Common Spontaneous Tumors and Tumor-like Lesions in 70 Pet Rodents and Negative MMTV Detection in Mammary Tumors.

Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary tumor virus (MMTV) is associated with mammary tumors in rodents. In this study, 77 tumors and tumor-like lesions of biopsy samples were collected from 70 pet rodents, including hamsters (n = 47), guinea pigs (n = 16), unknown species (n = 4), rats (n = 2), and a gerbil. Fifty tumors were collected from 47 hamsters, in which the most common tumors were mammary tumors (13/50), followed by fibrosarcoma (9/50), mast cell tumors (4/50), and squamous cell carcinoma (4/50). The collected subtypes of mammary tumors in hamsters included tubular carcinoma (n = 5), tubular adenoma (n = 4), carcinoma and malignant myoepithelioma (n = 1), simple tubular carcinoma (n = 1), adenosquamous carcinoma (n = 1), and tubulopapillary adenoma (n = 1). In addition, twenty tumors were collected from guinea pigs, in which the most common tumor was lipoma (6/20), followed by adenocarcinoma of the mammary gland (4/20), trichofolliculoma (2/20), and collagenous hamartomas (2/20). In guinea pigs, the subtypes of mammary gland tumors were tubular carcinoma (n = 2), tubular and solid carcinoma (n = 1), and tubulopapillary carcinoma (n = 1). In 20 cases of mammary tumors, MMTV was not detected, implicating no evidence of MMTV infection in mammary oncogenesis in pet rodents in Taiwan.

The Nutritional Value of Biowaste Bovine Slaughterhouse Meals for Monogastric Species Feeding: The Guinea Pig as an Animal Model.

Biowaste from slaughterhouses can be recovered to benefit food security and reduce contamination potential. More than 3 billion heads of livestock are consumed worldwide, which will increase by 17% by 2028, generating more biowaste, increasing infectious agents, and causing economic losses due to circular economy principles not being applied. This work evaluated the nutritional quality of four types of biowaste from bovine slaughter which were transformed into a meal for guinea pigs (rumen content (RCM), ears (EaM), blood (BM), and cheeks (CM)) according to their chemical composition, digestible components, energy contribution, and voluntary consumption. For the animal model, adult male guinea pigs were arranged in metabolic cages for feces collection without urinary contamination. Nine guinea pigs were used in each digestibility test. First, a direct digestibility test was conducted using a meal of barley as a reference diet (RD), the indigestibility coefficient of which allowed for the estimation of the digestibility of biowaste meals through indirect calculations; for this, diets composed of 80% of the RD and 20% of the corresponding biowaste meals were evaluated. The difference method was suitable for determining the digestibility of beef biowaste using the indigestibility coefficients of the reference diet to calculate the digestibility of ingredients which could not be offered as 100% of the meal but were incorporated as 20%. The digestible protein and metabolizable energy contents of RCM, EaM, BM, and CM were 10.2% and 2853 kcal/kg, 44.5% and 3325 kcal/kg, 70.7% and 2583 kcal/kg, and 80.8% and 3386 kcal/kg, respectively. The CM and BM feeds had the highest contributions of digestible protein due to their higher nitrogen content, and the CM and EaM feeds had the highest ME contents due to their higher fat contents. The biowaste meal consumption in descending order was CM > RCM > EaM > BM, which were consumed without problems. These results are indicative that these components can be part of guinea pigs' diets, and it is recommended to continue studies into guinea pig growth and fattening diets with different levels of these biowaste meals.

Ultrasonographic measurements of the normal adrenal glands in guinea pigs (Cavia Porcellus).

