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Biomedical subjects

M Okuno

Publications and source records attributed to M Okuno.

At least 37 records · Page 2Linked to original sources
PubMed2000

Histomorphometric study on high-strength hydroxyapatite/poly(L-lactide) composite rods for internal fixation of bone fractures.

The purpose of this study was to investigate the bone-implant interface of high-strength hydroxyapatite (HA)/poly(L-lactide) (PLLA) composite rods. As reinforcing particles, two types of HA particles-calcined HA (c-HA) and uncalcined HA (u-HA)-were applied to allow comparison of their suitability as bioactive fillers. Four types of composites (c-HA30, c-HA40, u-HA30, and u-HA40), which contained 30 or 40% by weight of each HA particle, were used. Unfilled PLLA rods were used as controls. A hole was drilled in the distal femora of 50 rabbits, and a composite or unfilled PLLA rod was implanted in a press-fit manner. Two, 4, 8, and 25 weeks after implantation, the samples were examined histologically by light microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). An image analyzer was used for histomorphometric analysis of the bone-implant interface. An affinity index was calculated for each material; this was the length of bone directly apposed to the rods expressed as a percentage of the total length of the rod surface. In all the composites, histologic examination showed new bone formation at 2 weeks after implantation. The bone gradually grew along the composite surface. SEM showed direct bone contact with the composites without intervening fibrous tissue. During follow-up, the affinity indices of all the composite rods were significantly higher than those of the unfilled PLLA rods (p < 0.01; two-way ANOVA). The maximum affinity index (41%) was attained at 4 weeks in c-HA40 rods. In contrast, little bone contact was seen in unfilled PLLA rods. The only significant difference in affinity indices among the composites was that c-HA40 had a higher affinity index than u-HA40 (p < 0.05 at 4 weeks). No disintegration of rods or polymer debris, which could elicit inflammatory tissue reactions, was observed even at 25 weeks. Our results indicate that osteoconductive bone formation on composites could enhance the stability between bone and implant in fracture repair.

Absorbable Implants↗
PubMed2000

Platelet-derived microparticles in patients with arteriosclerosis obliterans: enhancement of high shear-induced microparticle generation by cytokines.

We evaluated the plasma concentrations of cytokines and platelet-derived microparticles in patients with arteriosclerosis obliterans and studied the effect of cytokines on platelet-derived microparticle generation under high shear stress. Interleukin-6 levels peaked at 48 hours after vascular surgery, while thrombopoietin started to increase at 24 to 48 hours postoperatively and peaked on the seventh day. Platelet activation markers were increased in the arteriosclerosis obliterans patients preoperatively. Levels of P-selectin and CD63 both increased further, peaking at 6 to 24 hours postoperatively. Platelet-derived microparticle levels were also increased preoperatively. At 6 hours postoperatively, the plasma level of platelet-derived microparticles was significantly increased. Plasma platelet-derived microparticle level was lower at 12 hours but only returned to the preoperative value at 7 days after grafting. There was a difference in the platelet-derived microparticle level at 7 days between patients with or without antiplatelet therapy (cilostazol). The effect of cytokines on platelet activation under high shear stress was also studied. Interleukin-6 and thrombopoietin enhanced both P-selectin expression and platelet-derived microparticle generation under high shear stress. These results suggest that platelet-derived microparticles are released by platelet activation after vascular grafting when certain cytokines increase under high shear stress and that antiplatelet therapy may reduce platelet-derived microparticle levels postoperatively.

Aged↗
PubMed2000

Biodegradation behavior of ultra-high-strength hydroxyapatite/poly (L-lactide) composite rods for internal fixation of bone fractures.

