Influence of various carbohydrate sources on postprandial glucose, insulin and NEFA concentrations in obese cats.

Carbohydrate is an important source of energy, which can significantly affect postprandial blood glucose and insulin levels in cats. In healthy animals, this is not a big concern; however, in obese and diabetic animals, this is an important detail. In the present study, the impact of four different carbohydrate sources (glucose, maltose, corn starch, and trehalose) on short-term post-prandial serum glucose, insulin, and non-esterified fatty acid (NEFA) concentrations was investigated with four obese cats. Each of the carbohydrate sources was added to a commercial wet food diet for feeding the animals. A significant difference was observed in postprandial glucose, insulin, and NEFA area under the curve (AUC) values between each carbohydrate source in obese cats. Furthermore, glucose and maltose induced the highest postprandial glucose and insulin AUC values, whereas trehalose induced the lowest postprandial glucose and insulin AUC value amongst all carbohydrate sources, respectively, in obese cats. However, trehalose has a higher risk of inducing side effects, such as diarrhea, as compared to other carbohydrate sources. As such, different carbohydrate sources appear to have a very significant impact on post-prandial glycemia and subsequent insulin requirement levels in obese cats. These results might be useful when selecting a prescription diet for obese or diabetic cats. In addition, maltose appears to be capable of inducing experimentally evoked postprandial hyperglycemia in obese cats, which may serve as a good tool for use to check the impact and effectiveness of newly developed oral hypoglycemic drugs or supplements for cats in future experiments.

Assessment of feline hospitalization environment using a one-way mirror.

A separate, cat-specific hospitalization room away from dogs is recommended to reduce stress in cats; however, this can be difficult for some hospitals to provide. In such cases, measures are undertaken to reduce the cat's stress by providing a place to hide. However, inability to observe the cat's condition may be an obstacle to providing veterinary care. The use of a one-way mirror to create a sheltered environment while allowing observation of the cats was assessed. Five healthy cats were assessed using the Cat Stress Score (CSS) while in a cage with either a transparent panel or a one-way mirror. No significant differences in the CSS between the transparent panel and one-way mirror were observed. Variations in the CSS scores depended on the cat's personality, with friendlier and more sociable cats showing a lower CSS with the one-way mirror. A one-way mirror may be useful to reduce stress in hospitalized cats.

Remarkable Improvement of Cardiac Function After Pre-emptive Kidney Transplant in a Patient With Severe Mitral Regurgitation Accompanied by Low Cardiac Function: A Case Report.

Patients with end-stage renal disease are at a high risk for cardiovascular diseases. It is controversial whether end-stage renal disease patients with low cardiac function can safely accept kidney transplant. Here, we present a 42-year-old kidney transplant recipient with severe mitral regurgitation accompanied by low cardiac function. He wanted to undergo a pre-emptive kidney transplant from his uncle. We decided to perform living kidney transplant prior to cardiac surgery. Despite adequate ultrafiltration and hemodiafiltration before operation, the patient's ejection fraction still remained 35% 1 day before transplant. He showed complete recovery of cardiac function in only 2 days after pre-emptive kidney transplant, although his body weight did not change before and after the operation. Early removal of the uremic toxin or inflammatory cytokines may play a role in rapid improvement of the cardiac function. Increase of vasoactive substances by improvement of kidney function may lead to reduction of afterload and amelioration of cardiac microcirculation. This report also suggests that optimal timing for operation might be important.

Beta3-adrenoceptor agonist AJ-9677 reduces body fat in obese beagles.

A selective beta3-adrenoceptor agonist, AJ-9677, was reported to ameliorate obesity and insulin resistance in KK-Ay mice. We examined the acute and chronic effects of AJ-9677 on obese dogs. Oral administration of AJ-9677 (0.01 or 0.1 mg/kg) to overnight fasted obese beagles produced a dose-dependent rise in the plasma levels of non-esterified fatty acids and insulin in 1h, followed by a gradual drop of the plasma glucose level. It produced no apparent abnormal behaviors, but easily detectable cutaneous flushing. Daily treatment of AJ-9677 at a lower dose (0.01 mg/kg) for three weeks produced no notable change in body weight, but at a higher dose (0.1 mg/kg) it reduced the body weight compared to a placebo treatment after seven weeks. Computed tomographic examinations revealed a remarkable reduction of body fat after the AJ treatment, being consistent with the histological observations that the adipose tissue of AJ-9677-treated dogs consisted of smaller and some multilocular adipocytes. The plasma levels of leptin and adiponectin were decreased and increased, respectively, after the AJ treatment, reflecting the reduction of adiposity. It was concluded that AJ-9677 is useful for the treatment of obesity in the dog.

