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Background: Recently OPCAB has become more and more common in CABG, although one problem of OPCAB like the quality of anastomosis has not been solved yet. We discussed the usefulness of intra-operative angiography during OPCAB., Methods: During March 1997-July 2000, 55 patients underwent OPCAB (including 35 MIDCAB cases) in our institute. Graft flow and anastomosis were examined by intra-operative or immediate post-operative angiography., Results: Immediate postoperative angiography was performed in 22 MIDCAB cases. In 15 cases an excellent graft flow without stenosis could be confirmed, in 7 cases the native LAD was so small, which caused a poor flow of the LITA and three cases needed additional PTCA because of anastomosis stenosis. Intra-operative angiography was done in 9 MIDCAB and 17 OPCAB. As a result, re-anastomosis was performed in one case of MIDCAB because of severe anastomosis stenosis, one case of OPCAB had confirmed poor flow because of a small LAD, but in 24 cases an excellent graft flow could be seen on time. In 2 cases OPCAB was combined with PTCA to achieve complete revascularization., Conclusions: Intra-operative angiography is a useful strategy to confirm the surgical results quickly in OPCAB (included MIDCAB). Using such a strategy, combination of OPCAB and PTCA as a new approach for complete revascularization can be performed safe and smooth.

1. Acetylcholine-mediated (ACh-mediated) secretion of fluid and protein from rat submandibular glands was enhanced by intravenous injection of vasoactive intestinal peptide (VIP) and of secretin but not of peptide histidine isoleucine (PHI) or gastric inhibitory peptide (GIP). 2. When VIP and ACh were administered together, the enhancement of fluid secretion was inhibited by pretreatment with atropine or 4-DAMP and the enhancement of protein secretion was inhibited by pretreatment with atropine or phentolamine. 3. The enhancement of the ACh-induced secretion of fluid by secretin was strongly inhibited by pretreatment with atropine, and it was weakly inhibited by pretreatment with phentolamine or haloperidol. 4. These results suggest that the synergistic effects of VIP, PHI, secretin and GIP on the ACh-mediated secretion of fluid and protein from the rat submandibular gland do not reflect the extent of the structural homology of each peptide to VIP.

1. Noradrenaline-mediated secretion of fluid and protein from rat submandibular glands was enhanced by vasoactive intestinal peptide (VIP) and secretin but not by peptide histidine isoleucine (PHI) or gastric inhibitory peptide (GIP). 2. The synergistic effect of the combination of VIP with noradrenaline (NA) was antagonized by pretreatment with prazosin or phentolamine but not by pretreatment with yohimbine or propranolol. 3. These results suggest that VIP and secretin but not PHI and GIP can significantly enhance the secretion of fluid and protein that is mediated by NA in rat submandibular gland and that the synergistic effect of VIP and NA involves both alpha 1-adrenergic receptors and receptors for VIP.

The salivary secretion and the histopathological effects after administration of a single dose of cis-2-methylspiro (1,3-oxathiolane-5,3') quinuclidine hydrochloride hemihydrate (SNI-2011) were monitored in adult, male and female MRL/lpr mice, C57BL/6J mice and ICR mice. SNI-2011 (1-10 mg/kg, i.p.), dose-dependently increased the secretion of saliva in MRL/lpr mice. The flow rate decreased gradually over the course of 60 min. The total volume of saliva, secreted in response to SNI-2011, was significantly higher in male than in female MRL/lpr mice, but there was no significant difference in this parameter between male and female C57BL/6J and ICR mice. Degeneration, apparent as atrophy and necrosis of serous cells in MRL/lpr mice, was reversed by treatment with SNI-2011 (3 and 6 mg/kg). These results suggest that SNI-2011 could be useful in the treatment of xerostomia in patients with Sjögren's syndrome.

1. Vasoactive intestinal peptide (VIP) and secretin elicited slight secretion of saliva but peptide histidine isoleucine (PHI) and gastric inhibitory peptide (GIP) failed to elicit secretion of saliva from rat submandibular glands. 2. Substance P (SP)-mediated secretion of fluid and protein were enhanced by VIP and secretin but not by PHI or GIP. 3. These results suggest that the effects of VIP, PHI, secretin and GIP on the secretion of fluid from rat submandibular glands and the synergistic effects of VIP and its homologues on the SP-mediated secretion of fluid and protein do not correspond to the extent of the structural homology of each analogue to VIP.

