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Biomedical subjects

T Hayama

Publications and source records attributed to T Hayama.

At least 73 records · Page 4Linked to original sources

Lobule structure and somatotopic organization of the medullary facial lobe in the channel catfish Ictalurus punctatus.

Correlation of the somatotopic organization of the facial lobe (FL), a primary medullary gustatory nucleus in the channel catfish Ictalurus punctatus, with its lobular substructure was investigated to examine a possible structural basis for the excellent ability of ictalurid catfishes to localize a food source in the environment. The FL in the channel catfish is composed of six longitudinal columns (i.e., lobules) extending rostrocaudally and differing from each other in their length and location within the lobe. Each lobule receives segregated input from discrete portions of the external body surface. The three more medial lobules in the FL receive input (from medial to lateral) from the medial mandibular barbel, the lateral mandibular barbel, and the maxillary barbel, respectively. The proximal-distal axis of each of the barbels is represented in a posteroanterior lobule axis. The largest lobule, the face-flank lobule, is located dorsolaterally in the FL, whereas the anteroposterior body axis is represented in the posteroanterior lobule axis. This indicates that the neural representation of the external body surface of the channel catfish faces caudally in the FL. The two shortest lobules, positioned ventral to the face-flank lobule, receive input from the nasal barbel and the pectoral fin, respectively. The rostrocaudal dimensions of each of the barbel lobules correlate well with the relative lengths of the barbels. Taste-sensitive portions within the three barbel lobules examined were generally confined to the dorsal region, whereas tactile responses were observed throughout the lobules.2+ primarily tactile, zone.

Animals↗

Effect of albumin distribution. A simulation analysis of the effect of altered albumin distribution on the apparent volume of distribution and apparent elimination rate constant of drugs.

The effects of altered albumin distribution on the apparent volume of distribution (V) and the apparent elimination rate constant (kappa) of drugs were investigated by a simulation analysis. The Equations derived by Oie et al. were modified for this purpose. Within the range observed in normal healthy subjects and patients, the change in albumin distribution significantly affected V of drugs but, in general, not kappa. For drugs with more than 90% plasma-protein binding, V changed by more than 100%. The change in plasma-protein binding caused by an altered albumin distribution produced a greater effect on V than that caused by an altered albumin amount. These results suggest that albumin distribution is an important factor in controlling the kinetics of drugs which are highly bound to plasma protein. This is illustrated using midazolam as an example.

Blood Proteins↗

Nonlinear pharmacokinetics of intravenous sulphadimethoxine and its dosage regimen in pigs.

The time courses of the total (Ct) and unbound plasma (Cf) concentration after the i.v. injection of 20, 50 and 100 mg/kg of sulphadimethoxine (SDM) were examined in pigs. The area under the Ct-time curve per unit dose decreased dose-dependently. Vdarea and total body clearance of Ct increased dose-dependently. The concentration-dependent plasma protein binding of SDM was evident after 50 and 100 mg/kg. The time courses of Cf en Ct after 3 doses were analyzed by a one compartment open model with nonlinear plasma protein binding. The agreement between calculated curves of Cf and Ct and the observed values, and relative constancy of pharmacokinetic parameters were obtained over 3 doses. These results suggested that the nonlinear pharmacokinetics of SDM was caused by saturable plasma protein binding. The multiple i.v. dose of SDM was based on the dosage regimen using the nonlinear pharmacokinetic model (50 mg/kg, 24 hour interval, 4 days). The observed Cf was maintained in the intended range by the dosage regimen. Therefore, the dosage regimen based on the nonlinear pharmacokinetics may allow the unbound concentration after i.v. injection of SDM in pigs to be controlled.

Animals↗

Experimental induction of splayleg in piglets by pyrimethamine.

Dietary administration of 3.6 mg/kg (BW)/day of pyrimethamine (PYR) to the 10 pregnant Goettingen minipigs for the 1st quarter (during days 11 to 16) or the 2nd quarter (during days 17 to 22) of the organogenetic period elicited the congenital splayleg (CSL) in 20 out of 27 live newborns. Only a splayleg piglet out of 18 was found in the control group. The incidence of stillbirth was higher in the PYR groups than the control group, but no major external malformation was observed in the piglets of the PYR groups. Histological and biochemical examinations of the muscles from the hindleg, foreleg and truncus were carried out. The severity of myofibrillar hypoplasia depended on neither CSL symptoms nor PYR administration. Although a significant decrease of protein content of the muscles was observed in the piglets of the PYR groups, the mechanism underlying the pathogenesis of induced splayleg was obscure.

Animals↗

Thermal sensitivity of neurons in a rostral part of the rat solitary tract nucleus.

