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The influence of gastric acidity and taste masking agent on in situ gelling pectin formulations for oral sustained delivery of acetaminophen.

Dilute solutions of pectin containing complexed calcium ions form gels when these ions are released in the acidic environment of the stomach. The aim of this study was to examine the influence of a variation of gastric pH and the addition of a taste masking agent on the gelation of the pectin solutions and on the in vitro and in vivo release of acetaminophen from the gels. Increase of pH above 2.5 and addition of 10% (w/v) D-sorbitol significantly affected the ability of 1.5% (w/v) pectin solutions to form coherent gels in vitro. Gelation of sorbitol-free formulations was observed at pH 1.2 and in vitro release of acetaminophen from the gels followed diffusion-controlled kinetics; in vitro gelation of these formulations, however, was incomplete at pH 3.0 resulting in poor sustained release characteristics. Inclusion of 10% (w/v) D-sorbitol in the formulations inhibited the in vitro gelation of the 1.5% (w/v) pectin sols and poor sustained release properties were noted from these formulations even at pH 1.2. The bioavailability of acetaminophen from gels formed in the stomach of gastric-acidity controlled rabbits following oral administration of the liquid formulations was not, however, significantly affected either by the inclusion of 10% (w/v) D-sorbitol or increase of pH to 3.6. Visual observation showed in situ gelation of 1.5% (w/v) pectin formulations containing D-sorbitol at pH 4.3 suggesting that normal variations of gastric acidity in the fasting state will have no effect on the bioavailability of acetaminophen when delivered using these formulations.

Acetaminophen↗

Reduction of catechin astringency by the complexation of gallate-type catechins with pectin.

The reductive effect of pectin on tea catechin astringency was investigated by using a taste sensor system and (1)H-NMR spectroscopy. The sensor analysis revealed that the astringency of gallate-type catechins (EGCg and ECg) was reduced by the addition of pectin, whereas that of non-gallate-type catechins (EGC and EC) hardly changed. Changes in the (1)H-NMR chemical shifts of the catechins and pectin in mixed solutions showed that the gallate-type catechins formed complexes with pectin more closely than the non-gallate-type catechins. These results demonstrate that complexation between the gallate-type catechins and pectin is a factor for reducing catechin astringency.

Biosensing Techniques↗

Occupational asthma caused by pectin inhalation during the manufacture of jam.

We report a case of pectin-induced occupational asthma in a 35-year-old man. His job involved mixing powdered pectin into a fruit puree during the manufacture of jam. Within minutes of adding pectin, he developed coryza, rhinorrhea, coughing, and wheezing. His symptoms cleared during weekends while away from work and improved with the use of a protective face mask at work. Peak flow rates were significantly lower while at work compared with those at home, and a prick skin test with the pectin powder was positive. We conclude that pectin should be added to the list of the substances known to induce occupational asthma.

Adult↗

Effects of pectin on glycaemia and insulinaemia after starch loading in normal, alloxan diabetic, and pancreatic duct-occluded rats.

In normal rats, and in rats with reduced intraluminal amylolytic activity, acute administration of low methoxyl pectin with soluble starch via an oro-gastric tube was found to delay starch digestion. In normal rats pectin slightly lowered plasma glucose levels after a starch load. In pancreatic duct-occluded rats, in which intestinal pancreatic digestive enzyme activities are markedly reduced, an increased insulin secretion and a reduced glucose response were seen after starch loading even without the addition of pectin, when compared to normal control rats. In these duct-occluded rats pectin was found to further reduce starch digestion, and markedly suppress plasma glucose levels after a starch load without changing plasma insulin levels. In moderately alloxan diabetic rats, in which intestinal amylase activity also was substantially reduced, pectin reduced the glucose response to starch to a similar extent (about 30%) as in duct-occluded rats without changing the impaired insulin response. The results suggest that pancreatic insufficiency accompanied by reduced intraluminal activities of pancreatic digestive enzyme activities may be associated with a decreased glucose and an increased insulin response to starch loading and that the ability of dietary fibre to reduce postprandial glycaemia may, inter alia, involve an inhibiting action by fibre on starch digestion, especially manifested in conditions of amylolytic insufficiency.

