Pulmonary arterial hypertension (PAH) is a chronic, progressive disease characterized by an increase in blood pressure in the lungs' arteries. It can occur in a variety of species, including humans, ...dogs, cats, and horses. To date, PAH has a high mortality rate in both veterinary and human medicine, often due to complications such as heart failure. The complex pathological mechanisms of PAH involve multiple cellular signalling pathways at various levels. IL-6 is a powerful pleiotropic cytokine that regulates several phases of immune response, inflammation, and tissue remodelling. The hypothesis of this study was that the use of an IL-6 antagonist in PAH could interrupt or mitigate the cascade of events that leads to the progression of the disease and the worsening of clinical outcome, as well as tissue remodelling. In this study, we used two pharmacological protocols with an IL-6 receptor antagonist in a monocrotaline-induced PAH model in rats. Our results showed that the use of an IL-6 receptor antagonist had a significant protective effect, ameliorating both haemodynamic parameters, lung and cardiac function, tissue remodelling, and the inflammation associated with PAH. The results of this study suggest that the inhibition IL-6 could be a useful pharmacological strategy in PAH, in both human and veterinary medicine.
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Endometriosis (EMS) is a gynecological disease characterized by inflammation, oxidative stress, and apoptosis dysregulation. This study aims to evaluate the effect of Boswellia serrata gum resin ...extract (BS) on the endometriotic lesions in a rat model of endometriosis. We divided female rats into three groups, including Sham, EMS, EMS + BS. In the EMS and EMS + BS groups, pathology was induced and after 7 days by the abdominal high-frequency ultrasound (hfUS) analysis the presence of the endometriotic lesions was confirmed. Subsequently, the EMS + BS group was administered with BS (100 mg/Kg) daily for another 7 days. At the end of the experiment, the hfUS analysis was repeated and the animals were sacrificed to evaluate the size and histoarchitecture of the endometriotic implants. Pelvic ultrasound showed increased size of the endometriotic lesions in the Endo group, while BS administration reduced the lesion size. The macroscopic analysis confirmed the reduced area and volume of the endometriotic lesions of the EMS + BS group. The histological analysis showed reduced characteristic of ectopic stroma and glands in the animals treated with BS. Western blot analyses were conducted to evaluate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. BS increases the expression of Nfr2 in the nucleus and the expression of its downstream antioxidant proteins NQO-1 and HO-1. Moreover, it reduced lipid peroxidation and increased glutathione (GSH) levels, and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. BS administration also restored the impaired apoptotic pathway in the lesions by reducing Bcl-2 expression and increasing Bax and cleaved caspase 9 levels. The BS apoptotic effect was also confirmed by the cleavage of PARP, another specific marker of apoptosis, and by the TUNEL assay. Our results show that BS administration resulted in an effective and coordinated suppression of Endo owing to its antioxidant and antiapoptotic activities.
The aim of the study was to compare the analgesic efficacy of tramadol and lidocaine for local anesthesia during umbilical hernia repair in swine. The study was performed on 66 large white crossbred ...swine. The swine received a mixture of tiletamine/zolazepam at 5 mg/kg and romifidine at 80 µg/kg, administered intramuscularly. Then, they were divided into three groups (n = 22) that received different treatments with lidocaine at 4 mg/kg and tramadol at 4 mg/kg. The LL group received lidocaine both by infiltration of the surgical planes and intraperitoneally. The LT group received lidocaine by infiltration of the surgical planes and tramadol intraperitoneally. The TT group received tramadol both by infiltration of the surgical planes and intraperitoneally. In all groups, the infiltration of the surgical planes into the umbilical region involved both the skin and muscle planes. Heart rate, noninvasive arterial blood pressure, and respiratory frequency were recorded during surgery. The response to the surgical stimulus was evaluated using a cumulative pain scale (the cut-off point for rescue analgesia was set to 10). Postoperative pain was assessed using the UNESP-Botucatu pig composite acute pain scale (the cut-off point was set to 4). The trend of physiological variables was adequate for patients under anesthesia. No subject required intraoperative and postoperative rescue analgesia. Tramadol could therefore be used for pain management in livestock.
