CT findings of an incidental segmental aplasia of the caudal vena cava with azygos continuation in a guinea pig (Cavia porcellus).

Background: Segmental aplasia of the caudal vena cava (CVC) with azygos continuation is a congenital malformation macroscopically described in mammals including humans, dogs, and rodents. It is usually detected as an incidental finding and the final diagnosis is reached by computed tomography (CT), fluoroscopy, or post-mortem dissection. Case Description: A 3-year-old guinea pig (Cavia porcellus) presented with subacute dyspnea. A computed tomographic examination was performed for the evaluation of subtle pulmonary changes previously suspected on conventional radiography, and a segmental aplasia of the CVC with azygos continuation was identified as an incidental finding. Conclusion: According to database negative results, this is the first report describing a segmental aplasia of the CVC and azygos continuation in a guinea pig by CT.

miR-92b-3p protects retinal tissues against DNA damage and apoptosis by targeting BTG2 in experimental myopia.

BACKGROUND: Myopia is one of the eye diseases that can damage the vision of young people. This study aimed to explore the protective role of miR-92b-3p against DNA damage and apoptosis in retinal tissues of negative lens-induced myopic (LIM) guinea pigs by targeting BTG2. METHODS: Biometric measurements of ocular parameters, flash electroretinogram (FERG), and retinal thickness (RT) were performed after miR-92b-3p intravitreal injection in LIM guinea pigs. The apoptotic rate was detected by Annexin V-FITC/PI double staining, and the change in mitochondrial membrane potential was measured by JC-1 staining. Retinal apoptosis and expression of p53, BTG2, and CDK2 were explored by TdT-mediated dUTP-biotin nick labeling (TUNEL) and immunofluorescence staining assays, respectively. BTG2 and its upstream and downstream molecules at gene and protein levels in retinal tissues were measured by real-time quantitative PCR (qPCR) and Western blotting. RESULTS: Compared with normal controls (NC), the ocular axial length of LIM guinea pig significantly increased, whereas refraction decreased. Meanwhile, dMax-a and -b wave amplitudes of ERG declined, retinal thickness was decreased, the number of apoptotic cells and apoptotic rate in LIM eyes was exaggerated, and the mitochondrial membrane potential significantly decreased. In addition, results of qPCR and Western blot assays showed that the expression levels of p53, BTG2, CDK2, and BAX in LIM guinea pigs were higher than the levels of the NC group, whereas the BCL-2 expression level was decreased. By contrast, the miR-92b-3p intravitreal injection in LIM guinea pigs could significantly inhibit axial elongation, alleviate DNA damage and apoptosis, and thus protect guinea pigs against myopia. CONCLUSION: In conclusion, p53 and BTG2 were activated in the retinal tissue of myopic guinea pigs, and the activated BTG2 could elevate the expression of CDK2 and BAX, and attenuate the expression of BCL-2, which in turn promote apoptosis and eventually lead to retinal thinning and impaired visual function in myopic guinea pigs. The miR-92b-3p intravitreal injection can attenuate the elongation of ocular length and retinal thickness, and inhibit the CDK2, BAX, and p53 expression by targeting BTG2, thereby ameliorating DNA damage and apoptosis in LIM guinea pigs and protecting ocular tissues.

Antifungal activity of aminopyrrolnitrin against Trichophyton verrucosum in a guinea pig model of dermatophytosis.

