Inflammation is an organism's response to environmental assaults. It can be classified as acute inflammation that leads to therapeutic recovery or chronic inflammation, which may lead to the development of cancer and other ailments. Genetic changes that occur within cancer cells themselves are responsible for many aspects of cancer development but are dependent on ancillary processes for tumor promotion and progression. Inflammation has long been associated with the development of cancer. The distinct characteristics of cancer cells to proliferate, metastasize, evade apoptotic signals, and develop chemoresistance have been linked to the inflammatory response. Due to the involvement of multiple genes and various pathways, current drugs that target single genes have not been effective in providing a therapeutic cure. On the other hand, natural products target multiple genes and therefore have better success compared to drugs. Tocotrienols, the potent isoforms of vitamin E, are such a natural product. This review will discuss the relationship between cancer and inflammation with particular focus on the roles played by NF-κB, STAT3, and COX-2.
Orangutan survival is threatened by habitat loss and illegal killing. Most wild populations will disappear over the next few decades unless threats are abated. Saving orangutans is ultimately in the hands of the governments and people of Indonesia and Malaysia, which need to ensure that habitats of viable orangutan populations are protected from deforestation and well managed to ensure no hunting takes place. Companies working in orangutan habitat also have to play a much bigger role in habitat management. Although the major problems and the direct actions required to solve them-reducing forest loss and hunting-have been known for decades, orangutan populations continue to decline. Orangutan populations in Sumatra and Borneo have declined by between 2,280 and 5,250 orangutans annually over the past 25 years. As the total current population for the two species is some 60,000 animals in an area of about 90,000 km(2) , there is not much time left to make conservation efforts truly effective. Our review discusses what has and has not worked in conservation to guide future conservation efforts.
A pig-borne virus causing viral encephalitis amongst human beings in Malaysia was detected in 1997 by the Ministry of Health. Initially, the disease was considered to be Japanese encephalitis. Subsequently, it was thought to be a Hendra-like viral encephalitis, but on 10th April, 1999 the Minister of Health announced this mysterious and deadly virus to be a new virus named Nipah virus. The virus was characterized at CDC, Atlanta, Georgia. The gene sequencing of the enveloped virus revealed that one of the genes had 21% difference in the nucleotide sequence with about 8% difference in the amino acid sequence from Hendra virus isolated from horses in Australia in 1994. The virus was named after the village Nipah. In all, the Ministry of Health declared 101 human casualties, and 900,000 pigs were culled by April, 1999. The worst affected area in Malaysia was Negri Sembilan. The symptoms, incubation period in human being and pigs, animal to human transmission, threat of disease to other livestock, and control program adopted in Malaysia is described.
Kunjin (KUN) is a flavivirus in the Japanese encephalitis antigenic complex that was first isolated from Culex annulirostris mosquitoes captured in northern Australia in 1960. It is the etiological agent of a human disease characterized by febrile illness with rash or mild encephalitis and, occasionally, of a neurological disease in horses. KUN virus shares a similar epidemiology and ecology with the closely related Murray Valley encephalitis (MVE) virus, the major causative agent of arboviral encephalitis in Australia. Based on traditional antigenic methods, KUN was initially found to be similar to, but distinct from, reference strains of West Nile (WN) virus and designated as a new species. However, more recent phylogenic analyses have revealed that some strains of WN virus, including the isolates from New York, are more similar to KUN virus and form a separate lineage to other WN viruses. An unusual KUN isolate from Malaysia and the African virus Koutango appear to form additional lineages within the WN group of viruses. While these findings are in agreement with the Seventh Report of the International Committee for the Taxonomy of Viruses that designates KUN as a subtype of West Nile, they also suggest that the species should be further subdivided into additional subtypes.
The last three decades have seen an alarming number of high-profile outbreaks of new viruses and other pathogens, many of them emerging from wildlife. Recent outbreaks of SARS, avian influenza, and others highlight emerging zoonotic diseases as one of the key threats to global health. Similar emerging diseases have been reported in wildlife populations, resulting in mass mortalities, population declines, and even extinctions. In this paper, we highlight three examples of emerging pathogens: Nipah and Hendra virus, which emerged in Malaysia and Australia in the 1990s respectively, with recent outbreaks caused by similar viruses in India in 2000 and Bangladesh in 2004; West Nile virus, which emerged in the New World in 1999; and amphibian chytridiomycosis, which has emerged globally as a threat to amphibian populations and a major cause of amphibian population declines. We discuss a new, conservation medicine approach to emerging diseases that integrates veterinary, medical, ecologic, and other sciences in interdisciplinary teams. These teams investigate the causes of emergence, analyze the underlying drivers, and attempt to define common rules governing emergence for human, wildlife, and plant EIDs. The ultimate goal is a risk analysis that allows us to predict future emergence of known and unknown pathogens.
