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Fulltext A clinical tool to predict Plasmodium vivax recurrence in Malaysia

Mat Ariffin N, Islahudin F, Kumolosasi E, Makmor-Bakry M

BMC Infect Dis, 2017 12 08;17(1):759.
PMID: 29216842 DOI: 10.1186/s12879-017-2868-9

BACKGROUND: Recurrence rates of Plasmodium vivax infections differ across various geographic regions. Interestingly, South-East Asia and the Asia-Pacific region are documented to exhibit the most frequent recurrence incidences. Identifying patients at a higher risk for recurrences gives valuable information in strengthening the efforts to control P. vivax infections. The aim of the study was to develop a tool to identify P. vivax- infected patients that are at a higher risk of recurrence in Malaysia.
METHODS: Patient data was obtained retrospectively through the Ministry of Health, Malaysia, from 2011 to 2016. Patients with incomplete data were excluded. A total of 2044 clinical P. vivax malaria cases treated with primaquine were included. Data collected were patient, disease, and treatment characteristics. Two-thirds of the cases (n = 1362) were used to develop a clinical risk score, while the remaining third (n = 682) was used for validation.
RESULTS: Using multivariate analysis, age (p = 0.03), gametocyte sexual count (p = 0.04), indigenous transmission (p = 0.04), type of treatment (p = 0.12), and incomplete primaquine treatment (p = 0.14) were found to be predictors of recurrence after controlling for other confounding factors; these predictors were then used in developing the final model. The beta-coefficient values were used to develop a clinical scoring tool to predict possible recurrence. The total scores ranged between 0 and 8. A higher score indicated a higher risk for recurrence (odds ratio [OR]: 1.971; 95% confidence interval [CI]: 1.562-2.487; p ≤ 0.001). The area under the receiver operating characteristic (ROC) curve of the developed (n = 1362) and validated model (n = 682) was of good accuracy (ROC: 0.728, 95% CI: 0.670-0.785, p value

Matched MeSH terms: Life Cycle Stages
In vivo study of human Plasmodium knowlesi in Macaca fascicularis

Anderios F, Noorrain A, Vythilingam I

Exp Parasitol, 2010 Feb;124(2):181-9.
PMID: 19765587 DOI: 10.1016/j.exppara.2009.09.009

Plasmodium knowlesi is a malaria parasite of Old World monkeys and is infectious to humans. In this study Macaca fascicularis was used as a model to understand the host response to P. knowlesi using parasitological and haematological parameters. Three M. fascicularis of either sex were experimentally infected with P. knowlesi erythrocytic parasites from humans. The pre-patent period for P. knowlesi infection in M. fascicularis ranged from seven to 14 days. The parasitemia observed was 13,686-24,202 parasites per microL of blood for asexual stage and 88-264 parasites per microL of blood for sexual stage. Periodicity analysis adopted from microfilaria periodicity technique of asexual stage showed that the parasitemia peak at 17:39h while the sexual stage peaked at 02:36 h. Mathematical analysis of the data indicates that P. knowlesi gametocytes tend to display periodicity with a peak (24:00-06:00) that coincides with the peak biting activity (19:00-06:00) of the local vector, Anopheles latens. The morphology of P. knowlesi resembled P. falciparum in early trophozoite and P. malariae in late trophozoite. However, it may be distinguishable by observing the appliqué appearance of the cytoplasm and the chromatin lying inside the ring. Haematological analysis on macaques with knowlesi malaria showed clinical manifestations of hypoglycaemia, anaemia and hyperbilirubinemia. Gross examination of spleen and liver showed malaria pigments deposition in both organs.

Matched MeSH terms: Life Cycle Stages
Newcastle disease virus Malaysian strain AF2240 induces apoptosis in MCF-7 human breast carcinoma cells at an early stage of the virus life cycle

