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1.
J Ethn Subst Abuse ; : 1-14, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270145

RESUMO

This study examined how minoritized U.S. Army Reserve/National Guard service members perceive cannabis use amid a continuously evolving societal and legal landscape in the United States. Logistic regression analyses were conducted to examine relationships between cannabis perceptions and race while considering illicit drug use norms, posttraumatic stress disorder symptomatology, and current drug use. Non-Hispanic Black soldiers had lower odds of approval for medicinal cannabis use and Hispanic soldiers had higher odds of perceived risk of cannabis use, both of which persisted when considering key covariates. These findings may be partly explained by a confluence of societal and cultural factors.

2.
Front Pharmacol ; 14: 1213763, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920212

RESUMO

Vincristine is the drug of choice for Hodgkin's lymphoma, acute lymphoblastic leukemia, and non-Hodgkin lymphoma. Despite its significant anticancer effects, it causes dose-dependent neuropathy, leading to compulsive dose reduction. The available drugs used for vincristine-induced neuropathic pain (VINP) have a range of safety, efficacy, and tolerability issues prompting a search for new therapies. 5,7-Dimethoxycoumarin (5,7-DMC) also known as citropten, is a natural coumarin found in the essential oils of citrus plants such as lime, lemons, and bergamots, and it possesses both antidepressant and anti-inflammatory effects. This study was designed to investigate the possible analgesic and antiallodynic effects of 5,7-DMC in a murine model of VINP. Vincristine was administered to groups of BALB/c male mice (0.1 mg/kg intraperitoneally) once daily for 14 days to induce VINP. Thermal hyperalgesia and mechanical allodynia were quantified using the tail immersion test and von Frey filament application method. The levels of monoamine neurotransmitters and vitamin C in frontal cortical, striatal and hippocampal tissues, as well as the TNF-α level in plasma, were quantified using high performance liquid chromatography and ELISA respectively. On day 15 of the protocol, acute treatment with 5,7-DMC clearly reversed VINP thermal hyperalgesia, mechanical static allodynia, mechanical dynamic allodynia, and cold allodynia. The activity of 5,7-DMC against hyperalgesia and allodynia was inhibited by pretreatment with ondansetron but not naloxone, implicating a 5-HT3 receptor involvement. VINP vitamin C levels were restored by 5,7-DMC in the frontal cortex, and changes in serotonin, dopamine, adenosine, inosine and hypoxanthine levels caused by vincristine were reversed either fully or partially. Additionally, the vincristine-induced rise in hippocampal serotonin, dopamine, inosine and striatal serotonin was appreciably reversed by 5,7-DMC. 5,7-DMC also reversed the vincristine-induced increase in the plasma level of TNF-α. In negating the changes in the levels of some neurotransmitters in the brain caused by vincristine, 5,7-DMC showed stronger effects than gabapentin. It was concluded that, there is a potential role of 5-HT3 receptors and monoamines in the amelioration of VINP induced by 5,7-DMC, and the use of this compound warrants further investigation.

3.
Front Pharmacol ; 14: 1232088, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37663254

RESUMO

Introduction: Post-traumatic stress disorder (PTSD) is a chronic mental illness triggered by traumatic experiences such as wars, natural disasters, or catastrophes, and it is characterized by anxiety, depression and cognitive impairment. Diosgenin is a steroidal sapogenin with known neuroprotective and antioxidant properties. This study aimed to assess the pharmacological potential of diosgenin in a single prolonged stress (SPS) model of PTSD, plus other behavioral models along with any consequent alterations in brain neurochemistry in male mice. Methodology: SPS was induced by restraining animals for 2 h, followed by 20 min of forced swim, recuperation for 15 min, and finally, exposure to ether to induce anesthesia. The SPS-exposed animals were treated with diosgenin (20, 40, and 60 mg/kg) and compared with the positive controls, fluoxetine or donepezil, then they were observed for any changes in anxiety/depression-like behaviors, and cognitive impairment. After behavioral screening, postmortem serotonin, noradrenaline, dopamine, vitamin C, adenosine and its metabolites inosine and hypoxanthine were quantified in the frontal cortex, hippocampus, and striatum by high-performance liquid chromatography. Additionally, animal serum was screened for changes in corticosterone levels. Results: The results showed that diosgenin reversed anxiety- and depression-like behaviors, and ameliorated cognitive impairment in a dose-dependent manner. Additionally, diosgenin restored monoamine and vitamin C levels dose-dependently and modulated adenosine and its metabolites in the brain regions. Diosgenin also reinstated otherwise increased serum corticosterone levels in SPS mice. Conclusion: The findings suggest that diosgenin may be a potential candidate for improving symptoms of PTSD.

