Fiber-reinforced composite full-arch prosthetic reconstructions supported by three standard, short or extra-short implants: a two-center retrospective study.

OBJECTIVES: To evaluate the survival of implants and prostheses, and marginal bone level of fiber-reinforced composite implant supported fixed complete prostheses supported by 3 implants. MATERIALS AND METHODS: Patients with fiber-reinforced composite fixed prostheses supported by 3 standard-length, short or extra-short implants were included in this retrospective cohort study. Kaplan-Meier survival was computed for implants and prostheses. Univariate and multivariate Cox proportional hazard regressions, clustered by patient, were used to analyze bone level differences as a function of different study covariates. Linear regressions were used to investigate the relationship between distal extension lengths and bone levels. RESULTS: Forty-five patients with 138 implants were followed for up to 10 years after prosthesis insertion (mean 52.8; SD 20.5 months). Kaplan-Meier survival analysis showed overall survival rates of 96.5% for implants and of 97.8% for prostheses. The 10-year success rate for prostheses was 90.8%. Extra-short implants survived at similar rates to short and standard implants. Marginal bone levels surrounding implants remained stable over time, even showing slight bone gain on average (mean + 0.1 mm/year; SD ± 0.5 mm/year) Acrylic denture teeth, overdentures on the opposing arch, and implant placement in the posterior maxilla were correlated with bone gain. Screw retention, opposed to telescopic retention, was correlated with bone loss. Longer distal extensions were correlated with bone gain on the implants closest to the distal extensions. CONCLUSIONS: Fiber-reinforced composite fixed prostheses supported by only 3 implants, most of which were extra-short, presented high survival rates with stable bone levels. CLINICAL RELEVANCE: An encouraging prognosis can be expected for restoration of atrophic maxillary and mandibular arches, when restored with fixed fiber-reinforced composite frameworks with long distal extensions and supported on only 3 short implants.

Severely Atrophic Mandibles Restored With Fiber-Reinforced Composite Prostheses Supported by 5.0-mm Ultra-Short Implants Present High Survival Rates Up To Eight Years.

PURPOSE: Encouraging results have been reported for ultrashort single implants; however, long-term investigations are warranted for full-arch reconstructions. This study evaluated marginal bone loss, implant, and reconstruction survival of fiber-reinforced composite full-arch prostheses supported by 4 ultrashort implants. METHODS: Patients with severely atrophic mandibles (Cawood and Howell class V and class VI) were included in this cohort study. Study predictors included time (initial and last follow-up) and vertical (epicrestally or subcrestally) and horizontal implant position (medial or lateral). Outcome variables included bone level changes over time, implant/prosthesis survival. Peri-implant bone level was measured on panoramic radiographs. Descriptive statistics, Kaplan-Meier, mixed model analysis of variance, and univariate and multivariate Cox Proportional Hazards Regression models, adjusted for multiple implants in the same patient, were used for data analyses. RESULTS: Eighteen patients (mean 61.22 years old), with 72 implants placed in atrophic mandibles with an average follow-up of 55.4 months (CI, ±4.6/ SD, ±10.6 months) were analyzed. The implant survival rate was 97.2% as 2 implants were not loaded due to non-osseointegration and sensorial disturbances. Average marginal bone level at baseline (1.93 mm) and at the time of last recall (1.91 mm) was not significantly different. While implants placed subcrestally showed no significant difference between baseline (1.91 mm) and last follow up bone level (2.12 mm), implants placed epicrestally demonstrated a significant reduction on their bone level over time (initial: 1.97 mm/ final:1.33 mm). Systemic disorders were a risk factor for implant survival and bone loss. Prostheses cumulative survival rate was 100% (mean observation period of 55 months). The estimated survival rate after the 96-month follow-up was 75% (1 framework fracture after 84 months). CONCLUSION: Fixed fiber-reinforced composite full-arch prostheses retained by 4 ultrashort implants showed a stable bone level and high implant/prostheses survival rates up to 8 years.

Antiresorptive therapy and dental implant survival: an up to 20-year retrospective cohort study in women.

