Observations on the Parathyroid Glands of Guinea Pigs Affected with Metastatic Calcification

Soft tissue calcification in guinea pigs has been attributed to a mineral imbalance, especially a relative or absolute magnesium deficiency. An associated chronic tubular nephritis has been reported and was substantiated in the present study. The location of the parathyroid glands of guinea pigs was established, and their size estimated by microscopic methods. The size and morphologic characteristics of parathyroids of guinea pigs affected with metastatic calcification were indistinguishable from parathyroids of healthy guinea pigs.     

Tissue levels of metaraminol and its metabolite, α-methylnorepinephrine,in control and 6-hydroxydopamine-pretreated guinea pigs

In guinea pigs, metaraminol disappeared from heart and liver during the first 4 days after its injection with a half-life of 31 and 30 hrs, respectively. In guinea pigs pretreated with 6-hydroxydopamine 24 hrs before metaraminol injection, tissue levels of metaraminol were lower, and the half-life was shortened to about 10 hrs in heart and 12 hrs in liver. Norepinephrine levels in 6-hydroxydopamine-treated guinea pigs were reduced by 93 percent in heart and 90 percent in liver, indicating nearly complete chemical sympathectomy in these tissues. α-Methylnorepinephrine, whose $\text{in vitro}$ formation by guinea pig liver homogenates previously had been shown to occur unchanged after 6-hydroxydopamine treatment, was present in heart and liver at lower levels in 6-hydroxydopamine-pretreated guinea pigs than in controls. The half-life of α-methylnorepinephrine both in heart and in liver was 39 hrs in control guinea pigs. In 6-hydroxydopamine-pretreated guinea pigs, α-methylnorepinephrine disappeared too rapidly to permit half-life estimation. These data support the idea that metaraminol and α-methylnorepinephrine are retained in noradrenergic fibers and that this retention is a dominant factor in their rates of disappearance from tissues.     

Diethylaminoethoxyhexestrol causes hypertriglyceridemia in guinea pigs

Treatment of rats, monkeys and man with diethylaminoethoxyhexestrol causes phospholipid storage in liver and other tissues. However, this drug has not been reported to alter plasma lipoprotein levels. When guinea pigs were treated with diethylaminoethoxyhexestrol, the fasting plasma triacylglycerol levels increased dramatically, from 43 to 1281 mg/dl, after only five doses of 12.5 mg/kg. Diethylaminoethoxyhexestrol-treated guinea pigs had reduced postheparin lipase activity. In addition, in vitro assays showed that this agent inhibited guinea pig postheparin lipoprotein lipase. It is hypothesized that diethylaminoethoxyhexestrol causes hypertriglyceridemia in guinea pigs because these animals are known to have low levels of serum activator for lipoprotein lipase and may be unusually susceptible to agents that inhibit lipoprotein lipase activity. The ability to produce hypertriglyceridemia in guinea pigs provides an animal model in which the metabolic consequences of hypertriglyceridemia can be studied.     

Immunogenicity of B-antigen in experimental plague and pseudotuberculosis

The results of the evaluation of the immunogenic properties of B-antigen, earlier identified in the culture fluid of Yersinia pseudotuberculosis submerged culture, with respect to experimental plague and pseudotuberculosis are presented. B-antigen has been shown to produce protective effect in guinea pigs and, probably, hamadryas baboons, but not in white mice infected with the causative agent of plague. Immunizaton with B-antigen protects guinea pigs from primary pneumonic plague caused by both capsule-forming and noncapsular Y. pestis virulent strains. Passive immunization with antibodies to B-antigen induces limitedly pronounced protective effect in guinea pigs and is not effective for white mice with respect to experimental plague. No active or passive protection of white mice or guinea pigs, infected with Y. pseudotuberculosis cultures, has been achieved by the injection of B-antigen or antibodies to it.     

Further regression of seminal vesicles of castrated guinea pig by administration of cyproterone acetate

It has been established that a low level of secretory activity persisted in seminal vesicles of guinea pigs long after castration and that this may be due to a higher extratesticular androgen level in this animal. A RIA study revealed that the normal serum testosterone concentration of the guinea pigs was comparable to that of the rats, but the basal serum testosterone level after castration was ten times higher than rats under a similar condition. It was also shown that cyproterone acetate did not significantly lower the basal serum testosterone concentration in the castrated guinea pigs. The higher basal serum testosterone level is believed to be responsible for the slow and incomplete regression of this gland in the guinea pigs. There was a significant reduction in wet weight of the seminal vesicles after the treatment of castrated guinea pigs with cyproterone acetate. Ultrastructural study showed that there were both qualitative and quantitative changes in the cytoplasmic organelles. The Golgi apparatus further reduced in size and in the number of associated vesicles and vacuoles. There was a marked decrease in the number and size of secretory granules and lysosomes and an increase in the degree of undulation of the basement membrane. Accumulation of lipid droplets and glycogen was commonly observed. All these morphological evidences showed that further regression of the castrated guinea pig seminal vesicles can be achieved by cyproterone acetate treatment.     

