This study aims to investigate the hepatotoxicity of Psoraleae Fructus water extract and the underlying mechanism in rats. Forty-eight rats were randomly assigned into four groups: a blank group and low-(BZGL, 6.25 g·kg~(-1)), medium-(BGZM, 12.5 g·kg~(-1)), and high-dose(BGZH, 25 g·kg~(-1)) Psoraleae Fructus water extract groups. The rats were treated for 28 days, and toxicity and mortality were observed daily. After 28 days, the rats were sacrificed, and the body weight, liver index, and liver-to-brain ratio were calculated. The morphological changes in the liver tissue were observed, and the serum levels of related biochemical indicators were measured. The results showed that compared with the blank group, Psoraleae Fructus water extracts of different doses decreased the body weight, increased the liver index and liver-to-brain ratio, and caused liver hypertrophy and pathological changes. Pathological examination revealed that the rats in Psoraleae Fructus water extract groups had bile duct hyperplasia, inflammatory cell infiltration, and liver cell fibrosis. Compared with the blank group, BGZL elevated the levels of alanine transaminase(ALT), α-glutathione S-transferase(α-GST), and total bile acid(TBA)(P<0.05), and BGZM and BGZH elevated the levels of ALT, TBA, α-GST, γ-glutamyl transferase(γ-GT), purine nucleoside phosphorylase(PNP), ornithine carbamoyltransferase(OCT), and arginase(ArgI)(P<0.05). Compared with the blank group, Psoraleae Fructus water extracts of different doses down-regulated the mRNA and protein levels of bile salt export pump(BSEP) and farnesoid X receptor(FXR) and up-regulated the mRNA and protein levels of tumor necrosis factor-α(TNF-α), nuclear factor kappaB(NF-κB), and cholesterol 7 alpha-hydroxylase(CYP7A1)(P<0.05). The results suggested that Psoraleae Fructus water extract caused toxicity in rats, showing a dose-toxicity relationship. Psoraleae Fructus water extract may cause liver damage, which may be due to its effect on liver bile acid secretion and induction of inflammation.
Rats ; Animals ; Water ; Rats, Sprague-Dawley ; Liver ; NF-kappa B ; Liver Cirrhosis ; Bile Acids and Salts ; Body Weight ; RNA, Messenger

OBJECITVIE: To compare the liver protective activity of fresh/dried dandelion extracts against acetaminophen (APAP)-induced hepatotoxicity. METHODS: Totally 90 Kunming mice were randomly divided into 10 groups according to body weight (9 mice for each group). The mice in the normal control and model (vehicle control) groups were administered sodium carboxymethyl cellulose (CMC-Na, 0.5%) only. Administration groups were pretreated with high and low-dose dry dandelion extract (1,000 or 500 g fresh herb dried and then decocted into 120 mL solution, DDE-H and DDE-L); low-, medium- and high-dose dandelion juice (250, 500, 1,000 g/120 mL, DJ-L, DJ-M, and DJ-H); fresh dandelions evaporation juice water (120 mL, DEJW); dry dandelion extract dissolved by pure water (1 kg/120 mL, DDED-PW); dry dandelion extract dissolved by DEJW (120 g/120 mL, DDED-DEJW) by oral gavage for 7 days at the dosage of 0.5 mL solution/10 g body weight; after that, except normal control group, all other groups were intraperitonealy injected with 350 mg/kg APAP to induce liver injury. Twenty hours after APAP administration, serum and liver tissue were collected and serum alanine aminotransferase (AST), aspartate transaminase (ALT), alkaline phosphatase (AKP), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) activities were quantified by biochemical kits; tumor necrosis factor (TNF-α), interleukin (IL)-2, and IL-1 β contents in liver tissue were determined by enzyme linked immunosorbent assay kits. Histopathological changes in liver tissues were observed by hematoxylin and eosin staining; TUNEL Assay and Hoechst 33258 staining were applied for cell apoptosis evaluation. The expressions of heme oxygenase-1 (HO-1), nuclear factor erythroid-2-related factor 2 (Nrf-2), caspase-9, B-cell leukemia/lymphoma 2 (Bcl-2), Bax and p-JNK were determined by Western blot analysis. RESULTS: Pretreatment with fresh dandelion juice (FDJ, including DJ-L, DJ-M, DJ-H, DEJW and DDED-DEJW) significantly decreased the levels of serum ALT, AST, AKP, TNF-α and IL-1β compared with vehicle control group (P<0.05 or P<0.01). Additionally, compared with the vehicle control group, FDJ decreased the levels of hepatic MDA and restored GSH levels and SOD activity in livers (P<0.05 or P<0.01). FDJ inhibited the overexpression of pro-inflammatory factors including cyclooxygenase-2 and inducible nitric oxide synthase in the liver tissues (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that FDJ pretreatment inhibited activation of apoptotic signaling pathways via decreasing of Bax, and caspase-9 and JNK protein expression, and inhibited activation of JNK pathway (P<0.05 or P<0.01). Liver histopathological observation provided further evidence that FDJ pretreatment significantly inhibited APAP-induced hepatocyte necrosis, inflammatory cell infiltration and congestion. CONCLUSIONS FDJ pretreatment protects against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway, and the effect of fresh dandelion extracts was superior to dried dandelion extracts in APAP hepatotoxicity model mice.
Acetaminophen/toxicity* ; Alanine Transaminase ; Animals ; Apoptosis ; Body Weight ; Caspase 9/metabolism* ; Chemical and Drug Induced Liver Injury/prevention & control* ; Dichlorodiphenyl Dichloroethylene/pharmacology* ; Glutathione/metabolism* ; Liver ; Mice ; Oxidative Stress ; Plant Extracts/therapeutic use* ; Superoxide Dismutase/metabolism* ; Taraxacum/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Water/metabolism* ; bcl-2-Associated X Protein/metabolism*

