Somatostatin inhibits tooth-pulp-evoked rat cervical dorsal horn neuronal activity.

The aim of the present study is to investigate the effect of somatostatin (SST). It is well known that SST is a neuromodulator in the central nervous system and is involved in the regulation of metabolic and neuroendocrine functions. Recent experimental and clinical findings indicate a role for SST in the central processing of nociception. Therefore, we tested the hypothesis whether a local release of SST modulates the tooth-pulp (TP)-evoked upper cervical spinal dorsal horn (C(1)) neuronal activity, using microiontophoretic application and immunohistochemical techniques. Extracelluar single unit recordings were made from 35 C(1) neurons responding to TP electrical stimulation (TPS) in pentobarbital anesthetized rats. Microiontophoretic application of SST (30-70 nA) current dependently inhibited TP-evoked C(1) neuronal discharges (60%, 21/35). The inhibition of this discharge by 50 nA SST application was abolished by co-application of a SST(2) receptor antagonist (Cyanamid-154806, 50 nA). Immunoreactivity for SST(2A) receptor was found in the superficial layer (Iota-IotaIotaIota) of C(1) dorsal horn. These results suggest that a local release of SST modulates the TP-evoked C(1) neuronal activity and this may contribute to a useful therapeutic target for the alleviation of tooth pain and trigeminal hyperalgesia.

A new low density lipoprotein apheresis system using two dextran sulfate cellulose columns in an automated column regenerating unit (LDL continuous apheresis).

We describe a new low density lipoprotein (LDL) apheresis system using dextran sulfate cellulose column in an automated column regenerating unit (LDL continuous apheresis). Two columns containing 150 ml of dextran sulfate cellulose were used, and the whole extracorporeal circulation was about 400 ml in volume. After 600 ml of plasma was adsorbed into the first column, the second column was used as an adsorbent and meanwhile the first column was regenerated. Thus, the 2 columns were used alternately without losing the potency of the columns. As the apparatus was automatically controlled by a computerized unit, no extra manipulation is necessary compared with the conventional single-column method. By treating 4-5 liters of plasma, non-high density lipoprotein (HDL)-cholesterol levels decreased by 63-71%, and HDL-cholesterol levels remained unchanged. Thus, this new method of LDL apheresis can safely reduce LDL-cholesterol to any desired level and will be applicable for the treatment of child and adult family hypercholesterolemic patients with severe coronary heart disease.

T1 and T2 squamous cell carcinomas of the floor of the mouth: results of brachytherapy mainly using 198Au grains.

PURPOSE: To investigate the effectiveness of brachytherapy provided by this institution over a 25-year period, and to specifically verify the efficacy of 198Au grain therapy, this study evaluated the outcomes in patients given brachytherapy for T1 and T2 squamous cell carcinoma (SCCs) of the floor of the mouth. METHODS AND MATERIALS: A retrospective analysis of data from 90 patients with T1 and T2 SCCs of the floor of the mouth who underwent brachytherapy between 1965 and 1989. Therapy mainly consisted of 198Au grain implants with or without external irradiation. As for the brachytherapeutic source, 15 patients were treated with radon seeds, 60 with 198Au grains, 10 with radium needles, 3 with cobalt needles, and 2 with iridium hairpins. Based on the 1987 International Union Against Cancer (UICC) classification, the SCC stagings and number of cases per staging follow: Stage I (T1N0), 21 cases; Stage II (T2N0), 55 cases; and Stage III-IV (T1-2N1-2), 14 cases. The minimum follow-up time was 3 years. RESULTS: The local control rates of these SCCs, based on tumor size, were 89% for T1 lesions, 76% for T2a (< or = 3 cm) lesions, and 56% for T2b (> 3 cm) lesions, and 82% for T1-2 lesions without a gingival involvement, in contrast to 55% for lesions with a gingival involvement (p < 0.05). The 5-year, cause-specific survival rates by staging were 95% for T1N0, 79% for T2N0, and 54% for T1-2N1-2. For patients given 198Au grain brachytherapy, local control was achieved in 93% of the T1 lesions, 79% of the T2a lesions, and in 56% of the T2b lesions. Further, the incidence of severe complications requiring surgery was low (5%). CONCLUSIONS: For T1N0 and T2aN0 SCCs of the floor of the mouth, excluding lesions with a gingival involvement, 198Au grain brachytherapy alone or in combination with external radiotherapy was found to be efficacious.

The efficacy of radiation therapy for a malignant melanoma in the mucosa of the upper jaw: an analytic study.

