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Biomedical subjects

C D Liu

Publications and source records attributed to C D Liu.

18 recordsLinked to original sources

Intraluminal peptide YY induces colonic absorption in vivo.

INTRODUCTION: Peptide YY (PYY) is a 36 amino acid hormone released into the circulation and lumen of the intestine after a meal. Previous studies have shown that exogenous administration of intravenous PYY stimulates water and electrolyte absorption in both the small and large intestines. The purpose of this study was to examine the effects of intraluminal administration of PYY on colonic absorption of electrolytes and water. METHODS: Six conditioned 25-kg dogs had 20 cm of colonic Thiry-Vella fistulae surgically constructed under general anesthesia. After a two-week recovery period, the animals received intraluminal PYY at 600 pmol/kg/hour after a 90-minute steady-state basal period. The Thiry-Vella fistulae were perfused with an isotonic buffer solution containing [14C]polyethylene glycol as a volume marker. Ion and water transport were measured every 15 minutes. RESULTS: On intraluminal infusion of PYY, increased absorption of water, sodium, and chloride was observed in the colon. A twofold increase in absorption rates occurred compared with basal rates lasting more than one hour after cessation of intraluminal PYY (N = 6; P < 0.05 vs. basal by analysis of variance). CONCLUSION: PYY-secreting cells of the colon may contribute to the regulation of absorption after a meal. Exogenous administration of intraluminal PYY may also be a therapeutic treatment modality for malabsorption.

Animals

Overnight closed suction drainage after axillary lymphadenectomy for breast cancer.

Axillary lymphadenectomy in breast conservation surgery is associated with substantial morbidity in either seroma formation or infection. Seroma formation in the axilla requiring aspiration occurs in up to 42 per cent of patients treated without drainage. Prolonged outpatient suction drainage reduces but does not eliminate the incidence of seroma formation, while increasing cost, discomfort, and possibly infection rates. We studied the efficacy of overnight closed suction drainage in patients undergoing breast conservation surgery. Fifty consecutive patients undergoing a standard axillary dissection for breast cancer were studied. The axilla was drained with a 7-French closed suction drain. All drains were removed within 23 hours of surgery and prior to discharge from the outpatient surgical center. Patients were examined by the operating surgeon 7 to 10 days after surgery. One patient (2%) experienced a seroma postoperatively. No infections were observed in all 50 patients, and the remaining 49 patients did not experience visible or symptomatic seromas. The number of lymph nodes removed ranged between 5 and 33 with a mean of 15.5 +/- 0.6. Nine out of 50 (18%) patients had metastatic breast cancer to the axillary lymph nodes. Patients undergoing breast conservation surgery benefit from overnight closed suction drainage of the axilla. This short-term method reduces the incidence and the inherent morbidity of axillary seroma formation.

Ambulatory Care

Amiloride inhibits meal-stimulated colonic absorption.

Meal-stimulated colonic absorption has recently been described, but the cellular transport mechanisms mediating this response are unknown. The purpose of this study was to determine the contribution of Na+ transport pathways to colonic proabsorption. Distal colonic Thiry-Vella loops were constructed in six dogs. Absorption was measured by infusing the loops with a physiological electrolyte solution containing [14C] polyethylene glycol as the impermeant marker. In the first set of experiments, the dose dependence of amiloride-induced inhibition of basal colonic absorption was determined. In the second set of experiments the effect of amiloride, which inhibits both Na+ channels and Na+/H+ exchange in colonocytes, on meal-stimulated colonic absorption was determined. Luminal amiloride inhibited basal colonic absorption in a dose-dependent manner, with significant reductions in Na+ absorption occurring with concentrations of 10(-2)M and higher. Infusion with 10(-3)M amiloride, a concentration that did not alter basal absorption, resulted in significant reductions in postprandial water, Na+, and Cl- absorption. These results suggest that meal-stimulated colonic absorption is mediated, at last in part, by transcellular Na+ absorptive pathways.

Amiloride

Epidermal growth factor improves intestinal adaptation during somatostatin administration in vivo.