BACKGROUND: Dermatophytosis is a common and major public health concern worldwide. Despite the increasing availability of antifungal drugs, relapses and untreated cases of dermatophyte infections are reported. Therefore, novel antifungal agents are required. Aminopyrrolnitrin (APRN) shows promise for dermatophytosis treatment because of its antifungal activity. OBJECTIVES: This study aimed to assess the antifungal properties of APRN against Trichophyton verrucosum (T. verrucosum), in both laboratory settings and a guinea pig model. METHODS: The minimum inhibitory concentrations (MICs) of APRN and enilconazole against T. verrucosum were determined according to the CLSI M38 method. The skins of 16 male guinea pigs were infected with 1.0 × 108 conidia of T. verrucosum and the animals were grouped into sets of four: negative control group (NC) received normal saline; positive control group (PC) received 2 µg/mL of enilconazole; and APRN4 and APRN8 received 4 and 8 µg/mL of APRN, respectively. Clinical, mycological and histological efficacies were measured after 10 days. RESULTS: The MIC90 of APRN and enilconazole against T. verrucosum was 4 and 2 µg/mL, respectively. The clinical scores of PC, APRN4, and APRN8 were significantly lower than those of NC. Clinical and mycological efficacies were higher for APRN8, APRN4 and PC. No fungi were observed in the skin tissues of APRN4 and APRN8, while fungi were observed in 50% of the PC. CONCLUSION: APRN showed antifungal activity against T. verrucosum in vitro and in vivo and is a potential candidate for the treatment of dermatophytosis.

Inhibitory mechanisms of docosahexaenoic acid on carbachol-, angiotensin II-, and bradykinin-induced contractions in guinea pig gastric fundus smooth muscle.

We studied the inhibitory actions of docosahexaenoic acid (DHA) on the contractions induced by carbachol (CCh), angiotensin II (Ang II), and bradykinin (BK) in guinea pig (GP) gastric fundus smooth muscle (GFSM), particularly focusing on the possible inhibition of store-operated Ca2+ channels (SOCCs). DHA significantly suppressed the contractions induced by CCh, Ang II, and BK; the inhibition of BK-induced contractions was the strongest. Although all contractions were greatly dependent on external Ca2+, more than 80% of BK-induced contractions remained even in the presence of verapamil, a voltage-dependent Ca2+ channel inhibitor. BK-induced contractions in the presence of verapamil were not suppressed by LOE-908 (a receptor-operated Ca2+ channel (ROCC) inhibitor) but were suppressed by SKF-96365 (an SOCC and ROCC inhibitor). BK-induced contractions in the presence of verapamil plus LOE-908 were strongly inhibited by DHA. Furthermore, DHA inhibited GFSM contractions induced by cyclopiazonic acid (CPA) in the presence of verapamil plus LOE-908 and inhibited the intracellular Ca2+ increase due to Ca2+ addition in CPA-treated 293T cells. These findings indicate that Ca2+ influx through SOCCs plays a crucial role in BK-induced contraction in GP GFSM and that this inhibition by DHA is a new mechanism by which this fatty acid inhibits GFSM contractions.

Asymmetric pulses delivered by a cochlear implant allow a reduction in evoked firing rate and in spatial activation in the guinea pig auditory cortex.

Despite that fact that the cochlear implant (CI) is one of the most successful neuro-prosthetic devices which allows hearing restoration, several aspects still need to be improved. Interactions between stimulating electrodes through current spread occurring within the cochlea drastically limit the number of discriminable frequency channels and thus can ultimately result in poor speech perception. One potential solution relies on the use of new pulse shapes, such as asymmetric pulses, which can potentially reduce the current spread within the cochlea. The present study characterized the impact of changing electrical pulse shapes from the standard biphasic symmetric to the asymmetrical shape by quantifying the evoked firing rate and the spatial activation in the guinea pig primary auditory cortex (A1). At a fixed charge, the firing rate and the spatial activation in A1 decreased by 15 to 25 % when asymmetric pulses were used to activate the auditory nerve fibers, suggesting a potential reduction of the spread of excitation inside the cochlea. A strong "polarity-order" effect was found as the reduction was more pronounced when the first phase of the pulse was cathodic with high amplitude. These results suggest that the use of asymmetrical pulse shapes in clinical settings can potentially reduce the channel interactions in CI users.

Testosterone Enhances KV Currents and Airway Smooth Muscle Relaxation Induced by ATP and UTP through P2Y4 Receptors and Adenylyl Cyclase Pathway.

