Yoshiaki Hikasa

Cardiopulmonary effects of sevoflurane in cats: comparison with isoflurane, halothane, and enflurane

The cardiopulmonary effects of sevoflurane (mean, 2.6, 3.8-3.9 and 5.2 per cent) were compared with those of halothane (1.2, 1.8 and 2.4 per cent), enflurane (2.4, 3.6 and 4.8 per cent) and isoflurane (1.6, 2.4 and 3.2-3.3 per cent) at end-tidal concentrations equivalent to 1, 1.5 and 2 minimal alveolar concentrations (MACs) during spontaneous or controlled ventilation (SV or CV) in 57 cats. Cats were assigned to four groups of nine animals each in SV trial and four groups of five or six animals each in CV trial. During SV, respiration rate was decreased by sevoflurane and isoflurane at 2 MAC and by enflurane at each MAC multiple when compared with control values, whereas halothane increased respiration rate at 2 MAC. The degree of hypercapnia and acidosis induced by sevoflurane was not different from that induced by isoflurane and was less than that induced by halothane at 1 to 1.5 MAC or enflurane at 2 MAC. During SV and CV, four anaesthetics decreased heart rate at 2 MAC when compared with control values, but there was no significant difference between anaesthetics. Sevoflurane, like halothane and isoflurane, induced hypotension at 2 MAC when compared with 1 MAC.

Ventricular arrhythmogenic dose of adrenaline during sevoflurane, isoflurane, and halothane anaesthesia either with or without ketamine or thiopentone in cats

The doses of adrenaline required to induce ventricular arrhythmia during sevoflurane, isoflurane and halothane anaesthesia, either with or without infusions of ketamine (76 micrograms kg-1 min-1) or thiopentone (0.5 mg kg-1 min-1), were determined in cats. Groups of six to eight cats were maintained at end-tidal concentrations equivalent to 1.25 times the minimal alveolar concentration of each anaesthetic. The mean dose of adrenaline required to induce arrhythmia during sevoflurane anaesthesia (19.0 micrograms kg-1) was approximately 11 times higher than that required during halothane anaesthesia (1.66 micrograms kg-1) and the same as that required during isoflurane anaesthesia (19.0 micrograms kg-1). Ketamine tended to decrease the requirement of adrenaline during halothane anaesthesia, but not significantly, and did not change the requirement during isoflurane or sevoflurane anaesthesia. Thiopentone did not change the requirement for adrenaline during halothane, isoflurane or sevoflurane anaesthesia. It was concluded that either with or without ketamine or thiopentone, the effect of sevoflurane on the sensitisation of the feline myocardium to the arrhythmogenic effects of adrenaline was significantly less than that of halothane and not different from that of isoflurane.

In vitro evaluation of the growth inhibitory activities of 15 drugs against Babesia gibsoni (Aomori strain)

The in vitro growth inhibitory activities of 15 drugs against Babesia gibsoni were evaluated following establishment of a continuous culture isolate (Aomori isolate). The culture was successfully continued in an RPMI-1640 medium supplemented with 20% normal canine serum or fetal bovine serum in a humidified atmosphere containing 5% CO2 and 5% O2 at 37 degrees C. We used this isolate to evaluate the growth inhibitory effect of naphthoquinone (atovaquone), aromatic diamidine (diminazene and pentamidine), artemisinin compounds (artesunate and dihydroartemisinin), an iron chelator (deferoxamine), quinoline-containing compounds (quinine and chloroquine), macrolide antibiotics (azithromycin), lyncomycin antibiotics (clindamycin), tetracycline antibiotics (doxycycline and minocycline), imidazole antifungals (clotrimazole and ketoconazole), and a nitroimidazole antiprotozoal (metronidazole). Atovaquone and aromatic diamidine showed the highest activity; they were followed by artesunate compounds with nanomole levels of IC50. Metronidazole did not exhibit activity against the parasite. Other drugs exhibited intermediate in vitro activities with micromole levels of IC50. This is the first report to screen drug activities against B. gibsoni in vitro. The results of our study may support further in vitro drug evaluation for the establishment of therapeutic strategies against canine B. gibsoni infections.

Clinical, cardiopulmonary, hematological and serum biochemical effects of sevoflurane and isoflurane anesthesia in oxygen under spontaneous breathing in sheep.

