Search PubMed⌕ Search

Biomedical subjects

N Sato

Publications and source records attributed to N Sato.

At least 541 records · Page 30Linked to original sources
PubMed1998

[13C]-urea breath test for assessment of cure of Helicobacter pylori infection at 1 month after treatment.

Although the [13C]-urea breath test has been reported to provide high specificity and sensitivity, its reliability in determination of cure, including when and how the assessment of cure is made, is not fully established. Here we evaluate the reliability of judgment of cure after 1 month of therapy using the [13C]-urea breath test, including the appropriate time to assess its cure. Our subjects were 199 H. pylori-infected patients (144 men and 55 women; 50.5+/-0.76 years) who underwent cure therapy, took the breath test at 1 month, and underwent both the breath test and invasive tests using endoscopy at 6 months after completion of therapy. Accuracy of the breath test in judgment of cure at 1 month was investigated by comparing the results at 1 month with those at 6 months when cut-off value of the breath test was set at 5 per thousand. Chronologic alterations of the delta13C value were also analyzed in cured patients who underwent the breath test at 1, 3, and 6 months. In 167 (94.9%) of 176 patients whose breath test values were less than 5 per thousand, cure was reconfirmed at 6 months. In 14 (60.9%) of 23 patients whose values were greater than 5 per thousand, cure was demonstrated at 6 months. The mean delta13C values of 33 cured patients who took the breath test at 1 month and repeated the breath test at 3 and 6 months for any reasons were 4.14+/-0.74 per thousand, 2.02+/-0.23 per thousand, and 1.72+/-0.19 per thousand, respectively, and the value at 3 months was significantly smaller than that at 1 month. The reliability of assessment of cure by only the breath test at 1 month was sufficiently high (94.9%) once the patients were judged to be cured. However, because the breath test at 1 month yielded a high false-positive rate and the breath test values at 3 and 6 months were similar, evaluation of cure of H. pylori infection by the [13C]-urea breath test should preferably be done at 3 months after treatment to minimize false-positive results, or the concept of a borderline group should be established for patients with positive but relatively high delta13C values (5-10 per thousand) who repeated the breath test 3 months after treatment.

Breath Tests↗
PubMed1998

A radioiodinated biocytin derivative for in-vivo applications.

Radioiodinated biocytin derivatives are potentially useful for multi-step tumour targeting using the avidin-biotin system. We synthesized a radioiodinated biocytin derivative and evaluated its properties in vivo. We labelled biocytin with 125I by coupling biocytin to radioiodinated N-succinimidyl 3-(tri-n-butyl-stannyl) benzoate, and assessed its binding to avidin and its biodistribution in normal and tumour-bearing mice. When the synthesized biocytin was incubated with immobilized avidin, more than 94% of the radioactivity was bound. However, after 2 h incubation in serum, only 40% of the radioactivity was bound to the avidin. The iodinated biocytin derivative was characteristically taken up by the liver and the kidneys when injected intravenously into mice. In mice bearing an intraperitoneal tumour xeno-graft, 125I-biocytin and 111In-biotin were co-injected intraperitoneally 4 h after the intraperitoneal administration of avidin, which accumulated in the intraperitoneal tumours. At 2 and 24 h, the tumour uptake of 125I-biocytin was 8.2 and 3.8% ID/g respectively, whereas that of 111In-biotin was 20.0 and 18.7% ID/g respectively. When radioiodinated, biocytin retains its binding capacity to avidin, and it localizes well with high tumour-to-normal tissue ratios early post-injection using the two-step method, but compared to 111In-biotin it is unstable. We conclude that the stability of the product in serum needs to be improved prior to in-vivo applications.

Animals↗
PubMed1998

Molecular characterization of the PEND protein, a novel bZIP protein present in the envelope membrane that is the site of nucleoid replication in developing plastids.

