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1.
J Hazard Mater ; 478: 135473, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39151358

ABSTRACT

Widespread pesticide use in agriculture is a major source of soil pollution, driving biodiversity loss and posing serious threads to human health. The recalcitrant nature of most of these pesticides demands for effective remediation strategies. In this study, we assess the ability of soil microbial fuel cell (SMFC) technology to bioremediate soil polluted by the model pesticide atrazine. To elucidate the degradation mechanism and consequently define effective implementation strategies, we provide the first comprehensive investigation of the SMFC performance, in which the monitoring of the electrochemical performance of the system is combined with Quadrupole Time-of-Flight (QTOF) mass spectrometry and microbial analyses. Our results show that, while both SMFC and natural attenuation lead to a reduction on atrazine levels, the SMFC modulates the activity of different microbial pathways. As a result, atrazine degradation by natural attenuation leads to high levels of deisoproylatrazine (DIPA), a very toxic degradation metabolite, while DIPA levels in soil treated by SMFC remain comparatively low. The beta diversity and differential abundance analyses revealed how the microbial community evolves over time in the SMFCs degrading atrazine, demonstrating the enrichment of electroactive taxa on the anode, and the enrichment of a mixture of electroactive and atrazine-degrading taxa at the cathode. The detection and taxonomic classification of peripheral atrazine degrading genes, atzA, atzB and atzC, was carried out in combination with the differential abundance analysis. Results revealed that these genes are likely harboured by members of the order Rhizobiales enriched at the cathode, thus promoting atrazine degradation via the conversion of hydroxyatrazine (HA) into N-isopropylammelide (NIPA), as confirmed by mass spectrometry data. Overall, the comprehensive approach adopted in this work, provides fundamental insights into the degradation pathways of atrazine in soil by SMFC technology, which is critical for practical applications, thus suggesting an effective approach to advance research in the field.

2.
Soud Lek ; 69(2): 20-22, 2024.
Article in English | MEDLINE | ID: mdl-39138017

ABSTRACT

Death from positional asphyxia occurs when the victim is found in a position that interferes with adequate breathing. We present an unusual case of a 67-yearold man who was found deceased trapped in a badger sett. The autopsy revealed marked congestion, cyanosis and a multitude of pinpoint hemorrhages in the face, neck and upper chest. Confluent scleral and conjunctival hemorrhage were observed and numerous petechial bleedings were found in the oral mucosa and within the reflected scalp. Death was attributed to positional asphyxia due to head-down position in a badger sett.


Subject(s)
Asphyxia , Humans , Asphyxia/etiology , Male , Aged , Head-Down Tilt/adverse effects , Animals
3.
Cureus ; 16(6): e61796, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38975531

ABSTRACT

Sclerosing mesenteritis (SM) is a rare inflammatory disorder characterized by chronic inflammation and fibrosis of the mesenteric adipose tissue. While SM can manifest with various gastrointestinal symptoms, its association with small bowel obstruction (SBO) is infrequent. We present a case of a 78-year-old male with a history of systemic lupus erythematosus (SLE) who presented with acute abdominal pain and distention. The patient had multiple admissions with the same symptoms. A CT scan showed swirling of the proximal central mesentery, small bowel malrotation with volvulus, and high-grade mechanical obstruction of the proximal jejunum. The patient underwent exploratory laparotomy, with findings significant for multiple inflammatory nodules in the mesentery. These were causing adhesions between the bowel and mesentery, resulting in a volvulus of the bowel. One segment was resected, and subsequent histopathological examination revealed subserosal fibrosis and chronic inflammation. The clinical scenario was consistent with a diagnosis of SM. This case highlights the challenges of diagnosing and managing SBO in the presence of SM and SLE. Further research is needed to understand the underlying pathophysiological mechanisms and improve management techniques for this rare clinical condition.

