Laboratory indices of hospitalized sickle cell disease patients, prevalence and antimicrobial susceptibility of pathogenic bacterial isolates at MRCG ward in the Gambia.

BACKGROUND: The aim of this study was to determine the prevalence of invasive bacterial infections and their antimicrobial resistance patterns in sickle cell disease (SCD) patients admitted at the Medical Research Council the Gambia (MRCG) Ward in the era of PCV and Hib vaccination in the Gambia. METHODS AND RESULTS: This study was conducted in the clinical laboratory department of MRCG. We retrospectively generated haematological, and blood culture data from our electronic medical records from 2015 to 2022 of SCD patients admitted to MRCG Ward. Of 380 SCD patients, blood culture was requested only for 159. Of the 159 admitted SCD, 11 patients had qualified positive blood cultures. Five different types of bacterial pathogens were isolated from these positive blood cultures: 4 Staphylococcus aureus, 3 Streptococcus pneumoniae, 2 Salmonella species, 1 Enterococcus species, and 1 Shigella boydii. No episode of bacteremia caused by Haemophilus influenzae type b was identified. The molecular serotyping of the Streptococcus pneumoniae isolates revealed non-vaccine serotypes 10 A, 12 F and 12 F. Penicillin resistance was recorded in two of the three Streptococcus pneumoniae. The Staphylococcus aureus isolates were penicillin resistant but cefoxitin sensitive, hence no methicillin (oxacillin) resistant Staphylococcus aureus was reported. Generally, the isolated pathogens were all sensitive to chloramphenicol, and vancomycin. The haematological indices were not significantly varied between SCD patients with and without microbiologically confirmed bacterial infection. CONCLUSION: Streptococcus pneumoniae and Staphylococcus aureus were the most common cause of bacteremia in these admitted SCD patients. The presence of non-typhoidal Salmonella and Shigella infection coupled with penicillin resistance should be considered during penicillin prophylaxis and empirical treatment regimens for SCD patients and future SCD management policies in the Gambia. The haematological parameters may not be reliable biomarkers in differentiating bacterial from non-bacterial infections in SCD patients.

Aggressive-like behaviour and neurocognitive impairment in alcohol herbal mixture-fed mice are associated with increased neuroinflammation and neuronal apoptosis in the prefrontal cortex.

Alcohol-induced aggression and related violence is a serious and common social problem globally. Alcohol use is increasingly found in the form of alcoholic herbal mixtures (AHM) with indiscriminate and unregulated alcohol content. This study investigated the effects of AHM on aggressive-like, neurocognitive impairment and brain biochemical alteration in mice. Thirty-two male resident mice were paired housed with female mice for 21 days in four groups (n = 8). Resident mice were treated orally with normal saline, AHM, ethanol and AHM + ethanol daily for 14 days. Aggressive-like behaviour was scored based on the latency and frequency of attacks by the resident mouse on the intruder. Neurocognitive impairment was determined using the Y-maze test (YMT) and novel object recognition test (NORT). Acetylcholinesterase, glutamic acid decarboxylase (GAD), pro-inflammatory and oxidative stress parameters were determined in the prefrontal cortex (PFC). Neuronal morphology, cytochrome c (Cyt-c) and nuclear factor-kappa B (NF-ĸB) expressions were determined. AHM and in combination with ethanol showed an increased index of aggression typified by frequency of attack and reduced latency to attack when compared to normal saline-treated animals. Co-administration of AHM and ethanol significantly reduced cognitive correct alternation (%) and discrimination index in the YMT and NORT, respectively. AHM and ethanol increased acetylcholinesterase, Pro-inflammatory cytokines and oxidative stress parameters while they reduced GAD. There were significantly reduced neuronal counts and increased expression of Cyt-c and NF-ĸB, respectively Alcoholic herbal mixture increased aggressiveness and caused neurocognitive impairment via increased oxido-inflammatory stress in the prefrontal cortex.

Jobelyn® improves motor dysfunctions induced by haloperidol in mice via neuroprotective mechanisms relating to modulation of cAMP response-element binding protein and mitogen-activated protein kinase.