Amylases↗

Orally administered, insulin-loaded amidated pectin hydrogel beads sustain plasma concentrations of insulin in streptozotocin-diabetic rats.

We report successful oral administration of insulin entrapped in amidated pectin hydrogel beads in streptozotocin (STZ)-diabetic rats, with a concomitant reduction in plasma glucose concentration. The pectin-insulin (PI) beads were prepared by the gelation of humilin-pectin solutions in the presence of calcium. Separate groups of STZ-diabetic rats were orally administered two PI beads (30 micrograms insulin) once or twice daily or three beads (46 micrograms) once daily for 2 weeks. Control non-diabetic and STZ-diabetic rats were orally administered pectin hydrogel drug-free beads. By comparison with control non-diabetic rats, untreated STZ-diabetic rats exhibited significantly low plasma insulin concentration (0.32+/-0. 03 ng/ml, n=6, compared with 2.60+/-0.44 ng/ml in controls, n=6) and increased plasma glucose concentrations (25.84+/-1.44 mmol/l compared with 10.72+/- 0.52 mmol/l in controls). Administration of two PI beads twice daily (60 micrograms active insulin) or three beads (46 micrograms) once a day to STZ-diabetic rats increased plasma insulin concentrations (0.89+/-0.09 ng/ml and 1.85+/- 0.26 ng/ml, respectively), with a concomitant reduction in plasma glucose concentration (15.45+/-1.63 mmol/l and 10.56+/-0.26 mmol/l, respectively). However, a single dose of PI beads (30 micrograms) did not affect plasma insulin concentrations, although plasma glucose concentrations (17.82+/-2.98 mmol/l) were significantly reduced compared with those in untreated STZ-diabetic rats. Pharmacokinetic parameters in STZ-diabetic rats show that the orally administered PI beads (30 micrograms insulin) were more effective in sustaining plasma insulin concentrations than was s.c. insulin (30 micrograms). The data from this study suggest that this insulin-loaded amidated pectin hydrogel bead formulation not only produces sustained release of insulin, but may also reduce plasma glucose concentration in diabetes mellitus.

Administration, Oral↗

Interactions between food components and drugs. Part 8: Effect of pectins and bile acid preparations forming stable mixed micelles on transport of quinine in vitro.

Interactions between quinine and acetylated pectin, amidated pectin and pectin with blockwise arrangement of the free carboxyl groups as well as interactions between quinine and bile salt preparations forming stable mixed bicelles have been investigated. A diffusion cell with two compartments and an artificial lipid membrane and a filter-grown colon carcinoma cell line (Caco-2) have been used. Depending on structural parameters, pectin preparations diminished the rate of permeation of the drug. Above the critical micelle concentration, the bile salt preparations influence the quinine transport stronger than the pectin preparations. The strongest inhibition of the quinine permeation showed a stable mixed micelle preparation consisting of glycodeoxycholate, palmitic acid and lecithin. The Caco-2 cell line appears to be not as suitable as artificial lipid membranes to study drug transport in the presence of the bile salt preparations.

Antimalarials↗

[Oral administration of pectins for prophylaxis and treatment of purulent septic complications in patients with burns].

Clinical and laboratory evaluation of pectins application efficacy demonstrated that the patients treated with pectines has lower frequency of bacteriemia, intoxication, infectious complications and lethality. Pectins use per os resulted by acceleration of burns wounds healing and by lower microbial dissemination. Frequency of coagulase-positive staphylococci, streptococci and enterococci isolation was also lower in the treated group of patients when compared to the control group. Feces microbial profile also demonstrated positive trend--normal microflora (bifidobacteria and lactobacilli) enhanced, opportunistic bacteria diminished. Pectins application provided normalization of leucocytes, lymphocytes, B-lymphocytes, immunoglobulins A and G. The results of investigation demonstrated pectins efficacy at the complex treatment regimes of the patients with burns.

Adult↗

Effect of dietary alfalfa, pectin, and wheat bran on azoxymethane-or methylnitrosourea-induced colon carcinogenesis in F344 rats.

