A filterable virus as a causative agent of epidemic hepatitis

Summary In four patients suffering from epidemic hepatitis we succeeded in isolating from the blood during the fever period and from the urine during the jaundice, a filterable virus, which is pathogenic to the guinea pig and which can be inoculated to this animal in different ways, but by preference intraperitoneally. Fever, which sometimes lasts only one day, is the only morbid symptom observed in guinea pigs.In these animals the virus can be shown in the organs and in the blood during the fever period; after that it is excreted with the urine during apparently a short period. The virus has been grown on the chorioallantois of the chick embryo so far during 20 passages. The virus is resistant to glycerol, drying and low temperatures, not to formaline and heating.In the livers of the guinea pigs focal changes (degeneration, dissociation, necrobiosis, yellow liver-atrophy) may be found. After dulling through the disease immunity occurs, whilst in the serum of recovered patients and guinea pigs neutralizing antibodies can be detected.     

The effect of urine from castrated male or female guinea pigs and rats on the estrous cycle of guinea pigs and rats, respectively]

A 24-hour reduced cycle duration was observed in 5-day cyclic female rats exposed to the odor of urine from male or female castrated rats. A decrease in the duration of the period of vaginal closure, ranging from 2 to 5 days, was observed in female guinea pigs exposed to the odor of urine from male or female castrated guinea pigs. The pheromonal activity of urine in both species was concluded to be no dependent upon the gonadal function.     

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) does not destroy nigrostriatal neurons in the scorbutic guinea pig

Guinea pigs were injected subcutaneously with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in maximal tolerated doses (8 mg/kg, once daily) for 10 or 15 days. No neurological effects were noted, other than sedation and hypotonia lasting a few hours after each injection, either in animals maintained on normal diet or in animals fed an ascorbate-deficient diet and rendered severely scorbutic. Subsequent chemical analyses of the striatum showed no evidence of lasting damage to nigrostriatal dopaminergic neurons in MPTP treated guinea pigs on normal diet, and minimal evidence of permanent damage to these neurons in scorbutic animals. MPTP was undetectable in the urine of MPTP-treated animals, although a metabolite, presumably 1-methyl-4-phenylpyridinium ion (MPP+) was regularly present in urine. The relative lack of neurotoxicity of MPTP in the guinea pig remains unexplained. This species clearly is not a suitable small animal for MPTP-induced parkinsonism.     

A comparison of intestinal permeability between humans and three common laboratory animals

Intestinal permeability of humans and three species of experimental animals was assessed by the oral administration of the three non-metabolizable sugars: lactulose, rhamnose and mannitol and collecting all the urine produced in a specified time. The total percentage recovery of the permeability markers was determined by high performance liquid chromatographic assays of urinary aliquots. The permeability of the human gut to mannitol was substantially greater than that of rats, guinea pigs, or hamsters (18-, 6- and 29-fold increases, respectively). The permeability to lactulose in humans was somewhat less than that found in guinea pigs (P less than 0.05), but three times greater than that found in rats or hamsters (P less than 0.001). Human rhamnose permeability was substantially greater than that of rats, guinea pigs or hamsters (6-, 2.5-, and 7-fold increases, respectively). The results suggest that the permeability of the human gut to probe molecules is considerably different from that of three common laboratory rodents, but is closest to that of guinea pigs. Possible species differences in the physiological factors which control permeability are discussed.     

Tryptophan metabolism in animals with dermatitis. II) In guinea pigs

Tryptophan load in guinea pigs after induction of a photodermatitis from psoralen caused marked increase of urinary excretion of total metabolites "via kynurenine" in comparison with that obtained before dermatitis. Xanthurenic acid is the metabolite which showed the most increased levels in urine during dermatitis. This dermatitis from furocoumarin caused an alteration of tryptophan metabolism in guinea pigs as well as rats, but species differences in the excretion of metabolites after amino acid load are observed.     

Molecular weight as a factor in the excretion of monoquaternary ammonium cations in the bile of the rat, rabbit and guinea pig

