Hidradenitis suppurativa as a potential risk factor of periodontitis: a multi-center, propensity-score-matched cohort study.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with systemic symptoms. Periodontitis, a prevalent dental disease, shares immune-mediated inflammatory characteristics with HS. This cohort study aims to evaluate the association between HS and periodontitis. Methods: Using the TriNetX research network, a global-federated database of electronic health records, we conducted a retrospective cohort study. People being diagnosed of HS were identified and propensity score matching was performed to identify proper control group, via balancing critical covariates Within the follow-up time of 1 year, 3 year and 5 years, hazard ratios were calculated to assess the risk of periodontitis in HS patients compared to controls. Results: Within the 53,968 HS patients and the same number of matched controls, the HS patients exhibited a significantly increased risk of developing periodontitis compared to controls after 3 years of follow-up (HR: 1.64, 95% CI: 1.11, 2.44) and 5 years of follow-up (HR: 1.64, 95% CI: 1.21, 2.24) of follow-up. Sensitivity analyses supported these findings under various matching models and washout periods. While comparing with patients with psoriasis, the association between HS and periodontitis remained significant (HR: 1.73, 95% CI: 1.23, 2.44). Conclusion: The observed increased risk suggests the need for heightened awareness and potential interdisciplinary care for individuals with HS to address periodontal health.

Ganoderma microsporum immunomodulatory protein induces apoptosis and potentiates mitomycin C-induced apoptosis in urinary bladder urothelial carcinoma cells.

Current chemotherapy and immunotherapy treatments followed by transurethral resection for urinary bladder urothelial carcinoma (UC) usually suffer from poor prognosis and high recurrence rate. Design and modification of current formulation with the novel adjuvants are needed. A recombinant protein derived from Ganoderma microsporum named as Ganoderma microsporum immunomodulatory protein (GMIP) was used to treat UC cells. We found GMIP elicits a dose-dependent and time-dependent anti-UC cell proliferation effect, with a half-maximal inhibition concentration (IC50 ) comparable to mitomycin C (MMC), a commonly used chemotherapy agent. After GMIP treatment, UC cells showed apoptotic phenomenon including cell cycle arrest in the G1 phase, elevated sub-G1 population, mitochondrial membrane potential loss, up-regulated p21 expression, p21 nuclear translocation, caspase activation, and PARP cleavage in a p53-independent but p21-mediated pathways. Unlike lung cancer cells, GMIP treated UC cells showed no autophagic scheme including Beclin-1, an autophagy to apoptosis switch marker, was not cleaved by caspase 3 and slight LC3B-II accumulation. Also, the classic autophagic inhibitor, chloroquine had no effect in GMIP-mediated cell death made us conclude that GMIP induced apoptosis through caspase activation but not autophagy in UC cells. Additionally, GMIP showed synergistic effects with MMC in killing UC cells and thus decreased the concentration of MMC usage to reach the comparable apoptotic effects. Our results delineate novel strategies for treatment of UC by GMIP alone or in combination with MMC application and provide a promising therapeutic cocktail for better treatment of urinary bladder urothelial carcinoma.

Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression.

BACKGROUND/PURPOSE: We previously showed that subsequent intrathecal (i.t.) injection of resveratrol (30 µg) significantly reverses morphine-evoked neuroinflammation in morphine-tolerant rats. The present study examined the underlying mechanism. METHODS: Male Wistar rats were implanted with two i.t. catheters, one of which was connected to a miniosmotic pump and used for morphine (15 µg/h) or saline infusion for 120 hours. To examine the effects on spinal cord expression of histone deacetylase 1 (HDAC1), the inflammatory cytokine tumor necrosis factor-α (TNF-α), and TNF receptor (TNFR) 1 and TNFR2 during tolerance induction, a tail-flick test was performed prior to infusion and after 24 hours, 48 hours, 72 hours, 96 hours, and 120 hours of infusion. RESULTS: Resveratrol treatment prior to morphine challenge restored the antinociceptive effect of morphine in morphine-tolerant rats and reversed the morphine infusion-induced increase in HDAC1, TNF-α, and TNFR1 expression. Moreover, chronic morphine infusion increased TNFR1-specific expression in neuron in morphine-tolerant rat spinal cords, and this effect was almost completely inhibited by resveratrol treatment prior to morphine challenge. CONCLUSION: Resveratrol restores the antinociceptive effect of morphine by reversing morphine infusion-induced spinal cord neuroinflammation and increase in TNFR1 expression. The reversal of the morphine-induced increase in TNFR1 expression by resveratrol is partially due to reversal of the morphine infusion-induced increase in HDAC1 expression. Resveratrol pretreatment can be used as an adjuvant in clinical pain management for patients who need long-term morphine treatment or with neuropathic pain.

