Development In Hamsters Research Articles

Dietary Biotin Deficiency Affects Reproductive Function and Prenatal Development in Hamsters

The effects of maternal dietary biotin deficiency on hamster embryos were examined by adding different amounts of avidin (0, 10, 50, 100 or 1000 mg/kg diet) to a semipurified commercial diet during the entire period of gestation. On d 10 of gestation, reduced dietary biotin resulted in a high incidence of resorbed and dead embryos. In addition, both the crown-rump length and head length of dietary biotin-deficient embryos were lower, and their digit development was retarded. These embryos were characterized by pericardial cavity enlargement (40%) and zig-zag closure line of the neural tube (44%). Some embryos exhibited abnormalities of the craniofacial region and tail. On d 14 of gestation, embryonic growth retardation, morphological abnormalities and skeletal defects were seen in the dietary biotin-deficient group (fed 100 mg avidin/kg diet). The striking abnormalities were cleft palate, micromelia, micrognathia and rib deformities in approximately 10% of the fetuses. Histological examination of the placentae revealed some differences in the spongiotrophoblast and labyrinth layers between the control and dietary biotin-deficient groups. The teratogenic effect of dietary biotin deficiency previously observed in mice was confirmed in hamsters.

CagA+ Helicobacter pylori infection and N-nitrosodimethylamine administration induce cholangiocarcinoma development in hamsters.

Helicobacter pylori (HP) has been detected in the hepatobiliary tract of cholangiocarcinoma (CCA) patients in regions both endemic and non-endemic for Opisthorchis viverrini (OV) infection. However, whether H. pylori infection promotes CCA development remains unknown. We investigated CCA development in hamsters induced by a combination of infection with H. pylori and administration of N-nitrosodimethylamine (NDMA) and compared findings with those in an OV plus NDMA group. Eighty-five hamsters were divided into four groups: (1) normal, (2) administered NDMA, (3) infected with cagA+ H. pylori and administered NDMA (HN group), and (4) infected with OV and administered NDMA (ON group). Animals were euthanized at 3 and 6months post-infection. Histopathological changes of liver and the expression of markers associated with carcinogenesis were studied. At 3months post-infection (p.i.), cholangitis and lymphoid follicles without tumor appearance were noted in the HN group, whereas extensive fibrosis was seen in members of the ON group, 10% of which had developed tumors. At 6months p.i., 10% of hamsters administered NDMA alone had developed CCA, whereas in the HN and ON groups, 20% and 60% of hamsters, respectively, had developed CCA. Cytokeratin-19 (CK19) expression was observed in the CCA tissues of both the HN and the ON groups, confirming the bile duct origin of the CCA cells. CCA development in the HN group might be inflammation-mediated, as suggested by overexpression of HMGB1, PCNA, IL-8, and 8-OxodG in CCA tissues. cagA+ H. pylori infection and carcinogen intake can induce CCA development with slow progression.

(−)-Epicatechin protects from amebic liver abscess development in hamster

In this work the effect of (−)-epicatechin on the development of amebic liver abscess in hamsters was evaluated. (−)-epicatechin is a flavonoid present in plants that possesses various biological properties, including its activity against some protozoal parasites; however its antiamebic activity in a living model had not been evaluated. Syrian golden hamsters were intrahepatically inoculated with 1x106E. histolytica trophozoites, three days after inoculation they received nine intraperitoneal doses of (−)-epicatechin (10 mg/100 g) every 48 h. Animals without treatments and treated with metronidazole were included as controls. Macroscopic characteristics of the hepatic abscess, histopathological analysis of the tissue and the levels of inflammatory cytokines were determined. (−)-epicatechin produced a decrease in liver abscess progression being observed only 9.49% of damage compared to 84% shown by untreated animals. During treatment with (−)-epicatechin hepatic tissue showed signs of liver repair and absence of amoebae. Additionally, (−)-epicatechin produced a modulating effect on inflammatory cytokines TNF-α, IL-1β and IL-10. All these events observed in animals treated with (−)-epicatechin could contribute to the elimination of trophozoites and liver healing.

