NMR insights on nano silver post-surgical treatment of superficial caseous lymphadenitis in small ruminants

Caseous lymphadenitis (CL), caused by a pathogen of the second class of biosafety – Corynebacterium pseudotuberculosis, is a chronic and severe infectious disease that affects small ruminants and requires long, ineffective treatment which generally leads to animal sacrifice so as to stop the disease spreading. The infected animals suffer the excision of affected superficial lymph nodes and post-surgical treatment with iodine (10% solution in ethanol) and, sometimes, prolonged antibiotic use, but only if the sick animals are of great importance to breeding. Herein, we propose a cheap and easy to apply treatment of CL with excellent results using biogenic silver nanoparticles (AgNP) based technology. AgNP antibacterial properties were investigated in vitro against Corynebacterium pseudotuberculosis cells and in vivo on small ruminants with CL. Treatment of surgical wounds resulting from the excision of superficial CL lesions with a AgNP-based cream was compared to the standard post-surgical treatment method by iodine. Also, the effects of AgNP-based cream treatment were evaluated and compared with the effects of the iodine CL treatment by serum NMR-based metabolomics. Serum samples were collected from 29 animals, 9 sheep and 20 goats, during the treatments and analyzed. All animals showed stable serum metabolomes when iodine or AgNP-based cream effects were compared. The AgNP-based cream treatment showed excellent results, especially in accelerating the healing of wounds, which occurred two to three times faster in comparison with the iodine treatment. AgNP-based cream treatment also prevented CL reappearance and did not cause any side effects on animals. This is the first report on very effective post-surgical treatment of superficial CL in small ruminants based on biogenic silver nanoparticles, which might open up the possibility for a safe veterinary application of AgNP-based cream.

Biogenic nanosilver in a pharmaceutical cream for wound healing in animal and human healthcare.     

Effect of Saccharomyces boulardii and Bacillus cereus var. toyoi on the humoral and cellular response of mice to vaccines

The effect of Saccharomyces boulardii and Bacillus cereus var. toyoi on the humoral and cellular response of mice to the simultaneous inoculation of a tetravalent E. coli bacterin and a viable vaccine against Canine Parvovirus is reported. Thirty-six isogenic BALB-c female mice, seven weeks old, were vaccinated with 1/20th of the dose used for pigs and dogs, respectively, and randomly divided into three groups. Group 1 received non-supplemented feed, group 2 was supplemented with S. boulardii, and group 3 with Bacillus cereus var. toyoi. The humoral response was quantified through ELISAs using specific antigens, and the cellular response quantifying IL-4 and IFNg through ELISA. Means of seroconversions to the bacterin were always higher in supplemented mice than in controls, varying from 1.6-1.8 for group 2 and from 1.2-1.4 for group 3. Seroconversions against Parvovirus for group 2 were 5.2-12 times higher, and those of group 3 were 6.8-9.1 times higher than those of controls. IL-4 was produced by spleen cells of S. boulardii supplemented mice stimulated with E. coli fimbriae.     

Case Report of Small Cell Carcinoma of the Ovary,Hypercalcemic Type (Ovarian Rhabdoid Tumor) with SMARCB1 Mutation: A Literature Review of a Rare and Aggressive Condition

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive condition that is associated with the SMARCA4 mutation and has a dismal prognosis. It is generally diagnosed in young women. Here, we report a case of a young woman with SCCOHT harboring a rare molecular finding with a highly aggressive biological behavior. The patient had a somatic SMARCB1 mutation instead of an expected SMARCA4 alteration. Even though the patient was treated with high-dose chemotherapy followed by stem cell transplantation, she evolved with disease progression and died 11 months after her first symptoms appeared. We present a literature review of this rare disease and discuss the findings in the present patient in comparison to expected molecular alterations and options for SCCOHT treatment.     

Human gamma interferon induction by staphylococcal protein A: effector cells, kinetics and the effect of prostaglandin, indomethacin, ibuprofen and aspirin

Soluble staphylococcal protein A (SpA) induces the synthesis of gamma-interferon (gamma-IFN) by human peripheral blood lymphocytes (PBL). To investigate the kinetics of this gamma-IFN induction and the effector cells involved, we used a highly purified SpA preparation, PBL from healthy volunteers, and a CPE-inhibition gamma-IFN assay with Sindbis virus in human fibroblasts. The production of SpA-induced gamma-IFN (SpA-gamma-IFN) peaked 48 h after the addition of SpA to cultures of PBL and decreased after 72 h. Subpopulations of PBL were purified by depletion using specific monoclonal antibodies and complement; CD4+ or OKT4+ (T4: helper/inducer) cells were able to produce SpA-gamma-IFN in the absence of CD8+ or OKT8+ (T8: suppressor/cytotoxic) or B-cells. PBL pre-incubated with SpA for more than 72 h inhibited gamma-IFN production by autologous fresh PBL; this inhibition segregated with the T8 subpopulation and was not due to cytotoxicity. SpA-gamma-IFN titers increased markedly when CD3+ or OKT3+ (T3) or T4 cells were incubated with a small number (2-10%) of adherent monocytes, whereas larger numbers (greater than 20%) decreased the yield of SpA-gamma-IFN. This decreased yield was probably mediated by prostaglandin E2 (PGE2) of monocyte origin: the presence of PGE2 was demonstrable in these cultures by radioimmunoassay, and the addition of indomethacin reversed the inhibitory effect of large numbers of monocytes; further, treatment of T-cells with exogenous PGE2 also led to an inhibition of SpA-gamma-IFN. Ibuprofen and aspirin also had an effect comparable to indomethacin on SpA-gamma-IFN production. These observations indicate that the production of SpA-gamma-IFN is by T4 lymphocytes, is enhanced by limited numbers of accessory cells (monocytes), and is also regulated by T8 cells via monocyte PGE2.     

The Burden of Iron Deficiency in Heart Failure: Therapeutic Approach

Heart failure (HF) is highlighted by its burdening symptom-limited exercise capacity and recurrent hospitalizations. Despite substantial advances regarding disease-modifying drugs in HF with reduced ejection fraction, additional therapeutic strategies to improve quality of life are invaluable. Currently, iron deficiency (ID) is overwhelmingly recognized in over 30% to 50% of patients with stable chronic HF, which worsens prognosis. The established pathophysiological mechanisms of progressive HF may be intertwined with increasing myocardial iron scarcity, wherein one begets the other. Most importantly, ID constitutes a novel target for symptom relief in carefully selected patients. In this regard, intravenous iron may be a safe and efficacious intervention, potentially reducing HF hospitalizations. We discuss the evidence and gaps in knowledge concerning iron therapy in HF and propose a practical, comprehensive, clinically oriented algorithm for timely adequate iron replenishment in different clinical scenarios. Finally, we further debate imperative decision-making before intervention and the drawbacks of such a strategy.