Asymmetric Transfer Hydrogenation of Arylidene-Substituted Chromanones and Tetralones Catalyzed by Noyori-Ikariya Ru(II) Complexes: One-Pot Reduction of C═C and C═O bonds.

3-Arylidenechroman-4-ones and 2-arylidene-1-tetralones are hydrogenated to cis-benzylic alcohols in dr's and er's up to 99:1 via a C═C and C═O one-pot reduction in the presence of 2-5 mol % Noyori-Ikariya-type RuII chiral complexes and HCO2Na as a hydrogen source under asymmetric transfer hydrogenation-dynamic kinetic resolution (ATH-DKR) conditions. The oxidation of theses substrates resulted in the enantioselective synthesis of the natural homoisoflavanone dihydrobonducellin and its carba-analogues.

Incidence of pale, soft and exudative (PSE) pork meat in reason of extrinsic stress factors.

The incidence of PSE (pale, soft and exudative) pork meat is directly influenced by pre-slaughter handling of animals, compromising meat quality and resulting in economic losses for industry. Considering management, the main extrinsic stress factors are: the pre-slaughter rest time in lairage, the total fasting time and at farm and the transport time. To evaluate the effects of these factors on PSE meat incidence, pH of 1038 carcasses was measured at 45 minutes post mortem (pH45) in a pig slaughterhouse in Paraná, Brazil. Carcasses with pH45≤5.8 were classified as PSE, and those with pH45>5.8 as normal. In order to verify if the factors influence PSE meat appearance, it was divided into categories according to it duration, and according to the number of animals evaluated in each category, the PSE meat frequency was estimated, and which time intervals obtained the lower incidence of the change. The total incidence of PSE carcasses was 19.17%. The periods of rest in lairage, total fasting, fasting at farm and transport that minimized the occurrence of PSE meat were from 04h01 to seven hours, from 14h01 to 17h00, from 03h01 to five hours, and from 02h01 to three hours, respectively.

Tissue damage and cytotoxic effects of Tagetes minuta essential oil against Lucilia cuprina.

The blowfly Lucilia cuprina has great medico-sanitary and veterinary importance due to the ability of its larval form to develop in decaying organic matter, parasitizing vertebrates. Fly eradication is challenging and the essential oil (EO) of Tagetes minuta (TMEO) have been reported to have therapeutic properties. This study aimed to determine the activity of EO from the aerial parts of T. minuta against third instar larvae (L3) of L. cuprina. Groups of 20 L3 were placed on filter paper, which were impregnated with varying concentrations (0.19; 0.39; 0.79; 1.59; 2.38; 3.18; 4.77; and 6.36 µL/cm2) of TMEO solubilized in acetone, ethanol or Tween 20. Histological tissue damage of TMEO was measured in L3 after 24, 48 and 96 h of exposure. Dihydrotagetone (67.64%), trans-ocimene (16.23%), trans-tagetone (10.14%) and verbenone (2.98%) were obtained as major compounds of TMEO. Lethal concentrations of 50%, 24 and 48 h after TMEO exposure were 1.02 and 0.73 µL/cm2 for acetone; 3.37 and 1.75 µL/cm2 for ethanol; and 7.46 and 6.11 µL/cm2 for Tween 20, respectively. TMEO had a significant L3 mortality of 96.6% in acetone, 48 h after contact. Cuticle abnormalities were observed, as well as the loss of digestive tract architecture and vacuolization in fat bodies. TMEO presented time and concentration-dependent effects against L. cuprina. As our study demonstrated a strong insecticide activity of TMEO, we consider that it could be developed into an ecofriendly product against L. cuprina.

Insecticide activity of Curcuma longa (leaves) essential oil and its major compound α-phellandrene against Lucilia cuprina larvae (Diptera: Calliphoridae): Histological and ultrastructural biomarkers assessment.