4.
Cureus ; 16(3): e56991, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38681259

ABSTRACT

Background Bariatric surgeries aid weight loss in patients with morbid obesity, yet staple-line leaks pose safety concerns. Multiple methods are used to help identify these links. Intraluminal indocyanine green (ICG) has been shown to be useful in other applications, and its use in robotic bariatric surgeries is underexplored. Objective The primary objective of this research project was to demonstrate the usage of intraluminal ICG in detecting staple-line leaks during robotic sleeve gastrectomy and robotic gastric bypass. Settings The research was conducted at Bronxcare Health System between June 2022 and June 2023. Methods We studied 150 consecutive participants undergoing robotic sleeve gastrectomy or robotic gastric bypass. Intraluminal ICG was used in each case in order to identify leaks. Data on comorbidities, detected intraoperative leaks, and detected postoperative leaks were collected. Results Out of the 150 patients who underwent robotic bariatric surgeries (139 for sleeve gastrectomy and 11 for gastric bypass), four cases (two for each procedure) were identified with intraoperative leaks using ICG, resulting in an overall 2.66% incidence rate. In those four patients with intraoperative leaks, reinforcing sutures and a drain were placed. Following the surgeries, none of the patients had radiologic or clinical leaks identified. Conclusions Intraluminal ICG presents a novel approach for detecting staple-line leaks in robotic bariatric surgery. Future studies can be done to look at a larger series of patients and compare leak detection rates between ICG and other methods.

5.
Cardiovasc Pathol ; 71: 107650, 2024.
Article in English | MEDLINE | ID: mdl-38677635

ABSTRACT

We report an unexpected death of a 22-year-old primigravida who was admitted to the hospital with sudden abdominal pain two days before a scheduled delivery. During an emergency caesarean section due to intrauterine asphyxia, intraabdominal bleeding was observed with no apparent source of bleeding. Newly formed blood clots in the subdiaphragmatic space and arterial bleeding near the splenic hilum required a surgery on the next day. Hemorrhagic shock led to multiple organ failure on the fourth day of admission. The autopsy revealed ruptured splenic artery at the pancreatic tail and near the splenic hilum. Microscopically, different stages of segmental arterial mediolysis were observed in partially thinned and aneurysmatic artery.


Subject(s)
Shock, Hemorrhagic , Splenic Artery , Humans , Female , Pregnancy , Splenic Artery/pathology , Rupture, Spontaneous , Fatal Outcome , Young Adult , Shock, Hemorrhagic/etiology , Hemorrhage/etiology , Hemorrhage/pathology , Pregnancy Complications, Cardiovascular/pathology , Pregnancy Complications, Cardiovascular/surgery , Cesarean Section , Autopsy , Multiple Organ Failure/etiology
6.
Sci Total Environ ; 929: 172298, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38615778

ABSTRACT

A 30-month pilot study was conducted to evaluate the potential of in-situ metal(loid) removal through biostimulation of sulfate-reducing processes. The study took place at an industrial site in Flanders, Belgium, known for metal(loid) contamination in soil and groundwater. Biostimulation involved two incorporations of an organic substrate (emulsified vegetable oil) as electron donor and potassium bicarbonate to raise the pH of the groundwater by 1-1.5 units. The study focused on the most impacted permeable fine sand aquifer (8-9 m below groundwater level) confined by layers of non-permeable clay. The fine sands exhibited initially oxic conditions (50-200 mV), an acidic pH of 4.5 and sulfate concentrations ranging from 600 to 800 mg/L. At the central monitoring well, anoxic conditions (-200 to -400 mV) and a pH of 5.9 established shortly after the second substrate and reagent injection. Over the course of 12 months, there was a significant decrease in the concentration of arsenic (from 2500 to 12 µg/L), nickel (from 360 to <2 µg/L), zinc (from 78,000 to <2 µg/L), and sulfate (from 930 to 450 mg/L). Low levels of metal(loid)s were still present after 34 months (end of study). Mineralogical analysis indicated that the precipitates formed were amorphous in nature. Evidence for biologically driven metal(loid) precipitation was provided by compound specific stable isotope analysis of sulfate. In addition, changes in microbial populations were assessed using next-generation sequencing, revealing stimulation of native sulfate-reducing bacteria. These results highlight the potential of biostimulation for long-term in situ metal(loid) plume treatment/containment.


Subject(s)
Sulfates , Water Pollutants, Chemical , Belgium , Sulfates/chemistry , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Groundwater/chemistry , Metals/chemistry , Metals/analysis , Soil Pollutants/analysis , Pilot Projects , Biodegradation, Environmental , Chemical Precipitation
7.
Cureus ; 15(8): e43593, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37719507

ABSTRACT

Percutaneous tracheostomy (PT) is a commonly performed procedure in ICUs as a safe and cost-effective alternative to surgical tracheostomy (ST). Bronchoscopy is frequently used during PT for real-time confirmation of needle placement and tube positioning. We present a case of a 42-year-old female with a complex medical history who underwent PT and experienced acute airway loss due to endotracheal tube obstruction caused by accumulated secretions. To prevent such complications, vigilance regarding airway obstruction, cautious bronchoscope advancement, avoiding endotracheal tube puncture, and readiness to abort the procedure and replace the tube are crucial.

