Asian Biomedicine (Research Reviews and News)
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Item The three-dimensional structure of vascular smooth muscle cells: a confocal laser microscopic study of rabbit mesenteric arterioles.(2007-06) Nakano, Atsushi; Minamiyama, Motomu; Seki, JunjiBackground: Information of the three dimensional (3D) structure of vascular smooth muscle cells (VSMCs) is essential for understanding the regulatory mechanism of blood flow in the microvascular system. objective: To examine the 3D structure of individual VSMCs in rabbit mesenteric arterioles, using confocal laser scanning microscopy. Methods: Japanese white rabbits were anesthetized with urethane and α-chlorase. After intravital observation of the mesenteric microcirculation under a videomicroscope, the intestine with mesentery was extracted and perfused and fixed with paraformaldehyde under a static pressure (100 mmHg). A section of the mesentery was isolated from the intestine and spread out to simulate the in vivo geometry of the the vascular network. The mesenteric section was stained with fluorescein anti-smooth muscle myosin antibody and rhodamine-labeled anti-rabbit Ig antibody. The samples were observed using confocal laser microscopy, and the 3D images were reconstructed by means of sliced images. The cross-sectional image was re-sliced to measure two axes of the best-fitting ellipse. Single VSMCs were picked out from the vascular wall using the continuity law of density distribution of vessel wall. Results: The cross-sectional shapes of arterioles were not circular but elliptical. The aspect ratio (major to minor axis) of the best-fitting ellipse was in the range from 0.3 to 0.7 for 28 arterioles (diameters: 10-30 μm). On the 3D image of VSMCs, the cell width ranged from 2.2 to 4.5 μm. The cells were classified into round and spindle types. The cell width of round shape was significantly larger than that of spindle shape. The VSMCs appeared to arrange circumferentially and tightly along the cross-section along the axis of vessel. The mean length of single VSMCs was approximately 1.2 times of the circumferential length of the arteriole. This cellular arrangement may have influence on the distribution of mechanical stress by VSMC-induced myogenic force. Conclusion: Confocal laser microscopy is useful for quantitative analysis of the 3D arrangement of individual VSHCs.Item Australia is not rabies-free.(2007-06) Gherardin, TonyBackground: Human rabies is a disease transmitted mainly by bites from infected mammals. Australia has a lyssavirus present among various bat species. The risk to individuals in Australia is low, and bat-handlers within Australia are at greatest risk. For Australians travelling internationally, dogs in the developing world represent a greater risk. Objective: To highlight the major strategies for prevention of rabies infections, both within Australia and for Australians travelling overseas. Discussion: Prevention for individuals involves an understanding of risk and avoidance of vectors, the routine use of post-exposure prophylaxis and consideration of pre-exposure prophylactic immunisation. A new rabies vaccine for post-exposure prophylaxis and for pre-exposure immunisation has become available. Australian medical practitioners need to be familiar with these preventive strategies and vaccines. Travellers to Australia must beware of contact with bats.Item Crystalline composition and etiologic factors of kidney stone in Thailand : update 2007.(2007-06) Tosukhowong, Piyaratana; Boonla, Chanchai; Ratchanon, Supoj; Tanthanuch, Monthira; Poonpirome, Kanitta; Supataravanich, Pholasith; Dissayabutra, Thasinas; Tungsanga, KriangObjective: The etiology of kidney stone is multifactorial including environmental, behavioral and genetic. Insights about predisposing causes and mineral composition are mandatory for better management of kidney stone disease. The present hospital-based study aims to explore the mineral constituents and etiologic risks of kidney stones in Thai patients from the four geographic regions of the country. Method: Two hundred and fifty six kidney stone patients from four geographic regions of Thailand, including the northeastern (n=103), the northern (n=81), the central (n=47) and the southern (n=25) were recruited in this study. Of these, 144 patients completed the food frequency questionnaire to assess the kidney stone risk. Mineral composition of stones were analyzed by Fourier transformed infrared spectrometry. Results: Kidney stone frequently affected peoples aged 40-49 years. Only 31.9 % of patients had a positive family history of renal stone. Calcium oxalate (CaOx) stone was the most prevalent type (73.8 %). Uric acid (UA) stone was found in 16.0 % commonly affected peoples aged 60-70 years. Mixed stones, notably CaOx mixed with calcium phosphate (CaP), were more prevalent than pure stones. The food frequency questionnaire data showed that 59.7 % of stone patients consumed less than two liters of water per day. Low intakes of fruits and vegetables were notably present. In contrast, high consumption of rice was observed in over 65 % of stone patients. Conclusion: CaOx mixed with CaP was the most prevalent stone type. UA stone was more likely to occur in the elderly. Kidney stone patients were found to consume less-than-adequate amounts of water, food high in carbohydrates, along with low consumtion of fruits and vegetables. These dietary habits might be risk factors in stone development among the Thai population.Item Blood flow control in the brain: possible biphasic mechanism of functional hyperemia.