4.
Artigo em Inglês | MEDLINE | ID: mdl-37603224

RESUMO

OBJECTIVES: There are substantial racial/ethnic disparities in substance use and mental health among civilian populations, but few studies have examined these disparities in veterans using a nationally representative sample. Thus, we examined differences in substance dependence and serious psychological distress (SPD) by race/ethnicity among a national sample of US veterans. METHODS: We pooled cross-sectional data from the 2015-2019 waves of the National Survey on Drug Use and Health (N = 7,653 veterans aged 18-64 years). Regression models were utilized to examine racial/ethnic differences in DSM-IV substance dependence and SPD with a Benjamini-Hochberg correction applied. RESULTS: Compared to non-Hispanic White veterans: American Indian/Alaska Native veterans had significantly higher odds of past-year alcohol dependence (AOR = 2.55, 95% CI: 1.28, 5.08); Asian American veterans had significantly lower odds of past-year alcohol dependence (AOR = 0.12, 95% CI: 0.02, 0.62); non-Hispanic Black (AOR = 0.60, 95% CI: 0.48, 0.77), Hispanic (AOR = 0.47, 95% CI: 0.34, 0.65), and veterans of more than one race (AOR = 0.55, 95% CI: 0.36, 0.83) had significantly lower odds of past-month nicotine dependence; Asian American veterans had significantly lower odds of past-year illicit drug dependence (AOR = 0.05, 95% CI: 0.01, 0.35); and non-Hispanic Black veterans had significantly lower odds of past-year SPD (AOR = 0.69, 95% CI: 0.55, 0.85) after correction for multiple comparisons. CONCLUSION: Overall, racial/ethnic disparities in substance dependence and SPD among veterans are not as stark as in civilian populations, but some disparities remain.

5.
Methods Mol Biol ; 2684: 319-327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37410244

RESUMO

Oncolytic viruses are biological agents which can easily be delivered at high doses directly to the bladder through a catheter (intravesical), with low risk of systemic uptake and toxicity. To date, a number of viruses have been delivered intravesically in patients and in murine models with bladder cancer and antitumour effects demonstrated. Here, we describe in vitro methods to evaluate Coxsackie virus, CVA21, as an oncolytic virus for the treatment of human bladder cancer by determining the susceptibility of bladder cancer cell lines expressing differing levels of ICAM-1 surface receptor to CVA21.


Assuntos
Carcinoma , Terapia Viral Oncolítica , Vírus Oncolíticos , Neoplasias da Bexiga Urinária , Humanos , Animais , Camundongos , Vírus Oncolíticos/genética , Vírus Oncolíticos/metabolismo , Terapia Viral Oncolítica/métodos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Bexiga Urinária/metabolismo , Linhagem Celular , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/patologia , Linhagem Celular Tumoral
6.
Drug Des Devel Ther ; 17: 1793-1803, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37346999

RESUMO

Background and Objective: Gabapentin is a commonly prescribed antiepileptic agent for seizures, which is also used for pain and addiction management. Due to growing evidence of its abuse liability, there has been an incentive to synthesise potentially useful gabapentin derivatives devoid of adverse effects. A gabapentin adduct with a fluoxetine moiety, GBP1F, was assessed for any sedative, cognitive, anxiolytic, or antidepressant-like actions in murine behavioral models. Materials and Methods: Selected groups of mice were used for each behavioral paradigm, and the effect of GBP1F (5, 10, and 15 mg/kg) was assessed using spontaneous locomotor activity, the tail suspension test, elevated plus maze test, and the Y maze test models. Immediately following behavioral experiments, postmortem striatal and hippocampal tissues were evaluated for the effect of GBP1F on concentrations of dopamine, DOPAC, HVA, serotonin, 5-HIAA, vitamin C, and noradrenaline using high performance liquid chromatography with electrochemical detection. Results: GBP1F induced a mild suppression of locomotor activity, ameliorated anxiety and depression-like behavior, did not alter cognitive behavior, and raised serotonin and 5-HIAA concentrations in the hippocampus and striatum. GBP1F also positively enhanced dopamine and vitamin C tissue levels in the striatum. Thus, GBP1F represents a compound with anxiolytic- and antidepressant-like effects though further studies are warranted at the molecular level to focus on the precise mechanism(s) of action.


