An overview on the current available treatment for COVID-19 and the impact of antibiotic administration during the pandemic

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused several problems in healthcare systems around the world, as to date, there is no effective and specific treatment against all forms of COVID-19. Currently, drugs with therapeutic potential are being tested, including antiviral, anti-inflammatory, anti-malarial, immunotherapy, and antibiotics. Although antibiotics have no direct effect on viral infections, they are often used against secondary bacterial infections, or even as empiric treatment to reduce viral load, infection, and replication of coronaviruses. However, there are many concerns about this therapeutic approach as it may accelerate and/or increase the long-term rates of antimicrobial resistance (AMR). We focused this overview on exploring candidate drugs for COVID-19 therapy, including antibiotics, considering the lack of specific treatment and that it is unclear whether the widespread use of antibiotics in the treatment of COVID-19 has implications for the emergence and transmission of multidrug-resistant bacteria.

An overview on the current available treatment for COVID-19 and the impact of antibiotic administration during the pandemic.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused several problems in healthcare systems around the world, as to date, there is no effective and specific treatment against all forms of COVID-19. Currently, drugs with therapeutic potential are being tested, including antiviral, anti-inflammatory, anti-malarial, immunotherapy, and antibiotics. Although antibiotics have no direct effect on viral infections, they are often used against secondary bacterial infections, or even as empiric treatment to reduce viral load, infection, and replication of coronaviruses. However, there are many concerns about this therapeutic approach as it may accelerate and/or increase the long-term rates of antimicrobial resistance (AMR). We focused this overview on exploring candidate drugs for COVID-19 therapy, including antibiotics, considering the lack of specific treatment and that it is unclear whether the widespread use of antibiotics in the treatment of COVID-19 has implications for the emergence and transmission of multidrug-resistant bacteria.

Protein from Hevea brasiliensis "Hev b 13" latex attenuates systemic inflammatory response and lung lesions in rats with sepsis / Proteína do latex de Hevea brasiliensis "Hev b 13" atenua resposta inflamatória sistêmica e lesão pulmonar de ratos com sepse

Abstract Sepsis induces a severe systemic inflammatory response that may result in multiple organ dysfunction and death. Studies using a protein derived from natural Hevea brasiliensis (rubber tree) latex, denominated Hev b 13, have demonstrated important anti-inflammatory effects, but no data have been published regarding its effects on sepsis. The aim of this study was to investigate the effects of Hev b 13 on the inflammatory response and lung lesions of septal rats. Male Wistar rats were submitted to cecal ligation and puncture (CLP), randomized into groups and treated with subcutaneously administered doses of 0.5/2.0/3.0 mg/Kg of Hev b 13. Next, animals were subdivided into three different points in time (1, 6 and 24 hours after treatments) for collection of blood samples and euthanasia accompanied by organ removal. Total and differential leukocyte counts, cytokine dosage and histological assessment were analyzed. Treatment with Hev b 13 resulted in a significant decline in total and differential leukocytes as well as suppression of TNF-α and IL-6 production, associated with the increase in IL-10 and IL-4 in plasma and lung tissue. Moreover, it reduced morphological and pathological changes found in the lungs, including neutrophil infiltration, edema and alveolar thickening. The present study concluded that Hev b 13 exerts anti-inflammatory effects and attenuates lung lesions in septal rats, showing potential for clinical application.

