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SummaryBackground Refractory coeliac disease, enteropathy associated T-cell lymphoma and small bowel adenocarcinoma are rare but prognostically important complications in coeliac disease. Aim To analyse potential changes in occurrence of complicated coeliac disease over the last 25 years. Methods One thousand one hundred and thirty eight patients were included and evaluated based on their time of first presentation at the Medical University of Vienna, Austria. Occurrences of refractory coeliac disease and associated malignancies were evaluated for 5-year intervals from January 1990 until December 2014 and were compared over time. Results 2.6% (n = 29) were diagnosed with refractory coeliac disease (females 65.6%, mean age at diagnosis 62.8 years). The proportion of those patients was 2.6%, 3.1%, 3.3%, 2.7% and 0.5% for the 5 year intervals from 1990 onwards. Thus, the number of refractory cases has been decreasing since 2000 (P = 0.024). The number of patients presenting with lymphoma (n = 7) was 0.6%, 0.4%, 1.1%, 0.8% and 0% from 1990 to 2014. Similarly the number of patients with adenocarcinoma (n = 4) decreased to 0% until 2014. Overall mortality in patients suffering from refractory disease was 48%. Of all patients diagnosed with lymphoma 71.4% died with a 5-year survival rate of 28.6%. Conclusions Over the past 15 years the occurrence of complicated coeliac disease has been decreasing. This possibly reflects a higher awareness of coeliac disease and optimised diagnosis and treatment with avoidance of long-term immunological disease activity. Symptomatic disease and a delay in diagnosis are risk factors for refractory coeliac disease and related cancer.

A comparative randomized crossover study was conducted to determine the pharmacokinetics of theophylline in male and female camels (Camelus dromedarius) and goats (Caprus hircus). Theophylline is an established 'probe drug' to evaluate the drug metabolizing enzyme activity of animals. It was administered by the intravenous (i.v.) route and then intramuscularly (i.m.) at a dose of 2 mg/kg. The concentration of the drug in plasma was measured using a high-performance liquid chromatography (HPLC) technique on samples collected at frequent intervals after administration. Following i.v. injection, die overall elimination rate constant (lambda(z)) in goats was 0.006 +/- 0.00076/min and in camels was 0.0046 +/- 0.0008/min (P < 0.01). The elimination half-life (t(1/2lambdaz)) in goats (112.7 min) was lower than in camels (154.7 min) (P < 0.01). The apparent volume of distribution (V-z) and the total body clearance (Cl) in goats were 1440.1 +/- 166.6 ml/kg and 8.9 +/- 1.4 ml/min/ kg, respectively. The corresponding values in camels were 1720.3 +/- 345.3 ml/kg and 6.1 +/- 1.0 ml/ min/kg, respectively. After i.m. administration, theophylline reached a peak plasma concentration (C-max) of 1.8 +/- 0.1 and 1.7 +/- 0.2 mug/ml at a post-injection dine (T-max) of 67.5 +/- 8.6 and 122.3 +/- 6.7 min in goats and camels, respectively. The mean bioavailability (F) in both goats and camels was 0.9 +/- 0.2. The above data suggest that camels eliminate theophylline at a slower rate than goats.

This work examines the effects of lyophilized extracts of the medicinal plants Rhazya stricta, Balanites aegyptiaca and Haplophylum tuberculatum on liver damage induced by paracetamol in mice. Rapid HPLC finger prints for some of these extracts were made. The hepatoprotective effects of the plant extracts were compared with that of the standard hepatoprotective agent silymarin. The extracts (1 g/kg) and silymarin (0.1 g/kg) were given orally for 5 consecutive days .On the last day of treatment a hepatotoxic oral dose of paracetamol (0.6 g/kg) was given, and 3 h later, the hepatic function of mice was evaluated using pentobarbitone -induced sleeping time, the concentration of reduced glutathione (GSH) in liver, and the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT) and cholesterol concentration in plasma. The livers were weighed and examined for macro- and microscopic changes. Pretreatment with R. stricta or with silymarin protected the livers of treated mice against paracetamol hepatotoxicity as evidenced by a significant improvement of the above liver function tests. B. Aegyptiaca had a relatively modest hepatoprotective activity, while H. tuberculatum was almost ineffective. Oral pretreatment of mice for 5 consecutive days with an extract of R. stricta or silymarin protected about 57% and 92% of the treated mice, respectively, against the lethal effect of paracetamol (1 g/kg). B. aegyptiaca and H. tuberculatum protected only 27% and 16% of the animals, respectively. Copyright © 2001 John Wiley and Sons, Ltd.

