Impact of hyperlipidaemia on intermediary metabolism, faecal microbial metabolites and urinary characteristics of lipoprotein lipase deficient vs. normal cats.

Findings in humans and rats indicate that hyperlipidaemia may be associated with enhanced endogenous oxalate (Ox) synthesis, which may be relevant for calcium oxalate (CaOx) urolith formation. Moreover, changes in lipid metabolism are proposed to negatively affect gut microbiota. This study aimed to investigate those potential interactions in hyperlipidaemic cats. Therefore, 10 normal control cats and seven lipoprotein lipase (LPL)-deficient cats were fed a low-fat diet for seven weeks. During the last week of the study, cats were housed in metabolic cages to collect urine and faeces. Blood was taken on the last day of the study. The LPL-deficient cats had significantly higher serum triglyceride concentrations than normal cats, while lactate dehydrogenase (LDH) activity was not different. Urinary relative supersaturation with CaOx, urinary Ox, calcium, and citrate excretions, and urine pH did not differ between groups. Lower faecal acetic, propionic and total short-chain fatty acid concentrations were observed in the LPL-deficient cats. In conclusion, hyperlipidaemia does not appear to be a specific risk factor for CaOx urolith formation in cats. In contrast to results in rats, hyperlipidaemia was not accompanied by elevated serum LDH activity. As LDH can synthesise Ox from glycolate or other precursors, this might be one possible explanation for the similar urinary parameters in the LPL-deficient and normal cats. Non-diet-induced hyperlipidaemia was not associated with marked changes in faecal microbial metabolites, suggesting no differences in the composition of the intestinal microbiota.

Whole-Blood Taurine Concentrations in Cats With Intestinal Disease.

BACKGROUND: Increased delivery of taurine-conjugated bile acids to the distal bowel can lead to dysbiosis resulting in colitis in mouse models of inflammatory bowel disease. A similar situation also could occur in cats with intestinal disease and might therefore result in decreased whole-body taurine concentration. HYPOTHESIS/OBJECTIVES: To determine whether whole-blood taurine concentrations are decreased at the time of diagnosis in cats with intestinal disease and to correlate concentrations with clinical and laboratory variables. ANIMALS: Twenty-one cats with chronic inflammatory enteropathy and 7 cats with intestinal neoplasia from the University of Bristol. METHODS: Cats that had undergone a thorough investigation consisting of a CBC, serum biochemistry, serum cobalamin and folate concentrations, transabdominal ultrasound examination and histopathology of intestinal biopsy specimens, as well as additional testing if indicated, were included. Whole-blood from these cats collected at the time of histologic diagnosis and stored in ethylenediaminetetraacetic acid was retrospectively analyzed for taurine with an automated high-performance liquid chromatography amino acid analyzer. RESULTS: Although whole-blood taurine concentrations remained within the reference range, those cats with predominantly large intestinal clinical signs had significantly lower concentrations than did cats with small intestinal and mixed bowel clinical signs (P = 0.033) and this difference also was significant when assessed only in cats with chronic inflammatory enteropathy (P = 0.019). CONCLUSIONS AND CLINICAL IMPORTANCE: Additional studies are needed to determine whether large intestinal signs in cats with chronic inflammatory enteropathy are caused by alterations in the microbiota arising as a consequence of increased delivery of taurine-conjugated bile acids.

Determination of mammalian deoxyribonucleic acid (DNA) in commercial vegetarian and vegan diets for dogs and cats.