Plasma orosomucoid 2 as a potential risk marker of cholangiocarcinoma.

Cholangiocarcinoma (CCA), a malignant tumor of the biliary epithelium, is a tumor with an ineffective diagnosis and poor prognosis. We have previously identified an overexpression of orosomucoid 2 (ORM2) along with CCA development in hamsters using a proteomics technique. To evaluate plasma ORM2 as a candidate risk biomarker for CCA in humans. Overexpression of ORM2 in CCA patients was assessed by western blotting and immunohistochemistry. The diagnostic efficacy of ORM2 was investigated in the plasma of patients with hepatobiliary diseases - including 46 cholangitis patients and 70 CCA patients - compared with 20 healthy individuals, using enzyme-linked immunosorbent assay (ELISA). Overexpression of ORM2 was observed in the cytoplasm of bile duct tumor cells and in the adjacent normal hepatocytes at a much higher intensity than in normal bile duct cells. Western blot analysis revealed that its expression was significantly higher in the plasma of CCA patients compared with that of healthy individuals (P < 0.01). ELISA showed that plasma ORM2 levels were significantly elevated in CCA and cholangitis groups compared with healthy individuals (P < 0.0001). The sensitivity and specificity of ORM2 in distinguishing CCA patients from healthy patients were 92.86% and 73.68%, respectively. Plasma ORM2 could serve as a new risk marker for CCA.

MRI and 1H MRS findings of hepatobilary changes and cholangiocarcinoma development in hamsters infected with Opisthorchis viverrini and treated with N-nitrosodimethylamine

3T MRI and 1H MRS were useful for quantitative investigation of the serial development of hepatobiliary changes in Opisthorchis viverrini infection in hamsters, and the differential diagnosis of cholangiocacinoma (CCA) development from bile duct changes and normal condition is unclear. In this study, we investigated the serial development of hepatobiliary changes and CCAgenesis in O. viverrini-infected and N-nitrosodimethylamine (NDMA) treated hamsters (ON group) using 3T MRI and 1H MRS and the results were compared with those either in the O. viverrini-infected group (OV group) and uninfected normal controls. In the ON group, CCAs were first found at 9weeks post-infection, with sizes of ~2mm. The typical MR signal characteristics of CCA were hypo- and occasionally isointensity signal on T1-weighted images, and mild–moderate to hyper-intensity signal on T2-weighted images compared to the liver parenchyma. T2-weighted images with fat suppression revealed dilatation of the intra- and extrahepatic bile ducts, and often defined the anatomical level of biliary obstruction, cystic lesions, liver abscesses, and CCA which was starting seen of these noticeable abnormalities at 5weeks onwards. The results of fibrosis grading using MR images showed a positive correlation (r=0.90, P<0.038 by Spearman's rank correlation test) with those of the histopathological grading. In addition, 3.0T 1H MRS showed elevated choline and decreased lipids levels in the liver tissues of the ON group. In conclusion, MRI and 1H MRS are useful for the quantitative investigation of the serial development of hepatobilary changes and CCA in hamsters, and are potentially useful as early diagnostic tools for CCA.

Expression of alpha-smooth muscle actin as special and morphometric assessment in the small intestine during the postnatal development in hamster

