Anethole attenuates motor dysfunctions, striatal neuronal activity deficiency and blood brain barrier permeability by decreasing striatal α-synuclein and oxidative stress in rotenone-induced Parkinson's disease of male rats.

INTRODUCTION: Anethole is the main compound of the essential oil of anise and several other plants, which has antioxidant, anti-inflammatory, and neuroprotective properties. Oxidative stress is considered as an important factor in the pathogenesis of PD. In the present study, we aimed to investigate the effects of anethole against rotenone-induced PD. METHODS: Male Wistar rats were randomly divided into six groups. Control group received DMSO + sunflower oil, model group received rotenone (2 mg/kg, s.c, daily for 35 days), positive control group received L-Dopa, and test groups received anethole (62.5, 125, and 250 mg/kg, i.g, daily for 35 days) 1 hour before each rotenone injection. Body weight changes, rotarod test, stride length test, and extracellular single unit recording were performed after treatment. After behavioral test, Brain water content and blood brain barrier (BBB) permeability were evaluated, and the levels of malondialdehyde (MDA), superoxide dismutases (SOD), alpha-synuclein and MAO-B were measured in the striatum. RESULTS: Chronic administration of rotenone induced body weight loss and caused significant dysfunction in locomotor activity, neuronl firing rate, and BBB. Rotenone also decreased SOD activity, increased MDA level, and elevated the expression of alpha-synuclein and MAO-B in the striatum. However, treatment with anethole attenuated body weight loss, motor function, neuronal activity, and BBB function. Furthermore, Anethole treatment attenuated oxidative stress and decreased the expression of alpha-synuclein and MAO-B compared to the rotenone group. CONCLUSION: Our results show that through its antioxidant properties, aethole can improve the cellular, molecular and behavioral characteristics of rotenone-induced Parkinson's disease.

A Comparison of the Sedative Effect of Dexmedetomidine and Midazolam on Patients Undergoing Gastrointestinal Endosonography Outside the Operating Room.

Background: Patients may experience anxiety, discomfort, and pain during endoscopy, which cannot be tolerated without sedative drugs. Objectives: This study aimed to compare the sedative effects of dexmedetomidine and midazolam on patients undergoing endosonography outside the operating room. Methods: This randomized, double-blind clinical trial was conducted on 126 patients aged 18 - 65 years old with American Society of Anesthesiologists (ASA) physical status I - II undergoing elective endosonography. Patients were randomly divided into 2 groups. The dexmedetomidine group received dexmedetomidine (1 µg/kg) for 25 minutes with propofol (0.5 mg/kg) and fentanyl (1 µg/kg) at the start of the procedure. The midazolam group received midazolam (0.03 mg/kg) with propofol (0.5 mg/kg) and fentanyl (1 µg/kg). Heart rate, mean arterial pressure (MAP), and oxygen saturation (SpO2) were recorded before and 5, 10, and 15 minutes after starting the procedure. The Ramsay Sedation Scale (RSS) and the need for an additional dose of propofol were recorded during the procedure. The Numeric Pain Rating scale (Ambesh score) scores were recorded at the beginning, immediately after, and 1 hour after the procedure. Nausea and vomiting were assessed using the Visual Analogue Scale in cooperation with the patient. Results: The dexmedetomidine group had significantly higher SpO2 and RSS scores during sedation than the midazolam group (P = 0.02). Overall, specialist satisfaction was higher in the dexmedetomidine group than in the midazolam group. There was no clinically significant difference in pain score and nausea and vomiting frequencies between the 2 groups. Conclusions: Dexmedetomidine is more effective than midazolam for sedation during gastrointestinal endosonography.

Dexmedetomidine or Fentanyl, Which One Is Better as an Adjunct Drug in Epidural Anesthesia and Causes More Postoperative Pain Reduction? A Comparative Study, a Randomized Clinical Trial.

