Coffee consumption and digestive tract cancers.

The relationship between coffee drinking and the risk of digestive tract neoplasms was analyzed in a case-control study of 50 cases of cancer of the mouth or pharynx, 209 of the esophagus, 397 of the stomach, 455 of the colon, 295 of the rectum, 151 of the liver, 214 of the pancreas, and 1944 control subjects admitted for acute, non-digestive tract disorders. There was no significant or consistent association between coffee and cancers of the mouth or pharynx, esophagus, stomach, liver, or pancreas. In particular, for pancreatic cancer, the multivariate relative risks for the intermediate and upper tertiles were 1.05 and 1.01, respectively. There were significant inverse trends in risk with measures of coffee consumption for colon and rectal cancers, the multivariate relative risks according to tertiles of coffee consumption being 0.86 and 0.64 for colon and 0.97 and 0.66 for rectum. This apparent protection is in agreement with some (but not all) previous epidemiological evidence and finds a possible biological interpretation in terms of interference on bile secretion, causing reduced bile acid and neutral sterol concentrations in the bowel. In conclusion, the results of this study, the major interest of which lies in the opportunity of drawing up an overall pattern of risk for various digestive neoplasms, offer further reassurance as regards the effects of coffee on digestive tract carcinogenesis.

Development of Hepatozoon caimani (Carini, 1909) Pessôa, De Biasi & De Souza, 1972 in the Caiman Caiman c. crocodilus, the frog Rana catesbeiana and the mosquito Culex fatigans

The sporogony of Hepatozoon caimani has been studied, by light microscopy, in the mosquito Culex fatigans fed on specimens of the caiman Caiman c. crocodilus showing gametocytes in their peripheral blood. Sporonts iniciate development in the space between the epithelium of the insect gut and the elastic membrane covering the haemocoele surface of the stomach. Sporulating oocysts are clustered on the gut, still invested by the gut surface membrane. Fully mature oocysts were first seen 21 days after the blood-meal. No sporogonic stages were found in some unidentified leeches fed on an infected caiman, up to 30 days following the blood-meal. When mosquitoes containing mature oocysts were fed to frogs (Leptodactylus fuscus and Rana catesbeiana), cysts containing cystozoites developed in the internal organs, principally the liver. Feeding these frogs to farm-bred caimans resulted in the appearance of gametocytes in their peripheral blood at some time between 59 and 79 days later, and the development of tissue cysts in the liver, spleen, lungs and kidneys. Transmission of the parasite was also obtained by feeding young caimans with infected mosquitoes and it is suggested that both methods occur in nature. The finding of similar cysts containing cystozoites in the semi-aquatic lizard Neusticurus bicarinatus, experimentally fed with infected C. fatigans, suggests that other secondary hosts may be involved.

Trends in cancer mortality in Brazil, 1980-2004.

Scanty information, limited to selected areas of the country, is available on cancer mortality in Brazil. Age-standardized (world population) mortality rates between 1980 and 2004, derived from the WHO database, were computed for all cancers and 24 major cancer sites in Brazil. Joinpoint regression analyses were used to identify the significant changes in trends and estimate annual percent change (APC) in rates. Total cancer mortality rates increased over the last decade in men (APC = 0.5) to reach 101.2/100 000, and in women (APC = 0.3) to reach 71.3/100 000. In men, upward trends were observed for cancers of the oral cavity and pharynx with a rate of 5.9/100 000 in 2000-2004, intestines (whose rate, however was low, i.e. 7.6), prostate (12.2), and leukemias (3.4). Male lung cancer increased until 1993 (APC = 1.39) and decreased thereafter (APC = -0.29), with a relatively low rate of 16.2/100 000 in 2000-2004. In women, there were steady upward trends for cancers of the lung (APC = 2.3), reaching 6.2/100 000 in 2000-2004, and leukemias (2.5). Breast cancer mortality leveled off at around 10/100 000 in the last decade, whereas declines were observed for cancers of the uterus, whose rate (8.3) however, remained comparatively high. Declines were observed for stomach cancer in both sexes, with rates of 11.1 in men and 4.6 in women. In conclusion, the key issues of cancer mortality in Brazil are the high rates of head and neck cancers in men and (cervix) uterine cancer in women, that is, in principle cancers that are largely avoidable through prevention, screening, and early diagnosis.