Lucilia cuprina, known as the Australian blowfly, is of high medico-sanitary and veterinary importance due to its ability to induce myiasis. Synthetic products are the most frequent form of fly control, but their indiscriminate use has selected for resistant populations and accounted for high levels of residues in animal products. This study aimed to assess the effect of essential oil from leaves of Curcuma longa (CLLEO), and its major compound α-phellandrene against L. cuprina L3. An additional goal was to determine the morphological alterations in target organs/tissues through ultrastructural assessment (SEM) and light microscopy, as well as macroscopic damage to cuticle induced by CLLEO. Groups of 20 L3 were placed on filter paper impregnated with increasing concentrations of CLLEO (0.15 to 2.86 µL/cm2) and α-phellandrene (0.29 to 1.47 µL/cm2). Efficacy was determined by quantifying L3 mortality 6, 24 and 48 h after contact with CLLEO and by measuring the structural damage to L3. CLLEO and α-phellandrene inhibited adult emergence by 96.22 and 100%, respectively. Macroscopic cuticle damage, appeared as diffuse pigment and darkening of larval body, was caused by both extracts. The SEM revealed dryness on the cuticle surface, distortion of the sensorial structures and general degeneration in treated L3. Furthermore, alterations in target organs (digestive tract, fat body and brain) were noticed and shall be used as biomarkers in future attempts to elucidate the mechanism of action of these compounds. The vacuolar degeneration and pyknotic profiles observed in the brain tissue of treated larvae with both extracts and the decreased motility within <6 h after treatment leads us to suggest a neurotoxic activity of the products. This work demonstrates the potential use of CLLEO and α-phellandrene as bioinsecticides to be used against L. cuprina, representing an ecofriendly alternative for myiasis control in humans and animals.

Analysis In Vivo of the Hemifacial Transplantation Surgical Technique.

Approximately 35 facial transplants have been performed worldwide. Many under-explored aspects of this procedure remain, some emerging as the survivors age. Human-like preclinical trial models, including swine, can be explored and developed as a foundation for subsequent studies. A previously described surgical technique for face transplantation in swine carcasses has been employed herein, evaluating its reproducibility in a live pig and the viability of the vascular pedicles. METHOD: Flap construction was performed according to the experimental model developed in our service. Under general anesthesia, the structures of the left hemiface of a pig were dissected. Vascular pedicles were the facial artery, caudal auricular artery, and external jugular vein. After dissection, adequate tissue perfusion of the entire explant by those pedicles was documented through vessel filling, observation of the ischemic area, and posterior reperfusion. RESULTS: A capillary reperfusion test confirmed that the main arterial pedicle irrigating the hemiface flap was the facial artery. The same technique showed that despite divergent literary opinions on the irrigation of the auricular region, the caudal auricular artery provides the arterial supply for the external ear. Performing the surgical technique was more difficult in vivo due to the inherent complications of a live subject. CONCLUSION: The methodology for the facial transplant technique in swine carcasses was satisfactorily reproducible in a live animal. The main arterial pedicle responsible for flap irrigation is the facial artery, and the fact that the vessel supplying the outer ear is the caudal atrial artery was confirmed.

Synthesis of New Quinoline-Piperonal Hybrids as Potential Drugs against Alzheimer's Disease.

Six quinoline-piperonal hybrids were synthesized and evaluated as potential drugs against Alzheimer's disease (AD). Theoretical analysis of the pharmacokinetic and toxicological properties of the compounds suggest that they present good oral bio-availability and are also capable of penetrating the blood-brain barrier, qualifying as leads for new drugs against AD. Evaluation of their inhibitory capacity against acetyl- and butyrilcholinesterases (AChE and BChE) through Ellmann's test showed that three compounds present promising results with one of them being capable of inhibiting both enzymes. Further docking studies of the six compounds synthesized helped to elucidate the main interactions that may be responsible for the inhibitory activities observed.

Resorbable Self-Locking Implant for Lung Lobectomy Through Video-Assisted Thoracoscopic Surgery: First Live Animal Application.

The aim of this pilot test was to test a new self-locking resorbable implant for hilum occlusion during a video-assisted thoracoscopic lung lobectomy in a surviving pig model. Once the thoracic cavity was assessed and structures identified, the right middle lobe and its respective hilum were exposed. The implant was introduced with a semiclosed loop through a working channel and positioned around the pulmonary lobe. Occlusion was performed with a conventional Crile forceps and a laparoscopic Kelly forceps. Lobe section was done with laparoscopic Metzenbaum scissors and tissue removal through the dorsal access. No signs of pneumothorax or bleeding were observed during a 60-day follow-up. Necropsy findings showed minimal pleuritis in caudal access and in the lobar stump. A granulomatous formation was found around a dense, amorphous material, which was identified as remains of a small part of the implant. Histopathological findings showed signs of a chronic healing process without other alterations. The resorbable implant LigaTie appears to exhibit similar handling and application characteristics during surgery as nonsurgical tie wraps. The resorbable implant avoids the uncontrolled substances not suitable for implants of conventional ties. The results of this pilot test suggested the resorbable implant's mechanical properties provided effective tissue support to complete the healing of the pulmonary hilum.

Surgical Technique of Hemi-Face Transplant: A New Model of Training.