(2007-06) Tomita, MinoruBackground: About 120 years ago, Roy and Sherrington hypothesized that the cerebral blood flow (CBF) is closely coupled to metabolism, and metabolism is closely coupled to function. This concept has colored all subsequent inquiries. However, recent studies have revealed a temporal and spatial mismatch between changes in CBF and metabolism. Objective: This article aims to reappraise the nature of functional hyperemia in response to somatosensory stimuli. Method: Firstly, the author discusses what is known and unknown about the control of CBF, reviewing the traditional concepts of autoregulation, neurogenic control, metabolic control and the role of endothelial cells. Secondly, recent papers showing a mismatch or uncoupling between function, metabolism and flow are considered. Thirdly, the reviewer uses his own published and unpublished data to point out the intrinsic and largely unrecognized limitations of spectroscopic techniques for evaluation of oxygen metabolism. Finally, a novel hypothesis is presented concerning the nature of functional hyperemia. Results and conclusion: The reviewer deduces that the initial flow increase in functional hyperemia is elicited by central neural systems, since it is reported that the central cholinergic pathway increases CBF immediately after the onset of somatosensory stimuli. The flow increase occurs concurrently with neuronal activation, but is much faster than the increase of neuronal metabolism. The novel hypothesis is proposed that functional hyperemia is biphasic: an initial flow increase under central neural control and a delayed increase is under traditional metabolic control. The metabolic phase may supply more blood than is needed, and may last even after discontinuation of the stimulation (overcompensation). These two phases of hyperemia are suggested to be well mixed, presumably in glial processes, which coordinate blood redistribution in the surrounding microvascular network. Many stimuli from the environment might be managed simply by the neurogenic control of functional hyperemia, without the metabolic change.Item Drug addiction: a view from the law enforcement field(2007-06) -, -Item Prevalence of glucose-6-phosphate dehydrogenase deficiency in U.S. military.(2007-06) Chinevere, T D; Murray, C K; Grant, E Jr; Johnson, G A; Duelm, FItem The 2007 rabies in Asia congress at Bangalore, India(2007-06) -, -Item WHO guidelines dealing with immunoglobulin use impede rabies prevention.(2007-06) Anderson, David CItem Chromogenic in situ hybridization using routine tissue sections: MYCN in neuroblastoma.(2007-06) Thorner, Paul S; Ho, Michael; Zielenska, MariaBackground: Amplification of the MYCN (myc myelocytomatosis viral related oncogene, neuroblastoma derived) gene in neuroblastoma is associated with a poor prognosis. Methods for estimating MYCN gene copy number that are based on pooled cells do not address copy number heterogeneity at the cell level and can underestimate or even miss amplification. MYCN copy number can be directly assessed by fluorescence in situ hybridization, but evaluation of tissue histology is difficult if not impossible. Objective: This paper reviews chromogenic in situ hybridization (CJSH) as it applies to the MYCN gene in neuroblastoma. We compare this technique to other methods for determining gene copy number and highlight the advantages of CISH. Methods: We have developed a chromogenic method for in situ hybridization (CISH) that enables us to determine MYCN copy number on an individual cell basis. This technique uses light microscopy on routine paraffin sections, and therefore allows simultaneous assessment of tumour histology. Results: In a previous study, CISH identified 100 % of the cases that were known to be amplified by other techniques and proved to be more sensitive than Southern blotting or the quantitative DNA polymerase chain reaction. The MYCN copy number is generally believed not to vary within a tumour, nor between tumour samples, including primary vs. metastases, and pre-and post-treatment specimens. However, we found heterogeneity from cell to cell, with ~30 % of amplified tumours showing >50 % variation in MYCN copy between cells. Conclusion: For detection of gene amplification, CISH has all the advantages of FISH but in addition, needs no special microscopy or image capturing systems, and preparations are permanent. In the case of neuroblastoma, CISH has disclosed considerable heterogeneity in MYCN copy number between cells in a tumour. Heterogeneity reflects different tumour clones and its role has been under-recognized in neuroblastoma biology. Additional studies are needed to investigate the significance of tumour heterogeneity in neuroblastoma, and whether the aggressive (i.e., MYCN-amplified) clones are more likely to metastasize, survive treatment modalities, and ultimately kill the patient.Item D-dimer as an indicator of dengue severity.