Gastric pH Values Research Articles

Multiscale structure analysis of a pH-responsive gelatin/hydroxypropyl methylcellulose phthalate blend using small-angle scattering

HypothesisHydroxypropyl methylcellulose phthalate (HPMCP) is an enteric polymer that has been employed in drug delivery systems to delay the release of the encapsulated active pharmaceutical ingredients through its pH-responsive solubility change. This has been recently demonstrated as an effective means for delaying the drug release from gelatin/HPMCP hydrogels at gastric pH values. However, structural characteristics of HPMCP agglomeration in gelatin/HPMCP hydrogels is not well understood thus limiting further tailoring of their material properties. ExperimentsWe investigated the multiscale structure of a gelatin/HPMCP hydrogel (1:1 by weight) between pH 2 and 6 at 37 °C, i.e. above the upper critical solution transition temperature of gelatin, using small-angle X-ray scattering and contrast-variation small-angle neutron scattering to understand the pH-responsive structure of HPMCP and the cross-correlation between gelatin and HPMCP. FindingsAgglomeration of HPMCP between pH 2 and 4 was evidenced by the formation of mass fractal structures, with a fractal dimension ranging from 1.5 to 2.7, comprising primary particles with a radius of gyration ranging from 70 to 140 Å. Blending with gelatin influenced the fractal structure of HPMCP and the primary particle size. Gelatin and HPMCP exhibited negative cross-correlation in all probed length scales and pH values, which was attributed to volume-exclusion interaction in a double-network-like solution architecture.

Evaluation of Gastric pH and Gastrin Concentrations in Horses Subjected to General Inhalation Anesthesia in Dorsal Recumbency.

The prevalence of gastric disorders in high-performance horses, especially gastric ulceration, ranges from 50 to 90%. These pathological conditions have negative impacts on athletic performance and health. This study was designed to evaluate changes in gastric pH during a 24 h period and to compare gastrin concentrations at different time points in horses undergoing general inhalation anesthesia and dorsal recumbency. Twenty-two mixed-breed mares weighing 400 ± 50 kg and aged 8 ± 2 years were used. Of these, eight were fasted for 8 h and submitted to 90 min of general inhalation anesthesia in dorsal recumbency. Gastric juice samples were collected prior to anesthesia (T0), and then at 15 min intervals during anesthesia (T15-T90). After recovery from anesthesia (45 ± 1 min), samples were collected every hour for 24 h (T1 to T24) for gastric juice pH measurement. During this period, mares had free access to Bermuda grass hay and water and were fed a commercial concentrate twice (T4 and T16). In a second group (control), four non-anesthetized mares were submitted to 8 h of fasting followed by nasogastric intubation. Gastric juice samples were then collected at T0, T15, T30, T45, T60, T75, and T90. During this period, mares did not receive food or water. After 45 min, mares had free access to Bermuda grass hay and water, and gastric juice samples were collected every hour for four hours (T1 to T4). In a third group comprising ten non-fasted, non-anesthetized mares with free access to Bermuda grass hay and water, gastric juice samples were collected 30 min after concentrate intake (T0). In anesthetized mares, blood gastrin levels were measured prior to anesthesia (8 h fasting; baseline), during recovery from anesthesia, and 4 months after the anesthetic procedure, 90 min after the morning meal. Mean values of gastric juice pH remained acidic during general anesthesia. Mean pH values were within the physiological range (4.52 ± 1.69) and did not differ significantly between time points (T15-T90; p > 0.05). After recovery from anesthesia, mean gastric pH values increased and remained in the alkaline range throughout the 24 h period of evaluation. Significant differences were observed between T0 (4.88 ± 2.38), T5 (7.08 ± 0.89), T8 (7.43 ± 0.22), T9 (7.28 ± 0.36), T11 (7.26 ± 0.71), T13 (6.74 ± 0.90), and T17 (6.94 ± 1.04) (p < 0.05). The mean gastric juice pH ranged from weakly acidic to neutral or weakly alkaline in all groups, regardless of food and water intake (i.e., in the fasted, non-fasted, and fed states). Mean gastric pH measured in the control group did not differ from values measured during the 24 h post-anesthesia period or in the non-fasted group. Gastrin concentrations increased significantly during the post-anesthetic period compared to baseline (20.15 ± 7.65 pg/mL and 15.15 ± 3.82 pg/mL respectively; p < 0.05). General inhalation anesthesia and dorsal recumbency did not affect gastric juice pH, which remained acidic and within the physiological range. Gastric juice pH was weakly alkaline after recovery from anesthesia and in the fasted and fed states. Serum gastrin levels increased in response to general inhalation anesthesia in dorsal recumbency and were not influenced by fasting. Preventive pharmacological measures are not required in horses submitted to general anesthesia and dorsal recumbency.