The purpose of this study was to investigate the biodegradation behavior of the ultra-high-strength hydroxyapatite/poly(L-lactide) (HA/PLLA) composite rods for fracture repair. Two kinds of composite materials were used in this study: u-HA/PLLA. which contained 30% by weight of uncalcined HA as reinforcing particles, and c-HA/PLLA, which contained 30% by weight of calcined HA as reinforcing particles. These composite rods were implanted in the subcutis and in the medullary cavities of rabbits. The specimens were removed at specific intervals between 2 and 52 weeks and the mechanical strength was measured for the rods in the subcutis, and the molecular weight and crystallinity were measured for the rods in both the subcutis and medullary cavities. The rod surfaces were examined using a scanning electron microscope (SEM). The specimens were examined histologically by light microscopy. The bending strength of the composites implanted in the subcutis was maintained at more than 200 M Pa at 25 weeks and at 150 MPa at 52 weeks. The molecular weight dropped to 45% of the initial values at 8 weeks and to approximately 10% at 52 weeks. Significant differences in the molecular weight were seen between c-HA/PLLA and u-HA/PLLA, with u-HA/PLLA showing a faster rate of decrease than c-HA/PLLA after 8 weeks. SEM demonstrated that HA particles disappeared increasingly from the rod surfaces over time and that the spaces left by these HA particles formed many pores in the composite surfaces at 52 weeks. Histologically, a fibrous tissue layer was formed around the composite rod from 4 weeks in the subcutis and in the diaphyseal area of the medullary canal. This became more mature over time. Bony tissue contact to the composites without fibrous tissue layers was seen in the metaphyseal area of the medullary canal. During the experimental period, there were no inflammatory cells such as mono- or multi-nuclear phagocytes. Although further long-term studies for degradation are needed, the composites have promising mechanical strength and no adverse tissue reaction for use as fracture-fixation devices during the experimental periods.

Animals↗
PubMed2000

Expressional patterns of cytokines in a murine model of acute myocarditis: early expression of cardiotrophin-1.

To determine the role of cytokines in acute myocarditis, we examined expressional patterns of cardiotrophin-1 (CT-1), TNF-alpha, and IL-1alpha in a murine model of acute myocarditis. Ten-day-old Institute of Cancer Research mice were injected with Coxsackievirus B3 and killed on Days 1, 2, 3, 4, 5, 7, 10, 14, and 28 of injection. TNF-alpha and IL-1alpha expressions were investigated on histological sections from each heart, and mRNA expression of TNF-alpha, IL-1alpha, and CT-1 in the heart was examined by reverse transcription-polymerase chain reaction and RNase protection assay. To determine myocardial regeneration, cardiomyocytic DNA synthesis was investigated using bromodeoxyuridine on Days 3, 5, 7, and 10, and the labeling index was calculated in each heart. Age-matched uninfected mice were used as controls. TNFalpha and IL-1alpha expression was first detected in the cardiomyocytes on Day 3 and reached the maximum level on Day 7, when inflammatory changes were most prominent. Although an increased expression of TNFalpha and IL-1alpha mRNA was also detected on Day 3, CT-1 mRNA expression was distinctly augmented on Day 2. The labeling indices in the hearts with myocarditis were significantly higher than in those of the controls in all of the time points examined. CT-1 expression preceded TNF-alpha and IL-1alpha expressions and active DNA synthesis in a murine model of acute myocarditis. All CVB3-infected mice with anti-glycoprotein-130 antibody treatment died within 6 days. CT-1 may exert a protective role by modulating cytokine production and by inducing cardiomyocytic proliferation in CVB3-infected murine hearts.

Acute Disease↗
PubMed2000

Bone bonding ability of a new biodegradable composite for internal fixation of bone fractures.

Hydroxyapatite particles and poly(L-lactide) composites for internal fixation of bone fractures have been developed based on the hypothesis that incorporation of hydroxyapatite particles in a poly(L-lactide) matrix might enhance bone bonding. This study evaluated the bone bonding ability of these biodegradable composites. Two types of hydroxyapatite and poly(L-lactide) composite were used in this study: calcined hydroxyapatite/poly(L-lactide) and uncalcined hydroxyapatite/poly(L-lactide). Rectangular plates (2 x 10 x 15 mm) of each composite or poly(L-lactide) were implanted into the metaphysis of the tibiae of 33 male rabbits, and the failure load was measured by conducting a detaching test 8, 16, and 25 weeks after implantation. The failure loads of calcined hydroxyapatite/poly(L-lactide), uncalcined hydroxyapatite/poly(L-lactide), and poly(L-lactide), respectively, were 13.60, 13.95, and 0.46 N at 8 weeks; 29.84, 24.09, and 2.86 N at 16 weeks; and 25.50, 29.67, and 2.43 N at 25 weeks. Histologic observation revealed that the composites formed direct contact with the bone. The results in this study indicate that the composites improved the strength of the interface between bone and plate. This improved interfacial strength lead to a substantial decrease in the frequency of implant loosening in the treatment of fractured bones by internal fixation.

