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.     

Stage 1 acute kidney injury is independently associated with infection following cardiac surgery

ObjectivesSevere acute kidney injury (AKI) is a known risk factor for infection and mortality. However, whether stage 1 AKI is a risk factor for infection has not been evaluated in adults. We hypothesized that stage 1 AKI following cardiac surgery would independently associate with infection and mortality.MethodsIn this retrospective propensity score–matched study, we evaluated 1620 adult patients who underwent nonemergent cardiac surgery at the University of Colorado Hospital from 2011 to 2017. Patients who developed stage 1 AKI by Kidney Disease Improving Global Outcomes creatinine criteria within 72 hours of surgery were matched to patients who did not develop AKI. The primary outcome was an infection, defined as a new surgical-site infection, positive blood or urine culture, or development of pneumonia. Secondary outcomes included in-hospital mortality, stroke, and intensive care unit (ICU) and hospital length of stay (LOS).ResultsStage 1 AKI occurred in 293 patients (18.3%). Infection occurred in 20.9% of patients with stage 1 AKI compared with 8.1% in the no-AKI group (P < .001). In propensity-score matched analysis, stage 1 AKI independently associated with increased infection (odds ratio [OR]; 2.24, 95% confidence interval [CI], 1.37-3.17), ICU LOS (OR, 2.38; 95% CI, 1.71–3.31), and hospital LOS (OR, 1.30; 95% CI, 1.17-1.45).ConclusionsStage 1 AKI is independently associated with postoperative infection, ICU LOS, and hospital LOS. Treatment strategies focused on prevention, early recognition, and optimal medical management of AKI may decrease significant postoperative morbidity.     

Management of psychopharmacologic agents in children and adolescents

This article summarizes the ways in which a clinician should think about medication use in children and describes practical usage of the most frequently used child psychopharmacologic agents.Leena Ranade, M.D., and Aftab Qadir, M.D., were Fellows in Child Psychiatry, State University of New York at Stony Brook at the time of writing this article.     

Osteoclastic inhibition: an action of nitric oxide not mediated by cyclic GMP.

The osteoclast is unique in its ability to resorb bone, and excessive osteoclastic activity has been implicated in osteoporosis, Paget disease of bone, rheumatoid arthritis, and the growth of metastases in bone. The activity of this cell is controlled by the main circulating inhibitor, calcitonin, in association with locally produced modulators. We show that nitric oxide (NO) may be an important member of the latter group. NO is produced by the vascular endothelium and nervous system and is involved in both neurotransmission and the regulation of blood pressure. However, our results show that the autocoid is also a potent inhibitor of osteoclast function. NO (30 microM) produced a decrease to approximately 50% of the original osteoclast spread area. Similar effects were also produced by 3-morpholinosydnonimine or sodium nitroprusside, reagents that spontaneously release NO. These shape changes were associated with a reduction of bone resorption after a 24-hr incubation of isolated osteoclasts on devitalized bone slices. NO is thought to act by stimulating guanylate cyclase, with a consequent increase in cyclic GMP, but a different mode of action is likely in the osteoclast since dibutyryl or 8-bromo cyclic GMP have no effect. It should be noted that calcitonin can produce similar changes in shape and activity but is associated with an increase in osteoclast intracellular calcium and cessation of membrane movement; neither of these is produced by NO, suggesting that its mode of action is different. The abundance of NO-producing endothelial cells in bone marrow and their proximity to osteoclasts suggests that marrow endothelial cells may play a physiological role in the regulation of osteoclastic activity.     

Genome sequence based, comparative analysis of the fluorescent amplified fragment length polymorphisms (FAFLP) of tubercle bacilli from seals provides molecular evidence for a new species within the Mycobacterium tuberculosis complex.

Tuberculosis in seals is caused by a member of the Mycobacterium tuberculosis complex referred to as the 'seal bacillus'. Fluorescent amplified-fragment length polymorphism (FAFLP) analysis was applied to isolates from four Australian and six Argentinean seals and compared with FAFLP pattern for standard strains belonging to the M. tuberculosis complex. The FAFLP profiles derived from EcoRI/MseI restricted fragments of blind coded DNA samples differentiated the seal bacillus from other members of the M. tuberculosis complex. According to the phylogenetic analysis performed using FAFLP data, seal bacilli appear to have diverged significantly from other members of the M. tuberculosis complex. We describe the suitability of a panel of 19 highly polymorphic markers for rapid identification and comparative genomic analyses of the seal bacillus strains. It is likely that these bacilli got separated from the M. tuberculosis lineage as a result of different insertion deletion events occurring on a genome wide scale. Our analysis reveals that the seal bacillus and M. bovis are genetically related and therefore, might have originated from a common ancestor. Our data additionally support the hypothesis that seal bacillus occupies a unique taxonomic position within the M. tuberculosis complex.     

Increased mitral valve insufficiency during precordial "whoop"

A patient with rheumatic mitral valve stenosis and regurgitation presented with shortness of breath and a "noise" in her chest. Cardiac auscultation revealed an intermittent late systolic "whoop." An increase in severity of mitral valve insufficiency during the periods of "whoop" was observed by pulsed Doppler, hemodynamic tracings and left ventriculography.     

Wartime determinants of arteriographically confirmed coronary artery disease in Beirut

This study investigates the association of wartime stress variables and coronary artery disease as determined by coronary angiography in Lebanon in 1986, a country with an ongoing civil war for over a decade. A total of 127 patients who underwent coronary angiography at the American University of Beirut Medical Center were individually matched on age and sex with visitor controls free from any evidence of clinical coronary artery disease. Arteriographic cases (greater than or equal to 70% maximal stenosis) were compared with two control groups: arteriographic controls (entirely normal coronaries) and visitor controls. Findings suggest that there is a relation between exposure to both acute and chronic war events and coronary artery disease in this patient population. The reporting of exposure to acute war events was significantly higher in cases compared with both visitor controls (odds ratio (OR) = 2.4, 95% confidence interval (Cl) 1.17-4.90) and arteriographic controls (OR = 2.8, 95% Cl 0.93-8.47). Crossing the "green-lines" that separate two belligerent sides, considered as an attribute of war-related chronic stress, was more frequent in cases compared with visitor controls (OR = 3.25, 95% Cl 1.54-6.89) and arteriographic controls (OR = 5.38, 95% Cl 1.65-17.6). The relation observed between wartime stress and coronary artery disease could not be explained by possible overreporting of stressful events in patients with suspected coronary artery disease or by an increase in clinical awareness for the disease for those under continuous stress. Adjusting for the effect of the well-established coronary artery disease risk factors did not alter the above findings.