Showing papers by "Mahidol University published in 2008"

Vaccination greatly reduces disease, disability, death and inequity worldwide.

Abstract: In low-income countries, infectious diseases still account for a large proportion of deaths, highlighting health inequities largely caused by economic differences. Vaccination can cut health-care costs and reduce these inequities. Disease control, elimination or eradication can save billions of US dollars for communities and countries. Vaccines have lowered the incidence of hepatocellular carcinoma and will control cervical cancer. Travellers can be protected against "exotic" diseases by appropriate vaccination. Vaccines are considered indispensable against bioterrorism. They can combat resistance to antibiotics in some pathogens. Noncommunicable diseases, such as ischaemic heart disease, could also be reduced by influenza vaccination. Immunization programmes have improved the primary care infrastructure in developing countries, lowered mortality in childhood and empowered women to better plan their families, with consequent health, social and economic benefits. Vaccination helps economic growth everywhere, because of lower morbidity and mortality. The annual return on investment in vaccination has been calculated to be between 12% and 18%. Vaccination leads to increased life expectancy. Long healthy lives are now recognized as a prerequisite for wealth, and wealth promotes health. Vaccines are thus efficient tools to reduce disparities in wealth and inequities in health.

Qinghaosu (artemisinin): the price of success.

Abstract: Artemisinin and its derivatives have become essential components of antimalarial treatment. These plant-derived peroxides are unique among antimalarial drugs in killing the young intraerythrocytic malaria parasites, thereby preventing their development to more pathological mature stages. This results in rapid clinical and parasitological responses to treatment and life-saving benefit in severe malaria. Artemisinin combination treatments (ACTs) are now first-line drugs for uncomplicated falciparum malaria, but access to ACTs is still limited in most malaria-endemic countries. Improved agricultural practices, selection of high-yielding hybrids, microbial production, and the development of synthetic peroxides will lower prices. A global subsidy would make these drugs more affordable and available. ACTs are central to current malaria elimination initiatives, but there are concerns that tolerance to artemisinins may be emerging in Cambodia.

Screening for gastric cancer in Asia: current evidence and practice

Abstract: Gastric cancer is the second most common cause of death from cancer in Asia. Although surgery is the standard treatment for this disease, early detection and treatment is the only way to reduce mortality. This Review summarises the epidemiology of gastric cancer, and the evidence for, and current practices of, screening in Asia. Few Asian countries have implemented a national screening programme for gastric cancer; most have adopted opportunistic screening of high-risk individuals only. Although screening by endoscopy seems to be the most accurate method for detection of gastric cancer, the availability of endoscopic instruments and expertise for mass screening remains questionable--even in developed countries such as Japan. Therefore, barium studies or serum-pepsinogen testing are sometimes used as the initial screening tool in some countries, and patients with abnormal results are screened by endoscopy. Despite the strong link between infection with Helicobacter pylori and gastric cancer, more data are needed to define the role of its eradication in the prevention of gastric cancer in Asia. At present, there is a paucity of quality data from Asia to lend support for screening for gastric cancer.

Computer simulation study of fullerene translocation through lipid membranes.

Abstract: Recent toxicology studies suggest that nanosized aggregates of fullerene molecules can enter cells and alter their functions, and also cross the blood-brain barrier However, the mechanisms by which fullerenes penetrate and disrupt cell membranes are still poorly understood Here we use computer simulations to explore the translocation of fullerene clusters through a model lipid membrane and the effect of high fullerene concentrations on membrane properties The fullerene molecules rapidly aggregate in water but disaggregate after entering the membrane interior The permeation of a solid-like fullerene aggregate into the lipid bilayer is thermodynamically favoured and occurs on the microsecond timescale High concentrations of fullerene induce changes in the structural and elastic properties of the lipid bilayer, but these are not large enough to mechanically damage the membrane Our results suggest that mechanical damage is an unlikely mechanism for membrane disruption and fullerene toxicity