The determination of undeclared ingredients in pet food using different analytical methods has been reported in recent years, raising concerns regarding adequate quality control, dietary efficacy and the potential for purposeful adulteration. The objective of this study was to determine the presence or absence of mammalian DNA using multiplex polymerase chain reaction (PCR) on diets marketed as vegetarian or vegan for dogs and cats. The diets were tested in duplicate; two samples were purchased approximately 3 to 4 months apart with different lot numbers. Multiplex PCR-targeted mitochondrial DNA with two species-specific primers was used to amplify and sequence two sections of the cytochrome b gene for each of the 11 mammalian species. Half of the diets assessed (7/14) were positive for one or more undeclared mammalian DNA source (bovine, porcine, or ovine), and the result was repeatable for one or more species in six diets. While most of the detected DNA was found at both time points, in some cases, the result was positive only at one time point, suggesting the presence may have been due to unintentional cross-contact with animal-sourced ingredients. DNA from feline, cervine, canine, caprine, equine, murine (mouse and rat) and leporine was not identified in any samples. However, evidence of mammalian DNA does not confirm adulteration by the manufacturer nor elucidate its clinical significance when consumed by animals that may benefit from a vegetarian or vegan diet.

Nanoparticle Tracking Analysis for the Enumeration and Characterization of Mineralo-Organic Nanoparticles in Feline Urine.

Urinary stone disease, particularly calcium oxalate, is common in both humans and cats. Calcifying nanoparticles (CNP) are spherical nanocrystallite material, and are composed of proteins (fetuin, albumin) and inorganic minerals. CNP are suggested to play a role in a wide array of pathologic mineralization syndromes including urolithiasis. We documented the development of a clinically relevant protocol to assess urinary CNP in 9 healthy cats consuming the same diet in a controlled environment using Nanoparticle Tracking Analysis (NTA®). NTA® is a novel method that allows for characterization of the CNP in an efficient, accurate method that can differentiate these particles from other urinary submicron particulates. The predominant nanoscale particles in feline urine are characteristic of CNP in terms of their size, their ability to spontaneously form under suitable conditions, and the presence of an outer layer that is rich in calcium and capable of binding to hydroxyapatite binders such as alendronate and osteopontin. The expansion of this particle population can be suppressed by the addition of citrate to urine samples. Further, compounds targeting exosomal surfaces do not label these particulates. As CNP have been associated with a number of significant urologic maladies, the method described herein may prove to be a useful adjunct in evaluating lithogenesis risk in mammals.

Body composition and amino acid concentrations of select birds and mammals consumed by cats in northern and central California.

The diet of the feral domestic cat consists of primarily birds and small mammals, but the nutritional composition is relatively unknown. Because of the increasing popularity of natural diets for cats and other wild captive carnivores, the purpose of this study was to describe the body composition and AA concentrations of select birds and small mammals in northern and central California: wild-caught mice (n = 7), Norway rats (n = 2), roof rats (n = 2), voles (n = 4), moles (n = 2), gophers (n = 3), and birds (n = 4). Body water, crude fat (CFa), CP, ash, and AA composition for each specimen were determined. Results are reported as mean ± SD. All results are reported on a DM basis except body water (as-is basis) and AA (g/16 g N). Combined, carcasses had this mean composition: 67.35 ± 3.19% water, 11.72 ± 6.17% CFa, 62.19 ± 7.28% CP, and 14.83 ± 2.66% ash. Concentrations of Arg, Tau, Cys, and Met were 5.63 ± 0.46, 0.92 ± 0.33, 1.91 ± 0.89, and 1.82 ± 0.19 g/16 g N, respectively. Using NRC physiologic fuel values for CP, CFa, and carbohydrate by difference, the combined average energy content of the carcasses was 3,929 kcal/kg DM, but the fiber content was not determined. With the exception of mice and rats, little historical data exist regarding the body and AA composition of many of the species analyzed in this study. Wild-caught mice and rats were composed of less fat but more ash compared with previously reported data in their purpose-bred counterparts. The CP content of mice in this study was similar to previous reports in purpose-bred mice. The CP content of rats was similar or slightly greater compared with historical findings in purpose-bred rats. The N content of rats and AA concentrations on a per-N basis for both rats and mice were similar to previously published data on purpose-bred rodents. The discrepancies in nutrient composition, especially fat concentration, indicate that using purpose-bred animals to represent the diet of the feral domestic cat may not be valid in many instances. When consumed to meet energy needs, the nutrient content of the species reported in the present study exceed the NRC (2006) recommended allowances (RA) for total fat, CP, and essential AA for felines at all life stages.

