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1.
Transplant Proc ; 49(1): 78-83, 2017.
Article in English | MEDLINE | ID: mdl-28104164

ABSTRACT

BACKGROUND: Previously, we explored the histopathologic characteristics of medullary ray injury (MRI) inducing interstitial fibrosis and tubular atrophy (IF/TA) to determine its etiologies, which include calcineurin inhibitor (CNI) toxicity and urologic complications. However, we did not examine the effects of these etiologies on long-term kidney allograft prognosis, because biopsy timing differed among cases. AIM: We examined the influence of early MRI on kidney allograft prognosis using protocol biopsies taken within a 3-month time frame. METHODS: We defined early MRI as tubular degeneration with interstitial edema or mild fibrosis localized to the medullary ray. We divided 53 protocol biopsies into 2 groups, with and without early MRI. Early MRI+ cases with isometric vacuolization were classified as CNI toxicity; those with Tamm-Horsfall protein in the interstitium and a thyroidlike appearance were classified as urinary tract system abnormalities; remaining cases were classified as "others." We compared changes in serum levels of creatinine (sCr) over 3 years and fibrosis extent at 1 year. RESULTS: The sCr levels were significantly higher in the MRI+ group than the MRI- group at 3 years (P = .024). Examining the 3 MRI+ subgroups, only the MRI+ urinary tract system abnormalities group had significantly high sCr levels compared to the MRI- group (P = .019). The MRI+ group showed significant signs of IF/TA at 1 year. CONCLUSIONS: Early MRI after kidney transplantation was significantly more likely to develop IF/TA at 1 year and had higher sCr levels at 3 years. In such cases, intervention might preserve graft function over the long term.


Subject(s)
Graft Rejection/pathology , Kidney Transplantation/adverse effects , Kidney/pathology , Adult , Biopsy , Creatinine/blood , Female , Fibrosis/pathology , Humans , Male , Middle Aged
2.
Horm Metab Res ; 46(9): 656-62, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24995855

ABSTRACT

Patients with adult growth hormone deficiency exhibit visceral fat accumulation, which gives rise to a cluster of metabolic disorders such as impaired glucose tolerance and dyslipidemia. Plasma growth hormone levels are lower in obese patients with metabolic syndrome than in healthy subjects. Here we examined the hypothesis that exogenous growth hormone administration regulates function of adipose tissue to improve glucose tolerance in diet-induced obese mice. Twelve-week-old obese male C57BL/6 J mice received bovine growth hormone daily for 6 weeks. In epididymal fat, growth hormone treatment antagonized diet-induced changes in the gene expression of adiponectin, leptin, and monocyte chemoattractant protein-1, and significantly increased the gene expression of interleukin-10 and CD206. Growth hormone also suppressed the accumulation of oxidative stress marker, thiobarbituric acid-reactive substances, in the epididymal fat and enhanced the gene expression of anti-oxidant enzymes. Moreover, growth hormone significantly restored glucose tolerance in obese mice. In cultured 3T3-L1 adipocytes, growth hormone prevented the decline in adiponectin gene expression in the presence of hydrogen peroxide. These results suggest that growth hormone administration ameliorates glucose intolerance in obese mice presumably by decreasing adipose mass, oxidative stress, and chronic inflammation in the visceral fat.


Subject(s)
Adipose Tissue/drug effects , Blood Glucose/metabolism , Growth Hormone/administration & dosage , Obesity/drug therapy , Obesity/metabolism , Oxidative Stress/drug effects , Adiponectin/genetics , Adiponectin/metabolism , Adipose Tissue/immunology , Adipose Tissue/metabolism , Animals , Cattle , Glucose Intolerance/drug therapy , Glucose Intolerance/genetics , Glucose Intolerance/immunology , Glucose Intolerance/metabolism , Humans , Interleukin-10/genetics , Interleukin-10/immunology , Lectins, C-Type/genetics , Lectins, C-Type/immunology , Leptin/genetics , Leptin/metabolism , Male , Mannose Receptor , Mannose-Binding Lectins/genetics , Mannose-Binding Lectins/immunology , Mice , Mice, Inbred C57BL , Mice, Obese , Obesity/genetics , Obesity/immunology , Receptors, Cell Surface/genetics , Receptors, Cell Surface/immunology
3.
Kyobu Geka ; 64(7): 532-6, 2011 Jul.
Article in Japanese | MEDLINE | ID: mdl-21766700

