particles that leads to activate the physiological response.Even though exosomes have lavish functions,there are some challenges associated with every step of their preparation to bring potential therapeutic efficacy.So,overcoming the pitfalls would give a desired quantity of exosomes with high purity.

Protective and Regenerative Efficacy of a Plant Oil-Based Day and Night Cream: Investigated by a Novel Approach to Reveal the Impact of Blue Light Irradiation on Epidermal Barrier Integrity and Lipid Matrix

In recent years, the harmful effects of blue light (400 - 500 nm) as a component of visible light (400 - 700 nm) have increasingly gained attention of science, industry, and consumers. To date, only a few in vivo test methods for measuring the effects of blue light on the skin have been described. A direct measurement method that can detect the immediate effects of blue light on the epidermal permeability barrier (EPB) is still lacking. In this study, we present a new methodological approach that can be used to investigate both the protective and regenerative effects of cosmetic products on the EPB after blue light irradiation. In a study with 14 female volunteers, it was investigated whether the regular application of an O/W emulsion (day cream) can strengthen and protect the epidermal barrier against damaging blue light radiation of 60 J/cm2 (protective study design) and also whether a disruption of the epidermal barrier caused by blue light radiation is restored faster and better by the regular application of another O/W emulsion (night cream) than in product-untreated skin (regenerative study design). The two O/W emulsions are different in plant oil, active ingredient composition and texture. The seven-day treatment with the day cream initially led to a significant increase in the normalized lipid lamellae length in the intercellular space, whereas the irradiation with blue light after 24 hours led to a significant decrease in the lipid lamellae length in the untreated test area, but not in the area previously treated with the product. Regarding the regenerative study design, a two-day treatment with the night cream was able to restore a blue-light-induced decrease in lipid lamellae length in the intercellular space. In summary, with the study designs presented here, the protective and regenerative effect of two cosmetic products could be demonstrated for the first time on the integrity of the EPB after blue light irradiation and the data showed that the Lipbarvis® method is suitable for investigating the damaging effects of blue light on the EPB in vivo.

Traditional medicine in Tanzania:a review of historical perspective,current practices and challenges

The use of traditional medicine(TM)is essential for preventing and treating diseases and thus improving human health.Worldwide,TM has been used since time immemorial.In Tanzania,the use of TM was most common during precolonial era before it was discriminated during the Germany colonial rule.However,it regained the attention during the private sector emergence era(1985-2004).Currently,there are ongoing efforts to integrate TM and modern medicine to improve healthcare systems in developing countries for sustainable healthcare management.This review aims to provide an overview of the historical and current status,challenges,and future direction for TM in Tanzania.The analysis revealed that the development of TM was somehow underdeveloped during the colonial rule but regained its popularity after independence.Currently,there are many opportunities such as the presence of legal and institutional frameworks,a varied medicinal biodiversity,with some of them being endemic to Tanzania,political will etc.Despite the available opportunities,there are numerous challenges to the development and use of TM.These include inadequate financial and human resources for research,poor conservation of medicinal biodiversity;modernization;intellectual property rights of TM knowledge;lack of safety,efficacy,and quality data of medicinal products.The development and utility of TM as a resource is crucial to protect practise.Thus,the study recommends more capacity building in terms of finances,technology development,human resources training,advocacy and integration of TM into healthcare system.

Protective and Regenerative Anti-Pollution Efficacy of a Plant Oil-Based Day and Night Cream: Investigated by a Novel Approach to Reveal the Impact of Pollutants on Epidermal Barrier Integrity and Lipid Matrix

