Bacterial ecology of hospital workers' facial hair: a cross-sectional study.

It is unknown whether healthcare workers' facial hair harbours nosocomial pathogens. We compared facial bacterial colonization rates among 408 male healthcare workers with and without facial hair. Workers with facial hair were less likely to be colonized with Staphylococcus aureus (41.2% vs 52.6%, P = 0.02) and meticillin-resistant coagulase-negative staphylococci (2.0% vs 7.0%, P = 0.01). Colonization rates with Gram-negative organisms were low for all healthcare workers, and Gram-negative colonization rates did not differ by facial hair type. Overall, colonization is similar in male healthcare workers with and without facial hair; however, certain bacterial species were more prevalent in workers without facial hair.

[Surgical volume. An American perspective]. / Chirurgische Fallzahl. Die amerikanische Perspektive.

Due to an increasing interest in patient safety and quality health care, many studies attempt to show a relationship between procedural volume at the institutional and individual level and patient outcome. Despite the correlation between number of surgeons and institutional volume in major operative procedures such as coronary artery bypass graft, pancreatic resection, and esophagectomy, these parameters are likely to be proxy for individual factors such as experience and structural aspects. In general the relationship between case numbers and results is more convincing in cancer surgery than for cardiovascular procedures, and risk adjustment may play an important role for interpreting results of the various studies. Exact thresholds cannot be determined and thus remain speculative. It appears difficult to implement practical changes based on the observations, because the etiology and causality of the relationship between volume and outcome are still not understood. The simple focus on volume does not apply to measurements of quality but can be a starting point for further studies to identify more specific factors associated with surgical quality.

Collisional properties of cold spin-polarized metastable neon atoms.

We measure the rates of elastic and inelastic two-body collisions of cold spin-polarized neon atoms in the metastable 3P2 state for 20Ne and 22Ne in a magnetic trap. From particle loss, we determine the loss parameter of inelastic collisions beta=6.5(18) x 10(-12) cm(3) s(-1) for 20Ne and beta=1.2(3) x 10(-11) cm(3) s(-1) for 22Ne. These losses are caused by ionizing (i.e., Penning) collisions and occur less frequently than for unpolarized atoms. This proves the suppression of Penning ionization due to spin polarization. From cross-dimensional relaxation measurements, we obtain elastic scattering lengths of a=-180(40)a(0) for 20Ne and a = +150(+80)(-50)a(0) for 22Ne, where a(0)=0.0529 nm.

Focal adhesion kinase gene silencing promotes anoikis and suppresses metastasis of human pancreatic adenocarcinoma cells.

BACKGROUND: Inadequate or inappropriate cell-substrate contact triggers a subset of apoptotic cell death, termed anoikis. Resistance to anoikis is a characteristic of malignant cells that is associated with increased tumorigenesis and metastasis. Focal adhesion kinase (FAK) is an important regulator of cell survival and migration and cell cycle progression. We tested the hypothesis that FAK gene silencing would promote anoikis and reverse acquired anoikis resistance in human pancreatic adenocarcinoma cells. METHODS: FAK expression was assessed by Northern and Western blot analysis. Anoikis was induced in PANC1, BxPC3, MiaPaCa2, and Mia(AR) (an anoikis-resistant derivative of MiaPaCa2) with the use of polyHEMA culture. FAK expression was suppressed by RNA interference. Anoikis was detected by YO-PRO-1/propidium iodide staining and flow cytometry. Fluorometric caspase profiling was performed. Metastasis was assayed in a nude mouse orthotopic xenograft model. RESULTS: The cell lines that were tested showed marked variation in their anoikis resistance, greater resistance being associated with higher levels of FAK expression. FAK gene silencing promoted anoikis in all cell lines and reversed acquired anoikis resistance in Mia(AR), which was associated with increased caspase activation. Suppression of FAK expression also inhibited metastasis in the nude mouse model. CONCLUSION: FAK gene silencing suppresses anoikis resistance in pancreatic adenocarcinoma cells. FAK represents a potential target for novel antimetastatic therapies.

What is the value of telerobotic technology in gastrointestinal surgery?

