Naturally occurring Yersinia enterocolitica septicemia in patas monkeys (Erythrocebus patas)

Two cases of Yersinia enterocolitica septicemia occurred in a breeding group of 22 adult patas monkeys (Erythrocebus patas). Affected animals had acute clinical signs of depression, weakness, dehydration, hypothermia, hepatomegaly and pronounced leukopenia. Both animals died a few hours after treatment was initiated. Gross necropsy findings included jaundice, fluid in body cavities, hepatomegaly, splenomegaly, multiple white foci within the liver and spleen, generalized lymph node enlargement and numerous mucosal ulcerations in the colon. Primary histopathological lesions were multifocal hepatic necrosis, splenic necrosis, chronic ulcerative enteritis and diaphragmatic myositis with necrosis and edema. Yersinia enterocolitica was cultured from the liver, spleen, lung, jejunum and rectum. Wild rodents, particularly mice, may have been a source of infection for these animals, as the monkeys were housed in a rural, indoor-outdoor facility. A preliminary culture survey showed that some clinically normal patas monkeys harbored the organism in their intestinal tracts.     

A new mouse strain manifesting high proteinuria and kidney glomerular defect.

A mutant strain of mice manifesting high proteinuria, wasting syndrome, and kidney glomerular defect was established from the F5 offspring of an interstrain cross of CBA/Nga and RFM/Nga mice. Affected mice had high levels of proteinuria after 40 days of age. The body weight of about 22.6% of affected mice decreased rapidly and they died between 3 and 5 months of age. We learned that this abnormality is controlled by two pairs of autosomal recessive genes; the mutant strain of mice is designated FGS/Nga. The mutant strain has been characterized by high proteinuria and renal lesions with focal sclerosis of glomeruli and tubular atrophy with interstitial nephritis in the kidney resembling the human disease. The FGS/Nga mouse strain is a potential animal model for studying kidney glomerular defect in humans.     

Histopathology findings in common marmosets (<Emphasis Type="Italic">Callithrix jacchus</Emphasis> Linnaeus, 1758) with chronic weight loss associated with bile tract obstruction by infestation with <Emphasis Type="Italic">Platynosomum</Emphasis> (Loos, 1907)

Chronic weight loss in marmosets is often associated with wasting marmoset syndrome (WMS), an important disease that occurs in callitrichid colonies around the world. Even though its etiology is very difficult to determine, particular variables, such as weight loss, diarrhea and alopecia, associated or not with infestation in the pancreatic ducts with Trichospirura leptossoma (Nematoda: Thelazioidea), seem to be linked with the syndrome. This study investigated the histopathology of the lungs, duodenum, liver, gallbladder, extrahepatic bile ducts and pancreatic ducts of six common marmosets (Callithrix jacchus) suffering from severe non-diarrheic weight loss. Three individuals died naturally and the other three were euthanized. Microscopic findings showed the presence of adult flukes (Platynosomum) in the liver. These flukes, which provoke common infection in cats, were also observed inside the gallbladder as well as in the intra and extrahepatic bile ducts in common marmosets. Portal fibrosis was observed in two animals, which developed chronic fibrosing hepatopathy (biliary pattern, grade 3). The disease progresses without diarrhea and without pancreatic lesions or infestation. With the progression, the animals presented with ascending cholangitis, cholestasis and portal fibrosis, sometimes culminating in secondary biliary cirrhosis. Therefore, this infirmity, associated with chronic weight loss in common marmosets, could be another etiological factor linked with WMS.     

Naturally occurring fatal herpes simplex virus 1 infection in a family of white-faced saki monkeys (Pithecia pithecia pithecia)

A family of three white-faced saki monkeys (Pithecia pithecia pithecia) died 48-96 hours after the onset of anorexia, nasal discharge, pyrexia and oral ulceration. One animal also had clonic seizures. Lesions found post-mortem consisted of oral and esophageal ulcers, hepatic and intestinal necrosis, meningoencephalitis and sporadic neuronal necrosis. Intranuclear inclusion bodies and syncytial cells were present in oral lesions and affected areas of liver. Herpes simplex virus 1 (HSV-1) was identified as the etiology of disease by virus isolation, polymerase chain reaction, or in situ hybridization in all three animals. Immunohistochemistry for detection of apoptotic DNA and activated caspase-3 showed significant levels of apoptosis in oral and liver lesions and occasional apoptotic neurons in the brain. These findings demonstrate the vulnerability of white-faced saki monkeys to HSV-1 and provide initial insight into the pathogenesis of fatal HSV-1-induced disease, indicating that apoptosis plays a significant role in cell death.     