Survival and Expression of rpoS and grxB of Cronobacter sakazakii in Powdered Infant Formula Under Simulated Gastric Conditions of Newborns

Cronobacter sakazakii can cause severe illnesses in infants, predominantly in preterm newborns, with consumption of contaminated powdered infant formula (PIF) being the major vehicle of infection. Using a dynamic human gastrointestinal simulator called the SHIME, this study examined the effects of gastric acidity and gastric digestion time of newborns on the survival and expression of stress genes of C. sakazakii. Individual strains, inoculated at 7 log CFU/mL into reconstituted PIF, were exposed to gastric pH values of 4.00, 5.00 and 6.00 for 4 h with gradual acidification. The survival results showed that C. sakazakii grew in the stomach portion of the SHIME during a 4-h exposure to pH 4.00, 5.00 and 6.00 by 0.96–1.05, 1.02–1.28 and 1.11–1.73 log CFU/mL, respectively. The expression of two stress genes, rpoS and grxB, throughout gastric digestion was evaluated using reverse transcription qPCR. The upregulation of rpoS and grxB during the 4-h exposure to simulated gastric fluid at pH 4.00 showed that C. sakazakii strains may be experiencing the most stress in the pH 4.00 treatment. The gene expression results also suggest that C. sakazakii strains appeared to develop an acid adaptation response during the 4-h exposure that may facilitate their survival. Altogether, this study highlights that a combination of low gastric acidity, long digestion time in the presence of reconstituted PIF, created a favorable environment for the adaptation and survival of C. sakazakii in the simulation of a newborn’s stomach. This study gives directions for future research to further advance our understanding of the behavior of C. sakazakii in the GI tract of newborns.

Gastric residual volume, safety, and effectiveness of drinking 250 mL of glucose solution 2-3 hours before surgery in gastric cancer patients: a multicenter, single-blind, randomized-controlled trial.

Carbohydrate drinking 2-3 hours before surgery has been widely adopted in colorectal operations. However, there is little direct evidence regarding its application in gastric cancer surgery. We aimed to evaluate the gastric residual volume, safety, and effectiveness of drinking 250 mL of 5% glucose solution 2-3 hours before elective gastric cancer surgery. We conducted an investigator-initiated, multicenter, randomized-controlled, parallel group, and equivalence trial. Eighty-eight patients with gastric adenocarcinoma were randomized into study or control group. Patients in the control group followed the traditional routine of 6-8 hours preoperative fasting, while those in the study group drank 250 mL of 5% glucose solution 2-3 hours before surgery. Immediately following tracheal intubation, gastric contents were aspirated through gastroscopy. The primary outcome was preoperative gastric residual volume. Eighty-three patients were eventually analysed in the study (42 in the study group and 41 in the control group). Two groups were comparable at baseline characteristics. There were no statistical differences in residual gastric fluid volumes (35.86 ± 27.13 vs 27.70 ± 20.37 mL, P = 0.135) and pH values (2.81 ± 1.99 vs 2.66 ± 1.68, P = 0.708) between the two groups. Preoperative discomfort was significantly more decreased in the study group than in the control group (thirst score: 1.49 ± 1.23 vs 4.14 ± 2.07, P < 0.001; hunger score: 1.66 ± 1.18 vs 3.00 ± 2.32, P = 0.007). There was no statistical difference in the incidence of postoperative complications (19.05% vs 17.07%, P = 0.815). Drinking 250 mL of 5% glucose solution 2-3 hours before surgery in elective gastric cancer patients shows benefits in lowering thirst and hunger scores without increasing gastric residual volume and perioperative complications.

Huang-Qi-Jian-Zhong-Tang accelerates healing of indomethacin-induced gastric ulceration in rats via anti-inflammatory and antioxidant mechanisms