Significant differences were observed between the guinea-pig and the mouse in terms of the secretion of fluid, protein and secretory granules from submandibular glands in response to pilocarpine, phenylephrine and isoproterenol. In both the guinea-pig and the mouse, the secretory responses induced by pilocarpine, phenylephrine and isoproterenol were inhibited by pretreatment with 4-DAMP, phentolamine and propranolol, respectively. The results suggest that the submandibular glands of the guinea-pig and the mouse have M3-cholinoreceptors, as well as alpha- and beta-adrenoceptors, and that these receptors play different roles in the secretion of fluid, protein and secretory granules from guinea-pig and mouse submandibular glands.

1. We examined the sialogogic activities in rat major salivary glands of SNI-2011, in comparison with those of pilocarpine and McN-A-343, and we characterized the subtypes of muscarine receptors that are involved in the sialogogic responses to SNI-2011 and McN-A-343. 2. SNI-2011 at doses ranging from 1 to 10 mg/kg (i.v.) increased the secretion of saliva in a dose-dependent manner. The dose-response curves for SNI-2011 were approximately parallel to curves for pilocarpine but the potency of SNI-2011 was about 25-fold lower than that of pilocarpine. 3. The total volume of saliva secreted in response to McN-A-343 was very much less than that secreted in response to SNI-2011. 4. The salivation induced by SNI-2011 and by McN-A-343 was inhibited by various antagonists with the following rank order of potency: 4-DAMP >> pirenzepine >> AF-DX 116. 5. Our results suggest that the sialogogic effects of SNI-2011 and McN-A-343 are mediated by direct stimulation of M3 receptors in salivary glands and that SNI-2011 may prove useful in the management of xerostomia in patients with Sjögren's syndrome.

Sprague-Dawley rats were inoculated intravenously (i.v.) with Candida albicans, and limb joints showing signs of Candida-induced arthritis were subjected to radiographic and histologic examination. New bone formation and bone resorption were morbidly enhanced in bones sampled from the arthritic joints. Sparsely distributed needle-shaped calcified deposits began to be formed on bony surfaces in parallel with the onset of joint swelling. The calcified deposits gradually became denser and then covered the bony surfaces almost entirely, giving rise to an exostosis-like profile. In addition to the new bone formation, bone resorption was also observed in regions adjacent to the sites of new bone formation, and punched-out bone lesions were produced. Eventually, severe deformation of joint bones due to new bone formation and bone resorption was evident. Reflecting these unusual radiographic changes, abundant osteoblasts and osteoclasts were demonstrated histologically in the bones. On the basis of these results, possible mechanisms for the induction of arthritis by Candida infection are discussed.

1. Significant differences were observed between the hamster and the rat in terms of the secretion of fluid and protein from submandibular glands in response to pilocarpine, phenylephrine and isoproterenol. 2. In both the rat and the hamster the secretory responses induced by pilocarpine, phenylephrine and isoproterenol were inhibited by pretreatment with 4-DAMP, prazosin and metoprolol, respectively. 3. These results suggest that the submandibular glands of the hamster and the rat have M3-cholinoreceptors, as well as alpha 1- and beta 1-adrenoceptors, and that these receptors play different roles in the secretion of fluid and protein from hamster and rat submandibular glands.

The sialogogic response of submandibular glands to analogs of the C-terminal hexapeptide of substance P with various amino acids at the N-terminus was investigated in urethane-anesthetized rats. The rank order of potencies was as follows: SP greater than (pGlu6)SP6-11 much greater than (Dab6)SP6-11 greater than (Orn6)SP6-11 greater than (Gln6)SP6-11 greater than (Lys6)SP6-11 much greater than (Ala6)SP6-11. These results suggest that the sialogogic activity of the analogs of the C-terminal hexapeptide is influenced by the steric effects of the N-terminal amino acid, and the nature of its side chain is of particular importance.