PPAR-gamma agonist ameliorates kidney and liver disease in an orthologous rat model of human autosomal recessive polycystic kidney disease

In autosomal recessive polycystic kidney disease (ARPKD), progressive enlargement of fluid-filled cysts is due to aberrant proliferation of tubule epithelial cells and transepithelial fluid secretion leading to extensive nephron loss and interstitial fibrosis. Congenital hepatic fibrosis associated with biliary cysts/dilatations is the most common extrarenal manifestation in ARPKD and can lead to massive liver enlargement. Peroxisome proliferator-activated receptor γ (PPAR-γ), a member of the ligand-dependent nuclear receptor superfamily, is expressed in a variety of tissues, including the kidneys and liver, and plays important roles in cell proliferation, fibrosis, and inflammation. In the current study, we determined that pioglitazone (PIO), a PPAR-γ agonist, decreases polycystic kidney and liver disease progression in the polycystic kidney rat, an orthologous model of human ARPKD. Daily treatment with 10 mg/kg PIO for 16 wk decreased kidney weight (% of body weight), renal cystic area, serum urea nitrogen, and the number of Ki67-, pERK1/2-, and pS6-positive cells in the kidney. There was also a decrease in liver weight (% of body weight), liver cystic area, fibrotic index, and the number of Ki67-, pERK1/2-, pERK5-, and TGF-β-positive cells in the liver. Taken together, these data suggest that PIO inhibits the progression of polycystic kidney and liver disease in a model of human ARPKD by inhibiting cell proliferation and fibrosis. These findings suggest that PPAR-γ agonists may have therapeutic value in the treatment of the renal and hepatic manifestations of ARPKD.     

Studies on the Fatty Liver Diseases of Sciaenops ocellatus Caused by Different Ether Extract Levels in Diets

An experiment was conducted to study fatty liver disease caused by different ether extract levels in diets of juvenile Sciaenops ocellatus.Juvenile S.ocellatus(n=1,260;initial body weight approximately 2.73 g) were divided into nine treatment groups (triplicate groups per treatment) and fed in aquatic cases by a recirculated filtered rearing system;the temperature of the aquatic cases was maintained at 23.2±2.0°for 8 weeks.Nine kinds of diets containing different protein (38,42,46%) and ether extract levels (4,8,12%) were used.Results showed that the relative growth ratio and survival ratio of the fish fed on medium lipid diets (8%) or high ether extract diets (12%)were significantly lower than those of the fish fed on low ether extract diets (4%) (p<0.05).There was a positive correlation between the ether extract contents in hepatopancreas of fish and the ether extract contents of diets.At the end of the experimental period,the fish of the nine experimental groups suffered from different degrees of fatty liver disease and serious illness,and death occurred in a large number offish fed on medium (8%) and high ether extract diets (12%) from the third test week;mortality was highest in the fifth test week.The ill S.ocellatus showed symptoms of loss of appetite,lack of movement,black skin,and weight loss and eventually died.The main pathological change in ill fish was fatty liver disease.Their hepatopancreas were swollen and pale,accompanied by fatty degeneration,fatty necrosis of hepatocytes,and atrophy of the pancreas.Ultrastructural changes showed the presence of many lipid droplets and granules in the mitochondria,endoplasmic reticulum,and cell plasm of hepatocytes.Study results indicated that all the nine kinds of diets with different lipid or protein levels could cause nutritional fatty liver disease in juvenile S.ocellatus.The pathological severity and serious level of fatty liver disease in the tested fish positively correlated with the contents of the ether extract,but not with those of protein,in test diets.The increase in the level of ether extract in test diets was responsible for the direct cause of illness or death in juvenile S.ocellatus.     

Induction of monocyte chemotactic protein-1 (MCP-1) and TNF alpha by Trichinella spiralis in serum of mice in vivo

Effects of selenium deficiency, induced by thioacetamide, were investigated in rats. Thioacetamide (0.3 g/L) given in drinking water, as expected, caused a significant loss of selenium from the liver. It was accompanied by liver cirrhosis and a significant increase in the liver weight as well as liver to body weight ratio. A significant loss of selenium from spleen was also accompanied by an increase in its weight. Weights of lungs, testis and kidney, however, were not affected by thioacetamide and there was no change in their selenium content. Plasma levels of selenium were significantly reduced in the thioacetamide treated group. All these changes were confirmed to be due to selenium deficiency caused by thioacetamide, as supplementation with selenium reversed these changes. The mode of action of selenium is unknown but may involve anti-oxidant defense mechanisms.     

