Anatomopathological Aspects and Clinical Correlation of COVID-19: A Systematic Review.

OBJECTIVE: The objective of this systematic review was to analyze the main morphofunctional changes in the involvement of multiple organs in patients infected with SARS-CoV-2, correlating anatomopathological findings with the clinical picture. METHODS: The present study selected articles through electronic search of indexed journals in the PubMed and SciVerse Scopus databases, from December 2019 to May 2020, using the keywords "autopsy," "pathogenicity," and "COVID-19." Two hundred nine articles were identified, and the full texts of 18 articles were reviewed, 5 of them being selected for this review. RESULTS: The ACE2 receptor plays a role in introducing viral material into the cell, having high expression in type II alveoli. Histopathological analyzes of the lungs of patients with COVID-19 show that SARS-CoV-2 produces, in this organ, in addition to an inflammatory process, a diffuse alveolar damage (DAD), which can cause acute respiratory distress syndrome (ARDS). Macroscopically, the lungs become heavier, firmer, and redder. The clinical features of these patients are variable; the most common are respiratory symptoms associated with fever, myalgia, or fatigue. CONCLUSION: The observations points to the consensus that the lungs are the main targets of COVID-19, with morphological and functional changes of interest, including important sequels, and presenting diffuse alveolar damage as a substrate for an unfavorable outcome with ARDS. Changes in micro and macroscopic levels corroborate to the clinical progression of the disease and that these alterations are not specific, which ratify, in addition to the anatomopathological examination, a need to use the association of clinical and epidemiological data for diagnostic confirmation.

Epidemiology and Etiopathogeny of COVID-19.

Despite the recent announcement of the new pathogenic coronavirus to man, SARS-CoV2, a large number of publications are presented to the scientific community. An organized and systematic review of the epidemiological, etiological, and pathogenic factors of COVID-19 is presented. This is a systematic review using the databases MEDLINE, EMBASE, Web of Science, SCIELO; the descriptors coronavirus, SARS-CoV-2, etiology, epidemiology, pathophysiology, pathogenesis, COVID-19, with publications from December 2019 to January 2021, resulting in more than 800 publications and 210 selected. The data suggest that COVID-19 is associated with SAR-CoV-2 infection, with the transmission of contagion by fomites, salivary droplets, and other forms, such as vertical and fecal-oral. The bat and other vertebrates appear to be reservoirs and part of the transmission chain. The virus uses cell receptors to infect human cells, especially ACE2, like other coronaviruses. Heat shock proteins have different roles in the infection, sometimes facilitating it, sometimes participating in more severe conditions, when not serving as a therapeutic target. The available data allow us to conclude that COVID-19 is a pandemic viral disease, behaving as a challenge for public health worldwide, determining aggressive conditions with a high mortality rate in patients with risk factors, without treatment, but with the recent availability of the first vaccines.

Carvone Enantiomers Differentially Modulate IgE-Mediated Airway Inflammation in Mice.

Carvone is a monoterpene found in nature in the form of enantiomers (S- and R-). While previous research has demonstrated the anti-inflammatory and anti-allergic effects of carvone, the influence of carvone enantiomeric composition on its anti-allergic activity remains to be investigated. This study aimed to evaluate the anti-allergic activity of carvone enantiomers in a murine model of airway allergic inflammation induced by sensitization and challenge with ovalbumin (OVA). The oral treatment with R-carvone or S-carvone 1 h before each challenge inhibited the number of leukocytes and eosinophils in the bronchoalveolar lavage (BAL). R-carvone inhibited leukocyte infiltration and mucus production in the lung, which was correlated with decreased production of OVA-specific IgE in the serum and increased concentrations of IL-10 in the BAL. On the other hand, the administration of S-carvone had little inhibitory effect on inflammatory infiltration and mucus production in the lung, which might be associated with increased production of IFN-γ in the BAL. When administered 1 h before each sensitization, both enantiomers inhibited eosinophil recruitment to the BAL but failed in decreasing the titers of IgE in the serum of allergic mice. Our data indicate that carvone enantiomers differentially modulated IgE-mediated airway inflammation in mice. In conclusion, unlike S-carvone, R-carvone has the potential to be used in anti-allergic drug development.

