Effect of phosphoramidon - a selective enkephalinase inhibitor - on nociception and behaviour

Phosphoramidon (100-350 micrograms i.c.v.), a selective enkephalinase inhibitor, induced in the rat a decrease of nociception to pressure stimulation without evident respiratory depression. In addition, intensive behavioural changes such as grooming (licking the fur, face washing and scratching), mounting behaviour and wet dog shakes were observed. Naltrexone pretreatment (1 mg/kg i.p.) caused a significant decrease in the phosphoramidon-induced nociception and behavioural changes. Puromycin (30 micrograms i.c.v. or 7.5 mg/kg i.p.) caused no changes in nociception or behaviour.     

Sedative and Anxiolytic Effects of the Extracts of the Leaves of Stachytarpheta Cayennensis in Mice

The leaves are used ethnomedicinally in Nigeria and other parts of the world for insomnia and anxiety among other uses. The investigations sought scientific evidence for the ethnomedicinal use of the leaves for the management of insomnia and anxiety as well as the neural mechanisms for the activities. The sedative and anxiolytic effects of the extracts of the leaves of Stachytarpheta cayennensis were examined in this study. The methanolic extract (5–50 mg/kg, i.p.) as well as the ethylacetate (10–50 mg/kg, i.p.), butanol and aqueous fractions (5–50 mg/kg, i.p.) of the extract were examined. Sedation was assessed as reduced novelty-induced rearing (NIR), reduced spontaneous locomotor activity (SLA) and increased pentobarbitone-induced sleeping time (PIST) in mice. The anti-anxiety effect (methanol 2.5–5.0; butanol 5.0; aqueous 20.0; ethylacetate 25.0 mg/kg, i.p.) was assessed using an elevated plus maze. LD₅₀ was calculated for the extract and the fractions after the intraperitoneal route of administration using the Locke method. The methanolic extract, the butanol and the aqueous fractions inhibited rearing and spontaneous locomotion but prolonged pentobarbitone induced sleep. The ethylacetate fraction however increased both rearing and locomotion and decreased pentobarbitone sleeping time. The butanol and aqueous fractions, but not the methanol extract showed indices of open arm avoidance consistent with anti-anxiety effect. Naltrexone (2.5 mg/kg, i.p.) reversed the inhibition of rearing, locomotion and prolongation of pentobarbitone sleep due to the aqueous fraction of the extract. Flumazenil (2mg/kg, i.p.) abolished the effects of both methanolic extract and the butanol fraction on rearing, locomotion, pentobarbitone sleep and anxiety model. The methanolic extract, the butanol and aqueous fractions possess sedative activity while the ethylacetate fraction possesses stimulant property. The anxiolytic effect was found in both the aqueous fraction and the butanol fraction but not in the main methanol extract and also not in the ethylacetate fraction. Flumazenil, blocked the effect of the leaves of Stachytarpheta cayennensis on rearing, locomotion and elevated plus maze suggesting that GABA receptors are involved in the observed sedative and anxiolytic activities. This study also found opioid receptors involved in the sedative activity of the leaves of Stachytarpheta cayennensis. The rationale for the ethnomedicinal use of the leaves for the management of insomnia and anxiety were confirmed scientifically in this study.     

Prevalence of pterygium and pingueculum among motorcyclists in Nigeria

OBJECTIVES: To find out the prevalence of pingueculum and pterygium among commercial motorcyclists in Benin City, Nigeria and to note any associated or risk factors. DESIGN: A prospective, cross sectional, case control study. SETTING: A local Government Area (Oredo) and University of Benin Teaching Hospital, Benin City, Nigeria. SUBJECTS: One hundred and forty four commercial male motorcyclists in motorcycle parks in the local Government area and a control group of 114 male indoor workers. Main outcome measures: Presence of pterygium or pingueculum. RESULTS: One hundred and forty four male motorcyclists formed the subjects of this study. The age range was 18 to 65 years with a mean age of 34.9 +/- 8.0 years. The total number of motorcyclists with pingueculum was 37 with 26 bilateral cases, 63 eyes were involved. The prevalence rate was 25.7%. Pterygium was present in 18 patients including 12 bilateral cases making a total of 30 eyes. The prevalence rate was 12.5% The total number of indoor workers with pingueculum was 24 and it was present in 46 eyes. The prevalence rate was 21.05%. Pterygium was present in 12 eyes of nine persons in the control group and the prevalence rate was 7.9%. There was no association between the duration of work as a commercial motor cyclist and the presence of a pterygium or a pingueculum. The usage of a hat/cap was found to have a protective effect as motorcyclists who do not wear hats are more likely to develop pingueculum than those who wear them. The use of glasses and hats together was found to be protective against the development of pingueculum and pterygium in this study. CONCLUSION: The prevalence rate of 12.5% of pterygium and 25.7% of pingueculum in commercial motorcyclists in this study is quite high when compared with that of the controls. The wearing of face caps/hats was found to have a protective effect. They should be educated about the importance of wearing protective goggles and caps/brimmed hats.     