PHA advises 'breast is best'!

The Public Health Agency is using National Breastfeeding Awareness Week (NBAW) to emphasise the message that breastfeeding is the healthiest option for both you and your baby and that by deciding to breastfeed, you will be giving your child the best possible start in life. NBAW runs from 19-25 June and highlights the fact that any period of breastfeeding, however short, will benefit your baby.Breast milk is different to formula milk as it contains antibodies that cannot be manufactured in formula. Antibodies help protect babies from infection and stimulate their immune system.Northern Ireland has the lowest breastfeeding rate in the UK, with an average of 63% of women breastfeeding their baby at birth. Janet Calvert, Regional Breastfeeding Coordinator at the PHA, said: "This is an issue that clearly needs addressed, as breastfeeding has many important health benefits for both mother and baby. These include a reduced risk of ear, chest, kidney and stomach infections and less risk of childhood diabetes and obesity."Breastfeeding can also significantly reduce the risk of hospital admission of children for gastroenteritis and chest infections. The health benefits for mothers who choose to breastfeed include a reduced risk of developing illnesses such as breast cancer, ovarian cancer and osteoporosis."There are other benefits as well as those to your health. Breastfeeding is free - you don't have to buy formula, bottles, teats, sterilising equipment etc. Breast milk is always available, with the right ingredients, at the right temperature, so it's easier to feed at night or on the go.The PHA recognises the importance of breastfeeding to health and the need to ensure that mothers get off to a good start with breastfeeding. It is vital that mothers get the right support and encouragement from their family and friends should they decide to breastfeed. Breastfeeding can be difficult at the start and mothers need reassurance while they learn."There are many local initiatives in the community to improve breastfeeding support. These include improving support in the health service and through Sure Start programmes, which work in areas of need to help ensure children get the best start in life," Janet added."Mother to mother peer support programmes are in place in many areas and are working with expectant and new mothers to help them breastfeed for longer. There are also 70 breastfeeding support groups, which provide ongoing support for breastfeeding mothers throughout Northern Ireland. "The PHA is also working to improve attitudes to breastfeeding in public through the Breastfeeding Welcome Here scheme, which began in 2005 and now has over 200 businesses and public facilities signed up to support and welcome breastfeeding families. All these initiatives, along with support from partners and family, are vital to help expectant and new mothers stay with breastfeeding."Health Minister Edwin Poots said: "There is clear evidence that breastfeeding offers health benefits for both babies and mothers. We know that breast milk gives baby the best start in life by providing all the nutrients and protection a baby needs for the first six months of life. That is why my Department is committed to promoting and supporting breastfeeding".For further information on breastfeeding visit www.breastfedbabies.org.uk

