Differentiation of Tarchonanthus camphoratus L. and Tarchonanthus parvicapitulatus P.P.J. Herman (Asteraceae) using electron microscopy, and comparison of their biological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Tarchonanthus camphoratus L. complex has numerous medicinal uses amongst the sub-Saharan African populace, including treatment for bronchospasm. This study focused on providing scientific rationale for the traditional use of the extracts of T. camphoratus and T. parvicapitulatus. T. camphoratus L. complex has been published under diverse names by various taxonomists. Tarchonanthus parvicapitulatus was one of the newly described taxa, leaving Tarchonanthus camphoratus L. sens. strict. as a homogenous taxon. However, some of the morphological characters used tend to overlap, making it difficult to identify the different taxa. AIMS: The aim of this study was to evaluate the bronchodilatory, antioxidant and toxicological properties of the leaves of T. camphoratus L. and T. parvicapitulatus. This study also aimed to use scanning electron microscopy (SEM) to assess the differences between T. camphoratus L. and T. parvicapitulatus. MATERIALS AND METHODS: Thin layer chromatography (TLC) with vanillin as visualizing agent was used to qualitatively compare the phytoconstituents of the plant acetone extracts. The free radical scavenging antioxidant qualitative assay was done by spraying TLC plates with DPPH free radical. The bronchodilatory effects of the aqueous extracts were assessed using pre-contracted guinea pig trachea. The effects of the extracts of T. camphoratus L. and T. parvicapitulatus on superoxide and ATP production was also investigated on isolated human neutrophils. A micromorphology study was done using scanning electron microscopy to study the leaves. RESULTS: Different compounds were visualized on the TLC plates with more than 40 compounds of intermediate polarity. The TLC plates sprayed with DPPH revealed the presence of 20 and 23 antioxidant compounds for T. camphoratus and T. parvicapitulatus respectively. Upon pre-contraction of the tracheal smooth muscles, the aqueous extracts of T. parvicapitulatus significantly relaxed the trachea while the relaxation observed for T. camphoratus was not significant. All the tested concentrations had a dose dependent inhibitory effect on superoxide production. The crude extract of T. parvicapitulatus at the highest concentration (10 mg/ml) significantly decreased ATP production while a non-significant increase in ATP production was observed for T. camphoratus at the highest concentration (10 mg/ml) when compared with the control. The micromorphology study was useful in revealing the presence of trichomes on the upper leaf surface of the studied taxa. CONCLUSIONS: The results obtained from this study showed that the studied plant extracts had bronchodilatory effects on contracted guinea pig trachea and could also inhibit the production of free radicals including superoxide anions. To the best of our knowledge, this is the first report on the bronchodilatory activity of T. camphoratus and T. parvicapitulatus. The micromorphological studies were useful in distinguishing between the two species, confirming that T. camphoratus L. and T. parvicapitulatus are different taxa. This study provides evidence to support the traditional use of T. camphoratus and T. parvicapitulatus in managing bronchospasm.

Commercial herbal medicines used as African traditional medicines: Ngoma Herbal Tonic Immune Booster interferes with a rapid urine drug screening test.

BACKGROUND: The prevalent use of African traditional medicine by the general public has been reported. With commercialisation and marketing, some of the herbal medicines (HMs) used are readily available over the counter, most of them promoted as immune boosters. These commercial HMs have not been taken through clinical trials and other tests that would validate their composition and safety, and other properties such as their effect on laboratory diagnostic tests. OBJECTIVE: To investigate the cross-reactivity of selected HMs with commonly tested drugs of abuse (DoA) using a qualitative rapid urinalysis assay. METHODS: The six HMs selected were bought from local pharmacies. A rapid urinalysis screening test was performed with the Instant View Multi-Drug of Abuse Test kit from Labstix Diagnostics. Drug-free urine (DFU) was pooled from samples donated by healthy volunteers. Urine samples that had tested positive for DoA were obtained from a pharmacology laboratory. Aliquots of the urine samples were spiked with the HMs in neat and diluted form, and tested at various time intervals. RESULTS: The results for the DFU samples spiked with the HMs remained negative. There were no significant changes in pH or specific gravity of the samples. The results of samples that had tested positive for tetrahydrocannabinol (THC) were not altered by five of the HMs when spiked at 40% v/v. The HM Ngoma Herbal Tonic Immune Booster caused false-negative results for the THC test. CONCLUSION: An important finding is that the herbal mixture Ngoma Herbal Tonic Immune Booster caused false-negative results for the cannabinoid screening test. It adds to the list of substances that may be potential adulterants of urine for screening tests.

The effect of atropine on parasympathetic control of respiratory sinus arrhythmia in two ethnic groups.