Somatostatin (SMS) is administered to patients with short bowel syndrome and enterocutaneous fistulae. Previous studies have shown detrimental effects of SMS on intestinal adaptation after bowel resection. We examined whether administration of epidermal growth factor (EGF) could reverse the deleterious effects of SMS seen after enterectomy. Sixty-four Sprague-Dawley rats underwent an 80% small bowel resection or transection as control. Rats received either SMS at 50 ng x kg(-1) x h(-1), EGF/Urogastrone at 1.5 microg x kg(1-) x h(-1), or both via subcutaneous miniosmotic pumps. Samples were obtained at 1 day and 1 week after surgery for histologic examination, analysis of apical Na+/glucose cotransporter protein and mRNA expression, and analysis of basolateral Na+/K+ ATPase protein and mRNA expression. Protein expression was analyzed by Western blotting whereas mRNA expression was compared by ribonuclease protection assay. Histologically, villus to crypt length after intestinal resection showed increased adaptation in EGF/SMS vs SMS treated animals in both jejunum and ileum. Analysis of mRNA and protein of epithelial transporters show early increases when EGF is administered with SMS vs SMS only. We conclude that combination therapy using EGF and SMS may be beneficial to intestinal adaptation after small bowel resection. Both histologic and molecular data suggest an enhanced absorptive potential and adaptation of the remaining intestine when EGF is administered.

Analysis of Variance

Cholecystokinin mediation of colonic absorption via peptide YY: foregut-hindgut axis.

Peptide YY (PYY), a 36-amino-acid polypeptide, is found in abundance in the colon, a region where its physiologic roles are unknown. Previous studies have revealed a substantial increase in plasma PYY after cholecystokinin (CCK) administration. PYY is released from the hindgut in response to a meal and inhibits CCK release. In this study we evaluated the effects of CCK and PYY on intestinal absorption of water and electrolytes. Colonic, ileal, or jejunal Thiry-Vella fistulas (TVFs) were created in 12 dogs, and intestinal continuity was reestablished. The TVFs were perfused with an isotonic buffer solution containing [14C] PEG as a volume marker. Electrolyte and water transport were measured every 15 minutes, and plasma PYY and CCK levels were measured by radioimmunoassay. Group 1 dogs received an intravenous bolus of MK329, a specific CCK receptor antagonist, at 20 nmol/kg after a standard mixed meal; group 2 colonic TVF dogs received a meal and an intravenous bolus of PYY polyclonal antibody at 1 mg/kg. Postprandially, all three regions of the bowel became significantly proabsorptive for water, sodium, and chloride. In the colon postprandial absorption was abolished by MK329 starting 60 minutes after a meal, whereas specific CCK receptor blockade blunted ileal absorption. CCK receptor blockade did not affect postprandial absorption in the jejunum. Postprandial PYY levels did not rise in MK329-treated animals. PYY antibody reduced colonic absorption during the postprandial phase. Reduction of meal-induced colonic absorption and PYY release by MK329 in awake dogs suggests an important foregut-hindgut hormonal feedback loop. Foregut-derived CCK stimulates hindgut PYY release, which in turn stimulates colonic absorption while inhibiting further CCK release.

Animals

Adjuvant hormonal treatment with peptide YY or its analog decreases human pancreatic carcinoma growth.

BACKGROUND: Recent studies have revealed decreased pancreatic cancer cell growth upon administration of peptide YY (PYY). We examined whether adjuvant treatment with PYY or its synthetic analog, BIM-43004, would decrease human pancreatic adenocarcinoma growth. MATERIALS AND METHODS: Human pancreatic ductal adenocarcinomas, MiaPaCa-2 and BxPC-3, were cultured and assessed for growth by MTT assay. Pancreatic cancer cells received 500 pmol of PYY or BIM-43004 for 24 hours prior to 5-fluorouracil (5-FU; 10 micrograms/mL) and leucovorin (40 micrograms/mL) administration. Cell membrane epidermal growth factor (EGF) receptors were analyzed by Western blotting after exposure to peptides and chemotherapy. RESULTS: Cancer cell growth was reduced in all groups receiving hormonal pretreatment (23% PYY/5-FU/leucovorin versus control; 27% BIM-43004/5-FU/leucovorin versus control) as compared with groups receiving 5-FU and leucovorin only (16% versus control). The EGF receptor expression was reduced by 30% in cells treated with PYY/5-FU/leucovorin and by 45% in cells treated with BIM/5-FU/leucovorin as compared with control cells without treatment. CONCLUSION: Human pancreatic cancer cell growth is further decreased when pretreated with PYY or its synthetic analog prior to chemotherapy.

Carcinoma, Ductal, Breast

Peptide YY: a potential proabsorptive hormone for the treatment of malabsorptive disorders.

