Amazonian plant natural products:perspectives for discovery of new antimalarial drug leads

Plasmodium falciparum and P. vivax malaria parasites are now resistant, or showing signs of resistance, to most drugs used in therapy. Novel chemical entities that exhibit new mechanisms of antiplasmodial action are needed. New antimalarials that block transmission of Plasmodium spp. from humans to Anopheles mosquito vectors are key to malaria eradication efforts. Although P. vivax causes a considerable number of malaria cases, its importance has for long been neglected. Vivax malaria can cause severe manifestations and death; hence there is a need for P. vivax-directed research. Plants used in traditional medicine, namely Artemisia annua and Cinchona spp. are the sources of the antimalarial natural products artemisinin and quinine, respectively. Based on these compounds, semi-synthetic artemisinin-derivatives and synthetic quinoline antimalarials have been developed and are the most important drugs in the current therapeutic arsenal for combating malaria. In the Amazon region, where P. vivax predominates, there is a local tradition of using plant-derived preparations to treat malaria. Here, we review the current P. falciparum and P. vivax drug-sensitivity assays, focusing on challenges and perspectives of drug discovery for P. vivax, including tests against hypnozoites. We also present the latest findings of our group and others on the antiplasmodial and antimalarial chemical components from Amazonian plants that may be potential drug leads against malaria

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Do the Effects of Pentoxifylline on the Inflammatory Process and Pancreatic Infection Justify Its Use in Acute Pancreatitis?

Severe acute pancreatitis is associated with high morbidity and mortality rates. At the present time, no specific therapy has been shown to be uniformly effective in reducing morbidity and mortality in this disease. The aim of this study was to determine the effects of pentoxifylline on the pancreatic and systemic inflammatory process, pancreatic infection, and mortality rate in severe acute pancreatitis in rats. Methods: One hundred and twenty male Wistar rats were divided into 3 groups: sham, pancreatitis, and pentoxifylline (acute pancreatitis induction plus administration of 25 mg/kg pentoxifylline). Inflammatory response was measured by histological studies, inflammatory cytokine production (IL-6, IL-10, and TNF-alpha), and mortality rate. Pancreatic infection was evaluated by bacterial cultures expressed in colony-forming units per gram. Results: Pentoxifylline-treated animals had a statistically significant reduction of inflammatory cytokine levels, pancreatic histological damage, occurrence of bacterial translocation and pancreatic infection (p < 0.05), associated with a significant reduction in mortality rate. Conclusions: Pentoxifylline administration in this experimental model of acute pancreatitis reduces local and systemic inflammatory responses and decreases the pancreatic infection and the mortality rate. Copyright (C) 2009 S. Karger AG, Basel and IAPFAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo

Cardiovascular changes in patients with non-severe Plasmodium vivax malaria

Cardiovascular system involvement in patients with Plasmodium vivax malaria has been poorly addressed. The aim of this study was to evaluate cardiac structures and function, and serum markers of cardiovascular injury in patients with the non-severe form of vivax malaria in Manaus, Amazonas State, Brazil. We prospectively evaluated 26 patients with vivax malaria in an outpatient referral hospital and compared results with a control group of 25 gender- and age-matched healthy individuals. Patients underwent clinical evaluation, laboratory tests, and transthoracic echocardiography at first evaluation (day zero, D0) and seven days (D7) after malaria diagnosis. At D0 echocardiography showed higher left ventricular (LV) systolic diameter (28.8 ± 2.82 vs 30.9 ± 4.03 mm, p = 0.037) and LV diastolic volume (82.4 ± 12.3 vs 93.8 ± 25.9 ml, p = 0.05), and lower LV ejection fraction (Teicholz method: 73.2 ± 6.59 vs 68.4 ± 4.87%, p = 0.004) in patients compared to controls. Right ventricle (RV) fractional area change (54.7 ± 5.11 vs 50.5 ± 6.71%, p = 0.014) was lower, and RV myocardial performance index (0.21 ± 0.07 vs 0.33 ± 0.19, p = 0.007), and pulmonary vascular resistance (1.13 ± 0.25 vs 1.32 ± 0.26 Woods unit, p = 0.012) were higher in patients than controls. Patients presented higher serum levels of unconjugated bilirubin (0.24 ± 0.15 vs 1.30 ± 0.89 mg/dL, p < 0.001), soluble vascular cell adhesion molecule–1 (sVCAM-1, 453 ± 143 vs 1983 ± 880 ng/mL, p < 0.001), N-terminal prohormone brain natriuretic peptide (0.59 ± 0.86 vs 1.08 ± 0.81 pg/mL, p = 0.045), and troponin T (861 ± 338 vs 1037 ± 264 pg/mL, p = 0.045), and lower levels of plasma nitrite (13.42 ± 8.15 vs 8.98 ± 3.97 μM, p = 0.016) than controls. Most alterations had reversed by D7. Patients with non-severe Plasmodium vivax malaria present subclinical reversible cardiovascular changes

Treatment of chikungunya musculoskeletal disorders: a systematic review

<p><b>Introduction</b>: Chikungunya virus is amongst the fastest expanding vector transmissible diseases in recent years and has been causing massive epidemics in Africa, Asia, Latin America and the Caribbean. Despite human infection by this virus being first described in the 1950s, there is a lack of adequate therapeutic evaluations to guide evidence-based recommendations. The current guidelines rely heavily in specialists’ opinion and experience instead of using higher rated evidence.</p> <p><b>Areas covered</b>: A systematic review of the literature was performed- not restricted to clinical trials – reporting the therapeutic response against this infection with the intent to gather the best evidence of the treatment options against musculoskeletal disorders following chikungunya fever. The 15 studies included in the analysis were categorized considering the initiation of treatment during the acute, subacute and chronic phase.</p> <p><b>Expert commentary</b>: This review demonstrates the complexity of chikungunya fever and difficulty of therapeutic management. This review found no current evidence-based treatment recommendations for the musculoskeletal disorders following chikungunya fever. To provide an optimal treatment that prevents perpetuation or progression of chikungunya infection to a potentially destructive and permanent condition without causing more harm is an aim that must be pursued by researchers and health professionals working with this disease.</p

Oklahoma Times-Journal

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Challenges of acute febrile illness diagnosis in a national infectious diseases center in Rio de Janeiro: 16-year experience of syndromic surveillance.

IntroductionAcute febrile illnesses (AFI) are a frequent chief complaint in outpatients. Because the capacity to investigate the causative pathogen of AFIs is limited in low- and middle-income countries, patient management may be suboptimal. Understanding the distribution of causes of AFI can improve patient outcomes. This study aims to describe the most common etiologies diagnosed over a 16-years period in a national reference center for tropical diseases in a large urban center in Rio de Janeiro, Brazil.MethodsFrom August 2004-December 2019, 3591 patients > 12 years old, with AFI and/or rash were eligible. Complementary exams for etiological investigation were requested using syndromic classification as a decision guide. Results. Among the 3591 patients included, endemic arboviruses such as chikungunya (21%), dengue (15%) and zika (6%) were the most common laboratory-confirmed diagnosis, together with travel-related malaria (11%). Clinical presumptive diagnosis lacked sensitivity for emerging diseases such as zika (31%). Rickettsia disease and leptospirosis were rarely investigated and an infrequent finding when based purely on clinical features. Respiratory symptoms increased the odds for the diagnostic remaining inconclusive.ConclusionsNumerous patients did not have a conclusive etiologic diagnosis. Since syndromic classification used for standardization of etiological investigation and presumptive clinical diagnosis had moderate accuracy, it is necessary to incorporate new diagnostic technologies to improve diagnostic accuracy and surveillance capacity