OBJECTIVE: Face transplantation from cadaveric donors is an alternative that has been explored as a way to overcome the disadvantages of reconstructive plastic surgery for patients with severe facial deformities, when its approaches are not able to offer good aesthetic and functional results. In this study, the authors describe the surgical technique of face transplantation in swine, investigating the reproducibility of the methods as an experimental model in transplantation. METHODS: Seven swines were operated upon. After euthanasia, the left hemifacial area was removed and implanted onto the same location on the same animal from which it was removed. The vascular pedicle was based on the facial artery, the caudal auricular artery, and the external jugular vein. The ventral buccal and dorsal buccal branches of the facial nerve and the transverse facial branch of the auricular nerve were taken into the flap. RESULTS: The mean time of the procedure was 4.5 hours. Differences in vascularization were found as the vessel that provides blood supply to auricular region can be the caudal auricular artery, instead of the temporal artery, as described in the literature. Operative difficulty increases if the animal is more obese. The medical student had training in microsurgical procedures to be able to perform the entire procedure. CONCLUSION: This study describes an experimental model of face transplantation in swine, providing a good model for training of the surgical technique. The method is reproducible in any setting that offers resources in experimental surgery and microsurgery.

A comparison of inflammatory markers in depressed and nondepressed smokers.

INTRODUCTION: Both smoking and depression have been associated with increased inflammatory markers. As there are few studies on inflammatory markers that distinguish between depressed and nondepressed smokers, it is unclear if there is a cumulative impact of these mediators of inflammation. The aim of this study was to investigate inflammatory markers in tobacco smokers and compare depressed and nondepressed smokers. METHODS: Smokers (n = 155) were recruited from the Cigarette Smoking Cessation Service, Londrina. Mental health status was assessed using the Diagnostic Interview for Research, in accordance with the International Classification of the Disorders-10th (ICD-10). Demographic information was collected by self-report questionnaire, and the Fagerström Test for Nicotine Dependence was administered. Blood specimens were simultaneously collected and measured for C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). RESULTS: Depressed smokers had significantly higher levels of hs-CRP (p = .05), IL-6 (p = .039), and TNF-α (p = .021) compared with nondepressed smokers. Depressed smokers were also significantly more likely than nondepressed smokers to have been hospitalized in the previous month (p < .032), to suffer from cardiovascular disease (p < .001) and lung disease (p < .003), and to have more work-related disability (p = .001). CONCLUSIONS: These findings demonstrate that depressed smokers had higher hs-CRP, IL-6, and TNF-α levels than nondepressed smokers and had worse physical health outcomes and greater work-related disability. This may have important implications in identifying shared risk pathways for depressive and somatic disorders.

Searching for potential drugs against SARS-CoV-2 through virtual screening on several molecular targets.

The acute respiratory syndrome caused by the SARS-CoV-2, known as COVID-19, has been ruthlessly tormenting the world population for more than six months. However, so far no effective drug or vaccine against this plague have emerged yet, despite the huge effort in course by researchers and pharmaceutical companies worldwide. Willing to contribute with this fight to defeat COVID-19, we performed a virtual screening study on a library containing Food and Drug Administration (FDA) approved drugs, in a search for molecules capable of hitting three main molecular targets of SARS-CoV-2 currently available in the Protein Data Bank (PDB). Our results were refined with further molecular dynamics (MD) simulations and MM-PBSA calculations and pointed to 7 multi-target hits which we propose here for experimental evaluation and repurposing as potential drugs against COVID-19. Additional rounds of docking, MD simulations and MM-PBSA calculations with remdesivir suggested that this compound can also work as a multi-target drug against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

An abortion storm in dairy cattle associated with neosporosis in southern Brazil.

Between December 2016 and April 2017, a spate of abortions occurred in a closed dairy herd from the central eastern region of Paraná, Brazil, in which 75 cows aborted. To identify its cause, organ fragments were collected from an aborted fetus for histopathology, and the blood samples from a stillborn, 4 aborted fetuses, and 9 farm dogs for indirect fluorescent antibody technique (IFAT). These tests found multifocal non-suppurative encephalitis, periportal hepatitis, and multifocal lymphoplasmacytic myocarditis, and detected anti-Neospora antibodies in all aborted fetuses, and in 5 of the 9 dogs. DNA of Neospora caninum was detected in the brain tissue of an aborted fetus. Blood samples of 340 cows and 146 heifers showed 33.5% and 30.8% seropositivity, respectively. In this closed herd, the parasite was probably introduced by infected domesticated or wild carnivores inhabiting the farm, through the infective oocysts present in their stool.

Synthesis and Biological Activity of Hydrazones and Derivatives: A Review.