ABSTRACT

To acquire the pulmonary artery (PA) and pulmonary vein (PV) image separately, we scanned PA phase while X-ray source moved caudal direction, followed by continuous scan of PV phase by moving back reverse direction. We assessed some scanning conditions to shorten scanning time and determined the starting time for scanning to obtain the maximum intensity difference of radio-opaque contrast between PA and PV phase. Additional infusion of normal saline was followed after contrast medium administration. Finally, scanning could be finished almost 10 seconds with only 20 ml contrast medium for establish three-dimensional (3D) images of pulmonary vessels, and the residual contrast medium could be used for consecutive usual preoperative computed tomography (CT). Twenty-three patients who underwent lung resection were assessed their preoperative 3D-CT images using 5-point scale; 5 and 4 as good, 3 as fair, 2 and 1 as poor. As a result, 18 (78.3%) and 1 (4.3%) were categorized as good and poor, respectively. We successfully decreased the frequency of CT and contrast agent dose for 3D-CT in patients being scheduled for lung resection by the new methods reported herein. Additionally, the workload of building up 3D-CT images by medical workers was also reduced.


Subject(s)
Tomography, X-Ray Computed/methods , Humans , Imaging, Three-Dimensional , Pneumonectomy , Thoracic Surgery, Video-Assisted
4.
Clin Neurophysiol ; 120(3): 484-96, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19136298

ABSTRACT

OBJECTIVE: For motor activities, visual information is crucial for organizing a movement with respect to a given situation. The present study investigates how cognitive information processing is associated with this visuomotor process. METHODS: Brain dynamics in executing two perceptual-motor tasks were examined in terms of event-related synchronization (ERS) and event-related desynchronization (ERD) of EEG. Those tasks were (1) reaching toward and grasping a visual object with a pinch grip, and (2) matching the pinch grip size with respect to the perceived object size. RESULTS: According to the aperture size in the task execution, both the tasks were affected by the perceived object size inducing the Ebbinghaus illusion. The alpha-ERD patterns were associated with the movement execution and appeared to be identical in both the tasks, whilst the gamma-ERS appeared only for the grasping motion. CONCLUSIONS: These results suggest that cognitive processing was involved not only in the matching task but also in the grasping task. These ERD/ERS patterns are thought to reflect the similarity and difference in the perceptual-motor processes between the two tasks. SIGNIFICANCE: The analysis of ERD/ERS can provide insight on the qualitative feature in a visuomotor process associated with the involvement of cognitive processing.


Subject(s)
Cerebral Cortex/physiology , Cognition/physiology , Electroencephalography/methods , Evoked Potentials/physiology , Movement/physiology , Psychomotor Performance/physiology , Adult , Arm/physiology , Cortical Synchronization , Female , Hand Strength/physiology , Humans , Illusions/physiology , Male , Orientation/physiology , Signal Processing, Computer-Assisted , Space Perception/physiology , Time Factors , Young Adult
6.
J Neuroendocrinol ; 15(10): 916-24, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12969235

ABSTRACT

In rats, acute stress substantially increases corticotropin-releasing factor (CRF) type 1 receptor (CRFR-1) mRNA expression in the paraventricular nucleus (PVN) and osmotic stimulation induces both CRF and CRFR-1 mRNA in magnocellular PVN and supraoptic nucleus (SON). However, these phenomena have not been analysed in other species. We compared CRF and CRFR-1 expression in rat and mouse hypothalamus. Male C57BL/6 mice and Wistar rats were exposed to acute restraint stress for 3 h, or to hypertonic saline ingestion for 7 days. Restraint stress increased CRF and c-fos mRNA expression in both rat and mouse PVN. CRFR-1 mRNA was barely detectable in controls, whereas restraint stress substantially increased CRFR-1 mRNA in rat PVN, but not in mouse. Hypertonic saline ingestion induced CRF mRNA in magnocellular PVN and SON of the rat, but did not alter CRF mRNA levels in mouse hypothalamus. CRFR-1 mRNA was also induced in magnocellular PVN and SON of the rat in response to osmotic stimulation, but not in mouse. Immunohistochemistry demonstrated that CRFR-1-like immunoreactivity (ir) was distributed within parvocellular and magnocellular PVN of mouse and rat. CRFR-1-ir in rat PVN was increased by acute stress and osmotic stimulation. By contrast, these treatments did not alter CRFR-1-ir in mouse PVN. Combined immunohistochemistry and in situ hybridization revealed that CRFR-1-ir was most frequently colocalized to CRF in mouse PVN, whereas only a small percentage of oxytocin and vasopressin-producing cells coexpressed CRFR-1-ir. These results indicate that (i) by contrast to rats, neither acute stress nor osmotic stimulation induces CRFR-1 mRNA expression in the mouse PVN; (ii) osmotic stimulation does not alter CRF mRNA expression in parvocellular and magnocellular neurones of mouse PVN; and (iii) acute stress increases c-fos and CRF mRNA to a similar degree in mouse and rat PVN. Thus, differences may exist between mouse and rat in the regulation of CRF and CRFR-1 gene expression in hypothalamus following stress and osmotic stimulation.