Assuntos
Ansiolíticos , Fluoxetina , Camundongos , Animais , Fluoxetina/farmacologia , Gabapentina/farmacologia , Dopamina/farmacologia , Depressão/tratamento farmacológico , Serotonina , Ansiolíticos/farmacologia , Ácido Hidroxi-Indolacético/farmacologia , Modelos Animais de Doenças , Antidepressivos/farmacologia , Ansiedade , Cognição , Ácido Ascórbico/farmacologia , Comportamento Animal
7.
Front Pharmacol ; 14: 1128496, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37033637

RESUMO

Background: Neuropathy is a prevalent and debilitating complication of poorly managed diabetes, contributing towards poor quality of life, amputation risk, and increased mortality. The available therapies for diabetic neuropathic pain (DPN) have limitations in terms of efficacy, tolerability and patient compliance. Dysfunction in the peripheral and central monoaminergic system has been evidenced in various types of neuropathic and acute pain. The objective of the present study was to investigate 1-methyl 1, 2, 3, 4-tetrahydroisoquinoline (1MeTIQ), an endogenous amine found in human brain with a known neuroprotective profile, in a model of streptozotocin (STZ) induced neuropathic pain. Methods: Diabetic neuropathy in male BALB/c mice was induced by intraperitoneal injection of a single dose of STZ (200 mg/kg). Upon development of DPN after 4 weeks, mice were investigated for mechanical allodynia (von Frey filament pressure test) and thermal hyperalgesia (tail immersion test). Ondansetron (1.0 mg/kg i.p.), naloxone (3.0 mg/kg i.p.) and yohimbine (2.0 mg/kg i.p.) were used to elucidate the possible mechanism involved. Postmortem frontal cortical, striatal and hippocampal tissues were dissected and evaluated for changes in levels of dopamine, noradrenaline and serotonin using High-Performance Liquid Chromatography (HPLC) with UV detection. Results: Acute administration of 1MeTIQ (15-45 mg/kg i.p.) reversed streptozotocin-induced diabetic neuropathic static mechanical allodynia (von Frey filament pressure test) and thermal hyperalgesia (tail immersion test), these outcomes being comparable to standard gabapentin. Furthermore, HPLC analysis revealed that STZ-diabetic mice expressed lower concentrations of serotonin in all three brain regions examined, while dopamine was diminished in the striatum and 1MeTIQ reversed all these neurotransmitter modifications. These findings suggest that the antihyperalgesic/antiallodynic activity of 1MeTIQ may be mediated in part via supraspinal opioidergic and monoaminergic modulation since they were naloxone, yohimbine and ondansetron reversible. Conclusion: It was also concluded that acute treatment with 1MeTIQ ameliorated STZ-induced mechanical allodynia and thermal hyperalgesia and restored brain regionally altered serotonin and dopamine concentrations which signify a potential for 1MeTIQ in the management of DPN.

