scholarly journals Preoperative oral melatonin can reduce preoperative anxiety and postoperative analgesia in a dose-dependent manner

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Mohamed Lotfy ◽  
Mohamad Ayaad
Keyword(s):  
Study Groups ◽  
Preoperative Anxiety ◽  
Dependent Manner ◽  
Suprachiasmatic Nuclei ◽  
Dose Dependency ◽  
Early Recovery ◽  
Rescue Analgesia ◽  
Pain Scores ◽  
Analgesia Requirement ◽  
Dose Dependent

Abstract Background Preoperative anxiety has deleterious effects on patients’ outcome through its influence on intraoperative requirements of anesthetics and analgesics (Bayrak et al., J Coll Physicians Surg Pak 29:868–873, 2019), postoperative (PO) pain intensity, and analgesia requirement, and may even increase PO morbidity and mortality after certain types of surgery. Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland at night under control of an endogenous rhythm of secretion generated by the suprachiasmatic nuclei. The current study hypothesized that preoperative melatonin could reduce patients’ anxiety and reduce intraoperative (IO) and postoperative (PO) analgesic in a dose-dependent manner. Results Preoperative consultation was, to some extent, effective in reducing patients’ anxiety and apprehension. At 1 h after receiving premedication, Anxiety Specific to Surgery Questionnaire (ASSQ) scores were significantly lower in study groups in comparison to baseline scores and at 1 h scores of P group patients (patients who received 3 ml of plain distilled water), and this significant effect extended for 3-h PO. The reported ∆∆ASSQ between study groups was 25.9% between M2 (melatonin) and Z (midazolam) groups and 36.9% between groups M1 (received melatonin in a dose of 3 mg) and M2 (received melatonin in a dose of 6 mg). Preoperative anxiolytic therapy allowed reduction of PO pain scores and analgesia consumption with prolongation of duration till 1st request of rescue analgesia, and these effects were more pronounced with melatonin 6 mg in comparison to placebo, melatonin 3mg, or midazolam. Conclusion Preoperative melatonin is an appropriate policy for reduction of preoperative anxiety and provided reduction of PO anxiety, pain scores, and consumption of analgesia thus promoting early recovery and short PO hospital stay. Dose dependency was evident, and preoperative melatonin 6-mg dose provided satisfactory effect.

scholarly journals Incorporation of an intercostal catheter into a multimodal analgesic strategy for uniportal video-assisted thoracoscopic surgery: a feasibility study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jian Wei Tan ◽  
Jameelah Sheik Mohamed ◽  
John Kit Chung Tam
Keyword(s):  
Postoperative Pain ◽  
Length Of Stay ◽  
Urinary Retention ◽  
Feasibility Study ◽  
Thoracoscopic Surgery ◽  
Early Recovery ◽  
Rescue Analgesia ◽  
Video Assisted ◽  
Pain Scores ◽  
Video Assisted Thoracoscopic Surgery

Abstract Background Well-controlled postoperative pain is essential for early recovery after uniportal video-assisted thoracoscopic surgery (UVATS). Conventional analgesia like opioids and thoracic epidural anaesthesia have been associated with hypotension and urinary retention. Intercostal catheters are a regional analgesic alternative that can be inserted during UVATS to avoid these adverse effects. This feasibility study aims to evaluate the postoperative pain scores and analgesic requirements with incorporation of an intercostal catheter into a multimodal analgesic strategy for UVATS. Methods In this observational study, 26 consecutive patients who underwent UVATS were administered a multilevel intercostal block and oral paracetamol. All of these patients received 0.2% ropivacaine continuously at 4 ml/h via an intercostal catheter at the level of the incision. Rescue analgesia including etoricoxib, gabapentin and opioids were prescribed using a pain ladder approach. Postoperative pain scores and analgesic usage were assessed. The secondary outcomes were postoperative complications, days to ambulation and length of stay. Results No technical difficulties were encountered during placement of the intercostal catheter. There was only one case of peri-catheter leakage. Mean pain score was 0.31 (range 0–2) on post-operative day 1 and was 0.00 by post-operative day 5. 16 patients (61.6%) required only oral rescue analgesia. The number of patients who required rescue non-opioids only increased from 1 in the first 7 months to 8 in the next 7 months. There were no cases of hypotension or urinary retention. Median time to ambulation was 1 day (range 1–2). Mean post-operative length of stay was 4.17 ± 2.50 days. Conclusions Incorporation of an intercostal catheter into a multimodal analgesia strategy for UVATS is feasible and may provide adequate pain control with decreased opioid usage.