Ghrici M, El Zowalaty M, Omar AR, Ideris A

Int J Mol Med, 2013 Mar;31(3):525-32.
PMID: 23337979 DOI: 10.3892/ijmm.2013.1244

Newcastle disease virus (NDV) AF2240 Malaysian strain is a very virulent avian virus. NDV strain AF2240 was previously demonstrated to induce apoptosis in human breast carcinoma MCF-7 cells. However, at which stage of the NDV life cycle apoptosis is induced and whether NDV replication and protein synthesis are involved in apoptosis induction have yet to be determined. In the present study, we investigated the time course of NDV strain AF2240 nucleoprotein (NP) gene expression and the early apoptotic signs in the form of activation of caspase-8 and mitochondrial transition pore opening. In addition, the induction of apoptosis by both ultraviolet-inactivated and cycloheximide-treated NDV-infected MCF-7 cells were examined. Our findings showed that NDV strain AF2240 induced apoptosis at 1 h post-infection (pi) through activation of mitochondrial transition pore opening and at 2 h through activation of caspase-8, while the NP gene was expressed at 6 h pi. The induced apoptosis was independent of both virus replication and protein synthesis. In conclusion, NDV strain AF2240 induces apoptosis at an early stage of its life cycle, possibly during virus binding or fusion with the cell membrane. The mitochondrial-related pathway may be the central activator in NDV strain AF2240-induced apoptosis.

Matched MeSH terms: Life Cycle Stages
Fulltext Natural Flavonoids as Potential Angiotensin-Converting Enzyme 2 Inhibitors for Anti-SARS-CoV-2

Muchtaridi M, Fauzi M, Khairul Ikram NK, Mohd Gazzali A, Wahab HA

Molecules, 2020 Sep 01;25(17).
PMID: 32882868 DOI: 10.3390/molecules25173980

Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.

Matched MeSH terms: Life Cycle Stages
Fulltext Effect of selected local medicinal plants on the asexual blood stage of chloroquine resistant Plasmodium falciparum

Mohd Abd Razak MR, Afzan A, Ali R, Amir Jalaluddin NF, Wasiman MI, Shiekh Zahari SH, et al.

BMC Complement Altern Med, 2014;14:492.
PMID: 25510573 DOI: 10.1186/1472-6882-14-492

The development of resistant to current antimalarial drugs is a major challenge in achieving malaria elimination status in many countries. Therefore there is a need for new antimalarial drugs. Medicinal plants have always been the major source for the search of new antimalarial drugs. The aim of this study was to screen selected Malaysian medicinal plants for their antiplasmodial properties.

Matched MeSH terms: Life Cycle Stages
Fulltext Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation

Loughland JR, Minigo G, Sarovich DS, Field M, Tipping PE, Montes de Oca M, et al.

Sci Rep, 2017 06 01;7(1):2596.
PMID: 28572564 DOI: 10.1038/s41598-017-02096-2

Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection. pDC responsiveness to TLR7 and TLR9 stimulation was assessed in-vitro. Circulating pDC remained transcriptionally stable with gene expression altered for 8 genes (FDR

Matched MeSH terms: Life Cycle Stages
Fulltext Assessment of Aedes albopictus reference genes for quantitative PCR at different stages of development

Dzaki N, Azzam G

PLoS One, 2018;13(3):e0194664.
PMID: 29554153 DOI: 10.1371/journal.pone.0194664

Members of the Aedes genus of mosquitoes are widely recognized as vectors of viral diseases. Ae.albopictus is its most invasive species, and are known to carry viruses such as Dengue, Chikugunya and Zika. Its emerging importance puts Ae.albopictus on the forefront of genetic interaction and evolution studies. However, a panel of suitable reference genes specific for this insect is as of now undescribed. Nine reference genes, namely ACT, eEF1-γ, eIF2α, PP2A, RPL32, RPS17, PGK1, ILK and STK were evaluated. Expression patterns of the candidate reference genes were observed in a total of seventeen sample types, separated by stage of development and age. Gene stability was inferred from obtained quantification data through three widely cited evaluation algorithms i.e. BestKeeper, geNorm, and NormFinder. No single gene showed a satisfactory degree of stability throughout all developmental stages. Therefore, we propose combinations of PGK and ILK for early embryos; RPL32 and RPS17 for late embryos, all four larval instars, and pupae samples; eEF1-γ with STK for adult males; eEF1-γ with RPS17 for non-blood fed females; and eEF1-γ with eIF2α for both blood-fed females and cell culture. The results from this study should be able to provide a more informed selection of normalizing genes during qPCR in Ae.albopictus.

