Comparison of lesions induced in the Syrian golden hamster by diethylnitrosamine, dimethylhydrazine, and dibutylnitrosamine: influence of subsequent butylated hydroxyanisole treatment

The target organ specificity of the carcinogens diethylnitrosamine [(DENA) CAS: 55-18-5], dimethylhydrazine [(DMH) CAS: 57-14-7], and dibutylnitrosamine [(DBN) CAS: 924-16-3] was examined in Syrian golden hamsters. Groups of male animals were given 8 weekly injections of one of these carcinogens and then were maintained on a basal diet or a diet supplemented with 1% butylated hydroxyanisole [(BHA) CAS: 25013-16-5], or they were given the respective carcinogens in the drinking water until they were sacrificed at week 34. While DENA specifically induced tracheal polyps and hepatocellular foci and nodules, DMH administration was associated with development of both hepatocellular and hemangiocellular liver lesions as well as forestomach papillomas and adenocarcinomas of the large intestine. DBN induced lesions in the urinary bladder, forestomach, and trachea, in addition to a few preneoplastic foci in the liver and lungs. In all organs studied, preneoplastic and neoplastic populations were essentially similar to those observed in other experimental animals, with colon and tracheal lesions demonstrating alteration in polysaccharide metabolism. While inhibiting the development of hepatocellular lesions, especially in the group initiated with DENA, and while itself inducing extensive papillomatous forestomach hyperplasia, BHA administration did not exert a significant modifying influence on tumorigenesis in other organs. The present results demonstrate the efficacy of Syrian golden hamster studies for investigation of comparative neoplasia. Of particular interest in this respect were differences in the degree of phenotypic instability demonstrated by glutathione S-transferase placental form-positive foci induced by the 3 carcinogens, which indicated a possible qualitative variation in "initiation."     

TB, HIV-associated TB and multidrug-resistant TB on Thailand's border with Myanmar, 2006-2007

Objective To measure the burden and improve management of tuberculosis (TB), HIV‐associated TB and MDR TB in Tak Province, Thailand, which borders Myanmar. Methods From September 2006 to August 2007, we collected uniform data about TB cases and enhanced human immunodeficiency virus (HIV) counselling and testing. We provided mycobacterial culture and drug‐susceptibility testing in public or non‐governmental organization facilities. Patients were classified by nationality and, for non‐Thais, by migration status. Results Of 1662 TB cases in the 12‐month period, 1087 (65%) occurred in non‐Thais. Of non‐Thais, 415 (38%) lived in Myanmar but crossed the border for healthcare. HIV infection was diagnosed in 18% of Thais compared with 12% of non‐Thais (P < 0.01); HIV status was unknown for 22% of Thais and 27% of non‐Thais (P = 0.02). Overall, multidrug‐resistant (MDR) TB was diagnosed in 27 patients, 19 (70%) in non‐Thais. Among TB cases never previously treated for TB, no MDR cases were diagnosed in Thais or in Myanmar refugees, but six cases were diagnosed in migrants from Myanmar. Conclusions In Thailand, TB, HIV‐associated TB and MDR TB in migrants from Myanmar are important public health problems; they need to be resolved in both the countries.     

Time-dependent Modulation of Liver Lesion Development in Opisthorchis-infected Syrian Hamster by an Antihelminthic Drug, Praziquantel

In the North-east of Thailand, repeated antihelminthic therapy has been introduced for control of the opisthorchiasis known to be a major risk factor for cholangiocellular carcinomas. What influence this may have on tumorigenesis, however, remains unclear. The effects of administration of praziquantel, an antihelminthic drug, at different time points subsequent to infection with Opisthorchis viverrini (OV) on 2,2'-dihydroxy-di- n -propylnitrosamine (DHPN)-initiated lesion development in the liver of female Syrian hamsters were therefore investigated. Praziquantel (250 mg/kg body weight, i.p.) was given 4, 12 or 20 weeks after infection of DHPN-treated animals (two 1000 mg/kg i.p. injections at weeks 0 and 2) with 60 OV metacercariae (at week 4). Survivors at week 38 were killed and examined. It was found that whereas praziquantel administration at the earlier two time points was effective at reducing hepatocellular nodule development, the results for cholangiocellular lesions were less pronounced, significant reduction only being evident in hamsters treated 4 weeks after parasite infestation. The findings thus indicate that enhancement of DHPN-initiated bile duct carcinogenesis by opisthorchiasis is both rapid and to a large degree irreversible. Hepatocellular lesion development in this model, on the other hand, appears to correlate more closely with the duration of parasite-associated proliferative stimulus.     