The effect of dietary alfalfa, pectin, and wheat bran on colon carcinogenesis was studied in female inbred F344 rats. Weanling rats were fed semipurified diets containing 0 or 15% alfalfa, pectin, or wheat bran. At 7 weeks of age, all animals except controls were given azoxymethane (AOM) sc at a dose rate of 8 mg/kg body weight/week for 10 weeks or methylnitrosourea (MNU) intrarectally at a dose rate of 2 mg/rat twice a week for 3 weeks. The AOM-treated group was autopsied 40 weeks and the MNU-treated group 30 weeks after the first injection of the carcinogen. No tumors were observed in the colon or other organs of untreated rats fed the various diets. The animals fed the alfalfa diet and treated with MNU had a higher incidence of colon tumors than did those fed the control diet or the diets containing pectin or wheat bran. The incidence of MNU-induced colon tumors did not differ between the animals fed the control diet or the diets containing pectin or wheat bran. However, the incidence of AOM-induced colon tumors in rats fed diets containing pectin or wheat bran was lower than that in rats fed the control diet or the alfalfa diet. These results thus indicate that the effect of fiber in colon carcinogenesis depends on the type of fiber and, possibly, the fiber's mode of action.

Animals↗

Trial of pectin-enriched muffins in patients with severe dumping syndrome after gastric resection. Observations on symptoms and gastric emptying pattern.

Pectin is known to delay gastric emptying and alleviate dumping symptoms when ingested with hyperosmolar, glucose-containing meals. As the treatment of dumping syndrome includes frequent, small dry meals, the effect of pectin ingested in muffins was tested in five patients with severe, intractable dumping syndrome after gastric resection. Ingestion of 99mTc-DTPA-labelled muffins containing 5 g pectin did not alleviate dumping symptoms or delay gastric emptying compared with muffins without pectin. Pectin does not seem to be beneficial as a supplement in the conventional dietary management of post-gastrectomy dumping.

Aged↗

[Plasma insulin and glucagon after ingestion of meal enriched with increased doses of pectin in healthy man].

The effects of three doses of pectin (5, 10 and 15 g) included in a solid-liquid meal on the postprandial plasma insulin and glucagon responses were studied in 12 healthy men. The mean plasma glucagon level was significantly smaller with 5 g of pectin than the control values at 150 min (p less than 0.05) whereas plasma insulin values did not vary. No change in mean plasma glucagon and insulin levels was noted with 10 g and 15 g of pectin although the mean blood glucose levels were significantly higher than the control values at 180 min (p less than 0.05). Addition of pectin to a meal, even if the doses were relatively important, had little or no effect on the postprandial hormonal responses in healthy men. However, pectin could be of renewed interest because of the possibility of its action of satiety by means of sustained late blood glucose levels.

Adult↗

The effect of enteral feedings supplemented with pectin on the healing of colonic anastomoses in the rat.

The effect of the addition of pectin to an elemental diet on the healing of experimental colonic anastomoses was investigated. Transection and anastomosis of the ascending colon and feeding gastrostomy were performed in 24 Sprague-Dawley rats. All rats then received an elemental diet, and 12 of them had 1% (w/v) citrus pectin added to their diet. On the seventh postoperative day, animals that received pectin-supplemented diets had significantly greater bursting pressures at the anastomoses (266 versus 234 mm Hg, p less than 0.04) and significantly lower colonic mucosal pH (6.2 versus 6.8, p less than 0.001) than animals that received the elemental diet only. The colons from animals fed pectin also had significantly higher hydroxyproline content at the anastomosis than those of the control animals (46.6 versus 40.7 micrograms hydroxyproline nitrogen/mg tissue nitrogen, p less than 0.05). The decreased intracolonic pH is consistent with the hypothesis that improved healing is a local effect mediated by the presence of short-chain fatty acids resulting from the fermentation of pectin.

Animals↗

Hypocholesterolemic agents: a comparison of the relative effectiveness of cholestyramine and pectin in rats.

