Prescribing intranasal steroids in HIV-positive patients: systematic review of the literature.

BACKGROUND: There are significant drug-drug interactions between human immunodeficiency virus antiretroviral therapy and intranasal steroids, leading to high serum concentrations of iatrogenic steroids and subsequently Cushing's syndrome. METHOD: All articles in the literature on cases of intranasal steroid and antiretroviral therapy interactions were reviewed. Full-length manuscripts were analysed and the relevant data were extracted. RESULTS: A literature search and further cross-referencing yielded a total of seven reports on drug-drug interactions of intranasal corticosteroids and human immunodeficiency virus protease inhibitors, published between 1999 and 2019. CONCLUSION: The use of potent steroids metabolised via CYP3A4, such as fluticasone and budesonide, are not recommended for patients taking ritonavir or cobicistat. Mometasone should be used cautiously with ritonavir because of pharmacokinetic similarities to fluticasone. There was a delayed onset of symptoms in many cases, most likely due to the relatively lower systemic bioavailability of intranasal fluticasone.

Linear versus volumetric CT analysis in predicting tension-free fascial closure in abdominal wall reconstruction.

BACKGROUND: Improved outcomes of abdominal wall reconstruction (AWR) have been shown when tension-free fascial closure (TFFC) is achieved. Our objective was to determine the clinical and radiologic predictors of TFFC in patients undergoing AWR. STUDY DESIGN: We conducted a single institution retrospective cohort study of adults who underwent AWR between 2007 and 2018. Demographics, hernia characteristics and operative data were collected. Linear and volumetric variables were obtained from preoperative abdominal CT scans, the latter following 3D reconstruction. Logistic regression was used to evaluate predictors of TFFC. Area under the curve (AUC) ≥ 0.70 was considered to have acceptable discrimination. RESULTS: A total of 108 patients were eligible for analysis. The mean age was 57 ± 11 years and 53 (49%) were female. 42 (39%) hernias were recurrent, 10 (9%) patients had a stoma and 9 (8%) had a history of open abdomen. The mean defect width was 11 ± 4 cm and mean defect surface area was 150 ± 95 cm2. The most common AWR technique was endoscopic component separation 75 (69%). TFFC was achieved in 90 (83%) patients. No demographics or 3D volumetric measures were predictive of TFFC (all AUC < 0.7). European hernia society (EHS) class M1 was predictive of failure of TFFC [AUC = 0.70; odds ratio 7.0 (referent M3); 95% confidence interval, 2.1-23.8]. Linear variables of rectus muscle separation were the most predictive of TFFC (AUC 0.73-0.77). CONCLUSION: In contrast to clinical characteristics, radiologic characteristics of large incisional hernias requiring AWR are predictive of TFFC. In particular, EHS class M1 and linear variables of rectus muscle separation appear to be better predictors of TFFC than volumetric measurements.

An analysis of true- and false-positive results of vocal fold uptake in positron emission tomography-computed tomography imaging.

OBJECTIVES: Positron emission tomography-computed tomography with fluorine-18 fluorodeoxy-D-glucose has a major role in the investigation of head and neck cancers. Fluorine-18 fluorodeoxy-D-glucose is not a tumour-specific tracer and can also accumulate in benign pathology. Therefore, positron emission tomography-computed tomography scan interpretation difficulties are common in the head and neck, which can produce false-positive results. This study aimed to investigate patients detected as having abnormal vocal fold uptake on fluorine-18 fluorodeoxy-D-glucose positron emission tomography-computed tomography. METHODS: Positron emission tomography-computed tomography scans were identified over a 15-month period where reports contained evidence of unilateral vocal fold uptake or vocal fold pathology. Patients' notes and laryngoscopy results were analysed. RESULTS: Forty-six patients were identified as having abnormal vocal fold uptake on positron emission tomography-computed tomography. Twenty-three patients underwent positron emission tomography-computed tomography and flexible laryngoscopy: 61 per cent of patients had true-positive positron emission tomography-computed tomography scans and 39 per cent had false-positive scan results. CONCLUSION: Most patients referred to ENT for abnormal findings on positron emission tomography-computed tomography scans had true-positive findings. Asymmetrical fluorine-18 fluorodeoxy-D-glucose uptake should raise suspicion of vocal fold pathology, accepting a false-positive rate of approximately 40 per cent.