8.
J Cardiovasc Dev Dis ; 10(9)2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37754799

ABSTRACT

Cor triatriatum is a very rare cardiac malformation characterized by the presence of an abnormal interatrial membrane separating either the left or right atrial chamber into two compartments. It can be associated with other cardiac defects and is often symptomatic in childhood. The signs depend on the size and position of the interatrial membrane and other associated malformations. Here we report a case of right-sided cor triatriatum associated with an ostium primum-type interatrial septum defect and left-sided opening of the coronary sinus in a fetus. The cause of intrauterine death was asphyxia due to total placental abruption.

9.
Life Sci ; 328: 121878, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37392779

ABSTRACT

AIMS: Mitragynine (MG) is an alkaloid found in Mitragyna speciosa (kratom), a plant used to self-treat symptoms of opioid withdrawal and pain. Kratom products are commonly used in combination with cannabis, with the self-treatment of pain being a primary motivator of use. Both cannabinoids and kratom alkaloids have been characterized to alleviate symptoms in preclinical models of neuropathic pain such as chemotherapy-induced peripheral neuropathy (CIPN). However, the potential involvement of cannabinoid mechanisms in MG's efficacy in a rodent model of CIPN have yet to be explored. MAIN METHODS: Prevention of oxaliplatin-induced mechanical hypersensitivity and formalin-induced nociception were assessed following intraperitoneal administration of MG and CB1, CB2, or TRPV1 antagonists in wildtype and cannabinoid receptor knockout mice. The effects of oxaliplatin and MG exposure on the spinal cord endocannabinoid lipidome was assessed by HPLC-MS/MS. KEY FINDINGS: The efficacy of MG on oxaliplatin-induced mechanical hypersensitivity was partially attenuated upon genetic deletion of cannabinoid receptors, and completely blocked upon pharmacological inhibition of CB1, CB2, and TRPV1 channels. This cannabinoid involvement was found to be selective to a model of neuropathic pain, with minimal effects on MG-induced antinociception in a model of formalin-induced pain. Oxaliplatin was found to selectively disrupt the endocannabinoid lipidome in the spinal cord, which was prevented by repeated MG exposure. SIGNIFICANCE: Our findings suggest that cannabinoid mechanisms contribute to the therapeutic efficacy of the kratom alkaloid MG in a model of CIPN, which may result in increased therapeutic efficacy when co-administered with cannabinoids.


Subject(s)
Antineoplastic Agents , Cannabinoids , Mitragyna , Neuralgia , Secologanin Tryptamine Alkaloids , Mice , Animals , Cannabinoids/pharmacology , Endocannabinoids , Oxaliplatin , Tandem Mass Spectrometry , Antineoplastic Agents/adverse effects , Secologanin Tryptamine Alkaloids/adverse effects , Neuralgia/chemically induced , Neuralgia/drug therapy , Neuralgia/prevention & control , Receptors, Cannabinoid
10.
Article in English | MEDLINE | ID: mdl-37466474

ABSTRACT

Introduction: Chronic neuropathic pain is as a severe detriment to overall quality of life for millions of Americans. Current pharmacological treatment options for chronic neuropathic pain are generally limited in efficacy and may pose serious adverse effects such as risk of abuse, nausea, dizziness, and cardiovascular events. Therefore, many individuals have resorted to methods of pharmacological self-treatment. This narrative review summarizes the existing literature on the utilization of two novel approaches for the treatment of chronic pain, cannabinoid constituents of Cannabis sativa and alkaloid constituents of Mitragyna speciosa (kratom), and speculates on the potential therapeutic benefits of co-administration of these two classes of compounds. Methods: We conducted a narrative review summarizing the primary motivations for use of both kratom and cannabis products based on epidemiological data and summarize the pre-clinical evidence supporting the application of both kratom alkaloids and cannabinoids for the treatment of chronic pain. Data collection was performed using the PubMed electronic database. The following word combinations were used: kratom and cannabis, kratom and pain, cannabis and pain, kratom and chronic pain, and cannabis and chronic pain. Results: Epidemiological evidence reports that the self-treatment of pain is a primary motivator for use of both kratom and cannabinoid products among adult Americans. Further evidence shows that use of cannabinoid products may precede kratom use, and that a subset of individuals concurrently uses both kratom and cannabinoid products. Despite its growing popularity as a form of self-treatment of pain, there remains an immense gap in knowledge of the therapeutic efficacy of kratom alkaloids for chronic pain in comparison to that of cannabis-based products, with only three pre-clinical studies having been conducted to date. Conclusion: There is sufficient epidemiological evidence to suggest that both kratom and cannabis products are used to self-treat pain, and that some individuals actively use both drugs, which may produce potential additive or synergistic therapeutic benefits that have not yet been characterized. Given the lack of pre-clinical investigation into the potential therapeutic benefits of kratom alkaloids against forms of chronic pain, further research is warranted to better understand its application as a treatment alternative.