scholarly journals 1953. VE303, a Rationally Designed Bacterial Consortium for Prevention of Recurrent Clostridioides difficile (C. Difficile) infection (rCDI), Stably Restores the Gut Microbiota After Vancomycin (vanco)-Induced Dysbiosis in Adult Healthy Volunteers (HV)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S60-S60 ◽  
Author(s):  
Dmitri Bobilev ◽  
Shakti Bhattarai ◽  
Rajita Menon ◽  
Brian Klein ◽  
Shilpa Reddy ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Phase 1 ◽  
Dose Range ◽  
Bacterial Consortium ◽  
Dependent Manner ◽  
Metagenomic Sequencing ◽  
Early Recovery ◽  
Dose Escalation Study ◽  
Dose Dependent

Abstract Background Gut microbiota alterations and resulting changes in metabolites involved in colonization resistance and host responses, including bile acids (BA) and short-chain fatty acids (SCFA), are hallmarks of C. difficile infection. Reduction in rCDI was shown with fecal microbiota transplants (FMT), but FMT has limitations for routine use and carries unforeseen risks. VE303 is a first-in-class drug being developed for prevention of rCDI consisting of a rationally defined bacterial consortium manufactured under GMP conditions. VE303 comprises 8 distinct species belonging to Clostridium clusters IV, XIVa, and XVII, the commensal bacteria associated with clinical response in FMT, suppress C. difficile growth in vitro and improve survival in vivo. Methods A first-in-human Phase 1 dose-escalation study assessed safety and tolerability of VE303 in HV after vanco-induced dysbiosis. PK (strain colonization and durability) and PD (restoration of the resident microbiota, SCFA pool, and BA pool) were evaluated by metagenomic sequencing and metabolomics analysis of fecal material. Results HV (N = 23) received oral vanco 125 mg QID for 5 days followed by VE303 capsules at escalating single then multiple doses (total dose range 1.6 × 109 to 1.1 × 1011 CFU). VE303-related AEs, mostly gastrointestinal, all Grade 1 and transient, were observed in 35% of HV. Colonization with VE303 strains was abundant, durable (detected at 24 weeks), and dose-dependent. VE303 rapidly expanded 10- to 100-fold and each strain was detectable within 2 days after dosing. VE303 enhanced subjects’ microbiota and metabolic recovery after vanco treatment. When compared with the vanco-only cohort (N = 5), VE303 led to earlier and more complete recovery of beneficial taxa (eg, Bacteroidetes, Firmicutes), reduction in inflammatory taxa (e.g., Proteobacteria) (Figure 1.), and recovery of the secondary BA and SCFA pools. Conclusion VE303, a rationally designed microbial consortium, was safe, well tolerated, and efficiently restored microbiome composition after antibiotic-induced dysbiosis in a dose-dependent manner. VE303 was associated with early recovery of key PD markers of response, including microbiota composition, bile acid, and SCFA pools. A Phase 2 study of VE303 for prevention of rCDI is underway (NCT03788434). Disclosures All Authors: No reported Disclosures.

scholarly journals Simultaneous ingestion of high-methoxy pectin from apple can enhance absorption of quercetin in human subjects

2015 ◽  
Vol 113 (10) ◽  
pp. 1531-1538 ◽  
Author(s):  
Tomohiko Nishijima ◽  
Yoshiki Takida ◽  
Yasuo Saito ◽  
Takayuki Ikeda ◽  
Kunihisa Iwai
Keyword(s):  
Urinary Excretion ◽  
Healthy Volunteers ◽  
Human Subjects ◽  
Urine Samples ◽  
Dependent Manner ◽  
Dose Dependency ◽  
Apple Pectin ◽  
Enhancing Effect ◽  
Chronic Ingestion ◽  
Dose Dependent

