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Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its...
Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.
Topics: Gastric Emptying; Drug Liberation; Diclofenac; Water; Solubility; Tablets; Dipyridamole; Acetaminophen; Hydrogen-Ion Concentration; Kinetics; Administration, Oral; Glass
PubMed: 38815199
DOI: 10.2478/acph-2024-0016 -
PloS One 2024Functional dyspepsia (FD) refers to a group of clinical symptoms caused by gastric and duodenal dysfunction. Which is a chronic functional disorder of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Functional dyspepsia (FD) refers to a group of clinical symptoms caused by gastric and duodenal dysfunction. Which is a chronic functional disorder of the gastrointestinal tract with no cure. Zhishixiaopi decoction (ZSXP) is a type of Chinese herbal prescription that for treating FD. Although some randomized controlled trials (RCTs) report that ZSXP can significantly improve FD clinical symptoms and/or laboratory results, the trial design varies greatly among studies, making it challenging to draw a conclusion of the efficacy of ZSXP in treating FD.
DESIGN
A systematic review and a meta-analysis.
SETTING
Mianyang Central Hospital.
OBJECTIVE
We conducted a systematic review and a meta-analysis to evaluate the efficacy and safety of ZSXP for treating FD.
METHODS
We developed inclusion and exclusion criteria based on FD diagnosed criteria, interventions to treat FD, and outcomes of these interventions. Search strategies combined disease terms, symptom terms, anatomy terms and intervention terms. Literature search was conducted on eight online databases in English or Chinese, including Medline (via PubMed), Embase (via Ovid), The Cochrane Library, Web of Science, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Database.
INTERVENTION
The experimental group received oral administration of ZSXP and had a complete treatment process. ZSXP needs to fully contain the key herbal ingredients, regardless of whether the dosage of each herb is consistent with the original prescription. The Control group received monotherapy or combination therapy of other Western medicine and had a complete treatment process.
OUTCOMES
The primary outcomes appraised were Total effective rate (TER), serum levels of Motilin(MOT), Gastrin(GAS) and Somatostatin (SS), Gastric emptying rate (GER) using a Barium meal method (GER(B)) and Gastric half emptying time using an Ultrasonic method (GHET(T1/2)). The Cochrane Bias Risk Tool was used for quality critical appraisal, Review Manager (RevMan) version 5.3 was used for statistical analysis.
RESULTS
A total of 21 medium-quality RCTs were included in the meta-analysis. All 21 included studies were conducted and completed in Mainland China from 1998 to 2020. The treatment duration was between two weeks to two months. The meta-analysis suggests that, compared with the Western medicine treatment group, ZSXP treatment was more effective to improving the TER in FD [Odds ratio, OR = 3.54, 95%CI:(2.49, 5.05), Z = 6.99, P<0.00001] without significant increase in adverse events. However, no statistical significance was found between the groups in serum MOT levels [Standard mean difference, SMD = 1.05, 95%CI:(-0.42, 2.53), Z = 1.04, P = 0.16], serum GAS levels [SMD = -0.16, 95%CI:(-1.20, 0.88), Z = 0.31, P = 0.76], serum SS levels [SMD = -0.04, 95%CI:(-1.97, 1.89), Z = 0.04, P = 0.97], GER(B) [SMD = 1.09, 95%CI:(-0.81, 3.00), Z = 1.12, P = 0.26]or GHET(T1/2) [Mean difference, MD = -2.18, 95%CI:(-5.55, 1.19), Z = 1.27, P = 0.20].
CONCLUSIONS
The meta-analysis suggests that Zhishixiaopi treatment is a relatively effective and safe traditional Chinese medicine prescription and could be used for functional dyspepsia treatment. Considering the limitations of this study, the conclusion needs to be further confirmed by high-quality, multi-center, and large-sample randomized controlled trials.
Topics: Humans; Dyspepsia; Randomized Controlled Trials as Topic; Drugs, Chinese Herbal; Treatment Outcome
PubMed: 38809916
DOI: 10.1371/journal.pone.0301686 -
World Journal of Clinical Cases May 2024Gastroesophageal reflux disease (GERD) is a common complication of esophageal cancer surgery that can affect quality of life and increase the risk of esophageal...
BACKGROUND
Gastroesophageal reflux disease (GERD) is a common complication of esophageal cancer surgery that can affect quality of life and increase the risk of esophageal stricture and anastomotic leakage. Wendan Decoction (WDD) is a traditional Chinese herbal formula used to treat various gastrointestinal disorders, such as gastritis, functional dyspepsia, and irritable bowel syndrome. Mosapride, a prokinetic agent, functions as a selective 5-hydroxytryptamine 4 agonist, enhancing gastrointestinal motility.
