Region-specific control of microglia by adenosine A2A receptors: uncoupling anxiety and associated cognitive deficits in female rats

Epidemiologic studies have provided compelling evidence that prenatal stress, through excessive maternal glucocorticoids exposure, is associated with psychiatric disorders later in life. We have recently reported that anxiety associated with prenatal exposure to dexamethasone (DEX, a synthetic glucocorticoid) correlates with a gender-specific remodeling of microglia in the medial prefrontal cortex (mPFC), a core brain region in anxiety-related disorders. Gender differences in microglia morphology, the higher prevalence of anxiety in women and the negative impact of anxiety in cognition, led us to specifically evaluate cognitive behavior and associated circuits (namely mPFC-dorsal hippocampus, dHIP), as well as microglia morphology in female rats prenatally exposed to dexamethasone (in utero DEX, iuDEX). We report that iuDEX impaired recognition memory and deteriorated neuronal synchronization between mPFC and dHIP. These functional deficits are paralleled by microglia hyper-ramification in the dHIP and decreased ramification in the mPFC, showing a heterogeneous remodeling of microglia morphology, both postnatally and at adulthood in different brain regions, that differently affect mood and cognition. The chronic blockade of adenosine A_2A receptors (A_2AR), which are core regulators of microglia morphology and physiology, ameliorated the cognitive deficits, but not the anxiety-like behavior. Notably, A_2AR blockade rectified both microglia morphology in the dHIP and the lack of mPFC-dHIP synchronization, further heralding their role in cognitive function.     

A Double‐Blind,Randomized, Placebo and Active‐Controlled Study of Nebicapone for the Treatment of Motor Fluctuations in Parkinson's Disease

To determine the efficacy, safety and tolerability of nebicapone, a new catechol‐O‐methyltransferase inhibitor for the treatment of motor fluctuations in Parkinson's disease (PD), we conducted a multicenter, randomized, 8‐week double‐blind, placebo‐ and active‐controlled, parallel‐group study comparing nebicapone 50 mg, 100 mg, or 150 mg, entacapone 200 mg (active control) or placebo administered concomitantly with levodopa/carbidopa or levodopa/benserazide. Two hundred and fifty‐two PD patients with motor fluctuations treated with levodopa/carbidopa or levodopa/benserazide (4–8 daily doses) were enrolled and 250 patients were eligible for intention‐to‐treat (ITT) analysis on the basis of having at least one efficacy assessment. The primary endpoint was 8‐week change from baseline in absolute “Off” time duration noted in self‐scoring diaries. At 8 weeks of treatment the mean daily “Off” time decreased significantly compared to placebo for nebicapone 150 mg (?106 min; 95%CI: ?192; ?21) and entacapone 200 mg (?81 min; 95%CI: ?142; ?19). The decrease in “Off” time with nebicapone 50 mg or 100 mg did not reach statistical significance. Treatment‐emergent adverse events were reported by 32% to 49% of patients in any treatment group, with no observed dose relationship in the nebicapone groups. Clinically relevant elevations in aspartate transaminase (AST) and/or alanine transaminase (ALT) were observed in 4 of 46 patients with the nebicapone 150 mg dose. The results of this study show that nebicapone 150 mg is efficacious for the treatment of motor fluctuations in PD patients. However, the risk of increasing liver transaminases and its clinically relevance deserves further evaluation.     

Acrodermatitis enteropathica in a full-term breast-fed infant: case report and literature review

A male full‐term infant, who had been exclusively breast‐fed since birth, at 2 months of age developed an erythematous, scaling eruption involving the face (in a periorificial distribution, i.e. mouth, nose, ears, and eyes), hands, and feet, which did not respond to treatment with topical corticosteroids and oral antimicrobials. He was first seen at our institution at 5 months of age ( Figs 1 and 2 ). He had been irritable for the last 2 weeks, but had no diarrhea, alopecia, or anogenital lesions. A clinical diagnosis of acrodermatitis enteropathica was confirmed with a serum zinc level of 41.2 µg/dL (normal, 70–120 µg/dL). His mother had low–normal serum (70.5 µg/dL; normal, 70–120 µg/dL) and normal milk (0.43 µg/mL; normal, 0.2–0.72 µg/mL) zinc concentrations. Within 7 days of starting therapy with zinc sulfate, 10 mg/kg/day, all cutaneous lesions had resolved ( Fig. 3 ).