Factors associated with adverse outcomes during parenteral nutrition administration in dogs and cats.

BACKGROUND: Parenteral nutrition (PN) is increasingly used to support hospitalized dogs and cats. Published assessments of outcome are limited. OBJECTIVE: Evaluate type and prevalence of complications and risk factors for death and complications in dogs and cats receiving PN. ANIMALS: Three hundred and nineteen dogs and 112 cats that received PN at a teaching hospital between 2000 and 2008. METHODS: Retrospective case review. Diagnosis, duration of PN administration, concurrent enteral feeding, death, and mechanical, septic, and metabolic complications were abstracted from medical records. Association of each parameter with complications and death was analyzed by binary logistic regression. RESULTS: Pancreatitis was the most common diagnosis (109/319 dogs, 34/112 cats), and 137/319 dogs and 51/112 cats died. Dogs and cats received 113 ± 40% and 103 ± 32% of resting energy requirement, respectively. Mechanical (81/319 dogs, 16/112 cats) and septic (20/319 dogs, 6/112 cats) complications were not associated with death (P > .05). Hyperglycemia was the most common metabolic complication (96/158 dogs, 31/37 cats). Hypercreatininemia in dogs (8/79) was the only complication associated with death (P < .01). Chronic kidney disease in dogs, hepatic lipidosis in cats, and longer duration of inadequate caloric intake before PN in both species were negatively associated with survival (P < .05). Factors positively associated with survival included longer duration of PN administration in both species, enteral feeding in cats with any disease, and enteral feeding in dogs with respiratory disease (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: PN can be effectively used to provide the energy requirements of most critically ill dogs and cats. Most complications accompanying PN administration do not affect survival.

Bioavailability of lysine for kittens in overheated casein is underestimated by the rat growth assay method.

Growth assays were performed to determine lysine bioavailability for kittens and rats in untreated and heated casein; these values were compared with estimates obtained with an in vitro method. Body weight, food intake, nitrogen and dry matter digestibility, and plasma lysine were determined during an 80-day growth trial using kittens (n = 16). Body weight and food intake were determined during a 21-day growth trial using weanling rats (n = 80). The growth data showed bioavailable lysine to be 102.4% and 100.2% (for untreated casein) and 66.1% and 51.7% (for heated casein) for kittens and rats, respectively. There was no relationship between plasma lysine and dietary lysine concentrations for kittens. There were no significant differences in nitrogen or dry matter digestibility among diets for kittens. The chemically reactive lysine content of untreated casein was 99.6%, and of heated casein was 67.1%. Heat treatment of casein resulted in significantly decreased lysine bioavailability as estimated by all methods. For untreated casein, both growth assays showed good agreement with the in vitro method for available lysine. For heated casein, the rat growth assay significantly underestimated bioavailable lysine as determined in kittens while the in vitro method closely approximated this value for the cat.

Exercise recommendations for osteoporosis. A position statement of the Australian and New Zealand Bone and Mineral Society.

BACKGROUND: Individuals diagnosed with osteoporosis have a high risk of skeletal injury. Regular physical activity may contribute to preventing osteoporosis, but the efficacy of exercise intervention once the disease is established has not been rigorously investigated. OBJECTIVE: To provide recommendations focusing specifically on exercise goals for osteoporosis, taking into account evidence for maximisation and maintenance of bone strength and minimisation of trauma, and to identify the levels of evidence that support this. DISCUSSION: The primary benefit of exercise for adult bones is conservation, not acquisition. In elderly individuals, improved fitness and muscle strength contribute to the prevention of falls and a lower risk of fracture. Physical activity may also reduce the rate of bone loss. Exercise goals for osteoporosis should include pain reduction, increased mobility and improvements in muscle endurance, balance and stability. These are worthwhile end points because not only may they prevent falls but they may improve the quality of life. In conjunction with advice to increase dietary calcium, exercise plays a significant part in a lifestyle prescription for reducing fractures in later life. In postmenopausal women, although less effective than oestrogen for maintaining bone mineral density, exercise should be regarded as part of an overall treatment strategy.

