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.     

Functional reactivity of different central opioid receptor systems following clomipramine treatments

Intracerebroventricular administration of the enkephalinase inhibitor, phosphoramidon (PHA, 3.7 X 10(-7) moles, i.c.v.) induced distinct wet-dog-shakes (WDS) behaviour. Naltrexone (NX) given in a low dose (0.25 mg/kg, i.p.) did not antagonize the WDS induced by PHA. A higher dose of NX (2.5 mg/kg i.p.) decreased WDS behaviour. Morphine (25 mg/kg, i.p.) induced marked catalepsy. Ketocyclazocine (0.01-1.0 mg/kg, i.p.) induced a dose related decrease in spontaneous locomotor activity. Chronic (20 mg/kg, i.p. daily for 10 days and withdrawn, 24 h prior, C.CLO) and acute (20 mg/kg, i.p., 60 min prior, A.CLO) clomipramine treatments decreased PHA-induced WDS compared to saline pretreatments. However, C.CLO treatments antagonized the morphine-induced catalepsy and ketocyclazocine-induced sedation whereas A.CLO did not alter the opiate-induced cataleptic/sedative behaviours. It is suggested that chronic clomipramine treatment induced a functional deficiency of central mu and kappa opioid receptor systems without altering the delta opioid mechanisms.     

Correlation between the distribution of 3H-labelled enkephalin in rat brain and the anatomical regions involved in enkephalin-induced seizures

The correlation between the distribution of the intraventricularly (i.v.t.) administered δ agonist [³H](D-ala²,D-leu⁵)-enkephalin ([³H]DADL) and the anatomical regions involved in enkephalin-induced seizures has been studied in rat by using an autoradiographic method and recording of the electromyogram (EMG) and the electroencephalogram (EEG). The results indicate that within 10 min, the radioactivity of the intraventricularly administered drug reached all parts of the ventricular system, including the central canal of the spinal cord. However, within 2.5 min after the intraventricular administration of [³H]DADL, which corresponds to the onset of DADL-induced seizures, the substance appeared mainly in the left lateral ventricle and occasionally in the third ventricle. During the first 2.5 min the substance penetrated regularly into the surrounding periventricular tissue of the striatum, septum and hippocampus to a depth of about 100 μm. The most intensive and long-lasting epileptic discharges, exceeding 30 min were observed in the hippocampus, in contrast to the mild and short-lasting electrophysiological responses of the septum and corpus striatum. The experiments suggest that the short onset of enkephalin-induced excitatory phenomena is due to the rapid distribution and penetration of the substance in the surrounding periventricular tissue. According to these data, it is proposed that activation of δ opiate receptors, localized within the first 100 μm of the periventricular tissue, mainly in the hippocampus, is essential for the triggering of endorphin-induced seizure activity.     

Enkephalinase Inhibition Prevented Tolerance to Nitrous Oxide Analgesia in Rats

Tolerance to nitrous oxide (N₂O) antinociception was studied in rats in accordance with the Randall-Selitto pressure nociception test. Both N₂O (70% in 30% O₂) and the relatively selective enkephalinase inhibitor phosphoramidon (350 μg i.c.v.), which blocks the biotransformation of enkephalins, were administered. They both induced a significant analgesic effect which vanished within 45 min. The rapidly developed tolerance to N₂O analgesia does not affect the anaesthetic state since the animals remained motionless for the duration of exposure lasting 3 h. In the animals treated with the enkephalinase inhibitor phosphoramidon, no development of tolerance to N₂O-antinociception occurred during the exposure lasting 3 h. The results indicate that tolerance to N₂O analgesia can be abolished by activation of the enkephalinergic system, which might suggest a possible insufficiency of this system during tolerance to N₂O.     

Preoperative preparation of patients with renal diseases

If patients with renal diseases had to undergo surgical intervention, they should be prepared in such a way to be in a stable phase of the underlying surgical disease, without any infection, euvolemic, with satisfactory blood pressure and corrected electrolyte balance. These patients need to be hydrated well before intervention, the fall of blood pressure during intervention should be avoided and adequate hydration after the intervention must be continued (taking into account the condition of the kidneys, heart and age of patient). It is assumed that nephrotoxic drugs are to be evaded in renal patients or, if they were necessary, the dosage and dosing interval should be adjusted and prolonged, respectively. The use of radiographic contrast is not advisable, but if required, plentiful hydration will be needed, the least workable contrast dose and, if possible, with lower ionic charge and lower osmolarity will be administered. If surgical intervention was urgent and if there was not enough time for conservative therapy, i.e., correction of electrolytes, volemia, blood pressure and higher values of nitrate substances, a renal patient would be temporarily dialyzed in the immediate preoperative and postoperative course. Any surgical intervention in these patients may aggravate the renal function and bring the patient closer to dialysis treatment. Nevertheless, sometimes the benefit of surgical treatment for the acute surgical disease is higher (especially if it was life-threatening) than the risk of renal function exacerbation and coming closer to dialysis.     

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.     

REM sleep deprivation antagonizes morphine-induced akinesia and catalepsy

An examination was made of the effect of REM sleep deprivation (REMSD) on some forms of altered motor activity, such as akinesia and catalepsy, induced by intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of morphine in adult, male Wistar rats. Administration of morphine (25 mg/kg i.p.) induced an akinetic-cataleptic syndrome and decreased spontaneous vertical motor activity (SVMA) in animals allowed undisturbed sleep. REMSD decreased the morphine-induced akinesia and catalepsy that are known to be mediated by an inhibitory mu-opiate system. The locomotor depressant action of morphine was converted to excitation (manifested as increased SVMA and hopping behavior) by REMSD. Similarly, decreased motor activity following i.c.v. administration of morphine (25 micrograms) was replaced by excitation in the form of jumping behavior after REMSD. Naltrexone (1 mg/kg i.p.) blocked the akinetic and cataleptic effects, but not the excitatory effects, of morphine. It is suggested that REMSD is associated with a functional insufficiency of an inhibitory mu-opiate system, thus unmasking the excitatory morphine effects. The proposed insufficiency of an endogenous opioid system might explain an increase in neuronal excitation during REMSD and the therapeutic effect of REM deficiency in some types of depression.     

Enkephalinase inhibition antagonizes the increased susceptibility to seizure induced by REM sleep deprivation

In order to elucidate the relationship between REM sleep and the enkephalinergic system, the effects of REM sleep deprivation (REMSD), stress and the enkephalinase inhibitor phosphoramidon on handling-induced convulsions were studied in mice. REMSD, stress and phosphoramidon (25–500 g icv) increased the frequency of handling-induced convulsions (HIC) in normal mice. However, only in the last two groups were HIC antagonized by naloxone (1 mg/kg IP). In REMSD mice, phosphoramidon decreased the frequency of HIC, this effect being abolished by naloxone. The increase of neuronal excitability during REMSD is suggested to be associated with an insufficiency of the enkephalinergic system.