Michele Grassi

Drug mechanochemical activation

The aim of this review is to describe the theoretical background lying behind the solid drug mechanochemical activation by cogrinding pointing out its advantages and drawbacks. A brief historical introduction precedes the discussion about the mechanisms leading to solid drug activation. This allows to clarify the concept of solid activation whose main effect is to improve drug solubility and, thus, drug bioavailability. Then, the attention is focused on the experimental tools used to evaluate drug activation before the in vivo use. This, of course, permits to properly modulate the milling conditions (milling time, mill revolution speed, drug/carrier ratio and so on) in the light of the optimisation of milling process and activated system properties. Thereafter, the discussion shifts on the different kinds of mills that can be used and on mills classification based on the energy transferred to the materials. Fundamental tool to perform this task is the mathematical modelling of mill dynamics that is here shown for different mills kinds. Finally, some examples of activated systems performance both in vitro and in vivo are presented and discussed. In conclusion, mechanochemical activation improves drug bioavailability. Interestingly, this activation does not require the use of solvents whose elimination from the activated product can be difficult and expensive but a relatively simple mechanical treatment. On the other hand, this approach, usually, works only for poorly water soluble drugs (solubility <100 microg/mL) that do not exhibit permeability problems.

CircE: An R implementation of Browne’s circular stochastic process model

In confirmatory analysis of whether data have a circumplex structure, Browne’s (1992) model has played a major role. However, implementation of this model requires a dedicated program, CIRCUM, because the analysis routine is not integrated in any of the most widely used statistical software packages. Hence, data entry and graphical representation of the results require the use of one or more additional programs. We propose a package for the R statistical environment, termed CircE, that can be used to enter or import data, implement Browne’s confirmatory analysis, and graphically represent the results. Using this new software, we put forward a new approach to assess the sustainability of theoretical models when the analysis is carried out at the level of questionnaire items. The CircE package (for either Mac OS X or Windows) and additional files may be downloaded from http://brm.psychonomic-journals.org/content/supplemental.

Characterization of nucleic acid molecule/liposome complexes and rheological effects on pluronic/alginate matrices

The delivery of short nucleic acid molecules (NAM), complexed with liposomes, to diseased vessel walls is dramatically limited by blood wash. We thus started investigations to study the possibility of embedding NAM/liposome complexes into a novel polymeric blend focusing attention on their effects on the rheological properties of the selected polymeric blend. Two different liposomes, able to transduce NAM efficiently into vascular smooth muscle cells, were embedded into a thermosensitive alginate/pluronic polymeric blend. Liposome particles, with and without NAM, were characterized for their sizes, superficial charges, morphologies and initial delivery studies performed in vitro. Whereas both liposomes with and without NAM do not substantially affect the final polymeric blend properties, NAM presence differentially influences the structuring process. This behavior is attributed both to particle sizes and superficial charge, with this last parameter appearing more relevant. Moreover, the presence of the polymeric blend substantially retards the delivery of NAM/liposome to vascular smooth muscle cells. In conclusion, our results indicate that both types of liposome/NAM complexes are suitable for the development of a delivery system for NAM-liposome complexes to vessel walls.

Sustained-release solid dispersions of ibuprofen prepared by microwave irradiation

The paper is devoted to the investigation of microwave irradiation (MW) for the preparation of solvent free solid dispersion (SD). Precisely, sustained release solid dispersions containing different drug-to-polymer ratios were developed by means of microwave technology using ibuprofen (IBU) as a model drug and glyceryl monostarate (Imwitor 900, GM) as a lipophilic sustained release agent. Their physical characterizations were determined by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), hot-stage microscopy (HSM). Through the dissolution rates studies, the in vitro drug performance of the SD was evaluated. The physical characterizations revealed a substantial correspondence of the drug solid state before and after MW treatment while drug-carrier interactions in the SD were attested. The dissolution studies of the irradiated samples showed that the matrices based on Imwitor 900 were able to promote a sustained release of the drug. A mathematical approach suggested that IBU release from solid dispersion was essentially due to matrix erosion. In conclusion we can affirm that the microwave technique could be considered as a new and interesting method to prepare drug-carrier systems.

Action Observation Plus Sonification. A Novel Therapeutic Protocol for Parkinson’s Patient with Freezing of Gait

Freezing of gait (FoG) is a disabling symptom associated with falls, with little or no responsiveness to pharmacological treatment. Current protocols used for rehabilitation are based on the use of external sensory cues. However, cued strategies might generate an important dependence on the environment. Teaching motor strategies without cues [i.e., action observation (AO) plus Sonification] could represent an alternative/innovative approach to rehabilitation that matters most on appropriate allocation of attention and lightening cognitive load. We aimed to test the effects of a novel experimental protocol to treat patients with Parkinson’s disease (PD) and FoG, using functional, and clinical scales. The experimental protocol was based on AO plus Sonification. 12 patients were treated with 8 motor gestures. They watched eight videos showing an actor performing the same eight gestures, and then tried to repeat each gesture. Each video was composed by images and sounds of the gestures. By means of the Sonification technique, the sounds of gestures were obtained by transforming kinematic data (velocity) recorded during gesture execution, into pitch variations. The same 8 motor gestures were also used in a second group of 10 patients; which were treated with a standard protocol based on a common sensory stimulation method. All patients were tested with functional and clinical scales before, after, at 1 month, and 3 months after the treatment. Data showed that the experimental protocol have positive effects on functional and clinical tests. In comparison with the baseline evaluations, significant performance improvements were seen in the NFOG questionnaire, and the UPDRS (parts II and III). Importantly, all these improvements were consistently observed at the end, 1 month, and 3 months after treatment. No improvement effects were found in the group of patients treated with the standard protocol. These data suggest that a multisensory approach based on AO plus Sonification, with the two stimuli semantically related, could help PD patients with FoG to relearn gait movements, to reduce freezing episodes, and that these effects could be prolonged over time.