PHA urges 'freshers' to be smart and know their alcohol limits

As 'fresher's week' commences, the Public Health Agency is encouraging students across Northern Ireland to avoid binge drinking and to know their limits if they do choose to drink alcohol.Enjoying new freedoms, at college or university, means taking care of yourself and others and, if you choose to drink, staying within safe alcohol limits. Owen O'Neill, PHA Health and Social Wellbeing Improvement Manager for drugs and alcohol, said: "Some young people may drink more when they leave home, or join their friends in college or university for the first time. They might think that, as young people, they don't have to take care with alcohol, but staying within the safe drinking limits is important for everyone who drinks. Excessive and binge drinking can have lasting effects on health, such as damage to the liver, heart, brain and stomach. Drinking too much can also increase the risk of accidents and antisocial behaviour as well as sexually transmitted infections and unplanned pregnancy"."We would also strongly advise against drinking games. Although they are regarded as a 'bit of fun', in reality they can be very dangerous. As an extreme form of binge drinking, where large quantities of alcohol are consumed in a very short time, drinking games can result in alcohol poisoning, leading to brain damage, coma or death. The PHA encourages students to enjoy their new student life, but urges them to be aware of their alcohol intake and drink responsibly, especially throughout fresher's week, with the many cheap drink promotions currently available."Daily alcohol limits are recommended by the government in order to avoid the risks of excessive and binge drinking in any one session. These are:Men: No more than 3 to 4 units of alcohol a day and no more than 21 units over the course of the week.Women: No more than 2 to 3 units of alcohol a day and no more than 14 units over the course of the week.Examples of units:Can of extra strong lager - 4 unitsBottle of lager - 1.5 unitsPint of standard lager - 2.5 unitsPint of premium larger - 3 unitsSmall pub bottle of wine - 2.25 units70cl bottle of wine - 7 to 10 unitsStandard 275ml of alcopops - 1.5 to 1.8 units70cl bottle of alcopops - 3.75 to 4.5 unitsPub measure of spirits - 1.5 unitsPint of cider - 3 unitsPint of stout - 2.5 unitsIf you do choose to drink alcohol:DON'T:Ever drink and driveDrink on an empty stomachMix alcohol with other drugsDrink in rounds as this may speed up your drinkingLeave your drinks unattendedDO:Take sips rather than gulpsAlternate each alcoholic drink with a non alcoholic drink e.g. water or a soft drinkSet yourself a limit and try to stick to it (refer to daily alcohol limits) Take frequent breaks from drinking to give your body time to recoverTell friends and family where you are going and who you will be withRemember, that for each unit you drink over the daily limit, the risk to your health increases. It's important to spread the units throughout the week - you can't 'save up' your units for the weekend or your holiday. It is also important to drink plenty of water, ideally matching the amount of alcohol you have consumed.So students make smart choices this term - drink sensibly and know your limits!For further information on sensible drinking and alcohol units visit the Public Health Agency's website www.knowyourlimits.info

PHA reinforce sensible drinking in Alcohol Awareness Week

Recent health figures show that 20% of adults surveyed admitted to drinking over the weekly alcohol limits (1)so the Public Health Agency is using Alcohol Awareness Week (14-20th November) to reinforce the importance of drinking sensibly and staying within safe alcohol limits.Government guidelines on safe drinking are 21 units per week for males and 14 units per week for females. Staying within these limits is important as excessive and binge drinking can lead, in the short term, to increased risk of accidents, antisocial behaviour, impact on relationships, unplanned pregnancy. Longer term it can damage the liver, heart, brain and stomach, not to mention the other human costs, and costs to the economy and society as a whole.Owen O'Neill, PHA Health and Social Wellbeing Improvement Manager and Drugs and Alcohol Lead, said: "The Department of Health, Social Services and Public Safety's drinking limits are in place to encourage the public to develop safe and sensible drinking habits. However, these recent figures highlight that not everyone is adhering to these limits. It is crucial that those who do decide to have a drink do so in moderation and stick to the recommended limits to prevent any long or short term damages".The message is clear, if you drink, remember to be smart and enjoy alcohol within safe limits. People should follow the recommended daily alcohol intake. These are:Men: No more than 3 to 4 units of alcohol a day and no more than 21 units over the course of the week.Women: No more than 2 to 3 units of alcohol a day and no more than 14 units over the course of the week.Examples of units:Can of extra strong lager - 4 unitsBottle of lager - 1.5 unitsPint of standard lager - 2.5 unitsPint of premium larger - 3 unitsSmall pub bottle of wine - 2.25 unitsPub measure of spirits - 1.5 unitsPint of cider - 3 unitsPint of stout - 2.5 units. Remember, that for each unit you drink over the daily limit, the risk to your health increases. It's important to spread the units throughout the week - you can't 'save up' your units for the weekend or an upcoming holiday. It is also important to drink plenty of water, ideally matching the amount of alcohol you have consumed.For further information on sensible drinking and alcohol units visit the Public Health Agency's website www.knowyourlimits.infoReference(1) Health Survey Northern Ireland: first results from the 2010/2011 survey (2011) DHSSPS, http://dhsspsni.giv/index/stats_research/stats-public-health.htm

A New Year's Resolution - be smart about your drinking!

