Late Onset of Chronic Granulomatous Disease Revealed by Paecilomyces lilacinus Cutaneous Infection

Chronic granulomatous disease (CGD) is an inherited immunodeficiency due to defective leukocyte NADPH responsible for recurrent infections and aberrant inflammation. Mutations in the CYBB gene are responsible for the X-linked CGD and account for approximately 70% of the cases. CGD is diagnosed during childhood in males. Female carriers may have biased X-inactivation and may present with clinical manifestations depending on the level of residual NADPH oxidase activity. We report the case of a previously asymptomatic female carrier who was diagnosed at age 67 with a skin infection with the rare fungus Paecilomyces lilacinus as the first manifestation of CGD. Dihydrorhodamine 123 (DHR) activity was below 10%. Next-generation sequencing (NGS) revealed mutations in DNMT3A, ASXL1, and STAG2 suggesting that clonal hematopoiesis could be responsible for a progressive loss of NADPH oxidase activity and the late onset of X-linked CGD in this patient. Long-term follow-up of asymptomatic carrier women seems to be essential after 50 years old.

     

Cannabidiol reverses the mCPP‐induced increase in marble‐burying behavior

Cannabidiol (CBD), one of the main components of Cannabis sp., presents clinical and preclinical anxiolytic properties. Recent results using the marble‐burying test (MBT) suggest that CBD can also induce anticompulsive‐like effects. Meta‐chloro‐phenyl‐piperazine (mCPP) is a nonspecific serotonergic agonist (acting mainly at 5HT1A, 5HT2C and 5HT1D receptors) reported to increase symptoms in OCD patients and block the anticompulsive‐like effect of serotonin reuptake inhibitors (SRIs) in animal models. The aim of this study was to investigate the interference of CBD on mCPP effects in repetitive burying. Administration of mCPP showed dual effects in the MBT, increasing the number of buried marbles at lower (0.1 mg/kg) while decreasing it at higher doses (1 mg/kg), an effect not related to a general increase in anxiety‐like behavior. As found previously, CBD (30 mg/kg) and the positive control fluoxetine (FLX; 10 mg/kg) decreased burying behavior without changing general exploratory activity. A similar effect was found when subeffective doses of CBD (15 mg/kg) and FLX (3 mg/kg) were administered together. These subeffective doses alone were also able to block mCPP‐induced repetitive burying. The results, in addition to reinforcing a possible anticompulsive effect of CBD, also suggest that mCPP‐induced repetitive burying could be a useful test for the screening of compounds with presumed anticompulsive properties.     

When is injury potentially reversible in a lung ischemia–reperfusion model?

ObjectiveTo verify the impact of ischemic time on lung cell viability in an experimental model of lung ischemia–reperfusion (IR) injury and its repercussion on lung performance after reperfusion.MethodsTwenty-four animals were subjected to selective clamping of the left pulmonary artery and divided into four groups (n = 6) according to ischemic time: 15 (IR15), 30 (IR30), 45 (IR45), and 60 min (IR60). All animals were observed for 120 min after reperfusion. The hemodynamics, arterial blood gases measurements, and histologic changes were analyzed. Immunofluorescence assays for caspase 3 and annexin V were performed. Lipid peroxidation was assessed by thiobarbituric acid–reactive substances, and caspase 3 activity was assessed by colorimetric extract.ResultsThe partial pressure of arterial oxygen significantly decreased at the end of the observation period in the IR30, IR45, and IR60 groups (P < 0.05). The final mean arterial pressure significantly decreased in the IR60 group (P < 0.05). We observed a significant increase in caspase 3 activity and caspase 3–positive cells by immunofluorescence in the IR45 group compared with the other groups (P < 0.05). Additionally, there was an increase in necrotic cells assessed by annexin V in the IR60 group. The histologic score did not show differences among the different groups.ConclusionsThe degree of cell damage had a negative impact on lung performance. Sixty minutes of lung ischemia and posterior reperfusion resulted in an increased number of necrotic cells, suggesting that these cells may not be able to reverse the effects of the IR injury because of the lack of viable cells.     

COX-2 as a determinant of lower disease-free survival for patients affected by ameloblastoma

Ameloblastoma is a locally aggressive neoplasm with a poorly understood pathogenesis. Therefore, the aim of this study is to investigate whether COX-2 expression is associated with ameloblastoma microvascular density (MVD) and with tumor aggressiveness. Sixty-three cases of primary ameloblastomas arranged in tissue microarray were submitted to immunohistochemistry against cyclooxigenase-2 (COX-2) and CD34. Clinicopathological parameters regarding sex, age, tumour size, tumour duration, tumour location, treatment, recurrences, radiographic features, vestibular/lingual and basal cortical disruption and follow-up data were obtained from patients’ medical records and correlated with the proteins expression. The results on BRAF-V600E expression were obtained from our previous study and correlated with COX-2 and CD34 expressions. Log-rank univariate analysis and multivariate Cox regression model were done to investigate the prognostic potential of the molecular markers. Twenty-eight cases (44.4%) exhibited cytoplasmic positivity for COX-2, predominantly in the columnar peripheral cells, with a mean MVD of 2.2 vessels/mm². COX-2 was significantly associated with recurrences (p?<?0.001) and BRAF-V600E expression (p?<?0.001), whereas lower MVD was associated with the use of conservative therapy (p?=?0.004). Using univariate and multivariate analyses, COX-2 was significantly associated with a lower 5-year disease-free survival (DFS) rate (p?<?0.001 and p?=?0.012, respectively), but not with a higher MVD (p?=?0.68). In conclusion, COX-2 expression in ameloblastomas is not associated with MVD, but it is significantly associated with recurrences and with a lower DFS.