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Biomedical subjects

Mitsuru Saito

Publications and source records attributed to Mitsuru Saito.

At least 19 recordsLinked to original sources

Binding capacity of Intravenous immunoglobulin G to BK polyomavirus determines its anti-BK polyomavirus activity in infected cultures.

BK polyomavirus (BKPyV) causes disease in immunocompromised individuals. This study tested the hypothesis that the antiviral efficacy of intravenous immunoglobulin (IVIG) against BKPyV depends on the relationship between its virus-binding capacity and the viral burden. We first quantified the BKPyV-binding capacity of IVIG and then characterized BKPyV replication in kidney-derived HK-2 and HEK293&#x202f;cells and in HEL cells under IVIG treatment. Subsequently, we analyzed the efficacy of IVIG at 0.03-10&#x202f;mg/mL against low-multiplicity of infection (MOI) and high-MOI infection in relation to the BKPyV-binding capacity of IVIG. BKPyV productively infected all three cell lines, with 14-day replication cycles of 2.2, 4.0, and 7.0 in HK-2, HEK293, and HEL cells, respectively, indicating that HEL cells were the most permissive. IVIG bound approximately 108 copies of BKPyV DNA per milligram. In the low-MOI infection model, where the total viral load remained within this estimated binding capacity, IVIG showed clear neutralizing activity, significantly reducing viral spread, viral DNA levels, and the number of VP1-positive cells in a dose-dependent manner (p&#x202f;<&#x202f;0.001). In contrast, in the high-MOI infection model, the viral load appeared to be high relative to the estimated IVIG binding capacity even at 10&#x202f;mg/mL, and IVIG showed little or no neutralizing effect on viral production or spread of infected cells. These findings identify an experimental relationship between IVIG binding capacity, viral burden, and antiviral efficacy and suggest that the antiviral effect of IVIG is greatest when administered early, thereby supporting further clinical evaluation of early or preemptive IVIG administration.

Humans↗

Involvement of persistent Na+ current in spike initiation in primary sensory neurons of the rat mesencephalic trigeminal nucleus.

It was recently shown that the persistent Na(+) current (I(NaP)) is generated in the proximal axon in response to somatic depolarization in neocortical pyramidal neurons, although the involvement of I(NaP) in spike initiation is still unclear. Here we show a potential role of I(NaP) in spike initiation of primary sensory neurons in the mesencephalic trigeminal nucleus (MTN) that display a backpropagation of the spike initiated in the stem axon toward the soma in response to soma depolarization. Riluzole (10 muM) and tetrodotoxin (TTX, 10 nM) caused an activation delay or a stepwise increase in the threshold for evoking soma spikes (S-spikes) without affecting the spike itself. Simultaneous patch-clamp recordings from the soma and axon hillock (AH) revealed that bath application of 50 nM TTX increased the delay in spike activation in response to soma depolarization, leaving the spike-backpropagation time from the AH to soma unchanged. This indicates that the increase in activation delay occurred in the stem axon. Furthermore, under a decreasing intracellular concentration gradient of QX-314 from the soma to AH created by QX-314-containing and QX-314-free patch pipettes, the amplitude and maximum rate of rise (MRR) of AH-spikes decreased with an increase in the activation delay following repetition of current-pulse injections, whereas S-spikes displayed decreases of considerably lesser degree in amplitude and MRR. This suggests that compared to S-spikes, AH-spikes more accurately reflect the attenuation of axonal spike by QX-314, consistent with the nature of spike backpropagation. These observations strongly suggest that low-voltage-activated I(NaP) is involved in spike initiation in the stem axon of MTN neurons.

4-Aminopyridine↗

Influence of UGT1A8 and UGT2B7 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients.

