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1.
Nat Prod Res ; 32(1): 97-104, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28595450

ABSTRACT

A new malyngamide (1) was isolated along with seven known compounds (2-8) from the marine cyanobacterium Moorea producens collected in Hawaii. Compound 1 represented the first reported malyngamide with a hydroxy moiety at C-7 of the characteristic fatty acid portion of the compound. Compound 1 showed cytotoxicity against L1210 cell line at an IC50 value of 2.9 mM and lethal toxicity against the shrimp Palaemon paucidens at a LD100 value of 33.3 mg/kg. The bioactivity of compound 1 was approximately 10-100 times weaker than those of isomalyngamides A and B (3, 4). These results indicated that the methoxy group at C-7 of the fatty acid section confers a degree of bioactivity in malyngamides.


Subject(s)
Cyanobacteria/chemistry , Lipopeptides/chemistry , Lipopeptides/pharmacology , Amides/chemistry , Amides/pharmacology , Animals , Aquatic Organisms/chemistry , Cell Line, Tumor , Leukemia L1210 , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , Palaemonidae/drug effects , Pyrroles/chemistry , Pyrroles/pharmacology , Structure-Activity Relationship
2.
JAMA Surg ; 152(1): 90-95, 2017 01 01.
Article in English | MEDLINE | ID: mdl-27732710

ABSTRACT

Importance: Liposomal bupivacaine is a novel extended-duration anesthetic that has recently been used for local infiltration in total knee arthroplasty (TKA). Athough liposomal bupivacaine is widely used, it is unknown if the benefits justify the cost in the veteran population at our institution. Objective: To evaluate a change in practice: the effect of local infiltration of liposomal bupivacaine on perioperative outcomes in patients undergoing primary TKA. Design, Setting, and Participants: A retrospective cohort study was conducted among patients who underwent primary TKA at a Veterans Affairs Medical Center before (March 3, 2013-March 2, 2014) and after (March 3, 2014-March 2, 2015) the implementation of liposomal bupivacaine for local infiltration in TKA. Intervention: Drug utilization evaluation of liposomal bupivacaine for local infiltration in TKA. Main Outcomes and Measures: Use of opioids after discharge from the postanesthesia care unit. Results: Among 199 patients, those who received liposomal bupivacaine after primary TKA (mean [SD] age, 65.3 [6.9] years; 93 males and 5 females) had a reduced median opioid use in the first 24 hours after surgery compared with those who did not receive liposomal bupivacaine (mean [SD] age, 64.9 [8.4] years; 95 males and 6 females; [intravenous morphine equivalents, 12.50 vs 22.50 mg; P = .001]). The use of patient-controlled analgesia was also reduced among patients who received liposomal bupivacaine vs those who did not (49 vs 91; P < .001). A reduction in the use of antiemetics was observed in the first 24 hours after surgery (13 vs 34; P = .001) and in the postanesthesia care unit among those who received liposomal bupivacaine vs those who did not (4 vs 20; P = .001). The number of patients in the postanesthesia care unit with no pain was improved among those who received liposomal bupivacaine vs those who did not (44 vs 19; P < .001). Although median (interquartile range) pain scores in the postanesthesia care unit were improved among patients who received liposomal bupivacaine vs those who did not (4.0 [0.0-6.6] vs 5.5 [3.0-7.5]; P = .001), patients who received liposomal bupivacaine had greater median (interquartile range) pain scores 48 hours (5.5 [4.0-7.0] vs 5.0 [3.0-6.0]; P = .01), 72 hours (5.0 [4.0-6.0] vs 4.0 [2.0-6.0]; P = .002), and 96 hours (5.0 [3.0-6.5] vs 4.0 [1.0-5.0]; P = .003) after surgery than those who did not receive liposomal bupivacaine. There was no difference in the median length of stay between the 2 groups. Institutional cost savings was estimated at $27 000 per year. Conclusions and Relevance: Local infiltration of liposomal bupivacaine reduces use of opioids in the first 24 hours after primary TKA. Similarly, reduction in antiemetic use and improved postoperative pain are also seen in the first 24 hours after surgery but are limited to this time frame. Furthermore, a positive institutional cost savings was observed.


Subject(s)
Analgesics, Opioid/administration & dosage , Anesthesia, Local/methods , Anesthetics, Local/administration & dosage , Arthroplasty, Replacement, Knee , Bupivacaine/administration & dosage , Aged , Analgesia, Patient-Controlled , Analgesics, Opioid/economics , Anesthetics, Local/economics , Antiemetics/therapeutic use , Bupivacaine/economics , Cost Savings , Female , Humans , Interrupted Time Series Analysis , Liposomes , Male , Middle Aged , Pain Measurement , Pain, Postoperative/drug therapy , Postoperative Period , Retrospective Studies
3.
J Clin Anesth ; 34: 403-6, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27687421

ABSTRACT

Opioids are important for surgical pain control but may not be appropriate for patients with narcotic abuse histories or opioid intolerance. We describe a laparoscopic bilateral inguinal herniorrhaphy performed without perioperative or postoperative narcotics. Postoperative analgesia involves a novel technique using 2 different bupivacaine formulations that act synergistically to avoid lag time and provide extended pain relief during the acute surgical recovery phase.


