Analysis of Cardiac Events and the Subsequent Impact for Geriatric Patients Undergoing Hip Fracture Surgeries.

Perioperative complications, particularly cardiac events, compromised surgical outcomes for geriatric patients. This retrospective study intended to investigate the occurrence and subsequent impact of cardiac events for geriatric patients undergoing hip fracture surgeries. We collected 607 patients undergoing hip fracture surgeries from January 2017 to December 2022 that received transthoracic echocardiography (TTE) pre-operatively to screen for cardiac abnormalities. Except for demographic characteristics, the researchers recorded fracture type, surgical method, American Society of Anesthesiologists (ASA) class, anesthesia type, perioperative cardiac events, and in-hospital mortality. Statistical analysis was performed using SPSS 22.0 statistics software. Throughout the whole course of the study, 16 postoperative cardiac events occurred. The cardiac events included ten arrhythmias, three acute myocardial infarctions, two heart failures, and one sudden death. Notably, 12 of 16 patients with cardiac events presented with abnormal findings on TTE, except 15 of them had a history of cardiac disease. This study disclosed 93.7% of cardiac events developed in patients with a history of cardiovascular disease. Among patients that experienced cardiac events, 75% of patients had abnormal echocardiographic findings. Pre-operative transthoracic echocardiography deserves a recommendation for geriatric patients with histories of cardiac diseases undergoing hip fracture surgeries to detect the risk of developing cardiac events earlier.

Etoricoxib prevents progression of osteolysis in repeated intra-articular monosodium urate-induced gouty arthritis in rats.

Deposition of monosodium urate (MSU) crystals in the joint or synovium is the major factor in Gouty arthritis (GA). The clinical features of chronic and recurrent GA include pain and the subsequent development of chronic tophaceous GA with multiple tophi deposits accompanied by osteolysis. The majority of previous animal studies have focused on MSU-induced acute GA without making observations regarding osteolysis. In the study, intra-articular injections of MSU into the knee (2 times/week for 10 weeks) was used to induce chronic and recurrent attacks of GA that in turn induced progressive osteolysis. Moreover, we also evaluated whether the clinical, nonsteroidal anti-inflammatory drug (NSAID) etoricoxib attenuated the osteoclastogenesis of progressive osteolysis. The knee morphometry and the expression of osteoclastogenesis-related proteins (cathepsin K and matrix metalloproteinase-9 and -13) in the knee were examined by micro-CT and immunohistochemistry, respectively. Results showed that oral etoricoxib not only significantly attenuated the nociceptive behaviors of the rats but that it also inhibited the expression of osteoclastogenesis-related proteins in their knee joints in chronic and recurrent attacks of GA. Our findings thus suggest that NSAIDs not only inhibit nociception but also prevent the progression of osteolysis in chronic and repeated attacks of GA.

The COX-2 inhibitor etoricoxib reduces experimental osteoarthritis and nociception in rats: The roles of TGF-ß1 and NGF expressions in chondrocytes.

BACKGROUND: Osteoarthritis (OA) is the most common joint disease, especially affecting the knee joint. Etoricoxib, a highly selective cyclooxygenase (COX)-2 inhibitor which can reduce postoperative pain after orthopaedic surgery. The aim of this study was to investigate the effects of oral etoricoxib on the development of OA and to examine concomitant changes in the nociceptive behaviour of rats. METHOD: OA was induced in wistar rats by anterior cruciate ligament transection (ACLT) of the right knee. The ACLT + etoricoxib groups received 6.7 or 33.3 mg/kg of oral etoricoxib three times a week for 12 consecutive weeks, starting at week 8 after ACLT. Nociceptive behaviours and changes in knee joint width during OA development were analyzed. Histopathological studies were then performed on the cartilage. Immunohistochemical analysis was performed to examine the effect of etoricoxib on the expression of transforming growth factor-beta (TGF-ß) and nerve growth factor (NGF) in articular cartilage chondrocytes. RESULTS: OA rats receiving etoricoxib showed a significantly lower degree of cartilage degeneration than the rats receiving placebo. Nociceptive behaviour studies showed significant improvement in the ACLT + etoricoxib groups compared to that in the ACLT group. Moreover, etoricoxib attenuated NGF expression, but increased TGF-ß expression, in OA-affected cartilage. CONCLUSIONS: Oral etoricoxib in a rat OA model (a) attenuates the development of OA, (b) concomitantly reduces nociception, and (c) modulates chondrocyte metabolism, possibly by inhibiting NGF expression and increasing TGF-ß expression. SIGNIFICANCE: Oral administration of etoricoxib can attenuate the development of OA, with an associated attenuation of nociceptive behaviour in an experimental rat OA model. Moreover, etoricoxib attenuated NGF expression, but enhanced TGF-ß expression in OA-affected chondrocytes. These findings may pave the way for further investigations of etoricoxib as a potential therapeutic target for the treatment of the inflammatory component in OA.

