25(OH) vitamin D and functional outcomes in older adults admitted to rehabilitation units: the safari study.

Vitamin D (25(OH)D) deficiency is associated with poor physical performance; little is known about its impact on geriatric rehabilitation. We found a positive non-linear relationship between 25(OH)D and functional gain, stronger in levels < 16 ng/ml (below the cutoff for "deficiency"). An early 25(OH)D dosage may be advisable for this population. INTRODUCTION: Vitamin D (25(OH)D) deficiency is highly prevalent in older people, and it is associated with poor muscular strength and physical performance. Its impact on functional outcomes during geriatric rehabilitation has been poorly studied. We aim to analyze the association between 25(OH)D and functional recovery in geriatric rehabilitation units. METHODS: We conducted a prospective multi-center cohort study including patients ≥ 65 years old admitted to 3 geriatric rehabilitation units in Italy and Spain, after orthopedic events or stroke. Outcomes were absolute functional gain (AFG, discharge-admission Barthel index) and ability to walk (AW) at 3 months after admission. The association between 25(OH)D quartiles (Q1-Q2-Q3-Q4) and outcomes was explored using linear or logistic regression models. RESULTS: We included 420 patients (mean age = 81.2 years [SD = 7.7], 66.4% females, mean 25(OH)D concentration = 13.5 ng/ml [SD = 8.7]) (to convert to nmol/l multiply by 2.496). A non-linear relationship between 25(OH)D and AFG was found, with a stronger association for 25(OH)D levels < 16 ng/ml. Compared to Q1 (25(OH)D ≤ 6 ng/ml), participants in Q3 (25(OH)D 11.5-18.2 ng/ml) had the best AFG and AW (mean AFG [SD], Q1 = 28.9 [27.8], Q2 = 32.5 [23.5], Q3 = 43.1 [21.9], Q4 = 34.5 [29.3], R2 = 7.3%; AW, Q1-Q2 = 80%, Q3 = 91%, Q4 = 86%). Regression models adjusted for potential confounders confirmed these results (AGF Q2, ß = 2.614, p = 0.49; Q3, ß = 9.723, p < 0.01; Q4, ß = 4.406, p = 0.22; AW Q2, OR [95% CI] = 1.84 [0.67-5.33]; Q3, OR [95% CI] = 4.01 [1.35-13.48]; Q4, OR [95% CI] = 2.18 [0.81-6.21]). CONCLUSIONS: In our study, 25(OH)D concentration showed a positive association with functional outcomes at 3 months. The association is stronger below the usual cutoff for "deficiency." Dosage of 25(OH)D concentration may help identify geriatric rehabilitation patients at risk for a worse functional recovery.

Effectiveness of an Ayurveda treatment approach in knee osteoarthritis - a randomized controlled trial.

OBJECTIVE: Ayurveda is commonly used in South Asia to treat knee osteoarthritis (OA). We aimed to evaluate the effectiveness of Ayurvedic treatment compared to conventional conservative care in patients with knee OA. METHOD: According to American College of Rheumatology (ACR) criteria knee OA patients were included in a multicenter randomized, controlled, open-label trial and treated in 2 hospital clinics and 2 private outpatient clinics in Germany. Participants received either a multi-modal Ayurvedic treatment or multi-modal conventional care with 15 treatments over 12 weeks respectively. Primary outcome was the change on the Western Ontario and McMaster University Osteoarthritis (WOMAC) Index after 12 weeks. Secondary outcomes included WOMAC subscales; the pain disability index and a pain experience scale, numeric rating scales for pain and sleep quality, quality-of-life and mood, rescue medication use, and safety issues. RESULTS: One hundred fifty-one participants (Ayurveda n = 77, conventional care n = 74) were included. Changes of the WOMAC Index from baseline to 12 weeks were more pronounced in the Ayurveda group (mean difference 61.0 [95%CI: 52.4;69.6]) than in the conventional group (32.0 [95%CI: 21.4;42.6]) resulting in a significant between-group difference (p < 0.001) and a clinically relevant effect size (Cohen's d 0.68 [95% CI:0.35;1.01]). Similar trends were observed for all secondary outcomes at week 12. Effects were sustained at follow-ups after 6 and 12 months. CONCLUSION: Results suggest that Ayurvedic treatment is beneficial in reducing knee OA symptoms. Further studies should be conducted to confirm the magnitude of the effect and to clarify the role of different treatment components and non-specific effects. REGISTRATION: at clinicaltrials.gov (NCT01225133; initial release 10/06/2010).

Green tea polyphenol extract in vivo attenuates inflammatory features of neutrophils from obese rats.

