Female Hartley Guinea Pigs Research Articles

Antioxidants in bronchoalveolar lavage fluid cells isolated from ozone--exposed normal and ascorbate-deficient guinea pigs.

Previous studies have indicated that systemic deficiency in one of the critical antioxidants, ascorbate, does not significantly exacerbate ozone-induced lung injury and changes in lung antioxidants following longer-term exposure. Because alveolar cells encounter the highest ozone dose upon exposure and lack direct blood supply, systemic ascorbate deficiency may exacerbate ozone response on antioxidants within these cells. Female Hartley guinea pigs (30 days old) were fed either a regular guinea pig chow or chow that lacked ascorbate. The dietary regimen was started 1 week prior to exposure, continued through ozone exposure (0, 0.2, 0.4, or 0.8 ppm, 23 h/day, 1 week), and during 1 week recovery in clean air following exposure. Immediately after 1 week of exposure or recovery, lungs were lavaged and cells were counted in bronchoalveolar lavage fluid (BALF). Protein, ascorbate, uric acid, total glutathione (GSH), and alpha-tocopherol were analyzed in these cells. Ozone caused an increase in total BALF cells and total cellular protein after 0.4 and 0.8 ppm ozone. The increase was more pronounced in ascorbate-deficient guinea pigs. Protein per million cells, however, was not changed by ozone or diet. In ascorbate-sufficient guinea pigs, ascorbate levels were increased only after 0.2 ppm ozone. However, uric acid (at 0.4 and 0.8 ppm ozone) and GSH (at all concentrations of ozone) levels were increased in both dietary groups. Ascorbate deficiency did not affect basal uric acid or GSH levels in BALF cells. There was a small diet-related depletion in cellular alpha-tocopherol. Ozone exposure also decreased alpha-tocopherol regardless of diet. The above changes except for alpha-tocopherol appeared to be reversed after 1 week of recovery in both dietary groups. In summary, ozone is capable of inducing a mechanism that increases antioxidants such as ascorbate, GSH, and uric acid. GSH and uric acid are not affected by ascorbate deficiency, but alpha-tocopherol is depleted. GSH and uric acid may be critical in ozone-induced adaptation during ascorbate deficiency.

Antigenicity tests of a new antineoplastic agent S-1

The antigenicity was tested of a new antineoplastic agent S-1 (a combination of tegafur (FT), CDHP and potassium oxonate (Oxo)) in mice and guinea pigs. 1. Male BALB/c or C3H/He mice were sensitized with S-1, CDHP, Oxo, and conjugates of CDHP (or Oxo) and human serum albumin (HSA). S-1 was administered by oral gavage, and the other compounds were administered intraperitoneally with adjuvant (alum). In the heterologous passive cutaneous anaphylaxis (PCA) test, using Sprague-Dawley rats as recipients, no IgE antibodies against S-1, CDHP, or Oxo were detected to any serum obtained from the sensitized mice, and no eliciting antigenicities were seen for CDHP or Oxo. 2. Male Hartley guinea pigs were sensitized with S-1, CDHP, Oxo, and conjugates of CDHP (or Oxo) and HSA. S-1 was administered by oral gavage, and the other compounds were administered subcutaneously with Freund's complete adjuvant (FCA). The homologous PCA test, active systemic anaphylaxis test, and passive hemagglutination test showed no production of antibodies against S-1, CDHP, or Oxo in any sensitized guinea pig, and no eliciting antigenicities for CDHP or Oxo. 3. Female Hartley guinea pigs were sensitized with S-1 subcutaneously with FCA. The active cutaneous anaphylaxis test revealed that S-1 did not induce cell-mediated delayed type hypersensitivity. 4. These results indicated that S-1, Oxo, and CDHP were not antigenic in mice and guinea pigs.