Immunoreactivity of alpha-smooth muscle actin (ASMA), along, with morphometric values in the hamster small intestine, was examined during postnatal development. Twelve healthy hamsters were divided into three age groups of 2·5 months (group 1), 3 months (group 2), and 4 months (group 3). For morphometrical study, routine tissue processing was carried out by autotechnicon tissue processor, the processed tissues were embedded and sectioned serially into 5-μm thick sections. The sections were stained with hematoxylin and eosin (H&E). Immunohistochemistry (IHC) was performed by primary antibodies against alpha-smooth muscle actin (ASMA). All samples showed ASMA expression in the muscularis mucosa and circular and longitudinal layers of muscularis propria. The small intestine samples in group 1 showed minimal ASMA expression in total muscular layers. Alpha-smooth muscle actin labeling was increased in groups 2 and 3 in the muscularis mucosa and both layers of inner and outer circular muscle as compared to group 1. A more intense ASMA expression was observed in the longitudinal layers in both groups 2 and 3. The morphometrical results showed that there was a smaller increase in thickness of the mucosa, submucosa, and muscular layers from group 1 to group 2 that was followed by a larger increase between groups 2 and 3. There were significant increases in thickness of all morphometrical parameters (mucosa, submucosa, and muscularis) in groups 2 and 3 in comparison with group 1, and also group 3 compared with group 2. In groups 2 and 3, thickness of the submucosa and muscular layers were significantly higher in the jejunum compared with the ileum.

Protection against Amoebic Liver Abscess in Hamster by Intramuscular Immunization with an Autographa californica Baculovirus Driving the Expression of the Gal-Lectin LC3 Fragment.

In a previous study, we demonstrated that oral immunization using Autographa californica baculovirus driving the expression of the Gal-lectin LC3 fragment (AcNPV-LC3) of Entamoeba histolytica conferred protection against ALA development in hamsters. In this study, we determined the ability of AcNPV-LC3 to protect against ALA by the intramuscular route as well as the liver immune response associated with protection. Results showed that 55% of hamsters IM immunized with AcNPV-LC3 showed sterile protection against ALA, whereas other 20% showed reduction in the size and extent of abscesses, resulting in some protection in 75% of animals compared to the sham control group. Levels of protection showed a linear correlation with the development and intensity of specific antiamoeba cellular and humoral responses, evaluated in serum and spleen of hamsters, respectively. Evaluation of the Th1/Th2 cytokine patterns expressed in the liver of hamsters showed that sterile protection was associated with the production of high levels of IFNγ and IL-4. These results suggest that the baculovirus system is equally efficient by the intramuscular as well as the oral routes for ALA protection and that the Gal-lectin LC3 fragment is a highly protective antigen against hepatic amoebiasis through the local induction of IFNγ and IL-4.

Infección de fibroblastos de piel de animales con distinto grado de susceptibilidad a &lt;i&gt; Leishmania infantum y Leishmania mexicana&lt;/i&gt; (Kinetoplastida: Trypanosomatidae)

Infection and multiplication of Leishmania infantum and L. mexicana inside of skin fibroblasts from hamsters, mice and rats was achieved. This process was demonstrated either by counting parasites inside the stained cells or by electronic microscopy studies. In addition multiplication rate differences in the cells from these rodent species were determined, for L. infantum as well as for L. mexicana. Parasite development in hamsters and mice fibroblasts was evident but there was not multiplication in rat cells showing that apparently they are refractory to Leishmania infection. These results suggest that the parasite affinity for each animal, as well as any intracellular environment resistance, could involve genetic factors in the parasite multiplication. On the other hand, presence of amastigote multiplication inside of parasitophorus vacuole, showed by electronic microscopy images, probes a true parasite transformation. Therefore it is suggested that fibroblasts could work as host cells for parasite survival and permanency in the infected animals.

Preclinical investigations into the relationship between adolescent SSRI exposure and aggressive behavior: Response to commentary by Rubin and Walkup (2012).

