Healthy Hamsters Research Articles

Thymic alterations resulting from experimental visceral leishmaniasis in a Syrian hamster (Mesocricetus auratus)

BackgroundThe thymus is a lymphoid organ responsible for the development and maturation of T cells, which are part of the Th1, Th2, Th17, and Treg immune responses triggered by visceral leishmaniasis. The maturation and immunological development of T lymphocytes require a bidirectional interaction between the thymic microenvironment of epithelial cells, dendritic cells, and macrophages and the extracellular matrix with differentiating lymphocytes. ObjectivesWe evaluated the morphological characteristics and tissue distribution of hematopoietic and stromal cells in the thymuses of hamsters experimentally infected with Leishmania infantum, aiming to gain an insight into the pathophysiology of the disease. MethodsFifteen hamsters were subjected to intraperitoneal experimental infection with 107L. infantum promastigotes (MHOM/BR/1972/BH46). The animals were divided into three groups, each comprising five infected hamsters, and were then euthanized 15, 60, and 120 days postinfection. The control groups consisted of three groups of five healthy hamsters euthanized simultaneously with the infected ones. Thymic morphology was evaluated through histopathology and the cell composition through immunohistochemistry. We used antibodies to mark mesenchymal cells (anti-vimentin), epithelial cells (anti-cytokeratin), macrophages (anti-MAC387), B lymphocytes (anti-CD79a), and T lymphocytes (anti-CD3). Immunohistochemistry was also used to mark the parasite in the thymus. ResultsInfected and control hamsters showed no difference in thymic morphology and degree of atrophy. After 15 days of infection, CD3 + T lymphocytes in the thymus showed an increase that stabilized over time. At 120 days of infection, we detected a significant decrease in CD79a+ B lymphocytes. The parasite was present in the medullary and corticomedullary regions of 9 out of 15 hamsters. These findings confirm that the presence of a parasite can cause changes in a thymus cell population. However, further studies are needed to evaluate these changes’ effects on the immune response of infected animals.

Morphological, histological, and histochemical study of the adult golden hamster (Mesocricetus auratus) spleen.

The golden hamster is a choice model for investigating many visceral and splenic infections and neoplastic and retrospective lesions. To study hamsters' spleen's morphological, histological, and histochemical structure. Samples were collected from eight healthy adult golden hamsters and then fixed with 10% buffered formalin. Later, samples were processed, sectioned, and stained with Hematoxylin and Eosin as well as Masson's Trichrome stain. Other slides were further stained with Periodic Acid Schiff and Alcian blue 2.5 stain (PAS) for histochemical evolution; the gross measurement was performed for the splenic length, width, and thickness, while the histological measures included the splenic capsular and trabecula thickness, diameter of white pulp follicles, splenic sinusoids and central arteries and proportion of white and red pulps. The macroscopic findings revealed that the spleen was red-brown lanciform on the left side of the dorsolateral abdominal wall. The morphological measurements for splenic length, width, and thickness were 26.6 ± 7.67, 4.17 ± 1.65, and 1.70 ± 0.01 mm, respectively. The histological observations showed that the splenic capsule was composed of two layers (serosal and subserosal). The inner layer sends trabeculae dividing the splenic parenchyma irregularly, and the splenic parenchyma comprises the white and red pulp. The white pulp follicles included the mantle, marginal zones, and the PALS (periarterial lymphatic sheath), while the red pulp constituted splenic cords and sinuses. The histomorphological findings showed that white pulp follicles and the central artery mean diameter were 252.62 ± 8.07 µm and 54.45 ± 0.36 µm respectively, the proportion of white to a red pulp was 0.49 ± 0.01, the splenic capsule, trabecula and the wall of splenic arteries showed an intense positive activity to PAS stain and negative or weak in other splenic structures. The similarities and differences in the spleen between the laboratory animals and hamsters were apparent in this article, so understanding the morphological and histological structure of the spleen presents significant assistance with species identification to select the appropriate experimental animal model in future medical research.