Matched MeSH terms: Life Cycle Stages/genetics*
Description of raabeia, synactinomyxon and neoactinomyxum developing stages of myxosporeans (Myxozoa) infecting Isochaetides michaelseni Lastočkin (Tubificidae) in Lake Balaton and Kis-Balaton Water Reservoir, Hungary

Borkhanuddin MH, Cech G, Molnár K, Németh S, Székely C

Syst Parasitol, 2014 Jul;88(3):245-59.
PMID: 24935127 DOI: 10.1007/s11230-014-9496-1

Molecular and morphometric investigations were conducted on the actinosporean morphotypes of myxosporeans surveyed in oligochaetes of Lake Balaton and Kis-Balaton Water reservoir. Oligochaetes belonging to the species Isochaetides michaelseni Lastočkin and Branchiura sowerbyi Beddard as well as to the genera Nais Dujardin, Dero Müller and Aeolosoma Ehrenberg were studied during an 18-month period. Actinosporeans were obtained exclusively from I. michaelseni (7,818 specimens) with very low prevalence (0.01-0.06%). Four new actinosporean morphotypes of the collective groups raabeia (2 types), synactinomyxon (1 type) and neoactinomyxum (1 type) were found and described, including the first synactinomyxon collective group from Hungarian biotopes and a new raabeia morphotype. Except for Synactinomyxon type 1, the 18S rDNA analysis revealed that the spores did not match any myxospore entity found in the GenBank.

Matched MeSH terms: Life Cycle Stages
Fulltext Diversity of the Monstrilloida (Crustacea: Copepoda)

Suárez-Morales E

PLoS One, 2011;6(8):e22915.
PMID: 21853055 DOI: 10.1371/journal.pone.0022915

Monstrilloid copepods are protelean parasites of different groups of marine benthic invertebrates. Only their first naupliar, preadult, and adult phases are planktonic. Monstrilloids are currently represented by more than 115 nominal species contained in four genera. Its taxonomic knowledge has been hampered by nomenclatural and descriptive problems derived from their peculiar ontogeny and poor definitions of taxa. One of the most important difficulties is that of matching males to females. The only reliable methods to link the sexes of a species are the confirmation of particular apomorphies shared by both sexes, finding both sexes in the same host or as a pre-copulatory male-female pair in the plankton, or by the use of molecular markers. A general overview of the morphology of the group and its life cycle is provided herein. Recently, upgraded descriptive standards have been established and the relevance of redescribing taxa based on type and museum specimens has been demonstrated. The rate of species description per decade has had several peaks between 1840 and 2010: (1971-1980, 1991-2000, 2001-2010), each related to the activity of a few researchers. An analysis of the world distribution of published records of the Monstrilloida revealed that the Northeast Atlantic is the best studied region (45% of all records), followed by the Northwestern Atlantic (17%); the least surveyed areas include regions of the southern hemisphere (less than 3%). The Northeast Atlantic region harbors the highest number of known species (32 nominal species), followed by the Caribbean Sea/Gulf of Mexico (24), the Mediterranean/Black Sea (19), Indonesia-Malaysia-Philippines region (17), Japanese waters (17), and the Brazil-Argentina area (16). Other than these generalized patterns, little can be concluded concerning the biogeography of the group. Many species records are doubtful or improbable, and purportedly cosmopolitan nominal species are being revealed as species complexes yet to be studied.

Matched MeSH terms: Life Cycle Stages
The prevalence and intensity of Amblyomma javanense infestation on Malayan pangolins (Manis javanica Desmarest) from Peninsular Malaysia

Hassan M, Sulaiman MH, Lian CJ

Acta Trop, 2013 May;126(2):142-5.
PMID: 23416121 DOI: 10.1016/j.actatropica.2013.02.001

A parasitological survey of 16 pangolins, confiscated from the Department of Wildlife and Nature Park Peninsular Malaysia (DWNP) at Kelantan and Pulau Pinang, Malaysia was conducted in 2011. Amblyomma javanense (family: Ixodidae) was the only ectoparasite found on the pangolins. The prevalence, intensity and life cycle of A. javanense were observed together with the respective pangolins' age and sex. It was found that 68.8% of the pangolins were infected, and significant difference, χ(2)(1, N=16)=4.02, p=0.05 were observed with males higher in infestation (88.9%) as compared to the females (42.9%). However, the mean intensity was higher on females (72) as compared to males (31.6). In addition, significant difference, χ(2) (2, N=16)=6.73, p=0.05 was recorded between adults and juveniles with juveniles found to be 100% infected as compared to adult (63.6%). Nevertheless, the mean intensity was slightly higher on adults (47) than juveniles (35). Adult ticks were found in higher numbers as compared to the nymph and larvae with number of male ticks higher (236) as compared to the females (53). Similarly, a high significant difference χ(2)(2, N=469)=203.47, p=0.05 was recorded in the composition of the tick's life stages with a higher number of adult ticks (61.6%) followed by nymph (30.3%) and larvae (8.1%). As such, the results of this study revealed a picture of the A. javanense life cycle which is related to the age and gender of the Malayan Pangolin.

