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Abstract: Objective: Although protein malnutrition impairs immune functions, several studies have recently shown that protein restriction without malnutrition is beneficial to host defenses against invading pathogens and cancer. In an effort to establish the optimum diet for host resistance, we investigated the effect of different dietary protein levels on host resistance to Paracoccidioides brasiliensis. Methods: Mice were fasted for 2 days and then infected with P. brasiliensis. Immediately after challenge with this fungus, mice were refed on diets with three different levels (0%, 1.5%, or 20%) of casein. On days 0–7 after infection, antifungal activity and levels of proinflammatory mediators in the spleen and liver were measured. Results: Mice refed on the 1.5% casein diet showed higher antifungal activity in the spleen and liver compared with mice on the 20% casein diet. The antifungal activity in the spleens of mice refed on the 0% casein diet was intermediate between the antifungal activities of those refed the 1.5% and 20% casein diets. After infection, increases in spleen and liver levels of interleukin-6 and interferon-γ, liver mRNA levels of antimicrobial proteins (myeloperoxidase, cathepsin-G, and elastase-2), and liver mRNA levels of proinflammatory mediators (interleukin-18, chemokine C-X-C motif ligand 10, nuclear factor-κB, inducible nitric oxide synthase, and granulocyte–macrophage colony-stimulating factor) were less profound in mice on the 1.5% or 0% casein diet compared with mice refed the 20% casein diet. Conclusion: The present results suggest that protein restriction without malnutrition could be beneficial to host resistance to P. brasiliensis. [Copyright &y& Elsevier]

Abstract: Objective: The intake of ω-3 polyunsaturated fatty acids and psychological stress can each induce tissue lipid peroxidation. In our present study, we investigated their combined effects on the oxidative status of mouse tissues. Methods: Mice were group-housed (four mice/cage) and fed a diet containing fish oil (as a source of ω-3 polyunsaturated fatty acids), soybean oil, or olive oil for 3 wk. These animals were then 1) housed under the same conditions (four per cage, control group) or 2) individually housed to generate psychological stress conditions (isolation stress). After 2 wk of isolation stress, the levels of thiobarbituric acid-reactive substances (an index of lipid peroxidation) and antioxidants in the liver and kidney and the serum levels of triacylglycerol were measured. Results: Fish oil–fed mice showed increased levels of thiobarbituric acid-reactive substances in their livers and kidneys compared with soybean oil- or olive oil–fed mice. These increases in thiobarbituric acid-reactive substance levels in the fish oil–fed mice were less profound under isolation stress conditions when compared with the group-housed animals on the same diet. In the fish oil–fed mice, isolation stress led to an increase in liver vitamin E levels when compared with their group-housed counterparts. The fish oil–fed mice exhibited lower serum triacylglycerol levels compared with the soybean oil- or olive oil–fed mice, and this decrease was more profound under conditions of isolation stress when compared with group-housing conditions. Conclusion: Dietary fish oil combined with isolation stress results in lower levels of lipid peroxidation in the liver and kidney compared with dietary fish oil alone. [Copyright &y& Elsevier]

Although fluoroquinolones are used widely in the treatment of various infectious diseases, some of the drugs are known to cause hypoglycemia as a side-effect. We have investigated the effects of three fluoroquinolone derivatives, levofloxacin, gatifloxacin, and temafloxacin, on insulin secretion and pancreatic β-cell ATP-sensitive K+ channel (KATP channel) activity. While levofloxacin had only a small effect on insulin secretion and KATP currents, gatifloxacin and temafloxacin stimulated insulin secretion and inhibited KATP channel currents in a dose-dependent manner. We also determined the site of action of gatifloxacin and temafloxacin on the KATP channel. In a reconstituted system, gatifloxacin and temafloxacin inhibited Kir6.2ΔC26 channels, which function in the absence of the SUR subunit, indicating direct action of the drugs on the Kir6.2 subunits. These results suggest that stimulation of insulin secretion by inhibition of pancreatic β-cell KATP channels underlies the hypoglycemia caused by certain fluoroquinolones. [Copyright &y& Elsevier]