Endometriosis (Endo) is a chronic gynecological disease. This paper aimed to evaluate the modulation of autophagy, oxidative stress and apoptosis with Açai Berries in a rat model of endometriosis. ...Endometriosis was induced with an intraperitoneal injection of minced uterus tissue from a donor rat into a recipient one. The abdominal high-frequency ultrasound (hfUS) analysis was performed at 7 and 14 days from the endometriosis induction to evaluate the growth of the lesion during the experiment. Seven days from the induction, once the lesions were implanted, an Açai Berry was administered daily by gavage for the next seven days. At the end of the experiment, the hfUS analysis showed a reduced lesion diameter in animals given the Açai Berry. A macroscopical and histological analysis confirmed this result. From the molecular point of view, Western blot analyses were conducted to evaluate the autophagy induction. Samples collected from the Endo group showed impaired autophagy, while the Açai Berry administration inhibited PI3K and AKT and ERK1/2 phosphorylation and promoted autophagy by inactivating mTOR. Additionally, Açai Berry administration dephosphorylated ATG1, promoting the activity of the ATG1/ULK1 complex that recruited Ambra1/Beclin1 and Atg9 to promote autophagosome nucleation and LC3II expression. Açai Berry administration also restored mitophagy, which increased Parkin cytosolic expression. The Açai Berry increased the expression of NRF2 in the nucleus and the expression of its downstream antioxidant proteins as NQO-1 and HO-1, thereby restoring the oxidative imbalance. It also restored the impaired apoptotic pathway by reducing BCL-2 and increasing BAX expression. This result was also confirmed by the TUNEL assay. Overall, our results displayed that Açai Berry administration was able to modulate autophagy, oxidative stress and apoptosis during endometriosis.
Introduction. Sleep problems are common in bipolar disorder (BD) and may persist during the euthymic phase of the disease. The aim of the study was to improve sleep quality of euthymic BD patients ...through the administration of prefronto-cerebellar transcranial direct current stimulation (tDCS). Methods. 25 euthymic outpatients with a diagnosis of BD Type I or II have been enrolled in the study. tDCS montage was as follows: cathode on the right cerebellar cortex and anode over the left dorsolateral prefrontal cortex (DLPFC); the intensity of stimulation was set at 2 mA and delivered for 20 min/die for 3 consecutive weeks. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality at baseline and after the tDCS treatment. Results. PSQI total score and all PSQI subdomains, with the exception of “sleep medication,” significantly improved after treatment. Discussion. This is the first study where a positive effect of tDCS on the quality of sleep in euthymic BD patients has been reported. As both prefrontal cortex and cerebellum may play a role in regulating sleep processes, concomitant cathodal (inhibitory) stimulation of cerebellum and anodal (excitatory) stimulation of DLPFC may have the potential to modulate prefrontal-thalamic-cerebellar circuits leading to improvements of sleep quality.
Wound healing is a physiological process comprising several coordinated phases, such as inflammation, proliferation, and remodeling. For centuries, Helix aspersa Muller mucus has been known to have ...biological properties that are useful for treating skin disorders. In this study, we used a full-thickness excisional wound model in mice to test the hypothesis that Snail Secretion Filtrate (SSF) can improve the wound healing process. The mucus from Helix aspersa Muller was obtained mechanically by manually stimulating snails with a sterile cotton swab tip, and then the mucus was subjected to a series of filtrations to obtain SSF. After wounding, the mice were treated topically with SSF for 14 days. Our macroscopic results show that the SSF treatment significantly improved the speed and percentage of wound area closure. Furthermore, SSF improved several markers of proper wound healing, such as collagen deposition (Masson, COL3A1, matrix metalloproteinases (MMPs)) and the tissue remodeling process (α-sma, vascular-endothelial growth factor (VEGF)). SSF was also able to counteract the inflammatory process in injured wound tissue (myeloperoxidase (MPO) IL-1β, IL-6, TNF-α). In conclusion, our results show that SSF is able to enhance the speed and efficiency of wound healing and positively regulate several aspects of the wound healing process, such as the proliferative and remodeling phases.
Feline idiopathic cystitis is a common, chronic-relapsing disorder of the lower urinary tract. In addition to environmental modification/enrichment, long-term and safe treatment targeting specific ...pathophysiological changes may be of help. In this context, effective dietary interventions hold clinical promise. Palmitoyl-glucosamine (PGA) and hesperidin (HSP) are safe and authorized feed ingredients for animal nutrition under European regulations.
The current study aimed to investigate whether a 3:1 mixture of micronized PGA and HSP could represent a novel mechanism-oriented approach to chronic cystitis management. A newly validated rat model of cyclophosphamide (CYP)-induced chronic cystitis was used (40 mg/kg, three intraperitoneal injections every 3rd day). Animals were randomized to orally receive either vehicle or PGA-HSP at a low (72 + 24 mg/kg) or high (doubled) dose for 13 days, starting 3 days before the chronic CYP protocol, with mesna (2-mercaptoethane-sulfonate) being used as a reference drug.
