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Biomedical subjects

C A Buffington

Publications and source records attributed to C A Buffington.

At least 19 recordsLinked to original sources
PubMed2005

Altered inducible nitric oxide synthase expression and nitric oxide production in the bladder of cats with feline interstitial cystitis.

PURPOSE: Alterations in nitric oxide (NO) levels have been demonstrated in some humans with interstitial cystitis (IC) as well as in chemically induced animal models of cystitis. Thus, in the current study we investigated whether inducible NO synthase (iNOS) mediated NO production is altered in the bladder of cats with a naturally occurring model of IC termed feline IC (FIC). MATERIALS AND METHODS: We examined iNOS expression using Western immunoblotting and baseline NO production using an NO microsensor from smooth muscle and mucosal bladder strips in 9 healthy cats and 6 diagnosed with FIC. RESULTS: There was a significant increase in baseline NO production in cats with FIC compared with that in healthy cats in smooth muscle and mucosal strips. This production was not ablated in the absence of extracellular Ca (100 microM egtazic acid) or following incubation with the calmodulin antagonist trifluoroperazine (20 microM), indicating iNOS mediated Ca independent NO production. Release was significantly decreased following incubation with the NOS antagonist L-NAME (N-nitro-L-arginine methyl ester) (100 microM). Furthermore, immunoblotting revealed a trend toward increased iNOS expression in smooth muscle and mucosal strips from FIC cats but not from healthy cats. CONCLUSIONS: In light of previous findings that the barrier property of the urothelial surface is disrupted in FIC and iNOS mediated increase in NO alters barrier function in other types of epithelium our findings suggest that iNOS dependent NO production may have a role in epithelial barrier dysfunction in FIC.

Animals↗
PubMed2004

Alterations in P2X and P2Y purinergic receptor expression in urinary bladder from normal cats and cats with interstitial cystitis.

Purinergic mechanisms appear to be involved in motor as well as sensory functions in the urinary bladder. ATP released from efferent nerves excites bladder smooth muscle, whereas ATP released from urothelial cells can activate afferent nerves and urothelial cells. In the present study, we used immunohistochemical techniques to examine the distribution of purinoceptors in the urothelium, smooth muscle, and nerves of the normal cat urinary bladder as well as possible changes in the expression of these receptors in cats with a chronic painful bladder condition termed feline interstitial cystitis (FIC) in which ATP release from the urothelium is increased. In normal cats, a range of P2X (P2X(1), P2X(2), P2X(3), P2X(4), P2X(5), P2X(6), and P2X(7)) and P2Y (P2Y(1), P2Y(2), and P2Y(4)) receptor subtypes was expressed throughout the bladder urothelium. In FIC cats, there is a marked reduction in P2X(1) and loss of P2Y(2) receptor staining. Both P2X(3) and P2Y(4) are present in nerves in normal cat bladder, and no obvious differences in staining were detected in FIC. Smooth muscle in the normal bladder did not exhibit P2Y receptor staining but did exhibit P2X (P2X(2), P2X(1)) staining. In the FIC bladder smooth muscle, there was a significant reduction in P2X(1) expression. These findings raise the possibility that purinergic mechanisms in the urothelium and bladder smooth muscle are altered in FIC cats. Because the urothelial cells appear to have a sensory function in the bladder, it is possible that the plasticity in urothelial purinergic receptors is linked with the painful bladder symptoms in IC.

Adenosine Triphosphate↗
PubMed2003

Feline interstitial cystitis results in mechanical hypersensitivity and altered ATP release from bladder urothelium.

ATP can be released from a variety of cell types by mechanical stimulation; however, the mechanism for this release and the influence of pathology are not well understood. The present study examined intracellular signaling mechanisms involved in swelling-evoked (exposure to a hypotonic solution) release of ATP in urothelial cells from normal cats and cats diagnosed with interstitial cystitis (feline interstitial cystitis; FIC). Using the luciferin-luciferase bioluminescent assay, we demonstrate that swelling-evoked ATP release is significantly elevated in FIC cells. In both normal and FIC cells, ATP release was significantly decreased (mean 70% decrease) by application of blockers of stretch-activated channels (amiloride or gadolinium), as well as brefeldin A and monensin (mean 90% decrease), suggesting that ATP release occurs when ATP-containing vesicles fuse with the plasma membrane. Swelling-evoked release was reduced after removal of external calcium (65%), and release was blocked by incubation with BAPTA-AM or agents that interfere with internal calcium stores (caffeine, ryanodine, heparin, or 2-aminoethoxydiphenyl borate). In addition, agents known to act through inositol 1,4,5-triphosphate (IP3) receptors (thapsigargin, acetylcholine) release significantly more ATP in FIC compared with normal urothelium. Taken together, these results suggest that FIC results in a novel hypersensitivity to mechanical stimuli that may involve alterations in IP3-sensitive pathways.