The clinical efficacy of haloperidol in the treatment of psychosis has been limited by its tendency to cause parkinsonian-like motor disturbances such as bradykinesia, muscle rigidity and postural instability. Oxidative stress-evoked neuroinflammation has been implicated as the key neuropathological mechanism by which haloperidol induces loss of dopaminergic neurons and motor dysfunctions. This study was therefore designed to evaluate the effect of Jobelyn® (JB), an antioxidant supplement, on haloperidol-induced motor dysfunctions and underlying molecular mechanisms in male Swiss mice. The animals were distributed into 5 groups (n = 8), and treated orally with distilled water (control), haloperidol (1 mg/kg) alone or in combination with each dose of JB (10, 20 and 40 mg/kg), daily for 14 days. Thereafter, changes in motor functions were evaluated on day 14. Brain biomarkers of oxidative stress, proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), cAMP response-element binding protein (CREB), mitogen-activated protein kinase (MAPK) and histomorphological changes were also investigated. Haloperidol induces postural instability, catalepsy and impaired locomotor activity, which were ameliorated by JB. Jobelyn® attenuated haloperidol-induced elevated brain levels of MDA, nitrite, proinflammatory cytokines and also boosted neuronal antioxidant profiles (GSH and catalase) of mice. It also restored the deregulated brain activities of CREB and MAPK, and reduced the histomorphological distortions as well as loss of viable neuronal cells in the striatum and prefrontal cortex of haloperidol-treated mice. These findings suggest possible benefits of JB as adjunctive remedy in mitigating parkinsonian-like adverse effects of haloperidol through modulation of CREB/MAPK activities and oxidative/inflammatory pathways.

Repeated social defeat stress exacerbates lipopolysaccharide-induced behavioural deficits in mice: ameliorative role of Chrysophyllum albidum fruit extract through anti-neuroinflammation, antioxidant and neurochemical balance.

Development of neuropsychiatric disorder is associated with stress-related increase in pro-inflammatory cytokines. Chrysophyllum albidum fruit is an edible tropical fruit containing vitamins and phenolic compounds, well known for their anti-inflammatory and antioxidant activities. This study was designed to investigate the neuroprotective effect of C. albidum fruit extract (CAFE) on stress and lipopolysaccharide (LPS)-induced behavioral and neurochemical impairments in mice. Male Swiss mice were divided into 6 groups (n = 6). Groups 1-3 were orally treated daily for 14 days with normal saline (0.1 mL/10 g), CAFE (100 mg/kg) and Ferulic acid (FA, 10 mg/kg), and left in home cage as controls. Groups 4-6 were treated similarly but subjected to repeated social defeat (RSD) stress using the resident-intruder model from days 1-14. The RSD-animals were injected with LPS (125 µg/kg, i.p) 60 min after each RSD session from days 8-14. Neurobehavioral functions: locomotor, cognitive and anxiety-like behaviors were assessed 24 h after the last treatment. Pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α), dopamine, acetylcholinesterase, glutamic acid decarboxylase (GAD), malondialdehyde, nitrites, and reduced glutathione (GSH) were determined in brain tissue. CAFE significantly attenuated RSD and LPS-induced hypolocomotion, cognitive impairment and anxiety-like behavior when compared to the control. Treatment with CAFE also significantly reversed the negative effects of RSD and LPS on pro-inflammatory cytokines, dopamine, acetylcholinesterase, GAD, and oxidative-nitrosative stress levels. The findings clearly indicated that Chrysophyllum albidum fruit demonstrated neuroprotective effects and can play a key role in mitigating against chronic stress and inflammation linked to neuropsychiatric disorders.

Jobelyn® extends the life span and improves motor function in Drosophila melanogaster exposed to lipopolysaccharide via augmentation of antioxidant status.