Effects of sevoflurane and isoflurane anesthesia in oxygen on clinical, cardiopulmonary, hematological, and serum biochemical findings were compared in sheep breathing spontaneously undergoing minor surgical operations during short-term (60-80min) or long-term (3-4h) anesthesia. All sheep were premedicated with atropine sulfate (0.1mg/kg) intramuscularly, and 10min later, induced to anesthesia by intravenous infusion of sodium thiopental (mean 14.1+/-3.4 S.D. mg/kg). After intubation, they were anesthetized with either isoflurane or sevoflurane in oxygen at a total gas flow rate of 1.5l/min. The results revealed that recovery time with sevoflurane was more rapid than with isoflurane. Respiration rates, tidal volume, minute ventilation and heart rates during sevoflurane anesthesia were similar to those during isoflurane anesthesia. The degree of respiratory acidosis during sevoflurane anesthesia was also similar to that during isoflurane anesthesia. There were no significant differences between sevoflurane and isoflurane anesthesia in hematological and serum biochemical values.

Effects of Imidazoline and Non-Imidazoline α-Adrenergic Agents on Rabbit Platelet Aggregation

Background/Aims: Imidazoline α2-adrenergic agents exert complex effects on mammalian platelet aggregation. Although non-adrenergic, imidazoline (I) receptors have been revealed in human platelets, there is limited information about imidazoline’s action on platelet aggregation. This study aimed to investigate aggregatory and anti-aggregatory effects of various imidazoline or non-imidazoline α-adrenergic agents on rabbit platelets. Methods: Aggregatory responses of agents on rabbit platelets were examined by turbidimetric method. Radioligand binding assay to platelet I1 and I2 receptors was performed using [3H]-clonidine and [3H]-idazoxan, respectively. Results: Aggregation was not induced by α-adrenoceptor agonists alone. Adrenaline and noradrenaline produced dose-dependent potentiation of ADP- or collagen-induced aggregation. Imidazoline adrenoceptor agonists clonidine and p-aminoclonidine also potentiated ADP-induced platelet aggregation. The α2-adrenoceptor antagonists and/or certain imidazoline adrenergic agents inhibited adrenaline-potentiated aggregation in a dose-dependent manner, whereas α1-adrenoceptor antagonists and non-imidazoline α-adrenergic agents were either ineffective or less effective in inhibiting adrenaline-potentiated aggregation. Rabbit platelets did not have I1 receptors, but had I2 receptors, indicating that adrenaline-potentiated platelet aggregation was inhibited by idazoxan, but not by imidazoline compounds clonidine and oxymetazoline. Conclusions/Implications: These results demonstrated that α2-adrenoceptor-blocking agents and/or imidazoline α-adrenergic agents effectively inhibit adrenaline-potentiated platelet aggregation. It is proposed that imidazoline structure in part plays a role in the inhibition of adrenaline-potentiated aggregation.

Interleukin-3 and stem cell factor modulate cell cycle regulatory factors in mast cells: negative regulation of p27Kip1 in proliferation of mast cells induced by interleukin-3 but not stem cell factor.

OBJECTIVE Interleukin-3 (IL-3) and stem cell factor (SCF) are able to promote survival and proliferation of mast cells. However, the precise signal transduction cascades leading to mast cell proliferation are not clearly understood. Thus, we sought to define the mechanism of mast cell proliferation induced by IL-3 and SCF. MATERIALS AND METHODS We treated murine bone marrow-derived cultured mast cells (BMCMC) with recombinant IL-3 (rIL-3) or recombinant SCF (rSCF) and examined the effects of rIL-3 and rSCF on cell cycle regulatory factors. RESULTS Both rIL-3 and rSCF suppressed apoptosis of BMCMC. rSCF induced great proliferation of BMCMC with elevation of the proportions of cells in S and G2/M phases, whereas most BMCMC incubated with rIL-3 were arrested in the G1 phase. The G1/S phase transition is initiated by phosphorylated retinoblastoma protein (pRb), which was prominent in cells stimulated with rSCF. In contrast, rIL-3 relatively increased a dephosphorylated form of pRb in BMCMC. Compared with rIL-3, rSCF induced greater expression of cyclin-dependent kinase (CDK) 2 and CDK4, which are able to phosphorylate pRb, and cyclin D3, a partner of CDK4. BMCMC treated with rIL-3 contained a high amount of a CDK inhibitor p27Kip1 that was suppressed by pretreatment with Ro31-7549, a protein kinase C inhibitor, whereas rSCF induced weak expression of p27Kip1 in BMCMC. CONCLUSION The results suggest that IL-3 and SCF exert their respective mitogenic effects on mast cells by modulating the expression of pRb, CDK, cyclin, and p27Kip1.