无菌豚鼠与普通豚鼠血液学参数的比较

目的对普通级豚鼠进行剖宫产,培育无菌豚鼠模型,并比较无菌豚鼠和普通级豚鼠的血液学参数。方法行子宫摘除术摘除子宫,在无菌隔离器中将子宫剥离取仔,用人工哺乳的方法将仔豚鼠培育成无菌豚鼠,并在固定的周期检测豚鼠的无菌情况。采用全血细胞计数分析仪、全自动血液生化分析仪测定无菌豚鼠、普通豚鼠的血常规和血生化参数。用SPSS12.0进行统计分析。结果无菌豚鼠和普通豚鼠在白细胞(WBC)、嗜碱性粒细胞数(BA#)、单核细胞百分比(MO)、血红蛋白浓度(MCHC)、中性粒细胞数(NE#)、嗜酸性粒细胞数(EO#)、淋巴细胞数(LY#)七个血常规指标上有差异显著性,其他指标没有显著性差异;谷丙转氨酶(ALT)、乳酸脱氢酶(LDH)、总蛋白(TP)、白蛋白(ALB)、葡萄糖(GLU)、总胆固醇(CHO)、总胆红素(TBIL)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、球蛋白(GLO)、A/G、K、Na、谷酰转肽酶(GGT)15个指标上差异有显著性,其他指标差异无显著性。结论通过规范的子宫摘除术和人工喂养的方法获得符合标准的无菌豚鼠,与普通豚鼠在多项血液学指标上差异有显著性。     

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.     

Characterization of the major immunogen in the excretory-secretory products of exsheathed third-stage larvae of Trichostrongylus colubriformis

The excretory-secretory products of exsheathed third-stage larvae of Trichostrongylus colubriformis conferred some protection to guinea pigs against homologous challenge. A glycoprotein with an apparent molecular mass of approximately 94 kDa was the dominant immunogen in post-exsheathment products. Immunoblots revealed IgG antibodies to this glycoprotein in sera from multiply-infected guinea pigs and some sheep, and in sera of guinea pigs after three truncated infections which had been restricted by anthelmintic treatments to development of the third parasitic stage. IgA antibodies to this protein were also found in intestinal lymph of a naturally infected sheep. Fluorescent antibody studies indicated that this 94 kDa component was associated with cells in the central body cavity of third-stage larvae, but was absent from fourth-stage larvae or adult worms. Fractionation and protection assays in guinea pigs revealed that while the native and aggregated 94 kDa protein conferred some host protection, it was not the only protective component of the excretory-secretory products of exsheathed third-stage larvae of T. colubriformis.     

Synergistic effects of active specific immunotherapy and chemotherapy in guinea pigs with disseminated cancer

Sewall Wright strain 2 guinea pigs bearing pulmonary metastases of the syngeneic line 10 (L10) hepatocarcinoma were treated with a vaccine composed of 10(7) bacillus Calmette-Guérin admixed with 10(7) x-irradiated L10 tumor cells beginning 10 days after tumor inoculation. Although this treatment failed to cure most of the guinea pigs of their metastatic disease, histologic examination of the pulmonary tumors in the vaccinated guinea pigs provided evidence of a cell-mediated hypersensitivity response that disrupted the normally compact architecture seen in control tumors. When a monoclonal antibody against the L10 tumor was injected i.v. to evaluate the vascular permeability of the tumors, significantly more antibody localized in tumors of vaccinated guinea pigs than in tumors of untreated controls. These results suggested that blood-borne substances could be delivered more efficiently to L10 metastases after the tumor-bearing guinea pigs had been treated with vaccine. To determine whether such increased vascular permeability would enhance the antitumor effects of chemotherapeutic agents, combined immunotherapy and chemotherapy studies were performed. Although cyclophosphamide treatment by itself did not cure L10-bearing guinea pigs, cyclophosphamide used in conjunction with prior immunotherapy increased the survival rate of animals to more than twice that of animals treated with immunotherapy alone (74 vs 33%). These results suggest that one mechanism by which active specific immunotherapy enhances chemotherapy of disseminated tumors is by rendering tumor foci more permeable to subsequently administered cytotoxic drugs.     

