Pharmacological Evidence of Eugenia Brasiliensis Leaves in a Reserpine-Induced Fibromyalgia Model: Antinociceptive, Emotional, Anti-Inflammatory, and Neurotrophic Effects.

Fibromyalgia (FM) is a painful chronic condition that significantly impacts the quality of life, posing challenges for clinical management. Given the difficulty of understanding the pathophysiology and finding new therapeutics, this study explored the effects of a medicinal plant, E. brasiliensis, in an FM model induced by reserpine in Swiss mice. Animals were treated with saline 0.9% (vehicle), duloxetine 10 mg/kg (positive control), or hydroalcoholic extract of E. brasiliensis leaves 300 mg/kg (HEEb). Nociceptive parameters, as well as locomotion, motor coordination, strength, anxiety, and depressive-like behaviors, were evaluated for 10 days. After that, the brain and blood were collected for further analysis of cytokines (interleukin 1? and interleukin 6), brain-derived neurotrophic factor (BDNF), and the immunocontents of total and phosphorylated Tropomyosin receptor kinase B (TrkB). The results demonstrated that the acute and prolonged treatment with HEEb was able to reduce both mechanical and thermal nociception. It was also possible to observe an increase in the strength, without changing locomotion and motor coordination parameters. Interestingly, treatment with HEEb reduces anxious and depressive-like behaviors. Finally, we observed a reduction in inflammatory cytokines in the hippocampus of animals treated with HEEb, while an increase in BDNF was observed in the prefrontal cortex (PFC). However, no alterations related to total and phosphorylated TrkB receptor expression were found. Our study demonstrated the antinociceptive and emotional effects of HEEb in mice, possibly acting on neuroinflammatory and neurotrophic mechanisms. These data provide initial evidence about the E. brasiliensis potential for treating chronic pain.

Anetoderma after disseminated Mpox.

Anetoderma or macular atrophy is a rare skin condition of unclear pathogenesis, often associated with autoimmune diseases and skin damage from various infections. Human immunodeficiency virus (HIV), syphilis, and poxviruses have been implicated in the development of anetoderma. A 37-year-old male patient with HIV and recent unprotected sexual encounters presented with more than 400 skin lesions, consistent with Mpox. Symptomatic treatment for Mpox resulted in acute symptom resolution. However, 8 months later he developed papular anetoderma lesions in areas previously affected by Mpox. Biopsy confirmed the loss of elastic fibers in the affected skin areas, leading to the diagnosis of Mpox-induced anetoderma. This report presents a unique case of anetoderma following Mpox in an HIV-positive patient.

Dermoscopy as a diagnostic aid in pityriasis lichenoides et varioliformis acuta.

Diagnosis of pityriasis lichenoides et varioliformis acuta (PLEVA) is based on the characteristic pattern of lesions in different stages of development, ranging from erythematous maculopapules to papules with a crusted and/or necrotic centre. However, it may raise the differential diagnosis with other entities. It is therefore not uncommon to have to perform skin biopsies to reach a diagnosis, including in infants. In this study, we report the cases of three patients with PLEVA, highlighting the correlations between the clinical, dermoscopic and histological features. Observation of the dermatoscopic findings described, such as punctate or glomerular vessels and erythematous globules surrounding a homogeneous orange or crusty central area, may allow for a rapid diagnosis, avoiding the need for invasive techniques.

Differential expression of alpha-synuclein in the hippocampus of SHR and SLA16 isogenic rat strains.

Two inbred strains, Lewis (LEW) and Spontaneously Hypertensive Rats (SHR), are well-known for their contrasting behavior related to anxiety/emotionality. Studies with these two strains led to the discovery of the Quantitative Trait Loci (QTL) on chromosome 4 (Anxrr16). To better understand the influences of this genomic region, the congenic rat strain SLA16 (SHR.LEW-Anxrr16) was developed. SLA16 rats present higher hyperactivity/impulsivity, deficits in learning and memory, and lower basal blood pressure than the SHR strain, even though genetic differences between them are only in chromosome 4. Thus, the present study proposed the alpha-synuclein and the dopaminergic system as candidates to explain the differential behavior of SHR and SLA16 strains. To accomplish this, beyond the behavioral analysis, we performed (I) the Snca gene expression and (II) quantification of the alpha-synuclein protein in the hippocampus (HPC), prefrontal cortex (PFC), and striatum (STR) of SHR and SLA16 strains; (III) sequencing of the 3'UTR of the Snca gene; and (IV) evaluation of miRNA binding in the 3'UTR site. A Single Nucleotide Polymorphism (SNP) was identified in the 3'UTR of the Snca gene, which exhibited upregulation in the HPC of SHR compared to SLA16 females. Alpha-synuclein protein was higher in the HPC of SHR males compared to SLA16 males. The results of this work suggested that differences in alpha-synuclein HPC content could be influenced by miRNA regulation and associated with behavioral differences between SHR and SLA16 animals.