Matched MeSH terms: Life Cycle Stages
P-TEFb goes viral

Zaborowska J, Isa NF, Murphy S

Inside Cell, 2016 04;1(2):106-116.
PMID: 27398404

Positive transcription elongation factor b (P-TEFb), which comprises cyclin-dependent kinase 9 (CDK9) kinase and cyclin T subunits, is an essential kinase complex in human cells. Phosphorylation of the negative elongation factors by P-TEFb is required for productive elongation of transcription of protein-coding genes by RNA polymerase II (pol II). In addition, P-TEFb-mediated phosphorylation of the carboxyl-terminal domain (CTD) of the largest subunit of pol II mediates the recruitment of transcription and RNA processing factors during the transcription cycle. CDK9 also phosphorylates p53, a tumor suppressor that plays a central role in cellular responses to a range of stress factors. Many viral factors affect transcription by recruiting or modulating the activity of CDK9. In this review, we will focus on how the function of CDK9 is regulated by viral gene products. The central role of CDK9 in viral life cycles suggests that drugs targeting the interaction between viral products and P-TEFb could be effective anti-viral agents.

Matched MeSH terms: Life Cycle Stages
Fulltext Morphological descriptions on the larvae of Hypopygiopsis fumipennis (Walker, 1856) (Diptera: Calliphoridae)

Heo CC, Latif B, Silahuddin SA, Nazni WA, Omar B

Trop Biomed, 2015 Mar;32(1):151-9.
PMID: 25801265

The study on biodiversity of forensically important Diptera in the tropical rain forest in Malaysia is scarce. Thus, a preliminary survey was conducted at a jungle fringe near Kampung Bahagia Bukit Lagong, Sungai Buloh, Selangor. A rat carcass was offered to attract carrion flies and we collected an adult female calliphorid, Hypopygiopsis fumipennis (Walker, 1856) during the fresh stage of carcass decomposition. The female fly was allowed to oviposit on chicken liver in a container and the resulting larvae were reared to the adult stage. Along the developmental process, several individuals from each instar were collected and preserved in 70% ethanol and then processed on the slides. We recorded the duration of development for each instar and described its larval features for the first time. The third instar larvae of H. fumipennis showed accessory oral sclerite present, anterior spiracle with 13-15 papillae, intersegmental spines mostly unicuspid with pointed end, and posterior spiracles heavily sclerotized with inter-slit projections. Some larval differences between H. fumipennis and Hypopygiopsis violacea were noted.

Matched MeSH terms: Life Cycle Stages
Fulltext Predation on pupa of Chrysomya rufifacies (Marquart) (Diptera: Calliphoridae) by parasitoid, Exoristobia philippinensis Ashmead (Hymenoptera: Encyrtidae) and Ophyra spinigera larva (Diptera: Muscidae)

Chin HC, Ahmad NW, Lim LH, Jeffery J, Omar B, Dhang CC, et al.

Trop Biomed, 2009 Dec;26(3):369-72.
PMID: 20237454

A forensic entomological study was conducted using monkey carcasses (Macaca fascicularis Raffles) that were placed in either an outdoor or indoor environment at a coastal area in Tanjung Sepat, Selangor, Malaysia during May until August 2008. We collected pupae of Chrysomya rufifacies (Marquart) from the carcasses and kept them individually. The emergence of 13 parasitic microhymenopteran, from one of the pupae occurring within a week were identified as Exoristobia philippinensis Ashmead (Hymenoptera: Encyrtidae). Another observation was made whereby a pupa of C. rufifacies was predated by a muscid larva, Ophyra spinigera (Stein). The larva squeezed into the pupa and consumed the contents. This paper report C. rufifacies as a new host record for E. philippinensis in Malaysia and highlighted the predatory behavior of O. spinigera larva in natural environment.

