bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracranial empyema: literature review and two novel cases in cats
Authors: Barrs V. R. , Nicoll R. G. , Churcher R. K. , Beck J. A. , Beatty J. A.
Published: June 2007

Objectives:To review the literature on intracranial empyema and report two new cases in cats.

Methods:Literature review and case reports.

Results:Intracranial empyema has been rarely reported in small animals. In two novel cases in cats, the route of infection was postulated to be local extension from a retrobulbar abscess of odontogenic origin in one case and direct inoculation from a penetrating bite wound to the skull, confirmed at post‐mortem examination, in the other. On magnetic resonance imaging of the first case, there was a contrast‐enhancing large extra‐axial fluid collection overlying the right cerebral hemisphere, consistent with subdural empyema. Infection was caused by anActinomycesspp. This is the first report of successful treatment of intracranial empyema by craniotomy, drainage and antibiotics.

ClinicalSignificance:Intracranial empyema is a neurosurgical emergency. Favourable outcomes may be achieved with surgical decompression, antimicrobial therapy and intensive care.
Metabolic epidermal necrosis in a dog associated with pancreatic adenocarcinoma, hyperglucagonaemia, hyperinsulinaemia and hypoaminoacidaemia
Authors: Cave T. A. , Evans H. , Hargreaves J. , Blunden A. S.
Published: June 2007

A case of metabolic epidermal necrosis associated with a pancreatic carcinoma is described. Normoglycaemia, reduced serum fructosamine, and hypoaminoacidaemia were identified. Hyperinsulinaemia and hyperglucagonaemia were documented. Immunohistochemistry documented strong tumour expression of both insulin and glucagon supporting combined paraneoplastic production of both hormones by the tumour. Enteral protein and fatty acid supplementation and parenteral amino acid supplementation proved ineffective. Metastasis to regional lymph nodes was identified and the patient was euthanased.
Characteristics of the Cibaliung Gold Deposit: Miocene Low‐Sulfidation‐Type Epithermal Gold Deposit in Western Java, Indonesia
Authors: Harijoko Agung , Ohbuchi Yukiko , Motomura Yoshinobu , Imai Akira , Watanabe Koichiro
Published: June 2007

Middle Miocene (11.18–10.65 Ma) low sulfidation‐type epithermal gold mineralization occurred in the Cibaliung area, southwestern part of Java Island, Indonesia. It is hosted by andesitic to basaltic andesitic lavas of the Middle Miocene Honje Formation (11.4 Ma) and is covered by Pliocene Cibaliung tuff (4.9 Ma). The exploration estimates mineral resource of approximately 1.3 million tonnes at 10.42 g/t gold and 60.7 g/t silver at a 3 g/t Au cut‐off. This equates to approximately 435,000 ounces of gold and 2.54 million ounces of silver. That resource resulted from two ore shoots: Cibitung and Cikoneng. Studies on ore mineralogy, hydrothermal alteration, geology, fluid inclusion, stable isotopes and age dating were conducted in order to characterize the deposit and to understand a possible mechanism of preservation of the deposit. The ore mineral assemblage of the deposit consists of electrum, naumannite, Ag‐Se‐Te sulfide minerals, chalcopyrite, pyrite, sphalerite and galena. Those ore minerals occur in quartz veins showing colloform–crustiform texture. They are enveloped by mixed layer clay illite/smectite zone, which grades into smectite zone outward. The temperature of mineralization revealed by fluid inclusion study on quartz in the veins ranges from 170 and 220°C at shallow and deep level, respectively. The temperature range is in agreement with the temperature deduced from the hydrothermal alteration mineral assemblage including mixed layered illite/smectite and laumontite. The mineralizing fluid is dilute, with a salinity <1 wt% NaCl equivalent and has stable isotopes of oxygen and hydrogen composition indicating a meteoric water origin. Although the deposit is old enough that it would have been eroded in a tropical island arc setting, the coverage by younger volcanic deposits such as the Citeluk tuff and the Cibaliung tuff most probably prevented this erosion.
Origin of Ore‐forming Fluids Responsible for Gold Mineralization of the Pongkor Au‐Ag Deposit, West Java, Indonesia: Evidence from Mineralogic, Fluid Inclusion Microthermometry and Stable Isotope Study of the Ciurug–Cikoret Veins
Authors: Syafrizal  , Imai Akira , Watanabe Koichiro
Published: June 2007

The Pongkor gold–silver mine is situated at the northeastern flank of the Bayah dome, which is a product of volcanism in the Sunda–Banda Arc. The hydrothermal alteration minerals in the Ciurug–Cikoret area are typical of those formed from acid to near‐neutral pH thermal waters. On the surface, illite/smectite mixed layer mineral (I/Sm), smectite and kaolinite, and spotting illite, I/Sm and K‐feldspar alteration occur at the top of the mineralized zone. Silicification, K‐feldspar and I/Sm zones are commonly formed in the wall rock, and gradually grade outwards into a propylitic zone. The mineralization of precious metal ore zone is constrained by fluid temperatures between 180 and 220°C, and with low salinity (<0.2 wt% NaCl equivalent) and boiling condition. The minimum depth of vein formation below the paleo‐water table is approximately 90–130 m for the hydrostatic column. Hydrogen and oxygen isotope data for quartz and calcite show relatively homogeneous fluid composition (−53 to −68‰δD and −5.7 to +0.3‰δ18O H2O). There is no specific trend in the data with respect to the mineralization stages and elevation, which suggests that the ore‐forming fluids did not significantly change spatially during the vein formation. The stable isotope data indicate mixing between the hydrothermal fluids and meteoric water and interaction between the hydrothermal fluids and the host rock.
Gold‐Related Sulfide Mineralization and Ore Genesis of the Penjom Gold Deposit, Pahang, Malaysia
Authors: Ariffin Kamar Shah , Hewson Nick J.
Published: June 2007