Differential effects of maturation on nicotinic- and muscarinic receptor-induced ion secretion in guinea pig distal colon

The incidence of constipation increases with age. This has been linked to age-related changes in the structure and function of myenteric neurons regulating intestinal motility; however, the role of submucous neurons is unknown. The aim of this study was to determine the effect of maturation on cholinergic receptor-induced ion secretion in guinea pig colon. Changes in the short-circuit current (Isc) and tissue conductance were monitored in muscle-stripped colonic segments from young (3-4-month-old) and mature (12-15-month-old) male guinea pigs. Thirty-one percent of colonic segments from young guinea pigs exhibited ongoing neural activity, which was absent in mature animals. Baseline Isc was significantly higher only in young guinea pig tissues with ongoing activity. Tissue conductance was similar in all tissues. Electrical field stimulation caused a biphasic increase in the Isc. At 15 V/10 Hz, only Peak 1 was attenuated, whereas both peaks were reduced in mature guinea pigs at 10 V/5Hz. 1,1, dimethyl-4-phenyl-piperazinium(DMPP)-induced ion secretion was blunted in mature guinea pigs. Atropine reduced the 1,1, dimethyl-4-phenyl-piperazinium response only in young guinea pigs. Carbachol-induced ion secretion was similar in tissues from both age groups. In conclusion, nicotinic receptor-induced secretion mediated by both cholinergic and noncholinergic secretomotor neurons was blunted; however, epithelial muscarinic receptor activity was unaltered during maturation.     

The daily pattern of heart rate, body temperature, locomotor activity, and autonomic nervous activity in congenitally bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs.

We studied the characteristics of the rhythmicity of heart rate (HR), body temperature (BT), locomotor activity (LA) and autonomic nervous activity in bronchial-hypersensitive (BHS) and bronchial-hyposensitive (BHR) guinea pigs. For this purpose, HR, BT, LA, and electrocardiogram (ECG) were recorded from conscious and unrestrained guinea pigs using a telemetry system. Autonomic nervous activity was analyzed by power spectral analysis of heart rate variability. Nocturnal patterns, in which the values in the dark phase (20:00-06:00) were higher than those in the light phase (06:00-20:00), were observed in HR, BT and LA in both strains of guinea pigs. The autonomic nervous activity in BHS guinea pigs showed a daily pattern, although BHR guinea pigs did not show such a rhythmicity. The high frequency (HF) power in BHS guinea pigs was higher than that in BHR guinea pigs throughout the day. Moreover, the low frequency/high frequency (LF/HF) ratio in BHS guinea pigs was lower than that in BHR guinea pigs throughout the day. These results suggest that parasympathetic nervous activity may be predominant in BHS guinea pigs.     

Specific antibodies to hemoglobin A1 (anti-Glu) and hemoglobin S (anti-Val) in the guinea pig: immunologic and structural correlations.

Like goats and sheep, guinea pigs can produce, in response to human sickle cell hemoglobin (beta6 Glu leads to Val), an antibody population (anti-Val) that will bind sickle cell hemoglobin but not normal hemoglobin HbA. Unlike goats and sheep, guinea pigs can produce in response to human hemoglobin A1 an antibody fraction, anti-Glu, that will not react with human sickle cell hemoglobin. These anti-Glu antibodies have been isolated by affinity chromatography and their specificity confirmed by fluorescence-quenching titrations. The sequence of the first 10 amino acids of the beta-chain of guinea pig hemoglobin has been determined. This sequence differs from those of both hemoglobin HbA and sickle cell hemoglobin by two residues, those at positions 5 and 6. This explains the similarity of the immunogenicity of this site on the two human hemoglobins when administered to guinea pigs. Both goats and sheep are identical to hemoglobin A1 at the beta-6 position.     

增加环境丰富化模具对实验豚鼠生长及行为的影响

目的在实验豚鼠饲养盒内增加梯形和管形两种不同的模具,进行环境丰富化模具对豚鼠生长及行为影响的研究。方法每组豚鼠饲养4周,每周称1次体重,记录体重变化趋势,并观察豚鼠行为变化。结果放入模具的豚鼠生长情况优越于对照组,管形模具优于其他实验组。结论增加环境丰富化模具有利于豚鼠生长,且管形模具更接近豚鼠自然洞穴状态,更加有利于豚鼠实现自然躲藏行为和良好的生长、生活。     

Comparison of adjuvants with Leishmania antigens in a guinea pig model to induce delayed-type hypersensitivity responses.