OBJECTIVE: UGT1A8 and UGT2B7 are important uridine diphosphate-glucuronosyltransferase isoforms for the glucuronidation of mycophenolic acid (MPA). The aim of this investigation was to elucidate MPA pharmacokinetics in UGT1A8 and UGT2B7 genotypes in Japanese renal transplant recipients. METHODS: Seventy-two recipients received repeated doses of mycophenolate mofetil and tacrolimus. On day 28 after renal transplantation, plasma MPA concentrations were measured for the next 24 h using high-performance liquid chromatography. UGT1A8*2 (A(173)G) and UGT2B7*2 (Y(268)) were detected using a PCR-RFLP-based procedure. RESULTS: There were no significant differences in daytime and nighttime pharmacokinetics of MPA between UGT1A8 or UGT2B7 genotypes. The mean daytime dose-adjusted AUC(0-12) of MPA in UGT1A8*1/*1, *1/*2 and *2/*2 were 2.47, 2.33 and 2.57 ng.h/ml/mg/kg (P = 0.7711), and the mean nighttime AUC(0-12) were 2.15, 2.00 and 2.08 ng.h/ml/mg/kg (P = 0.4656). The mean daytime and nighttime dose-adjusted AUC(0-12) of MPA in UGT2B7*1/*1, *1/*2 and *2/*2 were 2.61, 2.24 and 2.03 ng.h/ml/mg/kg and 2.18, 1.94, and 1.45 ng.h/ml/mg/kg, respectively (P = 0.3475 and 0.2575). The mean nighttime C(max), t(max), and AUC(6-12)/AUC(0-12) ratio (enterohepatic circulation and recirculation ratio) of MPA in all UGT1A8 and UGT2B7 genotypes were lower, longer, and higher, respectively, than the daytime values. CONCLUSIONS: Both UGT1A8 and UGT2B7 allelic variants seem not to affect Japanese interindividual variability for plasma MPA concentration. Regardless of UGT1A8 and UGT2B7 genetic polymorphisms, the absorption of MPA through enterohepatic recirculation is higher at night.

Adult↗

Radical nephroureterectomy as initial treatment for carcinoma in situ of upper urinary tract.

OBJECTIVES: Transitional cell carcinoma in situ (CIS) of the upper urinary tract is a relatively rare disease, and treatment guidelines remain to be defined. In this study, we evaluated the outcomes after radical nephroureterectomy as the initial therapy for upper urinary tract CIS. METHODS: Eight patients treated with radical nephroureterectomy after the diagnosis of upper urinary tract CIS from December 1999 to May 2004 were entered in this study. The diagnosis criteria included positive voided urinary cytology; negative multiple random biopsies of the bladder; negative radiographic studies, including retrograde pyelography and computed tomography; and serial positive cytology results in selective ipsilateral urine samples. RESULTS: The median follow-up period was 56 months. The presence of CIS was confirmed pathologically in all patients. Two patients had more invasive lesions (pT1 and pT2), although retrospective evaluation revealed no infiltrative lesions. Intravesical recurrence was found in 5 patients, whose median recurrence-free period was 16 months. These heterotopic urothelial recurrences did not affect patient survival, and all 8 patients were alive without disease at last follow-up. CONCLUSIONS: Although radical nephroureterectomy may be overtreatment for some patients with upper urinary tract CIS, excellent survival outcomes can be accomplished. In addition, the presence of concomitant invasive lesions, which cannot be identified on pretreatment examination in a substantial subset of patients with CIS, should be taken into account. Although the number of patients in this study was small, the results support the view that nephroureterectomy should remain a standard option for the initial treatment of this disease.

Aged↗

Degree of mineralization-related collagen crosslinking in the femoral neck cancellous bone in cases of hip fracture and controls.

Based on the present definition of osteoporosis, both bone density and quality are important factors in the determination of bone strength. Collagen crosslinking is a determinant of bone quality. Cross-links can form enzymatically by the action of lysyl oxidase or non-enzymatically, resulting in advanced glycation end products. Collagen crosslinking is affected by tissue maturation as well as the degree of mineralization. Homocysteine and vitamin B6 (pyridoxal) are also regulatory factors of collagen crosslinking. We elucidate the relationship between the degree of mineralization and collagen cross-links in cancellous bone from hip fracture cases. We also determined plasma levels of homocysteine and pyridoxal. Twenty-five female intracapsular hip fracture cases (78 +/- 6 years) and 25 age-matched postmortem controls (77 +/- 6 years) were included in this study. Collagen crosslinking was analyzed after each bone specimen was fractionated into low (1.7-2.0 g/ml) and high (>2.0 g/ml) density fractions. The content of enzymatic (immature reducible and mature nonreducible cross-links) and nonenzymatic cross-link (pentosidine) were determined. In the controls, there was no difference in total enzymatic cross-links between low and high density bone, while pentosidine content was significantly higher in high density bone. In the fracture cases, not only reduced enzymatic cross-links in high density bone and increased pentosidine in both low and high density bone, but also higher plasma homocysteine and lower pyridoxal levels were evident compared with the controls. These results indicate that detrimental crosslinking in both low and high mineralized bone result in impaired bone quality in osteoporotic patients.