Plasmodium knowlesi: The Fifth Human Malaria Parasite

Abstract: In 1932, when Knowles and Das Gupta [ 1 ] succeeded in transmitting to humans the monkey malaria they had discovered, it appeared that a new agent for malaria therapy had been discovered. Since the Nobel Prize-winning research of Julius WagnerJauregg, malaria therapy had become widely used for the treatment of general paralysis of the insane (neurosyphilis), one of the main reasons for admission to psychiatric institutions. But it soon became apparent that this infection could rapidly become uncontrollable, and after several fatalities, its use was largely discontinued in favor of the less virulent human parasite Plasmodium vivax. Malaria parasites are generally rather choosy, both about their mammalian, avian, or reptilian hosts and their respective mosquito vectors. Transmission of Plasmodium knowlesiy for malaria therapy, from human to human was by blood passage. So initially, it was uncertain whether natural infection could take place and, thus, whether this could be a zoonosis. In 1960, Eyles et al. [2] demonstrated the first experimental mosquito transmission of a

Structure, mechanism and regulation of pyruvate carboxylase.

Abstract: effector domain. In the presence of the allosteric effector, acetyl- CoA, the biotin moiety transfers the carboxy group between the biotin carboxylase domain active site on one polypeptide chain and the carboxyltransferase active site on the adjacent antiparallel polypeptide chain. In addition, thebonafiderole of PCin the non- gluconeogenic tissues has been studied using a combination of classical biochemistry and genetic approaches. The first cloning of the promoter of the PC gene in mammals and subsequent transcriptional studies reveal some key cognate transcription factors regulating tissue-specific expression. The present review summarizes these advances and also offers some prospects in terms of future directions for the study of this important enzyme.

The academic environment: the students' perspective

Abstract: Dental education is regarded as a complex, demanding and often stressful pedagogical procedure. Undergraduates, while enrolled in programmes of 4-6 years duration, are required to attain a unique and diverse collection of competences. Despite the major differences in educational systems, philosophies, methods and resources available worldwide, dental students' views regarding their education appear to be relatively convergent. This paper summarizes dental students' standpoint of their studies, showcases their experiences in different educational settings and discusses the characteristics of a positive academic environment. It is a consensus opinion that the 'students' perspective' should be taken into consideration in all discussions and decisions regarding dental education. Moreover, it is suggested that the set of recommendations proposed can improve students' quality of life and well-being, enhance their total educational experience and positively influence their future careers as oral health physicians. The 'ideal' academic environment may be defined as one that best prepares students for their future professional life and contributes towards their personal development, psychosomatic and social well-being. A number of diverse factors significantly influence the way students perceive and experience their education. These range from 'class size', 'leisure time' and 'assessment procedures' to 'relations with peers and faculty', 'ethical climate' and 'extra-curricular opportunities'. Research has revealed that stress symptoms, including psychological and psychosomatic manifestations, are prevalent among dental students. Apparently some stressors are inherent in dental studies. Nevertheless, suggested strategies and preventive interventions can reduce or eliminate many sources of stress and appropriate support services should be readily available. A key point for the Working Group has been the discrimination between 'teaching' and 'learning'. It is suggested that the educational content should be made available to students through a variety of methods, because individual learning styles and preferences vary considerably. Regardless of the educational philosophy adopted, students should be placed at the centre of the process. Moreover, it is critical that they are encouraged to take responsibility for their own learning. Other improvements suggested include increased formative assessment and self-assessment opportunities, reflective portfolios, collaborative learning, familiarization with and increased implementation of information and communication technology applications, early clinical exposure, greater emphasis on qualitative criteria in clinical education, community placements, and other extracurricular experiences such as international exchanges and awareness of minority and global health issues. The establishment of a global network in dental education is firmly supported but to be effective it will need active student representation and involvement.

