Notes

Study Take note: Evaluation of quinine as a chemoprophylactic applicant towards histomoniasis in turkeys.
BACKGROUND Management of osteoporosis given reduced renal function is one of the largest challenges in the bone clinic. OBJECTIVES Identify the cut-off for renal function below which there would be no overall BMD benefit associated with bisphosphonate use. Track safety outcomes resulting in hospital encounters. METHODS Population-based, observational register-linked study of BMD trajectories in adults from the island of Funen (pop 465,000) as a function of estimated creatinine clearance (CKD-epi), treatment and adherence to oBP. One laboratory performed all the biochemical analyses for the area while all DXA scans were in a central facility. For inclusion, patients were required to have both a DXA scan and an eGFR measurement (CKD-EPI) within 1 year prior to their study index date. Medication Possession Ratio (MPR) was calculated from national data. RESULTS Out of 6176 incident BP users, 1789 had eGFR and DXA measurements at appropriate timepoints for the planned analysis, while this was the case for 3908 of patients with poor renal function - between CKD stage and adherence driven BMD change. There were no cases of acute renal injury resulting in hospital encounters. More data is needed on the efficacy and safety of bisphosphonates in CKD stage 3B to 5 and prescribers should reconsider the low use of DXA in patients with renal function impairment now that a wider range of treatment options are available. Harman, a natural β-carboline alkaloid, has recently gained considerable interest due to its anticancer properties. However, its physicochemical characteristics and poor oral bioavailability have been limiting factors for its pharmaceutical development. In this paper, we described the complexation of harman (HAR) with β-cyclodextrin (βCD) as a promising alternative to improve its solubility and consequently its cytotoxic effect in chemoresistant melanoma cells (A2058 cell line). Inclusion complexes (βCD-HAR) were prepared using a simple method and then characterized by FTIR, NMR and SEM techniques. Through in silico studies, the mechanism of complexation of HAR with βCD was elucidated in detail. Both HAR and βCD-HAR promoted cytotoxicity, apoptosis, cell cycle arrest and inhibition of cell migration in melanoma cells. Interestingly, complexation of HAR with βCD enhanced its pro-apoptotic effect by increasing of caspase-3 activity (p less then 0.05), probably due to an improvement in HAR solubility. In addition, HAR and βCD-HAR sensitized A2058 cells to vemurafenib, dacarbazine and 5FU treatments, potentializing their cytotoxic activity. These findings suggest that complexation of HAR with natural polymers such as βCD can be useful to improve its bioavailability and antimelanoma activity. Intra-articular (IA) drug delivery to treat osteoarthritis (OA) is limited by the short retention time of drugs in the joints due to poor specific targeting and non-responsiveness under acidic environment. A cartilage-targeting peptide was engineered to the surface of ferritin nanocages (CT-Fn) and loaded with an anti-inflammatory drug, metformin (Met), via the self-assembling nature of Fn nanocages. It demonstrated that the CT-Fn/Met could specifically bind to type II collagen, leading to the downregulation of catabolic markers of OA and promotion of cartilage-specific makers in IL-1β-induced chondrocytes. IA delivery of CT-Fn/Met prolonged the retention time for 3weeks and remarkably reduced inflammation. Moreover, better release under acidic conditions which enabling longer retention time of Met after IA delivery in OA joints for 1 more weeks. CT-Fn/Met could target and efficiently enter chondrocytes, further inducing prolonged IA accumulation and achieving enhanced therapeutic efficacy for OA treatment. Failure of intraoperative detection, early minimal lesion and microscopic residual tumor margins elimination causes metastatic diffusion and lethal recurrence. However, during surgical process, surgeons can only rely largely on palpation and visual examination. Intraoperative bioimaging with the aid of the second near-infrared fluorescent (NIR II FL) light has entered the surgical excision area to bridge the gap of preoperative bioimaging and intraoperative resection. Here, we demonstrate that the follicle-stimulating hormone peptide (FSHP) engineered NIR II downshifting nanoparticles (DSNPs@FSHP) selectively undergo efficient ovarian tumor targeting property. Owing to the special biocompatibility of nanoprobes, this strategy provided rapid body clearance and efficient tumor targeting with significantly tumor to background (T/B) ratio enhanced for surgical excision. Based on these, this strategy can successfully empowered the detection and surgical removal for both ovarian tumor lesions and ovarian tumor margins by NIR II FL bioimaging. Endovascular thrombectomy (EVT) has been recommended as the first line therapy for large artery occlusion (LAO) stroke. However, abrupt recovery of blood flow induces oxidative stress which breaks down the blood-brain-barrier (BBB), activate apoptosis and inhibit neurogenesis. Supplement of exogenous antioxidants to relieve the injuries related to oxidative stress is a rational treatment combined to EVT for acute LAO therapy. Resveratrol (RES), an antioxidant, was encapsulated into polymeric nanoparticles (RES-NPs). read more In transient middle cerebral artery occlusion (tMCAO) rats, intraarterial administration of RES-NPs demonstrated significant protection against cerebral ischemia/reperfusion (I/R) injuries. RES-NPs attenuated the oxidative stress induced by I/R, prevented brain edema, protected neurons from undergoing apoptosis, and contributed to neurogenesis through enhanced