Clinical features of simian acquired immunodeficiency syndrome (SAIDS) in rhesus monkeys

A syndrome of acquired immunodeficiency has been identified in a group of rhesus monkeys (Macaca mulatta) which died at the California Primate Research Center. Clinical evaluation of these animals revealed that 50% or more had lymphadenopathy, weight loss, and diarrhea. At least 30% had splenomegaly, fever, cutaneous abscesses and/or arthritis/myositis. Two animals had fibrosarcomas. Anemia was seen in 19 animals, lymphopenia in 14, granulocytopenia in four and thrombocytopenia in three. Hepatitis was diagnosed histopathologically in 13. Electrophoresis revealed hypoproteinemia, hypoalbuminemia and hypogammaglobulinemia. Numerous bacterial, protozoal, and viral agents were identified including cytomegalovirus and leukocyte-associated herpesvirus. Pathologic lesions included severe post-reactive depletion of lymphocytes in germinal centers and paracortical regions of lymph nodes. Clinical and pathologic changes indicate an acquired immunodeficiency syndrome which has some similarities to AIDS in humans. This disease in monkeys may provide a model for studying that disease.     

Fatal Angiostrongylus dujardini infection in callitrichid monkeys and suricates in an Italian zoological garden

This paper reports four fatal cases of metastrongylid nematode Angiostrongylus dujardini infection observed in a Saguinus oedipus and a Callimico goeldii monkey and in two suricates (Suricata suricatta). All animals were kept in captivity in a zoo of central Italy. The two monkeys died with no premonitory signs, while the two-month-old suricates showed malaise, anorexia and tachypnea for a few days prior to death. Cardiomegaly and/or granulomatous pneumonia were the major anatomo-pathological findings. Inflammatory lesions were observed in the liver, heart and kidney of the suricates at histology. A. dujardini diagnosis was confirmed through both morphological identification of adult worms recovered at necropsy and molecular characterization of larvae in tissue samples.Callitrichidae and suricates are active predators and maintain their hunting behaviour in captivity and it is then likely that they were exposed to infection by preying on parasitized gastropods, intermediate hosts of A. dujardini, entering zoo enclosures from the surrounding environment. This is the first report of A. dujardini in Italy and in S. suricatta.     

板齿鼠内脏器官的重量和含水量的季节变化

本文研究板齿鼠部分内脏器官的鲜重、相对重量（脏器指数）和含水量的季节变化.结果表明：板齿鼠肝、心、脾、肾脏指数存在季节性变化,同时肝脏指数存在年龄和性别差异;脾脏指数与体重呈正相关,肝、肾脏指数与体重呈负相关;脏器水分含量只有肝和心脏存在季节性差异,但不存在年龄和性别差异.说明季节因素对不同脏器指数影响不同.     

Studies on the Fatty Liver Diseases of Sciaenops ocellatus Caused by Different Ether Extract Levels in Diets

An experiment was conducted to study fatty liver disease caused by different ether extract levels in diets of juvenile Sciaenops ocellatus. Juvenile S. ocellatus (n=1,260; initial body weight approximately 2.73 g) were divided into nine treatment groups (triplicate groups per treatment) and fed in aquatic cases by a recirculated filtered rearing system; the temperature of the aquatic cases was maintained at 23.2±2.0° for 8 weeks. Nine kinds of diets containing different protein (38, 42, 46%) and ether extract levels (4, 8, 12%) were used. Results showed that the relative growth ratio and survival ratio of the fish fed on medium lipid diets (8%) or high ether extract diets (12%) were significantly lower than those of the fish fed on low ether extract diets (4%) (p < 0.05). There was a positive correlation between the ether extract contents in hepatopancreas of fish and the ether extract contents of diets. At the end of the experimental period, the fish of the nine experimental groups suffered from different degrees of fatty liver disease and serious illness, and death occurred in a large number of fish fed on medium (8%) and high ether extract diets (12%) from the third test week; mortality was highest in the fifth test week. The ill S. ocellatus showed symptoms of loss of appetite, lack of movement, black skin, and weight loss and eventually died. The main pathological change in ill fish was fatty liver disease. Their hepatopancreas were swollen and pale, accompanied by fatty degeneration, fatty necrosis of hepatocytes, and atrophy of the pancreas. Ultrastructural changes showed the presence of many lipid droplets and granules in the mitochondria, endoplasmic reticulum, and cell plasm of hepatocytes. Study results indicated that all the nine kinds of diets with different lipid or protein levels could cause nutritional fatty liver disease in juvenile S. ocellatus. The pathological severity and serious level of fatty liver disease in the tested fish positively correlated with the contents of the ether extract, but not with those of protein, in test diets. The increase in the level of ether extract in test diets was responsible for the direct cause of illness or death in juvenile S. ocellatus. Translated from Acta Hydrobiologica Sinica, 2005, 29(1) (in Chinese)     