Molecular gas in the halo fuels the growth of a massive cluster galaxy at high redshift.

The largest galaxies in the universe reside in galaxy clusters. Using sensitive observations of carbon monoxide, we show that the Spiderweb galaxy-a massive galaxy in a distant protocluster-is forming from a large reservoir of molecular gas. Most of this molecular gas lies between the protocluster galaxies and has low velocity dispersion, indicating that it is part of an enriched intergalactic medium. This may constitute the reservoir of gas that fuels the widespread star formation seen in earlier ultraviolet observations of the Spiderweb galaxy. Our results support the notion that giant galaxies in clusters formed from extended regions of recycled gas at high redshift.

How effective are common ENT operations?

OBJECTIVE: To review the literature on the outcomes of ENT operations in order to assess whether ENT operations are effective. METHODS: The value of evidence-based medicine in relation to ENT was appraised, as was the perception of effectiveness. Literature on common ENT operations, including grommet insertion, tonsillectomy and adenoidectomy, and correction of the nasal septum, was evaluated. RESULTS AND CONCLUSION: When evaluating the effectiveness of ENT operations, the patient's overall condition and improvements after surgery should be measured. Objective and subjective factors should both be considered as good evidence, especially with the increasing role that evidence-based medicine plays in decisions of whether to operate. The literature review provides evidence that ENT operations are effective.

Recipient outcomes for expanded criteria living kidney donors: the disconnect between current evidence and practice.

Older individuals or those with medical complexities are undergoing living donor nephrectomy more than ever before. Transplant outcomes for recipients of kidneys from these living expanded criteria donors are largely uncertain. We systematically reviewed studies from 1980 to June 2008 that described transplant outcomes for recipients of kidneys from expanded criteria living donors. Results were organized by the following criteria: older age, obesity, hypertension, reduced glomerular filtration rate (GFR), proteinuria and hematuria. Pairs of reviewers independently evaluated each citation and abstracted data on study and donor characteristics, recipient survival, graft survival, serum creatinine and GFR. Transplant outcomes for recipients of kidneys from older donors (> or =60 years) were described in 31 studies. Recipients of kidneys from older donors had poorer 5-year patient and graft survival than recipients of kidneys from younger donors [meta-analysis of 12 studies, 72% vs. 80%, unadjusted relative risk (RR) of survival 0.89, 95% confidence interval (CI) 0.83-0.95]. In meta-regression, this association diminished over time (1980s RR 0.79, 95% CI 0.65-0.96 vs. 1990s RR 0.91, 95% CI 0.85-0.99). Few transplant outcomes were described for other expanded criteria. This disconnect between donor selection and a lack of knowledge of recipient outcomes should give transplant decision-makers pause and sets an agenda for future research.

Performance and ergonomic characteristics of expert surgeons using a face-mounted display during virtual reality-simulated laparoscopic surgery: an electromyographically based study.

