Jararhagin and its multiple effects on hemostasis

Jararhagin is a 52 kDa hemorrhagic P-III metalloproteinase isolated from the venom of the medically important Brazilian pit-viper Bothrops jararaca. It is a member of the reprolysin family of zinc metalloproteinases containing a catalytic metalloproteinase domain followed by a disintegrin-like and a cysteine-rich domain. The impact of jararhagin on hemostasis has been extensively studied using in vitro and in vivo model systems as well as in clinical studies. Jararhagin-induced hemorrhage is the result of the degradation of sub-endothelial matrix proteins leading to the disruption of the blood vessel endothelium, with accompanying disturbances in platelet function. The versatility of jararhagin is further demonstrated by its direct action on von Willebrand factor, the degradation of fibrinogen, by its inhibition of platelet adhesion to collagen and by its inability to be affected by the plasma inhibitor ₂-macroglobulin. Collagen-induced platelet aggregation is inhibited by jararhagin though the binding of the molecule to the ₂ subunit I domain of the platelet surface ₂β₁ integrin (collagen receptor). Jararhagin also cleaves the β₁ subunit of the same integrin, inhibiting platelet interaction and ultimately causing impairment of signal transduction. The effect of jararhagin on cell systems other than platelets is evaluated; in fibroblasts, jararhagin functions as a collagen-mimetic substrate and, in endothelial cells, it causes apoptosis and indirectly inhibits cell proliferation by release of angiostatin-like compounds. Jararhagin induces a strong pro-inflammatory response characterized by intense leukocyte accumulation at the site of the injection. Although hemorrhage and edema are a response to the direct effect of jararhagin, jararhagin-induced inflammation and necrosis are dependent on macrophages and key pro-inflammatory cytokines or their receptors. Some data also indicate that the toxin possesses anti-tumorgenic properties. Methods for inhibiting jararhagin are reviewed; this encompasses the use of synthetic peptides to the isolation of naturally occurring mammalian peptides and the development of toxin-specific antibodies through DNA immunisation and monoclonal antibody technologies. The availability of jararhagin makes it an important tool for research into the mechanisms of action of similar toxins, for insights into cellular interactions and for clinical investigations into the treatment of envenomings from B. jararaca.     

Effect of reminder cards on compliance with antihypertensive medication

Objective Poor compliance to antihypertensive medications has been identified as a primary cause of uncontrolled blood pressure (BP), with consequent increases in hypertension‐related morbidity and mortality. Therefore, any measure known to improve compliance should be encouraged. This study assessed the impact of reminder cards on compliance to antihypertensive therapy. Method A field trial was undertaken in pharmacies located in the districts of Lisbon and Porto. Eligible participants comprised those aged 30–74 years, prescribed an angiotensin‐converting enzyme inhibitor (ACEI) in monotherapy, and taken on a once‐daily regimen. Patients were allocated to control group (CG) or intervention group (IG), the latter being provided with a reminder card, an alarm‐type device due to remind the patient of the time to take his medication. Patients were monitored monthly during 3 months for compliance and blood pressure control. Key findings Seventy‐one patients participated in the study (intervention: 35; control group: 36). Compliance was similar between the groups in the first 2 months of follow‐up (97.1% IG vs 94.9% CG at first follow‐up and 97.5% IG vs 94.2% CG at second follow‐up) and higher in the intervention group at the end of the study (97.3% IG vs 87.3% CG; P = 0.011). There were no mean blood pressure differences between compliant and non‐compliant subjects at the end of the study (P value for differences in systolic BP (P_syst) = 0.580; and P value for differences in diastolic BP (P_dlast) = 0.175). Conclusion This small‐scale study indicates a possible positive impact on patients' compliance resulting from the use of reminder cards. However, this needs confirming in larger scale studies with longer monitoring periods.     

Dantrolene protects hippocampal cells from damage induced by TsTX, an alpha-scorpion toxin from Tityus serrulatus.

We examined the effects of dantrolene, an inhibitor of intracellular calcium release, on alterations associated with the intrahippocampal injection of the TsTX scorpion toxin. Male Wistar rats (230-250 g) were injected with Ringer solution (1 microl; n = 6); TsTX toxin (1 microg/microl; n = 8); and dantrolene (10.0 mg/kg) plus TsTX toxin (1 microg/microl; n = 6). After injection, electroencephalographic (EEG) recordings and observation of animals behaviour were performed continuously for 4 h. One week later, animals were submitted to histopathological analysis. TsTX caused electrographic seizure expressed by moderate or intense discharges and neuronal loss in hippocampal areas in all injected animals (n = 8). Dantrolene reduced the effect of TsTX. Thus, 67% of rats (four out of six) treated with toxin and dantrolene had electrographic convulsions, but only for 30 min after injection and none of them presented neuronal damage. Dantrolene or Ringer had no effects on the EEG.     

Bactericidal and neurotoxic activities of two myotoxic phospholipases A2 from Bothrops neuwiedi pauloensis snake venom.

