Biomedical subjects

A Fujita

Publications and source records attributed to A Fujita.

At least 37 records · Page 2Linked to original sources

PubMed2001

Study on acid resistance of human dental enamel and dentin irradiated by semiconductor laser with Ag(NH3)2F solution.

OBJECTIVE: The purpose of this study was to investigate the acquired acid resistance of human dental enamel and dentin treated by 38% diamine silver fluoride [Ag(NH3)2F] solution and semiconductor (diode) laser irradiation in vitro. BACKGROUND DATA: There have been no reports on the acid-resistant effect by combined use of fluoride and semiconductor laser. METHODS: Sixty crowns of extracted human molars were divided into two groups for enamel and dentin samples, and each group was subdivided into three subgroups of 10 each. Each subgroup of enamel and dentin samples served as a control; one was treated with Ag(NH3)2F and the other was treated with Ag(NH3)2F and semiconductor laser irradiation at 2 W for 30 sec. Then all samples were immersed in 5 ml of 0.1 M lactic acid (pH 4.8) at 37 degrees C for 24 h. The concentration of calcium ion (Ca2+) dissolved in the solution was measured by atomic absorption spectrophotometry, and the samples were observed by stereoscopy and scanning electron microscopy (SEM). RESULTS: In both enamel and dentin samples, dissolved Ca2+ concentration in Ag(NH3)2F- or Ag(NH3)2F- and laser-treated group was significantly decreased compared with that in the control (p < 0.01). SEM findings showed that numerous cubic particles ranging from 0.1 to 0.5 mcirom were observed only in the combined treated groups of both enamel and dentin samples. CONCLUSIONS: A significantly decreased solubility of human enamel and dentin was acquired after treatment by Ag(NH3)2F and semiconductor laser irradiation, which suggested that this combined use has the capability of a more efficient acid-resistant effect on human dental hard tissues.

Cariostatic Agents↗

PubMed2001

An inwardly rectifying K(+) channel, Kir4.1, expressed in astrocytes surrounds synapses and blood vessels in brain.

Glial cells express inwardly rectifying K(+) (Kir) channels, which play a critical role in the buffering of extracellular K(+). Kir4.1 is the only Kir channel so far shown to be expressed in brain glial cells. We examined the distribution of Kir4.1 in rat brain with a specific antibody. The Kir4.1 immunostaining distributed broadly but not diffusely in the brain. It was strong in some regions such as the glomerular layer of the olfactory bulb, the Bergmann glia in the cerebellum, the ependyma, and pia mater, while little activity was detected in white matter of the corpus callosum or cerebellar peduncle. In the olfactory bulb, Kir4.1 immunoreactivity was detected in a scattered manner in about one-half of the glial fibrillary acidic protein-positive astrocytes. Immunoelectron microscopic examination revealed that Kir4.1 channels were enriched on the processes of astrocytes wrapping synapses and blood vessels. These data suggest that Kir4.1 is expressed in a limited population of brain astrocytes and may play a specific role in the glial K(+)-buffering action.

Animals↗

PubMed2001

Expression of Ca(2+)-activated K(+) channels, SK3, in the interstitial cells of Cajal in the gastrointestinal tract.

A role for small-conductance Ca(2+)-activated K(+) (SK) channels on spontaneous motility of the gastrointestinal tract has been suggested. Although four subtypes of SK channels were identified in mammalian tissues, the subtypes of SK channel expressed in the gastrointestinal tract are still unknown. In this study, we investigated the expression and localization of SK channels in the gastrointestinal tract. RT-PCR analysis shows expression of SK3 and SK4 mRNA, but not SK1 or SK2 mRNA, in the rat intestine. SK3 immunoreactivity was detected in the myenteric plexus and muscular layers of the stomach, ileum, and colon. SK3-immunoreactive cells were stained with antibody for c-kit, a marker for the interstitial cells of Cajal (ICC), but not with that for glial fibrillary acidic protein in the ileum and stomach. Immunoelectron microscopic analysis indicates that SK3 channels are localized on processes of ICC that are located close to the myenteric plexus between the longitudinal and circular muscle layers and within the muscular layers. Because ICC have been identified as pacemaker cells and are known to play a major role in generating the regular motility of the gastrointestinal tract, these results suggest that SK3 channels, which are expressed specifically in ICC, play an important role in generating a rhythmic pacemaker current in the gastrointestinal tract.