BACKGROUND: Display positions for laparoscopy in current operating rooms may not be optimal for surgeon comfort or task performance, and face-mounted displays (FMDs) have been forwarded as a potential ergonomic solution. Little is known concerning expert use characteristics of these devices that might help define their role in future surgical care. The authors report the performance and ergonomic characterization of an FMD using virtual reality simulation technology to recreate the surgical environment. METHODS: An FMD was studied in short- and long-duration trials of validated virtual reality-simulated surgical tasks. For the short-duration phase 7, expert surgeons were familiarized with a task on a conventional monitor, then returned on two separate occasions to repeat the task with the FMD while digital photos were taken during task performance and at the end in a standardized fashion. For the long-duration phase 5, expert surgeons performed two separate trials with repetitive groups of validated tasks for a minimum of 30 min while electromyelogram and performance data were measured. Photos of their gaze angle during and at the end of the trial were taken. RESULTS: All the participants consistently assumed a gaze angle slightly below horizontal during task performance. Performance scores on the FMD did not differ from those obtained with a conventional display, and remained stable with repetitive task performance. No participant had electromyelogram signals that exceeded the established thresholds for fatigue, but some had values within the threshold range. CONCLUSION: The natural gaze angle during simulated surgery was consistently a bit below horizontal during rigorous virtual reality-simulated tasks. Performance was not compromised during expert surgeons' use of an FMD, nor did muscle fatigue characteristics arise under these conditions. The findings suggest that these devices may represent a viable alternative to conventional displays for minimally invasive surgery, but definition of specific roles requires further investigation.

Challenges to the development of complex virtual reality surgical simulations.

Virtual reality simulation in surgical training has become more widely used and intensely investigated in an effort to develop safer, more efficient, measurable training processes. The development of virtual reality simulation of surgical procedures has begun, but well-described technical obstacles must be overcome to permit varied training in a clinically realistic computer-generated environment. These challenges include development of realistic surgical interfaces and physical objects within the computer-generated environment, modeling of realistic interactions between objects, rendering of the surgical field, and development of signal processing for complex events associated with surgery. Of these, the realistic modeling of tissue objects that are fully responsive to surgical manipulations is the most challenging. Threats to early success include relatively limited resources for development and procurement, as well as smaller potential for return on investment than in other simulation industries that face similar problems. Despite these difficulties, steady progress continues to be made in these areas. If executed properly, virtual reality offers inherent advantages over other training systems in creating a realistic surgical environment and facilitating measurement of surgeon performance. Once developed, complex new virtual reality training devices must be validated for their usefulness in formative training and assessment of skill to be established.

Laparoscopic versus open incisional hernia repair: a single-institution analysis of hospital resource utilization for 884 consecutive cases.

BACKGROUND: To analyze hospital resource utilization for laparoscopic vs open incisional hernia repair including the postoperative period. METHODS: Prospectively collected administrative data for incisional hernia repairs were examined. A total of 884 incisional hernia repairs were examined for trends in type of approach over time. Starting October 2001, detailed records were available, and examined for operating room (OR) time, cost data, length of stay (LOS), and 30-day postoperative hospital encounters. RESULTS: Of the total, 469 incisional hernias were approached laparoscopically (53%) and 415 open (47%). Laparoscopic repair had shorter LOS (1 +/- 0.2 days vs 2 +/- 0.6 days), longer OR time (149 +/- 4 min vs 89 +/- 4 min), higher supply costs (2,237 dollars +/- 71 dollars vs 664 dollars +/- 113 dollars), slightly lower total hospital cost (6,396 dollars +/- 477 dollars vs 7,197 dollars +/- 1,819 dollars), and slightly more postoperative hospital encounters (15% vs 13%). Use of laparoscopy increased over time (37% in 2000 vs 68% in 2004). CONCLUSIONS: Laparoscopic incisional hernia repair is becoming increasingly popular, and not at increased cost to the health care system.

Analysis of errors in laparoscopic surgical procedures.

BACKGROUND: The determination of laparoscopic surgeon ability is essential to training error avoidance. The present study describes a practical method of surgical error analysis. METHODS: After review of practice videotapes of the excisional phase of laparoscopic cholecystectomy, consensus on the identification of eight errors was achieved. Interrater agreement at the end of this phase was 84-96%. Fourteen study videotapes of gallbladder excision were then observed independently by expert reviewers blinded to surgical team identity. Procedures were assessed using a scoring matrix of 1-min segments with each error reported each minute. RESULTS: Interrater agreement was 84-100% for all error categories. CONCLUSIONS: The present study demonstrates that excellent interrater agreement of procedural errors can be achieved by carefully defining and training recognition of targeted events. Extension of this simple and reliable analysis tool to other procedures should be feasible to define behaviors leading to adverse clinical outcomes.