Ozone-induced tissue injury and changes in antioxidant homeostasis in normal and ascorbate-deficient guinea pigs

It has been reported previously that ozone (O 3) toxicity from acute (4 hr) exposure is enhanced by ascorbate (AH 2) deficiency in guinea pigs. We hypothesized that lung injury from continuous 1-week O 3 exposure would also be increased under conditions of AH 2 deficiency because of (1) a diminished antioxidant pool to counteract the oxidant challenge, (2) impaired reparation of tissue injury, and/or (3) altered antioxidant redox homeostasis. Female Hartley guinea pigs (260–330 g) were made AH 2 deficient by providing a diet similar to guinea pig chow, but having no AH 2. The dietary regimen was started 1 week prior to exposure and was continued during exposure to O 3 (0, 0.2, 0.4, or 0.8 ppm, 23 hr/day, 7 days) as well as 1 week post-exposure. Bronchoalveolar lavage (BAL) and tissue AH 2 were measured in subgroups at the beginning of exposure (1 week on the AH 2-deflcient diet), at its termination and 1 week post-exposure. AH 2 measured in ear tissue punches proved to be an easy and effective monitor for AH 2 deficiency. One week on the AH 2-deficient diet caused a 70–80% drop in ear, lung and liver AH 2, while AH 2 in BAL was decreased by 90%. Immediately after the exposure, total BAL protein and albumin (markers of lung permeability) were increased (~50%) at 0.8 ppm with no difference between the dietary groups. O 3 caused an increase in total BAL cells and neutrophils in a concentration-dependent manner with only a slight augmentation due to diet. Exposure to O 3 caused an increase in lung and BAL AH 2 in normal guinea pigs. Glutathione and uric acid were also increased in the lung and BAL after O 3 exposure (40–570%) in both dietary groups, and the levels remained elevated during the recovery period. Lung α-tocopherol was not changed due to O 3. A significant overall diet-related decrease was seen in AH 2-deficient guinea pigs, immediately after the exposure and recovery. In summary, lung injury/inflammation following 1 week O 3 exposure and recovery were minimally affected by AH 2 deficiency. Antioxidants also appeared to increase in response to O 3 exposure despite the deficiency in AH 2.

Use of the Guinea Pig Flank Flap in Skin Flap Research

A variety of flaps in laboratory animals have been designed that propose to parallel the behavior of human skin under different experimental conditions. In the search for a readily available and affordable island skin flap model that combines reliable anatomy with a pedicle of substantial size, we have designed in the guinea pig a cutaneous flap based on the superficial circumflex iliac artery and vein. In 22 adult female Hartley guinea pigs, an 8 x 4 cm flank flap based on the superficial circumflex iliac pedicle was raised, and its characteristics were evaluated for applications to skin flap research. Dermofluorometric studies were performed that confirm the vascularity of this flap, and 100% survival of the flap was seen 5 days after surgery in all animals. Of particular benefit was the demonstration that both afferent and efferent blood samples can be taken from the pedicle directly, which allows for the direct quantification of plasma markers after physiologic insults to the skin flap, such as burn or ischemia. This anatomically reliable and easily dissected flap lends itself well to preliminary skin flap research and may contribute to standardization of a model for further studies examining the behavior of skin microcirculation under adverse physiologic conditions.

Use of the guinea pig flank flap in skin flap research

A variety of flaps in laboratory animals have been designed that propose to parallel the behavior of human skin under different experimental conditions. In the search for a readily available and affordable island skin flap model that combines reliable anatomy with a pedicle of substantial size, we have designed in the guinea pig a cutaneous flap based on the superficial circumflex iliac artery and vein. In 22 adult female Hartley guinea pigs, an 8×4 cm flank flap based on the superficial circumflex iliac pedicle was raised, and its characteristics were evaluated for applications to skin flap research. Dermofluorometric studies were performed that confirm the vascularity of this flap, and 100% survival of the flap was seen 5 days after surgery in all animals. Of particular benefit was the demonstration that both afferent and efferent blood samples can be taken from the pedicle directly, which allows for the direct quantification of plasma markers after physiologic insults to the skin flap, such as burn or ischemia. This anatomically reliable and easily dissected flap lends itself well to preliminary skin flap research and may contribute to standardization of a model for further studies examining the behavior of skin microcirculation under adverse physiologic conditions. (OTOLARYNGOL HEAD NECK SURG 1995;112:723-7.)