Proper use of antiarrhythmic therapy for reduction of mortality after myocardial infarction.

In this review, we summarise Vaughan Williams' classification of antiarrhythmic agents and the trials that have explored their efficacy in reducing mortality after myocardial infarction (MI). After analysing the data, it is clear that there is no role for class I antiarrhythmic agents as prophylaxis after MI since their use has been associated with increased mortality. Class II agents, i.e. beta-blockers, have demonstrated a reduction in mortality in combined and individual trials which extended for up to 6 years after the initial event. The class III drug, d,l-sotalol has been shown to have possible benefit, whereas its isomer without any beta-blocking properties, dexsotalol, has been shown to increase the incidence of arrhythmias. Amiodarone appears to reduce the incidence of deaths due to arrhythmia and sudden deaths without changing overall mortality. As a group, the calcium antagonists, class IV agents, have not been shown to reduce mortality and, in the case of nifedipine, may even increase it. Verapamil has been shown to be beneficial in one large study and may have a role in those patients in whom the use of beta-blockers is contraindicated. At this time, we recommend early implementation of beta-blockers for all patients without contraindications after MI. Further studies evaluating implantable defibrillators as primary and secondary prevention have provided significant risk reductions in certain high risk patient subsets. Future efforts will need to focus on more accurate risk stratification of post-MI patients and the role of both defibrillators and, possibly, amiodarone in improving survival.

Issues of importance reported by persons with lower limb amputations and prostheses.

The purpose of this paper is to report prosthesis-related issues of importance that were identified by a diverse group of persons living with lower limb amputations (LLA) and prostheses. These perceptions and themes validate some old assumptions and challenge others, report both common and unusual experiences, and indirectly identify the information level of our respondents concerning prostheses. Persons with LLA were identified from computerized rosters at a level one regional trauma center and at the VA Puget Sound Health Care System-Seattle, Division. Inclusion criteria specified that respondents were to: 1) be one or more years post-unilateral amputation at the Syme's level (ankle disarticulation) or higher, 2) use their prosthesis at least 5 days a week, 3) read English, and 4) be able to provide informed consent. Respondents completed the Prosthesis Evaluation Questionnaire-field version (PEQ) and the standard form (SF)-36, a health status measure. Of 114 persons who agreed to participate, 92 (85% male, mean age 55 years) responded to the questionnaire and graded the personal importance of various characteristics and qualities of their prosthesis. The number of years since their last amputation ranged from 1 to 53 years. Four Themes of Interest were identified from responses to open-ended questions about living with a prosthesis. These themes included the fit of the socket with the residual limb, aspects of the mechanical functioning of the prosthesis, other nonmechanical qualities, and advice about adaptation to life with a prosthesis with support from others. Future research is recommended to adjust aspects of the fit of the prosthesis with the residual limb. Implementing periodic check-up visits could uncover problems and eliminate unnecessary suffering.

Effects of hormone replacement therapy on QT interval.

We evaluated the electrocardiograms of 208 postmenopausal women (ages 40 to > or = 70 years) without heart disease, medications that could alter the QT interval, use of vaginal estrogens, unknown hormone replacement therapy, or electrocardiographic abnormalities both with (n = 76) and without (n = 132) hormone replacement therapy, and found no significant effects of hormone replacement therapy status on heart rate, QT interval, or the corrected QT interval. Thus, estrogen and/or progesterone effect does not explain the gender differences in myocardial repolarization.

Effects of gender on cardiac arrhythmias.