Animals↗

PubMed2001

Interleukin-18 is elevated in the sera from patients with atopic dermatitis and from atopic dermatitis model mice, NC/Nga.

BACKGROUND: Several lines of in vitro and in vivo studies have demonstrated that interleukin-18 (IL-18) shows both antiallergic and allergy-promoting activities. But its expression in allergic diseases remains unknown. METHODS: Serum IL-18 levels from atopic dermatitis (AD) model mice, NC/Nga and control mice and from patients with AD and healthy volunteers were measured by ELISA. The relationship between IL-18 levels and serum IgE levels or clinical severity was also examined. RESULTS: Serum IL-18 levels from NC/Nga mice were significantly increased compared to those from control mice. The elevation of IL-18 in the sera was observed prior to the onset and during the development of dermatitis in NC/Nga mice. In addition, IL-18 levels in the sera from patients with AD were significantly (p < 0.05) elevated compared to those from healthy volunteers. However, serum IL-18 levels tended to correlate negatively with serum IgE levels in patients with AD and NC/Nga mice. CONCLUSION: IL-18 is overexpressed in AD.

Adolescent↗

PubMed2001

Localization of a mammalian homolog of diaphanous, mDia1, to the mitotic spindle in HeLa cells.

mDia1 is a mammalian homolog of Drosophila diaphanous and works as an effector of the small GTPase Rho. It is a member of the formin homology (FH) proteins and contains the Rho-binding domain and an FH3 region in its N terminus, an FH1 region containing polyproline stretches in the middle and an FH2 region in the C terminus. Several lines of evidence indicate that mDia1 and diaphanous are essential in cytokinesis. mDia1 is present in a large amount in the cytoplasm of both interphase and mitotic cells. Using the instantaneous fixation method that preferentially extracts soluble components, we have analyzed localization of mDia1 in mitotic HeLa cells. Immunocytochemistry using polyclonal anti-mDia1 antibody revealed specific immunofluorescence localized to the mitotic spindle. This localization was seen from prophase to telophase. Western blot analysis also detected anti-mDia1 immunoreactivity in the mitotic spindle fraction isolated from mitotic HeLa cells. Consistently, expression of full-length mDia1 as a fusion protein with green fluorescence protein (GFP) revealed the GFP fluorescence again in the mitotic spindle in HeLa cells. Expression of GFP fusions of various truncated mutants of mDia1 identified that this localization is determined by a 173 amino acid-long sequence between the Rho-binding domain and the FH1 region, which contains the C-terminal part of the FH3 region. Point mutation analysis revealed that Leu(434) and Leu(455) in the FH3 region are essential in localization to the mitotic spindle. Neither electroporation of botulinum C3 exoenzyme nor microinjection of Val14RhoA into mitotic cells affected the localization of endogenous mDia1 to the mitotic spindle, suggesting that mDia1 localizes to the mitotic spindle independent of Rho activity. The present study has thus established the mDia1 localization in the mitotic spindle. This localization suggests a role of mDia1 in the spindle-cleavage furrow interaction during cell division.

Adaptor Proteins, Signal Transducing↗

PubMed2001

[Activation of ATP-sensitive K+ channels by ADP and K+ channel openers: homology model of sulfonylurea receptor carboxyl-termini].