Objectives: This study compared dexmedetomidine to fentanyl as an adjunct to ropivacaine for epidural anesthesia in patients undergoing femoral neck fracture surgery. Methods: A total of 56 patients in two different groups with dexmedetomidine and fentanyl underwent the epidural anesthesia method by ropivacaine. This study compared the onset and duration of sensory block, duration of motor block, visual analog scale (VAS) analgesia, and sedation score. The VAS and hemodynamics (e.g., heart rate and mean arterial pressure) were measured every 5 to 15 minutes, then every 15 minutes to the end of the surgery, and then in the 1st, 2nd, 4th, 6th, 12th, and 24th hours after surgery. Results: In the fentanyl group, the onset time of the sensory block was longer (P < 0.001), and the duration of the block was shorter than in the dexmedetomidine group (P = 0.045). In the fentanyl group, the onset time of motor block was longer than in the dexmedetomidine group (P < 0.001). The mean highest VAS score for each patient in the dexmedetomidine group was 4.9 ± 0.6, compared to the fentanyl group (5.8 ± 0.9), with a significant difference between the two groups (P < 0.001). The sedation score was higher from the 30th minute (P = 0.01) to the 120th minute (P = 0.04) in the patients of the dexmedetomidine group than in the fentanyl group. Side effects, such as dry mouth, hypotension, and bradycardia, were more common in the dexmedetomidine group, and nausea and vomiting were more common in the fentanyl group; however, there were no differences between the groups. There was no respiratory depression in both groups. Conclusions: This study presented that dexmedetomidine as an adjuvant in epidural anesthesia for orthopedic femoral fracture surgery shortens the onset time of sensory and motor block, increases analgesia length, and prolongs anesthesia. Sedation with dexmedetomidine is better than fentanyl, with fewer side effects, and more effective as preemptive analgesia.

Anti-inflammatory, anti-apoptotic, and neuroprotective potentials of anethole in Parkinson's disease-like motor and non-motor symptoms induced by rotenone in rats.

Parkinson's disease (PD) is a complex neurological disorder characterized by a combination of motor and non-motor symptoms (NMS). Antioxidant and anti-inflammatory compounds are considered a potential therapeutic strategy against PD. The present study examined the neuroprotective effects of anethole as a potent antioxidant and anti-inflammatory agent against motor and non-motor deficits induced by rotenone toxicity. Rats were treated with anethole (62.5, 125, and 250 mg/kg, i.g) concomitantly with rotenone (2 mg/kg, s.c) for 5 weeks. After the treatment, behavioral tests were performed to evaluate motor function and depression-/anxiety-like behaviors. After the behavioral tests, rats were decapitated and brains were removed for histological analysis. Striatum samples were also isolated for neurochemical, and molecular analysis. Our data showed that rotenone-induced motor deficit, anxiety-and depression-like behaviors were significantly improved in rats treated with anethole. Furthermore, anethole treatment reduced inflammatory cytokines tumor necrosis factor α (TNFα) and Interleukin 6 (IL-6), and increased anti-inflammatory cytokine IL-4 in the striatum of rotenone-induced PD rats. Western blot analysis showed that treatment with anethole markedly suppressed caspase-3 activation induced by rotenone. Moreover, histological examination of striatum showed an increase in the number of surviving neurons after treatment with anethole. Anethole also significantly enhanced the striatal levels of dopamine in rotenone-induced PD rats. In addition, treatment with L-Dopa as a positive control group had effects similar to those of anethole on histological, neurochemical, and molecular parameters in rotenone-induced parkinsonian rats. Our results suggested the neuroprotective effects of anethole through anti-inflammatory, anti-apoptotic, and antioxidant mechanisms against rotenone-induced toxicity in rats.

Sex-specific effects of developmental morphine exposure and rearing environments on hippocampal spatial memory.