Adenosine Triphosphate↗
PubMed2001

Visceral pain in humans: lessons from animals.

Acute and persistent neuropathic and inflammatory injuries of healthy animals have contributed importantly to our current understanding of nociception and pain. Studies have differentiated somatic from visceral nociceptive input, and elucidated the pathways of transduction, transmission, perception, and modulation of the input. Other animal studies have identified important genetic and environmental influences on responses to nociception. Studies of naturally occurring visceral pain syndromes in animals also have added to our understanding of comparable syndromes in humans. Because of the aversive nature of pain, use of healthy animals to study pain in the service of other animals and humans is a decision to be taken carefully, and carries with it the responsibility of treating the animals as humanely as possible.

Animal Welfare↗
PubMed2001

Increased plasma norepinephrine concentration in cats with interstitial cystitis.

PURPOSE: Interstitial cystitis is a chronic urological syndrome affecting humans and domestic animals, including cats (feline interstitial cystitis). The symptoms of interstitial cystitis seem to be exacerbated by stress, suggesting involvement of the sympathetic nervous system and/or hypothalamic-pituitary-adrenal axis. Others have described sympathetic nervous system abnormalities in patients with interstitial cystitis but to our knowledge no data on plasma catecholamine concentrations or hypothalamic-pituitary-adrenal axis function in such patients have been reported. To evaluate the role of these systems in cats with feline interstitial cystitis we simultaneously measured baseline plasma concentrations of catecholamines and their metabolites to assess sympathetic activity, and the response of plasma adenocorticotropic hormone and cortisol concentrations to the infusion of corticotropin-releasing factor. MATERIALS AND METHODS: Eight healthy cats and 8 with feline interstitial cystitis were anesthetized and a catheter was placed in the external jugular vein. Four hours after recovery samples were obtained for high performance liquid chromatography analysis of plasma norepinephrine, dihydroxyphenylglycol, epinephrine, dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid. In 4 cats per group 1 microg. ovine corticotropin-releasing factor per kg. body weight was infused and blood samples were collected at intervals for 120 minutes for determining adenocorticotropic hormone and cortisol. RESULTS: Significant increases in plasma norepinephrine and dihydroxyphenylglycol as well as a trend toward increased epinephrine were found, whereas no effect on dihydroxyphenylalanine, dopamine, dihydroxyphenylacetic acid, adenocorticotropic hormone or cortisol was identified in cats with feline interstitial cystitis. CONCLUSIONS: These results support and extend previous studies identifying an increase in sympathetic activity in cats with feline interstitial cystitis.

Animals↗
PubMed2000

Effects of a synthetic facial pheromone on behavior of cats.

OBJECTIVE: TO evaluate the effects of a synthetic feline facial pheromone (FFP) on behavior and food intake of healthy versus clinically ill cats. DESIGN: Original study. ANIMALS: 20 cats were used in each of 2 studies. In each study, 7 cats were considered healthy, and 13 cats were determined to be clinically ill. PROCEDURE: In study 1, cats were assigned either to exposure to FFP (treated group; 4 healthy, 6 ill cats) or to exposure to the vehicle (70% ethanol solution; control group; 3 healthy, 7 ill cats). Cats were placed in a cage containing a small cotton towel that had been sprayed with FFP or vehicle 30 minutes previously. Cats were then videotaped for 125 minutes, and food intake was measured during this period. Videotapes were scored at 5-minute intervals for various behaviors. In study 2, cats were categorized in 1 of 2 groups; group 1 (2 healthy, 8 ill cats) had a cat carrier placed in their cages, and group 2 (5 healthy, 5 ill cats) did not. All cats were exposed to FFP, and 24-hour food intake was measured. RESULTS: Differences between behaviors of healthy versus clinically ill cats were not identified. In the first study, significant increases in grooming and interest in food were found in cats exposed to FFP compared with vehicle. For all cats, significant positive correlations were detected between grooming and facial rubbing, walking and facial rubbing, interest in food and facial rubbing, eating and facial rubbing, grooming and interest in food, and grooming and eating. In the second study, 24-hour food intake was significantly greater in cats exposed to FFP and the cat carrier, compared with cats exposed to FFP alone. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that exposure to FFP may be useful to increase food intake of hospitalized cats.

Animals↗
PubMed2000

Urothelial pathophysiological changes in feline interstitial cystitis: a human model.