Hyperadrenocorticism is an uncommon but important endocrine disease in guinea pigs, but due to its subtle clinical signs and the limited information in veterinary literature, it can be underdiagnosed or misdiagnosed. Ultrasound of the adrenal glands in patients with suspected hyperadrenocorticism can help in identifying adrenomegaly. The purpose of this prospective study was to identify ultrasonographic adrenal gland dimensions in presumed healthy guinea pigs using the same standardized method described for dogs and cats. A conscious ultrasound scan was conducted on twenty client-owned, presumed healthy guinea pigs, and their adrenal glands were measured. A possible correlation between adrenal dimensions with age, sex, and body weight was investigated. The mean length, cranial and caudal pole thickness for the left and right adrenal glands were, respectively, 12.64 ± 2.11 mm and 11.55 ± 1.52 mm; 4.83 mm ± 1.03 mm and 4.69 ± 1.34 mm; 4.8 ± 1.23 mm and 4.04 ± 0.75 mm. The thickness of the left caudal pole was significantly higher than the right (P = 0.02). A significant positive correlation was found between the length of the left adrenal gland and both age (r = 0.46; P = .03) and weight (r = 0.59; P = .01). Statistical correlation between the thickness of each cranial and caudal pole, with age, sex, or weight, was not found. The dimensions provided could prove a useful tool in the clinical evaluation of guinea pigs with suspected hyperadrenocorticism.

Protective Efficacy of Lyophilized Vesicular Stomatitis Virus-Based Vaccines in Animal Model.

We evaluated the in vitro effects of lyophilization for 2 vesicular stomatitis virus-based vaccines by using 3 stabilizing formulations and demonstrated protective immunity of lyophilized/reconstituted vaccine in guinea pigs. Lyophilization increased stability of the vaccines, but specific vesicular stomatitis virus-based vaccines will each require extensive analysis to optimize stabilizing formulations.

False positive findings associated with adenoviral vector-based vaccine underscore the regulatory necessity to eliminate abnormal toxicity test.

Accumulating evidence has shown that the abnormal toxicity test (ATT) is not suitable as a quality control batch release test for biologics and vaccines. The purpose of the current study was to explore the optimal ATT experimental design for an adenoviral vector-based vaccine product to avoid false positive results following the standard test conditions stipulated in the Pharmacopoeias. ATT were conducted in both mice and guinea pigs based on methods in Pharmacopeias, with modifications to assess effects of dose volume and amount of virus particles (VPs). The results showed intraperitoneal (IP) dosing at human relevant dose and volume (i.e., VPs), as required by pharmacopeia study design, resulted in false positive findings not associated with extraneous contaminants of a product. Considering many gene therapy products use adeno associated virus as the platform for transgene delivery, data from this study are highly relevant in providing convincing evidence to show the ATT is inappropriate as batch release test for biologics, vaccine and gene therapy products. In conclusion, ATT, which requires unnecessary animal usage and competes for resources which otherwise can be spent on innovative medicine research, should be deleted permanently as batch release test by regulatory authorities around the world.

Effective skin decontamination with RSDL® (reactive skin decontamination lotion kit) following dermal exposure to a Novichok class nerve agent.

In recent years, various poisoning incidents have been reported, involving the alleged use of the so-called Novichok agents, resulting in their addition to the Schedule I list of the Organisation for the Prohibition of Chemical Warfare (OPCW). As the physicochemical properties of these agents are different from the 'classical' nerve agents, such as VX, research is needed to evaluate whether and to what extent existing countermeasures are effective. Here, we evaluated the therapeutic potential of RSDL® (Reactive Skin Decontamination Lotion Kit) for the neutralization of percutaneous toxicity caused by Novichok agents, both in vitro and in vivo. Experiments showed the three selected Novichok agents (A230, A232, A234) could be degraded by RSDL lotion, but at a different rate. The half-life of A234, in the presence of an excess of RSDL lotion, was 36 min, as compared to A230 (<5 min) and A232 (18 min). Following dermal exposure of guinea pigs to A234, application of the RSDL kit was highly effective in preventing intoxication, even when applied up until 30 min following exposure. Delayed use of the RSDL kit until the appearance of clinical signs of intoxication (3-4 h) was not able to prevent intoxication progression and deaths. This study determines RSDL decontamination as an effective treatment strategy for dermal exposure to the Novichok agent A234 and underscores the importance of early, forward use of skin decontamination, as rapidly as possible.

New flavonoids with multiple bronchodilator activity pathways from Tephrosia purpurea L. (Pers.) growing in Saudi Arabia.