expression of brain-derived neurotrophic factor (BDNF). These results suggested that intra-arterial infusion of RES-NPs in conjunction with EVT could be a potential strategy for the LAO stroke therapy. Percutaneous absorption of drugs can be enhanced by ethosomes, which are nanocarriers with excellent deformability and drug-loading properties. link2 However, the ethanol within ethosomes increases phospholipid membrane fluidity and permeability, leading to drug leakage during storage. Here, we developed and characterized a new phospholipid nanovesicles that is co-hybridized with hyaluronic acid (HA), ethanol and the encapsulated volatile oil medicines (eugenol and cinnamaldehyde [EUG/CAH]) for transdermal administration. In comparison with EUG/CAH-loaded ethosomes (ES), the formulation stability and percutaneous drug absorption of EUG/CAH-loaded HA-immobilized ethosomes (HA-ES) were significantly improved. After transdermal administration of HA-ES, the interstitial cells of Cajal in the colon of rats with trinitrobenzene sulfonate-induced ulcerative colitis (UC) were significantly increased, and the stem cell factor/c-kit signaling pathway was partly repaired. Overall, HA-ES possesses excellent deformability and showed improved efficacy against UC compared with ES, which is demonstrated as a promising transdermal delivery vehicle for volatile oil medicines. Carboplatin, administered as a single drug or in combination with paclitaxel, is the standard chemotherapy treatment for patients with ovarian cancer (OVCA). Recent evidence suggests that miRNAs associated with small extracellular vesicles (sEVs) participate in the development of chemoresistance. We studied the effect of carboplatin in a heterogeneity population of OVCA cells and their derived sEVs to identify mechanisms associated with chemoresistance. sEVs were quantified using an engineered superparamagnetic material, gold-loaded ferric oxide nanotubes and a screen-printed electrode. miR-21-3p, miR-21-5p, and miR-891-5p are enriched in sEVs, and they contribute to carboplatin resistance in OVCA. Using a quantitative MS/MS, miR-21-5p activates glycolysis and increases the expression of ATP-binding cassette family and a detoxification enzyme. miR-21-3p and miR-891-5p increase the expression of proteins involved in DNA repair mechanisms. Interestingly, the levels of miR-891-5p within sEVs is significantly higher in patients at risk of ovarian cancer relapse. Identification of miRNAs in sEVs also provides the opportunity to track them in biological fluids to potentially determine patient response to chemotherapy. Quality-by-design (QbD) approach has been applied to optimize lipid-based nanosystems formulations, including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions, besides being increasingly requested by regulatory authorities. Different mathematical models and statistical tests have been used, with similar conclusions regarding the parameters that influence the physical features of the resulting nanosystems. These include, variations in composition (e.g. lipid(s) and/or emulsifier(s)) and manufacturing parameters (e.g. emulsification rate and/or time, sonication amplitude and/or time, and homogenization pressure and/or cycles). These are critical parameters that influence nanoparticle/globule mean size, polydispersity index, zeta potential, drug encapsulation efficiency and in vitro drug release. This review addresses the concepts and applications of QbD for the development of lipid-based nanosystems, reporting successful examples published in the last 2years. Although, some limitations have been identified, it is expected that in the upcoming years the application of QbD in pharmaceutical development will be an established approach. Background; The parasite Toxoplasma gondii (Tg) can cause congenital toxoplasmosis following primary infection in a pregnant woman. It is therefore important to distinguish between recent and past infection when both Tg-specific IgM and IgG are detected in a single serum in pregnant women. Tg-specific IgG avidity testing is an essential tool to help to date the infection. However, interpretation of its results can be complex. OBJECTIVES To review Tg-specific avidity testing benefits and limitations in pregnant women, in order to help practitioners to interpret the results and adapt the patient management. SOURCES PubMed search with the keywords avidity, toxoplasmosis and Toxoplasma gondii for articles published from 1989 to 2019. CONTENT Tg-specific IgG avidity testing remains a key tool for dating a Tg infection in immunocompetent pregnant women. Several commercial assays are available and display comparable performances. A high avidity result obtained on a first-trimester serum sample is indicative of a past infection, which occurred before pregnancy. link3 To date, a low avidity result must still be considered as non-informative to date the infection, although some authors suggested that very low avidity results are highly suggestive of recent infections depending on the assay. Interpretation of low or grey zone avidity results on a first-trimester serum sample, as well as any avidity result on a second or third-trimester serum sample, is more complex and requires recourse to expert toxoplasmosis laboratories. IMPLICATIONS Although used for about 30 years, Tg-specific avidity testing has scarcely evolved. The same difficulties in interpretation have persisted over the years. Some authors proposed additional thresholds to exclude an infection of less than 9 months, or in contrast to confirm a recent infection. Such thresholds would be of great interest to adapt management of pregnant women and avoid unnecessary treatment however, they need confirmation and further studies.
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