BACKGROUND AND PURPOSE: Guinea pigs have been a traditional model for studies of delayed-type hypersensitivity. They are the natural host of Leishmania enriettii and have been experimentally infected with other species of Leishmania. They have been used as a skin-test model to screen potential antigens for use in diagnostic tests for Leishmania. Use of complete Freund's adjuvant (CFA), along with whole promastigote Leishmania antigen, was necessary to sensitize guinea pigs to invoke a sufficient cell-mediated immune response. However, use of CFA has come under scrutiny by Animal Care and Use Committees due to the pathologic changes associated with its use. METHODS: Thirty-two specific-pathogen-free male Hartley guinea pigs were inoculated with Leishmania antigens alone or mixed with one of three adjuvants (CFA, TiterMax, and liposomes), and were skin tested 2 weeks later. RESULTS: For the Leishmania antigens tested, guinea pigs that received liposomes as an adjuvant had skin-test responses comparable to those of guinea pigs that received CFA. TiterMax was also tested, but cellular responses at antigen test sites were poor. CONCLUSIONS: Liposomes can be used in this model as a safe, effective adjuvant.     

Immune responses of inbred guinea pigs against random terpolymers containing L glutamic acid and L alanine.

The immune responses of the inbred guinea pig strains 2 and 13 have been determined against random terpolymers of L glutamic acid and L alanine and a third amino acid. Strain 2 guinea pigs responded against GAT10, GAT20(LLD), GAT10(NO2)15, GAT4, and GAL10. However, strain 13 guinea pigs responded only against GAT10. The explanation offered is that strain 2 guinea pigs, which have the Ir-GA gene, recognize the polymers via random GA determinants present in sufficient concentration in all of the above polymers. However, strain 13 guinea pigs recognize the GAT10 via the Ir-GT gene, and reduction in the concentration of tyrosyl residues below 10 mole % by various procedures alters the concentration of available random GT determinants necessary for interaction with the gene product of the Ir-GT gene.     

Complexity of chemical communication in mammals: urinary components mediating sex discrimination by male guinea pigs

Male guinea pigs are more attracted to urine from female guinea pigs than to urine from males. Separation of urine into fractions characterized by molecular weight and functionality through several different methods established that this discrimination and preference is based on a pattern of components which have widely different chemical character. The active compounds range from macromolecules (MW >10,000) to small, relatively volatile molecules. These studies establish a complexity in chemical signals that has not been previously documented for any other species.     

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.     

Induction of CD1-restricted immune responses in guinea pigs by immunization with mycobacterial lipid antigens

Group 1 CD1 molecules have been shown to present lipid and glycolipid Ags of mycobacteria to human T cells. However, a suitable animal model for the investigation of this component of antimycobacterial immunity has not yet been established. Previously, we found that guinea pigs express multiple isoforms of group 1 CD1 proteins that are homologous to human CD1b and CD1c. In this study, we show that CD1-restricted T cell responses can be generated in guinea pigs following immunization with lipid Ags from Mycobacterium tuberculosis. Splenic T cells from lipid Ag-immunized guinea pigs showed strong proliferative responses to total lipid Ags and partially purified glycolipid fractions from M. tuberculosis. These lipid Ag-reactive T cells were enriched in CD4-negative T cell fractions and showed cytotoxic activity against CD1-expressing guinea pig bone marrow-derived dendritic cells pulsed with M. tuberculosis lipid Ags. Using guinea pig cell lines transfected with individual CD1 isoforms as target cells in cytotoxic T cell assays, we found that guinea pig CD1b and CD1c molecules presented M. tuberculosis glycolipid Ags to T cells raised by mycobacterial lipid immunization. These results were confirmed using a T cell line derived from M. tuberculosis lipid Ag-immunized guinea pigs, which also showed CD1-restricted responses and cytolytic activity. Our results demonstrate that CD1-restricted responses against microbial glycolipid Ags can be generated in vivo by specific immunization and provide support for the use of the guinea pig as a relevant small animal model for the study of CD1-restricted immune responses to mycobacterial pathogens.     

Immunologic activity of myelin basic protein in strain 2 and strain 13 guinea pigs.

The resistance of Strain 2 guinea pigs to experimental allergic encephalomyelitis (EAE) induced by inoculation with whole CNS tissue in complete Freund's adjuvant (CFA) has been confirmed. The resistance is even more pronounced when myelin basic protein (BP) is used in attempts to induce EAE. Strain 2 guinea pigs are also resistant to an immunization schedule (multiple injections with BP in IFA followed by a single injection of BP in CFA) known to induce significant levels of antibody in susceptible strains. The poor response of Strain 2 guinea pigs to BP is not the result of lack of specific B cells--antibody equivalent to that produced by Strain 13 animals is obtained when the inoculum contains 0.5 mg BP and 2.5 mycobacteria.