8.
Front Pharmacol ; 14: 1135497, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37033640

RESUMO

Purpose: Chronic unpredictable stress (CUS) induces long-term neuronal and synaptic plasticity with a neurohormonal disbalance leading to the development of co-existing anxiety, depression, and cognitive decline. The side effects and delayed onset of current clinically used antidepressants has prompted a quest for antidepressants with minimum drawbacks. Fraxetin is a natural coumarin derivative with documented antioxidant and neuroprotective activity though its effects on stress are unknown. This study therefore aimed to investigate any possible acute effect of fraxetin in behavioral tests including a CUS paradigm in correlation with brain regional neurochemical changes. Methods: Mice were subjected to a series of mild stressors for 14 days to induce CUS. Furthermore, behavioral performance in the open field test, forced swim test (FST), Y-maze and elevated plus-maze were evaluated. Postmortem frontal cortical, hippocampal and striatal tissues were analyzed via high-performance liquid chromatography (HPLC) for neurochemical changes. Result: Acute administration of fraxetin (20-60 mg/kg, orally) decreased depression-like behavior in the FST and behavioral anxiety in both the open field test and elevated plus-maze. Memory deficits induced during the CUS paradigm were markedly improved as reflected by enhanced Y maze performance. Concurrent biochemical and neurochemical analyses revealed that only the two higher fraxetin doses decreased elevated serum corticosterone levels while diminished serotonin levels in the frontal cortex, striatum and hippocampus were reversed, though noradrenaline was only raised in the striatum. Concomitantly, dopamine levels were restored by fraxetin at the highest dose exclusively in the frontal cortex. Conclusion: Acute treatment with fraxetin attenuated CUS-induced behavioral deficits, ameliorated the increased corticosterone level and restored altered regional neurotransmitter levels and this may indicate a potential application of fraxetin in the management of anxiety and depression modeled by CUS. However, further studies are warranted regarding the chronic effects of fraxetin behaviorally and neurochemically.

9.
Drug Des Devel Ther ; 16: 1573-1593, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35665194

RESUMO

Purpose: Chronic ethanol exposure causes neurotoxicity and long-term learning and memory impairment along with hippocampal and frontal cortical dysfunction. Flavonoids possess antioxidant and anti-inflammatory properties believed to be contributory factors in reversing cognitive decline. 6-Methoxyflavone (6-MOF), a flavonoid occurring naturally in medicinal plants, has been reported to instigate neuroprotection by reversing cisplatin-induced hyperalgesia and allodynia. Consequently, this study was designed to investigate 6-MOF activity in models of chronic ethanol-induced cognitive impairment along with neurochemical correlates. Methods: Mice were given ethanol orally (2.0 g/kg daily) for 24 days plus either saline, 6-MOF (25-75mg/kg) or donepezil (4mg/kg) and then ethanol was withdrawn for the next 6 days. Animals were subsequently assessed for their cognitive performance in several models on days 1, 12, and 24, during abstinence (Day-26) and on the 7th day of the washout period. Following behavioral assessment, post-mortem dopamine, noradrenaline and vitamin C concentrations were quantified in the frontal cortex, hippocampus and striatum, using HPLC with UV detection. Results: Chronic ethanol treatment suppressed locomotor activity and impaired cognitive tasks, which included novel object recognition, performance in the Morris water maze as well as the Y-maze, socialization and nest-building behavior throughout the protocol and during withdrawal. These behavioral deficits were at least partially restored by the co-administration of 6-MOF or donepezil with ethanol as were ethanol-induced deficits in frontal cortical and hippocampal dopamine plus noradrenaline, together with striatal dopamine. 6-MOF co-administration with ethanol also modestly restored striatal vitamin C levels. Conclusion: It is postulated that, apart from donepezil, 6-MOF may be useful not only in the treatment of ethanol withdrawal severity but also in the management of chronic ethanol withdrawal induced cognitive impairment.


Assuntos
Disfunção Cognitiva , Etanol , Animais , Ácido Ascórbico , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Donepezila , Dopamina , Flavonas , Hipocampo , Aprendizagem em Labirinto , Camundongos , Norepinefrina
10.
Mol Ther Oncolytics ; 20: 434-446, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33665363