(2007-06) Setrkraising, Kittiya; Bongsebandhu-phubhakdi, Chansuda; Voraphani, Nipasiri; Pancharoen, Chitsanu; Thisyakorn, Usa; Thisyakorn, ChuleBackground: Dengue infection is a problem of global concern. The clinical spectrum of the disease varies from an acute febrile course accompanied by mild hemorrhagic manifestations with uneventful recovery to refractory shock and massive bleeding with high mortality. Several mechanisms may be involved in the pathogenesis of bleeding, namely: vasculopathy, thrombocytopenia, coagulopathy and dissiminated intravascular coagulopathy (DIC). Objective: To determine the relationship between D-dimer (DD) levels and clinical outcome in dengue patients. Method: Children with suspected dengue infection admitted to King Chulalongkorn Memorial Hospital were enrolled. D-dimer (DD) was sequentially measured during the course of illness using whole blood and a rapid semiquantitative system (SimpliRed). Diagnosis of dengue infection was confirmed by serology and WHO criteria were used for classifying dengue severity. Results: 41 dengue patients, 22 girls and 19 boys were recruited in the study. The mean age was 9.68 years. There were 12 (29.3 %) cases of dengue fever (DF) and 29 (70.7 %) cases of dengue hemorrhagic fever (DHF). DD was more significantly present in the DHF group (87 %) than in the DF group (13%) (P<0.03). The sensitivity and specificity of DD in predicting severe dengue infection (DHF) were 90% and 67 %, respectively. Sequential analysis of DD showed higher levels at all stages of dengue infection. It correlated with the disease severity. Conclusion: Semiquantitative DD assay measurements in children suffering from dengue infection significantly correlated with dengue severity.Item Oral appliances for the treatment of obstructive sleep apnea.(2007-06) Horchover, Robert LBackground: Obstructive sleep apnea (OSA) is a disabling condition which reduces the sufferer’s ability to work effectively due to somnolence during the day. It can be life threatening, resulting in nocturnal anoxia and cardiac arrythmias. OSA is due to intermittent cessation of airflow at the upper airway level of at least 10 seconds duration. Severe cases may stop breathing for 2-3 minutes. It is a rare condition with a prevalence of up to 4 percent in middle aged adults. OSA can be due to central apnea where the neural drive is transiently abolished. In obstructive apnea, the neural drive remains but there is occlusion of the oropharyngieal airway. Therapeutic approaches range from weight reduction, improving nasal patency, avoidance of alcohol and sleeping in the supine position and may include surgical procedures to increase the airway space. Continuous positive airway pressure (CPAP) at night is a common therapeutic modality but not always tolerated by the patient. Objective: This essay reviews current practices using airway dilators.Item History and evolution of western medicine in Thailand.(2007-06) Charuluxananan, Somrat; Chentanez, VilaiBackground: Western medicine entered into the Kingdom of Siam for the first time in Ayutthaya Period. In 1686, Chevalier de Forbin, a French military officer described a surgical operation in which the stomach and intestine of a patient were restored into the abdomen and the surgical wound closed by suturing, without complication. Soon after this the relationship between Thailand and Europe was severed until it was renewed in the Bangkok Period. Thailand’s first hospital was built in the province of Petchaburi in 1878. The first hospital built by the government of Thailand was Siriraj Hospital in 1887; and the Red Cross Society was founded in 1893. King Chulalongkorn Memorial Hospital was established in 1914. Chulalongkorn University was established with the Faculty of Medicine in 1916. In 1942, the Ministry of Public Health was established to regulate medical services and public health of the people of Thailand. Objective: To introduce the history and development of western medicine in Thailand.Item Therapeutic strategy towards renal restoration in chronic kidney disease.