In the wake of ever-increasing environmental pollution, human skin in the modern urban world is exposed to increased levels of harmful environmental pollutants. Many studies have shown that these pollutants can weaken the epidermal skin barrier and thus facilitate the penetration of these substances into the skin. An important goal of modern skin care against harmful environmental influences should therefore be to protect and strengthen the epidermal barrier and to repair occurring damage quickly and efficiently. With this in mind, in the present study we investigated what damage cigarette smoke causes to the epidermal barrier and 1) whether the regular application of a O/W emulsion (Day Cream) can protectively strengthen the epidermal barrier against environmental damage and 2) whether a cigarette smoke-induced disruption of the epidermal barrier is restored faster and better by the regular application of a another O/W emulsion (Night Cream) than in product-untreated skin. The two products are slightly different in plant-oil, active ingredient composition and texture. Firstly, the study has shown that the Lipbarvis? method is suitable for measuring the effect of cigarette smoke, in contrast to conventional biophysical measurement methods (transepidermal water loss, skin hydration). Secondly, both products were able to improve skin barrier function in the corresponding test scenario. This was demonstrated for both test products by a significantly reduced TEWL, significantly increased skin hydration and significantly improved length of the lipid lamellae in the intercellular space, as well as the protective effect of the day cream on the epidermal skin barrier and the regenerative properties of the tested night cream. .

Baseline radiologic features as predictors of efficacy in patients with pancreatic neuroendocrine tumors with liver metastases receiving surufatinib

Objective:Currently,pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases(PNELM)receiving surufatinib treatment was unsatisfying.Our objective was to examine the association between radiological characteristics and efficacy/prognosis.Methods:We enrolled patients with liver metastases in the phase III,SANET-p trial(NCT02589821)and obtained contrast-enhanced computed tomography(CECT)images.Qualitative and quantitative parameters including hepatic tumor margins,lesion volumes,enhancement pattern,localization types,and enhancement ratios were evaluated.The progression-free survival(PFS)and hazard ratio(HR)were calculated using Cox’s proportional hazard model.Efficacy was analyzed by logistic-regression models.Results:Among 152 patients who had baseline CECT assessments and were included in this analysis,the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters.In the multivariable analysis of patients receiving surufatinib(N=100),those with higher arterial phase standardized enhancement ratio-peri-lesion(ASER-peri)exhibited longer PFS[HR=0.039;95%confidence interval(95%CI):0.003−0.483;P=0.012].Furthermore,patients with a high enhancement pattern experienced an improvement in the objective response ratio[31.3%vs.14.7%,odds ratio(OR)=3.488;95%CI:1.024−11.875;P=0.046],and well-defined tumor margins were associated with a higher disease control rate(DCR)(89.3%vs.68.2%,OR=4.535;95%CI:1.285−16.011;P=0.019)compared to poorlydefined margins.Conclusions:These pre-treatment radiological features,namely high ASER-peri,high enhancement pattern,and well-defined tumor margins,have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib.

Efficacy and safety of vildagliptin in clinical practice-results of the PROVIL-study