We report the first case of disseminated nocardiosis due to trimethoprim/sulfamethoxazole-resistant Nocardia terpenica successfully treated with meropenem and clarithromycin. The patient travelled to Japan from Australia via Southeast Asia, which led to differential diagnoses of multiple lung nodules including miliary tuberculosis and melioidosis as well as nocardiosis. Because of variety of susceptibility depending on the Nocardia species, clinicians need to confirm the species and investigate its susceptibility. [ABSTRACT FROM AUTHOR]

A new linear polyketide, amphidinin G ( 1 ), has been isolated from a symbiotic marine dinoflagellate Amphidinium sp. The planar structure of 1 was established mainly based on the 2D NMR data and the stereochemistry was elucidated by the combination of J -value analysis, modified Mosher’s method, and NMR chemical shift comparison with synthetic analogues. Amphidinin G ( 1 ) was expected to be a biosynthetic precursor of amphidinin A ( 2 ), a known linear dinoflagellate polyketide. Amphidinin G ( 1 ) showed antifungal activity against Trichophyton mentagrophytes . [ABSTRACT FROM AUTHOR]

Summary A case of disseminated nocardiosis caused by Nocardia elegans in a 72-year-old man with rheumatoid arthritis, treated with tacrolimus and prednisolone, is reported herein. The patient had impaired vision and was diagnosed with endophthalmitis and an abdominal skin abscess. He was started on trimethoprim–sulfamethoxazole treatment, followed by cefepime. The patient was then switched to a combination of imipenem–cilastatin and minocycline. Although the patient survived as a result of surgery and prolonged antibiotic treatment, he eventually lost vision after the infection became resistant to antibiotic treatment. Molecular analysis of samples from the abscess and vitreous fluid confirmed the extremely rare pathogen N. elegans , which accounts for only 0.3–0.6% of infections caused by Nocardia species. This organism is almost always associated with pulmonary infection, and disseminated infections are rare. As with previously reported norcardial infections, the current case was treated successfully with trimethoprim–sulfamethoxazole, carbapenems, and aminoglycosides. However, the clinical characteristics of this organism remain unclear. Further studies are therefore required to develop more effective treatment protocols for disseminated nocardiosis caused by this problematic pathogen. [ABSTRACT FROM AUTHOR]

Highlights: [•] Diterpenes, hikiokoshins A–I, were isolated from Isodon japonicus leaves. [•] Their structures were elucidated on the basis of spectroscopic analysis. [•] Hikiokoshin A exhibited antifungal activity. [Copyright &y& Elsevier]

Abstract: Six new indole alkaloids, hyrtimomines F–K (1–6), were isolated from Okinawan marine sponges Hyrtios spp. The structures of 1–6 were elucidated on the basis of spectroscopic analysis. Hyrtimomine F (1) is a structurally unique bisindole alkaloid possessing an α-keto-ɛ-caprolactam ring, while hyrtimomine G (2) is a symmetrical bisindole alkaloid. Hyrtimomines H–K (3–6) are indole alkaloids possessing β-carboline skeleton with an imidazolium unit. Antimicrobial activities of hyrtimomines F–K (1–6) were evaluated. [Copyright &y& Elsevier]