RESUMO

Prostate cancers are considered "cold" tumors characterized by minimal T cell infiltrates, absence of a type I interferon (IFN) signature, and the presence of immunosuppressive cells. This non-inflamed phenotype is likely responsible for the lack of sensitivity of prostate cancer patients to immune checkpoint blockade (ICB) therapy. Oncolytic virus therapy can potentially overcome this resistance to immunotherapy in prostate cancers by transforming cold tumors into "hot," immune cell-infiltrated tumors. We investigated whether the combination of intratumoral oncolytic reovirus, followed by targeted blockade of Programmed cell death protein 1 (PD-1) checkpoint inhibition and/or the immunomodulatory CD73/Adenosine system can enhance anti-tumor immunity. Treatment of subcutaneous TRAMP-C2 prostate tumors with combined intratumoral reovirus and anti-PD-1 or anti-CD73 antibody significantly enhanced survival of mice compared with reovirus or either antibody therapy alone. Only combination therapy led to rejection of pre-established tumors and protection from tumor re-challenge. This therapeutic effect was dependent on CD4+ T cells and natural killer (NK) cells. NanoString immune profiling of tumors confirmed that reovirus increased tumor immune cell infiltration and revealed an upregulation of the immune-regulatory receptor, B- and T-lymphocyte attenuator (BTLA). This expression of BTLA on innate antigen-presenting cells (APCs) and its ligand, Herpesvirus entry mediator (HVEM), on T cells from reovirus-infected tumors was in keeping with a role for the HVEM-BTLA pathway in promoting the potent anti-tumor memory response observed.

11.
Gastroenterol Res Pract ; 2020: 4253174, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33204254

RESUMO

Combretum fragrans (Combretaceae) is a Cameroonian medicinal plant containing various secondary metabolites and traditionally used for the treatment of several pathologies. Two cycloartane-type triterpenes, Combretin A and Combretin B, were isolated from this plant. This study was aimed at evaluating the anti-inflammatory, antioxidant, and anticolitis effects of these compounds. In vitro anti-inflammatory properties were evaluated by inhibition of cyclooxygenase, 5-lipoxygenase, and denaturation of the protein; antioxidant properties were assessed by using 1,1-diphenyl-2-picrylhydrazyl (DPPH), (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid)) ABTS•+, capacity tests ferric reducing antioxidant (FRAP), and trapping nitric oxide. For in vivo analysis, we used the model of ulcerative colitis induced by Dextran Sulfate Sodium (DSS). Studies of the anti-inflammatory activity showed that Combretin A and Combretin B had maximal inhibitory activity on cyclooxygenase (71.92% and 89.59%), 5-lipoxygenase (76.68% and 91.21%), and protein denaturation (63.93% and 87.78%). Antioxidant activity on DPPH, ABTS•+, ferric reducing antioxidant capacity (FRAP), and nitric oxide scavenging showed that Combretin A and Combretin B showed good antioxidant activities. These compounds significantly reduced the signs of DSS-induced colitis in the treated animals by preventing the weight loss of the animals, by significantly reducing the disease activity index, improving the condition of the stool, preventing the reduction of the length of the colon, and preventing the degradation of the colon. This study revealed that Combretin A and Combretin B have anti-inflammatory, antioxidant, and curative properties against colitis experimentally induced by DSS in rats.

12.
Clin Cancer Res ; 25(19): 5818-5831, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31273010

RESUMO

PURPOSE: The CANON [CAVATAK in NON-muscle-invasive bladder cancer (NMIBC)] study evaluated a novel ICAM-1-targeted immunotherapeutic-coxsackievirus A21 as a novel oncolytic agent against bladder cancer. PATIENTS AND METHODS: Fifteen patients enrolled in this "window of opportunity" phase I study, exposing primary bladder cancers to CAVATAK prior to surgery. The first 9 patients received intravesical administration of monotherapy CAVATAK; in the second stage, 6 patients received CAVATAK with a subtherapeutic dose of mitomycin C, known to enhance expression of ICAM-1 on bladder cancer cells. The primary endpoint was to determine patient safety and maximum tolerated dose (MTD). Secondary endpoints were evidence of viral replication, induction of inflammatory cytokines, antitumor activity, and viral-induced changes in resected tissue. RESULTS: Clinical activity of CAVATAK was demonstrated by induction of tumor inflammation and hemorrhage following either single or multiple administrations of CAVATAK in multiple patients, and a complete resolution of tumor in 1 patient. Whether used alone or in combination with mitomycin C, CAVATAK caused marked inflammatory changes within NMIBC tissue biopsies by upregulating IFN-inducible genes, including both immune checkpoint inhibitory genes (PD-L1 and LAG3) and Th1-associated chemokines, as well as the induction of the innate activator RIG-I, compared with bladder cancer tissue from untreated patients. No significant toxicities were reported in any patient, from either virus or combination therapy. CONCLUSIONS: The acceptable safety profile of CAVATAK, proof of viral targeting, replication, and tumor cell death together with the virus-mediated increases in "immunological heat" within the tumor microenvironment all indicate that CAVATAK may be potentially considered as a novel therapeutic for NMIBC.


