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Made available in DSpace on 2019-10-04T11:57:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01 Practices described as traditional medicine may coexist with formalized, science-based medicine. In this context, the present study aimed to verify the profile of the elderly who consumed herbal medicines concomitantly with medications and to identify suspected adverse drug reactions (ADRs) in the Brazilian Amazon (Macapa, Amapa). The study was carried out in two steps: a cross-sectional study (structured questionnaire) and a clinical study (pharmacotherapeutic follow-up). Out of 208 participants, 78.8% were female with age between 60 and 69 years (58.7%), 59.1% used herbal medicines concurrently with medications, and 40.9% did not report use of herbal medicine. Losartan was the most used medication, and Lippia alba (Mill.) N.E. Br was the most common herbal medicine used. The total prevalence of suspected ADRs, among the elderly who answered the structured questionnaire, was 41.3%, with 27.4% being in the elderly who used herbal medicines and medications, and 13.9% being in the elderly who used only medications. Meanwhile, the total prevalence of suspected ADRs was 71.0% among the elderly patients who underwent pharmacotherapeutic follow-up, 60.5% in elderly who used herbal medicines and medications, and 10.5% in elderly who used only medications. The most reported ADR symptoms were related to disorders that affect the nervous system (38.4%) in the structured questionnaire and related to digestive disorders (36.4%) in the pharmacotherapeutic follow-up. The probability associated with the occurrence of a given ADR in the face of a set of demographic, socioeconomic, and clinical variables was estimated; the results showed that, in the studied population, only sex (p = 0.030) had an influence on the occurrence of ADR. The prevalence of ADRs with probable causality was high in this study population, but it was only sex-related, although more prevalent in the elderly who consume herbal medicines. Univ Fed Amapa, Dept Biol & Hlth Sci, Toxicol Lab, Pharm Course, Juscelino Kubitschek Highway KM-02, BR-68903419 Macapa, AP, Brazil Univ Fed Amapa, Dept Biol & Hlth Sci, Med Course, Juscelino Kubitschek Highway KM-02, BR-68903419 Macapa, AP, Brazil State Univ Paulista Julio Mesquita Filho, Fac Pharmaceut Sci, Rodovia Araraquara Jau KM 01, BR-14800901 Machados, SP, Brazil Univ Fed Amapa, Dept Biol & Hlth Sci, Pharm Course, Qual Control & Bromatol Lab, Juscelino Kubitschek Highway KM-02, BR-68903419 Macapa, AP, Brazil State Univ Paulista Julio Mesquita Filho, Fac Pharmaceut Sci, Rodovia Araraquara Jau KM 01, BR-14800901 Machados, SP, Brazil

The Density Functional Theory (DFT) method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS) and principal component regression (PCR) models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R(2) = ± 0.0106, R(2)(ajust) = ± 0.0125, s = ± 0.0234, F(4,11) = ± 12.7802, Q(2) = ± 0.0088, SEV = ± 0.0132, PRESS = ± 0.4808 and SPRESS = ± 0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set) with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA), cellular permeability (PCaCO2), cell permeability Maden Darby Canine Kidney (PMDCK), skin permeability (P(Skin)), plasma protein binding (PPB) and penetration of the blood-brain barrier (C(Brain/Blood)), and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers.

Cleydson Breno Rodrigues dos Santos1 2 3 ∗, Josinete Braga Vieira3, Adriane da Silva Formigosa3, Elizabeth Viana Moraes da Costa1, Mayara Tânia Pinheiro1 2, Jocivânia Oliveira da Silva1 3, Williams Jorge da Cruz Macedo4, and Jose Carlos Tavares Carvalho1 2 1Laboratory of Drug Research, School of Pharmaceutical Sciences, Federal University of Amapa, Rod JK km 2, Macapa-Amapa, 68902-280, Brazil 2Postgraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Amapa, Rod JK km 2, Macapa-Amapa, 68902-280, Brazil 3Laboratory of Modelling and Computational Chemistry, Federal University of Amapa, Rod JK km 2, Macapa, Amapa 68902-280, Brazil 4Secretary of State for Public Health, Central Laboratory of the State of Para-LACEN/PA, Rod Augusto Montenegro, km 10, Icoaraci, 66823-010, Belem-Para-Amazon-Brazil

