Tibial condylar valgus osteotomy (TCVO) for osteoarthritis of the knee: 5-year clinical and radiological results

According to one line of thought only propositions can be part of one’s evidence, since only propositions can serve the central functions of our ordinary concept of evidence. Ram Neta has challenged this argument. In this paper I respond to Neta’s challenge

Absorption, Metabolism, and Excretion by Freely Moving Rats of 3,4-DHPEA-EDA and Related Polyphenols from Olive Fruits ( Olea europaea

Absorption, metabolism, and excretion of 3,4-DHPEA-EDA, oleuropein, and hydroxytyrosol isolated from olive fruits were newly evaluated after oral and intravenous administration in freely moving rats cannulated in the portal vein, jugular vein, and bile duct. Orally administered 3,4-DHPEA-EDA, an important bioactive compound in olive pomace, was readily absorbed and metabolized to hydroxytyrosol, homovanillic acid, and homovanillyl alcohol, as shown by dose-normalized 4 h area under the curve (AUC0→4 h/Dose) values of 27.7, 4.5, and 4.2 μM·min·kg/μmol, respectively, in portal plasma after oral administration. The parent compound 3,4-DHPEA-EDA was not observed in the portal plasma, urine, and bile after oral and intravenous administration. Additionally, hydroxytyrosol, homovanillic acid, and homovanillyl alcohol in the portal plasma after oral administration of hydroxytyrosol showed 51.1, 22.8, and 7.1 μM·min·kg/μmol AUC0→4 h/Dose, respectively. When oleuropein, a polar glucoside, was injected orally, oleuropein in the portal plasma showed 0.9 μM·min·kg/μmol AUC0→4 h/Dose. However, homovanillic acid was detected from oleuropein in only a small amount in the portal plasma. Moreover, the bioavailability of hydroxytyrosol and oleuropein for 4 hours was 13.1% and 0.5%, respectively. Because the amount of 3,4-DHPEA-EDA in olive fruits is about 2-3 times greater than that of hydroxytyrosol, the metabolites of 3,4-DHPEA-EDA will influence biological activities

Simultaneous medial opening wedge high tibial osteotomy and revision anterior cruciate ligament reconstruction using a bone-patella tendon-bone graft: A case report

It is said that the clinical results of cases with anterior cruciate ligament reconstruction (ACLR) who have knee osteoarthritis (OA) are not very good. A case of simultaneous medial opening wedge high tibial osteotomy (MOWHTO) and revision ACLR using a bone-patella tendon-bone (BPTB) graft for medial knee OA after re-tear of a reconstructed ACL graft is reported. The patient was a 49-year-old man who underwent surgery for a right knee ACL injury by ACLR using an ipsilateral hamstring tendon graft 7 years earlier. He sprained his right knee while he was skiing and injured his reconstructed ACL graft. He had knee instability and pain at the medial side of his knee. X-ray showed a tibia vara deformity and medial knee OA of Kellgren-Lawrence grade II. It was thought that the medial knee pain would remain if he were treated by revision ACLR alone. Therefore, simultaneous MOWHTO and revision ACLR using an ipsilateral BPTB graft were performed. The excellent clinical results and radiological findings 3 years after the operation indicate the usefulness of this approach

High risk of elevated metal concentrations with 9/10-mm stem trunnions and highly cross-linked polyethylene grafted with poly(2-methacryloyloxyethyl phosphorylcholine) in total hip arthroplasty

Background: The risks of metal release due to fretting and corrosion at the head–neck junction and consequent adverse local tissue reaction (ALTR) have concerns in metal-on-polyethylene (MoP) total hip arthroplasty (THA). Although trunnions have become thinner in diameter to increase the range of motion, it has remained unclear whether this change affects metal release and ALTR in vivo. This study aimed to investigate serum metal concentrations and the prevalence of ALTR in MoP THA with a 9/10-mm stem trunnion.Patients and methods: A consecutive series of 37 hips that underwent THA using MoP grafted with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) with a 9/10-mm trunnion stem were retrospectively reviewed. Serum metal levels were assessed and compared with those in MoP THA with a 10/12-mm trunnion stem. ALTR was diagnosed with serum metal levels and cross-sectional images. The factors associated with serum metal levels were also assessed.Results: The median serum cobalt and chromium levels were 1.5 μg/L and 1.0 μg/L in the 9/10-mm group and 0.2 μg/L and 0.4 μg/L in the 10/12-mm group, respectively. ALTR was found in 5 hips of 3 patients. Revision surgery was performed in 4 hips, and all stem trunnions and femoral heads showed severe corrosion. Postoperative walking ability was associated with serum metal levels.Conclusion: It was found that a 9/10-mm stem trunnion with MoP grafted with PMPC had high risks of metal release in primary THA. Careful follow-up and cross-sectional imaging are needed to detect ALTR for early revision

