Mortality Predictors and Associated Factors in Patients in the Intensive Care Unit: A Cross-Sectional Study.

BACKGROUND: Mortality in the intensive care unit (ICU) has been associated to an array of risk factors. Identification of risk factors potentially contribute to predict and reduce mortality rates in the ICU. The objectives of the study were to determine the prevalence and the factors associated with the mortality and to analyze the survival. METHOD: A cross-sectional study conducted in two clinical and surgical ICU in the state of Sergipe, northeastern Brazil. We enrolled 316 patients with at least 48 h of hospitalization, minimum age of 18 years old, sedated or weaned, with RASS ≥ -3, between July 2017 and April 2018. We categorized data in (1) age and gender, (2) clinical condition, and (3) prevalence of delirium. Data from enrolled patients were collected from enrollment until death or ICU discharge. Patients' outcomes were categorized in (1) death and (2) nondeath (discharge). RESULTS: Twenty-one percent of participants died. Age (53 ± 17 years vs. 45 ± 18 years, p < 0.01), electrolyte disturbance (30.3% vs 18.1%, p=0.029), glycemic index (33.3% vs 18.2%, p=0.008), tube feeding (83.3% vs 67.1%, p=0.01), mechanical ventilation (50% vs 35.7%, p=0.035), sedation with fentanyl (24.2 vs 13.6, p=0.035), use of insulin (33.8% vs 21.7%, p=0.042), and higher Charlson score (2.61 vs 2.17, p=0.041) were significantly associated with death on the adjusted model. However, the regression model indicated that patients admitted from the emergency (HR = 0.40, p=0.006) and glycemic index alterations (HR = 1.68, p=0.047) were associated with mortality. There was no statistically significant difference (p=0.540) in survival between patients with and without delirium, based on the survival analysis and length of hospitalization. CONCLUSION: The prevalence of death was 21%, and age, electrolyte disturbance, glycemic index, tube feeding, mechanical ventilation, sedation with fentanyl, use of insulin, and higher Charlson score were associated with mortality.

Evidence for the involvement of IL-1ß and TNF-α in anti-inflammatory effect and antioxidative stress profile of the standardized dried extract from Miconia albicans Sw. (Triana) Leaves (Melastomataceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Miconia albicans (Melastomataceae), commonly known in Brazil as "canela-de-velho", is used in folk medicine for treating rheumatoid arthritis and reducing pain and inflammation. THE AIM OF THE CURRENT WORK WAS: to provide data on physicochemical characterization of the drug plant and dried extract from M. albicans leaves, as well as investigate the anti-inflammatory effect and antioxidant stress profile from the standardized dried extract of this species employing different model systems. MATERIALS AND METHODS: plant material (dried crushed leaves) was extracted by turboextraction using 50% ethanol (v/v). Different pharmacological techniques were performed to establish quality control parameters of the plant drug, and dried extract of M. albicans (DEMA) was chemically characterized by HPLC-PDA to selection of the chemical marker. Total phenolic and flavonoid contents were determined by the Folin-Ciocalteu and AlCl3 colorimetric methods, respectively. Antioxidant potential of the DEMA was investigated by employing different in vitro antioxidant assays, including DPPH and ABTS radical scavenging assays, ferric reducing antioxidant assay, NO scavenging assay, metal ion (Fe2+) chelating activity and antioxidant capacity by inhibition of lipid peroxidation (TBARS). Finally, anti-inflammatory activity of the DEMA was evaluated using two models of acute inflammation: carrageenan induced inflammation and mechanical hyperalgesia. RESULTS AND DISCUSSION: M. albicans leaves, after drying in forced air circulation chamber at ±40 °C for 48 h and crushing in knife mill, presented a moisture content below the maximum allowed for plant drugs (6.4%). The powder of M. albicans was classified as moderately coarse and total ash content was found to be 6.27%. Preliminary phytochemical screening of DEMA revealed the presence of flavonoids, tannins, saponins, leucoanthocyanins and steroids. DEMA had significant higher total phenolic (551.3 mg gallic acid equivalent/g of dried extract) and flavonoid contents (367.19 mg catechin equivalent/g of dried extract). Two major compounds (λ = 340 nm) were identified in DEMA by HPLC-PDA: the flavonoids rutin and quercetin. Rutin content, selected as chemical marker, was determined and found to be 1.16 mg/g dried extract (r = 0.9941). Regarding to antioxidant activity, our results revealed the DEMA exhibited good antioxidant activity on different models. M. albicans treatment also reduced the levels of TNF-α e IL-1ß and consequently inflammatory nociception and edema caused by carrageenan injection. Based on previous studies and our results, is possible to suggest a positive correlation between the flavonoids rutin and quercetin and the antioxidant and anti-inflammatory capacities. CONCLUSION: Together, these data suggest that M. albicans has the possibility of use in conditions such as arthritis or other joint pain, even needing other work to better consolidate this profile.