Toxicity and Antitumor Activity of a Thiophene-Acridine Hybrid.

The antitumor effects of thiophene and acridine compounds have been described; however, the clinical usefulness of these compounds is limited due to the risk of high toxicity and drug resistance. The strategy of molecular hybridization presents the opportunity to develop new drugs which may display better target affinity and less serious side effects. Herein, 2-((6-Chloro-2-methoxy-acridin-9-yl)amino)-5,6,7,8-tetrahydro-4H-cyclohepta[b]-thiophene-3-carbonitrile (ACS03), a hybrid thiophene-acridine compound with antileishmanial activity, was tested for toxicity and antitumor activity. The toxicity was evaluated in vitro (on HaCat and peripheral blood mononuclear cells) and in vivo (zebrafish embryos and acute toxicity in mice). Antitumor activity was also assessed in vitro in HCT-116 (human colon carcinoma cell line), K562 (chronic myeloid leukemic cell line), HL-60 (human promyelocytic leukemia cell line), HeLa (human cervical cancer cell line), and MCF-7 (breast cancer cell line) and in vivo (Ehrlich ascites carcinoma model). ACS03 exhibited selectivity toward HCT-116 cells (Half maximal inhibitory concentration, IC50 = 23.11 ± 1.03 µM). In zebrafish embryos, ACS03 induced an increase in lactate dehydrogenase, glutathione S-transferase, and acetylcholinesterase activities. The LD50 (lethal dose 50%) value in mice was estimated to be higher than 5000 mg/kg (intraperitoneally). In vivo, ACS03 (12.5 mg/kg) induced a significant reduction in tumor volume and cell viability. In vivo antitumor activity was associated with the nitric oxide cytotoxic effect. In conclusion, significant antitumor activity and weak toxicity were recorded for this hybrid compound, characterizing it as a potential anticancer compound.

Antitumor Effect of a Novel Spiro-Acridine Compound is Associated with Up-Regulation of Th1-Type Responses and Antiangiogenic Action.

Tumor cells have specific features, including angiogenesis induction, cell cycle dysregulation, and immune destruction evasion. By inducing a T helper type 2 (Th2) immune response, tumor cells may favor immune tolerance within the tumor, which allows progression of cancer growth. Drugs with potential antitumor activity are the spiro-acridines, which is a promising new class of acridine compounds. Herein, the novel spiro-acridine (E)-5'-oxo-1'-((3,4,5-trimethoxybenzylidene)amino)-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-17) was synthesized and tested for antitumor effects. Toxicity evaluation was performed in mice after acute treatment (2000 mg/kg, intraperitoneally, i.p.). The Ehrlich ascites carcinoma model was used to investigate the antitumor activity of AMTAC-17 (12.5, 25, or 50 mg/kg, i.p.) after seven days of treatment. Effects on the cell cycle, angiogenesis, and inflammatory responses were investigated. LD50 (lethal dose 50%) was estimated to be higher than 5000 mg/kg. AMTAC-17 reduced the Ehrlich tumor's total viable cancer cells count and peritumoral micro-vessels density, and induced an increase in the sub-G1 peak. Additionally, there was an increase of Th1 cytokine profile levels (IL-1ß, TNF-α, and IL-12). In conclusion, the spiro-acridine compound AMTAC-17 presents low toxicity, and its in vivo antitumor effect involves modulation of the immune system to a cytotoxic Th1 profile and a reduction of tumor angiogenesis.

High incidence of prostate cancer metastasis in Afro-Brazilian men with low educational levels: a retrospective observational study.

BACKGROUND: This study investigated factors related to ethnicity and educational level, their correlation with tumor stage at the time of diagnosis, and their influence on treatment outcomes in patients with prostate cancer. METHODS: In this retrospective observational study, we analyzed the medical records of 1,349 male patients treated for prostatic adenocarcinoma. We collected information about sociodemographic variables, including educational level and self-reported skin color. We also classified the disease according whether it was to more likely to present with metastasis and measured the tumor response to treatment. RESULTS: Less-educated (<8 years of education) individuals were 4.8 times more likely to develop metastasis than those with more education (>11 years of education; p < 0.001). Similarly, patients with a self-reported black skin color had a 300% increased risk of metastasis at diagnosis (p = 0.001). Distant metastasis was independently correlated with worse outcomes, such that individuals with distant metastasis were 10 times more likely to die than were those without distant metastasis. CONCLUSIONS: Patients with self-reported black skin color and <8 years of education were more likely to display advanced disease at the time of diagnosis compared with their counterparts. Only the presence of metastasis was independently associated with mortality or progressive disease.

