Adelmidrol, in combination with hyaluronic acid, displays increased anti-inflammatory and analgesic effects against monosodium iodoacetate-induced osteoarthritis in rats

Background Osteoarthritis (OA) is a degenerative joint disease produced by a cascade of events that can ultimately lead to joint damage. The aim of this study was to evaluate the effect of adelmidrol, a synthetic palmitoylethanolamide analogue, combined with hyaluronic acid on pain severity and modulation of the inflammatory response in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. Methods OA was induced by intra-articular injection of MIA in the knee joint. On day 21 post-MIA administration, the knee joint was analyzed. Rats subjected to OA were treated by intra-articular injection of adelmidrol in combination with sodium hyaluronate at different doses and time points after MIA induction. Limb nociception was assessed by the paw withdrawal latency and threshold measurement. Samples were examined macroscopically, histologically, and by immunohistochemistry. Results At day 21 post-MIA injection, the MIA\u2009+\u2009solvent and MIA\u2009+\u20091.0% sodium hyaluronate groups showed irregularities and fibrillation in the surface layer, a decrease in blood cells and multilayering in transition and radial zones, no pannus formation, and modified Mankin scores significantly higher than sham knees. The combination of hyaluronic acid and adelmidrol dose-dependently (adelmidrol 0.6%\u2009+\u20091.0% sodium hyaluronate and adelmidrol 2%\u2009+\u20091.0% sodium hyaluronate) reduced the histological alterations induced by MIA. Moreover, degeneration of articular cartilage, mast cell infiltration, and pro-inflammatory cytokine and chemokine plasma levels were significantly downregulated by treatment with a combination of hyaluronic acid and adelmidrol at the above doses. Conclusions Our results clearly demonstrate that the combination of hyaluronic acid and adelmidrol improves the signs of OA induced by MIA

The Quality of Five Natural, Historical Italian Cheeses Produced in Different Months: Gross Composition, Fat-Soluble Vitamins, Fatty Acids, Total Phenols, Antioxidant Capacity, and Health Index

Five natural historic cheeses of Southern Italy were investigated\u2014Caciocavallo Palermitano (CP), Casizolu del Montiferru (CdM), Vastedda della Valle del Bel\uecce (VVB), Pecorino Siciliano (PS), and Caprino Nicastrese (CN)\u2014which are produced with raw milk and with traditional techniques and tools, from autochthonous breeds reared under an extensive system. The effects of the month of production on gross composition, MUFA, PUFA, PUFA-\u3c96, PUFA-\u3c93, \u3b1-tocopherol, retinol, cholesterol, TPC, TEAC, and GHIC were evaluated. In CP, CLA, TPC, and GHIC were higher in April than in February. CdM showed higher values in terms of fat, saturated fatty acids, PUFA-\u3c93, \u3b1-tocopherol, TEAC, and GHIC in May than in February and September, while low values in terms of protein, moisture, and CLA were found. In VVB, MUFA, PUFA-\u3c96, and \u3b1-tocopherol increased in June compared with April; conversely, protein, FRAP, and TEAC were higher in April. In PS, protein, CLA, PUFA, PUFA-\u3c93, \u3b1-tocopherol, and GHIC increased in May compared with January; on the contrary, moisture, NaCl, and TEAC showed high values in January. CN showed higher values in terms of PUFA, PUFA-\u3c96, PUFA-\u3c93, TPC, TEAC, and GHIC in April and June compared with January. It is shown that each cheese is unique and closely linked to the production area. Cheeses produced in the spring months showed a high nutritional quality due to the greatest presence of healthy compounds originating from an extensive feeding system. For the purposes of raising awareness of five historical cheeses of Southern Italy that are less known by consumers, and of restoring dignity to the breeders and producers of these cheeses, we studied their quality in terms of chemical composition, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), conjugated linoleic acid (CLA), PUFA-\u3c96, PUFA-\u3c93, \u3b1-tocopherol, retinol, cholesterol, polyphenol content (TPC), total antioxidant capacity (FRAP and TEAC), and health index (GHIC). Two stretched-curd bovine cheeses, Caciocavallo Palermitano (CP) and Casizolu del Montiferru (CdM), two ovine cheeses, Vastedda della Valle del Bel\uecce (VVB) and Pecorino Siciliano (PS), and one caprine cheese, Caprino Nicastrese (CN), were evaluated. These cheeses are produced in different months, with raw milk from animals reared in an extensive feeding system. In April, the CP cheese showed high values for CLA, TPC, and GHIC, while the CN cheese exhibited high PUFA, PUFA-\u3c96, PUFA-\u3c93, TEAC, and GHIC. In May, the CdM cheese exhibited high content of fat, saturated fatty acids, PUFA-\u3c93, \u3b1-tocopherol, TEAC, and GHIC, while the PS cheese showed high values of protein, CLA, PUFA, PUFA-\u3c93, \u3b1-tocopherol, and GHIC. These measured parameters characterize and distinguish each cheese due to links with numerous factors: Species, breed, feeding system, pasture biodiversity, climate, production technology, traditional tools, and ripening type. It is highlighted that, in general, the highest nutritional quality, linked to the highest presence of healthy compounds, originates from the pasture of cheese production in the spring