The effects of low and high doses of atropine on respiratory sinus arrhythmia were assessed to ascertain whether any differences exist in the degree of parasympathetic control on cardiac rhythm between two ethnic groups. The standard deviation of the R-R interval (the R peak-to-peak interval of two QRS complexes of an electrocardiogram) has been used as a noninvasive parameter to measure the degree of parasympathetic cardiac control. Nine black and nine white healthy male volunteers took part in study after approval by the Research and Ethics Committee of the Medical University of South Africa. Thirty consecutive electrocardiographic complex were recorded during each of the following: 3 deep inspirations and expirations, incremental cumulative atropine injections of 0.001 mg/kg until 0.005 mg/kg, followed by two injections of 0.01 mg/kg and 0.015 mg/kg of atropine each. After each of the last two injections the deep inspiration and expiration procedure was repeated. No significant differences could be found at any stage for any parameter between the groups. In both groups the R-R interval variation increased threefold during voluntary induced respiratory sinus arrhythmia. This effect was blocked after 0.01 mg/kg of atropine. The degree of parasympathetic control was not affected by any respiratory maneuver, but was affected by atropine. A significant inverse quadratic relationship was found between parasympathetic control and heart rate change (R = .984 for whites, and R = .905 for blacks). A poor correlation was found between the R-R interval variation and heart rate changes. In conclusion, ethnicity does not affect parasympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Is ward evacuation for uncomplicated incomplete abortion under systemic analgesia safe and effective? A randomised clinical trial.

OBJECTIVE: To compare evacuation under systemic analgesia (fentanyl and midazolam) in a treatment room (ward group) with evacuation under general anaesthesia in theatre. DESIGN: A prospective randomised clinical trial. SETTING: A tertiary medical centre serving a black urban population. SUBJECTS: One hundred and forty-two patients with uncomplicated incomplete abortions. INTERVENTION: Randomisation into two groups, those for evacuation under systemic analgesia and those for evacuation under general anaesthesia. MAIN OUTCOME MEASURES: Both groups were compared in terms of safety, efficacy, acceptability, blood consumption and time delay between admission and evacuation. RESULTS: Significantly less blood was used in the ward group (37 units for 13 patients) than in the theatre group (65 units for 24 patients) (P < 0.03). Significantly less time was taken between admission and evacuation in the ward group (median 7 hours 15 minutes) than in the theatre group (median 12 hours 38 minutes) (P < 0.0003). Evacuation under fentanyl and midazolam was safe, effective and acceptable for the majority of patients compared with evacuation under general anaesthesia. CONCLUSION: Patients with uncomplicated incomplete abortions (uterine size equivalent to a pregnancy of 14 weeks' duration or less) can undergo evacuation safely and effectively under fentanyl and midazolam and have a significantly smaller chance of requiring a blood transfusion.

The cumulative dose response effect of eicosapentaenoic and docosahexaenoic acid on blood pressure, plasma lipid profile and diet pattern in mild to moderate essential hypertensive black patients.

In this study eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were given in a cumulative manner, every 6 weeks, starting with 10 mg, then 100 mg, 1000 mg and 10,000 mg EPA daily to mild to moderate essential hypertensive black patients. The corresponding DHA doses were 3, 33, 333 and 3333 mg. A control group was given olive oil as placebo for the entire 24 weeks. The placebo group had lower diastolic and systolic blood pressures after 24 weeks than the EPA and DHA group. No effect was seen on plasma triglycerides, cholesterol, HDL-cholesterol and gamma-glutamyltranspeptidase at any stage of the trial. In the EPA group plasma free-EPA increased significantly from 1000 mg onwards and plasma free-arachidonic acid (AA) decreased after 1000 mg EPA. No other plasma free essential fatty acid changed during the trial, although the HDL:cholesterol increased slightly but non-significantly with an increase in EPA and DHA. No significant changes in diet pattern or body mass was observed. It is therefore concluded that EPA and DHA supplementation had no beneficial effects in mild to moderate essential hypertensive black patients except for a lowering of plasma AA.

[The effect of enalapril and prazosin on mild to moderate hypertension in black South Africans]. / Die effekte van enalapril en prasosien op geringe tot matige hipertensie in swart Suid-Afrikaners. Resultate van 'n kliniese proef.