OBJECTIVES: To investigate the effects of antiresorptive treatment on the survival of plateau-root form dental implants. MATERIALS AND METHODS: Patients undergoing antiresorptive therapy via oral or intravenous administration as well as patients not undergoing antiresorptive therapy and healthy control patients were included in this retrospective cohort study. In total, 1472 implants placed in 631 postmenopausal patients (M: 66.42 ± 9.10 years old), who were followed for a period of up to 20 years (8.78 ± 5.68 years). Kaplan-Meier survival analysis was performed, and univariate and multivariate Cox regression, clustered by each patient, was used to evaluate and study factors affecting the survival of their implants. RESULTS: Implants placed in patients undergoing oral antiresorptive treatment presented significantly higher survival rates, than implants placed in the osteoporosis/osteopenia control cohort (p value < 0.001), and similar survival rates, when compared to healthy controls (p value = 0.03). Additionally, clustered univariate and multivariate Cox regression analysis also revealed higher implant survival when oral antiresorptive drugs (p value = 0.01 and 0.007, respectively) were used, and lower implant survival in the presence of untreated osteoporosis/osteopenia (p value = 0.002 and 0.005, respectively). Overall, the 20-year implant survival in osteoporotic patients undergoing antiresorptive therapy was 94%. For the failed implants, newly replaced implants in patients under antiresorptive treatment presented a 10-year survival of 89%. CONCLUSIONS: Long-term plateau-root form implant survival in osteoporotic patients taking oral antiresorptives was similar to a healthy population and significantly higher than the untreated controls. CLINICAL RELEVANCE: These results suggest that plateau-root form implants provide a robust solution for treating tooth loss in patients, who are undergoing antiresorptive therapy.

Comparable outcomes of recycled autografts and allografts for reconstructions in patients with high-grade osteosarcoma.

PURPOSE: This retrospective, single-centre study compares the clinical and radiographic outcomes of limb reconstruction using recycled autografts to that using allografts. METHODS: Patients with histopathologically verified high-grade osteosarcoma treated with wide bone resection and limb reconstruction using allografts or recycled autografts from January 1998 through December 2012 were retrospectively screened for enrolment eligibility. The final study cohort included 255 patients (allograft, 91; recycled autograft, 164). Data regarding post-operative complications, salvage treatment, and graft survival were collected. A modified International Society of Limb Salvage classification system was used to evaluate the radiographic findings. RESULTS: The time to graft-host union did not differ significantly between the two graft types. Patients receiving recycled autografts had fewer complications compared than did those receiving allografts (recycled autografts vs. allograft: structural failure, 4.3 vs. 13.2%; late infection, 2.4 vs. 7.7%; all p < 0.05). Complications occurred most frequently during the first three years after surgery, and the majority were manageable. The five year limb survival rate did not differ significantly between the two graft types (91.3 vs. 94.0%; p = 0.752). No local oncological recurrence was observed within the recycled autografts. CONCLUSION: Recycled autografts and allografts are feasible options for biological limb reconstructions in terms of complications and graft survival after wide resection of osteosarcoma.

A safety comparative study between freezing nitrogen ethanol composite and liquid nitrogen for cryotherapy of musculoskeletal tumors.

Freezing nitrogen ethanol composite (FNEC) showed effective cryoablative ability for bone tumor ex vivo and in vivo comparable to liquid nitrogen (LN). We therefore wished to compare the radiant cooling damage of the surrounding tissue between FNEC and LN. The evaluation of the radiant cooling damage was demonstrated human bone xenograft transplantation (HXT) in a mouse model. Characterizations and quantifications of the damaging effects on morphologic features and apoptosis of the cryoablative surrounding bone tissue, muscle and epidermal layer of skin were compared. The radiant cooled damaging effects including epidermal rupture, hair follicle atrophy, dermis and subcutaneous crystal vacuolation of skin were significantly greater in LN than FNEC. Muscular apoptosis, structural shrinkage and bone cellular apoptosis were supposedly 15%-33% destroying degrees of LN more than FNEC. We concluded that FNEC is an innovative cryogenic material, and it could cause less cryoablative damage to surrounding normal tissue than LN. The findings might support the safety of FNEC being applied in clinical cryoablation therapy.

Intraoperative Extracorporeal Irradiation and Frozen Treatment on Tumor-bearing Autografts Show Equivalent Outcomes for Biologic Reconstruction.

