Influence of specific gravity and food on movement of granules in the gastrointestinal tract of rats

The suitability of rats as an animal model for estimating the bioavailability of controlled-release granules in humans was investigated. Non-disintegrating granules (diameter of 0.8 mm; specific gravity of 0.9-1.85) were used as a model preparation. Twenty granules were administered to fed rats, fasted rats and rats given soft food, and the number of granules remaining in the gastrointestinal tract was counted at suitable intervals. Granules with a specific gravity of 1.25 administered to fasted rats were rapidly emptied from the stomach with a 50% gastric emptying time of 1 h as compared with granules with a specific gravity of less than 1.0 or with a high specific gravity such as 1.85. The presence of food in the stomach reduced the emptying rate of granules. The mean transit time of granules through the small intestinal tract was not influenced by the specific gravity or the presence of food. The mean transit time was about 3 h. It was found that the transit profile of granules through the gastrointestinal tract in rats was similar to that of granules in humans. Accordingly, it is possible to use rats at the preformulation stage for estimating the bioavailability of controlled-release granules in humans.     

The pharmacokinetics study of ginkgolide A,B and the effect of food on bioavailability after oral administration of ginkgolide extracts in beagle dogs

Ginkgolides are the primarily active components in Ginkgo products that are popular worldwide. However, few studies have evaluated the bioavailability of ginkgolides and the effects of food on it after oral administration of ginkgolides. In this article, pharmacokinetics and absolute bioavailability of the primary components in ginkgolide extracts were evaluated in beagle dogs. For the first time, we showed that the fed dogs had significantly increased area under the concentration–time curve and peak concentration relative to the fasted dogs based on the data from both the prototype form and total lactones of ginkgolide A (GA) and ginkgolide B (GB). In terms of the free form of the prototype ginkgolides, the absolute bioavailabilities of GA and GB were 34.8 and 5.2% in the fasted dogs, respectively, which significantly increased to an average of 78.6 and 17.0%, respectively, in the fed dogs. In terms of acidified total lactones, the absolute bioavailabilities of GA and GB were 7.5 and 14.5% in the fed dogs, and the percentages declined to 4.1 and 3.7% in the fasted dogs, respectively. It was suggested that administration of ginkgolides after meals could promote the in vivo exposure and the bioavailability of GA and GB, and hence potentially enhance therapeutic outcomes.     

Bioavailability study of commercial sustained-release preparations of diclofenac sodium in gastrointestinal physiology regulated-dogs.

The gastrointestinal (GI) physiology of beagle dogs was regulated with a combined-treatment of intramuscular pentagastrin (10 micrograms/kg x 2) and intravenous atropine sulfate (0.02 mg/kg x 1). Here, the gastric acidity, the gastric emptying time and the small intestinal transit time in the regulated-dogs were respectively around pH 2, 0.7h and 4h, approximating those in healthy humans. The superiority of the regulated-dogs over the intact dogs was confirmed in comparative bioavailability studies by using two classes of commercial preparations. Both the conventional tablet and the sustained-release capsule of diclofenac sodium exhibited simple and similar average plasma concentration-time curves of free diclofenac in the intact dogs, while the latter preparation is reported to reveal a bimodal plasma curve of the drug in healthy humans. The regulated-dogs, however, permitted a bimodal average plasma pattern of the drug for the capsules due to an approximation of the GI physiology between humans and these classes of the dogs. The combined-treatment of beagle dogs with pentagastrin and atropine sulfate seems to supply a useful animal model in predicting the absorption characteristics of the sustained-release preparations and poor water-soluble drugs.     

Measurement of gastric pH during digestion of a solid meal in dogs

The behavior of gastric pH during digestion of a solid meal in beagle dogs was determined by use of an ion-selective field effect transistor pH sensor. The pH in the stomach was 3.9 +/- 0.4 (mean +/- S.D., n = 6) at 0.5 h after meals. It was maintained at a mildly acidic (about pH 3) level for long periods.     