Unique barrier properties of the urothelial surface membrane permit urine storage. Interstitial cystitis causes disabling dysuria, and frequency. Similarly, feline interstitial cystitis (FIC) occurs in cats. These studies define the permeability and structural properties of normal and FIC urothelium. To determine the effects of bladder filling, groups were studied before and after hydrodistention. Normal urothelium with or without hydrodistention exhibited high transepithelial resistances (TER) and low water and urea permeabilities, resembling other species. Fluorescence confocal microscopy revealed localization of the marker AE-31 to the apical surface of all umbrella cells in normal urothelium, with the tight junction protein ZO-1 localized to tight junctions. Scanning and transmission electron microscopy revealed uniform distribution of luminal cells with characteristic apical membrane and tight junction morphology. Urothelium in FIC animals displayed reduced TER and increased water and urea permeability following hydrodistention. Structural studies in FIC revealed denuded urothelium, with appearance of AE-31 in underlying epithelial cells. The results demonstrate severe epithelial damage and dysfunction in FIC and suggest novel approaches toward examining the etiology and therapy of IC.

Animals↗
PubMed1999

Clinical evaluation of commercially available urinary acidification diets in the management of idiopathic cystitis in cats.

OBJECTIVE: To compare recurrence of signs of lower urinary tract disease (LUTD) in cats with idiopathic cystitis that were fed the dry or canned formulation of a commercial diet designed to result in production of an acidic urine. DESIGN: Prospective trial. ANIMALS: 54 client-owned cats with idiopathic cystitis that was diagnosed on the basis of a history of abnormal micturition, abnormal results on urinalysis, radiography, or cystoscopy, and lack of an alternative diagnosis. PROCEDURE: Cats were assigned to be fed the canned or dry formulation of the diet. Reevaluations conducted at 2 and 16 weeks, and at 6 and 12 months included a physical examination, CBC and serum biochemical analysis (except week 2), blood gas analysis, and urinalysis. Regular telephone contacts were also made. The study was discontinued after 12 months or if signs of LUTD recurred. RESULTS: Signs of LUTD did not recur in 16 of 18 cats fed the canned diet, and 17 of 28 cats fed the dry diet (chi 2, P < 0.05). Seven cats were reevaluated at recurrence. Owners of remaining cats in which signs of LUTD recurred declined to have their pets reexamined. A different problem (bacterial urinary tract infection) was identified in only 1 cat on reevaluation. Eight cats were lost to follow-up evaluation. CLINICAL IMPLICATIONS: Feeding this commercial canned urinary acidifying diet may reduce the proportion of cats with idiopathic cystitis that will have recurrence of signs of LUTD within a 12-month period.

Animal Feed↗
PubMed1999

Calcium oxalate urolithiasis in cats.

Urolithiasis has long been recognized as a cause of irritative voiding in cats. Before the late 1980s, sterile struvite was the most common urolith; today, however, 40% of feline uroliths are of calcium oxalate. This change may be partly attributable to the change to urine-acidifying, magnesium-restricted diets that were introduced to reduce the formation of struvite. However, it is possible that the diet modifications made by cat food manufacturers simply exposed a population of cats predisposed to calcium oxalate stone formation. Urolithiasis in cats appears to be diet sensitive rather than diet induced. As in humans, water is crucial in the prevention and treatment of feline stones.

Animal Feed↗
PubMed1998

Amitriptyline treatment for severe recurrent idiopathic cystitis in cats.

OBJECTIVE: To evaluate the safety and efficacy of amitriptyline hydrochloride in the treatment of severe recurrent idiopathic cystitis (IC) in cats. DESIGN: Prospective study. ANIMALS: 15 cats with IC that failed to respond to other treatments. PROCEDURE: Each cat received 10 mg of amitriptyline, PO, every 24 hours in the evening for 12 months or until signs recurred. Urinalysis, CBC, serum biochemical analysis, urine bacteriologic culture, and cystoscopy were performed initially, and after 6 and 12 months in responders. Severity scores of owner-observed signs of lower urinary tract (bladder and urethra) disease were recorded. RESULTS: During the first 6 months of treatment, 11 of the 15 cats had no owner-observed signs of lower urinary tract disease. During the next 6 months, 9 of 15 cats remained free of signs of cystitis. Despite clinical improvement, cystoscopic abnormalities persisted in all cats at the 6- and 12-month evaluations. Hematuria and proteinuria were decreased at the 12-month evaluation compared with the initial evaluation. Two of 15 cats initially appeared somnolent after amitriptyline treatment. Of 9 cats completing the study, 7 had increased body weight and 8 had decreased coat quality compared with the initial evaluations. Four cats developed small cystic calculi during the first 6 months of the study. Serum biochemical or hematologic abnormalities were not detected during the study. CLINICAL IMPLICATIONS: Amitriptyline treatment successfully decreased clinical signs of severe recurrent IC in 9 of 15 cats treated. Somnolence, weight gain, decreased grooming, and transient cystic calculi were observed during treatment in some cats.

