Structure elucidation of Sch 20562, a glucosidic cyclic dehydropeptide lactone--the major component of W-10 antifungal antibiotic.

A novel bacterium designated as Aeromonas sp. W-10 produces the antibiotic W-10 complex which comprises of two major and several minor components. The two major components from this complex, Sch 20562 (1) and Sch 20561 (1a), are of biological interest in view of their potent antifungal activity. The chemical degradation studies utilized for the assignment of structure 1 for Sch 20562 are described here. Some of the noteworthy diversity of structural features in this glucosidic cyclic dehydrononapeptide lactone 1 are: an N-terminal (D)-beta-hydroxymyristyl unit, three D-amino acid units, two (E)-alpha-aminocrotonyl units, and an O-alpha-D-glucosyl-N-methyl-L-allo-threonine unit. The structure determination of 1 utilized the selective cleavage of the dehydropeptide units by ozonolysis to form fragments that were sequenced by mass spectrometry. The stereochemistry of the amino acid units were assigned by isolation of the free amino acids from the hydrolysates of the fragments. The stereochemistry of the alpha-aminocrotonyl units and the glucosidic linkage were assigned by nmr spectroscopy and molecular rotation data.     

Reappraisal of Pseudomonas aeruginosa hospital-acquired pneumonia mortality in the era of metallo-β-lactamase-mediated multidrug resistance: a prospective observational study

Introduction  

Hospital-acquired pneumonia (HAP) due to Pseudomonas aeruginosa is associated with high mortality rates. The metallo-β-lactamases (MBLs) are emerging enzymes that hydrolyze virtually all β-lactams. We aimed to assess P. aeruginosa HAP mortality in a setting of high-rate MBL production     

Cytokine Profile in Pleural Fluid and Serum After Lung Transplantation

Background

Lung transplantation is the procedure of choice in several end-stage lung diseases. Despite improvements in surgical techniques and immunosuppression, early postoperative complications occur frequently.

Objective

To evaluate the pleural inflammatory response after surgery.

Patients and Methods

Twenty patients aged 18 to 63 years underwent unilateral or bilateral lung transplantation between August 2006 and March 2008. Proinflammatory cytokines interleukin (IL)-1β, IL-6, and IL-8 and vascular endothelial growth factor in pleural fluid and serum were analyzed. For cytokine evaluation, 20-mL samples of pleural fluid and blood (right, left, or both chest cavities) were obtained at 6 hours after surgery and daily until removal of the chest tube or for a maximum of 10 days. Data were analyzed using analysis of variance followed by the Holm-Sidak test.

Results

All effusions were exudates according to Light's criteria. Pleural fluid cytokine concentrations were highest at 6 hours after surgery. Serum concentrations were lower than those in pleural fluid, and IL-1β, IL-6, and IL-8 were undetectable at all time points.

Conclusions

There is a peak concentration of inflammatory cytokines in the first 6 hours after transplantation, probably reflecting the effects of surgical manipulation. The decrease observed from postoperative day 1 and thereafter suggests the action of the immunosuppression agents and a temporal reduction in pleural inflammation.     

Bioaccessibility of Hg, Cd and As in cooked black scabbard fish and edible crab

Regular consumption of seafood has been widely recommended by authorities. Yet, some species accumulate high levels of contaminants like Hg, Cd and As. In addition, the risks associated to the consumption of such seafood may increase if consumers use cooking practices that enhance the concentration of contaminants and their bioaccessibility. In this study, the bioaccessibility of Hg, Cd and As was assessed with in vitro human digestion of raw and cooked black scabbard fish (Hg; steamed, fried and grilled) and edible crab (Cd and As; steamed and boiled) tissues. Additionally, the toxicological hazards associated with the consumption of these products were also discussed. Generally, Hg, Cd and As bioacessibility increased throughout the digestion process. Cadmium and As revealed high bioaccessibility rates in raw and cooked samples (up to 100%), whereas lower bioaccessible fractions of Hg was observed (up to 40%). Furthermore, this study pointed out the importance of food matrix, elemental chemical properties and cooking practices in the bioaccessibility of Hg, Cd and As. The toxicological hazards revealed that edible crab brown meat (Cd) and grilled black scabbard fish (MeHg) consumption in children should be moderated. In contrast, edible crab muscle (Cd) and fried or steamed black scabbard fish (MeHg) should be consumed to minimize exposure. The use of bioaccessible contaminant data strongly reduced the toxicological risks of MeHg, whereas less risk reduction occurred with Cd and inorganic As.     

Aging-induced decrease of cholinergic response and calcium sensitivity on rat jejunum contractions

The role of aging on contraction or relaxation through muscarinic or alpha-adrenergic receptors, respectively, was studied in isolated rat jejunum. Furthermore, the influence of extracellular calcium was analyzed, through functional and radioligand binding assays. The rank order of potency for selective muscarinic antagonists for M(1), M(2), and M(3) receptor subtypes, measured from affinity (pA(2)) values, was p-fluorohexahydrosiladifenidol (pFHHSiD) (M(3)) > pirenzepine (M(1)) > methoctramine (M(2)), indicating a predominance of M(3) subtype. This order was unchanged with age. Contractions by muscarinic agonist methacholine (MCh) were diminished in aged rats, resulting in lower apparent affinity (pD(2)) values, compared with adult controls. A larger decrease of MCh contractions occurred in aged rats after Ca(2+) withdrawal or after the calcium channel blocker isradipine. Changes were not detected for relaxation by adrenergic agonists. In conclusion, aging caused a decrease of MCh potency, which is probably related to the reduction of calcium sensitivity in jejunum.