Total extract of Tephrosia purpurea (T. purpurea) expressed potent ex-vivo bronchodilator effect in isolated Guinea pigs' tracheal muscles. Fractionation of T. purpurea total extract (TPTE) using liquid-liquid technique followed by ex-vivo bronchodilator testing indicated that the activity was trapped to the chloroform (CHCl3) soluble fraction. Phytochemical study of the CHCl3 fraction guided by ex-vivo bronchodilator activity led to the isolation of 7 active flavones of which compounds 1 (epi-Tephroapollin G), 3 (Acetyltephroapollin C), 4 (4''-Dehydroxytephroapollin E), and 5 (epi-Tephroapollin F) were new. Structures were identified using relevant spectroscopic tools including optical rotations and CD data. Compounds 1, 3, 4 and lanceolatin A (6) behaved like papaverine by inhibiting carbachol (CCh) as well as high potassium (K+)-mediated contractions at equivalent concentrations with varied potencies whereas (-)-Tephroapollin G (2) selectively inhibited CCh-mediated contractions but was not found active against high K+. epi-Tephroapollin F (5) and (-)-Pseudosemiglabrin (7) in contrast were significantly more potent to abolish CCh induced contraction when compared with high K+ similar to dicyclomine. Papaverine like dual phosphodiesterase enzyme Ca++ ion inhibitory activities of 1, 3, 4 and 6 were confirmed indirectly by the bolster of the isoprenaline curves against CCh to the left whereas Ca++ inhibitory effect of 1 and 3-7 was confirmed by the rightward deflection of Ca++ concentration-response curves (CRCs) towards right with quashing of the maximum response in same fashion like verapamil. Moreover, compounds 2, 5 and 7 at lower concentrations showed selective blockade of muscarinic receptor similar to atropine. Oral administration of the TPTE, CHCl3 and 7 to guinea pigs significantly protected against bronchospasm induced by 0.2 % histamine aerosol in vivo.

Outer membrane vesicles as nanovaccine candidates against pathogenic Leptospira in experimental Guinea pig model.

Leptospira interrogans serovar Hardjo is a long slender bacterium of size 0.1-0.3 µm × 5-50 µm. It is one of the major causes of bovine leptospirosis and is of economical importance because of the reproductive failure, still birth, abortion, and reduced productivity in cattle. It is also a zoonotic disease-causing infection in humans characterized by headaches, fever, chills, sweats and myalgia, lethargy, aching joints, pulmonary haemorrhages, and death in severe cases. Control of the disease involves antibiotic therapy, management and vaccination, of which immunization is the cheapest and effective means of disease prevention. The present study was developed to isolate and characterize the outer membrane vesicles of Leptospira interrogans serovar Hardjo and to evaluate their vaccine potential in guinea pig model. The OMVs were isolated from the culture by sonication and ultracentrifugation. In transmission electron microscopy, the isolated OMVs appeared as small spherical structures of 50-200 nm size. In Western blot and indirect ELISA, antibodies specific to OMVs were observed as indicative of a good humoral immune response elicited by L. interrogans serovar Hardjo OMV. The OMV-based Leptospira vaccine was able to prevent kidney lesions and renal colonization compared to the control and bacterin vaccinated group as proven by histopathology and PCR.

Antibacterial activity of plant extracts against Streptococcus equi subsp. zooepidemicus isolates from guinea pigs with lymphadenitis in Ecuador.

Lymphadenitis is a commonly occurring and contagious disease in guinea pigs caused by different pathogens, including Streptococcus sp., Staphylococcus sp., and Corynebacterium sp. This study aimed to characterize the bacteria isolated from pus extracted from abscessed mandibular lymph nodes of diseased guinea pigs in Ecuador in 2019 and evaluate the in vitro antibacterial activity of the total extracts of three plant species. Isolates were recovered from three diseased guinea pigs with Lymphadenitis on a farm in Imbabura, Ecuador province. The bacteria were characterized through microbiological, biochemical, and molecular tests as Streptococcus equi subsp. zooepidemicus. Furthermore, the susceptibility of S. equi subsp. zooepidemicus to three plant extracts belonging to the Asteraceae family, Acmella ciliata, Bidens andicola, and Gazania splendens collected in Ecuador, were assessed in vitro by the microdilution method. Our data indicate that all the evaluated extracts showed activity, with a Minimum Inhibitory Concentration (MIC) of 22.50 mg/mL for Acmella ciliata, 11.25 mg/mL for Bidens andicola, and 5.60 mg/mL for Gazania splendens. Bidens andicola extract showed the highest efficacy with a % inhibition of 63.90 at the highest tested concentration (45 mg/mL). This is the first report on the bioactivity of these plant species against S. equi subsp. zooepidemicus.