While stimulating the entire oral cavity of anesthetized rats, we recorded 3 types of neurons in the solitary tract nucleus; taste, mechanoreceptive and cold neurons. Most of the taste neurons were sensitive to thermal as well as to mechanical stimulations. Taste neurons predominantly sensitive to sucrose responded to warming and those most excited by NaCl or HCl were sensitive to cooling, and significant correlations were found between sucrose and warming and between NaCl and cooling. Most of the cold-sensitive taste neurons had receptive fields (RFs) at the anterior tongue and warm-sensitive taste neurons had whole or part of the RFs at the nasoincisor duct. About half the number of mechanoreceptive neurons were sensitive to cooling, producing phasic responses. RFs of some thermosensitive mechanoreceptive neurons and cold neurons were located. Warm-sensitive mechanoreceptive neurons or warm neurons were not evident. Therefore, interaction between thermal and taste sensations in the oral cavity probably takes place in the solitary tract nucleus, as well as in the chorda tympani.

Action Potentials↗

Role of deacetylation in the nonlinear pharmacokinetics of sulfamonomethoxine in pigs.

The role of deacetylation in the pharmacokinetics of sulfamonomethoxine (SMM) in pigs was studied using 6 Goettingen minipigs and a pig from a commercial breed. The rapid decrease of plasma concentration of the parent compound followed by the rapid increase of plasma concentration of the deacetylated metabolite, SMM, was observed after an i.v. injection of N4-acetylsulfamonomethoxine (AcSMM; 10 mg/kg). The concentration of the metabolite, SMM, was greater than that of AcSMM and after reaching peak, both compounds decreased in parallel on a semilogarithmic graph. On the other hand, the acetylated compound of SMM (AcSMM) appeared in the plasma and reached peak after an i.v. injection of SMM. After reaching the peak, both SMM and AcSMM decreased in parallel. The slopes of the terminal phases of SMM and AcSMM after both injections showed no significant difference. After the i.v. injection of a high dose of SMM (100 mg/kg), a nonlinear pharmacokinetics profile with capacity limited elimination type of SMM was observed. The concentration of plasma AcSMM increased rapidly and the parallel decrease of SMM and AcSMM was observed in both nonlinear and linear phases, while the renal excretion of AcSMM was saturated in the nonlinear phase. The results suggest that the deacetylation in pigs is so strong that it largely affected the pharmacokinetics of SMM in both high and low doses. In spite of the saturation in renal excretion of the main metabolite, AcSMM, after the high dose, the profile of the parallel decrease remained unchanged, which may be due to the rapid conversion of the excess AcSMM to SMM. The converted SMM was added to the existing plasma SMM. As a result, the nonlinear pharmacokinetics of SMM may have occurred after a high dose of SMM in pigs.

Acetylation↗

Increased vascular permeability in the thymus of the autoimmune New Zealand mouse.

The thymus glands of non-autoimmune BDF1 and C3H mice and autoimmune NZB/WF1 mice were studied histologically at intervals ranging from one hour to 60 days after systemic administration of carbon. In NZB/WF1 mice over 9 weeks of age, many circulating carbon-laden macrophages were seen to have penetrated the walls of blood vessels, and to have then entered the thymic parenchyma. Carbon was also taken up by many perivascular macrophages stretched out along blood vessels and by many resident tissue macrophages scattered throughout the thymic parenchyma. In contrast, no carbon was seen at any time in the extravascular tissues of the thymus in BDF1 and C3H mice of comparable age. These results indicate a great increase in the permeability of blood vessels in the thymus of NZB/WF1 mice. This increase in carbon permeability occurs both in the cortex and the medulla, particularly at the corticomedullary junction. There is little increase in the permeability to carbon in NZB/WF1 mice at the age of 4 weeks, suggesting that the increase in vascular permeability begins between the ages of 4 and 9 weeks. The possible role of this greatly increased blood vessel permeability in the thymus on the aetiology and pathogenesis of autoimmune disease is discussed.

Animals↗

Electrophysiological evidence of collateral projections of parabrachio-thalamic relay neurons.

We studied axonal branching of 14 parabrachial nucleus neurons, activated antidromically from 2 of the 3 stimulation sites, i.e. the ipsi- and contralateral thalamic taste area (TTAs) and the ipsilateral central nucleus of the amygdala (CA). Making use of antidromic latencies, collision times and refractory periods at the 2 sites of stimulation, the conduction times were calculated for the distance between the branching point of the axon and the stimulation sites or the recording site at the soma. Nine of these 14 neurons had a significant length of axon branches terminating at 2 of the 3 sites of stimulation. Five neurons sent axon branches to the bilateral TTAs, 3 to both the CA and the ipsilateral TTA and the remaining one to both the CA and the contralateral TTA. Four of these 9 neurons with collateral branches responded to taste stimulation.

