Anti-dermatophytic activity of marine sponge,Sigmadocia carnosa (Dendy) on clinically isolated fungi

Objective

To screen the anti-fungal effects and find out the active metabolites from sponge, Sigmadocia carnosa (S. carnosa) against four dermatophytic fungi.

Methods

The methanol, ethyl acetate and acetone extract of marine sponge, S. carnosa was examined against Trichophyton mentagrophytes (T. mentagrophytes), Trichophyton rubrum (T. rubrum), Epidermophyton floccosum (E. floccosum) and Microsporum gypseum (M. gypseum) and qualitative analysed to find out the active molecules.

Results

The methanol extract of sponge was expressed significant activity than ethyl acetate and acetone. The minimum inhibitory concentration (MIC) of methanol extract of sponge that resulted in complete growth inhibition of T. mentagrophytes, T. rubrum, E. floccosum and M. gypseum were found to 125, 250, 250 and 250 µg/mL respectively. But, 100 % inhibition of fungal spore germination was observed in T. mentagrophytes at 500 µg/mL concentration followed by T. rubrum, E. floccosum and M. gypseum at 1 000 µg/mL concentration. Other two extracts showed weak anti spore germination activity against the tested dermatophytic fungi. Methanol extracts showed presence of terpenoids, steroids, alkaloids, saponins and glycosides.

Conclusion

Based on the literature, this is the first study which has conducted to inhibit the growth and spore germination of dermatophytic fungi with S. carnosa. Further research also needs to purify and characterize the secondary metabolites from the sponge, S. carnosa for the valuable source of novel substances for future drug discovery.     

Review article: Interventions for people presenting to emergency departments with a mental health problem: A systematic scoping review

The number of people presenting to EDs with mental health problems is increasing. To enhance and promote the delivery of safe and efficient healthcare to this group, there is a need to identify evidence‐based, best‐practice models of care. This scoping review aims to identify and evaluate current research on interventions commenced or delivered in the ED for people presenting with a mental health problem. A systematic search of eight databases using search terms including emergency department, mental health, psyc* and interventions, with additional reference chaining, was undertaken. For included studies, level of evidence was assessed using the NHMRC research guidelines and existing knowledge was synthesised to map key concepts and identify current research gaps. A total of 277 papers met the inclusion criteria. These were grouped thematically into seven domains based on primary intervention type: pharmacological (n = 43), psychological/behavioural (n = 25), triage/assessment/screening (n = 28), educational/informational (n = 12), case management (n = 28), referral/follow up (n = 36) and mixed interventions (n = 105). There was large heterogeneity observed as to the level of evidence within each intervention group. The interventions varied widely from pharmacological to behavioural. Interventions were focused on either staff, patient or institutional process domains. Few interventions focused on multiple domains (n = 64) and/or included the patient's family (n = 1). The effectiveness of interventions varied. There is considerable, yet disconnected, evidence around ED interventions to support people with mental health problems. A lack of integrated, multifaceted, person‐centred interventions is an important barrier to providing effective care for this vulnerable population who present to the ED.     

Plasma disposition, metabolism and excretion of the experimental antitumour agent 5,6-dimethylxanthenone-4-acetic acid in the mouse, rat and rabbit