Jobelyn® (JB), a dietary supplement, derived from polyphenol-rich leaf sheath of Sorghum bicolor, has been reported to attenuate sensorimotor deficits and oxidative stress evoked by complete Freund-adjuvant in mice. This present study evaluated its effects on the life span, motor function and changes in oxidative stress parameters as well as acetylcholinesterase activity in Drosophila melanogaster exposed to lipopolysaccharide (LPS). The flies (50 per vial), in 5 replicates were fed with LPS (250 µg/kg diet) alone or in combination with JB (0.25-1.0 mg/kg diet) daily for 7 days. The mortality rate and motor function were evaluated on day 7. The flies were afterwards processed for determination of oxidative stress parameters and acetylcholinesterase activity. The effects of JB (0.25-1.0 mg/g diet) on the longevity of Drosophila was also investigated wherein the flies were monitored daily for mortality throughout their lifespan. The flies exposed to LPS (250 µg/kg diet) had reduced life span and elevated oxidative stress when compared with control. However, JB (0.25 and 1.0 mg/kg diet) improved the motor function and also reduced the mortality rate of the flies exposed to LPS. It also restored the cellular antioxidant status and reduced acetylcholinesterase activity, accumulation of hydrogen peroxide as well as nitric oxide in Drosophila fed with LPS. JB also extended the longevity of the flies relative to control. The findings that JB improves motor function and extended the lifespan of Drosophila flies by boosting the antioxidant status and cholinergic function, suggest it might be helpful in delaying the onset of neuropsychiatric illnesses associated with the aging processes.

Molecular mechanisms involved in the prevention and reversal of ketamine-induced schizophrenia-like behavior by rutin: the role of glutamic acid decarboxylase isoform-67, cholinergic, Nox-2-oxidative stress pathways in mice.

Mounting evidences have shown that nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox-2) pathway modifies glutamic-acid decarboxylase-67 (GAD67) (GABAergic enzyme) and cholinergic systems via oxidative-nitrergic mechanisms in schizophrenia pathology. Rutin, a neuroactive antioxidant compound, with proven neuroprotective property has been shown to reduce schizophrenic-like behavior in mice. This study sought to investigate the mechanisms of action of the psychopharmacological activity of rutin in the preventive and reversal effects of ketamine-induced schizophrenic-like behavior, oxidative-nitrergic stress, cholinergic and GABAergic derangements in mice. In the preventive treatment, male mice were given rutin (0.1, 0.2 and 0.4 mg/kg) or risperidone (0.5 mg/kg) orally for 14 days prior to ketamine (20 mg/kg, i.p.) treatment from the 8 to 14th day. However, in the reversal treatment, ketamine was given for 14 days prior to rutin and risperidone. Behavioral (open-field, social-interaction and Y-maze tests), biochemical (oxidative/nitrergic stress markers, acetylcholinesterase activity), immunohistochemical (GAD67, Nox-2) and neuronal cell deaths in the striatum, prefrontal cortex, and hippocampus were evaluated. Ketamine-induced behavioral impairments were prevented and reversed by rutin. Exposure of mice to ketamine increased malondialdehyde, nitrite contents, acetylcholinesterase activity, neuronal cell death and Nox-2 expressions in the striatum, prefrontal cortex and hippocampus. Conversely, these derangements were prevented and reversed by rutin. The decreased glutathione levels due to ketamine were marked increased by rutin. Rutin only prevented ketamine-induced decrease in GAD67 expression in the striatal-hippocampal region. Altogether, the study showed that the prevention and reversal treatments of mice with rutin attenuated ketamine-induced schizophrenic-like behaviors via reduction of Nox-2 expression, oxidative/nitrergic stresses, acetylcholinesterase activity, and increased GAD67 enzyme.

The antioxidant and neuroprotective effects of the Psychotria camptopus Verd. Hook. (Rubiaceae) stem bark methanol extract contributes to its antiepileptogenic activity against pentylenetetrazol kindling in male Wistar rats.

A substantial number of epileptic patients are resistant to the current medication thus necessitating the search for alternative therapies for intractable forms of the disease. Previous studies demonstrated the acute anticonvulsant properties of the methanol extract of the stem bark of Psychotria camptopus (MEPC) in rats. This study investigated the effects of MEPC on pentylenetetrazole-kindled Wistar rats. Kindling was induced by intraperitoneal injection of pentylenetetrazole (37.5 mg/kg) on every alternate day, 1 h after each daily oral pretreatment of rats (8 ≤ n ≤ 10) with MEPC (40, 80 and 120 mg/kg), vehicle or diazepam (3 mg/kg) for 43 days. The kindling development was monitored based on seizure episodes and severity. Rats' brains were collected on day 43 for the determination of oxidative stress parameters. The histomorphological features and neuronal cell viability of the prefrontal cortex (PFC) and hippocampus were also assessed using H&E and Cresyl violet stains. Chronic administration of pentylenetetrazole time-dependently decreased the latency to myoclonic and generalized seizures, and increased seizure scores and the number of kindled rats. MEPC and diazepam significantly increased the latencies to myoclonic jerks and generalized tonic-clonic seizures. These substances also reduced seizure score and the number of rats with PTZ-kindling. MEPC improved glutathione status and decreased lipid peroxidation in the brains of kindled rats. MEPC also exhibited neuroprotection against pentylenetetrazole-induced hippocampal and PFC neuronal damages. These results suggest that P. camptopus has antiepileptogenic activity, which might be related to the augmentation of antioxidant and neuroprotective defense mechanisms, and further confirm its usefulness in the management of epilepsy.

