Asian Biomedicine (Research Reviews and News)

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    Martin George Netsky: teacher in medical school
    (2007-10) Shuangshoti, Samruay
    Martin George Netsky, a teacher in the Medical School, was interested in neurology and pathology especially neuropathology and medical education. He helped to develop medical education at Chiang Mai Medical School, and neuropathology and immunohistochemistry at Chulalongkorn Medical School. For this, Dr Netsky arranged for Thai neuropathologists and an immunohistochemist to be trained in the United States. These persons, upon their return, established satisfactory services, teaching and research in neuropathology and immunohistochemistry. The immunohistochemistry was first utilized in neuropathology only but later was put to service in anatomic pathology by the Department of Pathology. Today, immunohistochemical laboratories have been set up in several places in Thailand.
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    Gene-modified bone marrow-derived stem cells: an attractive gene delivery system in inherited retinal disorders.
    (2007-10) Chotima, Boettcher
    Background: In spite of the therapeutic potential in several experimental models of inherited retinal degeneration, gene replacement therapy remains limited by technical/surgical difficulties of therapeutic gene delivery, and it seems to be effective only in young/neonatal animals. Bone marrow-derived stem cell (BMSC)-based therapy has been proposed as an alternative for treatment of retinal disorders. BMSC is a rich, inexhaustible source of potentially autologous adult stem cells. Despite numerous experimental evidences of their plasticity and therapeutic potential, the possibility that BMSC can populate the retina and differentiate into functionally retinal neurons and/or glia remains controversial. Objective: The issues of BMSC plasticity in the ocular system are reviewed. The therapeutic benefit of BMSC per se and gene-modified BMSC (as a vehicle for gene therapy) in inherited retinal disorders is discussed. Result: Recently, it was convincingly demonstrated that subpopulation of BMSC could restore the retinal function and structure by promoting/preserving the retinal vascularization rather than differentiating to retinal neurons/glia. In animal models of brain disorders, such as Parkinson s disease, BMSCs has been demonstrated as a promising vehicle for the delivery of therapeutic genes. Although little is known about the therapeutic potential of gene-modified BMSC in the ocular system, long-term engraftment and stable gene expression of gene-modified BMSCs have been shown in rodent retinas. Conclusion: The experimental evidences published over the past decade imply a possibility to use BMSC as a gene delivery system which can be simply transplanted and provide a stable long-term gene expression in the retina.
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    Curcumin as a therapeutic agent against cancer.
    (2007-10) Patumraj, Suthiluk; Yoysungneon, Pornprom
    Background: Curcumin is an important chemopreventive agent against cancer. Recently, it has been reported that curcumin has also anti-angiogenic effects in tumor. Objective: This article reviews the effect of curcumin against tumor angiogenesis from view-points of cancer microcirculation and biomarkers. Results and conclusion. We demonstrated an anti-angiogenic effect of curcumin in tumors using nude mice. We studied the inhibitory effects of curcumin on tumor-induced neocapillaries and proangiogenic factors, based on our intravital fluorescent observation. Finally, we hypothesized a possible mechanism for curcumin effect in tumor.
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    Tissue engineering for bone regeneration: stem cells and growth factors in biomaterial scaffolds.
    (2007-10) Honsawek, Sittisak; Parkpian, Vinai
    Background: Bone tissue engineering requires a scaffold conducive to cell attachment and maintenance of cell function, together with a rich source of osteoprogenitor cells in combination with osteoinductive growth factors. Bone loss as a result of trauma or disease is an increasingly serious health problem. The requirement for new bone to replace or restore the function of injured, damaged, or lost bone is a major clinical and socioeconomic need. Bone defects still represent a major challenge for orthopaedic and reconstructive surgeons. Objective: This review aims at outlining the role of stem cells and growth factors in scaffolds, focusing on the use of mesenchymal stem cells and bone morphogenetic proteins as applied to the research and practice of bone tissue engineering. Results and conclusion: Bone tissue engineering has been emerging as a valid approach to the current therapies for bone regeneration. Therefore, tissue engineering offers a number of possible strategies to the generation of living prosthesis that could integrate with host tissue reducing the need for further surgery or possible implant failure.
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    In memory of Vikit Viranuvatti, father of Thai gastroenterology.
    (2007-08) Manatsathit, Sathaporn
    Vikit 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.
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    Renoprotective effects of erythropoietin.
    (2007-08) Katavetin, Pisut; Eiam-Ong, Somchai; Nangaku, Masaomi
    Background: Accumulating evidences during the past decade suggest that erythropoietin (EPO) may have many beneficial actions other than on erythropoiesis because many non-hematopoietic cells, including kidney cells, also express EPO receptors. Objective: To summarize evidences of the renoprotective effects of EPO and review the possible mechanisms of renoprotection provided by EPO. Results: Experimental studies have demonstrated the renoprotective effects of EPO in acute as well as chronic renal injury models. These renoprotective actions are likely to be mediated by several mechanisms, either directly or indirectly. However, EPO therapy is also associated with adverse effects. Conclusion: EPO is potentially a novel renoprotective drug. Clinical use of EPO for renoprotection could not be beneficial if adverse side effects of EPO have been overcome.
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    Optical coherence tomography: a novel technique for the study of tissue microcirculation.
    (2007-08) Seki, Junji
    Background: 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.
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    Quantitative PCR analysis for methylation level of genome: clinical implications in cancer.
    (2007-08) Mutirangura, Apiwat
    Background: 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.
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    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, F
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    History and evolution of western medicine in Thailand.
    (2007-06) Charuluxananan, Somrat; Chentanez, Vilai
    Background: 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.
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    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, Kriang
    Objective: 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.
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    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, Junji
    Background: 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.
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    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, Suthiluk
    Objective: 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.
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    A prospective study of enterovirus infection in Thai infants presenting as sepsis.
    (2007-06) Petwijit, Taninee; Desudchit, Tayard; Punnahitanonda, Santi; Wacharapluesadee, Supaporn; Hemachudha, Thiravat
    Objective: 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.