Alterations in cellular levels of the second messenger 3',5'-cyclic adenosine monophosphate ([cAMP]i ) regulate a wide range of physiologically important cellular signaling processes in numerous cell types. Osteoclasts are terminally differentiated, multinucleated cells specialized for bone resorption. Their systemic regulator, calcitonin, triggers morphometrically and pharmacologically distinct retraction (R) and quiescence (Q) effects on cell-spread area and protrusion-retraction motility, respectively, paralleling its inhibition of bone resorption. Q effects were reproduced by cholera toxin-mediated Gs -protein activation known to increase [cAMP]i , unaccompanied by the [Ca2+ ]i changes contrastingly associated with R effects. We explore a hypothesis implicating cAMP signaling involving guanine nucleotide-exchange activation of the small GTPase Ras-proximate-1 (Rap1) by exchange proteins directly activated by cAMP (Epac). Rap1 activates integrin clustering, cell adhesion to bone matrix, associated cytoskeletal modifications and signaling processes, and transmembrane transduction functions. Epac activation enhanced, whereas Epac inhibition or shRNA-mediated knockdown compromised, the appearance of markers for osteoclast differentiation and motility following stimulation by receptor activator of nuclear factor kappa-Β ligand (RANKL). Deficiencies in talin and Rap1 compromised in vivo bone resorption, producing osteopetrotic phenotypes in genetically modified murine models. Translational implications of an Epac-Rap1 signaling hypothesis in relationship to N-bisphosphonate actions on prenylation and membrane localization of small GTPases are discussed.
Despite improvements in operative strategies for esophageal resection, anastomotic leaks, fistula, postoperative pulmonary complications, and chylothorax can occur. Our review seeks to identify potential risk factors, modalities for early diagnosis, and novel interventions that may ameliorate the potential adverse effects of these surgical complications following esophagectomy.
Alpha-Fetoprotein (AFP) levels of 1,335 males (15 years and older) of seven ethnic groups (Chinese, Indians, and Malays from Singapore, Caucasians from Lyon, and Blacks from Nairobi, forest, and the savanna region of the Ivory Coast) were determined by radioimmunoassay. A few elevated levels (up to 30 nanounits/ml) were detected in some normal individuals, especially in the older age-groups. In addition, there was a systematic age-dependency of AFP levels particularly evident in the groups from Singapore-Lyon, in which there was a 50% AFP increase between the ages of 20 and 40. Comparison between Africans on the one hand and people from Singapore-Lyon on the other hand revealed highly significant differences (p less than 0.001), especially in the younger groups, whereas Chinese, Malays, and Indians from Singapore had very similar AFP pattern; this suggests an important role for environmental factors in the regulation of AFP levels. The age dependency of the presumed effect of environmental factors is in keeping with experimental data showing that young animals respond more vigorously to AFP-stimulating factors. Although the incidence of hepatocellular carcinoma (HCC) differs in the three Singapore groups (the highest in Chinese and the lowest in Indians), no relationship was observed in this study between mean AFP level and HCC incidence in Singapore.
In this paper we first present methods and preliminary results of pilot surveys of "serious" mental retardation (IQ less than or equal to 55); the surveys included screening and diagnostic components and were carried out in the less-developed world. Next we discuss two problems raised by these surveys: one is the diagnosis of a case and its clinical dimensions, and the other is the interpretation of prevalence. In the next section we illustrate epidemiological approaches to the analysis of such data, in particular their relevance to prevention. Lastly, we propose that the two-stage survey approach developed in the course of the pilot work can provide a valuable basis for planning and prevention, if certain key conditions can be met.
Malaysia is steadily progressing toward an aging population demographic pattern. While aging is a natural process, its impact can be painful individually as well as for the nation. Individually there is a loss of a paying job after retirement, loss of physical and mental fitness, and also occasionally the loss of social integration due to lack of mobility. For a nation, an aging population means a growing dependency ratio, a greater need of care, and more medical facilities for this age group. This article looks at the various economic and social implications of the aging population in Malaysia in general, and in the rural and urban setting specifically. The paper focuses on a research sample of 132 (66 rural, 66 urban) elderly persons. The findings suggest that the demographic patterns of the elderly vary from the rural to the urban setting, with differing issues that need to be addressed to alleviate problems encountered related to loneliness, lack of financial stability, and emotional strain. Policy suggestion will be geared toward providing a solution to problems at hand as well as aiding the working group members to prepare and sustain a comfortable livelihood for the aged in their later years.
Nipah virus (NiV) is a highly pathogenic paramyxovirus, which emerged in 1998 from fruit bats in Malaysia and caused an outbreak of severe respiratory disease in pigs and fatal encephalitis in humans with high mortality rates. In contrast to most paramyxoviruses, NiV can infect a large variety of mammalian species. Due to this broad host range, its zoonotic potential, its high pathogenicity for humans, and the lack of effective vaccines or therapeutics, NiV was classified as a biosafety level 4 pathogen. This article provides an overview of the molecular characteristics of NiV focusing on the structure, functions, and unique biological properties of the two NiV surface glycoproteins, the receptor-binding G protein, and the fusion protein F. Since viral glycoproteins are major determinants for cell tropism and virus spread, a detailed knowledge of these proteins can help to understand the molecular basis of viral pathogenicity.
