Pancreatic polypeptie (PP) is released from the pancreas in response to vagal stimulation. Amongst other effects, PP has been reported to inhibit pancreatic exocrine function. Apart from any potential physiological role, such inhibition could have important consequences for in vitro studies of pancreatic function employing acetylcholine as a stimulus. We have therefore tested the effect of bovine PP on two in vitro pancreatic preparations: the incubated, uncinate pancreas of young rats and the perfused cat pancreas. In the former, PP (10(-10)-10(-8)M) had little or no effect on enzyme discharge or45Ca efflux under basal conditions or during stimulation with caerulein, CCK-PZ or acetylcholine. In the perfused cat pancreas, similar concentrations of PP were also without effect on fluid secretion evoked by secretin infusion, or enzyme discharge evoked by CCK-PZ injection or infusion. We conclude that bovine PP has no direct effects on the cellular mechanisms responsible for pancreatic electrolyte secretion or enzyme discharge in the species studied.
Acetylcholine/pharmacology ; Amylases/secretion* ; Animal ; Caerulein/pharmacology ; Calcium/metabolism* ; Cats ; Cholecystokinin/pharmacology ; Electrolytes/secretion* ; In Vitro ; Pancreas/drug effects ; Pancreas/metabolism* ; Pancreatic Polypeptide/pharmacology* ; Perfusion ; Rats ; Secretin/pharmacology

Following the acute diarrhea in patients (n = 24) overnight with commonly used laxatives for bowel preparation, the changes in electrolytes and acid-base balance in blood and urine were investigated. Though no alterations of serum sodium or potassium concentrations were noted, mild but significant reduction of mean values (+/- SEM) of plasma pH and HCO3 after diarrhea when compared to those before it developed (pH, from 7.42 +/- 0.01 to 7.39 +/- 0.01, p<0.01; HCO3, from 25.8 +/- 0.6 to 23.7 +/- 0.6 mEq/L, p<0.05). However, significant reduction of concentration in spot urine sodium from 150 +/- 12.3 to 93 +/- 14 mEq/g of crea. (p<0.01) and increase in spot urine potassium from 33 +/- 3.2 to 51 +/- 6.0 mEq/g of crea. (p<0.05) following diarrhea were seen with significant reduction of urine pH from 6.67 +/- 0.21 to 5.5 +/- 0.13 (p<0.001). Also, with this effective urinary acidification following diarrhea, a significant reduction of urinary anion gap as well as significant increment of spot urine ammonium was accompanied (anion gap, from 80.4 +/- 11.1 to 44 +/- 8.5 mEq/g of crea. p<0.001; ammonium, from 87 +/- 18.5 to 229 +/- 37 mg/g of crea. p<0.001) in addition to the significant inverse correlation between these changes in spot urine from basal levels in 24 study subjects (y = -1.13 x +61, r = 0.7, p<0.001). In conclusion, we observed that the acute diarrhea with laxatives used for bowel preparation caused a mild degree of metabolic acidosis with no changes in blood electrolytes.
Acid-Base Equilibrium/*drug effects ; Acute Disease ; Cathartics/pharmacology ; Diarrhea/*metabolism ; Electrolytes/*metabolism ; Human ; Hydrogen-Ion Concentration

OBJECTIVEZanthoxylum heitzii is a medicinal plant widely used in central Africa for the treatment of many diseases, especially cardiovascular diseases and hypertension. The diuretic effects of crude stem bark extraction were determined and its safety in rats was evaluated.

METHODSThe diuretic effects of crude stem bark extraction of Z. heitzii 250 g ± 10 g) of both sexes. The crude stem bark extraction of Z. heitzii at the doses of 225, 300 and 375 mg/kg was administered to rats at 5 mL/kg body weight. Urine volume was determined 1, 2, 3, 4, 5, 6 and 24 h after administration of the extract. Kinetics of electrolyte elimination in response to a single oral administration dose of acute treatment was measured. The experiments were performed under the same conditions with two synthetic pharmacological diuretics considered as reference (furosemide and hydrochlorothiazide). Urinary and plasma concentrations of sodium and potassium ions were determined using flame photometry. Concentrations of creatinine, urea, glucose, albumin and electrolytes in the plasma and urine samples were evaluated using a two-way digital bidirectional spectrophotometer. The osmolarity of plasma and urine samples was measured by cytometry using an osmometer. Aldosterone was measured by radioimmunoassay.