The Penjom gold deposit lies on the eastern side of the Raub‐Bentong Suture line within the Central Belt of Permo‐Triassic rocks, near Kuala Lipis, Pahang, Malaysia. The geology of the deposit is dominated by a sequence of fine‐ to coarse‐grained rhyolitic to rhyodacitic tuff, tuff‐breccia and a minor rhyolitic–rhyodacitic volcanic series, associated with argillaceous marine sedimentary rocks consisting of shale with subordinate shalely limestone of Padang Tungku Formation and Pahang Volcanic Series. Fine‐ to coarse‐grained tonalite and quartz porphyry intruded this unit. The main structural features of the area are north–south‐trending left‐lateral strike‐slip faults and their subsidiaries, which generally strike north–south and dip moderately to the east (350°–360°/40°–60°). Mineralization at the Penjom gold deposit is structurally controlled and also erratic laterally and vertically. The gold mineralization can be categorized as (i) gold associated with carbonate‐rich zones hosted within dilated quartz veins carrying significant amount of sulfides; (ii) gold disseminated within stockwork of quartz–carbonate veins affiliated with tonalite; and (iii) gold often associated with arsenopyrite and pyrite in quartz–carbonate veins and stringers hosted within shear zones of brittle–ductile nature in all rock types and in brittle fractured rhyodacitic volcanic rocks. Sphalerite, chalcopyrite, tetrahedrite and pyrrhotite are the minerals accompanying the early stage of gold mineralization. These minerals also suffered from local brittle deformation. However, most of the gold mineralization took place after the deposition of these sulfides. Galena appears somewhat towards the end of gold mineralization, whereas tellurium and bismuth accompanied gold contemporaneously. The gold mineralization occurred most probably due to the metamorphogenic deformational origin concentrated mostly in the shear zone. The mineralization is strongly controlled by the wall rock (e.g. graphitic shale), the sulfide minerals and fluid–rock interaction.
Fluid Inclusion Microthermometry and Implications for the Mechanisms of Ore‐Grade Gold Mineralization in Epithermal System, Lalab Orebody, Sibutad, Zamboanga del Norte, Philippines
Authors: Jimenez Francisco A. , Yumul Graciano P. , Maglambayan Victor B.
Published: June 2007

The Sibutad gold deposit has gold associated in quartz veins. The most important of these is the Lalab orebody, which contains ore‐grade gold, predominantly, in milky quartz veins and veinlets. Here, alteration quartz and fine‐grained crystalline clear and milky quartz were formed from hydrothermal fluids in three stages, namely stages I, II and III. Fluid inclusion microthermometry was carried out on stage I milky quartz, stage II fine‐grained alteration quartz and stage III milky quartz ± barite veins and veinlets. Homogenization temperatures (TH) are >248°C in stage I, 214–232°C in stage II and 186–239°C in stage III. These fluid inclusions have salinity between 1 and 2 wt% NaCl equivalent. In terms of gold assay, stage I drill‐core samples have gold grades 0.53–0.76 g/ton Au, stage II samples have 1.12–3.70 g/ton Au and stage III samples have 9.06–23.88 g/ton Au. This correlation suggests that gold was precipitated from the stage II and III fluids.
Temporal Geochemical Evolution of Neogene Magmatism in the Baguio Gold–Copper Mining District (Northern Luzon, Philippines)
Authors: Polve Mireille , Maury Rene C. , Jego Sebastien , Bellon Herve , Margoum Ahmed , Yumul Graciano P. , Payot Betchaida D. , Tamayo Rodolfo A. , Cotten Joseph
Published: June 2007

Baguio, in the Central Cordillera of Northern Luzon, is a district that displays porphyry copper and epithermal gold mineralization, associated with Early Miocene–Pliocene–Quaternary calc‐alkaline and adakitic intrusions. Systematic sampling, K‐Ar dating, major and trace elements, and Sr, Nd, Pb isotopic analyses of fresh magmatic rocks indicate three magmatic pulses: an Early Miocene phase (21.2–18.7 Ma), a Middle–Late Miocene phase (15.3–8 Ma) and finally a Pliocene–Quaternary event (3–1 Ma). The first phase emplaced evolved calc‐alkaline magmas, essentially within the Agno Batholith complex, and is thought to be related to the westward‐dipping subduction of the West Philippine Basin. After a quiescence period during which the Kennon limestone was deposited, magmatic activity resumed at 15.3 Ma, in connection with the start of the subduction of the South China Sea along the Manila Trench. It emplaced first petrogenetically related and relatively unradiogenic low‐K calc‐alkaline lavas and intermediate adakites. Temporal geochemical patterns observed from 15.3 to 1 Ma include progressive enrichment in K and other large ion lithophile elements, increase in radiogenic Sr and Pb and corresponding decrease in radiogenic Nd. These features are thought to reflect the progressive addition to the Luzon arc mantle wedge of incompatible elements largely inherited from South China Sea sediments. The origin of the long quiescence period, from 8 to 3 Ma, remains problematic. It might represent a local consequence of the docking of the Zambales ophiolitic terrane to Northern Luzon. Then, magmatic activity resumed at 3 Ma, emplacing chemically diversified rocks ranging from low K to high K and including a large proportion of adakites, especially during the Quaternary (dacitic plugs). The authors tentatively relate this diversity to the development of a slab tear linked with the subduction of the fossil South China Sea ridge beneath the Baguio area.
Occurrences of Ore Minerals and Fluid Inclusion Study on the Kingking Porphyry Copper–Gold Deposit, Eastern Mindanao, Philippines
Authors: Suerte Leilanie O. , Nishihara Sho , Imai Akira , Watanabe Koichiro , Yumul Graciano P. , Maglambayan Victor B.
Published: June 2007

