Application of disaccharides alone and in combination,for the improvement of stability and particle properties of spray-freeze dried IgG

Purpose: Spray-freeze drying (SFD) is a recently applied method to develop pharmaceutical powders. This study aimed to analyze the competence of Trehalose, Mannitol, Lactose, and Sorbitol instability and aerosolization of Immunoglobulin G (IgG) via SFD.

Methods: Induced soluble aggregates were quantified at 0 and 3?months, and 45?°C using size-exclusion chromatography. Conformation and thermogravimetric assessments were done by Fourier transform infrared spectroscopy and differential scanning calorimetry. Laser light scattering was performed to determine the particle sizes. Aerodynamic features were characterized by twin stage impinger and scanning electron microscopy.

Results: Although sugars/polyols preferably stabilized IgG following the process, storage stabilization was achieved in Trehalose, Trehalose-Lactose, Lactose, and Trehalose-Mannitol-based powders with soluble aggregates <5%. The conformation of antibody was preserved with β sheet content from 66.28% to 76.37%. Particle sizes ranged from 5.23 to 8.12?µm. Mannitol exhibited the best aerodynamic behavior, fine particle fraction (FPF: 70%) but high degree of protein aggregation during storage.

Conclusions: SFD could favorably stabilize antibody using Trehalose and its combination with Lactose and Mannitol, and also, Lactose alone. Sorbitol disturbed IgG powder recovery. Incorporation of other types of excipient is required for efficient respiratory delivery of IgG molecules.     

A case of group A streptococcal meningitis following acute otitis media.

Group A streptococcal meningitis is less common than other forms of meningitis; however, the occurrence of this infection is associated with high mortality and morbidity. Early recognition and a prompt treatment are therefore essential. We review one case of an Asian women admitted with group A streptococcal meningitis as a complication of otitis media.     

To screen or not to screen? The development of a prediction model for aorto-iliac stenosis in kidney transplant candidates

Screening for aorto-iliac stenosis is important in kidney transplant candidates as its presence affects pre-transplantation decisions regarding side of implantation and the need for an additional vascular procedure. Reliable imaging techniques to identify this condition require contrast fluid, which can be harmful in these patients. To guide patient selection for these imaging techniques, we aimed to develop a prediction model for the presence of aorto-iliac stenosis. Patients with contrast-enhanced imaging available in the pre-transplant screening between January 1st, 2000 and December 31st, 2018 were included. A prediction model was developed using multivariable logistic regression analysis and internally validated using bootstrap resampling. Model performance was assessed with the concordance index and calibration slope. Three hundred and seventy-three patients were included, 90 patients (24.1%) had imaging-proven aorto-iliac stenosis. Our final model included age, smoking, peripheral arterial disease, coronary artery disease, a previous transplant, intermittent claudication and the presence of a femoral artery murmur. The model yielded excellent discrimination (optimism-corrected concordance index: 0.83) and calibration (optimism-corrected calibration slope: 0.91). In conclusion, this prediction model can guide the development of standardized protocols to decide which patients should receive vascular screening to identify aorto-iliac stenosis. External validation is needed before this model can be implemented in patient care.     

Developmental toxicity of deltamethrin and 3-phenoxybenzoic acid in embryo–larval stages of zebrafish (Danio rerio)

Synthetic pyrethroids are the major insecticides used widely in agriculture and household pest control. Deltamethrin (DM), a widely used type II pyrethroid insecticide, is a relatively potent neurotoxicant. 3-Phenoxybenzoic acid (PBA) is the major metabolite formed due to metabolism of DM. In order to illustrate the toxic response of zebrafish embryos/larvae to DM and PBA the present research was carried out. For this 4hpf embryos were treated with two concentrations of DM (100 and 200?μg/L) for 48?h and PBA (1000 and 2000?μg/L) for 96?h or 99.9% ethanol (solvent control). Early life stage parameters were observed at specified time points. DM-treated embryo/larvae exhibited increased mortality, delay in hatching time, decrease in percentage of hatched embryos, increase of heartbeat rate and decrease in blood flow; lightening of body and eye pigmentation in a dose dependent manner. Pericardial and yolk sac edema along with were also caused by DM. Along with these crooked notochord, tail deformation was noticed in hatched and unhatched embryos. In case of PBA treated embryos and larvae, increased embryos/larvae length and yolk sac size were observed. Other abnormalities like edema (yolk sac and pericardial), decreased eye and body pigmentation were also observed but in some embryos only. These were not as severe as observed in parental compound indicating that DM is more toxic than its metabolite PBA. The data contributes to a better understanding of the potential consequences of fish exposed to DM and PBA.     