11.
Article in English | MEDLINE | ID: mdl-37450169

ABSTRACT

Self-stabbing and self-cutting represents an uncommon method of suicide. We present a case of a 30-year-old man who was found dead in the forest. The body was naked and showed multiple cut and stab wounds on different parts of the body (face, neck, chest, abdomen, and extremities). A single-edged kitchen knife was found approximately 20 m from the body. Parts of both ears, the fifth toe of the right foot, and the scrotum were cut off. At the autopsy, two of the severed body parts-the toe and the part of the left ear-were found in the stomach. The cause of death was asphyxiation due to blood aspiration resulting from a cut throat injury. A police investigation uncovered a history of substance abuse and two previous suicidal attempts using a knife. Upon complex analysis of all the evidence, the manner of death was ruled a suicide, which was preceded by actions of major self-mutilation and self-cannibalism, both considered rare behavioral patterns.

12.
Environ Sci Ecotechnol ; 16: 100276, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37206316

ABSTRACT

Increasing energy demands and environmental pollution concerns press for sustainable and environmentally friendly technologies. Soil microbial fuel cell (SMFC) technology has great potential for carbon-neutral bioenergy generation and self-powered electrochemical bioremediation. In this study, an in-depth assessment on the effect of several carbon-based cathode materials on the electrochemical performance of SMFCs is provided for the first time. An innovative carbon nanofibers electrode doped with Fe (CNFFe) is used as cathode material in membrane-less SMFCs, and the performance of the resulting device is compared with SMFCs implementing either Pt-doped carbon cloth (PtC), carbon cloth, or graphite felt (GF) as the cathode. Electrochemical analyses are integrated with microbial analyses to assess the impact on both electrogenesis and microbial composition of the anodic and cathodic biofilm. The results show that CNFFe and PtC generate very stable performances, with a peak power density (with respect to the cathode geometric area) of 25.5 and 30.4 mW m-2, respectively. The best electrochemical performance was obtained with GF, with a peak power density of 87.3 mW m-2. Taxonomic profiling of the microbial communities revealed differences between anodic and cathodic communities. The anodes were predominantly enriched with Geobacter and Pseudomonas species, while cathodic communities were dominated by hydrogen-producing and hydrogenotrophic bacteria, indicating H2 cycling as a possible electron transfer mechanism. The presence of nitrate-reducing bacteria, combined with the results of cyclic voltammograms, suggests microbial nitrate reduction occurred on GF cathodes. The results of this study can contribute to the development of effective SMFC design strategies for field implementation.

13.
Wien Klin Wochenschr ; 135(21-22): 631-636, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37256420

ABSTRACT

Serratia marcescens is a gram-negative bacillus that is an opportunistic agent in respiratory tract infections, urinary tract infections, and septicemia. It is rarely also a cause of infective endocarditis which follows a rapid and devastating course, typically in persons with history of intravenous drug use (IDU). This article reports a fatal case of a 27-year-old patient with a known history of IDU, who presented with clinical symptoms concerning right-sided endocarditis as well as signs of acute respiratory distress syndrome. Finally, a detailed review of the literature is provided concerning the acute endocarditis of a tricuspid valve, especially associated with Serratia marcescens infection.