REM sleep deprivation (REMSD) antagonizes naloxone-precipitated withdrawal in acute morphine-dependent rats

In rats allowed undisturbed sleep (control and stress) the administration of naloxone (10 mg/kg, s.c.) to morphine (7.5 mg/kg, s.c. 90 min prior) pretreated animals precipitated a jumping behaviour. REM sleep deprivation (REMSD 96 h, prior) significantly decreased the frequency of the naloxone-precipitated jumping behaviour compared with control and stressed animals. In second animal model for morphine withdrawal, naloxone (10 mg/kg, s.c.) provoked myoclonic twitch activity (MTA) in rats previously exposed to morphine (7.5 mg/kg, s.c., 90 min prior). The intensity of naloxone-induced MTA in REM sleep deprived rats was significantly lower compared to stressed animals, but it is not different from the control group. It is suggested that REMSD interferes with a neural mechanism involved in the development of acute dependence. Results are discussed in light of a possible functional insufficiency of a mu-opioid system during REMSD.     

An analgesic effect of enkephalinase inhibition is modulated by monoamine oxidase-B and REM sleep deprivations

Summary Both the MAO-B inhibitor deprenyl (2.5–10 mg/kg, ip, 60 min prior) and the MAO-B substrate -phenylethylamine (PEA, 40 g, icv) potentiated the analgesic action of the enkephalinase inhibitor phosphoramidon (250 g, icv) in animals allowed normal sleep. The enhancing effect of PEA on phosphoramidon analgesia was further potentiated by deprenyl (5 mg/kg, ip) pretreatment. Deprenyl (5 mg/kg, ip) or PEA (40 g, iv) given alone did not induce analgesia in animals allowed undisturbed sleep.REM sleep deprivation (REMSD) decreased the basal pain threshold and abolished the analgesic effect of phosphoramidon. The administration of deprenyl and/or PEA failed to restore the analgesic effect of phosphoramidon in REM sleep deprived animals.The results indicate that excess PEA has a stimulatory effect on the analgesic activity of endogenously released enkephalins in rats allowed undisturbed sleep but not in REM sleep deprived animals.It is suggested that the failure of phosphoramidon to induce analgesia after REMSD, is probably due to a functional insufficiency of an enkephalinergic system.     

Effect of Fractionated Extracts and Isolated Pure Compounds of Spondias Mombin (L. Anacardiaceae) Leaves on Novelty-Induced Rearing and Grooming Behaviours in Mice

This study attempted to elucidate the neurotransmitter systems involved in the neurophysiological properties of ethanolic extract, fractions and pure isolates of Spondias mombin leaves in mice (n = 6) after intraperitoneal (i.p.) route of administration.The crude ethanolic extract of Spondian mombin leaves was fractionated using the partitioning method to obtain the ethylacetate, butanolic and aqueous fractions. Open column chromatographic fractionation of the ethylacetate fraction yielded seven sub-fractions, out of which the pure coumaroyl, quercetin and gallic acid derivatives were obtained after purification on Sephadex LH 20. The ethanolic extract, butanolic fraction, ethylacetate subfractions and pure isolates of the Spondian mombin leaves were tested on novelty-induced rearing and grooming behaviours in mice with standard pharmacological tools using the open field method. The extract and its fractions decreased novelty-induced rearing in a dose-dependent manner. While the Coumaroyl derivative had no effect on novelty-induced rearing, it significantly reversed the inhibitory effect of yohimbine, propranolol and haloperidol on novelty-induced rearing. Quercetin significantly potentiated the inhibitory effect of yohimbine on novelty-induced rearing. Naloxone significantly potentiated the quercetin-induced suppression of novelty-induced rearing. Gallic acid derivative significantly potentiated the inhibitory effect of yohimbine on novelty-induced rearing. Naloxone, atropine and haloperidol pretreatments significantly potentiated gallic acid derivative-induced suppression of novelty-induced rearing.The extract and its fractions had biphasic effect on novelty-induced grooming in mice. Coumaroyl derivative significantly increased novelty-induced grooming, while quercetin and gallic acid derivative decreased novelty-induced grooming significantly. The three pure isolates significantly reversed the effects of yohimbine and atropine on the novelty-induced grooming in mice. Propranolol-induced increase in novelty-induced grooming was significantly reversed by coumaroyl and gallic acid derivatives. Pre-treatment with naloxone significantly increased the gallic acid derivative-induced suppression of novelty-induced grooming. Pre-treatment with haloperidol reversed the effect of coumaroyl derivative and potentiated the inhibitory effect of quercetin derivative and gallic acid derivative significantly. This study suggested that adrenergic and dopaminergic neuro-transmissions are strongly involved in the neural mechanisms of the effect of the three pure isolates derivative, while opioid neuro-transmission is strongly linked with the neural mechanism of behavioural effect of coumaroyl derivative.     

The challenges of diagnosis and treatment of malaria in pregnancy in low resource settings

Malarial infestation in pregnancy is a major public health concern in endemic countries and ranks high amongst the commonest complications of pregnancy, especially in large areas of Africa and Asia. It is an important preventable cause of significant maternal morbidity and mortality with associated fetal as well as perinatal wastage. The burden of malaria is greatest in sub-Saharan Africa where it contributes directly or indirectly to maternal and perinatal morbidity and mortality. The need for prompt and accurate diagnosis as well as prevention and treatment of malaria during pregnancy cannot, therefore, be overemphasized. This commentary focuses on the challenges of diagnosis and treatment of malaria in pregnancy.