Ethnopharmacological relevanceHuang-Qi-Jian-Zhong-Tang (HQJZT) is a canonical traditional Chinese medicine (TCM) formula that has been widely used in both the prevention and treatment of gastrointestinal diseases, including gastric ulcer, duodenal ulcer, and chronic atrophic gastritis, in China. Aim of the studyIn the present study, we investigated the gastroprotective potential of HQJZT in a rat model of indomethacin (IND)-induced gastric ulcer and explained the biochemical, cellular, and molecular mechanisms involved. Materials and methodsObservations were conducted at the macroscopic level to ascertain the ulcer index (UI) and the curative index (CI). Histopathological examinations were conducted, and a microscopic score (MS) was computed. The gastric juice volume, total acidity, pH value, and pepsin activity were quantified. Antioxidant and oxidative parameters were assessed, namely GSH, CAT, SOD, and MDA content. The RFLSI Pro instrument was employed to measure the blood flow within the gastric mucosa continuously. The mRNA levels of the inflammatory cytokines were assessed using droplet digital PCR (ddPCR). Molecular docking was employed to examine the interaction between representative active components of HQJZT and the binding sites associated with the NF-κB and STAT signaling pathways. The protein expression and localization of p-JAK, p-STAT, p-IκBβ, and p–NF–κB were evaluated through immunofluorescence analysis. ResultsThe administration of HQJZT treatment demonstrated a significant reduction in gastric lesions induced by IND, leading to a notable decrease in the UI. Additionally, HQJZT treatment significantly decreased gastric juice volume, acidity, and pepsin activity, accompanied by increased pH value. IND-treated stomachs exhibited severe hemorrhagic necrosis, submucosal edema, and epithelial cell destruction. However, the administration of HQJZT effectively counteracted these pathological changes. Furthermore, HQJZT administration significantly increased blood flow to the gastric mucosa. HQJZT enhanced antioxidant defenses and modulated oxidative stress by increasing SOD, CAT, and GSH activities while reducing MDA levels. Moreover, HQJZT reversed IND-induced increases in mRNA expression levels of inflammatory cytokines. Molecular docking analysis revealed that the representative active components of HQJZT could bind to the NF-κB and STAT signaling pathways. In addition, immunofluorescence microscopy revealed that HQJZT markedly attenuated the phosphorylation of IκΒβ, NF-κB, JAK, and STAT. ConclusionsThe therapeutic and protective effect of HQJZT on gastric ulcers is attributed to its ability to suppress gastric acid secretion, enhance antioxidative defenses and blood flow, mitigate proinflammatory cytokines, and inhibit the activation of NF-κB and STAT signaling pathways.

Novel Natrosol/Pectin-co-poly (acrylate) based pH-responsive polymeric carrier system for controlled delivery of Tapentadol Hydrochloride

Background & ObjectivesThis study aimed to create a controlled delivery system for Tapentadol Hydrochloride by developing interpenetrating networks (IPNs) of Natrosol-Pectin copolymerized with Acrylic Acid and Methylene bisacrylamide, and to analyze the effects of various ingredients on the physical and chemical characteristics of the IPNs. MethodsNovel Tapentadol Hydrochloride-loaded Natrosol-Pectin based IPNs were formulated by using the free radical polymerization technique. Co-polymerization of Acrylic Acid (AA) with Natrosol and Pectin was performed by using Methylene bisacrylamide (MBA). Ammonium persulfate (APS) was used as the initiator of crosslinking process. The impact of ingredients i.e. Natrosol, Pectin, MBA, and Acrylic Acid on the gel fraction, porosity, swelling (%), drug loading, and drug release was investigated. FTIR, DSC, TGA, SEM and EDX studies were conducted to confirm the grafting of polymers and to evaluate the thermal stability and surface morphology of the developed IPNs. ResultsSwelling studies exhibited an increase in swelling percentage from 84.27 to 91.17% upon increasing polymer (Natrosol and Pectin) contents. An increase in MBA contents resulted in a decrease in swelling from 85 to 67.63%. Moreover, the swelling was also observed to increase with higher AA contents. Significant drug release was noted at higher pH instead of gastric pH value. Oral toxicological studies revealed the nontoxic and biocompatible nature of Natrosol-Pectin IPNs. Interpretation & ConclusionThe developed IPNs were found to be an excellent system for the controlled delivery of Tapentadol Hydrochloride.

Develop adult extrapolation to pediatrics and pediatric dose optimization based on the physiological pharmacokinetic model of azithromycin.