BACKGROUND: Immediately recycling the resected bone segment in a biologic limb salvage reconstruction is an option after wide resection of bone. Intraoperative extracorporeal irradiation and freezing are the two major tumor-killing techniques applied on the fresh tumor-bearing autografts. However, graft-derived tumor recurrence and complications are concerns affecting graft survival. QUESTIONS/PURPOSES: We therefore asked: (1) Is there a difference in the proportion of patients achieving union by 18 months after surgery between the groups with extracorporeal-irradiated autografts and frozen-treated autografts? (2) Is there any difference in the frequency of graft-related complications for patients receiving either an extracorporeal-irradiated or a frozen-treated autograft? (3) Is there a difference between the techniques in terms of graft-derived recurrence? (4) Are there differences in failure-free grafts, and limb and overall survivorship between autografts treated by extracorporeal irradiation or by freezing? METHODS: During the study period we treated a total of 333 patients with high-grade osteosarcoma. One hundred sixty-nine patients were excluded. Overall, 79 of the enrolled 164 patients received recycled autografts treated with extracorporeal irradiation whereas the other 85 received frozen-treated autografts. The mean followup was 82 ± 54 months for the extracorporeal irradiation group and 70 ± 25 months for the frozen autograft group, and one patient was lost to followup. Complications and graft failure (revision required for primary graft removal) were characterized by adapting the International Society of Limb Society (ISOLS) system modified for inclusion of biologic and expandable reconstruction. The primary study endpoints were the proportion of patients in each group who achieved radiographic union, and had an ISOLS grade of fair or good host graft fusion at 6, 9, 12, and 18 months after surgery. Five-year survival data for graft failure and limb amputation were analyzed by a cumulative incidence function regression model whereas the Kaplan-Meier function was used to test the 5-year overall survival rate between the two techniques. RESULTS: With the numbers available, no differences were found in the accumulated proportion of patients achieving union between the groups at 6, 9, 12, and 18 months. Radiographic evaluation did not show differences in the average scores of compared criteria. However in the subchondral bone subcriterion, more patients receiving frozen-treated autografts had higher scores (p = 0.03). Complications leading to a second surgery were not different between extracorporeal irradiation and frozen autografts in aspects of soft tissue failure (Type 1B), nonunion (Type 2B), structural failure (Type 3A and Type 3B), or infection (Type 4A and Type 4B). No graft-originating tumor recurrence was found and there was no difference in Type 5A tumor progression originating from soft tissue in the groups (odds ratio, 0.8; 95% CI, 0.3-2.1; p = 0.7). Neither group showed a difference in the cumulative incidence for graft failure and limb amputation. Five-year overall survival rates were 83% and 84% (p = 0.69) for extracorporeal-irradiated and frozen autografts respectively. A decrease in survivorship was seen at 50 to 100 months after surgery for the extracorporeal irradiation group. CONCLUSION: We segregated the ISOLS criteria evaluating the graft-mediated tumor progression into host- or graft-derived complications (Types 5B and 5C) in this study. With the available data, there was no difference in the incidence of tumor recurrence derived from irradiation- or frozen-treated autografts. Ongoing evaluations comparing 10-year survivorship for both groups will be helpful to elucidate the possible difference found after 100 months. LEVEL OF EVIDENCE LEVEL: III, therapeutic study.

Endoplasmic reticulum stress-induced cell death in podocytes.

Endoplasmic reticulum (ER) stress occurs in a variety of pathophysiological mechanisms, and there has been great interest in managing this pathway for the treatment of clinical diseases. Increased ER stress can block integrin-ß1 glycosylation, decrease integrin-ß1 protein expression and enhance cell death in podocytes. Autophagy is closely interconnected with ER stress to counteract the possible injurious effects related to the impairment of protein folding and is one of the intracellular protein degradation systems. Studies have shown that podocytes exhibit a high rate of autophagy to maintain as terminally differentiated cells. We have attempted to induce autophagy in podocytes with ER stress to increase the longevity of proteins and the degradation of damaged organelles. However, regardless of ER stress or autophagy that protects the cells at early stages, cells cannot adapt to this situation when the stress is already well established, and podocytes will undergo severe injury finally. In summary, ER stress may induce cell death in podocyte, and autophagy mediate to salvage the injuries caused by ER stress in the short term. It seems that adequate, but not excessive, autophagy is crucial to help maintain the cell viability of podocytes.