A Comprehensive Morphometric Study of Visceral and Subcutaneous Adipose Tissue Depots in Mice, Hamsters and Rats

Adipose tissue morphology of different fat tissue depots can be described using the number of adipocytes and cell surface of adipocytes. This study deals with characteristics and morphometric analysis of white and brown adipose tissue depots in healthy adult laboratory mice, hamsters and rats of both sexes. The number of unilocular adipocytes in white adipose tissue differs from one adipose tissue depot to another, with the largest number of adipocytes in mice and a similar number in hamsters and rats. The smallest surface area and the largest percentage of small unilocular adipocytes were found in mice. White adipose tissue in hamsters and rats was predominantly made out of a larger percentage of medium-sized adipocytes and a smaller percentage of small and medium-sized adipocytes. Uncoupling protein 1 positive multilocular adipocytes were found in classic brown adipose tissue depots with larger percentages in mice (93.20 %) and hamsters (91.30 %), while rats had a smaller percentage (78.10 %). In white and brown adipose tissue, significant differences between species and both sexes within the same species were found, indicating the influence of sexual dimorphism. The presented morphometric results could serve as a basis for further studies concerning experimental animal models of metabolic disorders and obesity.

Effects of long-term anti-ischemic drug treatment on Na,K-ATPase isoforms in cardiomyopathic hamsters.

We investigated the effects of long-term anti-ischemic therapy with trimetazidine on Na,K-ATPase (NKA) activity and protein expression in cardiomyopathy. NKA isoforms in membrane fractions from cardiomyopathic hamsters of the BIO 14.6 strain were studied and compared with those from healthy Syrian golden hamsters (F1B). Trimetazidine was orally administered to a subset of cardiomyopathic hamsters in the early stage of active disease (30 days) until the congestive stage (350 days). In the congestive stage of cardiac failure, the cardiomyopathic hamsters displayed altered NKA activity (-55 % vs. F1B; p<0.01), which was related to a specific decrease in abundance of the membrane NKA ?1 isoform (-27 % vs. F1B). Trimetazidine partially prevented the cardiomyopathy-induced changes in NKA activity (+38 %) and ?1 membrane expression (+ 66 %) without inducing changes in the expression of the ?2 isoform or 1 isoform of NKA. Cardiac hypertrophy and remodeling were reduced after trimetazidine treatment. Additionally, the abundance of NKA ?1 in membranes was negatively correlated with the ventricular weight/body weight ratio (an index of cardiac hypertrophy) (r2 = 0.99; p<0.0015). These findings suggest that some of the cardioprotective effect of trimetazidine during long-term cardiomyopathy may be achieved via regulation of cardiac remodeling and selective modulation cardiac NKA isoforms.

Preclinical Assessment of Ursolic Acid Loaded into Nanostructured Lipid Carriers in Experimental Visceral Leishmaniasis.

Ursolic acid, a triterpene produced by plants, displayed leishmanicidal activity in vitro and in vivo; however, the low solubility of this triterpene limits its efficacy. To increase the activity of ursolic acid (UA), this triterpene was entrapped in nanostructured lipid carriers (UA-NLC), physical-chemical parameters were estimated, the toxicity was assayed in healthy golden hamsters, and the efficacy of UA-NLC was studied in experimental visceral leishmanisis. UA-NLC exhibited a spherical shape with a smooth surface with a size of 266 nm. UA-NLC displayed low polydispersity (PDI = 0.18) and good colloidal stability (−29.26 mV). Hamsters treated with UA-NLC did not present morphological changes in visceral organs, and the levels of AST, ALT, urea and creatinine were normal. Animals infected with Leishmania (Leishmania) infantum and treated with UA-NLC showed lower parasitism than the infected controls, animals treated with UA or Amphotericin B (AmB). The therapeutic activity of UA-NLC was associated with the increase in a protective immune response, and it was associated with a high degree of spleen and liver preservation, and the normalization of hepatic and renal functions. These data indicate that the use of lipid nanoparticles as UA carriers can be an interesting strategy for the treatment of leishmaniasis.

Neoangiogenesis in the Econiche of Opisthorchis Felineus After Partial Hepatectomy Accompanied by Superinvasive Opisthorchiasis