Rapid residue analysis of fluoroquinolones in raw bovine milk by online solid phase extraction followed by liquid chromatography coupled to tandem mass spectrometry

Online solid phase extraction followed by liquid chromatography coupled to tandem mass spectrometry was used for the determination of 15 fluoroquinolones and one quinolone antibiotic in raw bovine and skimmed commercial milk. Milk samples were partially deproteinized and defatted by 15 min centrifugation and then subjected to online solid phase extraction. Chromatographic separation was achieved in less than 15 min. Identification and quantification of the compounds of interest were performed by selected reaction monitoring, using an electrospray ionization source. Relative recoveries were calculated for raw milk (at 0.5, 1 and 1.5 times the MRL, or assuming 30 ng/mL for non permitted compounds) and skimmed milk (at 30 ng/mL) and ranged between 65% and 123% (raw milk) or 78% and 109% (skimmed milk). Matrix interferences were also assessed and yielded significant suppression and enhancement effects, which, at the time of quantification, were corrected by the use of six isotopically labeled standards. Quality parameters of the method were established, and limits of detection of selected antibiotics in raw milk ranged from 0.01 to 1.93 ng/mL, while in skimmed milk from 0.03 to 4.23 ng/mL. The validation of the method has been carried out according to the requirements set by the 2002/657/EC regulation. Finally, the applicability of the method was tested by analysing 28 milk samples.     

Effect of small intestinal transit time on gastrointestinal absorption of 2-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-1-yl ] ethyl acetate, a new non-steroidal anti-inflammatory agent

The gastrointestinal absorption of 2-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-1- ly]ethyl acetate (1), a new non-steroidal anti-inflammatory agent was investigated in dogs. A method using acetaminophen and salicylazosulfapyridine as the markers (double-marker method) was applied to trace the gastrointestinal transit of orally dosed 1. The mean absorption time of acetaminophen in plasma was used as an indication of gastric emptying, and the first appearance time of sulfapyridine (a metabolite of salicylazosulfapyridine) in plasma was employed to detect the arrival of the marker to the colon. A remarkable inter-individual variation was observed in the absorption of 1. The extent of bioavailability was little affected by the gastric emptying time, but significantly influenced by the small intestinal transit time. Under a pretreatment with atropine, the transit time was prolonged to result in a significant enhancement of the bioavailability. Consequently, the absorption of 1 is confirmed to take place mainly in the small bowel.     

Use of isotopically labelled octanoic acid to assess the effect of meal size on gastric emptying

It has been proposed that the (13)C-octanoic acid breath test (OBT) provides a safe, non-radioactive means of measuring gastric emptying. However, deuterated octanoic acid provides a better marker when compared with scintigraphy, as the kinetics are less complex than those of the (13)C label. The appearance of (2)H in saliva is modelled as a two-compartment body water system, using an asymmetric triangular gastric emptying function. This study compared the (2)H-octanoic acid saliva test (OST) with the OBT in measuring altered states of gastric emptying in the nutritional context of diet manipulation. Gastric emptying was measured using the OST and OBT in a three-way crossover study involving 12 healthy male and female subjects (mean BMI = 23.4 kg/m(2), aged 24-57 years). Following an overnight fast, subjects were given an egg meal, labelled with 10 microL/kg body weight (2)H-octanoic acid and 100 microL (13)C-octanoic acid. The meal was nutritionally manipulated to provide a 1 MJ, 2 MJ or 3 MJ meal. Breath and saliva samples were collected at regular intervals for 6 h, with further saliva samples being collected over four subsequent days. (2)H isotopic enrichment in saliva and (13)C isotopic enrichment in breath were analysed using isotope ratio mass spectrometry and the data fitted to the respective gastric emptying models. The half excretion time (T(1/2) (D)), time to maximum emptying rate (T(1) (D)) and time when emptying is complete (T(2) (D)) were calculated from the (2)H saliva test data, and the lag time (T(lag) (C)), half excretion time (T(1/2) (C)), latency phase (T(lat) (C)) and ascension time (T(asc) (C)) were calculated from the (13)C breath test data. Overall, the OBT correlated well with the OST, with a significant relationship between T(1/2) (C) and T(1/2) (D), a significant relationship between T(lat) (C) and T(1) (D) and finally a significant relationship between T(asc) (C) and T(2) (D). Gastric emptying measured using the OST was significantly faster with the 1 MJ meal (DeltaT(1/2) (D) = -0.77 h vs. 2 MJ, p = 0.004). Increases were also seen when the meal size was increased from 2 MJ to 3 MJ (DeltaT(1/2) (D) = +0.44 h vs. 2 MJ), but these were not significant. These trends were mirrored in the OBT data, with significant differences between 1 MJ and 2 MJ (DeltaT(1/2) (C) = -0.63 h vs. 2 MJ, p = 0.013) and non-significant increases with the larger 3 MJ meal (DeltaT(1/2) (C) = +0.10 h vs. 2 MJ). Total meal calorie content was shown to have an effect on gastric emptying using both the OBT and the OST. The deuterium method allows the direct calculation of the gastric emptying function and could be used as an alternative to gamma scintigraphy, allowing further validation of the (13)C-octanoic acid breath test.     

