Biomedical subjects

T Sakai

Publications and source records attributed to T Sakai.

At least 361 records · Page 20Linked to original sources

PubMed1999

Prevalence of calf diarrhea caused by bovine group A rotavirus carrying G serotype 8 specificity.

One hundred and seventeen rectal fecal specimens were collected in 1995 and 1996 from calves with diarrhea in Kagoshima Prefecture in Japan. The bovine group A rotavirus was detected by enzyme immunoassay in 43 of 117 specimens and isolated from 33 of the 43 specimens that were positive. G serotype, P serotype, and P genotype of 33 isolates were identified by reverse transcription-polymerase chain reaction, and 20 of 33 isolates (60.6%) were identified as G serotype 8. Thus, we discovered that calf diarrhea caused by bovine group A rotavirus carrying G serotype 8 specificity was prevalent in this research area during this research period. To our knowledge, this is the first report on the prevalence of calf diarrhea caused by the bovine group A rotavirus carrying G serotype 8 specificity.

Animals↗

PubMed1999

Expression and role of heat-shock protein 65 (HSP65) in macrophages during Trypanosoma cruzi infection: involvement of HSP65 in prevention of apoptosis of macrophages.

The 65-kDa heat-shock protein (HSP65) is thought to play a role in host defense against infections with various microbial pathogens and in autoimmune inflammatory disorders. We investigated the biological function and expression mechanism of HSP65 in macrophages of mice infected with Trypanosoma cruzi. BALB/c mice, which are susceptible to T. cruzi, showed high levels of parasitemia, and 80% of these mice died within 42 days after the infection, whereas resistant C57BL/6 or DBA/2 mice showed low levels of transient parasitemia and all survived. HSP65 expression was correlated with resistance to T. cruzi infection; HSP65 was more strongly expressed in macrophages of resistant C57BL/6 and DBA/2 mice than in macrophages of susceptible BALB/c mice. Immunodeficient BALB/c-nu/nu (nude) and C.B-17 scid/scid (SCID) mice were shown to be highly susceptible to this infection, and they did not express detectable levels of HSP65, suggesting that T cells play essential roles in the expression of HSP65 as well as in protective immunity against the infection. CD4(+) T cells, but not CD8(+) T cells or gammadelta T cells, were the cell population responsible for the induction of HSP65 expression in macrophages. Furthermore, depletion of asialo GM-1(+) NK cells made resistant C57BL/6 mice more susceptible to the infection, and HSP65 expression in their macrophages was abolished. Semiquantitative reverse transcription PCR analyses showed that both interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) mRNA levels in CD4(+) T cells became low when resistant C57BL/6 mice were depleted of NK cells, suggesting that NK cells contribute to functional differentiation of CD4(+) T cells and thereby affect the induction of HSP65 expression. To determine the function of HSP65, macrophages were treated in vitro with antisense oligonucleotide for HSP65 prior to inducing HSP65 with IFN-gamma plus TNF-alpha or T. cruzi infection. This treatment did not affect the production of nitric oxide following activation, but the treated macrophages became susceptible to apoptosis. These results indicate that HSP65 plays a role in preventing the apoptosis of macrophages and thereby contributes to host resistance against T. cruzi infection.

Animals↗

PubMed1999

DNA immunization with Plasmodium falciparum serine repeat antigen: regulation of humoral immune response by coinoculation of cytokine expression plasmid.

We immunized mice with plasmid expressing the 47-kDa amino-terminal domain of the Plasmodium falciparum serine repeat antigen (SERA) using gene gun and investigated humoral immune response to SERA antigen. Significant SERA-specific IgG was observed in BALB/c mice after immunization three times with SERA expression plasmid. Furthermore, these levels were increased by the coinoculation of cytokine (IFN-gamma, IL-4, GM-CSF, or IL-12) expression plasmid. In respect to the SERA-specific Ig subclasses, coinoculation of IFN-gamma, GM-CSF, or IL-12 expression plasmid increased the levels of SERA-specific IgG2a, and these were much higher than that in mice immunized with SERA expression plasmid alone. In contrast to the SERA-specific IgG2a, coinoculation of any cytokine expression plasmid did not change the levels of SERA-specific IgG1. These results indicate that cytokine expression plasmid enhances and regulates humoral immune response elicited by SERA DNA immunization.