Subject(s)
Drug Users , Endocarditis, Bacterial , Endocarditis , Substance Abuse, Intravenous , Humans , Adult , Tricuspid Valve , Serratia marcescens , Substance Abuse, Intravenous/complications , Endocarditis, Bacterial/complications , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/drug therapy , Endocarditis/complications
14.
Rechtsmedizin (Berl) ; 33(3): 218-222, 2023.
Article in English | MEDLINE | ID: mdl-36778761

ABSTRACT

This article reports the autopsy findings of a 1.5-year-old girl with no history of previous hospital admission who suddenly collapsed at home. After 45 minutes of resuscitation efforts, the cardiac activity was restored. During hospitalization, she had ventricular arrhythmia and extremely elevated cardiac troponin levels. Internal examination and immunohistochemistry revealed cardiac fibromas of the right and left ventricles and extensive hypoxic myocardial damage. The right ventricular fibroma demonstrated interdigitating and entrapped myocardium visible at the edges and within the central portion of the tumor. The left ventricular fibroma originated in the subepicardial region and propagated towards the endocardium.

15.
Drug Alcohol Depend ; 242: 109719, 2023 01 01.
Article in English | MEDLINE | ID: mdl-36521236

ABSTRACT

Riluzole, approved to manage amyotrophic lateral sclerosis, is mechanistically unique among glutamate-based therapeutics because it reduces glutamate transmission through a dual mechanism (i.e., reduces glutamate release and enhances glutamate reuptake). The profile of riluzole is favorable for normalizing glutamatergic dysregulation that perpetuates methamphetamine (METH) dependence, but pharmacokinetic and metabolic liabilities hinder repurposing. To mitigate these limitations, we synthesized troriluzole (TRLZ), a third-generation prodrug of riluzole, and tested the hypothesis that TRLZ inhibits METH hyperlocomotion and conditioned place preference (CPP) and normalizes METH-induced changes in mesolimbic glutamate biomarkers. TRLZ (8, 16 mg/kg) reduced hyperlocomotion caused by METH (1 mg/kg) without affecting spontaneous activity. TRLZ (1, 4, 8, 16 mg/kg) administered during METH conditioning (0.5 mg/kg x 4 d) inhibited development of METH place preference, and TRLZ (16 mg/kg) administered after METH conditioning reduced expression of CPP. In rats with established METH place preference, TRLZ (16 mg/kg) accelerated extinction of CPP. In cellular studies, chronic METH enhanced mRNA levels of glutamate carboxypeptidase II (GCPII) in the ventral tegmental area (VTA) and prefrontal cortex (PFC). Repeated METH also caused enhancement of GCPII protein levels in the VTA that was prevented by TRLZ (16 mg/kg). TRLZ (16 mg/kg) administered during chronic METH did not affect brain or plasma levels of METH. These results indicate that TRLZ, already in clinical trials for cerebellar ataxia, reduces development, expression and maintenance of METH CPP. Moreover, normalization of METH-induced GCPII levels in mesolimbic substrates by TRLZ points toward studying GCPII as a therapeutic target of TRLZ.


Subject(s)
Amphetamine-Related Disorders , Central Nervous System Stimulants , Methamphetamine , Rats , Animals , Methamphetamine/pharmacology , Central Nervous System Stimulants/pharmacology , Glutamate Carboxypeptidase II/therapeutic use , Riluzole/therapeutic use , Amphetamine-Related Disorders/drug therapy , Glutamates/therapeutic use
17.
J Infect Dis ; 227(3): 344-352, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36214810

ABSTRACT

BACKGROUND: Four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants predominated in the United States since 2021. Understanding disease severity related to different SARS-CoV-2 variants remains limited. METHOD: Viral genome analysis was performed on SARS-CoV-2 clinical isolates circulating March 2021 through March 2022 in Cleveland, Ohio. Major variants were correlated with disease severity and patient outcomes. RESULTS: In total 2779 patients identified with either Alpha (n 1153), Gamma (n 122), Delta (n 808), or Omicron variants (n 696) were selected for analysis. No difference in frequency of hospitalization, intensive care unit (ICU) admission, and death were found among Alpha, Gamma, and Delta variants. However, patients with Omicron infection were significantly less likely to be admitted to the hospital, require oxygen, or admission to the ICU (2 12.8, P .001; 2 21.6, P .002; 2 9.6, P .01, respectively). In patients whose vaccination status was known, a substantial number had breakthrough infections with Delta or Omicron variants (218/808 [26.9] and 513/696 [73.7], respectively). In breakthrough infections, hospitalization rate was similar regardless of variant by multivariate analysis. No difference in disease severity was identified between Omicron subvariants BA.1 and BA.2. CONCLUSIONS: Disease severity associated with Alpha, Gamma, and Delta variants is comparable while Omicron infections are significantly less severe. Breakthrough disease is significantly more common in patients with Omicron infection.


