Effect of cardiopulmonary bypass on cytochrome P450 enzyme activity: implications for pharmacotherapy

For patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, there are well-documented changes in the pharmacokinetics (PK) of commonly administered drugs. Although multiple factors potentially underpin these changes, there has been scant research attention on the impact of CPB to alter the activities of cytochrome P450 (CYP) isoenzymes. PK changes during cardiac surgery with CPB have the potential to adversely affect the safety and efficacy of pharmacotherapy and increase the risk of drug–drug interactions. Clinically significant changes in drug PK during CPB are likely to be prominent for drugs where CYP metabolism is a major clearance (CL) mechanism. However, clinical data from patients undergoing CPB surgery in support of this hypothesis are lacking, leaving a significant knowledge gap. In this review, we address the effects of CPB on the release of pro-inflammatory cytokines, in surgeries with and without CPB, both pre and post initiation of surgery. We reviewed literature to explore the relationship between the release of pro-inflammatory cytokines, and the expression and activities of CYP enzymes. Through this approach, we provide new insight on the effects of CPB on the PK of drugs administered to patients in the clinical setting. Future research to address this knowledge gap will have considerable impact to assist clinicians with optimizing pharmacotherapy in this patient population.     

12-month efficacy and safety of OROS® MPH in children and adolescents with attention-deficit/hyperactivity disorder switched from MPH

PURPOSE: The aim of this study was to evaluate long-term clinical treatment with OROS methylphenidate (MPH) (Concerta) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) who had been previously treated with immediate release (IR) MPH. METHODS: Subjects aged 6-16 years (n=105) who were stable on IR MPH (10-60 mg/day) were switched to 18, 36 or 54 mg OROS MPH once daily for 21 days, depending on prestudy MPH dose. Subjects who benefited from OROS MPH could continue in a 12-month extension period. ADHD symptoms and treatment response were assessed by parents/caregivers and investigators. RESULTS: Out of 105 enrolled children, 101 completed the 21-day treatment phase. In all, 89 parents/caregivers (88.1%) wanted their child to continue with the study treatment into the extension phase, and 56 children (63 %) completed the 1-year trial. The parent/caregiver global assessment of satisfaction ranged from 49 to 69% during the extension phase, and 49 to 71% of investigators rated the treatment as adequate. Efficacy and satisfaction were found more commonly in patients in the older age group (10-16 years), those on a higher dose (36 mg or 54 mg) and with the predominantly inattentive ADHD subtype. OROS MPH was well tolerated. CONCLUSIONS: Children and adolescents can effectively and safely be switched from IR MPH to OROS MPH with improved symptom control and compliance.     

Auxotrophic mutant of the cyanobacterium Nostoc muscorum showing absolute requirement of Cs+ or Rb+ for diazotrophy and autotrophy

Caesium-resistant (Cs(+)-R) mutant clones of the cyanobacterium Nostoc muscorum were characterized for diazotrophic growth in a medium devoid of Cs(+) or Rb(+) or both. Cs(+)-R phenotype suffered severe genetic damage of a pleiotropic nature affecting diazotrophic growth, chlorophyll a content, nitrogenase activity and photosynthetic O(2) evolution. Mutation leading to development of Cs(+)-R phenotype could be overcome by availability of Cs(+)/Rb(+). Parent and mutant strains were similar with respect to their Cs(+)/Rb(+) uptake. Available data suggests operation of an efficient coupling of the two incompatible reactions viz. oxygenic photosynthesis and oxygen sensitive N(2) fixation in this cyanobacterium.     

The Zika virus and pregnancy: evidence,management, and prevention

Objective: To comprehensively review the available evidence and existing consensus reports and guidelines regarding the pregnancy and reproductive implications of the mosquito-transmitted Zika virus (ZIKV) infection. A primary focus was to provide pertinent information to aid clinicians in the management of pregnancies at risk for, exposed to, or with confirmed ZIKV infection.

Method: An extensive literature review was performed using Pubmed. Practice guidelines and consensus reports were accessed from international, national, and professional organizations’ websites. The clinical articles for ZIKV infection testing varied from case reports to small epidemiologic studies.

Results: A ZIKV epidemic has been declared in several countries in the Americas. Fifty-two travel-associated ZIKV infection cases have been reported throughout the USA (as of February 10, 2016). The consequences of congenital fetal/newborn ZIKV infection could potentially have devastating consequences including miscarriage, fetal death, and major anomalies such as microcephaly, brain and brain-stem defects, and long-term neurologic sequelae. While not definitive, current evidence suggests the existence of nonvector-borne transmission through sexual activity with an infected male partner. For women at risk for sexual transmission, condom use is advised, especially during pregnancy.