Subject(s)
Paraventricular Hypothalamic Nucleus/metabolism , RNA, Messenger/biosynthesis , Receptors, Corticotropin-Releasing Hormone/biosynthesis , Stress, Psychological/metabolism , Animals , Autoradiography , DNA Probes , Immunohistochemistry , In Situ Hybridization , Male , Mice , Mice, Inbred C57BL , Osmotic Pressure , Rats , Rats, Wistar , Restraint, Physical
8.
Am J Respir Crit Care Med ; 164(10 Pt 1): 1879-84, 2001 Nov 15.
Article in English | MEDLINE | ID: mdl-11734440

ABSTRACT

Nitric oxide (NO) produced in the airways can be either detrimental or protective to the host. To investigate the role of NO in the pathogenesis of exercise-induced bronchoconstriction (EIB), we measured exhaled NO (ENO) after exercise challenge in 39 asthmatic and six normal children. FEV(1) and ENO were measured before and at 0, 5, 10, and 15 min after exercise performed on a treadmill for 6 min. EIB was defined as a decrease in FEV(1) of more than 15% after the exercise. Normal children (control group) did not have EIB. Twenty-one patients with asthma had EIB (EIB group) whereas the remaining 18 patients did not (non-EIB group). The baseline ENO value was significantly higher in the asthmatic children than in the normal children, and there was a positive correlation between the maximal percent decrease in FEV(1) and the baseline ENO value (r = 0.501, p = 0.012). At the end of the exercise, ENO had decreased in all the subjects. In the non-EIB and control groups, ENO rebounded to above the baseline at 5 min after the exercise and thereafter. In contrast, ENO remained at a decreased level in the EIB group. The change in ENO did not correlate with the change in minute ventilation, and beta-agonist inhalation at the peak of EIB that accelerated the recovery of FEV(1) did not affect the depressed level of ENO, demonstrating that the reduction of ENO is not a simple consequence of increased ventilation nor airway obstruction. Among the EIB group, steroid-treated patients showed sooner recovery in ENO after the exercise than steroid-naive patients. Our study suggests that NO production in response to exercise may be impaired in patients with EIB, and that ENO represents not only airway inflammation but also a protective function of NO in EIB.


Subject(s)
Asthma, Exercise-Induced/metabolism , Breath Tests , Nitric Oxide/analysis , Nitric Oxide/physiology , Administration, Inhalation , Adolescent , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Agonists/therapeutic use , Analysis of Variance , Anti-Inflammatory Agents/therapeutic use , Asthma, Exercise-Induced/diagnosis , Asthma, Exercise-Induced/drug therapy , Asthma, Exercise-Induced/physiopathology , Bronchodilator Agents/pharmacology , Bronchodilator Agents/therapeutic use , Case-Control Studies , Child , Drug Therapy, Combination , Exercise Test , Female , Forced Expiratory Volume/drug effects , Heart Rate/drug effects , Humans , Male , Procaterol/pharmacology , Procaterol/therapeutic use , Steroids , Time Factors
9.
J Exp Psychol Hum Percept Perform ; 27(5): 1163-84, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11642701

ABSTRACT

Rhythmically bouncing a ball with a racket was investigated and modeled with a nonlinear map. Model analyses provided a variable defining a dynamically stable solution that obviates computationally expensive corrections. Three experiments evaluated whether dynamic stability is optimized and what perceptual support is necessary for stable behavior. Two hypotheses were tested: (a) Performance is stable if racket acceleration is negative at impact, and (b) variability is lowest at an impact acceleration between -4 and -1 m/s2. In Experiment 1 participants performed the task, eyes open or closed, bouncing a ball confined to a 1-dimensional trajectory. Experiment 2 eliminated constraints on racket and ball trajectory. Experiment 3 excluded visual or haptic information. Movements were performed with negative racket accelerations in the range of highest stability. Performance with eyes closed was more variable, leaving acceleration unaffected. With haptic information, performance was more stable than with visual information alone.