Physiologically-based pharmacokinetic (PBPK) models are more frequently used for supporting pediatric dose selection in small-molecule drugs. Through literature research, drug parameters of azithromycin and clinical data from different studies were obtained. Through parameter optimization of the absorption and dissolution process, the adult intravenous model was extended to the adult oral model. The adult intravenous and oral PBPK models are precise to meet the AAFE<2 standard, and the pharmacokinetic parameters of the predicted values of the model are all within the mean standard deviation of the clinical observations. The values of plasma protein unbound fraction, renal clearance, and gastric juice pH between adults and pediatrics were changed by using the age-dependent pediatric organ maturity formula, and the adult model was extrapolated to the pediatric model. The final developed pediatric PBPK model was used to evaluate optimal dosing for children of different developmental ages. The relationship between the frist dose and age was as follows: 8.8mg/kg/day from 0.5 to 2years old, 9.2mg/kg/day from 3 to 6years old, 9.4mg/kg/day from 7 to 12years old, and 8.2mg/kg/day from 13 to 18years old, taken in half for 2-5days. Simultaneously, the simulated exposures achieved with the dosing regimen proposed were comparable to adult plasma exposures for treatment of community-acquired pneumonia. A reasonable azithromycin pharmacokinetic-pharmacodynamic model for adults and pediatrics has been established, which can be demonstrated by the use of literature pediatric data to develop pediatric PBPK models, expanding the scope of this powerful modeling tool.

Description of Gastric Acidity (pH) with Simple Method in Lipopolysaccharide Induced Mice

The gastrointestinal acidity/pH can considerably influence the stability and absorption of oral medications. As a result, understanding the circumstances for drug delivery requires knowledge of gastrointestinal pH. Mice injected with lipopolysaccharide (LPS) are used in the most well-studied animal models of sepsis. However, information on gastrointestinal pH in sepsis mice is still insufficient. This study was conducted to identify gastric pH values in mice induced by lipopolysaccharide. The LPS was injected intraperitoneally as well as 0.9% NaCl as control groups. Treated groups (LPS) consisted of four groups and the control group (0.9% NaCl) consisted of four groups. Ten mice were used in each group. Gastric pH measurement was conducted using pH meter Lutron PH-201. Based on this study, the factors that influenced gastric pH in sepsis animal models were the LPS doses and the time after LPS injection. The results of gastric pH measurement in sepsis mice did not show a decrease in the pH compared to the normal conditions. The dose of LPS significantly influences the gastric pH change.

Phenolic acids-rich fraction from Ficus drupacea leaves for the prevention and treatment of ethanol-induced gastric mucosal injury in rats

Bioactivity-guided fractionation of F. drupacea Thunb. extract revealed that the water fraction (FDWF) increased pH of the artificial gastric juice from 1.2 to 5.67 ± 0.015. The gastroprotective effect of FDWF against ulcer induced by ethanol was evaluated in rats. In ulcerogenic rats, increase in the gastric juice volume and ulcer lesions, and decrease in the gastric pH were evident. However, pretreatment with FDWF (100 mg/kg b.wt., p.o.) significantly inhibited lesion index, reduced gastric juice volume by 56.09% and increased gastric pH value. When given after ethanol, the same dose of FDWF led to significant healing of the gastric ulcer, with 75.60% reduction of gastric juice volume, and increase in pH value. In both prophylactic and therapeutic-treated groups, the level of superoxide dismutase and reduced glutathione in gastric homogenate were increased, while that of malondialdehyde was decreased. Also, the levels of succinate dehydrogenase and lactate dehydrogenase were increased, while that of acid phosphatase was decreased. In addition, the inflammatory markers; IL-10 and PGE2 were significantly increased. The histopathological results confirmed the above findings and indicated that the antiulcer effect of FDWF is mediated, at least in part, through antioxidant and anti-inflammatory mechanisms. Twenty-three compounds were tentatively identified in FDWF using UPLC−PDA−ESI–MS/MS and most of them were found to be phenolic acid derivatives. FDWF was standardized to contain 23.66 ± 2.62 mg/g and 8.86 ± 0.29 mg/g of quinic acid and chlorogenic acid, respectively. Accordingly, FDWF is a potential natural product that could increase the healing of gastric mucosal injury and prevents the development of ethanol-induced gastric mucosal injury in rats.

Characterization of lactic acid bacteria isolated from budu, a West Sumatra fish fermentation product, and their ability to produce exopolysaccharides

Background: Probiotics are instrumental in maintaining the equilibrium of the gut microbiota and improving the health of the human body. This study examined the presence and physiological features, including the ability to produce exopolysaccharides, of lactic acid bacteria from fermented Tenggiri (Scomberomorus guttatus) and Talang (Chorinemus spp.) fish, also known as budu fish. Methods: Lactic acid bacteria were isolated from budu fish. These bacteria were characterized to determine tolerance to gastric pH values, growth curve, inhibitory ability against pathogenic bacteria, and ability to produce exopolysaccharides and to perform a molecular identification. Results: Twenty-nine lactic acid bacteria isolates from budu fish were determined to be of the Pediococcus species. Assessment of the physiological characteristics showed that Pediococcus sp. had a high acidifying activity and could grow at a pH between 2 and 11; the pH of the supernatant after 36 hours of incubation was 4.49. In terms of inhibitory activity against pathogenic bacteria, Pediococcus sp. demonstrated an inhibitory diameter of 20.5 mm against Escherichia coli, 23.0 mm against Staphylococcus aureus, and 21.0 mm against Salmonella thypi. The Pediococcus sp. strain produced exopolysaccharides ranging from 870 to 1910 mg/l and had 100% similarity with Pediococcus pentosaceus strain 4942. Conclusions: This study confirmed the presence of Pediococcus pentosaceus strain 4942 in budu fish, which can be used as a new probiotic based on its capabilities to kill pathogenic bacteria and produce exopolysaccharide compounds.