Absorptiometry, Photon↗

Circadian pharmacokinetics of mycophenolic Acid and implication of genetic polymorphisms for early clinical events in renal transplant recipients.

BACKGROUND: We investigated the mycophenolic acid (MPA) chronopharmacokinetics and the relation between MPA circadian exposure and the incidence of acute rejection (AR). The association between selected genetic polymorphisms and clinical events or MPA circadian exposure was also studied. METHODS: Thirty recipients were studied one month after renal transplantation. Mycophenolate mofetil (MMF) was administered twice a day at a single dose of 0.5 g in four patients, 0.75 g in eight patients, and 1 g in 18 patients. RESULTS: The daytime area under the concentration-time curve (AUC0-12) was larger than the nighttime AUC0-12 (55.09 vs. 50.54 microg.hr/ml, P=0.049). The Cmax and tmax of MPA after the morning dose were respectively higher and shorter than those after the night dose. Seven patients (23.3%) had AR episodes. The MMF single dose per body weight (12.46 mg/kg in patients with AR vs. 16.99 in patients without AR), daytime and nighttime AUC0-12 (32.41 vs. 62.00 and 24.44 vs. 57.88 microg.hr/ml) and morning trough level of MPA (1.03 vs. 3.83 microg/ml) were significantly lower in patients with AR than in those without AR. The percentage of patients requiring diminished dose of MMF due to diarrhea was higher among patients with the multidrug resistance 1 (MDR1) C3435T T allele than among those with the CC genotype (P=0.049). CONCLUSION: MPA pharmacokinetics showed circadian variations, and a lower MPA AUC in both daytime and nighttime was associated with the occurrence of AR in the early stage after renal transplantation. The MDR1 C3435T polymorphism might be associated with diarrhea due to MPA.

Adult↗

Modulation of the control of muscle sympathetic nerve activity during severe orthostatic stress.

We tested the hypothesis that arterial baroreflex (ABR)-mediated beat-to-beat control over muscle sympathetic nerve activity (MSNA) is progressively modulated as orthostatic stress increases in humans, but that this control becomes impaired just before the onset of orthostatic syncope. In 17 healthy subjects, the ABR control over MSNA (burst incidence, burst strength and total MSNA) was evaluated by analysing the relationship between beat-to-beat spontaneous variations in diastolic blood pressure (DAP) and MSNA during supine rest (control) and during progressive, stepwise increases in lower body negative pressure (LBNP) that were incremented by -10 mmHg every 5 min until presyncope (nine subjects) or -60 mmHg was reached. (1) The linear relationships between DAP and burst strength and between DAP and total MSNA were shifted progressively upward as LBNP increased until the level at which syncope occurred. The relationship between DAP and burst incidence, however, gradually shifted upward from control only to LBNP = -30 mmHg; there was no further upward shift at higher LBNPs. (2) Although the slope of the relationship between DAP and burst strength and between DAP and total MSNA remained constant at all LBNPs tested, except at the level where syncope occurred, the slope of the relationship between DAP and burst incidence was reduced at LBNPs of -40 mmHg and higher (versus control). (3) In syncopal subjects, the slopes of the relationships between DAP and burst incidence, burst strength, and total MSNA were all substantially reduced during the 1-2 min period prior to the onset of syncope. Taken together, these results suggest baroreflex control over MSNA is progressively modulated as orthostatic stress increases, so that its sensitivity is substantially reduced during the period immediately preceding the severe hypotension associated with orthostatic syncope.

Adult↗

Two opposing roles of 4-AP-sensitive K+ current in initiation and invasion of spikes in rat mesencephalic trigeminal neurons.

The axon initial segment plays important roles in spike initiation and invasion of axonal spikes into the soma. Among primary sensory neurons, those in the mesencephalic trigeminal nucleus (MTN) are exceptional in their ability to initiate soma spikes (S-spikes) in response to synaptic inputs, consequently displaying two kinds of S-spikes, one caused by invasion of an axonal spike arising from the sensory receptor and the other initiated by somatic inputs. We investigated where spikes are initiated in such MTN neurons and whether there are any differences between the two kinds of S-spikes. Simultaneous patch-clamp recordings from the soma and axon hillock revealed a spike-backpropagation from the spike-initiation site in the stem axon to the soma in response to 1-ms somatic current pulse, which disclosed the delayed emergence of S-spikes after the current-pulse offset. These initiated S-spikes were smaller in amplitude than S-spikes generated by stimulation of the stem axon; however, 4-AP (< or =0.5 mM) eliminated the amplitude difference. Furthermore, 4-AP dramatically shortened the delay in spike initiation without affecting the spike-backpropagation time in the stem axon, whereas it substantially prolonged the refractory period of S-spikes arising from axonal-spike invasion without significantly affecting that of presumed axonal spikes. These observations suggest that 4-AP-sensitive K(+) currents exert two opposing effects on S-spikes depending on their origins: suppression of spike initiation and facilitation of axonal-spike invasion at higher frequencies. Consistent with these findings, strong immunoreactivities for Kv1.1 and Kv1.6, among 4-AP-sensitive and low-voltage-activated Kv1 family examined, were detected in the soma but not in the stem axon of MTN neurons.

