Study on the Stability of Antitumor Candidate Gedatolisib in Plasma in vitro and Simulated Gastric/intestinal Fluid and Its Catabolites Analysis / 中国药房

OBJECTIVE：To investigate th e stabilities of antitumor candid ate Gedatolisib in plasma in vitro and simulated gastric/intestinal fluids ，and to analyze the possible catabolites in plasma. METHODS ：HPLC method was adopted. Using indometacin as internal standard ，the contents of Gedatolisib incubated in plasma of SD rats （male）for 0，0.5，1.0，1.5，2.0，3.0 h and blank simulated gastric fluid （pH 1.3，no enzyme ），blank simulated intestinal fluid （pH 6.8，no enzyme ），simulated gastric fluid（pH 1.3，containing pepsin ）and simulated intestinal fluid （pH 6.8，containing trypsin ）for 0，0.5，1.0，2.0，3.0，4.0，6.0 h were determined. The remaining percentage of Gedatolisib was calculated. UPLC-Q-TOF/MS was used to analyze the TIC of blank plasma and incubated samples. The differential peaks were compared， and catabolites were inferred by MS 1Z073）.gzwjkj2019-1- chromatograms. RESULTS ： The remaining percentage in plasma of rats for 2.0 h was about 63％，and there was nosignificant change after continued incubation. The remaining percentage of Gedatolisib incubated in blank simulated intestinal fluid for different time ranged （99.18 ± 2.15）％ -（103.20 ± 3.41）％ . The remaining percentage in simulated com intestinal fluids for 2.0 h ranged （88.76 ± 1.53）％ . The remaining percentage in blank simulated gastric fluids for 2.0 h was ranged （85.63±1.55）％，and there was no significant change after continued incubation. The remaining percentage in simulated gastric fluid was from （94.94±3.52）％（0 h）to（16.19±1.17）％ （6.0 h）. TIC of UPLC-Q-TOF/MS showed that the differential peaks of incubated samples and blank plasma was 6.42 min under positive mode scanning ，molecular ion peak of m/z 616.335 1，simulated 632.327 7，630.317 0，602.278 6 [M+H]+ could be found in scanning channel. It was speculated that Gedatolisib could generate 1-（4-（3-（4，6-dimorpholino-1，3，5-triazin-2-yl）phenyl）urea） benzoyl）-N，N-dimethylpiperidin-4-amine oxide ，1-（4-（4-（dimethylamino）piperidine-1-carbonyl）phenyl）-3-（4-（4-morpholino-6- （3-oxomorpholino）-1，3，5-triazin-2-yl）phenyl）urea and 1-（4-（3-（4-（4，6-dimorpholino-1，3，5-triazin-2-yl）phenyl）urea） benzoyl）-N-methylpiperidine. CONCLUSIONS ：Gedatolisib is not stable in rat plasma ，and it may undergo terminal N oxidation， morpholine ring oxidation and terminal N demethylation. Gedatolisib is stable in artificial intestinal fluid and blank artificial gastric/ intestinal fluid ，and degrades obviously in the presence of pepsin.

Evaluation of pH and residual gastric volume after colon preparation with mannitol: prospective randomized study comparing procedure performed after 3 hours versus 6 hours

OBJECTIVES: Our goal was to compare the hydrogen potential (pH) and residual gastric volume (RGV) of patients undergoing colonoscopy after 3 and 6 hours of colon preparation with mannitol. METHODS: We described a prospective randomized trial with a 50:50 allocation rate of two distinct times of colonoscopy after colon preparation with 10% mannitol. We included outpatients aged over 18 years, with no history of gastric surgeries and an American Society of Anesthesiologists (ASA)-rated anesthetic risk below III. Colonoscopy was performed after upper digestive endoscopy at two different times: 3 versus 6-hour after mannitol ingestion. During upper gastrointestinal endoscopy, we measured RGV and evaluated pH with a digital pH meter. Clinical trials.gov: 71123317.9.3001.0065 RESULTS: We randomized a total of 100 participants to the 3 and 6-hour groups, with the patients in the 6-hour group being younger and presenting a higher body mass index (BMI). The intervention did not result in any statistically significant differences between the two groups, neither for the RGV (p=0.98) or the pH (p=0.732). However, the subgroup of patients with diabetes mellitus showed statistically significant higher RGV values in the 3-hour group. CONCLUSION There was no difference between RGV and pH values at 3 versus 6-hour after bowel preparation with mannitol, except for RGV in diabetic patients at 3 hours. As prolonged fasting protocols may result in adverse events such as dehydration and electrolyte imbalance, we can infer that colonic preparation with mannitol in shorter fasting periods, such as 3 hours, can be adopted safely and routinely.