(+)-Naloxone inhibits morphine-induced chemotaxis via prevention of heat shock protein 90 cleavage in microglia.

BACKGROUND/PURPOSE: Microglia have a crucial role in maintaining neuronal homeostasis in the central nervous system. Immune factors released from microglia have important roles in nociceptive signal transduction. Activation of microglia seems to be a shared mechanism in pathological pain and morphine tolerance because pharmacological attenuation of microglia activation provides satisfactory management in both situations. METHODS: In the present study, we investigated the effect of 1nM (+)-naloxone, which is not an opioid receptor antagonist, on morphine-induced activation of microglia EOC13.31 cells. RESULTS: Our results showed that 1µM morphine enhanced microglia activation and migration, decreased α-tubulin acetylation, and induced heat shock protein 90 (HSP90) fragmentation and histone deacetylase 6 (HDAC6) expression. Morphine-induced α-tubulin deacetylation and HSP90 fragmentation were HDAC6-dependent. Pretreatment with (+)-naloxone (1nM) inhibited morphine-evoked microglia activation and chemotaxis and prevented α-tubulin deacetylation and HSP90 fragmentation by inhibiting HDAC6 expression. CONCLUSION: Based on the findings of the present study, we suggest that (+)-naloxone inhibits morphine-induced microglia activation by regulating HDAC6-dependent α-tubulin deacetylation and HSP90 fragmentation.

Baicalin ameliorates neuropathic pain by suppressing HDAC1 expression in the spinal cord of spinal nerve ligation rats.

BACKGROUND/PURPOSE: In a recent study, we found that baicalin exhibited a potent analgesic effect on carrageenan-evoked thermal hyperalgesia. The underlining mechanisms may be associated with inhibition of inflammatory mediator overproduction, including proinflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). In the present study, we examined the effect of baicalin on the antinociceptive effect of morphine and histone deacetylase 1 (HDAC1) expression in the spinal cord dorsal horn in neuropathic pain rats. METHODS: Neuropathic pain was induced by tight ligation of the left L5 spinal nerve of the rats. An intrathecal catheter was implanted for drug administration. Nociception was assessed by using the plantar test with the Hargreaves radiant heat apparatus, and the von Frey test with the dynamic plantar anesthesiometer. Spinal cords were removed for histone acetyl-H3 and HDAC1 western blot analysis at the end of the nociceptive assessment. RESULTS: The results showed that hyperalgesia and allodynia were observed in the spinal nerve ligated (SNL) left hindlimb; it was companied by histone-H3 deacetylation and HDAC1 overexpression on the ipsilateral side of the spinal cord dorsal horn. Intrathecal injection of baicalin (10 µg) significantly attenuated the allodynia and hyperalgesia, and enhanced the antinociceptive effect of morphine (15 µg). Moreover, baicalin reversed the histone-H3 acetylation and suppressed HDAC1 expression on the ipsilateral side of the spinal cord dorsal horn of SNL rats. CONCLUSION: The present findings suggest that baicalin can ameliorate neuropathic pain by suppressing HDAC1 expression and preventing histone-H3 acetylation in the spinal cord dorsal horn of SNL rats.

New-Onset Hidradenitis Suppurativa in Psoriasis Patients: A Multi-Center, Retrospective Cohort Study.

