A hyperuricemic rat model induced by adenine and ethambutol was established to investigate the anti-hyperuricemia activity and its mechanism of the flavonoid extract from saffron floral bio-residues. Sixty-seven SD rats were randomly divided into control group, model group, positive control group, and flavonoid extract groups(with 3 doses), respectively, and each group contained 11 or 12 rats. The hyperuricemic model was established by continuous oral administration of adenine(100 mg·kg~(-1)) and ethambutol(250 mg·kg~(-1)) for 7 days. At the same time, the positive control group was given allopurinol(20 mg·kg~(-1) per day) and the flavonoid extract groups were given the flavonoid extract at doses of 340, 170 and 85 mg·kg~(-1) per day, respectively. On day 8, rat serum, liver, kidney, and intestinal tissues were collected, and the levels of uric acid in serum and tissue, the xanthine oxidase activities and antioxi-dant activities in serum and liver were evaluated, and the kidney histopathology was explored. In addition, an untargeted serum metabolomics study was performed. According to the results, the flavonoid extract effectively reduced the uric acid levels in serum, kidney and ileum and inhibited the xanthine oxidase activities and elevated the antioxidant activities of serum and liver in hyperuricemic rat. At the same time, it reduced the levels of inflammation factors in kidney and protected renal function. Moreover, 68 differential metabolites of hyperuricemic rats were screened and most of which were lipids and amino acids. The flavonoid extract significantly retrieved the levels of differential metabolites in hyperuricemic rats, such as SM(d18:1/20:0), PC[18:0/18:2(92,12Z)], palmitic acid and citrulline, possibly through the following three pathways, i.e., arginine biosynthesis, glycine, serine and threonine metabolism, and histidine metabolism. To sum up, the flavonoid extract of saffron floral bio-residues lowered the uric acid level, increased the antioxidant activity, and alleviated inflammatory symptoms of hyperuricemic rats, which may be related to its inhibition of xanthine oxidase activity and regulation of serum lipids and amino acids metabolism.
Rats ; Animals ; Flavonoids/pharmacology* ; Uric Acid ; Crocus ; Xanthine Oxidase ; Ethambutol/adverse effects* ; Rats, Sprague-Dawley ; Hyperuricemia/drug therapy* ; Kidney ; Antioxidants/pharmacology* ; Plant Extracts/adverse effects* ; Amino Acids ; Adenine/adverse effects* ; Lipids

OBJECTIVES: To study the relationship between early parenteral nutrient intake and the development of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age less than 32 weeks who could not receive enteral nutrition within one week after birth. METHODS: A retrospective study was conducted on preterm infants born between October 2017 and August 2022 with gestational age less than 32 weeks who were admitted to the Neonatal Intensive Care Unit in Children's Hospital of Soochow University within 24 hours after birth and relied solely on parenteral nutrition within the first week of life. The study population included 79 infants with BPD and 73 infants without BPD. Clinical data during hospitalization were compared between the two groups. RESULTS: The proportions of infants with weight loss of more than 10% after birth, extrauterine growth retardation, and parenteral nutrition-associated cholestasis in the BPD group were higher than in the non-BPD group (P<0.05). The time to regain birth weight, time to achieve full enteral feeding, and corrected gestational age at discharge were longer in the BPD group than in the non-BPD group. The Z-scores of physical growth at corrected gestational age of 36 weeks were lower in the BPD group than in the non-BPD group (P<0.05). The BPD group had a higher fluid intake and a lower calories intake in the first week than the non-BPD group (P<0.05). The starting dose and total amount of amino acids, glucose, and lipids in the first week were lower in the BPD group than in the non-BPD group (P<0.05). The BPD group had a higher glucose-to-lipid ratio on the third day and higher energy-to-nitrogen and glucose-to-lipid ratios on the seventh day after birth than the non-BPD group (P<0.05). CONCLUSIONS Preterm infants with BPD had lower intake of amino acids and lipids and a lower proportion of calories provided by amino acids and lipids in the first week of life, which suggests an association between early parenteral nutrition intake and the development of BPD.
Infant ; Child ; Infant, Newborn ; Humans ; Infant, Premature ; Bronchopulmonary Dysplasia/therapy* ; Retrospective Studies ; Gestational Age ; Amino Acids ; Parenteral Nutrition/adverse effects* ; Glucose ; Lipids