Laparoscopic treatment of fulminant ulcerative colitis.

BACKGROUND: The complexity and risks of the surgical treatment of ulcerative colitis are greater in patients with fulminant disease. Subtotal colectomy is frequently offered to such patients to control acute disease and restore immunological and nutritional status prior to a restorative procedure. The role of laparoscopy in this setting is poorly defined. METHODS: The records of 18 patients with poorly controlled fulminant colitis on aggressive immunosuppressive therapy who underwent laparoscopic subtotal colectomy were reviewed. RESULTS: Postoperative complications occurred in six patients (33%). Postoperative length of stay was 5.0 +/- 0.3 days vs 8.8 +/- 1.8 days (p<0.05) for a group of six patients who had undergone open subtotal colectomy for the same indications. Systemic steroids were withdrawn in all patients, and 17 patients subsequently underwent proctectomy and pelvic pouch construction. CONCLUSIONS: The relatively high morbidity rate in these patients is likely related to their compromised status at the time of surgery. Laparoscopic subtotal colectomy in patients with fulminant ulcerative colitis allows for earlier hospital discharge, facilitates subsequent pelvic pouch, construction, and provides an excellent alternative to conventional two- and three-stage surgical treatment.

Impaired hepatocyte glucose transport protein (GLUT2) internalization in chronic pancreatitis.

Chronic pancreatitis (CP) is associated with impaired glucose tolerance and with reduced hepatic sensitivity to insulin. We have previously shown that in normal and sham-operated rats, insulin suppresses hepatic glucose production, and this suppression is associated with a decrease in the hepatocyte plasma membrane-bound quantity of the facilitative glucose transport protein GLUT2. The insulin-mediated reduction in membrane-bound GLUT2 is impaired in CP, and may play a role in the glucose intolerance associated with CP. To determine whether GLUT2 is actively internalized and whether this mechanism is disordered in CP, livers from fed and fasting rats in whom CP had been induced 2-3 months earlier by pancreatic duct oleic acid infusion, and in sham-operated (sham) rats, were fractionated to yield endosome (E)- and plasma membrane (PM)-enriched fractions. Forty-five minutes after duodenal intubation alone (fasting) or intubation plus duodenal feeding, livers were removed, homogenized and ultracentrifuged, and microsomal pellets were separated by sucrose density gradient ultracentrifugation. GLUT2 content of fractions was determined by Western blotting and scanning densitometry. The E:PM ratio of GLUT2 increased from 0.68 +/- 0.11 (mean +/- SEM) in fasting sham livers (n = 8) to 1.04 +/- 0.09 in fed sham livers (n = 8; p < 0.05). However, there was no change in the E:PM ratio of GLUT2 in CP livers after duodenal feeding (0.90 +/- 0.12 vs. 0.86 +/- 0.10; n = 8,8; p = NS). To test our findings using confocal laser scanning microscopy, liver specimens from fed and fasting CP and sham rats were minced, fixed in 4% paraformaldehyde, sectioned, and stained with rabbit antirat GLUT2 antibody followed by rhodamine-labeled secondary antibody. GLUT2 was quantified by mean pixel intensity in an 8 x 16-pixel area of PM and a 16 x 16-pixel area of cytosol (CYT) in each of 30 random cells/field (400x) in each of three rats per group. As in the fractionation study, duodenal feeding increased the CYT:PM ratio of GLUT2 from 0.75 +/- 0.01 in fasting sham liver to 0.86 +/- 0.01 in fed sham liver (p < 0.0001), while the CYT:PM ratio in CP remained unchanged. We conclude that feeding induces a shift in GLUT2 from the plasma membrane to the endosomal pool. The feeding-induced internalization of GLUT2 is absent in livers from rats with CP and may play a role in the glucose intolerance associated with CP.

