Biomedical subjects

Akira Yabuki

Publications and source records attributed to Akira Yabuki.

At least 19 recordsLinked to original sources

PubMed2006

Immunohistochemical localization of ghrelin in rodent kidneys.

Ghrelin is a novel peptide hormone, originally identified in the rat and human stomach that plays various important roles. In the present study, we report the intra-renal localization of ghrelin in laboratory rodents. Kidneys from 3 month-old mice, rats and hamsters of both sexes were analyzed by immunohistochemistry. Positive signals were clearly observed in the epithelium of the distal tubules, whereas other segments of the nephron or interstitial cells, including juxtaglomerular cells, showed negative reactions. Pre-embedding immunoelectron microscopy revealed positive signals exclusively on the basolateral membrane in the distal tubular cells and in the collecting ducts. In addition, prepro-ghrelin gene expression was assessed by RT-PCR, and the expected 329-bp prepro-ghrelin mRNA was clearly detected in the kidney. On Western blot analysis, although a specific band for ghrelin (3 kDa) was not detected in the kidney, the expected band for prepro-ghrelin (13 kDa) was clearly detected in both the stomach and the kidney. This paper clarified the intra-renal localization of ghrelin.

Animals↗

PubMed2006

Inhibitory effects of edaravone on the production of tumor necrosis factor-alpha in the isolated heart undergoing ischemia and reperfusion.

We evaluated the effects of edaravone, a hydroxyl radical scavenging agent, on the production of tumor necrosis factor-alpha (TNF-alpha) in myocardium, and the release of TNF-alpha and P-selectin from myocardium after ischemia-reperfusion injury in isolated Langendorff-perfused rat hearts. Cardiodynamic function at stable points during perfusion and 5, 15, 30, and 60 min after the initiation of reperfusion was evaluated by left ventricular developed pressure, rate of increase in left ventricular pressure and rate of decrease in ventricular pressure, coronary flow, and heart rate. At 60 min after the initiation of reperfusion, myocardial infarct size was estimated microscopically using triphenyltetrazolium chloride staining, and expression of TNF-alpha in myocardium was detected by Western blot and immunohistochemistry. At the same time points as the measurement of cardiodynamic function, TNF-alpha and the soluble form of P-selectin in coronary effluent were measured by enzyme immunoassay. At all time points during reperfusion, edaravone markedly improved cardiodynamic function and reduced myocardial infarct size in comparison to the control. In myocardium in the control, TNF-alpha was detected in the endothelial cells and other cells bearing some resemblance to interstitial cells and monocyte cells. Edaravone suppressed this cytokine expression in the corresponding sites. P-selectin as well as TNF-alpha was found in the coronary effluent of the control, and edaravone significantly decreased soluble P-selectin levels in comparison to the control (P < 0.01). Edaravone might have protective effects on cardiac function through reduction of infarct size via decrease of production of TNF-alpha in myocardium induced by ischemia-reperfusion injury and through reduction of the release of adhesion molecules such as P-selectin from vascular endothelial cells.

Analysis of Variance↗

PubMed2006

Effect of decrease in both postprandial blood glucose (PBG) and fasting blood glucose (FBG) levels in normal beagle dogs with nateglinide enteric coated granules and immediate release tablets.