Reliability and validity of the Thai version of the PHQ-9

Abstract: Most depression screening tools in Thailand are lengthy. The long process makes them impractical for routine use in primary care. This study aims to examine the reliability and validity of a Thai version Patient Health Questionnaire (PHQ-9) as a screening tool for major depression in primary care patients. The English language PHQ-9 was translated into Thai. The process involved back-translation, cross-cultural adaptation, field testing of the pre-final version, as well as final adjustments. The PHQ-9 was then administered among 1,000 patients in family practice clinic. Of these 1,000 patients, 300 were further assessed by the Thai version of the Mini International Neuropsychiatric Interview (MINI) and the Thai version of the Hamilton Rating Scale for Depression (HAM-D). These tools served as gold-standards for diagnosing depression and for assessing symptom severity, respectively. In the assessment, reliability and validity analyses, and receiver operating characteristic curve analysis were performed. Complete data were obtained from 924 participants and 279 interviewed respondents. The mean age of the participants was 45.0 years (SD = 14.3) and 73.7% of them were females. The mean PHQ-9 score was 4.93 (SD = 3.75). The Thai version of the PHQ-9 had satisfactory internal consistency (Cronbach's alpha = 0.79) and showed moderate convergent validity with the HAM-D (r = 0.56; P < 0.001). The categorical algorithm of the PHQ-9 had low sensitivity (0.53) but very high specificity (0.98) and positive likelihood ratio (27.37). Used as a continuous measure, the optimal cut-off score of PHQ-9 ≥ 9 revealed a sensitivity of 0.84, specificity of 0.77, positive predictive value (PPV) of 0.21, negative predictive value (NPV) of 0.99, and positive likelihood ratio of 3.71. The area under the curve (AUC) in this study was 0.89 (SD = 0.05, 95% CI 0.85 to 0.92). The Thai version of the PHQ-9 has acceptable psychometric properties for screening for major depression in general practice with a recommended cut-off score of nine or greater.

Molecular Characterization and Epidemiology of Extended-Spectrum- β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Isolates Causing Health Care-Associated Infection in Thailand, Where the CTX-M Family Is Endemic

Abstract: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae have rapidly spread worldwide and pose a serious threat for health care-associated (HA) infection. We conducted molecular detection and characterization of ESBL-related bla genes, including bla TEM , bla SHV , bla CTX-M , bla VEB , bla OXA , bla PER , and bla GES , among 362 isolates of ESBL-producing E. coli ( n = 235) and ESBL-producing K. pneumoniae ( n = 127) collected from patients who met the definition of HA infection at two major university hospitals in Thailand from December 2004 to May 2005. The prevalence of ESBL-producing E. coli and ESBL-producing K. pneumoniae , patient demographics and the susceptibilities of these bacteria to various antimicrobial agents were described. A total of 87.3% of isolates carried several bla genes. The prevalence of bla CTX-M was strikingly high: 99.6% for ESBL-producing E. coli (CTX-M-14, -15, -27, -40, and -55) and 99.2% for ESBL-producing K. pneumoniae (CTX-M-3, -14, -15, -27, and -55). IS Ecp1 was found in the upstream region of bla CTX-M in most isolates. Up to 77.0% and 71.7% of ESBL-producing E. coli and ESBL-producing K. pneumoniae , respectively, carried bla TEM ; all of them encoded TEM-1. ESBL-producing K. pneumoniae carried bla SHV at 87.4% (SHV-1, -2a, -11, -12, -27, -71, and -75) but only at 3.8% for ESBL-producing E. coli (SHV-11 and -12). bla genes encoding VEB-1 and OXA-10 were found in both ESBL-producing E. coli (8.5% and 8.1%, respectively) and ESBL-producing K. pneumoniae (10.2% and 11.8%, respectively). None of the isolates were positive for bla PER and bla GES . Pulsed-field gel electrophoresis analysis demonstrated that there was no major clonal relationship among these ESBL producers. This is the first study to report CTX-M-3, CTX-M-27, CTX-M-40, SHV-27, SHV-71, and SHV-75 in Thailand and to show that CTX-M ESBL is highly endemic in the country.

The transcriptome of Plasmodium vivax reveals divergence and diversity of transcriptional regulation in malaria parasites

Abstract: Plasmodium vivax causes over 100 million clinical infections each year. Primarily because of the lack of a suitable culture system, our understanding of the biology of this parasite lags significantly behind that of the more deadly species P. falciparum. Here, we present the complete transcriptional profile throughout the 48-h intraerythrocytic cycle of three distinct P. vivax isolates. This approach identifies strain specific patterns of expression for subsets of genes predicted to encode proteins associated with virulence and host pathogen interactions. Comparison to P. falciparum revealed significant differences in the expression of genes involved in crucial cellular functions that underpin the biological differences between the two parasite species. These data provide insights into the biology of P. vivax and constitute an important resource for the development of therapeutic approaches.

