Dual Action of NAMI-A in inhibition of solid tumor metastasis: selective targeting of metastatic cells and binding to collagen.

NAMI-A is a ruthenium complex endowed with a selective effect on lung metastases of solid metastasizing tumors. The aim of this study is to provide evidence that NAMI-A's effect is based on the selective sensitivity of the metastasis cell, as compared with other tumor cells, and to show that lungs represent a privileged site for the antimetastatic effects. The transplantation of Lewis lung carcinoma cells, harvested from the primary tumor of mice treated with 35 mg/kg/day NAMI-A for six consecutive days, a dose active on metastases, shows no change in primary tumor take and growth but a significant reduction in formation of spontaneous lung metastases. Transmission electron microscopy examination of lungs and kidney shows NAMI-A to selectively bind collagen of the lung extracellular matrix and also type IV collagen of the basement membrane of kidney glomeruli. The half lifetime of NAMI-A elimination from the lungs is longer than for liver, kidney, and primary tumor. NAMI-A bound to collagen is active on tumor cells as shown in vitro by an invasion test, using a modified Boyden chamber and Matrigel, and it inhibits the matrix metallo-proteinases MMP-2 and MMP-9 at micromolar concentrations, as shown in vitro by a zimography test. These data show NAMI-A to significantly affect tumor cells with metastatic ability. Binding to collagen allows NAMI-A to exert its selective activity on metastatic cells during dissemination and particularly in the lungs. These data also stress the wide spectrum of daily doses and treatment schedules at which NAMI-A is active against metastases.     

Suppression of maintenance of alcohol-drinking behavior by the concurrent availability of saccharin in Sardinian alcohol-preferring (sP) rats.

In the current study, we investigated the effect of the concurrent presentation of saccharin on the maintenance of alcohol-drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats. Rats were initially given access to alcohol [10% (volume/volume) in water] and water under the home cage, two-bottle, free-choice regimen, with unlimited access for 24 h/day for eight consecutive weeks. Next, a third bottle, containing saccharin [0%, 0.01%, 0.1%, 1%, or 3% (weight/volume) in water], was concomitantly offered for an additional 10 consecutive days. Intake of saccharin solution resulted as an inverted-U function of saccharin concentration, with the 0.1% saccharin solution being the highest accepted. Alcohol intake was a U function of saccharin concentration, being reduced by 65%-95% in the group of rats exposed to the 0.1% saccharin solution. These results indicate that (1) the concurrent presentation of highly palatable solutions of saccharin markedly reduced alcohol intake in alcohol-experienced sP rats and (2) the reducing effect of saccharin solutions on the alcohol intake in sP rats was positively related to their degree of acceptability. We hypothesized that saccharin solutions may have functioned as a reinforcer, partially substituting for alcohol reinforcement and rendering alcohol drinking less urgent.     

Nutrient-based dietary patterns and prostate cancer risk: a case–control study from Italy

Purpose

The role of various foods and nutrients, and their combinations, on prostate cancer risk remains largely undefined. We addressed therefore the issue of complex dietary patterns.

Methods

We analyzed data from an Italian case–control study, including 1,294 men with prostate cancer and 1,451 hospital controls. We carried out an exploratory principal component factor analysis on 28 selected nutrients in order to identify dietary patterns. We estimated odds ratios (ORs) and corresponding confidence intervals (CIs) using logistic regression models on quintiles of factor scores, adjusting for major confounding variables.

Results

We identified five dietary patterns, labeled “Animal Products,” “Vitamins and Fiber,” “Starch-rich,” “Vegetable Unsaturated Fatty Acids (VUFA),” and “Animal Unsaturated Fatty Acids (AUFA).” We found positive associations between prostate cancer and “Animal Products” (OR for the highest vs. the lowest score quintile: 1.51, 95 % CI 1.16–1.96), “Starch-rich” (OR 1.50, 95 % CI 1.16 1.93), and “AUFA” (OR 1.32, 95 % CI 1.02–1.70) patterns. No significant associations emerged with “Vitamins and Fiber” (OR 0.93) and “VUFA” (OR 1.16) patterns.

Conclusions

Our findings suggest that a diet rich in animal products, including several types of meat and dairy products, as well as of (refined) cereals and sugars has an unfavorable role on prostate cancer.     

Customized Titanium Mesh for Guided Bone Regeneration with Autologous Bone and Xenograft

The augmentation of the alveolar crest after the loss of one or several teeth can be carried out using different bone augmentation techniques. These techniques include bone distraction, ridge expansion, bone block grafts, etc. Guided bone regeneration is an alternative to increase the volume of the hard tissues for the subsequent placement of the implants in the optimal three-dimensional position. The objective of this paper is to show a case report of the use of customized titanium mesh for posterior vertical bone regeneration. Case report and Results: A 59-year-old woman comes to rehabilitate edentulous spaces with implants. After taking the anamnesis and the intra and extraoral exploration, a vertical and horizontal bone defect is observed in the third quadrant. After the radiological study with CBCT, a bone height of 6.04 mm to the inferior alveolar nerve and a width of the bone crest of 3.95 mm was observed. It was decided to carry out a regeneration with a preformed titanium mesh (Avinent^®, Santpedor, Spain) and four microscrews (Avinent^®, Santpedor, Spain). The flap was closed without tension. Regular check-ups were performed without complications. At 7 months, the mesh was removed and two osteoingrated implants (Avinent^®, Santpedor, Spain) were placed with a torque greater than 45 N/cm and an ISQ of 82 and 57 N/cm, respectively. The bone gain obtained was 1.84 and 1.92 mm in width and 4.2 and 3.78 mm in height for positions 3.5 and 3.6. The newly formed bone, obtained by trephine, was well-structured and histologically indistinguishable from the previous bone. Conclusion: The use of a customized pre-formed titanium mesh together with the mixture of autologous bone and xenograft is a feasible and predictable technique for vertical bone regeneration.     