Adelmidrol, in combination with hyaluronic acid, displays increased anti-inflammatory and analgesic effects against monosodium iodoacetate-induced osteoarthritis in rats

Background: Osteoarthritis (OA) is a degenerative joint disease produced by a cascade of events that can ultimately lead to joint damage. The aim of this study was to evaluate the effect of adelmidrol, a synthetic palmitoylethanolamide analogue, combined with hyaluronic acid on pain severity and modulation of the inflammatory response in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis. Methods: OA was induced by intra-articular injection of MIA in the knee joint. On day 21 post-MIA administration, the knee joint was analyzed. Rats subjected to OA were treated by intra-articular injection of adelmidrol in combination with sodium hyaluronate at different doses and time points after MIA induction. Limb nociception was assessed by the paw withdrawal latency and threshold measurement. Samples were examined macroscopically, histologically, and by immunohistochemistry. Results: At day 21 post-MIA injection, the MIA + solvent and MIA + 1.0% sodium hyaluronate groups showed irregularities and fibrillation in the surface layer, a decrease in blood cells and multilayering in transition and radial zones, no pannus formation, and modified Mankin scores significantly higher than sham knees. The combination of hyaluronic acid and adelmidrol dose-dependently (adelmidrol 0.6% + 1.0% sodium hyaluronate and adelmidrol 2% + 1.0% sodium hyaluronate) reduced the histological alterations induced by MIA. Moreover, degeneration of articular cartilage, mast cell infiltration, and pro-inflammatory cytokine and chemokine plasma levels were significantly downregulated by treatment with a combination of hyaluronic acid and adelmidrol at the above doses. Conclusions: Our results clearly demonstrate that the combination of hyaluronic acid and adelmidrol improves the signs of OA induced by MIA

The association of aloe and β-carotene supplementation improves oxidative stress and Inflammatory state in pregnant buffalo cows

The complex polysaccharides of Aloe have been reported to improve immunity and oxidative status either in vitro or in vivo studies. Further, β-carotene has been shown to influence immune function and health in the cow. In this study, the effects of VigoorsanTM, a commercial supplement containing Aloe arborescence and β-carotene, on biochemical profile and oxidative/inflammatory status, were evaluatedin pregnant buffalo cows. VigoorsanTM was supplied (50 g/day/head) to pluriparae buffalo cows for 30 days before delivery. A significant increase of BAP and OXY and a decrease of d-ROMs (P<0.01) were detected in blood from cows supplemented with VigoorsanTM. Further, a decrease of TNF-α, IL1-βand MCP-1 and an increase of IL-10 were showed (P<0.01). Blood chemistry profiles showed no adverse effects on health status. Results showed that VigoorsanTM supplementation improves oxidative and inflammatory status with no negative effects on metabolism in water buffalo cow

Milk from cows fed a diet with a high forage:concentrate ratio improves inflammatory state, oxidative stress, and mitochondrial function in rats.

Excessive energy intake may evoke complex biochemical processes characterized by inflammation, oxidative stress, and impairment of mitochondrial function that represent the main factors underlying noncommunicable diseases. Because cow milk is widely used for human nutrition and in food industry processing, the nutritional quality of milk is of special interest with respect to human health. In our study, we analyzed milk produced by dairy cows fed a diet characterized by a high forage:concentrate ratio (high forage milk, HFM). In view of the low n-6:n-3 ratio and high content of conjugated linoleic acid of HFM, we studied the effects of this milk on lipid metabolism, inflammation, mitochondrial function, and oxidative stress in a rat model. To this end, we supplemented for 4 wk the diet of male Wistar rats with HFM and with an isocaloric amount (82 kJ, 22 mL/d) of milk obtained from cows fed a diet with low forage:concentrate ratio, and analyzed the metabolic parameters of the animals. Our results indicate that HFM may positively affect lipid metabolism, leptin:adiponectin ratio, inflammation, mitochondrial function, and oxidative stress, providing the first evidence of the beneficial effects of HFM on rat metabolism