1. The excretion in the bile and urine of intraperitoneally injected (14)C-labelled monoquaternary ammonium or pyridinium cations was measured in bile-duct-cannulated rats (ten compounds) and in guinea pigs and rabbits (six compounds). 2. Seven of these, namely N-methylpyridinium, tetraethylammonium, trimethylphenylammonium, diethylmethylphenylammonium, methylphenyldipropylammonium, dibenzyldimethylammonium and tribenzylmethylammonium, were excreted largely unchanged in the bile and urine. 3. 3-Hydroxyphenyltrimethylammonium, 3-bromo-N-methylpyridinium and cetyltrimethylammonium were metabolized to an appreciable extent in the rat. 4. In intact rats intraperitoneally injected trimethylphenylammonium (mol.wt. 136) was excreted mainly in the urine, dibenzyldimethylammonium (mol.wt. 226) was excreted in roughly equal amounts in the urine and faeces, and tribenzylmethylammonium (mol.wt. 302) was excreted mainly in the faeces. The faecal excretion of these compounds corresponded to their biliary excretion in bile-duct-cannulated rats. About 3-4% of tribenzyl[(14)C]methylammonium was eliminated as (14)CO(2). 5. In rats the extent of biliary excretion of four cations with molecular weights in the range 94-164 was less than 10% of the dose, whereas that of five cations with molecular weights 173-302 was greater than 10%. These results and other data from the literature suggested that the molecular weight needed for the biliary excretion of such cations to an extent of 10% or more of the dose was about 200+/-50. Studies with six cations in guinea pigs and rabbits suggest that this value applies also to these species. 6. The results suggest that the threshold molecular weight for the appreciable (>10%) biliary excretion of monoquaternary cations is different from that for anions (Millburn et al., 1967a; Hirom et al., 1972b). With rats, guinea pigs and rabbits, no significant species difference was noted, whereas with anions there is a marked species difference.     

豚鼠气管平滑肌化学介质敏感性与体征表型的相关性

目的研究豚鼠体征表型与气管平滑肌化学介质敏感性的相关性。方法根据体征表型眼睛颜色、毛色、性别差异选取36只豚鼠,将动物按体征表型分为白色黑眼雌性组（WBEF）,白色黑眼雄性组（WBEM）,白色红眼雌性组（WREF）,白色红眼雄性组（WREM）,杂色黑眼雌性组（VBEF）,杂色黑眼雄性组（VBEM）,每组动物各6只。用旋割法制备离体豚鼠气管螺旋条,以组胺histamine（浴槽浓度2.0×10^-3g/L）和乙酰胆碱acetylcholine（浴槽浓度2.0×10^-4g/L）诱导气管螺旋条收缩,用BL420生物信号采集系统与张力传感器测定标本张力变化值,分析豚鼠眼睛颜色、毛色、性别与组胺、乙酰胆碱诱导的气管螺旋条收缩效应强弱的关系。数据采用SPSS 11.5软件在α=0.05的信度下进行单因素方差检验。结果豚鼠毛色与眼睛颜色表型其气管平滑肌化学介质敏感性差异有显著性（P〈0.05）,白色体征表型豚鼠的气管平滑肌化学介质敏感性较杂色表型高,红色眼睛表型较黑色眼睛表型高。性别表型对其介质敏感性差异不显著。结论毛色、眼睛颜色表型不同其豚鼠气管平滑肌化学介质敏感性差异显著,性别表型不同其介质敏感性差异不显著,平喘动物模型宜优先选择白色红眼表型豚鼠。     

Identification and purification of immunosuppressive activity in the urine of rats and a human patient treated with niridazole.

Administration of the antischistosomal compound niridazole to mice, guinea pigs, and humans results in the suppression of several manifestations of cell-mediated immunity. Sera from animals treated with niridazole blocked the in vitro production of migration inhibitory factor (MIF) while niridazole itself was inactive, suggesting that these effects are caused by water soluble mediators. We now report that crude extracts prepared from the urine of rats and a patient receiving nirdazole, but not from pretreatment control urine, similarly suppress antigen-induced inhibition of migration of peritoneal exudate cells from sensitized guinea pigs. With immunosuppressive activity monitored by the direct MIF assay, combined solvent extraction and chromatographic techniques were used to fractionate immunosuppressive activity from the urine of niridazole-treated rats and the patient; the most active fractions, purified about 100-to 1000-fold as compared to methanol-water extracts of dried voided urine, inhibited MIF production at 0.1 to 0.01 ng/ml of assay mixture. These purified fractions also showed immunosuppressive activity by an in vivo assay wherein doses as low as 1 mug/kg injected intravenously (i.v.) into mice suppressed cell-mediated granuloma formation around Schistosoma manisoni eggs. Identically purified fractions prepared from urine of rats and the patient before they received niridazole showed no immunosuppressive activity either in the MIF or in the granuloma assay systems.     