An analysis has been made of the effect of radiation therapy in 28 patients with a malignant melanoma (Stage I: 18 cases; Stage II: 10 cases) in the mucosa of the upper jaw. Treatment had been provided by one of the following methods: intraoral mold (10 cases), interstitial brachytherapy (two cases), intraoral electron therapy (nine cases), or external irradiation (seven cases). The results have shown that the survival rate for all 28 patients was 25%, and that the survival rate for stage I patients treated by intraoral electron or brachytherapy was 47%. The primary tumor control rate in percentages was 79% (22/28) in all 28 radiotherapy patients; 92% (11/12) for tumors treated by a mold or an interstitial implant; 67% (6/9) for tumors treated by an intraoral cone; and 71% (5/7) for tumors treated by external irradiation with or without surgery. A neck metastasis that was found in 19 patients was treated by surgery, radiotherapy, and/or immunochemotherapy, and the result was successful in nine patients. The major factor in the failure of treatment was a distant, metastatic dissemination. This analysis revealed that radiotherapy has achieved similar or better results than surgery and may be advocated for the management of a localized malignant melanoma in the mucosa of the upper jaw.

Brachytherapy for stage I & II oral tongue cancer: an analysis of past cases focusing on control and complications.

An analysis of the therapy used for 370 tongue cancer patients has been made, said patients having been treated by interstitial irradiation alone or by combined external irradiation and brachytherapy (Stage I:90 cases, IIa: 196 cases; and IIb: 84 cases). The neck was followed by close follow-up (304 cases), treated by elective neck irradiation (56 cases), or underwent operation at the time of local recurrence (10 cases). The results have shown that the 5-year survivals for Stages I, IIa, and IIb were 84%, 78%, and 72%, respectively. further, the 5-year primary control was 85% for tumors of the superficial type, 79% for tumors of the exophytic type, and 45% for tumors of the infiltrative type (p < 0.004). In non-electively irradiated patients, a neck metastasis occurred in 31% in Stage I, 41% in Stage IIa, and 51% in Stage IIb. Finally, 110 patients incurred radiation-induced complications (110/291 = 38%) and 11 patients (11/291 = 4%) required a surgical procedure. Brachytherapy for tongue cancer achieved results that are comparable with surgery. The analysis also revealed that the introduction of computer dosimetry and the use of a spacer (a dental guard) in brachytherapy have achieved superior results in the management of a tongue cancer.

Factors affecting mandibular complications in low dose rate brachytherapy for oral tongue carcinoma with special reference to spacer.

PURPOSE: To evaluate the efficacy of a spacer in the prevention of mandibular complications in low dose rate (LDR) brachytherapy (BRT) for oral tongue carcinoma. METHODS AND MATERIALS: A retrospective analysis was conducted using 103 patients with T1 or T2 tongue carcinoma treated by a single plane implantation of iridium (192Ir) pins between 1979-1994. Of these patients, 60 were treated by BRT alone, and the rest were combined with external irradiation (Ext) and/or chemotherapy (CHT). Forty-eight and 55 patients were given BRT with and without a spacer, respectively. Spacers were individually made of acrylic resin according to a prosthetic technique so as to obtain the thickness of 7-10 mm at the lingual part of the implanted side. Variables, including a spacer, which may be associated with the development of osteoradionecrosis (ORN) of the mandible, were analyzed by the Cox proportional hazards regression analysis. RESULTS: Our spacer reduced about 50% of the absorbed dose at the lingual side surface of the lower gingiva (LSG) to that in the absence of a spacer. Absolute incidence of ORN was 2.1% (1 of 48) and 40.0% (22 of 55), with and without a spacer, respectively, and the difference was statistically significant by univariate analysis (p = 0.0004). It was revealed by the Cox analysis that the spacer (p = 0.0247), combined CHT (p = 0.0295), and combined Ext (p = 0.0279) were significant independent factors associated with the development of ORN. The spacer was shown to be a significant factor by univariate analysis (p = 0.0037), but not by multivariate analysis when analysis was restricted to the patients who did not receive CHT. The absorbed dose, dose rate, and biological effective dose (BED) reflecting early or late response were estimated at the LSG, and prognosticators associated with the incidence of ORN were also determined by the Cox analysis. Particularly, BED for late response by BRT, the total absorbed dose, and any BED by Ext plus BRT were highly significant factors in the whole population. Essentially similar results were obtained in the patients without receiving CHT. CONCLUSIONS: It was clarified that our spacer effectively prevents mandibular complications in LDR BRT by 192Ir for oral tongue carcinoma. Furthermore, introduction of a spacer provided novel information concerning the development of ORN, where BED particularly for late response given by BRT, the total absorbed dose, and any BED by Ext plus BRT could be good prognostic factors only when estimated at the LSG.