Research goal: revealing the liver vessels formation mechanisms after partial hepatectomy accompanied by superinvasive opisthorchiasis (SO).Material and methods. The study was carried out on Syrian hamsters, weighing 98.0–110.0 g, mature animals of both genders. The animals were divided into three groups. Group I (n=168): a model of SO. Group II (n=40): partial liver resection in healthy animals. Group III (n=86): partial hepatectomy accompanied by SO. The histological specimens were stained with Mayer's hematoxylin and eosin by the methods of Van Gieson, Slinchenko, V.V. Kupriyanov. Immunohistochemical reactions were performed using primary antibodies to CD31, CD34, CD117, Oct4, and α-fetoprotein. The results were statistically processed, the differences were considered significant at p&lt;0.05.Results. In animals of group I accompanied by SO, proliferation of progenitor cells (CD31+, CD34+, CD117+, Oct4+) was observed in the portal tracts and perivascular space with the development of vascular formations, cholangiocellular and hepatocellular differnеntiations. Liver regeneration in healthy hamsters during 1– 3 days consisted in an active reaction of mitotic and amitotic division of hepatocytes with the development of avascular islets. In the subsequent periods (the 7th day), the cells of preexisting vascular structures (sinusoids, capillaries) multiplied. After partial hepatectomy accompanied by SO (group III), there was an intensive proliferation of stem and progenitor cells with differentiation into endothelial cells, elements of cholangio- and hepatocellular differnеntiations; endotheliocytes and capillary pericytes multiplied.Conclusion. Neoangiogenesis during regeneration after partial hepatectomy in healthy animals is implemented like angiogenesis; in case of partial liver resection accompanied by SO, it is followed by the vessels formation mainly from progenitor cells (vasculogenesis), advancing the development of elements of cholangio- and hepatocellular differnеntiations.

EFFECTS OF ALTERNATIVE NATURAL AND NANOTHERAPIES VERSUS METRONIDAZOLE ON GIARDIASIS INFECTED HAMSTERS

Giardia lamblia is one the most common human zoonotic protozoan affecting about 200 million peopleannually, but recurrent symptoms and drug resistance were reported in giardiasis patients. The presentstudy assessed the therapeutic effect of Tomex® and probiotics against giardiasis as well as evaluatedefficacy of chitosan nanoparticles and metronidazole. Sixty healthy male hamsters were dividedinto 6 groups. Each group consists of 10 hamsters as following: GI non-infected hamsters, GII infectedcontrol, GIII, GIV, GV & GVI infected with G. lamblia and treated with tomex, probiotics, chitosannanoparticles (CsNPs), and metronidazole (MTZ) respectively. Hamsters were orally infected with10,000 Giardia cysts. After 3 weeks stool samples were examined for Giardia samples and contentsfor intestinal histopathology and electron microscopy of Giardia trophozoite ultrastructure. The highestreduction in Giardia cyst and trophozoite were in hamsters received MTZ but with natural alternativetherapies chitosan nanoparticles showed a therapeutic effect with highest reduction in cyst andtrophozoite counts (80.59% & 76.55%) respectively and best recovery in intestinal pathology. MTZgave higher reduction rates (91.04% & 90.75%) respectively with normal intestinal histopathology.

Hypertension Associated With Hyperlipidemia Induced Different MicroRNA Expression Profiles in Plasma, Platelets, and Platelet-Derived Microvesicles; Effects of Endothelial Progenitor Cell Therapy.

Aim: The aim of this study was to analyze the expressed profiles of miRNAs in plasma, platelets, and platelet-derived microvesicles (PMVs) obtained from experimental induced atherosclerosis animal model and to investigate the effect of EPC transplantation on these profiles.Methods: Seventeen selected circulating miRNAs (miR-19a,-21,-126,-146a,-223,-26b,-92a,-222,-210,-221,-143,-10a,-145,-155,-34a,-204, and miR-214) were individually analyzed in plasma, platelets, and PMVs isolated from peripheral blood of hypertensive-hyperlipidemic hamsters treated or not with endothelial progenitor cells (EPCs), and of healthy hamsters taken as control group.Results: Comparative with control group, in hypertension associated with hyperlipidemia the investigated miRNA expression profiles were different: (i) in plasma, the levels of all investigated miRNAs were significantly increased, the highest enhances being noticed for miR-21,-146a,-221,-143,-34a, and miR-204; (ii) in platelets, the expressions of almost all miRNAs were significantly elevated, remarkable for miR-126,-146a,-223,-222, and miR-214, while levels of miR-143, miR-10a, and miR-145 were significantly reduced; (iii) in PMVs, numerous miRNAs were found to have significantly increased levels, especially miR-222,-221,-210, and miR-34a, whereas expressions of various miRNAs as miR-223,-214,-146a,-143,-10a, and miR-145 were significantly decreased. The treatment with EPCs had the following reverse effects: (i) in plasma, significantly reduced the expression of miR-26b,-143,-34a,-204, and miR-214; (ii) in platelets, significantly decreased the levels of almost investigated miRNAs, with remarkably diminishing for miR-126 and miR-221; and (iii) in PMVs, significantly lowered the expression of some miRNAs, with considerably reductions for miR-222,-221,-210, and miR-19a, while the level of miR-214 was found elevated.Conclusions: The present study revealed that miRNAs have differential expression profiles in plasma, platelets, and PMVs under hypertension associated with hyperlipidemia conditions. The different miRNA profile in PMVs compared with platelets indicated an active mechanism of selective packing of miRNAs into PMVs from maternal cells; various miRNAs such as miR-19a,-21,-126,-26b,-92a,-155,-204,-210,-221,-222, and−34a delivered by PMVs may contribute to enrichment of circulating plasma miRNA expression. In addition, our study showed that the EPC-based therapy can regulate the expressions of investigated miRNAs into the three sources. These results provide novel information that could help in finding potential targets for the development of new therapeutic strategies in the cardiovascular disease.

