Glucagon infusion alters the circulating metabolome and urine amino acid excretion in dogs.

Glucagon plays a central role in amino acid (AA) homeostasis. The dog is an established model of glucagon biology, and recently, metabolomic changes in people associated with glucagon infusions have been reported. Glucagon also has effects on the kidney; however, changes in urinary AA concentrations associated with glucagon remain under investigation. Therefore, we aimed to fill these gaps in the canine model by determining the effects of glucagon on the canine plasma metabolome and measuring urine AA concentrations. Employing two constant rate glucagon infusions (CRI) - low-dose (CRI-LO: 3 ng/kg/min) and high-dose (CRI-HI: 50 ng/kg/min) on five research beagles, we monitored interstitial glucose and conducted untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) on plasma samples and urine AA concentrations collected pre- and post-infusion. The CRI-HI induced a transient glucose peak (90-120 min), returning near baseline by infusion end, while only the CRI-LO resulted in 372 significantly altered plasma metabolites, primarily reductions (333). Similarly, CRI-HI affected 414 metabolites, with 369 reductions, evidenced by distinct clustering post-infusion via data reduction (PCA and sPLS-DA). CRI-HI notably decreased circulating AA levels, impacting various AA-related and energy-generating metabolic pathways. Urine analysis revealed increased 3-methyl-l-histidine and glutamine, and decreased alanine concentrations post-infusion. These findings demonstrate glucagon's glucose-independent modulation of the canine plasma metabolome and highlight the dog's relevance as a translational model for glucagon biology. Understanding these effects contributes to managing dysregulated glucagon conditions and informs treatments impacting glucagon homeostasis.

Advances in Confocal Microscopy and Selected Applications.

Over the last 30 years, confocal microscopy has emerged as a primary tool for biological investigation across many disciplines. The simplicity of use and widespread accessibility of confocal microscopy ensure that it will have a prominent place in biological imaging for many years to come, even with the recent advances in light sheet and field synthesis microscopy. Since these more advanced technologies still require significant expertise to effectively implement and carry through to analysis, confocal microscopy-based approaches still remain the easiest way for biologists with minimal imaging experience to address fundamental questions about how their systems are arranged through space and time. In this review, we discuss a number of advanced applications of confocal microscopy for probing the spatiotemporal dynamics of biological systems.

The Limited Role of Glucagon for Ketogenesis During Fasting or in Response to SGLT2 Inhibition.

Glucagon is classically described as a counterregulatory hormone that plays an essential role in the protection against hypoglycemia. In addition to its role in the regulation of glucose metabolism, glucagon has been described to promote ketosis in the fasted state. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a new class of glucose-lowering drugs that act primarily in the kidney, but some reports have described direct effects of SGLT2i on α-cells to stimulate glucagon secretion. Interestingly, SGLT2 inhibition also results in increased endogenous glucose production and ketone production, features common to glucagon action. Here, we directly test the ketogenic role of glucagon in mice, demonstrating that neither fasting- nor SGLT2i-induced ketosis is altered by interruption of glucagon signaling. Moreover, any effect of glucagon to stimulate ketogenesis is severely limited by its insulinotropic actions. Collectively, our data suggest that fasting-associated ketosis and the ketogenic effects of SGLT2 inhibitors occur almost entirely independent of glucagon.

Magnetic properties of lunar samples.

The magnetic properties of samples of rock, fines, and magnetic separate from the fines from Apollo 11 have been measured. Native iron, or possibly nickel-iron, of submicroscopic particle size is the most important constituent, with minor contributions from ilmenite, paramagnetic iron minerals, and other iron-titanium oxides. The remanent magnetization of a sample of the micro-breccia rapidly acquires a viscous magnetization and does not appear to have a significant stable remanence. The crystalline sample has a weak natural remanence showing some stability.

Glucagon lowers glycemia when ß-cells are active.