Usefulness of 198Au grain implants in the treatment of oral and oropharyngeal cancer.

A series of 177 patients with squamous cell carcinoma of the oral cavity and oropharynx were treated with 198Au grain (gold grain) implants. Sites of the lesion included the tongue, mouth floor, buccal mucosa and oropharynx, especially the soft palate and faucial arch. Three-fourths of the patients were treated in combination with prior external beam irradiation. A permanent implant dose (total decay) of 80-90 Gy was given in the form of gold grains alone and in combination with an external dose of no more than 30 Gy, and 60-70 Gy, total decay, was given after an external dose greater than 30 Gy. The 2-year recurrence-free rate was 86.2% in the case of T1N0, 72.6% in T2N0 and 72.2% in T3N0. The difference in the results of implant therapy alone and combined therapy was not significant. Late complications were minimal after grain implantation alone, and when used in combination, less than 70 mCi of grain activity after a 40 Gy external dose did not seem to be a serious hazard with respect to bone damage except in the case of cancer of the mouth floor. Gold grain implants were useful and easily applied under local anesthesia to early or superficial lesions at sites where a rigid linear source could not be used. Exposure of the radiology staff was only 5-10 mrad in the case of the usual 10-15 (50-75 mCi) implant grains.

Interconversion of Mn(2+)-dependent and -independent protein phosphatase 2A from human erythrocytes: role of Zn(2+) and Fe(2+) in protein phosphatase 2A.

Human erythrocyte Mn(2+)-dependent (C'A') and -independent (CA) protein-serine/threonine phosphatase (PP) 2A are composed of 34-kDa catalytic C' and C subunits, in which the metal dependency resides, and 63-kDa regulatory A' and A subunits, respectively. Each catalytic and regulatory subunit gave the same V8- and papain-peptide maps, respectively. Stoichiometric zinc and substoichiometric iron were detected in CA but not in C'A' [Nishito et al. (1999) FEBS Lett. 447, 29-33]. The Mn(2+)-dependent protein-tyrosine phosphatase (PTP) activity of C'A' was about 70-fold higher than that of CA. Pre-incubation of CA with 25 mM NaF changed CA to a Mn(2+)-dependent form with higher PTP activity. The same NaF treatment had no effect on C'A'. Pre-incubation of C'A' with ZnCl(2), zinc-metallothionein, or FeCl(2) activated the Mn(2+)-independent PP activity, but pre-incubation with FeCl(3) did not. Ascorbate in the pre-incubation and assay mixture significantly stimulated the effect of FeCl(2). Pre-incubation of C'A' with 5 microM ZnCl(2) and 15 microM FeCl(2) in the presence of 1 mM ascorbate synergistically stimulated the Mn(2+)-independent PP activity, with concomitant suppression of the Mn(2+)-dependent PP and PTP activities. The PP and PTP activities of CA were unaffected by the same zinc and/or iron treatment. Micromolar concentrations of vanadate strongly inhibited the Mn(2+)-dependent PP activity of C'A' but only slightly inhibited the PP activity of CA. Using the distinct effect of vanadate as an indicator, the interconversion between CA and C'A' with the above mentioned treatments was proved. These results support the notion that Mn(2+)-independent CA is a Zn(2+)- and Fe(2+)-metalloenzyme, whose apoenzyme is Mn(2+)-dependent C'A'.

Systemic-to-pulmonary shunt in a patient with isolation of the subclavian artery.

A surgical procedure is described that was carried out to treat an 18-month-old boy with tetralogy of Fallot, right aortic arch, and isolation of the left subclavian artery. The patient underwent a descending aorta-right pulmonary artery shunt using a polytetrafluoroethylene graft, as a systemic-pulmonary shunt. The effectiveness of this procedure in patients with some special conditions is discussed.

Successful conduit repair using aortic homograft in a Jehovah's Witness child.

A 10-year-old female child of the Jehovah's Witness faith presented with congenitally corrected transposition of the great arteries (S,L,L), pulmonary atresia, and a ventricular septal defect. A successful surgical correction was performed using an aortic homograft as a valved extracardiac conduit without the use of homologous blood or blood products. We used permanent splinting of the sternum with a methyl methacrylate resin plate to prevent compression of the conduit.

Malignant lymphoma of the gingiva: MR evaluation.