Abstract: Unhealthy eating behaviors increase the risk of metabolic diseases, but the underlying mechanisms are not fully elucidated. Because inflammation contributes to the pathogenesis of metabolic diseases, it is important to understand the effects of unhealthy eating on the inflammatory state. The objective of our present study was to address the effects of a fasting–refeeding regime, a model of irregular eating, on the hepatic inflammatory responses in mouse. The animals were fasted for 48 h and then refed either a standard or low-carbohydrate/high-fat diet. Inflammatory gene expression in the liver was then sequentially measured for the first 17 h after initiation of refeeding. To assess the roles of dietary carbohydrates and toll-like receptor 2 (TLR2) in the refeeding-induced inflammatory changes, gene expression levels in mice refed only carbohydrates (α-corn starch and sucrose) at different doses and in TLR2-deficient mice refed a standard diet were also analyzed. Refeeding with a standard diet increased the liver expression of Tlr2, proinflammatory mediators (Cxcl10, Cxcl1, Cxcl2, Icam-1) and negative regulators of TLR-signaling (A20 and Atf3). These increases were attenuated in mice refed a low-carbohydrate/high-fat diet. Refeeding only α-corn starch and sucrose also increased the expression of these inflammatory pathway genes depending on the doses. TLR2 deficiency significantly attenuated the refeeding-induced increase in the liver expression of Cxcl10, Cxcl1, Icam-1 and A20. These findings suggest that an irregular eating behavior can elicit a liver inflammatory response, which is at least partly mediated by TLR2, and that dietary carbohydrates play critical roles in this process. [Copyright &y& Elsevier]

Abstract: Three new polyketides, manzamenones L–N (1–3), have been isolated from an Okinawan marine sponge of the genus Plakortis. The structures of 1–3 were elucidated on the basis of spectroscopic data. Manzamenones L–N (1–3) were new dimeric fatty-acid derivatives consisting of a tetrahydroindenone with three carboxy groups and two hexadecanyl chains. Manzamenones M (2) and N (3) showed antimicrobial activity against several bacteria and fungi. [Copyright &y& Elsevier]

Abstract: New diterpene alkaloids, agelasines O–U (1–7), have been isolated from an Okinawan marine sponge Agelas sp. The gloss structures and relative stereochemistries of 1–7 were elucidated from the spectroscopic data. Agelasines O–R (1–4) were the third examples of diterpene alkaloid with a 9-N-methyladenine and a pyrrole units. Agelasine O (1) has a halimane skeleton, while agelasines P–R (2–4) have a clerodane skeleton. Agelasines S–U (5–7) were new diterpene alkaloids with a 9-N-methyladenine unit consisting of a halimane skeleton, a labdane skeleton, and a clerodane skeleton, respectively. Agelasines O–R (1–4) and T (6) showed antimicrobial activities against several bacteria and fungi. [Copyright &y& Elsevier]

Abstract: The structures of seven new secondary metabolites isolated from an Okinawan marine sponge Suberites sp., nakijinamines A (1), B (2), and F–I (3–6) and 6-bromoconicamin (7), have been elucidated on the basis of spectroscopic analysis, chemical conversion, and conformational analysis. These analyses disclosed that 1–6 were heteroaromatic alkaloids having the hybrid structures of an aaptamine-type alkaloid and an indole alkaloid, while 7 was a bromoindole alkaloid. Nakijinamine I (6) is the first example of an aaptamine-type alkaloid possessing a 1,4-dioxane ring. Antimicrobial activities of 1–7 were evaluated. [Copyright &y& Elsevier]

Abstract: Five new prenylated acylphloroglucinols, yojironins E–Ι (1–5), were isolated from the whole plants of Hypericum yojiroanum. Their structures were elucidated by spectroscopic data. Yojironin E (1) exhibited antimicrobial activity against Aspergillus niger, Candida albicans, Cryptococcus neoformans, and Trichophyton mentagrophytes. [Copyright &y& Elsevier]

Abstract: Five new isomalabaricane-type triterpenoids, stelliferins J–N (1–5), were isolated from Okinawan marine sponge Rhabdastrella cf. globostellata. The structures of 1–5 were elucidated from the spectroscopic data and chemical means including application of a modified Mosher’s method and an exciton chirality method. [Copyright &y& Elsevier]

Abstract: Two new meroterpenoids, yojironins A (1) and B (2), were isolated from the whole plants of Hypericum yojiroanum, together with two new prenylated acylphloroglucinols, yojironins C (3) and D (4). Their structures were elucidated by spectroscopic data. Yojironins A (1) and B (2) are biogenetically unique meroterpenoids, which seem to be composed of two acetate units with a 2-methylbutanoyl group and three isoprene units. Yojironin A (1) exhibited antimicrobial activity. [Copyright &y& Elsevier]

