Total Pelvic Exenteration surgery - Considerations for healthcare professionals.

BACKGROUND: Associated with considerable risk of morbidity, Total Pelvic Exenteration (TPE) is a life-altering procedure involving a significant prolonged recovery. As a result, and with the view of achieving the best outcomes and lessen short and long-term morbidities, a well-thought-out and coordinated multidisciplinary team approach, is crucial to the provision of safe and high-quality care. METHOD: Using a nominal group technique and qualitative methodology, this article explores the current practices in the care of oncology patients who undergo TPE surgery, in a tertiary cancer centre, by highlighting considerations of a collaboratively multi-disciplinary team. RESULTS: This article provides guidance on the multi-disciplinary team approach, relating to TPE surgery, with discussion of clinical concerns, and with the goal of high patient satisfaction, provision of effective care and the lessening of short and long-term morbidities. CONCLUSION: Oncology patients that undergo TPE surgery benefit from the contribution of a diversified multidisciplinary team as skilled and competent care that meets patient's health and social care needs is provided in a holistic, comprehensive, and timely care manner. Improving patient's care, pathway and postoperative outcomes, with the use of clinical expertise and support from professionals in the multidisciplinary team, can maximise care.

Endoperoxide-8-aminoquinoline hybrids as dual-stage antimalarial agents with enhanced metabolic stability.

Hybrid compounds may play a critical role in the context of the malaria eradication agenda, which will benefit from therapeutic tools active against the symptomatic erythrocytic stage of Plasmodium infection, and also capable of eliminating liver stage parasites. To address the need for efficient multistage antiplasmodial compounds, a small library of 1,2,4,5-tetraoxane-8- aminoquinoline hybrids, with the metabolically labile C-5 position of the 8-aminoquinoline moiety blocked with aryl groups, was synthesized and screened for antiplasmodial activity and metabolic stability. The hybrid compounds inhibited development of intra-erythrocytic forms of the multidrug-resistant Plasmodium falciparum W2 strain, with EC50 values in the nM range, and with low cytotoxicity against mammalian cells. The compounds also inhibited the development of P. berghei liver stage parasites, with the most potent compounds displaying EC50 values in the low µM range. SAR analysis revealed that unbranched linkers between the endoperoxide and 8-aminoquinoline pharmacophores are most beneficial for dual antiplasmodial activity. Importantly, hybrids were significantly more potent than a 1:1 mixture of 8-aminoquinoline-tetraoxane, highlighting the superiority of the hybrid approach over the combination therapy. Furthermore, aryl substituents at C-5 of the 8-aminoquinoline moiety improve the compounds' metabolic stability when compared with their primaquine (i.e. C-5 unsubstituted) counterparts. Overall, this study reveals that blocking the quinoline C-5 position does not result in loss of dual-stage antimalarial activity, and that tetraoxane-8- aminoquinoline hybrids are an attractive approach to achieve elimination of exo- and intraerythrocytic parasites, thus with the potential to be used in malaria eradication campaigns.

Solanum paniculatum L. decreases levels of inflammatory cytokines by reducing NFKB, TBET and GATA3 gene expression in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum paniculatum L., popularly known as jurubeba, is a common subtropical plant from Brazil, Paraguay, Bolivia and Argentina, that is used in folk medicine for the treatment of anemia, gastrointestinal disorders and inflammatory conditions in general. In addition to that, an ethnobotanical survey in "Todos os Santos" Bay have pointed out S. paniculatum as an herb to treat asthma. Previous publications have shown that S. paniculatum possesses antibiotic, antioxidant and modulatory effects on gastric acid secretion; however, its anti-inflammatory potential remains unexplored. AIM OF THE STUDY: Herein, we analyzed the S. paniculatum fruits hexane extract (SpE) for the presence of stigmasterol and ß-sitosterol and investigated the anti-inflammatory effect of SpE in vitro. MATERIALS AND METHODS: SpE was subjected to high-performance liquid chromatography (HPLC) for standardization and quantification of stigmasterol and ß-sitosterol. Spleen cells from BALB/c mice were cultivated and stimulated with pokeweed mitogen and also exposed to 15, 30 and 60µg/mL of SpE. Following treatment, levels of IFN-γ, IL-4 and IL-10 in the culture supernatants were assessed by ELISA. We also evaluated nitric oxide (NO) production by murine LPS-stimulated peritoneal macrophages using the Griess technique. In addition, the ability of SpE to stabilize membranes was assessed using a model of hemolysis induced by heat on murine erythrocytes. Gene expression of Th1-cell-specific Tbx21 transcription factor (TBET), zinc-finger transcription factor-3 (GATA3), and nuclear factor-κB (NFKB) in murine spleen cells were assessed by quantitative Polymerase Chain Reaction (qRT-PCR). RESULTS: SpE at 15, 30 and 60µg/mL significantly attenuated cell proliferation, decreased IL-4 release, reduced NO production and improved erythrocyte membrane stabilization in a concentration-dependent manner. SpE was also able to decrease the release of IFN-γ without altering IL-10 levels. The mechanism whereby SpE decreased inflammatory markers may be related to the reduction of NFKB, TBET and GATA3 gene expression. CONCLUSIONS: This study is the first to test the anti-inflammatory action of S. paniculatum. Herein, we provided evidence for the popular use of S. paniculatum in inflammatory conditions. Additional studies must be conducted to further explore the anti-inflammatory potential of SpE and to elucidate possible clinical applications.