Subject(s)
Motion Perception , Adult , Biomechanical Phenomena , Female , Humans , Male , Models, Psychological , Nonlinear Dynamics , Periodicity , Random Allocation , Tennis , Visual Perception
10.
J Synchrotron Radiat ; 8(Pt 2): 226-8, 2001 Mar 01.
Article in English | MEDLINE | ID: mdl-11512734

ABSTRACT

Temperature dependence of the Debye-Waller factors in EXAFS is studied for monatomic fcc lattice by use of the perturbation approach in terms of temperature Green's function. We apply the theory to the temperature dependence of EXAFS for Kr and Ni crystals. Furthermore we make a comparison among sc, bcc and fcc lattices for the present ab initio calculations.

11.
Neuroendocrinology ; 73(5): 293-301, 2001 May.
Article in English | MEDLINE | ID: mdl-11399902

ABSTRACT

We have previously proposed the existence of ultrashort loop-positive feedback regulation of corticotropin-releasing hormone (CRH) in the hypothalamus. To gain a better understanding of this effect, we performed double-label in situ hybridization to identify the neurons in the paraventricular nucleus (PVN) that express CRH type 1 receptor (CRH-R1) following stress. We also conducted immunohistochemistry to determine whether CRH-R1 mRNA was translated to CRH-R1 protein in the PVN. Thirty-minute restraint stress given to male Wistar rats increased c-fos mRNA expression primarily in the CRH-producing neurons of the parvocellular PVN. Small numbers of vasopressin and oxytoxin-producing cells were also labeled by c-fos probes. Approximately 70% of CRH-R1 positive neurons exhibited CRH mRNA 2 h after the beginning of stress, while only a small percentage of the vasopressin and oxytocin-producing cells coexpressed CRH-R1 mRNA. CRH-R1 immunoreactivity, which was detected in the perikarya and fibers of PVN neurons, appeared to increase in response to stress, though this was not statistically significant. Pretreatment with a selective CRH-R1 antagonist, CP-154,526, significantly attenuated stress-induced corticotropin (ACTH) secretion as well as c-fos mRNA expression in the PVN. These results demonstrate that acute stress increases neuronal activation and CRH-R1 mRNA expression primarily in CRH-producing neurons of the parvocellular PVN, that CRH-R1 message is translated to CRH-R1 protein, and that PVN neurons are activated at least in part through CRH-R1 under acute stress. The data further support the possibility of feedback regulation of CRH itself in CRH-producing neurons.


Subject(s)
Gene Expression , Paraventricular Hypothalamic Nucleus/metabolism , Receptors, Corticotropin-Releasing Hormone/genetics , Stress, Physiological/metabolism , Adrenocorticotropic Hormone/metabolism , Animals , Corticotropin-Releasing Hormone/genetics , In Situ Hybridization , Male , Oxytocin/biosynthesis , Paraventricular Hypothalamic Nucleus/chemistry , Proto-Oncogene Proteins c-fos/genetics , Pyrimidines/pharmacology , Pyrroles/pharmacology , RNA, Messenger/analysis , Rats , Rats, Wistar , Receptors, Corticotropin-Releasing Hormone/antagonists & inhibitors , Receptors, Corticotropin-Releasing Hormone/physiology , Vasopressins/biosynthesis
12.
Drug Dev Ind Pharm ; 27(4): 365-71, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11411905