D-Ribose-L-cysteine exhibits adaptogenic-like activity through inhibition of oxido-inflammatory responses and increased neuronal caspase-3 activity in mice exposed to unpredictable chronic mild stress.

Adaptogens are substances that act nonspecifically to combat stress by regulating the key elements involved in stress-induced pathologies. D-Ribose-L-cysteine (DRLC), a potent glutathione (GSH) booster, has been recommended for relief of stress. Hence, we investigated its adaptogenic-like effect in mice subjugated to unpredictable chronic mild stress (UCMS). Thirty six male Swiss mice were assigned to 6 groups (n = 6): group 1 received saline (p.o, non-stress control), group 2 (stress-control) also had saline, groups 3 to 5 received DRLC (25, 50 and 100 mg/kg, p.o) whereas group 6 had ginseng (50 mg/kg, p.o). The animals in groups 2-6 were subjugated to UCMS 30 min later, daily for 21 days and afterwards, tested for memory and anxiety. Blood glucose, serum corticosterone concentrations and adrenal weight were determined. The brain tissues were processed for estimation of malondialdehyde (MDA), GSH, superoxide-dismutase (SOD), catalase, tumor necrosis factor-alpha (TNF-α), interleukin-6, acetyl-cholinesterase, and caspase-3 activities. The histomorphologic features and neuronal viability of the hippocampus, amygdala and prefrontal cortex were also determined. DRLC (25-100 mg/kg) reduces anxiety, memory deficit, adrenal gland enlargement, glucose, and corticosterone concentrations in UCMS-mice. The increased brain contents of MDA, TNF-α, interleukin-6, acetyl-cholinesterase and decreased antioxidant (GSH, SOD and catalase) status induced by UCMS were attenuated by DRLC. The DRLC increased caspase-3 activity and reduces histomorphological distortions of neuronal cells of the hippocampus, amygdala and prefrontal cortex of stressed-mice. These findings suggest that DRLC has adaptogenic-like effect which might be related to modulation of corticosterone-mediated oxido-inflammatory processes and altered caspase-3 activity.

D-ribose-L-cysteine enhances memory task, attenuates oxidative stress and acetyl-cholinesterase activity in scopolamine amnesic mice.

d-Ribose-l-cysteine (DRLC) is an analogue of cysteine that has been shown to boost cellular antioxidant capacity by enhancing intracellular biosynthesis of glutathione (GSH). Deficiency of GSH has been implicated in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder associated with loss of memory. Thus, the use of antioxidants to prevent or retard the progression of memory deteriorations in persons with AD has been the focus of intense investigations. This study was carried out to evaluate the effects of DRLC on memory and scopolamine-induced amnesia, acetyl-cholinesterase activity, and oxidative stress in mice. Male Swiss mice were given oral administration of saline (10 ml/kg), DRLC (25, 50, and 100 mg/kg) or donepezil (1 mg/kg) 30 min before testing for memory performance using Y-maze and object recognition models. Another set of mice were also pretreated orally with saline, DRLC (25, 50, and 100 mg/kg) or donepezil (1 mg/kg) but in combination with scopolamine (3 mg/kg, i.p.) daily for 7 days. Thirty minutes after treatment on Day 7, memory function was then evaluated. The brain levels of acetyl-cholinesterase and oxidative stress parameters were assayed. DRLC significantly (p < .05) enhanced memory performance and attenuated scopolamine-induced amnesia. Increased acetyl-cholinesterase activity and oxidative stress, as shown by decreased antioxidant substrates (glutathione and catalase) and elevated malondialdehyde contents in mice with scopolamine amnesia were also attenuated by DRLC. Our findings suggest that inhibition of oxidative stress and acetyl-cholinesterase activity might contribute to the potential benefit of DRLC in persons with amnesia.