RRM2B-Mediated Regulation of Mitochondrial Activity and Inflammation under Oxidative Stress.

RRM2B is a critical ribonucleotide reductase (RR) subunit that exists as p53-inducible and p53-dependent molecule. The p53-independent regulation of RRM2B has been recently studied, and FOXO3 was identified as a novel regulator of RRM2B. However, the p53-independent regulation of RRM2B, particularly under oxidative stress, remains largely unknown. In this study, we investigated the role of RRM2B underoxidative stress-induced DNA damage and further examined the regulation of mitochondrial and inflammatory genes by RRM2B. Our study is the first to report the critical role of RRM2B in mitochondrial homeostasis and the inflammation signaling pathway in a p53-independent manner. Furthermore, our study provides novel insights into the role of the RR in inflammatory diseases.

Hypervitaminosis D is correlated with adverse dental implant outcomes: A retrospective case-control study.

OBJECTIVES: To investigate vitamin-D levels effect on the survival/success and on marginal bone levels of dental implants. METHODS: Patients with peri-implant disease and healthy control patients with functionally loaded dental implants were included in this retrospective case-control study. Forty patients with 201 implants were in the diseased-cohort, while thirty-three patients with 90 implants were in the control-cohort. Patient blood 25(OH)D levels were assessed through quantitative blood test. The correlation between abnormal 25(OH)D levels and disease status of each patient was assessed using Fisher's exact tests. The correlation of each implant's outcomes with vitamin-D status was assessed using Kaplan-Meier survival analysis and Mann-Whitney U tests. RESULTS: Patients with blood 25(OH)D levels >70 ng/mL (hypervitaminosis-D) had a 21.1-fold increase in the risk of implant failure or severe peri-implant bone loss regarding patients with intermediate (>30, ≤70 ng/mL) levels. Kaplan-Meier survival analysis revealed that implants in the hypervitaminosis-D cohort had a survival probability of 73.7 % (95 % CI:56.5-84.5 %) at 19-years after surgery, compared to 95 % for implants in patients with intermediate 25(OH)D levels (95 % CI:88.3-97.9 %). Additionally, implants in the hypervitaminosis-D cohort lost bone faster than implants in the intermediate cohort. These results were specific to the patient cohort with elevated blood 25(OH)D levels and not observed in patients taking vitamin-D supplementation. The impact of hypervitaminosis-D was enriched for implants in the maxilla, and not as apparent for implants in the mandible. CONCLUSIONS: Blood 25(OH)D levels >70 ng/mL were correlated with adverse implant outcomes, including implant failure and peri-implant bone loss, especially in the maxilla. CLINICAL RELEVANCE: These results suggest that hypervitaminosis D may be a previously unidentified risk factor for dental implant complications and should be further investigated to elucidate the underlying mechanism.

Partial fixed dental prostheses fabricated using fiber-reinforced composite resin supported by short and extra-short implants: A case series.

PURPOSE: This study aimed to evaluate the 10-year outcomes of partial fixed dental prostheses (P-FDPs) fabricated using metal-free fiber-reinforced composite (FRC) resin frameworks veneered with composite resin and supported by short and extra-short implants. METHODS: This study included 28 patients with 38 FRC prostheses supported by 96 implants. Implant and prosthesis survival and success rates were evaluated using Kaplan-Meier analysis. RESULTS: The 10-year implant survival and success rate, as determined by Kaplan-Meier analysis, was 96.9%, and the prosthesis survival and success rates were 94.7% and 92.0%, respectively. None of the parameters under investigation were significantly correlated with prosthetic survival or successful outcomes, but three parameters were correlated with higher peri-implant bone levels: implant placement in the mandible as opposed to the maxilla, shorter P-FDP spans, and natural teeth on the opposing arch. CONCLUSIONS: FRC P-FDPs supported by short and extra-short implants presented high, up to 10-year, survival and success rates, when used to restore partially edentulous arches.

Towards sustainable management of polyacrylamide in soil-water environment: Occurrence, degradation, and risk.