Protective Effect of Anwulignan on Gastric Injury Induced by Indomethacin in Mice.

Anwulignan (AN) is a monomer lignan from Schisandra sphenanthera Rehd. et Wits (Schisandra sphenanthera fructus, Schisandra sphenanthera). The protective effect of AN against the indomethacin (IND)-induced gastric injury to mice and the related mechanism of action was investigated in this study. The effect of AN was mainly assessed by observing the gastric tissue morphology, gastric ulcer index (GUI), ulcer inhibition rate (UIR), gastric juice volume (GJV) and pH value. Chemical colorimetry, immunofluorescence, ELISA, and Western blot were used to detect related factors in the gastric tissue. The results showed that AN reduced the GUI, increased the UIR, inhibited the GJV, and increased the gastric pH value. AN significantly increased cyclooxygenase-1, cyclooxygenase-2, and prostaglandin E2 expression levels in the gastric tissue, activated nuclear factor (erythroid-derived 2)-like 2 (Nrf2), increased heme oxygenase-1 expression, enhanced the activity of superoxide dismutase and glutathione peroxidase, and decreased the malondialdehyde content. AN reduced the phosphorylation of nuclear factor-κ gene binding (NF-κB) p65 and its nuclear translocation, the key protein of NF-κB signaling pathway in the gastric tissue, and the content of the pathway downstream signaling molecules, including interleukin-6, interleukin-1β, and tumor necrosis factor-α, to play an anti-inflammatory role. AN inhibited the downstream signals B-cell lymphoma 2-associated x protein and cleaved caspase-3 in gastric tissue, and activated B-cell lymphoma 2, to play an antiapoptotic role, which were further verified by Hoechst staining. Therefore, AN has a significant protection against the gastric injury induced by IND in mice, and the mechanism may be concerned in its activation of Nrf2, inhibition of NF-κB signaling pathway, and anti-apoptotic effect. SIGNIFICANCE STATEMENT: Anwulignan (AN) significantly reduced the indomethacin-induced gastric injury in mice, and its antioxidation, anti-inflammation, and antiapoptosis were considered to be involve in the effect, suggesting that AN should be a potential drug or food supplement for gastric injury induced by indomethacin.

Nasogastric tube in mechanical ventilated patients: ETCO2 and pH measuring to confirm correct placement. A pilot study.

Nasogastric tube (NGT) placement is a procedure commonly performed in mechanically ventilated (MV) patients. Chest X-Ray is the diagnostic gold-standard to confirm its correct placement, with the downsides of requiring MV patients' mobilization and of intrinsic actinic risk. Other potential methods to confirm NGT placement have shown lower accuracy compared to chest X-ray; end-tidal CO2 (ETCO2) and pH analysis have already been singularly investigated as an alternative to the gold standard. Aim of this study was to determine threshold values in ETCO2 and pH measurement at which correct NGT positioning can be confirmed with the highest accuracy. This was a prospective, multicenter, observational trial; a continuous cohort of eligible patients was allocated with site into two arms. Patients underwent general anesthesia, orotracheal intubation and MV; in the first and second group we respectively assessed the difference between tracheal and esophageal ETCO2 and between esophageal and gastric pH values. From November 2020 to March 2021, 85 consecutive patients were enrolled: 40 in the ETCO2 group and 45 in the pH group. The ETCO2 ROC analysis for predicting NGT tracheal misplacement demonstrated an optimal ETCO2 cutoff value of 25.5 mmHg, with both sensitivity and specificity reaching 1.0 (AUC 1.0, p < 0.001). The pH ROC analysis for predicting NGT correct gastric placement resulted in an optimal pH cutoff value of 4.25, with mild diagnostic accuracy (AUC 0.79, p < 0.001). In patients receiving MV, ETCO2 and pH measurements respectively identified incorrect and correct NGT placement, allowing the identification of threshold values potentially able to improve correct NGT positioning. NCT03934515 (www.clinicaltrials.gov).

