Porous materials as carriers of gasotransmitters towards gas biology and therapeutic applications.

The discovery of NO, CO, and H2S as gasotransmitters and their beneficial role in multiple physiological functions opened an era of research devoted to exogenously delivering them as therapeutic agents. However, the gaseous nature of these molecules demands new forms of administration that enable one to control the location, dosage and timing of their delivery. Porous materials are among the most suitable scaffolds to store, deliver and release gasotransmitters due to their high surface area, tunable composition and reactivity. This review highlights the strategies employed to load and release gasotransmitters from different kinds of porous materials, including zeolites, mesoporous silica, metal-organic frameworks and protein assemblies.

Light responsive metal-organic frameworks as controllable CO-releasing cell culture substrates.

A new carbon monoxide (CO)-releasing material has been developed by embedding a manganese carbonyl complex, MnBr(bpydc)(CO)3 (bpydc = 5,5'-dicarboxylate-2,2'-bipyridine) into a highly robust Zr(iv)-based metal-organic framework (MOF). Efficient and controllable CO-release was achieved under exposure to low intensity visible light. Size-controllable nanocrystals of the photoactive MOF were obtained and their CO-releasing properties were correlated with their crystal sizes. The photoactive crystals were processed into cellular substrates with a biocompatible polymer matrix, and the light-induced delivery of CO and its subsequent cellular uptake were monitored using a fluorescent CO-probe. The results discussed here demonstrate a new opportunity to use MOFs as macromolecular scaffolds towards CO-releasing materials and the advantage of MOFs for high CO payloads, which is essential in future therapeutic applications.

Light-induced nitric oxide release from physiologically stable porous coordination polymers.

The development of nitric oxide (NO) releasing materials has been of significant importance due to their application in cell biology and biomedicine. Besides the macromolecular scaffold dangling NO releasing moiety, porous materials have been used to host such NO releasing molecules. Here we synthesized a series of porous coordination polymers (PCPs), in which N-nitrosamine functional groups as photoactive NO donors were introduced into the framework scaffolds by post-synthetic nitrosation of amine functionalized analogous PCPs. We further demonstrated a controlled release of NO from the PCPs by light irradiation. Though isoreticular frameworks based on octanuclear clusters of titanium or aluminium ions were chosen due to their water-stability, the frameworks showed difference in stability in cell culture media; while aluminium frameworks were less stable in water and physiological media, the titanium analogue was highly stable even under physiological conditions.

Localized cell stimulation by nitric oxide using a photoactive porous coordination polymer platform.

Functional cellular substrates for localized cell stimulation by small molecules provide an opportunity to control and monitor cell signalling networks chemically in time and space. However, despite improvements in the controlled delivery of bioactive compounds, the precise localization of gaseous biomolecules at the single-cell level remains challenging. Here we target nitric oxide, a crucial signalling molecule with site-specific and concentration-dependent activities, and we report a synthetic strategy for developing spatiotemporally controllable nitric oxide-releasing platforms based on photoactive porous coordination polymers. By organizing molecules with poor reactivity into polymer structures, we observe increased photoreactivity and adjustable release using light irradiation. We embed photoactive polymer crystals in a biocompatible matrix and achieve precisely controlled nitric oxide delivery at the cellular level via localized two-photon laser activation. The biological relevance of the exogenous nitric oxide produced by this strategy is evidenced by an intracellular change in calcium concentration, mediated by nitric oxide-responsive plasma membrane channel proteins.

Programmed crystallization via epitaxial growth and ligand replacement towards hybridizing porous coordination polymer crystals.

Hybridized porous coordination polymers (PCPs) are synthesized through epitaxial growth or ligand replacement. Whereas epitaxial growth on the core crystal leads to a sandwich type PCP, ligand replacement near the surface of core crystal results in a core-shell type PCP.

The effect of OROS methylphenidate on the sleep of children with attention-deficit/hyperactivity disorder.