Antagonism of the emetic action of xylazine by α-adrenoceptor blocking agents

The intramuscular injection of xylazine (2 mg/kg) evoked vomiting in 81% of the dogs studied. Adrenoceptor antagonists showing α2-blocking activity, yohimbine, tolazoline and phentolamine, antagonized the xylazine-induced vomiting in a dose-dependent manner. Of these antagonists, yohimbine was the most effective, since the maximal antagonistic effect was seen at 0.5 mg/kg yohimbine, a dose at which the other drugs had less or no effect. The adrenoceptor antagonists showing α1-blocking activity, prazosin and phenoxybenzamine, at the doses studied did not prevent the emesis induced by xylazine. A β-adrenoceptor antagonists, propranolol, was ineffective in reducing xylazine-induced vomiting. The dopamine receptor antagonists, metoclopramide and domperidone, did not prevent xylazine-induced vomiting nor did yohimbine antagonize apomorphine-induced vomiting. The xylazine-induced vomiting was not prevented by atropine, naloxone or hexamethonium. These results indicate that the xylazine-induced vomiting is mediated by α2-adrenoceptors and does not appear to involve β-adrenoceptors, cholinoceptors, dopamine or opiate receptors in the emetic pathway.

Bone Regeneration by Lactoferrin Released from a Gelatin Hydrogel

The objective of this study is to evaluate the potential of lactoferrin (LF), an iron-binding glycoprotein, to induce bone regeneration. A biodegradable gelatin hydrogel was prepared to allow LF release in vivo in a sustained fashion. When subcutaneously implanted into the back of mice, the gelatin hydrogel incorporating LF showed a longer LF retention period at the site of implantation than that of LF solution injection. An in vitro culture experiment with 3T3E1 cells (mouse-derived osteoblasts) revealed that the cells were proliferated to a significantly greater extent by the repeated addition of LF compared with a single addition of LF at the same dose. Following the implantation of gelatin hydrogels incorporating LF into a skull bone defect of rats, a significantly stronger bone regeneration at the defect was observed than in LF-free- or low-LF-treated rats. It is concluded that the sustained release from the gelatin hydrogels enables LF to enhance the in vivo activity of bone regeneration.

The efficacy of artemisinin, artemether, and lumefantrine against Babesia gibsoni in vitro

Artemisinin has many derivatives, and it is effective against Plasmodium spp. However, only a limited number of reports have confirmed the efficacy of artemisinin derivatives against Babesia spp. In this study, whether artemisinin and artemether could inhibit the growth of Babesia gibsoni was evaluated in vitro. In addition, the interaction between artemether and lumefantrine was evaluated. These drugs inhibited the growth of B. gibsoni, but artemisinin and artemether showed lower sensitivity against atovaquone-resistant B. gibsoni than against wild-type B. gibsoni. The interaction between artemether and lumefantrine showed synergism against B. gibsoni. Although further study is needed, the combination of artemisinin derivatives could be useful for babesiosis.

Vascularization Around Poly(tetrafluoroethylene) Mesh with Coating of Gelatin Hydrogel Incorporating Basic Fibroblast Growth Factor

For successful mesh hernia treatment with medical meshes, it is important to induce angiogenesis and fibroplasia around the site of the mesh implanted. The objective of this study is to combine a mesh with a gelatin hydrogel for basic fibroblast growth factor (bFGF) release and evaluate the angiogenic activity in vivo. The MotifMesh® (MM) of poly(tetrafluoroethylene) was treated with corona discharge to make the surface hydrophilic. This corona discharge treatment increased the bonding strength between the gelatin hydrogel coated and the mesh surface. When implanted into the back subcutis of mice, the MM coated with the gelatin hydrogel incorporating bFGF showed significant angiogenesis around the implanted site, in contrast to the MM alone and that without gelatin hydrogel or bFGF incorporation. It is concluded that the coating of hydrogel incorporating bFGF is a promising technology to give the mesh angiogenic properties.