RESULTSThe plant extract accelerated the elimination of overloaded fluid and increased urine volume and the excretion of Na+, K+ and Cl- 24 h after administration (P<0.05). The increase in elimination of Na+, K+, and Cl- induced by caused alkalinization of the urine, and showed a strong inhibitory effect on carbonic anhydrase and saluretic. These effects were mainly observed at the dose of 375 mg/kg. At the maximum diuretic response, urinary osmolarity decreased significantly (P<0.05) when compared to controls. The stability of aldosterone level, the absence of correlation with the plasma levels of Na+, and increased clearance of free water in the animals treated with indicated that increased diuresis and natriuresis were tubular in origin. No significant (P>0.05) changes were observed in the body temperature of the animals.

CONCLUSIONThe significant increase in urine volume 24 h after treatment followed a dose-response pattern. The excretion of Na+, K+ and Cl- caused a decrease in urine osmolarity. The stability of aldosterone, the absence of correlation with the plasma levels of sodium, and increased clearance of free water in animals treated with aqueous extract suggest that increased diuresis and moderate natriuresis elevation were of tubular origin.

Animals ; Carbonic Anhydrase Inhibitors ; pharmacology ; Diuretics ; pharmacology ; Electrolytes ; metabolism ; Female ; Furosemide ; pharmacology ; Hydrochlorothiazide ; pharmacology ; Kidney ; drug effects ; physiology ; Male ; Plant Bark ; Plant Extracts ; pharmacology ; Rats ; Rats, Wistar ; Zanthoxylum ; chemistry

The aims of the study were to prepare polyelectrolyte nanocapsules effected by acid phosphatease (ACP) and to study prolonged-releasing performance of the nanocapsules in vitro. Using the layer by layer (LbL) self-assembly technique, polyelectrolyte-beta-glycerophosphoric acid nanocapsules were prepared. The morphologies of the nanocapsules were characterized by transmission electron microscopy (TEM) and biocompatibility was well examined by cell-culture method. The drug adriamycin would be loaded in nanocapsules for concentration gradient, the encapsulation efficiency could be calculated. Nanocapsules were reacted with acid phosphatease standard and HepG2 cells that express the ACP, respectively. The prolonged-releasing of adriamycin was verified and tumor cells apoptosis were measured. TEM images showed that the nanocapsule sizes were between 200-300 nm. The material biocompatibility was good until the concentration of nanacapsule was up to 250 microg/mL. The drug encapsulation efficiency reached 68.12%. The release rate of polyelectrolyte (PAH/PSS-beta-glycerophosphoric acid)s nanocapsules was higher than in the control nanocapsules at 48 h (38% Vs 15%) after its reaction to the ACP standard (P < 0.05). Compared with the control, nanocapsules could significantly inhibit the growth of HepG2 cells that expressed the ACP, and the efficiency of cell apoptosis was 7.59% higher at 24 h (13.73 Vs 6.14, P < 0.05). Polyelectrolytes (PAH/PSS-beta-glycerophosphoric acid) nanocapsules in vitro have response to acid phosphatease by which prolonged-releasing can be affected. This property can be used for treatment of some malignant and benign diseases with elevated acid phosphatease level.
Acid Phosphatase ; pharmacology ; Antibiotics, Antineoplastic ; administration & dosage ; Delayed-Action Preparations ; chemical synthesis ; Doxorubicin ; administration & dosage ; Electrolytes ; chemistry ; Hep G2 Cells ; Humans ; Nanocapsules