Gingival-derived mesenchymal stem cell therapy regenerated the radiated salivary glands: functional and histological evidence in murine model.

BACKGROUND: Radiotherapy in head and neck cancer management causes degeneration of the salivary glands (SG). This study was designed to determine the potential of gingival mesenchymal stem cells (GMSCs) as a cell-based therapy to regenerate irradiated parotid SG tissues and restore their function using a murine model. METHODS: Cultured isolated cells from gingival tissues of 4 healthy guinea pigs at passage 3 were characterized as GMSCSs using flow cytometry for surface markers and multilineage differentiation capacity. Twenty-one Guinea pigs were equally divided into three groups: Group I/Test, received single local irradiation of 15 Gy to the head and neck field followed by intravenous injection of labeled GMSCs, Group II/Positive control, which received the same irradiation dose followed by injection of phosphate buffer solution (PBS), and Group III/Negative control, received (PBS) injection only. Body weight and salivary flow rate (SFR) were measured at baseline, 11 days, 8-, 13- and 16-weeks post-irradiation. At 16 weeks, parotid glands were harvested for assessment of gland weight and histological and immunohistochemical analysis. RESULTS: The injected GMSCs homed to degenerated glands, with subsequent restoration of the normal gland histological acinar and tubular structure associated with a significant increase in cell proliferation and reduction in apoptotic activity. Subsequently, a significant increase in body weight and SFR, as well as an increase in gland weight at 16 weeks in comparison with the irradiated non-treated group were observed. CONCLUSION: The study provided a new potential therapeutic strategy for the treatment of xerostomia by re-engineering radiated SG using GMSCs.

The Pharmacokinetics of CPZEN-45, a Novel Anti-Tuberculosis Drug, in Guinea Pigs.

CPZEN-45 is a novel compound with activity against drug-susceptible and drug-resistant tuberculosis (TB). The present study was undertaken to determine the best dose and dosing regimen of inhalable CPZEN-45 powders to use in efficacy studies with TB-infected guinea pigs. The disposition of CPZEN-45 after intravenous, subcutaneous (SC), and direct pulmonary administration (INS) was first determined to obtain their basal pharmacokinetic (PK) parameters. Then, the disposition of CPZEN-45 powders after passive inhalation using consecutive and sequential doses was evaluated. Plasma concentration versus time curves and PK parameters indicated that the absorption of CPZEN-45 after INS was faster than after SC administration (Ka = 12.94 ± 5.66 h-1 and 1.23 ± 0.55 h-1, respectively), had a longer half-life (2.06 ± 1.01 h versus 0.76 ± 0.22 h) and had higher bioavailability (67.78% and 47.73%, respectively). The plasma concentration versus time profiles and the lung tissue concentration at the end of the study period were not proportional to the dose size after one, two, and three consecutive passive inhalation doses. Three sequential passive inhalation doses maintained therapeutic concentration levels in plasma and lung tissue for a longer time than three consecutive doses (10 h vs. 3 h, respectively). Future studies to evaluate the efficacy of inhaled CPZEN-45 powders should employ sequential doses of the powder, with one nominal dose administered to animals three times per day.

Electroacupuncture alleviates ciliary muscle cell apoptosis in lens-induced myopic guinea pigs through inhibiting the mitochondrial signaling pathway.

