Comparison of ion-activated in situ gelling systems for ocular drug delivery. Part 1: physicochemical characterisation and in vitro release

Cytarabine (1-β-D-arabinofuranosylcytosine, Ara-C), a pyrimidine nucleoside analogue, is an attractive therapeutic agent for the treatment of both acute and chronic myeloblastic leukemias. 1,1',2-tris-nor-Squalene acid (squaleneCOOH) has been conjugated to cytarabine with the formation of the squalenoyl-cytarabine prodrug, in order to improve the drug lipophilicity and, consequently, the affinity towards the environment of biological membranes, as well as of lipophilic carriers. The interaction of cytarabine and its prodrug with dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles and monolayers has been studied by the differential scanning calorimetry and the Langmuir-Blodgett techniques. The interaction has been evaluated considering the effect of the compounds on the DMPC MLV and monolayers behaviour. The aim was to have information on the interaction of the drug and the prodrug with the biological membranes and on the possibility to use liposomes as carriers for the prodrug. The results showed an improved affinity of the prodrug with MLV and monolayers with respect to the free drug.     

Comparative accuracy of manual versus computerized electrocardiographic measurement of J-, ST- and T-wave deviations in patients with acute coronary syndrome

Accurate and rapid electrocardiographic interpretation is of crucial importance in acute coronary syndrome (ACS). Computerized electrocardiographic algorithms are often used in out-of-hospital settings. Their accuracy should be carefully validated in ACS, particularly in ST-elevation myocardial infarction. This study evaluated the comparative accuracy of lead-specific computer-based versus manual measurements of the J-point, ST-segment, and T-wave deviations in standard 12-lead electrocardiograms (ECGs) (excluding lead aVR). Sixty-nine consecutive patients with suspected ACS were included. The interobserver reliability in the determination of ST-segment deviation>or=0.2 mV in leads V2 and V3 was very good (kappa=0.94 and 0.93, respectively). Agreement between a cardiologist and the computer regarding ST elevation>or=0.2 mV in lead V2 was moderate (kappa=0.72) and in V3 was very good (kappa=0.85). For ST depression or elevation>or=0.05 mV in lead LIII, agreement was good and moderate (kappa=0.79 and 0.51, respectively). Bland-Altman analysis demonstrated clinically acceptable limits of agreement comparing measurements of the J point and the T wave, but clinically inadequate limits of agreement with respect to ST-segment deviation, between the electrocardiographer and the computer. The optimal cut-off points were 0.115 mV (sensitivity 89%, specificity 98%) for the computer program to detect ST elevation>or=0.2 mV and 0.045 mV (sensitivity 74%, specificity 99%) for revealing ST elevation>or=0.1 mV. It was found that automatically measured ST-segment deviations were smaller than those manually measured. In conclusion, a correction should be performed to obtain optimal results in the automated analysis of ECGs, because the results have important implications for clinical decision making.     

Action potentials and release of neurohypophysial hormones in vitro

1. Isolated rat neurohypophyses were studied in vitro and the hormones released on electrical stimulation of the pituitary stalk or on exposure to excess potassium were estimated by a milk-ejection assay.2. The stalk was stimulated with trains of 500 stimuli, or multiples thereof, applied at different frequencies. Below frequencies of ca. 35 c/s, hormone release was found to depend on the total number of stimuli applied as well as on the frequency of stimulation. Above ca. 35 c/s, identical numbers of stimuli were progressively less effective as the frequency of stimulation was increased, and the dependence of the hormone output on the total number of stimuli was less apparent.3. The amplitude of the compound action potential recorded from the neurohypophysis following electrical stimulation of the stalk was found to decrease as a function of the frequency of stimulation. Stimulation at 50 c/s reduced its amplitude about sevenfold within 30 sec.4. The addition of tetrodotoxin (TTX) to the incubation media abolished the compound action potential recorded from the neural lobe as well as the release of hormones evoked by electrical stimulation. Resting release, however, was unaffected by TTX.5. In TTX-treated neural lobes, excess potassium was still effective in eliciting graded secretory responses. This indicates the independence of the release process from the action potential generating mechanism and suggests that TTX-paralysed preparations represent a useful model for the study of hormone release in the absence of conducted action potentials.6. The release of hormones from the neurohypophysis and the release of neurotransmitters at chemical synapses both depend on the entry of calcium into the nerve terminals following their depolarization by invading action potentials. In both systems, experimental separation of the release mechanism can be achieved by the use of TTX. These and other parallels suggest that the release process is similar.     