Effect of microfluidization parameters on the physical properties of PEG-PLGA nanoparticles prepared using high pressure microfluidization

The objective of this work was to develop uniformly distributed poly(ethylene glycol) grafted poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles of mean size range ～100–200 nm using ethyl acetate as the solvent. In the multiple emulsion solvent evaporation method a high pressure microfluidization process was adopted to produce the W/O/W multiple emulsion. Non-toxic ethyl acetate was used to solubilize PEG-PLGA. The mean size of nanoparticles obtained was less than 180 nm. The particle size and size distribution were dependent on the microfluidization conditions applied. Mean particle size steadily increased from 121 nm at three passes to 172 nm at 20 passes of the microfluidizer, indicating that over-processing may be detrimental to PEG-PLGA nanoparticles prepared using this technique. There was no significant alteration of the PEG-PLGA matrix, as evidenced from the differential scanning calorimetric studies.     

Clinical aspects of infertile 47,XYY patients: a retrospective study

47,XYY syndrome is a sex chromosomal anomaly in men, which may be associated with infertility and has an incidence of 0.1% of male births. The clinical and paraclinical characteristics of men suffering from this anomaly have not been fully described. In this retrospective study, we present 37 cases of 47,XYY infertile men with sperm counts varying from normal to azoospermia, referred to the Genetics Laboratory at the Royan Institute, Iran. Thirteen individuals were mosaic and 24 non-mosaics. Non-mosaic patients were classified as azoospermic (nine cases) and normospermic/oligozoospermic men (15 cases). Two of the non-mosaic and three mosaic patients had secondary infertility. In addition, 13 of them underwent IUI, IVF or ICSI, and in seven cases, there was a biochemical pregnancy. The remaining 14 patients did not have ART. The 47,XYY syndrome is relatively unusual and can be missed clinically because of the lack of symptoms and of diverse phenotypes. Diagnosis of this aneuploidy can provide valuable data for counselling and early management of the patients who undergo fertility evaluation.     

Circulating Irisin Levels and Redox Status Markers in Patients with Gastric Cancer: A Case-Control Study

Objective: Irisin, mostly known as an exercise-induced fat browning myokine, has been recently detected in several cancer cells, and its potential for being utilized as a biomarker for early diagnosis of some cancers, such as Gastric cancer (GC), is the subject of speculation. The present study aims to compare serum irisin levels in GC patients and healthy controls and assess the interrelation between irisin and oxidative stress markers. Methods: In this case-control study, 22 newly diagnosed GC patients and 29 healthy controls were recruited based on the inclusion criteria. Serum levels of irisin were quantified in duplicates by ELISA. Oxidative stress indices, including total antioxidant power in sera, thiol group, malondialdehyde, and superoxide dismutase concentrations, were also measured in both groups. An independent-sample t-test was used to compare the means between the two studied groups. Results: Serum levels of irisin were significantly higher in the GC group compared with those of their healthy counterparts (p =0.032). No significant differences were observed between the two groups in terms of the serum total antioxidant power or the oxidative stress marker, including MDA, thiol groups, and SOD concentration in sera. Furthermore, there was no significant association between irisin, FRAP, the Thiol group, and the SOD activity. Conclusion: According to the finding, the increased serum levels of irisin in GC patients can play a potential role in the early diagnosis of the GC patients; hence, this peptide can be employed as a new diagnostic indicator of GC.     

Brain metastasis from ovarian cancer: a systematic review

This topic review discusses the evolving clinical challenges associated with the implementation of electronic personal health records (PHR) that are fully integrated with electronic medical records (EMR). The benefits of facilitating patient access to the EMR through web-based, PHR-portals may be substantial; foremost is the potential to enhance the flow of information between patient and healthcare practitioner. The benefits of improved communication and transparency of care are presumed to be a reduction in clinical errors, increased quality of care, better patient-management of disease, and better disease and symptom comprehension. Yet PHR databases allow patients open access to newly-acquired clinical data without the benefit of concurrent expert clinical interpretation, and therefore may create the potential for greater patient distress and uncertainty. With specific attention to neuro-oncology patients, this review focuses on the developing conflicts and consequences associated with the use of a PHR that parallels data acquisition of the EMR in real-time. We conclude with a discussion of recommendations for implementing fully-integrated PHR for neuro-oncology patients.