The Kingking deposit is a gold‐rich porphyry copper deposit and the southernmost deposit at the eastern Mindanao mineralized belt, Philippines. It is underlain by Cretaceous–Paleogene sedimentary and volcanic rocks that are intruded by mineralized Miocene diorite porphyries and by barren Miocene–Pliocene dacite and diorite porphyries. The main alteration zones in the deposit are the inner potassic zone and the outer propylitic zone. The biotite‐bearing diorite and hornblende diorite porphyries are the primary host rocks of mineralization. Two dominant copper minerals, bornite and chalcopyrite, which usually occur as fracture fillings, are associated with fine crystalline quartz veinlet stockworks in the mineralized diorites. Minor secondary covellite, chalcocite and digenite are also observed. The primary Cu‐Fe sulfide phases initially deposited from ore fluids consisted of bornite solid solution (bnss) and intermediate solid solution (iss), which decomposed to form the bornite and chalcopyrite. Peculiar bornite pods that are different from dissemination and are associated with volcanic rock xenoliths in biotite‐bearing diorite porphyry are noted in a drill hole. These pods of bornite are not associated with quartz veinlet stockworks. Fluid inclusion analyses show three types of inclusions contained in Kingking samples: two‐phase fluid‐rich and vapor‐rich inclusions and polyphase hypersaline inclusions from porphyry‐type quartz veinlet stockworks. The liquid–vapor homogenization temperatures (TH) and the dissolution temperature of halite daughter crystals (TM) from the polyphase hypersaline inclusions predominantly range from 400°C up to >500°C. The wide range of TH and TM may be due to heterogeneous trapping of variable ratios of vapor and brine. For some inclusions, TH > TM and in some cases, TH < TM, indicating that some of the brine was supersaturated or saturated with NaCl at the time of entrapment. Calculated salinity of the polyphase hypersaline inclusions ranges from 40 to 60% NaCl equivalent. Temperature and vapor pressure of mineralized fluid were estimated to be 400°C and 16 MPa.
Ore and Alteration Types of the Gold and Copper Mineralization in the Lascogon Project, Surigao del Norte, Mindanao Island, Philippines
Authors: Crisostomo Jonelle Nikolai , Parian Jeddalyn , Ishiyama Daizo , Baluda Redempta , Eguia Sonia , Galapon Jocelyn , Comia Gerry , Segura Jessie , Laroco Maureen , Oliveros Noel , Maglambayan Victor B.
Published: June 2007

Two ore and three alteration types were identified in the Lascogon Project of Philex Gold Philippines, in Surigao del Norte, Mindanao Island, Philippines. The jasperoid ore is the host to the Carlin‐like gold mineralization in the Lascogon and Danao prospects. The ore occurs in a decalcified and silicified horizon, with minor chlorite and goethite, stibnite, pyrite and quartz crystals ranging from cryptocrystalline to botryoidal. The stringer–stockwork type Cu‐Au mineralization in the Suyoc prospect is hosted in argillized andesitic rocks of the Mabuhay Formation. The primary ore minerals are chalcopyrite with minor amounts of sphalerite. The alteration types identified are propylitic alteration, argillic alteration and silicification. The propylitized basaltic and andesitic flows of the Bacuag Formation bound the jasperoid mineralization in the Lascogon prospect. Stratigraphically, the relationship between propylitized basalts and stringer–stockwork Cu‐Au is not clear but a lateral change can be inferred from jasperoid in the center and stringer–stockwork towards the east.
Statistical Disclosure Control Methods for Census Frequency Tables
Authors: Shlomo Natalie
Published: June 2007

This paper provides a review of common statistical disclosure control (SDC) methods implemented at statistical agencies for standard tabular outputs containing whole population counts from a census (either enumerated or based on a register). These methods include record swapping on the microdata prior to its tabulation and rounding of entries in the tables after they are produced. The approach for assessing SDC methods is based on a disclosure risk–data utility framework and the need to find a balance between managing disclosure risk while maximizing the amount of information that can be released to users and ensuring high quality outputs. To carry out the analysis, quantitative measures of disclosure risk and data utility are defined and methods compared. Conclusions from the analysis show that record swapping as a sole SDC method leaves high probabilities of disclosure risk. Targeted record swapping lowers the disclosure risk, but there is more distortion of distributions. Small cell adjustments (rounding) give protection to census tables by eliminating small cells but only one set of variables and geographies can be disseminated in order to avoid disclosure by differencing nested tables. Full random rounding offers more protection against disclosure by differencing, but margins are typically rounded separately from the internal cells and tables are not additive. Rounding procedures protect against the perception of disclosure risk compared to record swapping since no small cells appear in the tables. Combining rounding with record swapping raises the level of protection but increases the loss of utility to census tabular outputs. For some statistical analysis, the combination of record swapping and rounding balances to some degree opposing effects that the methods have on the utility of the tables.
Modelling & Controlling Monetary and Economic Identities with Constrained State Space Models
Authors: Pandher Gurupdesh S.
Published: June 2007

The paper presents a method for modelling and controlling time series with identity structures. The approach is presented in the context of monetary targeting where the monetary identity (e.g. reserve money equals net foreign assets plus domestic credit) is modelled using a constrained state space model and next‐period changes in domestic credit (policy variable) are estimated to reach the target level of reserve money. The constrained modelling ensures that aggregation and identity relations among items are dynamically satisfied during estimation, leading to more accurate forecasting and targeting.