Reinvestigating Old Pharmacophores: Are 4-Aminoquinolines and Tetraoxanes Potential Two-Stage Antimalarials?

The syntheses and antiplasmodial activities of various substituted aminoquinolines coupled to an adamantane carrier are described. The compounds exhibited pronounced in vitro and in vivo activity against Plasmodium berghei in the Thompson test. Tethering a fluorine atom to the aminoquinoline C(3) position afforded fluoroaminoquinolines that act as intrahepatocytic parasite inhibitors, with compound 25 having an IC50 = 0.31 µM and reducing the liver load in mice by up to 92% at 80 mg/kg dose. Screening our peroxides as inhibitors of liver stage infection revealed that the tetraoxane pharmacophore itself is also an excellent liver stage P. berghei inhibitor (78: IC50 = 0.33 µM). Up to 91% reduction of the parasite liver load in mice was achieved at 100 mg/kg. Examination of tetraoxane 78 against the transgenic 3D7 strain expressing luciferase under a gametocyte-specific promoter revealed its activity against stage IV-V Plasmodium falciparum gametocytes (IC50 = 1.16 ± 0.37 µM). To the best of our knowledge, compounds 25 and 78 are the first examples of either an 4-aminoquinoline or a tetraoxane liver stage inhibitors.

The anti-allergic activity of Cymbopogon citratus is mediated via inhibition of nuclear factor kappa B (Nf-Κb) activation.

BACKGROUND: The prevalence of allergic diseases such as asthma has significantly increased worldwide, making it a public health concern. There is an urgent need for new anti-inflammatory agents with selective pharmacology and lower toxicity. Plant extracts have been used for centuries in traditional medicine to alleviate inflammatory diseases. In this work, we evaluated the anti-allergic activity of Cymbopogon citratus (Cy), a medicinal herb used by folk medicine to treat asthma. METHODS: We used a murine model of respiratory allergy to the mite Blomia tropicalis (Bt) and evaluated certain parameters known to be altered in this model. A/J mice were sensitized (100 µg/animal s.c.) and challenged (10 µg/animal i.n.) with Bt mite extract and treated with 60, 120 or 180 mg/kg of Cy standardized hexane extract. The parameters evaluated included: cellular infiltrate in bronchoalveolar lavage (BAL); eosinophil peroxidase activity (EPO); histopathological examination of the lung; serum levels of specific IgE, IgG1 and IgG2a; Th2 cytokine concentrations in BAL and expression of NF-κB. RESULTS: Our results showed that oral administration of a Cy hexane extract (especially 180 mg/Kg) reduced the numbers of leukocytes/eosinophils in BAL; the eosinophil peroxidase activity in BAL; the infiltration of leukocytes in lung tissue; the production of mucus in the respiratory tract; the level of IL-4 in BAL and the nuclear expression of NF-κB. CONCLUSIONS: The results presented demonstrate the potential of the Cy hexane extract to modulate allergic asthma; this extract may be an alternative future approach to treat this pathology.

Treatment of Plasmodium chabaudi Parasites with Curcumin in Combination with Antimalarial Drugs: Drug Interactions and Implications on the Ubiquitin/Proteasome System.