Glucagon and insulin are commonly believed to have counteracting effects on blood glucose levels. However, recent studies have demonstrated that glucagon has a physiologic role to activate ß-cells and enhance insulin secretion. To date, the actions of glucagon have been studied mostly in fasting or hypoglycemic states, yet it is clear that mixed-nutrient meals elicit secretion of both glucagon and insulin, suggesting that glucagon also contributes to glucose regulation in the postprandial state. We hypothesized that the elevated glycemia seen in the fed state would allow glucagon to stimulate insulin secretion and reduce blood glucose. In fact, exogenous glucagon given under fed conditions did robustly stimulate insulin secretion and lower glycemia. Exogenous glucagon given to fed Gcgr:Glp1rßcell-/- mice failed to stimulate insulin secretion or reduce glycemia, demonstrating the importance of an insulinotropic glucagon effect. The action of endogenous glucagon to reduce glycemia in the fed state was tested with administration of alanine, a potent glucagon secretagogue. Alanine raised blood glucose in fasted WT mice or fed Gcgr:Glp1rßcell-/- mice, conditions where glucagon is unable to stimulate ß-cell activity. However, alanine given to fed WT mice produced a decrease in glycemia, along with elevated insulin and glucagon levels. Overall, our data support a model in which glucagon serves as an insulinotropic hormone in the fed state and complements rather than opposes insulin action to maintain euglycemia.

Sixteen years of bathymetry and waves at San Diego beaches.

Sustained, quantitative observations of nearshore waves and sand levels are essential for testing beach evolution models, but comprehensive datasets are relatively rare. We document beach profiles and concurrent waves monitored at three southern California beaches during 2001-2016. The beaches include offshore reefs, lagoon mouths, hard substrates, and cobble and sandy (medium-grained) sediments. The data span two energetic El Niño winters and four beach nourishments. Quarterly surveys of 165 total cross-shore transects (all sites) at 100 m alongshore spacing were made from the backbeach to 8 m depth. Monthly surveys of the subaerial beach were obtained at alongshore-oriented transects. The resulting dataset consists of (1) raw sand elevation data, (2) gridded elevations, (3) interpolated elevation maps with error estimates, (4) beach widths, subaerial and total sand volumes, (5) locations of hard substrate and beach nourishments, (6) water levels from a NOAA tide gauge (7) wave conditions from a buoy-driven regional wave model, and (8) time periods and reaches with alongshore uniform bathymetry, suitable for testing 1-dimensional beach profile change models.

ß Cell tone is defined by proglucagon peptides through cAMP signaling.

Paracrine interactions between pancreatic islet cells have been proposed as a mechanism to regulate hormone secretion and glucose homeostasis. Here, we demonstrate the importance of proglucagon-derived peptides (PGDPs) for α to ß cell communication and control of insulin secretion. Signaling through this system occurs through both the glucagon-like peptide receptor (Glp1r) and glucagon receptor (Gcgr). Loss of PGDPs, or blockade of their receptors, decreases insulin secretion in response to both metabolic and nonmetabolic stimulation of mouse and human islets. This effect is due to reduced ß cell cAMP and affects the quantity but not dynamics of insulin release, indicating that PGDPs dictate the magnitude of insulin output in an isolated islet. In healthy mice, additional factors that stimulate cAMP can compensate for loss of PGDP signaling; however, input from α cells is essential to maintain glucose tolerance during the metabolic stress induced by high-fat feeding. These findings demonstrate an essential role for α cell regulation of ß cells, raising the possibility that abnormal paracrine signaling contributes to impaired insulin secretion in diabetes. Moreover, these findings support reconsideration of the role for α cells in postprandial glucose control.

Risk factors for hide contamination of Scottish cattle at slaughter with Escherichia coli O157.

