Intraluminal pH of Duodenum and Jejunum in Fasting Subjects with Normal and Abnormal Gastric Or Pancreatic Function

Benn, Ann; Cooke, W. T.

doi:10.3109/00365527109181126

Cited by 55 publications

(19 citation statements)

References 12 publications

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“…The diversity in molecular masses found after reduction suggests that the 'large fragment' is not a single unique combination of disulphide-linked peptides but rather a complex mixture. Nevertheless, these data indicate that peptides MSECCEQLEG(9-18), DESCRCEGLRMM (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) and AENIPSRCNL SPMRCPMGGS(54-73) (of total mass 4675 Da) are probably the main components of this fragment. Figure 6A shows the potential cleavage sites of pepsin defined by the peptide cutter tool of ExPASy (http:// us.expasy.org/tools/peptidecutter/).…”

Section: Identification Of Peptides Resulting From Digestionmentioning

confidence: 93%

“…Peptide peak 1 contained one mass, and peak 2 contained two masses that probably correspond to peptides derived from DESCRCEGLRMM (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) of the large subunit (Table 1). Pepsinolysis removed either the N-terminal Asp or the C-terminal Met, giving rise to peptides ESCRCEGLRM (21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and ESCRCE GLRMM(21-31), respectively.…”

Section: Identification Of Peptides Resulting From Digestionmentioning

confidence: 99%

“…Pepsinolysis removed either the N-terminal Asp or the C-terminal Met, giving rise to peptides ESCRCEGLRM (21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and ESCRCE GLRMM(21-31), respectively. These removals imply differences of 246 and 115 atomic mass units; such variations were also found in the peak corresponding to the large fragment under nonreducing conditions (Table 2), again supporting the conclusion that these peptides make up part of the 'large fragment'.…”

Section: Identification Of Peptides Resulting From Digestionmentioning

confidence: 99%

“…The predicted C-terminal fragment of the small subunit originating from pepsinolysis SHCRMYMRQQMEES (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) would have a molecular mass of 1815. When added to the other three peptides described above, it would give rise to a fragment of total mass 6484 Da (taking into account disulphide bond formation), which corresponds closely to the major molecular mass found in the 'large fragment' peak under nonreducing conditions (Table 2).…”

Section: Identification Of Peptides Resulting From Digestionmentioning

confidence: 99%

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Stability of the major allergen Brazil nut 2S albumin (Ber e 1) to physiologically relevant in vitro gastrointestinal digestion

et al. 2004

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2S storage albumins occur in a diverse range of plant seeds, are members of the prolamin superfamily [1] and constitute one of the most important major plant food allergens that sensitize via the gastrointestinal (GI) tract [2]. Among the tree nuts, Brazil nut is frequently associated with immunoglobulin E (IgE)-mediated food allergy [3], the 2S albumin, known as Ber e 1, being the major allergen [4]. 2S albumins are considered to be structurally homologous, typically heterodimeric (small and large subunits of 4000 and 9000 M r , respectively) globular proteins. They have a conserved skeleton of cysteine residues (typical of members of the prolamin superfamily), which form four intermolecular disulphide bonds that hold the two subunits together and contribute to their stability and compactness [5]. This rigid The major 2S albumin allergen from Brazil nuts, Ber e 1, was subjected to gastrointestinal digestion using a physiologically relevant in vitro model system either before or after heating (100°C for 20 min). Whilst the albumin was cleaved into peptides, these were held together in a much larger structure even when digested by using a simulated phase 1 (gastric) followed by a phase 2 (duodenal) digestion system. Neither prior heating of Ber e 1 nor the presence of the physiological surfactant phosphatidylcholine affected the pattern of proteolysis. After 2 h of gastric digestion, 25% of the allergen remained intact, 50% corresponded to a large fragment of M r 6400, and the remainder comprised smaller peptides. During duodenal digestion, residual intact 2S albumin disappeared quickly, but a modified form of the 'large fragment' remained, even after 2 h of digestion, with a mass of 5000 Da. The 'large fragment' comprised several smaller peptides that were identified, by using different MS techniques, as deriving from the large subunit. In particular, sequences corresponding to the hypervariable region (Q37-M47) and to another peptide (P42-P69), spanning the main immunoglobulin E epitope region of 2S albumin allergens, were found to be largely intact following phase 1 (gastric) digestion. They also contained previously identified putative T-cell epitopes. These findings indicate that the characteristic conserved skeleton of cysteine residues of 2S albumin family and, particularly, the intrachain disulphide bond pattern of the large subunit, play a critical role in holding the core protein structure together even after extensive proteolysis, and the resulting structures still contain potentially active B-and T-cell epitopes.Abbreviations GI, gastrointestinal; IgE, immunoglobulin E; SGF, simulated gastric fluid; PtdCho, egg l-phosphatidylcholine.