Low molecular weight heparin suppresses receptor for advanced glycation end products-mediated expression of malignant phenotype in human fibrosarcoma cells

医薬保健研究域医学系The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor and its engagement by ligands such as high mobility group box 1 (HMGB1) is implicated in tumor growth and metastasis. Low molecular weight heparin (LMWH) has an antagonistic effect on the RAGE axis and is also reported to exert an antitumor effect beyond the known activity of anticoagulation. However, the link between the anti-RAGE and antitumor activities of LMWH has not yet to be fully elucidated. In this study, we investigated whether LMWH could inhibit tumor cell proliferation, invasion, and metastasis by blocking the RAGE axis using in vitro and in vivo assay systems. Stably transformed HT1080 human fibrosarcoma cell lines were obtained, including human full-length RAGE-overexpressing (HT1080RAGE), RAGE dominant-negative, intracellular tail-deleted RAGE-overexpressing (HT1080dnRAGE), and mock-transfected control (HT1080mock) cells. Confocal microscopy showed the expression of HMGB1 and RAGE in HT1080 cells. The LMWH significantly inhibited HMGB1-induced NFκB activation through RAGE using an NFκB-dependent luciferase reporter assay and the HT1080 cell lines. Overexpression of RAGE significantly accelerated, but dnRAGE expression attenuated HT1080 cell proliferation and invasion in vitro, along with similar effects on local tumor mass growth and lung metastasis in vivo. Treatment with LMWH significantly inhibited the migration, invasion, tumor formation, and lung metastasis of HT1080RAGE cells, but not of HT1080mock or HT1080dnRAGE cells. In conclusion, this study revealed that RAGE exacerbated the malignant phenotype of human fibrosarcoma cells, and that this exacerbation could be ameliorated by LMWH. It is suggested that LMWH has therapeutic potential in patients with certain types of malignant tumors. © 2013 Japanese Cancer Association

Bone structural and metabolic response of caloric restriction in Wistar rats and a GH-IGF-1 axis-suppressed transgenic rat model.

The growth hormone?insulin-like growth factor-1 (GH?IGF-1) axis plays an important role in the effects of caloric restriction(CR) on lifespan extension and may elicit effects on bone metabolism in CR animals. We compared the effects of the GH?IGF-1 axis suppression and CR on bone metabolism. We used Wistar rats fed ad libitum (control group) or fed a 30% calorierestricted diet in CR group and heterozygous transgenic (F1) rats whose GH-IGF-1 axis is moderately suppressed. There was no significant difference in serum IGF-1 concentration between control and CR rats; however, IGF-1 was significantly lower inF1 rats than in other groups. The bone volume fraction (BV/TV) was significantly lower in CR than in the control. The mean SMI value in CR rats was marginally significant difference from that in control rats, Although there was no difference in serum IGF-1 concentrations between CR and control rats, bone volume was lower, and higher SMI was observed in the former. The serum IGF-1 levels in F1 rats were lower than those of controls, but the bone volume and SMI in F1 were not different. Therefore, the effects of bone metabolism in CR rats may be different from those in the GH-IGF-1 suppression rats

Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis

肉芽腫形成に特異的な代謝経路の発見 --ペントースリン酸回路の制御による新規治療--. 京都大学プレスリリース. 2023-12-01.More than skin-deep: Kyoto researchers discover metabolic pathway specific to granuloma formation in patients. 京都大学プレスリリース. 2023-12-07.Sarcoidosis is a disease of unknown etiology in which granulomas form throughout the body and is typically treated with glucocorticoids, but there are no approved steroid-sparing alternatives. Here, we investigated the mechanism of granuloma formation using single-cell RNA-Seq in sarcoidosis patients. We observed that the percentages of triggering receptor expressed on myeloid cells 2–positive (TREM2-positive) macrophages expressing angiotensin-converting enzyme (ACE) and lysozyme, diagnostic makers of sarcoidosis, were increased in cutaneous sarcoidosis granulomas. Macrophages in the sarcoidosis lesion were hypermetabolic, especially in the pentose phosphate pathway (PPP). Expression of the PPP enzymes, such as fructose-1, 6-bisphosphatase 1 (FBP1), was elevated in both systemic granuloma lesions and serum of sarcoidosis patients. Granuloma formation was attenuated by the PPP inhibitors in in vitro giant cell and in vivo murine granuloma models. These results suggest that the PPP may be a promising target for developing therapeutics for sarcoidosis