Absorbable Implants↗
PubMed2000

Skin hemodynamics during change from supine to lateral position.

The purpose of this study was to identify the skin hemodynamics during the position change from supine to lateral in patients with neurodegenerative diseases. The participants were 19 patients with neurodegenerative diseases and 12 healthy volunteers. The alteration in the total concentration of oxyhemoglobin and deoxyhemoglobin, indicative of change in blood volume, was measured in the skin of the left flank by using a portable noninvasive tissue oxygen monitor by near-infrared spectroscopy. The positions were changed from the left and right lateral with a return to the supine between each procedure. In healthy volunteers, total hemoglobin concentration (skin blood volume) increased when the position changed from supine to left lateral and decreased when changed from supine to right lateral. The decreased skin blood volume gradually recovered after a change from the supine to the right lateral position in healthy volunteers. However, it did not recover in three sporadic olivopontocerebellar atrophy (OPCA) patients with marked autonomic dysfunction and one Parkinsonian patient with severe orthostatic hypotension. Our study identified that the intracutaneous blood was changing dynamically during the position change from supine to lateral and was regulated by autonomic nerve function.

Autonomic Pathways↗
PubMed2000

Effects of intracoronary tissue-type plasminogen activator treatment in kawasaki disease and acute myocardial infarction.

We retrospectively studied 3 patients with Kawasaki disease (KD) and acute myocardial infarction (AMI) who were treated with intracoronary administration of tissue-type plasminogen activator (t-PA). Two-dimensional echocardiogram on the next day of the treatment revealed reduction of thrombus and improvement of the cardiac function in all 3 patients. However, a 12-month-old patient treated with 200,000 U/kg of t-PA at 48 h after the onset of AMI died of recurrent myocardial infarction. The other 2 patients treated with 400,000 and 800,000 U/kg, respectively, showed clear, though not prompt, improvement in clinical symptoms and laboratory data. The intracoronary thrombolytic therapy using high-dose t-PA appears effective in treating AMI associated with KD.

Coronary Angiography↗
PubMed2000

A comparative study of rural clinics in remote islands and inland areas.

The social and professional isolation of physicians remains an important issue in rural areas. However, few studies have investigated the involvement of geographic factors in the isolation. This study investigates rural public clinics in inland and remote island locations and attempts to objectively compare the isolation of these physicians. A mailed questionnaire was sent to rural clinics where graduate physicians from Jichi Medical School were working in 1994 and 1995. Among the 198 clinics with one or more full-time physicians, 185 (93 percent) responded to the inquiry. Geographic and demographic factors of the communities were compared between 43 clinics located in remote islands and the other 142 rural inland clinics. Rural clinics in remote islands have smaller subject populations, fewer part-time physicians, a longer journey to the nearest city, and a longer distance and travel time to the base hospital than rural inland clinics. Physicians in remote island clinics had less medical training and are more isolated than other physicians. More than half of the clinic physicians in remote islands have no regular training schedule, in contrast to less than a quarter of the inland clinic physicians. Almost all clinics (97.7%) in remote islands do not have a part-time physician, whereas about 20 percent of the rural inland clinics do. Physicians in remote island clinics are more socially and professionally isolated than those in inland clinics. Strategies to reduce these problems should be given priority in rural health policy and measures tailored to rural clinics in remote islands.

Education, Medical, Continuing↗
PubMed2000

Nutritional pharmacotherapy of chronic liver disease: from support of liver failure to prevention of liver cancer.

