Article ultrasound-guided funicular block: Ropivacaine injection into the tissue around the spermatic cord to improve analgesia during orchiectomy in dogs

Orchiectomy is a common surgical procedure performed on small animals, and it requires postoperative pain management despite its relative simplicity. This study aimed to evaluate the hemodynamic stability, intraoperative administration of additional hypnotic and/or analgesic drugs, and postoperative pain scores following the combination of ultrasound-guided injection of ropiva-caine hydrochloride into the spermatic cord and infiltration by the same anaesthetic of the incisional prescrotal line (ROP) or general anaesthesia. Dogs in the ROP group showed greater intraoperative hemodynamic stability and lower pain scores than the control group. The locoregional approach used in this study proved effective in minimising the responses to the surgical stimulus and ensured ade-quate analgesia intra-and postoperatively. This method, called ultrasound-guided funicular block, allows orchiectomy to be performed under deep sedation without general anaesthesia

Use of spinal anaesthesia with anaesthetic block of intercostal nerves compared to a continuous infusion of sufentanyl to improve analgesia in cats undergoing unilateral mastectomy

Unilateral mastectomy is a common surgical procedure in feline species and requires postoperative pain management. Our study aimed to evaluate the analgesic efficacy of subarachnoid anaesthesia combined with an intercostal nerve block, in comparison with the use of sufentanyl citrate administered as a constant-rate infusion (CRI). Twenty cats were randomly divided into two groups (n = 10/group) based on the analgesic protocol used: the first received loco-regional anaesthesia with levobupivacaine (LR group), and the second received a CRI of sufentanyl (SUF group). The evaluation criteria during surgery were the need for a bolus of fentanyl in the event of an increased heart rate or increased blood pressure. In the postoperative period, the levels of comfort/discomfort and pain were used to obtain a score according to the UNESP-Botucatu multimodal scale. Subjects who scored above seven received analgesic drug supplementation. Intraoperative analgesia was satisfactory, with good haemodynamic stability in both groups. Four patients in the LR group required an extra dose of methadone after they achieved the sternal decubitus position, whereas those in the SUF group required many more doses. The analgesia achieved in the LR group was more satisfactory than that in the SUF group

Cucurbitacin IIa: a novel class of anti-cancer drug inducing non-reversible actin aggregation and inhibiting survivin independent of JAK2/STAT3 phosphorylation

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ROS-generating NADPH oxidase NOX4 is a critical mediator in oncogenic H-Ras-induced DNA damage and subsequent senescence

Activated Ras oncogene induces DNA-damage response by triggering reactive oxygen species (ROS) production and this is critical for oncogene-induced senescence. Until now, little connections between oncogene expression, ROS-generating NADPH oxidases and DNA-damage response have emerged from different studies. Here we report that H-RasV12 positively regulates the NADPH oxidase system NOX4-p22phox that produces H2O2. Knocking down the NADPH oxidase with small interference RNA decreases H-RasV12-induced DNA-damage response detected by γ-H2A.X foci analysis. Using HyPer, a specific probe for H2O2, we detected an increase in H2O2 in the nucleus correlated with NOX4-p22phox perinuclear localization. DNA damage response can be caused not only by H-RasV12-driven accumulation of ROS but also by a replicative stress due to a sustained oncogenic signal. Interestingly, NOX4 downregulation by siRNA abrogated H-RasV12 regulation of CDC6 expression, an essential regulator of DNA replication. Moreover, senescence markers, such as senescence-associated heterochromatin foci, PML bodies, HP1β foci and p21 expression, induced under H-RasV12 activation were decreased with NOX4 inactivation. Taken together, our data indicate that NADPH oxidase NOX4 is a critical mediator in oncogenic H-RasV12-induced DNA-damage response and subsequent senescence

The Rho-Rock-Myosin Signaling Axis Determines Cell-Cell Integrity of Self-Renewing Pluripotent Stem Cells

Background: Embryonic stem (ES) cells self-renew as coherent colonies in which cells maintain tight cell-cell contact. Although intercellular communications are essential to establish the basis of cell-specific identity, molecular mechanisms underlying intrinsic cell-cell interactions in ES cells at the signaling level remain underexplored. Methodology/Principal Findings: Here we show that endogenous Rho signaling is required for the maintenance of cell-cell contacts in ES cells. siRNA-mediated loss of function experiments demonstrated that Rock, a major effector kinase downstream of Rho, played a key role in the formation of cell-cell junctional assemblies through regulation of myosin II by controlling a myosin light chain phosphatase. Chemical engineering of this signaling axis by a Rock-specific inhibitor revealed that cell-cell adhesion was reversibly controllable and dispensable for self-renewal of mouse ES cells as confirmed by chimera assay. Furthermore, a novel culture system combining a single synthetic matrix, defined medium, and the Rock inhibitor fully warranted human ES cell self-renewal independent of animal-derived matrices, tight cell contacts, or fibroblastic niche-forming cells as determined by teratoma formation assay. Conclusions/Significance: These findings demonstrate an essential role of the Rho-Rock-Myosin signaling axis for the regulation of basic cell-cell communications in both mouse and human ES cells, and would contribute to advance i

Clinical evaluation of the efficacy of two different analgesic protocols during prescrotal orchiectomy in dogs