Bio-elimination and organ retention profile of benzanthrone in scorbutic and non-scorbutic guinea pigs

The retention and bio-elimination of benzanthrone (BA) in scorbutic and non-scorbutic guinea pigs was investigated to understand the protective role of ascorbic acid. Oral intubation of 14C-BA to scorbutic and non-scorbutic guinea pigs showed a total recovery of around 91% radioactivity through urine, faeces and tissues. Recovery of radiolabelled BA through urine (28%) and faeces (22%) up to 96 hrs averaged 50%, whereas residual radioactivity in liver and testis experienced a recovery of 29% in scorbutic animals. In non-scorbutic animals there was an increased recovery of radioactivity through urine (37%) and faeces (31%) with a decrease in retention (10%) in liver and testis. These results suggest that ascorbic acid facilitates the mobilization and bio-elimination of BA and thereby can decrease the toxicity of the compound.     

Morphometric analysis of the translocation of lumenal membrane between cytoplasm and cell surface of transitional epithelial cells during the expansion-contraction cycles of mammalian urinary bladder

The flow of membrane between the cytoplasm and the lumenal surface during the expansion-contraction cycle of urinary bladder was estimated by stereological examination of electron micrographs of urothelial cells from guinea pigs, gerbils, hamsters, rabbits, and rats. The quantitative data obtained allowed an approximation of the surface area, volume, and numbers of lumenal membranelike vesicles and infoldings per unit volume of cytoplasm. Depending upon the species, approximately 85 to approximately 94% of the membrane surface area translocated into and out of the cytoplasm was in the form of discoidal vesicles. The remainder was accounted for by infoldings of the lumenal plasma membrane. The density of vesicles involved in transfer of membrane was quite similar in all the species examined, except guinea pigs which yielded lower values. In contrast, the densities of the total cytoplasmic pools of discoidal vesicles potentially available for translocation varied greatly among the different species. In general, species of animals with a highly concentrated urine had a greater density of discoidal vesicles than species with a less concentrated urine. This correlation may indicate an authentic relationship between lumenal membranes and the tonicity of urine, such as increased membrane recycling or turnover with increasingly hypertonic urine; or it may signify the existence of some other, more obscure relationship.     

The biochemistry of aromatic amines: The metabolism of 2-naphthylamine and 2-naphthylhydroxylamine derivatives

1. 2-Naphthylhydroxylamine and 2-nitrosonaphthalene were present in urine of dogs but not of guinea pigs, hamsters, rabbits or rats dosed with 2-naphthylamine. N-Acetyl-2-naphthylhydroxylamine and its O-sulphonic acid and O-glucosiduronic acid were not detected in the urine of any of these species. 2. Bile from rats dosed with 2-naphthylamine contained (2-naphthylamine N-glucosid)uronic acid and 6- and 5,6-substituted derivatives of 2-acetamidonaphthalene. 2-Amino-1-naphthyl and 2-acetamido-1-naphthyl derivatives, 2-naphthylhydroxylamine and its N-acetyl derivative or conjugates of these were not detected. Bile from a dog dosed with 2-naphthylamine contained no 2-amino-1-naphthyl derivatives. 3. 2-Naphthylhydroxylamine was metabolized by the dog, rat and guinea pig to the same products as those formed by these species from 2-naphthylamine. Rabbits formed mainly 2-amino-1-naphthyl derivatives; these are minor metabolites of 2-naphthylamine in this species. 4. (N-Acetyl-2-naphthylhydroxylamine O-glucosid)uronic acid was excreted in the urine and the bile of rats and in the urine of guinea pigs and rabbits dosed with N-acetyl-2-naphthylhydroxylamine. 5. After the administration of 2-acetamidonaphthalene, (N-acetyl-2-naphthylhydroxylamine O-glucosid)uronic acid was detected in the urine of dogs, but not in the urine of other species. The dog excreted an acid-labile cysteine derivative of 2-acetamidonaphthalene, but only traces of the corresponding mercapturic acid. 6. After dosing with N-acetyl-2-naphthylhydroxylamine-O-sulphonic acid, rats excreted derivatives of 2-amino-1-naphthol. 7. 2-Nitrosonaphthalene, N-acetyl-2-naphthylhydroxylamine, N-acetyl-2-naphthylhydroxylamine-O-sulphonic acid, 2-naphthylhydroxylamine-N-sulphonic acid, N-benzyloxycarbonyl-2-naphthylhydroxylamine and N-benzyloxycarbonyl-2-naphthylhydroxylamine-O-sulphonic acid were synthesized.     

