Prevalence of anti-Leptospira antibodies and associated risk factors in the Malaysian refugee communities.

Background: Refugees in Malaysia, who are afflicted by poverty, conflict and poor health, are vulnerable to a range of zoonotic infections in the deprived environmental and social conditions under which they live. Exposure to infections such as leptospirosis, for which rodents are primary hosts, is of particular concern.

Methods: A wellness program was conducted to determine the presence of antibodies against Leptospira (seroprevalence) in 11 refugee community schools and centers in the Klang Valley, Malaysia.

Seroprevalence of Anti- IgG and IgM Antibodies and Risk Assessment of Leptospirosis among Urban Poor Communities in Kuala Lumpur, Malaysia.

Leptospirosis is a zoonotic bacterial disease caused by pathogenic species of the genus . Disease incidence is known to be attributed to environmental and social conditions which promote the spread of reservoir hosts, primarily rodents. A well-being program was conducted to determine the seroprevalence and risk factors associated with leptospirosis in urban poor communities occupying low-cost flat accommodation and squatter settlements in the vicinity of Wilayah Persekutuan, Kuala Lumpur.

Microorganisms as an Indicator of Hygiene Status Among Migrant Food Handlers in Peninsular Malaysia.

This study used microbial indicators to assess the hygiene status of 383 migrant food handlers from 3 urban cities in Peninsular Malaysia. Microbiological analysis revealed that all the hand swabs tested 99.5% positive for aerobic plate counts (mean [M] ± standard deviation [SD] = 3.

Characterization of Nontyphoidal Salmonella Isolates from Asymptomatic Migrant Food Handlers in Peninsular Malaysia.

Asymptomatic Salmonella carriers who work as food handlers pose food safety and public health risks, particularly during food preparation, and this has serious implications for the disease burden in society. Therefore, we conducted a study to determine the number of Salmonella carriers in a migrant cohort in several food establishments in three major cities in Peninsular Malaysia. Sociodemographic data and stool samples were collected and analyzed using standard methods of detection and isolation.

A duplex endpoint PCR assay for rapid detection and differentiation of Leptospira strains.

Introduction:: This study aimed to develop a duplex endpoint PCR assay for rapid detection and differentiation of Leptospira strains.

Methods:: Primers were designed to target the rrs (LG1/LG2) and ligB (LP1/LP2) genes to confirm the presence of the Leptospira genus and the pathogenic species, respectively.

Results:: The assay showed 100% specificity against 17 Leptospira strains with a limit of detection of 23.

Socio-demographic determinants of Toxoplasma gondii seroprevalence in migrant workers of Peninsular Malaysia.

Background: The number of migrants working in Malaysia has increased sharply since the 1970's and there is concern that infectious diseases endemic in other (e.g. neighbouring) countries may be inadvertently imported.

Migrant Workers in Malaysia: Current Implications of Sociodemographic and Environmental Characteristics in the Transmission of Intestinal Parasitic Infections.

A cross-sectional study of intestinal parasitic infections amongst migrant workers in Malaysia was conducted. A total of 388 workers were recruited from five sectors including manufacturing, construction, plantation, domestic and food services. The majority were recruited from Indonesia (n = 167, 43.

Tcf4 Regulates Synaptic Plasticity, DNA Methylation, and Memory Function.

Human haploinsufficiency of the transcription factor Tcf4 leads to a rare autism spectrum disorder called Pitt-Hopkins syndrome (PTHS), which is associated with severe language impairment and development delay. Here, we demonstrate that Tcf4 haploinsufficient mice have deficits in social interaction, ultrasonic vocalization, prepulse inhibition, and spatial and associative learning and memory. Despite learning deficits, Tcf4(+/-) mice have enhanced long-term potentiation in the CA1 area of the hippocampus.

Human Leptospirosis in Malaysia: Reviewing the Challenges After 8 Decades (1925-2012).

The history and epidemiology of human leptospirosis in Malaysia from 1925 to 2012 are described. Previous studies have demonstrated that leptospirosis is an endemic disease in Malaysia occurring in both urban and rural locations. The number of cases has risen dramatically since the Ministry of Health Malaysia highlighted leptospirosis as a notifiable disease in 2010, with reported cases increasing from 248 cases in 2004 to 3604 in 2012.

C7β-methyl analogues of the orvinols: the discovery of kappa opioid antagonists with nociceptin/orphanin FQ peptide (NOP) receptor partial agonism and low, or zero, efficacy at mu opioid receptors.