Animals↗

PubMed1999

Isolation and genetic determination of a Saccharomyces cerevisiae mutant that produces an endo-polygalacturonase.

A Saccharomyces cerevisiae mutant that produces an endo-polygalacturonase (PGase) was isolated. The PGase gene was revealed to be located on chromosome X in both the mutant and its parental strain. The 5'-upstream region of the PGase gene in the mutant was entirely identical with that of its parent. Crossing of the mutant with a PGase-negative strain showed that the phenotype of PGase production was recessive. These results suggest that the mutant is rendered defective in a transacting factor that normally represses the expression of the PGase gene.

Journal Article↗

PubMed1999

Kinetic study on thermal denaturation of hen egg-white lysozyme involving precipitation.

A kinetic study on the thermal denaturation accompanying precipitation of hen egg-white lysozyme was performed at temperatures between 50 and 90 degrees C. Visible precipitation occurred at lysozyme concentrations higher than 10(-5)M. Even at the concentration of 10(-6)M where no visible precipitation was observed, irreversible and reversible denaturation could be clearly discriminated. The former involves two different reactions with activation energies of approximately 93 and 50 kJ x mol(-1). On the other hand, enthalpy and entropy changes in the latter are 443 kJ x mol(-1) and 1280 J x K(-1) x mol(-1), respectively, indicating a large conformational change. The contradiction that the denaturation or deactivation reaction fitted first-order reaction kinetics while its rate constant depended on the protein concentration, was resolved by newly proposed schemes. The apparent first-order rate constant obtained experimentally depended on the initial protein concentration being on the order of almost unity. Moreover, it was revealed that the apparent first-order reaction involved a second-order reaction that characterized the aggregation of denatured protein molecules. The theory developed here explained reasonably the thermal denaturation accompanying precipitation that occurs at high protein concentration and at high temperature, and was also successfully applied to the lower concentration range with no accompanying precipitation.

Journal Article↗

PubMed1999

Identification and expression of the kosena radish (Raphanus sativus cv. Kosena) homologue of the ogura radish CMS-associated gene, orf138.

A CMS-associated gene, orf125, present in the Japanese radish cultivar Kosena, has a sequence homologous to that of the ogura CMS-associated gene, orf138, except for two amino acid substitutions and a 39 bp deletion in the orf138 coding region. In Kosena radish, orf125 is linked with orfB, whereas the orf125 locus differs in a Brassica napus CMS cybrid derived from protoplast fusion between Kosena radish and B. napus. A novel mtDNA sequence is present in the 3'-flanking region of orf125 in the B. napus kosena CMS cybrid. The orf125 is expressed both in the radish and the B. napus kosena CMS cybrid. Its accumulation is strongly associated with the CMS phenotype in B. napus. Fertility restoration was accompanied by a decrease in the amount of ORF125 in B. napus.

Amino Acid Sequence↗

PubMed1999

Direct evidence of gonadotropin-releasing hormone (GnRH)-stimulated nitric oxide production in the L beta T-2 clonal gonadotropes.