Chronic ingestion of apple pectin has been shown to increase the absorption of quercetin in rats. The present study was designed to elucidate whether the simultaneous ingestion of quercetin with apple pectin could enhance the absorption of quercetin in humans, and the effects of dose dependency and degree of pectin methylation on quercetin absorption were also investigated. Healthy volunteers (n 19) received 200 ml of 0·5 mg/ml of quercetin drinks with or without 10 mg/ml of pectin each in a randomised cross-over design study with over 1-week intervals; urine samples from all the subjects were collected within 24 h after ingestion of the test drinks, and urinary deconjugated quercetin and its metabolites were determined using HPLC. The sum of urinary quercetin and its metabolites excreted was increased by 2·5-fold by the simultaneous ingestion of pectin. The metabolism of methylated quercetin (isorhamnetin and tamarixetin) was not affected by pectin ingestion. In six volunteers, who received quercetin drinks containing 0, 3 and 10 mg/ml of pectin, the sum of urinary quercetin and its metabolites excreted also increased in a pectin dose-dependent manner. Furthermore, the simultaneous ingestion of quercetin with low-methoxy and high-methoxy pectin, respectively, increased the sum of urinary excretion of quercetin and its metabolites by 1·69-fold and significantly by 2·13-fold compared with the ingestion of quercetin without pectin. These results elucidated that apple pectin immediately enhanced quercetin absorption in human subjects, and that its enhancing effect was dependent on the dose and degree of pectin methylation. The results also suggested that the viscosity of pectin may play a role in the enhancement of quercetin absorption.

A chemically defined culture of VEGFR2+ cells derived from embryonic stem cells reveals the role of VEGFR1 in tuning the threshold for VEGF in developing endothelial cells

Blood ◽  
2003 ◽  
Vol 101 (6) ◽  
pp. 2261-2267 ◽  
Author(s):  
Masanori Hirashima ◽  
Minetaro Ogawa ◽  
Satomi Nishikawa ◽  
Kazuyoshi Matsumura ◽  
Kotomi Kawasaki ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Fetal Liver ◽  
Embryonic Stem ◽  
Vegf Receptor ◽  
Dependent Manner ◽  
Dose Dependency ◽  
Serum Free ◽  
Defined Culture ◽  
Dose Dependent

Vascular endothelial growth factor (VEGF) is a major growth factor for developing endothelial cells (ECs). Embryonic lethality due to haploinsufficiency of VEGF in the mouse highlighted the strict dose dependency of VEGF on embryonic vascular development. Here we investigated the dose-dependent effects of VEGF on the differentiation of ES cell–derived fetal liver kinase 1 (Flk-1)/VEGF receptor 2+ (VEGFR2+) mesodermal cells into ECs on type IV collagen under a chemically defined serum-free condition. These cells could grow even in the absence of VEGF, but differentiated mostly into mural cells positive for α-smooth muscle actin. VEGF supported in a dose-dependent manner the differentiation into ECs defined by the expression of VE-cadherin, platelet-endothelial cell adhesion molecule 1 (PECAM-1)/ CD31, CD34, and TIE2/TEK. VEGF requirement was greater at late than at early phase of culture during EC development, whereas response of VEGFR2+ cells to VEGF-E, which is a virus-derived ligand for VEGFR2 but not for Flt-1/VEGFR1, was not dose sensitive even at late phase of culture. Delayed expression of VEGFR1 correlated with increased dose dependency of VEGF. These results suggested that greater requirement of VEGF in the maintenance than induction of ECs was due to the activity of VEGFR1 sequestering VEGF from VEGFR2 signal. The chemically defined serum-free culture system described here provides a new tool for assessing different factors for the proliferation and differentiation of VEGFR2+ mesodermal cells.