Two basic myotoxic PLA(2)s, namely BnpTX-I and II, were isolated from Bothrops neuwiedi pauloensis snake venom through three chromatographic steps: ion-exchange chromatography on CM-Sepharose, gel filtration on Sephadex G-50 and reverse phase HPLC on a C18 column. Both PLA(2)s showed a M(r) around 14,000 for the monomer and 28,000 for the dimer (as estimated by SDS-PAGE), pI approximately 7.8 and approximately 121 amino acid residues cross-linked by seven disulfide bonds. The N-terminal sequences revealed significant homology with Asp49 basic myotoxic PLA(2)s from other snake venoms. The catalytic and anticoagulant activities of BnpTX-I were higher than those of BnpTX-II. Both were able to induce cytotoxicity in vitro, as well as, myotoxicity, edema and lethality in mice. BnpTX-I also induced neurotoxic effect on mouse neuromuscular preparations and bactericidal activity on Eschericia coli and Staphylococcus aureus. After chemical modification of BnpTX-I with BPB or incubation with EDTA or Mn(2+) ions, the catalytic activity was completely abolished, while the toxic and pharmacological activities were partially reduced. Interaction with heparin inhibited the cytotoxic and bactericidal effects. Anti-BthTX-I, anti-BthTX-II and anti-115-129-C terminal antibodies strongly recognize both BnpTX-I and II. It is shown that the neurotoxic effect induced by B. neuwiedi pauloensis venom is due to the presence of myotoxic PLA(2)s. The data also corroborate the hypothesis of a partial dissociation between toxic and enzymatic domains. In addition, BnpTX-I displays a heparin binding C-terminal region, which is probably responsible for the cytotoxic and bactericidal effects.     

Hydration status,body composition,and anxiety status in aeronautical military personnel from Spain: a cross-sectional study

Background: An adequate hydration status is critical to ensure efficiency during mental and physical activities.Our goal was to assess the hydration status of a Spanish group of aeronautical military men and to determine the association of hydration status with body composition and anxiety.Methods: A total of 188 men were evaluated through a validated hydration questionnaire, anthropometric and biochemical parameters, and an anxiety questionnaire. Based on these methods, the criteria of hydratio...     

Antibacterial activity and inhibition against Staphylococcus aureus NorA efflux pump by ferulic acid and its esterified derivatives

Objective: To evaluate the inhibitory activity of ferulic acid and four of its esterified derivatives (methyl, ethyl, propyl, and butyl) against resistance mech...     

Deprescripción en personas mayores: es el momento de pasar a la acción

El uso de fármacos conlleva innegables beneficios en las personas mayores, pero no está exento de efectos indeseables. La deprescripción es el proceso de revisión sistemática de la medicación con el objetivo de lograr la mejor relación riesgo-beneficio en base a la mejor evidencia disponible. Este proceso es especialmente importante en mayores polimedicados, sobretratados, frágiles, con enfermedades terminales y en el final de la vida.La deprescripción debe hacerse de forma escalonada, estableciendo un seguimiento estrecho por si aparecen problemas tras la retirada. En la toma de decisiones es muy importante contar con la opinión del paciente y de los cuidadores, valorando los objetivos del tratamiento según la situación clínica, funcional y social del enfermo.Existen múltiples herramientas para facilitar a los clínicos la tarea de seleccionar qué fármacos deprescribir (criterios Beers, STOPP-START…). Los grupos farmacológicos más susceptibles de intervención son: antihipertensivos, antidiabéticos, estatinas, benzodiacepinas, antidepresivos, anticolinérgicos, anticolinesterásicos y neurolépticos.Palabras clave: Polifarmacia, Envejecimiento, Comorbilidad, Prescripción inadecuada, Efectos adversos, Deprescripción     

Short-Term Pilot Study to Evaluate the Impact of Salbi Educa Nutrition App in Macronutrients Intake and Adherence to the Mediterranean Diet: Randomized Controlled Trial

Promoting a healthy diet is a relevant strategy for preventing non-communicable diseases. This study aims to evaluate the impact of an innovative tool, the SAlBi educa nutrition app, in primary healthcare dietary counseling to improve dietary profiles as well as adherence to the Mediterranean diet. A multi-center randomized control trial comprising 104 participants was performed. Both control (n = 49) and intervention (n = 55) groups attended four once-weekly sessions focusing on healthy eating habits and physical activity, over one month. As well as attending the meetings, the intervention group used the app, which provides self-monitoring and tailored dietary advice based on the Mediterranean diet model. In a second intervention (one arm trial), the potential of SAlBi educa was evaluated for three months during the COVID-19 pandemic. At 4 weeks, the intervention group had significantly increased their carbohydrate intake (7.7% (95% CI: 0.16 to 15.2)) and decreased their total fat intake (−5.7% (95% CI: −10.4 to −1.15)) compared to the control group. Significant differences were also found for carbohydrates (3.5% (95% CI: −1.0 to 5.8)), total fats (−5.9% (95% CI: −8.9 to −3.0)), fruits and vegetables (266.3 g/day (95% CI: 130.0 to 402.6)), legumes (7.7g/day (95% CI: 0.2 to 15.1)), starchy foods (36.4 g/day (95% CI: 1.1 to 71.7)), red meat (−17.5 g/day (95% CI: −34.0 to −1.1)), and processed meat (−6.6 g/day (95% CI: −13.1 to −0.1)) intakes during the COVID-19 pandemic. SAlBi educa is a useful tool to support nutrition counseling in primary healthcare, including in special situations such as the COVID-19 pandemic. Trial registration: ISRCTN57186362.