The fate of cyclamate in man and other species

1. (14)C-labelled cyclamate has been administered to guinea pigs, rabbits, rats and humans. When given orally to these species on a cyclamate-free diet, cyclamate is excreted unchanged. In guinea pigs some 65% of a single dose is excreted in the urine and 30% in the faeces, the corresponding values for rats being 40 and 50%, for man, 30-50% and 40-60%, and for rabbits, 90 and 5%, the excretion being over a period of 2-3 days. 2. Cyclamate appears to be readily absorbed by rabbits but less readily by guinea pigs, rats and humans. 3. If these animals, including man, are placed on a diet containing cyclamate they develop the ability to convert orally administered cyclamate into cyclohexylamine and consequently into the metabolites of the latter. The extent to which this ability develops is variable, the development occurring more readily in rats than in rabbits or guinea pigs. In three human subjects, one developed the ability quite markedly in 10 days whereas two others did not in 30 days. Removal of the cyclamate from the diet caused a diminution in the ability to convert cyclamate into the amine. 4. In rats that had developed the ability to metabolize orally administered cyclamate, intraperitoneally injected cyclamate was not metabolized and was excreted unchanged in the urine. The biliary excretion of injected cyclamate in rats was very small, i.e. about 0.3% of the dose. 5. The ability of animals to convert cyclamate into cyclohexylamine appears to depend upon a continuous intake of cyclamate and on some factor in the gastrointestinal tract, probably the gut flora.     

Comparison of in vitro platelet aggregation and its inhibition by three antithrombotic drugs between human and guinea pig

Platelets of guinea pigs are frequently used to evaluate the effect of new antiplatelet agents. Although several studies have compared the platelet aggregation between humans and guinea pigs, but so far the information is still limited. In this study, we compare the inhibitory effect of aspirin, dipyridamole and pentoxifylline on the platelet aggregation induced by adenosine diphosphate (ADP), collagen, arachidonic acid and thrombin between humans and guinea pigs. The results for humans and guinea pigs were compared and analysed by two-way analysis of variance (ANOVA). Our results showed: 1. The trends wherein these three drugs suppressed collagen-induced platelet aggregation was very similar in humans and guinea pigs. 2. In ADP-induced aggregation, the trend of inhibition caused by the three drugs was also similar in humans and guinea pigs except that a difference in platelet disaggregation at a late phase of platelet aggregation was noted. 3. In arachidonic acid- and thrombin-induced aggregations, the trend of inhibition caused by the three drugs was somewhat different in humans and guinea pigs. 4. Considering all activators as a whole, it was found that the status of platelet disaggregation at the late phase of platelet aggregation was different in humans and guinea pigs. Therefore, we concluded that: 1. Collagen was the most appropriate platelet activator when we used platelets of guinea pigs to study the effect of new antiplatelet agents. 2. When platelets of guinea pigs were used to study platelet aggregation, no matter which activator was used, we should avoid using the late phase of aggregation as the control index for comparison, because the results thus obtained might not be applicable to human platelets.     

Biochemical basis for the resistance of guinea pigs to carcinogenesis by 2-acetylaminofluorene

Studies were made on why guinea pigs are resistant to carcinogenesis by 2-acetylaminofluorene. Cytochrome P-448 and arylhydrocarbon hydroxylase were not induced in either the microsomes and nuclei of guinea pigs by 3-methylcholanthrene treatment. 3-Methylcholanthrene treatment caused only 2-fold increase in the binding of 2-acetylaminofluorene to DNA in nuclei isolated from guinea pigs, while it caused 17-fold increase in the binding in rat nuclei. Microsomes from 3-methylcholanthrene treated rats had 5 times more effect than Microsomes from 3-methylcholanthrene treated guinea pigs on the binding of 2-acetylaminofluorene to DNA of nuclei from untreated guinea pigs. N-Hydroxy-2-acetylaminofluorene combined equally well with the DNA of rats and guinea pigs. In guinea pigs, there was a good correlation between the low inducibility of cytochrome P-448 and the low binding of 2-acetylaminofluorene to DNA. Our results clearly showed that guinea pigs are resistant to tumor induction by 2-acetylaminofluorene through inability to carry out the first step of activation of 2-acetylaminofluorene.     

Ecological distribution of Legionella pneumophila.

Bacteria were concentrated 500-fold from 20-liter water samples collected from 67 different lakes and rivers in the United States. The data suggest that Legionella pneumophila is part of the natural aquatic environment and that the bacterium is capable of surviving extreme ranges of environmental conditions. The data further demonstrate the effectiveness of the direct fluorescent-antibody technique for detecting L. pneumophila in natural aquatic systems. Smears of the concentrated samples were screened microscopically for serogroups of L. pneumophila by the direct fluorescent-antibody technique. Virtually all of the 793 samples were found to be positive by this method. The 318 samples containing the largest numbers of positive bacteria which were morphologically consistent with L. pneumophila were injected into guinea pigs for attempted isolations. Isolates were obtained from habitats with a wide range of physical, chemical, and biological parameters. Samples collected monthly from a thermally altered lake and injected into guinea pigs demonstrated a seasonality of infection, with the highest frequency of infection occurring during the summer months.     