Hydrazones and their derivatives are very important compounds in medicinal chemistry due to their reported biological activity for the treatment of several diseases, like Alzheimer's, cancer, inflammation, and leishmaniasis. However, most of the investigations on hydrazones available in literature today are directed to the synthesis of these molecules with little discussion available on their biological activities. With the purpose of bringing lights into this issue, we performed a revision of the literature and wrote this review based on some of the most current research reports of hydrazones and derivatives, making it clear that the synthesis of these molecules can lead to new drug prototypes. Our goal is to encourage more studies focused on the synthesis and evaluation of new hydrazones, as a contribution to the development of potential new drugs for the treatment of various diseases.

Effects of Tagetes minuta essencial oil on Lucilia cuprina third instar larvae.

The activity of Tagetes minuta essential oil (TMEO) was tested against third instar larvae (L3) of the Australian blowfly Lucilia cuprina. We have determined the potential of the T. minuta EO as a new biopesticide candidate. To test this, groups of 20 L3 were placed on filter paper impregnated with ranging concentrations (from 0.19 to 6.36 µL/cm2) of TMEO, solubilized in acetone. Data show in this article is related to research article "Tissue damage and cytotoxic effects of Tagetes minuta essential oil against Lucilia cuprina" Chaaban et al., 2019. Thus, data of cuticle damage, color changes in L3 body and decrease in L3 motility were recorded 24 and 48 h after TMEO contact.

Data of insecticide effects of natural compounds against third instar larvae of Cochliomyia macellaria.

Morphological biomarkers can be used to establish a diagnosis of fly larvae structural damage and toxicity to target cells by biopesticide candidates. Insecticide activity of natural compounds such as Curcuma longa essential oil (CLLEO) extracted from leaves, and its major constituent α-phellandrene have proven to be a novel biopesticide candidate against third instar larvae (L3) of Cochliomyia macellaria. In this way, groups of 20 L3 were placed on filter paper impregnated with different concentrations of CLLEO, from 0.31 to 2.86 µL/cm2 and α-phellandrene, from 0.29 to 1.47 µL/cm2. The extracts were solubilized in ethanol. Data shown in this article is related to the research article "Can an overlooked by-product from turmeric industry be effective for myiasis control?" Chaaban et al., 2019. Data on L3 toxicity was observed after 6 and 24h of contact with both extracts, as well as a marked reduction of L3 movement, color changes in the cuticle and progressive darkening in their body. Major cuticle damage and L3 mortality were reported.

Cuticular damage of Lucilia cuprina larvae exposed to Curcuma longa leaves essential oil and its major compound α-phellandrene.

Morphological biomarkers as the histopathological assessment and scanning electron microscopy can be used to establish a diagnosis of structure damage and intoxication of target cells by new biopesticide candidate. In this sense, cuticle damage caused by active substances in larvae exposed to biopesticides can help to elucidate the mode action. Thus, insecticide activity analysis of essential oil of Curcuma longa leaves and its major compound α-phellandrene have proven to be a new biopesticide candidate against third instar larvae (L3) of the Australian blowfly Lucilia cuprina. In this way, groups of 20 L3 were placed on filter paper, impregnated with ranging concentrations (from 0.15 to 2.86 µL/cm2) of C. longa leaves EO and (0.29-1.47 µL/cm2) to α-phellandrene. The extracts were solubilized in ethanol. Progressive darkening in the body of L3, marked reduction of movement, color changes in larval cuticle and dead were observed 6 and 24 h after contact with both extracts.

Evaluation of the active concentration of two disinfectants based on glutaraldehyde and benzalkonium chloride and antimicrobial activity in vitro against Salmonella Heidelberg and Salmonella Typhimurium

Biosecurity, cleaning and disinfection of swine and poultry facilities are fundamental for the reduction of pathogenic microorganisms of importance for public and animal health. The objective of this work was to compare the levels of active ingredient described on the label and the real levels detected in high-performance liquid chromatography (HPLC) of two disinfectants., then evaluate the antimicrobial activity since, following the Germicidal Sanitizing Action and Disinfectant Detergent (Official Method AOAC 960.09) in four different dilutions with the presence of 3% organic matter during 15 min of contact, against Salmonella Heidelberg and Salmonella Typhimurium (ST). The product "A" presents active levels of agreement according to the label. The content of quantified assets for product "B" was lower than that recorded on the label. The disinfectant "A" was effective in microbiological evaluation while the disinfectant "B" had microbiocidal activity compromised by the deficit of assets.

Mycobacterium bovis in a European bison (Bison bonasus) raises concerns about tuberculosis in Brazilian captive wildlife populations: a case report.