Hybrid Ti6Al4V/Silk Fibroin Composite for Load-Bearing Implants: A Hierarchical Multifunctional Cellular Scaffold

Despite the tremendous technological advances that metal additive manufacturing (AM) has made in the last decades, there are still some major concerns guaranteeing its massive industrial application in the biomedical field. Indeed, some main limitations arise in dealing with their biological properties, specifically in terms of osseointegration. Morphological accuracy of sub-unital elements along with the printing resolution are major constraints in the design workspace of a lattice, hindering the possibility of manufacturing structures optimized for proper osteointegration. To overcome these issues, the authors developed a new hybrid multifunctional composite scaffold consisting of an AM Ti6Al4V lattice structure and a silk fibroin/gelatin foam. The composite was realized by combining laser powder bed fusion (L-PBF) of simple cubic lattice structures with foaming techniques. A combined process of foaming and electrodeposition has been also evaluated. The multifunctional scaffolds were characterized to evaluate their pore size, morphology, and distribution as well as their adhesion and behavior at the metal–polymer interface. Pull-out tests in dry and hydrated conditions were employed for the mechanical characterization. Additionally, a cytotoxicity assessment was performed to preliminarily evaluate their potential application in the biomedical field as load-bearing next-generation medical devices.     

Effects on Serum Inflammatory Cytokines of Cholecalciferol Supplementation in Healthy Subjects with Vitamin D Deficiency

The effects of different cholecalciferol supplementation regimens on serum inflammatory cytokines in healthy subjects with vitamin D deficiency are still lacking. This is a single-center, open-label, randomized, parallel group study involving healthy subjects deficient in vitamin D (baseline 25OHD < 20 ng/mL) receiving oral cholecalciferol with three different dosing regimens: Group A: 10,000 IU/day for 8 weeks followed by 1000 IU/day for 4 weeks; Group B: 50,000 IU/week for 12 weeks and Group C: 100,000 IU every other week for 12 weeks. IL-17A, IL-6, IL-8, IL-10, IL-23 and TNFα were measured at baseline and at week 4, 8, 12, and 16. 75 healthy subjects were enrolled (58.7% female), with an average age of 34.1 ± 10.2 years. No statistical differences were observed among groups at baseline for either IL-6, IL-17A, IL-23, IL-8 or IL-10 at any time point; TNFα was indetectable. Concerning the whole sample, the time trend analysis showed a statistically significant linear trend for decreasing values over the treatment period for IL-6 (p = 0.016) and IL-17A (p = 0.006), while no significant time trends were observed for the other teste cytokines. No significant differences were found in the serum concentrations of the tested cytokines between week 12 and week 16. In young healthy individuals deficient in vitamin D, cholecalciferol administration showed a decrease in the serum IL-6 and IL-17A concentrations, without marked differences using the three regimens.     

Correlation between diminished vagal tone and somatic dysfunction severity in very and extremely low birth weight preterm infants assessed with frequency spectrum heart rate variability and salivary cortisol

Osteopathic manipulative treatment (OMT) is evolving in the neonatal intensive care unit (NICU) setting. Studies showed its efficacy in length of stay and hospitalization costs reduction. Moreover, it was suggested that OMT has a modulatory effect on the preterm infants’ autonomic nervous system (ANS), influencing saturation and heart rate. Even if OMT is based on the palpatory examination of the somatic dysfunctions (SD), there are controversies about its identification and clinical relevance. The objective of this study was to evaluate the inter-rater reliability, clinical characteristics, and functional correlation of the SD Grade score with the heart rate variability (HRV) and the salivary cortisol (sCor) using a multivariate linear model approach. To evaluate those features, we implemented an ad hoc SD examination for preterm infants that was performed by 2 trained osteopaths. It was based on the new variability model of SD that includes an SD Grade assessment procedure. The ANS features were assessed by frequency parameters of HRV studying high frequency (HF), low frequency (LF), and HF/LF, whereas sCor was tested with a radioimmunoassay. The ANS assessment was standardized and performed before SD testing. Sixty-nine premature infants were eligible. SD Grade showed excellent concordance between the blinded raters. Using SD Grade as a grouping variable, the infants presented differences in GA, Apgar, pathological findings, length of stay, and ventilatory assistance. In our multivariate model, HF, LF, and LF/HF resulted linearly correlated with SD Grade. Instead, sCor presented a linear correlation with 5’ Apgar and respiratory distress syndrome but not with SD Grade. SD Grade was in line with the natural history of the underdevelopment due to prematurity. Our models indicate that the cardiac vagal tone is linearly related with SD Grade. This finding may improve the multidisciplinary decision making inside NICU and the management of modifiable factors, like SD, for cardiac vagal tone regulation.