Estimated causes of death in Thailand, 2005: implications for health policy

Background  

Almost 400,000 deaths are registered each year in Thailand. Their value for public health policy and planning is greatly diminished by incomplete registration of deaths and by concerns about the quality of cause-of-death information. This arises from misclassification of specified causes of death, particularly in hospitals, as well as from extensive use of ill-defined and vague codes to attribute the underlying cause of death. Detailed investigations of a sample of deaths in and out of hospital were carried out to identify misclassification of causes and thus derive a best estimate of national mortality patterns by age, sex, and cause of death.     

Cause-of-death ascertainment for deaths that occur outside hospitals in Thailand: application of verbal autopsy methods

Background  

Ascertainment of cause for deaths that occur in the absence of medical attention is a significant problem in many countries, including Thailand, where more than 50% of such deaths are registered with ill-defined causes. Routine implementation of standardized, rigorous verbal autopsy methods is a potential solution. This paper reports findings from field research conducted to develop, test, and validate the use of verbal autopsy (VA) methods in Thailand.     

Complete Recovery Following Electroacupuncture Therapy in Refractory Unilateral Sensorineural Hearing Loss

Role of electroacupuncture (EA) in refractory unilateral sensorineural hearing loss (SNHL) remains unclear but might be promising for the Meniere's disease. Two cases of unilateral SNHL who were unresponsive to conventional treatment of sudden SNHL showed complete recovery after receiving EA therapy. The first case was a 46-year-old woman who received EA in the seventh month after the acute onset of sudden right hearing loss and tinnitus. She had mild-to-moderate degree of SNHL at high frequencies in the right ear with episodic vertigo. The second case was a 55-year-old woman who received EA in the sixth year after developing sudden SNHL in the right ear. Before the EA began, her pure tone average of the affected ear was 45 dB and the phonetically balanced score was 88%. The regimen for both patients included 12 sessions of EA over four weeks at the main acupoints (Tinggong (SI 19), Ermen (TE 21), Qimai (TE 18) and Yifeng (TE 17) on the affected ear and the adjuvant acupoints (Zhongzhu (TE 3), Hegu (LI 4), Qihai (CV 6), Guanyuan (CV 4), Taixi (KI 3), and Taichong (LIV 3)). Both patients regained their normal hearing thresholds three weeks after the first EA. No adverse events were observed. Hence, EA may be a useful additional therapy in unilateral SNHL, even at the late phase when other treatments have failed because the possibility of Meniere's disease cannot be excluded.     

Carbazole alkaloids from <Emphasis Type="Italic">Murraya koenigii</Emphasis> trigger apoptosis and autophagic flux inhibition in human oral squamous cell carcinoma cells

Carbazole alkaloids, a major constituent of Murraya koenigii (L.) Sprengel (Rutaceae), exhibit biological effects such as anticancer activity via the induction of apoptosis, and they represent candidate chemotherapeutic agents. Oral squamous cell carcinoma (OSCC) is the most prevalent cancer of the oral cavity and a growing and serious health problem worldwide. In this study, we investigated the anticancer properties and mechanisms of action of two carbazole alkaloids derived from M. koenigii leaves, mahanine and isomahanine, in the OSCC cell line CLS-354. At 15 μM, mahanine and isomahanine were cytotoxic to CLS-354 cells, triggering apoptosis via caspase-dependent and -independent mechanisms. Autophagosomes, visualised using monodansylcadaverine (MDC) labelling, were numerous in carbazole alkaloid-treated cells. Mahanine and isomahanine markedly induced the expression of the autophagosome marker microtubule-associated protein 1 light chain 3, type II (LC3B-II). Genetic and chemical inhibition of autophagy via silencing of the Autophagy protein 5 gene and exposure to bafilomycin A1 (BafA1), respectively, did not arrest carbazole alkaloid-induced apoptosis, indicating that it occurs independently of autophagic activation. Surprisingly, both carbazole alkaloids caused increased accumulation of p62/sequestosome1 (p62/SQSTM1), with coordinated expression of LC3B-II and cleaved caspase-3, suggesting inhibition of autophagic flux. Our results suggest that inhibition of autophagic flux is associated with carbazole alkaloid-induced apoptosis. Our findings provide evidence of a novel cytotoxic action of natural carbazole alkaloids and support their use as candidate chemotherapeutic agents for the treatment of OSCC.     