BACKGROUND: Previous research has indicated a potential correlation between hidradenitis suppurativa (HS) and psoriasis (PSO), two chronic inflammatory dermatological diseases. However, there is a lack of comprehensive evaluations that consider a variety of clinical and demographic factors, and the risk of developing HS in PSO patients remains unclear. Our study aims to examine HS risk over time among PSO patients versus matched controls while considering the influence of confounders to provide insights into the potential link between these two diseases. METHOD: In this multi-institutional cohort study using the TriNetX database, we matched 202,318 patients with PSO with an equivalent number of individuals without PSO, using propensity score matching. The study period extended from 1 January 2005 to 31 December 2018. We computed hazard ratios and their respective 95% confidence intervals (CIs) to evaluate the probability of HS manifestation over a period of 5 years in patients with PSO in comparison to those without PSO. RESULTS: PSO patients demonstrated a consistently higher risk of developing HS than matched controls across all analytic models with the hazard ratios (HR) ranging from 1.43 (95% CI 1.30-1.56) to 5.91 (95% CI 2.49-14.04). Stratified analyses showed the increased HS risk was observed in both genders but only significant in those aged 18-64 years. Kaplan-Meier analysis indicated PSO patients had a higher cumulative probability of developing HS over time (HR 1.77, 95% CI 1.49-1.89). CONCLUSIONS: PSO was associated with increased HS risk, highlighting the importance of considering HS as a potential comorbidity in PSO patients and may have implications for early detection, prevention, and management strategies for both conditions. Shared inflammatory pathways, genetic components, and skin dysbiosis may contribute. Further research should elucidate underlying mechanisms.

Long-COVID impacts taste and olfactory in individuals with substance use disorder: A retrospective cohort study from the TriNetX US Collaborative Networks.

Substance use disorder (SUD) exacerbates the impact of Long-COVID, particularly increasing the risk of taste and olfactory disorders. Analyzing retrospective cohort data from TriNetX and over 33 million records (Jan 2020-Dec 2022), this study focused on 1,512,358 participants, revealing that SUD significantly heightens the likelihood of experiencing taste disturbances and anosmia in Long-COVID sufferers. Results indicated that individuals with SUD face a higher incidence of sensory impairments compared to controls, with older adults and women being particularly vulnerable. Smokers with SUD were found to have an increased risk of olfactory and taste dysfunctions. The findings underscore the importance of early screening, diagnosis, and interventions for Long-COVID patients with a history of SUD, suggesting a need for clinicians to monitor for depression and anxiety linked to sensory dysfunction for comprehensive care.

New-onset Fibromyalgia After Total Knee Replacement in Patients With Osteoarthritis: A Propensity-score-matched Cohort Study in the United States.

BACKGROUND/AIM: The risk of new-onset fibromyalgia after total knee replacement (TKR) in osteoarthritis patients is not well-established. This study aimed to assess the risk of developing fibromyalgia post-TKR, considering potential variations across age and sex. PATIENTS AND METHODS: Utilizing a multicenter retrospective cohort design and data from the TriNetX research network, electronic health records of osteoarthritis patients who underwent TKR and the same number of matched controls were analyzed. Propensity-score matching was performed by matching critical confounders. Hazard ratios were evaluated to assess fibromyalgia risk in the TKR cohort compared to non-TKR controls. RESULTS: The hazard ratio of future fibromyalgia for the TKR cohort was 2.08 (95% confidence interval=1.74-2.49) for 1 year after the index date, 1.81 (95% confidence interval=1.62-2.02) for 3 years, and 1.69 (95% confidence interval=1.54-1.86) for 5 years compared with non-TKR controls. The significant association remained in sensitivity models and stratification analyses in different age and sex subgroups. CONCLUSION: Clinicians should be vigilant about the potential for fibromyalgia development post-TKR and consider tailored interventions; our findings emphasize the need for further research to elucidate underlying mechanisms and identify modifiable risk factors.

Honey in Alleviating Severe Oral Mucositis Among Head and Neck Cancer Patients Undergoing Radiation Therapy.

BACKGROUND/AIM: Aiming to resolve debates on honey's efficacy for radiotherapy-induced severe oral mucositis in head and neck cancer, we conducted a meta-analysis focused on randomized trials, primarily assessing severe mucositis incidence. Secondary outcomes included weight loss, pain management, and honey types. MATERIALS AND METHODS: A comprehensive literature search was conducted in PubMed, Embase, WOS, and the Cochrane Library up to December 2023. The analysis concentrated on randomized controlled trials that assessed the efficacy of honey, targeting the incidence of mucositis as the main outcome. Additional outcomes explored were weight loss, intolerable pain, and the specific types of honey used in interventions. Data analysis was performed using CMA software, and a funnel plot was employed to identify publication bias. RESULTS: The analysis of 176 records resulted in the inclusion of 10 studies with 599 patients receiving radiotherapy. The research showed that honey significantly reduced the occurrence of grade 3-4 mucositis (severe mucositis), provided significant pain relief, and had a positive effect on reducing weight loss. Regarding the type of honey used, no significant differences were found in their effectiveness in alleviating severe mucositis. CONCLUSION: Honey serves as an effective intervention for individuals with oral mucositis. It can be considered as an adjuvant in the management of clinical radiotherapy-associated oral mucositis, particularly for patients requiring prolonged use of anti-analgesic or antifungal medications.