Polyacrylamide (PAM) possesses unique characteristics, including high water solubility, elevated viscosity and effective flocculation capabilities. These properties make it valuable in various sectors like agriculture, wastewater treatment, enhanced oil recovery, and mineral processing industries, contributing to a continually expanding market. Despite its widespread use globally, understanding its environmental fate at the soil-water interface remains limited. This article aims to provide an overview of the occurrence, degradation pathways, toxicity, and risks associated with PAM in the bioenvironment. The findings indicate that various degradation pathways of PAM may occur in the bioenvironment through mechanical, thermal, chemical, photocatalytic degradation, and/or biodegradation. Through a series of degradation processes, PAM initially transforms into oligomers and acrylamide (AM). Subsequently, AM may undergo biodegradation, converting into acrylic acid (AA) and other compounds such as ammonia. Notably, among these degradation intermediates, AM demonstrates high biodegradability, and the bioaccumulations of both AM and AA are not considered significant. Ensuring the sustainable use of PAM necessitates a comprehensive understanding among policymakers, scholars, and industry professionals regarding PAM, encompassing its properties, applications, degradation pathways, toxic effect on humans and the environment, and relevant regulations. Additionally, this study offers insights into future priority research directions, such as establishing of a reliable source-to-destination supply chain system, determining the maximum allowable amount for PAM in farmlands, and conducting long-term trials for the PAM-containing demolition residues.

Short and Extra Short Dental Implants in Osseous Microvascular Free Flaps: A Retrospective Case Series.

There is limited information regarding implant and prosthetic survival after osseous microvascular free flap (OMFF). This case series aims to describe the placement of short and extra short implants in osseous microvascular free flaps to support prostheses, and present an up to 40-month retrospective follow-up. Short and extra short dental implants were placed in six fibula free flaps (FFF) and in two microvascular deep circumflex iliac artery (DCIA) flaps. In total, 27 short and extra short dental implants have been placed into two different types of free flaps. Kaplan-Meyer (K-M) survival analyses were performed to evaluate the survival and success outcomes of implants and prostheses. Out of the eight patients reconstructed with free flap, five were rehabilitated with prostheses, one patient has a temporary prosthesis, and two patients are in the process of prosthetic rehabilitation. Twenty-seven implants were followed up for up to 40 months, and K-M analyses showed 100% implant survival probability (95% confidence interval: 100%), while the implant success probability was 91.0% (95% confidence interval: 68.6-97.7%). Short and extra short dental implants placed in OMFF presented high survival and success rates in a retrospective case series after up to 40 months.

Prefabricated shouldered abutments enable successful restoration of molar crowns on implants.

PURPOSE: This retrospective study evaluated the effect of selected clinical and patient factors on survival, success, and peri-implant bone level changes of locking taper implants supporting molar crowns on Bicon's prefabricated shouldered abutments. METHODS: A total of 234 patients, who received 274 single molar crowns supported by locking taper implants were included in this retrospective study. Kaplan-Meier survival analysis was used to assess overall implant survival, prostheses survival, and success. Crowns were either monolithic (resin based) or bilayered (milled fiber-reinforced composite coping veneered with indirect composite). Early and late changes in marginal bone levels were plotted and analyzed with equivalence testing to compare the effects of different factors on crestal bone levels. RESULTS: At 9.5 years after implant surgery, the implant survival probability was 94.2%, the probability of prosthesis survival was 91.4%, and the probability of prosthetic success was 90.4%. Neither the use of different crown materials, nor the choice of monolithic versus bilayered crown construction, significantly affected the probability of prosthetic success. Marginal bone levels, on average, trended downwards towards the top of the implant within the first 2 years after functional loading, and remained stable on average, since then. Factors affecting bone levels included the use of nonsteroidal anti-inflammatory drugs, which precluded early implant bone loss; and subcrestal implant placement, which was linked to significantly higher long-term bone levels. CONCLUSION: The implant and abutment system studied resulted in high implant and prosthetic survival rates, regardless of prosthetic material used, with stable bone levels over time.

The radiological prognostic factors of transcatheter arterial chemoembolization to hepatocellular carcinoma.

