Resistance emergence among P. aenrginosa in a rat thigh-abscess model. Comparison of imipenem and meropenem treatment

Resistance emergence to carbapenem antibiotics was studied in a rat-thigh abscess model. Abscesses were developed in three groups with a total of 15 P. aeruginosa strains (three rats per strain). Groups were assigned to imipenem or meropenem treatment while one was left antibiotic-free. Test strains were fully susceptible to these antibiotics and the "Mutant Preventing Concentrations" of imipenem and meropenem over these strains were comparable. Antibiotic serum levels, assessed by serum bioassay test, were similar among therats. After four days, rats (n=45) were sacrificed and carbapenem resistant mutants were selected on imipenem (4 mg/L) and meropenem (4 mg/L) supplemented agar plates. Resistant variants of three strains, from four abscesses, were detected; one in the meropenem group, two in the imipenem and one in the untreated group. The MICs of imipenem and meropenem for the mutants were increased fourfold times or even higher of their counterparts. Resistance emergence under antibiotic pressure in P. aeruginosa has been shown in various conditions. To our knowledge, however, resistance emergence in abscess and also the comparison of imipenem and meropenem in this regard has not been studied before.     

The protective effect of taurine pretreatment on carbon tetrachloride-induced hepatic damage--a light and electron microscopic study

Summary.  The results regarding taurine pretreatment on CCl₄-induced hepatic injury are controversial. To assess the therapeutic efficacy of taurine on rat liver injury, hepatic malondialdehyde, glutathione, and hydroxyproline levels together with morphologic alterations in the liver following CCl₄ administration were investigated. The rats were divided into three groups. Taurine-treated animals received 15 ml/kg/day of a 5% taurine solution by a gastric tube for 5 days before administering CCl₄ (2 ml/kg, intraperitoneally, in a single dose). CCl₄-treated rats received the same amount of saline solution. Control animals received no treatment. The increase of hepatic malondialdehyde formation in the CCl₄-treated group was partially prevented by taurine pretreatment, but taurine had no significant effect on the glutathione and hydroxyproline content in the CCl₄-treated rats. Taurine pretreatment induced a marked beneficial effect regarding the prevention of hepatocellular necrosis and atrophy as demonstrated morphologically. In conclusion, these results suggest that taurine pretreatment might not significantly change the biochemical parameters, but prevents the morphologic damage caused by CCl₄ in the early stages. Received March 17, 2001 Accepted July 18, 2001     

Development and distribution of the early life stages of the longfin pearleye <Emphasis Type="Italic">Benthalbella linguidens</Emphasis> (Aulopiformes: Scopelarchidae) in the western North Pacific

The early life history and development of the scopelarchid Benthalbella linguidens was studied, based on 203 specimens (from 5.3 to 89.7mm in body length: BL) collected from Kuroshio, Oyashio waters and transition waters of the western North Pacific. The early life stages of B. linguidens are distinguished from those of other species of Benthalbella that inhabit the North Pacific by the characters of 62–64 myomeres in the larval stage and 26–28 anal fin rays in juvenile and transforming specimen. Larvae are elongate; notochord flexion begins at ca. 12mm BL and is completed at ca. 15mm BL. The fin ray complements are established at ca. 40mm BL. The single transforming specimen (89.7mm BL) that has peritoneal pigment was collected from transition waters. All larvae were collected from Kuroshio and transition waters from winter to early summer; however, the size of larvae in Kuroshio waters was apparently smaller than that in transition waters, with ranges of 5.3–32.4mm BL (mean 17.1) and 15.3–35.3mm BL (mean 27.5), respectively. Juveniles were distributed in transition and Oyashio waters and were absent in Kuroshio waters, where adults are commonly distributed. These occurrences of larvae and juveniles in the western North Pacific indicate that B. linguidens spawns in Kuroshio waters in winter and uses transition waters as nursery grounds.     

Inorganic compounds have dual effect on recombinant protein production: influence of anions and cations on serine alkaline protease production

AIMS: Investigation of concerted effects of cations, i.e. Mg2+ and Mn2+, in combination with their anions, i.e. sulphate, chloride and acetate (Ac), on the physiology of Bacillus licheniformis carrying pHV1431::subC to improve the fermentation medium for serine alkaline protease (SAP) production, whereupon, determination of the acid that can be used in pH control. METHODS AND RESULTS: The cell concentrations increased with the increase in MnSO4 and Mn(Ac)2 concentrations, and the highest values were obtained at Co(MnSO4) = 0.20 mmol l-1 and Co(Mn(CH3COO)2) = 4.0 mmol l-1, as 2.3 and 2.2 g l-1, respectively. However, Co(MnCl2) did not influence biomass concentration. SAP production was inhibited with MnCl2 after Co(MnCl2) = 0.60 mmol l-1, but with MnSO4 SAP production was inhibited drastically. Whereas, at high concentrations of Mn(Ac)2 SAP production increased and the highest activity was obtained as ASAP = 1285 U ml-1 at t = 65 h. With the Mg compounds, cell concentrations increased with the increase in the concentrations of MgSO4, MgCl2 and Mg(Ac)2; and the anions did not show any influence on the cell growth. Similar to the results of Mn compounds, the glucose consumption rate increased with the increase in MgSO4 and MgCl2 concentrations; contrariwise, decreased with the increase in Mg(Ac)2 concentrations, due to the use of acetate as the second carbon source. Co(MgSO4) = 0.40 mmol l-1, Co(MgCl2) = 1.60 mmol l-1 and Co(Mg(Ac)2) = 0.40 mmol l-1 were the optimum concentrations separately, and the highest SAP activity was obtained with Mg(Ac)2 as ASAP = 1338 U ml-1 at t = 47 h. Consequently, ion acetate and its acid HAc appear, respectively, as the superior anion for the essential cations and the control agent for pH control in the bioreactor. Finally, optimum initial concentrations and the concerted effects of Mg(Ac)2 and Mn(Ac)2 were investigated, and the optimum concentrations were found respectively as 0.40 and 0.80 mmol l-1, while the maximum activity was obtained as ASAP = 1010 U ml-1 at a shortened cultivation time of t = 39 h. CONCLUSIONS: Mn(Ac)2 and Mg(Ac)2 together enhanced the cell formation and SAP synthesis rates, moreover, SAP synthesis started at an earlier cultivation time. SIGNIFICANCE AND IMPACT OF THE STUDY: Each inorganic compound with its cation and anion has dual effect on the metabolism. Mg2+ and Mn2+ at their specific concentrations influence the regulation of the pathways that might cause better coupling of supply and demand for the amino acids on the basis of the amino acid composition of the enzyme molecule.     