Amygdala↗

Response properties of the parabrachio-thalamic taste and mechanoreceptive neurons in rats.

A total of 66 taste and 33 mechanoreceptive neurons were isolated from the parabrachial nucleus (PB) of rats. Among them, 39 taste and 8 mechanoreceptive neurons were identified as parabrachio-thalamic relay (P-T) neurons on the basis of antidromic activation from either or both sides of the thalamic taste areas (TTAs). On average, the P-T taste neurons produced larger response magnitudes than the non-P-T taste neurons, and whereas about half the P-T taste neurons were NaCl-best, only a small number of the non-P-T taste neurons were NaCl-best. Both the P-T and non-P-T taste neurons showed a similar breadth of responsiveness to four basic taste stimuli. The response magnitudes of the P-T taste neurons to all taste stimuli were ca. 3 times larger than those of the solitario-parabrachial relay (SP) neurons (afferents to the PB); in particular, the response magnitudes of the NaCl-best P-T neurons were 4-5 times larger than those of the NaCl-best SP neurons. The response magnitudes and breadth of taste responsiveness of the P-T taste neurons were reciprocally correlated with the antidromic latencies from either side of the TTAs. A histological examination revealed that the P-T taste neurons in the ventral part of the PB had a shorter antidromic latency from the ipsilateral TTA than those in the dorsal part of the nucleus. Mechanoreceptive neurons were excited by stroking the tissue in the oral cavity or perioral tissue, or by pinching them with non-serrated forceps. The mechanoreceptive P-T neurons were also activated from either or both sides of the TTAs. No particular relation was noticed between the antidromic latency of the mechanoreceptive P-T neurons and their response properties or locations in the nucleus.

Afferent Pathways↗

Receptive field properties of the parabrachio-thalamic taste and mechanoreceptive neurons in rats.

Receptive fields (RFs) of 36 taste (the 22 parabrachio-thalamic relay (P-T) and 14 non-P-T) and 23 mechanoreceptive neurons (7 P-T and 16 non-P-T) were located in the oral cavity of rats. All of the taste and most of the mechanoreceptive units examined had an RF on the ipsilateral side of the tongue or palate, but some mechanoreceptive P-T and non-P-T units had RFs bilaterally. When the RFs of taste neurons were examined with the most effective of the four basic taste (the best stimulus) and non-best stimuli, no difference was noticed in the location of RFs between the P-T and non-P-T neurons. Though most of the P-T neurons (7/11) and all of the non-P-T neurons (6/6) had an RF for non-best stimuli at a region similar to that for the best stimulus, some P-T neurons (4/11) had an RFs for non-best stimulus outside the RF for the best stimulus and/or on the region separate from the RF for the best stimulus. The P-T neurons, responding vigorously to non-optimal stimuli as well as to the best stimulus, had an RF outside the RF for the best stimulus. RFs for mechanical stimulation were also examined in some taste and mechanoreceptive neurons. The mechanoreceptive P-T units rarely had an RF exclusively on the palate. Some mechanoreceptive units had an RF on the region where no taste RF has been found, e.g. the intermolar eminence and the folium of the hard palate.

Afferent Pathways↗

The effect of estriol on the production of alpha-fetoprotein by the liver in adult mice.

A single intraperitoneal injection with a 10 mg estriol (E3) in aqueous suspension induced a large and prolonged elevation of serum alpha-fetoprotein (AFP) in adult mice. E3 also raised the mitotic activity of hepatocytes in the absence of liver injury. Although both the AFP concentration and hepatocyte proliferation reached the peak on day 5 after E3 administration, a high level (about 12,500 ng/ml) of serum AFP persisted for a long period after hepatocyte proliferation declined. Five mg E3 showed a remarkable threshold effect on AFP elevation and 3 mg E3 on hepatocyte proliferation. Immunohistochemical studies indicated AFP production by hepatocytes in adult mice after the E3 administration.

Animals↗

Possible active tubular secretion of sulfamonomethoxine and its metabolites in pigs.