Risk of Keratitis and Keratopathy in Hidradenitis Suppurativa Patients: A Global Federated Health Network Analysis.

BACKGROUND/AIM: Hidradenitis suppurativa (HS) is linked to immune dysregulation and systemic inflammation. While previous studies indicate a higher prevalence of ocular manifestations in HS, the specific risk of keratopathy and keratitis remains unclear. The primary aim of this study was to assess the risk of keratitis and keratopathy in individuals with HS. PATIENTS AND METHODS: In this retrospective cohort study conducted with data from the TriNetX database, 53,716 patients with HS were matched to an equivalent number of non-HS controls using propensity score matching. The study covered the period from January 1st, 2005, to December 31st, 2017. Hazard ratios and their respective 95% confidence intervals (CIs), were computed to evaluate the occurrences of keratitis and keratopathy over a 5-year duration in patients with HS, compared to non-HS controls. RESULTS: HS was associated with a 1.52 times higher risk of keratitis over a 5-year period (95%CI=1.24-1.86) and a 1.47 times higher risk of keratopathy (95%CI=1.18-1.84). These risks remained consistent in sensitivity analyses. The elevated risk of keratitis was observed across both sexes. However, the risk of keratopathy was significantly higher in women with HS (HR=1.61, 95%CI=1.24-2.10) and individuals aged 18-64 years (HR=1.32, 95%CI=1.04-1.68). CONCLUSION: HS was linked to an elevated risk of both keratitis and keratopathy over a 5-year period. Ophthalmologic manifestations are recommended to be considered in HS standard care.

Early intraarticular injection of hyaluronic acid attenuates osteoarthritis progression in anterior cruciate ligament-transected rats.

SUBJECT: Hyaluronic acid (HA) is widely used to relieve the symptoms of osteoarthritis (OA). An association of reduction of glutamate content with the synovial fluid of OA rats was reported previously. DESIGN: Anterior cruciate ligament transaction (ACLT) was performed on one knee in male Wistar rats, the other knee was assigned to sham control and HA or saline was injected intraarticularly into the ACLT knee from week 3 to week 7. Knee dialysate was collected for amino acid measurement at week 20. Morphology and histopathology of the femoral medial condyles and synovium were examined and evaluated using Mankin and synovitis scores. RESULTS: HA injection provided better cartilage (3.38 ± 0.03 vs. 5.45 ± 0.0.02) and synovial condition (3 ± 0.02 vs. 6.03 ± 0.02) than saline controls. Moreover, HA injection reduced the concentration of glutamates in knee dialysates compared to saline controls (1.11 ± 0.14-folds and 2.21 ± 0.19-folds of the sham-operated knee, respectively). Cystine/glutamate antiporter system [Formula: see text] expression was significantly downregulated in the saline group, but not in the HA group (0.32 ± 0.08-folds and 0.71 ± 0.10-folds of the sham-operated knee, respectively). CONCLUSION: Early intraarticular injection of HA attenuates the progression of cartilage destruction in the ACLT knee, and the downregulation of the cystine/glutamate antiporter system [Formula: see text] was accompanied by the progression of OA.

Ultra-low dose (+)-naloxone restores the thermal threshold of morphine tolerant rats.

BACKGROUND/PURPOSE: As known, long-term morphine infusion leads to tolerance. We previously demonstrated that both co-infusion and post-administration of ultra-low dose (±)-naloxone restores the antinociceptive effect of morphine in morphine-tolerant rats. However, whether the mechanism of the action of ultra-low dose (±)-naloxone is through opioid receptors or not. Therefore, in the present study, we further investigated the effect of ultra-low dose (+)-naloxone, it does not bind to opioid receptors, on the antinociceptive effect of morphine. METHODS: Male Wistar rats were implanted with one or two intrathecal (i.t.) catheters; one catheter was connected to a mini-osmotic pump, used for morphine (15 µg/h), ultra-low dose (+)-naloxone (15 pg/h), morphine plus ultra-low dose (+)-naloxone (15 pg/h) or saline (1 µl/h) infusion for 5 days. On day 5, either ultra-low dose (+)-naloxone (15 pg) or saline (5 µl) was injected via the other catheter immediately after discontinued morphine or saline infusion. Three hours later, morphine (15 µg in 5 µl saline) or saline were given intrathecally. All rats received nociceptive tail-flick test every 30 minutes for 120 minutes after morphine challenge at different temperature (45-52°C, respective). RESULTS: Our results showed that, both co-infusion and post-treatment of ultra-low dose (+)-naloxone with morphine preserves the antinociceptive effect of morphine. Moreover, in the post administration rats, ultra-low dose (+)-naloxone further enhances the antinociceptive effect of morphine. CONCLUSION: This study provides an evidence for ultra-low dose (+)-naloxone as a therapeutic adjuvant for patients who need long-term opioid administration for pain management.