BACKGROUND: Although telerobotic technology has entered clinical application, its value for gastrointestinal surgery is unclear. Our objective was to evaluate the performance characteristics of telerobotically assisted laparoscopic cholecystectomy (TALC). METHODS: All TALCs performed using the da Vinci Surgical System between January 2000 and September 2001 at a tertiary academic medical center were analyzed. RESULTS: For this study, 20 patients (80% female) with a mean age of 47 +/- 4 years underwent TALC. All had symptomatic cholelithiasis, and all had successful TALC results without complications or need for conversion to conventional laparoscopic cholecystectomy (CLP). The mean procedure time was 152 +/- 8 min. The procedures were performed by one of three staff surgeons experienced in laparoscopic surgery who had training in telerobotic surgery. The perceived advantages of TALC over CLP included easier tissue dissection, enhanced dexterity, and stimulated interest in biliary surgery. The disadvantages included increased operating time and lack of tactile feedback. CONCLUSIONS: The TALC procedure is effective and safe when performed by appropriately trained surgeons. Telerobotic technology has the potential to reinvigorate gastrointestinal surgery.

Necrotizing pancreatitis: contemporary analysis of 99 consecutive cases.

OBJECTIVE: To analyze the impact of a conservative strategy of management in patients with necrotizing pancreatitis, reserving intervention for patients with documented infection or the late complications of organized necrosis. SUMMARY BACKGROUND DATA: The role of surgery in patients with sterile pancreatic necrosis remains controversial. Although a conservative approach is being increasingly used, few studies have evaluated this strategy when applied to the entire spectrum of patients with necrotizing pancreatitis. METHODS: The authors reviewed 1,110 consecutive patients with acute pancreatitis managed at Brigham and Women's Hospital between January 1, 1995, and January 1, 2000, focusing on those with pancreatic necrosis documented by contrast-enhanced computed tomography. Fine-needle aspiration, the presence of extraintestinal gas on computed tomography, or both were used to identify infection. RESULTS: There were 99 (9%) patients with necrotizing pancreatitis treated, with an overall death rate of 14%. In three patients with underlying medical problems, the decision was made initially not to intervene. Of the other 62 patients without documented infection, all but 3 were managed conservatively; this group's death rate was 11%. Of these seven deaths, all were related to multiorgan failure. Five patients in this group eventually required surgery for organized necrosis, with no deaths. Of the 34 patients with infected necrosis, 31 underwent surgery and 3 underwent percutaneous drainage. Only four (12%) of these patients died, all of multiorgan failure. Of the total 11 patients who died, few if any would have been candidates for earlier surgical intervention. CONCLUSIONS: These results suggest that conservative strategies can be applied successfully to manage most patients with necrotizing pancreatitis, although some will eventually require surgery for symptomatic organized necrosis. Few if any patients seem likely to benefit from a more aggressive strategy.

EGF and TGF stimulate proabsorption of glucose and electrolytes by Na+/glucose cotransporter in awake canine model.

Growth factor-stimulated intestinal absorption has recently been described, but the cellular transport mechanisms mediating this response are unknown. The purposes of this study were to examine the effect that intraluminal and systemic EGF and TGF have in intestinal absorption, elucidate a possible mechanism through which they exert their activity, and compare this response to that of a mixed meal only. Jejunal and ileal Thiry-Vella intestinal segments were constructed in six dogs. Absorption was measured by infusing the loops with a physiological electrolyte solution containing either 10 mmol or 50 mmol glucose and [14C]PEG as the impermeant marker. In vivo studies show that the addition of either EGF or TGF resulted in increased absorption of Na+, Cl-, H2O, and glucose in the intestine. This response was significantly greater than that seen when giving a mixed meal alone. Luminal phloridzin, an inhibitor of the SGLT-1 transporter, inhibited intestinal absorption observed in response to EGF and TGF. In conclusion, these results suggest that growth factors are capable of up-regulating intestinal absorption of electrolytes and nutrients and, these effects are mediated, at least in part, by SGLT-1 pathways.

Diurnal rhythmicity in intestinal SGLT-1 function, V(max), and mRNA expression topography.

Mechanisms underlying the circadian rhythmicity in intestinal sugar absorption remain unclear. To test whether this rhythmicity is caused by changes in Na(+)-glucose cotransporter 1 (SGLT-1) function, we measured phloridzin-inhibitable sugar fluxes as an index of SGLT-1 activity. Jejunum obtained from rats killed at 6-h intervals during a 12-h light-dark cycle (CT0 is circadian time 0 h, time of light onset) were mounted in Ussing chambers, and 3-O-methylglucose (3-OMG) fluxes were calculated before and after addition of phloridzin. 3-OMG-induced change in short-circuit current and absorptive flux were significantly greater at CT9 than at CT3. This increase was phloridzin inhibitable. Kinetic studies indicated a significant increase in SGLT-1 maximal velocity (V(max)) at CT9. Food intake between CT3 and CT9 was <10% of the daily total, indicating that the increased SGLT-1 activity was anticipatory. Diurnicity of SGLT-1 mRNA was confirmed by Northern blotting. Expression topography analyzed by in situ hybridization revealed more intense labeling along the entire villus axis at CT9 and CT15 compared with CT3 and CT21. We conclude that diurnicity in intestinal sugar absorption is caused by periodicity in SGLT-1 V(max).

