Fixed-point Monitoring of Vaccine Immune Effects on Severe Animal Diseases in Livestock and Poultry Breeding Fields

In order to reveal the immune antibody levels and immune effect of livestock and poultry in the locality,we performed antibody surveillance on severe animal diseases in 17 livestock and poultry fields in six administrative districts of Wuhan City. The results showed that the vaccines had a good protective efficacy on highly pathogenic avian influenza( HPAI) and Newcastle disease( ND) in Wuhan City. The whole antibody levels kept above the ministerial standard( 】 70%).However,the vaccine immunity of porcine reproductive and respiratory syndrome( PRRS),swine fever( SF) and foot and mouth disease( FMD) was still poorly protective. The data indicated that the vaccines are protecting the severe animal diseases well,but there are still some potential security holes in some administrative districts.

Fundus photography,fluorescein angiography,optical coherence tomography and electroretinography of preclinical animal models of ocular diseases

The eye is an immune-privileged and sensory organ in humans and animals.Anatomical,physiological,and pathobiological features share significant similarities across divergent species(1).Each compartment of the eye has a unique structure and function.The anterior and posterior compartments of the eye contain endothelium(cornea),epithelium(cornea,ciliary body,iris),muscle(ciliary body),vitreous and neuronal(retina)tissues,which make the eye suitable to evaluate efficacy and safety of tissue specific drugs(2).

Advances in Application of Biosensing Technology in Detection of Animal Epidemic Diseases

The development of rapid and sensitive detection technologies for animal epidemic diseases is very important to early diagnosis and disease control. Biosensing technology is a novel biological detection technology developed in recent years and has been listed as one of the five medical inspection technologies in the 21＂ century, which is considered as a rapid and effective technology for detection and diagnosis of animal epidemic diseases. In this paper, the latest research progresses on the application of biosensing technology in detection of bacterial infectious diseases, viral infectious diseases and parasitic diseases were summarized.

Call for papers of the special issue on Animal Models and Infectious Diseases

Primates and animal models are major areas of coverage for Zoological Research （ZR）. Over the past few years, ZR has released a series of special issues/topics addressing various aspects of these areas, e.g., ge- netics, immunology, and physiology neuroscience. A special issue for 2017 focusing on ＂Animal Models of Infectious Diseases＂ is under preparation and, so far, includes original research articles and reviews on filo- viruses and coxsackievirus involving guinea pigs, mice, and other species. Further to this, ZR would like to extend a very warm invitation to all peer researchers in the field to submit outstanding work to the journal on this special issue.

Rotating magnetic field inhibits Aβ protein aggregation and alleviates cognitive impairment in Alzheimer’s disease mice

Amyloid beta(Aβ)monomers aggregate to form fibrils and amyloid plaques,which are critical mechanisms in the pathogenesis of Alzheimer’s disease(AD).Given the important role of Aβ1-42 aggregation in plaque formation,leading to brain lesions and cognitive impairment,numerous studies have aimed to reduce Aβaggregation and slow AD progression.The diphenylalanine(FF)sequence is critical for amyloid aggregation,and magnetic fields can affect peptide alignment due to the diamagnetic anisotropy of aromatic rings.In this study,we examined the effects of a moderate-intensity rotating magnetic field(RMF)on Aβaggregation and AD pathogenesis.Results indicated that the RMF directly inhibited Aβamyloid fibril formation and reduced Aβ-induced cytotoxicity in neural cells in vitro.Using the AD mouse model APP/PS1,RMF restored motor abilities to healthy control levels and significantly alleviated cognitive impairments,including exploration and spatial and non-spatial memory abilities.Tissue examinations demonstrated that RMF reduced amyloid plaque accumulation,attenuated microglial activation,and reduced oxidative stress in the APP/PS1 mouse brain.These findings suggest that RMF holds considerable potential as a non-invasive,high-penetration physical approach for AD treatment.

Animal experiment and clinical study of effect of gamma-interferon on hepatic fibrosis

AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P【0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P【0.01).Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P 【0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P【0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.

Animal models of coronary heart disease

Cardiovascular disease,predominantly coronary heart disease and stroke,leads to high morbidity and mortality not only in developed worlds but also in underdeveloped regions.The dominant pathologic foundation for cardiovascular disease is atherosclerosis and,as to coronary heart disease,coronary atherosclerosis and resulting lumen stenosis,even total occlusions.In translational research,several animals,such as mice,rabbits and pigs,have been used as disease models of human atherosclerosis and related cardiovascular disorders.However,coronary lesions are either naturally rare or hard to be fast induced in these models,hence,coronary heart disease induction mostly relies on surgical or pharmaceutical interventions with no or limited primary coronary lesions,thus unrepresentative of human coronary heart disease progression and pathology.In this review,we describe the progress of animal models of coronary heart disease following either spontaneous or diet-accelerated coronary lesions.