Beneficial Effects of Drossinakis Bio-influence (With Infrared Thermal and Electromagnetic Fields) on the Development of Experimental Graffi Myeloid Tumors in Hamsters. Hematological Studies

The aim of the present experiments was to study the effect of bioinfluence - Infrared thermal field (ITF) and electromagnetic fields (e.m. fields) on the progression of experimental tumor – Graffi myeloid tumor in hamsters Spectral analysis methods called Non-equilibrium spectrum (NES) and Differential non-equilibrium spectrum (DNES) for 1% solutions of blood serum from hamsters with cancer and healthy hamsters were investigated. Drossinakis has a beneficial effect on the Graffi tumor-bearing hamsters. Results are obtained with the DNES method - compared to the control serum samples of hamsters with cancer and healthy hamsters. The spectrum was obtained in the range (-0.0937 eV; 13.23 μm; 755 cm -1 ) - (-0.1387 eV; 8.95; μm; 1117 cm -1 ). The average energy (∆E H...O ) of hydrogen Н…O-bonds among individual molecules H 2 O after treatment of Drossinakis was measured by NES- and DNES-methods. The result ∆E=-0.0071±0.0011 eV is according control serum samples of hamsters with cancer and ∆E=-0.0035±0.0011 eV is for healthy ones. These results suggest the restructuring of ∆E H...O values among H 2 O molecules with a statistically reliable increase of local extremums in DNES-spectra. Local extremum was obtained at (-0.1212) eV, which is an indicator of anti-inflammatory effect. Another local extremum was obtained at (-0.1387) eV, which is an indicator of the tumor-development inhibition at the cellular- and the molecular level. The beneficial effects of Drossinakis are characterized as the anti-inflammatory, anti-oxidant, anti-cancer, anti-stroke,etc. This article deals with the review of the basic biophysical-, biochemical- and biological processes - bio-influenced of Drossinakis. In this sense, the experimental research of Toshkova and co-authors has shown increased life span of the tumor-bearing hamsters, bio-influenced by Drossinakis. There are new analyses from hematological studies from Zvetkova. Keywords : Christos Drossinakis - bioinfluence, Infrared thermal field (ITF), Electromagnetic fields, Experimental myeloid tumor of Graffi , hematological studies - erythrocytes DOI : 10.7176/JMPB/54-02 Publication date : April 30 th 2019

Bioinfluence with Infrared Thermal and Electromagnetic Fields as a Therapeutic Approach of Hamsters with Experimental Graffi Myeloid Tumor