Now 2012 has arrived, the Public Health Agency is encouraging people to make a New Year's resolution to know their limits when it comes to alcohol, not to drink excessively and to cut back for a while, especially if the festive period led to a little too much consumption.Owen O'Neill, PHA Health and Social Wellbeing Improvement Manager and drugs and alcohol lead, explained: "The New Year is a great opportunity for us to be positive about our health, making resolutions that make us look and feel better. If people choose to drink, staying within the safe drinking limits is important. Excessive and binge drinking can have lasting effects on health, such as damage to the liver, heart, brain and stomach. Drinking too much can also increase the risk of accidents and antisocial behaviour as well as sexually transmitted infections and unplanned pregnancy. And it doesn't have to be drinking to extremes - regularly drinking over the recommended limits can have a damaging effect."Remember that for each unit you drink over the daily limit, the risk to your health increases. It's important to spread the units throughout the week and not 'save' them for the weekend and to drink plenty of water, ideally matching the amount of alcohol you have consumed."For those who have consumed a lot of alcohol over the festive season, cutting back in the New Year and being careful can have immediate, positive effects particularly on helping you to look and feel better, being less tired during the day, feeling fitter and perhaps losing weight. Longer term, the benefits include improved mood, sleep, memory and general health, particularly improving liver function, immunity to illness and preventing any damage caused by any excessive drinking getting any worse."Daily alcohol limits are recommended by the government to avoid the dangers of excessive and binge drinking in any one session. These are:MenNo more than 3 to 4 units of alcohol a day and no more than 21 units over the course of the week.WomenNo more than 2 to 3 units of alcohol a day and no more than 14 units over the course of the week.Examples of units:Can of extra strong lager - 4 unitsBottle of lager - 1.5 unitsSmall pub bottle of wine - 2.25 unitsPub measure of spirits - 1.5 unitsPint of stout - 2.5 unitsPint of cider - 3 unitsFor further information on sensible drinking and alcohol units visit the Public Health Agency's website www.knowyourlimits.info

Staying safe down on the farm

Visiting an animal attraction, zoo or wildlife park is a great way to get children out and about in the summer months. It's hugely popular with schools and parents, with at least 700,000 children visiting farms on the island of Ireland every year. It's also an environment where children can get up close with animals. Animals can carry germs which are harmless to them, but could make you verysick, so make sure your children know how to keep themselves safe. safefood's welly-wearing cow, Suzie Moo, has some simple advice.

Angiostrongylus costaricensis: complete redescription of the migratory pathways based on experimental Sigmodon hispidus infection

Angiostrongylus costaricensis lives in the cecal and mesenteric arteries of its vertebrate hosts, and causes an inflammatory disease in humans. To investigate unknown aspects of the abdominal angiostrogyliasis pathogenesis, infected Sigmodon hispidus were sequentially studied in different times of infection. The study revealed that L3 goes alternatively through two migratory courses during its development into an adult worm: lymphatic/venous-arterial and venous portal pathways. The former is considered the principal one, because it is used by most of the larvae. Like other metastrongylides, A. costaricensis passes over the pulmonary circulation to migrate from the lymphatic system to the arterial circulation, where they circulate during some days before reaching their definitive habitat. The oviposition by mature females began on 15th day. Eggs and L1 were detected mainly in the intestine and stomach, surrounded by inflammatory reaction constituted by macrophages, monocytes, and eosinophils. They were also spread to the lungs, mesenteric lymph nodes, pancreas, spleen, and kidneys. The larvae (L1) exhibited the centripetal capacity to invade the lymphatic and venous vessels of the intestine and mesentery. Adult worms that developed in the venous intrahepatic pathway migrated downstream to reach the mesenteric veins and laid eggs that embolized in the portal hepatic vessels.

