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Biomedical subjects

T Nakatsuka

Publications and source records attributed to T Nakatsuka.

At least 19 recordsLinked to original sources

Tramadol, but not its major metabolite (mono-O-demethyl tramadol) depresses compound action potentials in frog sciatic nerves.

BACKGROUND AND PURPOSE: Although tramadol is known to exhibit a local anaesthetic effect, how tramadol exerts this effect is not understood fully. EXPERIMENTAL APPROACH: The effects of tramadol and its metabolite mono-O-demethyl-tramadol (M1) on compound action potentials (CAPs) were examined by applying the air-gap method to frog sciatic nerves, and the results were compared with those of other local anaesthetics, lidocaine and ropivacaine. KEY RESULTS: Tramadol reduced the peak amplitude of the CAP in a dose-dependent manner (IC50=2.3 mM). On the other hand, M1 (1-2 mM), which exhibits a higher affinity for mu-opioid receptors than tramadol, did not affect CAPs. These effects of tramadol were resistant to the non-selective opioid receptor antagonist naloxone and the mu-opioid receptor agonist, DAMGO, did not affect CAPs. This tramadol action was not affected by a combination of the noradrenaline uptake inhibitor, desipramine, and the 5-hydroxytryptamine uptake inhibitor, fluoxetine. Lidocaine and ropivacaine also concentration-dependently reduced CAP peak amplitudes with IC50 values of 0.74 and 0.34 mM, respectively. CONCLUSIONS AND IMPLICATIONS: These results indicate that tramadol reduces the peak amplitude of CAP in peripheral nerve fibres with a potency which is less than those of lidocaine and ropivacaine, whereas M1 has much less effect on CAPs. This action of tramadol was not produced by activation of mu-opioid receptors nor by inhibition of noradrenaline and 5-hydroxytryptamine uptake. It is suggested that the methyl group present in tramadol but not in M1 may play an important role in producing nerve conduction block.

Action Potentials↗

Sprouting from arteriovenous shunt vessels with increased blood flow.

The purpose of this study was to evaluate the effect of increased blood flow on angiogenesis at the large vessels. The arteriovenous (AV) shunt was made on the thigh of male Wistar rats (n = 27) to increase blood flow, wrapped with artificial skin dermis, which consisted of a silicon outer layer, and isolated from surrounding tissues. Blood flow increased from 2.40 +/- 0.77 to 35.8 +/- 8.7 ml min(-1) (14.9 times), and the shear stress index (relative value of shear stress) increased from 10.7 +/- 3.6 to 73.4 +/- 18.1 (6.85 times) 60 min after the shunt formation. Newly formed vessels were observed around the AV shunt loop. Scanning electron micrographs at the AV shunt vessel lumen showed modified endothelial cells at day 7 and a remarkable number of pores at day 14. The volume of newly formed vessels was increased 12 times from day 5 to day 14. The mechanical factor of shear stress was considered the major stimulator of angiogenesis. This is the first report of electron-microscopic observation of sprouts from a large vessel lumen. The new AV shunt model is useful for basic research on angiogenesis at the large vessels in vivo and, furthermore, could generate vascularised tissues with various cultured cells.

Animals↗

Benefits of surgical reconstruction in pressure ulcers with a non-advancing edge and scar formation.

OBJECTIVE: To highlight the difficulty in treating pressure ulcers associated with scar formation and the benefits of surgical treatment in these cases by presenting a series of clinical cases. METHOD: Nine sacral ulcers surrounded by significant scar formation and 14 sacral ulcers without significant scars were treated using the same conservative management protocol. Healing status was quantitatively estimated using an assessment tool called DESIGN, which classifies pressure ulcer severity and allows healing to be monitored; a decreasing score indicates progressive improvement. RESULTS: Ulcers with scar formation showed little response to the treatment, while those without remarkable scars exhibited a significant decrease of the DESIGN scores. Surgical reconstruction was conducted in five ulcers surrounded by scar formation, and all showed complete healing within extremely short periods. CONCLUSION: Conservative treatment of pressure ulcers with a non-advancing edge surrounded by scar formation presents considerable difficulties. Surgical reconstruction offers many benefits for non-healing ulcers.

Adult↗

Evaluating dressing materials for the prevention of shear force in the treatment of pressure ulcers.