Application of nasorhal pylorus after the naso pylorus gastric tube reinfusion in ICU / 中国实用护理杂志

Objective To summarize the experience of naso pyloric posterior blind feeding tube and the application value and nursing strategy of gastric fluid reinfusion technique in critically ill patients. Methods A total of 100 patients with gastroduodenal retention were selected from February 2016 to April 2018 in our hospital. The gastrointestinal dysfunction was classified as class II to grade II, and the daily gastrointestinal decompression amount was more than 500 ml as the research object. All the 100 patients were treated with nasal blinded pylorus tube and were randomly divided into two groups. Based on prevention/ control infection and organ function support protection and so on, the self-made modified closed autologous gastric juice retransfusion system was used for enteroenteroenteral retransmission and enteral nutrition treatment, while the patients in the control group only carried out enteral nutrition and did not carry out gastric juice transfusion. The indexes of the patients during the treatment of gastric juice were monitored, including water electrolyte disturbance and acid-base balance disorder, the time required for the total enteral nutrition, the imbalance of intestinal flora, the average number of gastric fluid return and the feeding intolerance, etc., and the complications and the complications during the process of the gastric juice transfusion were recorded. The success rate of nutrient tube after blind pylorus pylorus was analyzed and its causes were analyzed. Results After naso pylorus pylorus, the success rate of the nutrient tube was 91%. The main reasons for failure included the patients is intolerant of nutrient tube and limited body position. There were no statistical difference in the incidence of dysbacteriosis, aspiration and primary metabolic acid-base disturbance between the experimental group and the control group (P>0.05). In the experimental group, the number of patients with serious electrolyte disturbance, feeding intolerance and the number of days required to achieve total enteral nutrition, and the average number of days required for gastric juice transfusion were 1, 6, 5, (5.74±1.42)d, respectively, were significantly less than those in the control group of 8, 15, 19,(13.94±3.53)d, with statistically significant differences (χ2=-15.239-7.294, P <0.05 or 0.01). Conclusions In the patients with ICU, it is easy to operate, easy to master, and to reduce the incidence of internal environment disorder and feeding intolerance, which is suitable for clinical popularization.

Application of nasorhal pylorus after the naso pylorus gastric tube reinfusion in ICU / 中国实用护理杂志