Applications to Germany, UK and USA show that the constrained state space model provides significant improvements in targeting and forecasting performance over the AR(1) benchmark and the unconstrained model. Reduction in the mean square error of targeting over AR(1) is in the range of 76–95% for the three countries while the gain in targeting efficiency over unconstrained modelling is between 21% and 55%. Beyond monetary targeting, the method has wide application to the dynamic modelling and control of economic and financial time series with identity and aggregation constraints (e.g. balance of payment, national income, purchasing power parity, company balance sheet).
Design‐Based Properties of Linear Calibrated Estimators of a Finite Population Total
Authors: Sugden Roger A. , Smith T.M. Fred
Published: June 2007

We extend Godambe's famous nonexistence theorem to classes of linear calibrated estimators. We also propose a new method for comparing sampling strategies in the design‐based framework without recourse to simulation.
Potent induction therapy with interferon and ribavirin combination therapy does not achieve a higher sustained virological response rate in chronic hepatitis C with genotype 1b and high hepatitis C virus RNA level
Authors: Enomoto Shotaro , Tamai Hideyuki , Oka Masashi , Shingaki Naoki , Shiraki Tatsuya , Takeuchi Machiko , Deguchi Hisanobu , Magari Hirohito , Inoue Izumi , Iguchi Mikitaka , Yanaoka Kimihiko , Arii Kenji , Fujishiro Mitsuhiro , Yahagi Naohisa , Yotsuyanagi Hiroshi , Ichinose Masao
Published: June 2007

Aims:  To compare twice‐daily interferon (IFN)‐β administration and once‐daily IFN‐α‐2b administration as induction therapy in ribavirin combination therapy in chronic hepatitis C with a high viral load of genotype‐1b hepatitis C virus (HCV).

Methods:  Sixty‐one chronic hepatitis patients with a high viral load of genotype‐1b HCV were randomly divided into three groups: group A was given IFN‐β 6 MU induction therapy twice daily for 2 weeks; group B was given IFN‐α‐2b 6 MU induction therapy once daily for 2 weeks; and group C was given no induction therapy. All three groups were then given IFN‐α‐2b 6 MU 3 days/week for the rest of the 24‐week study period. Ribavirin was given for the entire 24‐week study period.

Results:  Although the cumulative HCV‐RNA negative rates tended to be higher in group A than in group B, the differencewas not significant. The HCV‐RNA negative rate at week 2 was significantly higher in groups A and B than in group C (P < 0.05). The sustained virological response (SVR) rate was 16% overall, 21% for groups A and B, and 5% for group C; the SVR rate of groups A plus B tended to be higher than that of group C (P = 0.093).

Conclusions:  There was no difference between the effects of the two induction therapies; potent induction therapy does achieve higher early viral clearance but not a higher SVR rate.
HFE C282Y gene variant is a risk factor for the progression to decompensated liver disease in chronic viral hepatitis C subjects in the Czech population
Authors: Pácal Lukáš , Husa Petr , Znojil Vladimír , Kan̆ková Kater̆ina
Published: June 2007

Aim:  To determine the prevalence of selected HFE polymorphisms (C282Y, H63D and S65C) among patients with chronic viral hepatitis B and C and to investigate their role in the progression of liver disease.

Methods:  A total of 207 subjects with chronic B or C viral hepatitis and 243 healthy controls were enrolled in the case–control study. Cases were further classified into three groups according to the clinical stage of liver disease: (A) virus carriers; (B) compensated liver disease; and (C) decompensated liver disease. HFE polymorphisms were detected by polymerase chain reaction‐based methodology. Fisher's exact test, χ2 and Kruskal–Wallis tests were used to test for differences in variables studied between groups. Haplotypes were inferred in silico and their distribution compared by permutation test. Modified survival (time‐to‐event) analysis was used to test for the differences in the progression to the decompensated liver disease in carriers of C282Y wild‐type versus mutated genotypes.

Results:  The frequency of HFE genotypes, alleles and haplotypes differed neither between HBV nor HCV patients versus controls. In HCV subjects: (i) the frequency of the 282Y allele was significantly higher in the (C) group compared to (B) group (12.5 vs 2.2%, respectively, P = 0.002, Fisher's exact test); and (ii) carriers of the 282Y mutation exhibited significantly faster progression to decompensated liver disease than wild‐type carriers (P = 0.044, log–rank test).

Conclusion:  Carriage of the minor HFE C282Y polymorphism is associated with decompensated liver disease and its earlier onset in the subjects with chronic viral hepatitis C in the Czech population.
The Pro variant of the p53 codon 72 polymorphism is associated with hepatocellular carcinoma in Moroccan population
Authors: Ezzikouri Sayeh , El feydi Abdellah Essaid , Chafik Abdelaziz , Benazzouz Mustapha , El kihal Latifa , Afifi Rajae , Hassar Mohammed , Pineau Pascal , Benjelloun Soumaya
Published: June 2007

Aim:  Codon 72 polymorphism of the p53 gene has been implicated in cancer risk, and it has been suggested that it may have an impact on the clinical outcome of the disease. Our objective was to evaluate the association between p53 polymorphism at codon 72 and hepatocellular carcinoma (HCC) in the Moroccan population.

Methods:  Genomic DNA was extracted from peripheral blood cells of 96 patients with HCC and 222 controls without HCC matched for age, gender and ethnicity. Codon 72 polymorphism of p53 was identified by PCR‐restriction fragment length polymorphism, confirmed by sequencing.

Results:  Patients with HCC had higher frequencies of Pro/Pro (13.5% vs. 6.3%, P < 0.02) than controls and consequently a 2.3‐fold increased risk of liver cancer development (odds ratio [OR], 2.304; 95% confidence interval [CI], 1.014–5.234). In addition, we found a significant association between the p53Arg72Pro polymorphism and the female gender in HCC. Men with Pro/Pro genotype had a 1.57‐fold increased risk for HCC, whereas the corresponding genotype in women had a 4.4‐fold increased risk of HCC (OR, 4.4; 95% CI, 1.18–16.42). No correlation between the polymorphism and HCC risk was found when comparing the hepatitis C virus (HCV)‐positive cases to HCV‐positive controls. However, HCV‐negative subjects and Pro/Pro genotype had a 3.31‐fold increased risk for HCC.