The role of anti-malarial drugs in eliminating malaria

Abstract: Effective anti-malarial drug treatment reduces malaria transmission. This alone can reduce the incidence and prevalence of malaria, although the effects are greater in areas of low transmission where a greater proportion of the infectious reservoir is symptomatic and receives anti-malarial treatment. Effective treatment has greater effects on the transmission of falciparum malaria, where gametocytogenesis is delayed, compared with the other human malarias in which peak gametocytaemia and transmissibility coincides with peak asexual parasite densities. Mature Plasmodium falciparum gametocytes are more drug resistant and affected only by artemisinins and 8-aminoquinolines. The key operational question now is whether primaquine should be added to artemisinin combination treatments for the treatment of falciparum malaria to reduce further the transmissibility of the treated infection. Radical treatment with primaquine plays a key role in the eradication of vivax and ovale malaria. More evidence is needed on the safety of primaquine when administered without screening for G6PD deficiency to inform individual and mass treatment approaches in the context of malaria elimination programmes.

Antifungal potential of extracellular metabolites produced by Streptomyces hygroscopicus against phytopathogenic fungi.

Abstract: Indigenous actinomycetes isolated from rhizosphere soils were assessed for in vitro antagonism against Colletotrichum gloeosporioides and Sclerotium rolfsii. A potent antagonist against both plant pathogenic fungi, designated SRA14, was selected and identified as Streptomyces hygroscopicus. The strain SRA14 highly produced extracellular chitinase and β-1,3-glucanase during the exponential and late exponential phases, respectively. Culture filtrates collected from the exponential and stationary phases inhibited the growth of both the fungi tested, indicating that growth suppression was due to extracellular antifungal metabolites present in culture filtrates. The percentage of growth inhibition by the stationary culture filtrate was significantly higher than that of exponential culture filtrate. Morphological changes such as hyphal swelling and abnormal shapes were observed in fungi grown on potato dextrose agar that contained the culture filtrates. However, the antifungal activity of exponential culture filtrates against both the experimental fungi was significantly reduced after boiling or treatment with proteinase K. There was no significant decrease in the percentage of fungal growth inhibition by the stationary culture filtrate that was treated as above. These data indicated that the antifungal potential of the exponential culture filtrate was mainly due to the presence of extracellular chitinase enzyme, whereas the antifungal activity of the stationary culture filtrate involved the action of unknown thermostable antifungal compound(s).

Osseointegration of zirconia implants compared with titanium: an in vivo study.

Abstract: Titanium and titanium alloys are widely used for fabrication of dental implants. Since the material composition and the surface topography of a biomaterial play a fundamental role in osseointegration, various chemical and physical surface modifications have been developed to improve osseous healing. Zirconia-based implants were introduced into dental implantology as an altenative to titanium implants. Zirconia seems to be a suitable implant material because of its tooth-like colour, its mechanical properties and its biocompatibility. As the osseointegration of zirconia implants has not been extensively investigated, the aim of this study was to compare the osseous healing of zirconia implants with titanium implants which have a roughened surface but otherwise similar implant geometries. Forty-eight zirconia and titanium implants were introduced into the tibia of 12 minipigs. After 1, 4 or 12 weeks, animals were sacrificed and specimens containing the implants were examined in terms of histological and ultrastructural techniques. Histological results showed direct bone contact on the zirconia and titanium surfaces. Bone implant contact as measured by histomorphometry was slightly better on titanium than on zirconia surfaces. However, a statistically significant difference between the two groups was not observed. The results demonstrated that zirconia implants with modified surfaces result in an osseointegration which is comparable with that of titanium implants.

Randomized controlled trial and meta-analysis of oral decontamination with 2% chlorhexidine solution for the prevention of ventilator-associated pneumonia.