Developmental morphine (MOR) exposure (DME) detrimentally affects the cognitive abilities of the next generation. It is shown that postnatal rearing environments and prenatal conditions effectively impact memory. The present study investigated the effects of DME, postweaning rearing, and sex on spatial learning and memory. At molecular level, we evaluated mRNA levels of brain-derived neurotrophic factor, cyclic AMP response element-binding protein (CREB), µ-opioid receptor, and ΔFosB in the hippocampus of male offspring. Female Wistar rats were treated with escalating doses of MOR or saline before mating, gestation, and lactation. On Postnatal Day 22, the male and female pups were divided into 12 groups and raised for 2 months under different conditions: standard, isolated (ISO), or enriched environment. Afterward, the Morris water maze task measured spatial learning and reference memory; rats were then sacrificed to assess hippocampus gene expressions. Results indicated the DME and isolated rearing increased latency to find the hidden platform in male offspring. DME was insignificant in female offspring, whereas rearing environments significantly altered escape latency in both sexes. We also found that the enriched environment upregulated the brain-derived neurotrophic factor mRNA in both saline and MOR groups, whereas it downregulated the mRNA levels of CREB1, µ-opioid receptor, and ΔFosB in the MOR group. In addition, the DME enhanced CREB1, µ-opioid receptor, and ΔFosB gene expression in the MOR + isolated group. Our findings signified the effects of DME, rearing environment, and sex on the spatial learning abilities of offspring. Also, we showed that DME and rearing conditions could manipulate hippocampal neurochemistry.

Neuroprotective effect of anethole against rotenone induced non-motor deficits and oxidative stress in rat model of Parkinson's disease.

INTRODUCTION: Non-motor symptoms (NMS) have high prevalence in patients with Parkinson's disease (PD). These symptoms are mainly the result of increased oxidative stress and neuronal damage. In this study we investigated the possible neuroprotective effects of anethole as a potent antioxidant on rotenone-induced behavioral deficits, hippocampal neuronal death, and oxidative stress profile in rats. METHODS: Male Wistar rats were administered with anethole (62.5, 125, and 250 mg/kg, i.g) concomitantly with rotenone (2 mg/kg, s.c) for 35 days. Shuttle box and novel object recognition tests were performed to determine cognitive functions, and tail flick test was used to measure pain sensitivity. The levels of BDNF, MDA, SOD, and GPx were assayed in the hippocampus. Hippocampal neuronal damage was evaluated using cresyl violet staining technique. RESULTS: Chronic administration of rotenone induced cognitive deficit and reduced thermal pain threshold. Rotenone also decreased SOD and GPx activities, increased MDA level, and reduced the expression of BDNF in the hippocampus. In addition, hippocampal neuronal loss was increased in rotenone treated rats. Treatment with high dose of anethole (250 mg/kg) improved cognitive function and increased pain threshold in all three doses (62.5, 125, and 250 mg/kg). Despite the unchanged SOD and GPx activities, hippocampal levels of MDA was significantly decreased after high-dose anethole treatment. Moreover, High dose of anethole increased the number of surviving neurons in the hippocampus, but couldn't increase the BDNF expression. CONCLUSION: Our findings indicated that anethole has antioxidant and neuroprotective effects against non-motor disorders induced by rotenone toxicity.

Comparison of the effect of propofol and isoflurane on hemodynamic parameters and stress response hormones during Laparoscopic Cholecystectomy surgery.