A double-blind, placebo-controlled clinical trial with a parallel design was conducted on 35 black patients with mild to moderate hypertension. After a 4-week run-in on placebo, baseline values were recorded and only patients with diastolic pressures of 95 - 115 mmHg were admitted to the trial, which lasted 10 weeks. These patients were randomised in three groups, receiving daily initially either 5 mg enalapril, 2 mg prazosin or placebo. Blood pressures and heart rates were measured once every week and in poor responders dosages were increased on a 2-weekly basis. Enalapril was increased to 10, 20 and 40 mg during the last 4 weeks, and prazosin was respectively increased to 4, 10 and 20 mg. The only statistically significant difference between baseline and post-treatment values (week 10) was a reduction in heart rate in the prazosin group, but no differences in either systolic or diastolic pressure could be detected in this group or between any of the three measurements in the other two groups. When the mean values of 3 groups were compared on a weekly basis it transpired that there were no statistically significant differences between any of the baseline values but that the mean heart rate at week 2 and the mean diastolic pressure at week 9 in the prazosin group and the mean systolic pressures in the enalapril group at weeks 6, 8 and 10 were significantly lower than the corresponding placebo values. Cumulative sum techniques were used to measure the course of the effects of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of the effects of digoxin and digitoxin on systolic time intervals and colour vision.

Animal studies suggest that for the same inotropism hydrophilic cardiac glycosides produce greater depression of atrioventricular (AV) conduction than lipophilic ones. This has been explained on the basis of a greater vagomimetic effect with hydrophilic agents and a greater sympathomimetic effect with lipophilic agents. In this randomized, cross-over study we investigated the effects of placebo, digoxin (relatively hydrophilic), and digitoxin (relatively lipophilic) in twelve healthy volunteers. For both drugs steady-state serum concentrations in the mid-therapeutic range were achieved. Both drugs produced the same positive inotropic effect as measured by systolic time intervals (QS2c). There was a trend for digoxin to have a greater effect on AV conduction than digitoxin. After atropine or propranolol there was no difference between the effect of the two cardiac glycosides on AV conduction. No significant effects on colour vision were seen. We conclude that, there do not seem to be pharmacodynamic differences between digoxin and digitoxin at mid-therapeutic serum concentrations.

Penbutolol in the treatment of mild to moderate essential hypertension in black South Africans.

The antihypertensive effects of penbutolol, a nonselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity, was assessed in nonobese black South Africans aged 25 to 65 years with uncomplicated mild to moderate essential hypertension. After a 4-week placebo run-in period 50 patients entered a randomized placebo-controlled study with a crossover design. For 8 weeks they received a once daily dose of 40 mg penbutolol (or placebo) which was increased to 80 mg per day for the next 4 weeks in poor responders. This was followed by a 4-week placebo washout period after which a crossover of treatment was achieved and a second 12-week period of treatment initiated. Thirty-five patients completed the whole study and in 15 patients diastolic blood pressure was reduced below 95 mm Hg. The mean systolic pressures of these patients decreased by 21 mm Hg and their mean diastolic pressure decreased by 11 mm Hg during treatment with penbutolol. These results suggest that penbutolol monotherapy is an alternative therapeutic approach to hypertension in black South Africans.

Aspects of poisoning with traditional medicines in southern Africa.

During 1981-1985, 1306 patients were admitted to Ga-Rankuwa Hospital due to acute poisoning. The major causes were paraffin (59.0%) and traditional medicines (15.8%). The mortality from paraffin was low (2.1%), but poisoning from traditional medicine resulted in a high mortality (15.2%) and accounted for 51.7% of all deaths. The traditional healer was the main source (83.4%), of traditional medicines, while 11.6% was bought from African medicine shops. The rest was acquired from other sources. In 82.5% of cases traditional medicines were taken orally, and in 10.5% of cases they were administered as an enema. Poisoning by traditional medicines was always accidental and probably due to overdosage. Vomiting, diarrhea, and abdominal pain were the most frequently encountered symptoms while the lungs, liver, and central nervous system were commonly affected. Treatment consisted of ventilation, intravenous fluids, and other palliative measures. A great deal of secrecy still surrounds traditional medicine, hampering rational therapy. Questioning of patients and interviews with traditional healers facilitated the identification of a number of major etiological agents. This elucidated the problem and should promote effective treatment.

Effects of essential fatty acids on mild to moderate essential hypertension.

A double-blind placebo-controlled study with a crossover design was conducted on 25 non-obese black patients with mild-moderate uncomplicated essential hypertension. They were randomly assigned into two groups. After having received placebo capsules for 4 weeks, they received dietary supplementation with either Efamol-marine (containing desaturated n-6 and n3 essential fatty acids), or sunflower seed and linseed oil capsules for 12 weeks. Thereafter a second 4 weeks placebo phase and a subsequent second 12-week active phase were entered into during which a crossover of the dietary supplementation of the groups was brought about. The mean systolic blood pressure of patients receiving Efamol-marine was significantly lowered after 8 and 12 weeks, while those receiving sunflower/linseed oil supplementation had no significant reduction of blood pressure. This observation may indicate that defective desaturation of the essential fatty acids by the enzyme delta-6-desaturase, could play an important role in the etiology of essential hypertension.