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Section: Identification Of Peptides Resulting From Digestionmentioning

confidence: 93%

Section: Identification Of Peptides Resulting From Digestionmentioning

confidence: 99%

Section: Identification Of Peptides Resulting From Digestionmentioning

confidence: 99%

Section: Identification Of Peptides Resulting From Digestionmentioning

confidence: 99%

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Stability of the major allergen Brazil nut 2S albumin (Ber e 1) to physiologically relevant in vitro gastrointestinal digestion

et al. 2004

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“…With the relatively low buffer capacity of FaSSIF, pH 6.5, this would have not been possible since the resulting pH was measured to be pH ∼3. As the neutralizing capacity of the duodenum is relatively high and, with a normal pancreatic function in vivo, the average duodenal/jejunal pH range is rapidly attained (12), a pH of ∼3 would not be representative for our purpose. Moreover, such a low pH could contribute to the presence of the ionized and more soluble form of the drug and, thus, affect precipitation.…”

Section: Methodsmentioning

confidence: 99%

Miniaturized Transfer Models to Predict the Precipitation of Poorly Soluble Weak Bases upon Entry into the Small Intestine

Klein

Buchanan

2012

AAPS PharmSciTech

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Abstract. For poorly soluble weak bases, the possibility of drug precipitation upon entry into the small intestine may affect the amount of drug available for uptake through the intestinal mucosa. A few years ago, a transfer model was introduced which has been developed to simulate the transfer of a dissolved drug out of the stomach into the small intestine. However, this setup requires the use of clinically relevant doses of the drug, which are typically not available in the early stages of formulation development. The present series of tests was performed to check whether it is possible to create a miniaturized but physiologically relevant transfer model that can be applied in the early formulation development. Experiments were performed with two miniaturized setups: a 96-well plate model and a mini-paddle transfer system. Itraconazole and tamoxifen were used as model drugs. An appropriate amount of each drug formulation was dissolved in simulated gastric fluid and then transferred into an acceptor phase consisting of fasted/fed state simulated small intestinal fluid. The amount of drug dissolved in the acceptor phase was monitored over a period of 4 h. Results from both setups were very similar. The tamoxifen preformulation did not precipitate, whereas the itraconazole formulation precipitated to the same extent in both setups. Due to the possibility of generating physiologically relevant results but using smaller sample sizes and smaller volumes of media, both miniaturized transfer systems offer various advantages in terms of substance and analytical and material cost savings when evaluating the precipitation potential of poorly soluble weakly basic drug candidates.

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Pathophysiology of the Exocrine Pancreas

Wormsley¹

1976

Pankreas

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Intraluminal pH of Duodenum and Jejunum in Fasting Subjects with Normal and Abnormal Gastric Or Pancreatic Function

Cited by 55 publications

References 12 publications

Stability of the major allergen Brazil nut 2S albumin (Ber e 1) to physiologically relevant in vitro gastrointestinal digestion

Stability of the major allergen Brazil nut 2S albumin (Ber e 1) to physiologically relevant in vitro gastrointestinal digestion

Miniaturized Transfer Models to Predict the Precipitation of Poorly Soluble Weak Bases upon Entry into the Small Intestine

Pathophysiology of the Exocrine Pancreas

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