Studies were carried out to evaluate the comparative effectiveness of cholestyramine and pectin as hypocholesterolemic agents. Circulating levels of serum cholesterol and lipoprotein-associated cholesterol were measured in rats fed high cholesterol diet supplemented with either cholestyramine or pectin. When compared with controls, a significant decrease in the level of total cholesterol was observed in rats fed either cholestyramine or pectin (p less than 0.001, 43% reduction in cholesterol, and p less than 0.04, 25% reduction in cholesterol, respectively) and this was due exclusively to the lowering of low density lipoprotein. Further statistical evaluation of data revealed no significant difference between the cholesterol levels of rats fed either cholestyramine or pectin (p greater than 0.07). The data acquired in this study suggest that both cholestyramine and pectin are comparable and effective hypocholesterolemic agents and the observed hypocholesterolemic effect of these agents is mediated through lowering of cholesterol associated with the low density lipoprotein.

Animals↗

The effect of pectin and wheat bran on platelet function and haemostatis in man.

The hypothesis that dietary fibre might protect against the development of ischaemic heart disease through an effect on platelet aggregation and blood clotting has been tested in eleven healthy volunteers. In two separate studies the effect of pectin and wheat bran has been measured in subjects living on controlled diets in a metabolic suite. In the pectin study volunteers consumed a basal diet, typical of that normally eaten in the UK, for 6 weeks but for one 3-week period took an additional 36 g/d pectin (Bulmers Firmagel--high methoxy pectin). Although serum cholesterol concentrations were significantly lowered (5.73 +/- 0.36 mmol/l control; 5.18 +/- 0.35 mmol/l + pectin, P less than 0.025), platelet aggregation, platelet fatty acid composition, dilute blood clot lysis time and bleeding times were unaltered. In a similar study in which the volunteers took white bread for 3 weeks and brown and wholemeal breads for a further 3 weeks each, no change was seen in platelet function or in haemostasis. It is concluded that if dietary fibre does protect against heart disease it is probably not through an effect on platelet aggregation or haemostasis.

Adult↗

Effects of purified cellulose and pectin fiber diets on mutagenicity of feces and luminal contents of stomach, small and large bowel in rats.

The mutagenicity in extracts of fecal pellets and luminal contents obtained from specific sites along the gastrointestinal tract was examined in male Wistar rats fed a chemically-defined fiber-free diet or nutritionally and calorically equivalent diets containing different amounts of either cellulose or pectin (4.5 or 9.0%) or a mixture of cellulose and pectin (4.5% each). Mutagenicity was measured with the fluctuation test for weak mutagens using Salmonella typhimurium strains TA98 and TA1535 as test organisms. Dietary fiber reduced the mutagenicity of fecal pellets from most of the animals. However, given the number of animals studied, the reduction was only significant for the 9.0% pectin diet (TA98), the 9.0% cellulose diet (TA1535) and the mixed fiber diet (TA1535). Analysis of the contents of stomach, distal small bowel, cecum and colon after a period of 8 weeks on a fiber-free diet revealed that the distal small bowel content had a mutagen concentration that was several times that at any other site. The mutagenicity of the small bowel content of animals on diets containing either 9.0% cellulose or 9.0% pectin was significantly lower than that of animals on a fiber-free diet, as assayed by either of the test strains of S. typhimurium. A similar reduction was detected in animals on the 4.5% cellulose or 4.5% pectin diet by test strain TA1535, but a diet containing a mixture of the same fiber polymers did not reduce the mutagenicity of the small bowel content. The mutagenicity of the contents of the stomach, cecum and colon was not significantly influenced by dietary fiber.

Animals↗

[Protein isolation by means of complexing agents. 2. Formation of insoluble complexes of sunflower albumins with alginate or pectin].

The formation of insoluble complexes of sunflower seed albumin and alginate or pectin is studied by means of turbidimetric titration and by determining the pH-dependent precipitability of protein. The complex formation that is based on electrostatic interaction is a function of the pH value and the protein-polyanion ratio. Consequently, it is affected by the neutral salt content of the solutions. 90% and more of the dissolved protein may be precipitated if the proportion of the precipitant amounts to 20%. A sodium chloride content of 0.6% reduces the precipitability by alginate to 74%. In the presence of 0.3% sodium chloride, at most 55% of protein are still precipitated by pectin. The difference in strength between the albumin-alginate and the albumin-pectin complex is also expressed by the dye-binding power. Albumin-pectin complexes bind the same amount of amido black as free protein. On the contrary, albumin-alginate complexes exhibit reduced dye-binding power due to stronger binding of the protein to the polyanion. The results obtained by turbidimetric titration of model systems can, in principle, be extrapolated to the precipitation of albumins from protein extracts. In accordance with the heterogenicity of the protein, the turbidimetric titration of the albumin-alginate and the albumin-pectin complexes exhibits two maxima.