Many patients with liver cirrhosis are in a state of protein and energy malnutrition and require careful nutritional support. Our research has revealed that approximately 30% of the patients have protein-energy malnutrition, 40% protein malnutrition, and 10% energy malnutrition; 20% are in a normal nutritional state. Supplementation with branched-chain amino acids alleviates chronic liver failure, improves the protein nutritional state, and subsequently prolongs survival. In contrast, therapeutic modalities for energy malnutrition have not yet been fully elucidated and await further studies. Improved survival of the cirrhotic patients essentially brings a higher incidence of hepatocellular carcinoma (HCC). A synthetic analogue of vitamin A (acyclic retinoid or 4,5-dehydrogeranyl geranoic acid) prevents at least the development of second primary tumors after curative treatment of preceding HCC. The mechanism of this cancer chemo-prevention is clonal deletion of premalignant and latent malignant cells by the retinoid. We describe our clinical experiences with these two nutritional pharmacotherapies of chronic liver diseases and review their basic mechanisms.

Amino Acids, Branched-Chain↗
PubMed1999

Bonding behavior of ultrahigh strength unsintered hydroxyapatite particles/poly(L-lactide) composites to surface of tibial cortex in rabbits.

Unsintered hydroxyapatite particles/poly(L-lactide) (u-HA/PLLA) composites with an initial bending strength of up to 270 MPa were developed based on the hypothesis that inclusion of u-HA particles in a PLLA matrix might enhance bone bonding. The purpose of this study was to examine the bonding strength and behavior of these u-HA/PLLA composites on the surface of the bone cortex. Composites containing 30 (u-HA30), 40 (u-HA40), or 50 wt % (u-HA50) of fine u-HA particles (3-microm average particle size) were prepared. Semicolumnar plates of these composites and control PLLA plates were fixed with metal screws to the surface of both proximal tibial cortices in 45 rabbits. The loads required to detach the plates from the bone cortex surface, defined as the bonding strengths, were measured at 4, 8, and 25 weeks after implantation. Bonding strengths in the u-HA30 group at 8 weeks and in the u-HA40 and u-HA50 groups at each postimplantation time were significantly greater than in the PLLA group (post hoc test using Fisher's protected least significant difference method). At each postimplantation time histological examinations revealed direct contact between the bone and the u-HA/PLLA composite plates without any intervening fibrous tissue. There was no evidence of any inflammatory or foreign-body response in any group throughout the follow-up periods. The results of this study suggest that the biodegradable PLLA fixation plates amended with u-HA particles could be functionally superior to PLLA plates without particles.

Animals↗
PubMed1999

Regulation of microtubule sliding by a 36-kDa phosphoprotein in hamster sperm flagella.

Cyclic AMP has been shown essential for activation of sperm motility. When immotile hamster caudal epididymal spermatozoa were suspended in a Ca2+-deficient solution, they showed a sluggish motility. Spermatozoa were demembranated and transferred to an ATP-containing reactivation solution. Demembranated spermatozoa did not exhibit reactivated flagellar movement unless cAMP was added. Conversely, when the immotile epididymal spermatozoa were suspended in a Ca2+-containing solution, they were immediately activated to display a vigorous motility; demembranated spermatozoa also exhibited reactivated flagellar movement in the reactivation solution without cAMP. Further investigation of microtubule sliding properties revealed that the effects of Ca2+ on live spermatozoa were identical with the effects of cAMP on demembranated spermatozoa both in microtubule sliding velocity and sliding disintegration pattern. Moreover, a 36-kDa flagellar protein was found to be phosphorylated in a cAMP-dependent manner and coupled to the motility activation. A polyclonal antibody against this protein was developed and showed specific immunolocalization and significant inhibitory effects on microtubule sliding disintegration. These results indicate that extracellular Ca2+ owes its effect to triggering intracellular cAMP production, and cAMP-dependent phosphorylation of a 36-kDa phosphoprotein activates hamster sperm motility through regulation of microtubule sliding properties.