An immortal cell line (L beta T-2) with characteristics of gonadotropes, such as LH-containing secretory granules, and LH release responsiveness to GnRH, was used to investigate the effect of GnRH stimulation on nitric oxide (NO) production. RT-PCR analysis showed that mouse nNOS mRNA was expressed in cultured L beta T-2 cells. L beta T-2 cells were treated with the calcium ionophore, A23187, and NO levels were measured as nitrite using the Griess assay. The data clearly showed that NO production was increased dose-dependently by A23187 treatment (0-10(-5) M). Next, changes in the intracellular concentration of ionized calcium ([Ca2+]i) in L beta T-2 cells induced by GnRH were analyzed by quantitative fluorescence microscopy, and [Ca2+]i was found to be increased markedly by GnRH treatment. In fact, exposure of L beta T-2 cells to increasing concentrations of GnRH from 0 to 10(-6) M was found to enhance NO production in a dose dependent manner, with maximal augmentation at 10(-6) M. However, the stimulation of NO production by GnRH at this concentration was significantly attenuated by pretreatment with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME), a NO synthase inhibitor. Taken together, the present results suggest that GnRH treatment results in increased NO production in L beta T-2 clonal gonadotropes, and intracellular calcium augmentation produced by GnRH may be participate in this process. Our findings also indicate that the L beta T-2 cell line is a useful tool for in vitro studies of the autocrine and paracrine roles of NO in the anterior pituitary gland.

Animals↗

PubMed1999

The effect of ketamine on clinical endpoints of hypnosis and EEG variables during propofol infusion.

BACKGROUND: We studied the effect of variable doses of ketamine on the endpoints of hypnosis, e.g., unresponsiveness to verbal commands (UVC), loss of eyelash reflex (LER), and inhibition of body movement response with or without sneezing to nasal membrane stimulation (INBMR), and processed EEG variables, e.g., bispectral index (BIS), 95% spectral edge frequency (SEF) and median frequency (MF) during propofol infusion. METHODS: Forty-eight patients received either propofol infusion, 30 mg.kg-1.h-1 (Group P; n = 12) or ketamine bolus, 0.25, 0.5 or 0.75 mg i.v., followed by propofol infusion, 30 mg.kg-1.h-1 + variable dose ketamine infusion, 0.25, 0.5 or 0.75 mg.kg-1.h-1 (Groups PK0.25, PK0.5 and PK0.75; n = 12 each) until UVC, LER and INBMR. BIS, 95% SEF and MF values were monitored and recorded at the endpoints of hypnosis. Propofol and ketamine concentrations were measured at INBMR. RESULTS: Propofol infusion, 30 mg.kg-1.h-1, induced UVC, LER and INBMR at BIS: 65 +/- 2, 63 +/- 9 and 33 +/- 7; 95% SEF: 17 +/- 3, 17 +/- 4 and 14 +/- 3; and MF values of 5 +/- 2, 5 +/- 3 and 3 +/- 2, respectively. With adjunctive ketamine (Groups PK0.5 and PK0.75), the hypnotic endpoints were achieved at higher BIS and 95% SEF values and lower propofol doses and concentrations as compared to Groups P and PK0.25 (9.9 +/- 5.8 and 9.4 +/- 3.4 vs. 13.4 +/- 4.5 and 14 +/- 5.8 micrograms.ml-1). CONCLUSIONS: Our results suggest additive interaction between propofol and ketamine (Groups PK0.5 and PK0.75) for achieving the hypnotic endpoints; however, ketamine did not depress the EEG variables in proportion to its hypnotic effect. The paradoxically higher BIS and 95% SEF values at the hypnotic endpoints may be due to lower propofol concentrations and/or no effect of ketamine on the EEG variables.

Adult↗

PubMed1999

Diminution of 37-kDa laminin binding protein expression reduces tumour formation of murine lung cancer cells.