5,6-Dimethylxanthenone-4-acetic acid (DMXAA), an experimental antitumour agent currently undergoing phase I clinical trial, has a maximum tolerated dose (MTD) in male BDF₁ mice of 99 μmol/kg. We have found the male Sprague-Dawley rat and the New Zealand White rabbit to have greater tolerance to DMXAA, with MTDs being 990 and 330 μmol/kg, respectively. To investigate the causes of this difference, we measured plasma and urine DMXAA concentrations by high-performance liquid chromatography (HPLC) after single i.v. bolus injections of 99 and 990 μmol/kg in the rat and following a bolus dose of 99 μmol/kg and a 10-min infusion of 330 μmol/kg in the rabbit. Following administration of DMXAA at the MTD in the mouse, rat and rabbit the maximal concentrations were 600, 2,200 and 1,708 μM, respectively, whereas areas under the concentration-time curves were 2,400, 19,000 and 2,400 μMh, respectively, for unchanged DMXAA. Data obtained for mice and rabbits were satisfactorily fitted to a two-compartment model with Michaelis-Menten kinetics. DMXAA was highly bound to plasma proteins, with the highest degree of binding being found in the rabbit. A small proportion of the total dose (7.8%, 0.6% and 12.4%, respectively) was excreted unchanged in urine over 24 h. This proportion increased (to 11.6%, 3.5% and 72.4%, respectively) following alkaline hydrolysis, suggesting the presence of glucuronide metabolites. Examination of rat and mouse urine by HPLC revealed the presence of two metabolites, which were characterized by mass spectrometry and nuclear magnetic resonance to be the acyl glucuronide of DMXAA and 6-(hydroxymethyl)-5-methylxanthenone-4-acetic acid. Thus, both mice and rats metabolise DMXAA by similar pathways. The results demonstrate considerable interspecies variations in tolerance to DMXAA that cannot be explained by differences in pharmacokinetics. Received: 15 September 1997 / Accepted: 5 August 1998     

Bis(phenazine-1-carboxamides): structure-activity relationships for a new class of dual topoisomerase I/II-directed anticancer drugs

Ring-substituted bis(phenazine-1-carboxamides), linked by a -(CH(2))(3)NMe(CH(2))(3)- chain, were prepared from the corresponding substituted phenazine-1-carboxylic acids by reaction of the intermediate imidazolides with bis(3-aminopropyl)methylamine. The compounds were evaluated for growth inhibitory activity in a panel of tumor cell lines, including P388 leukemia, Lewis lung carcinoma, and wild-type (JL(C)) and mutant (JL(A) and JL(D)) forms of human Jurkat leukemia. The latter mutant lines are resistant to topoisomerase (topo) II targeted agents because of lower levels of the enzyme. Analogues with small, lipophilic substituents (e.g., Me, Cl) at the 9-position were the most potent inhibitors, superior to the corresponding dimeric bis(acridine-4-carboxamides) (bis-DACA analogues). Several of the compounds were preferentially (up to 2-fold) more cytotoxic toward the mutant Jurkat lines than the wild-type. To test whether this selectivity was related to topoisomerase action, the most potent of the compounds (9-methyl) was evaluated in a cell-free system. It poisoned topo I at drug concentrations of 0.25 and 0.5 microM and inhibited the catalytic activity of both topo I and topo II at concentrations of 1 and 5 microM, respectively. Results from the NCI human tumor cell line panel showed the compounds had preferential activity toward colon tumor lines (on average 9.5-fold more active in the HT29 line than in the cell line panel as a whole). Several analogues produced significant growth delays in the relatively refractory subcutaneous colon 38 tumor model in vivo. In particular, the 9-methyl compound was substantially more potent in this tumor model than the clinical dual topo I/II poison DACA (total dose 90 versus 400 mg/kg) with comparable activity. The bis(phenazine-1-carboxamides) are a new and interesting class of dual topo I/II-directed anticancer drugs.     

Magnetic resonance imaging of the heart: a review of the experience in 172 subjects

Gated magnetic resonance (MR) imaging was used to evaluate central cardiovascular anatomy in 172 subjects, 31 of whom were healthy volunteers. Using the spin-echo technique, images of diagnostic quality were obtained in 93% of cases with TE = 28 msec and in 65% of cases with TE = 56 msec. Transverse multisection sequences encompassing most of the left ventricle required approximately 6-8 minutes. Corroborative studies were available in 134 of 141 patients who had cardiovascular disease; two dimensional echocardiograms and angiography in 133 and 100 patients, respectively. Gated MR demonstrated the wall thinning and complications caused by prior myocardial infarctions and high signal intensity of the myocardium at the site of acute myocardial infarctions. MR accurately demonstrated anatomic abnormalities owing to hypertrophic and congestive cardiomyopathies, congenital abnormalities of the heart and great vessels, rheumatic heart disease, pulmonary hypertension, and cardiac and paracardiac masses. Depiction of cardiovascular anatomy and pathoanatomy was attained without the use of any contrast media. Consequently, gated MR is an effective technique for cardiac diagnosis. The short time required for tomographic examination of the entire heart using the multisection technique renders this a practical cardiac imaging modality.