Vitamin E is important not only for its cellular antioxidant and lipid-lowering properties, but also as an antiproliferating agent. It has also been shown to contribute to immunoregulation, antibody production, and resistance to implanted tumors. It has recently been shown that tocotrienols are the components of vitamin E responsible for growth inhibition in human breast cancer cells in vitro as well as in vivo through estrogen-independent mechanisms. Although tocotrienols act on cell proliferation in a dose-dependent manner and can induce programmed cell death, no specific gene regulation has yet been identified. In order to investigate the molecular basis of the effect of a tocotrienol-rich fraction (TRF) from palm oil, we performed a cDNA array analysis of cancer-related gene expression in estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cells. The human breast cancer cells were incubated with or without 8 mug/mL of tocotrienols for 72 h. RNA was subsequently extracted and subjected to reverse transcription before being hybridized onto cancer arrays. Tocotrienol supplementation modulated significantly 46 out of 1200 genes in MDA-MB-231 cells. In MCF-7 cells, tocotrienol administration was associated with a lower number of affected genes. Interestingly, only three were affected in a similar fashion in both cell lines: c-myc binding protein MM-1, 23-kDa highly basic protein, and interferon-inducible protein 9-27 (IFITM-1). These proteins are most likely involved in the cell cycle and can exert inhibitory effects on cell growth and differentiation of the tumor cell lines. These data suggest that tocotrienols are able to affect cell homeostasis, possibly independent of their antioxidant activity.
Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed.
Osteoporosis, a degenerative bone disease, is characterized by low bone mass and microstructural deterioration of bone tissue resulting in aggravated bone fragility and susceptibility to fractures. The trend of extended life expectancy is accompanied by a rise in the prevalence of osteoporosis and concomitant complications in the elderly population. Epidemiological evidence has shown an association between vitamin E consumption and the prevention of age-related bone loss in elderly women and men. Animal studies show that ingestion of vitamin E, especially tocotrienols, may benefit bone health in terms of maintaining higher bone mineral density and improving bone microstructure and quality. The beneficial effects of tocotrienols on bone health appear to be mediated via antioxidant/anti-inflammatory pathways and/or 3-hydroxy-3-methylglutaryl coenzyme A mechanisms. We discuss (1) an overview of the prevalence and etiology of osteoporosis, (2) types of vitamin E (tocopherols versus tocotrienols), (3) findings of tocotrienols and bone health from published in vitro and animal studies, (4) possible mechanisms involved in bone protection, and (5) challenges and future direction for research.
Although 193 states have committed to the Chemical Weapons Convention and 98% of the declared chemical weapons stockpiles have been destroyed so far, nerve agent poisoning remains a lingering threat. The recent dissemination of sarin in Syria, the assassination of Kim Jong-Nam in Malaysia, and the assault on Sergei Skripal in the United Kingdom underline the need for effective treatment. The current therapeutic options of a muscarinic receptor antagonist, an oxime, and an anticonvulsant have been unchanged for decades. Therefore, new therapeutic strategies, for example, bio scavengers and receptor-active substances, are promising concepts that have to be examined for their benefits and limitations. In order to facilitate rapid diagnosis in challenging clinical situations, point-of-care diagnostics and detection are of importance. Therapeutic guidance concerning the duration and success of the current oxime therapy via determination of the cholinesterase status can contribute to an optimal use of resources. In summary, the challenges of current and future therapies for nerve agent poisoning and key diagnostic devices will be discussed.
In symptomatic young patients with gastroesophageal reflux symptoms, early identification of progressive gastroesophageal reflux disease (GERD) is critical to prevent long-term complications associated with hiatal hernia, increased esophageal acid and nonacid exposure, release of proinflammatory cytokines, and development of intestinal metaplasia, endoscopically visible Barrett's esophagus, and dysplasia leading to esophageal adenocarcinoma. Progression of GERD may occur in asymptomatic patients and in those under continuous acid-suppressive medication. The long-term side effects of proton-pump inhibitors, chemopreventive agents, and radiofrequency ablation are contentious. In patients with early-stage disease, when the lower esophageal sphincter function is still preserved and before endoscopically visible Barrett's esophagus develops, novel laparoscopic procedures, such as magnetic and electric sphincter augmentation, may have a greater role than conventional surgical therapy. A multidisciplinary approach to GERD by a dedicated team of gastroenterologists and surgeons might impact the patients' lifestyle, the therapeutic choices, and the course of the disease. Biological markers are needed to precisely assess the risk of disease progression and to tailor surveillance, ablation, and management.