OBJECTIVE: Shear force is believed to affect pressure ulceration. Therefore, dressing materials that reduce shear force may prevent ulceration and facilitate healing. METHOD: We measured the following three properties: the coefficient of friction between the outer layer of the dressings and the patient's clothes; the degree of adhesiveness between the inner layer of the dressing and the patient's skin; the transmissibility of shear force of the dressing. RESULTS: The coefficients of static friction were 1.01 for hydropolymer, 0.72 for hydrofoam and 0.48 for hydrocolloid. Adhesiveness was tested by rolling different sized ball bearings down a slope and over the adhesive lining under both wet and dry conditions. Under dry conditions, the heaviest ball bearing that stopped rolling for five seconds was 111.9g for both hydrofoam and hydrocolloid. Under wet condition, it was 11.9g for hydrofoam and under 1g for hydrocolloid. Tests showed the very low transmissibility (I N buffer) of shear force for hydrofoam, with significant differences between the dressings. Clinical observation has identified good results for hydrofoam when used under highly exuding conditions and for hydrocolloid when used with relatively slight or decreased exudate. CONCLUSION: Existing dressing materials are being developed and evaluated for wound healing. However, if innovations in the raw materials from which dressings are manufactured could lead to a reduction in shear force and the prevention of pressure ulcers, then dressing materials could be discussed from a viewpoint that is quite different from wound healing.

Bandages↗

Analysis of receptive fields revealed by in vivo patch-clamp recordings from dorsal horn neurons and in situ intracellular recordings from dorsal root ganglion neurons.

It has been thought that spinal dorsal horn neurons receive convergent inputs from not only somatosensory but also visceral pathways. For instance, the referred pain is presumed to be due to the convergence of sensory inputs from cardiac and shoulder receptive fields. However, precise investigation has not been made from dorsal horn neurons yet, because of difficulty in studying the pathways from those regions by means of conventional electrophysiology. The purpose of this study is to clarify the convergent inputs to single dorsal horn neurons from wide receptive fields using an in vivo patch-clamp recording technique from the superficial spinal dorsal horn and an intracellular recording from dorsal root ganglion neurons that keep physiological connections with the peripheral sites. Identified dorsal root ganglion neurons received an input from a quite small area, about 1 x 1 mm in width of the skin. In contrast, substantia gelatinosa neurons in the spinal cord received inputs from an unexpectedly wide area of the skin. Previous extracellular recordings have, however, revealed that substantia gelatinosa neurons have small receptive field. This discrepancy is probably due mainly to an availability of the in vivo patch-clamp method to analyze sub-threshold synaptic responses. In contrast, the extracellular recording technique allows us to analyze predominantly the firing frequency of neurons. Thus, the in vivo patch-clamp recordings from dorsal horn neurons and the intracellular recordings from DRG neurons will be useful for well understanding the sensory processing in the spinal cord.

Animals↗

Functional reorganization of the spinal pain pathways in developmental and pathological conditions.

Following inflammation, a subpopulation of Abeta afferents that terminates preferentially in deeper laminae have been shown to extend their axons to the superficial dorsal horn, particularly substantia gelatinosa (SG). Similarly, SG neurons in immature spinal cord receive mainly Abeta afferent inputs. To clarify whether the reorganized sensory pathway in the inflamed rats has a functional similarity with that in the developmental state, we compared synaptic inputs from primary afferents using in vitro and in vivo patch-damp recordings from SG neurons. SG neurons in the mature state had monosynaptic inputs from Adelta and C afferents, while only a few neurons received inputs from Abeta afferents. Following inflammation, the Abeta afferents extended their axons to SG and established functional monosynaptic transmission. Meanwhile, SG neurons in the immature state received preferentially Abeta as well as Adelta afferent inputs, and the majority of Abeta afferent inputs were monosynaptic. These observations support the idea that the sprouting of the large afferent fibres observed in inflamed rats is, at least in part, a regeneration process. However, the process, maybe distinct at some point from the process during development, therefore, produces pathological pain. Though the idea that the regeneration mimics the developmental process has been widely accepted, other possibilities cannot be excluded.

Afferent Pathways↗

ATP P2X receptor-mediated enhancement of glutamate release and evoked EPSCs in dorsal horn neurons of the rat spinal cord.