A survey on Triatoma dimidiata in an urban area of the province of Heredia, Costa Rica

Triatoma dimidiata has been found in several cities and towns of those countries where the insect is a domestic or peridomestic pest. In Central America, urban infestations occur in the capitals of at least five countries. During 2001 and 2002 a survey was carried out in the county of San Rafael, Heredia province, located 15 km northwest of San José, capital of Costa Rica, in order to determine the degree of infestation by T. dimidiata in an entire city block. Six peridomestic colonies of the insect were detected in the backyards of eight households. The ecotopes occupied by the insects consisted of store rooms with old objects, wood piles or firewood, and chicken coops. A total of 1917 insects were found in the six foci, during two sampling periods, and a mean infection rate by Trypanosoma cruzi of 28.4% was found in 1718 insects examined. The largest colony found in one of the households yielded 872 insects that were thriving mainly at the expenses of two dogs. Opossums and adult insects were common visitors of the houses and it became evident that this marsupial is closely related to the peridomestic cycle of the Chagas disease agent. Lack of colonization of the insect inside the human dwellings is explained by the type of construction and good sanitary conditions of the houses, in contrast to the situation in most peridomiciliary areas. Stomach blood samples from the insects showed that the main hosts were, in order of decreasing frequency: rodents, dogs, fowl, humans, opossums, and cats. The fact that no indication of infection with Chagas disease could be detected in the human occupants of the infested houses, vis a vis the high infection rate in dogs, is discussed.

Effects of sarcoptic mange on the behaviour of the red fox and influence on other fox-born zoonoses in Geneva, Switzerland