Methyl jasmonate ameliorates rotenone-induced motor deficits in rats through its neuroprotective activity and increased expression of tyrosine hydroxylase immunopositive cells.

Decreased tyrosine hydroxylase (TH) activity, due to degeneration of dopaminergic neurons contributes to the low dopamine content and the motor deficits that characterized Parkinson's disease (PD). This study examines the effect of methyl jasmonate (MJ), a neuroprotective bioactive compound isolated from jasminum grandiflorum, on motor functions, immunopositive cells of TH, dendritic neurons and dopamine contents in rotenone (Rot)-treated rats. Rats pretreated daily with MJ (100 mg/kg, i.p) for 21 days also received Rot (2.5 mg/kg, i.p.) 30 min after each pretreatment for every 48 h for 21 days. Motor functions were assessed on day 22. The specific brain regions of the rats were processed for determination of dopamine contents, immunopositive cells of TH, neuronal cell morphology and dendritic aborizations. Rot impaired locomotion and rearing behavior, and decreased dopamine content in the striatum, prefrontal cortex and midbrain. It further reduced the expression of TH in the substantia nigra and striatum relative to vehicle-control (p < 0.05). Histopathologic studies revealed that Rot-treated rats had degenerated neurons with pyknotic nuclei and loss of nigrostriatal neuronal cells. Rot also altered the nigrostriatal dendritic neuronal networks, decreased the dendritic length and spine density. However, pretreatment with MJ improved motor deficits, increased TH activity and dopamine contents in the specific brain regions of Rot-treated rats. MJ also attenuated the cyto-architectural distortions, loss of neuronal cells and dendritic aborizations of the striatum of Rot-treated rats. These findings suggest that MJ may reverse the motor deficits associated with PD by modifying the key pathological abnormalities involved in the disease progression.

Jobelyn® ameliorates neurological deficits in rats with ischemic stroke through inhibition of release of pro-inflammatory cytokines and NF-κB signaling pathway.

The effects of Jobelyn® (JB) on neurological deficits and biochemical alterations associated with ischemic stroke induced by bilateral common carotid artery occlusion (BCCAO) in rats were investigated in this study. Male Wistar rats were divided into five groups (n = 8): group 1 served as Sham control; group 2, which served as negative control received normal saline while groups 3-5 were given JB (25, 50 and 100 mg/kg, p.o) daily for 28 days. Then, rats in groups 2-5 were subjected to BCCAO for 30 min and reperfusion afterwards. Neurological deficits were assessed 3 h post-reperfusion using a 9-point neurological scoring scale. The levels of biomarkers of oxidative stress and pro-inflammatory cytokines (tumour necrotic factor-α and interleukin-6), expressions of immunopositive cells of nuclear factor-kappa B (NF-κB) and acetyl-cholinesterase (AChE) activity were determined in brain tissues. Histology of the striatum, prefrontal cortex (PFC) and hippocampus (CA1) was also evaluated. JB improved BCCAO-induced neurological deficits and attenuated increased oxidative stress and AChE activity in rats subjected to BCCAO (p < 0.05). Increased brain levels of tumour necrotic factor-α and interleukin-6 as well as expressions of immunopositive cells of NF-κB were decreased by JB. JB reduced brain damage and also increased population of viable neurons in the striatum, PFC and hippocampus of ischemic stroke rats. These findings suggest that the positive effect of JB on neurological function in rats with ischemic stroke may be related to inhibition of oxidative stress, release of pro-inflammatory cytokines and expressions of immunopositive cells of NF-κB.

