Vitamin D and aromatase inhibitor-induced musculoskeletal symptoms (AIMSS): a phase II,double-blind,placebo-controlled,randomized trial

A double-blind placebo-controlled randomized phase II trial was performed to determine whether High Dose Vitamin D2 supplementation (HDD) in women receiving adjuvant anastrozole improves aromatase inhibitor-induced musculoskeletal symptoms (AIMSS) and bone loss. Patients with early breast cancer and AIMSS were stratified according to their baseline 25-hydroxy vitamin D (25OHD) level. Stratum A (20–29 ng/ml) received either HDD 50,000 IU capsules weekly for 8 weeks then monthly for 4 months or placebo. Stratum B (10–19 ng/ml) received either HDD for 16 weeks and then monthly for 2 months, or placebo. AIMSS was assessed by the Brief Pain Inventory-Short Form (BPI-SF), the Fibromyalgia Impact Questionnaire (FIQ), and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at baseline, 2, 4, and 6 months. Bone Mineral Density (BMD) was measured at baseline and at 6 months. The primary endpoint of the study was the change-from-baseline musculoskeletal pain. The secondary endpoint was the percent change in BMD at 6 months. Sixty women were enrolled. Baseline characteristics were comparable between the groups. At 2 months, FIQ pain (P = 0.0045), BPI worst-pain (P = 0.04), BPI average-pain (P = 0.0067), BPI pain-severity (P = 0.04), and BPI interference (P = 0.034) scores were better in the HDD than placebo group. The positive effect of HDD on AIMSS was stronger across all time points in Stratum B than Stratum A (FIQ pain, P = 0.04; BPI average, P = 0.03; BPI severity, P = 0.03; BPI interference, P = 0.04). BMD at the femoral neck decreased in the placebo and did not change in the HDD group (P = 0.06). Weekly HDD improves AIMSS and may have a positive effect on bone health. Vitamin D supplementation strategies for breast cancer patients on AI should be further investigated.     

MORPHOMETRIC AND MICROSCOPIC EVALUATION OF THE EFFECT OF GALLIUM NITRATE AS A ROOT CANAL DRESSING IN RAT TEETH SUBMITTED TO LATE REPLANTATION

The purpose of this study was to test a gallium nitrate solution, a resorption inhibitor, employed as a root canal dressing in teeth submitted to late replantation. Thirty maxillary right central incisors of rats were avulsed and kept dry for thirty minutes. The teeth were instrumented and the root surfaces were treated with 1% hypochlorite solution followed by application of 2% sodium fluoride. Thereafter, the teeth were divided into two groups according to the root canal dressing: Group I, solution of gallium nitrate; and Group II, calcium hydroxide paste. The teeth were then replanted in their respective sockets. The animals were killed at 15, 30 and 60 days after replantation and the samples were processed for morphometric and microscopic analysis. The results demonstrated that the gallium nitrate solution and the calcium hydroxide paste limited the root resorption, yet they did not impair its occurrence. It may be concluded that gallium nitrate solution and calcium hydroxide paste demonstrated similar performance.     

Heritability,genetic correlation and linkage to the 9p21.3 region of mixed platelet–leukocyte conjugates in families with and without early myocardial infarction

Background and aimsVariations in mixed platelet–leukocyte conjugate formation in human whole blood could be genetically determined. We quantified platelet and leukocyte activation and interaction in families with or without early myocardial infarction and evaluated their heritability, genetic correlation and linkage to the 9p21.3 region.Methods and resultsThe study population included 739 subjects (≥15 years old) from 54 large pedigrees, 23 with and 31 without familial myocardial infarction. Mixed platelet–leukocyte conjugates and markers of platelet or leukocyte activation (P-selectin, CD11b and L-selectin surface expression) were measured both before and after in vitro blood stimulation with collagen-ADP.All traits had significant genetic components (17.5–65.3% of the phenotypic variability), while shared household effects (0–39.6%) and environmental covariates (0–10.2%) tended to be smaller. Stimulated platelet-polymorphonuclear leukocyte (PMN) and platelet–monocyte conjugates showed the highest linkage to the 9p21.3 region (LOD = 0.94 and 1.33, respectively; empirical p value = 0.017 and 0.009). PMN markers resulted strongly genetically correlated between them in bivariate analysis among pairs of quantitative traits.ConclusionThis study supports a genetic regulation of human mixed platelet–leukocyte conjugates.     