(2007-06) Futrakul, Narisa; Sila-asna, Monnipha; Futrakul, PrasitBackground: The population with end-stage renal disease is increasing. This continued growth is related to: i) diagnostic failure in screening for early chronic kidney disease (CKD) associated with tubulointerstitial fibrosis (TIF), ii) failure in preventing renal disease progression due to lack of understanding of the precise determinants that induce TIF, and iii) delayed treatment which simply slows renal disease progression, but is unable to restore renal function. Objective: To review therapeutic strategy to restore renal function in CKD stressing fractional excretion of magnesium (FE Mg) as a sensitive biomarker for screening early CKD associated with TIF. Results: There is much evidence to support the crucial role of renal microvascular disease as the determinant of TIF and disease progression. A unique pattern of hemodynamic maladjustment is characterized by a preferential constriction of the efferent arteriole that induces peritubular capillary flow reduction in CKDs. Conclusion: The present information leads to a therapeutic strategy to restore renal function in early CKD patients.Item Prevention and control of thalassemia in Asia.(2007-06) Fucharoen, Suthat; Winichagoon, PraneeThalassemia and abnormal hemoglobin are the most common inherited diseases. The only treatment readily available in most countries is regular blood transfusion and iron chelation that is recommended in severely anemic patients with iron overload. In the last 20 years there has been much progress in terms of diagnosing, preventing and managing thalassemia. This has lead to the success of prevention and control of thalassemia in many Mediterranean countries such as Cyprus, Italy and Greece. Objective: To introduce approaches that may be applied for the control of thalassemia in developing countries including Asia where thalassemias are very prevalent.Item Leukocyte-endothelial cell interaction is attenuated by low-intensity exercise training and vitamin C supplementation in diabetic rats.(2007-06) Chakraphan, Daroonwan; Sridulyakul, Patarin; Thipakorn, Bundit; Bunnag, Srichitra; Huxley, Virginia H; Patumraj, SuthilukObjective: To determine the effects of vitamin C supplementation and low-intensity exercise training on diabetesinduced endothelial dysfunction. Methods: Male Spraque-Dawley rats were randomly divided into five groups: control (Con), diabetes (DM) (streptozotocin; 50 mg/kg BW, i.v.), diabetes with supplemented vitamin C (DM+Vit.C; 1 g/L mixed in drinking water), diabetes with low-intensity exercise-trained (DM+Ex; running 5 times/week with 13-15 m/min velocity for 30 minutes) and diabetes with supplemented vitamin C and exercisetrained (DM+Vit.C+Ex) groups. The number of leukocyte-endothelial cell (EC) interactions in mesenteric postcapillary venules was monitored using intravital fluorescence videomicroscopy. Liver malondialdehyde (MDA) level, an indicator for oxidative stress, was determined by using the thiobarbituric acid reaction. Results: At 24 weeks, the plasma vitamin C level was significantly increased (p<0.05) in DM+Vit.C and DM+Vit.C+Ex rats when compared with DM rats. DM+Ex and DM+Vit.C+Ex rats had lower triglyceride levels and heart weights when compared with DM rats (P<0.05). Mean arterial pressures were significantly decreased in all treatment groups. DM rats had significantly higher malondialdehyde (MDA) levels and lower activities of superoxide dismutase (SOD) than Con. The number of adherent leukocytes and levels of MDA were significantly lower in DM+Vit.C, DM+Ex and DM+Vit.C+Ex than those of DM rats. Conclusion: The increased leukocyte-EC adherence in diabetic rats is significantly related to increased ROS, based on lower MDA levels. Vitamin C supplementation and regular low-intensity exercise training can prevent these deleterious effects, including hypertension, cardiac hypertrophy, hypertriglyceridemia, and leukocyte-EC adherence. Vitamin C supplementation combined with low-intensity exercise training is highly effective in preventing diabetic cardiovascular complications.Item A prospective study of enterovirus infection in Thai infants presenting as sepsis.(2007-06) Petwijit, Taninee; Desudchit, Tayard; Punnahitanonda, Santi; Wacharapluesadee, Supaporn; Hemachudha, ThiravatObjective: To study prospectively the prevalence, clinical presentations and laboratory findings of enterovirus (EV) infection in infants under 3 months of age who present as a sepsis-like syndrome. Method: All infants less than 3 month of age admitted as a sepsis-like syndrome to King Chulalongkorn Memorial Hospital between April 2003 and February 2004 were included. Patients who were immunocompromised or who had been admitted for longer than 14 days before developing symptoms were excluded. A detailed history, physical and laboratory findings were recorded and analyzed. Specimens of blood and cerebrospinal fluid were tested for enteroviruses using Nucleic Acid Sequence-Based Amplification (NASBA). Patients were followed to determine the clinical outcome and duration of hospitalization. Results: Of 56 infants, thirty-six were admitted to the pediatric wards and 20 had been hospitalized since birth in the neonatal intensive care unit (NICU) or nursery wards. Enterovirus infection was diagnosed in 13 (36.1 %) of the patients admitted to the pediatric wards and