Dexmedetomidine versus sufentanil as adjuvants to bupivacaine for brachial plexus block during upper extremity surgery: a randomized clinical trial

Abstract Background: Brachial plexus block (BPB) has been accepted as a reliable alternative for general anesthesia in upper limb surgeries. Adding adjuvant drugs like dexmedetomidine and sufentanil has been shown to have clinical and pharmacologic advantages. In this randomized parallel clinical trial, we aim to compare the effects of these two adjuvants for bupivacaine in BPB. Methods: In this double-blinded study, by using computer-assisted block randomization, 40 patients ranged from 20 to 65 years old and scheduled for elective upper limb surgeries were assigned to two equal study groups (n = 20), receiving 1 mL of 5 μg.mL-1 sufentanil (group S) or 1 mL of 100 μg.mL-1 dexmedetomidine (group D) in adjunction to 30 mL of 0.5% bupivacaine for supraclavicular BPB under the guidance of ultrasonography. Characteristics of local anesthesia and postoperative analgesia were evaluated (n = 40). Results: The duration of blocks significantly improved in group S (sensory: estimated median difference (EMD) [95%CI] = 100.0 [70.0~130.0], p < 0.001; motor: EMD [95%CI] = 120.0 [100.0~130.0], p < 0.001). Group S also had significantly longer postoperative analgesia and lower opioid consumption within 24 hours after the surgery (EMD [95%CI] = 4.0 [3.0~7.0], p < 0.001; EMD [95%CI] = -5.0 [-5.0~-5.0], p < 0.001; respectively). None of the patients showed adverse effects concerning vital signs, nausea, or vomiting. Conclusion: Our study showed that during ultrasound-guided supraclavicular BPB, sufentanil is a fairly better choice than dexmedetomidine as an adjuvant for bupivacaine and can provide preferable sensory and motor blocks. No significant side effects were seen in either of the study groups.

Dexmedetomidine versus sufentanil as adjuvants to bupivacaine for brachial plexus block during upper extremity surgery: a randomized clinical trial.

BACKGROUND: Brachial plexus block (BPB) has been accepted as a reliable alternative for general anesthesia in upper limb surgeries. Adding adjuvant drugs like dexmedetomidine and sufentanil has been shown to have clinical and pharmacologic advantages. In this randomized parallel clinical trial, we aim to compare the effects of these two adjuvants for bupivacaine in BPB. METHODS: In this double-blinded study, by using computer-assisted block randomization, 40 patients ranged from 20 to 65 years old and scheduled for elective upper limb surgeries were assigned to two equal study groups (n = 20), receiving 1 mL of 5 ..g.mL-1 sufentanil (group S) or 1 mL of 100 ..g.mL-1 dexmedetomidine (group D) in adjunction to 30 mL of 0.5% bupivacaine for supraclavicular BPB under the guidance of ultrasonography. Characteristics of local anesthesia and postoperative analgesia were evaluated (n = 40). RESULTS: The duration of blocks significantly improved in group S (sensory: estimated median difference (EMD) [95%CI] = 100.0 [70.0...130.0], p < 0.001; motor: EMD [95%CI] = 120.0 [100.0...130.0], p < 0.001). Group S also had significantly longer postoperative analgesia and lower opioid consumption within 24 hours after the surgery (EMD [95%CI] = 4.0 [3.0...7.0], p < 0.001; EMD [95%CI] = -5.0 [-5.0...-5.0], p < 0.001; respectively). None of the patients showed adverse effects concerning vital signs, nausea, or vomiting. CONCLUSION: Our study showed that during ultrasound-guided supraclavicular BPB, sufentanil is a fairly better choice than dexmedetomidine as an adjuvant for bupivacaine and can provide preferable sensory and motor blocks. No significant side effects were seen in either of the study groups.

Effects of Myricitrin and Solid Lipid Nanoparticle-Containing Myricitrin on Reproductive System Disorders Induced by Diabetes in Male Mouse.