Subject(s)
COVID-19 , Humans , SARS-CoV-2/genetics , Patient Acuity , Breakthrough Infections
18.
Brain Behav Immun ; 107: 47-52, 2023 01.
Article in English | MEDLINE | ID: mdl-36174884

ABSTRACT

P2X7 receptors are dysregulated during psychostimulant exposure. Furthermore, P2X7 receptors enhance endogenous systems (e.g., cytokines, dopamine, and glutamate) that facilitate psychostimulant addiction. Therefore, using mouse locomotor, conditioned place preference (CPP), and intracranial self-stimulation (ICSS) assays, we tested the hypothesis that methamphetamine (METH) reward and acute locomotor activation requires P2X7 receptor activity. We also investigated effects of P2X7 blockade on METH-induced changes in cytokine levels in brain reward regions. A438079 (5, 10, 50 mg/kg), a P2X7 antagonist, did not affect spontaneous locomotor activity but reduced hyperlocomotion caused by acute METH (1 mg/kg) exposure. A438079 (10 mg/kg) also prevented expression of METH CPP without causing aversive or rewarding effects. For ICSS experiments, METH (1 mg/kg) facilitated brain reward function as interpreted from reductions in baseline threshold. In the presence of A438079 (50 mg/kg), METH-induced facilitation of ICSS was reduced. Repeated METH exposure (1 mg/kg × 7 d) caused enhancement of IL-17A levels in the prefrontal cortex (PFC) that was normalized by A438070 (10 mg/kg × 7 d). The present data suggest that P2X7 receptor activity contributes to rewarding and locomotor-stimulant effects of METH through a potential mechanism involving IL-17A, which has recently been implicated in anxiety.


Subject(s)
Methamphetamine , Animals , Mice , Methamphetamine/pharmacology , Receptors, Purinergic P2X7 , Purinergic P2X Receptor Antagonists , Interleukin-17
19.
J Surg Case Rep ; 2022(11): rjac520, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36415727

ABSTRACT

Cholecystocolonic fistulas (CCF) are a rare but significant complication of biliary disease, frequently presenting as gallstone ileus. Although there is no one agreed-upon procedure, enterolithotomy appears to be the initial treatment of choice; with a subsequent cholecystectomy performed ~4-8 weeks later. Alternatively, a patient may undergo a single-stage procedure, at which time an enterolithotomy, cholecystectomy and fistula closure are performed. Herein, we describe two patients with chronic cholecystitis and subsequent development of CCF with differing presentations. We report the clinical, radiographic and intraoperative findings and discuss the surgical treatment options for each patient, respectively.

20.
IBRO Neurosci Rep ; 13: 198-206, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36093282

ABSTRACT

Mitragynine (MG) is an alkaloid found in Mitragyna speciosa (kratom) that is used as an herbal remedy for pain relief and opioid withdrawal. MG acts at µ-opioid and α-adrenergic receptors in vitro, but the physiological relevance of this activity in the context of neuropathic pain remains unknown. The purpose of the present study was to characterize the effects of MG in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN), and to investigate the potential impact of sex on MG's therapeutic efficacy. Inhibition of oxaliplatin-induced mechanical hypersensitivity was measured following intraperitoneal administration of MG. Both male and female C57BL/6J mice were used to characterize potential sex-differences in MG's therapeutic efficacy. Pharmacological mechanisms of MG were characterized through pretreatment with the opioid and adrenergic antagonists naltrexone, prazosin, yohimbine, and propranolol (1, 2.5, 5 mg/kg). Oxaliplatin produced significant mechanical allodynia of equal magnitude in both male and females, which was dose-dependently attenuated by repeated MG exposure. MG was more potent in males vs females, and the highest dose of MG (10 mg/kg) exhibited greater anti-allodynic efficacy in males. Mechanistically, activity at µ-opioid, α1- and α2-adrenergic receptors, but not ß-adrenergic receptors contributed to the effects of MG against oxaliplatin-induced mechanical hypersensitivity. Repeated MG exposure significantly attenuated oxaliplatin-induced mechanical hypersensitivity with greater potency and efficacy in males, which has crucial implications in the context of individualized pain management. The opioid and adrenergic components of MG indicate that it shares pharmacological properties with clinical neuropathic pain treatments.

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