Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

Completeness and timeliness of diphtheria-tetanus-pertussis,measles-mumps-rubella,and polio vaccines in young children with chronic health conditions: A systematic review

Objective

To systematically review literature on uptake and timeliness of diphtheria-tetanus-pertussis, measles-mumps-rubella, and/or polio-containing vaccines in infants who were born preterm, with a low birth weight, and/or with chronic health conditions that were diagnosed within the first 6?months of life.

Attention,Externalizing, and Internalizing Problems of Youth Exposed to Parental Incarceration

Few studies have examined the effects of parental incarceration (PI) on outcomes above and beyond other risk and adverse childhood experiences (ACEs). The objectives of this study were to (1) the associations between PI and mental health problems (attention, externalizing, internalizing, and total behavioral problems) and (2) the mediating role of current socioeconomic status and cumulative ACEs. An observational and cross-sectional design was employed. Analyses included hierarchical multivariable linear regression modeling. The analytic sample included 613 adolescents (11–17?years). On average, youth exposed to PI experienced three times as many ACEs compared with youth unexposed. Youth exposed to PI were more likely to have behavioral problems than their unexposed peers. The main effect for all models was attenuated by current economic hardship as well as exposure to increasing numbers of ACEs. Exposure to PI can be viewed as a marker of accumulative risk for intervention since youth impacted by PI are more likely to experience behavioral difficulties and associated adverse childhood experiences. Due to the associated adversity that impact youth exposed to PI, mental health providers need to be able to identify and screen for symptoms associated with trauma.     

On the Relationship between Dynamic Contrast-Enhanced Ultrasound Parameters and the Underlying Vascular Architecture Extracted from Acoustic Angiography

Dynamic contrast-enhanced ultrasound (DCE-US) has been proposed as a powerful tool for cancer diagnosis by estimation of perfusion and dispersion parameters reflecting angiogenic vascular changes. This work was aimed at identifying which vascular features are reflected by the estimated perfusion and dispersion parameters through comparison with acoustic angiography (AA). AA is a high-resolution technique that allows quantification of vascular morphology. Three-dimensional AA and 2-D DCE-US bolus acquisitions were used to monitor the growth of fibrosarcoma tumors in nine rats. AA-derived vascular properties were analyzed along with DCE-US perfusion and dispersion to investigate the differences between tumor and control and their evolution in time. AA-derived microvascular density and DCE-US perfusion exhibited good agreement, confirmed by their spatial distributions. No vascular feature was correlated with dispersion. Yet, dispersion provided better cancer classification than perfusion. We therefore hypothesize that dispersion characterizes vessels that are smaller than those visible with AA.     

A review of approaches to 18F radiolabelling affinity peptides and proteins

Affinity peptide and protein‐ (APP) based radiotracers are an increasingly popular class of radiotracer in positron emission tomography (PET), which was once dominated by the use of small molecule radiotracers. Radiolabelled monoclonal antibodies (mAbs) are important examples of APPs, yet a preference for smaller APPs, which exhibit fast pharmacokinetics and permit rapid PET aided diagnosis, has become apparent. ¹⁸F exhibits favourable physical characteristics for APP radiolabelling and has been described as an ideal PET radionuclide. Notwithstanding, ¹⁸F radiolabelling of APP is challenging, and this is echoed in the literature where a number of diverse approaches have been adopted. This review seeks to assess and compare the approaches taken to ¹⁸F APP radiolabelling with the intention of highlighting trends within this expanding field. Generic themes have emerged in the literature, namely the use of mild radiolabelling conditions, a preference of site‐specific methodologies with an impetus for short, automated procedures which produce high‐yielding [¹⁸F]APPs.     

Contribution to the rheological testing of pharmaceutical semisolids

Rheological behaviour of pharmaceutical semisolid preparations significantly affects manufacturing process, administration, stability, homogeneity of incorporated drug, accuracy of dosing, adhesion in the place of application, drug release, and resulting therapeutic effect of the product. We performed test of consistency by penetrometry, rotational, oscillation and creep tests, and squeeze and tack tests of model samples to introduce methods suitable for characterization and comparison of semisolids in practice. Penetrometry is a simple method allowing sorting the semisolids to low and high stress-resistant materials but deficient for rheological characterization of semisolids. Value of yield stress, generally considered to be appropriate feature of semisolids, is significantly influenced by the method of testing and the way of evaluation. The hysteresis loops of model semisolids revealed incomplete thixotropy, therefore, three-step thixotropy test was employed. Semisolids showed nonlinear response in the creep phase of tests and partial recovery of structure by storing energy in the recovery phase. Squeeze and tack tests seem to be convenient ways for comparison of semisolids. Our study can contribute to a better understanding of different flow behaviour of semisolids given by different physicochemical properties of excipients and can bring useful approaches to evaluation and comparison of semisolids in practice.