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Journal of Visualized Experiments : JoVE Mar 2013This method is based on the intravenous injection of Evans Blue in mice as the test animal model. Evans blue is a dye that binds albumin. Under physiologic conditions...
This method is based on the intravenous injection of Evans Blue in mice as the test animal model. Evans blue is a dye that binds albumin. Under physiologic conditions the endothelium is impermeable to albumin, so Evans blue bound albumin remains restricted within blood vessels. In pathologic conditions that promote increased vascular permeability endothelial cells partially lose their close contacts and the endothelium becomes permeable to small proteins such as albumin. This condition allows for extravasation of Evans Blue in tissues. A healthy endothelium prevents extravasation of the dye in the neighboring vascularized tissues. Organs with increased permeability will show significantly increased blue coloration compared to organs with intact endothelium. The level of vascular permeability can be assessed by simple visualization or by quantitative measurement of the dye incorporated per milligram of tissue of control versus experimental animal/tissue. Two powerful aspects of this assay are its simplicity and quantitative characteristics. Evans Blue dye can be extracted from tissues by incubating a specific amount of tissue in formamide. Evans Blue absorbance maximum is at 620 nm and absorbance minimum is at 740 nm. By using a standard curve for Evans Blue, optical density measurements can be converted into milligram dye captured per milligram of tissue. Statistical analysis should be used to assess significant differences in vascular permeability.
Topics: Animals; Capillary Permeability; Endothelium, Vascular; Evans Blue; Extravasation of Diagnostic and Therapeutic Materials; Injections, Intravenous; Mice
PubMed: 23524912
DOI: 10.3791/50062 -
Endocrinology, Diabetes & Metabolism... 2016Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of...
UNLABELLED
Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of administration, in the UK oral ethinyl estradiol and the low-dose oral contraceptive pill are commonly used as hormone replacement therapy for practical reasons. We present five peripubertal girls (aged 12.5-14.9 years) with hypogonadism (two with primary hypogonadism due to Turner syndrome and three with central (secondary) hypogonadism as part of multiple pituitary hormone deficiency) who for a variety of reasons have received milligram doses of estradiol (E2) in error for between 6 weeks and 6 months, instead of the expected microgram doses of ethinyl estradiol. Although there are no direct comparisons in peripubertal girls between synthetic and natural estrogens, all girls had vaginal bleeding whilst receiving the milligram doses and have ended up with reduced final heights, below the 9th centile in 1 and below the 2nd centile in 4. Whilst reduction in final height may be part of the underlying condition (especially in Turner syndrome) the two girls with height predictions performed prior to receiving the estrogen overdose have not achieved their predicted height. Estrogen is one of the few drugs which is available in both milligram and microgram formulations. Clinicians need to be alert to the possibility of patients receiving the wrong formulation and dosage in error.
LEARNING POINTS
Girls with primary and secondary gonadal failure require assistance with pubertal induction.Although several different formulations and route of administration are available, for practical reasons, the majority of girls in the UK receive oral ethinyl estradiol.Estrogen preparations are available in both milligram and microgram formulations, with potential for receiving the wrong dose.Girls receiving milligram rather than microgram preparations all had vaginal bleeding and a short final height.
PubMed: 26843960
DOI: 10.1530/EDM-15-0096 -
Chemical Science May 2022The synthesis of secondary and tertiary amines through the reductive amination of carbonyl compounds is one of the most significant reactions in synthetic chemistry.... (Review)
Review
The synthesis of secondary and tertiary amines through the reductive amination of carbonyl compounds is one of the most significant reactions in synthetic chemistry. Asymmetric reductive amination for the formation of chiral amines, which are required for the synthesis of pharmaceuticals and other bioactive molecules, is often achieved through transition metal catalysis, but biocatalytic methods of chiral amine production have also been a focus of interest owing to their selectivity and sustainability. The discovery of asymmetric reductive amination by imine reductase (IRED) and reductive aminase (RedAm) enzymes has served as the starting point for a new industrial approach to the production of chiral amines, leading from laboratory-scale milligram transformations to ton-scale reactions that are now described in the public domain. In this perspective we trace the development of the IRED-catalyzed reductive amination reaction from its discovery to its industrial application on kg to ton scale. In addition to surveying examples of the synthetic chemistry that has been achieved with the enzymes, the contribution of structure and protein engineering to the understanding of IRED-catalyzed reductive amination is described, and the consequent benefits for activity, selectivity and stability in the design of process suitable catalysts.