Plastid nucleoids are known to bind to the envelope membrane in developing chloroplasts. Here, plastid DNA is extensively replicated. We previously detected a DNA binding protein in the inner envelope membranes of developing plastids in pea and named it PEND (for plastid envelope DNA binding) protein. In this study, we report on the structure and molecular characterization of a cDNA for the PEND protein. As a result of screening cDNA libraries in lambdagt11 with one of the target sequences of the PEND protein as a probe, we obtained a clone (PD2) for a novel DNA binding protein consisting of 633 amino acid residues. Analysis of the N-terminal sequence of the purified PEND protein indicated that the transit peptide is just 16 residues long. The PEND protein was detected specifically in the plastid envelope membrane of young unopened leaf buds by immunoblot analysis. The PEND protein consists of a basic region plus zipper region, an unprecedented sextuple repeat region, and a putative membrane-spanning region. The basic region with a zipper region seems to have diverged from that of other plant transcription factors. In addition, the PEND protein could be a distant homolog of the trans-Golgi network integral membrane proteins. The PEND protein is therefore a novel type of DNA binding protein that binds to the membrane as an intrinsic membrane protein.

Amino Acid Sequence↗
PubMed1998

Inhibition of liver metastasis of human pancreatic carcinoma by angiogenesis inhibitor TNP-470 in combination with cisplatin.

The anti-tumor and anti-metastatic effects of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), an angiogenesis inhibitor, and cisplatin (CDDP), an anti-neoplastic agent, were investigated using our established liver-metastasizing pancreatic carcinoma line, HPC-3H4. HPC-3H4 was injected into the spleens of nude mice. Mice were randomly divided into 5 groups; a control group given saline solution, a group receiving 45 mg/kg TNP-470, a group receiving 90 mg/kg TNP-470, a group receiving 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP, and a group receiving 0.25 mg/kg CDDP. In the control group, liver metastasis developed in 14 of 15 mice (93.3%). Liver metastasis developed in 9 of 11 mice (81.8%) receiving 0.25 mg/kg CDDP. It developed in 11 of 15 mice (73.3%) receiving 45 mg/kg TNP-470, in 17 of 18 mice (94.4%) receiving 90 mg/kg TNP-470, and in 4 of 10 mice (40%) receiving 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP. TNP-470 in combination with CDDP displayed a significant inhibitory effect on liver metastasis compared to the control. Although TNP-470 alone and CDDP alone had no effect on the tumor growth in vivo, 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP had a significant effect. In vitro examinations demonstrated that the growth of HPC-3H4 cells was only mildly inhibited by TNP-470, but the production of vascular endothelial growth factor (VEGF) by HPC-3H4 was clearly inhibited by TNP-470. The inhibitory effect on the production of VEGF was not strong with CDDP treatment. These results indicate that the angiogenesis inhibitor TNP-470 in combination with low-dose CDDP has inhibitory activity against liver metastasis of human pancreatic carcinoma.

Animals↗
PubMed1998

Usefulness of the [13C]-urea breath test for detection of Helicobacter pylori infection in fasting patients.

Most of the reported [13C]-urea breath test procedures use a test meal, which is believed to assist in the spread of the [13C]-urea solution into the entire stomach, as results without a test meal may mainly reflect urease activity in the antrum.Yet, procedures for the [13C]-urea breath test and interpretation of the obtained 13C excess value have not been well established. We carried out the present study to validate the usefulness of the [13C]-urea breath test in fasting subjects and to establish cut-off values. [13C]-Urea breath tests were performed on 258 Helicobacter pylori-positive and 151 -negative subjects (247 H. pylori positive and 26 negative prior to any H. pylori cure treatment and 125 H. pylori negative and 11 positive after undergoing H. pylori cure treatment). The breath test procedure was performed under the following conditions: an 8 h fast, mouth washing before and after dosing, administration of 100 mg [13C]-urea, collection of breath sample in a plastic bag, a baseline and a 20 min sampling point and subject in a sitting position. Delta-13C at the 20 min sampling point in H. pylori-positive and -negative subjects was 31.0+/-1.25 and 1.6+/-0.11%, respectively. Although the mean delta13C value was greatest in duodenal ulcer or ulcer scar patients, there were no significant differences among mean delta13C values in the various diseases. From Receiver Operator Characteristic curves and calculation of accuracy of the test, a cut-off value of 5.0% is considered to be appropriate for diagnosis of H. pylori infection, which provides 96.7% specificity and 96.5% sensitivity, suggesting that the [13C]-urea breath test in the fasting state is as effective in detecting the presence of H. pylori as other reported methods.

Adult↗
PubMed1998

A comparative study of nucleolar organizer region, proliferating cell nuclear antigen and epidermal growth factor receptor staining in colon tumours.