ABSTRACT

PURPOSE: A low-viscosity formulation for pulmonary delivery of rh-insulin as model peptide drugs was developed using a solution of sodium hyaluronate. METHOD: The effects of different concentrations and pH values of low-viscosity solutions of hyaluronate on the pulmonary absorption of rh-insulin were examined after intratracheal administration in rats. The permeation of fluorescein isothiocyanate (FITC)-dextran (molecular weight 4300; FD-4) and insulin through excised rat trachea in vitro were also examined. RESULTS: The hyaluronate (2140 kDa) solutions (0.1% and 0.2% w/v) at pH 7.0 significantly enhanced the pharmacological availability (PAB) of insulin compared to the aqueous solution of insulin at pH 7.0. The absorption-enhancing effect at a concentration of 0.1% w/v hyaluronate was greater than that at a concentration of 0.2% w/v hyaluronate. Furthermore, the greatest absorption-enhancing effect was obtained, regardless of the molecular weight of hyaluronate, when the concentration of hyaluronate was adjusted to 0.47 microM. Absorption-enhancing effects were consistent with the effect of a 0.1 w/v hyaluronate preparation at pH 4.0 and 7.0 on the permeation of FITC-dextran and insulin through excised rat trachea in vitro. CONCLUSION: Low-viscosity hyaluronate preparation was shown to be a useful vehicle for pulmonary delivery of peptide drugs.


Subject(s)
Adjuvants, Immunologic/chemistry , Hyaluronic Acid/chemistry , Hypoglycemic Agents/pharmacokinetics , Insulin/pharmacokinetics , Absorption , Animals , Biological Availability , Drug Delivery Systems , Hydrogen-Ion Concentration , Lung/drug effects , Male , Molecular Weight , Rats , Rats, Wistar , Viscosity
13.
Phys Rev E Stat Nonlin Soft Matter Phys ; 63(1 Pt 1): 011902, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11304282

ABSTRACT

On the basis of a modified bouncing-ball model, we investigated whether human movements utilize principles of dynamic stability in their performance of a similar movement task. Stability analyses of the model provided predictions about conditions indicative of a dynamically stable period-one regime. In a series of experiments, human subjects bounced a ball rhythmically on a racket and displayed these conditions supporting that they attuned to and exploited the dynamic stability properties of the task.


Subject(s)
Movement , Physics , Algorithms , Humans , Models, Biological , Models, Statistical , Models, Theoretical , Physical Phenomena , Reproducibility of Results , Tennis , Time Factors
14.
Eur J Pharm Sci ; 13(2): 179-85, 2001 May.
Article in English | MEDLINE | ID: mdl-11297902

ABSTRACT

The suitability of gelatin microspheres for nasal and intramuscular delivery of salmon calcitonin (sCT) was examined. Negatively and positively charged gelatin microspheres were prepared using acidic gelatin [isoelectric point (IEP) value of 5.0] and basic gelatin (IEP=9.0), respectively. The average diameters of positively charged gelatin microspheres in their dried state were 3.4, 11.2, 22.5 and 71.5 microm, while that of negatively charged gelatin microspheres was 10.9 microm. Both types of gelatin microspheres were capable of adhering to the nasal mucosa. The mucoadhesion of positively charged gelatin microspheres was significantly higher than that of their negatively charged counterparts. The absorption of sCT after intranasal and intramuscular administration was evaluated by calculating the area above the hypocalcemic-time curve (AAC) in rats. The AAC values after nasal administration of sCT in positively and negatively charged gelatin microspheres were significantly greater than that in pH 7.0 PBS. Therefore, the nasal absorption of sCT was enhanced by both types of gelatin microspheres. The hypocalcemic effect after administration of sCT in positively charged gelatin microspheres of 11.2 microm was significantly greater than that of negatively charged gelatin microspheres of the same size. On the other hand, AAC values were not affected by their particle sizes. The AAC values after the intramuscular administration of sCT in positively and negatively charged gelatin microspheres were significantly increased compared to that in PBS. Furthermore, the time-courses of the plasma calcium levels differed between positively and negatively charged gelatin microspheres. The hypocalcemic effect of the negatively charged gelatin microspheres tended to appear more slowly and last longer compared to that of positively charged gelatin microspheres. The hypocalcemic effects after intramuscular administration of sCT in gelatin microspheres were not affected by their particle sizes as well as those after intranasal administration. In conclusion, the gelatin microspheres have been shown to be a useful vehicle for nasal or intramuscular delivery of sCT.


