Larvicidal efficacy and biological stability of a botanical natural product,zedoary oil-impregnated sand granules,against <Emphasis Type="Italic">Aedes aegypti</Emphasis> (Diptera,Culicidae)

Chemical analysis on Curcuma zedoaria rhizome volatile oil, using gas chromatography-mass spectrometer techniques, demonstrated the presence of beta-tumerone (19.88%), 1,8-cineole (8.93%), and 7-zingiberene (7.84%) as major constituents. Larvicidal efficacy against Aedes aegypti mosquitoes of zedoary oil and its formulated preparation, zedoary oil-impregnated sand granules, were investigated and compared with that of Abate(R)sand (temephos). Zedoary oil exhibited pronounced potential against the fourth instar larvae of A. aegypti with an LC(50) and LC(99) of 33.45 and 83.39 ppm, respectively. Application of zedoary oil at a dosage yielding ten times that of LC(99) offered complete larval mortality (100% mortality) for a period of 3 days, and the larval mortality subsequently decreased to lower than 50% after application for more than 5 days. Zedoary oil-impregnated sand granules provided remarkably longer activity, with a larval mortality of 100% for a period of 9 days; and mortality below 50% was obtained in week 3 of application. The complete larval mortality that resulted from applying temephos at dosages of 0.1 and 1 ppm persisted for a period of 6 days and 4 weeks, respectively, and the larval mortality below 50% was reported on day 18 and week 11, respectively. Testing A. aegypti species against stored samples of zedoary oil-impregnated sand granules demonstrated that the product stored at 4 degrees C showed the longest larvicidal activity, followed by those kept at ambient temperature and 45 degrees C, yielding a complete larval mortality for 9, 8, and 6 days, respectively. Most samples of zedoary oil-impregnated sand granules stored at each temperature for 1 month showed slightly higher efficacy than those kept for 2 months. The larvicidal efficacy of samples stored at 4 degrees C seemed to be comparable to that of the fresh sample. The efficacy in killing A. aegypti larvae and good biological stability of zedoary oil-impregnated sand granules make this product promising as an alternative to essential oil in the development of new botanical natural larvicide for use in mosquito control programs.     

Alveolar bone response to light-force tipping and bodily movement in maxillary incisor advancement: A prospective randomized clinical trial

Objective:To compare alveolar bone thickness and height changes between untreated incisors (control), incisors advanced with light-force tipping, and incisors advanced with bodily movement mechanics.Materials and Methods:Forty-three subjects (aged 9.49 ± 1.56 years) with anterior crossbite were allocated into an untreated group (control), tipping group, or bodily movement group. Lateral cephalograms were taken before advancement (T₀) and after obtaining normal overjet (T₁). Changes in labial and palatal alveolar bone thickness and height surrounding maxillary incisors were evaluated with limited field-of-view cone-beam computed tomography before advancement (CT₀) and 4 months after normal overjet was obtained (CT₁). Wilcoxon matched-pairs signed-rank and Kruskal-Wallis one-way ANOVA tests were used to compare changes within and between groups, as appropriate. The significance level was set at .05.Results:Labial alveolar bone thickness at the midroot and apical levels were significantly decreased in the bodily movement group (P < .05). However, between groups, there was no statistically significant difference in labial bone thickness changes at any level. Palatal and total alveolar bone thickness at the midroot and apical levels were significantly decreased in the tipping group compared with the control and bodily movement groups (P < .05). Neither labial nor palatal bone height changes were significantly different among groups.Conclusions:Maxillary incisor advancement with light-force tipping and bodily movement in growing patients resulted in labial alveolar bone thickness and labial and palatal alveolar bone height changes that were similar to the untreated group.     

A pharmacokinetic study of paracetamol in Thai β-thalassemia/HbE patients

Background

Thalassemia may alter the pharmacokinetics of several drugs in thalassemic patients. Paracetamol is a commonly used analgesic and antipyretic drug which is extensively metabolized in the liver via glucuronidation. The aim of this study was to compare the pharmacokinetics of paracetamol (PCM) and its metabolites [paracetamol glucuronide (PCM-G), paracetamol sulfate (PCM-S), and paracetamol cysteine (PCM-C)] in 16 patients with 16 normal subjects.