4-Aminopyridine↗

Outcome of right hand-assisted retroperitoneoscopic living donor nephrectomy.

OBJECTIVES: To compare the results of right and left hand-assisted retroperitoneoscopic living donor nephrectomy (HARDN) and assess the usefulness and feasibility of right HARDN. METHODS: A total of 68 HARDNs performed from July 2001 to February 2005 in Akita University Medical Center were entered into this study. Of these, 12 cases were right-sided HARDN. The reasons for selecting right HARDN were wandering right kidney in 4, multiple left renal arteries in 3, lower glomerular function presenting in the right kidney in 2 patients, and left renal stone, right renal cyst, and right renal aneurysm in 1 patient each. We compared the perioperative and postoperative results of the 12 right-sided HARDNs with those of the 56 left HARDNs. RESULTS: No significant differences were found between the two groups in the demographic data (ie, age, sex, number of renal arteries), except for the body mass index. None of the right HARDNs resulted in major complications or open conversion, but two left HARDNs required conversion to open surgery. No difference was found between the two groups regarding estimated blood loss, warm ischemia time, or time to oral intake, although the right HARDN group had a longer mean operative time. No significant differences were found in the recipient's postoperative graft function or in the frequency of delayed graft function. CONCLUSIONS: Right HARDN provided almost similar perioperative and postoperative outcomes compared with those of left HARDN. Our results indicate that right HARDN is a choice for living donor nephrectomy because of its technical feasibility, safety, and minimal invasiveness, which are comparable to those of left HARDN.

Adult↗

Quantification and 24-hour monitoring of mycophenolic acid by high-performance liquid chromatography in Japanese renal transplant recipients.

We developed a rapid, simple, and sensitive high-performance liquid chromatography method with UV detection for the quantitative determination of mycophenolic acid (MPA) in human plasma. MPA and the internal standard (naproxen) were separated using a mobile phase of 0.04 M H(3)PO(4)-acetonitrile-methanol (3:3:4 v/v/v) over a CAPCELL PAK C18 MG column. A flow-rate of 0.5 ml/min was used at ambient temperature and sample detection was carried out at 254 nm. The assay required only 100 microl of plasma and involved liquid-liquid extraction, which gave high recovery (>94%). The lower limit of quantification for MPA was 0.05 microg/ml. Inter- and intra-day coefficients of variation were less than 9.6% and accuracies were within 9.3%. Additionally, we validated this method in 24-hour monitoring of plasma MPA concentrations after mycophenolate mofetil (MMF) morning and evening administration in 40 Japanese renal transplant recipients with 1.5 g/day MMF. The time to reach the maximum (11.7 microg/ml) and second peak (4.5 microg/ml) of MPA after morning 0.75 g MMF administration was 2.6 h and 9.0 h, and time to reach maximum (10.5 microg/ml) after evening 0.75 g administration was 4.0 h.

Asian People↗

[Poor bone quality in diabetes: detrimental collagen cross-link pattern reduces bone strength without change in bone mineral density].

Although type 2 diabetes is often characterized by normal or high bone mineral density (BMD), diabetes is associated with increased risk of fracture. This paradoxical phenomenon in type 2 diabetes may be explained by poorer "bone quality" by detrimental collagen cross-links in bone. Recently, we showed that the alteration of enzymatic and nonenzymatic crosslinking in bone could be important for explaining the variation of fracture susceptibility in diabetes (Osteoporos Int, 2006. Epub ahead of print). In this review, we describe that low turnover bone, hyperglycemia, mildly hyperhomocysteinemia, and vitamin B(6) insufficiency are crucial determinants of detrimental crosslinking of bone collagen in diabetes.

Animals↗

[Elevated plasma concentration of homocysteine, low level of vitamin B6, pyridoxal, and vitamin D insufficiency in patients with hip fracture: a possible explanation for detrimental cross-link pattern in bone collagen].