Experimental arthritis, caused by intravenously (IV) introduced Candida albicans, has been induced for the first time in rats. Four-week-old Sprague-Dawley rats were inoculated IV with three different strains of C. albicans and observed for 4 weeks. Each of the three strains tested was able to produce arthritis. The incidence of Candida arthritis increased in a dose-dependent manner and was more than 90% at sublethal doses. Joints of the limbs were affected predominantly, and at higher doses arthritis was produced in multiple (four or five) joints in individual animals, showing it to be polyarthritis. C. albicans was recovered from all cultures of affected limb joints, which were excised 12, 19 and 28 days after inoculation and showed different stages and degrees of joint swelling. Results of histopathology and radiography showed that the Candida arthritis involved not only periarticular inflammation but also changes in joint bones. In particular, metaphyseal enlargement, punched-out lesions at the diaphysis and the appearance of osteoclasts were the most prominent changes in affected bones. These pathological features are compared with those of Candida arthritis in humans.

Dose dependent effects of EDTPO on morphology and mineralization of hard tissues as well as calcium (Ca), inorganic phosphorus (IP) and alkaline phosphatase (ALP) levels in serum were examined in growing rats. Five groups of male S.D. rats weighing 110-120g were received s.c. injections of 0 (control), 1, 2, 4, and 8mg P/kg body wt. of EDTPO once daily (at noon) for 10 days respectively. Tetracycline (Tc.) were i.p. injected three times, one day before drug treatment (1st), 5th (2nd) and 10th (3rd) day of experimental period. All rats were received i.p. injection of 185kBq (5 microCi) of 45Ca six hours after the 10th injection of EDTPO. On the next day, blood samples were taken from the carotid artery. Then the animals were killed and both tibias, submandibular teeth and right femur were removed. Serum Ca, IP and ALP were determined by spectrophotometry. Wet, dry and ash bone weight were measured and bone calcium was determined by atomic absorption method. 45Ca activity was counted by the liquid scintillation counter. Serum Ca levels revealed decreasing tendency at the dose of 1mg P/kg and 2mg P/kg of EDTPO but increasing tendency at 4mg P/kg and significant increase at the dose of 8mg P/kg. Specific activity of 45Ca in serum increased slightly at 2mg P/kg, but at the dose of 8mg P/kg increased five times compared to that of control. Decrease of IP and increase of ALP level were observed only at the dose level of 8mg P/kg. Wet, dry, and ash weight, and Ca content of femur and 45Ca activity were decreased dose-dependently. In histological examination, changes of tibia and teeth were observed at the dose of 2mg P/kg and following dose increase these changes were more significantly. Ultraviolet line of Tc. appeared three in proximal metaphysis of tibia and dentin at the dose of 1mg P/kg and 2mg P/kg, but at the dose of 4mg P/kg and 8mg P/kg 2nd and 3rd line could not be detected. These result indicated that the effects of EDTPO on serum ingredients, long bone and teeth are initiated at the dose of 2mg P/kg, appeared at the dose of 4mg P/kg significantly, and at the dose of 8 mg P/kg severely. In addition, increase of the ratio of 45Ca specific activity between serum and bone observed at the dose of 4mg P/kg and 8mg P/kg suggested that these effects of EDTPO would be due to inhibitory action on mineralization.

The pathogenicity of a parent wild-type strain and three respiratory mutants of Candida albicans was examined in intravenously infected mice. The wild-type strain K grew well in the kidney and caused severe candidosis, and the 21-day LD50 value was 7.2 x 10(6) cells/mouse. A mutant with a low rate of respiration (KRD-8) whose growth rate in vitro was somewhat lower than that of the wild type, produced germ tubes in vitro to the same extent as the wild-type strain and was associated with mortality rates similar to those of the wild-type strain. Two respiration-deficient (petite) mutants (KRD-19 and KRD-51), whose growth rates in vitro were far lower than that of the wild-type strain, could neither colonize the kidney nor cause fatal infection, even at a dose of 10(8) cells/mouse. Formation of germ tubes and hyphal growth in vitro of the petite mutants were less extensive than those of the wild-type strain or KRD-8. Extracellular proteinase was produced at pH 3.5 by the wild-type strain and by KRD-8 but not by the petite mutants. From these results, it is most likely that the nonlethality of infection by the petite mutants in mice results primarily from the low capacity of growth of these mutants, even though the inability of the petite mutants to produce extracellular proteinase may be also related to some extent to their avirulence.