Background and Aims: General anesthesia induces endocrine, immunologic, and metabolic responses. Anesthetic drugs affect endocrine system by changing the level of stress hormones and hemodynamic of the patient . The purpose of this study was to compare the effects of propofol and isoflurane on hemodynamic parameters and stress-induced hormones in laparoscopic cholecystectomy (LC) surgery. Material and Methods: Seventy patients of elective LC were included in this study. Patients were randomly divided into two equal groups of 35 patients; group P received propofol (70-120 µg/kg/min) and group I received isoflurane (mac: 1.28%) as anesthesia maintenance. The following parameters were monitored, checked, and recorded from preanesthesia period to 10 min after PACU entry according to a planned method: hemodynamic parameters (heart rate and mean atrial pressure), level of blood sugar, and serum epinephrine level. Results: Heart rate and mean atrial pressure changes did not show significant differences between the two groups in all stage (P > 0.05), but isoflurane group tolerated lower fluctuating changes. Blood glucose and serum epinephrine level rise in the isoflurane group were significantly higher than the propofol group (P < 0.05). Conclusion: Maintenance anesthesia by inhalation gas base on isoflurane has not shown a significant difference with total intravenous anesthesia base on propofol on hemodynamic parameter. However, propofol has a consistent effect on decreasing stress hormone and suggested for LC surgery.

Analysis of CD4, CD8, CD19, CD56-16, CD64, QuantiFERON biomarkers in exudative lymphocyte-dominant pleural effusion.

Background: There are two main causes of exudative effusion including malignancy-induced effusion and tuberculosis. Considering that in reactive ejections, such as tuberculosis-induced effusion, the role of B lymphocytes and in the malignant effusion, the role of T lymphocytes are more important, in this study we analyzed the frequency of CD4, CD8, CD19, CD56-16, CD64, QuantiFERON in the pleural and serum samples of patients with exudative lymphocytic-dominant effusion. Methods: In total, 73 patients were enrolled in the study by exudative lymphocyte effusion, and finally, 63 patients had definite diagnoses. The patients were sorted into three groups including malignant, tuberculosis, and none. The sample of blood plasma and pleural effusion were collected and CD markers were analyzed using flow cytometry. Results: The mean age in the malignancy and tuberculous (TB) groups was 63.16 ± 12 and 52.15 ± 22.62, respectively. There was no significant difference in the frequency of CD8, CD4, and CD16-56 cells in blood samples of patients with tuberculosis and malignancy. Compared to those with tuberculosis, the percentage of CD64 cells was significantly higher in patients with tuberculosis than in malignant subjects. Moreover, a comparison of the frequency of cells with CD8, CD4, CD19, CD64, CD16-56, and CD14 markers in pleural samples showed no significant difference between groups. Other inflammatory factors were also investigated. The erythrocyte sedimentation rate (ESR) value for tuberculosis patients was significantly higher than malignancy. Also, QuantiFERON was positive in 14.3% of malignant patients, and 62.5% of patients with TB, which had a significant difference. Conclusion: Considering that there are many confounding variables in the study, such as previous medications, subtypes of Mycobacterium, and race of patients conducting studies in different groups and performing data mining for using a set of parameters can be used to detect the exact diagnosis.

Comparison of Nebulized Versus Intravenous Milrinone on Reducing Pulmonary Arterial Pressure in Patients with Pulmonary Hypertension Candidate for Open-cardiac Surgery: A Double-Blind Randomized Clinical Trial.

Background: Regardless of the cause, pulmonary hypertension can increase patient complications and mortality. This study compared the effect of nebulized versus intravenous (IV) milrinone on reducing pulmonary arterial pressure in patients with pulmonary hypertension candidates for open-cardiac surgery. Methods: This double-blind, randomized clinical trial was performed on 32 patients undergoing elective on-pump cardiac surgery during January 2021-January 2022 in the Cardiac Operating Room of Golestan Hospital, Ahvaz, Iran. Patients were randomly divided into test groups nebulize milrinone (N = 16) and IV milrinone (N = 16). The medication was administered after the cross-clamp of the aorta opening. The outcome variables included hemodynamic data, cardiac output, cardiac index, stroke volume, mean arterial pressure (MAP), central venous pressure, mean pulmonary artery pressure (mPAP), systemic vascular resistance, pulmonary vascular resistance, MAP/mPAP ratio, time until extubation, duration of hospitalization in the Intensive Care Unit (ICU), and duration of hospital stay. Results: In the nebulized group, MAP and MAP/mPAP were significantly higher than in the IV milrinone group (P = 0.09 and P < 0.0001, respectively). The time of extubation (P = 0.001), duration of hospitalization in the ICU (P = 0.009), and duration of hospital stay (P = 0.026) in the nebulized milrinone group were significantly shorter than in the IV milrinone group. Conclusions: Nebulized milrinone administration before weaning off cardiopulmonary bypass (CPB) can be accelerated and facilitate weaning off CPB. Moreover, despite maintaining MAP, nebulized milrinone significantly reduces mPAP. According to the results of this study, nebulized milrinone is recommended in patients undergoing cardiac surgery with pulmonary hypertension.