OBJECTIVE: To elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics. METHODS: Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software. RESULTS: The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels. CONCLUSIONS The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.
Mice ; Animals ; Colitis, Ulcerative/drug therapy* ; Tryptophan/adverse effects* ; Aspartic Acid ; Dextrans/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Colitis/drug therapy* ; Biomarkers/metabolism* ; Amino Acids/adverse effects* ; Glycerophospholipids/therapeutic use* ; Sphingolipids/adverse effects* ; Bile Acids and Salts/adverse effects* ; Glutamates/adverse effects* ; Alanine/adverse effects* ; Arachidonic Acids/adverse effects* ; Linoleic Acids/adverse effects* ; Terpenes

PURPOSE: To evaluate the clinical manifestations of adverse drug reactions (ADRs) of parenteral nutrition (PN) use in Korea. METHODS: The Korean Adverse Event Reporting System (KAERS) database records in 2015 on PN-treated patients were used. ADRs classified as “certain,”“probable,” and “possible” based on the WHO-Uppsala Monitoring Centre criteria were analyzed. RESULTS: In total, 21,436 ADRs from 2,346 patients were included for analysis. The mean patient age was 57.1 years and the mean number of ADRs per patient was 9.1. ADRs were reported frequently with amino acids solutions (682 events, 40.8%), followed by combinations products (519 events, 31.1%), and fat emulsions (363 events, 21.7%). The frequent ADRs were gastrointestinal (507 events, 30.3%), skin (343 events, 20.5%), general disorders (239 events, 14.3%), and central/peripheral nervous system disorders (165 events, 9.9%). The common clinical symptoms were nausea (321 events, 19.2%), vomiting (105 events, 6.3%), and vein pain (102 events, 6.1%). Serious ADRs accounted for 220 patients (9.4%) and dyspnea was the most frequent clinical manifestation. CONCLUSION: This study analyzed the KAERS data in 2015 from patients treated with PN and revealed gastrointestinal and skin disorders to be the leading ADRs.
Amino Acids ; Drug-Related Side Effects and Adverse Reactions ; Dyspnea ; Emulsions ; Humans ; Korea* ; Nausea ; Nervous System Diseases ; Parenteral Nutrition* ; Skin ; Veins ; Vomiting

Phyllanthus Urinaria L. (PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl-induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl-induced liver injury were screened out using nonparametric test and Pearson's correlation analysis (OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl-induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria.
Amino Acids ; metabolism ; Animals ; Carbon Tetrachloride ; adverse effects ; Chemical and Drug Induced Liver Injury ; metabolism ; prevention & control ; Drugs, Chinese Herbal ; administration & dosage ; Gas Chromatography-Mass Spectrometry ; Humans ; Liver ; drug effects ; enzymology ; metabolism ; Male ; Metabolomics ; Phyllanthus ; chemistry ; Rats ; Rats, Sprague-Dawley ; Taurocholic Acid ; metabolism

BACKGROUNDRecently, local sustained-release antibiotics systems have been developed because they can increase local foci of concentrated antibiotics without increasing the plasma concentration, and thereby effectively decrease any systemic toxicity and side effects. A vancomycin-loaded bone-like hydroxyapatite/poly-amino acid (V-BHA/PAA) bony scaffold was successfully fabricated with vancomycin-loaded poly lactic-co-glycolic acid microspheres and BHA/PAA, which was demonstrated to exhibit both porosity and perfect biodegradability. The aim of this study was to systematically evaluate the biosafety of this novel scaffold by conducting toxicity tests in vitro and in vivo.

