Efficacy and safety of a four-drug fixed-dose combination regimen versus separate drugs for treatment of pulmonary tuberculosis : a systematic review and meta-analysis

Introduction: tuberculosis, particularly multi-drug-resistant tuberculosis, is a major cause of morbidity and mortality worldwide. To the best of our knowledge, however, no study to date has assessed the combined use of the four available drugs for tuberculosis treatment, which is an issue of great clinical relevance. Objective: to determine whether the four-drug fixed-dose combination is safer or more effective than separate drugs for treatment of pulmonary tuberculosis. Methods: a systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: in pooled results from five randomized controlled trials with 3502 patients across Africa, Asia, and Latin America, four-drug fixed-dose combination therapy was no better than separate drugs therapy in terms of culture conversion after 2 and 6 months of treatment. There were no significant differences between the groups in overall incidence of adverse effects. However, the meta-analytic measure (log odds ratio) revealed that separate drugs treatment had a 1.65 [exp (0.5) = 1.65] increased chance of gastrointestinal adverse effects compared to four-drug fixed-dose combination treatment. Conclusions: the reviewed studies showed that four-drug fixed-dose combination therapy provides greater patient comfort by reducing the number of pills and the incidence of gastrointestinal adverse effects, as well as simplifying pharmaceutical management at all levels

Liquid-liquid extraction in the presence of electrolytes of nisin and green fluorescent protein (GFPuv)

In the biotechnology field, it has been suggested that extractions in two-phase aqueous complex-fluid systems can possibly be used instead of, or as complementary processes to, the more typical chromatographic operations, to reduce the cost of the downstream processing of many biological products (Lam et al., 2004; Mazzola et al., 2006). This method offer attractive conditions to be applied in this study, thereby two-phase systems can be exploited in separation science for the extraction/purification of desired biomolecules directly on the culture medium (Mazzola et al., 2008). This study aimed to evaluate the aqueous two phase system (ATPS) composed by a nonionic surfactant, Triton X-114 (TX), in presence or absence of electrolytes, to separate two interesting biomolecules: nisin and recombinant green fluorescent protein (GFP). Results indicated that nisin partitions preferentially to the micelle rich-phase, with significant antimicrobial activity increase (up to 10-fold). GFP partitioned evenly between the phases in TX system without electrolytes.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo, Brazil (FAPESP

α-Amylase inhibitors : a review of raw material and isolated compounds from plant source

ABSTRACTInhibition of α-amylase, enzyme that plays a role in digestion of starch and glycogen, is considered a strategy for the treatment of disorders in carbohydrate uptake, such as diabetes and obesity, as well as, dental caries and periodontal diseases. Plants are an important source of chemical constituents with potential for inhibition of α-amylase and can be used as therapeutic or functional food sources. A review about crude extracts and isolated compounds from plant source that have been tested for α-amylase inhibitory activity has been done. The analysis of the results shows a variety of crude extracts that present α-amylase inhibitory activity and some of them had relevant activity when compared with controls used in the studies. Amongst the phyto-constituents that have been investigated, flavonoids are one of them that demonstrated the highest inhibitory activities with the potential of inhibition related to number of hydroxyl groups in the molecule of the compound. Several phyto-constituents and plant species as α-amylase inhibitors are being reported in this article. Majority of studies have focused on the anti-amylase phenolic compounds

Methods of endotoxin removal from biological preparations : a review

ABSTRACTPURPOSE: Endotoxins, also called lipopolysaccharides (LPS), are major contaminants found in commercially available proteins or biologically active substances, which often complicate study of the biological effects of the main ingredient. The presence of small amounts of endotoxin in recombinant protein preparations can cause side effects in host organism such as endotoxin shock, tissue injury, and even death. Due to these reactions, it is essential to remove endotoxins from drugs, injectables, and other biological and pharmaceutical products. An overview of this subject is provided by this article. METHODS: An extensive review of literature with regard to methods for removal of endotoxin from biotechnological preparations was carried out. RESULTS: A short history of endotoxin is presented first. This is followed by a review of chemical and physical properties of endotoxin and its pathophysiological effects when the body is exposed to LPS excessively or systemically. The techniques of endotoxin determination and interaction of endotoxin with proteins is also presented, taking into consideration the established techniques as well as the state of the art technology in this field. A review of techniques of endotoxin mentioned with relatively high protein recoveries; however, special attention is given to two-phase aqueous micellar systems, which are valuable tools for endotoxin removal from pharmaceutical proteins on a small scale because they provide a mild environment for biological materials. CONCLUSIONS: Efficient and cost-effective removal of endotoxins from pharmaceutical and biotechnology preparations is challenging. Despite development of novel methods, such as the two- phase aqueous micellar systems, in recent years, more research is needed in this field