Excavatolide B Attenuates Rheumatoid Arthritis through the Inhibition of Osteoclastogenesis.

Osteoclasts are multinucleated giant cells of macrophage/monocyte lineage, and cell differentiation with the upregulation of osteoclast-related proteins is believed to play a major role in the destruction of the joints in the course of rheumatoid arthritis (RA). Pro-inflammatory cytokines, such as interleukin-17A (IL-17A) and macrophage colony-stimulating factor (M-CSF), can be overexpressed in RA and lead to osteoclastogenesis. In a previous study, we found that cultured-type soft coral-derived excavatolide B (Exc-B) exhibited anti-inflammatory properties. In the present study, we thus aimed to evaluate the anti-arthritic activity of Exc-B in in vitro and in vivo models. The results demonstrated that Exc-B inhibits LPS-induced multinucleated cell and actin ring formation, as well as TRAP, MMP-9, and cathepsin K expression. Additionally, Exc-B significantly attenuated the characteristics of RA in adjuvant (AIA) and type II collagen-induced arthritis (CIA) in rats. Moreover, Exc-B improved histopathological features, and reduced the number of TRAP-positive multinucleated cells in the in vivo AIA and CIA models. Immunohistochemical analysis showed that Exc-B attenuated the protein expression of cathepsin K, MMP-2, MMP-9, CD11b, and NFATc1 in ankle tissues of AIA and CIA rats. Level of interleukin-17A and macrophage colony-stimulating factor were also decreased by Exc-B. These findings strongly suggest that Exc-B could be of potential use as a therapeutic agent by inhibiting osteoclast differentiation in arthritis. Moreover, this study also illustrates the use of the anti-inflammatory marine compound, Exc-B, as a potential therapeutic strategy for RA.

Calcitonin attenuates cartilage degeneration and nociception in an experimental rat model of osteoarthritis: role of TGF-ß in chondrocytes.

We investigated the role of the calcitonin (Miacalcin) in the progression of osteoarthritis (OA) and in nociceptive behavior in an experimental rat model of OA and osteoporosis. OA was induced by anterior cruciate ligament transection (ACLT) of the right knee and by bilateral ovariectomy (OVX) in Wistar rats. Nociceptive behaviors (secondary mechanical allodynia and weight-bearing distribution of the hind paws) were analyzed prior to surgery and every week, beginning at 12 weeks after surgery, up to 20 weeks. At 20 weeks, histopathological studies were performed on the cartilage of the knee joints. Immunohistochemical analysis was performed to examine the effect of calcitonin on transforming growth factor (TGF)-ß1 expression in articular cartilage chondrocytes. Rats subjected to ACLT + OVX surgery showed obvious OA changes in the joints. Animals subjected to ACLT + OVX and treated with calcitonin showed significantly less cartilage degeneration and improved nociceptive tests compared with animals subjected to ACLT + OVX surgeries alone. Moreover, calcitonin increased TGF-ß1 expression in chondrocytes in ACLT + OVX-affected cartilage. Subcutaneous injection of calcitonin (1) attenuated the development of OA, (2) concomitantly reduced nociception, and (3) modulated chondrocyte metabolism, possibly by increasing cellular TGF-ß1 expression.

Lemnalol attenuates mast cell activation and osteoclast activity in a gouty arthritis model.

OBJECTIVES: In this study, we investigated the effects of a soft coral-derived anti-inflammatory compound, lemnalol, on mast cell (MC) function and osteoclast activity in rats with monosodium urate (MSU) crystal-induced gouty arthritis. METHODS: In this study, we examined the therapeutic effects of lemnalol on intra-articular injection of MSU induces gouty arthritis with the measurement of ankle oedema. Toluidine blue staining were used to analyse the infiltration and the percentage degranulation MCs. Immunohistochemical analysis showed CD117, transforming growth factor beta 1 (TGF-ß1), matrix metalloproteinase 9 (MMP-9), the osteoclast markers cathepsin K and tartrate-resistant acid phosphatase (TRAP) protein expression in ankle tissue. KEY FINDINGS: We found that both infiltration and degranulation of MCs increased at 24 h after MSU injection in the ankle joint. Immunohistochemical analysis showed that MSU induced upregulation of TGF-ß1, MMP-9, the osteoclast markers cathepsin K and TRAP in ankle tissues. Administration of lemnalol ameliorated MSU-induced TGF-ß1, MMP-9, cathepsin K and TRAP protein expression. CONCLUSIONS: Taken together, our results show that MSU-induced gouty arthritis is accompanied by osteoclast-related protein upregulation and that lemnalol treatment may be beneficial for the attenuation of MC infiltration and degranulation and for suppressing osteoclast activation in gouty arthritis.