PURPOSE: The present study investigates the effects of myricitrin and solid lipid nanoparticle (SLN) containing myricitrin on the reproductive system of type 2 diabetic male mice. MATERIALS AND METHODS: In this experimental study, SLN containing myricitrin was prepared by the cold homogenization method. Then, 90 adult male Naval Medical Research Institute mice were divided into 9 groups (n=10): control, vehicle, diabetic, diabetic+myricitrin or SLN containing myricitrin 1, 3, and 10 mg/kg. Diabetes was induced by streptozotocin (65 mg/kg) 15 minutes after nicotinamide (120 mg/kg) injection. Myricitrin and SLN containing myricitrin administered during 1 month. At the 34th days of the experiment, plasma and tissue samples were taken for experimental assessments. RESULTS: Testis weight and volume decreased in the diabetic group. These variables increased in diabetic treated mice by a high dose of myricitrin or all doses of SLN containing myricitrin (p<0.05). Total antioxidant capacity and superoxide dismutase levels decreased in diabetic mice, and administration of myricitrin 10 mg/kg or all doses of SLN containing myricitrin increased them (p<0.05). Luteinizing hormone, Follicle-stimulating hormone, testosterone, and sperm count decreased in the diabetic group, treatment with a high dose of myricitrin or all doses of SLN containing myricitrin recovered them (p<0.05). Diabetes induced vacuoles and apoptosis in testicular cells, meanwhile myricitrin and SLN containing myricitrin improved them (p<0.05). CONCLUSIONS: Diabetes induced reproductive problem via increased oxidative stress and decrease antioxidant capacity, administration of myricitrin or SLN containing myricitrin improved them. Further, SLN containing myricitrin was more potent than myricitrin.

Design, synthesis, and pharmacological evaluation of novel 1,2,4-triazol-3-amine derivatives as potential agonists of GABAA subtype receptors with anticonvulsant and hypnotic effects.

In the current study, a series of novel 1,2,4-triazol-3-amine derivatives were designed, synthesized, and biologically evaluated in vivo for their anticonvulsant and hypnotic effects in the pentylenetetrazole (PTZ)-induced seizures, maximal electroshock (MES)-induced seizures, and pentobarbital-induced sleeping tests. Furthermore, the possible side effects of the most potent compounds on the memory, motor coordination, and muscle strength were evaluated in passive avoidance, rotarod, and grip strength tests, respectively. The designed compounds with the main benzodiazepine pharmacophores including aromatic ring and proton accepting group completely mimiced the structure of zolpidem as an α1-selective agonist of GABAA receptor. Compounds 5c (ED50 ≈ 52.5 mg/kg) and 5 g (ED50 ≈ 16.5 mg/kg) in the PTZ test were the most potent compounds among the designed compounds. In the MES test, the observed ED50s for compounds 5c and 5 g were reduced to around 11.8 mg/kg and 10.5 mg/kg, respectively. The considerable hypnotic effect in a dose-dependent manner was observed following the administration of newly synthesized compounds. In all experiments administration of flumazenil as an antagonist of benzodiazepines receptor fully antagonized observed effects which indicated the involvement of GABAA receptors. Since there was no negative effect on memory, motor coordination, and muscle strength following the administration of compounds 5c and 5g as the most potent compounds, it could be concluded that the novel compounds most likely act through α1-containing GABAA receptors and possess no affinity for α5-containing receptors. The newly designed compounds could be considered as leading compounds in synthesizing novel GABAA receptor agonists with minimum side effects.

Gummosin, a sesquiterpene coumarin from Ferula assa-foetida is preferentially cytotoxic to human breast and prostate cancer cell lines.

OBJECTIVE: The present study was conducted to find cytotoxic compounds from oleo-gum-resin of Ferula assa-foetida (asafoetida). MATERIALS AND METHODS: A dichloromethane extract of asafoetida was subjected to different chromatography analyses (including column chromatography, preparative thin layer chromatography and high performance liquid chromatography) to isolate its bioactive sesquiterpene coumarins. The structures of isolated compounds were elucidated through 1H-NMR spectra interpretation and comparison with those reported in the literature. To measure the cytotoxic activity of pure compounds, a non-fluorescent substrate called resazurin (alamarBlue®) was used in this study. Human breast and prostate cancer cell lines (MCF-7 and PC-3, respectively) and a normal human embryonic stem cell (NIH) were treated with different concentrations (50, 25, 12.5 and 6.25 µg/mL) of pure compounds. RESULTS: In this study, 10 sesquiterpene coumarins were isolated from oleo-gum-resin of F. assa-foetida and cytotoxic activity of 6 compounds was tested against MCF-7 and PC-3 cell lines and NIH cells. Badrakemin acetate (7), ferukrinone (8) and deacetyl kellerin (10) were found for the first time in the oleo-gum-resin of F. assa-foetida. Gummosin (4) showed moderate cytotoxic activity with IC50 values of 30 and 32.1 µg/mL against PC-3 and MCF-7 cell lines, respectively. None of the isolated compounds showed toxicity against NIH as a normal human cell line. CONCLUSION: The preferential cytotoxic activity of gummosin against cancer cell lines is reported for the first time in this study.