Dose-dependent Reduction of the Minimum Local Analgesic Concentration of Bupivacaine by Sufentanil for Epidural Analgesia in Labor

1998 ◽  
Vol 89 (3) ◽  
pp. 626-632. ◽  
Author(s):  
Linda S. Polley ◽  
Malachy O. Columb ◽  
Deborah S. Wagner ◽  
Norah N. Naughton
Keyword(s):  
Epidural Analgesia ◽  
Analgesic Efficacy ◽  
Study Groups ◽  
Cervical Dilation ◽  
Double Blind ◽  
Pain Scores ◽  
Sequential Allocation ◽  
Study Participants ◽  
Dose Dependent ◽  
First Stage Of Labor

Background The minimum local analgesic concentration (MLAC) has been defined as the median effective local analgesic concentration in a 20-ml volume for epidural analgesia in the first stage of labor. The aim of this study was to determine the local anesthetic-sparing efficacy of epidural sufentanil by its effect on the MLAC of bupivacaine. Methods In this double-blind, randomized, prospective study, 147 parturients at < or = 7 cm cervical dilation who requested epidural analgesia were allocated to one of four study groups. After a lumbar epidural catheter was placed, study participants received 20 ml bupivacaine (n = 38), bupivacaine with sufentanil 0.5 microg/ml (n = 38), bupivacaine with sufentanil 1 microg/ml (n = 33), or bupivacaine with sufentanil 1.5 microg/ml (n = 38). The concentration of bupivacaine was determined by the response of the previous patient using up-down sequential allocation. The analgesic efficacy was assessed using 100-mm visual analog pain scores, with < or = 10 mm within 30 min defined as effective. Results The MLAC of bupivacaine alone was 0.104% wt/vol (95% CI, 0.090-0.117). The addition of sufentanil at doses of 0.5 microg/ml, 1 microg/ml, and 1.5 microg/ml resulted in significant reductions (P < 0.0001) in the MLAC of bupivacaine to 0.048% wt/vol (95% CI, 0.030- 0.065), 0.021% wt/vol (95% CI, 0-0.055), and 0.009% wt/vol (95% CI, 0-0.023), respectively. Conclusions This study showed a significant (P < 0.0001) dose-dependent reduction in the MLAC ofbupivacaine by sufentanil.

Aluminum exposure decreases dopamine D1 and D2 receptor expression in mouse brain

2007 ◽  
Vol 26 (9) ◽  
pp. 741-746 ◽  
Author(s):  
Sunyoun Kim ◽  
Jungmin Nam ◽  
Kisok Kim
Keyword(s):  
Mouse Brain ◽  
D2 Receptor ◽  
Receptor Expression ◽  
High Dose ◽  
Dependent Manner ◽  
Dose Dependency ◽  
Aluminum Exposure ◽  
Specific Effects ◽  
Dose Dependent ◽  
Al Treatment

Aluminum (Al) has been identified as a potential contributing factor in the etiology of several neurodegenerative disorders, but data regarding specific effects on neurotransduction, especially on dopaminergic neurotransduction, are lacking. The objective of this study was to determine the extent of expressional alterations in dopamine receptors (DRs) in two dopaminergic subtypes, D1 and D2, in low and high dose Al-treated mice. After administration of Al (four intraperitoneal injections of 30 or 60 mg/kg AlCl3·6H2O at 2 h intervals), expression of the dopamine D1-like and D2-like receptors (DRD1, DRD2) was examined in the cortex and striatum of mouse brain at bregma levels of 1.10, -0.10 and -1.34 mm. In the cortex, Al treatment decreased densities of DRD1 and DRD2 in a dose-dependent manner at all three bregma levels, especially in the high-dose Al group. Similarly, DRD1 and DRD2 expression in the striatum also exhibited dose dependency and statistically significant decreases were seen in the high-dose group, except in the striatum at bregma level - 1.34. These findings suggest that DR in the caudal striatum is more resistant to the effects of Al exposure than DR in the cortex or rostral striatum. In addition, our results suggest that disturbance of dopaminergic neurotransmission mediated by DRD1 and/or DRD2 may be involved in the pathogenesis of Al neurotoxicity. Human & Experimental Toxicology (2007) 26, 741 — 746