The ATP-sensitive K+ channels (KATP) are composed of Kir6.0 subunits and sulfonylurea receptors (SUR1, 2A and 2B). SUR2A and SUR2B are splice variants and differ only in the C-terminal 42 amino acid residue (C42). SURs are supposed to be the subunit that determines the different response of KATPs to intracellular nucleotides, K+ channel openers and inhibitors. In this study, we report that C42 of SURs plays critical roles in differential activation of various KATPs by ADP and K+ channel openers such as diazoxide and nicorandil. KATPs containing distinct SURs and Kir6.2 were reconstructed on HEK293T cells. Much higher concentrations of ADP were necessary to activate channels which SUR1 or SUR2B. In all KATPs containing different SUR, diazoxide increased the potency of ADP for channel activity without affecting its efficacy. From the electrophysiological data obtained from C-terminal chimeras and point mutants in the second nucleotide binding domain (NBDs), we developed the homology model of each SUR-NBD2 based on the crystallgraphically determined structure of HisP, a member of the ABC protein superfamily. In this model, C42 is located just beneath the Walker A motif of NBD2 and regulates the binding of nucleotide to NBD2 by affecting the 3-D construct of NBD2. This homology model well explains the different response of KATPs to ADP. Based on this model, it will be possible to develop new ligands for KATPs.

ATP-Binding Cassette Transporters↗

PubMed2001

Mechanism of a nitric oxide donor NOR 1-induced relaxation in longitudinal muscle of rat proximal colon.

We previously suggested that nitric oxide (NO)-mediated relaxation of the rat proximal colon is not associated with change in cyclic GMP content. We further studied the intracellular mechanism of NO-induced relaxation by measuring changes in tension and intracellular Ca2+ concentration ([Ca2+]i), simultaneously. NOR 1, NO donor, relaxed the longitudinal muscle of the rat proximal colon, which was precontracted by carbachol, with a concomitant decrease in [Ca2+]. ODQ, an inhibitor of soluble guanylate cyclase, partially inhibited the relaxant effect of only higher concentrations of NOR 1, but Rp-8-Br-cGMPS, an inhibitor of cyclic GMP-dependent protein kinase (PKG), did not have any effects on the relaxant effect of NOR 1. When the preparations were transferred to normal solution after the treatment with thapsigargin, an inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPase, in the absence of Ca2+, contraction with a concomitant increase in [Ca2+]i occurred. NOR 1 did not show significant effects on the tension and [Ca2+]i in thapsigargin-treated preparations. In high K+-precontracted preparations, NOR 1 relaxed the preparations with a slight change in [Ca2+]i. The relaxant effect was significantly inhibited by ODQ and Rp-8-Br-cGMPS. These results suggest that NO induces the relaxation preferentially by acting thapsigargin-sensitive function of SR and in turn decreasing [Ca2+]i, although a cyclic GMP-PKG pathway is suggested under the experimental conditions of a high K+ concentration.

Animals↗

PubMed2001

Effect of 1DMe, a neuropeptide FF analog, on acetylcholine release from myenteric plexus of guinea pig ileum.

Since neuropeptide FF (NPFF) is a putative neurotransmitter to exert anti-opioid activity, we examined the effects of [D-Tyr', (NMe)Phe3]neuropeptide FF (IDMe), a stable NPFF analog, on acetylcholine (ACh) release from a longitudinal muscle-myenteric plexus (LMMP) preparation of guinea pig ileum in which opioids were known to inhibit ACh release when muscarinic autoinhibition was not fully activated. In the presence of atropine, 1DMe increased spontaneous and electrical field stimulation (EFS)-evoked ACh release in a concentration-dependent manner. Naloxone also increased ACh release. The stimulatory effects of 1DMe and naloxone were not additive. In the absence of atropine, 1DMe did not affect ACh release. Morphine decreased spontaneous and EFS-evoked ACh release in the presence of 1 microM atropine. 1DMe as well as naloxone counteracted the inhibitory effects of morphine on EFS-evoked ACh release. The combination of 1DMe and naloxone was not more inhibitory than either drug alone. 1DMe had no appreciable effect on norepinephrine-induced inhibition of spontaneous and EFS-evoked ACh release. These results first demonstrated the effects of a NPFF analog on neurotransmitter release: 1DMe had a stimulatory effect on spontaneous and EFS-induced ACh release from the LMMP preparation of guinea pig ileum, probably by counteracting the inhibitory effect of endogenous opioids on ACh release.

Acetylcholine↗

PubMed2001

Origin of Ca2+ necessary for carbachol-induced contraction in longitudinal muscle of the proximal colon of rats.