A 9-aminoacridine derivative induces growth inhibition of Ehrlich ascites carcinoma cells and antinociceptive effect in mice.

Acridine derivatives have been found with anticancer and antinociceptive activities. Herein, we aimed to evaluate the toxicological, antitumor, and antinociceptive actions of N'-(6-chloro-2-methoxyacridin-9-yl)-2-cyanoacetohydrazide (ACS-AZ), a 9-aminoacridine derivative with antimalarial activity. The toxicity was assessed by acute toxicity and micronucleus tests in mice. The in vivo antitumor effect of ACS-AZ (12.5, 25, or 50 mg/kg, intraperitoneally, i.p.) was determined using the Ehrlich tumor model, and toxicity. The antinociceptive efficacy of the compound (50 mg/kg, i.p.) was investigated using formalin and hot plate assays in mice. The role of the opioid system was also investigated. In the acute toxicity test, the LD50 (lethal dose 50%) value was 500 mg/kg (i.p.), and no detectable genotoxic effect was observed. After a 7-day treatment, ACS-AZ significantly (p < 0.05) reduced tumor cell viability and peritumoral microvessels density, suggesting antiangiogenic action. In addition, ACS-AZ reduced (p < 0.05) IL-1ß and CCL-2 levels, which may be related to the antiangiogenic effect, while increasing (p < 0.05) TNF-α and IL-4 levels, which are related to its direct cytotoxicity. ACS-AZ also decreased (p < 0.05) oxidative stress and nitric oxide (NO) levels, both of which are crucial mediators in cancer known for their angiogenic action. Moreover, weak toxicological effects were recorded after a 7-day treatment (biochemical, hematological, and histological parameters). Concerning antinociceptive activity, ACS-AZ was effective on hotplate and formalin (early and late phases) tests (p < 0.05), characteristic of analgesic agents with central action. Through pretreatment with the non-selective (naloxone) and µ1-selective (naloxonazine) opioid antagonists, we observed that the antinociceptive effect of ACS-AZ is mediated mainly by µ1-opioid receptors (p < 0.05). In conclusion, ACS-AZ has low toxicity and antitumoral activity related to cytotoxic and antiangiogenic actions that involve the modulation of reactive oxygen species, NO, and cytokine levels, in addition to antinociceptive properties involving the opioid system.

Physical and mental health impacts during COVID-19 quarantine in adolescents with preexisting chronic immunocompromised conditions.

OBJECTIVE: To evaluate physical and mental health indicators in adolescents with preexisting chronic immunocompromised conditions during coronavirus disease 2019 (COVID-19) quarantine. METHODS: A cross-sectional study included 355 adolescents with chronic conditions and 111 healthy adolescents. An online self-rated survey was used to investigate socio-demographic features, healthcare routine, and the quarantine impact on physical and mental health. The validated self-reported version of the Strengths and Difficulties Questionnaire (SDQ) was also applied. RESULTS: The median of age [14 (10-18) vs. 15 (10-18) years, p = 0.733] and frequencies of female (61% vs. 60%, p = 0.970) were similar between adolescents with preexisting chronic conditions and healthy adolescents during quarantine of COVID-19 pandemic. The frequencies of abnormal total difficulties score of SDQ were similar in patients and controls (30% vs. 31%, p = 0.775). Logistic regression analysis showed that being female (OR = 1.965; 95% CI = 1.091-3.541, p = 0.024), fear of underlying disease activity/complication (OR = 1.009; 95%CI = 1.001-1.018, p = 0.030) were associated with severe psychosocial dysfunction in adolescents with chronic conditions, whereas school homework (OR = 0.449; 95% CI = 0.206-0.981, p = 0.045) and physical activity (OR = 0.990; 95% CI = 0.981-0.999, p = 0.030) were protective factors. Further analysis of patients with chronic immunocompromised conditions and previous diagnosis of mental disorders (9%) compared with patients without diagnosis showed higher median of total difficulties score (p = 0.001), emotional (p = 0.005), conduct (p = 0.007), peer problems (p = 0.001) and hyperactivity (p = 0.034) in the former group. CONCLUSION: Adolescents with preexisting chronic immunocompromised conditions during COVID-19 quarantine were not at higher risk of adverse health indicators. Being female, fear of underlying disease activity/complication, and household members working outside of the home were relevant issues for adolescents with preexisting chronic conditions. This study reinforces the need to establish mental health strategies for teens with chronic conditions, particularly during the pandemic.