Resumo Sepse induz uma resposta inflamatória sistêmica grave podendo resultar em disfunção de múltiplos órgãos e morte. Pesquisas utilizando uma proteína derivada do látex natural de Hevea brasiliensis (seringueira), denominada Hev b 13 tem demonstrado importantes efeitos anti-inflamatórios, mas nenhum dado foi publicado dos seus efeitos na sepse. O objetivo deste estudo foi investigar os efeitos da Hev b 13 na resposta inflamatória e na lesão pulmonar de ratos com sepse. Ratos machos da linhagem Wistar foram submetidos a ligação e perfuração do ceco (LPC), randomizados em grupos e tratados com as doses 0,5/2,0/3,0 mg/Kg de Hev b 13 subcutâneo. Após subdividiu-se os animais em três pontos diferentes de tempo (1, 6 e 24 horas após os tratamentos) para coleta de amostras sanguíneas e eutanásia com remoção dos órgãos. Contagem total e diferencial de leucócitos, dosagem de citocinas e avaliação histológica foram analisadas. O tratamento com a Hev b 13 resultou em diminuição significativa de leucócitos totais e diferenciais bem como suprimiu a produção de TNF-α e IL-6, associado ao aumento de IL-10 e IL-4 no plasma e tecido pulmonar. Além disso, reduziu as alterações morfológicas e patológicas encontradas nos pulmões, incluindo infiltrado de neutrófilos, edema e espessamento alveolar. Este estudo concluiu que a Hev b 13 tem efeitos anti-inflamatórios e atenua lesões pulmonares em ratos com sepse, apresentando potencialidades para aplicabilidade clínica.

Protein from Hevea brasiliensis "Hev b 13" latex attenuates systemic inflammatory response and lung lesions in rats with sepsis.

Sepsis induces a severe systemic inflammatory response that may result in multiple organ dysfunction and death. Studies using a protein derived from natural Hevea brasiliensis (rubber tree) latex, denominated Hev b 13, have demonstrated important anti-inflammatory effects, but no data have been published regarding its effects on sepsis. The aim of this study was to investigate the effects of Hev b 13 on the inflammatory response and lung lesions of septal rats. Male Wistar rats were submitted to cecal ligation and puncture (CLP), randomized into groups and treated with subcutaneously administered doses of 0.5/2.0/3.0 mg/Kg of Hev b 13. Next, animals were subdivided into three different points in time (1, 6 and 24 hours after treatments) for collection of blood samples and euthanasia accompanied by organ removal. Total and differential leukocyte counts, cytokine dosage and histological assessment were analyzed. Treatment with Hev b 13 resulted in a significant decline in total and differential leukocytes as well as suppression of TNF-α and IL-6 production, associated with the increase in IL-10 and IL-4 in plasma and lung tissue. Moreover, it reduced morphological and pathological changes found in the lungs, including neutrophil infiltration, edema and alveolar thickening. The present study concluded that Hev b 13 exerts anti-inflammatory effects and attenuates lung lesions in septal rats, showing potential for clinical application.

Avaliação da atividade angiogênica da solução aquosa do barbatimão (Stryphnodendron adstringens) / Angiogenic activity of the aqueous solution of Barbatimão (Stryphnodendron adstringens)

RESUMO O Barbatimão (Stryphnodendron adstringens) planta medicinal encontrada no bioma Cerrado apresenta propriedades físico-químicas que lhe garante importantes atividades farmacológicas tais como: anti-inflamatória, analgésica e uma atividade protetora da mucosa gástrica. A casca do tronco é a principal matéria-prima usada para o desenvolvimento de produtos medicinais. Neste estudo, o objetivo foi investigar a influência da solução aquosa da casca do barbatimão no processo de formação de vasos sanguíneos na membrana corioalontoide de ovo embrionado de galinha. Foram utilizadas 30g da casca triturada em um litro de água. Este processo permitiu a obtenção da Solução Aquosa de Barbatimão - SAB em uma concentração de 30mg/mL. A atividade angiogênica da solução aquosa do barbatimão foi avaliada mediante realização de testes laboratoriais “in vivo”, utilizando como modelo experimental a membrana do ovo embrionado de galinha (MCA). Utilizou-se como controle indutor o Regederm®, o qual apresenta atividade angiogênica conhecida. Os resultados demonstraram que a SAB apresentou um percentual de vascularização na MCA de (50.4%) não tendo diferença (p>0,05) aos valores detectados no controle indutor (52,9%). Com os resultados obtidos, percebe-se que o barbatimão apresenta atividade angiogênica no modelo experimental utilizado.