Assuntos
Imunoterapia/métodos , Molécula 1 de Adesão Intercelular/imunologia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/imunologia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Humanos , Imunoterapia/efeitos adversos , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Terapia Viral Oncolítica/efeitos adversos , Microambiente Tumoral/imunologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/virologia
13.
Mol Ther Oncolytics ; 9: 1-12, 2018 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-29989024

RESUMO

As a clinical setting in which local live biological therapy is already well established, non-muscle invasive bladder cancer (NMIBC) presents intriguing opportunities for oncolytic virotherapy. Coxsackievirus A21 (CVA21) is a novel intercellular adhesion molecule-1 (ICAM-1)-targeted immunotherapeutic virus. This study investigated CVA21-induced cytotoxicity in a panel of human bladder cancer cell lines, revealing a range of sensitivities largely correlating with expression of the viral receptor ICAM-1. CVA21 in combination with low doses of mitomycin-C enhanced CVA21 viral replication and oncolysis by increasing surface expression levels of ICAM-1. This was further confirmed using 300-µm precision slices of NMIBC where levels of virus protein expression and induction of apoptosis were enhanced with prior exposure to mitomycin-C. Given the importance of the immunogenicity of dying cancer cells for triggering tumor-specific responses and long-term therapeutic success, the ability of CVA21 to induce immunogenic cell death was investigated. CVA21 induced immunogenic apoptosis in bladder cancer cell lines, as evidenced by expression of the immunogenic cell death (ICD) determinant calreticulin, and HMGB-1 release and the ability to reject MB49 tumors in syngeneic mice after vaccination with MB49 cells undergoing CVA21 induced ICD. Such CVA21 immunotherapy could offer a potentially less toxic, more effective option for the treatment of bladder cancer.

14.
Biomed Pharmacother ; 103: 1043-1051, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29710662

RESUMO

BACKGROUND: Chemotherapy induced peripheral neuropathy (CIPN) is a painful side-effect of commonly used chemotherapeutic agents that profoundly impair the quality of life of patients as the current pharmacotherapeutic strategies are inefficient in providing adequate pain relief. Complementary and alternative medicine (CAM) therapies are preferred by patients with neuropathic pain as they experience insufficient control of pain with conventional medications. This study describes the antinociceptive effect of Tithonia tubaeformis (Jacq.) Cass. in a vincristine mouse model of established CIPN. METHODS: Tithonia tubaeformis hydromethanolic extract was tested for preliminary qualitative phytochemical analysis and acute oral toxicity test in mice. The antinociceptive effect was investigated using the abdominal constriction (writhing) and tail immersion tests (25-200 mg/kg). The anti-neuropathic effect was determined in the vincristine mouse model, established by daily administration of vincristine (0.1 mg/kg/day, i.p) for consecutive 14 days. Acute treatment with Tithonia tubaeformis (100 and 200 mg/kg) and the positive control, gabapentin (75 mg/kg) was carried out on the 15th day of the last vincrsitine dose and the animals were tested for allodynia and thermal hyperalgesia at 30-120 min post extract/drug administration. RESULTS: Vincristine produced significant temporal tactile allodynia and thermal hyperalgesia (P < 0.01 and P < 0.001 on day 7 and 14) and was maintained for the subsequent day (P < 0.001 during 30-120 min). Tithonia tubaeformis was effective in attenuating the vincristine-induced allodynia and thermal hyperalgesia at 100 mg/kg (P < 0.05, P < 0.01) and 200 mg/kg (P < 0.01, P < 0.001). Similarly, gabapentin also showed a robust antinociceptive effect in counteracting the vincristine associated behavioral alterations. CONCLUSIONS: Tithonia tubaeformis can be an effective CAM therapeutic remedy for established CIPN due to its potential antinociceptive effect in attenuating vincristine-induced neuropathy.