The use of medicinal plants in venous ulcers: a systematic review with meta-analysis.

The aim of this study was to systematically review the use of medicinal plants for the treatment of varicose ulcers. The databases used in the search were: Medline/Pubmed, Scopus, Cinhal, Lilacs and Web of Science. The selection process was divided into two phases: the reading of titles and abstracts and the full reading of selected articles. The item description was compared with the checklist of the Consolidated Standards of Reporting Trials. The initial search produced 3505 articles and seven were selected for inclusion in the systematic review. Of the included studies, 7 (100%) evaluated the reduction of the ulcer area, 4 (57·14%) evaluated reepithelisation, 2 (28·57%) evaluated bacterial flora and 1 (14·28%) evaluated the oxygen pressure and percutaneous carbon dioxide. The level of evidence rating indicated that five studies (71·42%) were rated at level 2 and two (28·57%) were rated at level 3. The quality assessment was performed using the Jadad scale, which is prevalent in the literature. The quality score of the Jadad questionnaire ranges from 0 to 5; here, the studies analysed had an average of 2·5. A meta-analysis was performed on two studies that analysed the effects of Mimosa tenuiflora hydrogel in the treatment of venous ulcer and included 42 patients with a mean age of 60·5 years and a mean duration of treatment of 10·5 weeks. Heterogeneity was assessed using I2 ; we obtained a high value of 84%. We concluded that, despite the efficacy of the incorporation of Ageratina pichinchensis into the gel, the hydrogel that incorporated M. tenuiflora appeared to be a promising candidate for the management of venous ulcers.

In vivo antitumor effect, induction of apoptosis and safety of Remirea maritima Aubl. (Cyperaceae) extracts.

BACKGROUND: Remirea maritima has been widely used in the treatment of diarrhea, kidney disease, and high fever and for therapeutic purposes, such as an analgesic and anti-inflammatory. However, few scientific research studies on its medicinal properties have been reported. PURPOSE: The present study aimed to investigate the anticancer potential of aqueous extract (AE), 40% hydroalcoholic extracts (40HA) and 70% (70HA) from R. maritima in experimental models and to identify its phytochemical compounds. METHODS: The chemical composition of AE, 40HA and 70HA was assessed by HPLC-DAD and ESI-IT-MS/MS. In vitro activity was determined on cultured tumor cell, NCI-H385N (Broncho-alveolar carcinoma), OVCAR-8 (Ovarian carcinoma) and PC-3M (prostate carcinoma) by the MTT assay, and the in vivo antitumor activity was assessed in Sarcoma 180-bearing mice. Toxicological parameters were also evaluated as well as the humoral immune response. RESULTS: Among the aqueous and hydroalcoholic extracts of R. maritima, only 40HA showed in vitro biological effect potential, presenting IC50 values of 27.08, 46.62 and >50µg/ml for OVCAR-8, NCI-H385M and PC-3M cells lines, respectively. Regarding chemical composition, a mixture of isovitexin-2''-O-ß-D-glucopyranoside, vitexin-2''-O-ß-D-glucopyranoside, luteolin-7-O-glucuronide and 1-O-(E)-caffeoyl-ß-D-glucose were identified as the major phytochemical compounds of the extracts. In the in vivo study, the tumor inhibition rates were 57.16-62.57% at doses of 25mg/kg and 50mg/kg, respectively, and the tumor morphology presented increasing numbers of apoptotic cells. Additionally, 40HA also demonstrated significantly increased of OVA-specific total Ig. CONCLUSIONS: 40HA exhibited in vitro and in vivo anticancer properties without substantial toxicity that could be associated with its immunostimulating properties.