Buprenorphine is a successful analgesic and treatment for opioid abuse, with both activities relying on its partial agonist activity at mu opioid receptors. However, there is substantial interest in its activities at the kappa opioid and nociceptin/orphanin FQ peptide receptors. This has led to an interest in developing compounds with a buprenorphine-like pharmacological profile but with lower efficacy at mu opioid receptors.

Selectively promiscuous opioid ligands: discovery of high affinity/low efficacy opioid ligands with substantial nociceptin opioid peptide receptor affinity.

Emerging clinical and preclinical evidence suggests that a compound displaying high affinity for μ, κ, and δ opioid (MOP, KOP, and DOP) receptors and antagonist activity at each, coupled with moderate affinity and efficacy at nociceptin opioid peptide (NOP) receptors will have utility as a relapse prevention agent for multiple types of drug abuse. Members of the orvinol family of opioid ligands have the desired affinity profile but have typically displayed substantial efficacy at MOP and or KOP receptors. In this study it is shown that a phenyl ring analogue (1d) of buprenorphine displays the desired profile in vitro with high, nonselective affinity for the MOP, KOP, and DOP receptors coupled with moderate affinity for NOP receptors.

Temperature stress and parasitism of endothermic hosts under climate change.

Climate change is a major threat to global environmental stability and is predicted to cause more frequent extreme weather events with higher levels of heat and cold stress. The physiological effects of such events on parasitic infections within endotherms are poorly studied and rarely considered in the context of climate change where an emphasis on ectothermic components of parasite life cycles (free-living stages and invertebrate hosts or vectors) predominates. However, thermal stress can affect parasite establishment, growth, fecundity, and development within endothermic hosts and may thus potentially influence transmission potential.

Macroparasite communities in stray cat populations from urban cities in Peninsular Malaysia.

The occurrence of macroparasites was studied from 543 stray cats in four urban cities from the west (Kuala Lumpur), east (Kuantan), north (Georgetown) and south (Malacca) of Peninsular Malaysia from May 2007 to August 2010. Five ectoparasites species were recovered namely, Ctenocephalides felis, Felicola subrostratus, Haemaphysalis bispinosa, Heterodoxus spiniger and Lynxacarus radovskyi. Two cats from Georgetown were infested with the dog louse, H.

Orvinols with mixed kappa/mu opioid receptor agonist activity.

Dual-acting kappa opioid receptor (KOR) agonist and mu opioid receptor (MOR) partial agonist ligands have been put forward as potential treatment agents for cocaine and other psychostimulant abuse. Members of the orvinol series of ligands are known for their high binding affinity to both KOR and MOR, but efficacy at the individual receptors has not been thoroughly evaluated. In this study, it is shown that a predictive model for efficacy at KOR can be derived, with efficacy being controlled by the length of the group attached to C20 and by the introduction of branching into the side chain.

Fumaroylamino-4,5-epoxymorphinans and related opioids with irreversible μ opioid receptor antagonist effects.

We have previously shown that cinnamoyl derivatives of 14β-amino-17-cyclopropylmethyl-7,8-dihydronormorphinone and 7α-aminomethyl-6,14-endoethanonororipavine have pronounced pseudoirreversible μ opioid receptor (MOR) antagonism. The present communication describes the synthesis and evaluation of fumaroylamino analogues of these cinnamoylamino derivatives together with some related fumaroyl derivatives. The predominant activity of the new ligands was MOR antagonism.

Helminth communities from two urban rat populations in Kuala Lumpur, Malaysia.

Background: The prevalence of parasitic infections among commensal animals such as black and brown rats in many tropical countries is high and in comparison with studies on rodents in temperate climates, little is known about the community structure of their parasites. Rodent borne parasites pose threats to human health since people living in close proximity to rodent populations can be exposed to infection.

Methods: The helminth community structures of two urban rat populations in Kuala Lumpur, Malaysia were investigated.

14-Amino-4,5-epoxymorphinan derivatives and their pharmacological actions.

14-Hydroxy-7,8-dihydromorphinone (oxymorphone) and its derivatives (oxycodone, naloxone, naltrexone) have become among the most important clinical agents to have been produced from opium. 14-Aminocodeinone and its 7,8-dihydro and morphinone derivatives are of more recent origin thanks to the work of Professor Gordon Kirby and his collaborators. The 14-amino parent compounds have proved of limited interest but their 14-acylamino- and 14-alkylamino derivatives have been extensively studied.