A soft coral-derived compound, 11-epi-sinulariolide acetate suppresses inflammatory response and bone destruction in adjuvant-induced arthritis.

In recent years, a significant number of metabolites with potent anti-inflammatory properties have been discovered from marine organisms, and several of these compounds are now under clinical trials. In the present study, we isolated 11-epi-sinulariolide acetate (Ya-s11), a cembrane-type compound with anti-inflammatory effects, from the Formosa soft coral Sinularia querciformis. Preliminary screening revealed that Ya-s11 significantly inhibited the expression of the proinflammatory proteins induced nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated murine macrophages. We also examined the therapeutic effects of Ya-s11 on adjuvant-induced arthritis (AIA) in female Lewis rats, which demonstrate features similar to human rheumatoid arthritis (RA). Animal experiments revealed that Ya-s11 (subcutaneously 9 mg/kg once every 2 days from day 7 to day 28 postimmunization) significantly inhibited AIA characteristics. Moreover, Ya-s11 also attenuated protein expression of cathepsin K, matrix metalloproteinases-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), and tumor necrosis factor-α (TNF-α) in ankle tissues of AIA-rats. Based on its attenuation of the expression of proinflammatory proteins and disease progression in AIA rats, the marine-derived compound Ya-s11 may serve as a useful therapeutic agent for the treatment of RA.

Soft coral-derived lemnalol alleviates monosodium urate-induced gouty arthritis in rats by inhibiting leukocyte infiltration and iNOS, COX-2 and c-Fos protein expression.

An acute gout attack manifests in the joint as dramatic inflammation. To date, the clinical use of medicinal agents has typically led to undesirable side effects. Numerous efforts have failed to create an effective and safe agent for the treatment of gout. Lemnalol-an extract from Formosan soft coral-has documented anti-inflammatory and anti-nociceptive properties. In the present study, we attempt to examine the therapeutic effects of lemnalol on intra-articular monosodium urate (MSU)-induced gouty arthritis in rats. In the present study, we found that treatment with lemnalol (intramuscular [im]), but not colchicine (oral [po]), significantly attenuated MUS-induced mechanical allodynia, paw edema and knee swelling. Histomorphometric and immunohistochemistry analysis revealed that MSU-induced inflammatory cell infiltration, as well as the elevated expression of c-Fos and pro-inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2) observed in synovial tissue, were significantly inhibited by treatment with lemnalol. We conclude that lemnalol may be a promising candidate for the development of a new treatment for gout and other acute neutrophil-driven inflammatory diseases.

Sinularin from indigenous soft coral attenuates nociceptive responses and spinal neuroinflammation in carrageenan-induced inflammatory rat model.

Three decades ago, the marine-derived compound sinularin was shown to have anti-edematous effects on paw edema induced by carrageenan or adjuvant. To the best of our knowledge, no new studies were conducted to explore the bioactivity of sinularin until we reported the analgesic properties of sinularin based on in vivo experiments. In the present study, we found that sinularin significantly inhibits the upregulation of proinflammatory proteins, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) and upregulates the production of transforming growth factor-ß (TGF-ß) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells according to western blot analysis. We found that subcutaneous (s.c.) administration of sinularin (80 mg/kg) 1 h before carrageenan injection significantly inhibited carrageenan-induced nociceptive behaviors, including thermal hyperalgesia, mechanical allodynia, cold allodynia, and hindpaw weight-bearing deficits. Further, s.c. sinularin (80 mg/kg) significantly inhibited carrageenan-induced microglial and astrocyte activation as well as upregulation of iNOS in the dorsal horn of the lumbar spinal cord. Moreover, s.c. sinularin (80 mg/kg) inhibited carrageenan-induced tissue inflammatory responses, redness and edema of the paw, and leukocyte infiltration. The results of immunohistochemical studies indicate that s.c. sinularin (80 mg/kg) could upregulate production of TGF-ß1 in carrageenan-induced inflamed paw tissue. The present results demonstrate that systemic sinularin exerts analgesic effects at the behavioral and spinal levels, which are associated with both inhibition of leukocyte infiltration and upregulation of TGF-ß1.