AIM:To investigate efficacy and safety of vildagliptin compared to other oral antidiabetics in clinical practice in Germany.METHODS:In this prospective,open,observational study,patients with type 2 diabetes mellitus(T2DM) previously on oral monotherapy were selected by their treating physician to receive either vildagliptin addon to metformin(cohort 1),vildagliptin+metformin single-pill combination(SPC)(cohort 2)or another dual combination therapy with oral antidiabetic drugs(OADs)(cohort 3).According to routine clinical practice,interim examinations occurred every 3 mo:at baseline,after approximately 3 mo and after approximately 6 mo.Parameters documented in the study included demographic and diagnostic data,history of T2DM,data on diabetes control,vital signs,relevant prior and concomitant medication and disease history.Efficacy was assessed by changes in HbA1c and fasting plasma glucose(FPG)3 mo and 6 mo after initiation of dual combination therapy.Safety was assessed by adverseevent reporting and measurement of specific laboratory values(serum creatinine,total bilirubin,alanine aminotransferase,aspartate aminotransferase,creatine kinase).RESULTS:Between October 2009 and January 2011,a total of 3881 patients were enrolled in this study.Since 47 patients were withdrawn due to protocol violations,3834 patients were included in the statistical analysis.There were no relevant differences between the three cohorts concerning age,body weight and body mass index.Average diabetes duration was approximately 6 years and mean HbA1c was between 7.6%and 7.9% at baseline.Antidiabetic treatment was recorded in 3648 patients.Patients were treated with vildagliptin add-on to metformin(n=603),vildagliptin+metformin(SPC)(n =2198),and other oral OADs including combinations of metformin with sulfonylurea(n=370),with glitazones(n =123),other dipeptidyl peptidase-4 inhibitors(n=99).After 6 mo of treatment,the absolute decrease in HbA1c(mean±SE)was significantly more pronounced in patients receiving vildagliptin add-on to metformin(-0.9% ±0.04%)and vildagliptin+metformin(SPC)(-0.9%± 0.03%)than in patients receiving other OADs(-0.6% ±0.04%;P<0.0001).In addition,significant cohort differences were observed for the improvement in FPG after 6 mo treatment(vildagliptin add-on to metformin:-291 mg/L±18.3 mg/L;vildagliptin+metformin(SPC):-305 mg/L±9.6 mg/L;other antidiabetic drugs:-209 mg/L±14.0 mg/L for(P<0.0001).Moderate decreases in body weight(absolute difference between last control and baseline:mean±SE)were observed for patients in all cohorts(vildagliptin add-on to metformin:-1.4 kg ±0.17 kg;vildagliptin+metformin(SPC):-1.7 kg± 0.09 kg;other OADs:?0.8 kg±0.13 kg).No significant differences in adverse events(AEs)and other safety measures were observed between the cohorts.When performing an additional analysis by age(patients<65 years vs patients≥65 years),there was no relevant difference in the most common AEs between the two age groups and the AE profile was similar to that of the overall patient population.CONCLUSION:Clinical practice confirms that vildagliptin is an effective and well-tolerated treatment in combination with metformin in T2DM patients.

Role of a probiotic (Saccharomyces boulardii) in management and prevention of diarrhoea

AIM： To assess the efficacy and safety of Saccharomyces boulardii （S. boulardii） in acute watery diarrhoea and its role in reducing the frequency of episodes of diarrhoea in subsequent two months. METHODS： Children from 2 mo to 12 years of age, with acute diarrhoea were selected according to inclusion criteria and randomised in S. boulardii group （treated with ORS, nutritional support and S. boulardii, 250 mg bid） and in control group （treated with ORS and nutritional support only）. Active treatment phase was 5 d and each child was followed for two months afterwards. Frequency and consistency of stools as well as safety of drug was assessed on every visit. A comparison of two groups was done in terms of number of diarrhoeal episode in subsequent two months. RESULTS： There were fifty patients in each group. Baseline characteristics such as mean age and the average frequency of stools were comparable in S. boulardii and control group at the time of inclusion in the trial. By d 3 it reduced to 2.7 and 4.2 stools per d respectively and by d 6 it reduced to 1.6 （5. boulardii Group） and 3.3 （control group）. The duration of diarrhoea was 3.6 d in S. boulardii group whereas it was 4.8 d in control group （P = 0.001）. In the following two months, S. boulardii group had a significantly lower frequency of 0.54 episodes as compared to 1.08 episodes in control group. The drug was well accepted and tolerated. There were no reports of the side effects during treatment period CONCLUSION： S. boulardii significantly reduces the frequency and duration of acute diarrhoea. The consistency of stool also improves. The drug is well-tolerated.