The effect of probenecid on the plasma kinetics of sulfamonomethoxine (SMM) was examined in conscious pigs. A linear kinetic dose of SMM (10 mg/kg) was injected with or without probenecid. Probenecid (25 mg/kg, i.v.) was injected immediately before SMM injection and against at 1, 2, 3, 4 and 6 h later. The AUCs of SMM and of the acetylated compound of SMM (AcSMM) in probenecid injected animals were significantly larger when compared with those of non-injected animals (p less than 0.05). Next, possible active secretion from the renal tubule of SMM and its metabolites was examined using probenecid and pyrazinoate. Ten commercial pigs with ureter cannulae were used under anesthesia. The plasma concentration of SMM and AcSMM was maintained at a steady state by a priming dose of SMM (5 mg/kg, i.v.) followed by sustaining infusion (4 micrograms/kg/min). Renal clearance of AcSMM was suppressed by bolus injection of probenecid (25 mg/kg), but that of SMM was not. The renal excretion of a water soluble metabolite was suppressed by probenecid. No marked changes in renal excretory kinetics were found by pyrazinoate injection (12.5 mg/kg, i.v.). Consequently, the saturation in the active tubular secretion of AcSMM may play an important role in the nonlinear pharmacokinetics of SMM in pigs.

Acetylation↗

Contribution of renal active secretion in renal excretion of N4-acetylsulfamonomethoxine in conscious pigs.

The contribution of renal active tubular secretion of N4-acetylsulfamonomethoxine (AcSMM) in renal excretion was examined using 3 conscious pigs with permanent ureter cannulae. AcSMM was the main metabolite of sulfamonomethoxine (SMM) in pigs. When AcSMM (100 mg/kg) was intravenously injected, the renal clearance of AcSMM increased with the decrease of AcSMM plasma concentration. Michaelis-Menten kinetics was demonstrated in the renal excretion of AcSMM. It can be concluded that AcSMM is mostly excreted through active tubular secretion. The decrease of renal clearance of AcSMM may be thought as the causal factor of nonlinear plasma kinetics of SMM in pig.

Animals↗

Migration of macrophages from the marginal zone to germinal centers in the spleen of mice.

Histological observations of the mouse spleen were carried out at different times after intravenous carbon injection. Large carbon-laden macrophages appeared in great numbers in the marginal zone soon after injection. They came together favorably around the germinal centers. Possible migration of these cells toward the germinal centers diffusely from the periphery of the white pulp or through the periarterial lymphoid sheath was suggested. These macrophages entered the germinal centers on a large scale and clustered for a long period--at least 180 days. Since the same type of macrophages were observed persistently in the marginal zone, it was thought that some of them might arise from the blood stream. Possible migration of these cells from the marginal zone toward the germinal centers was also persistently observed. A second type of much smaller carbon-laden macrophages was seen in the white pulp. However, they never showed any favorable localization in the germinal centers as did large carbon-laden macrophages.

Animals↗

Responses of solitary tract nucleus neurons to taste and mechanical stimulations of the oral cavity in decerebrate rats.

Physiological characteristics of 45 taste and 15 mechanoreceptive units were examined in the solitary tract nucleus (NTS) of rats decerebrated at the pre- or midcollicular level, and compared with previous findings in the intact rat. The rostro-caudal extent of the area, where taste and mechanoreceptive neurons were recorded, was almost the same in the decerebrate rat as that in intact rat. The spontaneous discharge rate was significantly lower in the decerebrate rat than in the intact rat. The taste profile of the NTS units in decerebrate rats was quite different from that in intact rats; significant decreases in correlation coefficients were found between certain pairs of taste stimuli and spontaneous discharge rate, e.g. NaCl-quinine, sucrose-quinine. A large number of taste (18 of 31) and mechanoreceptive (12 of 15) units examined had receptive fields (RFs) on the palate, and four taste and two mechanoreceptive units on the circumvallate area. This contrasts with the findings in the intact rat. Some taste (n = 1) and mechanoreceptive units (n = 2) had large RFs. Taste units with different RF locations showed different taste profiles. Acute i.v. injection of amobarbital sodium affected only the response magnitude of taste units, suggesting that most of the differences between intact and decerebrate rats might be caused by decerebration. The present findings indicate that neural structures above the pre- or midcollicular level have tonic inhibitory or facilitatory effects on the response properties of NTS taste units.

Amobarbital↗

Stimulating effect of natural estrogens on proliferation of hepatocytes in adult mice.

A single oral administration of natural principal estrogens, estrone (E1), 17 beta-estradiol (E2) and estriol (E3), caused active proliferation of hepatocytes of adult mouse liver. Steroid hormones tested (testosterone, progesterone and cortisone) other than estrogens were not stimulants of proliferation of hepatocytes. Among these three natural estrogens, E3 was found to be the most potent stimulant of hepatocyte proliferation and E1 was the weakest. The possible mechanism of the hepatocyte-proliferating potency of estrogens was discussed in close relationship to their stimulating effect on the reticuloendothelial system.

Animals↗