Peptide YY (PYY) is a 36 amino acid peptide that is released from the endocrine cells of the distal ileum, colon, and rectum following a meal. PYY is strongly proabsorptive in the small intestine. We studied the effects of intravenous PYY on colonic water and electrolyte transport in awake dogs. Dogs had 20 cm neurovascularly intact colon Thiry-Vella fistulas (TVS) surgically constructed. Colonic transport was studied in three experimental groups. Group 1 animals received a standard mixed meal. Group 2 animals were unfed and received intravenous PYY and 100 pmol/kg/hr for two hours. This dose of PYY has previously been shown to simulate the plasma levels of PYY normally seen after a meal. Group 3 received intravenous PYY at the same dose in addition to a mixed meal. Our study shows an increase in colonic water, Na+, and Cl- absorption after a meal (P < 0.05). Infusion of PYY at a 100 pmol/kg/hr was significantly proabsorptive beginning at 60 minutes (P < 0.01). Infusion of PYY in addition to a meal further increased absorption (P < 0.05). PYY is a potent proabsorptive agent in the colon of the conscious dog. PYY, or its analogs, may be useful clinical agents in intestinal malabsorptive disorders or after bowel resection.

Animals

Pancreatic peptide YY mRNA levels increase during adaptation after small intestinal resection.

Peptide YY (PYY) is a 36-amino-acid peptide known to inhibit pancreatic and gastrointestinal secretion. Immediately following small bowel resection, intestinal PYY mRNA and plasma PYY levels rise. The purpose of this study was to determine whether PYY expression changes in the pancreas during the adaptive period after extensive small bowel resection. Female Sprague-Dawley rats (250 g) underwent 70% small intestinal resection or transection alone as control. Animals were sacrificed at 6 hr, 24 hr, 1 week, or 2 weeks following operation (N = 5/time group). Pancreatic tissue was harvested and RNA was isolated by the guanididium-thiocyanate method. PYY mRNA was analyzed by reverse transcriptase PCR, standardized to glyceraldehyde-3-phosphate dehydrogenase, and semiquantitated by Southern blotting and 32P cpm. Ribonuclease protection assay was used to confirm PCR results. PYY mRNA expression was increased 9 1/2-fold beginning 6 hr after resection compared to transection (P < 0.05). PYY mRNA levels remain elevated, 2 1/4-fold greater than control after 2 weeks (P < 0.05) as analyzed by reverse transcriptase PCR and ribonuclease protection assay. Quantitation by ribonuclease protection assay reveals a gradual elevation of PYY mRNA levels in transected animals compared to a nonoperated rat starting at 1 and 2 weeks. Pancreatic PYY mRNA levels increase rapidly after extensive intestinal resection and remain elevated 2 weeks postoperatively. These results confirm for the first time that the increase in PYY seen after extensive intestinal resection also occurs in extraintestinal sites. In the pancreas, elevated PYY levels may inhibit exocrine secretion, reducing luminal volume, and thereby facilitating intestinal adaptation.

Adaptation, Physiological

Amino acids mediate postprandial jejunal proabsorption.

Ingestion of a meal stimulates small intestinal ion and water transport. Current evidence suggests that this response, termed proabsorption, is primarily mediated by the apical Na+/glucose cotransporter. Like glucose, the majority of amino acid absorption occurs by Na(+)-dependent, secondary active transport. The purpose of this study was to determine the role of amino acid transport in meal-induced jejunal ion and water absorption in vivo. Exteriorized, neurovascularly intact jejunal loops measuring 25 cm were created in six female mongrel dogs, and the dogs were allowed to recover for 2 weeks. After an overnight fast, the loops were perfused with a standard buffer containing 10 mM aspartate, leucine, glycine, or lysine. Net water and electrolyte absorption before and after a mixed meal was calculated using [14C]polyethylene glycol as a volume marker. Aspartic acid, leucine, glycine, and lysine are each transported by a separate transporter system. Except for lysine, each amino acid significantly (P < 0.05) potentiated sodium and water absorption after a meal. In addition, this effect was at least as great as that seen with 10 mM glucose. These results demonstrate that amino acid transporter, like the Na+/glucose cotransporter, mediates meal-induced jejunal sodium and water absorption and may be as important in the proabsorptive response.

Amino Acids

Human pancreatic cancer growth is inhibited by peptide YY and BIM-43004-1.