In Vitro Simulation of the Environment in the Upper Gastrointestinal Lumen After Drug Administration in the Fed State Using the TIM-1 System and Comparison With Luminal Data in Adults

We evaluated the environment in TIM-1 luminal compartments using paracetamol and danazol solutions and suspensions and the fed state configuration. Data were compared with recently published data in healthy adults. TIM-1 experiments were performed with a 3-fold downscale. Volumes of secretions in gastric and duodenal compartments adequately reflected the luminal data in adults up to 3 h post drug dosing. pH values in duodenal and jejunal compartments adequately reflected average pH values in adults. In gastric compartment pH values where initially higher than average values in adults and reached baseline levels earlier than in adults. The environment in the TIM-1 gastric compartment and jejunal compartment adequately reflected the average total paracetamol and danazol amounts per volume of contents in the adult stomach and upper small intestine, respectively. Total bile acids concentrations in the micellar phase of contents in duodenal and jejunal compartments overestimated micellar concentrations in the upper small intestine of adults. Adjustments in gastric emptying/acid secretion rates and bile acids identities in the duodenal and jejunal compartments, and application of dynamic bile acids secretion rates are expected to further improve the relevance of luminal conditions in TIM-1 compartments with those in adults.

Gastric pH and volume change in emergency and elective cesarean section: A randomized trial

Context: Pregnancy is a condition when a woman suffers numerous changes in the body. These changes can be physical and physiological. There are numerous factors which affect the volume and gastric pH of a pregnant lady. A lady has to bear a number of changes during pregnancy, mainly in her first trimester and after pregnancy. Vomiting is a normal symptom of pregnancy which effects a lady in her first trimester. This badly affects the gastric content and increase in pH as well as volume. In cesarian cases also the digestion is badly affected and anesthesia also plays a major role in distortion of proper gastric functions. Aim: To compare the gastric pH of the fluid in elective cesarean v/s emergency sections. Setting and Design: This study is a cross-sectional survey performed in Lahore from September 2009 to June 2010. Material and Methods: A total number of 150(n= 150) patients were studied and divided into two groups. These patient were with elevated caesarian section and emergency caesarian section. Statical analysis: The results were statistically significant. (p-value < 0> Result: Patients in emergency cesarean section group had a lower value of gastric pH ranging from (2.16 + 0.64) and higher value of, the volume of gastric acidic (26.33 + 10.59) as compared to that in elective cesarean section group (4.56 + 1.28 and 11.65 + 4.37 respectively). Conclusion: The study concluded that in emergency and elective caesarian section the level of gastric volume was significantly high whereas the level of gastric pH was low. Keywords: Gastric pH, Emergency cesareans section gastric fluid volume, Elective cesarean section.

Evaluating the impact of acid-reducing agents on drug absorption using biorelevant in vitro tools and PBPK modeling - case example dipyridamole

BackgroundIn vitro and in silico methods have become an essential tool in assessing metabolic drug-drug interactions (DDI) and avoiding reduced efficacy and increased side-effects. Another important type of DDI is the impact of acid-reducing agent (ARA) co-therapy on drug pharmacokinetics due to changes in gastric pH, especially for poorly soluble weakly basic drugs. MethodsOne-stage, two-stage and transfer dissolution experiments with dipyridamole tablets using novel biorelevant media representing the ARA effect were conducted and the results were coupled with a PBPK model. Clinical pharmacokinetic data were compared with the simulations from the PBPK model and with output from TIM-1 experiments, an evolved in vitro system which aims to simulate the physiology in the upper GI tract. ResultsTwo-stage and transfer experiments confirmed that these in vitro set-ups tend to overestimate the extent of dipyridamole precipitation occurring in the intestines in vivo. Consequently, data from one-stage dissolution testing under elevated gastric pH conditions were used as an input for PBPK modeling of the ARA/dipyridamole interaction. Using media representing the ARA effect in conjunction with the PBPK model, the ARA effect observed in vivo was successfully bracketed. As an alternative, the TIM-1 system with gastric pH values adjusted to simulate ARA pre-treatment can be used to forecast the ARA effect on dipyridamole pharmacokinetics. ConclusionDrug-drug interactions of dipyridamole with ARA were simulated well with a combination of dissolution experiments using biorelevant media representing the gastric environment after an ARA treatment together with the PBPK model. Adjustment of the TIM-1 model to reflect ARA-related changes in gastric pH was also successful in forecasting the interaction. Further testing of both approaches for predicting ARA-related DDIs using a wider range of drugs should be conducted to verify their utility for this purpose.