Higher PGA-HSP dose was effective at relieving chronic visceral pain, as measured by mechanical allodynia test (von Frey test). The severity of cystitis was also significantly improved, as shown by the reduced sonographic thickening of the bladder wall, as well as the decrease in edema, bleeding and bladder to body weight ratio compared to the vehicle treated group. A significant decrease of MPO activity, MDA level and fibrosis at Masson's trichrome staining was also observed in animals administered PGA-HSP in comparison to vehicle treated ones. The CYP-induced increase in bladder mRNA expression of pro-inflammatory cytokines was also significantly counteracted by the study mixture. Moreover, CYP-induced bladder mast cell accumulation and releasability were significantly decreased by PGA-HSP (even at the low dose), as determined by metachromatic staining, chymase and tryptase immunostaining as well as enzyme-linked immunosorbent assay for histamine and 5-hydoxytriptamine.
PGA-HSP is able to block CYP-induced decrease of tight junction proteins, claudin-1 and occludin, thus preserving the urothelial bladder function. Finally, neuroinflammatory changes were investigated, showing that dietary supplementation with PGA-HSP prevented the activation of neurons and non-neuronal cells (i.e., microglia, astrocytes and mast cells) at the spinal level, and counteracted CYP-induced increase of spinal mRNA encoding for pro-inflammatory cytokines. Altogether, the present findings confirm the uroprotective and pain-relieving effect of PGA-HSP and pave the way to potential and relevant clinical applications of the study supplement in feline idiopathic cystitis.
Pericardial effusion presents clinicians with a challenge when diagnosing the underlying cause and performing a prognosis. Different techniques have been suggested for canine thoracoscopic ...pericardiectomy with the creation of variable pericardial window size. The aim of this study was to statistically compare the surgical time and achieved window size of the paraxiphoid transdiaphragmatic and monolateral intercostal approaches. The paraxifoid and monolateral intercostal approaches showed a mean surgical time of 55 ± 20.08 (SD) minutes and 13.94 ± 4.61 (SD) minutes, and a mean pericardial window diameter of 4.23 ± 0.80 (SD) cm and 3.31 ± 0.43 (SD) cm, respectively. A significant correlation was observed between the dogs’ bodyweight and window size (r = 0.48; p = 0.04) for both surgical approaches, and between the dogs’ bodyweight and surgical time (r = 0.72; p = 0.0016) for monolateral intercostal approach. All treated dogs showed no clinical signs of recurrent cardiac tamponade during the follow-up. Our results provided useful information to help surgeons make the definitive choice of the surgical technique to treat the pericardial effusion.
Tramadol produces a significant reduction in both sevoflurane and isoflurane minimum alveolar concentrations in dogs under experimental conditions. This study aims to compare the effects of tramadol ...administered as a constant rate infusion (CRI) with those of tramadol administered as a single intravenous bolus on physiological parameters and isoflurane requirements in dogs undergoing ovariohysterectomy.
In this study, forty female dogs undergoing ovariohysterectomy were enrolled. The bitches were anesthetized with 5 mg/kg of tiletamine/zolazepam combined with 0.05 mg/kg of acepromazine intravenously. Anesthesia was maintained with isoflurane delivered in 100% oxygen. The group A (n = 20) received tramadol 4 mg/kg in a single intravenous bolus, whereas the group B (n = 20) received tramadol 1.5 mg/kg in an intravenous bolus followed by tramadol 2.6 mg/kg/h as a CRI. The following parameters were recorded: heart rate, respiratory rate, non-invasive blood pressure, body temperature, EtCO2, SpO2 and inspired and expired concentrations of isoflurane. Parameter measurements were performed from pre-preedication (baseline) to skin suturing.
The dogs were healthy subjects that demonstrated no abnormalities on laboratory investigations. Significant tachycardia was recorded after administration of tiletamine/zolazepam combined with acepromazine in both groups. Heart rate decreased after intubation but remained significantly higher compared to baseline values in both groups. Systolic blood pressure significantly decreased in both groups but the recorded values were within the physiological range. Mild reduction in body temperature was recorded in both groups. SpO2 and EtCO2 remained within the physiological range. Isoflurane requirement was significantly lower in the group B compared to the group A. Transient twitching was recorded in two dogs belonging to the group A after tramadol administration.
Compared to tramadol given as a single intravenous bolus injection during ovariohysterectomy in dogs, tramadol administered as a CRI reduces isoflurane requirements in dogs anesthetized with tiletamine/zolazepam combined with acepromazine. Both tramadol given as a CRI and a single intravenous bolus injection, induce decrease in heart rate, respiratory rate and in body temperature but the values of these parameters remain within physiological range in dogs undergoing ovariohysterectomy.
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