The aim of the present experiments was to study the effect of bioinfluence - Infrared thermal field (ITF) and electromagnetic fields (e.m. fields) on the progression of experimental tumor in hamsters.Spectral analysis methods called Non-equilibrium spectrum (NES) and Differential non-equilibrium spectrum (DNES) for 1% solutions of blood serum from hamsters with cancer and healthy hamsters were investigated. Drossinakis had an effect on hamsters with cancer. Results are obtained with the DNES method compared to the control serum samples of hamsters with cancer and healthy hamsters. The spectrum was obtained in the range (-0.0937 eV; 13.23 μm; 755 cm -1 ) - (-0.1387 eV; 8.95; μm; 1117 cm -1 ). The average energy (∆E H...O ) of hydrogen Н…O-bonds among individual molecules H 2 O after treatment of Drossinakis was measured by NES- and DNES-methods. The result ∆E=-0.0071±0.0011 eV is according control serum samples of hamsters with cancer and ∆E=-0.0035±0.0011 eV is for healthy ones. These results suggest the restructuring of ∆E H...O values among H 2 O molecules with a statistically reliable increase of local extremums in DNES-spectra. Local extremum was obtained at (-0.1212) eV, which is an indicator of anti-inflammatory effect. Another local extremum was obtained at (-0.1387) eV, which is an indicator of inhibition of development of tumor cells at the molecular level. The effects of Drossinakis influence– anti-inflammatory, antioxidant, and cancer development inhibition are shown. This article deals with the review of the basic biophysical-biochemical and biological processes underlying the influence of Drossinakis. The authors are studying their physical-chemical properties and biophysical and biological effects on the organism of hamsters. Another research by Toshkova has shown that the life span of cancer hamsters influenced by Drossinakis has been increased. Keywords : Infrared thermal field (ITF), electromagnetic fields (e.m. fields), experimental Graffi solid tumor DOI : 10.7176/JNSR/9-4-01

Results of Blood Serum from Cancer Treated Hamsters with Infrared Thermal Field and Electromagnetic Fields

A project of the influence of Christos Drossinakis on model biophysical, biochemical and biological systems has been conducted. His influence is with infrared thermal field and electromagnetic fields (e.m. fields). In this study an experiment on hamsters with malignant tumors was performed. The hamsters are prepared by Reneta Toshkova. Spectral analysis methods are Non-equilibrium spectrum (NES) and Differential non-equilibrium spectrum (DNES) for 1% solutions of blood serum from hamsters with cancer and healthy hamsters were investigated. Drossinakis had an effect on hamsters with cancer. Results are obtained with the DNES method according control serum samples of hamsters with cancer and healthy hamsters. The spectrum was obtained in the range (-0.0937 eV; 13.23 μm; 755 cm -1 ) - (-0.1387 eV; 8.95; μm; 1117 cm -1 ). The average energy (∆E H...O ) of hydrogen Н…O-bonds among individual molecules H 2 O after treatment of Drossinakis measured by NES- and DNES-methods. The result ∆E=-0.0071±0.0011 eV is according control serum samples of hamsters with cancer and is ∆E=-0.0035±0.0011 eV for healthy hamsters. These results suggest the restructuring of ∆E H...O values among H 2 O molecules with a statistically reliable increase of local extremums in DNES-spectra. Local extremum was obtained at (-0.1212) eV, which is an indicator of anti-inflammatory effect. Also, a local extremum was obtained at (-0.1387) eV, which is an indicator of inhibition of development of tumor cells at the molecular level. The effects of Drossinakis influence– anti-inflammatory, antioxidant, development inhibition of cancer cells are shown. This article deals with the review of the basic biophysical-biochemical and biological processes underlying the influence of Drossinakis. The authors are studying their physical-chemical properties and biophysical and biological effects on the organism of hamsters. Another research by Toshkova have shown that the cancer hamsters influenced by Drossinakis have increased their life span. Keywords : effect of Drossinakis, serum of hamsters, anti-inflammatory, antioxidant, NES, DNES. DOI : 10.7176/JHMN/58-11

Cord blood-derived mesenchymal stem cells with hepatogenic differentiation potential ameliorate chronic liver affection in experimental models.

The liver is one of the major target organs for which cell-based therapies are very promising. The limitations of various cellular therapies, including bone marrow (BM)-derived mesenchymal stem cells (MSCs), urges the exploration of stem cell sources more suitable for transplantation. Human umbilical cord blood (HUCB) can overcome these drawbacks with a favorable reparative outcome. The aim of this study was to evaluate the therapeutic potential of MSCs in 2 groups of chronic liver injury experimental models. Propagation and characterization of MSCs isolated from cord blood (CB) samples were performed and differentiation into osteogenic, adipogenic and hepatogenic lineages was induced. The 1st experimental model group (80 mice) included a negative control, a pathological control and 60 mice infected with Schistosoma mansoni (S. mansoni) and transplanted with MSCs. The 2nd experimental model group (30 hamsters) included 10 healthy hamsters serving as a negative control and 20 hamsters injected with repeated doses of carbon tetrachloride (CCl4) to induce liver fibrosis; 10 of them were treated with an intrahepatic (IH) injection of 3 × 106 MSCs and the other 10 were untreated pathological controls. Mice and hamsters were sacrificed 12 weeks post-transplantation and their liver sections were stained immunohistochemically for the detection of human hepatocyte-like cells. Moreover, the sections were examined for the levels of fibrosis. In both models, the transplantation of CB-derived MSCs (CB-MSCs) resulted in the engraftment of the fibrotic livers with newly formed hepatocytes, as evidenced by positive immunohistochemistry staining with human Hepatocyte Paraffin 1 (Hep Par 1), alpha-fenoprotein (AFP), cytokeratin 18 (CK18), cytokeratin 7 (CK7), and OV6 monoclonal antibody. The transplanted liver sections showed markedly reduced hepatic fibrosis with a significantly lower fibrotic index, as well as significantly improved liver functions compared to the pathological control (p < 0.001). This data provides hope that human CB-MSCs can be utilized as multipotent stem cells with unlimited potentiality in regenerative medicine and supports the concept of cellular therapy for the cure of hepatic fibrosis.