Reduced fat deposition in female guinea pigs fed an atherogenic diet

In guinea pigs fed atherogenic diets lipid metabolism is altered and atherosclerosis develops. The purpose of this study was to examine adipose fat storage in female Hartley guinea pigs fed for six weeks either a control (CON) or atherogenic (ATH) diet. Growth, body weight gain, and food intake (kcal/day) were not significantly different in the two groups. Total body fat was significantly higher in the CON (14.4±0.4 %) than for the ATH fed group (11.6±0.7 %). Three adipose depots were examined: inguinal, parametrial, and retroperitoneal. The sum of three depots was significantly smaller in the ATH (4.1 ± 0.1 g, mean ± SEM) group compared to the CON (6.7 ± 1.0 g) group. Fat cell size was significantly smaller in the inguinal depot from the ATH group compared to the CON group. Livers were twice as large in the ATH group compared to the CON group, and contained 6-fold more total lipid. Total plasma cholesterol increased nearly four fold during the first week of dietary treatment in the ATH group. Plasma triglyceride values were similar during the six weeks in the two groups. Thus, adipose fat deposition was reduced, and fat accumulated in the liver of the ATH diet fed group. These results suggest the ATH fed guinea pigs had a reduced ability to transport fat from the liver to adipose tissue or an enhanced ability to transport lipid from adipose tissue to the liver.

Ozone-Induced Pulmonary Functional, Pathological, and Biochemical Changes in Normal and Vitamin C-Deficient Guinea Pigs

Ozone-Induced Pulmonary Functional, Pathological, and Biochemical Changes in Normal and Vitamin C-Deficient Guinea Pigs. Kodavanti, U. P., Hatch, G. E., Starcher, B., Giri, S. N., Winsett, D., and Costa, D. L. (1995). Fundam. Appl. Toxicol. 24, 154-164.Since Vitamin C (ascorbate, AH2) is an important airway antioxidant and is an essential component of tissue repair, and since acute (4 hr) O3 toxicity is enhanced by AH2 deficiency, we hypothesized that longer-term O3 effects might also be increased. Female Hartley guinea pigs (260-330 g) were fed either and AH2-sufficient or an AH2-deficient diet 1 week prior to exposure, and were maintained on their respective diets during 1 week of continuous exposure to O3 (0, 0.2, 0.4, and 0.8 ppm, 23 hr/day), and during 1 week postexposure recovery in clean air. The AH2-deficient diet caused lung AH2 to drop to about 30% of control in 1 week, and to below 10% by the end of exposure and recovery. Body weight gains during exposure were decreased in the 0.8 ppm O3 group, while the AH2 deficiency began to affect body weights only during recovery. O3 caused a concentration-dependent decrease in total lung capacity, vital capacity, carbon monoxide diffusing capacity, nitrogen washout, and static compliance, while increasing forced expiratory flow rates and residual or end-expiratory volume (suggestive of pulmonary gas-trapping). The lung/body weight ratio and fixed lung displacement volume were also increased in O3-exposed animals. Lung pathology consisted of mononuclear cell and neutrophil infiltration, airway as well as alveolar epithelial cell hyperplasia, and general decrease in epithelial cell cytoplasm. Thickening of the interstitium and an apparent increase in collagen staining were seen at the terminal bronchiolar regions. Some of these effects were marginally exacerbated in AH2-deficient guinea pigs. One week postexposure to air reversed all O3-induced abnormalities, irrespective of AH3 deficiency. Whole lung hydroxyproline and desmosine were not changed at any time by either O3 or AH2 deficiency. Measurement of lung prolyl hydroxylase activity suggested that AH2 deficiency as well as O3 exposure may have increased the tissue levels of this enzyme. The lack of a significant increase in toxicity with the longer-term exposure scenario suggests that AH2 has minimal influence on other compensatory mechanisms developed over time.