Abstract: Objective. To determine the effectiveness of oral decontamination with 2% chlorhexidine solution for the prevention of ventilator‐associated pneumonia (VAP). Design. Randomized controlled trial and meta‐analysis. Setting. A tertiary care university hospital in Bangkok, Thailand. Participants. Adult patients who received mechanical ventilation and who were hospitalized in intensive care units and general medical wards. Methods. The patients were randomized to receive oral decontamination with 2% chlorhexidine solution or normal saline solution 4 times per day until their endotracheal tubes were removed. The outcome measures were the development of VAP and oropharyngeal colonization with gram‐negative bacilli. Meta‐analysis was performed by combining the results of the present study with those from another randomized controlled trial that also used a 2% chlorhexidine formulation for oral decontamination. Results. The characteristics of the patients in the chlorhexidine group ( \documentclass{aastex} \usepac...

The Relationship between Age and the Manifestations of and Mortality Associated with Severe Malaria

Abstract: P ! .001 decreased risk of death among children (adjusted odds ratio, 0.06; 95% confidence interval, 0.01–0.23; ) P ! .001 and the increased risk of death among patients aged 150 years (adjusted odds ratio, 1.88; 95% confidence interval, 1.01–3.52; ) was independent of the variation in presenting manifestations. The incidence of anemia and P p .046 convulsions decreased with age, whereas the incidence of hyperparasitemia, jaundice, and renal insufficiency increased with age. Coma and metabolic acidosis did not vary with age and were the strongest predictors of a fatal outcome. The number of severity signs at hospital admission also had a strong prognostic value. Conclusion. Presenting syndromes in severe malaria depend on age, although the incidence and the strong prognostic significance of coma and acidosis are similar at all ages. Age is an independent risk factor for a fatal outcome of the disease.

Direct In Vivo Assessment of Microcirculatory Dysfunction in Severe Falciparum Malaria

Abstract: Background This study sought to describe and quantify microcirculatory changes in the mucosal surfaces of patients with severe malaria, by direct in vivo observation using orthogonal polarization spectral (OPS) imaging. Methods The microcirculation in the rectal mucosa of adult patients with severe malaria was assessed by use of OPS imaging, at admission and then daily. Comparison groups comprised patients with uncomplicated falciparum malaria, patients with bacterial sepsis, and healthy individuals. Results Erythrocyte velocities were measured directly in 43 adult patients with severe falciparum malaria, of whom 20 died. Microcirculatory blood flow was markedly disturbed, with heterogeneous obstruction that was proportional to severity of disease. Blocked capillaries were found in 29 patients (67%) and were associated with concurrent hyperdynamic blood flow (erythrocyte velocity, >750 mm/s) in adjacent vessels in 27 patients (93%). The proportion of blocked capillaries correlated with the base deficit in plasma and with the concentration of lactate. Abnormalities disappeared when the patients recovered. In healthy individuals and in patients with uncomplicated malaria or sepsis, no stagnant erythrocytes were detected, and, in patients with sepsis, hyperdynamic blood flow was prominent. Conclusion Patients with severe falciparum malaria show extensive microvascular obstruction that is proportional to the severity of the disease. This finding underscores the prominent role that microvascular obstruction plays in the pathophysiology of severe malaria and illustrates the fundamental difference between the microvascular pathophysiology of malaria and that of bacterial sepsis.

Adiposity in women and children from transition countries predicts decreased iron absorption, iron deficiency and a reduced response to iron fortification

Abstract: Overweight is increasing in transition countries, while iron deficiency remains common. In industrialized countries, greater adiposity increases risk of iron deficiency. Higher hepcidin levels in obesity may reduce dietary iron absorption. Therefore, we investigated the association between body mass index (BMI) and iron absorption, iron status and the response to iron fortification in populations from three transition countries (Thailand, Morocco and India). In Thai women (n=92), we examined the relationship between BMI and iron absorption from a reference meal containing ∼4 mg of isotopically labeled fortification iron. We analyzed data from baseline (n=1688) and intervention (n=727) studies in children in Morocco and India to look for associations between BMI Z-scores and baseline hemoglobin, serum ferritin and transferrin receptor, whole blood zinc protoporphyrin and body iron stores, and changes in these measures after provision of iron. In the Thai women, 20% were iron deficient and 22% were overweight. Independent of iron status, a higher BMI Z-score was associated with decreased iron absorption (P=0.030). In the Indian and Moroccan children, 42% were iron deficient and 6.3% were overweight. A higher BMI Z-score predicted poorer iron status at baseline (P<0.001) and less improvement in iron status during the interventions (P<0.001). Adiposity in young women predicts lower iron absorption, and pediatric adiposity predicts iron deficiency and a reduced response to iron fortification. These data suggest the current surge in overweight in transition countries may impair efforts to control iron deficiency in these target groups. Interactions of the ‘double burden’ of malnutrition during the nutrition transition may have adverse consequences.