Effects of Low Molecular Weight Heparin and Unfragmented Heparin on Induction of Osteoporosis in Rats

1990 ◽  
Vol 63 (03) ◽  
pp. 505-509 ◽  
Author(s):  
Thomas Mätzsch ◽  
David Bergqvist ◽  
Ulla Hedner ◽  
Bo Nilsson ◽  
Per Østergaar
Keyword(s):  
Molecular Weight ◽  
Bone Mineral ◽  
Low Molecular Weight Heparin ◽  
Zinc Content ◽  
Low Molecular Weight ◽  
Dependent Manner ◽  
Bone Mineral Mass ◽  
Bone Ash ◽  
Dose Dependent ◽  
Mineral Mass

SummaryA comparison between the effect of low molecular weight heparin (LMWH) and unfragmented heparin (UH) on induction of osteoporosis was made in 60 rats treated with either UH (2 IU/ g b w), LMWH in 2 doses (2 Xal U/g or 0.4 Xal U/g) or placebo (saline) for 34 days. Studied variables were: bone mineral mass in femora; fragility of humera; zinc and calcium levels in serum and bone ash and albumin in plasma. A significant reduction in bone mineral mass was found in all heparin-treated rats. There was no difference between UH and LMWH in this respect. The effect was dose-dependent in LMWH-treated animals. The zinc contents in bone ash were decreased in all heparin-treated rats as compared with controls. No recognizable pattern was seen in alterations of zinc or calcium in serum. The fragility of the humera, tested as breaking strength did not differ between treatment groups and controls. In conclusion, if dosed according to similar factor Xa inhibitory activities, LMWH induces osteoporosis to the same extent as UH and in a dose-dependent manner. The zinc content in bone ash was decreased after heparin treatment, irrespective of type of heparin given.

Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

1996 ◽  
Vol 76 (01) ◽  
pp. 111-117 ◽  
Author(s):  
Yasuto Sasaki ◽  
Junji Seki ◽  
John C Giddings ◽  
Junichiro Yamamoto
Keyword(s):  
Blood Flow ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Red Cell ◽  
Cell Velocity ◽  
Red Cell Velocity ◽  
The Mean ◽  
Wall Shear ◽  
Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

Melatonin actions in the heart; more than a hormone

2018 ◽  
Vol 1 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Darío Acuña-Castroviejo ◽  
Maria T Noguiera-Navarro ◽  
Russel J Reiter ◽  
Germaine Escames
Keyword(s):  
Cell Membranes ◽  
Myocardial Cell ◽  
Rat Tissues ◽  
Dependent Manner ◽  
Broad Distribution ◽  
Multiple Organs ◽  
High Doses ◽  
Extrapineal Melatonin ◽  
Dose Dependent ◽  
Different Doses

Due to the broad distribution of extrapineal melatonin in multiple organs and tissues, we analyzed the presence and subcellular distribution of the indoleamine in the heart of rats. Groups of sham-operated and pinealectomized rats were sacrificed at different times along the day, and the melatonin content in myocardial cell membranes, cytosol, nuclei and mitochondria, were measured. Other groups of control animals were treated with different doses of melatonin to monitor its intracellular distribution. The results show that melatonin levels in the cell membrane, cytosol, nucleus, and mitochondria vary along the day, without showing a circadian rhythm. Pinealectomized animals trend to show higher values than sham-operated rats. Exogenous administration of melatonin yields its accumulation in a dose-dependent manner in all subcellular compartments analyzed, with maximal concentrations found in cell membranes at doses of 200 mg/kg bw melatonin. Interestingly, at dose of 40 mg/kg b.w, maximal concentration of melatonin was reached in the nucleus and mitochondrion. The results confirm previous data in other rat tissues including liver and brain, and support that melatonin is not uniformly distributed in the cell, whereas high doses of melatonin may be required for therapeutic purposes.

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