PCR-based methodologies for detection and characterization of Listeria monocytogenes and Listeria ivanovii in foods and environmental sources

Listeria monocytogenes is an important foodborne pathogen responsible for listeriosis,a fatal disease.It is widely distributed in various foods and environmental sources.In this review,we focused on addressing PCR-based technologies,including conventional PCR,qPCR and droplet digital PCR(ddPCR).Specifically,we described(a)conventional PCR and mono-,duplex-and multiplex-qPCR methodologies;(b)development and applications of gene HlyA-,Iap-,PrfA–and SsrA-based conventional and qPCR assays as well as PCR assays targeting newly identified gene targets for specific detection of L.monocytogenes;differentiation of viable from dead L.monocytogenes by qPCR in conjugation with propidium monoazide pretreatment;PCR-based serotype identification of L.monocytogenes isolates;PCR-based detection of L.ivanovii,infecting ruminants,differentiation of L.monocytogenes from other Listeria species;and sigB-gene based PCR identification of Listeria spp;(c)applications of ddPCR in detection of L.monocytogenes;and(d)application of qPCR assays in detection and subtyping of L.monocytogenes in milk and dairy products;meats,meat products and meat-processing environment;and seafood,seafood products and processing environment.Our goal was to provide a relatively comprehensive overview of PCR-based methodologies available in detection,characterization and subtyping of various strains of L.monocytogenes in foods and environmental sources.

Prevalence and methodologies for detection,characterization and subtyping of Listeria monocytogenes and L.ivanovii in foods and environmental sources

Listeria monocytogenes,one of the most important foodborne pathogens,can cause listeriosis,a lethal disease for humans.L.ivanovii,which is closely related to L.monocytogenes,is also widely distributed in nature and infects mainly warm-blooded ruminants,causing economic loss.Thus,there are high priority needs for methodologies for rapid,specific,cost-effective and accurate detection,characterization and subtyping of L.monocytogenes and L.ivanovii in foods and environmental sources.In this review,we(A)described L.monocytogenes and L.ivanovii,world-wide incidence of listeriosis,and prevalence of various L.monocytogenes strains in food and environmental sources;(B)comprehensively reviewed different types of traditional and newly developed methodologies,including culture-based,antigen/antibody-based,LOOP-mediated isothermal amplification,matrix-assisted laser desorption ionization-time of flight-mass spectrometry,DNA microarray,and genomic sequencing for detection and characterization of L.monocytogenes in foods and environmental sources;(C)comprehensively summarized different subtyping methodologies,including pulsed-field gel electrophoresis,multi-locus sequence typing,ribotyping,and phage-typing,and whole genomic sequencing etc.for subtyping of L.monocytogenes strains from food and environmental sources;and(D)described the applications of these methodologies in detection and subtyping of L.monocytogenes in foods and food processing facilities.

Bimatoprost/timolol fixed combination(BTFC) in patients with primary open angle glaucoma or ocular hypertension in Greece

AIM：To evaluate the efficacy and tolerability of the fixed combination of bimatoprost 0.03%and timolol 0.5%（BTFC）in patients in Greece with primary open angle glaucoma（POAG）or ocular hypertension（OHT）whose previous therapy provided insufficient lowering of intraocular pressure（IOP）.·METHODS：A multicenter,prospective,open-label,non-interventional,observational study of the use of BTFC in clinical practice was conducted at 41 sites in Greece.The primary endpoint was the reduction in IOP from baseline at study end,approximately 12wk after initiation of BTFC therapy.·RESULTS：A total of 785 eligible patients were enrolled in the study and 97.6%completed the study.The mean±SD IOP reduction from baseline at 12wk after initiation of BTFC was 6.3±2.8 mm Hg（=764;〈0.001）.In patients（=680）who replaced their previous IOP-lowering monotherapy（a single drug,or a fixed combination of 2drugs in a single ophthalmic drop）with once-daily BTFC,the mean±SD IOP reduction from baseline at 12wk was 6.2±2.8 mm Hg（〈0.001）.IOP was reduced from baseline in 99.2%of patients,and 58.0%of patients reached or exceeded their target IOP.Substantial mean IOP reductions were observed regardless of the previous therapy.BTFC was well tolerated,with 96.0%of patients who completed the study rating the tolerability of BTFC as＂good＂or＂very good.＂Adverse events were reported in 8.3%of patients;only 0.6%of patients discontinued the study due to adverse events.·C ONCLUSION：In clinical practice in Greece,BTFC is well tolerated and effectively lower the IOP in patients with POAG or OHT who requires additional IOP lowering on their previous therapy.