PURPOSE: Our purpose was to document the MR imaging findings of malignant lymphoma of the gingiva. METHODS: Five patients with histologically proved malignant lymphoma of the gingiva were studied by MR imaging. The MR images were analyzed for tumor size, extent, and signal characteristics, bone involvement, and associated cervical lymph node enlargement. RESULTS: Clinical examination tended to underestimate the size of lymphomatous lesions. The signal intensity of the lesions was isointense to hyperintense relative to muscle on noncontrast T1-weighted images and showed variable contrast enhancement patterns. On T2-weighted images, signal intensity was isointense to hypointense relative to the oral mucosa. In one case, the mass extended to the submandibular space; in the remaining cases, the masses were limited to the gingiva and the adjacent bone. MR imaging revealed that gingival lymphomatous masses were broad-based along the mandible or maxilla and eroded through the cortex into the marrow space, but the cortex was still recognizable. No nodal involvement was noted in any of the patients with malignant lymphoma. CONCLUSION: The signal characteristics of gingival lymphoma overlap those of other tumors. The cortex separating marrow involvement from the broad-based gingival mass generally appears to be permeated with small erosions but is still recognizable.

Suppressive effect of vagal afferents on the activity of the trigeminal spinal neurons related to the jaw-opening reflex in rats: involvement of the endogenous opioid system.

The purpose of the present study is to test the hypothesis that via the endogenous pain control system, vagal afferent input modulates the activity of the trigeminal spinal nucleus oralis (TSNO) related to the tooth pulp (TP)-evoked jaw-opening reflex (JOR). Extracellular single-unit recordings were made from 36 TSNO units responding to TP electrical stimulation with a constant temporal relationship to a digastric electromyogram (dEMG) signal in 26 pentobarbital-anesthetized rats. The activity of 36 TSNO neurons and the amplitude of the dEMG increased proportionally during 1.0-3.5 times the threshold for JOR. Some of these neurons (4 out of 5) were also excited by chemical stimulation (bradykinin, 1-2 microl, 1 mM) of TP. In 31 out of 36 TSNO neurons (86%), their activities during tooth pulp stimulation were suppressed by conditioning stimulation of the right vagus nerve. The suppressive effect of vagal afferent stimulation occurred at conditioning-test intervals of 20-150 ms after the onset of the stimulation, and its maximal suppressive effect occurred at approximately 50 ms. The mean time course of this suppressive effect paralleled that of the dEMG. After administration of naloxone (0.5 and 1.0 mg/kg, i.v.), an opiate receptor blocker, the suppressive effect on the activity of TSNO neurons (6 out of 8) was significantly attenuated at the conditioning-test interval of 50 ms compared to the control (p < 0.01). These results suggested that vagal afferent input inhibits nociceptive transmission in the TSNO related to TP-evoked JOR and this inhibitory effect may occur via the endogenous opioid system in rats.

Grooming behavior in mice induced by stimuli of corn oil in oral cavity.

Mice show a strong preference for corn oil, which was thought to be elicited by stimulation in the oral cavity. Grooming behavior is known to be induced by dopamine D(1) stimulation in rodents. Therefore, we evaluated stimulation by corn oil in the oral cavity and the contribution of D(1) receptors to corn-oil-induced grooming in mice. Intraoral injection (0.1 ml) of corn oil induced grooming behavior similarly to SKF 38393 (10 mg/kg i.p.), a D(1) agonist, and both were antagonized by pretreatment with SCH 23390, a D(1) antagonist. However, a higher dose was needed for antagonism of the corn-oil-induced grooming compared with that induced by SKF 38393. Long-chain fatty acids, their methyl esters and alcohol, their triglycerides, mineral oil and silicone oil but not glycerin, a short-chain triglyceride, xanthan gum solution, or sucrose solution also induced grooming in mice. Xanthan gum solution, which was suggested to mask oil-like texture, attenuated the silicone-oil- but not corn-oil-induced grooming when injected intraorally as a mixture with an equal volume of the oil (50% suspension). The silicone-oil-induced grooming was reduced by SCH 23390 similarly to that induced by corn oil. These results suggested that stimulation by the oil-like texture in the oral cavity in mice induced grooming behavior and that it might be mediated at least partially via D(1) receptors. Moreover, stimuli other than texture might also contribute to the corn-oil-induced grooming.

Stimulation of ascorbate-induced hypoxia by lignin.