A Commentary published in the October 2012 issue of Behavioral Neuroscience entitled "SSRIs, Adolescents, and Aggression: Tempering Human Implications Regarding SSRI-Induced Aggression in Hamsters: Comment on Ricci and Melloni (2012)", presents an interpretation of findings from our report published in the same issue of Behavioral Neuroscience entitled "Repeated Fluoxetine Administration During Adolescence Stimulates Aggressive Behavior and Alters Serotonin and Vasopressin Neural Development in Hamsters". The commentary was informative, especially in its review of the prescribing demographics for SSRIs in youth and its review of human and animal aggression subtypes, and in several instances offered alternative explanations and interpretations of evidence cited in our report, particularly regarding putative relationships between human and animal models of aggression. In our response, we reply to comments made by the authors regarding the animal model of choice for our studies, the methodologies employed and the greater implication(s) of our published study as well as offer a disparate view of the evidence cited by the authors in their commentary as they pertain to the relevance of the models of aggression used in our study.

β-Glucan Fiber from Spent Brewer’s Yeast Reduces Early Atherosclerosis Greater Than Psyllium in Hypercholesterolemic Syrian Golden Hamsters

β-Glucans, mostly from oats, have been shown to reduce blood concentrations of total and LDL-cholesterol in animals and humans. After processing, spent brewer’s yeast, a by-product of the fermentation process, contains 85% - 90% β-glucans. The purpose of this study was to evaluate the effect of yeast-derived β-glucan fiber on plasma lipids and early atherosclerosis development in hamsters consuming a semi-purified hypercholesterolemic diet (HCD). Animals were fed either the HCD or the HCD containing psyllium or β-glucan fiber from yeast for 12 weeks. Both the psyllium and β-glucan fiber from yeast showed significant decreases in plasma total cholesterol, non-HDL-C, triacylglycerol, and aortic fatty streak area when compared to the HCD. Also, the β-glucan fiber from yeast had significantly less aortic fatty streak area compared to the psyllium diet. Findings from this study show that while both β-glucan fiber from yeast and psyllium produced similar reductions in plasma lipid and lipoprotein concentrations, the β-glucan fiber from yeast prevented the development early atherosclerosis better than psyllium in the hamsters.

Repeated fluoxetine administration during adolescence stimulates aggressive behavior and alters serotonin and vasopressin neural development in hamsters.

Fluoxetine is the only selective serotonin reuptake inhibitor registered for the treatment of major depressive disorder in pediatric populations, despite reports that it is disproportionately associated with an array of adverse side effects that include agitation, hostility, and overt acts of pathological aggression and violence in youth. This study examined the effects of repeated adolescent fluoxetine administration on offensive aggression and the development of the serotonin (5HT) and vasopressin (AVP) neural systems modulating this behavior using pubertal Syrian hamsters (Mesocricetus auratus) as an adolescent-animal model. Adolescent hamsters administered fluoxetine were tested for offensive aggression using the resident/intruder test, sacrificed the following day, and, using immunohistochemistry, examined for 5HT and AVP afferent innervation/development to areas of the brain implicated in aggression control. Repeated exposure to a low dose (0.3 mg/kg/day) of fluoxetine during adolescence increased nearly all measures of offensive aggression (i.e., upright offensive attacks, lateral attacks, flank/rump bites, pursuits, flank marks), whereas measures of social interest (i.e., olfactory investigation, contact time), comfort (i.e., grooming), and locomotion (i.e., contact time, cage climbing) remained constant. Fluoxetine exposure also increased 5HT and AVP afferent development to brain areas implicated in aggressive behavior, most notably the latero-anterior hypothalamus (LAH)-an area of convergence for developmental and neuroplastic changes correlated with offensive aggression in hamsters. These data indicate that repeated administration of clinically relevant doses of fluoxetine during adolescent development directly stimulates aggressive behavior and alters LAH 5HT and AVP development, yet only alterations in AVP afferent development within the LAH correlate with the fluoxetine-induced aggressive behavioral phenotype.