Redox-Active Profile Characterization of Remirea maritima Extracts and Its Cytotoxic Effect in Mouse Fibroblasts (L929) and Melanoma (B16F10) Cells.

Remirea maritima is a tropical plant with a reticulated root system belonging to the family Cyperaceae, also known to have biologically active secondary metabolites. However, very few data on R. maritima's biological actions are available and there are no reports regarding the redox-active profile of this plant. In this study, we examined the total phenolic content of Remirea maritima hydroalcoholic (RMHA) extracts, redox properties against different reactive species generated in vitro and their cytotoxic effect against fibroblasts (L929) and melanoma (B16F10) cells. Total reactive antioxidant potential index (TRAP) and total antioxidant reactivity (TAR) results revealed that RMHA at all concentrations tested showed significant antioxidant capacity. RMHA was also effective against hydroxyl radical formation, reduction of Fe3+ to Fe2+ and in scavenging nitric oxide (NO) radicals. In vitro, the level of lipid peroxidation was reduced by RMHA extract and the data showed significant oxidative damage protection. The RMHA cytotoxicity was evaluated by a neutral red assay in fibroblast (L929) and melanome (B16F10) cells. The obtained results showed that the RMHA (40 and 80 µg/mL, respectively) reduced 70% of the viable cells. In conclusion, this study represents the first report regarding the antioxidant and anti-proliferative potential of R. maritima against B16F10 melanoma cells.

Development of standardized extractive solution from Lippia sidoides by factorial design and their redox active profile

AbstractThe aim of this study was to evaluate the influences of variables of preparation on total flavonoids content from extractive solution of Lippia sidoides Cham., Verbenaceae. Thus a 23 factorial design was used to study the importance of plant proportion, the extraction method and solvent on the extraction of flavonoid. The methodology of determination of chemicals in factorial design was validated according to the parameters required by Brazilian Health Agency. The extraction solution was selected through a full factorial design where the best conditions to achieve the highest content of flavonoids were: 7.5% (w/v) of plant with ethanol 50% (v/v) as solvent. The polyphenols content was determined by LC method and its relationship with the antioxidant and free radical scavenging activities was evaluated. The free radical scavenging activities and antioxidant potentials were determined for different concentrations using various in vitro models. Our results indicate that extracts exhibited a significant dose-dependent antioxidant effect as evaluated by TRAP/TAR assays. Besides, we observed an antioxidant activity against hydroxyl radicals and nitric oxide, and protection against lipid peroxidation in vitro. Our results suggest that the extract presents significant in vitro antioxidant potential indicating promising perspectives for its use as pharmaceutical/or food additive.

Antioxidant, antinociceptive, and anti-inflammatory properties of the ethanolic extract of Combretum duarteanum in rodents.

The antioxidant, antinociceptive, and anti-inflammatory activities of the ethanolic extract from leaves of Combretum duarteanum (EEC) were assessed in rodents through in vitro tests. The antioxidant activity was investigated by using thiobarbituric acid reactive species (TBARS), hydroxyl radical-scavenging, and scavenging activity of nitric oxide assays. The antinociceptive activity was investigated by using acetic acid-induced writhing, formalin, and hot-plate tests in mice. The anti-inflammatory activity was assessed in rats by using the carrageenan-induced hind-paw edema test and arachidonic acid-induced paw edema test. EEC possesses a strong antioxidant potential according to the TBARS, nitric oxide, and hydroxyl radical-scavenging assays; it also presented scavenger activity in all in vitro tests. After intraperitoneal injection, EEC (100, 200, and 400 mg/kg) significantly reduced the number of writhes (38.1%, 90.6%, and 97.8%, respectively) in a writhing test and the number of paw licks during phase 1 (30.5% and 69.5%, higher doses) and phase 2 (38.1%, 90.6%, and 97.8%, all doses) of a formalin test when compared with the control group. Naloxone (1.5 mg/kg, intraperitoneally) antagonized the antinociceptive action of EEC (400 mg/kg), and this finding suggests participation of the opioid system. Administration of 200 and 400 mg/kg (intraperitoneally) of EEC exhibited an anti-inflammatory activity in the carrageenin test, which was based on interference with prostaglandin synthesis. This finding was confirmed by the arachidonic acid test. Together, these results indicate that properties of EEC might be further explored in the search for newer tools to treat painful inflammatory conditions, including those related to pro-oxidant states.