Effect of growth hormone on intestinal Na+/glucose cotransporter activity.

BACKGROUND: Growth hormone (GH) has been used alone or as part of a defined regimen in the treatment of patients with short bowel syndrome; however its mode of action remains unclear. Growth hormone has been shown to increase amino acid, water, and electrolyte absorption from the small intestine. The acute effect of growth hormone on intestinal sugar transport has not been described previously. METHODS: Mucosal preparations of rat jejunum were mounted in the Ussing chamber. Growth hormone (2 x 10(-6) M or 8 x 10(-6) M) or vehicle was added to the serosal chamber 1, 3, or 5 hours later. Twenty or 40 minutes after growth hormone addition, 30 mmol/L 3-O-methylglucose was added to both chambers, and the change in short-circuit current (deltaIsc) was recorded. In separate experiments, tissues were pretreated with phloridzin, an inhibitor of Na+/glucose cotransport, before the addition of 3-O-methylglucose. In the final set of experiments, kinetic studies were performed. RESULTS: GH did not induce any alterations in baseline electrical parameters. Only tissues left in the chambers for 5 hours, but not 1 or 3 hours, before GH treatment displayed a greater 3-O-methylglucose-induced deltaIsc than controls (p < .05). The increase in Isc induced by 3-O-methylglucose was 100% phloridzin-inhibitable. Kinetic analysis showed that growth hormone administration is associated with an increase in Na+/glucose cotransporter maximal velocity (Vmax) but no significant change in carrier affinity for substrate (Km). CONCLUSIONS: Growth hormone increases intestinal sugar transport, but only in tissue that has not been exposed to endogenous GH for over 3 hours.

Luminal osmolarity downregulates gene expression of Na+/H+ exchanger (NHE3) in rat colon mucosa.

Water-coupled Na&sup+ absorption in the colon is mediated principally by Na+/H+ exchange (isoforms NHE2 and NHE3). To determine whether luminal ion composition or osmolarity influences NHE expression in colon mucosa, two groups (n = 6 in each) of adult male Sprague-Dawley rats underwent sham laparotomy or loop ileostomy. In these studies, diversion did not markedly alter mRNA levels for NHE2, NHE3, or Na+/K+, at 8 or 21 days, indicating that loss of luminal volume does not alter NHE gene expression. To evaluate the effects of specific luminal components, we infused equal volumes of half-normal (154 mOsm) or iso-osmolar (308 mOsm) solutions of saline and mannitol into the diverted colon. All solutions elicited significant (45% to 60%; P <0.05) decreases in mRNA levels for NHE3, with iso-osmolar mannitol eliciting the greatest changes. Decreases in NHE2 and Na+/K+ mRNA levels were observed following these infusions but were not as marked as the changes for NHE3. These findings suggest that (1) loss of luminal Na+ is not, in itself, a signal that regulates NHE expression and (2) infusion of any solute, including Na+ itself, provides a signal to downregulate expression of NHE3 in colon mucosa.

Glucagon-like peptide 2: a new treatment for chemotherapy-induced enteritis.