Subject(s)
Anesthesia, Local/methods , Bupivacaine/administration & dosage , Bupivacaine/therapeutic use , Herniorrhaphy/methods , Pain Management/methods , Pain, Postoperative/drug therapy , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/therapeutic use , Anesthesia, General/methods , Anesthesia, Spinal , Anesthetics, Local/administration & dosage , Anesthetics, Local/therapeutic use , Atracurium/administration & dosage , Atracurium/analogs & derivatives , Drug Synergism , Hernia, Inguinal/surgery , Humans , Laparoscopy , Liposomes , Male , Middle Aged , Neuromuscular Blockade/methods , Pain Measurement/methods
4.
JAMA Surg ; 151(12): 1108-1114, 2016 12 01.
Article in English | MEDLINE | ID: mdl-27653293

ABSTRACT

Importance: Quality of recovery (directly associated with patient satisfaction) is an important clinical outcome measurement and a surrogate of anesthetic/surgical care quality. Objectives: To compare the efficacy of a transversus abdominis plane (TAP) block with dexamethasone sodium phosphate and preperitoneal instillation of local anesthetic (PILA) with dexamethasone vs control on postoperative quality of recovery following a bilateral total extraperitoneal inguinal hernia repair (TEP-IHR) (>24 hours). Secondary objectives included efficacy of this technique on postoperative opioid use, nausea and vomiting, and pain scores. Design, Setting, and Participants: Conducted from November 2013 to August 2015, this randomized, prospective, single-blinded study compared 2 groups (a TAP block and PILA) with a standard anesthetic technique with no regional technique (control) following bilateral TEP-IHR. This study at the Veterans Affairs Medical Center (Indianapolis, Indiana) included patients ages 18 to 80 years with an American Society of Anesthesiologists physical status of 1 to 3 scheduled for an outpatient bilateral TEP-IHR. Nurses assigning pain scores and administrating opioids for pain and staff anesthesiologists administering the Quality of Recovery-40 (QoR-40) questionnaire were blinded. Interventions: Patients randomized to receive a TAP block with local anesthetics and dexamethasone, PILA with dexamethasone, or no regional technique (3 groups). Main Outcomes and Measures: Patient's response to the QoR-40 questionnaire following a TEP-IHR surgery. Results: The mean (SD) ages in the TAP block (n = 19), PILA (n = 24), and control (n = 23) groups were 58.2 (9.4) years, 62.5 (8.1) years, and 62.9 (7.8) years, respectively. The global QoR-40 scores on postoperative day 1 for the TAP block group (median [interquartile range (IQR)], 178 [173-188]) were comparable with the control group (median [IQR], 174 [150-181]), while the PILA group had better global QoR-40 scores (median [IQR], 184 [175.5-190.75]) (P = .002). The effects of the TAP block and PILA on pain in the postoperative care unit (PACU) (median [IQR], 1 [0-5] and 3.5 [0-6.8], respectively), pain after discharge (median [IQR], 3 [2-5] and 3 [1-5.5], respectively), opiate use after discharge (median [IQR], 6.7 [5-10] and 6.7 [3.3-10], respectively), and incidence of nausea and vomiting in the PACU (4 of 19 [21.1%] and 6 of 24 [25%], respectively) were not significantly different from the control group (median [IQR], 4 [3-6] for pain scores in the PACU; 4 [3-7] for pain scores after discharge; 6.7 [3.3-10] for opioid use after discharge; and 6 of 23 [26.1%] for incidence of nausea/vomiting in the PACU). While there was a significant reduction of opioid use in the PACU in the TAP block group (median [IQR], 0 [0-1.3]) when compared with the control group (median [IQR], 4 [1.3-6.7]) (P = .001), this was not seen in the PILA group (median [IQR], 2 [0-6.4]). Conclusions and Relevance: This study demonstrates a better quality of recovery in patients' receiving PILA with dexamethasone compared with control for a TEP-IHR surgery. Trial Registration: clinicaltrials.gov Identifier: NCT02036983.


Subject(s)
Anesthesia, Local/methods , Anesthetics, Local , Anti-Inflammatory Agents/administration & dosage , Bupivacaine , Dexamethasone/analogs & derivatives , Herniorrhaphy/adverse effects , Pain, Postoperative/prevention & control , Aged , Analgesics, Opioid/therapeutic use , Convalescence , Dexamethasone/administration & dosage , Female , Humans , Inguinal Canal/surgery , Instillation, Drug , Male , Middle Aged , Nausea/etiology , Nerve Block , Pain Measurement , Pain, Postoperative/drug therapy , Prospective Studies , Single-Blind Method , Vomiting/etiology
6.
Mar Drugs ; 12(12): 5788-800, 2014 Dec 01.
Article in English | MEDLINE | ID: mdl-25470181