Medicinal plants encompass a rich source of active compounds that can neutralize snake venoms or toxins. Costus spicatus (Jacq.) Sw. (Costaceae) is used by the Amazonian population to treat inflammation, pain and other pathological manifestations.To evaluate the influence of C. spicatus aqueous extract on edema, peritonitis, nociception, coagulation, haemorrhage and indirect haemolytic activity induced by Bothrops atrox venom (BAV).Dried and pulverized leaves were extracted with distilled water. Envenoming was induced by administration of B. atrox snake venom in Swiss Webster mice. The experimental groups consisted of BAV (at the minimum dose to induce measurable biological responses) and C. spicatus extract (CSE, 1.25, 2.5, 5.0, 7.5 and 10 mg/kg/25 μl phosphate-buffered saline) administered individually and in combination (BAVCSE). PBS was used as a control. In vitro assays were also conducted in order to evaluate phospholipase A2 coagulant activities (indirect haemolytic method).CSE significantly reduced the venom-induced edema and nociception at all concentrations tested and inhibited migration of inflammatory cells at the three least concentrations (5.0, 7.5 and 10 mg/kg/25 μl PBS). CSE was not effective in inhibiting coagulant, haemorrhagic and indirect haemolytic activities of the venom.The data suggest that CSE could exhibit a central mechanism for pain inhibition, and may also inhibit prostaglandin synthesis. These findings corroborate the traditional administration of C. spicatus decoction to treat inflammatory disorders, including those caused by B. atrox envenomation.

Bothrops atrox is responsible for the majority of snakebite accidents in Brazilian Amazon and its venom can cause prominent local tissue damage. Experimental groups consisted of five male mice, each administered either B. atrox Venom (VB), B. atrox Venom + Antivenom (VAV), B. atrox Venom + Laser (VL), B. atrox Venom + Antivenom + Laser (VAVL), or Sterile Saline Solution (SSS) alone. Paw oedema was induced by intradermal administration of 0.05 mg kg-1 of B. atrox venom and was expressed in mm of directly induced oedema. Mice were subcutaneously injected with 0.10 mg kg-1 of venom for evaluation nociceptive activity and the time (in seconds) spent in licking and biting responses of the injected paw were taken as an indicator of pain response. Inflammatory infiltration was determined by counting the number of leukocytes present in the gastrocnemius muscle after venom injection (0.10 mg kg-1). Myotoxicity was studied by determining the plasmatic rise of creatine kinase activity after venom injection (0.20 mg kg-1). For histological examination of myonecrosis, venom (0.10 mg kg-1) was administered intramuscularly. The site of venom injection was irradiated by GaAs laser and some animals received antivenom intraperitoneally. GaAs laser irradiation administered in conjunction with antivenom, reduced pain, oedema, inflammation and myonecrosis induced by B. atrox venom in mice. The combined antivenom and GaAs laser treatment was more effective than separately treatments. The results suggest that laser therapy may reduce the local effects induced by B. atrox venom when associated with antivenom.

Antivenom therapy has been ineffective in neutralizing the tissue damage caused by snakebites. Among therapeutic strategies to minimize effects after envenoming, it was hypothesized that a low level laser would reduce complications and reduce the severity of local snake venom effects. In the current study, the effect of a low-level semiconductor gallium arsenide (GaAs) laser on the local pathological alterations induced by B. moojeni snake venom was investigated. The experimental groups consisted of five male mice, each administered either B. moojeni venom (VB), B. moojeni venom + antivenom (VAV), B. moojeni venom + laser (VL), B. moojeni venom + antivenom + laser (VAVL), or sterile saline solution (SSS) alone. Paw oedema was induced by intradermal administration of 0.05 mg kg(-1) of B. moojeni venom and was expressed in mm of directly induced oedema. Mice received by subcutaneous route 0.20 mg kg(-1) of venom for evaluating nociceptive activity and the time (in seconds) spent in licking and biting the injected paw was taken as an indicator of pain response. Inflammatory infiltration was determined by counting the number of leukocytes present in the gastrocnemius muscle after venom injection (0.10 mg kg(-1)). For histological examination of myonecrosis, venom (0.10 mg kg(-1)) was administered intramuscularly. The site of venom injection was irradiated by the GaAs laser and some animals received antivenom intraperitoneally. The results indicated that GaAs laser irradiation can help in reducing some local effects produced by the B. moojeni venom in mice, stimulating phagocytosis, proliferation of myoblasts and the regeneration of muscle fibers.