ABSTRACT The Barbatimão (Stryphnodendron adstringens) medicinal plant found in the Cerrado biome has physicochemical properties which guarantee important pharmacological activities such as anti-inflammatic, analgesic and protective activities of gastric mucosa. The bark of the trunk is the main raw material used for the development of medicinal products. In this study, the objective was to investigate the influence of the aqueous solution of barbatimão bark in the formation of blood vessels in the membrane of embryonated chicken egg corioalontoid. 30g of shredded bark was used in one liter of water. This process enabled the obtention of aqueous Barbatimão - BSA at a concentration of 30mg / ml. The angiogenic activity of the aqueous solution of barbatimão was assessed by laboratory testing “in vivo”, using the chorioallantoic membrane of embryonated chicken egg (MCA) as an experimental model. TheRegederm® controlinductor was used, which exhibits known angiogenic activity. The results showed that the percentage of BSA showed a vascularization of the MCA (50.4%) there was no difference (p> 0.05) in the values detected in the control inductor (52.9%). With the obtained results, it is clear that barbatimão shows angiogenic activity under the experimental model used.

Angiogenic activity of latex from Euphorbia tirucalli Linnaeus 1753 (Plantae, Euphorbiaceae).

To assess the pro-angiogenic activity of Euphorbia tirucalli, commonly known as "avelós" plant, we performed a series of tests by applying an aqueous E. tirucalli latex solution (10 mg/mL) to the chorioallantoic membranes (CAMs) of 80 fertilized chicken eggs incubated in a temperature- and humidity-controlled automatic incubator. The results indicated that the aqueous latex solution increased vascular network formation compared to that with the negative control (p < 0.05) and the inhibitor control (p < 0.05). This suggests that under the experimental conditions tested, the aqueous latex solution induced an inflammatory response leading to neoangiogenesis.

Assessment of the cytotoxic, genotoxic, and antigenotoxic activities of sucupira oil (Pterodon emarginatus).

The present study aimed to assess the cytotoxic, genotoxic, and antigenotoxic activities of sucupira oil (Pterodon emarginatus), which is commonly used as an anti-rheumatic, analgesic, antimicrobial, anticercariae, and anti-inflammatory. We used the mouse bone marrow micronucleus test as an experimental model. The experimental groups, which consisted of 5 animals, was administered sucupira oil (100 mg/kg body weight) intraperitoneally and evaluated 24 h after the treatment. The negative control group was treated with sterile distilled water, and the positive control group received an intraperitoneal dose of 4 mg/kg mitomycin C, a dose that corresponds to 80% of its median lethal dose. Cytotoxicity was determined by the polychromatic to normochromatic erythrocytes ratio (PCE/NCE). Sucupira oil had no significant effects (P > 0.05) on the frequency of micronucleated polychromatic erythrocytes as compared to the negative control group. However, the difference was significant (P < 0.005) as compared to the positive control group. The PCE/NCE (100 mg/kg oil and 4 mg/kg mitomycin) ratio did not differ between the experimental group and the positive control group, but it differed significantly when compared to the negative control group (P < 0.05). Thus, these findings suggested that the P. emarginatus oil showed no cytotoxic, mutagenic, or antimutagenic activities at a dose of 100 mg/kg.

Brain SPECT imaging in children and adolescents with obsessive-compulsive disorder.