Presynaptic ATP P2X receptors have been proposed to play a role in modulating glutamate release from the first sensory synapse in the spinal cord. Using spinal cord slice preparations and patch-clamp recordings from dorsal horn neurons in lamina V of the rat spinal cord, we showed that the activation of P2X receptors by alpha,beta-methylene-ATP (alphabetam-ATP) resulted in a large increase in the frequency of spontaneous EPSCs (sEPSCs) and miniature EPSCs (mEPSCs). The increases in mEPSC frequency by alphabetam-ATP were not blocked by the Ca(2+) channel blocker, 30 microm La(3+), but were abolished in a bath solution when Ca(2+) was omitted. The increases in mEPSC frequency by alphabetam-ATP were blocked completely by the P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) at 10 microm. Furthermore, the EPSCs evoked by dorsal root stimulation were potentiated by alphabetam-ATP as well as by the ecto-ATPase inhibitor ARL67156 and were depressed in the presence of P2 receptor antagonists PPADS (10 microm) and suramin (5 microm). The effects of these compounds on the evoked EPSCs were associated with the changes in glutamate release probability of primary afferent central terminals. Our results indicate that alphabetam-ATP-sensitive P2X receptors play a significant role in modulating excitatory sensory synaptic transmission in the spinal cord, and the potential role of endogenous ATP is suggested.

Adenosine Triphosphate↗

Developmental toxicity of orally administered thiabendazole in ICR mice.

Thiabendazole (TBZ) is a potent anthelmintic and fungicide used in the treatment of parasitic infections in humans and domestic animals and post-harvest protection of agricultural commodities. TBZ is not teratogenic or selectively foetotoxic in rats or rabbits, in contrast to several other benzimidazole derivatives. However, when administered orally to pregnant (Jcl:ICR) mice at lethal dosages, malformations were observed in treated fetuses. To assess whether the effects found in this previous study were attributable to maternal toxicity or TBZ the present study was conducted. TBZ doses of 25, 100 or 200 mg/kg/day were selected based on a preliminary range-finding study in which maternotoxicity was evident at doses of 200 mg/kg/day or above. The compound was administered during gestation days 6-15 as a solution in olive oil. Caesarean sections were completed on gestation day 18 and complete fetal examinations conducted. Decreases in maternal weight gain relative to controls were found at doses of 100 mg/kg/day or above, which paralleled decreases in foetal weights in these same dose groups. However, there were no treatment-related external, visceral or skeletal anomalies in any treatment group. Therefore, TBZ was not teratogenic or selectively foetotoxic in mice, with no-observed-effect levels (NOEL) of 25 and greater than 200 mg/kg/day for maternal and fetal weight effects and teratogenicity, respectively. These results indicate that foetal effects noted in previous studies in mice were probably secondary to severe maternal toxicity.

Abnormalities, Drug-Induced↗

Depletion of substance P from rat primary sensory neurons by ATP, an implication of P2X receptor-mediated release of substance P.

Effects of ATP on substance P immunoreactivity were examined in cultured dorsal root ganglion neurons. We found that treatment of dorsal root ganglion neurons with ATP significantly depleted substance P immunoreactivity on the neurites and somata of the neurons. The effects of ATP were significantly inhibited by the purinergic P2 receptor antagonists suramin (30 microM) and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (10 microM). We also showed that ATP-induced depletion of substance P immunoreactivity from dorsal root ganglion neurons depended on the entry of Ca(2+). In a spinal cord slice preparation, we also found the internalization of neurokinin-1/substance P receptors in many dorsal horn neurons following the application of ATP or alpha,beta-methylene-ATP. Together these results indicate that activation of P2X receptors may result in release of substance P from primary afferent neurons.

Adenosine Triphosphate↗

Deep circumflex iliac perforator flap with iliac crest for mandibular reconstruction.

The deep circumflex iliac myocutaneous perforator (DCIP) flap with iliac crest was used to reconstruct oromandibular defects in 10 patients. In seven of the patients a dominant perforator was found preoperatively using a Doppler flowmeter; in five of these seven patients a DCIP flap was successfully transferred. In two of the seven patients the dominant perforators were too narrow: one patient underwent a standard osteocutaneous flap transfer and one patient underwent a second flap transfer. In three patients no dominant perforator was found before or during surgery. The freedom of the DCIP flap from the harvested iliac crest facilitates correct positioning. However, to ensure that the DCIP flap can be safely elevated, the presence of perforators must be confirmed preoperatively. Even when a perforator has been identified, complicated dissection may be necessary. We stress the importance of a thorough knowledge of the anatomy of second flaps and of obtaining informed consent to use them.