Plasma leptin concentration in dogs: effects of body condition score, age, gender and breeds.

Leptin is a cytokine produced by adipocytes, and plays a key role in the regulation of energy balance. In the present study, we measured plasma leptin concentrations of 166 normal and obese dogs visiting veterinary practices, and clarified the influence of age, gender and breed on plasma leptin levels in dogs. Leptin levels were higher in the dogs with higher body condition scores. There was no noticeable influence of age, gender and breed, but those in optimal puppies and obese Miniature Dachshund tended to be lower than those in corresponding groups. We conclude that plasma leptin is a reliable marker of adiposity in dogs regardless of age, gender and breed variations, and thereby useful as a blood biochemistry test for health examinations and treatment of obesity.

The canine prostate cancer cell line CHP-1 shows over-expression of the co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α.

Although androgen therapy resistance and poor clinical outcomes are seen in most canine prostate cancer cases, there are only a few tools for analysing canine prostate cancer by using a cell biological approach. Therefore, to evaluate androgen-independent neoplastic cell growth, a new canine prostate cancer cell line (CHP-1) was established in this study. CHP-1 over-expressed the co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA), which is over-expressed in human androgen-independent prostate cancer. The CHP-1 xenograft also showed SGTA over-expression. Although CHP-1 shows poor androgen receptor (AR) signalling upon dihydrotestosterone stimulation, forced expression of AR enabled evaluation of AR signalling. Taken together, these results suggest that CHP-1 will be a useful model for investigating the pathogenesis of androgen-dependent and androgen-independent canine prostate cancer.

Canine adiponectin: cDNA structure, mRNA expression in adipose tissues and reduced plasma levels in obesity.

Adiponectin is a protein synthesized and secreted by adipocytes. Decreased adiponectin is responsible for insulin resistance and atherosclerosis associated with human obesity. We obtained a cDNA clone corresponding to canine adiponectin, whose nucleotide and deduced amino acid sequences were highly identical to those of other species. Adiponectin mRNA was detected in adipose tissues, but not in other tissues, of dogs. When 22 adult beagles were given a high-energy diet for 14 weeks, they became obese, showing heavier body weights, higher plasma leptin concentrations, but lower plasma adiponectin concentrations. The adiponectin concentrations of plasma samples collected from 71 dogs visiting veterinary practices were negatively correlated to plasma leptin concentrations, being lower in obese than non-obese dogs. These results are compatible with those reported in other species, and suggest that adiponectin is an index of adiposity and a target molecule for studies on diseases associated with obesity in dogs.

Diurnal variations of serum leptin in dogs: effects of fasting and re-feeding.

Leptin is a protein synthesized and secreted primarily by adipocytes, and plays a key role in the regulation of energy balance. We have reported that serum leptin is elevated in obese dogs. In the present study, we examined diurnal variations of serum leptin in the dog, with special references to feeding and fasting cycles. Four male beagles were accustomed to feed once a day at 10:00 h, and blood samples were taken every 3 h for 24-36 h. Serum leptin concentration showed clear diurnal variations, being lowest before food intake (2.3+/-0.5 ng/mL) at 09:00 h, and highest (10.5+/-2.4 ng/mL) at 18:00 h. Such diurnal variations disappeared when the dogs were fasted. Serum insulin also showed diurnal variation with higher levels at 12:00-15:00 h. When insulin or glucose was injected in the fasted dogs to mimic the post-prandial insulin rise, serum leptin concentration was significantly increased in 4-8 h, but in both cases to a lesser extents than those after food intake. The results indicate that serum leptin concentrations change diurnally in association with feeding-fasting cycles in the dog, partially due to changes in insulin secretion.

Energetics of the negative and positive inotropism of pentobarbitone sodium in the canine left ventricle.

