The brazilian Amaryllidaceae as a source of acetylcholinesterase inhibitory alkaloids

Nine Brazilian Amaryllidaceae species were studied for their alkaloid composition and acetylcholinesterase (AChE) inhibitory activity via GC-MS and a modified Ellman assay, respectively. A total of thirty-six alkaloids were identified in these plants, of which Hippeastrum papilio and H. glau-cescens exhibited the highest galanthamine content and the best IC50 values against AChE. Furthermore, Hippeastrum vittatum and Rhodophiala bifida also showed notable AChE inhibitory effects. X-ray crys-tallographic data for four galanthamine-type com-pounds revealed significant differences in the orientation of theN-methyl group, which are shown to be related to AChE inhibition

Observation of <i>Bothrops atrox</i> Snake Envenoming Blister Formation from Five Patients: Pathophysiological Insights

In the Brazilian Amazon, Bothrops atrox snakebites are frequent, and patients develop tissue damage with blisters sometimes observed in the proximity of the wound. Antivenoms do not seem to impact blister formation, raising questions regarding the mechanisms underlying blister formation. Here, we launched a clinical and laboratory-based study including five patients who followed and were treated by the standard clinical protocols. Blister fluids were collected for proteomic analyses and molecular assessment of the presence of venom and antivenom. Although this was a small patient sample, there appeared to be a correlation between the time of blister appearance (shorter) and the amount of venom present in the serum (higher). Of particular interest was the biochemical identification of both venom and antivenom in all blister fluids. From the proteomic analysis of the blister fluids, all were observed to be a rich source of damage-associated molecular patterns (DAMPs), immunomodulators, and matrix metalloproteinase-9 (MMP-9), suggesting that the mechanisms by which blisters are formed includes the toxins very early in envenomation and continue even after antivenom treatment, due to the pro-inflammatory molecules generated by the toxins in the first moments after envenomings, indicating the need for local treatments with anti-inflammatory drugs plus toxin inhibitors to prevent the severity of the wounds

Observation of Bothrops atrox Snake Envenoming Blister Formation from Five Patients: Pathophysiological Insights

In the Brazilian Amazon, Bothrops atrox snakebites are frequent, and patients develop tissue damage with blisters sometimes observed in the proximity of the wound. Antivenoms do not seem to impact blister formation, raising questions regarding the mechanisms underlying blister formation. Here, we launched a clinical and laboratory-based study including five patients who followed and were treated by the standard clinical protocols. Blister fluids were collected for proteomic analyses and molecular assessment of the presence of venom and antivenom. Although this was a small patient sample, there appeared to be a correlation between the time of blister appearance (shorter) and the amount of venom present in the serum (higher). Of particular interest was the biochemical identification of both venom and antivenom in all blister fluids. From the proteomic analysis of the blister fluids, all were observed to be a rich source of damage-associated molecular patterns (DAMPs), immunomodulators, and matrix metalloproteinase-9 (MMP-9), suggesting that the mechanisms by which blisters are formed includes the toxins very early in envenomation and continue even after antivenom treatment, due to the pro-inflammatory molecules generated by the toxins in the first moments after envenomings, indicating the need for local treatments with anti-inflammatory drugs plus toxin inhibitors to prevent the severity of the wounds

Venom Composition of Neglected Bothropoid Snakes from the Amazon Rainforest: Ecological and Toxinological Implications

Snake venoms have evolved in several families of Caenophidae, and their toxins have been assumed to be biochemical weapons with a role as a trophic adaptation. However, it remains unclear how venom contributes to the success of venomous species for adaptation to different environments. Here we compared the venoms from Bothrocophias hyoprora, Bothrops taeniatus, Bothrops bilineatus smaragdinus, Bothrops brazili, and Bothrops atrox collected in the Amazon Rainforest, aiming to understand the ecological and toxinological consequences of venom composition. Transcriptomic and proteomic analyses indicated that the venoms presented the same toxin groups characteristic from bothropoids, but with distinct isoforms with variable qualitative and quantitative abundances, contributing to distinct enzymatic and toxic effects. Despite the particularities of each venom, commercial Bothrops antivenom recognized the venom components and neutralized the lethality of all species. No clear features could be observed between venoms from arboreal and terrestrial habitats, nor in the dispersion of the species throughout the Amazon habitats, supporting the notion that venom composition may not shape the ecological or toxinological characteristics of these snake species and that other factors influence their foraging or dispersal in different ecological niches