Conclusion: While ZIKV infection appears to be a mild disease in the general population the potential consequences to the fetus and newborn could be profound. Management guidelines are currently evolving and will be significantly impacted as new evidence develops. It is therefore imperative that obstetric health-care providers keep abreast of this rapidly evolving information landscape that has so far characterized this outbreak.     

Receiver Operating Characteristic (ROC) to Determine Cut-Off Points of Biomarkers in Lung Cancer Patients

The role of biomarkers in disease prognosis continues to be an important investigation in many cancer studies. In order for these biomarkers to have practical application in clinical decision making regarding patient treatment and follow-up, it is common to dichotomize patients into those with low vs. high expression levels. In this study, receiver operating characteristic (ROC) curves, area under the curve (AUC) of the ROC, sensitivity, specificity, as well as likelihood ratios were calculated to determine levels of growth factor biomarkers that best differentiate lung cancer cases versus control subjects. Selected cut-off points for p185^erbB-2 and EGFR membrane appear to have good discriminating power to differentiate control tissues versus uninvolved tissues from patients with lung cancer (AUC = 89% and 90%, respectively); while AUC increased to at least 90% for selected cut-off points for p185^erbB-2 membrane, EGFR membrane, and FASE when comparing between control versus carcinoma tissues from lung cancer cases. Using data from control subjects compared to patients with lung cancer, we presented a simple and intuitive approach to determine dichotomized levels of biomarkers and validated the value of these biomarkers as surrogate endpoints for cancer outcome.     

Insecticidal Evaluation of essential oils of <Emphasis Type="BoldItalic">Citrus sinensis</Emphasis> L. (Myrtales: Myrtaceae) against housefly, <Emphasis Type="BoldItalic">Musca domestica</Emphasis> L. (Diptera: Muscidae)

The housefly, Musca domestica L., is one of the most common insects, associated with vectoring of various etiological agents. In order to search for effective control agent, the essential oil of sweet orange [Citrus sinensis (L.) Osbeck] was evaluated for its insecticidal activity against the larvae and pupae of housefly using contact toxicity and fumigation bioassays. In the contact toxicity assay, lethal concentration, LC₅₀ of C. sinensis essential oil against housefly larvae, varied between 3.93 and 0.71 μl/cm² for different observation days, while lethal time, LT₅₀, varied between 5.8 to 2.3 days. Mortality of larvae were significant with different concentrations (F = 2.79, df = 4, P < 0.05) and time (F = 6.69, df = 3, P < 0.01). In fumigant assay for housefly larvae, LC₅₀ of 71.2 and 52.6 μl/l was obtained in 24 and 48 h, respectively. Scanning electron microscopy of oil treated larvae revealed extreme dehydration and surface distortion while control larvae were free from any of the above symptoms and presented smooth surface, conforming effect of essential oil on housefly larvae. Percentage inhibition rate of oil against housefly pupae was 27.3–72.7% for contact toxicity and 46.4–100% for fumigation assay. Compositional analysis of C. sinensis essential oil using gas chromatography/mass spectrometry (GC-MS) revealed d-limonene (73.24%), α-pinene (5.86%) and myrcene (4.45%) as major components whereas its vapour profile (solid-phase micro extraction-GC/MS) was dominated by d-limonene at 92.57%. Significant activity of C. sinensis essential oil against larvae and pupae of housefly, pave the way for its use as eco-friendly housefly control measure.     

Cytodiagnosis of primary thyroid lymphoma with histologic correlation: A case report

Primary thyroid lymphoma is a very rare disease. Here, we present a case of primary diffuse large B-cell lymphoma (DLBCL) in a 48-year-old female involving thyroid gland. The patient had thyroid swelling for 15 years which rapidly increased during last 5 months. Fine needle aspiration cytology revealed monomorphic large cells arranged discretely. The cells have high nuclear-cytoplasmic ratio with prominent single to multiple nucleoli. Aggregates of thyroid follicular cells were absent in the smears. A cytodiagnosis of DLBCL was made and a differential diagnosis of lymphocytic thyroiditis was also included. Subsequent histologic examination revealed a high-grade non-Hodgkin lymphoma (NHL). Immunohistochemistry showed the tumor cells expressing CD45, CD20, BCl-6, and tumor cells were negative for cytokeratin, epithelial membrane antigen, CD3, CD5, and CD30. Proliferative index (Ki-67) was very high (70%). Thus, a final diagnosis of NHL of DLBCL subtype was established. The patient was treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristin, prednisone) and radiotherapy. The patient is under one-year follow-up which is uneventful.