Several studies have reported that proliferating cell nuclear antigen (PCNA), nucleolar organizer regions (NOR) and epidermal growth factor receptor (EGF-R) are cellular proliferation parameters in malignant tumours. However, the correlation of EGF-R with PCNA and NOR has not been reported in colon tumours. To clarify this, we investigated the correlation of the expression of EGF-R with PCNA and NOR in colonic epithelial tumours. Using immunohistochemical staining and one-step silver staining techniques, the expressions of EGF-R-, PCNA- and NOR-associated protein were studied in paraffin sections from five normal mucosae, 10 adenomas with mild atypia, 16 adenomas with moderate atypia, 32 adenomas with severe atypia including carcinoma in situ and 47 with invasive colon carcinomas. Significant differences were found among the respective degrees of atypia in Ag-NOR counts, PCNA labelling index (LI), and the expression of EGF-R. However, there were no significant differences among the Ag-NOR counts of the severe atypia and invasive carcinoma. There was a significant positive correlation between Ag-NOR counts and PCNA LI (P < 0.001). The Ag-NOR counts and PCNA LI in EGF-R-positive cases were higher than in EGF-R-negative cases (P < 0.001). These results indicate that each of the parameters increased significantly with the increase in atypia and the progression of cancer. Epidermal growth factor receptor provokes an exacerbation of protein synthesis and the cell cycle in colonic epithelial tumours.

Adenoma↗
PubMed1998

Lack of desensitization and enhanced efficiency of calcium channel promoter in conscious dogs with heart failure.

The goal of this study was to compare responses to a calcium promoter, BAY y 5959, and dobutamine (Dob) in heart failure (HF). Dogs (n = 9) were chronically instrumented and studied in the conscious state before and after pacing-induced HF. In the control state, BAY y 5959 (20 microgram. kg-1. min-1) increased the first derivative of left ventricular (LV) pressure (dP/dt) by 83 +/- 8% and mean arterial pressure (MAP) by 8 +/- 2% and decreased heart rate (HR) by 30 +/- 3%. With Dob (10 microgram. kg-1. min-1) LV dP/dt rose similarly (+80 +/- 6%), but HR also rose (+25 +/- 4%) (P < 0.05 vs. BAY y 5959). After HF developed, BAY y 5959 still increased LV dP/dt by 108 +/- 8% and MAP by 21 +/- 2% and decreased HR by 28 +/- 4%, whereas Dob increased LV dP/dt by only 50 +/- 7% (P < 0.05 vs. BAY y 5959) and MAP by 7 +/- 3%, and HR did not change (+3 +/- 3%) (P < 0.05 vs. BAY y 5959). In HF, cardiac work increased more (P < 0. 05) with BAY y 5959 (+105 +/- 13%) compared with Dob (+47 +/- 11%), yet myocardial oxygen consumption increased similarly with the two drugs. Accordingly, mechanical efficiency increased more (P < 0.05) with BAY y 5959 (+73 +/- 14%) than with Dob (+17 +/- 12%). These data indicate that 1) increases in contractility mediated directly by Ca2+ are relatively resistant to desensitization in HF; and 2) the calcium-channel promoter can produce increases in myocardial contractility and cardiac work similar to those of Dob at a significantly lower oxygen cost, thereby enhancing mechanical efficiency in HF.

Animals↗
PubMed1998

Differential contribution of various adhesion molecules to leukocyte kinetics in pulmonary microvessels of hyperoxia-exposed rat lungs.

To elucidate the differential role of various adhesion molecules in distorting leukocyte behavior in the microvasculature of hyperoxia-exposed rat lungs, we investigated fluorescein-labeled leukocyte and erythrocyte kinetics in isolated lungs taken from the animals exposed to 90% O2 for 48 h under conditions in which endothelial intercellular adhesion molecule-1 (ICAM-1) and P-selectin were inhibited by appropriate monoclonal antibodies (1A29 for ICAM-1 and ARP2-4 for P-selectin), while leukocyte L-selectin was restrained with fucoidin. Measurements of blood cell kinetics were made by a confocal laser luminescence microscope coupled with a high-speed video camera. In addition, we histologically examined leukocyte accumulation within the alveolar septa and ICAM-1 as well as P-selectin expressions in the lung. We found that P-selectin expression was sparsely enhanced only in arterioles, whereas ICAM-1 was significantly induced in both venules and capillaries. Firm adhesion of leukocytes was not identified in arterioles and venules, whereas leukocyte rolling was evident in both the vessels. Arteriolar rolling was regulated via a P-selectin- and ICAM-1-independent but L-selectin-dependent mechanism, whereas venular rolling was mediated via a P-selectin-independent but ICAM-1- and L-selectin-dependent pathway. Leukocyte sequestration within capillaries was augmented by an ICAM-1-related mechanism. These findings may suggest that, in hyperoxia-exposed lungs, induction of adhesion molecules and their obstacles to leukocyte behavior are qualitatively different among arterioles, venules, and capillaries.