Antimalarial drug resistance remains a major obstacle in malaria control. Evidence from Southeast Asia shows that resistance to artemisinin combination therapy (ACT) is inevitable. Ethnopharmacological studies have confirmed the efficacy of curcumin against Plasmodium spp. Drug interaction assays between curcumin/piperine/chloroquine and curcumin/piperine/artemisinin combinations and the potential of drug treatment to interfere with the ubiquitin proteasome system (UPS) were analyzed. In vivo efficacy of curcumin was studied in BALB/c mice infected with Plasmodium chabaudi clones resistant to chloroquine and artemisinin, and drug interactions were analyzed by isobolograms. Subtherapeutic doses of curcumin, chloroquine, and artemisinin were administered to mice, and mRNA was collected following treatment for RT-PCR analysis of genes encoding deubiquitylating enzymes (DUBs). Curcumin was found be nontoxic in BALB/c mice. The combination of curcumin/chloroquine/piperine reduced parasitemia to 37% seven days after treatment versus the control group's 65%, and an additive interaction was revealed. Curcumin/piperine/artemisinin combination did not show a favorable drug interaction in this murine model of malaria. Treatment of mice with subtherapeutic doses of the drugs resulted in a transient increase in genes encoding DUBs indicating UPS interference. If curcumin is to join the arsenal of available antimalarial drugs, future studies exploring suitable drug partners would be of interest.

A review of antimalarial plants used in traditional medicine in communities in Portuguese-speaking countries: Brazil, Mozambique, Cape Verde, Guinea-Bissau, São Tomé and Príncipe and Angola.

The isolation of bioactive compounds from medicinal plants, based on traditional use or ethnomedical data, is a highly promising potential approach for identifying new and effective antimalarial drug candidates. The purpose of this review was to create a compilation of the phytochemical studies on medicinal plants used to treat malaria in traditional medicine from the Community of Portuguese-Speaking Countries (CPSC): Angola, Brazil, Cape Verde, Guinea-Bissau, Mozambique and São Tomé and Príncipe. In addition, this review aimed to show that there are several medicinal plants popularly used in these countries for which few scientific studies are available. The primary approach compared the antimalarial activity of native species used in each country with its extracts, fractions and isolated substances. In this context, data shown here could be a tool to help researchers from these regions establish a scientific and technical network on the subject for the CPSC where malaria is a public health problem.

A review of antimalarial plants used in traditional medicine in communities in Portuguese-Speaking countries: Brazil, Mozambique, Cape Verde, Guinea-Bissau, São Tomé and Príncipe and Angola

The isolation of bioactive compounds from medicinal plants, based on traditional use or ethnomedical data, is a highly promising potential approach for identifying new and effective antimalarial drug candidates. The purpose of this review was to create a compilation of the phytochemical studies on medicinal plants used to treat malaria in traditional medicine from the Community of Portuguese-Speaking Countries (CPSC): Angola, Brazil, Cape Verde, Guinea-Bissau, Mozambique and São Tomé and Príncipe. In addition, this review aimed to show that there are several medicinal plants popularly used in these countries for which few scientific studies are available. The primary approach compared the antimalarial activity of native species used in each country with its extracts, fractions and isolated substances. In this context, data shown here could be a tool to help researchers from these regions establish a scientific and technical network on the subject for the CPSC where malaria is a public health problem.

Extraesophageal manifestations associated with gastroesophageal reflux

Approximately 25 per cent of the patients with gastroesophageal reflux disease (GERD) present only extraesophageal manifestations. GERD may be defined as clinical manifestations and tissue lesions associed to gastroesophageal reflux. GERD results from excessive exposure of the mucosa to aggressors, prominently acid and pepsin, associated with diminished esophageal defense mechanisms. This review aims to characterize extraesophageal GERD symptoms. Most patients with reflux-related otolaryngologic symptoms present relatively preserved motor function and esophageal clearance, but exhibit poor upper esophageal sphincter function, which leads to a "high" (pharyngeal) symptom. Acidification in the distal esophagus is likely to activate vagovagal reflexes. These reflexes. These reflexes also induce respiratory symptoms and bronchoconstriction. Nonspecific laryngitis, granuloma, posterior comissure hypertrophy, cricoarytenoid arthritis and come cases of globus pharyngeus have been attributed to larynx and pharynx irritations produced by repeated GER episodes. Otolaryngologic patients with reflux respond better to treatment than those patients whose symptoms are typically gastrointestinal.