Exogenous peptide YY (PYY) decreases pancreatic exocrine secretion, pancreatic endocrine function, and pancreatic blood flow. We hypothesized that pancreatic cancer cell growth may be inhibited by PYY and a new synthetic analog, BIM-43004-1. Two human pancreatic ductal adenocarcinomas, PANC-1 and Mia PaCa-2, were examined in tissue cultures. Viable pancreatic cancer cells were counted with trypan blue on a hemocytometer slide. Cells (10K, 20K, 40K, and 80K) were cultured and allowed to grow for 36 hr (n = 14/cell concentration). Pancreatic cancer cells received either PYY or BIM-43004-1 at various concentrations. Control tissue cultures received an equivalent volume of saline inoculation. After incubation with the above peptides for 24 hr, MTT tetrazolium bromide was added to assay mitochondrial activity of pancreatic cancer cells in response to PYY and its analog. MTT assay reveals a significant decrease in pancreatic cancer cell growth when PYY and BIM-43004-1 are added to the cell culture. Results in Mia PaCa-2 reveal a 24% cell growth reduction after exposure to PYY and a 23% reduction in cell growth when treated with BIM-43004-1. In PANC-1 cells, a 25% reduction in growth of cells is noted after PYY treatment and a 24% reduction in growth after BIM-43004-1 treatment. (means +/- SEM, P < 0.05 by Student's t test). Our results reveal a significant reduction in human ductal pancreatic cancer growth when treated with either PYY or its analog, BIM-43004-1. These agents may be useful hormonal adjuncts in the chemotherapy of pancreatic adenocarcinoma.

Cyclic AMP

A novel synthetic analog of peptide YY, BIM-43004, given intraluminally, is proabsorptive.

Peptide YY (PYY), a proabsorptive hormone, is released into the circulation and lumen of the small intestine after a meal. We have recently found that intraluminal PYY is proabsorptive in the ileum. The purpose of this study was to examine the effects of intraluminal administration of a new substituted PYY (22-36) analog on intestinal absorption of electrolytes and water. Twelve conditioned 20-kg dogs had 25-cm jejunal, 25-cm ileal, or 20-cm colonic Thiry-Vella fistulas (TVF) surgically constructed under general anesthesia (jejunal and ileal TVF, N = 6, and colonic TVF, N = 6). After a 2-week recovery period, the animals received the intraluminal PYY analog, BIM-43004, in the ileum (200 pmole/kg) or colon (300 pmole/kg) for 60 min after a 90-min steady-state basal period was confirmed. The TVF were perfused with an isotonic buffer solution containing [14C]polyethylene glycol as a volume marker. Ion and water transport were measured every 15 min. Net water absorptions were significant in the ileum and colon but not in the jejunum upon intraluminal administration of the PYY analog, BIM-43004. Colonic water absorptions were increased more than twofold above basal absorption rates and ileal absorptions were increased more than 1.5-fold upon addition of intraluminal BIM-43004. Sodium and chloride ion absorption in the colon and ileum paralleled water fluxes. We are describing for the first time a synthetic peptide analog of PYY that produces significant water and electrolyte absorption in the ileum and colon when administered luminally. This synthetic analog may have therapeutic potential in patients with malabsorptive disorders.

Animals

Y2 receptors decrease human pancreatic cancer growth and intracellular cyclic adenosine monophosphate levels.

BACKGROUND: Peptide YY (PYY), a 36 amino acid enteric hormone, is known to decrease pancreatic exocrine and endocrine function. Previous studies with BIM-43004-1, a modified PYY(22-36) Y2 receptor agonist, have revealed diminished mitochondrial activity in pretreated pancreatic cancer cells in vitro. We investigated the effects of both PYY and BIM-43004-1 on pancreatic cancer growth in vivo. METHODS: The 100,000 to 150,000 human pancreatic cancer cells, Mia PaCa-2, were orthotopically transplanted into 48 male athymic mice. After 1 week animals were treated with either PYY or BIM-43004-1 at 200 pmol/kg/hr via miniosmotic pumps for 2, 3, or 4 weeks. Paired controls received saline solution. At death tumor size and mass were measured. Receptor binding studies and intracellular cyclic adenosine monophosphate (cAMP) levels were measured in vitro. RESULTS: All mice had significant human cancer growth within the pancreas by histologic sections at 2, 3, and 4 weeks. Tumor mass was decreased by 60.5% in BIM-43004-1 treated mice and 27.1% in PYY treated mice. Receptor binding studies revealed binding of [125I]-BIM-43004-1 and displacement of ligand on competitive addition of nonradioactive BIM-43004-1. K dissociation constant of 4.5 nmol and 27,000 receptors per cell were quantitated by receptor binding studies. In BIM-43004-1 treated pancreatic cells a 52.5% decrease in intracellular cAMP levels was noted, whereas a 15.3% decrease was seen in PYY treated cells. CONCLUSIONS: BIM-43004-1, a novel Y2 synthetic agonist, specifically binds to human pancreatic cancer cells, decreases intracellular cAMP levels, and suppresses tumor growth in vivo. Adjuvant hormonal treatment with this Y2 receptor analog may be beneficial in the treatment of patients with pancreatic adenocarcinoma.