Phytochemical, pharmacological and toxicological properties of the medicinal plant Rhazya stricta Decne. are reviewed. Several types of alkaloids and a few flavonoids have been isolated and their structures and stereochemistry characterized. However, in most cases the biological activity of these compounds has not been studied. Most of the pharmacological activity of the plant resides in its alkaloidal fractions which cause depression of the central nervous system and hypotension. Extracts of R. stricta appear to have low toxicity, although its use in pregnant women may be inadvisable.

The present work examines the effects of hexane, ethyl acetate and methanol extracts of Psidium guajava leaves (20,100,500 and 1250 mg/kg) on the central nervous system in mice. The three extracts exhibited mostly dose-dependent antinociceptive effects in chemical and thermal tests of analgesia. The extracts also produced dose-dependent prolongation of pentobarbitone-induced sleeping time. However, they had variable and mostly non-significant effects on locomotor coordination, locomotor activity or exploration. In the pharmacological tests used, the ethyl acetate extract seemed to be the most active, followed by the hexane and then the methanol extracts.

Haematological, biochemical and pathological effects in rats produced by the salt-tolerant plant Avicennia marina given at oral doses of 1 or 4 g kg(-1) for three consecutive days or 0.5 g kg(-1) day(-1) for 28 consecutive days are reported. No overt behavioral changes, moribundity or mortality were seen in either of the two experiments. A dose of 1 g kg(-1) did not affect significantly either body or liver weights. However, at a dose of 4 g kg(-1) the extract reduced both body and liver weights. The extract at both doses significantly increased leucocyte (mainly neutrophil) counts but did not affect significantly erythrocyte counts, haemoglobin concentration or the haematocrit. Except for a slight, but statistically significant, decrease in plasma glucose concentration and an increase in Na, Ca, Cu, Mg and cholesterol concentrations and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, the extract exerted no significant effects on plasma biochemistry. The treatment produced dose-related mild cellular degeneration in the liver and congestion in the central veins. There were also prominent Kupffer's cells and monocellular infiltrations. In the kidneys there was shrinkage and cellular degeneration of glomeruli and patches of medullary haemorrhage. In the spleen a slight activation of the germinal centre in the white pulp was noted. Subchronic treatment with the extract did not affect significantly the body and liver weights, the water intake, faecal and urinary output, leucocyte and erythrocyte counts, haemoglobin or haematocrit. There was a significant decrease in the number of platelets and an increase in the number of neutrophils. No significant changes in plasma biochemistry were observed, except for a 15% increase in AST activity. Subchronic treatment produced a significant reduction in glutathione concentration, amounting to about 20%. Histopathological findings after the subchronic treatment were similar in nature but milder than those seen after the acute treatment.

The strongly basic alkaloidal fraction of the traditional medicinal plant Rhazya stricta (RS) was given orally to mice, in a single dose of 10 mg/kg (group 1) or, twice daily for 3 days at the same dose (group 2). A third group (control) received normal saline. Liver homogenates from all animals were used to assess the microsomal activity of cytochrome P450 and its isoforms as well as its catalytic activity (using theophylline as a substrate). RS alkaloidal fraction had no significant effect on the total amount of microsomal cytochrome P450, but it caused a significant increase in the cytochrome P450 isoforms CYPs 1A1 and 1A2. It also significantly increased the concentrations of some metabolites of theophylline. These results suggest that RS has the potential to interact with other drugs that are biotransformed by cytochrome P450, when given concomitantly with it.

The effects of a leaf extract of the traditional medicinal plant Rhazya stricta (0.25, 1.0 and 4.0 g/kg/day for 3 days) on reduced glutathione (GSH), lipid peroxidation (LP) and ascorbic acid (AA) concentrations in the liver and kidneys were studied in rats 24 h after the last dose. The plant extract, at a dose of 0.25 g/kg, did not significantly affect the concentrations of GSH, LP or AA in the liver or kidneys. At a dose of 1.0 g/kg, the plant extract significantly increased the GSH concentration in the liver, but did not affect the GSH concentration in the kidneys, or LP or AA in the liver or kidneys. The plant extract (4.0 g/kg) significantly increased the GSH and decreased LP peroxidation, but did not affect the AA concentrations in the liver and kidneys. It may be concluded that the R. stricta extract, at some of the doses used, has antioxidant actions in the rat.

Sixty samples of materials implicated in traditional Sudanese medicine, representing 42 plant species, 31 genera and 22 families, were tested for molluscicidal activity. Tacca leontopetaloides (Taccaceae) was identified as a potent material which could be developed as a natural snail control agent. Several active fractions containing steroidal saponins were isolated.

The original article to which this Erratum refers was published in Phytotherapy Research 14(2) 2000, 107-111. Following publication of this paper in the March 2000 issue of Phytotherapy Research (14(2), 107-111), it has come to our attention that Figure 3 was printed incorrectly. The correct Figure 3 appears below. The publishers would like to apologise for any confusion caused.