Antinociceptive activity of atranorin in mice orofacial nociception tests.

Physicochemical characterization and antinociceptive and anti-inflammatory activities of atranorin (AT) extracted from Cladina kalbii Ahti in formalin- and capsaicin-induced orofacial pain and anti-inflammatory tests in rodents were studied. Physicochemical characterization showed that AT has the general formula C19H18O8. Male Swiss mice were pretreated with AT (100, 200, and 400 mg/kg, i.p.), morphine (3 mg/kg, i.p.), or vehicle (0.9% saline with two drops of 0.2% Tween 80) before formalin (20 microl, 2%) or capsaicin (20 microl, 2.5 microg) were injected into the right vibrissa. Our results showed that i.p. treatment with AT displayed marked inhibitory effects in different orofacial pain tests in mice. AT (400 mg/kg, i.p.) was effective in reducing the nociceptive face-rubbing behavioural response in both phases of the formalin test, which was also naloxone-sensitive. Additionally, AT produced a significant antinociceptive effect at all doses in the capsaicin test. Such results were unlikely to be provoked by motor abnormality, since AT-treated mice exhibited no performance alteration on the rota rod apparatus. AT exhibited significant anti-inflammatory activity in the acute model of inflammation (leukocyte migration to the peritoneal cavity), carrageenan- and arachidonic acid-induced hind paw edema in rats. Additionally, AT exhibited a dose-dependent antioxidant activity in vitro, as assessed by total radical-trapping antioxidant parameter and total antioxidant reactivity assays. All these findings suggest that AT might represent an important tool for the management of orofacial pain and/or inflammatory disorders.

Bioassay-guided evaluation of antioxidant and antinociceptive activities of carvacrol.

We examined the antioxidant properties in vitro and the antinociceptive effect of carvacrol (CARV) in several models of pain in mice. CARV presented a strong antioxidant potential according to the TRAP/TAR evaluation; it also presented scavenger activity against nitric oxide and prevented lipid peroxidation in vitro. In mice, when evaluated against acetic acid-induced abdominal writhing, CARV (25, 50 and 100 mg/kg, i.p.) reduced (p < 0.001) the number of writhing compared to the control group, without opioid participation. In the formalin test, CARV also significantly inhibited both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking, with inhibition percentage values of 56.8% (100 mg/kg) for the neurogenic phase and 41.2% (25 mg/kg), 73.8% (50 mg/kg) and 99.7% (100 mg/kg) for the inflammatory phase. CARV also produced a significant inhibition of the pain caused by capsaicin (63.1, 67.1 and 95.8%, p < 0.001) and glutamate (46.4, 61.4 and 97.9%, p < 0.01). When assessed in a thermal model of pain, CARV (100 mg/kg, i.p.) caused a significant increase (p < 0.05) in the latency response on the hot-plate test. Such results were unlikely to be provoked by motor abnormality. Together, these results indicate that the properties of CARV should be more thoroughly examined in order to achieve newer tools for management and/or treatment of painful conditions, including those related to pro-oxidant states.

Phenolic content and antioxidant and antimicrobial properties of fruits of Capsicum baccatum L. var. pendulum at different maturity stages.

The phenolic content, antioxidant potential, and antimicrobial activity of extracts of different parts of the fruit from Capsicum baccatum L. var. pendulum were investigated. The analysis of phenolic content was performed by the Folin-Ciocalteu method and reversed-phase high-performance liquid chromatography. The in vitro antioxidant activity was assessed by the total reactive antioxidant potential and total antioxidant reactivity index. The antioxidant activity was positively correlated with the amount of phenolics found in each sample. The ex vivo antioxidant potential was assessed using the rat liver slice model. The antimicrobial activity was screened using Gram-positive and Gram-negative bacteria and fungi. All the extracts revealed antioxidant activity and a weak antimicrobial activity.