Predictors of Neurodevelopment in Microcephaly Associated with Congenital Zika Syndrome: A Prospective Study.

The municipality of Salvador, situated in Brazil, distinguished itself as the epicenter of the emergence of microcephaly related to congenital manifestations of Zika syndrome. Despite the anticipated significant developmental setbacks in these children, research has indicated a varied range of outcomes, with certain instances even reflecting minimal developmental delay. Our objective was to pinpoint determinants that could forecast developmental anomalies in children diagnosed with microcephaly associated with congenital Zika syndrome (CZS). METHODOLOGY: A forward-looking clinical and neurodevelopmental examination was conducted focusing on neonates diagnosed with microcephaly with CZS, birthed between September 2015 and April 2016 at the Hospital Geral Roberto Santos, in Salvador city. That infants were monitored up to their third year by a multiprofessional team. Child development was assessed using the composite Bayley III score. Undertaken by two blinded experts, cranial CT scan analysis was performed during the neonate period for the detection of brain abnormalities and to quantify ventricle enlargement, measured by Evans' index (EI). RESULTS: Fifty newborns were evaluated with a median head circumference of 28 cm (interquartile range 27-31 cm). EI was associated with neurodevelopmental delay at three years and remained significant after adjustment for head circumference. A 0.1-point increase in EI was associated with a delay of 3.2 months in the receptive language (p = 0.016), 3.4 months in the expressive language (p = 0.016), 3.4 months in the cognitive (p = 0.016), 2.37 months in the gross motor (p = 0.026), and 3.1 months in the fine motor (p = 0.021) domains. CONCLUSIONS: EI predicted neurodevelopmental delay in all Bayley domains in children with microcephaly associated with CZS.

Regulation of FGF2-induced proliferation by inhibitory GPCR in normal pituitary cells.

Introduction: Intracellular communication is essential for the maintenance of the anterior pituitary gland plasticity. The aim of this study was to evaluate whether GPCR-Gαi modulates basic fibroblast growth factor (FGF2)-induced proliferative activity in normal pituitary cell populations. Methods: Anterior pituitary primary cell cultures from Wistar female rats were treated with FGF2 (10ng/mL) or somatostatin analog (SSTa, 100nM) alone or co-incubated with or without the inhibitors of GPCR-Gαi, pertussis toxin (PTX, 500nM), MEK inhibitor (U0126, 100µM) or PI3K inhibitor (LY 294002, 10 µM). Results: FGF2 increased and SSTa decreased the lactotroph and somatotroph BrdU uptak2e (p<0.05) whereas the FGF2-induced S-phase entry was prevented by SSTa co-incubation in both cell types, with these effects being reverted by PTX, U0126 or LY294002 pre-incubation. The inhibition of lactotroph and somatotroph mitosis was associated with a downregulation of c-Jun expression, a decrease of phosphorylated (p) ERK and pAKT. Furthermore, SSTa was observed to inhibit the S-phase entry induced by FGF2, resulting in a further increase in the number of cells in the G1 phase and a concomitant reduction in the number of cells in the S phases (p< 0.05), effects related to a decrease of cyclin D1 expression and an increase in the expression of the cell cycle inhibitors p27 and p21. Discussion: In summary, the GPCR-Gαi activated by SSTa blocked the pro-proliferative effect of FGF2 in normal pituitary cells via a MEK-dependent mechanism, which acts as a mediator of both anti and pro-mitogenic signals, that may regulate the principal effectors of the G1 to S-phase transition.