Orchiectomy is a common surgical procedure in small animal practice. In spite of the relative technical simplicity of execution, orchiectomy requires a serious approach to perioperative analgesic management. Neuroaxial (epidural) and loco-regional (infiltration of the incision line and testicular parenchyma) techniques of anaesthesia have been reported to improve the quality of sedation and/or general anaesthesia (1). The purpose of this study was to evaluate the analgesic efficacy of administration of ropivacaine hydrochloride by ultrasound-guided injection into the spermatic cord, together with infiltration of the same anaesthetic into the prescrotal incisional line (4). Fifty privately-owned dogs presented for clinical orchiectomy were randomly divided into two groups of 25 each (ROP group and Control group). The dogs were approximately 2 - 4 y of age and 15-25 kg body weight. They received the same combination of drugs for sedative-analgesic purposes: 3 mcg/kg of dexmedetomidine + 0,25 mg/kg of methadone (2,3). Subjects in the ROP group were administered only ropivacaine, injected into the tissue around the spermatic cord at the level of its starting point from the superficial inguinal ring, and also injected into the incision line (0,2 ml/kg of ropivacaine 0,5% at each injection site). In the Control Group (25 dogs), 20 min after sedation, propofol were administered i.v. to induce general anaesthesia. Parameters taken into consideration were haemodynamic stability, the need for additional administration of hypnotic and/or analgesic drugs in the intraoperative period, and the need for analgesics in the postoperative period. Dogs in the ROP group showed a greater hemodynamic stability intraoperatively (considering heart rate, electrocardiogram, pulse oximetry and blood pressure) compared with the Control group, and did not react on surgical stimulation. Dogs in the ROP group and in Control group had no requirement for hypnotics during the procedure. Immediately after surgery, evaluation of pain by the Glasgow pain scale demonstrated that both group did not present signs of pain. In the postoperative period at home, owners reported no signs of pain or discomfort in two group. The loco-regional approach used in this study has been shown to be effective in minimizing responses to the surgical stimulus, and ensured adequate analgesia in the both the intraoperative and postoperative period. This method allows the procedure to be performed under deep sedation and therefore avoids the use of general anaesthesia. REFERENCES: 1) Almeida RM, Escobar A, Maguilnik S et al., 2010 ‘Comparison of analgesia provided by lidocaine, lidocaine-morphine or lidocaine-tramadol delivered epidurally in dogs following orchiectomy’ , Vet Anaesth Analg. 37(6):542-9. 2) Cardoso CG, Marques DR, da Silva TH, de Mattos-Junior E, 2014 ‘Cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone or in combination with methadone, morphine or tramadol in dogs’Vet Anaesth Analg. 41(6):636-43. 3) Ingvast-Larsson C, Holgersson A, Bondesson U, Lagerstedt AS, Olsson K., 2010, ‘Clinical pharmacology of methadone in dogs’, Vet Anaesth Analg.37(1):48-56. 4) Kushnir Y, Toledano N, Cohen L, Bdolah-Abram T, Shilo-Benjamini Y., 2017, ‘Intratesticular and incisional line infiltration with ropivacaine for castration i

Evaluation of the analgesic effect of the Fentanyl patch during ovariectomy and the postoperative period in bitch.

For several years now, routine surgical procedures such as ovariectomy are performed as outpatient surgery. Post-operative care turns out to be much more comfortable for the patient than hospitalization, particularly at home in reducing the risk of nosocomial infections. However, this approach rises the problem of the administration of analgesic drugs by the owners at home. The potent opioid fentanyl is market in the form of a patch (DURAGESIC®, Jannsen), which fentanyl is gradually released for approximately 72 hours after application (1). The aim of this study was to evaluate the convenience and the analgesic efficacy of this patch, in comparison to other analgesic protocols usually utilized in ovariectomized bitches. This study involved 20 privately-owned bitches, ovariectomized at the Veterinary Hospital of the Department of Veterinary Medicine (Bari). Only bitches housed without other domestic animals were selected, to allow the owners to perform a strict control in the postoperative period. The animals (healthy and from 2 to 5 years of age) were randomly divided into two 2groups. In both groups after premedication with acepromazine, anesthesia was induced by propofol and maintained with isofluorane. The following parameters were monitored during the procedure in all animals: heart rate, electrocardiogram, EtCO2, pulse oximetry, blood pressure and body temperature. The analgesic protocols in the Fentanyl group and Control group were different. The Fentanyl patches were applied 12 hours before the surgery. Transdermal fentanyl patches were placed on the neck skin, which had been previously shaved and disinfected. The size of individual patch was chosen based on the patient's body weight: <10 kg = 25 mcg/h; 10-20 kg = 50 mcg/h; 20-30 kg = 75 mcg/h, and 30-40 kg = 100 mcg/h (2). The patches were affixed with adhesive tape, and left on site for 72 hours after application (3). In the control group standard analgesic protocol pre-surgically was with methadone and oral administration of analgesic drugs at home was administered (robenacoxib). In the clinic, after the dog awakened from anesthesia, the behavior and level of pain/discomfort were evaluated using the Glasgow Pain Scale. The owners filled out a questionnaire with a numerical scale (from 0 to 10) to assess their dogs behavior and the owners satisfaction, regarding the management of their animals postoperative. All the animals in the study hade an uneventful recovery from anesthesia. The owners of the bitches in Fentanyl group were more satisfied with post-operative management than were the owners of the control group (administration of drugs orally). More pain was reported in the control group, related to bitches refusing oral medication. The bitches in the Fentanyl group tolerated the Fentanyl patch well, without any side effects noted. The data obtained from this study shows that the fentanyl patch is a valid aid for effective analgesia post-ovariectomy in bitches