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Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 217 records · Page 12Linked to original sources

Evaluation of antibody class in response to endoscopic subureteral collagen injection in patients with vesicoureteral reflux.

PURPOSE: Clinical problems after glutaraldehyde cross-linked collagen injection for vesicoureteral reflux are the appearance of anticollagen antibodies and a decrease in collagen with time. We evaluated whether antibody production affects reflux recurrence and implanted collagen absorption. MATERIALS AND METHODS: We treated 27 patients (39 ureters) who had vesicoureteral reflux with endoscopic subureteral glutaraldehyde cross-linked collagen injection. The maximum diameter of the elevated ureteral orifice was measured 3-dimensionally and the numerical value calculated by multiplying each diameter by approximately pi/6 was used as the ultrasound estimate of injected collagen volume. The 1-to-6-month collagen volume ratio was used as an index of the decrease in implant collagen volume. The antibody class against bovine collagen was characterized by indirect enzyme-linked immunosorbent assay. RESULTS: Seroconversion in 6 patients was noted a mean 6.8 months after the first injection. In these patients the antibody class was IgG dominant and IgA or IgM was not detected. There was no significant difference in the total injected collagen volume, total number of injections or collagen volume ratio in the seropositive and seronegative groups. Reflux recurred in 4 patients and the curve of the reflux-free rate was similar regardless of antibody appearance. CONCLUSIONS: The immune response to bovine collagen injection for vesicoureteral reflux does not depend on injected collagen volume or an increased number of treatments. Antibody production had no effects on absorption of the implanted collagen or reflux recurrence.

Adult↗

Successful subcutaneous pancreatic islet transplantation using an angiogenic growth factor-releasing device.

INTRODUCTION: Although the subcutaneous tissue is considered as an attractive site for pancreatic islet transplantation, the success rate has been extremely low. AIMS: To use basic fibroblast growth factor (bFGF) to induce neovascularization and sufficient blood flow around the space formed for grafted islets in the subcutaneous tissue to improve the islet survival. METHODOLOGY: In the experimental group, two bFGF-releasing devices were implanted bilaterally into the subcutaneous tissue (back) of diabetic Lewis rats. One week after implantation, in the same site, isolated rat islets were syngeneically transplanted after the removal of the devices. In the control group, two devices without bFGF were implanted before subcutaneous islet transplantation of the same number of islets. RESULTS: One week after the implantation of the bFGF-releasing devices in the experimental animals, the devices induced angiogenesis by slow release of bFGF. After transplantation of islets, the neovascularized recipient rats showed significant decreases in nonfasting blood glucose concentration and maintained normoglycemia for more than 3 months. However, in the control group, all rats failed to achieve normoglycemia after transplantation in the absence of neovascularization. CONCLUSION: This study provides evidence that the subcutaneous tissue is a promising site for pancreatic islet transplantation, which suggests the acceptability of this treatment for diabetic recipients.

Animals↗

Cold preservation of rat pancreatic islets just above the freezing point using University of Wisconsin solution.

AIMS: To confirm whether rat islets stored at a temperature just above the freezing point using University of Wisconsin (UW) solution would remain viable for the short term. METHODOLOGY: Rat islets were stored for 24 hours in UW solution, either at 4 degrees C or at -0.6 degrees C (just above the specific freezing point of the UW solution). After cold storage, the islets were assessed for in vitro viability by static incubation and for in vivo viability by a transplantation study. One thousand islets preserved under different conditions were injected intraportally into a streptozotocin-induced diabetic rat as an isograft. Four weeks after the transplantation, an intravenous glucose tolerance test was performed. RESULTS: Islets stored at -0.6 degrees C showed higher insulin secretion rates than those stored at 4 degrees C on a static challenge. The interval from transplantation to the achievement of normoglycemia was also shorter in the -0.6 degrees C group than in the 4 degrees C group. After islet transplantation, the daily nonfasting plasma glucose concentration was higher in the 4 degrees C group than in the -0.6 degrees C group. When compared with the 4 degrees C group, the -0.6 degrees C group showed lower blood glucose values during all investigational periods on an intravenous glucose tolerance test. CONCLUSION: Islet preservation at -0.6 degrees C using UW solution is more advantageous for short term.

Animals↗

Characterization of (+/-)-bufuralol hydroxylation activities in liver microsomes of Japanese and Caucasian subjects genotyped for CYP2D6.