Impaired bone quality has been proposed as a cause of increased bone fragility in osteoporosis. Collagen crosslinking is a candidate for determining the material properties of bone. Collagen cross-links are of two types; lysyl oxidase (LOX) and lysyl hydroxylase (PLOD1; LH1, PLOD2; LH2b) controlled cross-links, and advanced glycation end products, pentosidine. Homocysteine and vitamin B(6) (pyridoxal) are also regulatory factors of collagen crosslinking. Recently, we reported that in the femoral neck fracture cases, not only reduced enzymatic cross-links in old osteon and increased pentosidine in both young and old osteons from cortical and cancellous bone, but also higher plasma homocysteine and lower pyridoxal levels were evident compared with the controls (Osteoporos Int 2006. Calcif Tissue Int, 2006). In this review, we describe that mildly hyperhomocysteinemia, and vitamin B(6) or vitamin D insufficiency are crucial determinants of detrimental crosslinking of bone collagen in patients with hip fracture.

Aged↗

Clinical and genetic risk factors for posttransplant diabetes mellitus in adult renal transplant recipients treated with tacrolimus.

BACKGROUND: The present study investigated the incidence of posttransplant diabetes mellitus (PTDM) and calculated the risk of developing PTDM under a tacrolimus-based immunosuppression based on clinical characteristics, tacrolimus pharmacokinetics, and genetic polymorphisms related to tacrolimus pharmacokinetics or diabetes mellitus. METHODS: Seventy nondiabetic adult kidney recipients were studied. Patients with continuous high plasma glucose levels, over 6.5 mg/dl of hemoglobin A1c, or requiring insulin and/or oral antidiabetic agents for more than 3 months after transplantation 6 months postoperatively were diagnosed as having PTDM. Twelve genomic polymorphisms were assessed. RESULTS: Six months after transplantation, 10 recipients (14.3%) developed PTDM. Positive risk factors were age (P=0.019) and body mass index (P=0.038). There were no significant differences in acute rejection rate, total steroid doses, tacrolimus pharmacokinetics or its related to genetic polymorphisms between the two groups. The frequency of PTDM was significantly higher in patients with the vitamin D receptor (VDR) TaqI t allele than in those with the TT genotype (P=0.013). On multivariate analysis, age over 50 years (odds ratio 9.28, P=0.003) and the presence of the VDR TaqI t allele (odds ratio 7.05, P=0.048) were correlated with the development of PTDM. CONCLUSION: The incidence of PTDM was 14.3% in our cohort. Age over 50 years was a risk factor. The presence of the VDR TaqI t allele may also be a risk factor for PTDM, suggesting that genotyping of diabetes-related polymorphisms is a possible method of predicting a patient's risk for developing PTDM and would be a valuable asset in selecting appropriate immunosuppressive regimens for individuals.

Adiponectin↗

Time-dependent modulation of arterial baroreflex control of muscle sympathetic nerve activity during isometric exercise in humans.

We investigated the time-dependent modulation of arterial baroreflex (ABR) control of muscle sympathetic nerve activity (MSNA) that occurs during isometric handgrip exercise (IHG). Thirteen healthy subjects performed a 3-min IHG at 30% maximal voluntary contraction, which was followed by a period of imposed postexercise muscle ischemia (PEMI). The ABR control of MSNA (burst incidence and strength and total activity) was evaluated by analyzing the relationship between spontaneous variations in diastolic arterial pressure (DAP) and MSNA during supine rest, at each minute of IHG, and during PEMI. We found that 1) the linear relations between DAP and MSNA variables were shifted progressively rightward until the third minute of IHG (IHG3); 2) 2 min into IHG (IHG2), the DAP-MSNA relations were shifted upward and were shifted further upward at IHG3; 3) the sensitivity of the ABR control of total MSNA was increased at IHG2 and increased further at IHG3; and 4) during PEMI, the ABR operating pressure was slightly higher than at IHG2, and the sensitivity of the control of total MSNA was the same as at IHG2. During PEMI, the DAP-burst strength and DAP-total MSNA relations were shifted downward from the IHG3 level to the IHG2 level, whereas the DAP-burst incidence relation remained at the IHG3 level. These results indicate that during IHG, ABR control of MSNA is modulated in a time-dependent manner. We suggest that this modulation of ABR function is one of the mechanisms underlying the progressive increase in blood pressure and MSNA during the course of isometric exercise.