Resveratrol regulates N-methyl-D-aspartate receptor expression and suppresses neuroinflammation in morphine-tolerant rats.

BACKGROUND: In the present study, we examined the effects and mechanisms of the Chinese herb resveratrol on attenuation of morphine tolerance in rats. METHODS: Male Wistar rats were implanted with 2 intrathecal catheters; one catheter was connected to a mini-osmotic pump, used for either morphine (15 µg/h) or saline (1 µL/h) infusion for 5 days. On day 5, resveratrol (7.5, 15, 30, or 60 µg), dimethyl sulfoxide (5 µL), or saline (5 µL) was injected via the other catheter immediately after the discontinued morphine infusion. Three hours later, intrathecal morphine (15 µg in 5 µL saline) was given. All rats received the nociceptive tail-flick test every 30 minutes for 120 minutes after the morphine challenge. RESULTS: Long-term morphine infusion induced antinociceptive tolerance and up-regulated N-methyl-D-aspartate receptor (NMDAR) subunit NR1 and NR2B expression in the synaptosome fraction of the tolerant spinal cord dorsal horn. Resveratrol pretreatment provided a significant antinociceptive effect of morphine in morphine-tolerant rats, and it was associated with reversal of the up-regulated NR1 and NR2B subunits in the synaptosome fraction of morphine-tolerant rat spinal cords. NR1/NR2B-specific antagonist ifenprodil treatment produced a similar effect as that of resveratrol. Furthermore, an increase of postsynaptic density-95/NR1/NR2B complex immunoprecipitation in morphine-tolerant rat spinal cord was also inhibited by resveratrol pretreatment. Moreover, chronic morphine infusion activated glial cells with an increase of proinflammatory cytokine tumor necrosis factor-α, interleukin-1ß, and interleukin-6 mRNA expression in morphine-tolerant rat spinal cords and these effects were suppressed by resveratrol pretreatment before the morphine challenge. CONCLUSIONS: Resveratrol attenuates morphine tolerance by inhibiting neuroinflammation and down-regulating NMDAR NR1 and NR2B subunit expression. Resveratrol regulates the NMDAR expression, which might be involved in a loss of scaffolding postsynaptic density-95 protein.

The association of Caveolin-1 genotypes with oral cancer susceptibility in Taiwan.

BACKGROUND: Caveolin-1, which has been proposed as a candidate tumor suppressor, plays a regulatory role in several signaling pathways. The aim of this study was to evaluate the association between oral cancer susceptibility and Cav-1 genotypes. In this hospital-based case-control study, the association of Cav-1 polymorphisms with oral cancer risk in a central Taiwanese population was investigated. METHODS: Six hundred patients with oral cancer and 620 age- and sex-matched healthy control subjects were genotyped and analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: There were significant differences between oral cancer and control groups in the distributions of their genotypes (P = 1.7 × 10(-18) and 2.6 × 10(-4)) and allelic frequencies (P = 3.3 × 10(-19) and 9.5 × 10(-6)) in the Cav-1 G14713A (rs3807987) and T29107A (rs7804372) polymorphisms, respectively. As for the combined genotype analysis, those who had GG/AT or GG/AA at Cav-1 G14713A/T29107A showed a 0.72-fold (95% confidence interval = 0.52-0.99) decreased risk of oral cancer compared to those with GG/TT, while those of any other combinations were of increased risk. The presence of metastasis was also correlated to both Cav-1 G14713A AA and Cav-1 T29107A TT genotypes. CONCLUSIONS: Cav-1 is involved in oral cancer, the A allele of the Cav-1 G14713A is risky, the A allele of the Cav-1 T29107A is protective, and AA/TT on these two polymorphisms may be the most risky combined genotype for the development of oral cancer and may be novel risk markers for early detection and prediction of distant metastasis.