PURPOSE: Our study aimed to evaluate whether obesity induced by cafeteria diet changes the neutrophil effector/inflammatory function and whether treatment with green tea extract (GT) can improve neutrophil function. METHODS: Male Wistar rats were treated with GT by gavage (12 weeks/5 days/week; 500 mg/kg of body weight), and obesity was induced by cafeteria diet (8 weeks). Neutrophils were obtained from the peritoneal cavity (injection of oyster glycogen). The following analyses were performed: phagocytic capacity, chemotaxis, myeloperoxidase activity (MPO), hypochlorous acid (HOCl), superoxide anion (O 2 (·-) ), hydrogen peroxide (H2O2), IL-1ß, IL-6 and TNFα, mRNA levels of inflammatory genes, calcium mobilisation, activities of antioxidant enzymes, hexokinase and G6PDH. RESULTS: Neutrophils from obese rats showed a significant decrease in migration capacity, H2O2 and HOCl production, MPO activity and O 2 (·-) production. Phagocytosis and CD11b mRNA levels were increased, while inflammatory cytokines release remained unmodified. mRNA levels of TLR4 and IκK were enhanced. Treatment of obese rats with GT increased neutrophil migration, MPO activity, H2O2, HOCl and O 2 (·-) production, whereas TNF-α and IL-6 were decreased (versus obese). Similar reductions in TLR4, IκK and CD11b mRNA were observed. Catalase and hexokinase were increased by obesity, while SOD and G6PDH were decreased. Treatment with GT reduced catalase and increased the GSH/GSSG ratio. CONCLUSION: In response to a cafeteria diet, we found a decreased chemotaxis, H2O2 release, MPO activity and HOCl production. We also showed a significant immunomodulatory effect of GT on the obese condition recovering some of these factors such H2O2 and HOCl production, also reducing the levels of inflammatory cytokines.

Green tea catechins alone or in combination alter functional parameters of human neutrophils via suppressing the activation of TLR-4/NFκB p65 signal pathway.

The purpose of this study was to evaluate the potential of a mixture containing the four main catechins found in green tea, as well it separately, as modulators of the functional parameters of human neutrophils. The cells were obtained from peripheral blood of healthy individuals isolated and cultured with a mix: 30 µM of EGCG, 3 µM of EGC, 2 µM of ECG and 1.4 µM of EC, as well as each one alone. We evaluated the cytotoxicity of catechins, production of several reactive oxygen species (ROS), antioxidant enzymes (SOD, CAT, GPx and GR), Nrf2, TLR4/IKK/NFκB, CD11b mRNA levels, intracellular calcium release, chemotactic and phagocytic capacity, myeloperoxidase (MPO), and G6PDH activities, hypochlorous acid (HOCl) and pro-inflammatory cytokines release, protein levels of TLR4, p38 MAPK, iNOS and p-65 NFκB. The actions of the catechins were evidenced by the reduction in inflammatory parameters, including the suppression of TLR4, NFκB and iNOS protein expression, decreased release of TNF-α, IL-1ß and IL-6, migration capacity, MPO activity and HOCl production and the suppression of ROS, nitric oxide and peroxynitrite production, while inducing antioxidant enzyme activities and Nrf2 mRNA levels, phagocytic capacity and calcium release. Our results demonstrate that catechins present marked immunomodulatory actions, either alone or in combination.

Fucoxanthin in association with vitamin C acts as modulators of human neutrophil function.

INTRODUCTION: Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing and digesting bacteria and fungi. During this process, neutrophils produce reactive oxygen species (ROS), which in excess, can damage the cells themselves and surrounding tissues. The carotenoid fucoxanthin (Fc) has been studied concerning its antioxidant and anti-inflammatory actions. Vitamin c (Vc) also demonstrates potent antioxidant action. This study aimed to evaluate the effect of Fc (2 µM) in association with Vc (100 µM) on functional parameters of human neutrophils in vitro. MATERIALS AND METHODS: We evaluated the migration and phagocytic capacity, intracellular calcium mobilization, ROS production (O2(·)⁻, H2O2, HOCl), myeloperoxidase activity, profile of antioxidant enzymes, phosphorylation of p38 MAPK and p65 NFκB subunit, GSH/GSSG ratio and release of pro-inflammatory cytokines (TNF-α and IL-6) in neutrophils under different stimuli. RESULTS: We verified an increase in phagocytic capacity for all treatments, together with an increase in intracellular calcium only in cells treated with Fc and Fc + Vc. ROS production was reduced by all treatments, although Vc was a better antioxidant than Fc. Phosphorylation of the p-65 subunit of NFκB was reduced in cells treated with Fc + Vc and release of TNF-α and IL-6 was reduced by all treatments. These findings indicate that the regulation of inflammatory cytokines by neutrophils is not exclusively under the control of the NFκB pathway. Fc reduced the activity of some antioxidant enzymes, whereas Vc increased GR activity and the GSH/GSSG ratio. CONCLUSION: In conclusion, the results presented in this study clearly show an immunomodulatory effect of the carotenoid fc alone or in combination with Vc on the function of human neutrophils.

