Tuesday, 21 May 2019

Study Shows Intrathecal Bupivacaine Effective for Long-Term Cancer Pain Treatment

Study Shows Intrathecal Bupivacaine Effective for Long-Term Cancer Pain Treatment

Boston-Patients suffering from cancer pain refractory to systemic opioids may find relief in an unlikely source, according to a pilot study by Swedish researchers: intrathecal bupivacaine. They concluded that the therapy can be effectively used for long-term pain management in these individuals with little increase in dose and few of the side effects that often accompany opioid-related treatment.

“Treating cancer pain with morphine is often effective, but it’s not without its problems,” said Anders Wincent, MD, a senior consultant at the Karolinska University Hospital in Stockholm. “Previously we found there was no analgesic benefit to adding morphine to intrathecal bupivacaine in severe cancer-related pain [Int J Clin Pharmacol Ther 2017;55(6):525-532]. So in this study we wanted to see if we could address this pain only with intrathecal bupivacaine.”


Putting It to the Test
To help answer this question, Dr. Wincent and his co-investigator Karl-Fredrik Sjolund, MD, PhD, enrolled 30 adult patients (17 women; median age, 55 years) with cancer-related pain, who presented to the institution between November 2013 and June 2017, into the longitudinal case series; each was receiving systemic opioid therapy. All patients were started on an intrathecal bupivacaine infusion of 2 mg/mL; flow rates and subsequent bolus doses were titrated as necessary. The catheter tip was positioned cranially to the individual’s most painful dermatome; catheter tip position was verified with fluoroscopy. After subcutaneous tunneling, the catheter was attached to a subcutaneous port and connected to an external pump.

Before intrathecal bupivacaine therapy, the participants completed a pain-related questionnaire. Follow-up was performed by nurses via a structured telephone interview with the patients, their families or staff at a palliative care facility or hospital. Pain intensity at rest and during activity was measured using the numerical rating scale (NRS); other tools included the short form of the Brief Pain Inventory, the revised Edmonton Symptom Assessment Scale and ECOG Performance Status.

Motor function was graded with the modified Bromage scale (0-3); daily systemic opioid data were extracted from electronic health records. Patient data were collected on the day before and day of catheter insertion; one day after catheter insertion; on days 3, 7, 14, 21 and 28; and once monthly thereafter.

Monday, 20 May 2019

Structure of Sesquisabinene Synthase 1, a Terpenoid Cyclase That Generates a Strained [3.1.0] Bridged-Bicyclic Product

                                                                                  

Structure of Sesquisabinene Synthase 1, a Terpenoid Cyclase That Generates a Strained [3.1.0] Bridged-Bicyclic Product


The natural product sesquisabinene is a key component of the fragrant essential oil of the sandalwood tree, currently valued at $5,000/L. Sesquisabinene contains a highly strained [3.1.0] bicyclic ring system and is generated from farnesyl diphosphate in a reaction catalyzed by a class I terpenoid cyclase. To understand how the enzyme directs the formation of a strained hydrocarbon ring system, we now report the X-ray crystal structure of sesquisabinene synthase 1 (SQS1) from the Indian sandalwood tree (Santalum album). Specifically, we report the structure of unliganded SQS1 at 1.90 Å resolution and the structure of its complex with three Mg2+ ions and the inhibitor ibandronate at 2.10 Å resolution. The bisphosphonate group of ibandronate coordinates to all three metal ions and makes hydrogen bond interactions with basic residues at the mouth of the active site. These interactions are similarly required for activation of the substrate diphosphate group to initiate catalysis, although partial occupancy binding of the Mg2+B ion suggests that this structure represents the penultimate metal coordination complex just prior to substrate activation. The structure of the liganded enzyme enables a precise definition of the enclosed active site contour that serves as a template for the cyclization reaction. This contour is very product-like in shape and readily fits an extended conformation of sesquisabinene and its precursor, the homobisabolyl cation. Structural comparisons of SQS1 with epi-isozizaene synthase mutants that also generate sesquisabinene suggest that [3.1.0] ring formation is not dependent on the isoprenoid tail conformation of the homobisabolyl cation.

Friday, 17 May 2019

Get Help with Your Nurse Corps Scholarship Application Today!


Get Help with Your Nurse Corps Scholarship Application Today!

The 2019 Nurse Corps Scholarship Program application cycle will close Tuesday, May 21 at 7:30 p.m. ET. Nurse Corps Scholarship Program staff will be available to address any questions regarding the program components, requirements, and obligations, as well as to support you as you complete the application process. Don’t miss this unique opportunity!
Nurse Corps Scholarship Application Technical Assistance Call
Thursday, May 16
3:00 - 4:30 p.m. ET
Dial-in: 1-888-455-2923 | Passcode: 2458846
Prior to participating, we encourage you to review the 2019 Nurse Corps Scholarship Application and Program Guidance and the Nurse Corps Scholarship Application Webinar Recording, which review the eligibility requirements, application process, and more!

Lifestyle is a threat to gut bacteria: Ötzi proves it, study shows

The intestinal microbiome is a delicate ecosystem made up of billions and billions of microorganisms, bacteria in particular, that support ...