OBJECTIVES: The metabolomics technique of LC-MS/MS combined with data analysis was used to detect changes and differences in metabolic profiles in the vitreous humor of early rat carcasses found in water, and to explore the feasibility of its use for early postmortem submersion interval (PMSI) estimation and the cause of death determination. METHODS: The experimental model was established in natural lake water with 100 SD rats were randomly divided into a drowning group (n=50) and a postmortem (CO₂ suffocation) immediately submersion group (n=50). Vitreous humor was extracted from 10 rats in each group at 0, 6, 12, 18 and 24 h postmortem for metabolomics analyses, of which 8 were used as the training set to build the model, and 2 were used as test set. PCA and PLS multivariate statistical analysis were performed to explore the differences in metabolic profiles among PMSI and causes of death in the training set samples. Then random forest (RF) algorithm was used to screen several biomarkers to establish a model. RESULTS: PCA and PLS analysis showed that the metabolic profiles had time regularity, but no differences were found among different causes of death. Thirteen small molecule biomarkers with good temporal correlation were selected by RF algorithm. A simple PMSI estimation model was constructed based on this indicator set, and the data of the test samples showed the mean absolute error (MAE) of the model was 0.847 h. CONCLUSIONS The 13 metabolic markers screened in the vitreous humor of rat corpses in water had good correlations with the early PMSI. The simplified PMSI estimation model constructed by RF can be used to estimate the PMSI. Additionally, the metabolic profiles of vitreous humor cannot be used for early identification of cause of death in water carcasses.
Animals ; Biomarkers/metabolism* ; Cadaver ; Chromatography, Liquid ; Immersion ; Postmortem Changes ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Vitreous Body/metabolism* ; Water/metabolism*

For patients with short bowel syndrome who undergo ileostomy, nutritional management is essential to prevent complications associated with a high-output stoma (HOS). We report a practical example of ostomic, medical nutrition therapy provided by an intensive nutritional support team (NST). A 42-year-old male with a history of Crohn's disease visited Seoul National University Hospital for treatment of mechanical ileus. He underwent loop ileostomy after extensive small bowel resection. As his remaining small bowel was only 160 cm in length, the stomal output was about 3,000 mL/day and his body weight fell from 52.4 to 40.3 kg. Given his clinical condition, continuous tube feeding for 24 h was used to promote adaptation of the remnant bowel. Thereafter, an oral diet was initiated and multiple, nutritional educational sessions were offered by dietitians. Constant infusion therapy was prescribed and included in the discharge plan. Two months after discharge, his body weight had increased to 46.6 kg and his hydration status was appropriately maintained. This case suggests that the critical features of medical nutritional therapy for ostomy management are frequent assessments of fluid balance, weight history, and laboratory data and after nutritional interventions.
Adult ; Body Weight ; Crohn Disease ; Diet ; Diet Therapy ; Enteral Nutrition ; Humans ; Ileostomy ; Ileus ; Male ; Nutrition Therapy ; Nutritional Support ; Nutritionists ; Ostomy ; Seoul ; Short Bowel Syndrome ; Water-Electrolyte Balance