Numerous studies suggest the involvement of adenosine-5'-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5'-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y2 and P2Y4 receptors and K+ channel opening. We previously demonstrated that TES increased the expression of voltage-dependent K+ (KV) channels in ASM. This study investigates how TES may potentiate ASM relaxation induced by ATP and UTP. Tracheal tissues treated with or without TES (control group) from young male guinea pigs were used. In organ baths, tracheas exposed to TES (40 nM for 48 h) showed enhanced ATP- and UTP-evoked relaxation. Tetraethylammonium, a K+ channel blocker, annulled this effect. Patch-clamp experiments in tracheal myocytes showed that TES also increased ATP- and UTP-induced K+ currents, and this effect was abolished with flutamide (an androgen receptor antagonist). KV channels were involved in this phenomenon, which was demonstrated by inhibition with 4-aminopyridine. RB2 (an antagonist of almost all P2Y receptors except for P2Y2), as well as N-ethylmaleimide and SQ 22,536 (inhibitors of G proteins and adenylyl cyclase, respectively), attenuated the enhancement of the K+ currents induced by TES. Immunofluorescence and immunohistochemistry studies revealed that TES did not modify the expression of P2Y4 receptors or COX-1 and COX-2, while we have demonstrated that this androgen augmented the expression of KV1.2 and KV1.5 channels in ASM. Thus, TES leads to the upregulation of P2Y4 signaling and KV channels in guinea pig ASM, enhancing ATP and UTP relaxation responses, which likely limits the severity of bronchospasm in young males.

Revealing nitrogenous VX metabolites and the whole-molecule VX metabolism in the urine of guinea pigs.

VX, a well-known organophosphorus nerve agent (OPNA), poses a significant threat to public safety if employed by terrorists. Obtaining complete metabolites is critical to unequivocally confirm its alleged use/exposure and elucidate its whole-molecular metabolism. However, the nitrogenous VX metabolites containing 2-diisopropylaminoethyl moiety from urinary excretion remain unknown. Therefore, this study applied a newly developed untargeted workflow platform to discover and identify them using VX-exposed guinea pigs as animal models. 2-(N,N-diisopropylamino)ethanesulfonic acid (DiPSA) was revealed as a novel nitrogenous VX metabolite in urine, and 2-(Diisopropylaminoethyl) methyl sulfide (DAEMS) was confirmed as another in plasma, indicating that VX metabolism differed between urine and plasma. It is the first report of a nitrogenous VX metabolite in urine and a complete elucidation of the VX metabolic pathway. DiPSA was evaluated as an excellent VX exposure biomarker. The whole-molecule VX metabolism in urine was characterized entirely for the first time via the simultaneous quantification of DiPSA and two known P-based biomarkers. About 52.1% and 32.4% of VX were excreted in urine as P-based and nitrogenous biomarkers within 24 h. These findings provide valuable insights into the unambiguous detection of OPNA exposure/intoxication and human and environmental exposure risk assessment.

Noise-induced hearing loss alters potassium-chloride cotransporter KCC2 and GABA inhibition in the auditory centers.

Homeostatic plasticity, the ability of neurons to maintain their averaged activity constant around a set point value, is thought to account for the central hyperactivity after hearing loss. Here, we investigated the putative role of GABAergic neurotransmission in this mechanism after a noise-induced hearing loss larger than 50 dB in high frequencies in guinea pigs. The effect of GABAergic inhibition is linked to the normal functioning of K + -Cl- co-transporter isoform 2 (KCC2) which maintains a low intracellular concentration of chloride. The expression of membrane KCC2 were investigated before and after noise trauma in the ventral and dorsal cochlear nucleus (VCN and DCN, respectively) and in the inferior colliculus (IC). Moreover, the effect of gabazine (GBZ), a GABA antagonist, was also studied on the neural activity in IC. We show that KCC2 is downregulated in VCN, DCN and IC 3 days after noise trauma, and in DCN and IC 30 days after the trauma. As expected, GBZ application in the IC of control animals resulted in an increase of spontaneous and stimulus-evoked activity. In the noise exposed animals, on the other hand, GBZ application decreased the stimulus-evoked activity in IC neurons. The functional implications of these central changes are discussed.

Chamaecyparis lawsoniana and Its Active Compound Quercetin as Ca2+ Inhibitors in the Contraction of Airway Smooth Muscle.