The daily pattern of heart rate, body temperature, and locomotor activity in guinea pigs.

We studied the characteristics of the rhythmicity of heart rate (HR), body temperature (BT), and locomotor activity (LA) in conscious and unrestrained guinea pigs using a telemetry system. HR and/or LA in some guinea pigs clearly showed circadian rhythms, but in others there were no significant daily patterns; BT did not show significant daily rhythms. These results suggest that guinea pigs might have different individual characteristics of rhythmicity, and we should, therefore, be careful when using guinea pigs in chrono-biomedical research. We believe that the results of this study may be useful for future biomedical studies using guinea pigs.     

Species and subspecies specificity in urine and scent marks of saddle-back tamarins (Saguinus fuscicollis)

Saguinus fuscicollisproduces scent marks which consist mainly of a mixture of urine and the secretions of circumgenital scent glands. The present study investigates the ability of saddle-back tamarins to discriminate between scent material from conspecifics and corresponding material from other species and to differentiate material from two subspecies of Saguinus fuscicollis.When choices between urine samples from conspecifics and from guinea pigs and choices between urine samples from conspecifics and from common marmosets were offered, the tamarins investigated samples from conspecifics more frequently. Similar responses were obtained when choices between scent marks from saddle-back tamarins and from common marmosets and between scent marks from saddle-back and red-chested moustached tamarins were offered. The tamarins also discriminated between scent marks and between extracts of scent marks from Saguinus f. fuscicollisand Saguinus f. illigeri.In these choice tests, subjects of both subspecies tended preferentially to investigate material from Saguinus f. fuscicollis.The results of these studies show that urine and scent marks contain chemical cues on which recognition of conspecifics can be based. Moreover, the scent marks of closely related subspecies also offer cues which could enable the tamarins to discriminate between them.     

Morquio's disease type A: Absence of material cross reacting with antibodies against N-acetylgalactosamine-6-sulfate sulfatase

Summary An antiserum was raised in guinea pigs against purified normal human N-acetylgalactosamine-6-sulfate sulfatase, the enzyme affected in Morquio's disease type A. The antiserum precipitated most of N-acetylgalactosamine-6-sulfate sulfatase from a concentrate of normal human urine. The antigen-antibody complex was enzymatically active. Urine concentrates from five patients with Morquio's disease type A did not contain material competing with the normal enzyme for binding to soluble or Sepharose-bound antibodies. No precipitin arc was obtained on immunodiffusion of antiserum and urine from the single patient investigated by this method. From the sensitivity of the indirect immunoassay it was concluded that the urine of the five patients contained less than 5% of the normal amount of cross-reacting material.     

Studies on the Tuberculin Reactivity of Tuberculin-Active Peptide

A comparative study of the tuberculin potency and reactivity to TAP and PPD-S was made in humans and guinea pigs. A comparison of reactions elicited by TAP and PPD-S was made in two groups of guinea pigs previously inoculated with killed bacilli or with living bacilli. The tuberculin reactions produced by TAP and PPD-S in human beings was studied in school children from rural districts. These children were divided randomly into three groups and each group was given a different amount of TAP and PPD-S. The results obtained are as follows: (1) While relative potency of TAP was relatively much weaker than PPD-S in guinea pigs sensitized with tubercle bacilli, in human beings the tuberculin potency of TAP was approximately 1/2 or 1/3 that of PPD-S. (2) There was a marked difference in the tuberculin reactivity to TAP and PPD-S between guinea pigs immunized with killed bacilli and guinea pigs immunized with living bacilli.     

缺氧条件下FMMU白化豚鼠和杂色豚鼠心肌线粒体形态变化比较研究

目的　比较研究在缺氧条件下FMMU白化豚鼠和杂色豚鼠心肌线粒体的形态变化。方法　将FMMU白化豚鼠和杂色豚鼠置于常压缺氧舱内分别缺氧 7d、14d、2 1d ,复制常压缺氧模型 ,分别取FMMU白化豚鼠和杂色豚鼠心肌 ,电镜下观察心肌线粒体形态的变化。结果　在同一缺氧时间 ,二者的超微结构变化程度不同 ;在不同缺氧时间 ,同种豚鼠的变化程度也不同。结论　在缺氧条件下 ,FMMU白化豚鼠心肌线粒体的变化程度较杂色豚鼠轻 ,提示可能白化豚鼠对缺氧的耐受性优于杂色豚鼠