The actions of dobutamine (DOB) and terbutaline (TER) on the secretion of marker glycoprotein (GP) from the secretory cells of the glands and secretion of fluid from rat submandibular gland (SMG) were investigated in combination with two antagonists, metoprolol (MET) and ICI-118551 (ICI). The ED50 value of fluid secretion was 8.7 mg/kg for DOB and 5.9 mg/kg for TER. MET, administered prior to either agonists at a dose of 40 mg/kg, inhibited the fluid secretion. However, the blocking effects of ICI were considerably lower than those of MET. The electrophoretic profiles of GP in DOB-evoked saliva were similar to those in TER-evoked saliva, and included two characteristic main bands of GP I (130 KDa) and GP IV (21.5 KDa) from the acinar cells and a minor band of GP III (31 KDa) which originated in the cells of the granular tubules. When MET was administered at a dose of 5 mg/kg prior to DOB, the intensity of band I decreased, whereas that of band III did not change. These results showed that the SMG of rats contains both beta 1- and beta 2-adrenoceptors and that beta-receptors which mediate the secretion of GP from the acinus and fluid from the gland are mainly of the beta 1-subtype.

The action of dopamine (DA) on salivation and the secretion of marker glycoproteins (GP) from secretory cells of the rat submandibular gland (SMG) was investigated using various blockers at doses of 1 or 2 mg/kg (i.v.). DA at doses from 5 to 40 mg/kg (i.p.) dose-dependently increased salivation and the concentration of protein in SMG saliva. The order of inhibitory potency on salivation was propranolol (PPR) greater than phentolamine (PHN) much greater than haloperidol (HAL) when DA was administered i.p. at a dose of 10 mg/kg and PHN much greater than HAL much greater than PPR when the dose of DA was 40 mg/kg. The concentration of protein in saliva after pretreatment with HAL or PHN increased significantly at a dose of 40 mg/kg of DA, but did not increase at a dose of 10 mg/kg of DA. Moreover, pretreatment with PPR decreased it at both doses of DA. The electrophoretic profiles of GP in DA-evoked saliva showed two characteristic main bands of GP I (130 KDa) and GP IV (21.5 KDa) contained in the acinar cells (AC) and a minor band of GP III (31 KDa) which originated from the granular tubular cells (GT). The profile was not changed by pretreatment with PHN and HAL when DA was administered at a dose of 10 mg/kg, but at a dose of 40 mg/kg, the intensity of band I increased. Pretreatment with PPR, when DA was administered at 40 mg/kg, caused an increase in the intensity of band III and a reduction in that of band I. These results suggest that DA, at low doses, affects the AC, whereas at a higher dose, it affects both the AC and GT.

Yeast cells of Candida albicans were brought to germ tube formation and hyphal growth in liquid synthetic medium. The behaviour of mitochondria and mitochondrial nucleoids (mt-nucleoids) during morphological conversion was examined by fluorescence staining with 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide (DASPMI) and 4',6-diamidino-2-phenylindole (DAPI). Parent yeast cells possessed one or very few branched giant mitochondria which were stained intensely with DASPMI. When a germ tube emerged from the parent cell, one end of a giant mitochondrion extended into the germ tube and developed into the elongated form. In mycelia, apical hyphal cells contained giant mitochondria, whereas older hyphal compartments near the parent cells were vacuolated and possessed small, peripherally located mitochondria. The vacuolated hyphal compartments resynthesized cytoplasm before producing branches and contained giant mitochondria. The cytological model for germ tube formation and hyphal growth proposed by Gow and Gooday (1984) is discussed.