Pharmacokinetics and disposition of miltefosine in healthy mice and hamsters experimentally infected with Leishmania infantum

Miltefosine is the only currently available oral drug for treatment of leishmaniasis. However, information on the pharmacokinetics (PK) of miltefosine is relatively scarce in animals. PK parameters and disposition of the molecule was determined in healthy NMRI mice and Syrian hamsters infected and treated with different miltefosine doses and regimens. Long half-life of the molecule was confirmed and differential pattern of accumulation of the drug was observed in analyzed organs in mice and hamster. Long treatment schedules produced miltefosine levels over IC50 value against L. infantum intracellular amastigotes for at least 24 days in spleen and liver of infected hamsters. The observed differential pattern of organ accumulation of the drug in mice and hamster supports the relevance of both species for translational research on chemotherapy of leishmaniasis.

In vivo studies of the effectiveness of novel N-halomethylated and non-halomethylated quaternary ammonium salts in the topical treatment of cutaneous leishmaniasis.

The physicochemical properties of four N-halomethylated and one non-halomethylated ammonium salts, with proven in vitro antileishmanial activity, were determined according to pharmaceutical standard procedures. The effectiveness and toxicity of these compounds were assessed in hamsters infected with Leishmania (Viannia) braziliensis and compared to that showed by meglumine antimoniate. Animals were followed during 90days after the completion of treatment. Therapeutic response was determined according to the reduction of size of skin lesions. Toxicity was determined by the effect of compounds on body weight changes and serum levels of renal and hepatic metabolites. The effectiveness of compound 4 was similar to that showed by intralesional administration of meglumine antimoniate and better than that of the other ammonium salts. Levels of creatinine, alanine amino transferase, and blood urea nitrogen in serum were not significantly different between treatment groups, including healthy or untreated hamsters. Results imply that compound 4 has potential as a pharmaceutical active ingredient in the development of new and better formulations for the treatment of cutaneous leishmaniasis.

Observation of pancreatic microcirculation in hyperlipidemic acute pancreatitis of hamster model

Objective To observe the effect of hyperlipidemia on pancreatic microcirculation in an intact hyperlipidemic acute pancreatitis animal moldel. Methods Among 30 healthy hamsters enrolled, 20 were fed normally while, the other 10 were given high fat feed for four weeks.Then 10 animals given normal feed with normal serum lipids and no ultrasonic changes in the organs including liver, biliary tract and pancreas, were randomly(random number) selected and divided into normal control group (C group) and acute pancreatitis group (AP group) averagely.Five animals given high fat feed with 3 times serum normal triglyceride level and no ultrasonic changes in the organs including liver, biliary tract and pancreas, were randomly selected as hyperlipidemic acute pancreatitis group(HLAP). The animals in C group were undergone fake surgery.While the animals in other two groups were carried out surgery based on Schmidt method and were injected 3.5% taurocholic acid sodium into pancreatic duct with a infusion pump. Acridine orange (2 mL/kg) was injected in the inferior vena cava 6 hours later, then laser confocal microscope fluorescence imaging system were utilized to dynamically observe pancreatic microcirculation in living animal models and the variables including average microvascular diameter (MVD), functional capillary density (FCD), microvessel flow velocity (MFV) and leukocyte adhesion were recorded. Pancreatic tissue were collected and cut slices for pathological grading. Result When compared with AP group and C group, pancreas microcirculation function index MVD(μm), FCD(piece/mm2), MFV(μm/s) in the HLAP group decreased, while leukocyte adhesion (piece/mm2) increased significantly[MVD: HLAP group 2.40±0.26 vs.AP group 5.54±0.43, C group 7.56±0.42 (P<0.05); FCD: HLAP group 4.20±0.84 vs.AP group 7.56±1.14, C group 11.40±1.14(P<0.05); MFV: HLAP group 58.80±9.63 vs.AP group 131.00±12.94, C group 224.40±15.63 (P<0.05); leukocyte adhesion: HLAP group 343.60±13.86 vs.AP group 114.00±8.03, C group 18.80±2.28; (P<0.05)]. The pancreatic pathology score was higher in HLAP group [HLAP group 10.00±1.59 vs.AP group 6.60±1.14, C group 1.00±0.71(P<0.05)]. Conclusion Hyperlipidemia may aggravate the impair ment of pancreatic microcirculation and promote microcirculation dysfunction. Key words: Pancreatitis; Hyperlipidemia; Hamster; Animal model; Microcirculation system of pancreas