Neuropathy experienced by colorectal cancer patients receiving oxaliplatin: A qualitative study to validate the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale

BACKGROUND Although oxaliplatin is widely established as a standard treatment in colorectal cancer(CRC),oxaliplatin-induced neuropathy has emerged as a prominent doselimiting side effect associated with quality of life decrements.Ongoing monitoring and management of neuropathy is important for CRC patient quality of life and adherence to treatment.Therefore,a validated self-reported measure of neuropathy would aid in the management and assessment of oxaliplatininduced neuropathy in clinical practice and research.We sought to evaluate the content validity of the 13-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity subscale(FACT/GOGNtx)for CRC patients receiving oxaliplatin.AIM To understand the neuropathy experiences of CRC patients and assess content validity of the FACT/GOG-Ntx.METHODS Semi-structured concept elicitation and cognitive debriefing interviews were conducted with 31 CRC patients experiencing peripheral neuropathy from current or previous oxaliplatin treatment.Interview data were analyzed using a constant comparative approach,and data were mapped to the FACT/GOG-Ntx to assess content validity.RESULTS Mean age of the sample was 54(range 34-82).The sample was primarily Caucasian(84%)and consisted of nearly equal numbers of men and women.Participants described 28 unique neuropathy symptoms;hand tingling(experienced by 87%of respondents);feet tingling(81%);hand numbness(68%);and feet numbness(84%)were most frequently mentioned.Neuropathy symptoms occurring on the feet were most often identified as most bothersome by participants.Eleven of the 13 FACT/GOG-Ntx items exhibited moderate to strong evidence of content validity.Two items related to trouble hearing and ringing in the ears had weak support;however,these items represent severe neuropathy and could be useful for a patient reported outcome measure.CONCLUSION The FACT/GOG-Ntx represents the key neuropathy experiences of CRC patients treated with oxaliplatin.

Impurity Profiling of Solid Oral Drug Products to Sail through GDUFA-II Requirements

Defining impurity profile is key element to ensure safe, efficacious and quality human drugs. Impurity profiling changed/transformed drastically over the years. Guidelines, specifications and requirements are evolving. Initially impurity profiling was based on simple methods later by degradation studies, then to understand drug strength and efficacy chiral impurities and stereo isomers were included followed by residual solvents, polymorphic forms, genotoxic impurity studies. Currently, elemental impurities are the latest addition. As per the GDUFA II guidelines to improve review efficiency and reduce review cycles, data requirements have changed. Based on recent guidance and review points, Impurity profiling has significant importance in ANDA filing and to ensure approval within 10 months (first cycle approval) which is an exiling aspect for industries to enter into the generic market quickly. Hence, Impurity profile is a key aspect scientifically, regulatory wise and commercially also. This is a review article on impurity profiling of Solid oral drug substances and products as per GDUFA II requirements the reference documents for the review are ICH guidance, relevant FDA GDUFA guidance and common industry practices.

Control strategy and methods for continuous direct compression processes

We presented a control strategy for tablet manufacturing processes based on continuous direct compression.The work was conducted by the experts of pharmaceutical companies,machine suppliers,academia,and regulatory authority in Japan.Among different items in the process,the component ratio and blended powder content were selected as the items requiring the control method specific to continuous manufacturing different from the conventional batch manufacturing.The control and management of the Loss in Weight(LIW)feeder were deemed the most important,and the Residence Time Distribution(RTD)model were regarded effective for setting the control range and for controlling of the LIW feeder.Based on these ideas,the concept of process control using RTD was summarized.