The origin of Ca2+ necessary for carbachol (CCh)-induced contraction of longitudinal muscle of the proximal colon of rats was studied. CCh induced contraction of the muscle consisting of two phases, phasic and tonic phases, with a concomitant biphasic increase in [Ca2+]i. After removal of Ca2+ from the bathing solution of the colonic segments, CCh-induced contraction was rapidly inhibited; there was almost complete inhibition 1 min after the removal. Nicardipine, a blocker of voltage-dependent calcium channel, also significantly inhibited CCh-induced contraction. On the other hand, treatment of the colonic segments with thapsigargin, an inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPase, did not significantly affect the contraction except causing a slight decrease in the rate of contraction. These results suggest that Ca> entering through voltage-dependent calcium channels, but not released from SR, is essential for CCh-induced contraction of longitudinal muscle of the proximal colon of rats. This strict dependency of the CCh-induced contraction on extracellular Ca2+ was discussed in relation to the results obtained in the fundus of rats.

Aminobenzoates↗

PubMed2001

Combination chemotherapy in patients with malignant pleural effusions from non-small cell lung cancer : cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony-stimulating factor support.

OBJECTIVES: Malignant pleural effusions develop frequently in patients with non-small cell lung cancer (NSCLC), and the prognosis for these patients is very poor. We evaluated the role of systemic chemotherapy for patients with malignant pleural effusions from NSCLC. METHODS: We analyzed 34 patients who were found to have malignant pleural effusions in the course of diagnosis of 118 patients enrolled in three consecutive clinical trials on advanced NSCLC assessing combination chemotherapy of cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony-stimulating factor support. The objective response in the malignant pleural effusion was evaluated by CT scans every course with the response criteria of the Japan Lung Cancer Society. RESULTS: All patients had adenocarcinoma. The pleural effusion showed a complete response in 13 patients, a partial response in 7 patients, and no response in 14 patients. In the assessment of the efficacy of the treatment for the measurable primary or metastatic lesions, there was a partial response in 25 patients, no change in 8 patients, and progressive disease in 1 patient. The response rate in pleural effusions was 58.8%, and overall response in mensurable lesions was 73.5%. The median time to response and duration of response for pleural effusions were 54 days and 151 days, respectively. The median survival time and 1-year survival rates were 362 days and 48.5%, respectively. CONCLUSIONS: Both the response rate and survival data in this retrospective study suggest a high degree of activity of this combination chemotherapy in patients with malignant pleural effusions from NSCLC.

Adenocarcinoma↗

PubMed2001

Effects of erbium,chromium:YSGG laser irradiation on canine mandibular bone.

BACKGROUND: Only relatively few reports have described the morphological effects on bone produced by erbium,chromium: yttrium,scandium,gallium,garnet (Er,Cr:YSGG) laser irradiation, and none has investigated the atomic changes or estimated the temperature increases involved. The objectives of this study were to investigate the morphological, atomic, and temperature changes in irradiated areas during and after laser irradiation, and to evaluate the cutting effect on canine mandibular bone in vitro. METHODS: Two canine mandibular bones were cut into 3 to 5 cm pieces and irradiated by an Er,Cr:YSGG laser utilizing a water-air spray at 5 W and 8 Hz for 10 or 30 seconds. During and after laser irradiation, temperature increases in the irradiated areas were measured by thermography. The samples were then observed by stereoscopy and scanning electron microscopy to determine morphological changes and by energy dispersive x-ray spectroscopy to evaluate atomic alterations. RESULTS: Regular holes or grooves having sharp edges and smooth walls were produced, but no melting or carbonization was observed. The maximum temperature increase was an average 12.6 degrees C for 30-second irradiation. The continuous time of a temperature increase of more than 10 degrees C was consistently less than 10 seconds. An atomic analytical examination revealed that the calcium:phosphorus ratio was not significantly changed between the lased and unlased areas (P>0.0 1). CONCLUSION: These results showed that the Er,Cr:YSGG laser cuts canine mandibular bone effectively without burning, melting, or altering the calcium:phosphorus ratio of the irradiated bone.