Direct,noninvasive measurement of brain glycogen metabolism in humans

The concentration and metabolism of the primary carbohydrate store in the brain, glycogen, is unknown in the conscious human brain. This study reports the first direct detection and measurement of glycogen metabolism in the human brain, which was achieved using localized 13C NMR spectroscopy. To enhance the NMR signal, the isotopic enrichment of the glucosyl moieties was increased by administration of 80 g of 99% enriched [1-13C]glucose in four subjects. 3 h after the start of the label administration, the 13C NMR signal of brain glycogen C1 was detected (0.36+/-0.07 micromol/g, mean+/-S.D., n=4). Based on the rate of 13C label incorporation into glycogen and the isotopic enrichment of plasma glucose, the flux through glycogen synthase was estimated at 0.17+/-0.05 micromol/(gh). This study establishes that brain glycogen can be measured in humans and indicates that its metabolism is very slow in the conscious human. The noninvasive detection of human brain glycogen opens the prospect of understanding the role and function of this important energy reserve under various physiological and pathophysiological conditions.     

Effect of caffeic acid phenethyl ester on treatment of experimentally induced methicillin-resistant Staphylococcus epidermidis endophthalmitis in a rabbit model

This study investigated the anti-inflammatory effects of caffeic acid phenethyl ester (CAPE), a natural bee-produced compound, and compared it with corticosteroids in the treatment of experimentally induced methicillin-resistant Staphylococcus epidermidis (MRSE) endophthalmitis in addition to intravitreal antibiotics. An experimental endophthalmitis model was produced in 24 New Zealand albino rabbits by unilateral intravitreal injection of 0.1 ml of 4.7 x 10(4) colony-forming units (CFU) methicillin-resistant S. epidermidis. The animals were then divided randomly into three treatment groups and a control group, group 1 (six rabbits), received only intravitreal vancomycin (1.0 mg/0.1 ml); group 2 (six rabbits), received both intravitreal vancomycin (1.0 mg/0.1 ml) and intravitreal dexamethasone (400 microg/0.1 ml) and group 3 (six rabbits), received both intravitreal vancomycin (1.0 mg/0.1 ml) and subtenon CAPE (10 mg/0.3 ml) after 24 h post-infection. No treatment was given to the control group. Treatment efficacy was assessed by clinical examination, vitreous culture and histopathology. There were no statististically significant differences between clinical scores of all groups in examinations at 24 and 48 h post-infection (p = 0.915 and p = 0.067 respectively), but in examinations at 72 h post-infection and after 7 days post-infection, although the clinical scores of treatment groups were not significantly different from each other, they were significantly lower than the control group (p < 0.05). The culture results of all groups were sterile. As a result, CAPE was found to be as effective as dexamethasone in reducing inflammation in the treatment of experimental MRSE endophthalmitis when used with antibiotics. More studies are needed to determine the optimal administration route and effective dosage of this compound.     

Viable mice with compound mutations in the Wnt/Dvl pathway antagonists nkd1 and nkd2

Gradients of Wnt/beta-catenin signaling coordinate development and physiological homeostasis in metazoan animals. Proper embryonic development of the fruit fly Drosophila melanogaster requires the Naked cuticle (Nkd) protein to attenuate a gradient of Wnt/beta-catenin signaling across each segmental anlage. Nkd inhibits Wnt signaling by binding the intracellular protein Dishevelled (Dsh). Mice and humans have two nkd homologs, nkd1 and nkd2, whose encoded proteins can bind Dsh homologs (the Dvl proteins) and inhibit Wnt signaling. To determine whether nkd genes are necessary for murine development, we replaced nkd exons that encode Dvl-binding sequences with IRES-lacZ/neomycin cassettes. Mutants homozygous for each nkd(lacZ) allele are viable with slightly reduced mean litter sizes. Surprisingly, double-knockout mice are viable, with subtle alterations in cranial bone morphology that are reminiscent of mutation in another Wnt/beta-catenin antagonist, axin2. Our data show that nkd function in the mouse is dispensable for embryonic development.