Abstract 2478: Early and enhanced development of N-nitrosobis(2-oxopropyl)amine-induced hamster pancreatic adenocarcinomas by high-fat diet

Abstract Epidemiologically, obesity is associated with pancreatic cancer risk, but the mechanisms of obesity-associated carcinogenesis have not yet been clearly understood. Hypertrophic white adipose tissues secrete many adipokines and inflammatory factors, which are expected to enhance cancer development. Syrian golden hamsters, which are used in pancreatic carcinogenesis studies, are in a hyperlipidemic state even under normal diet conditions. We previously have shown that pioglitazone, a PPAR γ ligand, improves hyperlipidemia and suppresses N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic ductal carcinoma development. In the present study, effects of a high-fat diet (HFD) on hyperlipidemia and pancreatic carcinogenesis in BOP-treated hamsters were examined. Six-week-old female Syrian golden hamsters were subcutaneously injected with BOP (10 mg/kg body weight) four times in a week and from 8 weeks of age, the animals in the HFD groups were fed Quick Fat Diet (CLEA Japan, crude fat 14.3 %) for 6 or 17 weeks. At 14 weeks of age, serum levels of triglycerides, total cholesterol, free fatty acids and leptin were significantly elevated in hamsters fed the HFD, and pancreatic ductal adenocarcinomas were already observed in the BOP + HFD group. Pancreatic fatty infiltration was observed to increase in BOP-treated and HFD-fed hamsters. At 25 weeks of age, serum levels of total cholesterol and free fatty acids were further increased in each group and pancreatic ductal adenocarcinomas developed both in the BOP + standard diet group and BOP + HFD group. The numbers of dysplasia and adenocarcinomas in the pancreas were significantly higher in the BOP + HFD group than in the BOP + standard diet group. Apparent fatty infiltration was observed in relatively large adenocarcinomas in the BOP + HFD group. In conclusion, the HFD aggravated the hyperlipidemia, shortened the latency periods of cancer and increased numbers of BOP-induced pancreatic precancerous lesions and adenocarcinomas. Fatty infiltration was apparent in the pancreas of the HFD group and may be associated with pancreatic cancer development in hamsters. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2478.

Mitochondrial distribution and function in oocytes and early embryos.

Active mitochondria relocate during oocyte maturation or fertilization in several species. Detailed studies with hamster oocytes and early embryos reveal a pattern of active mitochondria migrating to surround the pronuclei to form a pattern that persists through the early cleavage stages. Although the functional significance of this relocation is unknown, it appears to be an important part of normal development in hamsters. Treatments that disrupt embryo development in vitro (such as the presence of inorganic phosphate or alteration of intracellular pH) also disrupt the normal pattern of mitochondrial distribution. Active mitochondria also reorganize during maturation in bovine oocytes and during fertilization in rhesus monkey oocytes. Examination of these changes in mitochondrial organization may provide insights into the regulation of normal embryo development and might serve as predictors of oocyte or embryo developmental competence.

Housing conditions effect plasma lipid concentrations and early atherogenesis independent of treatment in hamsters

