Amyotrophic lateral sclerosis immunoglobulins G enhance the mobility of Lysotracker-labelled vesicles in cultured rat astrocytes

Aim: We examined the effect of purified immunoglobulins G (IgG) from patients with amyotrophic lateral sclerosis (ALS) on the mobility and exocytotic release from Lysotracker‐stained vesicles in cultured rat astrocytes. Methods: Time‐lapse confocal images were acquired, and vesicle mobility was analysed before and after the application of ALS IgG. The vesicle counts were obtained to assess cargo exocytosis from stained organelles. Results: At rest, when mobility was monitored for 2 min in bath with Ca²⁺, two vesicle populations were discovered: (1) non‐mobile vesicles (6.1%) with total track length (TL) < 1 μm, averaging at 0.33 ± 0.01 μm (n = 1305) and (2) mobile vesicles (93.9%) with TL > 1 μm, averaging at 3.03 ± 0.01 μm (n = 20 200). ALS IgG (0.1 mg mL^?1) from 12 of 13 patients increased the TL of mobile vesicles by approx. 24% and maximal displacement (MD) by approx. 26% within 4 min, while the IgG from control group did not alter the vesicle mobility. The mobility enhancement by ALS IgG was reduced in extracellular solution devoid of Ca²⁺, indicating that ALS IgG vesicle mobility enhancement involves changes in Ca²⁺ homeostasis. To examine whether enhanced mobility relates to elevated Ca²⁺ activity, cells were stimulated by 1 mm ATP, a cytosolic Ca²⁺ increasing agent, in the presence (2 mm ) and in the absence of extracellular Ca²⁺. ATP stimulation triggered an increase in TL by approx. 7% and 12% and a decrease in MD by approx. 11% and 1%, within 4 min respectively. Interestingly, none of the stimuli triggered the release of vesicle cargo. Conclusion: Amyotrophic lateral sclerosis‐IgG‐enhanced vesicle mobility in astrocytes engages changes in calcium homeostasis.     

Delivery of a healthy twin after intrauterine demise and expulsion of a first twin

We report on a diamniotic-dichorionic twin pregnancy after in vitro fertilization. The first twin was diagnosed with Down syndrome and spontaneously aborted at 24 weeks of gestation after intrauterine death at week 18. The second healthy twin was delivered by cesarean section 11 weeks later. We discuss management aspects and review the literature.     

Platinum-resistant ovarian cancer: Prematurely stopped phase II Austrian AGO chemotherapy studies

AIM: To report the results of two phase II studies of chemotherapy in patients with platinum-resistant and platinum-refractory ovarian cancer and discuss the current status of systemic therapy in this disease. METHODS: Two subsequent Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) phase II studies have been carried out. Patients either had platinum-refractory or platinum-resistant disease, i.e., disease progression during first line platinum-based therapy or recurrence within 6 mo following the last platinum-containing chemotherapy, respectively. In the first study, 6 cycles of irinotecan at 55 mg/m² and docetaxel 25 mg/m² were both administered on days 1, 8 and 15 of a 4 wk cycle. In the second phase II study, either non-pegylated (PEG) liposomal doxorubicin (L-DXR) 60 mg/m² monotherapy on day 1 and PEG filgrastim on day 2 (arm A) or L-DXR at 50 mg/m² and gemcitabine (GEM) at 650 mg/m² on day 1 and GEM on day 8 (arm B) were administered every 4 wk. Patients in arm B received prophylactic filgrastim 5 μg/kg per day from days 3 to 6 and from days 9 to 12, respectively. RESULTS: Response rates in studies were 14% and 17%, respectively. The progression-free survival was less than 3 mo. Diarrhea was most prevalent in patients treated with irinotecan + docetaxel, while stomatitis/mucositis occurred in a quarter of patients treated with L-DXR +/- GEM + granulocyte colony stimulating factor, respectively. Following treatment with the latter regimen, a total of 11 serious adverse events were recorded among the 12 patients included. The rate of remissions of the regimens used in these two Austrian AGO studies was low and their toxicity significant. Due to their low therapeutic index, neither of these regimens can be recommended in this heavily pretreated patient population with platinum-resistant ovarian cancer exhibiting a high tumor-associated symptom burden. CONCLUSION: The two reported phase II studies of the Austrian AGO in platinum-resistant disease had to be terminated prematurely due to a low therapeutic index. Treatment of this disease remains a clinical dilemma. Bevacizumab seems to be active at this late-stage disease but may be associated with significant bowel toxicity.     