SHORT COMMUNICATION: Promotion of cholangiocarcinogenesis in the hamster liver by bile duct ligation after dimethylnitrosamine initiation

Administration of hepatocardnogenic nitrosamines before or afterinfection with the liver fluke, Opisthorchis viverrini (OV),results in marked development of cholangiocellular and hepatocellularprecancerous and cancerous lesions in the hamster liver. Thepromoting effects of OV are believed to be exerted either mechanically,chemically or immuno-logically. To test the influence of possiblemechanical effects, Syrian hamsters were initiated with a singlei.p. injection of dimethylnitrosamine (DMN) 20 mg/kg and subjected2 weeks later either to a sham operation or to complete ligationof the extrahepatic bile duct to the left lateral lobe. At theend of week 40, the animals receiving DMN-initiation and ligationhad a 60.9% incidence of cholangiofibrosis, 21.7% of mucouscystadenomas and 39.1% of cholangiocarcinomas, whereas the groupgiven DMN alone only developed cholangiofibrosis, limited to5% of the animals. In the latter case neither cystadenomas norcholangiocarcinomas were observed. The incidence of hepatocellularnodules did not differ between the two groups and no tumorouslesions developed in either the ligated or the untreated groupswithout DMN pretreatment. Complete ligation of the bile ductitself led to a series of events; obstruction of bile flow beingfollowed by dilatation, cyst formation, and necrosis of thebile duct epithelium and surrounding affected areas leadingto regenerative proliferation. The results are in line withthe conclusion that parasite-associated proliferation in targetcell populations is, at least in part, responsible for the influenceof OV on liver tumor development.     

Detection of antibodies in sera from patients with Opisthorchiasis

The indirect immunofluorescent antibody technique (IFA) was used for detection of antibodies in sera of patients with Opisthorchiasis. Antibodies to fluke worm and egg antigens were detected in 166 of 205 (81%) patients. The test showed that only the IgG class of antibodies reacting exclusively with integumental wall of the worm (AW) were positive in 46.8% (96/205), reacting only with the wall of intact eggs in 11 out of 205 (5.4%) and antibodies to both fluke and their egg antigens were present in 28.8% (59/205). In addition, 5.4% (11/205) of patients' sera were positive for autoantibodies producing a speckled antinuclear antibodies (ANA) pattern. The sera positive for only AW contained detectable autoantibodies to other cell antigens including: anti-smooth muscle antibodies of 9.4% (9/96), antimitochondrial antibodies of 3.1% (3/96), anti-liver/kidney microsomes of 1% (1/96) and anti-parietal cell antibodies of 1% (1/96). Autoantibodies were undetectable in sera from normal subjects. Among the ANA positive sera, 55% (6/11) exhibited antibodies against an extractable nuclear antigen (ENA) by a tanned red cell hemagglutination assay. This finding may suggest that the autoantibody response was due to the cross reaction between worm antigen and self antigen or it may be the result of polyclonal activation of B lymphocytes in these patients.     

Immunohistochemically demonstrated suppressed expression of tryptophan oxygenase, a marker for liver differentiation, within putative preneoplastic rat liver lesions

The behaviour of rat liver putative preneoplastic lesions withrespect to the enzyme tryptophan oxygenase (TO), a liver-specificdifferentiation marker, and a possible growth-related marker,glucose-6-phosphate dehydrogenase (G6PD) was investigated duringand after their induction by diethylnitros-amine initiationand subsequent ‘selection pressure’. Using specificantibodies to rat liver TO and G6PD and the avidin-biotin complexmethod for immunohistochemical staining it was demonstratedthat all of the nodular lesions showing increased expressionof G6PD during the induction phase were also negative or deficientin TO enzyme protein. With the onset of ‘phenotypic instability’or loss of marker enzymes, a gradual return to normal expressionof TO activity was evident. Administration of dexamethasoneand L-tryptophan 11 weeks after cessation of carcinogen treatmentallowed differentiation between morphologically altered, apparentlypersisting lesions in which no, or little, enzyme inductionwas apparent and instable lesions showing a strong increasein levels of TO protein. Thus, persisting nodular lesions sharea common lack of response to normal homeostatic physiologicalcontrol.     

Vibrotactile activation of the auditory cortices in deaf versus hearing adults

Neuroplastic changes in auditory cortex as a result of lifelong perceptual experience were investigated. Adults with early-onset deafness and long-term hearing aid experience were hypothesized to have undergone auditory cortex plasticity due to somatosensory stimulation. Vibrations were presented on the hand of deaf and normal-hearing participants during functional MRI. Vibration stimuli were derived from speech or were a fixed frequency. Higher, more widespread activity was observed within auditory cortical regions of the deaf participants for both stimulus types. Life-long somatosensory stimulation due to hearing aid use could explain the greater activity observed with deaf participants.     

Development of an airborne lead analysis kit and its application

We developed a method to analyze airborne lead concentrations in the field. It was a modification of the colorimetric method using the reaction between 4(2-pyridylazo)-resorcinol (PAR) and lead with cyanex302 in an acid medium to reduce interfering metals. The lead concentration was detected with a photometer made in Thailand. The developed method uses an impinger containing 1% nitric acid solution as an absorbing agent to collect airborne lead at a flow rate of less than or equal to one liter/minute. Cyanex302 solution in toluene was used to extract metals from the samples and 0.1M nitric acid was used to extract just lead. The lead solution was reacted in 0.5 ml of 0.03% PAR solution, with 1 ml ammonium chloride buffer; the absorption of this solution was measured by a photometer. The results show the limit of detection (LOD) was 0.01 mg/l. The limit of quantification (LOQ) was 0.03 mg/l. The percent recovery of the lead concentrations of 0.05 - 3.0 mg/l was 94.0 to 103.5%. The precision presented as %CV ranged from 0.65 to 10.27%. Lead concentration in a lead smelting factory detected by this method was not significantly different from that detected by the NIOSH method: 7,303 at a 95% confidence level.