Nateglinide is a new quick action/short duration (QRSD) type of oral blood glucose regulator, and nateglinide immediate release tablets are used for patients with mild diabetes under the trade name of Fastic((R)) tablets. In this study, we attempted to determine if it was possible to control both post-prandial blood glucose level (PBG) and fasting blood glucose level (FBG) for moderate or severe diabetes through controlled release of nateglinide. Enteric coated granules were selected for the administration form for controlled release of nateglinide, and three types of enteric coated granules were prepared having dissolution pH values of 5.5, 6.5 and 7.2. The three types of enteric coated granules were each administered separately or the enteric coated granules having an dissolution pH of 6.5 were administered simultaneous to administration of nateglinide immediate release tablets to normal beagle dogs just before feeding followed by measurement of plasma nateglinide concentration, plasma insulin concentration and blood glucose level. In the case of administering enteric coated granules alone (nateglinide: 9 mg/kg), the absorption of nateglinide was confirmed to tend to be delayed as the dissolution pH increased. In the case of an dissolution pH of 5.5, decreases in both PBG and FBG were observed. In the case of dissolution pH values of 6.5 and 7.2, only decrease in FBG was observed. In case of nateglinide immediate release tablets (nateglinide: 9 mg/kg), only decrease in PBG was observed. Decreases in both PBG and FBG were observed in the case of simultaneous administration of dissolution pH 6.5 enteric coated granules and nateglinide immediate release tablets just before feeding (nateglinide: 90 mg/head+60 mg/head). A correlation was observed between plasma nateglinide concentrations and blood glucose levels. On the other hand, there were no correlations observed between changes in plasma insulin concentrations and blood glucose levels. In case of nateglinide immediate release tablets (nateglinide: 150 mg/head), Decreases in both PBG and FBG were observed. However, the nateglinide controlled release formulation is more useful than the nateglinide immediate release tablets from the view point of avoidance of side effect, or of easy control of both PBG and FBG. On the basis of these results, the design of a controlled release formulation that contains nateglinide was suggested to enable control of both PBG and FBG for moderate and severe diabetes patients.

Administration, Oral↗

PubMed2006

Strain differences in morphometrical characteristics of rat kidneys.

To clarify the strain differences in the morphology of the rat kidneys, we investigated the morphometrical characteristics of the kidneys of Slc:Wistar, Slc:SD, and F344/NSlc rats. The diameter of the renal corpuscles in female F344/N rats is smaller than that in female Wistar rats. Although sex differences (males>females) were shown in SD and F344/N rats, no effects of castration were detected in any of the groups. Strain-dependent differences in the percentage of renal corpuscles with a cuboidal parietal layer were found in both male and female groups. The highest percentage of them was noted in male Wistar rats. Effects of castration were observed in female Wistar and male F344/N rats, and the values after castration were significantly higher than those in the intact animals. As for the number of proximal convoluted tubular nuclei, no strain differences were detected in either the male or female groups. Although a sex difference was found in SD rats (female>male), no effects of castration were detected in any of the groups. In female F344/N rats, numerous numbers of PAS-positive granules, which were observed in the proximal convoluted and straight tubular epithelia, were noted. Orchiectomy induced an increase of these granules in male SD and F344/N rats, but ovariectomy showed no effects on them in any strains. This is the first study to clarify the strain differences in the morphological characteristics of the kidneys in ordinary rat strains.

Animals↗

PubMed2006

Rodent renal structure differs among species.

In the present study, we histologically and morphometrically investigated species differences in renal structure using laboratory rodents (mice, gerbils, hamsters, rats, and guinea pigs). Morphometric parameters were as follows, 1) diameter of the cortical renal corpuscles, 2) diameter of the juxtamedullary renal corpuscles, 3) percentage of the renal corpuscles with a cuboidal parietal layer, 4) number of nuclei in proximal convoluted tubules (PCTs) per unit area of cortex, 5) semi-quantitative score of the periodic acid-Schiff (PAS) -positive granules in PCTs, and 6) semi-quantitative score of the PAS-positive granules in proximal straight tubules (PSTs). Significant species differences were detected for each parameter, and particularly severe differences were observed in the PAS-positive granules of PCTs and PSTs. Granular scores varied among species and sexes. Vacuolar structures that did not stain with PAS or hematoxylin-eosin were observed in the renal proximal tubules. The appearance and localization of these vacuolar structures differed remarkably between species and sexes.

Animals↗

PubMed2006

Neuronal nitric oxide synthase and cyclooxygenase-2 in diabetic nephropathy of type 2 diabetic OLETF rats.