Leishmania donovani: cellular and humoral immune responses after primary and challenge infections in squirrel monkeys, Saimiri sciureus

Cellular and humoral immune responses were studied in squirrel monkeys after primary and challenge infection with a Khartoum strain (WR 378) of Leishmania donovani. Each of 7 squirrel monkeys, Saimiri sciureus, was inoculated intravenously with 5 X 10(7) amastigotes/kg body weight, and one other monkey (control) was inoculated with uninfected hamster spleen homogenate. Five infected monkeys recovered from visceral leishmaniasis and two infected monkeys died. Three of the five squirrel monkeys which recovered from the primary infection demonstrated acquired resistance when challenged with an intravenous inoculation of 1.0 X 10(8) amastigotes of L. donovani/kg of body weight. Each of these same three monkeys, the two remaining monkeys which recovered from the primary infection and an uninfected control monkey, were challenged subsequently with an intradermal injection of 2.2 X 10(7) promastigotes of L. braziliensis panamensis (WR539) and developed cutaneous lesions. The reactivity of peripheral blood leukocytes from infected squirrel monkeys to phytohemagglutinin was depressed 2 to 10 weeks after infection, and the reactivity to concanavalin A was not affected. Data on responses to pokeweed mitogen were inconclusive. Reactivity to leishmanial antigens was detected at 12 weeks after infection, which coincided with a marked decrease or disappearance of parasites in liver imprints. Two of five surviving squirrel monkeys developed weak delayed skin test responses to leishmanin antigens after 23 weeks; the three remaining monkeys were anergic during the primary infection but developed strong delayed skin test responses to leishmanin antigens at 7 weeks after a challenge with L. donovani. All squirrel monkeys inoculated with L. donovani developed a hyperproteinemia, hypergammaglobulinemia, hypoalbuminemia, and a reversal of the albumin/globulin ratio between 4 to 18 weeks after infection. Plasma IgM and IgG levels were increased between 2 to 18 weeks after infection; much of this increase was due to IgG. Class-specific antileishmanial antibodies, with generally low IgM and high IgG titers, reached a maximum after 14 and 16 weeks, respectively. A correlation was observed between concentration of gamma-globulins and plasma IgM and IgG levels, but not gamma-globulin concentrations and maximum titers of class-specific antileishmanial antibodies. Squirrel monkeys challenged with L. donovani again developed hyperproteinemia, hypergammaglobulinemia, and increased concentrations of plasma IgM and IgG which correlated with high titers of IgG class-specific antileishmanial antibody 4 weeks after reinoculation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Failure to induce weight gain with palatable diets in monkeys (Macaca mulatta)

Three diets popularly used to produce obesity in rodents were offered to male rhesus monkeys. A high fat diet (fat: 50% of calories) enhanced the daily caloric intake of the monkeys, but only slight and non-significant increases in body weight were observed over a period of six weeks. However, an increase in feeding efficiency was observed. Providing monkeys with an assorted, palatable supermarket diet failed to induce them to overeat. There were no changes in total caloric intake or in body weight. When the monkeys were supplemented with a bottle of 32% sucrose solution, in addition to a commercial monkey biscuit and tap water, a significant increase in caloric intake was observed, but no change in body weight occurred. Thus, palatable and calorically dense diets failed to induce sufficient increases in intake to produce change in body weight in non-human primates. Based on these results, only the high fat diet has greatest potential to produce obesity, and such obesity, if it occurs, will likely require long term experiments.     

食蟹猴肾移植模型的建立

目的建立食蟹猴的肾移植模型。方法通过显微外科手术对食蟹猴进行同种异体移植,将供体肾动脉、肾静脉分别端侧吻合到受体腹主动脉、下腔静脉,供体输尿管端端吻合到受体输尿管。结果154例肾移植食蟹猴无一只在手术过程中因意外死亡;无一只因手术感染死亡;无一只因手术并发症死亡;肾热缺血时间（30±4.5）min。结论应用食蟹猴建立肾移植模型,技术成熟,方法可靠。应用此模型评价新型免疫抑制药物,进行免疫耐受、异种移植研究可为临床试验提供更为准确可靠的依据。     