Maternal Morphine Exposure and Post-Weaning Social Isolation Impair Memory and Ventral Striatum Dopamine System in Male Offspring: Is an Enriched Environment Beneficial?

Maternal opioids abuse has some deleterious consequences on next generations. Besides, children's rearing conditions can affect the behavioral states and brain plasticity in their later life. In the present study, we investigated the effects of maternal morphine (MOR) treatment and post-weaning rearing conditions on memory, pain threshold, and the ventral striatum dopaminergic activity in male offspring. Female Wistar rats were treated twice daily either with escalating doses of MOR or with normal saline (NS) one week before mating, during pregnancy and lactation. After weaning, the male pups were assigned to six groups and then raised for an 8-week period under three different conditions: standard (STD), isolated (ISO) or enriched environment (EE). The behavioral tests, including passive avoidance task, novel object recognition, and tail-flick test, were also performed. Moreover, the ventral striatum dopamine's content (DA), mRNA expressions of dopamine receptor 1(D1R) and dopamine receptor 2 (D2R), and dopamine transporter (DAT) were evaluated. The obtained data showed that maternal MOR exposure and post-weaning social isolation could dramatically impair memory in offspring, while EE could reverse these adverse outcomes. Moreover, results of tail flick latency indicated the increased pain threshold in EE animals. At molecular level, maternal MOR injections and social isolation reduced DA levels and altered expressions of D1R, D2R, and DAT within the ventral striatum of these male offspring. However, post-weaning EE partially buffered these changes. Our finding signified the effects of maternal MOR exposure and social isolation on the behaviors and neurochemistry of brain in next generation, and it also provided evidence on reversibility of these alterations following EE.

Comparison of the Effect of Propofol and Dexmedetomidine on Hemodynamic Parameters and Stress Response Hormones During Laparoscopic Cholecystectomy Surgery.

BACKGROUND: General anesthesia induces endocrine, immunologic, and metabolic responses. Anesthetic drugs affect the endocrine system by changing the level of stress hormones and hemodynamic variables of the patient. OBJECTIVES: The purpose of this study was to compare the effects of propofol and dexmedetomidine on hemodynamic parameters and stress-induced hormones in laparoscopic cholecystectomy (LC) surgery. METHODS: Seventy patients of elective LC were included in this study. The patients were randomly assigned into two equal groups of propofol (75 µg/kg/min) and dexmedetomidine (0.5 µg/kg/hour) as anesthesia maintenance. Hemodynamic parameters (heart rate and mean atrial pressure), blood sugar, and serum epinephrine level were monitored and recorded from pre-anesthesia period to 10 min after entry to post-anesthesia care unit (PACU) according to a planned method. RESULTS: Heart rate and mean atrial pressure changes were significantly lower in dexmedetomidine group in all stages compared to propofol group (P < 0.001). Also, the rises in blood glucose and serum epinephrine levels in the dexmedetomidine group were significantly higher than in the propofol group (P < 0.001). CONCLUSIONS: Anesthesia maintenance by dexmedetomidine showed a significant difference in hemodynamic parameters in comparison with propofol. While dexmedetomidine had better effects on controlling hemodynamic parameters, propofol showed better effects on decreasing stress hormones, and it can be suggested for LC surgery.