AIM: To investigate the effect of electroacupuncture (EA) on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lens-induced myopia (LIM). METHODS: Guinea pigs were randomly divided into normal control (NC) group, LIM group, LIM+SHAM acupoint (LIM+SHAM) group, and LIM+EA group. Animals in the NC group received no intervention, while those in other three groups were covered with -6.0 diopter (D) lenses on right eyes. Meanwhile, animals in the LIM+EA group received EA at Hegu (LI4) combined with Taiyang (EX-HN5) acupoints, while those in the LIM+SHAM group were treated at sham points. After treatments for 1, 2, and 4wk, morphological changes in ciliary muscles were observed with hematoxylin and eosin (H&E) staining and nick end labeling (TUNEL), and the expression of the mitochondrial apoptotic signaling pathway-related molecules in ciliary muscles was measured by real-time quantitative polymerase chain reaction (qPCR) and Western blot. Additionally, the adenosine triphosphate (ATP) contents were also determined in ciliary muscles. RESULTS: Axial length increased significantly in the LIM and LIM+SHAM groups and decreased in the LIM+EA group. The ciliary muscle fibers were broken and destroyed in both LIM and LIM+SHAM groups, whereas those in the LIM+EA group improved significantly. TUNEL assay showed the number of apoptotic cells increased in the LIM and LIM+SHAM groups, whereas reduced in the LIM+EA group. ATP contents showed a significant decrease in the LIM and LIM+SHAM groups, whereas increased after EA treatment. Compared with the NC group, the dynamin-related protein 1 (DRP1), Caspase3, and apoptotic protease activator 1 (APAF1) levels were significantly increased in the LIM group and decreased in the LIM+EA group. CONCLUSION: The results provide evidence of EA inhibiting the development of myopia by regulating the mitochondrial apoptotic signaling pathway.

Temporal bright light at low frequency retards lens-induced myopia in guinea pigs.

Purpose: Bright light conditions are supposed to curb eye growth in animals with experimental myopia. Here we investigated the effects of temporal bright light at very low frequencies exposures on lens-induced myopia (LIM) progression. Methods: Myopia was induced by application of -6.00 D lenses over the right eye of guinea pigs. They were randomly divided into four groups based on exposure to different lighting conditions: constant low illumination (CLI; 300 lux), constant high illumination (CHI; 8,000 lux), very low frequency light (vLFL; 300/8,000 lux, 10 min/c), and low frequency light (LFL; 300/8,000 lux, 20 s/c). Refraction and ocular dimensions were measured per week. Changes in ocular dimensions and refractions were analyzed by paired t-tests, and differences among the groups were analyzed by one-way ANOVA. Results: Significant myopic shifts in refractive error were induced in lens-treated eyes compared with contralateral eyes in all groups after 3 weeks (all P < 0.05). Both CHI and LFL conditions exhibited a significantly less refractive shift of LIM eyes than CLI and vLFL conditions (P < 0.05). However, only LFL conditions showed significantly less overall myopic shift and axial elongation than CLI and vLFL conditions (both P < 0.05). The decrease in refractive error of both eyes correlated significantly with axial elongation in all groups (P < 0.001), except contralateral eyes in the CHI group (P = 0.231). LFL condition significantly slacked lens thickening in the contralateral eyes. Conclusions: Temporal bright light at low temporal frequency (0.05 Hz) appears to effectively inhibit LIM progression. Further research is needed to determine the safety and the potential mechanism of temporal bright light in myopic progression.

Prevalence and molecular characterization of Enterocytozoon bieneusi and a new Enterocytozoon sp. in pet hairless guinea pigs (Cavia porcellus) from China.

Enterocytozoon bieneusi, the most common microsporidian species, has been detected in humans and a variety of animals worldwide. However, limited information is available on the prevalence and molecular characterization of this parasite in guinea pigs. In this study, we conducted the first investigation of E. bieneusi infection in hairless guinea pigs recently introduced into China as new exotic pets. A total of 324 fecal samples were collected from hairless guinea pigs from a pet market and four breeding facilities in China. Sequence alignment of the internal transcribed spacer (ITS) revealed an infection rate of 14.2% (46/324) and two known ITS genotypes, S7 and PGP. Genotype S7 was the dominant genotype in these animals (42/46, 91.3%). Due to significant ITS sequence divergence, four and two PGP isolates from hairless and regular guinea pigs, respectively were further identified by PCR and phylogenetic analysis based on the small subunit (SSU) rRNA gene, as well as phylogenetic analysis of the ITS locus using E. hepatopenaei and two related genera Enterospora and Nucleospora as the outgroup. Three out of the six PGP isolates were successfully sequenced and generated the same sequences. Phylogenetic analysis of SSU rRNA and ITS loci revealed that PGP isolates formed a separate clade that was distinct and far away from E. bieneusi, suggesting that they represent a new species of Enterocytozoon. These findings indicate the dominance of zoonotic E. bieneusi genotype S7 in hairless guinea pigs and the existence of a cryptic Enterocytozoon species in guinea pigs.