Twenty-four genetic polymorphisms in the CYP2D6 gene were analysed in liver DNA samples of 39 Japanese and 44 Caucasians and compared with CYP2D6 protein levels and bufuralol 1'- and 6-hydroxylation activities in liver microsomes of these human samples. We detected 13 types of CYP2D6 genetic polymorphisms and classified these into 20 genotypes; nine types were found in Japanese and 14 types in Caucasian samples. CYP2D6*10B, but not CYP2D6*10A, was the most frequent (34.6%) in Japanese. In Caucasians, several CYP2D6 polymorphisms including CYP2D6*4, *4D, *4E, *4L, *3, *9, *5 and *2E (frequencies of 6.8, 3.4, 4.5, 9.1, 1.1, 2.3, 2.3 and 4.5%, respectively) were detected. A Caucasian having CYP2D6*3/*5 had a protein with slower gel mobility (immunoblotting with anti-CYP2D6 antibody) and very low activity for bufuralol 1'-hydroxylation. Five Caucasian samples (CYP2D6*4/*4, *4/*4L, or *4D/*4L) had no measurable CYP2D6 protein and very low bufuralol 1'-hydroxylation activities. Seven Japanese subjects with CYP2D6*10B/*10B had CYP2D6 protein at levels of approximately 20% of those present in humans with CYP2D6*1 and *2 and catalysed bufuralol 1'-hydroxylation at low rates. Kinetic analysis of bufuralol 1'- and 6-hydroxylation indicates that (i) the Km values for 1'-hydroxylation were lower in individuals with CYP2D6*1/*1, *1/*2, *1/*2X2, and *2/*2 than those with CYP2D6*4/*4, *4/*4L, *4D/*4L, or *10B/*10B and Vmax values tended to be higher in the former groups (*1, *2), and (ii) individuals with heterozygous CYP2D6*1/*4D, *1/*4L, and *1/*5 had relatively high Vmax/Km ratios, whereas individuals with heterozygous CYP2D6*1/*9, *2/4D, *2/*5, *2/*10B, *2E/*4E, *3/*5, *4L/*9, and *10B/*39 had lower Vmax/Km ratios for bufuralol 1'-hydroxylation. Quinidine inhibited bufuralol 1'-hydroxylation in liver microsomes, particularly at low substrate concentrations, in individuals with CYP2D6*1/*1, and 1/1*2, but not those with CYP2D6*4/*4 and very slightly in individuals with CYP2D6*10B/*10B. The latter two groups were found to be more sensitive to alpha-naphthoflavone than the former groups, indicative of the contribution of CYP1A2. These results support the view that CYP2D6*3, *4, *4D, and *4L are major genotypes producing poor metabolizer phenotypes in CYP2D6 in Caucasians, whereas CYP2D6*10B is a major factor in decreased CYP2D6 protein expression and catalytic activities in Japanese.

Asian People↗

Rapid progression of hepatocellular carcinoma after transcatheter arterial chemoembolization and percutaneous radiofrequency ablation in the primary tumour region.

We report one patient who showed rapid progression of hepatocellular carcinoma (HCC) after undergoing transcatheter arterial chemoembolization (TACE) and percutaneous radiofrequency ablation (PRFA) for a small HCC measuring 2.5 cm in diameter. Enhanced magnetic resonance imaging (MRI) following treatment showed complete tumour necrosis and did not reveal the presence of a tumour around the treated area. Furthermore, the serum alpha-fetoprotein (AFP) level decreased at the completion of therapy. However, the HCC advanced in a very short time. Numerous tumours around the treated area were observed on enhanced computed tomography (CT) 50 days after PRFA. It is strongly suspected that the tumour was disseminated through the portal system because of the presence pattern of tumours. We believe this to be the first case illustrating a hepatic cancer that progressed rapidly following TACE and PRFA.

Aged↗

The 1.4-Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes.