OBJECTIVE: Pentobarbitone (sodium) is an anaesthetic widely used in animal experiments. It is known to be a cardiovascular depressant and a coronary dilator, but its effects on myocardial energetics in relation to its negative and positive (due to Gregg's phenomenon) inotropism have not been studied. The aim of this study was therefore to determine whether and how pentobarbitone affects cardiac mechanoenergetics compared with other negative inotropic agents for which data are already available. METHODS: The effects of graded doses of intracoronary pentobarbitone on mechanoenergetics were studied in the excised cross circulated left ventricles of 12 dogs. The framework of the Emax (a contractility index)--VO2 (myocardial oxygen consumption)--PVA (systolic pressure-volume area, a measure of total mechanical energy) relationships was fully utilised. RESULTS: Pentobarbitone increased Emax at low doses in five of the 12 hearts. In two of these five hearts, a marked coronary dilatation was found. Pentobarbitone decreased Emax dose dependently at high doses in all the hearts and lowered the VO2 intercept but not the slope (oxygen cost of PVA) of the VO2-PVA relation. There was no difference in oxygen cost of Emax between pentobarbitone and CaCl2, although they have opposite inotropism. These findings suggest that pentobarbitone depresses myocardial mechanoenergetics via suppression of total calcium handling in the excitation-contraction-relaxation coupling. CONCLUSIONS: Pentobarbitone at low doses partly acts as a positive inotropic agent, but at high doses it acts as a negative inotropic agent like beta blockers and calcium antagonists on cardiac mechanoenergetics in canine blood perfused hearts.

Molecular analysis of the Pseudomonas aeruginosa genes, ruvA, ruvB and ruvC, involved in processing of homologous recombination intermediates.

In Escherichia coli, the products of the ruvA, ruvB and ruvC genes are all involved in the processing of recombination intermediates (Holliday structures) into recombinant molecules. We cloned a 9.4-kb DNA fragment from Pscudomonas aeruginosa PAO1 in a plasmid by functional complementation of the UV sensitivity of an E. coli strain with ruvABC deleted. In P. aeruginosa, the ruv region seemed to form a non-SOS regulated single operon consisting of orf26-ruvC-ruvA-ruvB, while in this region of E. coli, ruvA and ruvB form an SOS-regulated operon, orf26 and ruvC form a non-SOS operon, and these two operons are split by orf23. The deduced amino acid sequences of P. aeruginosa RuvA, RuvB and RuvC proteins were 55, 72 and 55% identical to those of the corresponding E. coli Ruv proteins. The individual ruv genes of P. aeruginosa complemented the corresponding single ruv mutations of E. coli, suggesting that the P. aeruginosa Ruv proteins can interact functionally with their E. coli Ruv partners in forming heterologous complexes. The sequence alignments of the Ruv proteins were extended by incorporation of data about the putative ruv genes obtained from data banks, and the RuvB sequences were conspicuously more conserved than the RuvA and RuvC sequences.

Roles of the recG gene product of Escherichia coli in recombination repair: effects of the delta recG mutation on cell division and chromosome partition.

The products of the recG and ruvAB genes of Escherichia coli are both thought to promote branch migration of Holliday recombination intermediates by their junction specific helicase activities in homologous recombination and recombination repair. To investigate the in vivo role of the recG gene, we examined the effects of a recG null mutation on cell division and chromosome partition. After UV irradiation at a low dose (5J/m2), delta recG mutant filamentous cells with unpartitioned chromosomes. A mutation in the sfiA gene, which encodes and SOS-inducible inhibitor of septum formation, partially suppressed filamentation of recG mutant cells, but did not prevent the formation of anucleate cells. The sensitivity of UV light and the cytological phenotypes after UV irradiation of a recA recG double mutant were similar to a recA single mutant, consistent with the role of recG, which is assigned to a later stage in recombinant repair than recA. The recG ruvAB and recG ruvC double mutants were more sensitive to UV, almost as sensitive as the recA mutant and showed more extreme phenotypes concerning filamentation and chromosome nondisjunction, both after UV irradiation and without UV irradiation than either recG or ruv single mutants. The recG polA12 (Ts) mutant, which is temperature sensitive in growth, formed filamentous cells with centrally located chromosome aggregates when grown at nonpermissive temperature similar to the UV irradiated recG mutant. These results support the notion that recG is involved in processing Holliday intermediates in recombination repair in vivo. We suggest that the defect in the processing in the recG mutant results in accumulation of nonpartitioned chromosomes, which are linked by Holliday junctions.