Neuronal nitric oxide synthase (nNOS) and cyclooxygenase-2 (COX-2) regulate the tubuloglomerular feedback (TGF) and renin-angiotensin system (RAS) in the kidney. In type 1 diabetic rats, renal overproduction of these enzymes and their relationship to the pathogenesis of diabetic nephropathy has been demonstrated. In the present study, we histologically and immunohistochemically investigated the kidneys of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as a model of type 2 diabetes, at 62 weeks of age (chronic phase of diabetes). The kidneys of OLETF rats showed typical diabetic nephropathy. Quantitative scores for glomerulosclerosis and interstitial fibrosis in OLETF rats were significantly higher than those of age-matched control Long-Evans Tokushima Otsuka (LETO) rats. nNOS- and COX-2-positive immunoreactions were observed in the distal tubules and collecting ducts. These reactions appeared to be more widely distributed in OLETF, and the number of nNOS-and COX-2-positive sites in the OLETF were significantly more than those in LETO rats. Expression of renin, angiotensin II, and inducible nitric oxide synthase (iNOS) were also examined immunohistochemically, and no differences between OLETF and LETO rats were observed in the distributions and the number of immunoreactive-sites. In conclusion, the overproduction of nNOS and COX-2 in the kidney of OLETF rats was confirmed, suggesting that the overproduction of nNOS and/or COX-2 does not affect the intrarenal RAS or iNOS production but does affect TGF.

Angiotensin II↗

PubMed2006

Morphometric study of gender differences with regard to age-related changes in the C57BL/6 mouse kidney.

To investigate gender differences with regard to age-related changes in the mouse kidney, kidneys from male and female C57BL/6Cr mice were morphometrically examined at 2, 4, 12, 27 and 33 months of age. Gender differences were clearly observed in age-related changes in renal corpuscle diameter, in addition to semiquantitative scores of glomerular damage and interstitial fibrosis. A greater relative increase in renal corpuscle diameter was observed in females compared to males, and scores indicating glomerular damage and interstitial fibrosis were more severe in males than in females.

Aging↗

PubMed2006

Species specific differences in the ratio of short to long loop nephrons in the kidneys of laboratory rodents.

The ratio of short to long loop nephrons (SLNs and LLNs, respectively) in laboratory rodents (mice, rats, hamsters, gerbils, and guinea pigs) was investigated using the air cast method. In mice and rats, the percentage of SLNs was significantly higher than that of LLNs, while in hamsters and gerbils, the reverse was true (% of LLNs >% of SLNs). In guinea pigs, no significant difference in the percentages of LLNs and SLNs was noted.

Animals↗

PubMed2005

Development of gender differences in DBA/2Cr mouse kidney morphology during maturation.

Although we recently clarified sex-based differences in mouse kidney morphology, the developmental processes responsible for these gender differences during maturation remain unclear. The present study analyzed the morphometry of kidneys from 20-, 30-, 50-, 60-, 70-, 90-, 120- and 150-day-old DBA/2Cr mice. Total kidney weight and ratio of kidney weight to body weight were larger in males than females beginning at 50 days of age. The percentage of renal corpuscles exhibiting a cuboidal parietal layer was higher in males than in females in the 70-day and older mice. The diameter of cortical renal corpuscles was larger in males than in females beginning on day 90. The number of proximal convoluted tubular cell nuclei was higher in females than in males from day 90 onward. Vacuolar structures in the proximal convoluted tubular epithelium became prominent in 70-day-old males. PAS-positive granules in the proximal straight tubular epithelium became prominent in females on day 50. This paper is the first to describe the development of gender differences in mouse kidney morphology.

Age Factors↗

PubMed2005

SAMP1/Sku as a murine model for tubulointerstitial nephritis: a study using unilateral ureteral obstruction.