Objective@#To summarize the experience of naso pyloric posterior blind feeding tube and the application value and nursing strategy of gastric fluid reinfusion technique in critically ill patients.@*Methods@#A total of 100 patients with gastroduodenal retention were selected from February 2016 to April 2018 in our hospital. The gastrointestinal dysfunction was classified as class II to grade II, and the daily gastrointestinal decompression amount was more than 500 ml as the research object. All the 100 patients were treated with nasal blinded pylorus tube and were randomly divided into two groups. Based on prevention/control infection and organ function support protection and so on, the self-made modified closed autologous gastric juice retransfusion system was used for enteroenteroenteral retransmission and enteral nutrition treatment, while the patients in the control group only carried out enteral nutrition and did not carry out gastric juice transfusion. The indexes of the patients during the treatment of gastric juice were monitored, including water electrolyte disturbance and acid-base balance disorder, the time required for the total enteral nutrition, the imbalance of intestinal flora, the average number of gastric fluid return and the feeding intolerance, etc., and the complications and the complications during the process of the gastric juice transfusion were recorded. The success rate of nutrient tube after blind pylorus pylorus was analyzed and its causes were analyzed.@*Results@#After naso pylorus pylorus, the success rate of the nutrient tube was 91%. The main reasons for failure included the patients is intolerant of nutrient tube and limited body position. There were no statistical difference in the incidence of dysbacteriosis, aspiration and primary metabolic acid-base disturbance between the experimental group and the control group (P>0.05). In the experimental group, the number of patients with serious electrolyte disturbance, feeding intolerance and the number of days required to achieve total enteral nutrition, and the average number of days required for gastric juice transfusion were 1, 6, 5, (5.74±1.42)d, respectively, were significantly less than those in the control group of 8, 15, 19, (13.94±3.53) d, with statistically significant differences (χ2=-15.239-7.294, P <0.05 or 0.01).@*Conclusions@#In the patients with ICU, it is easy to operate, easy to master, and to reduce the incidence of internal environment disorder and feeding intolerance, which is suitable for clinical popularization.

Comparative study on basic chemical dissolubility of Shenzhu Yichang Pills fine and ultrafine powders / 中草药

Objective: To compare the differences in the dissolution behavior of puerarin, paeoniflorin, and liquiritin between ultrafine powder and fine powder of Shenzhu Yichang Pills to provide experimental evidence for optimize the production technology. Methods: The relative cumulative dissolution rates of powders of Shenzhu Yichang Pills in different dissolution mediums were quantitatively studied by HPLC column of Agilent Eclipse XDB-C18 (150 mm × 4.6 mm, 5 μm), mobile phase of CH3CN-0.1% H3PO4 (1189), flow rate of 1.5 mL/min, detection wavelength of 230 nm, and the volume of injection was 10 μL. Results: The relative cumulative dissolution rates of puerarin and liquiritin in distilled water and artificial gastric fluid for fine powder were bigger than that for ultrafine powder, but the relative cumulative dissolution rates of paeoniflorin in distilled water and artificial gastric fluid for fine powder were smaller than that for ultrafine powder. The dissolution behavior of fine powder was similar to that of ultrafine powder in artificial intestinal fluid. Conclusion: An appropriate degree of ultrafine grinding can promote the dissolution of active ingredients of Shenzhu Yichang Pills, and the dissolution is influenced by the dissolution medium. Further research is needed to the application of ultrafine grinding technology for Shenzhu Yichang Pills.

Clinical Significance of Newborn Gastric Inflammatory Mediators

PURPOSE: We performed this study to determine (1) whether the levels of inflammatory mediators, including matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-3 (ICAM-3), in gastric fluid (GF) in premature newborns are associated with those in amniotic fluid (AF) in their mothers and (2) whether the levels of the inflammatory mediators in newborn GF are associated with the presence of intrauterine inflammation (IUI). METHODS: Sixty-two pairs of pregnant women and their premature newborns born at <35 weeks' gestation by cesarean delivery were enrolled in this study. AF and newborn GFs were obtained during cesarean section procedures. Levels of MMP-9, ICAM-3, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) were measured and compared between the AF and newborn GFs in each dyad, according to the presence or absence of chorioamnionitis (CA), preterm prelabor rupture of membranes (PPROM), and preterm labor (PTL). RESULTS: The levels of MMP-9, ICAM-3, IL-6, IL-8, and TNF-alpha in newborn GF were significantly correlated with those in AF in each dyad. The premature newborns and their mothers with CA had significantly higher GF MMP-9, IL-8, and TNF-alpha levels than those without CA. Those with PPROM or PTL showed similar findings in terms of GF MMP-9, IL-8, and TNF-alpha levels. CONCLUSION: The newborn GF immediately after birth can be a useful alternative source of information on whether a premature infant has been exposed to IUI at the time of delivery.

Syzygium sp (Myrtaceae) Extracts: Inhibition of Alpha Amylase.