Conclusion:  These results provide evidence that p53 polymorphism at codon 72 is a modifier of hepatocarcinogenesis, especially in women and HCV‐negative subjects.
Keratin inclusions alter cytosolic protein localization in hepatocytes
Authors: Hanada Shinichiro , Harada Masaru , Kawaguchi Takumi , Kumemura Hiroto , Taniguchi Eitaro , Koga Hironori , Yanagimoto Chikatoshi , Maeyama Michiko , Ueno Takato , Sata Michio
Published: June 2007

Aim:  Mallory bodies have been observed in various liver diseases, however, the precise mechanism and significance of these structures have yet to be determined.

Methods:  Previously we reported on the redistribution of cytosolic proteins to keratin inclusions in mutant keratin 18‐transfected cells. In this study, we treated green fluorescent protein‐tagged wild‐type keratin 18‐transfected cells with several proteasome inhibitors and performed immunofluorescent analyses.

Results:  Proteasome inhibitors induced intracellular keratin inclusions, and desmoplakin, zonula occludens‐1 and β‐catenin were relocated to keratin inclusions, while theintegral membrane proteins were intact. The cytosolic proteins, 14‐3‐3 ζ protein and glucose‐6‐phosphate dehydrogenase were also relocated to inclusions. Moreover, E‐cadherin, a basolateral membrane protein, was present on both the apical and basolateral domains in inclusion‐containing cells.

Conclusion:  These data are identical to those in the mutant keratin 18 transfection study and suggest that keratin inclusions induced by different treatments affect localization of various cytosolic components, which may influence cellular functions performed by these proteins.
Potentiation of isoniazid‐induced liver toxicity by rifampicin in a combinational therapy of antitubercular drugs (rifampicin, isoniazid and pyrazinamide) in Wistar rats: A toxicity profile study
Authors: Tasduq Sheikh Abdullah , Kaiser Peerzada , Sharma Subhash Chander , Johri Rakesh Kamal
Published: June 2007

Aim: Biochemical characterization of long‐term toxic manifestations of anti‐tubercular (anti‐TB) drugs – rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) – individually and in two combinations: (i) RIF + INH, and (ii) RIF + INH + PZA in Wistar rats.

Methods: Animals received anti‐TB drugs – alone or in combination – once daily p.o. for up to 90 days (doses, in mg/kg: RIF, 250; INH, 50; PZA, 100). Assays for alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin (serum) and lipid peroxidation (LPO), glutathione (GSH), glutathione peroxidase (GPx), catalase, Na+K+‐ATPase and CYP 2E1 (liver) were performed to assess liver toxicity. Clinical biochemistry was done by commercial kits. Determinations were made at 0, 15, 30 and 90 days of treatment schedule.

Results: Anti‐TB drugs‐treated animals showed abnormal rises or falls (>1.5–2 fold) in the serum/liver parameters. Mild hyperlipidemia, hypercholesterolemia and hyperuricemia were the other pathologies. Of all the treated groups, INHalone or in combination with other drugs produced a progressive enhancement of toxicity over 15–90 days. Thein vivoresults were further supported byin vitroresults (MTT assay, GSH and LPO) in primary cultures of rat hepatocyte. Results indicated that anti‐TB drugs in combination: (i) caused membrane damage resulting in leakage of ALT, ALP and bilirubin; (ii) caused imbalance in endogenous enzymatic oxidant–antioxidant defense via increased lipid peroxidation and in glutathione homeostasis; and (iii) enhanced the CYP 2E1‐mediated bioactivation mechanism.

Conclusion: Toxicity manifestations seemed to be heptocytic injury targeted at hepatocytes, bile ducts or sinusoidal cells related to hepatitis and primary biliary cholestasis.
Protective effect of non‐mitogenic human acidic fibroblast growth factor on hepatocyte injury
Authors: Xu Hua , Hai Guang‐fan , Xiang Ji‐zhou , Yao Cheng‐can , Zheng Qing , Zhang Qi‐hao , Hong Hai
Published: June 2007

Aim:  To study whether non‐mitogenic human acidic fibroblast growth factor (nm‐haFGF) has protective effects on H2O2‐induced hepatocyte injury in vitro and CCl4‐induced hepatocyte injury in vivo.

Methods:  (i) HL‐7702 hepatocytes were incubated with different concentrations of nm‐haFGF for 12 h, and then the activity of lactate dehydrogenase (LDH) in culture medium was detected, and genomic DNA electrophoresis analysis was observed after being exposed to H2O2 (8 mmol/L) for 4 h. Proximately, apoptotic rates and protein expressions of Bcl‐2 and Bax of HL‐7702 cell were detected after being exposed to H2O2 (0.2 mmol/L) for 20 h. (ii) Being injected intraperitoneally with nm‐haFGF, mice were treated with CCl4 intraperitoneally to induce hepatic injury. Twenty‐four hours later, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured and histopathologic changes were evaluated.

Results:  (i) In vitro tests: LDH activities and apoptotic rates decreased, the protein expression of Bcl‐2 increased and Baxdecreased in nm‐haFGF‐treated groups at the concentrations of 100 150 and 200 ng/mL, compared with that in the model control group, which was treated with H2O2 alone. The genomic DNA remained nearly intact at the concentrations of 150 and 200 ng/mL. (ii) In vivo tests: serum ALT and AST in nm‐haFGF‐treated groups (10 μg/kg and 20 μg/kg) were much lower as compared to the model control group, which was treated with CCl4 alone. Histological examination showed that nm‐haFGF markedly ameliorated hepatocytes vacuolation, cloudy swelling and inflammatory cells infiltration induced by CCl4.

