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

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

Stat3 promotes metastatic progression of prostate cancer

There are currently no effective therapies for metastatic prostate cancer because the molecular mechanisms that underlie the metastatic spread of primary prostate cancer are unclear. Transcription factor Stat3 is constitutively active in malignant prostate epithelium, and its activation is associated with high histological grade and advanced cancer stage. In this work, we hypothesized that Stat3 stimulates metastatic progression of prostate cancer. We show that Stat3 is active in 77% of lymph node and 67% of bone metastases of clinical human prostate cancers. Importantly, adenoviral gene delivery of wild-type Stat3 (AdWTStat3) to DU145 human prostate cancer cells increased the number of lung metastases by 33-fold in an experimental metastasis assay compared with controls. Using various methods to inhibit Stat3, we demonstrated that Stat3 promotes human prostate cancer cell migration. Stat3 induced the formation of lamellipodia in both DU145 and PC-3 cells, further supporting the concept that Stat3 promotes a migratory phenotype of human prostate cancer cells. Moreover, Stat3 caused the rearrangement of cytoplasmic actin stress fibers and microtubules in both DU145 and PC-3 cells. Finally, inhibition of the Jak2 tyrosine kinase decreased both activation of Stat3 and prostate cancer cell motility. Collectively, these data indicate that transcription factor Stat3 is involved in metastatic behavior of human prostate cancer cells and may provide a therapeutic target to prevent metastatic spread of primary prostate cancer

Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy

Background This phase I/II study determined the maximal tolerable dose, dose limiting toxicities, antitumor activity, the pharmacokinetics and pharmacodynamics of ruthenium compound NAMI-A in combination with gemcitabine in Non-Small Cell Lung Cancer patients after first line treatment. Methods Initial dose escalation of NAMI-A was performed in a 28 day cycle: NAMI-A as a 3 h infusion through a port-a-cath at a starting dose of 300 mg/m(2) at day 1, 8 and 15, in combination with gemcitabine 1,000 mg/m(2) at days 2, 9 and 16. Subsequently, dose escalation of NAMI-A in a 21 day schedule was explored. At the maximal tolerable dose level of this schedule an expansion group was enrolled of which 15 patients were evaluable for response. Results Due to frequent neutropenic dose interruptions in the third week, the 28 day schedule was amended into a 21 day schedule. The maximal tolerable dose was 300 and 450 mg/m(2) of NAMI-A (21 day schedule). Main adverse events consisted of neutropenia, anemia, elevated liver enzymes, transient creatinine elevation, nausea, vomiting, constipation, diarrhea, fatigue, and renal toxicity. Conclusion NAMI-A administered in combination with gemcitabine is only moderately tolerated and less active in NSCLC patients after first line treatment than gemcitabine alone

Redox regulation of Rac1 by thiol oxidation

The Rac1 GTPase is an essential and ubiquitous protein that signals through numerous pathways to control critical cellular processes, including cell growth, morphology, and motility. Rac1 deletion is embryonic lethal, and its dysregulation or mutation can promote cancer, arthritis, cardiovascular disease, and neurological disorders. Rac1 activity is highly regulated by modulatory proteins and posttranslational modifications. Whereas much attention has been devoted to guanine nucleotide exchange factors that act on Rac1 to promote GTP loading and Rac1 activation, cellular oxidants may also regulate Rac1 activation by promoting guanine nucleotide exchange. Herein, we show that Rac1 contains a redox-sensitive cysteine (Cys(18)) that can be selectively oxidized at physiological pH because of its lowered pK(a). Consistent with these observations, we show that Rac1 is glutathiolated in primary chondrocytes. Oxidation of Cys(18) by glutathione greatly perturbs Rac1 guanine nucleotide binding and promotes nucleotide exchange. As aspartate substitutions have been previously used to mimic cysteine oxidation, we characterized the biochemical properties of Rac1(C18D). We also evaluated Rac1(C18S) as a redox-insensitive variant and found that it retains structural and biochemical properties similar to those of Rac1(WT) but is resistant to thiol oxidation. In addition, Rac1(C18D), but not Rac1(C18S), shows greatly enhanced nucleotide exchange, similar to that observed for Rac1 oxidation by glutathione. We employed Rac1(C18D) in cell-based studies to assess whether this fast-cycling variant, which mimics Rac1 oxidation by glutathione, affects Rac1 activity and function. Expression of Rac1(C18D) in Swiss 3T3 cells showed greatly enhanced GTP-bound Rac1 relative to Rac1(WT) and the redox-insensitive Rac1(C18S) variant. Moreover, expression of Rac1(C18D) in HEK-293T cells greatly promoted lamellipodia formation. Our results suggest that Rac1 oxidation at Cys(18) is a novel posttranslational modification that upregulates Rac1 activity