Aims: The aims of this study were: a) prepare crude extracts of commercial teas Syzygium sp by different methods (maceration, decoction and infusion) in different proportions (1:20, 1:50 and 1:100) and b) submit them the inhibition assays digestive enzyme alpha-amylase before and after exposure to a simulated gastric fluid. Place and Duration of Study: Laboratório de Bioquímica, Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Brazil, between August 2012 and July 2013. Methodology: Five samples of Syzygium sp teas were purchased commercially from pharmacies, drugstores and health food stores. Results: In the first step - inhibition of enzymatic extracts of the teas without simulated gastric fluid - the results showed significant inhibition of alpha-amylase (mean 92.84%, CV = 3.86%). However, when these extracts were placed in contact with the simulated gastric fluid was observed decreased inhibition of alpha – amylase, suggesting a possible reduction of hypoglycemic potential of these teas under physiological conditions. Conclusion: Aqueous extract Syzygium sp have high percentages of inhibition of the enzyme amylase, suggesting a potential hypoglycemic effect. Additional studies aiming at elucidating the chemical compounds present in the extracts of Syzygium sp using chromatographic techniques will be performed.

Intestinal Microbial Community Profiles of a Newborn Preterm Infant Using Pyrosequencing Analysis: Pilot Study

DNA pyrosequencing, one of the advanced methods for DNA sequencing, has been employed for phylogenetic analysis of bacterial communities using the conserved 16S rRNA gene. We performed a pilot study on a mother-neonate pair utilizing the DNA pyrosequencing assays to investigate the diversity of microbial communities in maternal amniotic fluid (AF), vagina, and rectum and newborn gastric fluid (GF) and stool. Phylum level analysis revealed that bacterial community was dominated by Firmicutes (63.2%) in maternal feces, and Actinobacteria (84.9%) in maternal vaginal swab. The bacterial communities in both the AF and GF were dominated by Proteobacteria (67.8%). Interestingly, the bacterial community in the newborn's meconium was quite similar to that in the AF. However, the composition of the bacterial community in newborn's feces was different on day 14 and dominated by Firmicutes (91.1%). Genus-level analysis revealed that the bacterial community in maternal feces was dominated by Anaerococcus (19.5%) and Prevotella (18.7%), whereas that in the maternal vaginal swab was dominated by Atopobium (83.6%). The bacterial communities in both the AF and GF were dominated by Sphingomonas (38.5%). The bacterial community in the newborn's meconium was quite similar to that in the AF, which was dominated by Sphingomonas (45.2%). However, the composition of bacterial community in the newborn's feces on day 14 was relatively different. Future studies with a large number of infants are needed to determine the factors involved in the changing profile of newborn's fecal bacterial communities.

<b>Three Stroke Cases with Gastric Reflux during Nasogastric Tube Feeding Successfully Treated with Rikkunshito Extract</b> / 日本東洋医学雑誌

We report three cases of stroke in which rikkunshito was administered to improve the reflux of gastric fluid from a nasogastric tube in a short time.<br>Case 1 : a 63-year old female with right cerebellar hemorrhage who underwent surgical evacuation. Reflux of up to 650 ml gastric fluid from a nasogastric tube was observed after surgery. By the 4 th day of rikkunshito administration, the reflux decreased to 10 ml.<br>Case 2 : a 44-year old male whose consciousness had deteriorated before surgical treatment because of subarachnoid hemorrhage and re-rupture. Endovascular embolization and bilateral external ventricular drainage were performed for the anterior communicating artery aneurysm. Several days later, rikkunshito administration was initiated because of a reflux of 550 ml gastric fluid from the nasogastric tube. By the 3 rd day of rikkunshito administration, almost no episodes of reflux during tube feeding were observed.<br>Case 3 : a 72-year old male who suffered from intratumoral hemorrhage after undergoing surgery for metastatic brain tumor. The intratumoral hemorrhage was treated conservatively. Reflux of 200 ml gastric fluid from the nasogastric tube was observed. By the 3 rd day of rikkunshito administration, the reflux decreased to 10 ml.<br>These findings suggest that rikkunshito is useful in stroke cases with considerable reflux from a nasogastric tube.