METHODSAccording to the ISO rules for medical implant biosafety, for in vitro tests, the scaffold was incubated with L929 fibroblasts or rabbit noncoagulant blood, with simultaneous creation of positive control and negative control groups. The growth condition of L929 cells and hemolytic ratio were respectively evaluated after various incubation periods. For in vivo tests, a chronic osteomyelitis model involving the right proximal tibia of New Zealand white rabbits was established. After bacterial identification, the drug-loaded scaffold, drug-unloaded BHA/PAA, and poly (methyl methacrylate) were implanted, and a blank control group was also set up. Subsequently, the in vivo blood drug concentrations were measured, and the kidney and liver functions were evaluated.

RESULTSIn the in vitro tests, the cytotoxicity grades of V-BHA/PAA and BHA/PAA-based on the relative growth rate were all below 1. The hemolysis ratios of V-BHA/PAA and BHA/PAA were 2.27% and 1.42%, respectively, both below 5%. In the in vivo tests, the blood concentration of vancomycin after implantation of V-BHA/PAA was measured at far below its toxic concentration (60 mg/L), and the function and histomorphology of the liver and kidney were all normal.

CONCLUSIONAccording to ISO standards, the V-BHA/PAA scaffold is considered to have sufficient safety for clinical utilization.

Amino Acids ; chemistry ; Animals ; Bone and Bones ; Durapatite ; chemistry ; Microspheres ; Polymers ; chemistry ; Rabbits ; Tissue Scaffolds ; chemistry ; Vancomycin ; adverse effects

OBJECTIVETo study the short-term response and tolerance of different doses of amino acids in parenteral nutrition among preterm infants.

METHODSThis study included 86 preterm infants who had a birth weight between 1 000 to 2 000 g and were admitted to the hospital within 24 hours of birth between March 2013 and June 2014. According to the early application of different doses of amino acids, they were randomized into low-dose group (n=29, 1.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.5 g/kg per day), medium-dose group (n=28, 2.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.7 g/kg per day), and high-dose group (n=29, 3.0 g/kg per day with an increase of 0.5-1.0 g/kg daily and a maximum of 4.0 g/kg per day). Other routine parenteral nutrition and enteral nutrition support were also applied.

RESULTSThe maximum weight loss was lower and the growth rate of head circumference was greater in the high-dose group than in the low-dose group (P<0.05). The infants in the medium- and high-dose groups had faster recovery of birth weight, earlier attainment of 100 kcal/(kg·d) of enteral nutrition, shorter duration of hospital stay, and less hospital cost than those in the low-dose group (P<0.05). Blood urea nitrogen (BUN) levels in the high-dose group increased compared with the other two groups 7 days after birth (P<0.05). The levels of creatinine, pH, bicarbonate, bilirubin, and transaminase and the incidence of complications showed no significant differences between groups (P>0.05).

CONCLUSIONSParenteral administration of high-dose amino acids in preterm infants within 24 hours after birth can improve the short-term nutritional status of preterm infants, but there is a transient increase in BUN level.

Amino Acids ; administration & dosage ; Birth Weight ; Blood Urea Nitrogen ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Nutritional Status ; Parenteral Nutrition ; adverse effects

OBJECTIVETo investigate risk factors for parenteral nutrition-associated cholestasis (PNAC) in preterm infants.

METHODSA retrospective case-control study was performed on 244 preterm infants who received parenteral nutrition (PN) for over 14 days from January 2000 to October 2011.

RESULTSCompared with those without PNAC (n=221), preterm infants with PNAC (n=23) had a longer total duration of PN, a higher total amino acid intake, a higher total lipid intake, a higher maximum daily amino acid intake, a higher maximum daily lipid intake, a higher intravenous calorie intake on the 14th day of PN, a lower birth weight and higher incidence rates of neonatal infection and anemia. Compared with those with PNAC, preterm infants without PNAC who showed a higher total amino acid intake also had a higher total lipid intake, a longer total duration of PN, a higher rate of mechanical ventilation and a lower gestational age. The preterm infants without PNAC who showed a higher total lipid intake also had a lower gestational age. Preterm infants without PNAC who showed a longer total duration of PN also had a lower gestational age.