Adaptation, Physiological↗

The "ligamentization" process in human anterior cruciate ligament reconstruction with autogenous patellar and hamstring tendons: a biochemical study.

BACKGROUND: There is little information documenting whether the phenomenon of "ligamentization," as proposed by Amiel, occurs in the human anterior cruciate ligament after clinically effective reconstruction. To clarify this point, we analyzed biochemical differences between the native anterior cruciate ligament; the patellar, semitendinosus, and gracilis tendons; and anterior cruciate ligaments reconstructed with autografts. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Fifty patients who underwent arthroscopically assisted anterior cruciate ligament reconstruction using either semitendinosus and gracilis tendon or bone-patellar tendon-bone autografts were selected for the study. Samples of grafted tissue were collected during arthroscopy and quantitatively analyzed for collagen content and the amount of reducible and nonreducible crosslinks at 4 to 6 postoperative months in patients with semitendinosus and gracilis tendon grafts and at 11 to 13 months in all patients with semitendinosus and gracilis tendon or bone-patellar tendon-bone grafts. RESULTS: The total collagen content and nonreducible/reducible crosslink ratios increased significantly during the postoperative period (P < .05). The dihydroxylysinonorleucine/hydroxylysinonorleucine ratio was 3.11 +/- 0.56 in the native anterior cruciate ligament, 1.21 +/- 0.47 in the patellar tendon, and 3.59 +/- 1.58 in the anterior cruciate ligaments reconstructed with bone-patellar tendon-bone autografts 1 year after surgery. The dihydroxylysinonorleucine/hydroxylysinonorleucine ratio in both semitendinosus and gracilis tendons was less than 1.0. However, in anterior cruciate ligaments reconstructed with semitendinosus and gracilis tendon autografts, it was 2.34 +/- 0.98 at 4 to 6 months and 3.43 +/- 1.61 at 11 to 13 months after the operation. CONCLUSIONS: After anterior cruciate ligament reconstruction with autografts, biochemical characteristics of the graft resembled those of the native anterior cruciate ligament. These findings suggest that, regarding the amount of collagen crosslinks and their architecture, the phenomenon of ligamentization occurs in the successfully reconstructed human anterior cruciate ligament within 1 year after operation.

Adolescent↗

Effects of a phenolic compound, resveratrol, on the renal function and costimulatory adhesion molecule CD86 expression in rat kidneys with ischemia/reperfusion injury.

Recent studies have suggested that an ischemia/reperfusion (I/R) injury enhances the expression of costimulatory adhesion molecules on the vascular endothelium. In the present study, we investigated the protective effects of resveratrol, a phenolic product, on the renal function and expression of CD86 in rat kidneys with I/R injury. Wistar rats were divided into four groups; 1) an I/R group with right nephrectomy and 1-hour clamping of the left renal pedicle; 2) a vehicle group, I/R plus 10% ethanol (0.1 ml/kg/day) administered by intra-peritoneal injection from day -1 through to 7; 3) a resveratrol group, I/R plus 4 mg/kg/day of resveratrol; and 4) a sham group. Blood samples were obtained via the tail vein at 1 day before, and 1, 3, and 7 days after the operation (day 0) for the measurement of serum creatinine (Scr) levels. The expression of CD86 protein was analyzed by immunofluorescence staining, and the level of CD86 messenger RNA (mRNA) was evaluated quantitatively by a real-time reverse transcription-polymerase chain reaction (RT-PCR) in the renal cortex at day 3. Scr levels of the resveratrol group were significantly lower than those of the I/R and vehicle groups on days 1 and 3 after the operation. From the immunohistochemical study, the expression of CD86 in the glomerular endothelium and peritubular vessels was found to be attenuated in the resveratrol group compared with the I/R or vehicle group. In the resveratrol group, the CD86 mRNA level was significantly lower than that in the I/R or vehicle group, and it was significantly decreased by about one fifth of that in the sham group. Our results suggest that resveratrol markedly reduces renal dysfunction and attenuates the mRNA and protein expression of CD86 following I/R injury.

Animals↗

[Correlation between degree of mineralization and collagen cross-links as determinants of bone quality].

Little is known about the correlation between degree of mineralization and collagen properties (enzymatic and non-enzymatic cross-links) in bone. In the patients with femoral neck fracture, not only the mineral embrittlement but also the qualitative changes in collagen cross-links were observed in both low and high mineralized bone fractions. These results suggest that this trend towards an increased loss of collagen quality may have led to accelerated increase of fragility in osteoporosis.

Bone and Bones↗