Denaturing Gradient Gel Electrophoresis for Detection of Bacterial Population and Diversity in Amniotic Fluids and Neonatal Gastric Fluids

PURPOSE: Intra-amniotic infection (IAI) is often polymicrobial, and the 16S rDNA PCR assay has a major limitation that its interpretation is difficult in the presence of multiple 16S rDNAs. Denaturing gradient gel electrophoresis (DGGE) can overcome this limitation by separating PCR products based on sequence. We performed the DGGE analysis to investigate bacterial prevalence and diversity in amniotic fluids from pregnant women with preterm births and gastric fluids from their newborns. METHODS: DNA was extracted from bacterial cells in amniotic fluid (AF) and gastric fluid (GF) and was amplified with universal 16S rDNA primers. For DGGE analysis, the PCR products were loaded onto polyacrylamide gels that were made with denaturing gradients. RESULTS: Bacterial 16S rDNA was detected by PCR from all AF and GF samples. The bacterial species in AF samples were the following: Lactobacillus reuteri (87.0%), uncultured Enterococcus species (65.2%), Ureaplasma urealyticum (13.0%), and Enterococcus faecalis (4.3%). The bacterial species in GF samples were the following: Lactobacillus reuteri (95.2%), uncultured Enterococcus species (42.9%), and Ureaplasma urealyticum (4.8%). Two or more species were identified from 69.6% of AF and 47.6% of GF samples. CONCLUSION: We suggest that DGGE analysis allows improved understanding of microbial diversity and community in AF and GF.

Fluorescent Antibody Method for Detection of Helicobacter pylori in Dental Plaque and Gastric Fluid: An Evaluation / 中华医院感染学杂志

OBJECTIVE To screen for a simple,accurate and no-traumatic detecting method of Helicobacter pylori(Hp). METHODS Hp in gastric fluid and dental plaque was detected with fluorescent antibody method,bacterial culture,urease test and Hp diagnosis card at the same time in 62 cases with gastric and duodenal disease.The gather of gastric fluid applied the capsule method. RESULTS The detective rates of Hp in gastric fluid by four methods were 85.5%,9.7%,61.3%,and 56.5%;the detective rates of Hp in dental plaque by four methods were 88.7%,25.8%,69.4%,and 90.3%,respectively. CONCLUSIONS Fluorescent antibody method combined with capsule method detecting Hp in gastric fluid is specific,sensitive and without trauma.Thus,it is suggested to be used clinically.

Effects of Preoperative NPO and Oral Fluid on Gastric Fluid Volume and pH / 대한마취과학회지

BACKGROUND: To reduce the risk of Mendelson's syndrome, it is customary to fast patients for 8 hours before anesthesia. However preoperative fast is unpleasant for patients, who complain frequently of thirst and dry mouth, and this conventional fast may be over-cautious. We have studied the effect of ingestion of barley tea, a Korean popular beverage, 3 hours before anesthesia on gastric contents (volume and pH), blood sugar level, thirst, and anxiety. METHODS: We studied prospectively 284 adult patients undergoing elective surgery. The patients in the control group (n=142) fasted for at least 8 hours, and those in the experimental group (n=142) received 250 ml of barley tea 3 hours before anesthesia. On arrival in the operating room, subjects were asked to assess thirst and anxiety. After induction of anesthesia, gastric contents were aspirated via 18 French Salem sump tube and gastric volume, pH and blood sugar level were measured. RESULTS: There were no statistically significant differences in gastric fluid volume and pH and blood sugar level between control and experimental groups. However, patients in experimental group complained of less thirst than those in control group. CONCLUSIONS: This study demonstrates that in adult patients undergoing elective surgery, allowing patients to drink 250 ml of barley tea until 3 hours before anesthesia may relieve patients from thirst without compromising safety.