Polysaccharide-based hydrogels are achieving remarkable performances in chronic wounds treatment. In this work, a carboxymethyl cellulose-based hydrogel film was developed to support skin repair. The ...hydrogel was loaded with berberine, a polyphenolic molecule endowing antioxidant and cytoprotective features. The film was physico-chemically characterized and in vitro tested on keratinocytes and fibroblasts subjected to oxidative stress. The biocomposite showed high thermal stability (onset decomposition temperature 245 °C) and significant fluid uptake performances, both in free conditions (up to 6510%) and under external pressure (up to 3400%). Moreover, it was able to control oxidative stress and inflammation markers involved in wound chronicity. Keratinocytes hyperproliferation, features that normally hamper injury restoration, was reduced of 25%. Our results showed that the combination of berberine and hydrogel provides a synergic improvement of the material properties. The biocomposite represents a promising candidate for dermatological applications against oxidative stress at the chronic wound site, promoting the healing process.
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High-temperature requirement A1 (HtrA1), a multidomain serine protease acting on Extracellular matrix (ECM) rearrangement, is also secreted by osteoblasts and osteoclasts. Recent and conflicting ...literature highlights HtrA1's role as a controller of bone remodeling, proposing it as a possible target for pathologies with unbalanced bone resorption, like Osteoporosis (OP). To add knowledge on this molecule function in bone physiopathology, here we compared HtrA1 distribution in the ECM of healthy (H) and OP bone tissue, also examining its localization in the sites of new bone formation. HtrA1 was homogeneously expressed in the mature bone ECM of H tissue showing a 55.6 ± 16.4% of the stained area, with a significant (p=0.0001) decrease in OP percentage stained area (21.1 ± 13.1). Moreover, HtrA1 was present in the endosteum and cells involved in osteogenesis, mainly in those “entrapped” in woven bone, whereas osteocytes in mature lamellar bone were negative. Based on our previous observation in OP tissue of a significantly increased expression of Decorin and Osteocalcin, both involved in bone mineralization and remodeling and equally substrates for HtrA1, we speculate that HtrA1 by controlling the proper amount of Decorin and Osteocalcin favors normal bone maturation and mineralization. Besides, we suggest that late-osteoblasts and pre-osteocytes secrete HtrA1 in the adjacent matrix whilst proceeding with their maturation and that HtrA1 expression is further modified during the remodeling from woven to the lamellar bone. Overall, our data suggest HtrA1 as a positive regulator of bone matrix formation and maturation: its reduced expression in mature OP bone, affecting protein content and distribution, could hamper correct bone remodeling and mineralization.
•HtrA1 was homogeneously expressed in the mature bone ECM of H tissue, with an evident decrease in OP.•MEPE localized in cells nearby and embedded in the woven bone whilst DMP-1 was mostly expressed in pre-osteocytes.•HtrA1 was detected in pre-osteocytes of the newly formed bone, as evidenced by the co-localization between HtrA1/MEPE and HtrA1/DMP-1.•We suggest that late-osteoblasts and pre-osteocytes secrete HtrA1 in the adjacent matrix whilst proceeding with their maturation and that HtrA1 expression is further modified during the remodeling from woven to the lamellar bone.
High temperature requirement A1 (HtrA1) is a secreted protease involved in placental development. Fibronectin (FN) is involved in important process such as wound healing, cell adhesion and spreading, ...growth, migration, and differentiation. The purpose of this study was to analyse the expression patterns of HtrA1 in relationship to FN and to the key growth zones of placenta such as mesenchymal villi as well as cell islands and cell columns. We demonstrated that FN and HtrA1 are localized in the placental key growth zones suggesting a pivotal role in maintaining the balance among the molecules involved in the placental development and differentiation.