Involvement of l-arginine-nitric oxide pathway in the antidepressant and memory promoting effects of morin in mice.

l-Arginine-nitric oxide pathway has been reported to be involved in the mediation of the psychopharmacological effects of many psychotropic drugs. Previous studies have shown that morin, a psychotropic compound isolated from mulberry leaf produces functional psychopharmacological effects indicative of antidepressant, antipsychotic, anxiolytic and nootropic properties. However, the role of l-arginine-nitric oxide pathway in the psychotropic effects of morin has not been fully investigated, hence, the need for this study. Male Swiss mice were pretreated individually or in combination with nitric oxide precursor [l-arginine (750 mg/kg, i.p.)], competitive nonselective nitric oxide synthase (NOS) inhibitor [N(G)-nitro-l-arginine methyl ester (l-NAME, i.p) (50 mg/kg)] or selective neuronal NOS inhibitor [methylene blue (3.75 mg/kg, i.p)] prior to morin (100 mg/kg, i.p.) or saline (10 mL/kg, i.p.) treatment. Psychopharmacological activities were then evaluated 30 min later using open field, Y-maze, and forced swim tests. l-Arginine significantly reversed the effects of morin on locomotion, memory and depression in mice. The reduced motor activity and enhanced memory function produced by morin were significantly attenuated by methylene blue but augmented the antimobility activity of morin in the FST. Moreover, l-NAME potentiated the psychopharmacological effects of morin in the open field and forced swim tests but reduced its memory promoting effect. Meanwhile, morin supplementation reversed the effects of l-arginine on l-NAME-treated mice in all behavioral models. The results of this study suggest that l-arginine-nitric oxide pathway might play a role in the modulation of the antidepressant and memory promoting effects of morin in mice.

Morin Attenuates Neurochemical Changes and Increased Oxidative/Nitrergic Stress in Brains of Mice Exposed to Ketamine: Prevention and Reversal of Schizophrenia-Like Symptoms.

Previous studies have revealed that morin (MOR), a neuroactive bioflavonoid, with proven psychotropic and neuroprotective properties reduced schizophrenic-like behaviors in mice. This study further evaluated the ability of MOR to prevent and reverse ketamine-induced schizophrenic-like behaviors and the underlying neurochemical changes and increased oxidative/nitrergic stress in mice. In the preventive protocol, mice received intraperitoneal injection of MOR (100 mg/kg), reference antipsychotic drugs [haloperidol (1 mg/kg), risperidone (0.5 mg/kg)], or saline daily for 14 consecutive days prior to i.p. injection of ketamine (KET) (20 mg/kg/day) from the 8th to the 14th day. In the reversal protocol, the animals received KET or saline for 14 days prior to MOR, haloperidol, risperidone, or saline treatments. Schizophrenic-like behaviors: positive (open-field test), negative (social-interaction test) and cognitive (Y-maze test) symptoms were evaluated. Thereafter, the brain levels of dopamine, glutamate, 5-hydroxytryptamine and acetyl-cholinesterase, as well as biomarkers of oxidative/nitrergic stress were measured in the striatum, prefrontal-cortex (PFC) and hippocampus (HC). Morin prevented and reversed KET-induced hyperlocomotion, social and cognitive deficits. Also, MOR or risperidone attenuated altered dopaminergic, glutamatergic, 5-hydroxytryptaminergic and cholinergic neurotransmissions in brain region-dependent manner. The increased malondialdehyde and nitrite levels accompanied by decreased glutathione concentrations in the striatum, PFC and HC in KET-treated mice were significantly attenuated by MOR or risperidone. Taken together, these findings suggest that the anti-schizophrenic-like activity of MOR may be mediated via mechanisms related to attenuation of neurochemical changes and oxidative/nitrergic alterations in mice.

Toxicity and Protective Effect of Phenolic-Enriched Ethylacetate Fraction of Ocimum gratissimum (Linn.) Leaf against Acute Inflammation and Oxidative Stress in Rats.

Preclinical Research Ocimum gratissimum L. leaves have attracted considerable attention from researchers because of their medicinal value that include anti-inflammatory, analgesic, antimicrobial, and antioxidant activities. In the present study, the toxicity and the protective effect of phenolic extract of O. gratissimum leaf (EAFOg) against acute inflammation and oxidative stress in rats was assessed. EAFOg, enriched in phenols had no cytotoxic effect against CHO-k1 cells, and no lethality against brine shrimp eggs or mice at a dose of 2000 mg/kg. EAFOg (50 and 100 mg/kg) reduced paw edema by 47% and 61%, compared to 29% with the COX-2 inhibitor, SC58125 (1 mg/kg) and 81% with indomethacin (5 mg/kg), respectively. In the rat carrageenan-induced air pouch model, EAFOg reduced exudate volume, leucocyte count, nitrite, TNF-α, and myeloperoxidase activity. EAFOg also protected against carrageenan-induced lipid peroxidation and glutathione depletion. These results provide evidence of the protective effects of EAFOg against acute inflammation and oxidative stress in rats. Drug Dev Res 78 : 135-145, 2017. © 2017 Wiley Periodicals, Inc.