Preconcentration of milk proteins using octadecylated monolithic silica microchip

Sample preparation is a bottleneck in systems for chemical analysis and it is a required step in order to remove interference and preconcentrate the target analytes. Much research in recent years has focused on porous monolithic materials since they are highly permeable to liquid flow and show high mass transfer compared with common packed beds. This study has focused on the use of a glass microchip containing an inorganic silica-based monolithic material modified with octadecyl groups for preconcentration of milk proteins from skimmed cows’ milk that vary in molecular weight, hydrophobicity, and abundance. Comparison between the fabricated device and a commercial cartridge for the preconcentration of proteins in skimmed cows’ milk showed the ability of the device to successfully enrich protein mixtures from the sample. The three replicate experiments showed that the RSD of the mass to charge ratio of milk proteins ranged from 0.01 to 0.46%. In addition, it was found that there were no significant differences between the observed and reported masses of the milk proteins and the relative percentage error of the molecular masses ranged between 0.03 and 0.90%. The fact that the small amounts of sample required and short sample preparation time suggest that this new microfluidic device may be a viable alternative to existing procedures for protein extraction from real samples.     

Determination of selected persistent organochlorine pollutants in human milk using solid phase disk extraction and narrow bore capillary GC-MS

Summary A simple and rapid procedure based on solid phase disk extraction (SPDE), adsorption chromatography on acidified silica gel and GC-MS analysis was developed for the determination of 8 organochlorine pesticides and 19 PCB congeners in human milk. By using the SPDE procedure, a high throughput and parallel sample processing could be achieved. Method variables were optimized on whole cow's milk (3.5% fat) fortified at levels close to concentrations found in human milk. Recoveries of target analytes were acceptable and ranged from 69 to 102% and 86 to 120% for whole and skimmed milk, respectively. By the use of two stage clean-up and narrow bore capillary columns, detection limits as low as 20 pg mL⁻¹ could be obtained. The method was used for the determination of organochlorine pollutants in human milk from 19 individuals from Romania. The concentrations of PCBs were low, whereas those of organochlorine pesticides were higher than the values reported from other European countries.     

Pyrolysis of meat-meal and bone-meal blends in a mechanically fluidized reactor

Nowadays, meat and bone meal produced in animal slaughterhouses and farms has become an important waste. Landfilling this residue means that its energy is lost. The pyrolysis of meat and bone meal produces a solid fraction which can be used as a fuel or as solid adsorbent, a liquid fraction with possible chemical applications and a low heating value gas.In this work, meat and bone meal has been pyrolyzed with a new technology, a mechanically fluidized reactor (MFR). This MFR is a stainless steel cylinder with 7.7 cm i.d., and an internal height of 15.6 cm. The meat and bone meal pyrolysis was carried out at 500 °C of temperature. The effect of several factors (mixer speed, heating rate and feed composition) on the product yields, bio-oil phases yield, bio-oil heating value and char heating value was studied. The amount of pure meat meal in the feed had a strong impact on product yields and compositions. The liquid yield, which has two phases, varies from 22 wt% to 52 wt% when the raw material fed changed from pure bone meal to pure meat meal.     

Ratios between content of fatty acids as markers for mixture of cow and goat milk

The fat of mixture of goat and cow milk, extracted by di-ethylic ether, was gas chromatographically analysed in order to propose an analytical procedure suitable to reveal small additions of cow milk to goat milk. The obtained results show evident differences in the percentages of some fatty acids. An attempt to apply the peak area ratios, corresponding to the methyl esters of fatty acids, suggested by the literature for cow milk did not yield good results. Other ratios suitable to reveal even the presence of low percentages (up to 5 %) of cow milk in goat milk were found and proposed in this paper. Such ratios are sensitive and can be defined markers towards cow or goat milk and also towards extraneous fat like lard or colza seeds oil.     