Human insulin receptor and insulin signaling proteins in hepatic disease.

Insulin regulates hepatocellular metabolism and growth following insulin receptor (IR) autophosphorylation and activation of the intracellular adapter protein, insulin receptor substrate 1 (IRS-1). IRS-1 activates SH2 domain proteins such as Grb2, which may be vital to hepatocyte growth. To determine if these substances are abnormally expressed under pathophysiologic conditions, IR, IRS-1, Grb2 protein, and IR mRNA were studied in normal human liver (n = 10), cirrhotic liver (n = 10), and hepatocellular carcinoma (HCC) (n = 10) that had been procured during operative procedures. IR mRNA was quantified by S1-nuclease assay using a 195-bp digoxigenin-labeled IR DNA probe and normalized to the level of expression of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene. Protein concentrations were determined by immunoblot analysis following SDS-PAGE of liver homogenate samples. Labeled DNA and antibody-complexed protein were detected by chemiluminescent means and quantified by densitometric analysis (mean densitometric units +/- standard error). Similar levels of IR mRNA were observed in normal tissue, cirrhosis, and HCC. IR protein concentration was significantly greater in HCC than in normal liver (1.82 +/- 0.2 vs 1. 25 +/- 0.17; P < 0.05). IRS-1 was significantly increased in cirrhosis compared to normal liver (1.61 +/- 0.31 vs 0.86 +/- 0.21; P < 0.05). No differences were observed in Grb2 in the three tissue types. Insulin receptor overexpression, previously seen in other tumor types, may confer an insulin-mediated growth advantage in HCC if added receptors reflect functional high affinity binding sites. Although an altered mass of IRS-1 protein was not observed in HCC, an IRS-1 increase in cirrhosis may favor hepatic regeneration.

Overexpression of hepatic pancreatic polypeptide receptors in chronic pancreatitis.

Pancreatic polypeptide (PP) receptors have recently been demonstrated on liver microsomal membranes although the mechanisms of PP action on hepatocytes remain uncertain. The binding characteristics of these high affinity receptors under pathophysiologic conditions were studied in rats with oleic acid-induced chronic pancreatitis (CP), a state associated with diminished pancreatic PP content. Sixteen pancreatitic and 11 sham-operated control animals either were 16-h fasted or were given free access to food prior to organ removal. Competitive binding studies were performed by incubating hepatocyte microsomal preparation with 125I-labeled PP (20-40 pM) and increasing concentrations of nonlabeled PP (1 x 10(-10) to 1 x 10(-6) M). After total and nonspecific binding was quantified by gamma counting, coefficients of dissociation (Kd) and maximal binding sites (Bmax) were determined by Scatchard analysis of specifically bound radioactivity. Binding data were normalized to membrane protein content and expressed as means +/- standard error. Bmax was significantly greater in tissue from fed control animals than from fasted controls (4.46 +/- 0.36 versus 2.83 +/- 0.25, P < 0.05). Bmax was significantly greater under fasted conditions in tissue from CP animals than from controls (5.25 +/- 0.94 versus 2.83 +/- 0.25, P < 0.01). Under fed conditions, this differences was abolished by the increase in maximal binding in the control group. The fasting-associated decrease in maximal binding sites observed in controls did not occur in CP specimens. Increased Bmax in fed versus fasted control, as well as fasted CP versus fasted control, were associated with slight reciprocal decreases in receptor affinity. These data indicate that hepatic PP receptor concentration is upregulated in this model of chronic pancreatitis, most likely due to diminished exposure to ligand. Furthermore, normal PP receptor responses to the fed/fasted state are blunted in this condition. Regulatable PP receptor changes may play a role in altered hepatic metabolism previously observed in chronic pancreatitis.

Achalasia in a sixty-four-year-old man.