Adult↗

Characterization of vitamin B12 compounds from edible shellfish, clam, oyster, and mussel.

Vitamin B12 content of various edible shellfish was determined by both Lactobacillus leichmannii ATCC 7830 microbiological and intrinsic factor-chemiluminescence methods. The values determined by the microbiological method were 1.2-19.8 (M/C ratio) fold greater in the shellfish than the values determined by the chemiluminescence method. Vitamin B12 compounds were purified from most eaten shellfish, oyster (M/C, 1.5), mussel (M/C, 1.2), and short-necked clam (M/C, 2.7), and partially characterized. TLC and HPLC patterns of each red-colored vitamin B12 compound (M/C, 1.0-1.2) purified from these shellfish were identical to those of authentic vitamin B12. Although the higher values in the determination of vitamin B12 by the microbiological method may be due to the occurrence of vitamin B12-substitutive compounds, the edible shellfish would be excellent vitamin B12 sources judging from the values (> or = 6 micrograms/100 g) determined by the chemiluminescence method.

Animals↗

Mandibular reconstruction using microvascular free flaps: a statistical analysis of 178 cases.

For this article, 178 consecutive cases of mandibular reconstruction using microvascular free flaps and performed from 1979 to 1997 were studied. The purpose of this report is to compare flap success rates, complications, and aesthetic and functional results. The ages of the 131 men and 47 women ranged from 13 to 85 years, with an average of 55 years. Donor sites included the rib (11 cases), radius (one case), ilium (36 cases), scapula (51 cases), fibula (34 cases), and soft-tissue flaps with implant (45 cases). Complications included total flap necrosis, partial flap necrosis, major fistula formation, and minor fistula formation. The rate of total flap necrosis involving the ilium and fibula was significantly higher than that of all other materials combined (p < 0.05). The overall rate of implant plate removal, which resulted from the exposure or fracture of the plate, was 35.6 percent (16 of 45 cases). Each mandibular defect was classified by the extent of the bony defect and by the extent of the soft-tissue defect. The extent of the mandibular bony defect was classified according to the HCL method of Jewer et al. The extent of the soft-tissue defect was classified into four groups: none, skin, mucosal, and through-and-through. According to these classifications, functional and aesthetic assessments of deglutition and contour were performed on 115 subjects, and speech was evaluated in 110. To evaluate the postoperative results, points were assigned to each assessment of deglutition, speech, and mandibular contour. Statistical analysis between pairs of bone-defect groups revealed that there was no significant difference in each category. Regarding deglutition, statistical analysis between pairs of soft-tissue-defect groups revealed there were significant differences (p < 0.05) between the none and the mucosal groups and also between the none and the through-and-through groups. Regarding speech, there was a significant difference (p < 0.05) between the none and the through-and-through groups. Regarding contour, there were significant differences (p < 0.01) between the none and the through-and-through groups and between the mucosal and the through-and-through groups. The points given for each function, depending on the reconstruction material, revealed that there was no significant difference between pairs of material groups. From this prospective study, the authors have developed an algorithm for oromandibular reconstruction. When the bony defect is lateral, the ilium, fibula, or scapula should be chosen as the donor site, depending on the extent of the soft-tissue defect. When the bony defect is anterior, the fibula is always the best choice. When the soft-tissue defect is extensive or through-and-through with an anterior bony defect, the fibula should be used with other soft-tissue flaps.

Adolescent↗

Clinical use of amrinone (a selective phosphodiesterase III inhibitor) in reconstructive surgery.

Amrinone is a selective phosphodiesterase III inhibitor that increases cyclic adenosine monophosphate by preventing its breakdown. It is effective in the treatment of congestive heart failure because of its ability to increase myocardial contractility and vascular smooth muscle relaxation. This study was designed to clarify the potential efficacy of amrinone in plastic surgery by clinically assessing its ability to enhance flap blood flow after reconstructive surgery and relieve intraoperative vasospasm. Its effects were compared with those of prostaglandin E1 and lidocaine, which are widely approved agents for improving the hemodynamics of flaps. In the first clinical study, the effects on flap blood flow after flap transfers were investigated. Twenty-six patients underwent reconstructive surgery with vascularized free or pedicled flaps. Blood flow was measured before and 60 minutes after intravenous infusion of lactated Ringer solution (control), amrinone (10 microg/kg/min), or prostaglandin E1 (10 ng/kg/min) using a laser Doppler flowmeter. In the second study, the effects on relief of vasospasm during operation were evaluated. The blood flow of 28 island flaps was measured by laser Doppler flowmetry immediately after flap elevation and 10 minutes after topical application of saline (control), amrinone (5 mg/ml), or lidocaine (10%) to the pedicle in an attempt to resolve the vasospasm. In both clinical studies, the effects of amrinone were statistically no less than those of prostaglandin E1 and lidocaine. The results show that amrinone positively influences the microcirculatory blood flow of transferred flaps and relieves intraoperative vasospasm in clinical cases. The present study suggests that amrinone could be useful for postoperative and intraoperative care in reconstructive surgery.