Ethnic differences in response to beta-blockade: fact or artefact? A study with bisoprolol and propranolol.

A randomized, double-blind, placebo-controlled study was performed in 8 white and 8 black volunteers matched for sex, age and mass. The effect of 3 intravenous doses of a new, cardioselective beta-adrenergic blocker, bisoprolol, on the heart rate increase after standardized exercise was compared to that of 3 doses of propranolol. As described previously for propranolol, black volunteers showed less response than whites to beta-blockade assessed in terms of the reduction in exercise-induced tachycardia. The effects of the two beta-blockers were similar and the apparent ethnic difference was seen with both drugs. It has previously been shown that black volunteers have a higher intrinsic heart rate (i.e. heart rate after parasympathetic and beta-adrenergic blockade of the heart) than whites, but their resting heart rates are similar because of greater parasympathetic tone in blacks. When exercise-load was calculated as increase in heart rate above that after atropinization, no ethnic differences were seen. It is suggested that in populations that are heterogenous in terms of the heart rate increase after atropine, work load should be standardized in terms of the increase in heart rate over the atropine heart rate rather than on absolute heart rate. The apparent ethnic difference represents a flaw in methodology as applied to a heterogenous volunteer population.

Penbutolol in black hypertensive patients.

A single-blind placebo-controlled study was conducted on black hypertensive patients with a once-daily dose of penbutolol (Betapressin; Hoechst); a non-selective beta-blocker. Of 29 patients who participated in a 4-week run-in period, 18 were entered into a 20-week trial of the active medication. Fourteen patients were adequately controlled, 2 did not respond satisfactorily and 2 dropped out of the study. On cessation of therapy all patients became hypertensive again. No significant changes in mean heart rates were observed during active medication as opposed to placebo. Penbutolol can therefore be used as a sole antihypertensive agent in blacks.

Ethnic differences in human lymphocytic cyclic AMP production after isoprenaline stimulation and propranolol blockade.

The stimulatory effects of isoprenaline on human lymphocytic cyclic AMP (cAMP) and blockade by propranolol were studied in vitro in healthy Black and White volunteers. Basal levels of lymphocytic cAMP were significantly higher in Blacks than in Whites. Stimulation with isoprenaline caused a dose-related increase in cAMP, which was in concentrations of 10(-9) to 10(-5)M significantly greater in Blacks than in Whites. Blockade by 10(-4)M propranolol did not affect basal cAMP levels significantly, but increases in cAMP levels were significantly smaller in both groups after 10(-9) to 10(-2)M isoprenaline, while differences between cAMP levels in Blacks and Whites were still significant at concentrations 10(-9) to 10(-3)M. The increased cAMP concentration in lymphocytes of Blacks probably reflects a higher degree of beta 2-adrenoceptor activity which could be due to either a greater number and/or greater sensitivity of lymphocytic beta 2-adrenoceptors in Blacks than in Whites.

The effect of a 1-deoxynojirimycin derivative on post-prandial blood glucose and insulin levels in healthy black and white volunteers.

BAY m1099 (a 1-deoxynojirimycin derivative) is a glucose analogue which is an alpha-glucosidase inhibitor. Its effects on post-prandial blood glucose and insulin levels was compared with a placebo in 12 healthy male volunteers (6 Blacks and 6 Whites). It produced a similar, significant depression of post-prandial blood glucose and insulin levels when the groups were assessed separately and when the data were pooled. Although blood insulin levels in Whites were higher than in Blacks, as previously reported, the difference was not statistically significant and did not appear to influence the response to the drug. BAY 1099 produced no objective or subjective untoward effects and appears to warrant further investigation as an adjuvant to dietary control of diabetes mellitus.

A comparison of the cardiovascular effects and subjective tolerability of binedaline and amitriptylene in healthy volunteers.

Binedaline is a new antidepressant drug which is not a tricyclic compound. In animal investigations it showed a greater therapeutic index than imipramine and amitriptylene and a smaller ED50. It also showed less anticholinergic and antihistaminic activity. In this study the effects of 100 mg (females) and 150 mg (males) of binedaline was compared with 50 mg and 75 mg of amitriptylene and placebo in healthy volunteers. Binedaline was better tolerated than amitriptylene and produced less sedation and fewer instances of dry mouth. Binedaline was devoid of the marked postural hypotension produced by amitriptylene but caused the same degree of tachycardia as amitriptylene at rest, when subjects were tilted and when subjected to ergometry. It was concluded that binedaline causes less alpha-adrenergic blockade than amitriptylene but that the sympathomimetic effects were similar. At the doses employed no major changes in electrocardiogram or systolic time intervals occurred.