Ultrastructural changes in the cochlea of the inner ear in guinea pigs with hypercholesterolemia

Although sensory neural hearing loss stemming from hypercholesterolemia has received attention in recent year, nothing has been made known about inner ear injuries resulting from this condition.In this study, we prepared guinea pig models with hypercholesterolemia and observed inner ear with a transmission electron microscope, and also investigated the effect of vitamin E therapy on injuries.Materials and Methods: Ninetyth white female Hartley guinea pigs weighing 250-300g each were divided into three groups. Group A consisted of the control animals, which were fed by a stock diet. Group B was fed by a hyperlipid diet (2.5% cholesterol, 0.25% bile acid, and 7.5% cattle fat). Group C was given a vitamin Eadded hyperlipid diet. All animals were sacrificed at either one, two or three months after treatment, and cochlear duct vasculature was observed with a transmission electron microscope. Cholesterol, triglyceride, and TBARS values were concurrently measured in serum.Results: In group B and C, cholesterol and triglyceride levels remainedon control levels. The TBARS level was elevated in group B but remained unchanged in groups A and C.

Assessment of a selective inhibitor of herpes simplex virus thymidine kinase (L-653,180) as therapy for experimental recurrent genital herpes.

Herpes simplex virus (HSV)-coded thymidine kinase (TK) is important in efficient reactivation of latent infection. These studies were designed to investigate whether treatment of latently infected animals with a TK inhibitor altered the natural history of recurrent HSV disease. 9-([(Z)-2-(hydroxymethyl)cyclohexyl]methyl) guanine (L-653,180) is a potent and selective nonsubstrate inhibitor of HSV TK which can suppress or delay reactivation of HSV-1 from latently infected cells in vitro without affecting viral replication. In an initial study, six female Hartley guinea pigs were treated with L-653,180 in their diet (25 mg/30 g of food) and water (300 mg/liter) for 7 days. Blood, urine, kidney, liver, spinal cord, and cerebral cortex specimens were collected. L-653,180 was detected in all specimens at concentrations which, although low, were higher than the in vitro 50% inhibitory concentration of the drug against HSV TK. In the second study, 20 female Hartley guinea pigs were randomized into two groups following recovery from primary genital HSV-2 infection. One group received L-653,180 in diet and water for 4 weeks beginning 21 days postinoculation. Animals were examined daily for recurrent lesions for 10 weeks. Treated animals experienced fewer recurrences during the treatment period but the results were not significantly different from results with controls. During the first 2-week posttreatment period, L-653,180-treated animals had significantly fewer recurrences than control animals (P = 0.02). Over the entire 10-week observation period, treated animals experienced fewer recurrences (P = 0.06). These results suggest that inhibitors of viral TK may be useful in limiting reactivation of latent virus and thus recurrent infections. In these experiments, the amount of drug that could be administered to the animals was limited by its poor solubility. Further studies with more potent and soluble inhibitors of HSV TK appear to be warranted.

Drug-specific immune responses induced by procainamide, hydralazine and isoniazid in guinea-pigs

The drug-induced graft vs host reaction (GVHR) hypothesis requires, as the first step, specific T-cell immune responses to the drug-modified self. Procainamide, isoniazid and hydralazine are known to provoke various allergic reactions including GVHR-like adverse effects in man. We now report that drug-specific immune responses can easily be included by these drugs in guinea-pigs. Twenty-five milligrams of each of these drugs and penicillin G, which is known to make covalent bonds with proteins and to also induce drug-specific immune responses, were mixed complete Freund's (CFA) and subcutaneously (s.c.) injected twice at an interval of 2 weeks into female Hartley guinea-pigs. The antibodies to these drugs were assessed by means of an enzyme-linked immunosorbent assay (ELISA). Two weeks after the last injection, all animals treated with isoniazid, hydralazine and penicillin G produced high titers of antibodies to these drugs. Antibodies to procainamide were also detected, although their antibody titers were low. The specificity of the antibodies produced were tested by the inhibition of ELISA and concentration-dependent inhibition was observed. Delayed type hypersensitivity (DTH) reactions were also observed in the animals treated with procainamide, isoniazed and hydralazine 2 weeks after the last injection. The results suggest that the allergic reactions observed in clinical use ate related to the inducing potential of drug-specific immune responses in an animal system. therefore, immunization of guinea-pigs with test drugs and CFA may give useful information for predicting the occurence of allergic reactions in man.

