Technique of injection of onabotulinumtoxin A for chronic migraine: the PREEMPT injection paradigm.

In 2013 the Italian Pharmacy Agency (AIFA) approved onabotulinumtoxin A injection to prevent headaches in adult patients with chronic migraine (headaches on at least 15 days per month of which at least 8 days are with migraine) that has not responded to at least three prior pharmacological prophylaxis therapies and whose condition is appropriately managed for medication overuse. In the present paper we report the method of injection of Onabotulinumtoxin A for chronic migraine based on the PREEMPT paradigm as described by Blumenfeld et al. (Headache 50:1406-1418, 2010) adapted to our clinical setting.

Cerebral haemodynamics in early puerperium: A prospective study.

AIM: Prospective study on 900 consecutive puerperae to assess normal values and range of the blood flow velocity in the middle cerebral artery in both hemispheres. MATERIAL AND METHOD: M1 and M2 segments of both middle cerebral arteries were assessed in all subjects within 96 hours of delivery. Mean flow velocity was recorded after adjusting for insonation angle. Lindegaard index (LI = middle cerebral artery-Internal Carotid Artery mean flow velocity ratio) was calculated whenever the mean flow velocity exceeded 100 cm/second. Asymmetry indexes were calculated inter hemispherically for M1 and M2 segments separately. RESULTS: Mean flow velocities were 74 ± 17 and 72 ± 17 in right and 73 ± 17 and 72 ± 17 cm/second in the left M1 and M2, respectively. A total of 136 subjects (12.1%) exceeded the threshold of 100 cm/second, but LI was consistently <3 in all of them. Mean flow velocity was inversely and independently correlated to haemoglobin levels and to parity. Mean asymmetry indexes were 0.25 ± 23 in M1 and 0.45 ± 25 in M2. CONCLUSION: Mean flow velocity in the middle cerebral artery of healthy subjects in early puerperium is higher than in age-matched non-puerperal women and may exceed the threshold of 100 cm/second with no evidence of intracranial spasm, because of blood loss during delivery. Mean flow velocity is independently correlated with parity. Right-to-left mean flow velocity asymmetry may reach 50% as a consequence of a transient imbalance in vascular tone regulation.

Comparative analysis of new peptide conjugates of antitubercular drug candidates-Model membrane and in vitro studies.

Novel peptide conjugates of two antitubercular drug candidates were synthesised and characterised using new tuftsin peptide derivative (OT14) as carrier moiety. As antitubercular drug candidates two pyridopyrimidine derivatives, TB803 (2-allylamino-4-oxopyrido[1,2-a]pyrimidine-3-carbaldehyde) and TB820 (4-oxo-2-(pyrrolidin-1-yl)-pyrido[1,2-a]pyrimidin-3-carbaldehyde) inhibiting vital enzyme of Mycobacterium tuberculosis were applied. Membrane affinity of the compounds TB803 and TB820 and their peptide conjugates was evaluated using experimental lipid mono- and bilayer models. Penetration ability was assessed tensiometrically from Langmuir monolayer study and applying quartz crystal microbalance for the supported lipid bilayer (SLB) system. Minimal inhibitory concentration (MIC) values remained in a similar micromolar range for both of the conjugates while their cellular uptake rate was improved significantly compared to the drug candidates. A correlation was found between membrane affinity properties and results of in vitro biological investigations. Analysis of physical/structural properties of SLB in contact with bioactive components and visualization of the structural change by atomic-force microscopy (AFM) provided information on the type and route of molecular interaction of drug construction with lipid layers. The possible role of electrostatic interactions between lipid layer and drug candidates was tested in Langmuir-balance experiments using negatively charged lipid mixture (DPPC+DPPG). Especially the peptide conjugates presented increased membrane affinity due to cationic character of the peptide sequence selected for the conjugate formation. That is supposed to be one reason for the enhanced cellular uptake observed in vitro on MonoMac6 cell line. The conjugation of antitubercular agents to a peptidic carrier is a promising approach to enhance membrane affinity, cellular uptake rate and in vitro selectivity.

European larch phenology in the Alps: can we grasp the role of ecological factors by combining field observations and inverse modelling?

Vegetation phenology is strongly influenced by climatic factors. Climate changes may cause phenological variations, especially in the Alps which are considered to be extremely vulnerable to global warming. The main goal of our study is to analyze European larch (Larix decidua Mill.) phenology in alpine environments and the role of the ecological factors involved, using an integrated approach based on accurate field observations and modelling techniques. We present 2 years of field-collected larch phenological data, obtained following a specifically designed observation protocol. We observed that both spring and autumn larch phenology is strongly influenced by altitude. We propose an approach for the optimization of a spring warming model (SW) and the growing season index model (GSI) consisting of a model inversion technique, based on simulated look-up tables (LUTs), that provides robust parameter estimates. The optimized models showed excellent agreement between modelled and observed data: the SW model predicts the beginning of the growing season (B(GS)) with a mean RMSE of 4 days, while GSI gives a prediction of the growing season length (L(GS)) with a RMSE of 5 days. Moreover, we showed that the original GSI parameters led to consistent errors, while the optimized ones significantly increased model accuracy. Finally, we used GSI to investigate interactions of ecological factors during springtime development and autumn senescence. We found that temperature is the most effective factor during spring recovery while photoperiod plays an important role during autumn senescence: photoperiod shows a contrasting effect with altitude decreasing its influence with increasing altitude.

Ochratoxin A determination in ham by immunoaffinity clean-up and a quick fluorometric method.

A simple and rapid method for the determination of ochratoxin A (OA) in ham was developed using a basic methanolic extraction, immunoaffinity column clean-up and a fluorometric determination of the toxin contamination levels. A mean recovery of OA from ham samples spiked at levels from 0.7 to 9.7 microg kg(-1) was 83 +/- 6% using the fluorometric method, with a detection limit of 0.7 microg kg(-1). Recovery data were compared statistically with those obtained using reversed-phase high-performance liquid chromatography with acetonitrile-water-acetic acid (99:99:2) as mobile phase and fluorescence detection, commonly used for OA determination in food. A good correlation between the two analytical techniques was obtained. Both methods were successfully applied to 42 ham samples, 21 in the middle of the ripening period (after 6 months from the process beginning) and the other 21 at the end of the maturation, after 12 months. Twenty-seven samples (64%) showed an OA contamination level <1.0 microg kg(-1), the Italian Ministry of Health guideline. The maximum contamination level found was 2.3 microg kg(-1). A good agreement (R(2) = 0.980) between HPLC and fluorometer analysis on naturally contaminated samples was obtained.