The Cupressaceae family includes species considered to be medicinal. Their essential oil is used for headaches, colds, cough, and bronchitis. Cedar trees like Chamaecyparis lawsoniana (C. lawsoniana) are commonly found in urban areas. We investigated whether C. lawsoniana exerts some of its effects by modifying airway smooth muscle (ASM) contractility. The leaves of C. lawsoniana (363 g) were pulverized mechanically, and extracts were obtained by successive maceration 1:10 (w:w) with methanol/CHCl3. Guinea pig tracheal rings were contracted with KCl, tetraethylammonium (TEA), histamine (HIS), or carbachol (Cch) in organ baths. In the Cch experiments, tissues were pre-incubated with D-600, an antagonist of L-type voltage-dependent Ca2+ channels (L-VDCC) before the addition of C. lawsoniana. Interestingly, at different concentrations, C. lawsoniana diminished the tracheal contractions induced by KCl, TEA, HIS, and Cch. In ASM cells, C. lawsoniana significantly diminished L-type Ca2+ currents. ASM cells stimulated with Cch produced a transient Ca2+ peak followed by a sustained plateau maintained by L-VDCC and store-operated Ca2+ channels (SOCC). C. lawsoniana almost abolished this last response. These results show that C. lawsoniana, and its active metabolite quercetin, relax the ASM by inhibiting the L-VDCC and SOCC; further studies must be performed to obtain the complete set of metabolites of the extract and study at length their pharmacological properties.

C-Phycocyanin Attenuates Noise-Induced Cochlear Synaptopathy via the Inhibition of Oxidative Stress and Intercellular Adhesion Molecule-1 in the Cochlea.

The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy results from the disruption of these synapses following noise exposure and is considered the main cause of poor speech understanding in noisy environments, even when audiogram results are normal. Cochlear synaptopathy leads to the degeneration of SGNs if damaged IHC-SGN synapses are not promptly recovered. Oxidative stress plays a central role in the pathogenesis of cochlear synaptopathy. C-Phycocyanin (C-PC) has antioxidant and anti-inflammatory activities and is widely utilized in the food and drug industry. However, the effect of the C-PC on noise-induced cochlear damage is unknown. We first investigated the therapeutic effect of C-PC on noise-induced cochlear synaptopathy. In vitro experiments revealed that C-PC reduced the H2O2-induced generation of reactive oxygen species in HEI-OC1 auditory cells. H2O2-induced cytotoxicity in HEI-OC1 cells was reduced with C-PC treatment. After white noise exposure for 3 h at a sound pressure of 118 dB, the guinea pigs intratympanically administered 5 µg/mL C-PC exhibited greater wave I amplitudes in the auditory brainstem response, more IHC synaptic ribbons and more IHC-SGN synapses according to microscopic analysis than the saline-treated guinea pigs. Furthermore, the group treated with C-PC had less intense 4-hydroxynonenal and intercellular adhesion molecule-1 staining in the cochlea compared with the saline group. Our results suggest that C-PC improves cochlear synaptopathy by inhibiting noise-induced oxidative stress and the inflammatory response in the cochlea.

miRNA Expression Profiles in Isolated Ventricular Cardiomyocytes: Insights into Doxorubicin-Induced Cardiotoxicity.

