Does SARS‐Cov‐2 invade the brain? Translational lessons from animal models

The current coronavirus disease (COVID‐19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS‐CoV‐2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS‐CoV‐2. One key finding that may unify these pathogens is that all require angiotensin‐converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS‐CoV‐2 binds to cell membranes, binds angiotensin‐converting enzyme 2 with a higher affinity compared with SARS‐CoV. The expression of this receptor in neurons and endothelial cells hints that SARS‐CoV‐2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune‐mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune‐mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID‐19.     

Pseudoathetosis: report of three patients.

We report on 3 patients with pseudoathetosis, which are involuntary, slow, writhing movements due to loss of proprioception.     

Effect of the menstrual cycle and oral contraceptives on aromatase and cyclooxygenase-2 expression in adenomyosis.

OBJECTIVES: To determine whether aromatase expression in the eutopic endometrium and adenomyotic foci is affected by previous use of oral contraceptives containing gestodene, and to determine whether changes in cyclooxygenase-2 (COX-2) expression occur in adenomyosis during the menstrual cycle. PATIENT AND METHODS: This was a retrospective cohort study carried out in paraffin-embedded endometrial tissue obtained from patients with a histological diagnosis of adenomyosis obtained during the proliferative (n = 25) and luteal (n = 10) phases of the menstrual cycle and following the use of continuous oral contraception with gestodene/ethinyl estradiol (n = 7). COX-2 and aromatase expression were measured in both eutopic endometrium and adenomyotic foci using immunohistochemical methods. RESULTS: Aromatase expression was detected in 80% of the endometrial slices by immunohistochemistry. In positive cases, aromatase was mainly detected in the stromal cells of the eutopic endometrium, whereas in the adenomyotic foci this expression was negative in the majority of the cases. Oral contraceptives containing gestodene, on the other hand, were effective in suppressing aromatase expression in both eutopic and ectopic endometrium. COX-2 expression was detected by immunohistochemistry in the glandular epithelium of both eutopic endometrium and adenomyotic foci and there were no significant changes in its intensity throughout the menstrual cycle. CONCLUSION: Aromatase expression in the eutopic endometrium and adenomyotic foci is suppressed by oral contraceptives containing gestodene. Increased aromatase activity may be responsible for the persistent COX-2 expression during the luteal phase.     

Cementoblastoma related to a primary tooth: a case report

Cementoblastomas are benign lesions of the odontogenic ectomesenchyme that rarely occur related to the primary dentition, especially on the left side of the mandible. This study describes a case of a true cementoblastoma related to the left second primary mandibular molar in a 7-year-old child (the largest one seen in the left side of the mandible). Additionally, the radiographic and histologic findings of the lesion are described in details.     

Moisturizing effect of cosmetic formulations containing Aloe vera extract in different concentrations assessed by skin bioengineering techniques

BACKGROUND/PURPOSE: The polysaccharide-rich composition of Aloe vera extracts (Aloe barbadensis Miller), often used in cosmetic formulations, may impart moisturizing properties to the product. The aim of this study was to evaluate the effect of cosmetic formulations containing different concentrations of freeze-dried Aloe vera extract on skin hydration, after a single and a 1- and 2-week period of application, by using skin bioengineering techniques. METHODS: Stable formulations containing 5% (w/w) of a trilaureth-4 phosphate-based blend were supplemented with 0.10%, 0.25% or 0.50% (w/w) of freeze-dried Aloe vera extract and applied to the volar forearm of 20 female subjects. Skin conditions in terms of the water content of the stratum corneum and of transepidermal water loss (TEWL) (Corneometer CM 825 and Tewameter TM 210) were analysed before and after a single and 1- and 2-week period of daily application. RESULTS: After a single application, only formulations supplemented with 0.25% and 0.50% (w/w) of Aloe vera extract increased the water content of the stratum corneum, while after the 2-week period application, all formulations containing the extract (0.10%, 0.25% and 0.50%) had the same effect, in both cases as compared with the vehicle. TEWL was not modified after a single and after 1- and 2-week period of application, when compared with the vehicle. CONCLUSION: Our results show that freeze-dried Aloe vera extract is a natural effective ingredient for improving skin hydration, possibly through a humectant mechanism. Consequently, it may be used in moisturizing cosmetic formulations and also as a complement in the treatment of dry skin.     

Medullar expression of type-A natriuretic peptide receptor in an animal model of hypertension induced by renal mass ablation.

INTRODUCTION: The biological activity of the natriuretic peptide (NP) system is dependent on the balance between NP tissue levels and the local expression of their receptors. In the kidney, the natriuretic peptide receptor type A (NPR-A) is the principal receptor mediating NP activity and is mainly expressed in the renal medulla. An increase in circulating NP levels is well documented in chronic renal failure (CRF); however, the renal expression of NPR-A has not been evaluated in this condition. METHODS: Wistar-Han rats were submitted to right nephrectomy plus ablation of both poles of the left kidney (3/4nx; n=27) or were sham operated (Sham; n=22) and followed for up to 26 weeks post surgery. Blood pressure measurements were performed weekly. Two, 10 and 26 weeks after surgery, renal sodium and creatinine excretion were evaluated and the kidneys removed for NPR-A mRNA quantification by real-time PCR. The results of mRNA quantification are expressed in arbitrary units (AU) set as the mean value of the Sham group (Sham=1 AU), after normalization for GAPDH (p<0.05). weeks after surgery) and in elevated fractional sodium excretion (+270%, 26 weeks after surgery). Although sodium intake was similar in 3/4nx and Sham rats, blood pressure was higher in 3/4nx rats and increased progressively throughout the study. This was accompanied by a marked decrease in NPR-A mRNA levels in the renal medulla from 3/4nx animals at 2, 10 and 26 weeks post surgery. Conclusion: In 3/4nx rats, the expression of NPR-A in the renal medulla of the remnant kidney is markedly reduced from 2 weeks up to 26 weeks post surgery. It is suggested that this may contribute to the progressive increase in blood pressure, as well as to the renal fibrosis observed in 3/4nx rats.     

Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.