Animals↗
PubMed1999

Quantitative evaluation of gait pattern in patients with osteoarthrosis of the knee before and after total knee arthroplasty. Gait analysis using a pressure measuring system.

Using a pressure measuring system, we quantitatively evaluated gait pattern in patients with osteoarthrosis (OA) of the knee before and after total knee arthroplasty (TKA). In the OA group, the stance time was longer, and the average vertical component of the floor reaction force (AVF) was lower than the values in normal age-matched subjects. These gait parameters correlated with the clinical score. These results suggest that changes in the gait parameters reflect gait patterns that reduce load on the knee. The center of pressure (COP) under the foot was correlated with the axial alignment of the lower limb in the mid-stance phase. In the TKA group, the clinical scores and gait parameters were improved 12 months after surgery compared with the preoperative values. The COP in the mid-stance phase moved inward after the TKA. However, in patients examined more than 2 years after a TKA, stance time and AVF did not reach normal levels, despite the patients' good clinical scores. These findings indicate that the gait pattern before surgery continues although pain on walking is reduced early after a TKA. Gait evaluation with a simple pressure measuring system revealed the changes in gait that are difficult to define by subjective clinical assessment.

Aged↗
PubMed1999

Bioresorbable devices made of forged composites of hydroxyapatite (HA) particles and poly-L-lactide (PLLA): Part I. Basic characteristics.

Compounds that had neither calcined nor sintered hydroxyapatite (u-HA) particles (particulate size 0.2-20 microns, averaging 3.0 microns, Ca/P = 1.69, and containing CO3(2-) uniformly distributed in a poly-L-lactide (PLLA, Mv: 400 KDa) matrix with a content of 20-50 wt% (with 10% increment) were reinforced into composites by a forging process, which was a unique compression molding, and were then machined on a lathe in order to produce practical radiopaque internal bone fixation devices having high mechanical strength which was maintained during bony union, total resorbability and bioactivity such as bone bonding capability and osteoconductivity. From the results of measurement of various mechanical properties, it was confirmed that the composites generally showed the highest mechanical strength among this type of reinforced bioceramic fibers or particles/bioresorbable polymer composite known to date. The bending strength (Sb) of about 270 MPa was far higher value than that for cortical bone, and the modulus (Eb) of 12 GPa was almost equivalent to that for cortical bone. In particular, the impact strength (Si) was extremely high at about two times the value (166 KJ/m2) of polycarbonate. The in vitro change in Sb, Mv (viscosity average molecular weight), Mw/Mn (molecular weight distribution) and crystallinity, and their relationship with each other was also examined by immersing samples in a phosphate buffer solution (PBS). An immediate decrease in the initial Mv could be found in composites with high u-HA contents (30-50 wt%), although a time-lag stage for degradation where the initial Mv hardly changes was apparent in cases of PLLA-only or in a composite with a low u-HA content (20 wt%). The Sb changed with corresponding decremental curves for the Mv and retained over 200 MPa for up to 24 weeks, the period of time necessary for full bony union, so that the composite satisfied initial mechanical strengths while maintaining them for as long as necessary for internal bone fixation devices. These results supported the idea that there is a difference in the degradation process such that PLLA alone required a period of time to achieve the possibility of hydrolysis into the inner side, whereas composites with high u-HA contents (30-50 wt%) immediately filled with water through to the inner side and were hydrolyzed homogeneously. Many hydroxyapatite crystals deposited and grew on the surface after 3-6 d and generously covered the surface with a fairly thick layer after 7 d of post-immersion in simulated body fluid (SBF) as evaluated by means of energy dispersive X-ray (EDX). This suggested the ability of the radiopaque composites to bond to bone. Since the composites were dense and had ultra-high strength, and the processability was so excellent, many kinds of fine and accurate screws, pins, plates, and other internal bone fixation devices for orthopedic, oral and maxillofacial, craniofacial, and plastic and reconstructive surgeries could be produced by machining treatment. These devices have potential applications for clinical use following the assessment of adaptation during in vivo studies.

Absorbable Implants↗