Broncasma Berna®下気道への影響-組織学的・免疫学的検討

Female Hartley guinea pigs (SPF) were divided into three groups. In the first group, Broncasma Berna®(B. B. ) solution was administered by Jet nebulization every day for one week and this treatment was repeated after an interval of seven days during a four-week period. In the second group,0.4% phenolsolution was administered acccording to the same schedule as the first group. The third group was the control group which received no treatment.Histologically, the lower airway did not show any changes suggesting inflammation such as bronchitis following the administration of B. B. Anti-B. B. antibody could not be clearly detected either in serum or in bronchial washing by ELISA or PCA reaction.On the other hand, the cells from paratracheal lymph nodes in the first gro u p exhibited a higher response to PHA than those in the other groups. Also, the culture medium of lung macrophages enhanced the proliferation of the fibroblasts.The in vitro study with human blood leukoc y tes or with normal human nasal mucosa, enhanced expression of TNF a was observed after the administration of B. B.These findings suggest that B. B. inhalation with Jet nebulization is safe a nd that B. B. influences the products of TNF a in the nasal mucosa.

Protection against anthrax with recombinant virus-expressed protective antigen in experimental animals

We previously described the cloning and expression of the protective antigen (PA) gene of Bacillus anthracis in both vaccinia virus and a baculovirus. The antigenicity of the PA products was characterized. PA expressed by the recombinant vaccinia viruses elicited a partial protective immune response against a lethal B. anthracis spore challenge in guinea pigs and mice. The WR strain vaccinia virus recombinant (WR-PA) protected 60% of male mice and 50% of guinea pigs. WR-PA elicited high anti-PA antibody titers in mice but not in guinea pigs. Connaught strain vaccinia virus recombinants failed to protect any immunized animals. PA purified from baculovirus recombinant-infected cultures plus adjuvant partially protected male CBA/J mice and completely protected female Hartley guinea pigs from challenge. Both the recombinant and nonrecombinant PA preparations combined with adjuvant elicited high anti-PA antibody titers in Hartley guinea pigs and CBA/J mice. These data demonstrate that the recombinant baculovirus- and vaccinia virus-produced PAs were immunogenic in both guinea pigs and mice, that the baculovirus-PA recombinant was a useful source of immunogenic PA, and that vaccinia virus-PA recombinants may be feasible live anthrax vaccine candidates worthy of consideration for further development as live vaccines.

Increased Gut Permeability Following Burn Trauma

Twenty female Hartley guinea pigs, weighing 350 to 400 g, were given a 30% full-thickness burn injury. Gastrointestinal permeability was assessed before burn and on postburn days 1 through 3, 7, and 14 by administering 5 mL of an isotonic mixture of 8% lactulose and 1.15% L-rhamnose by gavage and measuring the urinary excretion for the next 7 hours. In normal guinea pigs, lactulose (molecular weight, 342d) is mostly absorbed by the paracellular route, whereas L-rhamnose (molecular weight, 164 d) is mostly absorbed by the transcellular route. Gut permeability to L-rhamnose did not increase after burn injury (211 micrograms before burn vs 230, 260, 180, 238, and 221 micrograms on days 1, 2, 3, 7, and 14, respectively, after burn). By contrast, gut permeability to lactulose increased significantly and was greatest in the first 48 hours after burn injury (60 micrograms before burn vs 380, 354, 203, 364, and 279 micrograms on days 1, 2, 3, 7, and 14, respectively, after burn). Gut permeability to low-molecular-weight compounds increases immediately after burn trauma, and this may be by a paracellular rather than transcellular mechanism.

Influence of Weight on Pulmonary Function in the Adult Guinea Pig

We examined a group of 63 adult female Hartley strain guinea pigs with weight ranging from 625 to 1,200 g in order to ascertain whether pulmonary function tests including lung volumes, pressure-volume curves, and flow-volume curves were affected by the weight of the animal. We found that there was a weight effect on total lung capacity, vital capacity, residual volume, and the forced expiratory flow between 25 and 75% of total lung capacity, although there was no effect on other parameters of airflow. Flow-volume curves for each animal could be accurately fitted to a mathematical equation, and this equation did not vary with the animals' weight. Pressure-volume curves were affected by animal weight, but could be accurately fitted to a weight-corrected equation. We conclude that when pulmonary function tests are performed on adult guinea pigs, lung volumes may be altered in proportion to the weight of the animal. When pressure-volume or flow-volume curves are being considered, although weight can either be corrected for or has no bearing on the shape of the curve, there is a large between-animal variation, and it may be necessary to use large experimental groups when it is impossible to use the same animal as its own control.