AIM
To evaluate the therapeutic effects of WDD combined with mosapride on GERD after esophageal cancer surgery.
METHODS
Eighty patients with GERD were randomly divided into treatment (receiving WDD combined with mosapride) and control (receiving mosapride alone) groups. The treatment was conducted from January 2021 to January 2023. The primary outcome was improved GERD symptoms as measured using the reflux disease questionnaire (RDQ). The secondary outcomes were improved esophageal motility (measured using esophageal manometry), gastric emptying (measured using gastric scintigraphy), and quality of life [measured the Short Form-36 (SF-36) Health Survey].
RESULTS
The treatment group showed a notably reduced RDQ score and improved esophageal motility parameters, such as lower esophageal sphincter pressure, peristaltic amplitude, and peristaltic velocity compared to the control group. The treatment group showed significantly higher gastric emptying rates and SF-36 scores (in both physical and mental domains) compared to the control group. No serious adverse effects were observed in either group.
CONCLUSION
WDD combined with mosapride is an effective and safe therapy for GERD after esophageal cancer surgery. It can improve GERD symptoms, esophageal motility, gastric emptying, and the quality of life of patients. Further studies with larger sample sizes and longer follow-up periods are required to confirm these findings.
PubMed: 38808341
DOI: 10.12998/wjcc.v12.i13.2194 -
Frontiers in Physiology 2024Gastrointestinal motility symptoms may be closely related to thyroid diseases. Sometimes, such symptoms are the only thyroid disease-related clue although the degree of... (Review)
Review
Gastrointestinal motility symptoms may be closely related to thyroid diseases. Sometimes, such symptoms are the only thyroid disease-related clue although the degree of the symptoms may vary. The exact mechanism of action of thyroid hormones on gastrointestinal motility is not completely understood, however, a clue lies in the fact that muscle cell receptors can be directly acted upon by thyroxines. Both hypo- and hyperthyroidism can cause impairment of gastrointestinal motility, modifying structure and function of pharynx and esophagus, and regulating esophageal peristalsis through neuro-humoral interaction. In hyperthyroid patients, alterations of postprandial and basic electric rhythms have been observed at gastro-duodenal level, often resulting in slower gastric emptying. Gastric emptying may also be delayed in hypothyroidism, but an unrelated gastric mucosa-affecting chronic modification may also cause such pattern. Hyperthyroidism commonly show malabsorption and diarrhoea, while hypothyroidism frequently show constipation. In summary, it can be stated that symptoms of gastrointestinal motility dysfunction can be related to thyroid diseases, affecting any of the gastrointestinal segment. Clinically, the typical thyroid disease manifestations may be missing, borderline, or concealed because of intercurrent sicknesses. Motility-linked gastrointestinal problems may easily conceal a misdetected, underlying dysthyroidism that should be carefully analyzed. Here, we aim to elaborate on the associations between thyroid disorders and GI dysmotility and the common clinical manifestations associated with GI dysmotility.
PubMed: 38803365
DOI: 10.3389/fphys.2024.1389113 -
European Journal of Pharmaceutics and... May 2024Mathematical models that treat the fed stomach content as a uniform entity emptied with a constant rate may not suffice to explain pharmacokinetic profiles recorded in...
Drug dissolution and transit in a heterogenous gastric chyme after fed administration: Semi-mechanistic modeling and simulations for an immediate-release and orodispersible tablets containing a poorly soluble drug.
Mathematical models that treat the fed stomach content as a uniform entity emptied with a constant rate may not suffice to explain pharmacokinetic profiles recorded in clinical trials. In reality, phenomena such as the Magenstrasse or chyme areas of different pH and viscosity, play an important role in the intragastric drug dissolution and its transfer to the intestine. n this study, we investigated the data gathered in the bioequivalence trial between an immediate-release tablet (Reference) and an orally dispersible tablet (Test) with a poorly soluble weak base drug administered with or without water after a high-fat high-calorie breakfast. Maximum concentrations (C) were significantly greater after administering the Reference product than the Test tablets, despite similar in vitro dissolution profiles. To explain this difference, we constructed a novel semi-mechanistic IVIVP model including a heterogeneous gastric chyme. The drug dissolution in vivo was modeled from the in vitro experiments in biorelevant media simulating gastric and intestinal fluids in the fed state (FEDGAS and FeSSIF). The key novelty of the model was separating the stomach contents into two compartments: isolated chyme (the viscous food content) that carries the drug slowly, and aq_chyme open for rapid Magenstrasse-like routes of drug transit. Drug distribution between these two compartments was both formulation- and administration-dependent, and recognized the respective drug fractions from the clinical pharmacokinetic data. The model's assumption about the nonuniform mixing of the API with the chyme, influencing differential drug dissolution andl transit kinetics, led to simulating plasma concentration profiles that reflected well the variability observed in the clinical trial. The model indicated that, after administration, the Reference product mixes to a greater extent with aq_chyme, where the released drug dissolves better and transfers faster to the intestine. In conclusion, this novel approach underlines that diverse gastric emptying of different oral dosage forms may significantly impact pharmacokinetics and affect the outcomes of bioequivalence trials.