Antioxidant Activity of Apis Mellifera Bee Propolis: A Review

BackgroundPropolis is a natural product manufactured by bees from balsamic materials collected from plants that surround the hive, undergoing subsequent modification by the enzymes of these insects. It has several functions in the hive, such as sealing cracks and antimicrobial action. Folk medicine worldwide has used this resin in their health practices, and modern research turns its eyes to natural materials to become sources of new molecules to treat the most diverse ailments. AimsThis work collected information on studies that test the antioxidant activity of propolis, produced by Apis mellifera bees, using different antioxidant methods available. MethodsThe search for this review was carried out in the following databases: SciELO, Google Scholar, PubMed, MEDLINE, Catalog of Dissertations and Theses of CAPES, BVS, CRD, Embase, Science Direct, Scopus and Cochrane Library. Publications in Portuguese, English and Spanish in the last decade were included.ResultsThe 173 articles chosen showed quantitative and qualitative data about the potential of this natural product in the area of interest. Propolis extracts reached amazing values in antioxidant tests; they were as active as isolated substances already recognized as standard patterns. Many studies have brought information about the antioxidant mechanisms of propolis, such as free radical scavenging, metal chelation, and electron donation.ConclusionThis review brings scientific evidence, in vitro and in vivo, that supports the idea that propolis is a good candidate for producing new antioxidant pharmaceutical and food formulations in the future

Optimization and partial purification of beta‑galactosidase production by Aspergillus niger isolated from Brazilian soils using soybean residue

β-Galactosidases are widely used for industrial applications. These enzymes could be used in reactions of lactose hydrolysis and transgalactosylation. The objective of this study was the production, purification, and characterization of an extracellular β-galactosidase from a filamentous fungus, Aspergillus niger. The enzyme production was optimized by a factorial design. Maximal β-galactosidase activity (24.64 U/mL) was found in the system containing 2% of a soybean residue (w/v) at initial pH 7.0, 28 °C, 120 rpm in 7 days. ANOVA of the optimization study indicated that the response data on temperature and pH were significant (p < 0.05). The regression equation indicated that the R2 is 0.973. Ultrafiltration at a 100 and 30 kDa cutoff followed by gel filtration and anion exchange chromatography were carried out to purify the fungal β-galactosidase. SDS-PAGE revealed a protein with molecular weight of approximately 76 kDa. The partially purified enzyme showed an optimum temperature of 50 °C and optimum pH of 5.0, being stable under these conditions for 15 h. The enzyme was exposed to conditions approaching gastric pH and in pepsin’s presence, 80% of activity was preserved after 2 h. These results reveal a A. niger β-galactosidase obtained from residue with favorable characteristics for food industries

Asparaginase induces selective dose- and time- dependent cytotoxicity, apoptosis, and reduction of NFκB expression in oral cancer cells

Asparaginase is fundamental to the treatment of haematological malignancies. However, little has been studied on the effects that asparaginase could exert on solid tumours. Thus, this study aimed to evaluate the effects of asparaginase on an oral carcinoma cell line. The cytotoxicity of asparaginase in SCC- 9 (tongue squamous cell carcinoma) and HaCaT (human keratinocyte) cell lines was evaluated with MTT cell viability assay. The cells were treated with asparaginase at 0.04, 0.16, 0.63, 1.0, 1.5, 2.5, and 5.0 IU/mL. Dose- response curves and IC50 values were obtained and the Tumour Selectivity Index (TSI) was calculated. The effect of asparaginase on procaspase- 3 and nuclear factor κB (NFκB) expression was evaluated with western blot because it was reported that the overexpression of NFκB has been shown to contribute to tumour cell survival, proliferation, and migration. Caspase 3/7 staining was performed to identify cell death using flow cytometry. Effective asparaginase concentrations were lower for SCC- 9 cells when compared to HaCaT cells. The cytotoxicity results at 48 and 72 hours were significantly different for SCC- 9 cells. The TSI indicated that asparaginase was selective for the tumour cells. A decrease in procaspase- 3 and NFκB protein levels was observed in SCC- 9 cells. Furthermore, asparaginase resulted in significant apoptosis after 48 and 72 hours. Based on these results, asparaginase was cytotoxic in a dose- and time- dependent manner, induces apoptosis, and reduces NFκB expression in oral cancer cells. These results encourage further studies on the effectiveness of this enzyme as a treatment for solid tumours, especially head and neck cancer.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154950/1/cep13256.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154950/2/cep13256_am.pd

COVID-19 : is there evidence for the use of herbal medicines as adjuvant symptomatic therapy?