In the slaughter processing of cattle, contaminated hides have been identified as one of the major sources of Escherichia coli O157 carcase contamination. Logistic regression analysis was applied to data collected in a large scale study in Scotland involving 222 cattle forming 34 groups sent for slaughter from 30 farms to 10 slaughterhouses. Aspects of individual animal characteristics, farm management practices and slaughterhouse features were examined to identify potential risk factors for hide contamination at harvest. Two models were developed, the first in which slaughterhouse was modelled as a fixed effect, and a second model where slaughterhouse and farm groups were modelled as random effects. In the first model, there was a significantly increased risk of a carcase testing positive for E. coli O157 on the hide if either the hide of the carcase immediately before or after it on the line was contaminated (OR 3.6; 95% CI: 1.4-9.9). If both adjacent carcases had contaminated hides, the odds ratio for the study carcase having a contaminated hide rose to 11.5 (95% CI: 4.4-32.5). If animals were held in lairage, receiving hay as feed appeared to have a protective effect on hide contamination. Transportation to the slaughterhouse by haulier, as opposed to transport by the farmer, was associated with a 5.4 increase in the odds of E. coli O157 contamination. The use of a crush in the lairage, often employed when reading ear tags, was also found to significantly increase the odds of hide contamination with E. coli O157. In the second model, the inclusion of slaughterhouse and farm group as random effects resulted in two of the previously identified factors being associated with hide contamination. If at least one of the adjacent carcases on the line had a contaminated hide, the associated odds ratio was 6.6 (95% CI: 2.8-15.9), which rose to 22.7 (95% CI: 9.3-55.5) if both adjacent hides were contaminated. Receiving hay in lairage was found to be important to the model, although not significant in itself (OR 0.005; 95% CI: 1.2e(-6)-20.7). These results suggest that modifiable risk factors for hide contamination exist. However, in order best to reduce the prevalence of hide contamination at slaughter, individual slaughterhouse risk assessment and intervention strategies are appropriate.

Action and localization of vasoactive intestinal peptide in the coronary circulation: evidence for nonadrenergic, noncholinergic coronary regulation.

Vasoactive intestinal polypeptide, a neurotransmitter peptide detected in animal and human hearts, has been found in nerves of coronary arteries. To determine the amount and distribution of vasoactive intestinal polypeptide in the large coronary vessels and its possible participation in coronary vasoregulation, two groups of animals were studied. In the first group, 11 anesthetized dogs were sacrificed to collect three (1 cm) segments along the circumflex and left anterior descending coronary arteries. These segments represented proximal (I), middle (II) and distal (III) portions of the two arteries. Concentrations (ng/g) of vasoactive intestinal polypeptide-like immunoreactive substance were determined by radioimmunoassay. Vasoactive intestinal polypeptide-like immunoreactivity was present in the left anterior descending (I = 7.28 +/- 1.65, II = 3.74 +/- 0.57, III = 2.29 +/- 0.53) and circumflex (I = 4.16 +/- 1.52, II = 4.58 +/- 1.13, III = 4.00 +/- 0.81) coronary arteries. The difference in vasoactive intestinal polypeptide-like immunoreactivity among epicardial segments of the anterior descending artery was significant, but there was no significant difference among segments of the circumflex coronary artery. In the second group (eight closed chest anesthetized dogs), the effects of vasoactive intestinal polypeptide intracoronary infusion on epicardial coronary constriction were examined at rest and with the artery constricted by serotonin. Left anterior descending (segments I, II and III) artery responses (% area change) to vasoactive intestinal polypeptide and vasoactive intestinal polypeptide plus serotonin were examined using quantitative coronary angiography. Vasoactive intestinal polypeptide infusion resulted in significant vasodilation in all the segments (I, II and III) of the left anterior descending artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Survey of zoonoses recorded in Scotland between 1993 and 2002.