Doxorubicin (DOX), widely used as a chemotherapeutic agent for various cancers, is limited in its clinical utility by its cardiotoxic effects. Despite its widespread use, the precise mechanisms underlying DOX-induced cardiotoxicity at the cellular and molecular levels remain unclear, hindering the development of preventive and early detection strategies. To characterize the cytotoxic effects of DOX on isolated ventricular cardiomyocytes, focusing on the expression of specific microRNAs (miRNAs) and their molecular targets associated with endogenous cardioprotective mechanisms such as the ATP-sensitive potassium channel (KATP), Sirtuin 1 (SIRT1), FOXO1, and GSK3ß. We isolated Guinea pig ventricular cardiomyocytes by retrograde perfusion and enzymatic dissociation. We assessed cell morphology, Reactive Oxygen Species (ROS) levels, intracellular calcium, and mitochondrial membrane potential using light microscopy and specific probes. We determined the miRNA expression profile using small RNAseq and validated it using stem-loop qRT-PCR. We quantified mRNA levels of some predicted and validated molecular targets using qRT-PCR and analyzed protein expression using Western blot. Exposure to 10 µM DOX resulted in cardiomyocyte shortening, increased ROS and intracellular calcium levels, mitochondrial membrane potential depolarization, and changes in specific miRNA expression. Additionally, we observed the differential expression of KATP subunits (ABCC9, KCNJ8, and KCNJ11), FOXO1, SIRT1, and GSK3ß molecules associated with endogenous cardioprotective mechanisms. Supported by miRNA gene regulatory networks and functional enrichment analysis, these findings suggest that DOX-induced cardiotoxicity disrupts biological processes associated with cardioprotective mechanisms. Further research must clarify their specific molecular changes in DOX-induced cardiac dysfunction and investigate their diagnostic biomarkers and therapeutic potential.

Integration of bioinformatics analysis, molecular docking and animal experiments to study the therapeutic mechanisms of berberine against allergic rhinitis.

Allergic rhinitis is a prevalent inflammatory condition that impacts individuals of all age groups. Despite reports indicating the potential of berberine in alleviating allergic rhinitis symptoms, the specific molecular mechanisms and therapeutic targets of berberine remain unclear. This research aims to explore the pharmacological mechanism of berberine in the treatment of allergic rhinitis through bioinformatic analyses and experimental validation. The research utilized public databases to identify potential targets of berberine. Furthermore, differentially expressed genes (DEGs) related to allergic rhinitis were pinpointed from the GSE52804 dataset. Through bioinformatics techniques, the primary targets were discovered and key KEGG and GO-BP pathways were established. To confirm the therapeutic mechanisms of berberine on allergic rhinitis, an OVA-induced allergic rhinitis model was developed using guinea pigs. We identified 32 key genes responsible for the effectiveness of berberine in treating allergic rhinitis. In addition, five central genes (Alb, Il6, Tlr4, Ptas2, and Il1b) were pinpointed. Further examination using KEGG and GO-BP pathways revealed that the main targets were primarily involved in pathways such as NF-kappa B, IL-17, TNF, and inflammatory response. Molecular docking analysis demonstrated that berberine exhibited strong affinity towards these five key targets. Furthermore, the expression levels of IL-6, TLR4, PTGS2, and IL-1ß were significantly upregulated in the model group but downregulated following berberine treatment. This research has revealed the mechanism through which berberine combats allergic rhinitis and has identified its potential to regulate pathways linked to inflammation. These discoveries provide valuable insights for the development of novel medications for the treatment of allergic rhinitis.

[New drugs for horses and production animals in 2023]. / Neue Arzneimittel für Pferde und landwirtschaftliche Nutztiere 2023.

In 2023, no new active pharmaceutical ingredients were released on the German market for horses and food-producing animals. Two established veterinary active pharmaceutical ingredients became available for additional species: The phosphorus compound butafosfan was also approved for horses, dogs, and cats and the mineral sodium chloride as an isotonic sodium chloride solution was also approved for rabbits and guinea pigs. In addition, for small animals, there were new releases of an agent (pergolidmesilate) in a novel pharmaceutical formulation and a lower content of the active ingredient, one drug (fluralaner) in a smaller package size as well as one drug (oxalic acid dehydrate) with a new route of administration. Furthermore, one combination of active ingredients (diprophylline+heptaminol) is available on the market for horses and food producing animals again.

Effect of exogenous calcitriol on myopia development and axial length in guinea pigs with form deprivation myopia.