Résumé : Une épidémie de gale sarcoptique (Sarcoptes scabiei) touche le canton de Genève depuis 1996. Nous avons étudié l'impact de cette maladie sur différents caractères comportementaux du renard roux (Vulpes vulpes) : l'écologie alimentaire, les comportements spatiaux et l'activité, ainsi que les contacts sociaux. Nous avons également évalué si la gale pouvait influencer la composition et la transmission de la communauté helminthique intestinale du renard. En effet, cette espèce est l'hôte de parasites qui sont liés à des zoonoses importantes, en particulier le ténia échinocoque du renard (Echinococcus multilocularis) pour lequel Genève est considérée comme une zone de haute endémie. Durant 5 années, des carcasses de renards ont été récoltées sur l'ensemble du canton. Nous les avons disséquées et avons conservé différents échantillons pour des analyses ultérieures. Des données sur le poids, l'âge et le statut reproductif des femelles ont ainsi pu être obtenues. Les contenus stomacaux ont été analysés pour déterminer le régime alimentaire, les intestins pour collecter des helminthes, des échantillons de sang pour faire des sérologies et des échantillons de peau pour récupérer les sarcoptes. Des renards sauvages ont également été capturés et équipés de colliers émetteurs afin de déterminer leur activité et leur utilisation de l'espace. Finalement, nous avons réalisé des affûts sur des terriers et des observations nocturnes à l'aide d'un détecteur thermique afin d'étudier les contacts sociaux. Nous avons ensuite considéré tous ces aspects pour comparer les renards galeux aux individus sains. Trois catégories de gale ont été prises en compte selon l'importance de l'infection. L'épidémie a traversé le canton en 8 ans environ et elle a provoqué une forte diminution des populations de renard. Les animaux malades étaient caractérisés par un poids réduit, ils utilisaient des domaines vitaux réduits et présentaient un rythme d'activité irrégulier. En ce qui concerne le régime alimentaire, les renards galeux avaient souvent des estomacs vides ou contenant peu d'aliments d'origine animale. Cette réduction de l'alimentation ne semble pas seulement être liée à des capacités de prédation réduite, mais également à un désintérêt face à la nourriture. Tous les changements de comportement cités étaient plus marqués chez les animaux soumis à une forte infestation. Dix taxons d'helminthes ont été identifiés dans les intestins des renards analysés. Deux d'entre eux représentent un risque de santé publique: Echinococcus multilocularis et Toxocara carvis. Pour ces helminthes, nous n'avons pas identifié de différences de prévalence entre les renards galeux et les animaux sains, mais la charge parasitaire était significativement supérieure chez les individus galeux, en particulier ceux souffrant d'une infestation importante. Ceci est probablement lié à une susceptibilité accrue des individus qui présentent une condition physique amoindrie et des défenses immunitaire affaiblies. Selon nos résultats, nous pouvons conclure que la gale induit des changements comportementaux importants et que ces changements ont une influence potentielle sur la transmission de la gale elle-même, mais également sur la transmission du reste de la communauté parasitaire de l'hôte. Les individus qui souffrent d'une infestation importante sont susceptibles de provoquer une contamination de l'environnement accrue en ce qui concerne des helminthes pouvant provoquer des zoonoses. La gale apparaît être un facteur à ne pas négliger dans le cadre de la gestion de la faune sauvage, mais également en ce qui concerne des problématiques de santé publique. Summary An epidemic outbreak of sarcoptic mange (Sarcoptes scabiei) has struck the canton of Geneva since 1996. The impact of the disease on various behavioural traits of the main host, the red fox (Vulpes vulpes), was investigated: feeding ecology, spatial behaviour and activity, and social contacts. We also evaluated if mange might have an influence on the composition and transmission of the intestinal helminth community of foxes. Indeed, this species is host of parasites with potential zoonotic importance, particularly the fox tapeworm (Echinococcus multilocularis) for which Geneva is reported as endemic area. During 5 years, red fox carcasses have been collected throughout the canton. They were then dissected and various samples conserved for further analysis. Data on weight, age, and reproductive status of females were obtained. Stomach content were analysed for diet analysis, intestines to recover helminths, blood to proceed to ELISAs and skin samples to check for the presence of Sarcoptes mites. Further, wild foxes were captured and fitted with transmitters in order to determine their activity pattern and space use. Finally, we proceeded to direct observations at dens and using a thermal imaging sensor at night to gain information about social contacts. A comparison between healthy and mangy foxes was made for all these aspects. Three categories of mangy foxes were considered from moderately to severely infected. The epidemic wave crossed the canton in about 8 years and induced a significant reduction in fox densities. Mangy individuals appeared to have reduced body weights, to use more restricted home ranges and exhibited an irregular activity pattern. Regarding food, sick foxes often had empty stomachs and consumed less food items of animal origin. The reduction in food intake appeared to be linked not only to a reduced ability to hunt, but also to a reduced interest in food. The changes observed were particularly pronounced in individuals with severe infestation. Ten helminth taxa were recovered from the intestines on the analysed fox carcasses. Two of them have an importance with regard to human public health: Echinococcus multilocularis and Toxocara cams. The prevalence of these helminths did not differ between healthy and mangy foxes, however the worm burden was significantly higher in mangy foxes, particularly those with severe mange. This is probably linked to an increased susceptibility in individuals with a reduced body condition and weakened immune defences. From our observations, we can conclude that mange induces pronounced behavioural changes in the red fox, and that those changes influence the transmission risks of mange itself, but also of the rest of the parasite community of the host. Individuals with severe mange are for example likely to increase the environment contamination of free living stages of helminths with zoonotic importance. Mange appears thus to represent a factor not to be neglected for the management of wild species and for public health issues.

Epithelial effects of proteinase-activated receptors in the gastrointestinal tract

The intestinal epithelium plays a crucial role in providing a barrier between the external environment and the internal milieu of the body. A compromised mucosal barrier is characteristic of mucosal inflammation and is a key determinant of the development of intestinal diseases such as Crohn's disease and ulcerative colitis. The intestinal epithelium is regularly exposed to serine proteinases and this exposure is enhanced in numerous disease states. Thus, it is important to understand how proteinase-activated receptors (PARs), which are activated by serine proteinases, can affect intestinal epithelial function. This review surveys the data which demonstrate the wide distribution of PARs, particularly PAR-1 and PAR-2, in the gastrointestinal tract and accessory organs, focusing on the epithelium and those cells which communicate with the epithelium to affect its function. PARs have a role in regulating secretion by epithelia of the salivary glands, stomach, pancreas and intestine. In addition, PARs located on subepithelial nerves, fibroblasts and mast cells have important implications for epithelial function. Recent data outline the importance of the cellular site of PAR expression, as PARs expressed on epithelia may have effects that are countered by PARs expressed on other cell types. Finally, PARs and their ability to promote epithelial cell proliferation are discussed in terms of colon cancer.