Expression of the 37-kDa laminin binding protein (37LBP/p40), a precursor of the 67-kDa laminin receptor, is well-correlated with the biological aggressiveness of cancer cells. To elucidate the direct role played by 37LBP/p40 in cancer cells, a murine lung cancer cell line T11, the 37LBP/p40 expression of which was remarkably diminished, was established by the introduction of the antisense 37LBP/p40-RNA using a retroviral vector. As a result, the population doubling time of T11 was prolonged (60 h) compared with that of P29, the non-transfected parental cell line (42 h), and TN2, a transfectant with vehicle only (40 h). In-vitro studies also showed that T11 cells adhered to immobilized laminin less firmly than P29 cells did. When 5 x 10(5) cells were subcutaneously inoculated into syngenic mice, the mean survival time of T11-recipients (77.0+/-14.8 days) was also significantly prolonged compared with that for P29 (34.8+/-5.5 days) and TN2 (36.7+/-6.1 days) recipients (P < 0.001). The electron-microscopic view of the tumour tissue revealed that T11 cells were loosely apposed and their intercellular space was markedly widened. Some of the T11 cells sporadically degenerated with the infiltration of lymphocytes and neutrophils. These results suggest that the suppressed expression of 37LBP/p40 reduces the capability of lung cancer cell proliferation in vitro and tumour formation in vivo.

Animals↗

PubMed1999

Enhancement of membrane-type 1-matrix metalloproteinase (MT1-MMP) production and sequential activation of progelatinase A on human squamous carcinoma cells co-cultured with human dermal fibroblasts.

Matrix metalloproteinase 2 (MMP-2)/gelatinase A plays an important role in tumour invasion and metastasis. Since MMP-2 is secreted as an inactive form (proMMP-2) from tumour and neighbouring stroma cells, the activation process is necessary to express the enzymic activity for degradation of extracellular matrix components. We herein reported that the activation of proMMP-2 was induced in human squamous carcinoma cells co-cultured with normal human dermal fibroblasts. When A431 cells were co-cultured with human fibroblasts at various cell ratios, 72-kDa proMMP-2 was converted to a 62-kDa active form through the appearance of a 64-kDa intermediate. The activation of proMMP-2 by co-culture was also observed in other carcinoma cell lines, HSC-4 and SAS, but not in normal human keratinocytes. We characterized by in vitro invasion assay that A431 cells in co-culture preferentially invaded through Matrigel and the increased invasive activity was inhibited by exogenously adding tissue inhibitor of metalloproteinases 2. The augmented proMMP-2 activation by co-culture was achieved by the increase in membrane type 1-MMP (MT1-MMP) production along with that of its mRNA level. The predominant appearance of MT1-MMP was immunologically observed in A431 cells, but not human fibroblasts of the co-culture. Furthermore, epidermal growth factor (EGF) enhanced the co-culture-mediated proMMP-2 activation by increasing the production and gene expression of MT1-MMP, and thereby tumour invasive activity was further augmented. These results suggest that the cell-cell contact between carcinoma cells and normal fibroblasts enhances the production of MT1-MMP followed by sequential activation of proMMP-2 on the tumour cell surface, which may be closely implicated in tumour invasion in vivo.

Carcinoma, Squamous Cell↗

PubMed1999

A functional polymorphism in the promoter region of monoamine oxidase-A gene and mood disorders.

A polymorphism of a variable number tandem repeat (VNTR), that was recently found in the promoter region of the monoamine oxidase-A (MAOA) gene, was shown to be associated with its transcriptional activity. This study examined whether this functional polymorphism of the MAOA gene is associated with the risk of developing mood disorders in a Japanese sample of 161 patients with bipolar disorder, 98 with unipolar depression, and 258 controls. There was no significant genotypic or allelic association, suggesting that the functional VNTR polymorphism in the MAOA gene is unlikely to play a major role in the pathogenesis of bipolar disorder or unipolar depression. Furthermore, we found no association between the polymorphism and a history of suicide attempt.

Analysis of Variance↗

PubMed1999

Reliability of the omeprazole hydroxylation index for CYP2C19 phenotyping: possible effect of age, liver disease and length of therapy.