Senescent terminal weight loss in the male F344 rat

Loss of weight, often of unknown cause and culminating in death, commonly occurs in humans at advanced ages. Rats that live to old ages, such as the Fischer 344 (F344) strain, also exhibit a terminal loss in body weight. A presently held hypothesis is that the terminal weight loss in the F344 rat model is due to reduced food intake because of an alteration in hypothalamic function resulting in early satiation. We report findings on terminal weight loss and food intake in male F344 rats fed ad libitum (AL group) or a life-prolonging dietary regimen in which caloric intake was restricted (DR group). Rats in both dietary groups that did not exhibit a terminal weight loss died at younger ages than those exhibiting the loss. Terminal weight loss in the AL group was not associated with decreased food intake; indeed, half of the rats in this group had an increased food intake during the period of terminal weight loss. This finding is not in accord with the presently held hypothesis. In the DR group, terminal weight loss was associated with reduced food intake. Pathology (renal disease and neoplasms) did not explain the presence or absence of the association between reduced food intake and weight loss in either dietary group. The duration of the period of terminal weight loss was similar for the AL and DR groups. Apparently, restricting calories delays the occurrence but does not affect the duration of senescent terminal weight loss.     

Comparison of kidney weight and volume to selected anatomical parameters in the adult female rhesus monkey (Macaca mulatta).

In this study, the normal distribution of renal weight and volume was determined and the correlation between the weight and volume and various skeletal measurements taken from radiographs and at necropsy was assessed. Values from 136 female monkeys with complete data (including all bone, radiographic, and kidney measurements) were analyzed. The mean kidney weight was 13 g with a standard deviation (SD) of 2 g. The mean kidney volume was 12 ml, SD 2 ml. The estimation of kidney weight and volume from bone length, age, or body weight was not reliable according to statistical analysis of our data. We did find that all apparently normal adult female rhesus monkeys typically have similar sized kidneys. This information is useful in that it reduces concerns about consistency in experimental subjects.     

Fatty liver and kidney syndrome in chicks. I. Effect of biotin in diet.

Fatty liver and kidney syndrome, a disorder of young chicks, was studied under laboratory conditions. Affected chicks had enlarged livers (hepatomegaly), an increased content of lipid in the liver, and an increased level of palmitoleic acid in the liver lipids. The disorder was observed mainly in chicks from young parent flocks, and was associated either with commerical diets which were subsequently found to be low in biotin, or with specially formulated low-biotin diets. A third factor, imposition of stress, was required to initiate the disorder. There was evidence of increased lipogenesis causing an increase of triacylglycerols in the liver lipids and an increased production of saturated fatty acids, particularly palmitic acid. Increased levels of palmitoleic acid resulted from an increased desaturation of palmitic acid. Under stress, affected chicks had low blood glucose levels, suggesting that gluconeogenesis was impaired. Since biotin-dependent enzymes are involved in both gluconeogenesis and lipogenesis, it would appear that the relevant enzymes respond differently to a deficiency of biotin.     

Selective estrogen receptor modulator promotes weight loss in ovariectomized female rhesus monkeys (Macaca mulatta) by decreasing food intake and increasing activity

The effect of hormone replacement therapy (HRT) on body weight in postmenopausal women is controversial, with studies reporting an increase, a decrease, and no change in body weight. To examine estrogen receptor actions on body weight, we investigated the effects of treatment with a selective estrogen receptor modulator (SERM) on body weight, food intake, and activity and metabolic rate in a nonhuman primate model. Eighteen ovariectomized female rhesus monkeys were treated with a nonsteroidal SERM (GSK232802A, 5 mg/kg po) for 3 mo. GSK232802A decreased lutenizing hormone (P < 0.0001) and follicle-stimulating hormone levels (P < 0.0001), consistent with the estrogenic action of the compound. GSK232802A treatment produced a small but sustained weight loss (4.6 ± 1.0%, P < 0.0001) and reduced adiposity (P < 0.0001), which was due at least in part to a suppression of food intake (3.6 ± 3.7%, P < 0.0001). Physical activity increased during the 3rd mo of treatment (P = 0.04). Baseline activity level and the change in activity due to treatment were correlated, with the most sedentary individuals exhibiting increased physical activity during the 1st mo of treatment (P = 0.02). Metabolic rate did not change (P = 0.58). These results indicate that GSK232802A treatment reduces body weight and adiposity in ovariectomized nonhuman primates by suppressing food intake and increasing activity, particularly in the most sedentary individuals. These findings suggest that SERM treatment may counteract weight gain in postmenopausal women.