Alkali-lignin, lignin sulfonate or protein-bound polysaccharide (PSK) significantly enhanced the ascorbyl radical intensity and cytotoxic activity of ascorbate, but inhibited the intracellular incorporation of [14C]ascorbic acid. These natural products also enhanced ascorbate-induced oxygen consumption, resulting in the rapid depletion of oxygen from culture medium. Enhancement of oxygen consumption was coupled with elevation of oxidation potential. These data suggest that lignin and PSK stimulate the cytotoxic activity of ascorbate by hypoxia.

Hypochlorite scavenging activity of polyphenols.

Chemiluminescence, generated by the mixture of sodium hypochlorite solution and luminol, was completely eliminated by polyphenols, such as natural lignins, phenylpropenoid monomers and polymers, and epigallocatechin gallate. On the other hand, hypochlorite scavenging activity of polysaccharides, such as PSK (Krestin) and Schizophyllan, was relatively weak. Human myelogenous leukemic cell lines (HL-60, ML-1) showed higher production of active oxygen(s) (detected by luminol chemiluminescence) and iodination capacity, than six other cultured cell lines. Since lignin did not completely eliminate the active oxygen production by HL-60 cells, possible stimulation of hypochlorite production by lignin was suggested.

Effect of cobalt ion on radical intensity and cytotoxic activity of antioxidants.

The effect of CoCl2 on the cytotoxic activity of various antioxidants against human oral tumor cell lines (HSC-2, HSG) and normal human gingival fibroblasts (HGF) was investigated. Noncytotoxic concentrations of CoCl2 significantly reduced the cytotoxic activity of sodium ascorbate, gallic acid, epigallocatechin gallate (EGCG), curcumin and dopamine, but not that of sodium 5,6-benzylidene-L-ascorbate (SBA) and benzaldehyde. Among these compounds, benzaldehyde showed the most prominent tumor-specific cytotoxic action. ESR spectroscopy showed that these antioxidants produced radicals under alkaline condition and that their radical intensity was transiently enhanced and finally disappeared by addition of CoCl2. Antioxidants which are sensitive to CoCl2 generally had higher cytotoxic activity and oxidation potential (measured by NO monitor) and addition of CoCl2 significantly reduced their oxidation potential. The present study suggests that cobalt ion stimulates the oxidation of antioxidants to their inactive products.

Stimulation of iodination and cytokine production by dehydrogenation polymers of phenylpropenoids.

Dehydrogenation polymers of phenylpropenoids (so-called 'synthetic lignins') stimulated the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood monocytes and polymorphonuclear cells (PMN). The stimulation activity of the polymers strongly depended on the amount of hydrogen peroxide used during sample preparation, and on the temperature during iodination assay. These polymers also stimulated the production of interleukin-1 and tumor necrosis factor by peripheral blood mononuclear cells. On the other hand, neither iodination nor cytokine production was significantly affected by the phenylpropenoid monomers. Although the polymers stimulated the iodination of human leukemic cell lines (HL-60, ML-1), they did not induce cytokine production in these cells. The results suggest that stimulation of iodination and cytokine production by dehydrogenation polymers of phenylpropenoids might be regulated differently.

Stimulation of mouse peritoneal macrophages by lignin-related substances.

Various lignified materials, including pine cone extract and a commercial lignin, stimulated the morphological change (spreading) of mouse peritoneal macrophages, and their functional maturation as judged by increase in NBT-reducing activity. When these materials were treated with NaClO2 to decompose the phenolic structure, their activity was completely eliminated, whereas the activity was rather enhanced when they were treated with H2SO4 to decompose their sugar moiety. Some monomeric phenolic compounds structurally related to lignin components and several antitumor glucan derivatives had little or no macrophage stimulating activity. The results strongly suggest the importance of lignin-structure in macrophage activation.

O2- scavenging activity of lignins, tannins and PSK.

Iodination stimulators, such as the dehydrogenation polymer of caffeic acid (DHP-CA), a protein-bound polysaccharide (PSK), and a commercially available tannic acid, potently inhibited the luciferin-dependent chemiluminescence (LDCL) generated by opsonized zymosan-stimulated human peripheral blood polymorphonuclear cells (PMN). Continuous presence of these substances was necessary to express their inhibitory activity. The extent of inhibition paralleled their ability to scavenge the chemiluminescence generated by the xanthine-xanthine oxidase reaction. They also scavenged the chemiluminescence generated by potassium superoxide solution, but less effectively. An electron paramagnetic resonance spin-trapping technique revealed that DHP-CA significantly, but incompletely, scavenged O2-. The results suggest that O2- might be scavenged both directly by iodination stimulators, and by other oxygen radicals produced by activation of myeloperoxidase-mediated reaction.