OBJECTIVE: Lurasidone is an antipsychotic drug that shows a relative lack of weight gain common to many antipsychotics. Aripiprazole and ziprasidone also show little weight gain and can reduce olanzapine-induced food intake and weight gain in animals, paralleling some clinical findings. We hypothesized that lurasidone would have similar actions. METHODS: Female Lister-hooded rats received intraperitoneal injection either 2× vehicle (saline), lurasidone (3 mg/kg) and vehicle, olanzapine (1 mg/kg) and vehicle, or olanzapine and lurasidone. Following drug administration food intake was measured for 60min. A further series of rats underwent a seven-day regime of once-daily administration of the above doses and free access to food and water. Weight gain over the course of the study was monitored. RESULTS: Olanzapine induced a significant increase in food intake while lurasidone showed no significant effect. Co-administration of lurasidone with olanzapine suppressed the increase in food intake. Repeated dosing showed an increase in body weight after seven days with olanzapine, and no significant effect observed with lurasidone, while repeated administration of lurasidone with olanzapine reduced the effect of olanzapine on the increase in body weight. CONCLUSION: These findings support our hypotheses in that lurasidone, in addition to a lack of effect on acute food intake and short term weight gain, can reduce olanzapine-induced food intake and weight gain in rats. This indicates the drug to have an active anti-hyperphagic mechanism, rather than solely the absence of a drug-induced weight gain that is such a severe limitation of drugs such as olanzapine.
Animals ; Antipsychotic Agents ; Aripiprazole ; Body Weight ; Eating ; Female ; Humans ; Injections, Intraperitoneal ; Lurasidone Hydrochloride ; Rats ; Water ; Weight Gain

OBJECTIVES: The emergence of multidrug-resistant tuberculosis (MDR-TB) is a major challenge for the global control of tuberculosis (TB). The aim of this study was to determine the risk factors associated with MDR-TB in Sudan. METHODS: This case-control study was conducted from May 2017 to February 2019. Patients newly diagnosed with MDR-TB were selected as cases, and controls were selected from TB patients who responded to first-line anti-TB drugs. A questionnaire was designed and used to collect data from study participants. Logistic regression was used to evaluate associations between risk factors and MDR-TB infection. The best multivariate model was selected based on the likelihood ratio test. RESULTS: A total of 430 cases and 860 controls were selected for this study. A history of previous TB treatment (adjusted odds ratio [aOR], 54.85; 95% confidence interval [CI], 30.48 to 98.69) was strongly associated with MDR-TB infection. We identified interruption of TB treatment (aOR, 7.62; 95% CI, 3.16 to 18.34), contact with MDR-TB patients (aOR, 5.40; 95% CI, 2.69 to 10.74), lower body weight (aOR, 0.89; 95% CI, 0.87 to 0.91), and water pipe smoking (aOR, 3.23; 95% CI, 1.73 to 6.04) as factors associated with MDR-TB infection. CONCLUSIONS: Previous TB treatment and interruption of TB treatment were found to be the main predictors of MDR-TB. Additionally, this study found that contact with MDR-TB patients and water pipe smoking were associated with MDR-TB infection in Sudan. More efforts are required to decrease the rate of treatment interruption, to strengthen patients’ adherence to treatment, and to reduce contact with MDR-TB patients.
Body Weight ; Case-Control Studies ; Humans ; Logistic Models ; Odds Ratio ; Risk Factors ; Smoking ; Sudan ; Tuberculosis ; Tuberculosis, Multidrug-Resistant ; Water

BACKGROUND: Chronic kidney disease (CKD) is associated with fluid retention, which increases total body water (TBW) and leads to changes in intracellular water (ICW) and extracellular water (ECW). This complicates accurate assessments of body composition. Analysis of bioelectrical impedance may improve the accuracy of evaluation in CKD patients and multiple machines and technologies are available. We compared body composition by bioimpedance spectroscopy (BIS) against multi-frequency bioimpedance analysis (BIA) in a multi-ethnic Asian population of stable, non-dialysis CKD patients. METHODS: We recruited 98 stable CKD patients comprising 54.1% men and 70.4% Chinese, 9.2% Malay, 13.3% Indian, and 8.2% other ethnicities. Stability was defined as no variation in serum creatinine > 20% over three months. Patients underwent BIS analyses using a Fresenius body composition monitor, while BIA analyses employed a Bodystat Quadscan 4000. RESULTS: Mean TBW values by BIS and BIA were 33.6 ± 7.2 L and 38.3 ± 7.4 L; mean ECW values were 15.8 ± 3.2 L and 16.9 ± 2.7 L; and mean ICW values were 17.9 ± 4.3 L and 21.0 ± 4.9 L, respectively. Mean differences for TBW were 4.6 ± 1.9 L (P < 0.001), for ECW they were 1.2 ± 0.5 L (P < 0.001), and for ICW they were 3.2 ±1.8 L (P < 0.001). BIA and BIS measurements were highly correlated: TBW r = 0.970, ECW r = 0.994, and ICW r = 0.926. Compared with BIA, BIS assessments of fluid overload appeared to be more associated with biochemical and clinical indicators. CONCLUSION: Although both BIA and BIS can be used for body water assessment, clinicians should be aware of biases that exist between bioimpedance techniques. The values of body water assessments in our study were higher in BIA than in BIS. Ethnicity, sex, body mass index, and estimated glomerular filtration rate were associated with these biases.
Adult ; Asian Continental Ancestry Group ; Bias (Epidemiology) ; Body Composition ; Body Mass Index ; Body Water ; Creatinine ; Electric Impedance ; Glomerular Filtration Rate ; Humans ; Kidney Diseases ; Male ; Methods ; Nutrition Assessment ; Renal Insufficiency, Chronic ; Spectrum Analysis ; Water