Motor unit number index (MUNIX) in children and adults with 5q-spinal muscular atrophy: Variability and clinical correlations

Spinal muscular atrophy (SMA) is a motor neuron disease associated with progressive muscle weakness and motor disability. The motor unit number index (MUNIX) is a biomarker used to assess loss of motor units in later-onset SMA patients. Twenty SMA patients (SMA types 3 and 4), aged between 7 and 41 years, were clinically evaluated through the Hammersmith Motor Functional Scale Expanded and the Spinal Muscular Atrophy-Functional Rating Scale. The patients underwent compound motor action potential (CMAP) and MUNIX studies of the right abductor pollicis brevis, abductor digiti minimi and tibialis anterior (TA) muscles. Age-matched healthy controls (n = 20) were enrolled to obtain normative CMAP and MUNIX values from the same muscles. Compared to healthy controls, SMA patients showed significant reductions in MUNIX values among all muscles studied, whereas CMAP showed reductions only in the weaker muscles (abductor digiti minimi and TA). MUNIX variability was significantly higher in the SMA group than in the control group. MUNIX variability in TA correlated with CMAP variability. Motor functional scores correlated with TA MUNIX. The MUNIX study is feasible in later-onset SMA patients, and TA MUNIX values correlate with disease severity in patients with mild motor impairment.     

Screening of plants from the Brazilian Atlantic Forest led to the identification of Athenaea velutina (Solanaceae) as a novel source of antimetastatic agents

Plant biodiversity is a source of potential natural products for the treatment of many diseases. One of the ways of discovering new drugs is through the cytotoxic screening of extract libraries. The present study evaluated 196 extracts prepared by maceration of Brazilian Atlantic Forest trees with organic solvents and distilled water for cytotoxic and antimetastatic activity. The MTT assay was used to screen the extract activity in MCF‐7, HepG2 and B16F10 cancer cells. The highest cytotoxic extract had antimetastatic activity, as determined in in vitro assays and melanoma murine model. The organic extract of the leaves of Athenaea velutina (EAv) significantly inhibited migration, adhesion, invasion and cell colony formation in B16F10 cells. The phenolic compounds and flavonoids in EAv were identified for the first time, using flow injection with electrospray negative ionization‐ion trap tandem mass spectrometry analysis (FIA‐ESI‐IT‐MSⁿ). EAv markedly suppressed the development of pulmonary melanomas following the intravenous injection of melanoma cells to C57BL/6 mice. Stereological analysis of the spleen cross‐sections showed enlargement of the red pulp area after EAv treatment, which indicated the activation of the haematopoietic system. The treatment of melanoma‐bearing mice with EAv did not result in liver damage. In conclusion, these findings suggest that A velutina is a source of natural products with potent antimetastatic activity.     

Phytic acid protects porcine intestinal epithelial cells from deoxynivalenol (DON) cytotoxicity

The purpose of this study was to evaluate the effects of phytic acid (IP₆) as a possible inhibitor of cellular damage induced by toxic substances such as mycotoxins on a porcine intestinal epithelial cell line (IPEC-1). We first observed that a dose of 5 mM phytic acid decreases cell viability and transepithelial electrical resistance (TEER) of cell monolayer. We next investigate the effect of non-cytotoxic dose of phytic acid on the deoxinivalenol (DON) induced decreased TEER. We showed that treatment with 0.5 mM or 1.0 mM phytic acid restores the decrease in TEER caused by 25 μM DON. In conclusion this study demonstrates that phytic acid decreased the negative effects of deoxynivalenol on the membrane integrity of the IPEC-1 intestinal epithelial cell line.