Animals↗
PubMed1998

Impaired hypoxic vasoconstriction in intraacinar microvasculature in hyperoxia-exposed rat lungs.

To assess the effects of exposure of the lung to hyperoxic conditions on reactivity of pulmonary microcirculation to hypoxic stimulation, we measured hypoxia-elicited overall pulmonary pressor changes (HPV) and microvascular diameter changes in intraacinar arterioles, venules, and capillaries in isolated perfused rat lungs exposed to a hyperoxic environment (90% O2). To estimate the importance of vasoactive prostaglandins and nitric oxide (NO) for HPV modification, we examined the roles of constitutive and inducible forms of cyclooxygenase (COX-1 and COX-2) and those of NO synthase (eNOS and iNOS). Indomethacin was used for inhibiting both COX-1 and COX-2, while NS-398 was used as a selective inhibitor of COX-2. Both eNOS and iNOS were suppressed by L-NAME, whereas iNOS alone was inhibited by aminoguanidine. Microvascular diameter was measured with a real-time confocal laser scanning luminescence microscope. We found that (1) exposure to hyperoxia caused overall HPV and arteriolar constriction to be attenuated; (2) the blunted HPV was restored by L-NAME but not by aminoguanidine, indomethacin, or NS-398; and (3) arteriolar constriction was improved by either L-NAME, aminoguanidine, or indomethacin but only slightly by NS-398. In conclusion, attenuation of overall HPV in hyperoxia-exposed lungs is explicable mainly by excessive NO generated via eNOS, while impaired arteriolar constriction is caused by NO yielded by eNOS and iNOS as well as by vasodilating prostaglandin(s) produced by COX-1.

Animals↗
PubMed1998

Troglitazone (CS-045) inhibits beta-cell proliferation rate following stimulation of insulin secretion in HIT-T 15 cells.

Thiazolidinedione analogs are new antidiabetic agents that attenuate peripheral insulin resistance in noninsulin-dependent diabetic patients; however, the effects of these agents on insulin secretion are not known. We determined the short-term and long-term effects of troglitazone (CS-045) on insulin secretion in a Syrian hamster clonal beta-cell line, HIT-T 15 cells. The direct effect of troglitazone (CS-045: 10(-6)-10(-4) M) on insulin secretion was examined in F-12 K incubation medium containing 7 mM glucose. CS-045 significantly stimulated insulin secretion within 10 min at the concentration of 10(-4) M and dose dependently stimulated insulin secretion within 60 min at the concentration of 10(-6)-10(-4) M. The addition of 10(-5) M CS-045 showed an immediate increase of cytoplasmic free Ca2+ concentrations ([Ca2+]i). Removal of extracellular Ca2+ by the addition of 1.5 mM EGTA completely abolished the 10(-4) M CS-045-induced insulin secretion for 10-min. Long-term incubation (24 h) with 10(-4) M CS-045 significantly decreased beta-cell insulin content and inhibited insulin secretion. During a 5-day incubation, CS-045 showed a dose-dependent reduction of insulin secretion measured during the final 24 h. Long-term incubation with CS-045 over 3 days inhibited the beta-cell proliferation rate, assessed with [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay. CS-045 dose dependently increased the amount of DNA fragmentation measured by ELISA. The addition of nifedipine failed to attenuate the reduction of beta-cell proliferation rate and insulin secretion by CS-045, nifedipine antagonized an increase in the amount of DNA fragmentation caused by 10(-4) M CS-045. The present studies provide evidence that CS-045 inhibits beta-cell function following an acute stimulation of insulin secretion in HIT-T 15 cells. The immediate stimulation of insulin secretion by CS-045 may be mediated by an increase in Ca2+ influx from extracellular space. The induction of apoptosis may partially involves the reduction of beta-cell number by CS-045.