Hyperbaric oxygen therapy mitigates left ventricular remodeling, upregulates MMP-2 and VEGF, and inhibits the induction of MMP-9, TGF-ß1, and TNF-α in streptozotocin-induced diabetic rat heart.

AIMS: Hyperbaric oxygen (HBO) therapy has been widely used for the adjunctive treatment of diabetic wounds, and is currently known to influence left ventricular (LV) function. However, morphological and molecular repercussions of the HBO in the diabetic myocardium remain to be described. We aimed to investigate whether HBO therapy would mitigate adverse LV remodeling caused by streptozotocin (STZ)-induced diabetes. MAIN METHODS: Sixty-day-old Male Wistar rats were divided into four groups: Control (n = 8), HBO (n = 7), STZ (n = 10), and STZ + HBO (n = 8). Diabetes was induced by a single STZ injection (60 mg/kg, i.p.). HBO treatment (100% oxygen at 2.5 atmospheres absolute, 60 min/day, 5 days/week) lasted for 5 weeks. LV morphology was evaluated using histomorphometry. Gene expression analyzes were performed for LV collagens I (Col1a1) and III (Col3a1), matrix metalloproteinases 2 (Mmp2) and 9 (Mmp9), and transforming growth factor-ß1 (Tgfb1). The Immunoexpression of cardiac tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) were also quantified. KEY FINDINGS: HBO therapy prevented LV concentric remodeling, heterogeneous myocyte hypertrophy, and fibrosis in diabetic rats associated with attenuation of leukocyte infiltration. HBO therapy also increased Mmp2 gene expression, and inhibited the induction of Tgfb1 and Mmp9 mRNAs caused by diabetes, and normalized TNF-α and VEGF protein expression. SIGNIFICANCE: HBO therapy had protective effects for the LV structure in STZ-diabetic rats and ameliorated expression levels of genes involved in cardiac collagen turnover, as well as pro-inflammatory and pro-angiogenic signaling.

S-methyl cysteine sulfoxide mitigates histopathological damage, alleviate oxidative stress and promotes immunomodulation in diabetic rats.

OBJECTIVES: S-methyl cysteine sulfoxide (SMCS) is a hydrophilic cysteine-containing natural compound found in plants and is known to possess antidiabetic and antioxidant properties. We investigated the antioxidant and immunomodulatory properties of SMCS, as well as histopathological changes in the liver and pancreas in streptozotocin (STZ)-induced diabetic rats. METHODS: The rats were divided into the following groups: control (CG), comprising non-diabetic rats; STZ-DB, comprising STZ-induced diabetic rats; and STZ-SMCS, comprising STZ-induced diabetic rats treated with SMCS. SMCS (200 mg/kg) was administered by gavage daily for 30 days. Biochemical and cytokine analyses, catalase (CAT) and superoxide dismutase (SOD) activities assays and histopathological analysis of liver and pancreas tissues were performed. RESULTS: SMCS treatment reduced glycemia (p<0.05), decreased triglyceride (p<0.01) and very-low-density lipoprotein (VLDL) levels (p<0.01), and increased SOD and CAT activity in the liver (both p<0.01) compared with STZ-DB group. Higher activity values of IL-10 were observed in the STZ-SMCS group than in the other groups (p<0.001). Liver glycogen was significantly improved in the STZ-SMCS group compared with the STZ-DB group. SMCS also ameliorated damage to pancreatic islets, which resulted in restoration of their morphology. CONCLUSIONS: Oral treatment of SMCS showed improvement of the morphological alterations in liver and pancreatic islet in diabetic rats. These beneficial morphological effects of SMCS can be partially explained by IL-10 modulation associated with antioxidant action.