Conclusion:  nm‐haFGF had protective effects against H2O2‐induced hepatocyte injury in vitro and CCl4‐induced acute liver injury in vivo.
Local interaction of apoptotic hepatocytes and Kupffer cells in a rat model of systemic endotoxemia
Authors: Eipel Christian , Hirschmann Martin , Abshagen Kerstin , Menger Michael D. , Vollmar Brigitte
Published: June 2007

Aim:  There is strong evidence that hepatocellular apoptosis is not only initiated by circulating blood cells which become adherent within the endotoxemic liver, but also contributes to further sustain the inflammatory cell–cell response.

Methods:  Because previous studies assumed the importance of the role of cellular cross‐talk in mediating inflammatory liver injury, we herein examined the activation of Kupffer cells (KCs) and their spatial coincidence with intrahepatic leukocyte adherence and hepatocellular apoptosis at 6 h after intraperitoneal exposure of rats with lipopolysaccharide (10 mg/kg).

Results:  In vivo multifluorescence microscopy revealed liver injury including nutritive perfusion failure, tissue hypoxia, leukocyte accumulation, as well as KC activation and parenchymal apoptotic cell death. Detailed spatial analysis revealed frequent colocalization of activated KCs with apoptotic hepatocytes. Colocalization was absent in saline‐treated controls.Colocalization was confirmed by histochemistry, which showed ED1‐positive KCs neighboring and engulfing TUNEL‐positive hepatocytes. Colocalization of KCs with leukocytes ranged between 4% and 5% and did not increase in endotoxemic animals. Taken together, the present results indicate that apoptotic cell death of hepatocytes may stimulate phagocytosis by neighboring KCs. Direct KC–leukocyte contact seems not to be mandatory for cellular communication in the process of hepatocellular apoptosis.

Conclusion:  With respect to the fundamental importance of cell apoptosis, improved knowledge of these cell–cell interactions might allow the development of new therapeutic strategies through the regulation of apoptotic cell death.
Small hepatocellular carcinoma presenting with massive metastasis in the peritoneum, mimicking sarcomatous tumor
Authors: Kim Soo Ryang , Ikawa Hirotsugu , Ando Kenji , Mita Keiji , Fuki Shuichi , Imoto Susumu , Shimizu Kenji , Kanbara Yoshihiro , Sugimoto Koji , Fujii Masahiko , Kudo Masatoshi , Matsuoka Toshiyuki , Hayashi Yoshitake
Published: June 2007

The case of a 51‐year‐old man with hepatitis C virus (HCV)‐related hepatocellular carcinoma metastasizing to the peritoneal cavity and mimicking a sarcomatous tumor is presented. A 12 × 12 cm mass, disclosed by computed tomography (CT), in the peritoneal cavity was predominantly isodense to muscle but had hypodense areas that suggested necrosis. T1‐weighted magnetic resonance imaging (MRI) showed a large mass, slightly hyperintense to muscle, with local hyperintense areas of suspected hemorrhagic necrosis.T2‐weighted MRI of the same region revealed a markedly non‐homogeneous and hyperintense mass with inner high signals and peripheral brush‐like linear striations. From such imaging studies, sarcomatous tumors, such as fibrosarcoma, leiomyosarcoma, and gastrointestinal stromal tumors, can be distinguished. Pathological findings at autopsy revealed necrotic tissue with a small portion of moderately differentiated HCC. Further studies may provide insights into the metastatic modes of HCC.
Sertraline, a selective serotonin reuptake inhibitor, affects thirst, salt appetite and plasma levels of oxytocin and vasopressin in rats
Authors: De Magalhães‐Nunes Ana Paula , Badauê‐Passos Daniel , Ventura Renato Rizo , Da Silva Guedes Daniel , Araújo Jacqueline Pereira , Granadeiro Priscila Camargo , Milanez‐Barbosa Hevellyn Katarine , Da Costa‐e‐Sousa Ricardo Henrique , De Medeiros Magda Alves , Antunes‐Rodrigues José , Reis Luís Carlos
Published: June 2007

We investigated the effects of chronic administration of sertraline (SERT; ∼20 mg kg−1 day−1 in drinking water), a selective serotonin reuptake inhibitor, on water and sodium intake and on plasma levels of oxytocin (OT) and vasopressin (AVP) in basal and stimulated conditions. Basal water intake was reduced in SERT‐treated rats. After 24 h of water deprivation, rats treated with SERT for 21 days ingested less water than the control rats (9.7 ± 0.5 versus 20.0 ± 0.9 ml, respectively, at 300 min after water presentation, P < 0.0001). Subcutaneous injection of 2 m NaCl or isoproterenol evoked a lower dipsogenic response in rats treated with SERT for 21 days. Fluid and food deprivation also induced a weaker dipsogenic response in SERT‐treated rats (1.6 ± 0.5 versus 10.2 ± 1.2 ml, at 300 min, P < 0.0001) but had no effect on saline intake. Sodium depletion induced a higher natriorexigenic response in the SERT group (5.6 ± 1.3 versus 1.2 ± 0.3 ml, at 300 min, P < 0.0002). Higher urinary density and lower plasma sodium levels were observed after SERT treatment. Sertraline also increased plasma levels of vasopressin and oxytocin (AVP, 2.65 ± 0.36 versus 1.31 ± 0.16 pg ml−1, P < 0.005; OT, 17.16 ± 1.06 versus 11.3 ± 1.03 pg ml−1, P < 0.0009, at the third week post‐treatment). These data constitute the first evidence that chronic SERT treatment affects water and sodium intake in rats. These effects seem to be related to the hyponatraemia caused by the higher plasma levels of AVP and OT.
Temporal variability of repolarization in rat ventricular myocytes paced with time‐varying frequencies
Authors: Zaniboni Massimiliano , Cacciani Francesca , Salvarani Nicolò
Published: June 2007