PubMed: 35655886
DOI: 10.1039/d2sc00124a -
Saudi Journal of Biological Sciences Jan 2021Microbial surfactants are amphipathic molecules that consist of hydrophilic and hydrophobic domains, which allow partition of two fluid phases of varying degree of... (Review)
Review
Microbial surfactants are amphipathic molecules that consist of hydrophilic and hydrophobic domains, which allow partition of two fluid phases of varying degree of polarity. They are classified into two main groups: bioemulsifier and biosurfactant, depending on their molecular weight. Microbial surfactants occur in various categories according to their chemical nature and producing organisms. These biomolecules are produced by diverse groups of microorganisms including fungi, bacteria, and yeasts. Their production is significantly influenced by substrate type, fermentation technology and microbial strains. Owing to inherent multifunctional properties and assorted synthetic aptitude of the microbes, microbial surfactants are mostly preferred than their chemical counterparts for various industrial and biomedical applications including bioremediation, oil recovery; as supplements in laundry formulations and as emulsion-stabilizers in food and cosmetic industries as well as therapeutic agents in medicine. The present review discusses on production of microbial surfactants as promising and alternative broad-functional biomolecules for various biotechnological applications.
PubMed: 33424354
DOI: 10.1016/j.sjbs.2020.10.058 -
Substance Abuse : Research and Treatment 2017"Doctor shopping" as a means of prescription opioid diversion is examined. The number and percentage of prescriptions and morphine-equivalent milligrams diverted in this... (Review)
Review
OBJECTIVES
"Doctor shopping" as a means of prescription opioid diversion is examined. The number and percentage of prescriptions and morphine-equivalent milligrams diverted in this manner are estimated by state and molecule for the period 2008-2012.
METHODS
Eleven billion prescriptions with unique patient, doctor, and pharmacy identifiers were used to construct diversion "events" that involved between 1 and 6 unique doctors and between 1 and 6 unique pharmacies. Diversion thresholds were established based on the probability of each contingency.
RESULTS
A geographically widespread decline occurred between 2008 and 2012. The number of prescriptions diverted fell from approximately 4.30 million (1.75% of all prescriptions) in 2008 to approximately 3.37 million (1.27% of all prescriptions) in 2012, and the number of morphine-equivalent milligrams fell from approximately 6.55 metric tons (2.95% of total metric tons) in 2008 to approximately 4.87 metric tons (2.19% of total metric tons) in 2012.
CONCLUSIONS
Diversion control efforts have likely been effective. But given increases in opioid-related deaths, opioid-related drug treatment admissions, and the more specific resurgence of heroin-related events, it is clear that additional public health measures are required.
PubMed: 28469426
DOI: 10.1177/1178221817696077 -
American Journal of Obstetrics and... Jul 2018Women commonly receive opioid prescriptions following hospitalization. The rise of the opioid epidemic in the United States underscores the importance of a better...
BACKGROUND
Women commonly receive opioid prescriptions following hospitalization. The rise of the opioid epidemic in the United States underscores the importance of a better understanding of prescribing patterns. Although delivery is the most frequent reason for hospitalization in the United States, there is inadequate knowledge regarding opioid prescribing at postpartum hospital discharge.
OBJECTIVE
We sought to describe opioid prescribing patterns at the time of discharge following delivery in a large, diverse cohort, and to describe the relationship of these patterns with objective and subjective measures of pain prior to discharge.