Animals↗
PubMed1998

Effect of epalrestat, an aldose reductase inhibitor, on the generation of oxygen-derived free radicals in neutrophils from streptozotocin-induced diabetic rats.

Neutrophil function is impaired by a known mechanism in diabetic patients, thus increasing susceptibility to infections. We studied the effect of epalrestat, an aldose reductase inhibitor, on the generation of oxygen-derived free radicals and cytosolic sorbitol concentration in neutrophils from streptozotocin-induced diabetic rats. There were four groups: treated and untreated control and diabetic rats. Treated groups were given 0.075% epalrestat in their diet for 4 weeks from the induction of diabetes and were untreated for the subsequent 4 weeks. Oxygen radicals were measured as chemiluminescence amplified by a luciferin analog [Cypridina luciferin analog-dependent chemiluminescence (CLA-DCL), which is dependent on O2- generation] and luminol (L)-DCL, which is highly dependent on OCl- generation) in response to formyl-methonyl-leucyl-phenylalanine. Diabetes resulted in a significant decrease in CLA/L-DCL and a significant increase in sorbitol (P < 0.01); there was a negative correlation between sorbitol and CLA-DCL (P < 0.05) in diabetic groups. The 4-week treatment with epalrestat in the diabetic group completely prevented the increase in sorbitol and partially improved the CLA-DCL, although L-DCL was not significantly affected. After 4 weeks off treatment, CLA-DCL decreased and sorbitol increased. Treatment had no effect on serum insulin or glucose concentration. We conclude that an increase in sorbitol in neutrophils causes, in part, an impaired generation of O2-. Epalrestat improves the impaired O2- generation by preventing the sorbitol increase in streptozotocin-induced diabetic rats.

Aldehyde Reductase↗
PubMed1998

Localization of pNT22 70 kDa heat shock cognate-like protein in the plasma membrane.

It has been argued that 70 kDa heat shock cognate (hsc73)-like molecules may be expressed on the surface of certain cells, but direct evidence of this has yet to be found. To clarify whether this molecule belongs to hsc73 itself, the membrane protein fraction of Daudi cells was isolated by Triton X-114 phase separation and the reactivity of this membrane protein fraction was assessed with monoclonal antibodies (mAbs) which react with 70 kDa heat shock protein (hsp) family, i.e., NT22, A15 and 3A3. In western blotting analysis, mAb NT22-defined protein (pNT22) was clearly detected as a membrane protein of Daudi cells with an approximate molecular size of 70 kDa, whereas pNT22 was not recognized by anti-cytoplasmic hsc73/hsp72 mAbs A15 or 3A3. By using deleted recombinant hsc73 proteins, it was determined that mAb NT22 recognizes the N-terminal 350-372 amino acid stretches of the hsc73 protein. mAb NT22 also reacted with the cell surface protein of Daudi cells in FACS analysis. Taken together, our present data strongly suggest that pNT22 may be a novel hsc73-like protein that is localized in the plasma membrane.

Antibodies, Monoclonal↗
PubMed1998

Use of hemoglobin as an iron source by Bacillus cereus.

The hemoglobin binding activity of Bacillus cereus cells was measured with fluoresceinisothiocyanate (FITC)-conjugated hemoglobin using flow cytometry. Growth of B. cereus was markedly inhibited by the addition of apo-transferrin. B. cereus could not use transferrin-bound iron as an iron source in serum. The growth inhibition was reversed by the addition of a FeCl3 solution, erythrocytes or hemoglobin. B. cereus released hemolysin; these findings suggested that the hemoglobin released from erythrocytes by B. cereus hemolysin binds to B. cereus and is thus used as an iron source.

Apoproteins↗
PubMed1998

A case of cardiac sarcoidosis: significance of ventricular tachycardia originating from the septum.

A 65-year-old woman was admitted for assessment of recurrent tachycardia. Cross-sectional echocardiography showed that the anterobasal portion of the ventricular septum was thin and dyskinetic. An electrophysiologic study revealed ventricular tachycardia, during which marked fragmented potentials could be obtained from the anterior septal aspect of the right ventricle. The site of earliest activation was in the vicinity of the His bundle. A diagnosis of cardiac sarcoidosis was made by based on endomyocardial biopsy combined with the clinical manifestations. Ventricular tachycardia originating from the anterior septum may be an indicator of underlying cardiac sarcoidosis.

