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Biomedical subjects

I Hatakeyama

Publications and source records attributed to I Hatakeyama.

At least 19 recordsLinked to original sources
PubMed2000

Mechanochemical solid-state polymerization (X): the influence of copolymer structure in copolymeric prodrugs on the nature of drug release.

From the standpoint of the mechanism of mechanochemical polymerization, two kinds of copolymeric prodrug, whose monomer sequence distribution (MSD) is different from each other, can be prepared by this polymerization under appropriate operational conditions: one is a random copolymer abundant in the longer block consisting of the same repeating units (multi-block copolymer), and the other is a block copolymer. To confirm the difference of MSD, the 13C-NMR spectra of poly(acrylamide-co-sodium acrylate) prepared by mechanochemical polymerization were measured and compared with the spectrum of that synthesized by a conventional radical-initiated solution polymerization, which produces the random copolymer normally. The results show that MSD in copolymers depends on the polymerization method (operational condition). We prepared three kinds of copolymeric prodrug consisting of acrylamide and vinyl monomer of 5-fluorouracil, whose MSD is different from one another. These copolymeric prodrugs had almost the same number average molecular weight, particle diameter and composition, and differed only in MSD. We compared the rate of drug release of these copolymeric prodrugs. The rate of drug release was the highest with the random copolymer, followed by the mechanochemically produced multi-block copolymer and the block copolymer. This result suggests that the rate of drug release depends on MSD of copolymeric prodrugs. These results are useful as they give a fundamental insight into the synthesis of copolymeric prodrugs having the desired rate of drug release.

Antimetabolites↗
PubMed1998

Mechanochemical solid-state polymerization. IX. Theoretical analysis of rate of drug release from powdered polymeric prodrugs in a heterogeneous system.

We theoretically derived the rate equation of drug release from a simple model in a heterogeneous system. Four assumptions were used to simplify the model. Two kinds of rate equations for drug release derived from two possible limiting cases, that the rate-determining step is a diffusion or hydrolysis controlled process, can predict the experimental results up to 50% hydrolysis. However, the predictions at the later stage by these equations are insufficient. These results suggest that the process of drug release from powdered polymeric prodrugs in a heterogeneous system must be described by both diffusion and hydrolysis. The rate equation derived from a model considering both the diffusion and hydrolysis processes can successfully predict the experimental results for several kinds of polymeric prodrugs. It is also shown that the diffusion coefficient and rate constant for hydrolysis calculated from this equation thoroughly express the character of the comonomer. The rate equation derived from the model that considers both diffusion and hydrolysis is very useful to analyze drug release from various kinds of polymeric prodrugs in a heterogeneous system.

Hydrolysis↗
PubMed1989

Application of electrocapacitography to investigation of cephalic and cerebral circulation in the rabbit.

Electrocapacitography devised for medical purposes by Hatakeyama was applied as a noninvasive volumetric method to investigate circulation in the rabbit head and brain. The effective electric capacitance was measured by means of a highly sensitive device. An electrocapacitogram (ECPG) of the head, considered to reflect the volume of intracranial as well as extracranial blood vessels, varied rhythmically with cardiac beat and respiratory movement. In general, the pulsatile variations of ECPG in synchronization with cardiac beat (ECPG pulse) bore a resemblance to arterial pulse. Occlusion of the common carotid artery caused the ECPG level corresponding to mean vascular volume to fall markedly and in most cases the amplitude of ECPG pulse was diminished. By rapid infusion of 5 ml of the blood into intracranial blood vessels via the internal carotid artery or into extracranial blood vessels via the external carotid artery, ECPG level was raised transitorily, the effect of extracranial infusion being larger than that of intracranial infusion. Stimulation of the central cut end of the cervical sympathetic nerve reduced ECPG level considerably. This response was greatly diminished by carotid occlusion and sometimes a temporary rise of ECPG was observed at the beginning of the stimulation. In several cases the effect was reversed completely by carotid occlusion and an increase of ECPG during the stimulation was observed. These findings suggest the existence of a sympathetic vasoconstrictor in the head as well as a sympathetic vasodilator of the brain, although in confirmation of this review further investigation is required. ECPG of the head is demonstrated to be a useful method for investigating circulation in the head including brain.

Animals↗
PubMed1988

Transitory cardiovascular responses to rapid infusion of blood into aorta of rabbit.

Blood (5 to 15 ml) was infused into aorta of the anesthetized rabbit through the carotid artery or femoral artery at a constant rate (0.55 to 8.3 ml/s). The carotid sinuses were occluded. The systemic arterial pressure (SAP) began to rise immediately at the onset of the infusion and dropped gradually in most cases during the infusion. SAP continued to decline after the infusion and in many cases became lower than the preinfusion pressure. Within seconds, SAP tapered off to its lowest point and resumed a gradual rise, leveling off higher than its initial pressure. A depressor effect caused by the rapid infusion of blood into the aorta (DRIA) was observed in every rabbit. DRIA was not suppressed much by the section of aortic or vagal nerves. DRIA was markedly suppressed by the administration of alpha-adrenergic blockade, but beta-adrenergic blockade had little effect on DRIA. By using a hydraulic model of the closed circulatory system, a theoretical analysis was made on the basis of the "theory of active fluid element," a theory developed by Hatakeyama, one of the authors, and it was demonstrated that DRIA must not be considered to be a passive hemodynamic phenomenon. The results obtained suggest that a nervous regulatory mechanism--rather than the reflex via the carotid sinus or aortic baroreceptors, or other mechanoreceptors--plays an important part in the venous and the cardiac regions.

Adrenergic alpha-Antagonists↗
PubMed1981

[Response types of the stomach movement induced by diencephalic stimulation (author's transl)].

The stomach movements were detected using strain gauges from chloralose-urethane anesthetized rabbits. The gauges were fixed on the serosal surface of the fundic part a week before each experiment. The intensity, frequency, or pulse width of the stimuli exercised little influence basically on the response patterns; thus, 40-Hz continuous pulses were delivered to the diencephalon. A total of 110 out of 259 stimulating points in the diencephala affected either the rhythmic movement (RM) or the fundamental muscle tone (FT) of the stomach. Five main types of response patterns were recognized: (1) facilitatory responses showing an increase in amplitude and frequency of RM, (2) inhibitory responses showing a decrease in amplitude and frequency of RM, (3) an elevation of FT, (4) a descent of FT, and (5) after-effect type only exhibiting a significant response after the turn-off of a given stimulus. An attempt was made to correspond each of the stomach responses to the anatomical location of the responsive points. The corresponding points were distributed throughout the hypothalamic area. The functional localization was indistinct except of the anterior region of the hypothalamus which was more responsible for the facilitatory effect.

Animals↗