Volume and pH of Gastric Contents in Patients Undergoing Gynecologic Laparoscopic Surgery during Emergence from General Anesthesia: A Prospective Observational Study

Objective: To find out the volumes and pH values of the digestive contents during emergence in patients undergoing elective gynecologic laparoscopic surgery under general anesthesia. Materials and Methods: One hundred patients scheduled for surgery under general balanced anesthesia with standard monitoring were allocated in the present study. Gastric volumes greater than 0.4 mL/kg and pH of less than 2.5 were set as cut-off points to establish the risk of aspirated pneumonitis. Prior to insufflation of CO₂ gas into the participants’ abdominal cavity and placing them in lithotomy or Trendelenburg position, anesthetists inserted an orogastric tube to deflate the patients’ stomach. Then gastric volumes and pH values were measured at hourly intervals through the operation. Results: Eighty-nine participants completed the study. The pH and gastric volumes of high-risk and non-high-risk groups showed statistically significant differences (p&lt;0.001), as 1.1±0.4 and 1.1±0.8 mL/kg, and 2.8±2.2 and 0.3±0.4 mL/kg, respectively. Though their ages (p=0.047), body mass index (BMI) (p=0.015), and pre-medication drugs (p&lt;0.001) showed significant differences, they were not apparent in the pre-fluid loading, fasting, and surgical time. Conclusion: During emergence from general anesthesia, 65.2% of the patients undergoing gynecologic laparoscopic surgery were exposed to a high risk of aspirated pneumonitis. The present study showed significant association with age, BMI, and pre-medication drugs. Investigators suggested that patients with a BMI greater than 25 kg/m², administering H₂ receptor antagonist or a proton pump inhibitor as premedication, and having gastric content drainage prior to endotracheal tube extubation should have a low risk of pulmonary aspiration. Keywords: Anesthesia, Gynecology, Gastric content, Laparoscopic surgery

A Colon-Targeted Oral Probiotics Delivery System Using an Enzyme-Triggered Fuse-Like Microcapsule.

Probiotics are closely related to human health. However, it is hard to find an appropriate disintegration mode for encapsulation to balance the survival, release, and adhesion of probiotics simultaneously during the current colon-targeted oral delivery, which leads to limited colonization. In this study, an enzyme-triggered fuse-like microcapsule is constructed using alginate and protamine via the electrostatic droplet combined with the layer by layer self-assembly. The multilayer microcapsule can protect the probiotics in the stomach and disintegrate layer by layer under the catalysis of trypsin in the intestine. The formulation with two protamine layers showed the best protection for Escherichia coli MG1655 (EM) during the oral delivery; as well the minimal release at the gastric pH value but a burst release after 1 h at the intestinal pH value. In particular, the adhesion strength of EM is improved with the increase of the layer number. In vivo experiments demonstrate that the EM enters into the stationary phase within 12 h in the colon. Moreover, the blood biochemistry and histological analysis demonstrates the safety of the microcapsule formulation. It can be concluded that this microcapsule can help the probiotics survive during the delivery, then release and colonize in the colon.

Synergistic Interactions of Plant Protein Microgels and Cellulose Nanocrystals at the Interface and Their Inhibition of the Gastric Digestion of Pickering Emulsions.

It is possible that Pickering emulsions can optimize the transport of nutraceuticals, pharmaceuticals, and other bioactive compounds in human physiology. So-called ultrastable Pickering emulsions are often destabilized in the gastric digestion regime if the particles are proteinaceous in nature. The present study seeks to test how the interfacial structure can be engineered via synergistic particle-particle interactions to impact the gastric coalescence of Pickering emulsions. In this study, we designed plant-based protein-particle-stabilized oil-in-water emulsions (PPM-E, with 20 wt % sunflower oil) via pea protein microgels (PPM at 1 wt %). The PPM hydrodynamic diameter is ∼250 nm. In vitro gastric digestion of PPM-E confirmed droplet coalescence within 30 min of pepsin addition. Supposedly surface-active cellulose nanocrystals (CNCs, 1-3 wt %) were added to PPM-E at pH 3.0 to determine if they could act as a barrier to interfacial pepsinolysis due to the CNC and PPM being oppositely charged at this gastric pH value. A combination of confocal microscopy, zeta potential, and Langmuir trough measurements suggested that CNCs and PPMs might form a combined layer at the O/W interface, owing to the electrostatic attraction between them. CNCs at >2 wt % inhibited the pepsinolyis of the adsorbed PPM film and thus droplet coalescence. However, increasing concentrations of CNC also increased the bulk viscosity of the PPM-E and eventually caused gelation of the emulsions, which would also delay their gastric breakdown. In conclusion, tuning the bulk and interfacial structure of Pickering emulsions via synergistic interactions between two types of particles could be an effective strategy to modify the enzymatic breakdown of such emulsions, which would have important applications in pharmaceuticals, foods, and other soft-matter applications.