BACKGROUND: Glucagon-like peptide 2 (GLP-2) is a recently identified intestinal epithelium-specific growth factor that has been shown to reduce the severity of inflammatory disorders of the intestine in rodent models. We hypothesized that GLP-2 administration would be beneficial in chemotherapy-induced enteritis either by preventing injury or by promoting recovery. MATERIAL AND METHODS: Rats received no drug (control), chemotherapy alone [5-fluorouracil (5-FU), 190 mg/kg, ip] (Chemo), 5-FU followed by 3 days of GLP-2 analog (ALX-0600, 0.1 microg, sc twice daily) (CH-G), or GLP-2 analog for 6 days prior to 5-FU and for 3 days afterward (G-CH-G). Animals were pair fed. Rats received 5-bromo-2-deoxyuridine (Br-dU, 50 mg/kg, 2.5 h prior to sacrifice on Day 3 postchemotherapy) for immunohistochemical assessment of cellular proliferation. RESULTS: Chemotherapy induced significant reductions in body weight, villus height, and crypt depth compared with controls. Intestinal wet weight, villus height, and crypt depth were significantly higher for the CH-G group compared with the Chemo group. The CH-G group also showed a significant improvement in villus height compared with the G-CH-G group. Crypt depth, but not jejunal wet weight or villus height, was significantly improved in the G-CH-G group compared with the Chemo group. The percentage of Br-dU-labeled cells in the intestinal crypts did not differ among the groups. CONCLUSIONS: These results suggest, for the first time, that GLP-2 treatment initiated after chemotherapy administration enhances intestinal recovery. In contrast, GLP-2 treatment initiated prior to chemotherapy administration to prevent injury has less beneficial effect. GLP-2 administration may be beneficial to patients suffering from chemotherapy-induced enteritis.

Signaling mechanisms of glucagon-like peptide 2-induced intestinal epithelial cell proliferation.

BACKGROUND: Glucagon-like peptide 2 (GLP-2) stimulates intestinal epithelial growth with high potency and specificity. However, the intracellular signaling pathways responsible for the growth-stimulatory action of GLP-2 are not clearly understood. Here we report possible signaling pathways mediating GLP-2's proliferative actions in the human intestinal epithelial cell line Caco-2. MATERIALS AND METHODS: Caco-2 cells were subcultured under serum-deprived conditions in the presence or absence of GLP-2 (10 microM) and varying concentrations of inhibitors of three candidate kinases: genistein, a global tyrosine kinase inhibitor; LY294002, a phosphatidylinositide (PI) 3-kinase inhibitor; and PD 098059, a mitogen-activated/extracellular signal-regulated kinase (MEK) inhibitor. Proliferation was assessed using [(3)H]thymidine incorporation. Relative abundance of the phosphorylated forms of two specific mitogen-activated protein kinases (MAPKs), ERK1 and ERK2, was assessed by Western blotting. RESULTS: GLP-2-treated cells demonstrated a greater than 10-fold increase in proliferation. This response was inhibited by genistein, LY294002, and PD 098059 in a dose-dependent fashion. A significantly greater abundance of the phosphorylated forms of both ERK-1 and ERK-2 was present in cells within 5 min of treatment with GLP-2. CONCLUSIONS: GLP-2 stimulates the proliferation of Caco-2 cells in vitro. This increase in Caco-2 proliferation in response to GLP-2 may be due, at least in part, to the involvement of both the PI 3-kinase and the MAPK pathways.

Role of Na+-glucose cotransport in jejunal meal-induced absorption.

In awake dogs, meal ingestion stimulates the absorption of water and electrolytes from neurovascularly intact jejunal Thiry-Vella loops, even though these loops are isolated from the remainder of the gut. This study was designed to investigate the role of Na+-glucose cotransport in mediating this event. Meal ingestion enhanced absorption when the jejunal lumen was perfused with an isotonic solution containing D-glucose, D-galactose, or 3-O-methylglucose. This response was absent when the perfusate contained mannitol or when phlorizin was added to the D-glucose solution. Mucosa from the jejunal loops was serially biopsied and assayed for brush-border Na+-glucose cotransporter (SGLT1) mRNA and protein expression. Although no changes in SGLT1 mRNA levels were observed, protein levels significantly increased within 30 min following meal ingestion. The time course of SGLT1 protein expression corresponded with that of increased Na+ and water absorption. These results suggest that meal-stimulated jejunal absorption may be mediated through an induction of mucosal SGLT1.

Selective decreases in levels of mRNA encoding a water channel (AQP3) in ileal mucosa after ileostomy in the rat.

Water channels (aquaporins) provide pathways for water permeation in a variety of epithelia. Aquaporin-3 (AQP3) has been localized to the basolateral membranes of epithelial cells in the small intestine, but mechanisms that regulate its expression and function have not been explored. To determine whether luminal content may influence intestinal AQP3 gene expression, adult Sprague-Dawley rats underwent sham laparotomy (N = 11) or loop ileostomy (N = 9) and were killed 8 days after procedures. Northern blot analysis was used to measure messenger RNA (mRNA) levels for AQP3 and the Na(+)/K(+) ATPase, a housekeeping transporter that regulates cellular levels of Na(+) and K(+). At sacrifice, histologic examination revealed only minimal changes in mucosal morphology. In sham animals, Na/K mRNA levels increased moderately in distal regions of the small intestine. Ileostomy did not alter these levels in any region. In contrast, in sham animals, AQP3 mRNA levels increased along the length of the intestine and were markedly higher in the distal ileum. Diversion of luminal contents decreased AQP3 mRNA levels in the postileostomy region by 30% to 50%. These findings indicate regional variations in expression of the AQP3 water channel in mucosa of the small intestine. In addition, they suggest that AQP3 gene expression may depend on the presence of luminal contents.