The SAMP1/Sku mouse is a substrain of the SAMP1 (senescence-accelerated-mouse prone 1) which exhibits renal mononuclear cell infiltration from a younger age. We hypothesized that this renal characteristic is related to the incidence of tubulointerstitial nephritis (TIN). The purpose of the present study was to evaluate the applicability of the SAMP1/Sku mouse as a murine model for TIN. TIN was experimentally induced by unilateral ureteral obstruction (UUO). The SAMP1/Sku and control ICR of both sexes received either a sham or UUO operation and were sacrificed 7 days after the operation. The kidneys of the mice were observed histopathologically, immunohistochemically and semiquantitatively. UUO kidneys showed mononuclear cell infiltration, tubular atrophy and interstitial fibrosis. In males, semiquantitative scores of mononuclear cell infiltration, tubular atrophy, and F4/80, alpha-smooth muscle actin (alpha-SMA) and transforming growth factor (TGF)-beta1 reactions were significantly higher in SAMP1/Sku than in ICR. Likewise, in females, tubular atrophy and F4/80 reaction scores were significantly higher in SAMP1/Sku than in ICR. In conclusion, induction of TIN damage by UUO was more serious in SAMP1/Sku mice than in ICR. Therefore, we propose that SAMP1/Sku mice, especially male SAMP1/Sku, have congenital risk factors for the development of TIN.

Actins↗

PubMed2004

Characterization and species differences in gastric ghrelin cells from mice, rats and hamsters.

Ghrelin is a newly identified gastric peptide hormone that has various important functions, including growth-hormone release and appetite stimulation. Ghrelin-immunoreactive cells (ghrelin cells) are characterized by X-type endocrine cells in the rat stomach. In the present study, we analysed ghrelin cells in fundi of stomach from ICR mice and Syrian hamsters immunohistochemically, immunoelectron microscopically and morphometrically, and compared the results with those from Wistar rats. Immunohistochemistry revealed that ghrelin cells were sparsely distributed in the proper gastric glands in all species. The number of ghrelin cells per unit area in hamsters was significantly lower than that in rats. Immunoelectron microscopy detected ghrelin immunolabelling in granules in the X-type endocrine cells. However, the diameter of granules in the hamsters was significantly smaller than that in the mice and rats. Gastric ghrelin contents were determined by radioimmunoassay, and levels in the hamsters were significantly lower than those in mice and rats. The results from mice were identical to those from rats. In conclusion, gastric ghrelin cells in mice and hamsters are characterized by X-type endocrine cells, as has been observed in rats. However, the data indicated that gastric ghrelin production was lower in hamster than in mouse or rat.

Animals↗

PubMed2004

Morphometrical analysis of the kidney from nonobese diabetic (NOD) mice in the non-diabetic stage.

The kidneys of non-diabetic NOD and wild type ICR mice were examined morphometrically at 3 and 6 months of age. Kidney weights and diameter of renal corpuscles of non-diabetic NOD mice were less than those of ICR mice. No lesions were observed in glomeruli or uriniferous tubules. Renin-positive areas were more common in NOD mice than in ICR mice, but no differences were detected in the Western blot analyses.

Age Factors↗

PubMed2004

The effects of microwave-irradiated fixation for postmortem changes of the kidney.

In the present study, we evaluated the advantages of microwave-irradiated fixation for postmortem autolysis of the kidney. Mouse kidneys, sampled at 0, 1, 3, 5, 10, 15, 20 and 25 hr after death, were fixed with 10% neutral formalin by microwave irradiation (MWI; 20 sec/500 W) and by conventional immersion. They were then examined with light and electron microscopy, morphometrics and immunohistochemicals. Light microscopic and morphometric observations showed that structural preservation effect of MWI was limited to the proximal convoluted tubules at 25 hr. Contrary, mild ultrastructural damage by MWI was found in the glomeruli at 0 and 15 hr. Immunohistochemistry for renin and alpha-smooth muscle actin showed no apparent differences between MWI and the immersion.

Actins↗

PubMed2004

Renin, cyclooxygenase-2 and neuronal nitric oxide synthase in the kidneys of transgenic Tsukuba hypertensive mouse.

The transgenic Tsukuba hypertensive mouse (THM), which expresses the human renin and angiotensinogen genes, develops hypertension secondary to increased renin-angiotensin system activity. The aim of the present study was to assess expression of the renin, cyclooxygenase-2 (COX-2), and neuronal nitric oxide synthase (nNOS) proteins in THM kidneys by immunohistochemical stainings. Renin expression was decreased in the THM kidneys when compared to kidneys from heterozygotes or control mice. Although no differences were observed in nNOS expression, overexpression of the COX-2 protein was observed in the macula densa cells in THM kidneys.