Consumer Panel Size in Sensory Cosmetic Product Evaluation: A Pilot Study from a Statistical Point of View

Subjective evaluations are nowadays applied more commonly in cosmetic product assessment. They are used in quality control, product development steps and efficacy studies for claim support. Several studies have been published to determine the adequate number of panelists, but recommendations and guidelines dealing with this topic are rare in the cosmetic sector. The aim of the present pilot study was to recommend a suitable study plan and define the adequate consumer panel size for cosmetic consumer assessment. A questionnaire-based product evaluation study, with three different cosmetic products, was organized as a consumer test using a seven-point scale. As a last step, a specific statistical calculation was performed to define the minimum sample size. It showed that the minimum sample size, besides the obvious statistical parameters of standard deviation and confidence interval, also depends on age and gender of the panelists and product assessment item. Utilizing a CI of 95% a minimum of 60 panelists seems to be sufficient for home-use-test (HUT) with a given seven-point scale. A minimum of 101 panelists are shown to be sufficient utilizing a CI of 99%.

Protective effect of Pisonia aculeata on thioacetamide induced hepatotoxicity in rats

Objective:To evaluate the protective effect of Pisonia aculeata(P.aculeata) on thioacetamide induced hepatotoxicity in rats.Methods:Male Wistar rats were administered 250 or 500 mg/kg p.o.of P.aculeata extract for 21 days and simultaneously administered thioacetamide(TAA) 50 mg/kg bw s.c.1 h alter the respective assigned treatments every 72 h.At the end of all experimental methods,all the animals were sacrificed by cervical decapitation.Blood samples were collected.Serum was separated and analyzed for various biochemical parameters.Results:TAA induced a significant rise in aspartate amino transferase(AST),alanine amino transferase(ALT),alkaline phosphatase(ALP),total bilirubin,gamma glutamate transpeptidase(GGTP),lipid peroxidase(LPO)with a reduction of total protein,superoxide dismutase(SOD),catalase,glutathione peroxidase(GPx) and glutathione S-transferase(GST).Treatment of rats with different does of plant extract(250 and 500 mg/kg) significantly(P<0.001) altered serum marker enzymes and antioxidant levels to near normal against TAA treated rats.The activity of the extract at a dose of 300 tug/kg was comparable to the standard drug,silymarin(50 mg/kg.p.o.).Conclusions:It can be concluded that P.aculeata extract possesses a remarkable hepaloprolective and antioxidant activity against TAA induced hepatotoxicitv.Wore research is required lo derive an optimal therapeutic dose.

Matrix Extension with Fitness for Purpose and Stability Assessment of DHA and Additional Fatty Acids in Individual Whole Chicken Eggs

The consumption of long chain polyunsaturated fatty acids (LC-PUFA) is associated with several human health benefits. Most notable of these LC-PUFA is docosahexaenoic acid (DHA C22:6) whose inclusion is considered essential for optimum human health. Biofortification of common foods such as eggs with DHA has emerged as a specific approach to increase the intake of DHA in human populations. This can be achieved by supplementing poultry rations with feeds like microalgae or fish oil that are rich in DHA, which results in an increased uptake in the egg. Gas chromatography with flame ionization detection (GC-FID) is the method of choice when analyzing food such as eggs for DHA and other fatty acids. For regulatory studies it is desirable to demonstrate that the method is specifically suitable for the analysis of DHA and fatty acids in eggs. The purpose of this paper is to further extend the scope of the AOAC 996.06 methodology examined in the paper by Dillon et al., and to demonstrate the fitness for purpose of the method by examining specific validation parameters. It is a further objective to investigate the stability of DHA and other fatty acids of short and long timepoints. A validation of the method for the determination of DHA and three other fatty acids in eggs is thus presented.