The incidence and nature of surgical adverse events in Colorado and Utah in 1992.

BACKGROUND: Despite more than three decades of research on iatrogenesis, surgical adverse events have not been subjected to detailed study to identify their characteristics. This information could be invaluable, however, for guiding quality assurance and research efforts aimed at reducing the occurrence of surgical adverse events. Thus we conducted a retrospective chart review of 15,000 randomly selected admissions to Colorado and Utah hospitals during 1992 to identify and analyze these events. METHODS: We selected a representative sample of hospitals from Utah and Colorado and then randomly sampled 15,000 nonpsychiatric discharges from 1992. With use of a 2-stage record-review process modeled on previous adverse event studies, we estimated the incidence, morbidity, and preventability of surgical adverse events that caused death, disability at the time of discharge, or prolonged hospital stay. We characterized their distribution by type of injury and by physician specialty and determined incidence rates by procedure. RESULTS: Adverse events were no more likely in surgical care than in nonsurgical care. Nonetheless, 66% of all adverse events were surgical, and the annual incidence among hospitalized patients who underwent an operation or child delivery was 3.0% (confidence interval 2.7% to 3.4%). Among surgical adverse events 54% (confidence interval 48.9% to 58.9%) were preventable. We identified 12 common operations with significantly elevated adverse event incidence rates that ranged from 4.4% for hysterectomy (confidence interval 2.9% to 6.8%) to 18.9% for abdominal aortic aneurysm repair (confidence interval 8.3% to 37.5%). Eight operations also carried a significantly higher risk of a preventable adverse event: lower extremity bypass graft (11.0%), abdominal aortic aneurysm repair (8.1%), colon resection (5.9%), coronary artery bypass graft/cardiac valve surgery (4.7%), transurethral resection of the prostate or of a bladder tumor (3.9%), cholecystectomy (3.0%), hysterectomy (2.8%), and appendectomy (1.5%). Among all surgical adverse events, 5.6% (confidence interval 3.7% to 8.3%) resulted in death, accounting for 12.2% (confidence interval 6.9% to 21.4%) of all hospital deaths in Utah and Colorado. Technique-related complications, wound infections, and postoperative bleeding produced nearly half of all surgical adverse events. CONCLUSION: These findings provide direction for research to identify the causes of surgical adverse events and for targeted quality improvement efforts.

Paracellular glucose transport plays a minor role in the unanesthetized dog.

Traditionally, intestinal glucose absorption was thought to occur through active, carrier-mediated transport. However, proponents of paracellular transport have argued that previous experiments neglected effects of solvent drag coming from high local concentrations of glucose at the brush-border membrane. The purpose of this study was to evaluate glucose absorption in the awake dog under conditions that would maximize any contribution of paracellular transport. Jejunal Thiry-Vella loops were constructed in six female mongrel dogs. After surgical recovery, isotonic buffers containing L-glucose as the probe for paracellular permeability were given over 2-h periods by constant infusion pump. At physiological concentrations of D-glucose (1-50 mM), the fractional absorption of L-glucose was only 4-7% of total glucose absorption. Infusion of supraphysiological concentrations (150 mM) of D-glucose, D-maltose, or D-mannitol yielded low-fractional absorptions of L-glucose (2-5%), so too did complex or nonabsorbable carbohydrates. In all experiments, there was significant fractional water absorption (5-19%), a prerequisite for solvent drag. Therefore, with even up to high concentrations of luminal carbohydrates in the presence of significant water absorption, the relative contribution of paracellular glucose absorption remained low.

Selective increase in gastric mucosal mRNA encoding basolateral Na-K-2C1 cotransporter following ileostomy in the rat.