S-methyl cysteine sulfoxide ameliorates duodenal morphological alterations in streptozotocin-induced diabetic rats.

Diabetes mellitus (DM) is a metabolic disease associated with several intestinal disorders. S-methyl cysteine sulfoxide (SMCS) ​​is an amino acid present in Allium cepa L with hypoglycemic effects. However, the effects of SMCS on diabetic intestinal changes are unknown. Thus, we aimed to investigate the effects of SMCS on duodenal morphology and immunomodulatory markers in diabetic rats. Twenty-six rats were divided into three groups: control (C), diabetic (D) and diabetic +200 mg/kg SMCS (DSM). DM was induced by intraperitoneal injection of streptozotocin (50 mg/kg). After 30 days, duodenum samples were processed to assess histopathological and stereological alterations in volume, villus length, and immunohistochemical expression of NF-kB, IL-10, BCL-2, and caspase-3. SMCS reduced hyperglycemia and mitigated the increase in total reference volume of the duodenum, the absolute volume of the mucosa, and the length of the intestinal crypts in the DMS group when compared to D. IL-10 immunostaining was reduced in D when compared to C, while NF-kB was increased in D in comparison to the other groups. SMCS ​​supplementation could decrease the NF-kB immunostaining observed in D. Positive staining for BCL-2 and caspase-3 were not statistically different between groups. In summary, SMCS decreased hyperglycemia and mitigated the morphological changes of the duodenum in diabetic animals, and these beneficial effects can be partially explained by NF-kB modulation.

Poor Sleep quality and health-related quality of life impact in adolescents with and without chronic immunosuppressive conditions during COVID-19 quarantine.

OBJECTIVE: To assess the possible factors that influence sleep quality in adolescents with and without chronic immunosuppressive conditions quarantined during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This cross-sectional study included 305 adolescents with chronic immunocompromised conditions and 82 healthy adolescents. Online surveys were completed, which included questions on socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and the following validated questionnaires: the Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0), and Pediatric Outcome Data Collection Instrument (PODCI). RESULTS: The median current age [14 (10-18) vs. 15 (10-18) years, p=0.847] and frequency of female sex (62% vs. 58%, p=0.571) were similar in adolescents with chronic conditions compared with healthy adolescents. The frequency of poor sleep quality was similar in both groups (38% vs. 48%, p=0.118). Logistic regression analysis, including both healthy adolescents and adolescents with chronic conditions (n=387), demonstrated that self-reported increase in screen time (odds ratio [OR] 3.0; 95% confidence interval [CI] 1.3-6.8; p=0.008) and intrafamilial violence report (OR 2.1; 95% CI 1.2-3.5; p=0.008) were independently associated with poor sleep quality in these adolescents. However, the PODCI global function score was associated with a lower OR for poor sleep quality (OR 0.97; 95% CI 0.94-0.99; p=0.001). Further logistic regression, including only adolescents with chronic conditions (n=305), demonstrated that self-reported increase in screen time (OR 3.1; 95% CI 1.4-6.8; p=0.006) and intrafamilial violence report (OR 2.0; 95% CI 1.2-3.4; p=0.011) remained independently associated with poor quality of sleep, whereas a lower PODCI global function score was associated with a lower OR for sleep quality (OR 0.96; 95% CI 0.94-0.98; p<0.001). CONCLUSION: Self-reported increases in screen time and intrafamilial violence report impacted sleep quality in both healthy adolescents and those with chronic conditions. Decreased health-related quality of life was observed in adolescents with poor sleep quality.

Anticancer Effect of a Spiro-acridine Compound Involves Immunomodulatory and Anti-angiogenic Actions.