Assessing the Interpersonal Circumplex Model in Late Childhood The Interpersonal Behavior Questionnaire for Children

The authors developed the Interpersonal Behavior Questionnaire for Children with the aim of assessing the constructs of the interpersonal circumplex model, that is, Dominance and Love and their possible combinations, via third- to fifth-grade children’s self- and peer reports. In the three studies presented herein, the authors examined several psychometric properties of the questionnaire. Results demonstrated that children’s ratings along the questionnaire yielded the hypothesized circumplex structure of the interpersonal variables; that they reached significant association levels with external criteria; and that they were reliable. Specifically, interrater correlations were shown to reach substantive levels when inspected in older children, when scores were aggregated over raters, and when dominant behaviors were evaluated. Overall, the findings demonstrated the tenability of the circumplex model in young ages via children’s ratings. The authors suggest that both personality assessment and personality development research may take advantage from using children’s evaluations, in addition to adults’ ratings of their children’s personality.

New multidrug (dexamethasone and theophylline) PEG-conjugate: synthesis, in vitro release studies and intestinal permeability

A branched high-molecular weight multimeric PEG (MultiPEG), synthesized with a simple assembling procedure that devised the introduction of functional groups with divergent and selective reactivity, was employed as a drug carrier. Dexamethasone (DXM) and theophylline (THEO), examples of different but synergistic drugs, were covalently linked to the same MultiPEG unit. The hydrolytic stability of the mixed MultiPEG-conjugate (DXM-MultiPEG-THEO8) was evaluated at physiological pH, in an artificial gastric juice, in simulated duodenal fluids and in mouse plasma. The results demonstrated that this new branched PEG conjugate exhibited a slow degradation rate in simulated gastro-intestinal fluids, while in plasma a more rapid breakdown was observed. The permeation process across the intestinal membrane of the same macromolecular conjugate was investigated, mathematically discussed and interpreted according to “Fick’s law”.

Postural control deficit during sit-to-walk in patients with Parkinson’s disease and freezing of gait

INTRODUCTION The intricate linkage between Freezing of Gait (FoG) and postural control in Parkinsons disease (PD) is unclear. We analyzed the impact of FoG on dynamic postural control. METHODS 24 PD patients, 12 with (PD + FoG), 12 without FoG (PD-FoG), and 12 healthy controls, were assessed in ON state. Mobility and postural control were measured with clinical scales (UPDRS III, BBS, MPAS) and with kinematic and kinetic analysis during three tasks, characterized by levels of increasing difficulty to plan sequential movement of postural control: walk (W), gait initiation (GI) and sit-to-walk (STW). RESULTS The groups were balanced by age, disease duration, disease severity, mobility and balance. During STW, the spatial distribution of COP trajectories in PD + FoG patients are spread over medial-lateral space more than in the PD-FoG (p < .001). Moreover, the distribution of COP positions. in the transition between sit-to-stand and gait initiation, is not properly shifted toward the leading leg, as in PD-FoG and healthy controls, but it is more centrally dispersed (p < .01) with a delayed weight forward progression (p < .05). In GI task and walk task, COM and COP differences are less evident and even absent between PD patients. CONCLUSION PD + FoG show postural control differences in STW, compared with PD-FoG and healthy. Different spatial distribution of COP trajectories, between two PD groups are probably due to a deficit to plan postural control during a more demanding motor pattern, such as STW.

Imagined Intergroup Physical Contact Improves Attitudes Toward Immigrants

In this set of research, we investigated the effects of intergroup physical contact on intergroup attitudes by relying on indirect contact strategies, namely the imagined contact paradigm. We implemented the imagined contact paradigm by leading participants to shape the mental imagery upon pictorial information. Specifically, in Study 1 participants saw a picture of a white hand touching a black hand [i.e., intergroup physical contact condition (InterPC)] or a picture of an outdoor scene (i.e., control condition), and were asked to imagine being either the toucher or in the outdoor scene, respectively. Results demonstrated that InterPC compared to control condition reduced intergroup bias. In Study 2 we compared the InterPC condition to a condition in which participants saw a white hand touching another white hand [i.e., intragroup physical contact (IntraPC)], and imagined to be the toucher. Again, we found that participants in the InterPC condition showed reduced intergroup bias compared to the IntraPC. Study 3 replicated results of Studies 1 and 2 by using an implicit measure of prejudice. Also, Study 3 further showed that asking participants to merely look at the picture of a white hand touching a black hand, without imagining being the toucher was not effective in reducing implicit prejudice. Results were discussed with respect to the literature on physical contact and prejudice reduction processes.