The annual increase in myopia prevalence poses a significant economic and health challenge. Our study investigated the effect of calcitriol role in myopia by inducing the condition in guinea pigs through form deprivation for four weeks. Untargeted metabolomics methods were used to analyze the differences in metabolites in the vitreous body, and the expression of vitamin D receptor (VDR) in the retina was detected. Following form deprivation, the guinea pigs received intraperitoneal injections of calcitriol at different concentrations. We assessed myopia progression using diopter measurements and biometric analysis after four weeks. Results indicated that form deprivation led to a pronounced shift towards myopia, characterized by reduced choroidal and scleral thickness, disorganized collagen fibers, and decreased scleral collagen fiber diameter. Notably, a reduction in calcitriol expression in vitreous body, diminished vitamin D and calcitriol levels in the blood, and decreased VDR protein expression in retinal tissues were observed in myopic guinea pigs. Calcitriol administration effectively slowed myopia progression, preserved choroidal and scleral thickness, and prevented the reduction of scleral collagen fiber diameter. Our findings highlight a significant decrease in calcitriol and VDR expressions in myopic guinea pigs and demonstrate that exogenous calcitriol supplementation can halt myopia development, enhancing choroidal and scleral thickness and scleral collagen fiber diameter.

Fast freezing inhibits melanin synthesis of melanocytes by modulating the Wnt/ß-catenin signalling pathway.

Skin hyperpigmentation is mainly caused by excessive synthesis of melanin; however, there is still no safe and effective therapy for its removal. Here, we found that the dermal freezer was able to improve UVB-induced hyperpigmentation of guinea pigs without causing obvious epidermal damage. We also mimic freezing stimulation at the cellular level by rapid freezing and observed that freezing treatments <2.5 min could not decrease cell viability or induce cell apoptosis in B16F10 and Melan-A cells. Critically, melanin content and tyrosinase activity in two cells were greatly reduced after freezing treatments. The dramatic decrease in tyrosinase activity was associated with the downregulation of MITF, TYR, TRP-1 and TRP-2 protein expression in response to freezing treatments for two cells. Furthermore, our results first demonstrated that freezing treatments significantly reduced the levels of p-GSK3ß and ß-catenin and the nuclear accumulation of ß-catenin in B16F10 and Melan-A cells. Together, these data suggest that fast freezing treatments can inhibit melanogenesis-related gene expression in melanocytes by regulating the Wnt/ß-catenin signalling pathway. The inhibition of melanin production eventually contributed to the improvement in skin hyperpigmentation induced by UVB. Therefore, fast freezing treatments may be a new alternative of skin whitening in the clinic in the future.

Serum Prestin After Ototoxin Exposure Is Not Dependent on Outer Hair Cell Loss.

HYPOTHESIS: Cyclodextrin (CDX)-induced serum prestin burst is not dependent on outer hair cell (OHC) loss. BACKGROUND: Serum prestin has been proposed as a biomarker for ototoxicity. We recently used an automated Western approach to quantify serum prestin changes in a newly introduced model of CDX ototoxicity. To gain insights into prestin as a biomarker, here we further characterize serum prestin in the CDX model. METHODS: Guinea pigs were treated with 750, 3,000, or 4,000 mg/kg CDX, and serum samples were obtained through up to 15 weeks after exposure. Serum prestin levels were quantified using automated Western, and hair cell counts were obtained. RESULTS: All three doses induced an N -glycosylated ~134-kDa prestin burst; however, only the 3,000 and 4,000 mg/kg resulted in robust OHC loss. Prestin levels returned to baseline where they remained up to 15 weeks in the absence of OHCs. CONCLUSION: The ~134-kDa prestin burst induced after CDX administration is N -glycosylated, representing a posttranslational modification of prestin. Serum prestin seems to be a promising biomarker when using therapeutics with ototoxic properties because it is not dependent on OHC loss as a necessary event, thus affording the opportunity for early detection and intervention.

Humanization of a mouse anti-human complement C6 monoclonal antibody as a potential therapeutic for certain complement-mediated diseases.