Targeting the receptor tyrosine kinase RET sensitizes breast cancer cells to tamoxifen treatment and reveals a role for RET in endocrine resistance.

Endocrine therapy is the main therapeutic option for patients with estrogen receptor (ERalpha)-positive breast cancer. Resistance to this treatment is often associated with estrogen-independent activation of ERalpha. In this study, we show that in ERalpha-positive breast cancer cells, activation of the receptor tyrosine kinase RET (REarranged during Transfection) by its ligand GDNF results in increased ERalpha phosphorylation on Ser118 and Ser167 and estrogen-independent activation of ERalpha transcriptional activity. Further, we identify mTOR as a key component in this downstream signaling pathway. In tamoxifen response experiments, RET downregulation resulted in 6.2-fold increase in sensitivity of MCF7 cells to antiproliferative effects of tamoxifen, whereas GDNF stimulation had a protective effect against the drug. In tamoxifen-resistant (TAM(R)-1) MCF7 cells, targeting RET restored tamoxifen sensitivity. Finally, examination of two independent tissue microarrays of primary human breast cancers revealed that expression of RET protein was significantly associated with ERalpha-positive tumors and that in primary tumors from patients who subsequently developed invasive recurrence after adjuvant tamoxifen treatment, there was a twofold increase in the number of RET-positive tumors. Together these findings identify RET as a potentially important therapeutic target in ERalpha-positive breast cancers and in particular in tamoxifen-resistant tumors.

Anti-inflammatory action of AGF44, a ganglioside ester derivative.

Gangliosides (GA) have been shown to promote axonal sprouting and growth of injured peripheral nerves, and enhance functional biochemical and morphologic recovery after CNS damage. Moreover, it has recently been shown that the natural ganglioside mixture (GM1 + GD1a + GD1b + GT1b) from bovine brain is endowed with powerful anti-inflammatory activity in rodents. Here we report that the novel semisynthetic ganglioside derivative AGF44, the isopropyl ester of monosialoganglioside GM1, displays a potent anti-inflammatory activity when orally or topically administered in various models of acute inflammation. AGF44 was effective (0.5-5 mg/kg p.o. or 0.5% gel topical application) in reducing rat paw oedema induced by either carrageenin, histamine, bradykinin, serotonin, nystatin or kaolin. Moreover, crossed confrontation with the effects elicited by other anti-inflammatory agents revealed that AGE44 seems to act through a different pathway than NSAIDs, steroids or antihistaminic/antiserotoninic agents.

[Autologous blood transfusion in elective heart surgery: prospective study of 189 consecutive patients]. / L'autoemotrasfusione in cardiochirurgia elettiva: studio prospettico in 189 pazienti consecutivi.

Blood autotransfusion has entered a new phase in blood transfusion technique, since it represents an important alternative in eliminating the risks connected with blood transfusion: viral hepatitis, AIDS, blood transfusion reactions, and alloimmunization. Transfusion requirements during cardiac surgical procedures have steadily decreased; nowadays most adult patients require no transfusion during surgery. Patients (pts) receiving bank-blood may develop infectious diseases (hepatitis, AIDS, etc.). We have studied how to avoid the risk of infections with homologous blood transfusions. We present our experience of day-hospital pre-operative autologous blood collection. One-hundred-eighty-nine patients undergoing primary myocardial revascularization or valvular replacement were submitted to the drainage of 350 ml of blood three times every four days before surgery. The blood was centrifuged at once, to separate red cells from plasma. Surgeries were performed 21 days after the first drainage; iron therapy was recommended. After surgery pts received blood only if haematocrit was lower than 28%. The following data were recorded: no. of pts who received homologous blood; blood loss and homologous total blood volume used for each pt. Average blood loss was 1230 cc for ischemic pts and 701 cc for valvular pts. Non-A non B hepatitis occurred in 3/189 pts (1.5%). All of them had received homologous blood transfusions. Our data show clearly that autotransfused pts had a better post-operative period; less bank-blood and fewer transfusions have been used. No pt had collateral effects such as angina or hypotension from blood drawing. Our data show that severe cardiac diseases do not represent an absolute contraindication to heavy blood drainage.(ABSTRACT TRUNCATED AT 250 WORDS)