Animals↗

PubMed2001

[A case of primary malignant hemangiopericytoma of the lung with marked response to combination chemotherapy with cisplatin, ifosfamide and gemcitabine].

A 51-year-old man was admitted because of complaints of cough and bloody sputa. A chest CT scan revealed a giant mass lesion in the right middle and lower lobes of the lung and mediastinal lymphadenopathy. Bronchoscopic findings showed a tumor which almost completely obstructed the intermediate bronchus. Histopathological examination of a biopsy specimen demonstrated malignant hemangiopericytoma. Two courses of chemotherapy that combined cisplatin, ifosfamide and gemcitabine were performed every 3 weeks. Both primary lesion and mediastinal lymph node metastases showed marked reduction and toxicity was manageable.

Antimetabolites, Antineoplastic↗

PubMed2001

[Multiple dural arteriovenous fistulas involving both the cavernous sinus and the posterior fossa: report of two cases and review of the literature].

Multiple dural arteriovenous fistulas (DAVFs) are rare, accounting for 7% of all intracranial DAVFs. The authors describe two cases of multiple DAVFs involving both the cavernous sinus and the posterior fossa. The first patient was a 45-year-old man who presented with visual disturbance, chemosis, exophthalmus, and tinnitus. Angiograms demonstrated DAVFs involving the right cavernous sinus and the ipsilateral sigmoid sinus. Soon after transarterial embolization via the right occipital artery, the patient's symptoms completely disappeared. Six months later, follow-up angiograms showed disappearance of the cavernous DAVF and a subtle opacification of the sigmoid sinus DAVF. The patient has been free from symptoms for four years. The second patient was a 75-year-old woman who presented with progressive tinnitus two years after stereotactic radiosurgery for right cavernous DAVF. Angiograms showed a new lesion in the contralateral transverse and sigmoid sinuses. Transvenous embolization (TVE) of the affected sinuses was successful and the patient's symptoms disappeared. The patient's course has been uneventful after treatment, and follow-up MR angiograms have not shown any recurrence of lesions. To our knowledge, 25 cases of multiple DAVFs have been reported in the literature, of which we reviewed 12 cases of multiple DAVFs affecting the cavernous sinus. The patients' ages ranged from 43 to 75 years with a mean of 57.4 and their distribution showed female predominance. Other DAVFs occurred mostly in the transverse and sigmoid sinuses. With the exception of our case (second patient), the posterior fossa lesions were located on the same side as the cavernous sinus DAVF. Multiple DAVFs were detected simultaneously in 5 of the 12 cases with the initial angiograms. In the other 7 cases, cavernous DAVFs had been treated, but were followed by posterior fossa lesions occurring after various intervals (4 months to 2.5 years). All the patients presented with ocular signs due to cavernous DAVFs. Based upon our review of the literature, we discuss here three possible hypotheses. The first possibility for formation of multiple DAVFs concerns their primary etiology, viz. that they develop after a huge sinus thrombosis involving several sinuses and its recanalization. A second possibility is the secondary formation of DAVFs. Preexisting cavernous sinus DAVFs induce sinus thrombosis and/or venous hypertension, which results in the formation of multiple lesions. A third possibility is that they are due to other factors, including increased angiogenic activity and some technical problems associated with TVE. Our review indicates that careful follow-up for several years should be made after treatment of cavernous DAVFs.

Aged↗

PubMed2000

Multigenerational cortical inheritance of the Rax2 protein in orienting polarity and division in yeast.

Diploid yeast cells repeatedly polarize and bud from their poles, probably because of highly stable marks of unknown composition. Here, Rax2, a membrane protein, was shown to behave as such a mark. The Rax2 protein itself was inherited immutably at the cell cortex for multiple generations, and Rax2 was shown to have a half-life exceeding several generations. The persistent inheritance of cortical protein markers would provide a means to couple a cell's history to the future development of a precise morphogenetic form.

Cell Division↗

PubMed2000

C-terminal tails of sulfonylurea receptors control ADP-induced activation and diazoxide modulation of ATP-sensitive K(+) channels.