Transcatheter arterial chemoembolization (TACE) is the recommended treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the HCC radiological characteristics associated with prognosis of patients with intermediate stage HCC receiving TACE. Patients with HCC BCLC stage B from January 2005 to December 2009 were collected. According to mRECIST criteria, patients with complete response and partial response were assigned to the objective response (OR) group, while those with stable disease and progressive disease were assigned to the nonobjective response (non-OR) group. Among a total of 128 enrolled patients, there were 66 (51.6%) and 62 (48.4%) patients in the OR group and non-OR group, respectively. The clinical parameters in the two groups were similar, although HCC size was smaller in the OR group. Logistic analysis found combined radiological characteristics including complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush were significant correlated with achievement of OR (odds ratio 2.46, 95% CI 1.08-5.61, P = .032). However, no radiological characteristics had significant strength to predict overall survival. Patients with OR after TACE had significantly longer survival time than those with non-OR. Combined characteristics of complete lipiodol retention, tumor feeding artery blockage, and no residual tumor blush had a positive impact on OR in TACE. In patients receiving TACE, those who achieved OR had a better overall survival.

Fiber-reinforced composite partial fixed dental prostheses supported by short or extra-short implants: A 10 year retrospective study.

INTRODUCTION: This study evaluated the 10-year survival and success of partial fixed dental prostheses (P-FDPs) fabricated with a milled fiber-reinforced composite (FRC) framework, supported by short or extra-short implants. METHODS: Patients restored with FRC P-FDPs supported by short or extra-short implants were included in this retrospective study. Kaplan-Meier analysis was used to calculate the survival and success rates of the prostheses. Univariate and multivariate Cox regression models, clustered to adjust for multiple implants and prostheses being placed in the same patient, were used to correlate changes in peri-implant bone levels with patient, implant, and prosthesis-related covariates. RESULTS: This study followed 121 FRC P-FDPs supported by 261 implants, placed in 96 patients. At 118 months in function, the P-FDP survival rate was 95.9% (95% CI: 87.5%-98.7%), and the success rate was 89.8% (95%CI: 80.4%-94.8%). Differences in prosthesis span length, abutment/pontic ratio, and the presence of distal extensions (cantilevers) did not affect the prosthetic outcomes. Bone levels around implants were stable, with an average rate of change of -0.01 ± 0.05 mm/month. Cox regression revealed that grafted sites were correlated with peri-implant bone loss, while longer prosthetic spans were correlated with bone gain. CONCLUSION: P-FDPs comprised of milled fiber-reinforced composite frameworks, supported by short and extra-short implants, had high survival and success rates for up to 10 years.

Loganin Ameliorates Painful Diabetic Neuropathy by Modulating Oxidative Stress, Inflammation and Insulin Sensitivity in Streptozotocin-Nicotinamide-Induced Diabetic Rats.

Loganin is an iridoid glycoside with antioxidant, anti-inflammatory, glucose-lowering activities which may address the pathological mechanisms of painful diabetic neuropathy (PDN) related to inflammation, oxidative stress, and hyperglycemia. This study investigated the underlying mechanisms of action of loganin on PDN. The in vivo model of PDN was established by streptozotocin-nicotinamide (STZ-NA) induction in Sprague Dawley (SD) rats. Subsequently, loganin (5 mg/kg) was administered by daily intraperitoneal injection. High-glucose stimulated human SH-SY5Y cells co-incubated with loganin were used to mimic the in vitro model of PDN. Loganin improved PDN rats' associated pain behaviors (allodynia and hyperalgesia), insulin resistance index (HOMA-IR), and serum levels of superoxide dismutase (SOD), catalase and glutathione. Loganin also reduced pain-associated channel protein CaV3.2 and calcitonin gene-related peptide (CGRP) in the surficial spinal dorsal horn of PDN rats. Loganin inhibited oxidative stress and NF-κB activation and decreased the levels of mRNA and protein of proinflammatory factors IL-1ß and TNF-α. Moreover, loganin attenuated insulin resistance by modulating the JNK-IRS-1 (insulin receptor substrate-1)-Akt-GSK3ß signaling pathway in PDN rats. These results suggested that loganin improved PDN-mediated pain behaviors by inhibiting oxidative stress-provoked inflammation in the spinal cord, resulting in improved neuropathic pain.

The correlation with tumor radiological characteristics and prognosis of patients with early-stage hepatocellular carcinoma receiving transcatheter arterial chemoembolization.