Subject(s)
Calcitonin/administration & dosage , Gelatin/chemistry , Administration, Inhalation , Animals , Calcitonin/pharmacokinetics , Chemistry, Pharmaceutical , Drug Delivery Systems , Injections, Intramuscular , Male , Microspheres , Rats , Rats, Wistar
15.
J Neuroendocrinol ; 13(4): 328-38, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11264720

ABSTRACT

The expression of corticotropin releasing factor (CRF) and urocortin in hypothalamic magnocellular neurones increases in response to osmotic challenge. To gain a better understanding of the physiological roles of CRF and urocortin in fluid homeostasis, CRF, urocortin and CRF type 1 receptor (CRFR-1) gene expression was examined in the hypothalamic-hypophyseal system usingin situ and double-label in situ hybridization following chronic salt loading. CRFR-1 expression was further examined by immunohistochemistry and receptor binding. Ingestion of hypertonic saline by Sprague-Dawley rats for 7 days induced CRF mRNA exclusively in the oxytocin neurones of the magnocellular paraventricular nucleus (PVN) and the supraoptic nucleus (SON), but induced CRFR-1 mRNA in both oxytocin and vasopressin-containing magnocellular neurones. Hypertonic saline treatment also increased urocortin mRNA expression in the PVN and the SON. In the SON, urocortin was localized to vasopressin and oxytocin neurones but was rarely seen in CRF-positive cells. Changes in CRFR-1 mRNA expression in magnocellular neurones by hypertonic saline treatment were accompanied by changes in CRFR-1 protein levels and receptor binding. Hypertonic saline treatment increased CRFR-1-like immunoreactivity in the magnocellular PVN and SON, and decreased it in the parvocellular PVN. CRF receptor binding in the PVN and SON was also increased in response to osmotic stimulation. Finally, hypertonic saline treatment increased CRFR-1 mRNA, CRFR-1-like immunoreactivity and CRF receptor binding in the intermediate pituitary. These results demonstrate that the increase in the expression of CRF and urocortin message in magnocellular neurones induced by salt loading is accompanied by an increase in CRF receptor levels and binding in the hypothalamus and intermediate pituitary. Thus, CRF and urocortin may exert modulatory effects locally within magnocellular neurones as well as at the pituitary gland in response to osmotic stimulation.


Subject(s)
Corticotropin-Releasing Hormone/biosynthesis , Hypothalamo-Hypophyseal System/metabolism , Receptors, Corticotropin-Releasing Hormone/biosynthesis , Water-Electrolyte Balance/physiology , Animals , Autoradiography , Corticotropin-Releasing Hormone/genetics , Hypothalamo-Hypophyseal System/cytology , Hypothalamo-Hypophyseal System/drug effects , Immunohistochemistry , In Situ Hybridization , Male , Neurons/metabolism , Oxytocin/genetics , Oxytocin/metabolism , Paraventricular Hypothalamic Nucleus/cytology , Paraventricular Hypothalamic Nucleus/metabolism , Pro-Opiomelanocortin/genetics , Pro-Opiomelanocortin/metabolism , RNA, Messenger/biosynthesis , Rats , Rats, Sprague-Dawley , Receptors, Corticotropin-Releasing Hormone/genetics , Saline Solution, Hypertonic/pharmacology , Supraoptic Nucleus/cytology , Supraoptic Nucleus/metabolism , Urocortins , Vasopressins/genetics , Vasopressins/metabolism
16.
Horm Res ; 56(5-6): 165-71, 2001.
Article in English | MEDLINE | ID: mdl-11910202

ABSTRACT

BACKGROUND: Recently, an endothelin (ET-1) with a potent vasoconstrictive activity and stimulative activity of vascular muscular cell growth was discovered and blood ET-1 levels were higher in diabetic patients than in healthy subjects, suggesting that high ET-1 levels assist development and progression of diabetic microangiography. METHODS: We examined renal function, and serum and tissue ET-1 levels in streptozotocin (STZ)-induced diabetic rats treated with a prostaglandin (PG) I(2) derivative to investigate the effect of PGI(2) in diabetic vascular disturbance. RESULTS: Renal weight, urinary albumin, urinary N-acetyl-beta,D-glucosaminidase (NAG) and serum ET-1 levels increased in STZ-induced diabetic rats, and a tendency to increase in renal tissue ET-1 levels was observed. Furthermore, electron-microscopic findings in the kidneys showed mesangial cell proliferation and mesangial matrix expansion which might be caused by diabetic nephropathy. The PGI(2) derivative reduced urinary albumin and NAG levels in STZ-induced rats. It was considered, therefore, that the PGI(2) derivative is effective in diabetic nephropathy. As the PGI(2) derivative also reduced renal tissue ET-1 levels, improvement of diabetic nephropathy partially was considered to result from the reduction of renal tissue ET-1 levels. CONCLUSION: In STZ-induced rats, increased serum ET-1 levels and a tendency to increase in renal tissue ET-1 levels were associated with increases in urinary albumin and NAG levels, and these levels were decreased by a PGI(2) derivative. These findings suggested that increased ET-1 concentrations assist development and progression of diabetic nephropathy, especially diabetic microangiopathy, and the PGI(2) derivative may be effective for inhibition of diabetic microangiopathy mediated by reduction of ET-1 concentrations.