Animals↗

PubMed2003

Effects of sex hormones on the development of giant lysosomes in the proximal tubules of DBA/2Cr mouse kidney.

The DBA/2Cr mouse strain is characterized by giant lysosomes that are located in the proximal convoluted tubules of males and in the proximal straight tubules of females. In the present study, we used light microscopy and electron microscopy to investigate the effects of sex hormones on the development of these giant lysosomes. In the proximal convoluted tubules of males, giant lysosomes (large vacuolar structures observed under light microscopy) disappeared after orchiectomy but reappeared after testosterone treatment. No changes were observed after ovariectomy or estradiol treatment. In the proximal straight tubules of females, giant lysosomes (periodic acid Schiff-positive giant granules observed under light microscopy) disappeared after ovariectomy but reappeared after estradiol treatment. After orchiectomy and testosterone treatment, the giant lysosomes did not appear. However, a number of small lysosomes (smaller than a nucleus), which were periodic acid Schiff-positive, increased after orchiectomy and decreased after testosterone treatment. These findings suggest that lysosomes in DBA/2Cr mice are regulated by testosterone or estradiol as follows: (1) in the proximal convoluted tubules, the development of lysosomes is stimulated by testosterone but not by estradiol; (2) in the proximal straight tubules, development of lysosomes is stimulated by estradiol and inhibited by testosterone.

Animals↗

PubMed2003

Age-related morphological changes in kidneys of SPF C57BL/6Cr mice maintained under controlled conditions.

Age-related morphological changes were examined in the kidneys of inbred C57BL/6Cr mice maintained in a controlled environment. The specific pathogen free status of animals used in the present study was confirmed by microbiological monitoring. Kidneys were histologically and histometrically investigated at 3, 5, 12, 15, 24 and 27-months-old. Kidney weights did not change with age. Renal corpuscles increased in number at 24- and 27-months-old, but diameter remained constant. The percentage of renal corpuscles with a cuboidal glomerular capsule decreased at 24- and 27-months-old. Score indicating glomerular damage increased from 5- to 27-months-old. Changes to the proximal convoluted tubules were severe. Vacuolar degeneration was observed from 12-months-old. Tubular atrophy was observed at 24- and 27-months-old, with number of nuclei per unit area increasing at the same ages. Amyloidosis and scar lesions were observed at 27-months-old. Focal cell infiltration around vessels was found at 24- and 27-months-old. Electron microscopy at 27-months-old revealed expansion of the mesangial matrices and fusion of foot processes in the glomeruli. Enlarged lysosomes with lipid content were observed in the proximal convoluted tubules.

Aging↗

PubMed2003

Giant lysosomes in the renal proximal tubules--a morphological characteristic of DBA/2 and DBA/1 mouse kidneys.

The DBA/2Cr mouse is characterized by the presence of giant lysosomes located in the proximal convoluted tubules of males and proximal straight tubules of females. However, it remains unclear whether these giant lysosomes in the proximal tubules are characteristic of DBA/2Cr specifically, or are common to other DBA/2 substrains and DBA/1. The present study investigated the morphology of kidneys from DBA/2CrSlc, DBA/2JJcl, DBA/2NCrj and DBA/1JNCrj mice of both sexes. Giant lysosomes in the renal proximal tubules were found to represent common morphological characteristic of both DBA/2 and DBA/1JN.

Animals↗

PubMed2003

Fine structure of the parotid and mandibular glands of the cotton rat (Sigmodon hispidus).

The parotid and mandibular glands of the cotton rat were examined by light and transmission electron microscopy. Parotid gland: Acinar cells were serous in nature, and contained electron-dense granules. Intercalated duct cells contained electron-dense granules. Striated duct cells had small granules of moderate and high electron densities. Mandibular gland: Acinar cells were seromucous in nature, and contained granules of low and moderate electron densities. Intercalated duct cells contained granules of moderate and high electron densities. Striated ducts were comprised of two portions - a secretory portion and a striated portion without granules. The secretory portion had many electron-dense granules. A sexual dimorphism was obserbed in these granules, which were smaller and fewer in females than in males.

Animals↗