Aged↗
PubMed1998

Do adhesion molecules importantly regulate leukocyte kinetics within intraacinar microvessels of the lung?

Precise assessment of blood cell kinetics in the pulmonary microcirculation is extremely difficult because pulmonary microvascular architecture contains arterioles, venules and capillaries in an exceedingly intricate and densely convoluted fashion. Conventional epiluminescence microscopy may not be suitable for investigation of blood cell kinetic in the pulmonary microcirculation, in which arterioles, venules and capillary networks are not located in the same plane. To overcome these impediments, we recently developed a real-time confocal laser luminescence microscope with a high-speed analysis component having the capacity to yield confocal-images of rapidly moving cells at a rate of 1,000 frames/sec and at sufficiently high magnification. In the current review, we will first introduce the details of our newly developed observation system constructed with a view to estimation of blood cell dynamics in the intraacinar microcirculation of the lung. Applying this novel method to isolated perfused rat lungs, we will secondly address the issue of whether or not leukocyte-endothelium interactions in the pulmonary microcirculation qualitatively differ from those serving in the systemic microcirculation. We will particularly shed light on possible roles of endothelial ICAM-1, endothelial P-selectin and leukocyte L-selectin in distorting leukocyte kinetics in the intraacinar microvessels under a variety of diseased conditions, including prolonged exposure to a hyperoxic environment inducing a significant upregulation of ICAM-1 as well as P-selectin on the pulmonary microvascular endothelium, and stimulation of leukocytes by an IL-8 analog causing downregulation of leukocyte L-selectin but inverse upregulation of CD18-related integrins.

Animals↗
PubMed1998

Modulating activity of indomethacin to vincristine cytotoxicity in various human carcinoma cells.

The modulating activity of indomethacin to vincristine (VCR) was investigated in thirty human pulmonary carcinoma cell lines (adenocarcinoma 9, large cell carcinoma 9, squamous cell carcinoma 6, small cell carcinoma 6) and five other cell lines (colon carcinoma 2, melanoma 1, teratocarcinoma 1, thymoma 1). The survival of these cell lines treated with VCR with or without indomethacin (2 microg/ml) for 72 hours were examined using MTT assay, and IC50 values were calculated. When the cutoff level of potent combined effect in clinical use was set at 2-fold increase of sensitivity, the positive rate was 100% for adenocarcinomas and large cell carcinomas, 25% for squamous cell carcinomas, 33% for small cell carcinomas. Mean modulating index was 2.91 in adenocarcinomas, 1.92 in squamous cell carcinomas, 3.06 in large cell carcinomas and 1.67 in small cell carcinomas. Of the cell lines of other tumors, three cell lines (colon carcinoma 1, melanoma 1, teratocarcinoma 1) showed the potent combined effect of VCR and indomethacin, while indomethacin was not effective in modulating activity to VCR in a thymoma cell line and fibroblast cells. In conclusion, it is considered that modulating activity of indomethacin for VCR is a general effect for various human cancer cells, and combined use with VCR and indomethacin may be a useful modulation therapy for the advanced lung cancer.

Adult↗
PubMed1998

Hypothalamic corticotropin-releasing hormone is a mediator of the anorexigenic effect of leptin.

Leptin, ob gene product, inhibits feeding behavior and stimulates energy expenditure in rodents. Corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY), which act in the hypothalamus to influence energy homeostasis, may mediate the anorexic effect of leptin. The present studies were undertaken to examine the possible involvement of hypothalamic CRH in the anorexigenic action of leptin in male Wistar rats. Recombinant leptin (2 microg/rat), microinjected into the third ventricle, inhibited food intake at 2 h by 33.3% (P < 0.01) in rats that were deprived of food for 18 h. The intracerebroventricular injection of 2 microg leptin also increased hypothalamic CRH content (P < 0.05) at 2 h after its administration. Simultaneous intracerebroventricular administration of 5 microg/rat alpha-helical CRH 9-41 (alpha-hCRH), a CRH antagonist, with 2 microg/rat leptin attenuated the anorexic effect of leptin by 2 h. In contrast, single intracerebroventricular injection of alpha-hCRH did not affect food consumption in food-deprived rats. These results implicate hypothalamic CRH as an important mediator of the anorexic effect of leptin in food-deprived rats.

Animals↗