STUDY DESIGN
This is a retrospective cohort study of all deliveries at a single, high-volume tertiary care center over a 1-year period. Women were excluded from analysis if they had evidence of recent opioid use, or their labor, delivery, or postpartum course was notable for rare, nonroutine events anticipated to increase pain. Medical records were queried for demographic and clinical data, including whether an opioid prescription was provided at discharge, and if so, details of that prescription. The primary outcome was amount of opioid morphine milligram equivalents prescribed at discharge, described separately for women after vaginal and cesarean deliveries. Among women who received a prescription, we additionally assessed associations between prescription quantity and subjective (patient-reported pain score) and objective (inpatient opioid requirement during the final 24 hours of hospitalization) assessments of pain. Descriptive and bivariable analyses were performed.
RESULTS
Of the total 12,611 women, 12,326 were eligible for inclusion. Of 9038 women postvaginal delivery and 3288 women postcesarean delivery, 30.4% and 86.7% received an opioid prescription at discharge, respectively. Of women receiving discharge opioid prescriptions, median morphine milligram equivalents received was 200 (interquartile range: 120-300) following vaginal and 300 (interquartile range: 200-300) following cesarean delivery. Nearly half (45.7%) of women postvaginal delivery and 18.5% of women postcesarean delivery who received an opioid prescription used 0 morphine milligram equivalent during the final hospital day. Similarly, 26.5% and 18.5% of women after vaginal and cesarean delivery, respectively, reported a pain score of 0 of 10 prior to discharge. Regardless of delivery mode, the amount of opioids prescribed did not differ between those who reported a pain score of 0 of 10 and those who reported a pain score of >0 of 10 immediately prior to discharge. Similarly, for women who underwent cesarean delivery, the morphine milligram equivalents prescribed did not differ between those who used 0 morphine milligram equivalents and those who used >0 in the 24 hours prior to hospital discharge.
CONCLUSION
Postpartum women are commonly prescribed opioids at the time of postpartum hospital discharge. There is a wide range of morphine milligram equivalents prescribed at hospital discharge following delivery, highlighting a lack of standardization. Furthermore, regardless of objective and subjective measures of pain prior to discharge, women received similar amounts of prescription morphine milligram equivalents following either vaginal or cesarean deliveries.
Topics: Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Cesarean Section; Cohort Studies; Delivery, Obstetric; Female; Humans; Pain Measurement; Pain, Postoperative; Patient Discharge; Postnatal Care; Practice Patterns, Physicians'; Pregnancy; Retrospective Studies
PubMed: 29630887
DOI: 10.1016/j.ajog.2018.04.003 -
Lidocaine patches for postcesarean pain control in obese women: a pilot randomized controlled trial.American Journal of Obstetrics &... Jan 2021Obesity increases the risk of opioid-related morbidity. Lidocaine patches have been shown to reduce postoperative pain after noncesarean surgeries. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Obesity increases the risk of opioid-related morbidity. Lidocaine patches have been shown to reduce postoperative pain after noncesarean surgeries.
OBJECTIVE
This study aimed to determine whether the application of lidocaine patches around the cesarean incision in women with obesity reduces the total dose of opioids administered in the first 24 hours after cesarean delivery.
STUDY DESIGN
This was a pilot single-blind randomized controlled trial of 61 women with obesity undergoing cesarean delivery at a community tertiary referral hospital staffed by academic physicians. After cesarean delivery, the allocated patches (either 5% lidocaine patches or placebo patches) were applied superior and lateral to the incision dressing and remained in place for 12 hours. The average cumulative opioid dose received within the first 24 hours after cesarean delivery was measured in morphine milligram equivalents. We also assessed pain and patient satisfaction. A sample size of 60 (30 per group) was determined to be adequate to inform a future appropriately powered randomized controlled trial. The primary outcome of morphine milligram equivalents was compared using the Student t test, and pain scores were compared using the Wilcoxon rank sum test.