All the human and animal laboratory reports of zoonoses sent to Health Protection Scotland between 1993 and 2002 were identified. There were 24,946 reports from veterinary laboratories, and 94,718 (20 per cent) of the 468,214 reports from medical laboratories were considered to be zoonotic. The most common reports of zoonoses from people were Campylobacter, Salmonella, Cryptosporidium and Giardia species and Escherichia coli o157. The most common reports of zoonoses from animals were Salmonella, Cryptosporidium, Chlamydia and Campylobacter species and Mycobacterium avium paratuberculosis. For all the zoonoses in people, the National Health Service Board areas Borders, Dumfries and Galloway, Forth Valley, Grampian, Lanarkshire and Lothian had a higher than expected standardised incidence rate of infection, whereas Ayrshire and Arran, Fife, Greater Glasgow, Shetland, Tayside and Western Isles had a lower than expected rate. The organisms and diseases considered to be new and emerging were Rhodococcus species, Cyclospora cayetanensis, Leishmania species, Pneumocystis carinii (jiroveci) and bovine spongiform encephalopathy/variant Creutzfeldt-Jakob disease.

Differential photoimmunoprotection by sunscreen ingredients is unrelated to epidermal cis urocanic acid formation in hairless mice.

A series of experimental sunscreen preparations based on a common vehicle, containing increasing concentrations of either octyl-N-dimethyl-p-aminobenzoate (o-PABA) or 2-ethylhexyl-p-methoxycinnamate (2-EHMC) as the ultraviolet B (UVB) absorber, has been tested in the hairless mouse for the ability to protect from erythema, from the systemically suppressive effects of UVB (280-320 nm) radiation on contact hypersensitivity, and from photoisomerization of epidermal urocanic acid. All the preparations protected efficiently from the edema component of the erythema response when mice were exposed to UVB radiation equivalent to three times the minimal erythema dose (MED). However, when mice were exposed to UVB radiation equivalent to 15 x MED, protection from erythema was observed only at the higher concentrations of each UVB absorber (10% 2-EHMC and 10% or 15% o-PABA). Protection from the UVB-induced suppression of contact hypersensitivity was shown to be dependent on both the nature of the UVB absorber and its concentration. Photoimmunoprotection by the sunscreens containing 2-EHMC was evident at lower concentrations (5% and 10% 2-EHMC) than with o-PABA, following both 3 x MED and 15 x MED of UVB exposure. Photoimmunoprotection by o-PABA-containing sunscreens was observed only at 15% o-PABA following 3 x MED, and failed at all tested concentrations after 15 x MED of UVB exposure. Regardless of the photoimmunoprotective capacity, sunscreen preparations containing either of the UVB absorbers prevented the UVB-induced formation of cis urocanic acid in the mouse epidermis and in vitro under all conditions tested. Thus, there appeared to be a correlation between protection from edema and from cis urocanic acid formation at 3 x MED of UVB, but a dissociation of these variables at 15 x MED of UVB. There was no relation apparent at either UVB dose between either edema or cis urocanic acid formation and protection from suppression of contact hypersensitivity.

A phase II study of repetitive cycles of dose-intense carboplatin plus paclitaxel chemotherapy and peripheral blood stem cells in metastatic breast cancer.

To assess the feasibility of administering sequential cycles of dose-intensive therapy, 14 patients without prior chemotherapy for metastatic breast cancer were registered to be treated with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) at an initial dose of 250 mg/m2 over 24 hours (day 1), followed by carboplatin dosed to an area under the concentration-time curve of 16 (calculated according to the Calvert formula), every 3 weeks for four cycles. This combination was supported with peripheral blood stem cells collected following granulocyte colony-stimulating factor with or without cyclophosphamide and paclitaxel. One patient failed to peripheralize CD34 cells after cyclophosphamide/paclitaxel therapy and was taken off protocol. The remaining 13 patients entered the paclitaxel/carboplatin phase of the program, and nine completed all four cycles. The median duration of severe neutropenia (absolute neutrophil count < 100/microL) was 6 days, despite the absence of routine use of granulocyte colony-stimulating factor. Only five of a total of 42 chemotherapy cycles (12%) were associated with febrile neutropenia requiring hospitalization. Most patients did not require platelet transfusions. The most significant nonhematologic toxicity was gastrointestinal (grade 3 in three patients, two of whom had received local radiation for relapse before chemotherapy). Most patients developed grade 1 or 2 sensory neuropathy by the final cycle. Of the nine patients who entered the paclitaxel/carboplatin phase and were evaluable for response, five achieved a complete remission. This doublet of high-dose therapy can be given in an entirely ambulatory setting and is associated with modest hematologic toxicity. The value of this option in the treatment of metastatic breast cancer compared with more conventional approaches to high-dose therapy will require a greater number of patients evaluable for response and longer follow-up.