AIMS: To evaluate the reliability of the omeprazole hydroxylation index as a marker for polymorphic CYP2C19 activity in a Japanese population of healthy young subjects (n = 78) and patients with peptic ulcer (n = 72). METHODS: Healthy subjects were administered a single dose of omeprazole (20 mg), whereas patients received 20 mg daily for at least 1 week. The ratio of the serum concentration of omeprazole to hydroxyomeprazole at 3 h postdose was determined and used as a measure of CYP2C19 activity. The CYP2C19 wild type (wt) gene and four mutant alleles associated with the poor metaboliser phenotype of (S)-mephenytoin, CYP2C19*2 in exon 5, CYP2C19*3 in exon 4, CYP2C19m4 in exon 9, and CYP2C19m3 in the initial codon were analysed. RESULTS: In the healthy volunteer study there was complete concordance between genotype and phenotype. However, eight of the patients who had the EM genotype had a high value for their hydroxylation index, and were classified as phenotypic PMs. No CYP2C19m4 and CYP2C19m3 mutations were detected in the eight mismatched patients. They were all genotypic heterozygous EMs, elderly (> or = 65 years) and/or had hepatic disease. Therefore, impaired CYP2C19 activity combined with partial saturation of omeprazole metabolism during multiple dosing may have contributed to the discrepancy between CYP2C19 genotyping and phenotyping. CONCLUSION: Although omeprazole has been used instead of mephenytoin as a probe for polymorphic CYP2C19, it does not appear to be reliable enough for clinical application in Japanese patients.

Adult↗

PubMed1999

Hypnotic endpoints vs. the bispectral index, 95% spectral edge frequency and median frequency during propofol infusion with or without fentanyl.

Hypnotic endpoints and/or EEG variables, e.g. bispectral index, 95% spectral edge frequency and median frequency, have been studied to monitor anaesthetic (hypnotic) depth during total intravenous anaesthesia. In this study, the relation between the hypnotic endpoints of unresponsiveness to verbal commands, loss of eyelash reflex and body movement response to mechanical nasal membrane stimulation vs. bispectral index, 95% spectral edge frequency and median frequency during propofol anaesthesia with or without fentanyl is presented. Forty-two patients were randomly assigned to receive either propofol infusion, 30 mg kg-1 h-1 (n = 22), or propofol infusion, 30 mg kg-1 h-1 + fentanyl bolus, 2 micrograms kg-1 i.v. (n = 20). Bispectral index, 95% spectral edge frequency and median frequency and propofol doses were monitored and recorded at unresponsiveness to verbal commands, loss of eyelash reflex and inhibition of nasal body movement response. The bispectral index values were significantly higher in the propofol + fentanyl compared with the propofol group, i.e. 74.7 +/- 10.9, 73.1 +/- 10.5 and 47.1 +/- 9.2 vs. 65.8 +/- 9.8, 59.6 +/- 10 and 33.8 +/- 5.7 at unresponsiveness to verbal commands, loss of eyelash reflex and inhibition of nasal body movement response respectively. Doses of propofol for achieving the hypnotic endpoints were significantly lower in the propofol + fentanyl compared with the propofol group. Plasma propofol concentrations at inhibition of nasal body movement response were lower in the propofol + fentanyl compared with the propofol group (9.2 +/- 2.0 micrograms mL-1 vs. 14.1 +/- 4.2 micrograms mL-1). Our results suggest that fentanyl pretreatment potentiates the effects of propofol and achieves the hypnotic endpoints at higher bispectral index values and lower propofol doses and concentrations (measured at inhibition of nasal body movement response).

Adjuvants, Anesthesia↗

PubMed1999

Renin-aldosterone in elderly patients with hyperkalaemia under anaesthesia.