Poor efficacy of preemptive amoxicillin clavulanate for preventing secondary infection from <i>Bothrops</i> snakebites in the Brazilian Amazon: A randomized controlled clinical trial

<div><p>Background</p><p>Secondary bacterial infections from snakebites contribute to the high complication rates that can lead to permanent function loss and disabilities. Although common in endemic areas, routine empirical prophylactic use of antibiotics aiming to prevent secondary infection lacks a clearly defined policy. The aim of this work was to estimate the efficacy of amoxicillin clavulanate for reducing the secondary infection incidence in patients bitten by <i>Bothrops</i> snakes, and, secondarily, identify risk factors for secondary infections from snakebites in the Western Brazilian Amazon.</p><p>Methods and findings</p><p>This was an open-label, two-arm individually randomized superiority trial to prevent secondary infection from <i>Bothrops</i> snakebites. The antibiotic chosen for this clinical trial was oral amoxicillin clavulanate per seven days compared to no intervention. A total of 345 patients were assessed for eligibility in the study period. From this total, 187 accomplished the inclusion criteria and were randomized, 93 in the interventional group and 94 in the untreated control group. All randomized participants completed the 7 days follow-up period. Enzyme immunoassay confirmed <i>Bothrops</i> envenoming diagnosis in all participants. Primary outcome was defined as secondary infection (abscess and/or cellulitis) until day 7 after admission. Secondary infection incidence until 7 days after admission was 35.5% in the intervention group and 44.1% in the control group [RR = 0.80 (95%CI = 0.56 to 1.15; p = 0.235)]. Survival analysis demonstrated that the time from patient admission to the onset of secondary infection was not different between amoxicillin clavulanate treated and control group (Log-rank = 2.23; p = 0.789).Secondary infections incidence in 7 days of follow-up was independently associated to fibrinogen >400 mg/dL [AOR = 4.78 (95%CI = 2.17 to 10.55; p<0.001)], alanine transaminase >44 IU/L [AOR = 2.52 (95%CI = 1.06 to 5.98; p = 0.037)], C-reactive protein >6.5 mg/L [AOR = 2.98 (95%CI = 1.40 to 6.35; p = 0.005)], moderate pain [AOR = 24.30 (95%CI = 4.69 to 125.84; p<0.001)] and moderate snakebites [AOR = 2.43 (95%CI = 1.07 to 5.50; p = 0.034)].</p><p>Conclusions/Significance</p><p>Preemptive amoxicillin clavulanate was not effective for preventing secondary infections from <i>Bothrops</i> snakebites. Laboratorial markers, such as high fibrinogen, alanine transaminase and C-reactive protein levels, and severity clinical grading of snakebites, may help to accurately diagnose secondary infections.</p><p>Trial registration</p><p>Brazilian Clinical Trials Registry (ReBec): <a href="https://clinicaltrials.gov/ct2/show/RBR-3h33wy" target="_blank">RBR-3h33wy</a>; UTN Number: <a href="https://clinicaltrials.gov/ct2/show/U1111-1169-1005" target="_blank">U1111-1169-1005</a>.</p></div

Final model of factors associated to secondary infection until 7 days of the snakebite patients attended in the hospital in Manaus.

<p>Final model of factors associated to secondary infection until 7 days of the snakebite patients attended in the hospital in Manaus.</p

Time free of secondary infection at snakebite site, until 7 days after hospital admission, for both groups.

<p>Survival analysis demonstrating that the time from patient admission to the onset of secondary infection was not different between amoxicillin clavulanate treated and control group (Log-rank = 2.23; p = 0.789).</p

Flow chart of inclusion.

<p>Recruitment of the patients attended by snakebite at FMT-HVD, allocation and follow-up in the clinical trial.</p

Demographic end epidemiological characteristics of the randomized patients according to the experimental group.

<p>Demographic end epidemiological characteristics of the randomized patients according to the experimental group.</p