Pharmacokinetics of N1-acetyl- and N4-acetylsulphamethoxazole in man.

The pharmacokinetics of N1-acetylsulphamethoxazole and N4-acetylsulphamethoxazole in man are described. N1-Acetylsulphamethoxazole is deacetylated to sulphamethoxazole and acetylated to N4-acetylsulphamethoxazole. N4-Acetylsulphamethoxazole is excreted almost unchanged in the urine. The renal excretion rate is independent of the urine flow and urinary pH. N4-Acetylsulphonamides are less lipid soluble and more acidic than their corresponding parent sulphonamides.

Determination of the acetylator phenotype and pharmacokinetics of some sulphonamides in man.

The pharmacokinetics of sulphamethizole, sulphamethoxazole, sulphadiazine, sulphapyridine and sulphadimidine have been studied in man. Renal clearance values of the metabolite N4-acetylsulphonamide are 6 to 20 times higher than those of the corresponding parent compound. The renal clearance of sulphonamides is dependent on the urine flow. N4-Acetylsulphonamide concentration-time profiles for plasma and urine have been constructed for the sulphonamides. The percentage N4-acetylsulphonamide-time profiles for plasma are excellent tools for establishing the acetylator phenotype, while those constructed from urine samples are less useful. Evidence is obtained that sulphadimidine is metabolically processes by 2 different isoenzymes, while sulphadiazine, sulphapyridine and sulphamethoxazole are processes by 1 acetylating isoenzyme. Sulphamethizole is acetylated to very little extent.

Pharmacokinetic model for the successive demethylation and biliary secretion of methyl orange in the rat.

1. A one-compartment pharmacokinetic model was developed in which a drug underwent two successive metabolical reactions (for example, metabolism followed by conjugation) and free drug and both metabolites were excreted.2. Techniques were described whereby graphical estimates of the first-order rate constants may be derived from cumulative excretion data on the drug and its metabolites. Computer simulation techniques were used to show that the experimental data permit reasonably accurate estimation of the rate constants of the model by graphical and computer methods.3. Tritiated methyl orange (2 mg) was administered to five groups of six rats with biliary cannulation. The bile produced by each animal was collected at hourly intervals for 6 h and the amounts of methyl orange and its metabolites, 4'sulpho-4-methylaminoazobenzene and 4'sulpho-4-aminoazobenzene, determined by thin layer chromatography and radioactive counting techniques.4. The data were analysed graphically and with an iterative digital computer programme to yield the first-order rate constants for the successive demethylation steps in the metabolism of methyl orange. The removal of the first methyl group had a rate constant of 0.684+/-0.142 h(-1) (+/-S.D.) and the second methyl group 1.00+/-0.302 h(-1). The rate constant for biliary excretion of the free methyl orange was 0.164+/-0.042 h(-1), for the monomethyl derivative 0.672+/-0.461 h(-1), and for the demethylated metabolite 6.413+/-3.222 h(-1).

Efficacy of fusion peptide homologs in blocking cell lysis and HIV-induced fusion.