Urinary cyclic AMP and cyclic GMP in rats given three different concentrations of cadmium in the diet for one year.

Male and female weanling rats of the SPF Fisher strain were fed purified diets containing three different levels of cadmium (0.008, 0.3, 30 micrograms Cd/g feed). Urine was collected from each animal 1 year after the start of the experiment, and cyclic AMP and cyclic AMP in the urine were measured by radioimmunoassay. Urinary excretion of cyclic AMP and GMP changed in proportion to the intake of Cd. The ratio of cyclic AMP: cyclic GMP, which combined the changes of these two cyclic nucleotides, increased with Cd intake, and these relationships were statistically significantly different in males and females.

Studies on mutations in male germ cells of transgenic mice following exposure to isopropyl methanesulfonate, ethylnitrosourea or X-ray.

Transgenic mice have recently been used for mutagenesis assays in vivo. The present study was undertaken to clarify whether such assays can detect mutations induced after treatment of male germ cells in mouse with isopropyl methanesulfonate (iPMS), ethylnitrosourea (ENU) or X-ray irradiation. The transgenic mice used for assay are Muta Mouse (MM) strain, which carries 80 copies of the bacterial lacZ gene per cell as targets for mutagenesis. Male MM animals were given a single intraperitoneal injection of 200 mg/kg iPMS, 150 mg/kg ENU or were irradiated with 500 rads of X-rays. Vasa deferential sperm, caudal epididymal sperm and/or whole testes were extracted at various times after treatment with each agent. After the genomic DNA was extracted from each tissue, mutation analysis at the lacZ locus was carried out by the method of Myhr et al. The spontaneous lacZ- mutant frequencies were on the order of 10(-5)-10(-6). The lacZ- mutant frequencies in all treatment groups were increased over the control animals. The iPMS-induced mutant frequency in postmeiotic stages was low. However, ENU induced relatively high mutant frequencies in the spermatogonia. X-rays induced mutant frequencies in the late spermatid and early spermatid stages that were higher than the mutant frequencies in spermatogonia. Mutant frequencies in MM detected after treatment of male germ cells with ENU or X-rays were lower than mutant frequencies detected by the mouse specific-locus test in previous reports. Hence, considering the lower resolution power of the transgenic animal mutagenesis assays using the target lacZ gene compared with the specific locus test, to detect mutations induced in male germ cells, it is not clear whether this assay is a practical alternative to the specific locus test.

Investigation on parametric analysis of dynamic EMG signals by a muscle-structured simulation model.

In the analysis of electromyographic (EMG) signals during dynamic movement, we have proposed an estimation algorithm for the time-varying parameters of an autoregressive model. The parameters correspond to less biased time-varying reflection coefficients. We determined the less biased estimation using a locally quasi-stationary model and named these parameters "k parameters." We estimated k parameters up to the fifth order for the surface EMG signals of a masseter muscle during rapid open-close movement of the lower jaw, a ballistic contraction, and fatigue. According to the results, the time courses of the k parameters displayed remarkable properties. In order to study the behavior of k parameters physiologically, we produced a muscle-structured simulation model based on anatomical and physiological data. The simulation results suggested that the behavior of the third parameter is related to the number of active motor units (MU's) at the shallow layer of a muscle. The detailed recruitment mechanism in terms of the MU's types has not yet been solved. Although further study is required, the parametric analysis using k parameters offers a new perspective for evaluation of muscle dynamics during several movements.

A muscle fatigue index based on the relationship between preceding background activity and myotatic reflex response (MRR).