The purpose of this study is to review published data regarding gender differences in cardiac electrophysiology and in the occurrence of clinical arrhythmias. ECG differences between men and women include a faster resting heart rate in women, a longer corrected QT interval, and a lower QT dispersion than in men. The faster resting heart rate in women appears to be primarily related to differences in physical conditioning. The mechanism for the longer corrected QT interval in women is not completely known, but does not appear to be related to acute effects of estrogen or progesterone or differences in autonomic innervation. Women also appear to have a lower incidence of atrial fibrillation, a difference in the age distribution of supraventricular tachycardia, and a lower incidence of sudden death than men. Much of the lower incidence of sudden death in women may relate to a difference in the prevalence of coronary artery disease, but other factors such as inherent differences in repolarization, which may be reflected by a gender difference in the corrected QT interval, also may be operative. The paradox of a longer corrected QT interval and higher incidence of torsades de pointes, but lower population-based incidence of sudden death in women, has not been completely resolved. Further studies will be required to help better understand the basic mechanisms involved in gender differences in electrophysiology and arrhythmias and determine the extent to which these differences have implications for clinical management of cardiac arrhythmias.

In vivo imaging of a stable paramagnetic probe by pulsed-radiofrequency electron paramagnetic resonance spectroscopy.

Imaging of free radicals by electron paramagnetic resonance (EPR) spectroscopy using time domain acquisition as in nuclear magnetic resonance (NMR) has not been attempted because of the short spin-spin relaxation times, typically under 1 microsecond, of most biologically relevant paramagnetic species. Recent advances in radiofrequency (RF) electronics have enabled the generation of pulses of the order of 10-50 ns. Such short pulses provide adequate spectral coverage for EPR studies at 300 MHz resonant frequency. Acquisition of free induction decays (FID) of paramagnetic species possessing inhomogenously broadened narrow lines after pulsed excitation is feasible with an appropriate digitizer/averager. This report describes the use of time-domain RF EPR spectrometry and imaging for in vivo applications. FID responses were collected from a water-soluble, narrow line width spin probe within phantom samples in solution and also when infused intravenously in an anesthetized mouse. Using static magnetic field gradients and back-projection methods of image reconstruction, two-dimensional images of the spin-probe distribution were obtained in phantom samples as well as in a mouse. The resolution in the images was better than 0.7 mm and devoid of motional artifacts in the in vivo study. Results from this study suggest a potential use for pulsed RF EPR imaging (EPRI) for three-dimensional spatial and spectral-spatial imaging applications. In particular, pulsed EPRI may find use in vivo studies to minimize motional artifacts from cardiac and lung motion that cause significant problems in frequency-domain spectral acquisition, such as in continuous wave (cw) EPR techniques.

Endoscopic, portographic, and hemodynamic evaluation of prolonged propranolol administration in pigs with experimental portal hypertension and esophageal varices.

The effect of long-term propranolol administration on esophageal varices, portocollateral shunting, portal pressure, hepatosplanchnic hemodynamics, and liver function was studied in a pig model with experimentally induced prehepatic portal hypertension and esophageal varices. Five pigs were treated with 160 mg propranolol daily from week 5 to week 24 after portal-vein banding, and five pigs served as nontreated controls. Administration of propranolol caused an initial, significant reduction (20%) of portal venous pressure, followed by a gradual increase to levels not different from control pressures. In contrast, a marked reduction of the caliber of the coronary vein and size of the esophageal varices was noticed. Twenty weeks of propranolol treatment did not change liver blood flow or liver function. We conclude that the size of the varices rather than portal venous pressure depicts the effect of propranolol treatment and suggest that the beneficial effect of propranolol on variceal bleeding can be explained by a reduction in the wall tension of the varices, initiated and maintained by a diminution of splanchnic blood flow.

Effect of endoscopic sclerotherapy of esophageal varices on liver blood flow and liver function. An experimental study.

In 10 Göttingen mini-pigs esophageal varices developed after banding of the portal vein. In five pigs the varices were treated by paravariceal injection of polidocanol, and the rest served as controls. As judged from endoscopy and portography, the varices disappeared after four sclerotherapy sessions within 4 weeks, and at the same time portal venous pressure rose from 19 to 38 mm Hg. No changes were seen in the control group. After 24 weeks of observation the hepatic blood flow in the untreated group was 10 ml/kg/min, and portal angiography showed that nearly all the portal blood bypassed the liver. In the pigs treated with sclerotherapy the hepatic blood flow increased to 28 ml/kg/min, angiography showed a normal hepatogram, and no filling of the collaterals was seen. Sclerotherapy induced only a few changes in liver function, and these may be related to the concomitant increase in liver blood flow.