Contrary to earlier reports, we have found that tri- and hexapeptides analogous or homologous with segments of the 23-residue N-terminal fusion sequence (FS) of the viral transmembrane glycoprotein gp41 (residues 517-539) did not significantly inhibit HIV-1-induced syncytium formation, using an uninfected cell-infected cell fusion assay. In contrast, we found that the high molecular weight apolipoprotein A-1 and a 23-residue analog of the FS, with the phenylalanine residues at positions 524 and 527 replaced with alanine residues, were effective inhibitors. Although the tripeptides were ineffective as inhibitors of syncytium formation, we found a number of them inhibited red cell lysis induced by the synthetic peptide AVGIGALFLGFLGAAGSTMGARS (based on the HIV-1 gp41 FS). This effect was also seen with apolipoprotein A-1. The Ala524,527 analog of the fusion sequence could not be tested in this system because it was hemolytic. We concluded that the smaller peptides were effective inhibitors of hemolysis because they interfered with pore formation by the fusion sequence peptide, either by disrupting the pores or by preventing the peptide from adopting the alpha-helical conformation found in the pores. On the other hand, membrane fusion, which is a prelude to syncytium formation, has been shown to require the fusion sequence in the beta-strand conformation. We argue that small peptides would be unable to block interaction between such strands, although larger molecules, such as apolipoprotein A-1 and the Ala524,527 analog, would be able to do so and thus inhibit fusion. It seems, therefore, that a successful drug directed against the FS-cell membrane interaction stage of syncytium formation would need to be of relatively high molecular weight and complexity.

Cryptosporidium in farmed animals: the detection of a novel isolate in sheep.

We describe the discovery of polymorphisms in the Cryptosporidium oocyst wall protein (COWP) gene conferring a novel restriction fragment length polymorphism (RFLP) pattern in 26/60 (43%) isolates from a flock of sheep sampled following a waterborne outbreak of human cryptosporidiosis. The sheep isolates showed identical PCR-RFLP patterns to each other by COWP genotyping but different from those of most currently recognised genotypes, including the major Cryptosporidium parvum genotypes 1 and 2. Sequence analysis of the 550bp amplicon from the COWP gene was compared with a DNA coding region employed in previous studies and showed the novel isolate to differ from other Cryptosporidium species and C. parvum isolates by 7-21%. The sheep-derived isolates were compared at this and further three Cryptosporidium gene loci with isolates from other farmed animals. The loci employed were one in the thrombospondin related adhesive protein (TRAP-C2) gene and two in the 70kDa heat shock protein (HSP70) gene (CPHSP1 and 2). Other animal samples tested in our laboratory were from clinically ill animals and all contained C. parvum genotype 2. The sheep in which the novel isolate was identified were healthy and showed no symptoms of cryptosporidiosis, and the novel sheep isolate could represent a non-pathogenic strain. Our studies suggest that a previously undetected Cryptosporidium sub-type may exist in sheep populations, reflecting the increasingly recognised diversity within the parasite genus.

Prevalence of combined fecal and urinary incontinence: a community-based study.

OBJECTIVE: To assess the prevalence of combined fecal and urinary incontinence. DESIGN: A cross-sectional, community-based study. SETTING: Olmsted County, Minnesota. PARTICIPANTS: Men (n = 778) and women (n = 762), aged 50 years or older, selected randomly from the population. MEASUREMENTS: Participants completed a previously validated self-administered questionnaire that assessed the occurrence of fecal and urinary incontinence in the previous year. RESULTS: The age-adjusted prevalence of incontinence was 11.1% (95% Confidence Interval (CI), 8.8-13.5) in men and 15.2% (95% CI, 12.5-17.9) in women for fecal incontinence; 25.6% (95% CI, 22.5-28.8) in men and 48.4% (95% CI, 44.7-52.2) in women for urinary incontinence; and 5.9% (95% CI, 4.1-7.6) in men and 9.4% (95% CI, 7.1-11.6) in women for combined urinary and fecal incontinence. The prevalence of fecal incontinence increased with age in men but not in women, from 8.4% among men in their fifties to 18.2% among men in their eighties (P for trend = .001). For women, the prevalence increased from 13.1% among 50-year-old women to 20.7% among women 80 years or older (P for trend = .5). Among persons with fecal incontinence, the prevalence of concurrent urinary incontinence was 51.1% among men and 59.6% among women (P = .001 and P = .003, respectively). Cross-sectionally, the age-adjusted, relative odds of fecal incontinence among persons with urinary incontinence was greater in men than in women (Odds Ratio (OR) = 3.0; 95% CI, 1.9-4.8 in men and OR = 1.8; 95% CI, 1.2-2.7 in women, P = .04). CONCLUSIONS: These findings suggest that persons with one form of incontinence are likely to have the other form as well. Despite the higher prevalence of urinary and fecal incontinence among women, the association between fecal incontinence and urinary incontinence was stronger among men than women. This finding, and the significant association between fecal incontinence and age observed in men but not in women, suggest that the etiologies may be more closely linked in men than in women.