Etanercept restores the antinociceptive effect of morphine and suppresses spinal neuroinflammation in morphine-tolerant rats.

BACKGROUND: In the present study we examined the effect of the tumor necrosis factor (TNF)-α antagonist etanercept on the antinociceptive effect of morphine in morphine-tolerant rats. METHODS: Male Wistar rats were implanted with 2 intrathecal catheters, and 1 was connected to a mini-osmotic pump for either morphine (15 µg/h) or saline (1 µL/h) infusion for 5 days. On day 5, either etanercept (5 µg, 25 µg, and 50 µg/10 µL) or saline (10 µL) was injected via the other catheter after morphine infusion was discontinued. Three hours later, morphine (15 µg/10 µL, intrathecally) was given and tail-flick latency was measured to evaluate the antinociceptive effect of morphine. Rats were then killed and their spinal cords were removed for quantitative real-time polymerase chain reaction and immunohistochemistry to measure proinflammatory cytokines expression. RESULTS: We found that acute etanercept (50 µg) treatment preserved a significant antinociceptive effect of morphine in morphine-tolerant rats. In addition, the expression of TNFα mRNA was increased by 2.5-fold, interleukin (IL)-1ß mRNA increased by 13-fold and IL-6 mRNA by 111-fold in the dorsal spinal cord of morphine-tolerant rats. The increase in TNFα, IL-1ß, and IL-6 mRNA expression was blocked by 50 µg etanercept pretreatment. The immunohistochemistry analysis revealed that 50 µg etanercept suppressed proinflammatory cytokines expression and neuroinflammation in the microglia. CONCLUSIONS: The present study demonstrates that etanercept restores the antinociceptive effect of morphine in morphine-tolerant rats by inhibition of proinflammatory cytokine TNF-α, IL-1ß, and IL-6 expression and spinal neuroinflammation. The results suggest that etanercept could also be an adjuvant therapy for morphine tolerance, which extends the effectiveness of opioids in clinical pain management.

Intrathecal etanercept partially restores morphine's antinociception in morphine-tolerant rats via attenuation of the glutamatergic transmission.

BACKGROUND: Long-term exposure to morphine leads to analgesic tolerance. In addition to an opioid receptor conformational change, enhancing the glutamatergic signal transmission is also involved in morphine tolerance. Tumor necrosis factor-α has been demonstrated to correlate with neuronal plasticity via activation of glutamatergic transmission. We examined the effect of etanercept, a tumor necrosis factor-α inhibitor on morphine tolerance in rats. METHODS: Male Wistar rats were implanted with 2 intrathecal (IT) catheters, and 1 IT catheter was connected to a mini-osmotic pump, used for either morphine infusion (15 µg/h) or saline (1 µL/h) infusion for 5 days. On day 5, either etanercept (50 µg) or saline (10 µL) was injected after discontinued morphine infusion. Three hours later, acute morphine (15 µg/10 µL, IT) treatment was given and all rats received a nociceptive tail-flick test. RESULTS: The results showed that acute etanercept (50 µg) treatment caused a significant antinociceptive effect of morphine in morphine-tolerant rats. Western blotting indicated that etanercept attenuated the downregulation of membrane glutamate transporters GLT-1 and GLAST in morphine-tolerant rats. Etanercept also inhibited the upregulation of surface AMPA-receptor and N-methyl-d-aspartate-receptor subunits, including GluR1/GluR2 and NR1/NR2A. CONCLUSIONS: These results demonstrate that etanercept partially restores the antinociceptive effect of morphine in morphine tolerance after a morphine challenge. Etanercept has potential for use in the clinical management of pain, particularly in patients who require long-term opioid treatment, and the effectiveness of which can be hampered by tolerance.

Significant association of caveolin-1 genotypes with bladder cancer susceptibility in Taiwan.