A new index of muscular fatigue was developed using the myotatic reflex response (MRR). The MRR of masseter muscles is evoked by periodical mechanical chin tapping during clenching. The MRR waveform is composed of somewhat synchronized action potentials of muscle fibers. We estimate the change of the MRR waveform due to fatigue using the instantaneous frequency pattern (IFP) with the Hilbert transform. As a result, the features of IFP were different from the monotonic changes that have been observed by the conventional fatigue indices. That is, a plateau IFP was observed ahead of considerable fatigue, whereas the IFP showed a monopeak pattern during other phase of an exercise. Also, the relationship between the preceding background mean power frequency and the instantaneous frequency around the first part of the MRR waveform was nonlinear during the whole process of fatigue. These features may allow us to estimate the degree of fatigue at each time instant. Although the details have not yet been solved, by using the computer simulations one of them seemed to be the alteration of the dominant frequency components. The dominant frequency components may be related to the active muscle fiber types.

The effects of hyperthermia on the spinal cord.

This study was conducted to obtain information about the critical temperature of the spinal cord in hyperthermia produced by radiofrequency waves applied to the spine. The first component of the spinal cord evoked potential was analyzed as an indicator of spinal cord function. The spinal cords were heated by radiofrequency waves to a maximum of 47 degrees C momentarily or for 30 minutes. The temperatures were measured with a thermosensor in the epidural space. In momentary heating, the reductions in amplitude were almost parallel with the increases in temperature. In maintained heating for 30 minutes, at 44 degrees C and below, the amplitudes decreased by one-quarter to three-quarters of the control value in the first 5 minutes and recovered to over three-quarters of the control value in 30 minutes. The amplitudes returned to almost the control value after restoration of normal spinal cord temperatures. At 45 degrees C and above, however, the amplitudes were prominently reduced or disappeared in the first 5 minutes and remained depressed during the remainder of the heating. On normalizing the temperature, the amplitudes did not return to the control value. These results suggest that 44 degrees C in the epidural space is the highest tolerable temperature for normal spinal cord function.

Myogenic expression in esophageal polypoid tumors.

Four cases of esophageal polypoid tumors composed of squamous cell carcinoma and spindle cell sarcomatous components were investigated. Squamous cell carcinoma was consistently present in the base of the polypoid lesions in all four cases and was also intermingled with spindle-shaped sarcomatous cells in two cases. Metastases in the lymph nodes were observed in two cases: one was squamous cell carcinoma with a sarcomatous component and the other consisted of a pure sarcomatous component. All tumors involved at least the muscularis mucosae. In the sarcomatous region, the tumor was composed of highly anaplastic cells with or without forming interlacing fascicles. Pleomorphism was marked and bizarre giant cell forms were frequent. Mitoses were frequently present. Immunohistochemical study revealed that the anaplastic cells in the sarcomatous component in all cases were immunoreactive to desmin, muscle actin, vimentin, and alpha 1-antichymotrypsin, but were negative for cytokeratin, even in the metastatic tumors of the lymph nodes. The immunohistochemical results favor myogenic differentiation of the anaplastic cells, and these tumors were considered to be true carcinosarcomas composed of squamous cell carcinoma and leiomyosarcoma.

Left ventricular ORS widening decreases Emax without lowering VO2-PVA relation in dog hearts.

We observed a few rare spontaneous cases of a suddenly widened QRS wave of left ventricular ECG associated with a simultaneous decrease in left ventricular (LV) contractility (Emax, end-systolic pressure-volume ratio) in excised cross-circulated dog heart experiments. The decreased Emax was not associated with a descent of the relation between cardiac oxygen consumption (VO2) and LV systolic pressure-volume area (PVA, a measure of total ventricular mechanical energy). This result is intriguing because ventricular VO2-PVA relation generally changes its elevation in proportion to Emax under various inotropic interventions. We suspected the unusual observation to reflect no change in myocardial contractility despite ventricular asynchrony augmented by an intraventricular conduction defect.

Nipradilol depresses cardiac contractility and O2 consumption without decreasing coronary resistance in dogs.

Nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino) propoxy-3-nitroxy-2H-1-benzopyran) is a newly synthesized chemical agent designed to possess beta-adrenoceptor blocking and vasodilating actions. Nipradilol decreased left ventricular contractility index (Emax, slope of the ventricular end-systolic pressure-volume relation), systolic pressure-volume area (PVA, a measure of ventricular total mechanical energy) and oxygen consumption in cross-circulated excised dog hearts. However, nipradilol did not decrease total coronary resistance. These results indicate that nipradilol, like propranolol, depresses myocardial mechanoenergetics and that the vasodilating action of nipradilol could not be detected in the present study.