Method

Following an overnight fast, a single dose of paracetamol (1,000 mg of Tylenol®) was given and blood samples were obtained at predose, 0.5, 1, 1.5, 2, 3, 4, 5, 7, and 9 h after dosing for determination of the plasma levels of PCM and its metabolites by high-performance liquid chromatography.

Results

There was no significant difference in maximum concentration of PCM between groups. However, a significantly shorter elimination half-life of PCM was observed in the thalassemic subjects (p<0.001). Total apparent clearance of PCM was significantly faster in thalassemic subjects (p<0.01) while the apparent volume of distribution of PCM did not change. The area under the concentration time curve (AUC_0->∞) of PCM-G and PCM-S increased in thalassemic subjects (p<0.05) whereas this parameter for PCM-C was slightly lower in the patients. The half-lives of PCM metabolites were significantly shorter (p<0.01) in thalassemic subjects.

Conclusion

The results indicate that the elimination of PCM and its metabolites in thalassemic subjects is faster than that in normal subjects. Our pharmacokinetic data provide additional evidence that plasma PCM-G is higher in thalassemic patients with hyperbilirubinemia, which could be a casual relationship in regulating the UDP-glucuronosyltransferase expression.     

Essential oils as potential adulticides against two populations of Aedes aegypti, the laboratory and natural field strains, in Chiang Mai province, northern Thailand

Essential oils derived from five plant species, celery (Apium graveolens), caraway (Carum carvi), zedoary (Curcuma zedoaria), long pepper (Piper longum), and Chinese star anise (Illicium verum), were subjected to investigation of adulticidal activity against mosquito vectors. Two populations of Aedes aegypti, the laboratory and natural field strains, collected in Chiang Mai province, northern Thailand were tested in pyrethroid-susceptibility bioassays. The results revealed that the natural field strain of A. aegypti was resistant to permethrin, with mortality rates ranging from 51 to 66%. A mild susceptibility, with mortality rates ranging from 82 to 88%, was observed in the natural field strain of A. aegypti exposed to lambdacyhalothrin, which suggested that this strain was tolerant and might be resistant to this insecticide. However, laboratory-reared A. aegypti exposed to discriminating dosages of permethrin and lambdacyhalothrin induced 100% mortality in all cases, thus indicating complete susceptibility of this strain to these insecticides. The adulticidal activity determined by topical application revealed that all five essential oils exerted a promising adulticidal efficacy against both laboratory and natural field strains of A. aegypti. Although the laboratory strain was slightly more susceptible to these essential oils than the natural field strain, no statistically significant difference was observed. Moreover, comparison of the adulticidal activity indicated that the performance of these essential oils against the two strains of A. aegypti was similar. The highest potential was established from caraway, followed by zedoary, celery, long pepper, and Chinese star anise, with an LC₅₀ in the laboratory strain of 5.44, 5.94, 5.96, 6.21, and 8.52 μg/mg female, respectively, and 5.54, 6.02, 6.14, 6.35, and 8.83 μg/mg female, respectively, in the field strain. These promising essential oils are, therefore, an alternative in developing and producing mosquito adulticides as an effective measure used in controlling and eradicating mosquito vectors.     

Asia-Pacific Working Group consensus on non-variceal upper gastrointestinal bleeding

Upper gastrointestinal bleeding (UGIB), especially peptic ulcer bleeding, remains one of the most important cause of hospitalisation and mortality world wide. In Asia, with a high prevalence of Helicobacter pylori infection, a potential difference in drug metabolism, and a difference in clinical management of UGIB due to variable socioeconomic environments, it is considered necessary to re-examine the International Consensus of Non-variceal Upper Gastrointestinal Bleeding with emphasis on data generated from the region. The working group, which comprised experts from 12 countries from Asia, recommended the use of the Blatchford score for selection of patients who require endoscopic intervention and which would allow early discharge of patients at low risk. Patients' comorbid conditions should be included in risk assessment. A pre-endoscopy proton pump inhibitor (PPI) is recommended as a stop-gap treatment when endoscopy within 24 h is not available. An adherent clot on a peptic ulcer should be treated with endoscopy combined with a PPI if the clot cannot be removed. Routine repeated endoscopy is not recommended. High-dose intravenous and oral PPIs are recommended but low-dose intravenous PPIs should be avoided. COX-2 selective non-steroidal anti-inflammatory drugs combined with a PPI are recommended for patients with very high risk of UGIB. Aspirin should be resumed soon after stabilisation and clopidogrel alone is no safer than aspirin plus a PPI. When dual antiplatelet agents are used, prophylactic use of a PPI reduces the risk of adverse gastrointestinal events.     