Abstract: Three new bromotyrosine alkaloids, ceratinadins A–C (1–3), were isolated from an Okinawan marine sponge Pseudoceratina sp. and the structures of 1–3 were elucidated on the basis of spectroscopic data. Ceratinadin A (1) was a novel bromotyrosine alkaloid possessing an N-imidazolyl-quinolinone moiety. Ceratinadins A (1) and B (2) showed antifungal activity. [Copyright &y& Elsevier]

Abstract: Four new prenylated acylphloroglucinols, petiolins J−M (1−4), were isolated from aerial parts of Hypericum pseudopetiolatum var. kiusianum, and the structures were elucidated by spectroscopic data and a single-crystal X-ray diffraction analysis. Petiolin J (1) exhibited antimicrobial activity. [Copyright &y& Elsevier]

Multi-azole resistant Aspergillus fumigatus carrying TR 46 /Y121F/T289A was isolated from a patient in Japan in Dec 2013. This strain grouped into the same clade of the ones which were clinically isolated in France and Germany. A. fumigatus harboring this mutation could be rapidly diffused outside the Eurasian continent. [ABSTRACT FROM AUTHOR]

Two new bromotyrosine alkaloids, tyrokeradines G ( 1 ) and H ( 2 ), have been isolated from an Okinawan marine sponge of the order Verongida. The structures of 1 and 2 were elucidated on the basis of spectroscopic data. Tyrokeradine G ( 1 ) is the first bromotyrosine alkaloid possessing a β-alanine unit, while tyrokeradine H ( 2 ) is a rare bromotyrosine alkaloid possessing a N -substituted pyridinium ring. Tyrokeradines G ( 1 ) and H ( 2 ) showed antifungal activity. [ABSTRACT FROM AUTHOR]

ATP-sensitive potassium channels of the inner mitochondrial membrane (mtKATP) are blocked by ATP. They are suggested to be involved in protective mechanisms such as ischemic preconditioning (IPC). Here we identify this channel type for the first time in a human cell line (Jurkat cells). Vesicles of the inner mitochondrial membrane (mitoplasts) were prepared by hypoosmotic shock. Single-channel currents were measured by means of the patch-clamp technique. We identified an outward-rectifying channel with a slope conductance of 15 and 82 pS at negative and positive potentials, respectively. The block by 5-hydroxydecanoic acid and inhibition by ATP characterize this channel as the mtKATP channel. ATP also increased the frequency of events within the burst. This effect was modulated by the Ca2+-bath concentration. We also show that the human mtKATP channel is a direct target for nitric oxide that blocked the channel activity. Although the molecular structure of this channel type is still unknown, its characterization as an outward-rectifying channel and modulation by calcium ions and nitric oxide may help to elucidate its functional significance, which possibly implicates a role in cell survival after IPC. [Copyright &y& Elsevier]

Abstract: Two new alkaloids, hyrtimomines D (1) and E (2), were isolated from an Okinawan marine sponge Hyrtios sp. The structures of 1 and 2 were elucidated on the basis of spectroscopic analysis. Hyrtimomines D (1) and E (2) are structurally unique bisindole alkaloids possessing the canthin-6-one skeleton with a hydroxyindole and an imidazolium units. Hyrtimomines D (1) and E (2) exhibited antimicrobial activity. [Copyright &y& Elsevier]

Abstract: Three new structurally unique bromopyrrole alkaloids, nagelamides U–W (1–3), were isolated from a marine sponge Agelas sp. Nagelamides U (1) and V (2) possess a γ-lactam ring with an N-ethanesulfonic acid and guanidino moieties, while nagelamide W (3) has two aminoimidazole moieties in the molecule. The structures of 1–3 were elucidated on the basis of spectroscopic data. Nagelamides U (1) and W (3) exhibited antimicrobial activity against Candida albicans. [Copyright &y& Elsevier]