Effects of propofol on proliferation and anti-apoptosis of neuroblastoma SH-SY5Y cell line: new insights into neuroprotection.

Recently, it has been suggested that anesthetic agents may have neuroprotective potency. The notion that anesthetic agents can offer neuroprotection remains controversial. Propofol, which is a short-acting intravenous anesthetic agent, may have potential as a neuroprotective agent. In this study, we tried to determine whether propofol affected the viability of human neuroblastoma SH-SY5Y cells by using the MTT assay. Surprisingly, our results showed that propofol at a dose of 1-10 µM could improve cell proliferation. However, at higher doses (200 µM), propofol appears to be cytotoxic. On the other hand, propofol could up-regulate the expression of key proteins involved in neuroprotection including B-cell lymphoma 2 at a dose range of 1-10 µM, activation of phospho-serine/threonine protein kinase at a dose range of 0.5-10 µM, and activation of phospho-extracellular signal-regulated kinases at a dose range of 5-10 µM. Similarly, we demonstrate that propofol (10 µM) could elevate protein levels of heat shock protein 90 and heat shock protein 70. Therefore, we choose to utilize a 10 µM concentration of propofol to assess neuroprotective activities in our studies. In the following experiments, we used dynorphin A to generate cytotoxic effects on SH-SY5Y cells. Our data indicate that propofol (10 µM) could inhibit the cytotoxicity in SH-SY5Y cells induced by dynorphin A. Furthermore, propofol (10 µM) could decrease the expression of the p-P38 protein as well. These data together suggest that propofol may have the potential to act as a neuroprotective agent against various neurologic diseases. However, further delineation of the precise neuroprotective effects of propofol will need to be examined.

Simultaneous detection of multiple single-nucleotide polymorphisms by a simple membrane chip.

Technologies that screen multiple single-nucleotide polymorphisms (SNPs) could be very valuable in predicting patients' susceptibilities to diseases or responses to therapeutic interventions. In this study, we developed a chip that can accurately detect four SNPs at same time. This chip is cost-effective and user-friendly because it uses a detection protocol analogous to dot blotting and does not require sophisticated instruments. To establish this chip, we designed and blotted onto a nylon membrane SNP-specific oligonucleotide probes for human angiotensinogen, cholesteryl ester transfer protein, and apolipoprotein E. This chip detected the corresponding SNPs harbored within the angiotensinogen, cholesteryl ester transfer protein, and apolipoprotein E sequences from 20 donors. Importantly, the SNPs detected by our chip matched exactly with the direct sequencing results, thereby highlighting the accuracy of this chip. In conclusion, our chip is a robust tool for multiple SNP screening and holds the potential to future refinement in detecting diseases-associating genes in patients.

Importance of serum albumin level in the preoperative tests conducted in elderly patients with hip fracture.

BACKGROUND: Preoperative testing is commonly performed in patients undergoing surgery for hip fractures. The purpose of this study was to determine the appropriate preoperative tests after implementation of the case-payment reimbursement system and clinical pathway. METHODS: We analysed 242 patients admitted to a regional hospital for hip fracture. Preoperative comorbidities and laboratory test results were measured and evaluated for their association with the occurrence of postoperative adverse outcomes. RESULTS: Univariate analysis showed that abnormal chest X-ray, haemoglobin, albumin, and total protein were associated with concomitant pulmonary diseases. Abnormal electrocardiogram (ECG), Na, creatinine, and aspirate aminotransferase (AST) levels were associated with heart disease. On the base of the univariate analysis, the significant preoperative variables for increased postoperative complications at 30 days included abnormal chest X-ray (odds ratio, 4.45; 95% confidence interval (CI), 2.24-8.84), ECG (odds ratio, 3.95; 95% CI, 1.96-7.95), Hct (odds ratio, 2.22; 95% CI, 0.96-5.16), Hb (odds ratio, 2.68; 1.29-5.58), blood urine nitrogen (odds ratio, 2.69; 95% CI, 1.34-5.42), creatinine (odds ratio, 4.49; 2.31-8.75), albumin (odds ratio, 9.68; 95% CI, 3.16-29.65), and AST (odds ratio, 2.36; 95% CI, 1.12-4.98). After adjustment for age, sex, and comorbidities, the risk factors that improved the predictability of postoperative complications were found to be abnormal chest X-ray (odds ratio, 6.03; 95% CI, 1.84-19.82) and albumin level (odds ratio, 6.23; 95% CI, 1.90-20.42). CONCLUSION: Serum albumin level and preoperative chest X-rays should be included in the preoperative routine tests recommended for elderly patient with hip fracture.