none in the group of NICU/nursery patients. The most common clinical presentations were high grade fever (92 %), rashes (77 %) and lethargy (54 %) as compared to fever (78.3 %), poor feeding (60.9 %) and lethargy (56.5 %) in the EV negative group. Ten (76.9 %) of the enterovirus positive infants had evidence of central nervous system (CNS) involvement as evidenced by the presence of EV RNA in cerebrospinal fluid (CSF) or CSF pleocytosis plus EV RNA in blood and/or CSF. Nevertheless, CSF pleocytosis was found in only 7 infants (53.8 %). Average duration of illness was 3.2 days as compared to 3.5 days in the nonenteroviral group with similar clinical features. All enterovirus positive patients had an uncomplicated recovery. Ten (76.9 %) received parenteral antibiotics for a mean of 5 days (versus 4.8 days in enterovirus negative group). The average length of stay was 8.1 days as compared to 15 days in enterovirus negative group. Conclusion: Enterovirus infections are important causes of a sepsis-like syndromes in infants under 3 months of age. Most enterovirus infected patients presented with fever without localizing signs and rashes. Detection of enterovirus RNA by NASBA in serum and/or CSF represents a rapid method for the diagnosis of enterovirus infection in infants presenting with a sepsis-like syndrome.Item Quantitative PCR analysis for methylation level of genome: clinical implications in cancer.(2007-08) Mutirangura, ApiwatBackground: Cancer cells are frequently characterized by hypomethylation of the genome including repetitive sequences. This epigenetic process is believed to be associated with several biological causes and consequences in cancer. Therefore, LINE-1 repetitive sequences demethylation in cancer should result in different clinical outcomes. Objective: Recently, we have developed an improved quantitative combined bisulfite restriction analysis PCR protocol that efficiently evaluates the methylation status of LINE-1s; the method is referred to as PCR “COBRALINE-1”. This article reviewed what have been learned by applying this technique to study methylation level of repetitive sequences from several sources of genomic DNA. Results: We have found that LINE-1 methylation patterns among normal tissues are distinct. Therefore, this epigenetic event may be continuously altered in adult tissues by the process of cellular differentiation. Moreover, we confirmed that global hypomethylation is an ongoing process that develops during tumor progression, in addition to previous evidence of genomic and LINE-1 hypomethylation occurring as an early event in carcinogenesis. COBRALINE-1 is a highly effective technique for evaluating the genome-wide level of methylation, in particular from tissue samples with minute amounts of low quality DNA. The technique has been applied to study samples from micro-dissected archived paraffin-embedded tissues and sera of several types of cancer. Conclusion: The COBRALINE-1 technique demonstrated its potential to be a tumor marker and a great tool to explore the biology of global hypomethylation.Item In memory of Vikit Viranuvatti, father of Thai gastroenterology.(2007-08) Manatsathit, SathapornVikit Viranuvatti was a pioneer of modern medicine and the virtual father of gastroenterology in Thailand. His achievements, especially in tropical liver diseases, were recognized worldwide. He published more than 219 articles and several international book chapters dealing with liver cancer, amoebiasis, hepatic abscess, hepatitis as well as topics in medical education.Item Optical coherence tomography: a novel technique for the study of tissue microcirculation.(2007-08) Seki, JunjiBackground: Three-dimensional (3D) observation techniques are useful for understanding organ microcirculation. Optical coherence tomography (OCT) is one of the 3-D imaging techniques and is increasingly applied for tissue microcirculatory studies. Objective: This article reviews the current and prospective usages of OCT in microcirculation. Methods: OCT is an optical technique to obtain tomographic images of highly scattering media like living tissues by means of coherence gating, whose spatial resolution is down to 10 μm. It is also capable of obtaining velocity profiles of blood flow by use of Doppler frequency shift (Doppler OCT). Results: The OCT technique has been applied for observation of microvessels in rat skin, hamster dorsal skin, rat brain etc. Small microvessels down to 20 μm have been detected with the aid of Doppler OCT. Doppler OCT also revealed that the blood flow in microvessels is a quasi-steady laminar flow. The OCT signal from the cerebral cortex was found to change following neural activation, probably reflecting the functional hyperemia. Conclusion: The OCT technique combined with Doppler OCT technique has a great potential for in vivo observation of 3-D structures of microvessels and blood flow distribution. Further OCT is expected to be a depth-dependent imaging tool for the study of brain function.Item