Increasing evidence supports the hypothesis that TGFb1 signalling may be mediated by high temperature requirement A1 (HtrA1) serine protease, acting on important regulatory mechanisms such as cell ...proliferation and mobility. Evidence is now accumulating to suggest that HtrA1 is involved in the development and progression of several pathologies. The aim of this study was to evaluate: i) if HtrA1 and TGFb1 expressions differ in eutopic and ectopic endometrium in women with endometriosis; ii) if HtrA1 correlates to TGFb1, pSmad and Ki67. This study was carried out including 10 women with ovarian endometriosis (cases) and 10 women with non endometriotic diseases (controls). Endometrial tissue underwent immunohistochemical H-score analysis for HtrA1, TGFb1, pSmad and Ki67 molecules. Data evaluation was performed by a nonparametric Kruskal-Wallis test and Spearman correlation was applied to evaluate the relationship among the molecules investigated in the epithelial and in the stromal compartment. The HtrA1 was significant decreased in ectopic and eutopic endometrium of women with endometriosis when compared with control endometrium in epithelial compartment. TGFb1was significantly increased in eutopic endometrium and decreased in ectopic endometrium in epithelial and stromal compartment. In addition, Ki67 was significant increased and an increase, but not significant, was detected for pSMAd2 in eutopic and ectopic endometrium compared to control one. In summary, the significant direct correlation between TGFb1 and pSmad2 as well as between HtrA1 and TGFb1 and the very significant increase of Ki67 in stromal compartment of eutopic endometrium suggest a possible involvement of HtrA1 in the pathogenesis of endometriosis.
Increasing evidence supports the hypothesis that TGFβ1 signalling may be mediated by high temperature requirement A1 (HtrA1) serine protease, acting on important regulatory mechanisms such as cell ...proliferation and mobility. Evidence is now accumulating to suggest that HtrA1 is involved in the development and progression of several pathologies. The aim of this study was to evaluate: i) if HtrA1 and TGFβ1 expressions differ in eutopic and ectopic endometrium in women with endometriosis; ii) if HtrA1 correlates to TGFβ1, pSmad and Ki67. This study was carried out including 10 women with ovarian endometriosis (cases) and 10 women with non endometriotic diseases (controls). Endometrial tissue underwent immunohistochemical H-score analysis for HtrA1, TGFβ1, pSmad and Ki67 molecules. Data evaluation was performed by a nonparametric Kruskal-Wallis test and Spearman correlation was applied to evaluate the relationship among the molecules investigated in the epithelial and in the stromal compartment. The HtrA1 was significantly decreased in ectopic and eutopic endometrium of women with endometriosis when compared with control endometrium in epithelial compartment. TGFβ1was significantly increased in eutopic endometrium and decreased in ectopic endometrium in epithelial and stromal compartment. In addition, Ki67 was significantly increased and an increase, but not significant, was detected for pSMAd2 in eutopic and ectopic endometrium compared to control one. In summary, the significant direct correlation between TGFβ1 and pSmad2 as well as between HtrA1 and TGFβ1 and the very significant increase of Ki67 in stromal compartment of eutopic endometrium suggest a possible involvement of HtrA1 in the pathogenesis of endometriosis.
