Acute Reduction of Anandamide‐Hydrolase (FAAH) Activity is Coupled With a Reduction of Nociceptive Pathways Facilitation in Medication‐Overuse Headache Subjects After Withdrawal Treatment

Objectives.— We investigated (1) a possible relationship between the functional activity of the endocannabinoid system and the facilitation of pain processing in migraineurs with medication‐overuse headache, and (2) the effect of withdrawal treatment on both. Background.— The endocannabinoid system antinociception effect includes prevention of nociceptive pathways sensitization. The sensitization of the pain pathways has been demonstrated to be pivotal in the development and maintenance of chronic form of migraine, including medication‐overuse headache. Methods.— We used the temporal summation threshold of the nociceptive withdrawal reflex to explore the spinal cord pain processing, and the platelet activity of the enzyme fatty acid amide hydrolase to detect the functional state of the endocannabinoid system in 27 medication‐overuse headache subjects before and 10 and 60 days after a standard withdrawal treatment and compared results with those of 14 controls. Results.— A significantly reduced temporal summation threshold and increased related pain sensation was found in subjects before withdrawal treatment when compared with controls. A significant fatty acid amide hydrolase activity reduction coupled with a significant improvement (reduction) in facilitation of spinal cord pain processing (increase in temporal summation threshold and reduction in related pain sensation) was found in medication‐overuse headache subjects at both 10 and 60 days after withdrawal treatment when compared with medication‐overuse headache subjects before withdrawal treatment. Conclusions.— We demonstrated a marked facilitation in spinal cord pain processing in medication‐overuse headache before withdrawal treatment when compared with controls. Furthermore, the acute reduction of the fatty acid amide hydrolase activity coupled with a reduction of the facilitation in pain processing immediately (10 days) after withdrawal treatment and its persistence 60 days after withdrawal treatment could represent the consequence of a mechanism devoted to acutely reduce the degradation of endocannabinoids and aimed to increase the activity of the endocannabinoid system that results in an antinociceptive effect.     

Angiopoietin-like 4 Stimulates STAT3-mediated iNOS Expression and Enhances Angiogenesis to Accelerate Wound Healing in Diabetic Mice

Impaired wound healing is a major source of morbidity in diabetic patients. Poor outcome has, in part, been related to increased inflammation, poor angiogenesis, and deficiencies in extracellular matrix components. Despite the enormous impact of these chronic wounds, effective therapies are lacking. Here, we showed that the topical application of recombinant matricellular protein angiopoietin-like 4 (ANGPTL4) accelerated wound reepithelialization in diabetic mice, in part, by improving angiogenesis. ANGPTL4 expression is markedly elevated upon normal wound injury. In contrast, ANGPTL4 expression remains low throughout the healing period in diabetic wounds. Exogenous ANGPTL4 modulated several regulatory networks involved in cell migration, angiogenesis, and inflammation, as evidenced by an altered gene expression signature. ANGPTL4 influenced the expression profile of endothelial-specific CD31 in diabetic wounds, returning its profile to that observed in wild-type wounds. We showed ANGPTL4-induced nitric oxide production through an integrin/JAK/STAT3-mediated upregulation of inducible nitric oxide synthase (iNOS) expression in wound epithelia, thus revealing a hitherto unknown mechanism by which ANGPTL4 regulated angiogenesis via keratinocyte-to-endothelial-cell communication. These data show that the replacement of ANGPTL4 may be an effective adjunctive or new therapeutic avenue for treating poor healing wounds. The present finding also confirms that therapeutic angiogenesis remains an attractive treatment modality for diabetic wound healing.     

Fading an Auditory Model by Volume to Teach Mands to Children with Autism Spectrum Disorder

The effectiveness of an audio model faded by volume on manding for materials was evaluated within an interrupted behavior chain with two children with autism. Behavior chains were interrupted to contrive an establishing operation (EO) by providing broken items and were interspersed with abolishing operation (AO) trials. An auditory model to teach mands was faded systematically by volume. Using a multiple probe design across three preferred activities, it was found that both participants were manded for some items in the absence of an audio prompt after it was faded systematically. Following the introduction of a prompt delay, participants learned to mand across remaining targets. Across participants, manding generalized to a novel interruption form (i.e., in sight but out of reach materials), to novel materials, and were maintained. Goals, procedures, and outcomes of the intervention were rated socially valid by clinicians.     

Effect of photoactivation on the reduction of composite resin contamination

Composite resins are predominantly marketed in developing countries in tube form, and the contents of the tube may be used in numerous procedures for different patients. This represents a problem because of the risk of cross‐contamination. This study aimed to evaluate contamination in vitro of the internal contents of composite resin tubes in the dental clinics of a higher‐education institution, as well as the effect of photoactivation on the level of contamination. Twenty‐five tubes containing composite resin were randomly chosen (by lottery). From each tube, two samples of approximately 2 mm of composite resin were removed, and then one sample, but not the other, was photoactivated. These samples were plated on Brain–Heart Infusion (BHI), Sabouraud and MacConkey agars, and the plates were incubated at 37°C for 24–48 h. Colony counting and Gram staining were performed for subsequent microscopic identification of fungi and bacteria. The non‐photoactivated composite resin group presented significantly higher microbial contamination in relation to the photoactivated composite resin group. The photoactivation of camphorquinone present in composite resin produces reactive oxygen species, which might promote cell death of contaminant microorganisms. Thus, although the same tube of composite resin may be used for a number of different patients in the dental clinics of developing countries, the photoactivation process potentially reduces the risk of cross‐contamination.