Methyl Jasmonate Ameliorates Unpredictable Chronic Mild Stress-Induced Behavioral and Biochemical Alterations in Mouse Brain.

Preclinical Research The effects of methyl jasmonate (MJ; 5, 10, 20 mg/kg, i.p), a natural product widely used for the relief of stress, depression, and exhaustion on unpredictable chronic mild stress (UCMS)-induced depression-like behaviors in mice was assessed and compared to those of imipramine (IMP; 10 mg/kg, i.p). MJ and IMP were given 30 min before exposure to UCMS with the procedure repeated daily for 2 weeks; 24 h after the stress session, the tail suspension test (TST) and sucrose preference test were assessed. MJ decreased immobility time in the TST and reversed impaired intake of sucrose relative to the stressed control suggesting antidepressant-like activity. MJ also reduced UCMS-induced increases in corticosterone and MDA (malondialdehyde) levels and attenuated UCMS-induced decreases in GSH and TNF-α levels and SOD activity. These findings suggest that MJ attenuated UCMS-induced depressive-like behaviors through decreased levels of corticosterone and decreasing oxidative stress and neuroinflammation in mouse brain.Drug Dev Res 78 : 381-389, 2017. © 2017 Wiley Periodicals, Inc.

Possible Mechanisms Involved in Attenuation of Lipopolysaccharide-Induced Memory Deficits by Methyl Jasmonate in Mice.

This present study was carried out to investigate the likely mechanisms by which methyl jasmonate (MJ), 'an agent widely used in aromatherapy for neurological disorders, attenuates lipopolysaccharide (LPS)-induced memory deficits in mice. Mice were given intraperitoneal administration of LPS (250 µg/kg) alone or in combination with MJ (10-40 mg/kg), donepezil, DP (1 mg/kg), or vehicle for 7 successive days. Thereafter, memory was assessed using object recognition test (ORT). Acetylcholinesterase and myeloperoxidase activities were estimated in brain tissue homogenates. Brain levels of nitric oxide and markers of oxidative stress as well as histopathologic changes of the prefrontal cortex and cornu ammonis 1 (CA1) of the hippocampal region were also assessed. MJ (10-40 mg/kg) attenuated LPS-induced memory impairment in ORT. Moreover, the increased brain activities of acetylcholinesterase and myeloperoxidase enzymes were suppressed by MJ when compared with control (p < 0.05). Increased brain oxidative stress and nitric oxide levels in LPS-treated mice were significantly decreased by MJ. It offers protection against LPS-induced neuronal degeneration of the prefrontal cortex and CA1 of the hippocampus, suggesting neuroprotective effect. Taken together, these findings showed that MJ offers protection against LPS-induced memory deficits via mechanisms related to inhibition of acetylcholinesterase, myeloperoxidase, oxidative stress and neuronal degeneration.

Comparative and stability study of glucose concentrations measured in both sodium fluoride and serum separator tubes.

Introduction: Sodium fluoride/potassium oxalate (NaF/KOx) tubes has been regarded as the gold-standard tubes for glucose analysis. Even though their ineffectiveness in immediately inhibiting glycolysis has been reported in several studies especially in the first 1-4h, they are still used in our clinical biochemistry laboratory for glucose measurement. However, in its absence, only serum separator tubes are employed for glucose measurement. We aim to determine whether serum separator tubes (SSTs) can replace NaF/KOx tubes for laboratory measurement of blood glucose and to assess the stability of glucose concentrations for 3 days period. Methods and findings: NaF/KOx tube type was the reference method while SSTs type was the candidate method for glucose measurement. A total of 50 paired samples collected separately in NaF/KOx tubes and SSTs from healthy adult participants in the Gambia Adults Reference Intervals Study (GARIS) project were used as the project sample size. Following blood collection and separation, the glucose concentration was measured within 2 h, and at 24h, 42h and 72h time-points. Our data analysis showed no significant difference in the mean glucose concentrations between the reference tube and candidate tube types (Mean difference = 0.06 mmol/L; P = 0.38) recorded in the different timepoints. Using growth trajectory and mixed effects model, the study data further showed no significant change in the glucose concentrations (p = 0.25) for three days period. Conclusions: The study confirms that SSTs can produce similar glucose results when employed in the absence of NaF/KOx tubes. Besides, the glucose concentrations were stable in both tubes for three days when the samples were separated within 2 h and refrigerated in 2-8°C.