Subject(s)
Diabetic Nephropathies/metabolism , Endothelin-1/metabolism , Albuminuria/urine , Animals , Blood Glucose/analysis , Body Weight , Diabetes Mellitus, Experimental , Diabetic Nephropathies/pathology , Endothelin-1/blood , Epoprostenol/pharmacology , Fasting/blood , Hypoglycemic Agents/urine , Kidney/metabolism , Male , Microscopy, Electron , Organ Size , Rats
17.
Am J Nephrol ; 20(4): 263-7, 2000.
Article in English | MEDLINE | ID: mdl-10970977

ABSTRACT

In this report, we describe 5 patients with cholesterol atheroembolic renal failure. In 3 of the 5 patients, combined therapy with corticosteroids and plasma exchange was performed. These 3 patients survived, with 2 showing an improvement in renal function. The 2 remaining patients died of multifactorial causes. The literature on therapy for cholesterol atheroembolic renal failure is reviewed and the efficacy of combined therapy by use of corticosteroids and plasma exchange is evaluated.


Subject(s)
Embolism, Cholesterol/therapy , Glucocorticoids/therapeutic use , Methylprednisolone/therapeutic use , Plasma Exchange , Prednisolone/therapeutic use , Prednisone/therapeutic use , Renal Circulation , Acute Kidney Injury/etiology , Aged , Embolism, Cholesterol/complications , Evaluation Studies as Topic , Fatal Outcome , Humans , Male , Middle Aged
18.
J Pharm Pharmacol ; 52(6): 611-7, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10875536

ABSTRACT

The use of negatively and positively charged gelatin microspheres for pulmonary delivery of salmon calcitonin was examined in rats. The microspheres were prepared using acidic gelatin (isoelectric point (IEP):, 5.0) and basic gelatin (IEP, 9.0) for the negatively and positively charged microspheres, respectively. The average diameters of positively charged gelatin microspheres in the dry state were 3.4, 11.2, 22.5 and 71.5 microm, and that of negatively charged gelatin microspheres was 10.9 microm. Neither positively nor negatively charged gelatin microspheres underwent any degradation in pH 7.0 PBS and there was less than 8% degradation in bronchoalveolar lavage fluid (BALF) after 8 h. In in-vitro release studies in pH 7.0 PBS, salmon calcitonin was rapidly released from positively charged gelatin microspheres within 2 h, and its cumulative release was approximately 85%. In addition, the release profiles were not influenced by particle sizes. The release rates of salmon calcitonin from negatively charged gelatin microspheres were lower than that from positively charged gelatin microspheres. The cumulative release was approximately 40% after 2 h, but there was no evidence of any sustained release. The pulmonary absorption of salmon calcitonin from gelatin microspheres was estimated by measuring its hypocalcaemic effect in rats. The pharmacological availability after administration of salmon calcitonin in positively and negatively charged gelatin microspheres was significantly higher than that in pH 7.0 PBS. The pharmacological availability after administration of salmon calcitonin in positively charged gelatin microspheres was significantly higher than that in negatively charged gelatin microspheres. Administration of salmon calcitonin in positively charged gelatin microspheres with smaller particle sizes led to a higher pharmacological availability. The pharmacological availability after pulmonary administration of salmon calcitonin in positively charged gelatin microspheres with particle sizes of 3.4 and 11.2 microm was approximately 50%. In conclusion, the gelatin microspheres have been shown to be a useful vehicle for pulmonary delivery of salmon calcitonin.