OBJECTIVE: To evaluate the patterns of regional cerebral blood flow (rCBF) in cortical and subcortical regions by Brain SPECT imaging, in children and adolescents with obsessive-compulsive disorder (OCD) before and after treatment. METHOD: Fourteen OCD patients (6 to 17 years old) underwent brain SPECT; ten of those subjects were reexamined after successful treatment. rCBF ratios were correlated with clinical parameters on the 14 patients in symptomatic state, and we compared rCBF ratios of the ten patients before and after treatment. RESULTS: There was no statistically significant difference in average ratios of rCBF before and after treatment. There were significant clinical correlations between current age and age of onset of OCD and rCBF in the bilateral superior frontal, and bilateral parietal cortical regions. CONCLUSIONS: Further investigations on abnormal neurodevelopment of cortical-subcortical circuits possibly involved in symptomatology of paediatric OCD are warranted.

Self-exposure therapy for panic disorder with agoraphobia: randomised controlled study of external v. interoceptive self-exposure.

BACKGROUND: Exposure to external phobic cues is an effective therapy for panic/agoraphobia but the value of exposure to interoceptive cues is unclear. AIMS: Randomised controlled comparison in panic/agoraphobia of the effects of (a) external, (b) interceptive or (c) combined external and interoceptive self-exposure to (d) control subjects. METHOD: Eighty out-patients were randomised to a control group or to one of three forms of self-exposure treatment (external, interoceptive, or combined). Each treatment included seven sessions over 10 weeks and daily self-exposure homework. Assessments were at pre- and post-treatment and up to 1 year post-entry. Assessors remained blind during treatment. RESULTS: The three self-exposure groups improved significantly and similarly at post-treatment and up to 1-year followup, and significantly more than did the control subjects. Rates of improvement on main outcome measures averaged 60% at post-treatment and 77% at follow-up. CONCLUSIONS: The three methods of self-exposure were equally effective in reducing panic and agoraphobic symptoms in the short- and long-term.

Experience with demucosalized ileum for bladder augmentation.

OBJECTIVE: To assess the use of demucosalized ileum for bladder augmentation, following the same principles previously used with the sigmoid colon. PATIENTS AND METHODS: Eleven patients with bladder exstrophy or a neurogenic bladder had their bladders augmented with demucosalized ileum instead of the sigmoid colon, but following the same technique. The use of a Foley catheter with an inflated balloon greatly facilitated the dissection of the mucosa from the muscle. A silicone model, inserted in the bladder, was used to avoid shrinkage of the patch. An animal model was also used for total bladder replacement following the same principle. RESULTS: The mean (range) follow-up was 15.4 (2-25) months. There was a significant increase in bladder compliance in all patients. A bladder of good shape and compliance was obtained in the animal model, with epithelial growth detected in all cases. CONCLUSIONS: Demucosalized ileum can be used safely for bladder augmentation in the same way as with the sigmoid colon. The distension of the isolated patch greatly facilitates dissection between the mucosa and muscle. The animal model supported this method of bladder replacement.

Further experience with the periurethral expander: a new type of artificial sphincter.

OBJECTIVE: To determine the long-term effects of the periurethral expander, a new device for the treatment of urinary incontinence in children. PATIENTS AND METHODS: Twenty-five patients (mean age 11.2 years, range 3-22) had a periurethral expander implanted around the bladder neck within the last 41 months. Twelve of these patients had neurogenic bladders as a result of myelomeningocele, 12 had undergone unsuccessful exstrophy reconstructions and one had megalourethra. Bladder augmentations were carried out in 23 of the patients. The mean follow-up was 23 months. RESULTS: Ten patients had the device removed due to erosion and/or infection; patients with exstrophy were more susceptible to complications. Patients with neurogenic bladders use clean intermittent catheterization and the remainder void spontaneously. The mean pressure in the cuff was 58.7 cmH2O. CONCLUSION: The periurethral expander seems to be a valid option in the treatment of selected cases of urinary incontinence in children and young adults. There were more complications in patients with exstrophy/epispadias and such patients must be considered unsuitable for this treatment.

Early compliance and other factors predicting outcome of exposure for obsessive-compulsive disorder.