Duplication and deletion of the 1.4-Mb region in 17p12 that is delimited by two 24-kb low copy number repeats (CMT1A-REPs) represent frequent genomic rearrangements resulting in two common inherited peripheral neuropathies, Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsy (HNPP). CMT1A and HNPP exemplify a paradigm for genomic disorders wherein unique genome architectural features result in susceptibility to DNA rearrangements that cause disease. A gene within the 1.4-Mb region, PMP22, is responsible for these disorders through a gene-dosage effect in the heterozygous duplication or deletion. However, the genomic structure of the 1.4-Mb region, including other genes contained within the rearranged genomic segment, remains essentially uncharacterized. To delineate genomic structural features, investigate higher-order genomic architecture, and identify genes in this region, we constructed PAC and BAC contigs and determined the complete nucleotide sequence. This CMT1A/HNPP genomic segment contains 1,421,129 bp of DNA. A low copy number repeat (LCR) was identified, with one copy inside and two copies outside of the 1.4-Mb region. Comparison between physical and genetic maps revealed a striking difference in recombination rates between the sexes with a lower recombination frequency in males (0.67 cM/Mb) versus females (5.5 cM/Mb). Hypothetically, this low recombination frequency in males may enable a chromosomal misalignment at proximal and distal CMT1A-REPs and promote unequal crossing over, which occurs 10 times more frequently in male meiosis. In addition to three previously described genes, five new genes (TEKT3, HS3ST3B1, NPD008/CGI-148, CDRT1, and CDRT15) and 13 predicted genes were identified. Most of these predicted genes are expressed only in embryonic stages. Analyses of the genomic region adjacent to proximal CMT1A-REP indicated an evolutionary mechanism for the formation of proximal CMT1A-REP and the creation of novel genes by DNA rearrangement during primate speciation.

Animals↗

The evolutionary chromosome translocation 4;19 in Gorilla gorilla is associated with microduplication of the chromosome fragment syntenic to sequences surrounding the human proximal CMT1A-REP.

Many genomic disorders occur as a result of chromosome rearrangements involving low-copy repeats (LCRs). To better understand the molecular basis of chromosome rearrangements, including translocations, we have investigated the mechanism of evolutionary rearrangements. In contrast to several intrachromosomal rearrangements, only two evolutionary translocations have been identified by cytogenetic analyses of humans and greater apes. Human chromosome 2 arose as a result of a telomeric fusion between acrocentric chromosomes, whereas chromosomes 4 and 19 in Gorilla gorilla are the products of a reciprocal translocation between ancestral chromosomes, syntenic to human chromosomes 5 and 17, respectively. Fluorescence in situ hybridization (FISH) was used to characterize the breakpoints of the latter translocation at the molecular level. We identified three BAC clones that span translocation breakpoints. One breakpoint occurred in the region syntenic to human chromosome 5q13.3, between the HMG-CoA reductase gene (HMGCR) and RAS p21 protein activator 1 gene (RASA1). The second breakpoint was in a region syntenic to human chromosome 17p12 containing the 24 kb region-specific low-copy repeat-proximal CMT1A-REP. Moreover, we found that the t(4;19) is associated with a submicroscopic chromosome duplication involving a 19p chromosome fragment homologous to the human chromosome region surrounding the proximal CMT1A-REP. These observations further indicate that higher order genomic architecture involving low-copy repeats resulting from genomic duplication plays a significant role in karyotypic evolution.

Animals↗

Downregulation of caffeic acid 3-O-methyltransferase and caffeoyl CoA 3-O-methyltransferase in transgenic alfalfa. impacts on lignin structure and implications for the biosynthesis of G and S lignin.

Transgenic alfalfa plants were generated harboring caffeic acid 3-O-methyltransferase (COMT) and caffeoyl CoA 3-O-methyltransferase (CCOMT) cDNA sequences under control of the bean phenylalanine ammonia-lyase PAL2 promoter. Strong downregulation of COMT resulted in decreased lignin content, a reduction in total guaiacyl (G) lignin units, a near total loss of syringyl (S) units in monomeric and dimeric lignin degradation products, and appearance of low levels of 5-hydroxy guaiacyl units and a novel dimer. No soluble monolignol precursors accumulated. In contrast, strong downregulation of CCOMT led to reduced lignin levels, a reduction in G units without reduction in S units, and increases in beta-5 linked dimers of G units. Accumulation of soluble caffeic acid beta-d-glucoside occurred only in CCOMT downregulated plants. The results suggest that CCOMT does not significantly contribute to the 3-O-methylation step in S lignin biosynthesis in alfalfa and that there is redundancy with respect to the 3-O-methylation reaction of G lignin biosynthesis. COMT is unlikely to catalyze the in vivo methylation of caffeic acid during lignin biosynthesis.

Base Sequence↗

Phage display cloning and characterization of monoclonal antibody genes and recombinant Fab fragment against the CD98 oncoprotein.