3',5'-Cyclic-AMP Phosphodiesterases↗

P2X1 receptor subunit immunoreactivity and ATP-evoked fast currents in adult rat dorsal root ganglion neurons.

Triple fluorescent staining for P2X1 and P2X3 subunits and isolectin I-B4 (IB4) were performed on acutely dissociated rat DRG neurons. Immunoreactivity for P2X1 and P2X3 subunits was present separately or together in DRG neurons. P2X1 immunoreactivity was present in both IB4-positive and IB4-negative cells. When combining patch-clamp recordings with immunostaining for the P2X1 and P2X3 subunits on single recorded cells, ATP-evoked fast currents were shown to be present on DRG neurons that have immunoreactivity for the P2X3 subunit only, the P2X1 subunit only, or both P2X1 and P2X3 subunits. These results raised a possibility that, in addition to the P2X3 receptor subunit, the P2X1 subunit may also contribute to functional P2X receptors with fast kinetics in DRG neurons.

Adenosine Triphosphate↗

High-intensity static magnetic fields modulate skin microcirculation and temperature in vivo.

We investigated the acute effect of static magnetic fields of up to 8 T on skin blood flow and body temperature in anesthetized rats. These variables were measured prior to, during, and following exposure to a magnetic field in a superconducting magnet with a horizontal bore. The dorsal skin was transversely incised for 1 cm to make a subcutaneous pocket. Probes of a laser Doppler flowmeter and a thermistor were inserted into the pocket and positioned at mid-dorsum to measure skin blood flow and temperature. Another thermistor probe was put into the rectum to monitor rectal temperature. After baseline measurement outside the magnet, the rat was inserted into the bore for 20 min so that mid-dorsum was exactly positioned at the center, where the magnetic field was nearly homogeneous. Post-exposure changes were then recorded for 20 min outside the bore. Sham-exposed animals were submitted to exactly the same conditions, except that the superconducting magnet was not energized. Skin blood flow and temperature decreased significantly during magnetic field exposure and recovered after removal of the animal from the magnet. The rectal temperature showed a tendency to decrease while the animal was in the magnet. The microcirculatory and thermal reactions in the present study were consistent and agreed with some of the predictions based on mathematical simulations and model experiments.

Animals↗

Topical application of amrinone (a selective phosphodiesterase III inhibitor) for relief of vasospasm.

BACKGROUND: Amrinone, a selective phosphodiesterase III inhibitor, is an agent that possesses a combination of positive inotropic and vasodilating properties as a result of preventing the degradation of cAMP, and it has recently been licensed for the treatment of heart failure. The aim of this study was to investigate the potential therapeutic application of amrinone to resolve vasospasm, which is the major problem in reconstructive surgery. In this study its effect was compared with that of lidocaine, the most commonly used topical vasodilating agent clinically. MATERIALS AND METHODS: The probe of an ultrasonic transit-time volume flowmeter was applied to the femoral artery of rats to measure blood flow. After a baseline recording was obtained, 0.03 ml of epinephrine was applied topically to induce vasospasm. The vessels were then immersed in 1 ml of amrinone (5 mg/ml), 10% lidocaine hydrochloride, or normal physiological saline solution for 1 min in an attempt to resolve the spasm. In another group of animals, no solution was used following administration of epinephrine to allow observation of spontaneous resolution of the vasospasm over time. RESULTS: The results showed an essentially immediate spasm-resolving effect in both the amrinone group and the lidocaine group. The amrinone group showed a significantly greater degree of maximum increase in blood flow than the lidocaine group. The effect of lidocaine decreased with time, whereas amrinone had a more lasting effect. CONCLUSIONS: The findings suggest that amrinone could be used as an effective topical vasodilating agent to resolve vasospasm in reconstructive surgery.

Administration, Topical↗