BACKGROUND: Identifying predictors of treatment outcome can suggest ways to improve treatment delivery and understanding of its mechanism of action. METHOD: Predictors of treatment outcome were sought among 46 out-patients with obsessive-compulsive disorder who completed a nine-week randomised controlled trial of two forms of exposure therapy with ritual prevention. RESULTS: In both exposure conditions the best predictor of good outcome at the end of treatment (week 9) and of follow-up (week 32) was early compliance in doing exposure homework within a week of starting treatment. A weaker predictor of good outcome at follow-up was within-session reduction in anxiety from weeks 0 to 4. CONCLUSION: The strongest and most consistent predictor of better outcome to weeks 9 and 32 was compliance with exposure and ritual prevention in the first week of treatment.

Combined use of enterocystoplasty and a new type of artificial sphincter in the treatment of urinary incontinence.

PURPOSE: We report the results of the combination of enterocystoplasty and a periurethral expander, a simplified type of artificial sphincter, in the treatment of urinary incontinence. MATERIALS AND METHODS: The new 1-piece device has an adjustable cuff connected to a port positioned at the subcutaneous space in the abdomen. The cuff is adjusted to the bladder neck and the pins are fixed according to the diameter of the urethra. The port is punctured percutaneously and saline is injected until continence is achieved. Eight boys and 3 girls underwent nonsecretory sigmoid cystoplasty and placement of the device at a single operation. Nine patients had neurogenic bladder and in 2 exstrophy reconstruction had failed. Followup ranged from 4 to 26 months. RESULTS: All patients were continent with improved bladder compliance 6 to 8 weeks after the operation, when the device was activated. In 1 case the device was extracted after 2 months due to frequent episodes of hematuria and edema at the port site. Two patients had erosion of the skin at the port site. Urodynamics were repeated at the time of activation. Maximal urethral closing pressure increased from 16.27 to 157.44%. Two patients needed a second injection to achieve continence. The patients with exstrophy void spontaneously and those with neurogenic bladder are on clean intermittent catheterization. CONCLUSIONS: Although more followup is needed, the combination of these procedures seems to offer a new option for the treatment of urinary incontinence in children.

Comparisons among the Yale-Brown Obsessive-Compulsive Scale, compulsion checklist, and other measures of obsessive-compulsive disorder.

BACKGROUND: The Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Compulsion Checklist (CC) were compared with one another and with five other measures to assess their place in measuring the outcome of obsessive-compulsive disorder (OCD). METHOD: Data came from a randomised trial of 46 patients with OCD who completed eight Weeks of treatment by exposure and response prevention. Using a structured modelling analysis, the YBOCS and the CC were compared with a latent factor derived from five other variables (Target Rituals, Target Obsession, Clinical Global Impression, Avoidance, Disability) of baseline severity and change after treatment, and also directly with those variables. RESULTS: Both the YBOCS and the CC were accurate and sensitive measures of OCD. The YBOCS related slightly more than did the CC to the latent factor and to Disability directly. The YBOCS related slightly more to Disability than it did to other measures. Inter-assessor and self kappa assessor reliability was high. CONCLUSIONS: The 10-Item YBOCS plus the 4-item Disability scale are a simple and efficient way to measure important aspects of OCD in clinical practice.

How to perform enterocystoplasty without opening the intestine.

OBJECTIVES: To introduce a new technique for intestinal anastomosis when performing demucosalized enterocystoplasty. METHODS: In 8 dogs, a vascularized seromuscular patch of sigmoid colon was harvested without opening the bowel lumen. The bowel mucosa was invaginated into the intestinal lumen and the sigmoid musculature was reapproximated. Twelve patients underwent a nonsecretory sigmoid cystoplasty following the same principle. RESULTS: No complications occurred in the experimental animals. The animals were fed normally starting on the first postoperative day. Prolapse of the excess mucosa occurred in 3 cases and disappeared spontaneously. In the clinical group, the postoperative course was normal. Oral intake was resumed on the first day after the operation. The hospital stay was shorter than that of patients in whom the bowel lumen was opened. CONCLUSIONS: The use of demucosalized intestinal patches without opening the intestinal lumen appears to be feasible and is expected to reduce perioperative morbidity. Extensive bowel preparation can be reduced, as can the prophylactic use of antibiotics.