Pretreatment with Lactobacillus fermentum XY18 Relieves Gastric Injury Induced by HCl/Ethanol in Mice via Antioxidant and Anti-Inflammatory Mechanisms.

AimLactobacillus fermentum XY18 (LF-XY18) is a bacterial strain with satisfactory antioxidant properties in vitro that we previously isolated from Xinjiang yogurt. This article will explore the preventive effect of LF-XY18 on acute gastric injury and provide the basis for the innovative development and application of lactic acid bacteria (LAB).MethodsKunming mice underwent gastric injury induced by hydrochloric acid and ethanol. LF-XY18 isolated from yogurt in Xinyuan County in the Yili region of Xinjiang was subsequently administered intragastrically to mice for 2 weeks to explore the mechanism of LF-XY18 in preventing gastric injury via its antioxidant effects.ResultsThere was decreased gastric juice volume, gastric injury area, and formation of gastric mucosal lesions in the LF-XY18 mice as compared to those in the control mice, while LF-XY18 prevented the decrease in the gastric juice pH value in mice. Compared with the gastric injury model group mice, LF-XY18 reduced the serum levels of motilin, substance P, interleukin-6, interleukin-12, tumor necrosis factor-α, and interferon-γ but increased the serum levels of somatostatin and vasoactive intestinal peptide. The activities of superoxide dismutase, glutathione peroxidase, glutathione, and nitric oxide were increased in the gastric tissue of the LF-XY18 mice compared with the control mice, but malondialdehyde activity was decreased in the LF-XY18 mice. Quantitative polymerase chain reaction analysis illustrated that in the gastric tissue of LF-XY18 mice, the messenger RNA (mRNA) expression of occludin, epidermal growth factor (EGF), EGF receptor, vascular EGF, inhibitor kappa-B-α, neuronal nitric oxide synthase, endothelial nitric oxide synthase, cuprozinc superoxide dismutase, manganese superoxide dismutase, and catalase was stronger than that in the control mice, but the mRNA expression of activated B cells (NF-κB), inducible nitric oxide synthase, and cyclooxygenase-2 was weaker than in the control mice.ConclusionThese results indicate that LF-XY18 has a potential role in the prevention of gastric injury through antioxidant effects, and a high concentration (1.0 × 109 CFU/kg b.w.) of LF-XY18 has a stronger anti-gastric injury effect than a low concentration (1.0 × 108 CFU/kg b.w.).

The Role of Hydrogen Sulfide in Chronic Unpredictable Stress-Induced Gastric Lesions.

The aim of this study was to investigate the possible protective role of Hydrogen sulfide on chronic unpredictable stress (CUS) -induced gastric lesions. Materials and methods: 40 rats were divided into 4 groups: control group, stressed rats group, stressed + Aminooxyacetic acid (AOAA) (inhibitor of H2S synthesis; 50mg/kg/48hour; IP), stressed + Sodium hydrosulfide (NaHS) (donor of H2S, 5mg/kg/48hour; IP). In all the groups exposed to CUS, a set of chronic unpredictable stressors was applied for 6 weeks in random order. At the end of experimental protocol blood samples, gastric content and gastric tissues samples were collected. Gastric tissues histopathological changes were evaluated by macroscopic and microscopic examination. Gastric content pH, serum MDA level, whole blood GSH level were estimated. Expression of Caspase-3 (apoptotic marker) and BCL-xl (anti-apoptotic marker) was assessed by immunohistochemistry. Results: In all the groups exposed to CUS, there was a significant reduction in gastric pH value and a range of gastric lesions ranging from superficial to deep ulceration as evident by macroscopic and microscopic examination. Also, there was significant elevation in MDA serum level and significant reduction in anti-oxidant GSH blood level. In all stressed rats, the expression of Caspase-3 was significantly higher whereas a significant decrease in expression of anti-apoptotic protein BCL-xl was observed. These findings were aggravated by AOAA while using NaHS improved them. Conclusion: it seems that increasing bioavailability of H2S could have a protective role against CUS induced gastric lesions. The results suggest that this protection could be through anti-oxidant and anti-apoptotic effects.