Achalasia is an esophageal motility disorder characterized by increased lower esophageal sphincter pressure and absence of peristalsis in the lower esophagus. Patients typically present with complaints of progressive difficulty swallowing over a period of several years. Diagnosis is confirmed by esophageal manometry. Complications of achalasia include esophagitis, aspiration and possibly an increased risk of esophageal carcinoma. Medical treatment options include pneumatic dilatation, esophageal bougienage, nitrates, calcium channel blockers and botulinum toxin injections. The primary method of surgical treatment is the Heller myotomy, in which longitudinal incisions are made in the muscle fibers of the lower esophageal sphincter to reduce sphincter pressure. Frequently, a fundoplication is performed in addition to the myotomy to decrease the likelihood of development of gastroesophageal reflux. In recent years, the Heller myotomy has been performed both thoracoscopically and laparoscopically. An additional development has been the placement of an endoscope in the esophagus to provide transillumination during surgery; intraoperative endoscopy allows improved assessment of the depth of myotomy incisions and reduces the risk of esophageal perforation. The case report below describes a 64-year-old-man with achalasia who presented with persistent dysphagia despite multiple attempts at medical treatment. A laparoscopic Heller myotomy with Toupet fundoplication was performed with subsequent eradication of symptoms. A discussion of the epidemiology, etiology, clinical presentation, diagnosis and treatment of achalasia follows the case report.

Laparoscopic treatment of gastroesophageal reflux disease.

Laparoscopic fundoplication is technically feasible in treating gastroesophageal reflux disease (GERD). Although medication is the primary treatment for GERD, not all patients respond completely or are able to adhere to a medical regimen. In the present series, 59 patients were laparoscopically treated for GERD at three centers using a standardized technique. All patients had been medically treated prior to referral, although 84 per cent had heartburn and 2 per cent had laryngitis despite 20 to 40 mg/day of omeprazole. Fifteen per cent of patients were intolerant of or would no longer take omeprazole. Patients were evaluated by esophageal manometry (in 100%) and 24-hour pH studies (in 66%). Seventy-six per cent of patients had lower-esophageal sphincter pressure <15 mm Hg. Five patients had low esophageal body peristaltic pressures (<35 mm Hg). These patients underwent Toupet partial fundoplication, whereas 54 patients underwent Nissen fundoplication. Mean operative time was 158 +/- 7 minutes, and three patients (5%) were converted to an open procedure. Operative complications were minor and occurred in 13 per cent. In 45 patients evaluated 1 year after surgery, heartburn had resolved in 98 per cent. Thirty-nine of 56 patients (70%) had mild early (<1 month postoperatively) dysphagia, and 9 (19%) had severe early dysphagia, which improved in 7 after nonoperative dilatation. Two of these had continued mild dysphagia. Two patients had severe dysphagia and were laparoscopically converted from Nissen to Toupet fundoplications, which resulted in marked improvement. Early gas bloat symptoms occurred in 45 per cent and dropped to 5 per cent at 1 year. Laparoscopic treatment of GERD is safe and effective in preventing reflux symptoms. Although mild dysphagia occurs after the procedure, this is transient in most patients. Patients with severe dysphagia can be treated with nonoperative dilatation or laparoscopic partial fundoplication and maintain the antireflux characteristics of the wrap.

Discordant expression of major histocompatibility complex class II antigens and invariant chain in interstitial dendritic cells. Implications for self-tolerance and immunity.

BACKGROUND: The invariant chain plays a crucial role in antigen presentation by influencing the expression and peptide loading of major histocompatibility complex (MHC) class II molecules. Therefore, coordinate expression of these molecules is important for antigen presentation. METHODS: Immunohistological studies were performed on frozen sections of many rat tissues in order to examine expression of invariant chain and MHC class II antigens. RESULTS: Although coordinately regulated in most tissues, the interstitial dendritic cell (and the renal tubular epithelial cell) was always negative for invariant chain, while strongly positive for MHC class II antigens. However, renal tubular epithelial cells strongly expressed invariant chain during kidney graft rejection. CONCLUSIONS: The absence of invariant chain in interstitial dendritic cells is unexpected, in view of their presumed function as sentinel antigen-presenting cells in the connective tissues. This might have important implications for antigen presentation for tolerance and immunity.