The Fab gene of anti-CD98 heavy chain (h.c.) monoclonal antibody (mAb) HBJ127 was cloned and expressed as a recombinant Fab (rFab) fragment by means of a phage display system. The variable heavy and light chain genes of HBJ127 were found to be derived from VOx-1 and IgVk8-30 germline, respectively. Extensive somatic mutation was found in the heavy chain complementarity determining region 2. rFab fragment was purified homogeneously from crude bacterial lysates by Ni-chelate chromatography in a yield of 71.4 mg from 100 ml of culture. rFab fragment was reactive with the cell surface of CD98-positive cells irrespective of tissues of origin, but not with CD98-negative cells. The recognition site of the rFab fragment was identical to that of mAb since the binding of rFab fragment to HeLaS(3) cells was completely inhibited by pretreatment with an excess of mAb. The relative affinity values of rFab fragment and mAb were found to be 0.11 x 10(8) and 0.35 x 10(8) M(-1), respectively. Three-fold lower affinity of rFab fragment may be due to the difference of valency of the antibody preparation. Cell growth inhibition in vitro by rFab fragment preincubated with anti-Fab suggests that the rFab fragment produced by cloned gene-bearing Escherichia coli was identical to the Fab part of HBJ127 mAb. These results show that a small fragment with antigen binding activity similar to that of the parent mAb can easily be prepared by using a phage display system. To our knowledge, this is a first report of the production of anti-CD98 h.c. rFab fragment.

Amino Acid Sequence↗

A homozygous missense mutation in the tyrosine E kinase domain of the RET proto-oncogene in an infant with total intestinal aganglionosis.

Germline mutations of the RET proto-oncogene (RET), its ligand glial cell-derived neurotrophic factor (GDNF), and neurturin (NTN) gene have been reported in patients with Hirschsprung's disease. A targeted mutation in the tyrosine kinase domain of RET produced total intestinal aganglionosis and renal agenesis in homozygous transgenic mice. Here we describe a homozygous mutation of the human gene for the RET tyrosine kinase domain that was present in a male neonate with total intestinal aganglionosis. Gut wall biopsy specimens from the stomach to the anorectum showed no ganglion cells. No urinary tract abnormalities were detected. Genomic DNAs were isolated from peripheral blood lymphocytes of the infant and his parents. DNA sequences of all the RET/GDNF/NTN coding regions were determined using a direct DyeDeoxy Terminator Cycle method. A homozygous missense mutation (CGG-to-TGG) at RET codon 969 was identified in this patient, which resulted in an amino acid change from arginine to tryptophan. No germline RET/GDNF/NTN mutations were found in his parents. In this case, the homozygous RET mutation seemed to cause a critical alteration of the Ret tyrosine kinase activity, which resulted in total intestinal aganglionosis but not renal agenesis. Discrepancies in phenotypic expression between humans and mice suggest differing threshold values for RET signal transduction in species or organs.

Drosophila Proteins↗

Words of Tohkaku Wada: medical heritage in Japan.

The origins of Japan's medical ideas, which are deeply rooted in its religion, culture and history, are not widely understood in medical societies of other countries. We have taken up the task of summarising this tradition here so that some insight can be gained into the unique issues that characterise the practice of medicine in Japan. We borrow from the sayings of Tohkaku Wada, a medical philosopher of late eighteenth-century Japan, for a look at Japanese medical tradition. Wada's medical thought was very much reflective of the Buddhism, Zen, and swordsmanship that informed eighteenth-century philosophy in Japan. His central concepts were "chu" and "sei", that is, complete and selfless dedication to the patient and the practice of medicine. This paper explores Wada's thought, explaining it mainly from the standpoint of Japanese traditional culture.

Buddhism↗

Enhanced expression and release of C-type natriuretic peptide in freshwater eels.

C-type natriuretic peptide (CNP) is recognized as a paracrine factor acting locally in the brain and periphery. To assess the role of CNP in teleost fish, a cDNA encoding a CNP precursor was initially cloned from the eel brain. CNP message subsequently detected by ribonuclease protection assay, using the cDNA as probe, was most abundant in the brain followed by liver, gut, gills, and heart. Expression was generally higher in freshwater (FW) than in seawater (SW) eels, but not in the brain. Plasma CNP concentration measured by a newly developed homologous radioimmunoassay for eel CNP was higher in FW than in SW eels. The CNP concentration was also higher in the heart of FW eels but not in the brain. These results show that CNP is abundantly synthesized in peripheral tissues of FW eels and secreted constitutively into the circulation. Therefore, CNP is a circulating hormone as well as a paracrine factor in eels. Together with our previous demonstration that CNP-specific receptor expression is enhanced in FW eels, it appears that CNP is a hormone important for FW adaptation. Because atrial NP (ANP) promotes SW adaptation in eels, CNP and ANP, despite high sequence identity, appear to have opposite effects on environmental adaptation of the euryhaline fish.