Investigating the Effect of Near Infra-Red Spectroscopy (NIRS) on Early Diagnosis of Cardiac Surgery-Associated Acute Kidney Injury.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major adverse effect of cardiac surgery. The early detection of this complication can improve the quality of postoperative care and help prevent this phenomenon. METHODS: In this prospective descriptive-analytical study, 148 patients were enrolled, 107 of whom were selected for analysis between February and September 2019 in the Cardiac Surgery Unit of Golestan Hospital, Ahvaz, Iran. Kidney tissue oxygen saturation was measured at multiple definite times during surgery. Hemoglobin, blood urea nitrogen, creatinine, and lactate were measured during and 48 hours after the surgery. RESULTS: Forty-one patients were diagnosed with CSA-AKI according to the KDIGO criteria. Parametric and non-parametric analyses showed no significant difference between the CSA-AKI and non-CSA-AKI groups in the demographic parameters. Repeated measures ANOVA showed no significant difference in parameters, except for BUN. Repeated measures ANOVA showed a significant difference between both groups and time factors (P < 0.001, P = 0.0006, respectively). The ROC curve analyses showed that in a single point of time, the difference in the middle of CPB time from baseline had a high value in the prediction of AKI (AUC: 0.764; CI: 0.57 - 0.951). CONCLUSIONS: Kidney saturation monitoring could be considered in cardiac surgery for the rapid detection of CSA-AKI. Although kidney tissue saturation is not correlated directly to the arterial oxygen saturation, the physician and the surgery team can predict the chance of acute kidney injury.

Exposure to ambient dusty particulate matter impairs spatial memory and hippocampal LTP by increasing brain inflammation and oxidative stress in rats.

OBJECTIVES: Exposure of healthy subjects to ambient airborne dusty particulate matter (PM) causes brain dysfunction. This study aimed to investigate the effect of sub-chronic inhalation of ambient PM in a designed special chamber to create factual dust storm (DS) conditions on spatial cognition, hippocampal long-term potentiation (LTP), inflammatory cytokines, and oxidative stress in the brain tissue. METHODS: Adult male Wistar rats (250-300 g) were randomly divided into four groups: Sham (clean air, the concentration of dusty PM was <150 µg/m3), DS1 (200-500 µg/m3), DS2 (500-2000 µg/m3) and DS3 (2000-8000 µg/m3). Experimental rats were exposed to clean air or different sizes and concentrations of dust PM storm for four consecutive weeks (exposure was during 1-4, 8-11, 15-16 and 20-23 days, 30 min, twice daily) in a real-ambient dust exposure chamber. Subsequently, cognitive performance, hippocampal LTP, blood-brain barrier (BBB) permeability and brain edema of the animals evaluated. As well as, inflammatory cytokines and oxidative stress indexes in the brain tissue measured using ELISA assays. RESULTS: Exposing to dust PM impaired spatial memory (p < 0.001), hippocampal LTP (p < 0.001). These disturbances were in line with the severe damage to respiratory system followed by disruption of BBB integrity (p < 0.001), increased brain edema (p < 0.001), inflammatory cytokines (p < 0.001) excretion and oxidative stress (p < 0.001) in brain tissue. CONCLUSIONS: Our study showed that exposure to ambient dust PM increased brain edema and BBB permeability, induced memory impairment and hippocampal LTP deficiency by increasing the inflammatory responses and oxidative stress in the brain of the rats.

False-positive halo sign on testicular scintigraphy in a 2-year-old boy with epididymo-orchitis.

We reported a case of 2-year-old child where epididymo-orchitis was misdiagnosed as testicular torsion on scrotal scintigraphy. The scan showed that left hemiscrotum demonstrated a rim of increased activity with a photopenic center in the left testis (halo sign). At surgery, epididymo-orchitis was detected and there was no testicular torsion.