The assembly of tissue-damaging membrane attack complexes (MACs; C5b-9) is a major mechanism by which excessive complement activation causes diseases. We previously developed a mouse anti-human C6 monoclonal antibody (mAb) 1C9 that selectively inhibits the assembly of MACs in human and non-human primates. In this project, we found that 1C9 also cross-reacted with rat and guinea pig C6, and determined its binding domains on C6 using different truncated C6 proteins. We then humanized the anti-C6 mAb by molecular modeling and complementarity-determining region grafting. After screening a library of 276 humanized variants with different combinations of humanized light and heavy chains in biophysical assays, we identified clone 3713 with the best developability profile, and an increased affinity against C6 when compared with the parental 1C9 mAb. This humanized 3713 mAb inhibited human, monkey, and rat complement-mediated hemolysis in vitro, and more importantly, it significantly reduced complement-mediated hemolysis in vivo in rats. These results demonstrated the successful humanization of the anti-C6 mAb and suggested that the humanized 3713 mAb could be further developed as a new therapeutic that selectively targets MAC for certain complement-mediated pathological conditions.

Cloprostenol effect with and without male stimulation on oestrus synchronization in Peru guinea pigs.

Cloprostenol, a synthetic derivative of prostaglandin F2α, effectively triggers functional and morphological regression of the corpus luteum (luteolysis). In rural Peru, the guinea pig (Cavia porcellus) holds significance within the local economy and serves as a valuable protein source. Enhancing reproductive efficiency is crucial to achieve uniformity in weight, age, and litter size across commercial systems. Thus, our study aimed to evaluate the effect of cloprostenol with and without male stimulation on the onset, duration, and intensity of oestrus in Peru guinea pigs. A total of 128 guinea pigs (120 females and eight males) between 8 and 12 months of age, weighing between 800 and 1200 g, were distributed in cages of 15 females per treatment. Cloprostenol sodium (0 [control], 0.20, 0.25, and 0.30 mg/animal) was IM administered to the groups with and without male stimulation. Four isolated males in individual cages, different from the one used for the treatment, were considered to detect oestrus. The oestrus intensity was assessed by observing sexual behaviour signs such as restlessness, moaning, attempts to mount, pelvic elevation, loin stretching, and vulvar inflammation. The oestrus was manifested 2 days after the administration of cloprostenol sodium. At a dose of 0.30 mg/animal and with male stimulation, the earliest oestrus was observed at 46.9 h. There was a reduction in the oestrus duration (p < .05) in guinea pigs that received the three doses of cloprostenol sodium compared to the control group. The highest percentages of frank oestrus intensity (66.7%) were strongly associated with the administered doses of cloprostenol sodium (p < .01). In conclusion, the cloprostenol sodium administration was proper for rapid oestrus induction in Peru guinea pigs.

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.

pH- and Matrix Metalloproteinase-Responsive Multifunctional Bilayer Microneedles Platform for Treatment of Tinea Pedis.

Persistent foot odor and itchiness are common symptoms of tinea pedis, significantly disrupting the daily life of those affected. The cuticular barrier at the site of the tinea pedis is thickened, which impedes the effective penetration of antifungal agents. Additionally, fungi can migrate from the skin surface to deeper tissues, posing challenges in the current clinical treatment for tinea pedis. To effectively treat tinea pedis, we developed a platform of bilayer gelatin methacrylate (GelMA) microneedles (MNs) loaded with salicylic acid (SA) and FK13-a1 (SA/FK13-a1@GelMA MNs). SA/FK13-a1@GelMA MNs exhibit pH- and matrix metalloproteinase (MMP)-responsive properties for efficient drug delivery. The MNs are designed to deliver salicylic acid (SA) deep into the stratum corneum, softening the cuticle and creating microchannels. This process enables the antibacterial peptide FK13-a1 to penetrate through the stratum corneum barrier, facilitating intradermal diffusion and exerting antifungal and anti-inflammatory effects. In severe cases of tinea pedis, heightened local pH levels and MMP activity further accelerate drug release. Our research demonstrates that SA/FK13-a1@GelMA MNs are highly effective against Trichophyton mentagrophytes, Trichophyton rubrum, and Candida albicans. They also reduced stratum corneum thickness, fungal burden, and inflammation in a guinea pig model of tinea pedis induced by T. mentagrophytes. Furthermore, it was discovered that SA/FK13-a1@GelMA MNs exhibit excellent biocompatibility. These findings suggest that SA/FK13-a1@GelMA MNs have significant potential for the clinical treatment of tinea pedis as well as other fungal skin disorders.