Gastrointestinal absorption of chlorothiazide: evaluation of a method using salicylazosulfapyridine and acetaminophen as the marker compounds for determination of the gastrointestinal transit time in the dog

Gastrointestinal absorption properties of chlorothiazide was investigated in dogs by a double-marker method using acetaminophen and salicylazosulfapyridine as the markers. The mean absorption time of acetaminophen (MATAAP) and the time for first appearance of sulfapyridine in plasma (TFASP) were used for the assessment of gastric emptying and oro-colonic transit times, respectively. Chlorothiazide absorption efficiency was increased by pretreatment with atropine sulfate. There was a good correlation between MATAAP and the extent of bioavailability of chlorothiazide, however, there was no correlation between TFASP and the extent of bioavailability of the drug. These results indicate that chlorothiazide absorption takes place primarily in a limited segment of the upper small intestine, supporting the assumption reported previously. This double-marker method seems to be a useful tool for the investigation of the relationship between drug absorption and its gastrointestinal transit.     

Rapid and quantitative detection of the microbial spoilage in milk using Fourier transform infrared spectroscopy and chemometrics

Microbiological safety plays a very significant part in the quality control of milk and dairy products worldwide. Current methods used in the detection and enumeration of spoilage bacteria in pasteurized milk in the dairy industry, although accurate and sensitive, are time-consuming. FT-IR spectroscopy is a metabolic fingerprinting technique that can potentially be used to deliver results with the same accuracy and sensitivity, within minutes after minimal sample preparation. We tested this hypothesis using attenuated total reflectance (ATR), and high throughput (HT) FT-IR techniques. Three main types of pasteurized milk - whole, semi-skimmed and skimmed - were used and milk was allowed to spoil naturally by incubation at 15 degrees C. Samples for FT-IR were obtained at frequent, fixed time intervals and pH and total viable counts were also recorded. Multivariate statistical methods, including principal components-discriminant function analysis and partial least squares regression (PLSR), were then used to investigate the relationship between metabolic fingerprints and the total viable counts. FT-IR ATR data for all milks showed reasonable results for bacterial loads above 10(5) cfu ml(-1). By contrast, FT-IR HT provided more accurate results for lower viable bacterial counts down to 10(3) cfu ml(-1) for whole milk and, 4 x 10(2) cfu ml(-1) for semi-skimmed and skimmed milk. Using FT-IR with PLSR we were able to acquire a metabolic fingerprint rapidly and quantify the microbial load of milk samples accurately, with very little sample preparation. We believe that metabolic fingerprinting using FT-IR has very good potential for future use in the dairy industry as a rapid method of detection and enumeration.     

Novel benzamides as selective and potent gastrokinetic agents. III. Synthesis and structure-activity relationships of 4-amino-5-chloro-2-methoxy- and 2-ethoxy-N-[(4-substituted 2-morpholinyl)methyl]-benzamides.

A series of 4-amino-5-chloro-2-methoxy- and 2-ethoxy-N-[(4-substituted 2-morpholinyl)methyl]benzamides (11-64) were prepared and evaluated for gastrokinetic activity by determining their effects on the gastric emptying of phenol red semisolid meal in rats. The N-4 substituent includes alkyl, phenoxyalkyl, (4-fluorobenzoyl)alkyl, and heteroarylmethyl groups. The benzamide derivatives, having an isopropyl, isoamyl, neopentyl, 3-(4-chlorophenoxy)-propyl, or pyridylmethyl group at N-4, showed potent in vivo gastric emptying activity. In particular, 4-amino-5-chloro-2-ethoxy-N-[[4-(3-pyridylmethyl)-2- morpholinyl]methyl]benzamide (57b) was equipotent to the 4-fluorobenzyl analogue 1b (AS-4370 as its citrate) in the gastrokinetic activity on phenol red semisolid meal in rats and mice, and on resin pellet solid meal in rats. Moreover, compound 57b was free from dopamine D2 receptor antagonistic activity in both in vitro ([3H]spiperone binding) and in vivo (apomorphine-induced emesis in dogs) tests. Structure-activity relationships of compounds with various substituents at N-4 are also discussed.     

Improvements to arapid method for separating strontium from liquid milk by treatment with a chelating resin and crown ethers

In an attempt to improve on a previously reported method¹ for rapidly isolating Sr from liquid milk, the following investigations have been carried out: (1) elution of strontium from a chelating resin with dilute nitric acid, (2) separation of strontium from calcium by extracting from this eluate into chloroform solutions of dicyclohexyl-18-crown-6 (DC18C6), (3) transfer of the strontium into aqueous solution, and (4) removal of barium from this solution by extracting into dichloromethane solutions of 21-crown-7 (21C7). Based on the findings of these studies, a separation scheme was proposed and tested by participating in an interlaboratory comparison on the analysis of⁸⁹Sr and⁹⁰Sr in skimmed milk. The separation scheme requires about 3 hours, provides strontium recoveries greater than 90%, and ensures adequate decontamination factors for the nuclides that occur in milk.     