Results of previous studies suggest that major surgical resections or reconstructions of the distal small intestine can alter morphologic and functional properties of the stomach. Little is known about the effect of lesser surgical alterations such as construction of an ileostomy, on the morphology and transport properties of the gastric mucosa. To evaluate the effects of ileostomy, Sprague-Dawley rats underwent sham laparotomy (n = 10) or loop ileostomy construction (n = 10). After body weights had stabilized ( approximately 21 days) the animals were killed. Gastric mucosal scrapings were prepared for Northern blot analysis of messenger RNA levels for (1) H/K ATPase, found in parietal cells; (2) Na-K-2C1 cotransporter, found in both parietal and surface cells; and (3)Na/K ATPase, found in all gastric mucosal cells. Gastric mucosa from ileostomy animals was visibly hypertrophied compared to sham-operated animals. There was a 145% increase in the mRNA levels of the Na-K-2Cl cotransporter in gastric mucosa of the ileostomy group but no significant changes in H/K ATPase or Na/K ATPase mRNA levels. Construction of an ileostomy selectively enhances expression of the Na-K-C1 cotransporter in the gastric mucosa. Further studies are required to understand the neurohumoral stimuli underlying this selective response.

Percutaneous abdominal biopsy: cost-identification analysis.

PURPOSE: To determine the difference in cost to providers of percutaneous abdominal biopsy as the first strategy versus surgical biopsy. MATERIALS AND METHODS: Cost of tissue diagnosis determination with percutaneous biopsy as the first strategy in 439 patients with an abdominal mass was estimated. Costs included direct hospital costs and professional costs of initial and repeat biopsy, follow-up imaging and clinic visits, surgical biopsy (when needed), and treatment of complications. The sum of these costs was compared with the estimated cost had the same patients undergone surgical biopsy instead, with no complications or need for follow-up or repeat biopsy. RESULTS: The total estimated cost of percutaneous biopsy as the first strategy ($543,245) was less than the cost had surgical biopsy been used alone ($1,919,867). The average per patient direct hospital cost of percutaneous biopsy ($800) was lower than that of surgical biopsy ($3,419). The average per patient professional cost of percutaneous biopsy ($438) was also lower than that of surgical biopsy ($955). Savings averaged $3,136 per patient, or $1,376,622 for the study period. CONCLUSION: Substantial health care cost savings may result by using a diagnostic algorithm in which percutaneous biopsy is the first strategy for establishment of a diagnosis in patients suspected of having abdominal malignancy.

Relationship of necrosis to organ failure in severe acute pancreatitis.

BACKGROUND & AIMS: Pancreatic necrosis and organ failure are principal determinants of severity in acute pancreatitis. The purpose of this study was to determine the relationship of necrosis to organ failure in severe acute pancreatitis. METHODS: Patients with necrotizing pancreatitis from May 1992 to January 1996 were retrospectively studied. Pancreatic necrosis was identified by characteristic findings on dynamic contrast-enhanced computerized tomography scan and infected necrosis by computerized tomography-guided percutaneous aspiration. Organ dysfunction was defined in accordance with the Atlanta symposium. RESULTS: Organ failure was present in only 26 of 51 patients (51%). There was no difference in the prevalence of organ failure in infected necrosis compared with sterile necrosis (approximately 50% in both groups). Patients with increased amounts of necrosis did not have an increased prevalence of organ failure or infected necrosis compared with those with lesser amounts of necrosis. Patients with organ failure had an increased morbidity and mortality compared with those without organ failure. CONCLUSIONS: Organ failure occurred in only one half of patients with necrotizing pancreatitis. Because organ failure increases the severity of illness, studies of patients with necrotizing pancreatitis must stratify for organ failure to facilitate interpretation of results.

Antisecretory mechanisms of peptide YY in rat distal colon.

Peptide YY (PYY) is a potent regulator of intestinal secretion. These studies investigated the role of Y1 and Y2 receptor subtypes in mediating the antisecretory effects of PYY on mucosa-submucosa preparations of rat distal colon. Addition of vasoactive intestinal peptide (VIP) to these tissues resulted in a 140 +/- 18% increase in basal short-circuit current (Isc) and the induction of Cl- secretion. VIP-stimulated increases in Isc were abolished by the addition of each of PYY, (Pro34)-PYY, a Y1 receptor-selective agonist, and PYY-(3-36), an endogenous Y2 receptor-selective ligand. However, when tissue neural transmission was blocked with tetrodotoxin, neither PYY nor its receptor subtype-selective analogs were able to inhibit VIP-stimulated increases in Isc. These results suggest that in the rat distal colon, the antisecretory actions of PYY are mediated through a combination of Y1 and Y2 receptor subtypes or through a novel receptor subtype that is unable to discriminate between (Pro34)-PYY and PYY-(3-36).