Involvement of oxidative stress and pro-inflammatory cytokines in copper sulfate-induced depression-like disorders and abnormal neuronal morphology in mice.

Epidemiological studies have implicated copper as one of the key environmental risk factors for the pathogenesis of depression. However, the precise mechanism by which copper contribute to the genesis of depression particularly the involvement of oxidative stress-driven neuroinflammation is yet to be fully investigated. Thus, this study was designed to evaluate the effects of copper sulfate (CuSO4) on depression-like behaviors and the role of oxidative stress and pro-inflammatory cytokines in mice. Forty male Swiss mice were distributed into control and three test groups (n = 10), and were treated orally with distilled water (10 mL/kg) or CuSO4 (25, 50 and 100 mg/kg) daily for 28 days. Afterwards, the tail suspension, forced swim, and sucrose splash tests were used for the detection of depression-like effects. The animals were then euthanized and the brains were processed for the estimation of biomarkers of oxidative stress and pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6). The histomorphological features and neuronal viability of the prefrontal cortex, hippocampus and striatum were also determined. Mice exposed to CuSO4 displayed depression-like features when compared with controls. The brain concentrations of malondialdehyde, nitrite and pro-inflammatory cytokines were elevated in CuSO4-treated mice. Mice exposed to CuSO4 also had reduced brain antioxidant status (glutathione, glutathione-s-transferase, total thiols, superoxide-dismutase and catalase), as well as altered histomorphological features, and decreased population of viable neuronal cells. These findings suggest that CuSO4 increases oxidative stress and pro-inflammatory cytokines to elicit depression-like effects in mice.

Chemical characterization, anti-nociceptive and anti-inflammatory activities of Plukenetia conophora seed oil in experimental rodent models.

ETHNOPHARMACOLOGICAL RELEVANCE: The seed of the African walnut, Plukenetia conophora Mull.-Arg is well-known for its nutritional and medicinal values. The seed oil is widely used in massages to relieve pain, as nerve tonic and to enhance sexual performance. OBJECTIVE: The study aimed at investigating the chemical profile, antinociceptive and anti-inflammatory activities of P. conophora oil (PCO). METHODS: Seed oil of P. conophora was characterized using Gas-Liquid Chromatographic method (GC-MS) and oral acute toxicity evaluated at 2000 mg/kg. Antinociceptive effects were evaluated in hot plate, acetic acid and formalin-induced paw licking tests. The anti-inflammatory effects were investigated in egg albumin and carrageenan-, formalin and complete Freund adjuvant (CFA)-induced paw oedema models. The levels of pro-inflammatory cytokines in the fluid exudates were also evaluated in carrageenan air pouch model. RESULTS: PCO exhibited high content of alpha linolenic acid (ALA). No toxicity was observed at 2000 mg/kg of PCO. PCO (50-200 mg/kg) demonstrated significant anti-nociceptive activity in pain models. PCO exhibited anti-inflammatory activity against oedema formation by phlogistic agents. The increased inflammatory oedema and oxidative stress in CFA-treated rats were also attenuated by PCO. The PCO (100 and 200 mg/kg) significantly reduced the levels of TNF-α (59.3% and 85.2%) and IL-6 (27.5% and 72.5%) in carrageenan-induced air pouch model. CONCLUSION: The results of this study suggest that ALA-rich seed oil of Plukenetia conophora demonstrated anti-nociceptive and anti-inflammatory activities via inhibition of pro-inflammatory cytokines and oxidative stress, lending supportive evidences for its use in painful inflammatory conditions.