Elderly patients with hyperkalaemia often have low concentrations of plasma renin and aldosterone, perhaps secondary to reduced glomerular filtration and sympathetic insufficiency. The endocrine response to surgical stress and volume expansion during anaesthesia was studied in seven elderly patients with hyperkalaemia (mean age 87.7 +/- SD 5.3 years), 18 elderly patients without hyperkalaemia (86.5 +/- 5.5 years), and 18 younger patients (52.6 +/- 7.2 years) as controls. Base-line values, in hyperkalaemic elderly patients, for plasma renin activity and plasma aldosterone concentration were 0.8 +/- 0.3 ng mL-1 h-1 and 2.8 +/- 0.8 pg mL-1 respectively (significantly lower than in the younger patients), and 287 +/- 42 pg mL-1 for plasma atrial natriuretic peptide levels, which were significantly higher. The plasma renin activity and aldosterone concentrations in elderly patients with hyperkalaemia were at all times lower, but not significantly, than those of the elderly patients without hyperkalaemia. The atrial natriuretic peptide concentrations (351 +/- 48 pg mL-1) in the hyperkalaemic elderly were significantly higher 90 min after induction of anaesthesia than in the normokalaemic elderly (108 +/- 38 pg mL-1). Hormone concentrations in the hyperkalaemic patients did not change during anaesthesia, but plasma atrial natriuretic peptide concentrations increased significantly in the normokalaemic elderly, and plasma renin activity and aldosterone of the younger patients increased significantly during anaesthesia. These results indicate that plasma renin activity, and the concentrations of aldosterone and of atrial natriuretic peptide in elderly patients with hyperkalaemia are unresponsive to surgical stress and volume expansion.

Adult↗

PubMed1999

Movement response to skin incision: analgesia vs. bispectral index and 95% spectral edge frequency.

We studied the movement response to skin incision in 68 adult (males/females) ASA I-II patients receiving propofol +/- fentanyl intravenous anaesthesia using the bispectral index and 95% spectral edge frequency monitoring with an A-1050 EEG monitor. Following Ethics Committee approval, patients were randomly assigned to one of the following four treatments: Group P (n = 17): propofol infusion, 1 mg kg-1 min-1 intravenous for 2 min, followed by propofol infusion, 200 micrograms kg-1 min-1, until skin incision; Group PF1 (n = 17): fentanyl bolus, 1 microgram kg-1 intravenous + propofol infusion as in Group P; Group PF2 (n = 17): fentanyl bolus, 2 micrograms kg-1 intravenous + propofol infusion as in Group P; and Group PF3 (n = 17): fentanyl bolus, 3 micrograms kg-1 intravenous + propofol infusion as in Group P. The bispectral index and 95% spectral edge frequency were monitored continuously and recorded prior to induction of anaesthesia (base-line) and at skin incision. Twelve, 10, 4 and 4 patients responded to skin incision in Groups P, PF1, PF2 and PF3, respectively (P and PF1 vs. PF2 or PF3; P = 0.0001, and 0.006). The bispectral index and 95% spectral edge frequency were significantly lower at skin incision compared with the base-line values in all the four treatment groups. However, only bispectral index values were significantly lower in the nonmovement as compared with the movement (M) category (32.6 +/- 8.9 vs. 37.4 +/- 10.3; P = 0.04). Though deeper levels of hypnosis to lower bispectral index and 95% spectral edge frequency values may be effective in preventing the movement response to skin incision, provision of adequate analgesia rather than lower bispectral index and 95% spectral edge frequency (clinical maintenance) values may be more reliable for preventing the response to skin incision as bispectral index and 95% spectral edge frequency measure the hypnotic component of the anaesthetic effect. Lower bispectral index values may be more discriminatory as compared with 95% spectral edge frequency values for preventing the movement response to skin-incision.

Adolescent↗

PubMed1999

Macrophages expressing heat-shock protein 65 play an essential role in protection of mice infected with Plasmodium yoelii.

C57BL/6 (B6) mice are resistant to infection with the non-lethal (NL) strain of Plasmodium yoelii 17X, while being susceptible to that with the lethal (L) strain. The 65 000 MW heat-shock protein (hsp 65) was strongly expressed in splenic adherent cells of B6 mice 10 days after infection with the NL strain of P. yoelii but only slightly in those from mice infected with the L strain. Mice which had survived infection with the NL strain were resistant to challenge with the L strain and hsp 65 was strongly expressed in splenic adherent cells of these mice. Severe combined immunodeficient mice and nude mice were susceptible to malaria infection even with the NL strain and did not express hsp 65 after infection, suggesting that T cells are required for the expression of hsp 65 as well as for protective immunity. B6 mice treated intraperitoneally with carrageenan, which impairs the macrophage function, became susceptible to NL strain infection, indicating that macrophages play an important role as the final effectors in protective immunity. These results demonstrate that the hsp 65 expressed by macrophages correlates closely with protection against P. yoelii infection.