Subject(s)
Analgesics/administration & dosage , Analgesics/pharmacokinetics , Calcitonin/administration & dosage , Calcitonin/pharmacokinetics , Lung/drug effects , Animals , Biological Availability , Drug Delivery Systems , Gelatin , Male , Microspheres , Rats , Rats, Wistar , Trachea
19.
J Steroid Biochem Mol Biol ; 72(5): 265-72, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10822016

ABSTRACT

Sulfation of the 3-hydroxy group is assumed to be a major metabolic route of ursodeoxycholic acid (UDCA) which is used for treating various hepatobiliary diseases. We have developed a sensitive enzyme-linked immunosorbent assay (ELISA) for determining the total amount of nonamidated, glycine- and taurine-amidated ursodeoxycholic acid 3-sulfates (UDCA 3-Suls) using a newly established monoclonal antibody. In this study, 12 kinds of antibody-secreting hybridoma clones were generated by a fusion experiment between P3/NS1/1-Ag4-1 myeloma cells and the spleen cells from a BALB/c or an A/J mouse which had been immunized with a conjugate of nonamidated UDCA 3-Sul and bovine serum albumin. One of the monoclonal antibodies, Ba-10 (gamma2a, kappa), had suitable binding properties for clinical application, which was group-specific to the UDCA 3-Suls, and showed negligible cross-reactivities with various related bile acids including potentially interfering compounds, namely, the unconjugated UDCA, UDCA 7-N-acetylglucosaminide, the 3-sulfates of cholic acid, chenodeoxycholic acid and deoxycholic acid. The antibody Ba-10 allowed us to develop a sensitive competitive ELISA system whose measurable range was approximately 2-200 pg per assay. A serial dilution study indicated that the ELISA enables the direct measurement of the UDCA 3-Suls in human urine before and after the administration of exogenous UDCA. The daily urinary excretion rate of UDCA 3-Suls from healthy male volunteers (n = 5) was determined to be a mean of 131 +/- 61.2 (SD) microgram as the nonamidated UDCA 3-Sul equivalent.


Subject(s)
Antibodies, Monoclonal/immunology , Enzyme-Linked Immunosorbent Assay/methods , Sulfates/urine , Ursodeoxycholic Acid/urine , Animals , Antibodies, Monoclonal/metabolism , Antibody Specificity , Cell Fusion , Female , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Inbred Strains , Reference Values , Sensitivity and Specificity , Sulfates/immunology , Ursodeoxycholic Acid/immunology , Ursodeoxycholic Acid/pharmacology
20.
Nephron ; 85(1): 81-5, 2000 May.
Article in English | MEDLINE | ID: mdl-10773760

ABSTRACT

BACKGROUND/AIM: Interleukin-6 (IL-6) promotes the growth of renal mesangial cells. IL-6 may play a major role in such mesangial proliferation, but there has been little research on IL-6 in relation to diabetic nephropathy because of the difficulty in measuring urinary and serum IL-6 levels. Using a newly developed, highly sensitive IL-6 assay, we studied the relationship between serum and urinary IL-6 and diabetic nephropathy. METHODS: We investigated 72 patients with type 2 diabetes. Urinary and serum IL-6 concentrations were measured using a chemiluminescent enzyme immunoassay with a detection limit of 0.11 pg/ml. RESULTS: There was a significant increase of the serum IL-6 level as diabetic nephropathy progressed, with the level being 1.4 +/- 0.3 pg/ml in patients with normal albuminuria, rising to 2.4 +/- 0.6 pg/ml in patients with microalbuminuria and then to 4.4 +/- 0.8 pg/ml in those having proteinuria. The serum IL-6 level was also significantly correlated with fibrinogen and aortic pulse wave velocity. The urinary IL-6 level was also significantly increased in diabetic patients as nephropathy progressed. Both serum and urinary IL-6 levels were high in the group with nephropathy, but there was no correlation between the two. CONCLUSION: The urinary IL-6 level seems to be a good indicator of diabetic nephropathy, and atherosclerotic changes were related to the serum IL-6 level. The serum IL-6 may, therefore, be useful in the evaluation of atherosclerosis including nephropathy.


Subject(s)
Diabetic Nephropathies/blood , Diabetic Nephropathies/urine , Immunoassay/methods , Interleukin-6/blood , Interleukin-6/urine , Albuminuria/blood , Albuminuria/urine , Arteriosclerosis/blood , Arteriosclerosis/urine , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/urine , Female , Humans , Luminescent Measurements , Male , Middle Aged , Predictive Value of Tests , Sensitivity and Specificity
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