Effects of monthly intravenous ibandronate on bone mineral density and microstructure in patients with primary osteoporosis after teriparatide treatment: The MONUMENT study

Purpose: To investigate the effects of sequential therapy with monthly intravenous ibandronate on bone mineral density (BMD) and microstructure in patients with primary osteoporosis who received teriparatide treatment. Methods: Sixty-six patients with primary osteoporosis who had undergone teriparatide treatment for more than 12 months (mean 18.6 months) received sequential therapy with 1 mg/month intravenous ibandronate for 12 months. The patients were evaluated using dual-energy X-ray absorptiometry (DXA), quantitative ultrasound, bone turnover markers, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6 and 12 months after beginning administration. Results: At 12 months after beginning sequential therapy,the bone resorption marker, tartrate-resistant acid phosphatase-5b, decreased by 39.5%, with 82.3% of the patients exhibiting levels within the normal limit. DXA revealed that the BMD of the lumbar spine increased by 3.2%, with 79.0% of the patients exhibiting a response, and 40.3% experiencing an increase in BMD over 5%. HR-pQCT revealed that the cortical thickness of the distal tibia was increased by 2.6%. The cortical area increased by 2.5%, and the buckling ratio (an index of cortical instability) decreased by 2.5%. Most parameters of the trabecular bone showed no significant changes. These changes in the cortical bone were observed in both the distal radius and tibia and appeared beginning 6 months after treatment initiation. Conclusions: Sequential therapy with monthly intravenous ibandronate increased the BMD and improved the cortical bone microstructure of osteoporotic patients who had undergone teriparatide treatment

Randomized controlled trial of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate in patients with postmenopausal osteoporosis: The TERABIT study

Purpose: The effects of daily teriparatide (20 μg) (D-PTH), weekly high-dose teriparatide (56.5 μg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD), bone turnover markers (BTMs), volumetric BMD (vBMD), microarchitecture, and estimated strength were investigated in postmenopausal osteoporosis patients.Methods: The study participants were 131 women with a history of fragility fractures. They were randomized to receive D-PTH, W-PTH, or BPs (alendronate or risedronate) for 18 months. Dual-energy X-ray absorptiometry (DXA), BTMs, and high-resolution peripheral quantitative CT (HR-pQCT) parameters were evaluated at baseline and after 6 and 18 months of treatment. The primary endpoint was the change (%) in cortical thickness (Ct.Th) after 18 months\u27 treatment compared with baseline.Results: DXA showed that D-PTH, W-PTH, and BPs increased lumbar spine aBMD (+12.0%, +8.5%, and +6.8%) and total hip aBMD (+3.0%, +2.1%, and +3.0%), but D-PTH and W-PTH decreased 1/3 radius aBMD (− 4.1%, − 3.0%, − 1.4%) after 18 months. On HR-pQCT, D-PTH increased trabecular vBMD (Tb.vBMD) at the distal radius and tibia after 18 months (+6.4%, +3.7%) compared with the BPs group, decreased cortical volumetric tissue mineral density (Ct.vTMD) (− 1.8%, − 0.9%) compared with the other groups, increased Ct.Th (+1.3%, +3.9%), and increased failure load (FL) (+4.7%, +4.4%). W-PTH increased Tb.vBMD (+5.3%, +1.9%), maintained Ct.vTMD (− 0.7%, +0.2%) compared with D-PTH, increased Ct.Th (+0.6%, +3.6%), and increased FL (+4.9%, +4.5%). The BPs increased Tb.vBMD only in the radius (+2.0%, +0.2%), maintained Ct.vTMD (− 0.6%, +0.3%), increased Ct.Th (+0.5%, +3.4%), and increased FL (+3.9%, +2.8%).Conclusions: D-PTH and W-PTH comparably increased Ct.Th, the primary endpoint. D-PTH had a strong effect on trabecular bone. Although D-PTH decreased Ct.vTMD, it increased Ct.Th and total bone strength. W-PTH had a moderate effect on trabecular bone, maintained Ct.vTMD, and increased Ct.Th and total bone strength to the same extent as D-PTH