Assuntos
Analgésicos/uso terapêutico , Antineoplásicos Fitogênicos/toxicidade , Asteraceae/química , Dor/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Vincristina/toxicidade , Analgésicos/isolamento & purificação , Analgésicos/toxicidade , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Camundongos Endogâmicos BALB C , Dor/induzido quimicamente , Limiar da Dor/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Testes de Toxicidade Aguda
15.
Niger J Physiol Sci ; 32(2): 171-177, 2017 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-29485638

RESUMO

In Africa, a large number of pregnancies are exposed to Plasmodium falciparum infection. The in-utero environment extremely influences childhood neurodevelopment and behaviour. The complement 5a receptor (C5aR) is linked to several disease conditions. However, the influence of Plasmodium berghei during pregnancy on maternal complement 5a receptor and subsequently on fetal behaviour is unknown. Pregnant mice were intra-peritoneally inoculated on gestational day 13 with 1.02x105 infected red blood cells (iRBCs). iRBCs used in this experiment were gotten by in vivo passage of P. berghei in mice when the level of iRBCs have gotten to about 10-20%. A section of pregnant mice (both test and control groups) were earmarked to give birth and their offspring monitored up to postnatal day 42 when depression-like behaviour was evaluated using tail suspension test model. The other pregnant mice were subjected to cardiac puncture on gestational day 19 for C5a receptor estimation using Elisa assay. Results showed that pregnant mice infected with P. berghei had elevated C5a receptor compared with uninfected pregnant females. It was also shown that P. berghei-exposed offspring presented a depressive-like behaviour compared to unexposed controls. It may be concluded from this study, that complement 5a receptor demonstrates a pathogenic role in signaling and its possible role in mediating depression linked to Plasmodium berghei exposure in utero.


Assuntos
Malária/microbiologia , Transtornos do Humor/fisiopatologia , Plasmodium berghei/patogenicidade , Receptor da Anafilatoxina C5a/sangue , África , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Transtornos do Humor/sangue , Gravidez , Complicações Parasitárias na Gravidez/sangue , Complicações Parasitárias na Gravidez/parasitologia
16.
Phlebology ; 31(4): 283-95, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26036246

RESUMO

OBJECTIVE: To compare foam bubble size and bubble size distribution, stability, and degradation rate of commercially available polidocanol endovenous microfoam (Varithena®) and physician-compounded foams using a number of laboratory tests. METHODS: Foam properties of polidocanol endovenous microfoam and physician-compounded foams were measured and compared using a glass-plate method and a Sympatec QICPIC image analysis method to measure bubble size and bubble size distribution, Turbiscan™ LAB for foam half time and drainage and a novel biomimetic vein model to measure foam stability. Physician-compounded foams composed of polidocanol and room air, CO2, or mixtures of oxygen and carbon dioxide (O2:CO2) were generated by different methods. RESULTS: Polidocanol endovenous microfoam was found to have a narrow bubble size distribution with no large (>500 µm) bubbles. Physician-compounded foams made with the Tessari method had broader bubble size distribution and large bubbles, which have an impact on foam stability. Polidocanol endovenous microfoam had a lower degradation rate than any physician-compounded foams, including foams made using room air (p < 0.035). The same result was obtained at different liquid to gas ratios (1:4 and 1:7) for physician-compounded foams. In all tests performed, CO2 foams were the least stable and different O2:CO2 mixtures had intermediate performance. In the biomimetic vein model, polidocanol endovenous microfoam had the slowest degradation rate and longest calculated dwell time, which represents the length of time the foam is in contact with the vein, almost twice that of physician-compounded foams using room air and eight times better than physician-compounded foams prepared using equivalent gas mixes. CONCLUSION: Bubble size, bubble size distribution and stability of various sclerosing foam formulations show that polidocanol endovenous microfoam results in better overall performance compared with physician-compounded foams. Polidocanol endovenous microfoam offers better stability and cohesive properties in a biomimetic vein model compared to physician-compounded foams. Polidocanol endovenous microfoam, which is indicated in the United States for treatment of great saphenous vein system incompetence, provides clinicians with a consistent product with enhanced handling properties.


Assuntos
Polietilenoglicóis/química , Soluções Esclerosantes/química , Feminino , Humanos , Masculino , Polidocanol
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