Molecular characterization, prevalence and clinical relevance of Phodopus sungorus papillomavirus type 1 (PsuPV1) naturally infecting Siberian hamsters (Phodopus sungorus).

Phodopus sungorus papillomavirus type 1 (PsuPV1), naturally infecting Siberian hamsters (Phodopus sungorus) and clustering in the genus Pipapillomavirus (Pi-PV), is only the second PV type isolated from the subfamily of hamsters. In silico analysis of three independent complete viral genomes obtained from cervical adenocarcinoma, oral squamous cell carcinoma and normal oral mucosa revealed that PsuPV1 encodes characteristic viral proteins (E1, E2, E4, E6, E7, L1 and L2) with conserved functional domains and a highly conserved non-coding region. The overall high prevalence (102/114; 89.5 %) of PsuPV1 infection in normal oral and anogenital mucosa suggests that asymptomatic infection with PsuPV1 is very frequent in healthy Siberian hamsters from an early age onward, and that the virus is often transmitted between both anatomical sites. Using type-specific real-time PCR and chromogenic in situ hybridization, the presence of PsuPV1 was additionally detected in several investigated tumours (cervical adenocarcinoma, cervical adenomyoma, vaginal carcinoma in situ, ovarian granulosa cell tumour, mammary ductal carcinoma, oral fibrosarcoma, hibernoma and squamous cell papilloma) and normal tissues of adult animals. In the tissue sample of the oral squamous cell carcinoma individual, punctuated PsuPV1-specific in situ hybridization spots were detected within the nuclei of infected animal cells, suggesting viral integration into the host genome and a potential etiological association of PsuPV1 with sporadic cases of this neoplasm.

Effects of diurnal variation and anesthetic agents on intraocular pressure in Syrian hamsters (Mesocricetus auratus).

OBJECTIVE To determine effects of diurnal variation and anesthetic agents on intraocular pressure (IOP) in Syrian hamsters (Mesocricetus auratus). ANIMALS 90 healthy adult Syrian hamsters (45 males and 45 females). PROCEDURES IOP was measured with a rebound tonometer. In phase 1, IOP was measured in all hamsters 3 times during a 24-hour period (7 am, 3 pm, and 11 pm). In phase 2, hamsters were assigned to 5 groups (18 animals [9 males and 9 females]/group). Each group received an anesthetic agent or combination of anesthetic agents (ketamine hydrochloride, xylazine hydrochloride, diazepam, ketamine-diazepam [KD], or ketamine-xylazine [KX] groups) administered via the IP route. The IOP was measured before (time 0 [baseline]) and 10, 30, 60, 90, 120, and 150 minutes after administration of drugs. RESULTS Mean ± SD IOP values were 2.58 ± 0.87 mm Hg, 4.46 ± 1.58 mm Hg, and 5.96 ± 1.23 mm Hg at 7 am, 3 pm, and 11 pm, respectively. Mean baseline IOP was 6.25 ± 0.28 mm Hg, 6.12 ± 0.23 mm Hg, 5.75 ± 0.64 mm Hg, 5.12 ± 1.40 mm Hg, and 4.50 ± 1.30 mm Hg for the ketamine, xylazine, diazepam, KD, and KX groups, respectively. A significant decrease in IOP, compared with baseline IOP, was detected in only the KX group at 30, 60, and 90 minutes after drug administration. CONCLUSIONS AND CLINICAL RELEVANCE Maximum IOP in Syrian hamsters was detected at night. The ketamine-xylazine anesthetic combination significantly decreased IOP in Syrian hamsters.