Many articles have reported the caveolin-1 gene to be down-regulated thus suggesting that it might be a candidate tumor suppressor gene in many tumors. However, its involvement in bladder cancer is not clear and may be depending on pathological grade. In this case-control study, the association of Cav-1 polymorphisms with bladder cancer risk in a central Taiwanese population was investigated. Three hundred and seventy-five patients with bladder cancer and the same number of age- and gender-matched healthy controls were genotyped. There were significant differences between bladder cancer and control groups in the distributions of their genotypes (P = 1.0 x 10(-12) and 0.299) and allelic frequencies (P = 1.4 x 10(-14) and 6.2 x 10(-3)) in the Cav-1 G14713A (rs3807987) and T29107A (rs7804372) polymorphisms, respectively. As for haplotype analysis, subjects who had GG/AT or GG/AA at Cav-1 G14713A/T29107A showed a decreased risk of bladder cancer compared to subjects with GG/TT, while those of any other combinations were of increased risk. There were joint effects of Cav-1 G14713A and T29107A genotypes with smoking status on individual bladder cancer susceptibility. This is the first report providing evidence that Cav-1 was involved in bladder cancer in that the A allele of the Cav-1 G14713A is risky, the A allele of the Cav-1 T29107A is protective, and AA/TT on these two polymorphisms may be the most risky haplotype for the development of bladder cancer and may be novel useful genomic markers for early detection of bladder cancer.

A Pilot Study of Radiculopathy Following Osteoporotic Vertebral Fracture in Elderly Patients: An Algorithmic Approach to Surgical Management.

Background: Osteoporotic vertebral compression fractures (OVCF) due to severe and refractory back pain or neurological complications require surgical treatment. In this study, patients with radiculopathy due to foraminal stenosis following OVCF were surgically managed by performing transforaminal full-endoscopic lumbar foraminoplasty and/or discectomy (FELFD). Methods: From May 2015 to November 2019, fifteen patients underwent transforaminal FELFD. Patient data, Charlson comorbidity index (CCI), and American Society of Anesthesiologists (ASA) score were collected. Clinical outcomes, including pre- and postoperative Visual Analog Scale (VAS) scores for back and leg pain, Oswestry Disability Index (ODI), and MacNab criteria of response to surgical treatment, were evaluated. Results: Mean of age, bone mineral density (T-score), CCI, ASA, and follow-up duration were 69.5 ± 6.6 years, -2.6 ± 0.8, 5.2 ± 2.3, 2.4 ± 0.5, and 24.5 ± 8.8 months, respectively. Mean VAS for leg pain significantly decreased from 6.9 ± 0.8 preoperatively to 2.9 ± 1.1 (P < .05). Mean ODI decreased from 39.9 ± 3.2 preoperatively to 19.3 ± 4.6 postoperatively (P < .05). The satisfaction rate is 86.7% (based on Macnab criteria), showed six patients had excellent outcomes and seven had good outcomes. Conclusions: Transforaminal FELFD is an effective treatment option for patients with radiculopathy due to lumbar OVCF, including those with severe osteoporosis and elderly patients.

Purinergic P2X receptor regulates N-methyl-D-aspartate receptor expression and synaptic excitatory amino acid concentration in morphine-tolerant rats.

BACKGROUND: The present study examined the effect of P2X receptor antagonist 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP) on morphine tolerance in rats. METHODS: Male Wistar rats were implanted with two intrathecal catheters with or without a microdialysis probe, then received a continuous intrathecal infusion of saline (control) or morphine (tolerance induction) for 5 days. RESULTS: Long-term morphine infusion induced antinociceptive tolerance and up-regulated N-methyl-d-aspartate receptor subunits NR1 and NR2B expression in both total lysate and synaptosome fraction of the spinal cord dorsal horn. TNP-ATP (50 µg) treatment potentiated the antinociceptive effect of morphine, with a 5.5-fold leftward shift of the morphine dose-response curve in morphine-tolerant rats, and this was associated with reversal of the up-regulated NR1 and NR2B subunits in the synaptosome fraction. NR1/NR2B-specific antagonist ifenprodil treatment produced a similar effect as TNP-ATP; it also potentiated the antinociceptive effect of morphine. On day 5, morphine challenge resulted in a significant increase in aspartate and glutamate concentration in the cerebrospinal fluid dialysates of morphine-tolerant rats, and this effect was reversed by TNP-ATP treatment. Moreover, the amount of immunoprecipitated postsynaptic density-95/NR1/NR2B complex was increased in morphine-tolerant rats, and this was prevented by the TNP-ATP treatment. CONCLUSIONS: The findings suggest that attenuation of morphine tolerance by TNP-ATP is attributed to down-regulation of N-methyl-d-aspartate receptor subunits NR1 and NR2B expression in the synaptosomal membrane and inhibition of excitatory amino acids release in morphine-tolerant rats. The TNP-ATP regulation on the N-methyl-d-aspartate receptor expression may be involved in a loss of scaffolding proteins postsynaptic density-95.