Contribution of Upper Airways to Antigen-induced Late Airway Obstructive Responses in Guinea Pigs

The pathogenesis of the late asthmatic response has been of interest due to the fact that its development has been associated with airway obstruction, airway inflammation, and airway hyperresponsiveness: all features of chronic asthma. In order to study more precisely late responses, a number of animal models have been developed. Previous reports have described alterations in airway mechanics at both 3 to 6 and 17 h after antigen challenge in sensitized guinea pigs. In these experiments, however, animals were challenged through the nose with aerosolized antigen, and airway conductance was measured using whole body plethysmography while the animals breathed through the upper airways. In rats similarly challenged, the predominant immediate change in resistance occurs in the upper airways. The purpose of this study, therefore, was to evaluate the contribution made by both the upper and lower airways to late changes after allergen challenge in guinea pigs. Outbred female Hartley guinea pigs were actively or passively sensitized (IgG1 antibody response) to three different antigens and challenged either by direct tracheal insufflation (sheep gamma globulin [SGG] or oxazolone-human serum albumin [OX-HSA]) or by aerosolization (ovalbumin [OA]). Lung resistance (RL) and dynamic compliance (Cdyn) were measured in anesthetized guinea pigs through a tracheostomy tube, and specific airway conductance (SGaw) was measured in unanesthetized, nose-breathing guinea pigs using a whole body plethysmograph. Late responses were defined as a RL greater than the mean + 2 SD RL or as a decrease in SGaw from baseline greater than 2 SD from the placebo-challenged (bovine serum albumin) group.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine Supplementation and Its Effect on Established Peritonitis in Guinea Pigs

To evaluate the efficacy of supplemental arginine with nutritional support in the presence of sepsis, eighty-eight gastrostomized female Hartley guinea pigs were implanted with osmotic pumps effusing an Eschericia coli/Staphylococcus aureus mixture. Animals were randomized and infused for two weeks with isocaloric and isovolumetric diets containing 0%, 2%, 4%, or 6% supplemental arginine as arginine hydrochloride. Survival was 12/22 (54%) in 0%, 9/22 (41%) in 2% and 4%, and 2/22 (9%) in 6%. Analysis by chi-square test of independence was significant (p = 0.0141) with 6% survival lower than the others. Median survival was 11 days in 0%, 8 days in 2% and 6%, and 9 days in 4%. Median survival was longer in 0% than in 2% or 6% (Kruskal-Wallis ANOVA: p = 0.02). Nitrogen balance was significantly lower in 6% compared to 0% on days 2 through 10, and lower than 2% and 4% on days 6 and 9. Nitrogen balance was higher in 0% than in 2% on days 4, 6, 10, and 13. Serum albumin and C3 were lower in all experimental groups than normal controls (ANOVA: p = 0.01). Comparison of liver, spleen, adrenals, gastrocnemius, and carcass weights, cell-mediated immunity as determined by contact sensitivity to DNFB, and transferrin showed no significant differences. There was a positive dose-response effect seen amongst the experimental groups for the amino acids arginine, ornithine, and citrulline in relation to the amount of supplemental arginine. This study suggests that dietary arginine supplementation does not enhance survival in a guinea pig model of established peritonitis.

Dietary iron and recovery from peritonitis in guinea pigs

Ninety female Hartley guinea pigs underwent gastrostomy placement. One week later they underwent implantation of an osmotic pump, which allowed constant delivery of bacteria into the peritoneal cavity. Three days after pump implantation the animals were begun on enteral diets differing only in iron content (the None [no Fe], Low [1 X RDA], and High [10 X RDA] groups). When survivors were killed no differences were found in body, carcass, or organ weights among the three groups. Serum Fe and percent Fe-binding sites occupied were significantly lower in the None group although total Fe-binding capacity was similar. Mortality was not statistically different (p = 0.29): 18/32 in the None group (56%), 14/24 in the Low group (58%), and 25/34 in the High group (73%). We conclude that although deprivation of dietary sources of Fe does affect available circulating Fe, diet-induced hypoferremia does not alter mortality rates from bacterial peritonitis in the guinea pig.