Superior cervical ganglion (SCG)-mediated effect of Pilocarpine (pilo.) on salivation of the rat submandibular gland was investigated. A total of 32 SD male rats, aged 12 weeks was divided into 4 experimental groups I to IV. They were anesthetized by pentobarbital (75 mg/kg, i.p.) and tracheotomized to allow artificial respiration. These rats were then ectomized only right SCG, leaving left SCG and injected with pilo. (8 mg./kg, i.v.). Rats of group I which were treated in the manner stated above were used as a control. Rats of group II and IV, of which adrenal glands were removed 18 hr before, were pithed 20 min before the injection of pilo. Rats of group III and IV were administered hexamethonium (C6) (1 mg/kg, i.v.). 5 min before the injection of pilo. Saliva from groups I to IV were collected separately from both salivary glands and flow rate of saliva were measured. Concentration of Na and K were also measured and total amounts of Na and K were calculated. 1) The flow rate induced by pilo. showed a tendency of increase in SCG-ectomized rats. 2) The flow rate showed also a tendency of increase in pithed rats. 3) The concentration and total amount of protein in saliva were decreased by SCG-ectomy. 4) The concentration of K was decreased in only SCG-ectomized rats whereas the total amount of K was closed in group I and II in spite of pithing and/or SCG ectomy. This reduction in K concentration seems to be caused by the increased flow rate as mentioned in paragraph 1). 5) SCG stimulating effect by pilo. was not antagonized, but rather activated by C6. 6) Submandibular ganglion-stimulating effect of pilo. was revealed in group III receiving C6, but this effect was extinguished in pithed rats of group IV. Considering of these results, it is proposed that SCG-stimulating ability of pilo., as shown previously by others, would be caused by activation of M1 receptor, which has sympathetic nerve stimulating effect on salivary glands, and may modify the salivation induced by stimulating effect of pilo. on M2 receptor. Moreover, results obtained with group III suggest that pilo. has submandibular ganglion-stimulating activity, although it's detailed mechanism is unknown.

The actions of four choline esters, acetylcholine (ACH), methacholine (MET), carbachol (CAR) and bethanechol (BET), on the secretion of saliva and the specific glycoprotein (GP) contained in the secretory cells of the submandibular gland (SMG) of the rat were compared under conditions with and without physostigmine (PHY). The ED50 values with respect to salivation were 17 mg/kg for ACH, 1060 micrograms/kg for BET, 810 micrograms/kg for MET and 75 micrograms/kg for CAR, whereas after pretreatment with PHY, ED50 values were lowered to 7.5 mg/kg for ACH and 212 micrograms/kg for MET, but remained unchanged for CAR and BET. SDS-polyacrylamide gel electrophoresis demonstrated that the saliva from the SMG elicited by the four choline esters contained GP I (130 KDa) and GP IV (21.5 KDa), characteristic of the acinus, and a band of GP III (31 KDa), which originates from the granular tubules. The order of intensity of these bands was band I much greater than band III = band IV. Among these bands, band I increased in intensity in a dose-dependent manner. These results suggest that the four choline esters act mainly on the acinar cells, but exert some effects on the granular tubules of the rat SMG.

The effects of substance P, neurokinin A, physalamine, and eledoisin on the secretion of fluid and glycoproteins from the submandibular glands of various rodents were investigated. Following i.v. injection of each peptide at a dose of 20 micrograms/kg, the major glycoprotein species secreted from rats and guinea pigs were shown to be electrophoretically identical with those found in the acini. However, saliva was not elicited from the mice and hamsters. These results suggest that in both rats and guinea pigs, tachykinins act on the acinar cells of the submandibular gland only.

The characteristics of the glycoproteins contained in the secretory segments of the three major salivary glands of adult male rats and the secretion of these various glycoproteins in response to autonomic agents were examined by micro-disc electrophoresis. Characterization of the glycoproteins showed that the acinar segments from the three major salivary glands and the segments of the convoluted granular tubules from the submandibular gland each contain characteristic species of glycoproteins. The glycoproteins characteristic of the acinus of the submandibular gland were secreted into saliva in response to carbachol or dobutamine, those characteristic of the parotid gland by carbachol, methoxamine, or dobutamine, and those of the sublingual gland by carbachol, whereas glycoproteins characteristic of the convoluted granular tubules of the submandibular gland were only elicited by methoxamine. The secretory response of carbachol, methoxamine and dobutamine, respectively, were almost completely reduced by pretreatment with atropine, prazosin and metoprolol. The relative proportions of glycoproteins secreted into the oral cavity from secretory cells of the three major glands varied significantly with the nature of the stimulant.