Emiliano Petrò,1 Elena Ruffini,1 Melania Cappuccio,2 Valeria Guerini,2 Gloria Belotti,3 Sara Fascendini,4 Cristina Licini,4 Claudio Marcassa51Rehabiliation and Alzheimer Unit, San Pietro Polyclinic, ...Ponte San Pietro, 2Alzheimer Center, P. Gusmini Foundation, Vertova, 3Santa Maria Ausiliatrice Foundation, Bergamo, 4Alzheimer Center, Briolini Hospital FERB ONLUS, Gazzaniga, 5Cardiology, Maugeri Foundation IRCCS, Veruno, ItalyObjective: This pilot study evaluated the efficacy and safety of prolonged-release oxycodone/naloxone (OXN-PR) in older subjects with chronic pain and mild-to-moderate cognitive impairment.Methods: This was a prospective, observational, open-label study of 45-day duration. Patients with moderate-to-severe chronic pain and naïve to strong opioids were recruited from nursing homes and Alzheimer's disease centers. OXN-PR was initiated at low doses (5 mg od or bid) and increased to a maximum of 20 mg bid. The primary efficacy endpoint was a pain intensity reduction of ≥30% from baseline (T0) to 15 days after OXN-PR initiation, as assessed by a numerical rating scale or the Pain Assessment in Advanced Dementia scale. Other assessments included the Barthel activities of daily living index, Neuropsychiatric Inventory, Bowel Function Index, and adverse events.Results: The analysis included 53 patients (mean age, 83.0 years; mean Mini-Mental State Examination score, 18.6) with severe pain (median Numerical Rating Scale/Pain Assessment in Advanced Dementia 6) and substantial impairment in daily functioning (mean Barthel index, 32.2). The primary endpoint was achieved by 92.4% of patients. OXN-PR significantly reduced mean pain intensity from baseline to study end (numerical rating scale, 6.6±1.0 vs 2.3±1.1, P<0.0001; Pain Assessment in Advanced Dementia, 6.9±1.6 vs 0.9±0.8, P<0.0001). Substantial improvements from T0 to T45 in daily functioning (mean Barthel index, 32.2±16.8 vs 53.7±23.9, P<0.0001) and neuropsychiatric symptoms (mean Neuropsychiatric Inventory, 25.5±27.3 vs 8.8±9.0, P<0.0001) were also reported. OXN-PR was well tolerated and did not worsen bowel function.Conclusion: In this pilot study, OXN-PR was effective in improving pain and other symptoms associated with dementia, with a favorable safety and tolerability profile. Large-scale trials in people with dementia are needed to improve clinical guidance for the assessment and treatment of pain in these fragile individuals.Keywords: dementia, Alzheimer's disease, oxycodone/naloxone, elderly, cognitive impairment
Abstract Efforts continue to improve pain after total knee arthroplasty (TKA) in order to allow for accelerated rehabilitation. The purpose of this study was to evaluate pain control after TKA. A ...randomized prospective study of 80 consecutive patients was performed comparing Exparel versus femoral nerve block (FNB). Inpatient pain control was the primary outcome. Secondary outcome measures included ROM (extension and flexion), nausea and vomiting, narcotic consumption, ambulation distance, and length of stay (LOS). There were no statistically significant differences between the groups with regard to pain, nausea and vomiting, and narcotic consumption. The FNB group had greater flexion but the Exparel group had improved early ambulation and decreased LOS. Exparel provided similar pain relief to a FNB after TKA without compromising early rehabilitation.
Abstract Background Femoral component stability and resistance to subsidence is critical for osseointegration and clinical success in cementless total hip arthroplasty (THA). The purpose of this ...study was to radiographically evaluate the anatomic fit and subsidence of two different proximally tapered, porous coated modern cementless femoral component designs. Methods A retrospective cohort study of 126 consecutive cementless THAs was performed. Traditional fit-and-fill stems were implanted in the first 61 hips with the remaining 65 receiving morphometric tapered wedge stems. Preoperative bone morphology was radiographically assessed by the canal flare index. Canal fill in the coronal plane, subsidence, and the sagittal alignment of stems was measured digitally on immediate and 1-month postoperative radiographs. Results Demographics and canal flare indices were similar between groups. The percentage of femoral canal fill was greater in the tapered wedge compared to the fit-and-fill stem ( p = 0.001). There was significantly less subsidence in the tapered wedge design (0.3 mm) compared to the fit and fill design (1.1 mm) ( p = 0.001). Subsidence significantly increased as BMI increased in the fit-and-fill stems, a finding not observed in the tapered wedge design ( p = 0.013). Conclusion An anatomically designed morphometric tapered wedge femoral stem demonstrated greater axial stability and decreased subsidence with increasing BMI than a traditional fit-and-fill stem. The resistance to subsidence, irrespective of BMI, is likely due to the inherent axial stability of a tapered wedge design and may be the optimal stem design for obese patients.
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