Endoscopic sclerotherapy or selective embolisation of esophageal varices. An endoscopic and portographic study in an experimental model.

In an experimental animal model with portal hypertension and esophageal varices, endoscopic sclerotherapy of the varices with Aethoxysclerol was compared with selective embolisation of the coronary vein with absolute ethanol. After 4 courses of endoscopic sclerotherapy the varices were permanently obliterated, as documented by portography and endoscopy. Selective embolisation also caused obliteration of the coronary vein and varices, but early and repeated recanalisation occurred, and permanent obliteration was only obtained when embolisation was combined with endoscopic sclerotherapy. Portal vein thrombosis occurred when embolisation was repeated more than 3 times. Hepatic blood flow was significantly higher in animals treated by endoscopic sclerotherapy than in nontreated controls and animals treated by selective embolisation alone.

Chronic portal venous hypertension. The effect on liver blood flow and liver function and the development of esophageal varices.

Portal venous hypertension was induced in Göttingen minipigs by banding the portal vein. The pigs were checked repeatedly during the following 24 weeks. Portal pressure increased immediately on banding, from 8.4 +/- 0.7 mm Hg to 19.4 +/- 0.7 mm Hg, and remained constant throughout the observation period. Within 5 weeks all pigs developed esophageal varices, as demonstrated by portal angiography and endoscopy. The experimentally induced portal hypertension was accompanied by a 65% decrease in hepatic blood flow, most probably caused by almost complete shunting of portal venous blood. The hepatic arterial flow appeared to be within normal limits and sufficient to cover the oxygen demand of the liver; to judge from the splanchnic elimination rate of galactose, the hemodynamic changes did not affect the functional capacity of the liver.

Effect of acute portal hypertension on hepatosplanchnic hemodynamics and liver function.

Acute prehepatic portal hypertension was mechanically induced in Göttingen minipigs. A 125% increase in portal pressure resulted in a significant decrease in estimated hepatic blood flow. The decrease in blood flow was accompanied by a 25% reduction in the 'true' clearance of indocyanine green and an 18% decrease in splanchnic oxygen consumption. Judged from the splanchnic elimination rate of galactose, the functional liver cell mass was not altered by portal banding, and an unaltered lactate to pyruvate ratio in hepatic venous blood indicated that no functional parts of the liver became severely hypoxic.

Importance of perfusate hematocrit for insulin- and glucagon-induced choleresis in the perfused rat liver.

Insulin and glucagon stimulate bile production in the intact rat without affecting the biliary excretion rate of bile acids. This effect was not demonstrable in rat liver perfused with human erythrocytes suspended in a Krebs-Henseleit-bicarbonate buffer at a hematocrit of about 18%. The present experiments demonstrate that the choleretic effect of insulin and glucagon observed in the intact rat is reproducible in perfused rat liver if the hematocrit of the perfusate is raised to about 35%. An increase in perfusate hematocrit is also accompanied by a 65% rise in hepatic oxygen consumption and a 27% rise in the basic production of bile, due to an increase in bile acid-independent bile formation. The mechanism by which these changes in perfusate hematocrit influence the function of the perfused liver is obscure. The difference in oxygen content of the perfusates appears to be without importance. Judged from lactate-pyruvate and beta-hydroxybutyrate-acetoacetate ratios of perfusate as well as electron microscopy, maldistribution of perfusate flow and local hypoxia were not evident in perfusions with low hematocrit. A part of the increase in hepatic oxygen consumption seen with a rise in perfusate hematocrit can, however, be explained by an increase in lactate supply from erythrocyte glycolysis. The results stress the importance of perfusate hematocrit for optimal bile production of the perfused rat liver.