Study on Strengthening Animal Disease Prevention

With the in-depth development of China’s market economy,animal husbandry has become an important industry that affects China’s economic form.In order to effectively promote the healthy development of animal husbandry,attention should be paid to the prevention of animal diseases.This paper made a detailed analysis from the main problems encountered in the process of animal epidemic prevention work as an entry point,and put forward some effective measures for strengthening animal epidemic prevention work.

Whole mount of adult ear skin as a model to study vascular malformations

Background:Genetic analysis in human patients has linked mutations in PIK3CA,the catalytic subunit of PI-3′Kinase,to sporadic incidences of vascular malformations.Methods:We have developed a mouse model with inducible and endothelial-specific expression of PIK3CA H1047R,resulting in the development of vascular malformations.Systemic induction of this mutation in adult mice results in rapid lethality,limiting our ability to track and study these lesions;therefore,we developed a topical and local induction protocol using the active metabolite of tamoxifen,4OH-T,on the ear skin of adults.Results:This approach allows us to successfully model the human disease in a mature and established vascular bed and track the development of vascular malformations.To validate the utility of this model,we applied a topical rapamycin ointment,as rapamycin is therapeutically beneficial to patients in clinical trials.We found that the induced ear lesions showed significant attenuation after treatment,which was easily quantified.Conclusions:These data collectively provide evidence of a new model to study vascular malformations in adult tissues,which should be particularly useful in environments lacking specialized small-animal imaging facilities.

The effect of global warming on beef production in developing countries of the southern hemisphere

Developing countries from the southern hemisphere will be confronted by the same beef production challenges caused by global warming, because these countries are at the same geographical positions in southern latitudes. Global warming is expected to have a more extreme effect on the southern hemisphere than on other continents and will have a negative effect on the beef production environments in these countries. The negative effects will include high ambient temperatures, nutritional stress and altered patterns of animal diseases. Heat stress in beef cattle on veld/savannah is expected to increase as a result of changing weather patterns on a global and regional scale. This may negatively influence food production from beef cattle for the human food chain. Negative effects of increased temperatures and thus heat stress can include lower reproductive rates and weaning weights. The effect of heat stress can be partly addressed by nutritional strategies, such as replacing rapid fermentable carbohydrates with saturated fatty acids and the feeding of more by-pass protein and dietary electrolytes. Global warming will also alter the distribution pattern of animal diseases and the vectors of some of these diseases. This may even include the spread to South American countries. Likewise the nutritional value of natural pastures may be influenced. The effect of global warming on the quality of pastures will depend on whether the global warming is a result of increased carbon dioxide levels or not. An improved understanding of the adaptation of beef cattle to their production environments is important, but adaptation is complex and thus difficult to measure. Fortunately, several proxy-indicators for adaptation such as reproductive, production and health traits are available. The selection of animals and genotypes that are better adapted to the production system, including heat stress, is possible and should be persuade to ensure sustainable beef production in hotter climates.

Expression of cyclooxygenase-2 and its pathogenic effects in nonalcoholic fatty liver disease

Objective：To investigate the expression of cyclooxygenase-2 and its pathological effect in the experimental nonalcoholic fatty liver of rats, and to explore its possible mechanism. Methods：The rat NAFLD model was established by giving a fat-enriched diet. The blood samples were obtained form abdominal aorta and the levels of serum ALT, AST and IL-1, changes in the hepatic tissue 6-k-PGF1 α TXB2 were measured. The expression level of COX-2 in rats livers were assayed by immunohistochemistry, RT-PCR and Westernblot. Results： Light microscope analysis revealed that hepatocytes were injured in the model group and slightly in the treatment group. The levels of serum TXB2 and IL-1 in the fatty liver rats were increased. Compared with the model group, the IL-1 and TXB2 increased significantly（P〈 0.05）, on the contrary, compared with the normal group, the hepatic tissue 6-Keto-prostagland decreased significantly in the model group（P 〈 0.05）, the treatment group also increased but P 〉 0.05. There was no positive expression of COX-2 in hepatic tissue of normal rats. In the model group, there was positive expression of COX-2 antigen and the number of COX positive cells progressively increased at 4, 8, 12 wks. The intensity of expression of COX-2 had significantly increased（P 〈 0.05 ） and the intensity of COX-2 expression in the treated group decreased remarkably compared with the model group（P 〈 0.05）. The expression of COX-2 mRNA and the level of COX-2 protein were significantly stronger in the liver of model rats compared with normal rats, and significantly weaker in treated rats, than in 8W and 12W model rats（P 〈 0.05）. Conclusion：The increase of COX-2 expression in NAFLD is closely associated with the severity of liver inflammation and damage. COX-2 may play an important role in the progression of rat NAFLD, and the expression of COX-2 mRNA is downregulated by cyclooxygenase-2 inhibitor, which can depress the oxidative stress and control inflammatory response efficiently.