膳食纤维降血脂作用及其机制的研究进展

综述了近年膳食纤维降脂作用及其机制的研究进展.膳食纤维能使血清中胆固醇、甘油三酯、低密度脂蛋白水平降低,高密度脂蛋白水平升高.其主要机制为通过减少膳食中胆固醇的吸收、影响机体中胆固醇的代谢、促进胆固醇的排泄等降低血浆中胆固醇水平;通过增加食物在肠道内的过渡时间、延缓胃排空、减缓或降低脂肪的吸收等机制降低血浆中甘油三酯水...     

Amine decorated 2d hexagonal and 3d cubic mesoporous silica nanoparticles: A comprehensive dissolution kinetic study in simulated and biorelevant media

Highly ordered Bexarotene (BXR) encapsulated mesoporous silica nanoparticles in particular bare and amine functionalized MCM-41 and MCM-48 were designed employing a novel impregnation solvent evaporation strategy. The outcomes unveiled successful synthesis of mesoporous assembly having 2?D hexagonal and 3?D cubic framework for MCM-41 and MCM-48 respectively withholding large surface area, optimum pore size, pore volume along with uniform particle size distribution. Additionally, SXRD and TEM findings divulged retention of characteristic mesoporous features regardless of surface modification and drug incorporation. Eventually the release profile and release kinetics results in different dissolution media demonstrated complete drug release in simulated intestinal fluid (SIF) within 75?min and 45?min from BXR-41 and BXR-48 along with 3.33 and 5 fold increment in dissolution profile. Furthermore, lack of any interaction between gelatin of hard capsule shell and amine group in presence of enzyme were justified from the indistinguishable release pattern in enzyme free and enzyme enriched SIF media. The divergent release pattern in fed and fasted state condition having a higher release in former media strongly directs towards taking medicine after meal. Finally the release kinetics study exhibited Weibull and Higuchi model as a best fit models for bare and amine coated BXR nanoparticles respectively.     

Determination of total basicity and available lysine in proteins by nonaqueous titrimetry

A simple method is presented for the determination of the available lysine residues of proteins. The sample is titrated directly with 0.05 or 0.1 M perchloric acid in anhydrous acetic or propionic acid to a potentiometric end-point. The titration is repeated after acylation of the sample. The difference between the two basicity values gives the available lysine content of the proteins. Results are provided for the available lysine contents of bovine serum albumin, human γ-globulin, β-casein, soya bean meals meat meal and milk protein; in most cases, they agree closely with literature data obtained by other methods. The standard error for the procedure is <3.9%.     

Direct atomic absorption determination of cadmium and lead in strongly interfering matrices by double vaporization with a two-step electrothermal atomizer

Thermal pretreatment of a sample using double vaporization in a two-step atomizer with a purged vaporizer makes possible the direct analysis of samples with strongly interfering matrices including solids. A porous-graphite capsule or a filter inserted into the vaporizer is used for solid sample analysis. The technique was used for the direct determination of Cd and Pb in human urine, potatoes, wheat, bovine liver, milk powder, grass–cereal mixtures, caprolactam, bituminous-shale and polyvinyl chloride plastic without chemical modification or any other sample pretreatment.     

Matrix removal for the ion chromatographic determination of some trace elements in milk

An ion chromatographic method has been developed for the determination of some microelements in different types of milk. It involves oxidative photodegradation of the organic matrix with H₂O₂ in a UV digester, equipped with a high-pressure mercury lamp. The temperature of the sample is maintained at 85±5 °C by a combined air/water cooling system. This procedure provides an efficient alternative to traditional dry ashing and wet digestion methods. Milk degrades in less than 2 h, while inorganic constituents, except for iodide, nitrate, nitrite, sulfite and manganese (II), are unaffected by UV radiation. Depending upon the type of milk (whole, skimmed, powdered, evaporated, etc.) to be analysed, the amount of sample and the UV photolysis time can be adjusted as per requirements. The clear solution resulting from the UV digestion is diluted, filtered and injected onto an ion chromatograph equipped with both conductivity and variable-wavelength UV-Vis detectors. The method has been tested with standards and real milk samples and has been found to be satisfactory for the determination of total chloride, bromide, phosphorus (as phosphate) and sulfur (as sulfate), and of copper, nickel, zinc, cobalt, iron and lead.