Trends in cancer mortality in Mexico, 1981-2007.

The objective of this study was to provideinformation on recent trends in cancer mortality in Mexico. We analyzed data provided by the World Health Organization, using joinpoint analysis to detect changes in trends between 1981 and 2007. For most cancers, mortality was upward but started to decline in the late 1980's/early 1990's for both sexes. Overall cancer mortality was 75.53/100 000 men, world standard, and 69.2/100 000 women in 2005-2007. Mortality from uterine cancer declined by approximately 2.5% per year in the 1990s, and by approximately 5% per year in the last decade, but its rates remained exceedingly high (9.7/100 000 in 2005-2007). Other major declines over recent years were those of stomach cancer (approximately 2.5% per year, with rates of 6.6/100 000 in men and 4.9/100 000 in women in 2005-2007) and lung cancer (2-2.5% per year, 11.0/100 000 in men and 4.5/100 000 in women in 2005-2007). Mortality leveled off only since the early 1990s for breast and prostate, and since the late 1990s for colorectal cancer. Death rates from cancer in Mexico remained low on a worldwide scale and showed favorable trends over more recent calendar years. Mortality from (cervix) uterine cancer still represents a major public health priority in this country.

Aspartic protease activities of schistosomes cleave mammalian hemoglobins in a host-specific manner

We examined the efficiency of digestion of hemoglobin from four mammalian species, human, cow, sheep, and horse by acidic extracts of mixed sex adults of Schistosoma japonicum and S. mansoni. Activity ascribable to aspartic protease(s) from S. japonicum and S. mansoni cleaved human hemoglobin. In addition, aspartic protease activities from S. japonicum cleaved hemoglobin from bovine, sheep, and horse blood more efficiently than did the activity from extracts of S. mansoni. These findings support the hypothesis that substrate specificity of hemoglobin-degrading proteases employed by blood feeding helminth parasites influences parasite host species range; differences in amino acid sequences in key sites of the parasite proteases interact less or more efficiently with the hemoglobins of permissive or non-permissive hosts.

The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaC) in vitro.

TMPRSS3 encodes a transmembrane serine protease that contains both LDLRA and SRCR domains and is mutated in non-syndromic autosomal recessive deafness (DFNB8/10). To study its function, we cloned the mouse ortholog which maps to Mmu17, which is structurally similar to the human gene and encodes a polypeptide with 88% identity to the human protein. RT-PCR and RNA in situ hybridization on rat and mouse cochlea revealed that Tmprss3 is expressed in the spiral ganglion, the cells supporting the organ of Corti and the stria vascularis. RT-PCR on mouse tissues showed expression in the thymus, stomach, testis and E19 embryos. Transient expression of wild-type or tagged TMPRSS3 protein showed a primary localization in the endoplasmic reticulum. The epithelial amiloride-sensitive sodium channel (ENaC), which is expressed in many sodium-reabsorbing tissues including the inner ear and is regulated by membrane-bound channel activating serine proteases (CAPs), is a potential substrate of TMPRSS3. In the Xenopus oocyte expression system, proteolytic processing of TMPRSS3 was associated with increased ENaC mediated currents. In contrast, 6 TMPRSS3 mutants (D103G, R109W, C194F, W251C, P404L, C407R) causing deafness and a mutant in the catalytic triad of TMPRSS3 (S401A), failed to undergo proteolytic cleavage and activate ENaC. These data indicate that important signaling pathways in the inner ear are controlled by proteolytic cleavage and suggest: (i) the existence of an auto-catalytic processing by which TMPRSS3 would become active, and (ii) that ENaC could be a substrate of TMPRSS3 in the inner ear.