PubMed: 38795785
DOI: 10.1016/j.ejpb.2024.114341 -
Life (Basel, Switzerland) Apr 2024Pancreaticoduodenectomy (PD) is a complex and high-skill demanding procedure often associated with significant morbidity and mortality. However, the results have...
BACKGROUND AND AIMS
Pancreaticoduodenectomy (PD) is a complex and high-skill demanding procedure often associated with significant morbidity and mortality. However, the results have improved over the past two decades. However, there is a paucity of research concerning the learning curve for PD. Our aim was to report the outcomes of 100 consecutive PDs representing a single surgeon's learning curve and to depict the factors that influenced the learning process.
METHODS
We reviewed the first 121 PDs performed at our academic center (2013-2019) by a single surgeon; 110 were PDs (5 laparoscopic and 105 open) and 11 were total PDs (1 laparoscopic and 10 open). Subsequent statistics was performed on the first 100 PDs, with attention paid to the learning curve and survival rate at 5 years. The data were analyzed comparing the first 50 cases (Group 1) to the last 50 cases (Group 2).
RESULTS
The most frequent histopathological tumor type was pancreatic ductal adenocarcinoma (50%). A total of 39% of patients had preoperative biliary drainage and 45% presented with positive biliary cultures. The preferred reconstruction technique included pancreaticogastrostomy (99%), in situ hepaticojejunostomy (70%), and precolic gastro-jejunal anastomosis (88%). Postoperative complications included biliary fistula (1%), pancreatic fistula (8%), pancreatic stump bleeding (4%), and delayed gastric emptying (13%). The mean operative time decreased after the first 50 cases ( < 0.001) and blood loss after 60 cases ( = 0.046). R1 resections lowered after 25 cases ( = 0.025). Vascular resections (17%) did not influence the rate of complications ( = 0.8). The survival rate at 5 years for pancreatic adenocarcinoma was 32.93%.
CONCLUSIONS
Outcomes improve as surgeon experience increases, with proper training being the most important factor for minimizing the impact of the learning curve over the postoperative complications. Analyzing the learning curve from the perspective of a single surgeon is mandatory for accurate statistical results and interpretation.
PubMed: 38792572
DOI: 10.3390/life14050549 -
Scientific Reports May 2024Reliable in-vitro digestion models that are able to successfully replicate the conditions found in the human gastrointestinal tract are key to assess the fate and...
Reliable in-vitro digestion models that are able to successfully replicate the conditions found in the human gastrointestinal tract are key to assess the fate and efficiency of new formulations aimed for oral consumption. However, current in-vitro models either lack the capability to replicate crucial dynamics of digestion or require large volumes of sample/reagents, which can be scarce when working with nanomaterials under development. Here, we propose a miniaturised digestion system, a digestion-chip, based on incubation chambers integrated on a polymethylmethacrylate device. The digestion-chip incorporates key dynamic features of human digestion, such as gradual acidification and gradual addition of enzymes and simulated fluids in the gastric phase, and controlled gastric emptying, while maintaining low complexity and using small volumes of sample and reagents. In addition, the new approach integrates real-time automated closed-loop control of two key parameters, pH and temperature, during the two main phases of digestion (gastric and intestinal) with an accuracy down to ± 0.1 °C and ± 0.2 pH points. The experimental results demonstrate that the digestion-chip successfully replicates the gold standard static digestion INFOGEST protocol and that the semi-dynamic digestion kinetics can be reliably fitted to a first kinetic order model. These devices can be easily adapted to dynamic features in an automated, sensorised, and inexpensive platform and will enable reliable, low-cost and efficient assessment of the bioaccessibility of new and expensive drugs, bioactive ingredients or nanoengineered materials aimed for oral consumption, thereby avoiding unnecessary animal testing.
Topics: Humans; Digestion; Hydrogen-Ion Concentration; Models, Biological; Kinetics; Gastrointestinal Tract; Temperature; Miniaturization; Lab-On-A-Chip Devices
PubMed: 38789470
DOI: 10.1038/s41598-024-54612-w -
Animal : An International Journal of... Apr 2024Heat stress (HS) negatively impacts a variety of production parameters in growing pigs; however, the impact of biological sex on the HS response is largely unknown. To...