Adrenergic Uptake Inhibitors↗
PubMed1998

Agreement between two methods for measuring urine pH in cats and dogs.

OBJECTIVE: To compare urine pH of cats and dogs determined by use of a dipstrip and a pH meter. DESIGN: Prospective study. SAMPLE POPULATION: 109 urine samples from 88 cats that were clinically normal or had signs of irritative urination, 52 samples from 13 clinically normal dogs, and 3 samples from 3 dogs with urinary tract infections. PROCEDURE: Measurements of urine pH were obtained by use of a dipstrip and pH meter, and degree of agreement between measurements was evaluated. RESULTS: Mean difference (+/- 2 SD) between the 2 methods was 0.1 +/- 0.9 pH units. Only 65 of 164 (40%) samples measured by use of a dipstrip were within 0.25 pH units of results obtained by use of the pH meter. CLINICAL IMPLICATIONS: When an accurate measurement of urine pH is critical for clinical decision making, the measurement should be made by use of a pH meter. Dipstrips typically are not accurate enough to be clinically useful.

Animals↗
PubMed1998

Results of double-contrast cystography in cats with idiopathic cystitis: 45 cases (1993-1995).

OBJECTIVE: To determine results of double-contrast cystography in cats with idiopathic cystitis. DESIGN: Retrospective study. ANIMALS: 45 cats with clinical signs of nonobstructive lower urinary tract disease for which an underlying cause could not be determined. PROCEDURE: Medical records and double-contrast cystograms performed initially and during 6- and 12-month reevaluations were reviewed. RESULTS: 105 cystograms were reviewed. Fifteen (33%) cats had abnormalities evident on cystograms obtained at the time of initial examination. Of these, only 1 had abnormalities 6 and 12 months later. Thirty cats did not have abnormalities evident on cystograms obtained at the time of initial examination. Of these, 1 had abnormalities on a cystogram performed 6 months later and another had abnormalities on a cystogram performed 12 months later. Abnormalities evident on cystograms included focal thickening of the bladder wall (n = 11), diffuse thickening of the bladder wall (6), irregularities of the bladder mucosa (10), decreased opacity of the bladder wall (3), increased opacity of the bladder mucosa (3), filling defects (4), contrast medium in unexpected locations (3), and altered ureteral opacity (15). CLINICAL IMPLICATIONS: Results suggested that a large percentage of cats with idiopathic cystitis do not have cystographic abnormalities when initially examined but that abnormalities may be apparent during follow-up evaluations. In addition, a smaller percentage of cats with idiopathic cystitis may have nonspecific cystographic signs of cystitis or hemorrhage. Leakage of contrast medium into the peritoneal space during cystography does not necessarily require surgical management.

Animals↗
PubMed1998

Increased tyrosine hydroxylase immunoreactivity in the locus coeruleus of cats with interstitial cystitis.

PURPOSE: Environmental stressors seem to play a role in exacerbation of symptoms of interstitial cystitis (IC), both in cats and in human beings. These observations suggest a role for the sympathetic nervous system in the pathophysiology of IC. To begin to assess the underlying role in IC of the pontine nucleus locus coeruleus (LC), the most important source of norepinephrine in the central nervous system, we compared the intensity of tyrosine hydroxylase immunoreactivity (THIR) in sections of LC obtained from cats with IC and from healthy cats. Cats with IC were studied during quiescent periods in an attempt to avoid the risk of flare-induced activation of the LC. MATERIALS AND METHODS: Six cats diagnosed with IC and six healthy cats were studied. Cats with IC were monitored to ensure that no behavioral or urinary signs attributable to IC had been observed for at least two weeks prior to the study. Cats were euthanized and perfused with 4% paraformaldehyde, after which brainstem tissues were collected. Coronal sections (10 microns) of LC were prepared and examined for THIR. RESULTS: THIR in total LC, parabrachial nucleus and LC complex was significantly greater (p < 0.05) in samples from cats with IC than from healthy cats. CONCLUSIONS: The increased THIR in the LC of cats with IC provides additional evidence for increased sympathetic nervous system activity in patients with IC, even during periods of absence of clinical signs.

Animals↗