Title: Prévalence et caractérisation moléculaire d'Enterocytozoon bieneusi et d'une nouvelle espèce d'Enterocytozoon chez des cobayes sans poils (Cavia porcellus) en Chine. Abstract: Enterocytozoon bieneusi, l'espèce de microsporidies la plus commune, a été détectée chez les humains et chez divers animaux à travers le monde. Cependant, peu d'informations sont disponibles sur la prévalence et la caractérisation moléculaire de ce parasite chez le cobaye. Dans cette étude, nous avons mené la première enquête sur l'infection par E. bieneusi chez des cobayes sans poils récemment introduits en Chine en tant que nouveaux animaux de compagnie exotiques. Trois cent vingt-quatre échantillons fécaux ont été collectés sur des cobayes sans poils provenant d'un marché d'animaux de compagnie et de quatre établissements d'élevage en Chine. L'alignement des séquences de l'espaceur transcrit interne (ITS) a révélé le taux d'infection (14,2 %, 46 / 324) et deux génotypes ITS connus (S7 et PGP). Le génotype S7 était le génotype dominant chez ces animaux (42 / 46, 91,3 %). En raison d'une divergence significative des séquences ITS, quatre et deux isolats de PGP provenant respectivement de cobayes sans poils et ordinaires ont été identifiés par PCR, analyse phylogénétique basée sur le gène de l'ARNr de la petite sous-unité (SSU), ainsi que par analyse phylogénétique du locus ITS en utilisant E. hepatopenaei et deux genres apparentés Enterospora et Nucleospora comme groupe externe. Trois des six isolats de PGP ont été séquencés avec succès et ont généré les mêmes séquences. L'analyse phylogénétique de l'ARNr SSU et des loci ITS a révélé que les isolats de PGP formaient un clade distinct et éloigné de E. bieneusi, ce qui suggère qu'ils représentent une nouvelle espèce d'Enterocytozoon. Ces résultats indiquent la domination du génotype zoonotique E. bieneusi S7 chez les cobayes sans poils et l'existence d'une espèce cryptique d'Enterocytozoon chez les cobayes.

Effects of blue light exposure on ocular parameters and choroidal blood perfusion in Guinea pig.

PURPOSE: To investigate the impact of different duration of blue light exposure on ocular parameters and choroidal blood perfusion in guinea pigs with lens-induced myopia. METHOD: Three-week-old Guinea pigs were randomly assigned to different light-environment groups. All groups were subjected to 12-h light/dark cycle. The control (NC) group was conditioned without intervention. While lens-induced myopia (LIM) groups had a -10D lens placed in the right eye and 0D in the left eye. The guinea pigs were exposed to increasing periods of blue-light (420 nm) environment for 3,6,9,12 h per day. Changes in refraction, axial length (AL), the radius of corneal curvature (CCR), choroidal thickness (ChT), and choroidal blood perfusion (ChBP)were measured in both LIM-eye and fellow-eye during the second and fourth week of LIM duration. RESULTS: During the first two weeks of the experiment, blue light exposure raised ChBP and ChT, and the effect of suppressing myopia was proportional to the duration of blue light exposure. However, in the fourth week of the experiment, prolonged blue light (12BL) exposure led to a reduction in retinal thickness and the increase in ChT and ChBP ceased. Shorter blue light exposure had a better effect on myopia suppression, with all blue light groups statistically different from the LIM group. CONCLUSION: Exposure to blue-light appears to have the potential to improve ChBP and ChT, thereby inhibiting the development of myopia. we speculate that blue-light inhibits the development of myopia for reasons other than longitudinal chromatic aberration (LCA). However,long-term exposure to blue-light may have adverse effects on ocular development. The next step is to investigate in depth the mechanisms by which the rational use of blue light regulates choroidal blood flow, offering new hope for the treatment of myopia.