Therapeutic effect of ursolic acid in experimental visceral leishmaniasis

Leishmaniasis is an important neglected tropical disease, affecting more than 12 million people worldwide. The available treatments are not well tolerated and present diverse side effects in patients, justifying the search for new therapeutic compounds. In the present study, the therapeutic potential and toxicity of ursolic acid (UA), isolated from the leaves of Baccharis uncinella C. DC. (Asteraceae), were evaluated in experimental visceral leishmaniasis. To evaluate the therapeutic potential of UA, hamsters infected with L. (L.) infantum were treated daily during 15 days with 1.0 or 2.0 mg UA/kg body weight, or with 5.0 mg amphotericin B/kg body weight by intraperitoneal route. Fifteen days after the last dose, the parasitism of the spleen and liver was stimated and the main histopathological alterations were recorded. The proliferation of splenic mononuclear cells was evaluated and IFN-γ, IL-4, and IL-10 gene expressions were analyzed in spleen fragments. The toxicity of UA and amphotericin B were evaluated in healthy golden hamsters by histological analysis and biochemical parameters. Animals treated with UA had less parasites in the spleen and liver when compared with the infected control group, and they also showed preservation of white and red pulps, which correlate with a high rate of proliferation of splenic mononuclear cells, IFN-γ mRNA and iNOS production. Moreover, animals treated with UA did not present alterations in the levels of AST, ALT, creatinine and urea. Taken together, these findings indicate that UA is an interesting natural compound that should be considered for the development of prototype drugs against visceral leishmaniasis.

Topical Treatment of Leishmania tropica Infection Using (-)-α-Bisabolol Ointment in a Hamster Model: Effectiveness and Safety Assessment.

There is currently no reliable treatment for the management of cutaneous leishmaniasis, and intralesional antimonial injections remain the main treatment. The present work aims at evaluating the antileishmanial effectiveness and safety of (-)-α-bisabolol (1) in a novel topical formulation on a cutaneous leishmaniasis model involving Leishmania tropica-infected Syrian hamsters. The topical treatment with 1 reduced lesion thickness to 56% at 2.5%, showing a higher efficacy than the reference control, meglumine antimoniate. Other regimens (ointment at 1% and 5% and oral treatment at 200 mg/kg) reduced the footpad thickness as well. The skin parasite load decreased after the experiment in all treatment groups, particularly in those animals treated with the 2.5% formulation (83.2%). Treatment with (-)-α-bisabolol at different concentrations or through an oral route did not lead to the appearance of toxicity or side effects in healthy hamsters or infected animals. Therefore, topical (-)-α-bisabolol was more effective than meglumine antimoniate in this cutaneous leishmaniasis model without showing toxicity effects on the hamsters. These results are of great interest and might be used for the development of alternatives for the treatment of cutaneous leishmaniasis, either in monotherapy or in combination with other drugs whose skin permeability could be enhanced by this sesquiterpene.

Results of selected ophthalmic diagnostic tests for clinically normal Syrian hamsters (Mesocricetus auratus).

To determine values for tear production, horizontal palpebral fissure length (HPFL), eye blink frequency, and intraocular pressure (IOP) in healthy Syrian hamsters (Mesocricetus auratus). 40 healthy adult Syrian hamsters (80 eyes). Tear production was measured with the phenol red thread test (PRTT), modified Schirmer tear test (mSTT), and endodontic absorbent paper points tear test (EAPPTT). The IOP was measured by use of rebound tonometry. Correlations between test results and body weight were evaluated. Mean ± SD values for the IOP, PRTT, EAPPTT, mSTT, HPFL, and blink frequency for all 80 eyes were 4.55 ± 1.33 mm Hg, 5.57 ± 1.51 mm/15 s, 4.52 ± 1.55 mm/min, 2.07 ± 0.97 mm/min, 5.84 ± 0.45 mm, and 1.68 ± 0.43 blinks/min, respectively. For all variables, values did not differ significantly between the right and left eyes or between males and females. There was no correlation between measured variables and body weight. Results for this study provided information on values for the IOP, PRTT, mSTT, EAPPTT, HPFL, and eye blink frequency in healthy Syrian hamsters. It was important to determine reference intervals for this species because they commonly are kept as pets or used as research animals.