The purpose of these studies was to evaluate the affect of housing conditions on various lipid parameters and early atherogenesis. In experiment 1, 35 Golden Syrian hamsters, nine weeks of age, were initially housed five to a cage and fed a hypercholesterolemic diet (HCD) for 26 weeks. Plasma total lipoprotein cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were measured enzymatically at 4, 6, 9, 12, 14, 16, 19, 23, and 26 weeks of the study. At week 9, the animals were placed in individual cages for 7 weeks and then regrouped a second time at week 16 of the study. Three blood samples were taken during each of the 3 treatment periods. In experiment 2, part 1, two groups of hamsters (n=6) were either housed individually or grouped and fed the same HCD for 14 weeks. In part 2, two groups of hamsters (n=5) were either housed individually or grouped and fed a chow diet for 14 weeks. Plasma lipids were measured enzymatically at weeks 4, 7, 10, 12, and 14 in experiment 2. Also, the hamsters in part 1 of experiment 2 were euthanized at week 14 and examined for aortic fatty streak formation. In experiment 1, animals fed HCD that were grouped for the first 9 weeks had significantly higher plasma TC (59%, p < 0.008), LDL-C (71%, p < 0.007), and TG (77%, p < 0.007) than when the hamsters were housed individually. Also in experiment 1, the hamsters fed the HCD that were grouped for the last 9 weeks had significantly higher plasma TC (55%, p < 0.01), LDL-C (69%, p < 0.007), and TG (83%, p < 0.005) than when the hamsters were individually housed. In experiment 2, part 1, the hamsters fed HCD and group caged had significantly higher plasma TC (37%, p < 0.008), LDL-C (46%, p < 0.007), TG (53%, p < 0.003), body weights (11%, p < 0.009), and aortic fatty streak area (43%, p < 0.05) and significantly lower HDL-C (−33%, p < 0.0001) compared to the hamsters housed individually. In part 2, the hamsters fed the chow diet and group caged had significantly higher plasma TG (24%, p < 0.003) and body weights (22%, p < 0.004) compared to the hamsters housed individually. The results of the following study suggest that housing conditions by unknown mechanisms can significantly affect plasma lipids and early atherosclerosis development in hamsters fed a hypercholesterolemic diet.

Successful development in vitro of hamster 8-cell embryos to 'zona-escaped' and attached blastocysts: assessment of quality and trophoblast outgrowth.

The peri-implantation development involves zona escape (hatching) of blastocysts and their attachment and proliferation. These events are difficult to study in vivo, so in this study hamster 8-cell embryos were cultured through the hatched and attached blastocyst stages using different formulations of hamster embryo culture medium (HECM)-2. Supplementation of succinate, amino acids, vitamins (inositol, pantothenate, choline chloride) and bovine serum albumin (BSA) to HECM-2 supported 100% development of 'zona-escaped' blastocysts. In this medium (designated as hatching, i.e. HECM-2h) all blastocysts invariably deflated and escaped from focally lysed zonae, which underwent complete dissolution. In their presence, pre-morula stage embryos also escaped from zonae. Omission of BSA from HECM-2h failed to support zona escape whereas that of vitamins reduced zona escape (34.0% +/- 7.0). Blastocysts with the potential to undergo zona escape in HECM-2h were of high quality as they had a higher mean cell number (MCN) than the MCN of those developing in BSA-free HECM-2h (35.2 +/- 1.6 v. 24.3 +/- 1.1). Cell allocation (i.e. trophectoderm to inner cell mass ratio) in blastocysts remained unaltered in both media (2.6 +/- 0.2 v. 2.7 +/- 0.2). Supplementation of 10% bovine fetal serum (BFS) to HECM-2h was detrimental to the development of blastocysts (22.3% +/- 7.4) and none of them underwent zona escape. Interestingly, BFS was required either as a supplement to the medium or as a coating on dishes for azonal blastocysts to attach (> or = 70%) and exhibit trophoblast (TB) outgrowth (30.3 x 10(3) +/- 2.9 x 10(3) micron 2 at 48 h). These results show that HECM-2h supports maximal development of zona-escaped blastocysts with the potential to attach and exhibit TB outgrowth, and there is a developmental stage-specific requirement for serum during peri-attachment in hamster development.

Succinate and malate improve development of hamster eight‐cell embryos in vitro: Confirmation of viability by embryo transfer

Succinate and malate improve development of hamster eight‐cell embryos in vitro: Confirmation of viability by embryo transfer

Succinate and malate improve development of hamster eight-cell embryos in vitro: Confirmation of viability by embryo transfer

Succinate and malate improve development of hamster eight-cell embryos in vitro: Confirmation of viability by embryo transfer

Micromolar concentration of pentoxifylline improves development in vitro of hamster 8-cell embryos: confirmation of biological viability by embryo transfer.