Family first! Influence of parental investment in Guinea pigs (Cavia porcellus) prosocial choices.

Literature often assumed that prosocial behaviours (behaviours that benefit others with or without a cost for the actor) would have evolved many species to improve the effectiveness of parental care (Decety and Cowell 2014). While this hypothesis is rarely questioned at a phylogenetic scale, it was never tested at an individual scale to the best of our knowledge. Therefore, we chose to study the impact of effective parental care on prosociality by comparing the prosocial tendencies of Guinea pigs before mating, during mating and after parturition. We conducted Prosocial Choice Tests on three groups of Guinea pigs (males, multiparous females, and nulliparous females). Subjects had to choose between three options: a prosocial option (subject and recipient being rewarded), a selfish option (only subject was rewarded), and a null option (no reward). Our results showed high prosociality towards their mating partner and their young both in male and in female subjects. Males became selfish towards other males after parturition. Among other interesting results, we found a direct reciprocity phenomenon. We also highlighted an ability in our subjects to consider both the identity and relationship shared with the recipient, such as tolerance (enhancing prosociality), dominance rank (being tested with a dominant recipient increasing selfish responses), and its behaviour (begging calls eliciting prosociality, while threatening ones decreasing it), to choose an option. These findings suggested that prosociality could be modulated by many factors and that the constraints and stakes induced by breeding would highly influence prosocial strategies.

Increased vertical dimension of occlusion for varying periods differentially impairs learning and memory in guinea pigs.

There is an increasing number of studies showing that occlusal dysfunction impairs learning and memory. We previously demonstrated that the brain has a mechanism to calibrate between the activities of spindle afferents and periodontal-mechanoreceptor afferents for controlling the chewing movement, and the accurate calibration can be done only at the proper vertical dimension of occlusion (VDO). Then, the chewing at an inappropriate VDO may induce a severe mental stress due to a mal-calibration. However, it is not clear how the impairment of learning/memory progresses over the period of stress induced by occlusal dysfunction. We investigated by passive avoidance test how the behavior and learning/memory are altered in guinea pigs in which the VDO was raised by 2-3 mm over the period up to 8 weeks. We found that the guinea pigs reared under the raised occlusal-condition (ROC) for 1 week showed a very high sensitivity to electrical stimulation whereas this did not cause the memory consolidation in the 1st-day retention trial, suggesting that such hypersensitivity rather hampered the fear learning. In the guinea pigs reared under the ROC for 2 and 8 weeks, the learning ability was not largely affected and memory consolidation occurred similarly whereas the memory retention deteriorated more severely in the latter guinea pigs than in the former ones. In the guinea pigs reared under the ROC for 3 and 4 weeks, learning was severely impaired, and memory consolidation did not occur. These results suggest that the occlusal dysfunction for varying periods differentially impairs learning and memory.

Dietary Long-Chain Fatty Acids Accelerate Metabolic Dysfunction in Guinea Pigs with Non-Alcoholic Steatohepatitis.

The composition of dietary fatty acids may be important for the development and progression of metabolic syndrome and non-alcoholic steatohepatitis (NASH). This study investigated the effect of two high-fat diets based on coconut oil, containing predominantly medium-chain fatty acids (MCFA), or cocoa butter, containing mainly long-chain fatty acids (LCFA), on glucose homeostasis and NASH in guinea pigs following 16 and 32 weeks of diet. At week 16, glucose intolerance was increased in the LCFA animals compared to the MCFA animals (p < 0.001), with both groups differing from the controls by week 32 (p < 0.0001), supported by increased hemoglobin A1c (p < 0.05). NASH was present in both high-fat groups from week 16, with advancing fibrosis appearing more progressive in the LCFA animals at week 16. In agreement, gene expression showed overall increased expression of NASH target genes in the LCFA animals compared to the MCFA animals at weeks 16 and 32 (p < 0.05 and p < 0.0001, respectively). The LCFA animals also displayed increased plasma uric acid at both time points (p < 0.05), a phenomenon linked to NASH in humans. In conclusion, this study reports that a diet high in LCFA promotes metabolic imbalance and may accelerate NASH-associated hepatic fibrosis. This highlights the importance of a critical evaluation of fatty acid composition when investigating NASH-associated endpoints.