Analytical Method Assessment for the Determination of DHA and Fatty Acids Present in Unextracted <i>Aurantiochytrium limacinum</i>Biomass

Research into long-chain polyunsaturated fatty acids (LC-PUFA), such as docosahexaenoic acid (DHA C22:6 n-3), has shown that their inclusion in the human diet is linked with many health benefits. This has led to an increased interest in the enrichment of certain foodstuffs with DHA by supplementing animal fed with DHA-rich ingredients which can lead to an increased uptake in the meat, milk and eggs animal by-products. The microalgae Aurantiochytrium limacinum has been found to be especially useful in this pursuit. It is subsequently desirable to availably have a simple and robust method for the routine analysis of DHA and other fatty acids in the algal biomass. The AOAC method 996.06 is often followed for the analysis of fatty acids in foods and demonstrating that its fitness for purpose in the analysis of DHA and additional fatty acids in Aurantiochytrium limacinum is therefore the objective of this paper. A validation of the method for the determination of DHA and three other fatty acids in Aurantiochytrium limacinum is presented. The method was found to be linear over the following ranges for each fatty acid methyl ester (FAME) analyte;50 to 15,000 μg/ml (C14:0), 300 to 95,000 (C16:0), 25 to 15,000 (C18:0) and 300 to 59,375 (C22:6). The accuracy, precision and LOD and LOQ of the method were confirmed and its robustness tested. The application of the method to assess the stability of Aurantiochytrium limacinum containing two alternative antioxidants was further examined. The investigation showed that DHA was stable over six months with the inclusion of either Duralox? or ethoxyquin as an antioxidant and ethoxyquin could additionally stabilize DHA in Aurantiochytrium limacinum up to 24 months.

The effect of ethanol on the habit and in vitro aerodynamic results of dry powder inhalation formulations containing ciprofloxacin hydrochloride

In the case of dry powder inhalation systems(DPIs),the development of carrierfree formulations has gained increased attention.Thereby,spray-drying is a promising technology and is widely used to produce carrier-free DPIs.Numerous works have been published about the co-spray-drying of active ingredients with various solid excipients and their effect on the physicochemical characteristics and aerodynamic properties of the formulations.However,only a few studies have been reported about the role of the solvents used in the stock solutions of spray-dried formulations.In the present work,DPI microcomposites containing ciprofloxacin hydrochloride were prepared by spray-drying in the presence of different ethanol concentrations.The work expresses the roughness,depth and width of the dimples for particle size as a novel calculation possibility,and as a correlation between the MMAD/D_(0.5)ratio and correlating it with cohesion work,these new terms and correlations have not been published–to the best of our knowledge–which has resulted in gap-filling findings.As a result,different proportions of solvent mixtures could be interpreted and placed in a new perspective,in which the influence of different concentrations of ethanol on the habit of the DPI formulations,and thus on in vitro aerodynamic results.Based on these,it became clear why we obtained the best in vitro aerodynamic results for DPI formulation containing 30%ethanol in the stock solution.

Identity and Safety of a Novel <i>Aurantiochytrium sp.</i>for Terrestrial Heterotrophic Docosahexaenoic Acid Production

The objective of the studies in this paper was to expand on the published toxicological assessment of Aurantiochytrium limacinum (AURA) with further strain characterization and to investigate the potential for the biomass or extracted oil to have antimicrobial properties or undesirable substances. AURA is being investigated as a novel source of the omega-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) for enriching foods of animal origin by means of feed supplementation. In the first studies, we provided the 18S rRNA identification of the novel marine isolated thraustochytrid, established the nutritional composition of AURA biomass for application as a food or feed ingredient including proximate analysis and fatty acid profiling, and confirmed the DHA production potential of the strain. We determined through minimum inhibitory concentration (MIC) analysis that the unextracted AURA biomass was safe, showing no antimicrobial influence and no evidence of any deleterious effects of this product or its extracts at concentrations up to 1% w/w on the reference human intestinal bacteria tested. This would indicate that AURA should not stimulate selective pressure on the commensal microbiota and is therefore unlikely to aid development of antimicrobial resistance and the concomitant harm to humans and animals. Further analysis revealed that the AURA biomass produced through industrial heterotrophic fermentation was free from undesirables;toxic marine microalgal metabolites, heavy metals, pesticides, microbial contaminants, and mycotoxins. Including heterotrophically-grown AURA in food or feed, up to 1% w/w, is a safe and environmentally beneficial strategy for DHA supplementation.