Wheat germ cell-free system-based production of malaria proteins for discovery of novel vaccine candidates.

Abstract: One of the major bottlenecks in malaria research has been the difficulty in recombinant protein expression. Here, we report the application of the wheat germ cell-free system for the successful production of malaria proteins. For proof of principle, the Pfs25, PfCSP, and PfAMA1 proteins were chosen. These genes contain very high A/T sequences and are also difficult to express as recombinant proteins. In our wheat germ cell-free system, native and codon-optimized versions of the Pfs25 genes produced equal amounts of proteins. PfCSP and PfAMA1 genes without any codon optimization were also expressed. The products were soluble, with yields between 50 and 200 μg/ml of the translation mixture, indicating that the cell-free system can be used to produce malaria proteins without any prior optimization of their biased codon usage. Biochemical and immunocytochemical analyses of antibodies raised in mice against each protein revealed that every antibody retained its high specificity to the parasite protein in question. The development of parasites in mosquitoes fed patient blood carrying Plasmodium falciparum gametocytes and supplemented with our mouse anti-Pfs25 sera was strongly inhibited, indicating that both Pfs25-3D7/WG and Pfs25-TBV/WG retained their immunogenicity. Lastly, we carried out a parallel expression assay of proteins of blood-stage P. falciparum. The PCR products of 124 P. falciparum genes chosen from the available database were used directly in a small-scale format of transcription and translation reactions. Autoradiogram testing revealed the production of 93 proteins. The application of this new cell-free system-based protocol for the discovery of malaria vaccine candidates will be discussed.

Dural Arteriovenous Shunts: A New Classification of Craniospinal Epidural Venous Anatomical Bases and Clinical Correlations

Abstract: Dural arteriovenous shunts (DAVSs)are abnormal shunts within the dura. Theoretically, they can occur at any site within the dura, but most frequently they develop near the venous sinuses. Venous drainage may occur into the dural sinuses, into osteodural veins, retrogradely via leptome- ningeal veins toward the cortical cerebral, cerebellar, or perimedullary veins,or any combination thereof. Arterial supply is usually from adjacent branches of the dural arteries, less frequently from osseous branches, while pial supply is rare.

Effect of charged and non-ionic membrane additives on physicochemical properties and stability of niosomes.

Abstract: The aim of this study was to investigate an influence of different types of membrane additives including negative charge (dicetylphosphate, DCP), positive charge (stearylamine, STR) and non-ionic molecule (cholesteryl poly-24-oxyethylene ether, SC24) on the physicochemical properties of drug-free and drug-loaded niosomes. Salicylic acid having different proportions of ionized and unionized species at different pH was selected as a model drug. The niosomes were composed of 1:1 mole ratio of Span 60: cholesterol as vesicle forming agents. The results show that incorporation of salicylic acid to the niosomes did not affect zeta potential values; however, addition of the membrane additives changed the zeta potential depending on the type of the additives. Transmission electron microscopy revealed that niosomes had unilamellar structure. The particle sizes of all developed niosomes were between 217 to 360 nm. The entrapment efficiency (%E.E.) of all salicylic acid niosomes at pH 3 was higher than that of niosomes at pH 5, indicating that salicylic acid in unionized form was preferably incorporated in niosomes. Furthermore, the positively charged niosomes showed the highest %E.E. of salicylic acid owing to electrostatic attraction between STR and salicylic acid. After 3 months of storage at 4°C, the particle size of the niosomes remained in the nanosize range except for DCP salicylic acid niosomes at pH 3 whose size increased due to an instability of DCP at low pH. In addition, all niosomes showed no leakage of the salicylic acid after 3 months of storage indicating the good stability.