ABSTRACT: Transcatheter arterial chemoembolization (TACE) is a standard treatment modality for intermediate stage hepatocellular carcinoma (HCC). The aim of this study was to determine the tumor radiological characteristics associated with prognosis of patients with early-staged HCC receiving TACE.Patients with BCLC stage A HCC were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009. According to mRECIST criteria, patients with or without complete response (CR) were assigned to either the CR group or the non-CR group. Clinical and radiological characteristics were compared between the two groups.In 40 enrolled patients, 24 (60%) were in the CR group, and 16 (40%) in the non-CR group. Clinical parameters were similar between the 2 groups. Radiological characteristics including complete lipidol retention and the absence of residual tumor blush were significantly correlated with achievement of CR in the patients with small-sized HCC. Patients with CR after TACE had a significantly longer overall survival than those without (31.29 vs 22.63 months, P = .021).Complete lipidol retention and the absence of residual tumor blush were correlated with the radiological complete tumor response of these patients with small-sized early-stage HCC receiving TACE.

BKCa Channel Inhibition by Peripheral Nerve Injury Is Restored by the Xanthine Derivative KMUP-1 in Dorsal Root Ganglia.

This study explored whether KMUP-1 improved chronic constriction injury (CCI)-induced BKCa current inhibition in dorsal root ganglion (DRG) neurons. Rats were randomly assigned to four groups: sham, sham + KMUP-1, CCI, and CCI + KMUP-1 (5 mg/kg/day, i.p.). DRG neuronal cells (L4-L6) were isolated on day 7 after CCI surgery. Perforated patch-clamp and inside-out recordings were used to monitor BKCa currents and channel activities, respectively, in the DRG neurons. Additionally, DRG neurons were immunostained with anti-NeuN, anti-NF200 and anti-BKCa. Real-time PCR was used to measure BKCa mRNA levels. In perforated patch-clamp recordings, CCI-mediated nerve injury inhibited BKCa currents in DRG neurons compared with the sham group, whereas KMUP-1 prevented this effect. CCI also decreased BKCa channel activity, which was recovered by KMUP-1 administration. Immunofluorescent staining further demonstrated that CCI reduced BKCa-channel proteins, and KMUP-1 reversed this. KMUP-1 also changed CCI-reduced BKCa mRNA levels. KMUP-1 prevented CCI-induced neuropathic pain and BKCa current inhibition in a peripheral nerve injury model, suggesting that KMUP-1 could be a potential agent for controlling neuropathic pain.

Loganin prevents CXCL12/CXCR4-regulated neuropathic pain via the NLRP3 inflammasome axis in nerve-injured rats.

BACKGROUND: Neuropathic pain has been shown to be modulated by the activation of the chemokine C-X-C motif ligand 12 (CXCL12)/chemokine CXC receptor 4 (CXCR4) dependent nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. Loganin, an iridoid glycoside, was proven to prevent neuropathic pain, but its underlying mechanisms related to NLRP3 activation are still unknown. PURPOSE: This study investigated the underlying mechanisms of loganin's effect on chronic constriction injury (CCI)-induced NLRP3 inflammasome activation in the spinal cord. METHODS: Sprague-Dawley rats were randomly divided into four groups: sham, CCI, sham + loganin, and CCI + loganin. Loganin (5 mg/kg/day) was administered intraperitoneally starting the day after surgery. Paw withdrawal threshold (PWT) and latency (PWL) were assessed before CCI and on days 1, 3, 7 and 14 after CCI. Spinal cords were collected for western blots and immunofluorescence studies. RESULTS: Loganin prevented CCI-attenuated PWT and PWL, suggesting improved mechanical allodynia and thermal hyperalgesia. The expression of CXCL12, CXCR4, thioredoxin-interacting protein (TXNIP), NLRP3 inflammasome (NLRP3, ASC, and caspase-1), IL-1ß, and IL-18 were enhanced on day 7 after CCI, and all were reduced after loganin treatment. Dual immunofluorescence also showed that increased CXCL12, CXCR4, and NLRP3 were colocalized with NeuN (neuronal marker), GFAP (astrocyte marker), and Iba1 (microglial marker) on day 7 in the ipsilateral spinal dorsal horn (SDH). These immunoreactivities were attenuated in loganin-treated rats. Moreover, loganin decreased the assembly of NLRP3/ASC inflammasome after CCI in the ipsilateral SDH. Loganin appears to attenuate CCI-induced neuropathic pain by suppressing CXCL12/CXCR4-mediated NLRP3 inflammasome. CONCLUSION: Our findings suggest that loganin might be a suitable candidate for managing CCI-provoked neuropathic pain.