Amino Acid Sequence↗

Dye-staining stereomicroscopic examinations for fine mucosal structures of the gallbladder.

BACKGROUND: In order to diagnose an unsuspected gallbladder carcinoma and to examine whether a differential diagnosis could be made between cancer and noncancerous lesions during surgery, we evaluated the findings of fine structures of various types of gallbladder mucosa. METHODS: We used stereomicroscopy with a dye-contrast technique under water and measured the maximum blood vessel diameters of the gallbladder mucosa: normal gallbladder, chronic cholecystitis, and carcinoma. RESULTS: All normal gallbladders showed fine-reticular-type findings. In chronic cholecystitis, 5.8% of the specimens (n = 69) had fine reticular type, 87.0% had rough reticular type, and 7.2% had atrophic type. All the cases of adenomyomatosis (n = 16) showed rough reticular type. In eight specimens of pancreaticobiliary maljunction, 75% of them showed high reticular type, and the other 25% showed papillary type. The two adenoma specimens showed fine granular type. In five gallbladder carcinomas, the lattice-like pattern completely disappeared and showed rough granular type. The average of maximum vessel diameters in the gallbladder mucosa were 41.0 microm in normal gallbladders, 99.1 microm in patients with chronic cholecystitis, and 614.8 microm in patients with a carcinoma. There were significant differences among them (p < 0.05). CONCLUSION: This study showed that differential diagnosis between cancer and noncancerous lesion is possible by dye-staining mucosal pattern and measurement of maximum vessel diameters by stereoscopic examination.

Adenoma↗

Purification of the major allergen of red soft coral (Dendronephthya nipponica).

Red soft coral (RSC; Dendronephthya nipponica, a marine coelenterate) causes spiny lobster fishermen living along the Pacific coast of Miyazaki Prefecture in Japan to develop occupational allergies, such as conjunctivitis, rhinitis, dermatitis and bronchial asthma. The aim of this study was to purify and to characterize RSC allergen, which causes occupational asthma in spiny lobster fishermen. The allergic responsiveness of spiny lobster fishermen to RSC was examined. The examinations included specific IgE production, skin test responses, lymphocyte stimulation tests and specific IgG production. We found that RSC has a strong sensitizing activity in humans at a molecular weight of 10 kD or more, while it has no IgE-producing activity at a molecular weight of less than 10 kD. Neither the nonatopic controls nor the atopic non-coral-allergic controls exhibited any RAST-binding activity to any fraction. For the purification and the identification of this new allergen component, repeated gel filtration of the RSC extract was performed on a Sephacryl S-200 column, followed by gel filtration on a Superose-6 column. The purified major allergen component Den n 1, which is separated on a Mono-Q column, showed intradermal responses, lymphocyte stimulating activity and specific IgG-producing activity in RSC-induced bronchial asthma patients. The 53-kD component was electroblotted on a polyvinylidene difluoride membrane. The N-terminal amino acid sequence of this new allergen component (Den n 1) was determined as Asp-Asp-Ile-Asn-Arg-Tyr-Ala-Phe-Asp-Asn-Lys-Ile-Asn- Asp-Lys-Leu-Phe-Asp-His-Trp-Gln-Ser.

Adult↗

Homebound status in a community-dwelling elderly population in Japan.

The present study investigated the association between sociodemoraphic profiles, health condition and functional disabilities of subjects with a homebound status in a rural community setting. The subjects were residents aged 65 years or over in a mountain village of Japan. A comprehensive questionnaire was used to obtain their data. Among the 1,002 residents, the information of 866 residents (85%), who voluntarily completed the entire survey, was obtained for this study. All the subjects were native Japanese. Of the 866 subjects investigated, 301 (34.8%) were homebound as defined by the parameters of this study. Univariate analysis revealed age, female gender, functional impairment (vision, hearing and memory), all the ADL impairments, and the use of a portable toilet were associated with homebound status. Multivariate analysis revealed that older age, female gender, visual and two ADL impairments (moving inside the home and bathing) and use of a portable toilet remained significantly related to homebound status. Homebound elderly people have more functional limitation and disability related factor than their nonhomebound counterparts. Functional impairment, particularly in the mobility domain and sensory disturbances, was associated with homebound status. These data indicate the importance of assessment in the provision of home care for elderly people.