Two weekly vinorelbine: administration in patients who have received at least two prior chemotherapy regimes for advanced breast cancer

This study examined the response to and toxicity of two weekly vinorelbine administration in patients with at least two prior chemotherapeutic treatments for advanced breast cancer. This single centre study enrolled 20 patients, 19 of whom had received prior taxane treatment for advanced breast cancer. Taxane treatment was in the form of docetaxel for all but 1 patient who had received paclitaxel. All patients had received two or more prior chemotherapeutic regimes for advanced breast carcinoma, including anthracyclines (epirubicin) in 19 patients. Vinorelbine 25 mg/m2 two weekly was given for 6 months, until disease progression or toxicity precluded further treatment. 5 earlier studied patients started vinorelbine at 25 mg/m2/week; all changed to the two weekly schedule, limiting the incidence and severity of neutropenia. 7 partial responses (PRs) out of 20 assessable patients (35% overall response rate, 95% confidence interval 15-59%) were noted, all PRs occurring in taxane pretreated patients. The median duration of response was 4 months whilst the median time to progression was 2.75 months. Overall, there were 7 neutropenic events (35%) of 2 week median duration, spanning common toxicity criteria (CTC) grades 1-3 in severity. 5 neutropenia cases (25%) occurred in patients whilst on two weekly vinorelbine. 2 cases (10%) required granulocyte colony stimulating factor support, 1 having had febrile neutropenia (52%). One case of thrombocytopenia, neurotoxicity and nausea (each CTC grade 1) were recorded. Although this study involves a small number of cases, these preliminary results suggest that two weekly vinorelbine is effective in heavily pretreated (including taxane pretreated) advanced breast carcinoma. Response is comparable with that of traditionally used weekly regimes, with markedly less toxicity.     

Clinical trial of deferiprone iron chelation therapy in beta-thalassaemia/haemoglobin E patients in Thailand

Nine patients with either beta-thalassaemia/haemoglobin E (7) or homozygous beta-thalassaemia (2) not requiring regular transfusions were treated with the oral iron chelator, deferiprone 25-50 mg/kg/d for between 17 and 86 weeks (mean 49 weeks). There were significant decreases in serum ferritin (initial mean +/- standard deviation 2168 +/- 1142, final 418 +/- 247 micro g/l; t-test for paired samples, P = 0.005), hepatic iron (initial 20.3 +/- 6.26, final 11.7 +/- 4.83 mg/g/dry weight; P = < 0.02), red cell membrane iron (initial 76.2 +/- 3.64, final 7.2 +/- 0.56 mmol/mg protein; P = < 0.0005) and serum non-transferrin bound iron (initial 9.0 +/- 0.56, final 5.9 +/- 0.89 micro mol/l; P = < 0.0005). There was also a significant rise in serum erythropoietin (initial 240 +/- 195.1, final 433.2 +/- 269.2 U/l; P = 0.034). The haemoglobin level rose in three patients and transfusion requirements were reduced substantially in four patients. Serum thiobarbituric acid reactive substance (TBARS) also fell in six of eight patients. Patients generally improved clinically, with weight gain observed. Side-effects were mild and included gastrointestinal symptoms (6) and arthralgia (1), not requiring withdrawal of the drug. One patient died at 17 weeks of therapy as a result of an intercurrent infection. His neutrophil count was normal. We conclude that deferiprone is an effective, well-tolerated iron chelator for patients with thalassaemia intermedia. Further studies are needed to determine the optimum dose and length of treatment needed to reduce iron burden to a safe level in these patients.