Rainfall induces time-lagged changes in the proportion of tropical aquatic hosts infected with metazoan parasites.

Rainfall serves as a powerful driving force, shifting temporal abundance and prevalence patterns in parasites and free-living aquatic organisms in tropical environments. However, there is a lack of sound evidence showing the temporal scales at which rainfall influences infection parameters of parasites in the tropics either directly by affecting the parasite life cycle or indirectly by modifying host population abundance. In the present study, we demonstrate that changes in rainfall patterns lead to changes in the proportion of infected hosts with several parasite species, causing immediate or lagged favourable conditions for an increase in levels of infection.

Intestinal helminths of feral cat populations from urban and suburban districts of Qatar.

A survey of the helminths of 658 adult cats from feral urban and suburban populations in Qatar was conducted across all months in 2006 and 2007. Six species of helminths were identified, comprising two cestodes (Taenia taeniaeformis [73.6%] and Diplopylidium acanthotetra [47.

14beta-Arylpropiolylamino-17-cyclopropylmethyl-7,8-dihydronormorphinones and related opioids. Further examples of pseudoirreversible mu opioid receptor antagonists.

14beta-4'-Chlorocinnamoylaminodihydronormorphinone (2a), and analogues, are selective pseudoirreversible antagonists of the mu opioid receptor (MOR). The preparation of analogues with ethynic bonds, replacing the ethenic bond of 2a, is described. The new ligands, in mouse antinociceptive assays, had pseudoirreversible MOR antagonist activity, which, in the case of 8b was of longer duration than that of 2a.

Mixed kappa/mu opioid receptor agonists: the 6 beta-naltrexamines.

Ligands from the naltrexamine series have consistently demonstrated agonist activity at kappa opioid receptors (KOR), with varying activity at the mu opioid receptor (MOR). Various 6 beta-cinnamoylamino derivatives were made with the aim of generating ligands with a KOR agonist/MOR partial agonist profile, as ligands with this activity may be of interest as treatment agents for cocaine abuse. The ligands all displayed the desired high affinity, nonselective binding in vitro and in the functional assays were high efficacy KOR agonists with some partial agonist activity at MOR.

The dynamics of protein and metal metabolism in acclimated and Cd-exposed freshwater crabs (Potamonautes warreni).

Climatic and man-made impacts induced dynamic molecular responses in the South African freshwater crab, Potamonautes warreni. Adult crabs exhibited MT-like protein, binding Cd (0.02micromolg(-1) wet mass+/-0.

Cinnamoyl derivatives of 7alpha-aminomethyl-6,14-endo-ethanotetrahydrothebaine and 7alpha-aminomethyl-6,14-endo-ethanotetrahydrooripavine and related opioid ligands.

A new series of ligands has been synthesized where the cinnamoyl group of the 14-cinnamoylamino morphinones has been introduced to the 7alpha-substituent of the 6,14-bridged oripavine series. In vitro the compounds were mostly low efficacy partial agonists or antagonists with some selectivity for the mu opioid receptor, with evidence of micro efficacy in vivo. The similarity in SAR between these 6,14-bridged oripavines and the 14-cinnamoylamino series suggests a similar mode of interaction with the micro opioid receptor.

Formic acid catalysed rearrangement of 5beta-methyldihydrothevinols (= 3,6-dimethoxy-5,17-dimethyl-4,5-epoxy-6,14-ethanomorphinan-7-methanols): synthesis of new doubly bridged morphinan derivatives.

We recently showed that substitution of a 5beta-methyl group allows the isolation of 14-alkenyldihydrocodeinones from the action of hot formic acid on certain dihydrothevinols. It has now been shown that, in those dihydrothevinols which are converted to stable side chain olefins by such treatment, introduction of a 5beta-methyl group results in the formation of new doubly bridged morphinan derivatives in addition to the dihydrocodeinones or olefins. The new morphinans have low affinities for opioid receptors.

Structural determinants of opioid activity in derivatives of 14-aminomorphinones: effects of changes to the chain linking of the C14-amino group to the aryl ring.

The 14-aminodihydromorphinone and codeinone series of opioid ligands have produced a number of ligands of substantial interest. To investigate the importance of the 14-substituent, a series of analogues in which the side chain length is varied and the amide and alkene functions are reduced have been prepared. Binding affinity, particularly at the mu-opioid receptor (MOR), was largely determined by the aromatic group of the side chain.