BACKGROUND/AIM: Studies with acridine compounds have reported anticancer effects. Herein, we evaluated the toxicity and antitumor effect of the (E)-1'-((4-chlorobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-06), a promising anticancer spiro-acridine compound. MATERIALS AND METHODS: The toxicity of AMTAC-06 was evaluated on zebrafish and mice. Antitumor activity was assessed in Ehrlich ascites carcinoma model. Effects on angiogenesis, cytokine levels and cell cycle were also investigated. RESULTS: AMTAC-06 did not induce toxicity on zebrafish and mice (LD50 approximately 5000 mg/kg, intraperitoneally). No genotoxicity was observed on micronucleus assay. AMTAC-06 significantly reduced the total viable Ehrlich tumor cells and increased sub-G1 peak, suggesting apoptosis was triggered. Moreover, the compound significantly decreased the density of peritumoral microvessels, indicating an anti-angiogenic action, possibly dependent on the cytokine modulation (TNF-α, IL-1ß and IFN-γ). No significant toxicological effects were recorded for AMTAC-06 on tumor transplanted animals. CONCLUSION: AMTAC-06 has low toxicity and a significant antitumor activity.

A novel piperine analogue exerts in vivo antitumor effect by inducing oxidative, antiangiogenic and immunomodulatory actions.

Structural diversity characterizes natural products as prototypes for design of lead compounds. The aim of this study was to synthetize, and to evaluate the toxicity and antitumor action of a new piperine analogue, the butyl 4-(4-nitrobenzoate)-piperinoate (DE-07). Toxicity was evaluated against zebrafish, and in mice (acute and micronucleus assays). To evaluate the DE-07 antitumor activity Ehrlich ascites carcinoma model was used in mice. Angiogenesis, Reactive Oxygen Species (ROS) production and cytokines levels were investigated. Ninety-six hours exposure to DE-07 did not cause morphological or developmental changes in zebrafish embryos and larvae, with estimated LC50 (lethal concentration 50%) higher than 100 µg/mL. On the acute toxicity assay in mice, LD50 (lethal dose 50%) was estimated at around 1000 mg/kg, intraperitoneally (i.p.). DE-07 (300 mg/kg, i.p.) did not induce increase in the number of micronucleated erythrocytes in mice, suggesting no genotoxicity. On Ehrlich tumor model, DE-07 (12.5, 25 or 50 mg/kg, i.p.) induced a significant decrease on cell viability. In addition, there was an increase on ROS production and a decrease in peritumoral microvessels density. Moreover, DE-07 induced an increase of cytokines levels involved in oxidative stress and antiangiogenic effect (IL-1ß, TNF-α and IL-4). No significant clinical toxicological effects were recorded in Ehrlich tumor transplanted animals. These data provide evidence that DE-07 presents low toxicity, and antitumor effect via oxidative and antiangiogenic actions by inducing modulation of inflammatory response in the tumor microenvironment.

Effect of photobiomodulation and exercise on early remodeling of the Achilles tendon in streptozotocin-induced diabetic rats.

The aim of this study was to compare the treatment effects of laser photobiomodulation (LPBM) therapy and aerobic exercise on the biomechanical properties, tissue morphology and the expression of tendon matrix molecules during early remodeling of Achilles tendon (AT) injury in diabetic rats. Animals were randomly assigned to five groups: injured non diabetic (I, n = 15), injured diabetic (ID, n = 15), injured diabetic plus LPBM (IDL, n = 16), injured diabetic plus aerobic exercise (IDE, n = 16) and injured diabetic plus aerobic exercise and LPBM (IDEAL, n = 17). Type 1 diabetes was induced via a single intravenous injection of Streptozotocin at a dose of 40 mg/kg. A partial tenotomy was performed in the right AT. LPBM was performed with an indium-gallium-aluminum-phosphide 660 nm 10 mW laser device (spot size 0.04 cm2, power density 250 mW/cm2, irradiation duration 16 s, energy 0.16 J, energy density 4 J/cm2) on alternate days for a total of 9 sessions over 3 weeks (total energy 1.44 J), using a stationary contact technique to a single point over the dorsal aspect of the AT. Moderate aerobic exercise was performed on a motorized treadmill (velocity 9 m/min for 60 minutes). At 3 weeks post-injury, biomechanical analyzes as well as assessment of fibroblast number and orientation were performed. Collagen 1 (Col1) and 3 (Col3) and matrix metalloproteinases (MMPs) -3 and 13 protein distributions were studied by immunohistochemistry; while Col1 and Col3 and MMP-2 and 9 gene expression were assessed by quantitative RT-PCR (qRT-PCR). IDEAL exhibited significant increases in several biomechanical parameters in comparison to the other groups. Moreover, IDEAL presented stronger Col1 immunoreactivity when compared to ID, and weaker Col3 immunoreactivity than IDE. Both IDL and IDEAL demonstrated weaker expression of MMP-3 in comparison to I, while IDL presented no expression of MMP-13 when compared to ID. ID, IDL and IDE showed an increased number of fibroblasts in comparison to I, while IDEAL decreased the number of these cells in comparison to ID and IDE. IDL and IDEAL groups exhibited decreased angular dispersion among the fibroblasts when compared to I. The gene expression results showed that IDE demonstrated a downregulation in Col1 mRNA expression in comparison to I and ID. IDEAL demonstrated upregulation of Col1 mRNA expression when compared to IDL or IDE alone and increased MMP-2 expression when compared to IDL and IDE. MMP-9 expression was upregulated in IDEAL when compared to I, IDL and IDE. Our results suggest a beneficial interaction of combining both treatment strategies i.e., aerobic exercise and LPBM, on the biomechanical properties, tissue morphology and the expression of matrix molecules in diabetic tendons.