The ATP-sensitive K(+) (K(ATP)) channels are composed of the pore-forming K(+) channel Kir6.0 and different sulfonylurea receptors (SURs). SUR1, SUR2A, and SUR2B are sulfonylurea receptors that are characteristic for pancreatic, cardiac, and vascular smooth muscle-type K(ATP) channels, respectively. The structural elements of SURs that are responsible for their different characteristics have not been entirely determined. Here we report that the 42 amino acid segment at the C-terminal tail of SURs plays a critical role in the differential activation of different SUR-K(ATP) channels by ADP and diazoxide. In inside-out patches of human embryonic kidney 293T cells coexpressing distinct SURs and Kir6.2, much higher concentrations of ADP were needed to activate channels that contained SUR2A than SUR1 or SUR2B. In all types of K(ATP) channels, diazoxide increased potency but not efficacy of ADP to evoke channel activation. Replacement of the C-terminal segment of SUR1 with that of SUR2A inhibited ADP-mediated channel activation and reduced diazoxide modulation. Point mutations of the second nucleotide-binding domains (NBD2) of SUR1 and SUR2B, which would prevent ADP binding or ATP hydrolysis, showed similar effects. It is therefore suggested that the C-terminal segment of SUR2A possesses an inhibitory effect on NBD2-mediated ADP-induced channel activation, which underlies the differential effects of ADP and diazoxide on K(ATP) channels containing different SURs.

ATP-Binding Cassette Transporters↗

PubMed2000

Aggravation of ischemia/reperfusion-induced gastric lesions in streptozotocin-diabetic rats.

We examined the influence of diabetes on ischemia/reperfusion-induced gastric damage in rats, in relation to the antioxidative system. Animals were injected with streptozotocin (STZ: 70 mg/kg, i.p.) and used after 5 weeks of diabetes with blood glucose levels of >350 mg/dl. Gastric mucosal blood flow (GMBF) was measured before, during and after 20 min of ischemia (1.5 ml bleeding per 100 g body weight from the carotid artery) followed by a 15-min reperfusion in the presence of acid (100 mM HCI). At the end of each experiment, gastric damage was observed macroscopically. GMBF was reduced by ischemia in all groups of rats, followed by a gradual return after reperfusion. Ischemia/reperfusion produced hemorrhagic lesions in normal rat stomachs in the presence of 100 mM HCl. These lesions were significantly aggravated when the animals were pretreated with diethyldithiocarbamate, an inhibitor of superoxide dismutase (SOD). Ischemia/reperfusion-induced damage was also markedly exacerbated in STZ-diabetic rats, but this aggravation was significantly suppressed by pretreatment with exogenous SOD or glutathione (GSH). Diabetic rat stomachs showed significantly less SOD activity as well as GSH content than normal rat stomachs. In addition, the deleterious influence of diabetes on the gastric ulcerogenic response to ischemia/reperfusion was significantly mitigated by decreasing the blood glucose levels by daily insulin treatment. These results suggest that the gastric mucosa of diabetic rats is more vulnerable to ischemia/reperfusion-induced injury, and the mechanism may be partly accounted for by impairment of the antioxidative system associated with a reduced SOD activity and GSH content.

Animals↗

PubMed2000

Alkali and alkaline-earth metal ketyl complexes: isolation, structural diversity, and hydrogenation/protonation reactions