Oxidative stress and apoptosis are the key factors that limit the hypothermic preservation time of donor hearts to within 4-6 h. The aim of this study was to investigate whether the histone deacetylase 3 (HDAC3) inhibitor RGFP966 could protect against cardiac injury induced by prolonged hypothermic preservation. Rat hearts were hypothermically preserved in Celsior solution with or without RGFP966 for 12 h followed by 60 min of reperfusion. Hemodynamic parameters during reperfusion were evaluated. The expression and phosphorylation levels of mammalian STE20-like kinase-1 (Mst1) and Yes-associated protein (YAP) were determined by western blotting. Cell apoptosis was measured by the terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Addition of RGFP966 in Celsior solution significantly inhibited cardiac dysfunction induced by hypothermic preservation. RGFP966 inhibited the hypothermic preservation-induced increase of the phosphorylated (p)-Mst1/Mst1 and p-YAP/YAP ratios, prevented a reduction in total YAP protein expression, and increased the nuclear YAP protein level. Verteporfin (VP), a small molecular inhibitor of YAP-transcriptional enhanced associate domain (TEAD) interaction, partially abolished the protective effect of RGFP966 on cardiac function, and reduced lactate dehydrogenase activity and malondialdehyde content. RGFP966 increased superoxide dismutase, catalase, and glutathione peroxidase gene and protein expression, which was abolished by VP. RGFP966 inhibited hypothermic preservation-induced overexpression of B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and cleaved caspase-3, increased Bcl-2 mRNA and protein expression, and reduced cardiomyocyte apoptosis. The antioxidant and anti-apoptotic effects of RGFP966 were cancelled by VP. The results suggest that supplementation of Celsior solution with RGFP966 attenuated prolonged hypothermic preservation-induced cardiac dysfunction. The mechanism may involve inhibition of oxidative stress and apoptosis via inactivation of the YAP pathway.
Acrylamides/pharmacology* ; Animals ; Apoptosis/drug effects* ; Cryopreservation ; Disaccharides/pharmacology* ; Electrolytes/pharmacology* ; Glutamates/pharmacology* ; Glutathione/pharmacology* ; Heart/physiology* ; Heart Transplantation/methods* ; Hepatocyte Growth Factor/antagonists & inhibitors* ; Histidine/pharmacology* ; Histone Deacetylase Inhibitors/pharmacology* ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors* ; Male ; Mannitol/pharmacology* ; Oxidative Stress/drug effects* ; Phenylenediamines/pharmacology* ; Proto-Oncogene Proteins/antagonists & inhibitors* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; YAP-Signaling Proteins

We treated a 49-yr-old man with neostigmine, who had liver cirrhosis, acute hepatic encephalopathy, and acute intestinal pseudoobstruction. He was admitted in a state of hepatic confusion. On physical examination, the abdomen was distended; and bowel sound was absent. Plain abdomen film revealed multiple airfluid levels and distention of bowel loops. Initially, we gave him lactulose enemas every 6 hr for one day without improvement in his mental state. Furthermore, he became to a state of coma. Therefore, we gave him 0.5 mg of neostigmine subcutaneously to improve his peristaltic movement, and 2 L of polyethylene glycol electrolyte solution through a nasogastric tube for 4 hr to reduce the production and absorption of gutderived toxins of nitrogenous compounds. After these treatments, the venous ammonia level decreased to the normal range within 12 hr, and the coma disappeared after 2 days. We suggest that neostigmine may be one of the most effective treatments to initiate peristaltic movement and bowel cleansing in cirrhotic patients with acute hepatic encephalopathy and acute intestinal pseudoobstruction.
Air ; Ammonia/metabolism ; Blood Pressure ; Cholinesterase Inhibitors/*pharmacology ; Electrolytes/pharmacology ; Enema ; Fibrosis/*drug therapy ; Hepatic Encephalopathy/*diagnosis/*drug therapy/radiography ; Humans ; Intestinal Pseudo-Obstruction/*diagnosis/*drug therapy/radiography ; Lactulose/pharmacology ; Liver/metabolism ; Male ; Middle Aged ; Neostigmine/*pharmacology ; Peristalsis ; Polyethylene Glycols/pharmacology ; Time Factors

OBJECTIVETo investigate the effect of carbachol(CAR) on oxygen dynamic parameters and hyperlactacidemia during oral fluid resuscitation of burn shock.