Colonic impaction in guinea pigs fed a chemically defined diet: a case report.

Pathogen-free female Hartley guinea pigs were divided into four diet groups to determine optimal nitrogen requirements for growth, pregnancy and lactation. Three chemically defined test diets varying in total nitrogen were compared with commercial guinea pig feed. Within 13 days, 24 of 78 animals from the three test diet groups died or required euthanasia. Affected guinea pigs were depressed, lost weight and had distended abdomens. Distension, impaction and, in most cases, rupture of the spiral of the ascending colon and subsequent peritonitis were observed at necropsy. Husbandry changes which resulted in a decreased incidence of impactions included increased acclimatization time on commercial feed post-shipping, decreased animal density per cage and cessation of water medication with oxytetracycline.

1166 INFLUENCE OF AGE ON INITIAL AND RECURENT GENITAL HERPES SIMPLEX VIRUS TYPE 2 (HSV-2) INFECTION OF GUINEA PIGS

Host factors responsible for the marked person to person variability in the clinical course of initial and recurrent genital HSV-2 infection are undefined. We utilized a guinea pig model to investigate the influence of age on initial and recurrent genital herpes. Weanling (<200 g) and adult (>350 g) female Hartley guinea pigs were intravaginally inoculated with 5.7 log10 PFU HSV-2, MS strain. During the initial infection animals were scored for genital skin disese, urinary retention, hindlimb paralysis and death. In addition, vaginal HSV-2 replication was determined by plaque titration of vaginal swab samples. Following recovery from initial infection, the animals were examined daily for at least 6 weeks to determine the frequency and severity of clinically apparent recurrent genital herpetic lesions. The virologic course of initial genital infection was similar in weanling and adult animals as was the incidence of urinary retention (90%) and mortality (40%). However, weanling animals had earlier onset and a more severe course of genital skin disease as well as a higher incidence of hindlimb paralysis (60%) than adult guinea pigs (10%) (p <.05). Despite evidence of more severe initial infection in weanling guinea pigs, the frequency and severity of recurrent infection was similar for both age groups. This study indicates that the clinical manifestations of genital HSV infection may be influenced by age and suggests that further examination of endocrinologic and immunologic differences between young and old animals may permit definition of host factors important in the clinical expression of HSV-2 disease.

Pigment gallstone formation in the cholesterol-fed guinea pig.

Female Hartley guinea pigs fed a 0.5% cholesterol-supplemented diet were found to form pigmented gallstones after 6 weeks (17/23) and 12 weeks (11/11), while only 2 of 44 animals fed a trace cholesterol diet formed gallstones over a comparable period. The light brown stones consisted primarily of aggregates of fine granular crystals, morphologically similar to calcium bilirubinate crystals. The stones were soluble in 0.1 N sodium hydroxide and were found to contain a substance which co-migrated with unconjugated bilirubin during thin-layer chromatography. Despite hypercholesterolemia (202 +/- 34 vs. 59 +/- 22 mg per dl in controls, p less than 0.05) and fatty infiltration of the liver, cholesterol-fed animals had a lithogenic index of only 0.22 +/- 0.04 in gallbladder bile as compared to a lithogenic index of 0.02 +/- 0.01 in animals fed the trace cholesterol diet. Accordingly, no cholesterol monohydrate crystals were found in any animals. Hematocrits among cholesterol-fed animals (47.6 +/- 1.2%) were lower than those of controls (54.8 +/- 1.3%, p less than 0.05) probably as a result of the cholesterol-induced hemolytic anemia which has been reported by others in this species. Fasting gallbladder volume was greater in cholesterol-fed animals (2.4 +/- 0.18 ml) than in controls (1.7 +/- 0.11, p less than 0.0025), and a comparable increase in gallbladder dry tissue mass was found. There was no evidence of biliary obstruction, however, and the gallbladder contractile response to octapeptide cholecystokinin was comparable in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)