Norovirus transmission on cruise ship

An outbreak of norovirus gastroenteritis affected passengers on two consecutive cruises of ship X and continued on 4 subsequent cruises despite a 1-week sanitization. We documented transmission by food and person-to-person contact; persistence of virus despite sanitization onboard, including introductions of new strains; and seeding of an outbreak on land.     

Outbreaks of acute gastroenteritis on cruise ships and on land: identification of a predominant circulating strain of norovirus--United States, 2002

In 2002, a sharp increase in outbreaks of norovirus-associated illness, both on cruise ships and on land, encouraged us to examine the molecular epidemiology of detected noroviruses, to identify a common strain or source. Of 14 laboratory-confirmed outbreaks on cruise ships, 12 (86%) were attributed to caliciviruses; among these 12, outbreak characteristics included continuation on successive cruises in 6 (50%), multiple modes of transmission in 7 (58%), and high (>10%) attack rates in 7 (58%). Eleven of the 12 calicivirus outbreaks were attributed to noroviruses, 7 (64%) of which were attributed to a previously unreported lineage, provisionally named "the Farmington Hills strain." From May 2002 to December 2002, 10 (45%) of 22 land-based outbreaks also were attributed to this strain. Nucleotide-sequence analysis provided insights into norovirus transmission, by documenting links among outbreaks, the introduction of strains onto ships, and viral persistence on board (despite cleaning). Control measures for outbreaks should address all routes of transmission. Better outbreak surveillance and collection of data on sequences will help to monitor norovirus strains and to identify common sources.     

The Aral Sea disaster--human biomonitoring of Hg, As, HCB, DDE, and PCBs in children living in Aralsk-and Akchi, Kazakhstan

Mercury and arsenic have been measured in urine samples and HCB, DDE and PCBs in blood samples of children from Aralsk and Akchi, Kazakhstan. Due to the special situation of Aralsk in the desert left by the drying out Aral Sea, environmental pollution with heavy metals and organic contaminants is believed to be higher than elsewhere in Kazakhstan. Aralsk was formerly located at the shore of the Aral Sea and is now far away from it. Akchi is a similar village and was included in this study as a Kazakh reference site. Urine concentrations of arsenic were higher in Akchi (9.4 μg/l) than in Aralsk (5.5 μg/l) and compared to children from Mannheim, Germany (4.25 μg/l; Median values). Regarding Hg, differences between children of Aralsk and Akchi were not significant and concentrations were lower than reference values from Germany. DDE contamination of children from Aralsk (2.48 μg/l) was significantly higher compared to Akchi (1.35 μg/l). DDE concentrations in blood samples from children in both cities were also significantly higher than the German reference value (0.7 μg/l). HCB and PCBs levels differed significantly between both Kazakh groups. However, concentrations of these compounds were lower than German reference values and there was no significant difference to samples from Mannheim children.     

Pathobiology of hemophilic synovitis I: overexpression of mdm2 oncogene

Hemophilia is a genetic disease caused by a deficiency of blood coagulation factor VIII or IX. Bleeding into joints is the most frequent manifestation of hemophilia. Hemarthrosis results in an inflammatory and proliferative disorder termed hemophilic synovitis (HS). In time, a debilitating, crippling arthritis, hemophilic arthropathy, develops. Although the clinical sequence of events from joint bleeding to synovitis to arthropathy is well documented, the component or components in blood and the molecular changes responsible for hemophilic synovitis are not known. Iron has long been suspected to be the culprit but direct evidence has been lacking. Previously, we showed that iron increased human synovial cell proliferation and induced c-myc expression. Here we show that bleeding into a joint in vivo and iron in vitro result in increased expression of the p53-binding protein, mdm2. Iron induced the expression of mdm2 by normal human synovial cells approximately 8-fold. In a murine model of human hemophilia A, hemarthrosis resulted in pathologic changes observed in human hemophilic synovitis and a marked increase in synovial cell proliferation. Iron, in vitro, induced the expression of mdm2. The molecular changes induced by iron in the blood may be the basis of the increase in cell proliferation and the development of hemophilic synovitis.     

Synovitis in a murine model of human factor VIII deficiency

Recurrent joint bleeding is the most common musculoskeletal manifestation of haemophilia and leads to a target joint and synovitis. The pathobiology of haemophilic synovitis (HS) is not well understood. Here the histopathological changes that occur following haemarthrosis were examined in an animal model for human HS. After two haemarthrosis, there was soft tissue and joint swelling and histological changes of acute synovitis included infiltration of the sub-synovial layer by mononuclear cells and neutrophils, thickening of the synovial membrane with villus formation, and hyperplasia of blood vessels. Subacute changes were evident after three haemarthrosis; muscle atrophy was present and an intense mononuclear cell infiltrate filled the sub-synovial space. There was destruction of articular surfaces and loss of cartilage. Seventeen months after three haemarthrosis, chronic joint changes included gross deformity and loss of congruence due to dense fibrotic tissue filling the joint space. The mononuclear inflammatory cell infiltrate and thickened synovial membrane persisted. Pits and erosions of articular surfaces and sub-chondral cysts were present. There was fibro-cartilage and new bone formation. This model of human HS should be useful to fully evaluate the biochemical and molecular changes that occur following joint bleeding and to test novel therapeutics to prevent HS.     

Inhibitory effect of 4,4′-[ethane-1,2-diylbis(sulfandiylmethanediyl)]bis(3,5-dimethyl-1<Emphasis Type="Italic">H</Emphasis>-pyrazole) and its derivatives on alpha-amylase activity

In vitro evaluation of alpha-amylase inhibition was carried out using novel representatives of sulfanyl-substituted azoles such as 4,4′-[ethane-1,2-diylbis(sulfandiylmethanediyl)]bis(3,5-dimethyl-1H-pyrazole) (1), 4,4′-[ethane-1,2-diylbis(sulfandiylmethanediyl)]bis(3,5-dimethyl-1H-pyrazole)·2HCl (2), 4,4′-[ethane-1,2-diylbis(sulfandiylmethanediyl)]bis(3,5-dimethyl-1,2-isoxazole) (3), and 4-(phenylsulfanylmethyl)-3,5-dimethyl-1H-pyrazole (4). The inhibition of alpha-amylase with compound (1) was described by competitive mechanism with K _i equal to 0.15 mM defined from Dixon coordinates. Results of primary screening indicated that substances (2), and (4) acted as competitive inhibitors, while (3) demonstrated characteristics of a non-competitive inhibitor.