METHODSTwelve male Beagle dogs were surgically prepared for cannulation of carotid and jugular vein, and enterostomy, 24 hours later they were subjected to a 50% (total body surface area, TBSA) full-thickness flame injury under a 10-15 minute anesthesia by IV injection of propofol. The dogs were randomized to gastric fluid infusion group (GI group)and gastric fluid infusion plus CAR group (GI + CAR). Either a glucose-electrolyte solution(GES) or GES containing CAR (20 microg/kg) were intragastricly given to animals in GI group or GI+ CAR groups. The delivery rate and volume of GES was in accordance with that of Parkland formula. Mean arterial pressure (MAP), intestinal mucosal blood flow (IMBF) and blood lactic acid were determined, and blood gas analysis evaluated for oxygen delivery (DO2), oxygen consumption (VO2) and oxygen uptake (O2ext) at 0, 2, 4, 8, 24, 48 and 72 hours after injury.

RESULTSThe levels of MAP and IMBF markedly reduced, and LAC obviously increased in both groups after burn. MAP returned to 0 h level at 72 h post burn, while IMBF, and LAC were still higher or lower than 0 h levels. The level of MAP of GI + CAR group was significantly higher than that of GI group at 2 h, and those showed no significant differences between two groups after then. Carbochol administration led to a markedly higher levels of IMBF, and significant lower levels of LAC from 8 h after burn compared with those of GI group (P < 0.05 or P < 0.01). The levels of DO2 VO2 and Oext were reduced markedly after burn in both groups. At 72 h after burn, DOQ returned to 0 h level; while VO2 and Oext though still much lower than 0 h levels. The level of DO2. VO2 and Oext of GI + CAR group were significantly higher than those of GI group from 8 h after burn (P < 0.05 or P < 0.01). Three of six animals died in GI+ CAR group, which was lower than two of six in GI group.

CONCLUSIONThe results indicates that carbachol promotes intragastric fluid resuscitative effect of burn shock by increasing oxygen delivery and decreasing hyperlactacidemia.

Animals ; Burns ; complications ; physiopathology ; therapy ; Carbachol ; pharmacology ; Dogs ; Electrolytes ; administration & dosage ; Fluid Therapy ; methods ; Glucose ; administration & dosage ; Intestinal Absorption ; drug effects ; Male ; Oxygen ; metabolism ; Resuscitation ; methods ; Shock ; etiology ; physiopathology ; therapy

OBJECTIVETo evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction (, YCZFD) in the treatment of acute-on-chronic liver failure caused by hepatitis B virus (HBV-ACLF) with cold pattern in Chinese medicine (CM).

METHODSThis is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine (WM) for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM (integrative treatment) or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease (MELD) score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported.

RESULTSThe mortality was decreased 14.28% in the integrative treatment group compared with WM group (χ(2) =6.156, P=0.013). The integrative treatment was found to signifificantly improve the MELD score (t=2.353, P=0.020). There were statistically signifificant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups (P<0.05 or P<0.01). The complications of ascites (χ(2)=9.033, P=0.003) and spontaneous bacteria peritonitis (χ(2)=4.194, P=0.041) were improved signifificantly in the integrative treatment group. No serious adverse event was reported.

CONCLUSIONSThe integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle "treating cold pattern with hot herbs" remains valuable to the clinical therapy. (Trial registration No. ChiCTR-TRC-10000766).

Acute-On-Chronic Liver Failure ; complications ; drug therapy ; mortality ; virology ; Adult ; Ascites ; complications ; Demography ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Electrolytes ; Female ; Hepatitis B ; complications ; drug therapy ; mortality ; physiopathology ; Hepatitis B virus ; physiology ; Humans ; Integrative Medicine ; Liver ; drug effects ; pathology ; physiopathology ; virology ; Liver Function Tests ; Male ; Peritonitis ; complications ; Time Factors ; Treatment Outcome