Urinary incontinence in a community-based cohort: prevalence and healthcare-seeking.

OBJECTIVE: To estimate the prevalence of urinary incontinence and to assess care-seeking behavior for urinary symptoms among community-dwelling people. DESIGN: A community-based cross-sectional study. SETTING: Randomly selected men and women from Olmsted County, Minnesota. PARTICIPANTS: Two cohorts, one comprised of both men (n = 778) and women (n = 762) 50 years of age or older and a second comprised of men aged 40 years or older (n = 2150). MEASUREMENTS: Participants completed questionnaires assessing urinary incontinence in the previous 12 months, the number of days leaked, the amount leaked, and healthcare-seeking measures for urinary symptoms. RESULTS: In the first cohort, the prevalence of incontinence was 24% in men and 49% in women; 29% of men and 13% of women with incontinence had sought care for urinary symptoms. Urinary incontinence was more strongly associated with care-seeking measures for urinary symptoms in men (Odds Ratio (OR) = 4.3, 95% Confidence Interval (CI) = 2.4, 8.0) than in women (OR = 2.1, 95% CI = 1.2, 3.9). Moderate or severe urinary incontinence was associated significantly with care-seeking for urinary symptoms (OR = 10.5, 95% CI = 5.6, 19.8). In the second cohort, the prevalence of urinary incontinence was 17.3%; 8.5% of men with incontinence had sought care for urinary symptoms. Men with incontinence were 1.2 times (95% CI = .8, 1.9) as likely to seek care for urinary symptoms as men without incontinence. CONCLUSION: Our findings indicate that although urinary incontinence is relatively common in the community, care-seeking for urinary symptoms among persons with urinary incontinence is low, particularly among women, for whom the prevalence exceeds 40% between the ages of 50 and 70 years. These findings suggest that strategies to promote care-seeking for incontinence need to be investigated and employed in the community.

Identification and distribution of immunoreactive peptide YY in the human, canine, and murine gastrointestinal tracts: species-related antibody recognition differences.

A radioimmunoassay using two antisera (antibody 80 and antibody 213) from rabbits immunized with porcine peptide YY has been characterized for both sensitivity and specificity. To determine the distribution of peptide YY in the gut, fresh tissue specimens from the human and canine gut were separated into mucosal-submucosal and muscularis externa layers by microdissection. These tissues and transmural specimens from murine gut were acid-extracted and neutralized, followed by radioimmunoassay using each antiserum. Immunoreactive peptide YY in canine and murine gut was present in similar concentration and distribution using each antiserum, with highest concentrations in the mucosal-submucosal layer of the descending colon. Using antibody 213, immunoreactive peptide YY throughout the human gut was measured only at the lower detection limit of the radioimmunoassay. By contrast, using antibody 80, peptide YY in human gut was present in a distribution similar to canine and murine gut. Using antibody 80, one major immunoreactive species was identified with C18 reverse-phase high-performance liquid chromatography in extracts of human, canine, and murine colon. These results suggest species-related antibody recognition differences. The similar concentrations of peptide YY in canine and murine gut determined with the two antisera are consistent with the hypothesis that the amino acid sequences of canine and murine peptide YY are similar to porcine peptide YY. Using antibody 213, the low concentrations of immunoreactive peptide YY found in human gut are consistent with the hypothesis that human and porcine peptide YY have different amino acid sequences. Antisera prepared by immunization with porcine PYY must therefore be carefully characterized prior to studies using human sera or human tissue extracts.