Ethylenediamine-N,N,N',N'-tetrakis (methylenephosphonic acid) (EDTPO) is a potent inhibitor of both formation and dissolution of hydroxyapatite crystals in vitro as well as 1-hydroxyethylidene-1, 1-bisphosphonic acid (HEBP). The purpose of this study was to compare with the biological effects of the same molar level of EDTPO, HEBP and ethylenediamintetraaceticacid (EDTA), prototype of EDTPO, on bone, incisor dentin and serum chemistry in young rats. HEBP at 8mg P/kg does chosen based on it's toxicity, and 16mg P/kg of EDTPO and 48mg/kg of EDTA which were identical molar level with 8mg P/kg of HEBP, were injected subcutaneously at once a day for 10 days. At the end of treatment period blood for chemical analysis, and tibia and mandibular for histological examination were taken. Results obtained were; 1) EDTPO and HEBP impaired the net weight gain during experimental period, by about 80% of final body weight in control group, but EDTA did not affect. 2) The biochemical findings of serum were as follows; calcium (Ca) level increased in EDTPO and HEBP group, and inorganic phosphorus (IP) level decreased in EDTPO and HEBP group when compared to control group, and changes of Ca and IP level in EDTPO group was more remarkable than those of HEBP group. Alkalie phosphatase level was decreased in EDTPO group, but increased in HEBP group compared to control group. There were no significant differences between EDTA group and control group, excepting for decrease of Ca level. 3) In histological aspects of the tibia, EDTPO and HEBP groups revealed enlargement of growth plates, being greater in EDTPO group than HEBP group, over the control group, and showed expanded hypertrophic zone of growth plates and wide osteoid seams in the metaphysis. EDTPO group also inhibited the calcification of dentin of mandibular incisor more strongly than HEBP group. From these data, it was indicated that EDTPO is more potent inhibitor of calcification than HEBP. Both of EDTPO and HEBP group, moreover, revealed enlargement of tibial metaphysis. These phenomena suggest that EDTPO also inhibits bone resorption as well as HEBP. EDTA group did not reveal any differences compared to control group.

The actions of metaraminol on the secretion of fluid and glycoproteins from rat submandibular glands were investigated using phentolamine, propranolol and reserpine. Metaraminol at doses from 1 to 8 mg/kg (i.p.) increased the salivation and the amounts of protein in submandibular saliva in a dose-dependent manner. The salivation induced by metaraminol at 2 mg/kg was inhibited strongly by pretreatment with propranolol, whereas the salivation induced by metaraminol at 8 mg/kg was inhibited strongly by phentolamine. Reserpine inhibited the secretion of fluid caused by both doses of metaraminol. The electrophoretic profiles of saliva evoked by metaraminol at 2 mg/kg revealed two main bands of glycoprotein, I and IV, which originated from the acinus, and the intensities of these bands were decreased by treatment with propranolol, whereas the major band in saliva induced by 8 mg/kg of metaraminol was glycoprotein III, which originated from the granular tubules. The intensity of band III was decreased by pretreatment with phentolamine. These results suggest that metaraminol, at small doses, stimulates mainly the beta-adrenoceptor in the acinus, whereas at large doses, it prominently stimulates the alpha-adrenoceptors in the granular tubules, although metaraminol at small and large doses is able to stimulate alpha- and beta-adrenoceptors in rat submandibular gland.

The action of substance P on glycoprotein secretion from acinar cells of the rat submandibular gland was described in this report. Salivation elicited by i.v. injection of 0.5 to 20 micrograms/kg of substance P was increased dose-dependently, and its flow rate was highest at the first 1 min. Major glycoprotein species secreted into saliva by substance P-stimulus were shown to be electrophoretically identical with those found in acini, but not granular convoluted tubules. These results support the view that substance P acts on acinar cells of the submandibular gland and stimulates secretion of saliva from the cells.