Adaptation of action potential duration (APD) to pacing cycle length (CL) has been previously characterized in isolated cardiomyocytes for sudden changes in constant CL and for pre‐/postmature stimuli following constant pacing trains. However, random fluctuations characterize both physiological sinus rhythm (up to 10% of mean CL) and intrinsic beat‐to‐beat APD at constant pacing rate. We analysed the beat‐to‐beat sensitivity of each APD to the preceding CL during constant–sudden, random or linearly changing pacing trains in single patch clamped rat left ventricular myocytes, in the absence of the autonomic and electrotonic effects that modulate rate dependency in the intact heart. Beat‐to‐beat variability of APD at −60 mV (APD−60 mV), quantified as s.d. over 10‐beat sequences, increased with corresponding mean APD. When measured as coefficient of variability (CV), APD−60 mV variability was inversely proportional to pacing frequency (from 1.2% at 5 Hz to 3.2% at 0.2 Hz). It was increased, at a basic CL (BCL) of 250 ms, by 55% by the L‐type calcium current (ICaL) blocker nifedipine, and decreased by 23% by the transient‐outward potassium current (Ito) blocker 4‐aminopyridine. Variability of APD at BCL of 250 ms prevented the detection of random changes of CL smaller than ∼5%. Ten per cent random changes in CL were detected as a 40% increase in CV of APD and tended to correlate with it (r= 0.43). Block of ICaL depressed this correlation (r= 0.23), whereas block of Ito significantly increased it (r= 0.67); this was similar with linearly changing CL ramps (ranging ±10% and ±20% of 250 ms). We conclude that beat‐to‐beat APD variability, a major determinant of the propensity for development of arrhythmia in the heart, is present in isolated myocytes, where it is dependent on mean APD and pacing rate. Action potential duration shows a beat‐to‐beat positive correlation with preceding randomly/linearly changing CL, which can be pharmacologically modulated.
A
Bacillus anthracis
-Based In Vitro System Supports Replication of Plasmid pXO2 as Well as Rolling-Circle-Replicating Plasmids
Authors: Tinsley Eowyn , Khan Saleem A.
Published: June 2007

Capsule-encoding virulence plasmid pXO2 of
Bacillus anthracis
is predicted to replicate by a unidirectional theta-type mechanism. To gain a better understanding of the mechanism of replication of pXO2 and other plasmids in
B. anthracis
and related organisms, we have developed a cell-free system based on
B. anthracis
that can faithfully replicate plasmid DNA in vitro. The newly developed system was shown to support the in vitro replication of plasmid pT181, which replicates by the rolling-circle mechanism. We also demonstrate that this system supports the replication of plasmid pXO2 of
B. anthracis
. Replication of pXO2 required directional transcription through the plasmid origin of replication, and increased transcription through the origin resulted in an increase in plasmid replication.
Effectiveness of Standard UV Depuration at Inactivating
Cryptosporidium parvum
Recovered from Spiked Pacific Oysters (
Crassostrea gigas
)
Authors: Sunnotel O. , Snelling W. J. , McDonough N. , Browne L. , Moore J. E. , Dooley J. S. G. , Lowery C. J.
Published: June 2007

When filter-feeding shellfish are consumed raw, because of their ability to concentrate and store waterborne pathogens, they are being increasingly associated with human gastroenteritis and have become recognized as important pathogen vectors. In the shellfish industry, UV depuration procedures are mandatory to reduce pathogen levels prior to human consumption. However, these guidelines are based around more susceptible fecal coliforms and
Salmonella
spp. and do not consider
Cryptosporidium
spp., which have significant resistance to environmental stresses. Thus, there is an urgent need to evaluate the efficiency of standard UV depuration against the survival of
Cryptosporidium
recovered from shellfish. Our study found that in industrial-scale shellfish depuration treatment tanks, standard UV treatment resulted in a 13-fold inactivation of recovered, viable
C. parvum
oocysts from spiked (1 × 10
6
oocysts liter
−1
) Pacific oysters. Depuration at half power also significantly reduced (
P
< 0.05; ninefold) the number of viable oocysts recovered from oysters. While UV treatment resulted in significant reductions of recovered viable oocysts, low numbers of viable oocysts were still recovered from oysters after depuration, making their consumption when raw a public health risk. Our study highlights the need for increased periodic monitoring programs for shellfish harvesting sites, improved depuration procedures, and revised microbial quality control parameters, including
Cryptosporidium
assessment, to minimize the risk of cryptosporidiosis.
Evaluation of Culture Methods To Identify Bovine Feces with High Concentrations of
Escherichia coli
O157
Authors: Fox J. Trent , Renter David G. , Sanderson Michael W. , Thomson Daniel U. , Lechtenberg Kelly F. , Nagaraja T. G.
Published: June 2007

Our objective was to evaluate methods for identifying cattle with high concentrations of
Escherichia coli
O157 in their feces. In two experiments, feces were collected from cattle orally inoculated with nalidixic acid (Nal)-resistant
E. coli
O157, and direct plating of diluted feces on sorbitol MacConkey agar with cefixime and potassium tellurite (CT-SMAC) containing Nal was considered the gold standard (GS) method. In experiment 1, methods evaluated were preenrichment direct streak, immunomagnetic separation with most probable number (MPN), and postenrichment direct streak with MPN, all using CT-SMAC. The mean concentration of Nal-resistant
E. coli
O157 in samples (
n
= 59) by use of the GS was 3.6 log
10
CFU/g. The preenrichment streak detected >3.0 log
10
CFU/g samples with a 74.4% sensitivity and 68.8% specificity. Postenrichment direct streak-MPN and immunomagnetic separation-MPN concentrations were correlated significantly with GS concentrations (
r
= 0.53 and
r
= 0.39, respectively). In experiment 2 (480 samples), pre- and postenrichment direct streaking performed in triplicate and spiral plating on CT-SMAC were evaluated. For preenrichment streaks, sensitivity was 79.7% and specificity was 96.7% for detecting >3.0 log
10
CFU/g when the criterion was positive cultures on at least two plates. For spiral plating at that concentration, sensitivity and specificity were 83.9% and 56.3%, respectively. Postenrichment streaking performed relatively poorly. Triplicate preenrichment streaks of 1:10-diluted feces on CT-SMAC may be useful for identifying cattle shedding high concentrations of
E. coli
O157. Estimates of sensitivity and specificity enable appropriate application of methods and interpretation of results and may enhance applied research, surveillance, and risk assessments.
Lack of Electricity Production by
Pelobacter carbinolicus
Indicates that the Capacity for Fe(III) Oxide Reduction Does Not Necessarily Confer Electron Transfer Ability to Fuel Cell Anodes
Authors: Richter Hanno , Lanthier Martin , Nevin Kelly P. , Lovley Derek R.
Published: June 2007