RESULTS
Of the 146 women screened between February 2019 and September 2019, 61 consented and were analyzed: 30 women were allocated to lidocaine patch and 31 were allocated to placebo (hydrocolloid patch). Women who were allocated to the lidocaine patch used an average of 87.0 (standard deviation, 35.8) morphine milligram equivalents of opioids in the first 24 hours compared with an average of 83.9 (standard deviation, 27.5) morphine milligram equivalents among women who were allocated to the placebo patch (P=.702). Women who were allocated to the lidocaine vs placebo patches reported median pain scores of 3.0 (interquartile range, 2.1-4.9) and 3.5 (interquartile range, 2.5-5.0), respectively (P=.217). The time to the first dose of opioids, total number of opioid doses, and total morphine milligram equivalents in 48 hours and for the entire hospital stay did not differ. Patient satisfaction with both patches was high and not statistically different.
CONCLUSION
This pilot suggests that 5% lidocaine patches applied superior and lateral to the cesarean incision are not effective at reducing the average total dose of morphine milligram equivalents administered in the first 24 hours after cesarean delivery among women with obesity, and they did not seem to improve median pain scores. An appropriately powered randomized trial would not be expected to demonstrate reduction in opioid use or pain.
Topics: Female; Humans; Lidocaine; Obesity; Pain Measurement; Pain, Postoperative; Pilot Projects; Pregnancy; Single-Blind Method
PubMed: 33451596
DOI: 10.1016/j.ajogmf.2020.100281 -
British Journal of Anaesthesia Jul 2021Opioids have been linked to worse oncologic outcomes in surgical patients. Studies in certain cancer types have identified associations between survival and...
BACKGROUND
Opioids have been linked to worse oncologic outcomes in surgical patients. Studies in certain cancer types have identified associations between survival and intra-tumoural opioid receptor gene alterations, but no study has investigated whether the tumour genome interacts with opioid exposure to affect survival. We sought to determine whether intraoperative opioid exposure is associated with recurrence-specific survival and overall survival in early-stage lung adenocarcinoma, and whether selected tumour genomics are associated with this relationship. Associations between ketamine and dexmedetomidine and outcomes were also studied.
METHODS
Surgical patients (N=740) with pathological stage I-III lung adenocarcinoma and next-generation sequencing data were retrospectively reviewed from a prospectively maintained database.
RESULTS
On multivariable analysis, ketamine administration was protective for recurrence-specific survival (hazard ratio = 0.44, 95% confidence interval 0.24-0.80; P=0.007), compared with no adjunct. Higher intraoperative oral morphine milligram equivalents were significantly associated with worse overall survival (hazard ratio=1.09/10 morphine milligram equivalents, 95% confidence interval 1.02-1.17; P=0.010). Significant interaction effects were found between morphine milligram equivalents and fraction genome altered and morphine milligram equivalents and CDKN2A, such that higher fraction genome altered or CDKN2A alterations were associated with worse overall survival at higher morphine milligram equivalents (P=0.044 and P=0.052, respectively). In contrast, alterations in the Wnt (P=0.029) and Hippo (P=0.040) oncogenic pathways were associated with improved recurrence-specific survival at higher morphine milligram equivalents, compared with unaltered pathways.
CONCLUSIONS
Intraoperative opioid exposure is associated with worse overall survival, whereas ketamine exposure is associated with improved recurrence-specific survival in patients with early-stage lung adenocarcinoma. This is the first study to investigate tumour-specific genomic interactions with intraoperative opioid administration to modify survival associations.
Topics: Adenocarcinoma of Lung; Aged; Analgesics, Opioid; Female; Genomics; Humans; Intraoperative Care; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Pain, Postoperative; Prospective Studies; Retrospective Studies; Survival Rate
PubMed: 34147159
DOI: 10.1016/j.bja.2021.03.030