Pancreatic polypeptide administration improves abnormal glucose metabolism in patients with chronic pancreatitis.

Chronic pancreatitis (CP) is associated with lowered plasma levels and a blunted nutrient-induced release of pancreatic polypeptide (PP). To investigate the possible role of PP on glucose metabolism, we studied male patients with documented CP (n = 5) and obesity-matched control subjects (NL) (n = 6). Hepatic glucose production (HGP) and overall glucose disposal rates were determined by [3-3H]glucose infusion during a hyperinsulinemic-euglycemic clamp during three separate admissions. Basal rates of HGP were higher in CP patients. In response to an infusion of insulin (60 pmol.m-2.min-1), HGP fell 91 +/- 5% in NL subjects but only 68 +/- 8% in CP subjects (P < 0.05). One month later, the clamp was repeated during the final 2 h of an 8-h infusion of bovine PP (2 pmol.kg-1.min-1). HGP before the insulin infusion and its subsequent suppression (NL: 83 +/- 5%; CP: 86 +/- 15%) were nearly identical between groups. In follow-up studies 1 month after the PP infusion, HGP both basally and in response to insulin alone were similar to the first study. During oral glucose tolerance tests (OGTT) performed 18 h after the PP infusion, subjects with normal (n = 7) baseline OGTT responses showed no effect. All patients with diabetic (n = 3) or nondiagnostic (n = 1) OGTT responses, however, demonstrated lowered mean plasma glucose levels (approximately -2.3 mmol/L; range: -0.6 to -7.2 mmol/L). OGTTs repeated 1 month after the PP treatment showed a return to pretreatment responses. We conclude that chronic pancreatitis accompanied by PP deficiency is associated with partial hepatic resistance both in the basal state and in response to hyperinsulinemia. This impairment is reversed after iv PP administration. PP deficiency may therefore play a role in the development of pancreatogenic diabetes caused by pancreatic injury.

Regulation of hepatic insulin receptors by pancreatic polypeptide in fasting and feeding.

Pancreatic polypeptide (PP) increases hepatic insulin receptor (IR) binding activity in fasted PP-deficient rats, but not fasted normal animals. PP-induced alteration of hepatic IR levels in normal animals may be detectable in the fed state when IR concentrations are lower than during fasting. In the current study, the effect of exogenous PP on IR concentrations in the fed and fasted states was determined in healthy 300- to 350-g male Sprague-Dawley rats. Ten animals were administered PP 100 microgram/kg/day for 3 days by intraperitoneal injection and 10 weight-matched control animals received saline vehicle. Five PP- and five saline-administered rats were fasted for 12 hr prior to organ procurement, while 5 PP- and 5 saline-treated rats were given free access to food for this period. Livers were removed and snap-frozen. IRs were isolated from solubilized hepatocyte membranes by affinity chromatography with agarose-bound wheat germ agglutinin. Western blots were performed using a specific antibody to the beta subunit of the IR, which was detected by a chemiluminescence technique after 45-min exposure to X-ray film. Exposed films were examined by scanning densitometry and IR concentration was expressed as absorbance units per milligram of hepatic protein (mean +/- SE). Statistical comparisons were by Student's t test with significance taken at P < 0.05. Feeding was associated with a significantly lower IR concentration in saline-administered animals compared with the fasted state (24.2 +/- 4.0 vs 53.3 +/- 11.1). PP administration in fed rats resulted in significantly increased IR concentration as compared with that seen in saline-administered fed animals (43.8 +/- 8.9 vs 24.2 +/- 4.0). This difference may be due to increased IR synthesis with long-term PP administration, and supports the role of PP as a regulatory factor in hepatic carbohydrate metabolism.