The use of hexamethylphosphoric triamide (HMPA) as a stabilizing ligand allowed successful isolation of a series of structurally characterizable alkali metal and calcium ketyl complexes. Reaction of lithium and sodium with one equivalent of fluorenone and reaction of sodium with one equivalent of benzophenone in THF, followed by addition of two equivalents of HMPA, yielded the corresponding ketyl complexes 1, 2, and 11, respectively, as microketyl-bridged dimers. If one equivalent of HMPA was used in the reaction of sodium with fluorenone, a further aggregated complex, the mu3-ketyl-bridged tetramer 3, was isolated, whereas analogous reaction of benzophenone with sodium afforded the trimeric ketyl complex 13, rather than a simple benzophenone analogue of 3. In the reaction of potassium with fluorenone, the use of two equivalents of HMPA gave the tetramer 4, rather than a dimeric complex analogous to 1 or 2. Compared to the tetrameric sodium complex 3, there is an extra HMPA ligand that bridges two of the four K atoms in 4. When 0.5 equiv of HMPA was used in the above reaction, complex 5, a THF-bridged analogue of 4, was isolated. In the absence of HMPA, the reaction of sodium with an excess of fluorenone yielded the tetrameric ketyl complex 6, in which two of the four Na atoms are each terminally coordinated by a fluorenone ligand, and the other two Na atoms are coordinated by a THF ligand. Two bridging THF ligands are also observed in 6. Reaction of 1,2-bis(biphenyl-2,2'-diyl)ethane-1,2-diol (7) with two equivalents of LiN(SiMe3)2 or NaN(SiMe3)2 in the presence of four equivalents of HMPA easily afforded 1 or 2, respectively, via C-C bond cleavage of a 1,2-diolate intermediate. The reaction of calcium with two equivalents of fluorenone or benzophenone in the presence of HMPA gave the corresponding complexes that bear two independent ketyl ligands per metal ion. In the presence of 3 or four equivalents of HMPA, the fluorenone ketyl complex was isolated in a six-coordinate octahedral form (10), while the benzophenone ketyl complex was obtained as a five-coordinate trigonal bipyramid (13). The radical carbon atoms in both benzophenone ketyl and fluorenone ketyl complexes are still in an sp2-hybrid state. However, in contrast with the planar configuration of the whole fluorenone ketyl unit, the radical carbon atom in a benzophenone ketyl species is not coplanar with any of the phenyl groups; this explains why benzophenone ketyl is more reactive than fluorenone ketyl. Hydrolysis of 2 or 11 with 2N HCI yielded the corresponding pinacol-coupling product, while treatment of 2 or 11 with 2-propanol, followed by hydrolysis, gave the pairs fluorenone and fluorenol or benzophenone and benzhydrol, respectively. A possible mechanism for these reactions is proposed.

Journal Article↗

PubMed2000

Lack of gastric toxicity of nitric oxide-releasing aspirin, NCX-4016, in the stomach of diabetic rats.

We compared the gastric toxic effect of aspirin (ASA) in both normal and diabetic rats, with that of NCX-4016, a derivative of ASA with nitric oxide (NO) releasing moiety. Animals were injected with streptozotocin and used after 5 weeks of diabetes with blood glucose levels of >350 mg/dl in the presence of omeprazole. Oral administration of ASA (with 150 mM HCl) did not produce damage at 30 mg/kg in the conscious rat but caused hemorrhagic gastric lesions in STZ-diabetic rats. By contrast, NCX-4016 even at 190 mg/kg (a dose equimolar to 100 mg/kg of ASA) did not cause damage in both normal and STZ-diabetic rat stomachs. Plasma salicylic acid levels were not different between normal and diabetic rats after administration of ASA or NCX-4016, though the latter gave significantly lower levels as compared to ASA. Intragastric application of ASA (80 mM in 50 mM HCl) for 30 min caused a reduction of transmucosal PD and increase of luminal H+ loss with a minimal effect on mucosal blood flow (GMBF) in both normal and diabetic rats, yet resulting in much severe damage in the stomach of the latter group. Mucosal application of NCX-4016, however, did not cause PD reduction and luminal H+ loss, but produced a marked hyperemia, resulting in no damage in the stomach of both normal and STZ-diabetic rats. The increased gastric toxicity of ASA in STZ-diabetic rats was significantly mitigated by co-application of a NO donor FK-409 together with ASA, with an increase of GMBF, despite similar degrees of PD reduction and luminal H+ loss being observed. We conclude that NCX-4016 does not have a toxic effect in either normal or diabetic rat stomachs, although the diabetic rat stomach is more vulnerable to ASA-induced damage. NCX-4016, though absorbed more slowly than ASA, counteracts the injurious effect of aspirin on the gastric mucosa, probably by increasing GMBF mediated by NO.

Animals↗