Visceral hypersensitivity and altered colonic motility after subsidence of inflammation in a rat model of colitis

AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.

Protective effects of cyclosporine A on T-cell dependent ConA-induced liver injury in Kunming mice

INTRODUCTIONThe T-cell dependent specific liver injury in mice induced by concanavalin A(ConA) is a newly cstablished experimental liver injury model,which is considered more eligible for the study on pathophysiology of several human liver discascs,such as viral hepatitis and autommune hepatitis[1-9].T cell activation and several cytokines release had been proven to play a critical role in ConA -induced liver injury[10-19].Cyclosprine A(CsA),an effective inhibitor of activation of T lymphocytc,hes been used widely in clinical treatment,especially in autoimmune diseases and organ transplantation[20-25].In this study,we investigated the possible effect of CsA on ConA-induced liver injury in Kunning mice.

Effect of endotoxin on portal hemodynamic in rats

AIM: To study the effects of endotoxin on portal hemodynamic of normal and noncirrhotic portal hypertensive rats. METHODS: Normal rats were intraperitoneally injected with 0.1, 0.25, 0.5, 1.0, 2.0, 4.0mg.kg(-1) of lipopolysaccharide(LPS) respectively, portal vein ligation(PVL) and intrahepatic portal occlusion (IPO) rats as well as sham-operated rats were treated with an intraperitoneal injection of 1.0mg.kg(-1) of LPS, the portal vein pressure(PVP), portal venous flow(PVF), inferior vena cava pressure(IVCP) and portal vein resistance(PVR) were detected 4 hours after injection. RESULTS: PVF of the 5 groups of rats accepting intraperitoneal injection of LPS were increased from 14.0 to 18.0, 22.2, 26.2, 34.8, 39.6, 38.8 mL.min(-1) 4 hours after injection of LPS(P【0.01). PVP of the 4 groups of rats accepting more than 0.1mg/kg.b.w of LPS was increased from 1.04 to 1.25, 1.50, 1.80, 1.95, 2.05 kPa(P【0.01). The increments of PVF and PVP were in a dose-dependent manner of LPS. PVR of the 5 groups of rats was decreased from 51 to 42,44,48,45,44,47 kPa.min.L(-1) (P【0.05) and no dose-dependent manner was observed. PVF of PVL, IPO and sham-operated rats increased from 22.6 to 32.8, 22.0 to 28.0, 14.0 to 34.8 mL.min(-1) (P【0.01), and PVP increased from 1.86 to 2.24, 1.74 to 1.95, 1.04 to 1.80 kPa(P【0.01), PVR decreased from 71 to 61, 67 to 61, 52 to 44 kPa.min.L(-1) after intraperitoneal injection of 1mg.kg(-1) of LPS. The increments of PVF and PVP of PVL and IPO rats were significantly less than the sham-operated rats(P【0.01), There was no significant difference between the amounts of PVR decreased in the two groups of PHT model rats and sham-operated rats(P】0.05) after intraperitoneal injection 1mg.kg(-1) of LPS. CONCLUSION: Endotoxin could prompt portal hypertension of the normal and noncirrhotic portal hypertensive rats by increasing portal blood flow mainly.

Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of human HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesion molecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis,antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vitro and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.

Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

AIM: To establish a relevant animal model of human gastrointestinal cancer, which can be used for repetitive investigations, so as to improve our understanding and management of carcinogenesis and cancer metastasis. METHODS: Intact tissues of human colorectal and pancreatic cancers were transplanted in nude mice. The biological characteristics of the original and the corresponding transplanted tumors were investigated by HE staining, PAS staining and immunostaining. The metastases in the livers and lungs of nude mice were investigated by immunostaining with biotinylated mab KL-1 and by RT-PCR using CK20 specific primers. RESULTS: There were totally 9 of 16 surgical specimens growing in nude mice subcutaneously and/or orthotopically (4 of 6 colorectal and 5 of 10 pancreatic cancer). Tumor cell content of the specimens and freezing of tissue specimens are important factors influencing the growth of transplanted tumor. In the group of fresh tumor tissues with greater than 50% tumor cell content, the success rate of the transplantation was 100% (3 cases of pancreatic cancer and 3 cases of colorectal cancer). The orthotopically trans-planted tumors resemble the original tumor morphologically and biologically, including TAA expression such as CEA by immunohistochemistry, and CEA level in the serum of mice. Ki-67 labeling index and the expression of TAA especially K-ras, 17-1A and RA-96, are associated with the potential of tumor growth in nude mice. Micrometastases in the lungs and livers of tumor bearing mice can be detected by immunostaining with biotinylated mab KL-1 and CK20-specific RT-PCR. CONCLUSION: An orthotopic transplantation model for human colon and pancreatic cancer in nude mice has been set up. We have also established sensitive detection methods with CK-immunohistochemistry and CK20-RT-PCR to study xenotransplanted human cancer and its metastatic cancer cells in the liver and lung of nude mice. This study may be helpful in understanding the mechanism of cancer metastasis and in developing new diagnostic methods and therapeutic strategies for metastases including micrometastases.

Gastrin,somatostatin,G and D cells of gastric ulcer in rats

AIM: To investigate the relationship among gastrin, somatostatin, G and D cells in gastric ulcer and in its healing process in rats. METHODS: Fourty-nine Wistar rats were divided into 7 groups. The gastric ulcer model was induced by acetic acid successfully. The gastrin and the somatostatin in rat plasma, gastric fluid and antral tissue were measured by radioimmunoassay(RIA). G and D cells in antral mucosa were analyzed with polyclonal antibody of gastrin and somatostatin by immunohistochemical method and Quantimet 500 image analysis system. RESULTS: In gastric ulcer, the level of gastrin in plasma, gastric fluid, and antral tissue increased, that of somatostatin declined, and the disorder gradually recovered to the normal level in the healing process. Immunohistochemical technique of G and D cells in antral mucosa demonstrated that the number of G cells increased and that of D cells decreased, both areas of G and D cells declined, the ratio of number and area of G/D increased in gastric ulcer, and the disorder gradually recovered in the healing process. CONCLUSION: In gastric ulcer, the increased gastrin secreted by G cells, the declined somatostatin secreted by D cells, and the disordered G/D cell ratio can lead to gastrointestinal dysfunction.

L-arginine-induced experimental pancreatitis

Despite medical treatment,the lethality of severe acute pancreatitis is still high (20-30%).Therefore,it is very important to find good animal models to characterise the events of this severe disease.In 1984,Mizunuma et al. developed a new type of experimental necrotizing pancreatitis by intraperitoneal administration of a high dose of L-arginine in rats.This non-invasive model is highly reproducible and produces selective,dose-dependent acinar cell necrosis. Not only is this a good model to study the pathomechanisms of acute necrotizing pancreatitis,but it is also excellent to observe and influence the time course changes of the disease.By writing this review we iluminate some new aspects of cell physiology and pathology of acute necrotizing pancreatitis.Unfortunately,the reviews about acute experimental pancreatitis usually did not discuss this model. Therefore,the aim of this manuscript was to summarise the observations and address some challenges for the future in L-arginine-induced pancreatitis.

A new rat model of portal hypertension induced by intraportal injection of microspheres

IM To produce a new rat model of portal hypertension by intraportal injection of microspheres.METHODS Measured aliquots of single or differentsized microspheres (15, 40, 80μm) were injected into the portal vein to block intrahepatic portal radicals. The resultant changes in arterial, portal, hepatic venous and splenic pulp pressures were monitored. The liver and lungs were excised for histological examination.RESULTS Portal venous pressure was elevated from basal value of 089-102 kPa to a steadystate of 198-319 kPa following the sequential injections of single or differentsized microspheres, with a markedly lowered mean arterial pressure. However, a smalldose injection of 80μm microspheres (18×105) produced a steadystate portal venous pressure of 253±017 kPa, and all rats showed normal arterial pressures. In addition, numerous microspheres were found in the lungs in all experimental groups.CONCLUSION Portal hypertension can be reproduced in rats by intraportal injection of microspheres at a small dose of 80μm (18×105). Intrahepatic portalsystemic shunts probably exist in the normal rat liver..