Douglas McBean

Persistent cerebrovascular effects of MDMA and acute responses to the drug

Acutely, 3,4,‐methylenedioxymethamphetamine (MDMA) induces cerebrovascular dysfunction [ Quate et al., (2004)Psychopharmacol., 173, 287–295]. In the longer term the same single dose results in depletion of 5‐hydroxytrptamine (5‐HT) nerve terminals. In this study we examined the cerebrovascular consequences of this persistent neurodegeneration, and the acute effects of subsequent MDMA exposure, upon the relationship that normally exists between local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu). Dark agouti (DA) rats were pre‐treated with 15 mg/kg i.p. MDMA or saline. Three weeks later, rats from each pre‐treatment group were treated with an acute dose of MDMA (15 mg/kg i.p.) or saline. Quantitative autoradiographic imaging was used to measure LCBF or LCMRglu with [14C]‐iodoantipyrine and [14C]‐2‐deoxyglucose, respectively. Serotonergic terminal depletion was assessed using radioligand binding with [3H]‐paroxetine and immunohistochemistry. Three weeks after MDMA pre‐treatment there were significant reductions in densities of 5‐HT transporter (SERT)‐positive fibres (−46%) and [3H]‐paroxetine binding (−47%). In animals pre‐treated with MDMA there were widespread significant decreases in LCMRglu, but no change in LCBF indicating a persistent loss of cerebrovascular constrictor tone. In both pre‐treatment groups, acute MDMA produced significant increases in LCMRglu, while LCBF was significantly decreased. In 50% of MDMA‐pre‐treated rats, random areas of focal hyperaemia indicated a loss of autoregulatory capacity in response to MDMA‐induced hypertension. These results suggest that cerebrovascular regulatory dysfunction resulting from acute exposure to MDMA is not diminished by previous exposure, despite a significant depletion in 5‐HT terminals. However, there may be a sub‐population, or individual circumstances, in which this dysfunction develops into a condition that might predispose to stroke.

The Inhibition of Free Radical Generation by Preparations of Harpagophytum procumbens in vitro

Harpagophytum procumbens (Hp), commonly known as Devils Claw has been used as a traditional treatment for a variety of illnesses for centuries. Since the early twentieth century, it has become a popular antiinflammatory and analgesic preparation amongst European herbalists for supportive or adjuvant treatment of degenerative joint diseases. Extracts of Hp tubers have demonstrated antiinflammatory and analgesic effects in animal models of inflammation and in human trials. The mechanism(s) of action responsible for these attributes, however, remain to be elucidated. Reactive oxygen species generated in acute and chronic inflammatory diseases are known to be cytotoxic and can cause tissue damage. In this study, a root tuber extract (Hp extract) and commercially available tincture (Hp tincture) were investigated for antioxidant characteristics using in vitro test systems. Both preparations were found to effectively scavenge DPPH radical, inhibit nitrite levels in supernatants harvested from LPS‐stimulated RAW 264.7 macrophages, and cause dose‐dependent suppressions in the detection of fMLP‐ and AA‐induced neutrophil MPO. The antioxidant effects demonstrated for both preparations of Hp may contribute to the antiinflammatory and analgesic properties observed for the plant. Copyright

Cerebrovascular permeability in intracerebral implants of foetal basal forebrain cell suspensions.

Blood-brain barrier permeability was measured using [14C]-labelled a-aminoisobutyric acid (AIB) quantitative auto-radiography in rats which had previously received unilateral ibotenate-induced lesions of the nucleus basalis followed by intracortical implantation of foetal basal forebrain cell suspensions. The permeability characteristics of intracortical transplants were found to be dependent upon the site of implantation. Superficial transplants were invariably associated with AIB transfer constants (Ki) 3- to 4-fold higher than those in corresponding contralateral host cortex. In transplants sited deep in host neocortex, Ki values were not significantly different from those measured in surrounding host brain tissue.

An investigation into the effects of smoking on physical fitness parameters in adolescents

Smoking is associated both prognostically and aetiologically with numerous diseases of the respiratory system. Tobacco smoking is a major cause of an accelerated decline in ventilatory function and physical fitness. As most of the people take to smoking when they are young, it will be informative to study the effects of smoking on lungs in the initial stages. The aims of this study were to investigate the effects of smoking on forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and maximal oxygen consumption (VO2max) in adolescent smokers. Methods An experimental study subject design was carried out on 15 smoking and 15 non-smoking volunteers within the age group of 18–30 years who were recruited from the college campus. The non-smokers formed the control group. All the subjects underwent spirometric analysis and maximal treadmill test (Bruce protocol) for the estimation of VO2max. Appropriate statistical tests were performed to study the effects 30 min after smoking a cigarette. Results There was a statistically significant difference in the mean spirometric values of FVC/FEV1 of the smokers and the non-smokers; however, there was no statistically significant difference in the mean VO2max value in smokers and non-smokers. There was a statistically significant difference in the mean FVC/FEV1 of the smokers before and 30 min after smoking a cigarette. Again there was no statistically significant difference in the mean VO2max values before and after smoking a cigarette in the smokers. Conclusion Cigarette smoking does have a significant effect on the spirometric values of FVC/FEV1; however, its effect on the maximal oxygen consumption (VO2max) could not be ascertained accurately in adolescent smokers.