Novel Adjuvant S-540956 Targets Lymph Nodes and Reduces Genital Recurrences and Vaginal Shedding of HSV-2 DNA When Administered with HSV-2 Glycoprotein D as a Therapeutic Vaccine in Guinea Pigs.

Herpes simplex virus type 2 (HSV-2) is a leading cause of genital ulcer disease and a major risk factor for acquisition and transmission of HIV. Frequent recurrent genital lesions and concerns about transmitting infection to intimate partners affect the quality of life of infected individuals. Therapeutic vaccines are urgently needed to reduce the frequency of genital lesions and transmission. S-540956 is a novel vaccine adjuvant that contains CpG oligonucleotide ODN2006 annealed to its complementary sequence and conjugated to a lipid that targets the adjuvant to lymph nodes. Our primary goal was to compare S-540956 administered with HSV-2 glycoprotein D (gD2) with no treatment in a guinea pig model of recurrent genital herpes (studies 1 and 2). Our secondary goals were to compare S-540956 with oligonucleotide ODN2006 (study1) or glucopyranosyl lipid A in a stable oil-in-water nano-emulsion (GLA-SE) (study 2). gD2/S-540956 reduced the number of days with recurrent genital lesions by 56%, vaginal shedding of HSV-2 DNA by 49%, and both combined by 54% compared to PBS, and was more efficacious than the two other adjuvants. Our results indicate that S-540956 has great potential as an adjuvant for a therapeutic vaccine for genital herpes, and merits further evaluation with the addition of potent T cell immunogens.

Influenza C and D Viruses Demonstrated a Differential Respiratory Tissue Tropism in a Comparative Pathogenesis Study in Guinea Pigs.

Influenza C virus (ICV) is increasingly associated with community-acquired pneumonia (CAP) in children and its disease severity is worse than the influenza B virus, but similar to influenza A virus associated CAP. Despite the ubiquitous infection landscape of ICV in humans, little is known about its replication and pathobiology in animals. The goal of this study was to understand the replication kinetics, tissue tropism, and pathogenesis of human ICV (huICV) in comparison to the swine influenza D virus (swIDV) in guinea pigs. Intranasal inoculation of both viruses did not cause clinical signs, however, the infected animals shed virus in nasal washes. The huICV replicated in the nasal turbinates, soft palate, and trachea but not in the lungs while swIDV replicated in all four tissues. A comparative analysis of tropism and pathogenesis of these two related seven-segmented influenza viruses revealed that swIDV-infected animals exhibited broad tissue tropism with an increased rate of shedding on 3, 5, and 7 dpi and high viral loads in the lungs compared to huICV. Seroconversion occurred late in the huICV group at 14 dpi, while swIDV-infected animals seroconverted at 7 dpi. Guinea pigs infected with huICV exhibited mild to moderate inflammatory changes in the epithelium of the soft palate and trachea, along with mucosal damage and multifocal alveolitis in the lungs. In summary, the replication kinetics and pathobiological characteristics of ICV in guinea pigs agree with the clinical manifestation of ICV infection in humans, and hence guinea pigs could be used to study these distantly related influenza viruses. IMPORTANCE Similar to influenza A and B, ICV infections are seen associated with bacterial and viral co-infections which complicates the assessment of its real clinical significance. Further, the antivirals against influenza A and B viruses are ineffective against ICV which mandates the need to study the pathobiological aspects of this virus. Here we demonstrated that the respiratory tract of guinea pigs possesses specific viral receptors for ICV. We also compared the replication kinetics and pathogenesis of huICV and swIDV, as these viruses share 50% sequence identity. The tissue tropism and pathology associated with huICV in guinea pigs are analogous to the mild respiratory disease caused by ICV in humans, thereby demonstrating the suitability of guinea pigs to study ICV. Our comparative analysis revealed that huICV and swIDV replicated differentially in the guinea pigs suggesting that the type-specific genetic differences can result in the disparity of the viral shedding and tissue tropism.