Cutaneous angiosarcoma: report of three different and typical cases admitted in a unique dermatology clinic.

Angiosarcoma is a rare and aggressive tumor with high rates of metastasis and relapse. It shows a particular predilection for the skin and superficial soft tissues. We report three distinct and typical cases of angiosarcoma that were diagnosed in a single dermatology clinic over the course of less than a year: i) Angiosarcoma in lower limb affected by chronic lymphedema, featuring Stewart-Treves syndrome; ii) a case of the most common type of angiosarcoma loated in the scalp and face of elderly man and; iii) a skin Angiosarcoma in previously irradiated breast. All lesions presented characteristic histopathological findings: irregular vascular proliferation that dissects the collagen bundles with atypical endothelial nuclei projection toward the lumen.

Exercise training ameliorates matrix metalloproteinases 2 and 9 messenger RNA expression and mitigates adverse left ventricular remodeling in streptozotocin-induced diabetic rats.

BACKGROUND: The aim was to investigate whether exercise training (ExT) would ameliorate expression of key genes for myocardial morphostructure and mitigate adverse left ventricular (LV) remodeling in experimental type 1 diabetes (T1D). METHODS AND RESULTS: Male Wistar rats were divided into four groups: sedentary control (SC, n=9), trained control (TC, n=13), sedentary diabetic (SD, n=20), and trained diabetic (TD, n=17). T1D was induced by 40 mg/kg streptozotocin (single dose, i.v.). Training program consisted of 4-week treadmill running (60 min/day, 5 days/wk). Structure of the LV was evaluated using histomorphometric techniques. Gene expression changes of LV collagens I and III, metalloproteinases (MMPs) 2 and 9, and transforming growth factor-ß1 were detected by reverse transcriptase quantitative polymerase chain reaction. Compared with SC, SD rats presented LV eccentric remodeling, myocyte hypertrophy, and fibrosis, whereas TD animals showed normal LV geometry and collagen content but thinner myocytes. Expression of collagens and type I/III collagen messenger RNA (mRNA) ratio were diminished in diabetic hearts compared with SC. MMP-2 gene was down-regulated in SD, whereas TD group showed decreased MMP-9 mRNA levels and MMP-2 expression comparable to that of SC rats. CONCLUSIONS: Attenuation of MMP-2 down-regulation and reduction in MMP-9 mRNA expression may constitute an underlying mechanism by which ExT counteracts progression of adverse LV remodeling in T1D.

A new acridine derivative induces cell cycle arrest and antiangiogenic effect on Ehrlich ascites carcinoma model.