Animals

Laparoscopic surgery for inflammatory bowel disease.

In the setting of inflammatory bowel disease (IBD), laparoscopic approaches have been avoided because of the often fragile intestinal tissue, thickened mesentery, malnutrition, immunosuppression, and the presence of dense adhesions. In this article, we report 10 successfully managed laparoscopic cases in IBD patients (five with ulcerative colitis, five with Crohn's Disease). Patients with ulcerative colitis underwent total abdominal colectomies, mucosal proctectomies, J-pouch construction, and diverting ileostomies. Procedures in patients with Crohn's disease included ileocecectomy (3), sigmoid colectomy with takedown of a transverse colonic fistula (1), and stricturoplasty (1). One of the 10 cases was converted to an open technique for technical reasons. Six of the 10 patients were on high dose corticosteroids for disease control. Hospital stay ranged from 6-13 days, with a median of 7 days. The morbidity rate was 20 per cent, and included one case of mild postoperative pancreatitis in a Crohn's disease patient and one delayed peri-ileostomy fistula in an ulcerative colitis patient. There was no mortality. Based on these results, we conclude that laparoscopic intestinal surgery is both feasible and safe in selected patients with inflammatory bowel disease. Use of laparoscopic techniques in these patients may reduce hospital stay, lessen adhesion formation, and improve cosmetic results in this generally young group of patients.

Adolescent

Peptide YY immunoneutralization inhibits meal-induced absorption in vivo.

BACKGROUND: Plasma peptide YY (PYY) levels rise after a meal and have recently been shown to increase small bowel-absorption. The purpose of this study was to determine whether immunoneutralization of PYY would block postprandial absorption in vivo. METHODS: Exteriorized, neurovascularly intact jejunal and ileal segments (25 cm) were created in six mongrel dogs. After a 2-week recovery luminal perfusion with an isotonic buffer, containing [14C]-polyethylene glycol as a volume marker, was used to analyze water and sodium flux after an oral meal. Each meal was accompanied by either intravenous anti-PYY (0.5 mg.kg-1.h-1) or nonspecific immunoglobulin IG (control). PYY antibody binding was determined by radioimmunoassay. RESULTS: Displacement studies showed complete PYY neutralization. In control experiments feeding increased absorption of sodium and water in both segments. PYY immunoneutralization had no effect on jejunal absorption but significantly diminished ileal absorption (p < 0.05). CONCLUSIONS: These results suggest that PYY acts selectively in the ileum to increase postprandial fluid and electrolyte absorption after a meal. Agents directed at PYY-stimulated absorption may prove to be of therapeutic benefit in patients with malabsorptive conditions.

Animals

[Association of HLA antigens with thyrotoxic periodic paralysis].

Periodic paralysis is a rare and peculiar complication of thyrotoxicosis, especially in Chinese and Japanese patients. The susceptibility to autoimmune thyroid disease has recently been reported to be strongly linked with certain immunogenetic factors. The objective of this study was to seek a genetic marker by HLA typing in Chinese patients with thyrotoxic periodic paralysis (TPP). The distribution of HLA-A, B, C, DR and DQ antigens in 20 thyrotoxic patients with periodic paralysis and 51 thyrotoxic patients without periodic paralysis was compared with that in 100 controls. The results showed that among the patients with TPP, these was a highly significantly increase of HLA-B51 frequency and B51 appeared to be linked with Cw3 in a state of dysequilibrium.

Adult

[Etiological and influential factors of involutional osteoporosis in old Chinese].

A comprehensive analysis is reported in 376 healthy middle and old-age persons, including measurements of bone mineral content (BMC) of the mid-radias, pituitary sex hormones (RIA), serum calcium, phosphate, albumin, alkaline phosphatase, urinary calcium, phosphate, hydroxyproline (BCA), daily intake of protein and calcium, physical exercise and activity, body weight, amenorrhea etc. Results showed that the preponderance of bone resorption over bone formation is the essential pathophysiological change of involutional osteoporosis. For females, bone loss is regulated mainly by estrogen in presenile group, co-regulated by estrogen and androgen in senile group. For males, urinary hydroxyproline excretion is also regulated by estrogen A remarkable correlation was observed between BMC and the following factors: serum calcium, urinary calcium, hydroxyproline, body weight, physical exercise, amenorrhea, intake of protein and calcium. Our data indicated that the intake of calcium daily in old chinese should not be lower than 700 mg (male) and 900 mg (female), protein should not be lower than 60-70 g. The age of onset, prevalence rate and BMC average reduction rate of osteoporosis in chinese were also observed in the studies.

Aged