A Green,Simple and Facile Way to Synthesize Silver Nanoparticles Using Soluble Starch. pH Studies and Antimicrobial Applications

Along with the progress of nanoscience and nanotechnology came the means to synthesize nanometric scale materials. While changing their physical and chemical properties, they implicitly changed their application area. The aim of this paper was the synthesis of colloidal silver nanoparticles (Ag-NPs by ultrasonic disruption), using soluble starch as a reducing agent and further as a stabilizing agent for produced Ag-NPs. In this context, an important parameter for Ag-NPs preparation is the pH, which can determine the particle size and stability. The physical-chemical behavior of the synthesized Ag-NPs (shape, size, dispersion, electric charge) is strongly influenced by the pH value (experiment being conducted for pH values in the range between 8 and 13). The presence of a peak located at 412 nm into the UV-VIS spectra demonstrates the presence of silver nano-spheres into the produced material. In UV/VIS spectra, we observed a specific peak for yellow silver nano-spheres located at 412 nm. Samples characterization was performed by scanning electron microscopy, SEM, energy-dispersive X-ray spectroscopy, EDX, Fourier-transform infrared spectroscopy, and FT-IR. For all Ag-NP samples, we determined the zeta and observed that the Ag-NP particles obtained at higher pH and have better stability. Due to the intrinsic therapeutic properties and broad antimicrobial spectrum, silver nanoparticles have opened new horizons and new approaches for the control of different types of infections and wound healing abilities. In this context, the present study also aims to confirm the antimicrobial effect of prepared Ag-NPs against several bacterial strains (indicator and clinically isolated strains). In this way, it was confirmed that the antimicrobial activity of synthesized Ag-NPs was good against Staphylococcus aureus (ATCC 25923 and S. aureus MSSA) and Escherichia coli (ATTC 25922 and clinically isolated strain). Based on this observation, we conclude that the prepared Ag-NPs can represent an alternative or auxiliary material used for controlling important nosocomial pathogens. The fungal reference strain Candida albicans was more sensitive at Ag-NPs actions (zone of inhibition = 20 mm) compared with the clinically isolated strain (zone of inhibition = 10 mm), which emphasizes the greater resistance of fungal strains at antimicrobial agent’s action.     

Recent developments in the palliative treatment of breast cancer: ASCO 2013

Purpose

Highly selected abstracts from the ASCO meeting are reported.

Results and conclusions

Abstract #1040: Subgroup analysis of TURANDOT (first-line paclitaxel and bevacizumab (T + BEV) versus capecitabine and BEV) was presented; 130 patients had triple-negative disease. One-year overall survival of T + BEV-treated patients with triple-negative disease was 78 %. Thus, T + BEV may represent a preferred regimen. Abstract #514: Evidence for drug penetration of capecitabine and lapatinib was demonstrated in resected brain metastases from breast cancer. Patients scheduled for brain surgery received pre-operative therapy. Drug concentrations were detected in all lesions. Thus, capecitabine and lapatinib may penetrate the blood-brain barrier. Abstract #505: In BOLERO-3, everolimus (EVE) or placebo plus trastuzumab/vinorelbine were administered to trastuzumab-resistant, HER2-positive breast cancer after previous taxanes. In the EVE versus placebo group, median progression-free survival (PFS) was 7.0 versus 5.7 months, respectively. Thus, a positive effect of EVE was found. Abstract #555: Prognostic factors in HER2-negative breast cancer patients receiving first-line bevacizumab (BEV) plus non-anthracycline therapy were investigated. Negative factors were disease-free interval £ 24 months, liver metastases or ³ 2 involved organs, triple-negativity and adjuvant taxanes/anthracyclines, respectively. Thus, established prognostic factors were also confirmed in BEV-treated patients. Abstract #1049: Subgroup analyses of the phase-III trial of eribulin versus capecitabine in metastatic breast cancer pre-treated with anthracyclines/taxanes was carried out. Overall survival was predicted by non-visceral disease, > 2 organs involved, and PFS of < 6 months after last chemotherapy. Eribulin was superior in patients with > 2 metastatic sites, HER2-negative, ER-negative, and triple-negative disease, respectively. The latter patients may preferentially benefit from eribulin therapy.