BACKGROUND: Acridine derivatives, including amsacrine, have antitumor activity. However, side effects, development of resistance and their low bioavailability, have limited their use. Herein, we described the synthesis, and evaluated the toxicity and antitumor activity of a new amsacrine analogous, the N'-(2-chloro-6-methoxy-acridin-9-yl)-2-cyano-3-(4-dimethylaminophenyl)-acrilohidrazida (ACS-AZ10). METHODS: The compound was obtained in a linear pathway where the ASC-Az intermediate was obtained by coupling of 6,9-dichloro-3-methoxy-acridine and 2-ciany-acethohidrazide followed by condensation with the corresponding aldehyde. The toxicity of ACS-AZ10 was evaluated in mice using acute toxicity and micronucleus assays. Ehrlich ascites carcinoma model was used to investigate the antitumor activity and toxicity of ACS-AZ10 (7.5, 15 or 30mg/kg, i.p.), after nine days of treatment. Cell cycle and angiogenesis were also evaluated. RESULTS: The ASC-AZ10 was obtained with satisfactory yields and its structure was confirmed by spectroscopic and spectrometric techniques. On acute toxicity study, ACS-AZ10 (2000mg/kg, i.p.) induced transient depressant effects on central nervous system. The LD50 was approximately 2500mg/kg. ACS-AZ10 (15 or 30mg/kg) displayed significant antitumor activity considering the tumor weight and volume, cell viability, and total Ehrlich cell count. ACS-AZ10 (7.5mg/kg) induced an increase in sub-G1 peak, suggesting apoptosis. At 15mg/kg ACS-AZ10 induced cell cycle arrest in G2/M phase and a reduction in the percentage of cells in G0/G1 and S phases, suggesting a pre-mitotic blockade. ACS-AZ10 reduced the microvessel density, indicating an antiangiogenic effect. Weak hematological, biochemical and histopathological toxicity were observed. The compound doesn't show genotoxicity in micronucleus assay. CONCLUSIONS: ACS-AZ10 has potent antitumor activity in vivo along with low toxicity.

Physical and mental health impacts during COVID-19 quarantine in adolescents with preexisting chronic immunocompromised conditions

Abstract Objective: To evaluate physical and mental health indicators in adolescents with preexisting chronic immunocompromised conditions during coronavirus disease 2019 (COVID-19) quarantine. Methods: A cross-sectional study included 355 adolescents with chronic conditions and 111 healthy adolescents. An online self-rated survey was used to investigate socio-demographic features, healthcare routine, and the quarantine impact on physical and mental health. The validated self-reported version of the Strengths and Difficulties Questionnaire (SDQ) was also applied. Results: The median of age [14 (10-18) vs. 15 (10-18) years, p = 0.733] and frequencies of female (61% vs. 60%, p = 0.970) were similar between adolescents with preexisting chronic conditions and healthy adolescents during quarantine of COVID-19 pandemic. The frequencies of abnormal total difficulties score of SDQ were similar in patients and controls (30% vs. 31%, p = 0.775). Logistic regression analysis showed that being female (OR = 1.965; 95% CI = 1.091-3.541, p = 0.024), fear of underlying disease activity/complication (OR = 1.009; 95%CI = 1.001-1.018, p = 0.030) were associated with severe psychosocial dysfunction in adolescents with chronic conditions, whereas school homework (OR = 0.449; 95% CI = 0.206-0.981, p = 0.045) and physical activity (OR = 0.990; 95% CI = 0.981-0.999, p = 0.030) were protective factors. Further analysis of patients with chronic immunocompromised conditions and previous diagnosis of mental disorders (9%) compared with patients without diagnosis showed higher median of total difficulties score (p = 0.001), emotional (p = 0.005), conduct (p = 0.007), peer problems (p = 0.001) and hyperactivity (p = 0.034) in the former group. Conclusion: Adolescents with preexisting chronic immunocompromised conditions during COVID-19 quarantine were not at higher risk of adverse health indicators. Being female, fear of underlying disease activity/complication, and household members working outside of the home were relevant issues for adolescents with preexisting chronic conditions. This study reinforces the need to establish mental health strategies for teens with chronic conditions, particularly during the pandemic.

Bacillary angiomatosis with bone invasion.

Bacillary angiomatosis is an infection determined by Bartonella henselae and B. quintana, rare and prevalent in patients with acquired immunodeficiency syndrome. We describe a case of a patient with AIDS and TCD4+ cells equal to 9/mm3, showing reddish-violet papular and nodular lesions, disseminated over the skin, most on the back of the right hand and third finger, with osteolysis of the distal phalanx observed by radiography. The findings of vascular proliferation with presence of bacilli, on the histopathological examination of the skin and bone lesions, led to the diagnosis of bacillary angiomatosis. Corroborating the literature, in the present case the infection affected a young man (29 years old) with advanced immunosuppression and clinical and histological lesions compatible with the diagnosis.