Does imagined exposure to the consequences of not ritualising enhance live exposure for OCD? A controlled study. I. Main outcome.

BACKGROUND: This randomised controlled study tested whether adding imagined to live exposure plus ritual prevention would enhance gains in obsessive-compulsive disorder (OCD). METHOD: Out-patients with OCD were randomly allocated to either have nine sessions of daily live self-exposure and ritual prevention to external cues alone (Ex) (n = 23) or to have, in addition to Ex, daily self-exposure to the imagined internal cues of the consequences of not ritualising (group Exi) (n = 23). All patients had the same sessional exposure time of 1 h 30 min (Exi 1 h live, 30 min imagined; Ex 1 h 30 min live), and had to practise either Exi or Ex daily for the same duration and to keep diaries of that self-exposure homework throughout treatment. Patients were followed up to week 32. Outcome measures were YBOCS for rituals and obsessions, compulsion checklist, target rituals and obsession, general anxiety, depression (Beck, Hamilton), work and social disability, clinical global impression (CGI). RESULTS: At weeks 4, 9, 20 and 32 the two groups improved similarly with no significant difference between them, neither for washers nor for checkers. Imagined exposure was more difficult to do than live exposure and there were more drop-outs. CONCLUSIONS: Daily imaged exposure to internal cues did not enhance exposure to external cues. Perhaps longer imagined exposure would have been more enhancing.

Does imagined exposure to the consequences of not ritualising enhance live exposure for OCD? A controlled study. II. Effect on behavioural v. subjective concordance of improvement.

BACKGROUND: This study tested whether adding imagined exposure to live exposure would increase the concordance between behavioural and subjective improvement in obsessive-compulsive disorder (OCD). METHOD: 46 OCD out-patients were randomly allocated to 9 weekly sessions of either combined live+imagined exposure/ritual prevention (Exi, n = 23), or only live exposure/ritual prevention (Ex, n = 23). Patients were asked to do 90 min of daily self-exposure at home (corresponding to Exi or Ex). Measures were: (A) behavioural; (B) subjective; (C) clinical global impression (CGI). RESULTS: After 9 weeks of treatment, improvement was greater on behavioural than subjective measures (similar for the Exi and Ex groups). At 20 weeks (3-month follow-up) each group had improved slightly more on subjective measures and slightly less on behavioural ones. Two subjective measures improved less during Exi than Ex, but this difference disappeared at follow-up. The greater difference between behavioural and subjective improvement scores in Exi than in Ex did not relate to clinical outcome at the end of treatment or follow-up. CONCLUSIONS: Compared to live exposure alone, combined imagined plus live exposure did not enhance behavioural/subjective concordance.

Nonsecretory sigmoid cystoplasty: experimental and clinical results.

We report the results of experimental and clinical studies in which a de-epithelialized segment of sigmoid colon was used to cover the bladder dome where the mucosa was exposed (auto-augmentation) to increase bladder capacity. Experimentally, the technique was performed in 10 healthy female mongrel dogs and the intestinal segments established continuity perfectly over the exposed bladder mucosa. Histology 30 and 60 days postoperatively showed transitional epithelium lining the intestinal segment at the site of implantation. One island of intestinal mucosa was found. The technique was performed in 10 patients, including 9 with neurogenic bladder secondary to myelomeningocele and 1 with posterior urethral valves. Bladder capacity improved in all cases and intravesical pressure was reduced. Followup ranged from 6 to 43 months. The technique is proposed as a valuable alternative to traditional full-thickness patches of the digestive tract and auto-augmentation.