Animals↗

PubMed1999

Characterization of TSH-positive cells in foetal rat pars tuberalis that fail to express Pit-1 factor and thyroid hormone beta2 receptors.

The thyroid stimulating hormone (TSH)-immunoreactive cells (TSH cells) in the pars tuberalis (PT-TSH cell) of the male rat pituitary gland show an intense spot-like TSH immunoreaction in the paranuclear cytoplasm. However, the ontogenic origin and characteristics of these spot-like stained PT-TSH cells remain to be elucidated. The present study was designed to investigate the distribution and characteristics of PT-TSH cells in the foetal and adult rat pituitary by immunostaining for Pit-1 factor and thyroid hormone receptors (TRs) and reverse transcriptase-polymerase chain reaction (RT-PCR). TSH cells first appeared in the PT at 15.5 days of gestation and were either stained diffusely throughout the cytoplasm or displayed a strongly stained, spotty appearance in the paranuclear region. By 15.5 days of gestation, the rostral part of the PT consisted of columnar epithelium, in which TSH immunoreactivity was spot-like in the apical region of cytoplasm corresponding to the Golgi apparatus. At the 16.5 days of gestation, TSH cells were present in the pars distalis (PD); however, the cells were mostly larger and polygonal with strong staining throughout the cytoplasm. These differences between the PT and PD were retained throughout foetal and neonatal rat development. The TSH cells in the PD of the adult or gestational rat were observed to contain Pit-1 factor by double immunostaining. However, TSH cells in the PT lacked Pit-1 factor. RT-PCR confirmed the absence of Pit-1 and TRbeta2 mRNA in the PT of the adult and late gestation rat pituitary gland. These results suggest that apparently distinct types of TSH cells in the PT develop independently from TSH cells in the PD.

Animals↗

PubMed1999

Selective effects of lomerizine, a novel diphenylmethylpiperazine Ca2+ channel blocker, on cerebral blood flow in rats and dogs.

1. In the present study we examined the effects of a new Ca2+ channel blocker (lomerizine), an antimigraine drug, on cerebral cortical blood flow (CBF) in anaesthetized rats (laser Doppler flowmetry) and on vertebral blood flow in anaesthetized beagle dogs (electromagnetic flowmeter). 2. Lomerizine (1.25-10 mg/kg, p.o.) dose-dependently increased CBF in rats without affecting blood pressure (BP) or heart rate (HR). 3. The plasma concentration of lomerizine (free base) in anaesthetized rats at 30 and 60 min after the initial administration of 5 mg/kg, p.o., time at which there was a significant increase in CBF, was similar to that reported in healthy subjects receiving lomerizine at 10 mg (2 x 5 mg)/day, p.o., a dose that significantly reduces the frequency and mean duration of headache attacks. 4. Flunarizine (10 mg/kg, p.o.) did not increase CBF significantly. Flunarizine (20 mg/kg, p.o.) did not increase CBF, but did decrease BP 30-120 min after its administration. 5. Lomerizine (2.5 and 5 mg/kg, intraduodenally) dose-dependently increased vertebral blood flow in dogs without significantly changing BP or HR. With 10 mg/kg intraduodenal lomerazine, vertebral blood flow remained elevated from 20 to 240 min after administration and BP was decreased from 20 to 120 min. 6. Thus, lomerizine had a greater effect on CBF than on BP and HR and, therefore, it may be clinically effective in conditions associated with circulatory disturbances in the brain, such as migraine, without producing systemic effects (e.g. hypotension) generally seen with other Ca2+ channel blockers.

Animals↗