In vitro blood compatibility and in vitro cytotoxicity of amphiphilic poly-N-vinylpyrrolidone nanoparticles.

This study focused on defining the in vitro behavior of amphiphilic poly-N-vinylpyrrolidone (Amph-PVP) nanoparticles toward whole blood, blood plasma and blood cells in order to assess nanoparticle blood compatibility. In addition, possible effects on endothelium cell growth/viability were evaluated. The Amph-PVP nanoparticles were formed via self-assembling in aqueous media and composed of a hydrophobic alkyl core and a hydrophilic PVP outer shell. Their blood compatibility was evaluated by investigating their effect on red blood cells (RBCs) or erythrocytes, white blood cells (WBCs) or leukocytes, platelets (PLTs) and on complement system activation. Our results clearly demonstrate that the Amph-PVP nanoparticles are stable in presence of blood serum, have no significant effects on the function of RBCs, WBCs, PLTs and complement system activation. The Amph-PVP nanoparticles did not show considerable hemolytic or inflammatory effect, neither influence on platelet aggregation, coagulation process, or complement activation at the tested concentration range of 0.05-0.5 mg/ml. The Amph-PVP nanoparticles did not exhibit any significant effect on HMEC-1 microvascular skin endothelial cells' growth in in vitro experiments. The excellent blood compatibility of the Amph-PVP nanoparticles and the lack of effect on endothelium cell growth/viability represent a crucial feature dictating their further study as novel drug delivery systems.

Cardioprotective effects of insulin on carbon monoxide-induced toxicity in male rats.

Carbon monoxide (CO) poisoning is a significant cause of death especially in developing countries. The current study investigated cardioprotective effects of insulin in CO-poisoned rats. Male rats were exposed to 3000 ppm CO for 1 h. Insulin (100 and 120 U/kg intraperitoneally) was immediately administered after CO exposure and on the next 4 days, on a daily basis (a total of 5 doses). On day 5, animals were euthanized, and the hearts were harvested for Western blotting and histopathological studies. The electrocardiograms (ECG) were recorded postexposure to CO and after the completion of insulin treatment period. Histopathological evaluations showed reduction of myocardial necrosis in insulin-treated animals compared to controls. BAX/BCL2 ratio, as a proapoptotic index, was significantly reduced in treatment groups ( p < 0.01). The ECG findings showed no differences among groups; also, compared to control animals, myocardial Akt levels were not markedly affected by insulin. The current study showed that insulin significantly reduces myocardial necrotic and apoptotic indices in CO-poisoned rats.

Molecular and clinical aspects of embryotoxicity induced by acetylcholinesterase inhibitors.

Acetylcholinesterase inhibitors are widely used for a variety of medical, agricultural and public health purposes. Consequently, exposure is highly possible during lifetime. However, their systematic use raises concerns for the potential impact on the fetus and newborn since these substances may affect angiogenesis, the neonatal and maternal intensive care, neuroimmune function and response, mammary growth/lactation via cholinergic/non-cholinergic central and peripheral neuroendocrine pathways. New methodologies, neuroscientific technologies and research studies are needed to harness existing knowledge along with the proper management, availability for new acetylcholinesterase inhibitors, with stable pharmacodynamics and clinical outcomes.

Comparative efficacy of oral contraceptive versus local treatment versus intense pulsed light combined with vacuum in endocrine acne in women.

Acne is the most common affection of adolescents, although it can be also found in adult women. Our study was aimed at the comparative assessment of three different therapies over a three-month period, applied to women with moderate comedogenic and papulo-pustular endocrine acne. In the study 116 female patients with endocrine localized face acne were included and divided into three groups: group I with 42 patients was treated with a combination of contraceptive pill + local treatment + pulsed-vacuum light; group II with 38 patients was treated with contraceptives and pulsed-vacuum light and group III with 36 patients was treated only with local treatment. The acne evaluation was made using the Global Acne Grading System (GAGS). Statistical data processing was carried out using the STATA software. For the comedogenic form of acne, the good and very good results were superior in group I vs group II and III (83.33% vs 31.58% vs 5.56%) at the end of the three months of treatment. For the papulo-pustulous form of acne, good and very good results were similar in groups I and II (92.86% vs 73.68%) both after the first month of treatment and at the end of the study, well above the local treatment group (13.99%). Our study highlighted the superiority of laser treatment combined with hormonal treatment, compared to hormonal and local treatment in the comedogenic form of acne, and the superiority of hormonal treatment combined (or not) with laser treatment in the papulo-pustular form compared to local treatment.

Simulating real-life exposures to uncover possible risks to human health: A proposed consensus for a novel methodological approach.

In real life, consumers are exposed to complex mixtures of chemicals via food, water and commercial products consumption. Since risk assessment usually focuses on individual compounds, the current regulatory approach doesn't assess the overall risk of chemicals present in a mixture. This study will evaluate the cumulative toxicity of mixtures of different classes of pesticides and mixtures of different classes of pesticides together with food additives (FAs) and common consumer product chemicals using realistic doses after long-term exposure. Groups of Sprague Dawley (CD-SD) rats (20 males and 20 females) will be treated with mixtures of pesticides or mixtures of pesticides together with FAs and common consumer product chemicals in 0.0, 0.25 × acceptable daily intake (ADI)/tolerable daily intake (TDI), ADI/TDI and 5 × ADI/TDI doses for 104 weeks. All animals will be examined every day for signs of morbidity and mortality. Clinical chemistry hematological parameters, serum hormone levels, biomarkers of oxidative stress, cardiotoxicity, genotoxicity, urinalysis and echocardiographic tests will be assessed periodically at 6 month intervals. At 3-month intervals, ophthalmological examination, test for sensory reactivity to different types of stimuli, together with assessment of learning abilities and memory performance of the adult and ageing animals will be conducted. After 24 months, animals will be necropsied, and internal organs will be histopathologically examined. If the hypothesis of an increased risk or a new hazard not currently identified from cumulative exposure to multiple chemicals was observed, this will provide further information to public authorities and research communities supporting the need of replacing current single-compound risk assessment by a more robust cumulative risk assessment paradigm.