ABSTRACT

The toxin-producing cyanobacterium, Moorea producens, is a known causative organism of food poisoning and seaweed dermatitis (also known as "swimmer's itch"). Two new toxic compounds were isolated and structurally elucidated from an ethyl acetate extract of M. producens collected from Hawaii. Analyses of HR-ESI-MS and NMR spectroscopies, as well as optical rotations and CD spectra indicated two new lyngbyatoxin derivatives, 2-oxo-3(R)-hydroxy-lyngbyatoxin A (1) and 2-oxo-3(R)-hydroxy-13-N-desmethyl-lyngbyatoxin A (2). The cytotoxicity and lethal activities of 1 and 2 were approximately 10- to 150-times less potent than lyngbyatoxin A. Additionally, the binding activities of 1 and 2 possessed 10,000-times lower affinity for the protein kinase Cδ (PKCδ)-C1B peptide when compared to lyngbyatoxin A. These findings suggest that these new lyngbyatoxin derivatives may mediate their acute toxicities through a non-PKC activation pathway.


Subject(s)
Cyanobacteria/chemistry , Lyngbya Toxins/chemistry , Hawaii , Marine Toxins/chemistry , Protein Kinase C/chemistry
7.
Mar Drugs ; 12(5): 2748-59, 2014 May 12.
Article in English | MEDLINE | ID: mdl-24824022

ABSTRACT

Lyngbyatoxin A from the marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) is known as the causative agent of "swimmer's itch" with its highly inflammatory effect. A new toxic compound was isolated along with lyngbyatoxin A from an ethyl acetate extract of M. producens collected from Hawaii. Analyses of HR-ESI-MS and NMR spectroscopies revealed the isolated compound had the same planar structure with that of lyngbyatoxin A. The results of optical rotation and CD spectra indicated that the compound was a new lyngbyatoxin A derivative, 12-epi-lyngbyatoxin A (1). While 12-epi-lyngbyatoxin A showed comparable toxicities with lyngbyatoxin A in cytotoxicity and crustacean lethality tests, it showed more than 100 times lower affinity for protein kinase Cδ (PKCδ) using the PKCδ-C1B peptide when compared to lyngbyatoxin A.


Subject(s)
Cyanobacteria/chemistry , Lyngbya Toxins/chemistry , Lyngbya Toxins/pharmacology , Animals , Antineoplastic Agents/pharmacology , Hawaii , Humans , Lethal Dose 50 , Leukemia L1210/drug therapy , Lyngbya Toxins/toxicity , Molecular Conformation , Palaemonidae , Protein Kinase C/antagonists & inhibitors , Protein Kinase C/metabolism
9.
J Clin Anesth ; 24(1): 58-61, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22284321

ABSTRACT

A 45 year old man with metastatic colon cancer presented with uncontrollable abdominal wall pain. Transversus abdominis plane (TAP) block with ropivacaine and methylprednisolone was performed with excellent pain relief, which allowed a significant weaning of the patient's opioid requirements. A second TAP block was performed with a 33% ethanol solution (ethanol and ropivacaine) with excellent pain relief. The neurolytic block appeared to offer better pain control for more than 5 days after placement until the patient finally succumbed to his illness.


Subject(s)
Abdominal Pain/drug therapy , Colonic Neoplasms/complications , Nerve Block/methods , Abdominal Pain/etiology , Abdominal Wall , Amides/administration & dosage , Analgesics, Opioid/administration & dosage , Colonic Neoplasms/pathology , Ethanol/administration & dosage , Glucocorticoids/administration & dosage , Humans , Male , Methylprednisolone/administration & dosage , Middle Aged , Neoplasm Metastasis , Ropivacaine
10.
J Nat Prod ; 72(9): 1573-8, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19739598

ABSTRACT

A lipophilic extract of an eastern Caribbean collection of Lyngbya majuscula yielded two new halogenated fatty acid amides, grenadamides B (1) and C (2), and two new depsipeptides, itralamides A (3) and B (4), along with the known compounds hectochlorin and deacetylhectochlorin. The recently reported depsipeptide carriebowmide (5) was also present in the extract and isolated as its sulfone artifact (6). Compounds 1-4 were identified by spectroscopic methods. The configurations of the amino acid residues of 3, 4, and 6 were determined by LC-MS analyses of diastereomeric derivatives of the acid hydrolysates (advanced Marfey's method). Based on the configurational analysis of 6, in direct comparison with authentic carriebowmide (5), a minor structural revision of 5 is proposed. Compounds 1 and 2 displayed marginal activity against the beet armyworm (Spodoptera exigua). Compounds 1-4 and 6 were assessed for general cell toxicity in human embryonic kidney (HEK293) cells. Only itralamide B (4) displayed significant cytotoxicity, showing an IC(50) value of 6 +/- 1 muM.


Subject(s)
Amides , Depsipeptides/isolation & purification , Fatty Acids, Unsaturated/isolation & purification , Hydrocarbons, Halogenated/isolation & purification , Animals , Cyanobacteria/chemistry , Depsipeptides/chemistry , Depsipeptides/pharmacology , Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/pharmacology , Female , Grenada , Humans , Hydrocarbons, Halogenated/chemistry , Hydrocarbons, Halogenated/pharmacology , Kidney/cytology , Kidney/drug effects , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Spodoptera/drug effects
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