Identification of patients at risk for early death after conventional chemotherapy in solid tumours and lymphomas

1–5% of cancer patients treated with cytotoxic chemotherapy die within a month after the administration of chemotherapy. Risk factors for these early deaths (ED) are not well known. The purpose of this study was to establish a risk model for ED after chemotherapy applicable to all tumour types. The model was delineated in a series of 1051 cancer patients receiving a first course of chemotherapy in the Department of Medicine of the Centre Léon Bérard (CLB) in 1996 (CLB-1996 cohort), and then validated in a series of patients treated in the same department in 1997 (CLB-1997), in a prospective cohort of patients with aggressive non-Hodgkin's lymphoma (NHL) (CLB-NHL), and in a prospective cohort of patients with metastatic breast cancer (MBC series) receiving first-line chemotherapy. In the CLB-1996 series, 43 patients (4.1%) experienced early. In univariate analysis, age > 60, PS > 1, lymphocyte (ly) count ≤ 700 μl−1 immediately prior to chemotherapy (d1), d1-platelet count ≤ 150 Gl−1, and the type of chemotherapy were significantly correlated to the risk of early death (P ≤ 0.01). Using logistic regression, PS > 1 (hazard ratio 3.9 (95% Cl 2.0–7.5)) and d1-ly count ≤ 700 μl−1 (3.1 (95% Cl 1.6–5.8)) were identified as independent risk factors for ED. The calculated probability of ED was 20% (95% Cl 10–31) in patients with both risk factors, 6% (95% Cl 4–9) for patients with only 1 risk factor, and 1.7% (95% Cl 0.9–3) for patients with none of these 2 risk factors. In the CLB-97, CLB-NHL and MBC validation series, the observed incidences of early death in patients with both risk factors were 19%, 25% and 40% respectively and did not differ significantly from those calculated in the model. In conclusion, poor performance status and lymphopenia identify a subgroup of patients at high risk for early death after chemotherapy. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Factors Affecting Sentinel Node Metastasis in Thin (T1) Cutaneous Melanomas: Development and External Validation of a Predictive Nomogram

PURPOSE Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB. PATIENTS AND METHODS The development cohort comprised 3,666 patients with T1 disease consecutively treated at the Istituto Nazionale Tumori (Milan, Italy) between 2001 and 2018; 4,227 patients with T1 disease treated at 13 other European centers over the same period formed the validation cohort. A random forest procedure was applied to the development data set to select characteristics associated with SN status for inclusion in a multiple binary logistic model from which a nomogram was elaborated. Decision curve analyses assessed the clinical utility of the nomogram. RESULTS Of patients in the development cohort, 1,635 underwent SNB; 108 patients (6.6%) were SN positive. By univariable analysis, age, growth phase, Breslow thickness, ulceration, mitotic rate, regression, and lymphovascular invasion were significantly associated with SN status. The random forest procedure selected 6 variables (not growth phase) for inclusion in the logistic model and nomogram. The nomogram proved well calibrated and had good discriminative ability in both cohorts. Decision curve analyses revealed the superior net benefit of the nomogram compared with each individual variable included in it as well as with variables suggested by current guidelines. CONCLUSION We propose the nomogram as a decision aid in all patients with T1 melanoma being considered for SNB

Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice

Introduction N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, anti-inflammatory and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). Methods CIA was induced by an intradermally injection of 100 \u3bcl of the emulsion (containing 100 \u3bcg of bovine type II collagen (CII)) and complete Freund\u2019s adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered with PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or with coultramicronized PEA + luteolin (1mg/kg, i.p.) every 24 hours, starting from day 25 to 35. Results Mice developed erosive hind paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as peri-articular erythema and edema in the hind paws. The incidence of CIA was 100% by day 28 in the CII challenged mice and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histological status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin treated mice as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the pro-inflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment. Conclusions We demonstrated PEA co-ultramicronized with luteolin exerts an anti-inflammatory effect during chronic inflammation and ameliorates CI

Impact of heart magnetic resonance imaging on chelation choices, compliance with treatment and risk of heart disease in patients with thalassaemia major

This study aimed to verify the impact of heart magnetic resonance imaging on chelation choices and patient compliance in a single-institution cohort as well as its predictive value for heart failure and arrhythmias. Abnormal cardiac T2* values determined changes in treatment in most subjects. Heart T2* was confirmed to be highly predictive over 1 year for heart failure and arrhythmias. The choice of chelation regimens known to remove heart iron efficiently was not sufficient by itself to influence the risk. Compliance with treatment had a more remarkable role