Activities of Daily Living↗

Effects of stimulus intensity on latency and conduction time of short-latency somatosensory evoked potentials.

We studied the effect of stimulus intensity on latencies of short-latency somatosensory evoked potentials (SSEP) by measuring both onset and peak latencies individually. The latencies of N9, N13, N20 and N9-N13 peripheral conduction time (PCT) of median nerve (MN) SSEP, and N8, N23, P37 and N8-N23 PCT of tibial nerve (TN) and sural nerve (SN) SSEP significantly shortened with increasing stimulus intensity by onset latency measurement. However, those latencies by peak latency measurement were less significantly shortened or had only a trend of latency shortening without statistical significance. In contrast to PCT, N13-N20 central conduction time (CCT) of MN-SSEP and N23-P37 CCT of TN- or SN-SSEP showed no latency changes with the increased stimulus intensity by both onset and peak latencies measurement. As peak latencies had greater interindividual variability than onset latencies shown by larger standard deviation, shortening of onset latencies were more consistent than that of peak latencies. We think shortening of onset latencies indicates the recruitment of faster conduction fiber along with increased stimulus intensity. As the degree of latency shortening was less if stimulus intensity was above 2.5 times sensory threshold, the stimulus intensity greater than 2.5 times the sensory threshold should be used for clinical application.

Adult↗

Prolactin-releasing peptide as a novel stress mediator in the central nervous system.

A1/A2 noradrenergic neurons in the medulla oblongata are well known to mediate stress signals in the central nervous system. Stress activates A1/A2 noradrenergic neurons, and then noradrenaline (NA) stimulates ACTH secretion through hypothalamic CRH. On the other hand, PRL-releasing peptide (PrRP) was recently isolated and was found to be produced by some A1/A2 neurons and the dorsomedial hypothalamic nucleus. We previously demonstrated that PrRP neurons make synapse-like contact with hypothalamic CRH neurons. In fact, we demonstrated that the central administration of PrRP stimulates CRH-mediated ACTH secretion. Furthermore, it has been reported that PrRP neurons in A1/A2 cell groups are colocalized with tyrosine hydroxylase (TH), which is known as the marker enzyme of catecholaminergic neurons. These data strongly suggest that PrRP is related to stress-responsive signal transduction, and PrRP and NA cooperatively modulate the hypothalamo-pituitary-adrenal axis. We therefore examined the effect of water immersion-restraint stress on c-Fos protein accumulation in PrRP- and TH-immunoreactive neurons. The synergistic effects of PrRP and NA on plasma ACTH elevation were also examined. The results clearly showed that c-Fos protein accumulation dramatically increased in the nuclei of A1/A2 and dorsomedial hypothalamic nucleus PrRP neurons. In addition, it was revealed that c-Fos protein was specifically expressed in the PrRP/TH double positive cells in the A1/A2 cell groups. We also demonstrated that the central administration of PrRP and NA in combination at subactive (noneffective) doses clearly induced plasma ACTH elevation. Here we report that PrRP is a novel and important mediator of the hypothalamo-pituitary-adrenal axis for the stress response.

Adrenocorticotropic Hormone↗

Effects of the 5-HT2 receptor antagonist, ritanserin on hyperthermia and depletion of 5-HT in frontal cortex induced by a 5-HT releasing drug, p-chloroamphetamine (PCA) in mice.

Effects of the 5-HT2 receptor antagonist, ritanserin on hyperthermia and depletion of 5-HT induced by the 5-HT-releasing drug, p-chloroamphetamine (PCA) were investigated. Ritanserin significantly suppressed PCA-induced hyperthermia in mice. PCA elicited decreases in 5-HT levels in the mouse frontal cortex. 5-HT reduction elicited by PCA was also attenuated by pretreatment with ritanserin. Since hyperthermia facilitates neurotoxicity induced by amphetamine analogue, ritanserin may inhibit PCA-induced 5-HT neurotoxicity by inhibiting hyperthermia.

Animals↗