CONCLUSIONSTotal duration of PN, total amino acid intake, maximum daily amino acid intake, total lipid intake, maximum daily lipid intake, intravenous calorie intake on the 14th day of PN, low birth weight, and neonatal infection and anemia are the risk factors for PNAC. Other risk factors need further investigation.

Amino Acids ; administration & dosage ; Case-Control Studies ; Cholestasis ; etiology ; Dietary Fats ; administration & dosage ; Energy Intake ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Parenteral Nutrition ; adverse effects ; Retrospective Studies ; Risk Factors

OBJECTIVETo investigate whether a simulated He-O2 saturation dive to 65 msw would affect oxidative balance in humans.

METHODSSeven divers participated in a simulated saturation dive to 0.75 MPa (65 msw). 24-h urine samples were collected twice before, twice during, and twice after the dive, then were analyzed for contents of superoxide dismutase (SOD), malondialdehyde (MDA), total amino acid (T-AA) and total anti-oxidant capacity (T-AOC). Meanwhile, total urine volume and body weight were measured.

RESULTSThe content of T-AA was higher. (P < 0.05) than the base value in final decompression, but reverse to normal at one week after decompression. There were no changes in contents of SOD, MDA and T-AOC during and after the dive compared with their basic value. Total urine volume was lower (P < 0.05, vs basic value) at first day in chamber, then returned to normal. Body weight gradually increased after compression till the end of decompression (higher than basic value, P < 0.05).

CONCLUSIONThese data indicate that simulated saturation dive to 65 msw may not induce obvious oxidative damage, but it is necessary to monitor 24-h urine volume and oxidative sress by time in order to prevent from tissue injury.

Adult ; Amino Acids ; urine ; Decompression ; Diving ; physiology ; Helium ; chemistry ; Humans ; Male ; Malondialdehyde ; urine ; Oxidative Stress ; physiology ; Oxygen ; adverse effects ; chemistry

OBJECTIVETo evaluate the efficacy and safety of the parenteral administration of various quantities of amino acid in preterm infants.

METHODSPreterm infants (birth weight 1000-2000 g) recruited into the study were randomized into three groups. High amino acid group (HP): 2.4 g/(kg.d) of amino acid IV within 24 hours after birth increasing by increments of 1.2 g/(kg.d) to a maximum of 3.6 g/(kg. d); medium amino acid group (MP): 1.0 g/(kg.d) of amino acid IV 24 hours after birth, increasing by increments of 0.5 g/(kg.d) until a maximum of 3.0 g/(kg.d); and low amino acid group (LP): 0.5 g/(kg.d) of amino acid on D3, increasing by increments of 0.5 g/(kg.d) until a maximum of 3.0 g/(kg.d) as the final dose.

RESULTSTotally 96 preterm infants were recruited: HP 34, MP 32 and LP 30. There were no significant differences in demographic or clinical characteristics among the 3 groups. HP group showed lower postnatal weight loss (43.4 g, 95% CI 74.3, 12.6) and weight loss% (2.84%, 95% CI 4.79%, 0.71%) than LP group. HP group showed shorter length of stay in NICU (5.25 d), days to reach 2000 g (7.03 d) and days to tolerate 100 kcal/(kg.d) enteral nutrition (4.52 d) than LP group. Cost of hospitalization was significantly lower in HP group than in LP group (-6275 RMB, 1 US$=8 RMB) and MP group (-5715 RMB). Mean serum RBP (D4), threonine and tyrosine levels were significantly higher in HP group than in LP group. Serum insulin levels were similar; mean serum glucose level was lower in HP group than in LP group. HP infants had lower incidence of sepsis than LP infants (21.9% vs 40.0%). There were no significant differences in the levels of blood ammonia, acid-base balance (as determined by pH and NaHCO3-), BUN, Cr, AST, and ALT.

CONCLUSIONSIntensive and early administration of intravenous amino acid [2.4 g/(kg.d)] improves preterm infants' growth and the tolerance of enteral feeding. It also reduces the cost of hospitalization, and the incidence of sepsis.

Amino Acids ; administration & dosage ; adverse effects ; Humans ; Infant, Newborn ; Infant, Premature ; Parenteral Nutrition