Background: Current recommendations for the self-management of SARS-Cov-2 disease (COVID-19) include self-isolation, rest, hydration, and the use of NSAID in case of high fever only. It is expected that many patients will add other symptomatic/adjuvant treatments, such as herbal medicines. Aims: To provide a benefits/risks assessment of selected herbal medicines traditionally indicated for “respiratory diseases” within the current frame of the COVID-19 pandemic as an adjuvant treatment. Method: The plant selection was primarily based on species listed by the WHO and EMA, but some other herbal remedies were considered due to their widespread use in respiratory conditions. Preclinical and clinical data on their efficacy and safety were collected from authoritative sources. The target population were adults with early and mild flu symptoms without underlying conditions. These were evaluated according to a modified PrOACT-URL method with paracetamol, ibuprofen, and codeine as reference drugs. The benefits/risks balance of the treatments was classified as positive, promising, negative, and unknown. Results: A total of 39 herbal medicines were identified as very likely to appeal to the COVID-19 patient. According to our method, the benefits/risks assessment of the herbal medicines was found to be positive in 5 cases (Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix, and Sambucus nigra), promising in 12 cases (Allium sativum, Andrographis paniculata, Echinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil, Justicia pectoralis, Magnolia officinalis, Mikania glomerata, Pelargonium sidoides, Pimpinella anisum, Salix sp, Zingiber officinale), and unknown for the rest. On the same grounds, only ibuprofen resulted promising, but we could not find compelling evidence to endorse the use of paracetamol and/or codeine. Conclusions: Our work suggests that several herbal medicines have safety margins superior to those of reference drugs and enough levels of evidence to start a clinical discussion about their potential use as adjuvants in the treatment of early/mild common flu in otherwise healthy adults within the context of COVID-19. While these herbal medicines will not cure or prevent the flu, they may both improve general patient well-being and offer them an opportunity to personalize the therapeutic approaches

Seasonal monitoring of the antioxidant activity of Erythroxylum suberosum A. St.-Hil. leaves: Correlation with hyperoside and isoquercitrin contents

373-382This study evaluated the seasonal effects of two flavonoids on antioxidant activity and chromatographic profiles by thin layer chromatography and high-performance liquid chromatography (HPLC) in Erythroxylum suberosum A. St.-Hil, a species used by the Brazilian indigenous community. These variables were observed from August 2013 to May 2014 in correlation with climatic variables, such as temperature, rainfall index and global radiation. The chromatographic profiles were found to be similar in the aqueous and ethanol extracts, and flavonoid hyperoside and isoquercitrin were identified and quantified. In the inhibition of the DPPH• radical, the most active was the aqueous extract from the 2nd collection (IC50: 4.45 μg/mL). For the phosphomolybdenum complex reduction method, the ethanol extract from the 1st collection was the most active (206.39 μg/mL equivalent ascorbic acid). Regarding the environmental correlations, it was observed that a higher global radiation index had a strong influence on the concentrations of hyperoside and contributed to the antioxidant activity. On the other hand, higher temperatures contributed to a higher isoquercitrin content in the aqueous extracts. These results indicate that August is the best month for the collection of Erythroxylum suberosum A. St.-Hil. leaves which have the highest isoquercitrin and hyperoside content and, thus, a high antioxidant activity

Plants from Brazilian cerrado with potent tyrosinase inhibitory activity

The increased amount of melanin leads to skin disorders such as age spots, freckles, melasma and malignant melanoma. Tyrosinase is known to be the key enzyme in melanin production. Plants and their extracts are inexpensive and rich resources of active compounds that can be utilized to inhibit tyrosinase as well as can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation. Using in vitro tyrosinase inhibitory activity assay, extracts from 13 plant species from Brazilian Cerrado were evaluated. The results showed that Pouteria torta and Eugenia dysenterica extracts presented potent in vitro tyrosinase inhibition compared to positive control kojic acid. Ethanol extract of Eugenia dysenterica leaves showed significant (p<0.05) tyrosinase inhibitory activity exhibiting the IC50 value of 11.88 µg/mL, compared to kojic acid (IC50 value of 13.14 µg/mL). Pouteria torta aqueous extract leaves also showed significant inhibitory activity with IC50 value of 30.01 µg/mL. These results indicate that Pouteria torta and Eugenia dysenterica extracts and their isolated constituents are promising agents for skin-whitening or antimelanogenesis formulations