The kidney collecting duct (CD) is a tubular segment of the kidney where the osmolality and final flow rate of urine are established, enabling urine concentration and body water homeostasis. Water reabsorption in the CD depends on the action of arginine vasopressin (AVP) and a transepithelial osmotic gradient between the luminal fluid and surrounding interstitium. AVP induces transcellular water reabsorption across CD principal cells through associated signaling pathways after binding to arginine vasopressin receptor 2 (AVPR2). This signaling cascade regulates the water channel protein aquaporin-2 (AQP2). AQP2 is exclusively localized in kidney connecting tubules and CDs. Specifically, AVP stimulates the intracellular translocation of AQP2-containing vesicles to the apical plasma membrane, increasing the osmotic water permeability of CD cells. Moreover, AVP induces transcription of the Aqp2 gene, increasing AQP2 protein abundance. This review provides new insights into the transcriptional regulation of the Aqp2 gene in the kidney CD with an overview of AVP and AQP2. It summarizes current therapeutic approaches for X-linked nephrogenic diabetes insipidus caused by AVPR2 gene mutations.
Aquaporin 2 ; Arginine Vasopressin ; Body Water ; Cell Membrane ; Diabetes Insipidus, Nephrogenic ; Gene Expression Regulation ; Homeostasis ; Kidney ; Kidney Tubules, Collecting ; Osmolar Concentration ; Permeability ; Phenobarbital ; Receptors, Vasopressin ; Water

There are several diagnostic findings required for confirming a postmortem diagnosis of drowning. However, postmortem diagnosis of drowning remains challenging for forensic pathologists. In previous reports, several biochemical tests using various body fluids have been studied for their potential use in the postmortem diagnosis of drowning. In this study, the concentration of sodium and chloride was tested in various postmortem body fluids (vitreous humor, sphenoid sinus fluid, pleural fluid, cerebrospinal fluid, etc.) and their results were interpreted for their potential use in postmortem diagnosis of drowning. We examined 67 autopsy cases (freshwater drowning, 12 cases; seawater drowning, 16 cases; control group, 39 cases). The sodium and chloride concentration in the vitreous humor, sphenoid sinus fluid, and pleural fluid significantly correlated with each other. Furthermore, the concentrations of sodium, chloride, and the sum of the concentrations of the two in the various postmortem body fluids were significantly different in the three groups, when compared with each other (generally the concentration being the highest in the seawater drowning group, followed by the control group and the freshwater drowning group). Biochemical tests using various postmortem body fluids may serve as useful indicators for the postmortem diagnosis of drowning and for the differential diagnosis between freshwater and seawater drowning.
Autopsy ; Biochemistry ; Body Fluids ; Cerebrospinal Fluid ; Diagnosis ; Diagnosis, Differential ; Drowning ; Fresh Water ; Seawater ; Sodium ; Sphenoid Sinus ; Vitreous Body

BACKGROUND: Direct-to-implant breast reconstruction following nipple-sparing mastectomy is becoming increasingly common. The weight of the breast specimen informs implant selection. However, specimens of the same weight may have different volume. Therefore, identifying the factors affecting the density of breast specimens may facilitate the selection of implants with an appropriate volume. METHODS: From December 2015 to May 2018, 108 patients underwent direct-to-implant reconstruction following nipple-sparing mastectomy. The weight of the breast specimens was measured using an electronic scale in the operating room. Furthermore, the volume of specimens was measured using the water displacement technique. Multiple regression analysis was performed on factors that can affect breast density, such as menopause, neoadjuvant chemotherapy (CTx), age, body mass index, and diabetes mellitus. RESULTS: The average density of breast specimens in patients older than 50 years (n=36) was 0.96±0.04 g/mL, which was significantly lower than the 1.01±0.08 g/mL observed in patients younger than 50 years (n=72) (P=0.007). The mean density of breast specimens in patients who underwent neoadjuvant CTx (n=25) was 0.96±0.06 g/mL, which was significantly lower than the value of 1.00±0.08 g/mL in those who did not (n=83). CONCLUSIONS: It is advisable to select an implant slightly larger than the mastectomy specimen weight in patients older than 50 years or in those who have undergone neoadjuvant CTx.
Body Mass Index ; Breast Implants ; Breast ; Diabetes Mellitus ; Drug Therapy ; Female ; Humans ; Mammaplasty ; Mastectomy ; Menopause ; Operating Rooms ; Water