Targeting of oxidative stress and inflammation through ROS/NF-kappaB pathway in phosphine-induced hepatotoxicity mitigation.

AIMS: Poisoning with aluminium phosphide (AlP) commonly has a high rate of mortality and morbidities. Phosphine gas is the main cause of AlP poisoning that has deleterious effect on multi-organs especially heart, kidney, and liver. Furthermore, several studies reported that resveratrol has cytoprotective effects through its pleiotropic property. The purpose of this study was to estimate the dose-dependent role of resveratrol on phosphine induced acute hepatic toxicity in rat model. MAIN METHODS: The rats have been exposed to LD50 of AlP (12 mg/kg) by gavage, and resveratrol doses (20, 40, and 80 mg/kg) were injected 30 min after intoxication. After 24 h, the serum and liver tissue were collected for present study. KEY FINDINGS: The results indicated that phosphine causes an alteration in oxidative stress markers including elevation of ROS, and GSH level, MPO activity, reduction in SOD, catalase and G6PD activity as well as reduction in SOD1 and catalase expression. Furthermore, phosphine significantly induced phosphorylation of IkappaB, NF-kappaB and up-regulation of TNF-α, IL-1ß, IL-6, and ICAM-1 expression. Also, phosphine induces markedly reduced hepatocytes lives cell and elevated apoptosis and necrosis. Co-treatment of resveratrol in a dose-dependent manner reversed aforementioned alterations. All in all, histological analysis indicated a deleterious effect of phosphine on the liver, which is mitigated by resveratrol administration. SIGNIFICANCE: The results of the present study suggest targeting ROS/NF-kappaB signalling pathway by resveratrol may have a significant effect on the improvement of hepatic injury induced by phosphine. It also may be a possible candidate for the treatment of phosphine-poisoning.

Is There Any Relevance Between Serum Heavy Metal Concentration and BBB Leakage in Multiple Sclerosis Patients?

Sharp increase in multiple sclerosis (MS) incidence rate has been observed in Iranian people. In addition, it has been suggested that increased S100B level may be useful as an indicative factor of blood-brain barrier disruption. The propose of this study was to measuring blood arsenic, lead, and cadmium concentration and serum S100B concentration in a group of healthy and multiple sclerosis patients in Tehran as the most polluted city in Iran. All subjects were interviewed regarding age, medical history, possible chemical exposure, acute or chronic diseases, smoking, and dietary habits. Blood heavy metal level was measured by an atomic absorption spectrometer (Varian model 220-Z) conjugated with a graphite furnace atomizer (GTA-110). Also, a serum S100B protein concentration was determined using a commercial ELISA kit. It was observed that all male subjects had higher blood metal level in comparison with healthy controls. Also, MS patients had higher arsenic and cadmium blood concentration in comparison with healthy individuals. Regarding the S100B concentration, it was observed that it had a significant relationship with smoking habit (P value = 0.0001). In addition, arsenic had a greater correlation (63%) with increased serum S100B biomarker level among other elements. BBB leakage was higher in multiple sclerosis than in healthy subjects due to increased S100B release. In addition with regard to the heavy metal exposure especially arsenic and cadmium, these are associated with an increased BBB disruption and it is possible to play a crucial role as a developing agent of multiple sclerosis.

Analysis of the antiepileptic, ethosuximide impacts on neurogenesis of rat forebrain stem cells.

Specific GABAergic interneurons in the hilus are lost in animal models with temporal-lobe epilepsy (TLE). Some preclinical evidence has indicated that GABAergic cells may provide relief from seizures in these models. This study was aimed to examine the ability of ethosuximide, an anticonvulsant drug, to promote neurogenesis in 3-day-old rat forebrain cortex stem cells. Most of the cells were found to be nestin-positive undifferentiated neural stem cells prior to their exposure to ethosuximide. It was noted that the number and percentage of tubulin ß-III immunopositive neurons were increased after 6 days treatment with ethosuximide. Upon bFGF withdrawal, exposure to ethosuximide differentiated the stem cells to MAP2 positive neural cells (7.18 ± 0.43, 21.766 ± 0.55 and 41.57 ± 0.5 for control, 0.1 and 1 µM, respectively). GABA immunofluorescence images illustrated that ethosuximide increased GABAergic neurons (7.19 ± 0.32, 23.23 ± 0.55, and 46.30 ± 0.44 for control, 0.1 and 1 µM, respectively). Additionally, BrdU immunofluorescence assay showed that ethosuximide-enhanced nucleus proliferation in the neuronal stem cells. Therefore, the results of this study suggest that ethosuximide may compensate damage caused by seizure attacks and possibly other neuronal loss disorders.