BACKGROUND: Tuberculosis caused by Mycobacterium bovis is an important worldwide zoonosis and has been reported to cause clinical disease in several animal species, including captive wildlife. This report describes a case of M. bovis infection in a European bison from a Brazilian zoo and compiles a number of literature reports that raise concern regarding tuberculosis among captive wildlife in Brazil. CASE PRESENTATION: A 13 year-old captive-born male bison (Bison bonasus) from a Brazilian zoo began presenting weight loss, diarrhea and respiratory symptoms, which inevitably led to his death. At the animal's necropsy, inspection of the thoracic and abdominal cavities revealed multiple enlarged lymph nodes, ranging from 4 to 10 cm, and pulmonary nodules containing caseous masses with firm white materials consistent with mineralization. Histopathology findings showed a significant amount of acid-alcohol resistant bacilli compatible with Mycobacterium spp. Specimens from lymph nodes and lungs were cultured on Petragnani and Stonebrink media, and specific PCR assays of the bacterial isolate identified it as M. bovis. CONCLUSION: The European bison reported herein died from a severe form of disseminated tuberculosis caused by M. bovis. A review of the available literature indicates possible widespread occurrence of clinical disease caused by M. bovis or M. tuberculosis affecting multiple animal species in Brazilian wildlife-related institutions. These likely underestimated numbers raise concern regarding the control of the disease in captive animal populations from Brazil.

Methylmalonate Induces Inflammatory and Apoptotic Potential: A Link to Glial Activation and Neurological Dysfunction.

Methylmalonic acid (MMA) accumulates in tissues in methylmalonic acidemia, a heterogeneous group of inherited childhood diseases characterized by neurological dysfunction, oxidative stress and neuroinflammation; it is associated with degeneration of striatal neurons and cerebral cortical atrophy. It is presently unknown, however, whether transient exposure to MMA in the neonatal period is sufficient to trigger inflammatory and apoptotic processes that lead to brain structural damage. Here, newborn mice were given a single intracerebroventricular dose of MMA at 12 hours after birth. Maze testing of 21- and 40-day-old mice showed that MMA-injected animals exhibited deficit in the working memory test but not in the reference test. MMA-injected mice showed increased levels of the reactive oxygen species marker 2',7'-dichlorofluorescein diacetate, tumor necrosis factor, interleukin-1ß, caspases 1, 3, and 8, and increased acetylcholinesterase activity in the cortex, hippocampus and striatum. This was associated with increased astrocyte and microglial immunoreactivity in all brain regions. These findings suggest that transient exposure to MMA may alter the redox state and cause neuroinflammatory/apoptotic processes and glial activation during critical periods of brain development. Similar processes may underlie brain dysfunction and cognitive impairment in patients with methylmalonic acidemia.

Action of benzalkonium chloride in different pH

Ammonium quaternary compounds are widely used in poultry and swine production as disinfectants in the control of pathogens. They act on gram-positive bacteria, gram-negative bacteria, enveloped fungi and viruses. However, in some conditions of pH and presence of organic matter can be inactivated. This study evaluated the action of ammonium quaternary compounds at 1:1,000 and 1:2,000 dilutions against Salmonella enterica serovarTyphimurium and Salmonella enterica serovar Enteritidis in the presence of three different organic matter simulators, fetal bovine serum, skim milk and whole milk concentration of 1, 3, 5, and 7% and at pH 6 and 9, with 15 min of contact. It was possible to verify that the organic matter simulators adjusted in the same conditions of contact time and percentage, in the in vitro tests, presented different results and the fetal bovine serum did not inactivate the disinfectant. However, the best result against S. Typhimurium and S. Enteritidis was obtained at pH 6 at the dilution of 1:1,000 in all organic matter simulators.

Oxidative stress in hoof laminar tissue of horses with lethal gastrointestinal diseases.

Tissue damage caused by oxidative stress is involved in the pathogenesis of several diseases in animals and man, and is believed to play a role in the development of laminitis in horses. The aim of this study was to investigate the oxidative stress associated with laminar lesions in horses with lethal gastrointestinal disorders. Laminar tissue samples of the hoof of 30 horses were used. Tissue samples were divided as follows: six healthy horses (control group-CG), and 24 horses that died after complications of gastrointestinal diseases (group suffering from gastrointestinal disorders-GDG). Superoxide dismutase (SOD2) and nitrotyrosine immunostaining and the severity of laminar lesions were evaluated. Presence of laminar lesions and immunostaining for nitrotyrosine and SOD2 were only evident in horses from the GDG group. Thus, oxidative stress may play a role in the pathogenesis of laminar lesions secondary to gastrointestinal disorders.