Albumins↗

Effect of pectin on some electrolytes and trace elements in patients with hyperlipoproteinemia.

BACKGROUND: Water-soluble dietary fibres are widely used in preventive and curative nutrition, especially in cases of hyperlipoproteinemia. Occurrence of disturbances of the electrolyte and trace element metabolism causing adverse effects in long-term treatment with pectin can be theoretically substantiated. METHODS: Seventy three patients with hyperlipoproteinemia, aged from 40 to 69 years, were included in the study. They were treated with a natural product, based on high-esterified pectin granulated with sorbitol. The patients were examined prior to the treatment and once monthly during the three-month course of therapy. RESULTS: The results of the comparative assessment of the electrolytes (sodium, potassium, chloride, ionised calcium, total and ionised magnesium) failed to reach statistical significance during the administration of the pectin product. Neither did the serum level of trace elements (iron and copper) change significantly during the observed period. CONCLUSIONS: The biochemical analysis of the serum level of certain electrolytes and trace elements indicate that daily administration of 15 g of high-esterified apple pectin for a three-month period has no adverse effects. Therefore pectin products can be included in the therapeutic schedule in the treatment of hyperlipoproteinemia.

Adult↗

Effects of orange and apple pectin on cholesterol concentration in serum, liver and faeces.

To investigate the effects of pectin on cholesterol metabolism, normal rats were fed for three weeks a diet containing 2.5 or 5 % apple or orange pectin, or without pectin (control). Cholesterol concentrations were determined in faeces after 1, 2 and 3 weeks of treatment, and in liver and serum at the end of the experimental trials. Cholesterol concentration in faeces showed a significant increase by week 3 in rats fed 5 % orange or apple pectin. Hepatic cholesterol concentration declined significantly in all pectin-fed groups. Serum cholesterol only declined significantly in apple-fed groups. The decrease of cholesterol levels in liver and serum, and its increase in faeces could explain the beneficial effect of including these fibers in the diet to prevent some nowadays very frequent diseases.

Animals↗

Pectin methyl esterase from orange fruit: characterization and localization by in-situ hybridization and immunohistochemistry.

Pectin methyl esterase (PME) from orange (Citrus sinensis L.) fruit peels has been purified by ammonium sulphate precipitation, and ion-exchange and gel-filtration chromatography. Characterization of the enzyme revealed a 36-kDa protein with an isoelectric point > 9, a pH optimum at 7 and temperature optimum at 50 degrees C. The substrate specificity and kinetic experiments showed that the affinity of PME for pectin was highly dependent on the degree of esterification (DE) of the pectin, with K(m) values of 0.7 mg ml-1 for pectin with a DE of 70% and 17 mg ml-1 for pectin with a DE of 25%. The sequences of the NH2-terminal end of digested peptides from the mature protein were obtained. A DNA fragment of 501 bp was cloned by polymerase chain reaction amplification using degenerate primers and was further used for screening of a cDNA library. Two cDNA clones were isolated encoding PMEs of 584 amino acids and 362 amino acids, respectively, including a putative signal peptide. The deduced amino acid sequence showed full identity to the sequenced peptides. Polyclonal antibodies raised against orange peel PME were used for immunohistochemistry. The main localization of PMEs was in the outer cell layers of the juice vesicles, in the outer cell layers of the lamellae between the segments and in the inner cell layers of the albedo in the peel. In-situ hybridization showed that the mRNA is very abundant in the fruit and was found in the same cell layers as the native enzyme. A very intensive staining for PME mRNA was also seen in the core and in the flavedo close to the oil glands.

Amino Acid Sequence↗