The influence of the sperm motility stimulant pentoxifylline (PF) on preimplantation embryo development in hamsters was evaluated. Eight-cell embryos were cultured in hamster embryo culture medium (HECM)-2, with or without PF (0.023-3.6 mM). There was 90%, 37% and 29% inhibition of blastocyst development by 3.6 (used for human sperm), 0.9 and 0.45 mM PF, respectively. However, 23 microM PF (exposed to hamster oocytes during IVF) significantly (P < 0.05) improved blastocyst development (63.6% v. 51.8%); morulae development was, however, not curtailed by 0.45 mM or 0.9 mM PF (51.8%+/-6.0 or 50.5%+/-11.3, respectively). Post-implantation viability of PF-treated embryos was assessed by embryo transfer; 43% of 80 PF-treated embryos implanted compared with 40% of 79 control embryos. Of the 9 recipients, 6 females delivered pups (19, i.e. 16% of transferred embryos or 53% of implanted embryos). These data show that in hamsters, continuous presence of PF at 0.45-3.6 mM is detrimental to 8-cell embryo development whereas 23 microM PF improves the development of embryos to viable blastocysts which produce live offspring.

Induction of superovulation by immunoneutralization of endogenous inhibin through the increase in the secretion of follicle-stimulating hormone in the cyclic golden hamster.

The present study was conducted to study the effect of immunoneutralization against endogenous inhibin on FSH, LH, oestradiol-17 beta and progesterone secretion and to investigate the effect of removal of endogenous inhibin on subsequent follicular development in the hamster. After treatment with anti-inhibin serum (inhibin-AS) at 1100 h on day 2 of the oestrous cycle (day 1 = day of ovulation), a marked increase in plasma levels of FSH and a slight increase in plasma levels of LH were noted and pituitary contents of FSH, but not LH, were also increased. In the group treated with inhibin-AS, superovulation occurred on day 1 of the following cycle. Plasma levels of oestradiol-17 beta markedly increased with the increase in the number of ovulations induced by human chorionic gonadotrophin (hCG) as compared with those in control animals. In the second cycle, plasma concentrations and pituitary contents of FSH in the animals given 200 microliters inhibin-AS still showed high values as compared with those in the animals treated with control serum, although superovulation did not occur on day 1 of the third cycle. Plasma concentrations and pituitary contents of LH in the hamster given 200 microliters inhibin-AS tended to decrease as compared with those in control animals during the second cycle. Plasma concentrations of oestradiol-17 beta in the animals treated with 200 microliters inhibin-AS changed in a similar way to controls. A marked increase in plasma concentrations of progesterone was noted on days 1 and 2 of the second cycle in the group receiving inhibin-AS. The twice daily injection of 1 IU hCG during the second cycle to the animals given 200 microliters inhibin-AS induced superovulation on day 1 of the third cycle. These results indicate that circulating inhibin may be an important indicator of the number of developing follicles and may maintain the species-specific number of developing follicles through suppression of FSH secretion in the cyclic hamster. They also suggest that high levels of inhibin slightly suppress plasma levels of LH, indicating that plasma LH may also regulate follicular development in the cyclic hamster.

Equivocal evidence of complete carcinogenicity after repeated infection of Syrian hamsters with Opisthorchis viverrini.

The effects of repeated infection with Opisthorchis viverrini on liver lesion development in male and female Syrian hamsters were investigated over a 1-yr period. Ten monthly intragastric applications of 50, 25, 13, or 0 parasite metacercariae resulted in pronounced proliferative and inflammatory lesions involving the first- and second-order ducts in response to the presence of adult worms. Despite the development of small numbers of putative preneoplastic areas of cholangiofibrosis and morphologically altered hepatocellular foci, no neoplastic lesions were evident at sacrifice after 1 yr. The results thus suggest that parasite infestation is itself not strongly carcinogenic if at all but, rather, that it exerts a marked promoting influence on cholangiocellular and hepatocellular tumor development in the hamster via chronic irritation and increased cell turnover.