Heat stress (HS) negatively impacts a variety of production parameters in growing pigs; however, the impact of biological sex on the HS response is largely unknown. To address this, 48 crossbred barrows and gilts (36.8 ± 3.7 kg BW) were individually housed and assigned to one of three constant environmental conditions: (1) thermoneutral (TN) (20.8 ± 1.6 °C; 62.0 ± 4.7% relative humidity; n = 8/sex), (2) HS (39.4 ± 0.6 °C; 33.7 ± 6.3% relative humidity) for 1 d (HS1; n = 8/sex), or (3) or for 7 d (HS7; n = 8/sex). As expected, HS increased rectal temperature (Tr) following 1 d of HS (1.0 °C; P < 0.0001) and 7 d of HS (0.9 °C; P < 0.0001). By 7 d, heat-stressed gilts were cooler than barrows (0.4 °C; P = 0.016), despite identical heating conditions. There was a main effect of sex such that barrows had higher Tr than gilts (P = 0.031). Heat-stressed pigs on d 1 had marked reductions in feed intake and BW compared to TN (P < 0.0001). One day of HS resulted in negative gain to feed (G:F) in barrows and gilts and was reduced compared to TN (P < 0.0001). Notably, following 1 d of HS, the variability of G:F was greater in gilts than in barrows. Between 1 and 7 d of HS, G:F improved in barrows and gilts and were similar to TN pigs, even though HS barrows had higher Tr than gilts over this period. Heat stress for 1 and 7 d reduced empty gastrointestinal tract weight compared to TN (P < 0.0001). Interestingly, HS7 gilts had decreased gastrointestinal tract weight compared to HS1 gilts (2.43 vs 2.72 kg; P = 0.03), whereas it was similar between HS1 and HS7 barrows. Lastly, a greater proportion of gastrointestinal contents was in the stomach of HS1 pigs compared to TN and HS7 (P < 0.05), which is suggestive of decreased gastric emptying. Overall, HS barrows maintained an elevated Tr compared to HS gilts through the duration of the experiment but also maintained similar growth and production metrics compared to gilts, despite this higher temperature.
PubMed: 38762992
DOI: 10.1016/j.animal.2024.101168 -
Journal of Medical Case Reports May 2024Gastroparesis is a condition that affects the motility of the gastrointestinal (GI) tract, causing a delay in the emptying process and leading to nausea, vomiting,...
BACKGROUND
Gastroparesis is a condition that affects the motility of the gastrointestinal (GI) tract, causing a delay in the emptying process and leading to nausea, vomiting, bloating, and upper abdominal pain. Motility treatment along with symptom management can be done using antiemetics or prokinetics. This study highlights the diagnostic and therapeutic challenges of gastroparesis and suggests a potential link between facial trauma and symptom remission, indicating the need for further investigation.
CASE PRESENTATION
A 46-year-old Hispanic man with hypertension, type 2 diabetes (T2D), and hyperlipidemia on amlodipine 10 mg, lisinopril 5 mg, empagliflozin 25 mg, and insulin glargine presented with a diabetic foot ulcer with probable osteomyelitis. During hospitalization, the patient developed severe nausea and vomiting. The gastroenterology team advised continuing antiemetic medicine and trying very small sips of clear liquids. However, the patient didn't improve. Therefore, the gastroenterology team was contacted again. They advised having stomach emptying tests to rule out gastroparesis as the source of emesis. In addition, they recommended continuing metoclopramide, and starting erythromycin due to inadequate improvement. Studies found a 748-min stomach emptying time. Normal is 45-90 min. An uneventful upper GI scope was done. Severe gastroparesis was verified, and the gastroenterology team advised a percutaneous jejunostomy or gastric pacemaker for gastroparesis. Unfortunately, the patient suffered a mechanical fall resulting in facial trauma. After the fall, the patient's nausea eased, and emesis stopped. He passed an oral liquids trial after discontinuation of erythromycin and metoclopramide.
CONCLUSION
This case exemplifies the difficulties in diagnosing and treating gastroparesis. An interesting correlation between parasympathetic surges and recovery in gastroparesis may be suggested by the surprising remission of symptoms following face injuries.
Topics: Humans; Gastroparesis; Male; Middle Aged; Facial Injuries; Nausea; Vomiting; Diabetes Mellitus, Type 2; Antiemetics; Gastric Emptying; Treatment Outcome
PubMed: 38750592
DOI: 10.1186/s13256-024-04558-4