Potent anti-cervical cancer activity: Synergistic effects of Thai medicinal plants in recipe N040 selected from the MANOSROI III database

Ethnopharmacological relevances

One of the prestigious Thai/Lanna folklore wisdoms is the medicinal plant recipes. Thai/Lanna medicinal plant recipe database MANOSROI III has been developed by Prof. Dr. Jiradej Manosroi. It consists of over 200,000 recipes covering all diseases including cancer.

Aim of this study

To investigate the in vitro and in vivo anti-cervical cancer activity and the active constituents of the Thai medicinal plant recipe N040 selected from the MANOSROI III database.

Materials and methods

The extracts of recipe N040 and single medicinal plants in the recipe were prepared by hot water and methanol extraction, respectively. The n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH) and water fractions of Caesalpinia sappan, the plant which showed the highest anti-proliferative activity were prepared by liquid–liquid partition extraction. The fraction which showed the highest anti-proliferative activity was further isolated for active constituents. Anti-proliferative activity of recipe N040, methanolic extracts, fractions of Caesalpinia sappan and brazilin, an active constituent on HeLa cell were investigated using sulforhodamine B (SRB) assay. Anti-oxidative activities including free radical scavenging and metal ion-chelating activities, as well as the phenolic and flavonoid contents of these fractions were also determined. The in vivo anti-cancer activity of recipe N040 on HeLa cell xenograft and the subchronic toxicity were performed in nude mice and rats, respectively.

Results and conclusions

N040 showed the potent in vitro anti-proliferative activity on HeLa cell with the IC₅₀ value of 0.11 µg/ml. Phytochemicals detected in the plants were steroids/triterpenoids, tannins, flavonoids, saponins and alkaloids. For the single plant, methanolic extract of Caesalpinia sappan gave the highest anti-proliferative activity with the IC₅₀ of 33.46 µg/ml. EtOAc fraction of Caesalpinia sappan showed the highest anti-proliferative and free radical scavenging activities with the IC₅₀ and SC₅₀ of 17.81 and 21.95 µg/ml which were 1.88 and 0.83 folds of its methanolic extract and ascorbic acid, respectively. Poor metal chelating activity (MC₅₀>500 µg/ml) was observed in methanolic extract and all fractions. The highest phenolic and flavonoid contents were observed in the methanolic extract. Brazilin, the known compound isolated from the EtOAc fraction exhibited potent anti-proliferative activity with the IC₅₀ of 0.28 µg/ml which was higher than its methanolic extract and EtOAc fraction of 119.50 and 63.61 folds, respectively, but only 0.39 fold of the recipe extract N040. The tumor size of the HeLa cell xenograft nude mice treated with the recipe N040 at the dose of 44.50 mg/kg body weight per day was significantly smaller (p<0.05) than that of the control with the relative tumor weight inhibition of 57.23% which was 0.65 fold of cisplatin. In the subchronic toxicity study, N040 given orally at the dose of 1000 mg/kg body weight per day for 90 days showed no alteration in body weight gain, hematology [except the increase mean corpuscular hemoglobin (MCH) in the treated male rats] and clinical blood chemistry (except the increase blood glucose in the treated male rats) both in female and male rats. Only minor lesions of the organs including lung, liver, kidney and small intestine were observed in both sexes. This study has demonstrated the synergistic effect of the plants composed in the recipe which resulted in the potent anti-cancer activity and confirmed the traditionally use of the recipe N040. In addition, this study has also suggested the compound brazilin isolated from Caesalpinia sappan for its high potential to be further investigated as a novel anti-cervical cancer drug.