Evaluation of the genotoxic potential of dimethyl sulfoxide (DMSO) in meristematic cells of the root of Vicia faba

Dimethyl sulfoxide (DMSO) is an organic solvent with several biological applications. It is extensively used to dissolve compounds that hardly dissolve in water to detect their genotoxic activity in vitro. In this study DMSO will be tested to determine its genotoxic potential. The effect of DMSO on the frequency of chromosomal aberrations in anaphase as well as DNA fragmentation through the comet assay has been evaluated in the meristematic cells of the root tips of Vicia faba. It has been observed that the frequency of chromosomal aberrations increases when the concentration of DMSO increases, reaching its maximum value with 20% of DMSO and decreasing at 30 and 40% of DMSO, in comparison to this maximum value, but significantly higher than the values observed in the control. Similarly, the percentage of fragmentation and damage index evaluated through the comet assay showed the same behavior; some of the possible mechanisms of action are discussed.     

Tigecycline Potentiates Clarithromycin Activity against Mycobacterium avium In Vitro

The in vitro activities of clarithromycin and tigecycline alone and in combination against Mycobacterium avium were assessed. The activity of clarithromycin was time dependent, highly variable, and often resulted in clarithromycin resistance. Tigecycline showed concentration-dependent activity, and mycobacterial killing could only be achieved at high concentrations. Tigecycline enhanced clarithromycin activity against M. avium and prevented clarithromycin resistance. Whether there is clinical usefulness of tigecycline in the treatment of M. avium infections needs further study.     

Acidified seawater impacts sea urchin larvae pH regulatory systems relevant for calcification

Calcifying echinoid larvae respond to changes in seawater carbonate chemistry with reduced growth and developmental delay. To date, no information exists on how ocean acidification acts on pH homeostasis in echinoderm larvae. Understanding acid–base regulatory capacities is important because intracellular formation and maintenance of the calcium carbonate skeleton is dependent on pH homeostasis. Using H⁺-selective microelectrodes and the pH-sensitive fluorescent dye BCECF, we conducted in vivo measurements of extracellular and intracellular pH (pH_e and pH_i) in echinoderm larvae. We exposed pluteus larvae to a range of seawater CO₂ conditions and demonstrated that the extracellular compartment surrounding the calcifying primary mesenchyme cells (PMCs) conforms to the surrounding seawater with respect to pH during exposure to elevated seawater pCO₂. Using FITC dextran conjugates, we demonstrate that sea urchin larvae have a leaky integument. PMCs and spicules are therefore directly exposed to strong changes in pH_e whenever seawater pH changes. However, measurements of pH_i demonstrated that PMCs are able to fully compensate an induced intracellular acidosis. This was highly dependent on Na⁺ and HCO₃⁻, suggesting a bicarbonate buffer mechanism involving secondary active Na⁺-dependent membrane transport proteins. We suggest that, under ocean acidification, maintained pH_i enables calcification to proceed despite decreased pH_e. However, this probably causes enhanced costs. Increased costs for calcification or cellular homeostasis can be one of the main factors leading to modifications in energy partitioning, which then impacts growth and, ultimately, results in increased mortality of echinoid larvae during the pelagic life stage.     

The use of medical care and the prevalence of serious illness in an adult Prader–Willi syndrome cohort

IntroductionAdults with Prader–Willi syndrome (PWS) have an increased occurrence of several medical conditions. We report on the consequences of high morbidity rates such as prevalence rate of hospital admissions, medication use and surgery in a Dutch cohort of adults with PWS. Special attention is paid to causes and symptoms of serious illness.MethodParticipants were contacted via the Dutch Prader–Willi Parent Association and through physicians specializing in persons with ID. The persons with PWS and their main caregivers were visited at home. Information was collected through semi-structured interviews on 102 adults with PWS.ResultsThe need for medical care in the neonatal period is associated with hypotonia and feeding problems. Hospital admissions for respiratory tract infections are frequent. During childhood most hospital admissions were due to PWS syndrome specific surgery. During adolescence hospital admissions occurred for scoliosis surgery and endocrine evaluations. At adult age, hospitalization was associated with inguinal hernia surgery, diabetes mellitus, psychosis, erysipelas, water and drug intoxications. In the older group, respiratory infections were again the main reason for hospital admissions. Frequently used medications at adult age included psychotropics, laxatives, anti-diabetics and dermatologic preparations. Abnormal drinking patterns, problems with anesthesia, decreased ability to vomit, abnormal pain awareness and unpredictable fever responses were frequent and often lead to delayed diagnoses of serious conditions.DiscussionPeople with PWS are frequent users of medical-care. Reasons for hospitalization and medication use are age specific. Knowledge on the different presentation of symptoms in people with PWS is needed. In case of unexplained illness, disturbances of consciousness and behavioral changes in people with PWS, an infection should be ruled out in the first place. Information from this study may help in preventing conditions and recognizing conditions in an early stage. Adequate preventive management and treatment of PWS related morbidity, could reduce medical care use in the long term and could improve quality adjusted life years.     

Large Molecule Specific Assay Operation: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

The L2 Global Harmonization Team on large molecule specific assay operation for protein bioanalysis in support of pharmacokinetics focused on the following topics: setting up a balanced validation design, specificity testing, selectivity testing, dilutional linearity, hook effect, parallelism, and testing of robustness and ruggedness. The team additionally considered the impact of lipemia, hemolysis, and the presence of endogenous analyte on selectivity assessments as well as the occurrence of hook effect in study samples when no hook effect had been observed during pre-study validation.     

Mndical Mnemonics

In all cases of obstructive lung disease, smoking cessation, proper use of metered-dose inhalers, up-to-date immunizations, adequate nutrition, and general physical conditioning are important components of treatment. Dr Jacobs summarizes these components as well as stepwise pharmacologic approaches to controlling the inflammation of asthma, the bronchospasm of chronic bronchitis and emphysema, and the symptoms of secondary or coexisting conditions.