Figure 1 Open in figure viewer PowerPoint Infant at 5 months of age showing an erythematous, scaling eruption involving the face (periorificial distribution, i.e. mouth, nose, and eyes) and hands     

Changes in serotoninergic and noradrenergic descending pain pathways during painful diabetic neuropathy: the preventive action of IGF1

Painful diabetic neuropathy (PDN) induces neuronal hyperactivity at the spinal cord and periaqueductal gray (PAG), a key area in descending nociceptive modulation. Since the PAG uses relay stations at serotoninergic and noradrenergic brainstem areas, we determined the serotonin and noradrenaline levels at the spinal cord of streptozotocin-diabetic rats and at those brainstem areas (serotoninergic rostroventromedial medulla and noradrenergic A(5) and A(7) cell groups). Since, during diabetes, the levels of insulin growth factor 1 (IGF1) decrease, reducing its neurotrophic effect in the brain, we also studied the effects of IGF1 treatment. One week after diabetes induction, subcutaneous injections of IGF1 (2.5mg/kg) were performed during 3 weeks. Body weights, glycemia, and mechanical nociception were weekly evaluated until the end of the study, the time when the animals were subjected to a modified formalin test to study chemical allodynia. Serotonin and noradrenaline levels were quantified by ELISA at the spinal cord, whereas at the brainstem, the quantification was performed by immunohistochemistry against, respectively, tryptophan hydroxylase (TpH) or tyrosine hydroxylase (TH). STZ-diabetic rats exhibited mechanical hyperalgesia and chemical allodynia, along with higher spinal levels of serotonin and noradrenaline and higher numbers of neurons expressing TpH at the RVM and TH at the A(5) noradrenergic cell group. Treatment with IGF1 prevented the behavioral signs of PDN and reversed the neuronal hyperactivity at the spinal cord and ventrolateral PAG and the neurochemical changes at the spinal cord and at the brainstem. Based on the facilitatory role of serotoninergic and noradrenergic descending modulation during chronic pain, the increased serotonin and noradrenaline innervation of the dorsal horn in STZ-diabetic rats may probably account for enhanced pain during PDN. The benefits of IGF1 in PDN are probably due to blockade of the increased peripheral input to the somatosensory system, but direct central actions cannot be discarded. The value of IGF1 in PDN treatment deserves further evaluation.     

Composite resin color stability: influence of light sources and immersion media

Objective

This study evaluated the influence of light sources and immersion media on the color stability of a nanofilled composite resin.

Material and Methods

Conventional halogen, high-power-density halogen and high-power-density light-emitting diode (LED) units were used. There were 4 immersion media: coffee, tea, Coke^® and artificial saliva. A total of 180 specimens (10 mm x 2 mm) were prepared, immersed in artificial saliva for 24 h at 37±1ºC, and had their initial color measured with a spectrophotometer according to the CIELab system. Then, the specimens were immersed in the 4 media during 60 days. Data from the color change and luminosity were collected and subjected to statistical analysis by the Kruskall-Wallis test (p<0.05). For immersion time, the data were subjected to two-way ANOVA test and Fisher''s test (p<0.05).

Results

High-power-density LED (∆E=1.91) promoted similar color stability of the composite resin to that of the tested halogen curing units (Jet Lite 4000 plus - ∆E=2.05; XL 3000 - ∆E=2.28). Coffee (∆E=8.40; ∆L=-5.21) showed the highest influence on color stability of the studied composite resin.

Conclusion

There was no significant difference in color stability regardless of the light sources, and coffee was the immersion medium that promoted the highest color changes on the tested composite resin.     

Herpes simplex virus 2 vasculitis as cause of ischemic stroke in a young immunocompromised patient

Journal of NeuroVirology - Herpes simplex virus 2 (HSV-2) is a very rare cause of central nervous system (CNS) infections. We report a case of a young woman with a left middle cerebral artery (MCA)...     

Grafts of porcine intestinal submucosa for repair of cervical and abdominal esophageal defects in the rat.

Porcine small intestinal submucosa (SIS) is a cell-free collagen matrix that has demonstrated its ability as scaffold material for constructive remodeling of damaged or missing tissue. The purpose of this study was to evaluate the morphology and function of esophagoplasty in rat using a porcine SIS scaffold for the repair of a semi-circumferential defect in the cervical or in the abdominal esophagus. Sixty-seven rats underwent surgical excision of the anterior wall either of the cervical or of the abdominal esophagus and subsequent repair of the defect with an SIS patch graft. Outcomes of weight gain, signs of dysphagia, hematological and serum chemistry parameters, and barium swallow studies were used to assess the progress of healing and function over a 150-day time period. The grafts were studied for gross changes and histology at predetermined time points. Ninety-four percent of the SIS-treated rats survived, showing no significant differences in survival rate between groups. The grafted animals did well, without signs of dysphagia, and gaining weight. Barium swallow studies showed no evidence of fistula, significant stenosis, or diverticula. No hematological or serum biochemistry abnormalities were found. By 150 days, the SIS graft was replaced with esophageal-derived tissues. Specimens were completely lined by keratinized stratified squamous epithelium and showed complete regeneration of muscle fibers and scarce immunoreactivity for nerve. In the rat model, a patch graft technique using porcine SIS appears to induce esophageal regrowth either in cervical and abdominal esophagus. The repair mechanism occurred through a regenerative healing process.