Somatoform disorders: 30 years of debate about criteria! What about children and adolescents?

Objectives

The aim of this study was to evaluate the suitability of the complex somatic symptom disorder, proposed by the DSM-V Somatic Symptom Disorders Workgroup, in classifying children and adolescents who suffer severely from medically unexplained symptoms.

Methods

The existing knowledge about somatoform disorders (SDs) in children and adolescents was delineated by means of a comprehensive search in the psychological, psychiatric, and pediatric literature. It was analyzed to assess whether children and adolescents suffer from SDs according to DSM-IV-TR (prevalence, developmental course, comorbidity, risk factors, and impact on daily functioning). Subsequently, each criterion of the complex somatic symptom disorder was outlined and discussed with respect to its suitability in classifying children and adolescents. The suitability of the DSM-IV-TR criteria of SDs and that of the criteria of the complex somatic symptom disorder were compared.

Results

Current data of sufficient quality are limited but indicate that the DSM-IV-TR criteria are inappropriate for classifying most children and adolescents suffering from somatoform symptoms. The criteria for complex somatic symptom disorder are more appropriate. Nevertheless, it is recommended to include two additional parameters: “parental excessive concern and preoccupation with the child's symptoms” and “high parental health anxieties.”

Conclusions

The criteria for complex somatic symptom disorder are more appropriate for children and adolescents than the current DSM-IV-TR criteria; they should be better adapted to the special situation of children and adolescents.     

Nursing mothers' perception about their quality of life

Women usually describe breastfeeding as a period of high physical and emotional distress. The objective of this study is to understand the perception that nursing mothers' supported in a Primary Health Care Clinic located in the city of S?o Paulo have about their quality of life (QL). This is an exploratory qualitative study. Participants were 202 nursing mothers, who answered the Instrument of QL (WHOQOL-bref). The data was organized according to the Collective Subject Discourse. The nursing mothers, describing what is QL, use the objective and subjective aspects as qualifiers of their life experience. It was found that it is important to plan nursing care about breastfeeding since the prenatal period, especially as a way to encourage the father to participate in the care to his children and to prepare the family to support the mother, which will certainly improve her perception about her QL.     

Classic disease modifying anti-rheumatic drugs (DMARDs) in combination with infliximab. The Finnish experience

To assess the performance of infliximab in a clinical setting, 364 rheumatoid arthritis (RA) patients from the National Register of Biological Treatment in Finland (ROB-FIN) were analysed. Corticosteroid usage and dose diminished (p<0.05 and 0.001, respectively) in patients on infliximab, of whom 51% also used one, 28% two and 16% three other concomitant DMARDs. A 34% of the RA patients used methotrexate ± corticosteroids without any other DMARD. Methotrexate was most frequently used with sulphasalazine and/or hydroxychloroquine. Non-methotrexate patients most frequently used leflunomide or azathioprine combined with corticosteroids. The clinical effect of these combinations was similar to that of infliximab with methotrexate alone. The results indicate that infliximab can be used together with other DMARDs than methotrexate alone, quite according to the philosophy of the combination drug therapy, as the effectiveness is as good as or even slightly better than that of methotrexate and infliximab.D.C. Nordström and L. Konttinen: Equal contribution     

Screening of bacteria-binding peptides and one-pot ZnO surface modification for bacterial cell entrapment

Short functional peptides are promising materials for use as targeting recognition probes. Toll-like receptor 4 (TLR4) plays an essential role in pathogen recognition and in activation of innate immunity. Here, the TLR4 amino acid sequence was used to screen for bacterial cell binding peptides using a peptide array. Several octamer peptides, including GRHIFWRR, demonstrated binding to Escherichia coli as well as lipopolysaccharides. Linking this peptide with the ZnO-binding peptide HKVAPR, creates a bi-functional peptide capable of one-step ZnO surface modification for bacterial cell entrapment. Ten-fold increase in entrapment of E. coli was observed using the bi-functional peptide. The screened peptides and the simple strategy for nanomaterial surface functionalization can be employed for various biotechnological applications including bacterial cell entrapment onto ZnO surfaces.

Linking the screened bacteria-binding peptide with the ZnO-binding peptide HKVAPR, created a bifunctional peptide capable of one-step simple ZnO surface modification and of bacterial cell entrapment.