We evaluated the effect of OROS methylphenidate (MPH) on sleep quality and architecture in children with attention-deficit/hyperactivity disorder (ADHD) using both a parental sleep questionnaire and polysomnography. Twenty-four ADHD children who had no comorbid psychiatric or sleep disorders except for oppositional defiant disorder completed the 6-week, prospective, open-label, flexible-dose trial with OROS MPH (Concerta) monotherapy. After OROS MPH administration, the polysomnography data indicated that the percentage of stage 2 sleep was increased (P=0.024) and the Number of Awakenings was decreased (P=0.047). Relative to baseline, Parasomnias of the Children's Sleep Habits Questionnaire were decreased (P=0.033). Sleep Onset Latency was not changed during the treatment in general, but was increased in six children with subjective sleep difficulties (F(1)=5.832, P=0.025, eta(2)(p)=0.226). Bedtime Resistance and Sleep Onset Delay in Children's Sleep Habits Questionnaire were also increased during the treatment with OROS MPH only in individuals with sleep complaints (F1=5.001, P=0.036, eta(2)(p)=0.185; F(1)=7.237, P=0.013, eta(2)(p)=0.248). These results suggest that OROS MPH in open-label treatment does not seem to impair sleep and may even improve some aspects of sleep.

Multi-level comparison of empathy in schizophrenia: an fMRI study of a cartoon task.

Empathy deficits might play a role in social dysfunction in schizophrenia. However, few studies have investigated the neuroanatomical underpinnings of the subcomponents of empathy in schizophrenia. This study investigated the hemodynamic responses to three subcomponents of empathy in patients with schizophrenia (N=15) and healthy volunteers (N=18), performing an empathy cartoon task during functional magnetic resonance imaging. The experiment used a block design with four conditions: cognitive, emotional, and inhibitory empathy, and physical causality control. Data were analyzed by comparing the blood-oxygen-level-dependent (BOLD) signal activation between the two groups. The cognitive empathy condition activated the right temporal pole to a lesser extent in the patient group than in comparison subjects. In the emotional and inhibitory conditions, the patients showed greater activation in the left insula and in the right middle/inferior frontal cortex, respectively. These findings add to our understanding of the impaired empathy in patients with schizophrenia by identifying a multi-level cortical dysfunction that underlies a deficit in each subcomponent of empathy and highlighting the importance of the fronto-temporal cortical network in ability to empathize.

Thalamus surface shape deformity in obsessive-compulsive disorder and schizophrenia.

The authors performed a three-dimensional shape deformation analysis to clarify the various patterns of specific thalamic nuclei abnormality using three age-matched and sex-matched groups of 22 patients with obsessive-compulsive disorder (OCD), 22 patients with schizophrenia and 22 control participants. Compared with the healthy volunteers, the anterior, lateral outward surface deformities of the thalamus were significant in OCD patients, whereas the posterior, medial outward deformities of the thalamus were prominent in schizophrenia patients. In terms of thalamic asymmetry, both OCD and schizophrenia patients exhibited the loss of a leftward pattern of asymmetry on the posterior, medial surface of the thalamus. Different patterns of shape abnormality of specific thalamic nuclei may be related to the different phenomenology of OCD and schizophrenia.

Shape deformity of the corpus striatum in obsessive-compulsive disorder.

Volumetric changes of striatal structures based on magnetic resonance imaging (MRI) have been inconsistent in patients with obsessive-compulsive disorder (OCD) due to methodological limitations. The purpose of this study was to investigate shape deformities of the corpus striatum in patients with OCD. We performed 3-D shape deformation analysis of the caudate nucleus, the putamen, and the globus pallidus in 36 patients with OCD and 36 healthy normal subjects. Shape analysis showed deformity of the striatal structures, especially the caudate nucleus. Outward deformities in the superior, anterior portion of the bilateral caudate were observed in patients with OCD. In addition, an outward deformity in the inferior, lateral portion of the left putamen was also detected. These results suggest that patients with OCD have shape deformities of the corpus striatum, especially the caudate nucleus, compared with healthy normal subjects, and that shape analysis may provide an important complement to volumetric MRI studies in investigating the pathophysiology of OCD.

Volumetric investigation of the frontal-subcortical circuitry in patients with obsessive-compulsive disorder.

The pathophysiology of obsessive-compulsive disorder (OCD) is thought to involve disturbance of the frontal-subcortical circuitry. To investigate the morphological characteristics of this circuitry, we examined the volume of the orbitofrontal cortex, anterior cingulate, thalamus, caudate, and the putamen in 36 age- and sex-matched OCD patients and normal control subjects using three-dimensional magnetic resonance (MR) brain imaging. The left orbitofrontal volumes were found to be significantly smaller in the OCD patients and showed significant negative correlations with obsessive-compulsive symptom severity. These findings suggest that a structural abnormality of this brain region is implicated in the pathophysiology of OCD.