The ability of
Pelobacter carbinolicus
to oxidize electron donors with electron transfer to the anodes of microbial fuel cells was evaluated because microorganisms closely related to
Pelobacter
species are generally abundant on the anodes of microbial fuel cells harvesting electricity from aquatic sediments.
P. carbinolicus
could not produce current in a microbial fuel cell with electron donors which support Fe(III) oxide reduction by this organism. Current was produced using a coculture of
P. carbinolicus
and
Geobacter sulfurreducens
with ethanol as the fuel. Ethanol consumption was associated with the transitory accumulation of acetate and hydrogen.
G. sulfurreducens
alone could not metabolize ethanol, suggesting that
P. carbinolicus
grew in the fuel cell by converting ethanol to hydrogen and acetate, which
G. sulfurreducens
oxidized with electron transfer to the anode. Up to 83% of the electrons available in ethanol were recovered as electricity and in the metabolic intermediate acetate. Hydrogen consumption by
G. sulfurreducens
was important for ethanol metabolism by
P. carbinolicus
. Confocal microscopy and analysis of 16S rRNA genes revealed that half of the cells growing on the anode surface were
P. carbinolicus
, but there was a nearly equal number of planktonic cells of
P. carbinolicus
. In contrast,
G. sulfurreducens
was primarily attached to the anode.
P. carbinolicus
represents the first Fe(III) oxide-reducing microorganism found to be unable to produce current in a microbial fuel cell, providing the first suggestion that the mechanisms for extracellular electron transfer to Fe(III) oxides and fuel cell anodes may be different.
Transposon Insertion Reveals pRM, a Plasmid ofRickettsia monacensis
Authors: Baldridge Gerald D. , Burkhardt Nicole Y. , Felsheim Roderick F. , Kurtti Timothy J. , Munderloh Ulrike G.
Published: June 2007

Until the recent discovery of pRF inRickettsia felis, the obligate intracellular bacteria of the genusRickettsia(Rickettsiales:Rickettsiaceae) were thought not to possess plasmids. We describe pRM, a plasmid fromRickettsia monacensis, which was detected by pulsed-field gel electrophoresis and Southern blot analyses of DNA from two independentR. monacensispopulations transformed by transposon-mediated insertion of coupled green fluorescent protein and chloramphenicol acetyltransferase marker genes into pRM. Two-dimensional electrophoresis showed that pRM was present in rickettsial cells as circular and linear isomers. The 23,486-nucleotide (31.8% G/C) pRM plasmid was cloned from the transformant populations by chloramphenicol marker rescue of restriction enzyme-digested transformant DNA fragments and PCR using primers derived from sequences of overlapping restriction fragments. The plasmid was sequenced. Based on BLAST searches of the GenBank database, pRM contained 23 predicted genes or pseudogenes and was remarkably similar to the larger pRF plasmid. Two of the 23 genes were unique to pRM and pRF among sequenced rickettsial genomes, and 4 of the genes shared by pRM and pRF were otherwise found only on chromosomes ofR. felisor the ancestral group rickettsiaeR. belliiandR. canadensis. We obtained pulsed-field gel electrophoresis and Southern blot evidence for a plasmid inR. amblyommiiisolate WB-8-2 that contained genes conserved between pRM and pRF. The pRM plasmid may provide a basis for the development of a rickettsial transformation vector.
Activation of the
ADE
Genes Requires the Chromatin Remodeling Complexes SAGA and SWI/SNF
Authors: Koehler Rebecca N. , Rachfall Nicole , Rolfes Ronda J.
Published: June 2007

The activation of the
ADE
regulon genes requires the pair of transcription factors Bas1 and Pho2. In a genome-wide screen for additional regulators of the pathway, strains with mutations in multiple subunits of the chromatin remodeling complexes SAGA and SWI/SNF were uncovered. These mutants exhibited decreased expression of an
ADE5,7-lacZ
reporter and native
ADE
compared to the wild-type strains, but the expression of the
BAS1
and
PHO2
genes was not substantially decreased. An unregulated Bas1-Pho2 fusion protein depended upon SAGA and SWI/SNF activity to promote transcription of a reporter. A significant but low-level association of Gcn5-myc and Snf2-myc with the
ADE5,7
promoter was independent of adenine growth conditions and independent of the presence of the activator proteins Bas1 and Pho2. However, the increase in occupancy of Bas1 and Pho2 at
ADE5,7
depended on both SAGA and SWI/SNF. The loss of catalytic activity of both SAGA and SWI/SNF complexes in the
gcn5
Δ
snf2
Δ double mutant was severely detrimental to
ADE-lacZ
reporter expression and native
ADE
gene expression, indicating complementary roles for these complexes. We conclude that Bas1 and Pho2 do not recruit the SAGA and SWI/SNF complexes to the
ADE5,7
promoter but that the remodeling complexes are necessary to increase the binding of Bas1 and Pho2 in response to the adenine regulatory signal. Our data support the model that the SAGA and SWI/SNF complexes engage in global surveillance that is necessary for the specific response by Bas1 and Pho2.