Matched MeSH terms: Life Cycle Stages
Fulltext Characterization on malathion and permethrin resistance by bioassays and the variation of esterase activity with the life stages of the mosquito Culex quinquefasciatus

Selvi S, Edah MA, Nazni WA, Lee HL, Azahari AH

Trop Biomed, 2007 Jun;24(1):63-75.
PMID: 17568379 MyJurnal

Larvae and adults of Culex quinquefasciatus were used for the test undertaken for malathion resistant strain (F61 - F65) and permethrin resistant strain (F54 - F58). The results showed that the LC50 for both malathion (F61 - F65) and permethrin (F54 - F58) resistant Cx. quinquefasciatus increased steadily throughout the subsequent five generations, indicating a marked development of resistance. The adult female malathion resistant strain have developed a high resistance level to malathion diagnostic dosage with a resistance ratio of 9.3 to 17.9 folds of resistance compared with the susceptible Cx. quinquefasciatus. Permethrin resistance ratio remained as 1.0 folds of resistance at every generation. It was obvious that malathion resistance developed at a higher rate in adult females compared to permethrin. Enzyme-based metabolic mechanisms of insecticide resistance were investigated based on the biochemical assay principle. From the results obtained obviously shows that there is a significant difference (p < 0.05) in esterase level in both malathion and permethrin selected strains. Female malathion selected strain has the higher level of esterase activity compared to the female permethrin selected strain at (0.8 to 1.04) alpha-Na micromol/min/mg protein versus (0.15 to 0.24) alpha-Na micromol/min/mg protein respectively. This indicated increased level of non-specific esterase is playing an important role in resistance mechanism in female malathion selected strain. Permethrin selected strain exhibited non-specific esterase activity at a very low level throughout the different life stages compared to malathion selected strain. This study suggests that life stages play a predominant role in conferring malathion and permethrin resistance in Cx. quinquefasciatus.

Matched MeSH terms: Life Cycle Stages
Fulltext Evaluation of reference genes at different developmental stages for quantitative real-time PCR in Aedes aegypti

Dzaki N, Ramli KN, Azlan A, Ishak IH, Azzam G

Sci Rep, 2017 03 16;7:43618.
PMID: 28300076 DOI: 10.1038/srep43618

The mosquito Aedes aegypti (Ae. aegypti) is the most notorious vector of illness-causing viruses such as Dengue, Chikugunya, and Zika. Although numerous genetic expression studies utilizing quantitative real-time PCR (qPCR) have been conducted with regards to Ae. aegypti, a panel of genes to be used suitably as references for the purpose of expression-level normalization within this epidemiologically important insect is presently lacking. Here, the usability of seven widely-utilized reference genes i.e. actin (ACT), eukaryotic elongation factor 1 alpha (eEF1α), alpha tubulin (α-tubulin), ribosomal proteins L8, L32 and S17 (RPL8, RPL32 and RPS17), and glyceraldeyde 3-phosphate dehydrogenase (GAPDH) were investigated. Expression patterns of the reference genes were observed in sixteen pre-determined developmental stages and in cell culture. Gene stability was inferred from qPCR data through three freely available algorithms i.e. BestKeeper, geNorm, and NormFinder. The consensus rankings generated from stability values provided by these programs suggest a combination of at least two genes for normalization. ACT and RPS17 are the most dependably expressed reference genes and therefore, we propose an ACT/RPS17 combination for normalization in all Ae. aegypti derived samples. GAPDH performed least desirably, and is thus not a recommended reference gene. This study emphasizes the importance of validating reference genes in Ae. aegypti for qPCR based research.

Matched MeSH terms: Life Cycle Stages
Labor markets and economic development in Malaysia

Smith JP

Res Popul Econ, 1991;7:131-56.
PMID: 12317026
Matched MeSH terms: Life Cycle Stages*
Surface contact toxicity and synergism of several insecticides against different stages of the tropical bed bug, Cimex hemipterus (Hemiptera: Cimicidae)

How YF, Lee CY

Pest Manag Sci, 2011 Jun;67(6):734-40.
PMID: 21370390 DOI: 10.1002/ps.2123

Five formulated insecticides (lambda-cyhalothrin at 10 mg m⁻², bifenthrin at 50 mg m⁻², fipronil at 10 mg m⁻², fenitrothion at 50 mg m⁻², imidacloprid at 5 mg m⁻²) and one active ingredient (DDT at 500 mg m⁻²) were evaluated using a surface contact method against early and late instars and adults of two strains of the tropical bed bug, Cimex hemipterus (F.). Synergism of lambda-cyhalothrin and fipronil using piperonyl butoxide (PBO) was also assessed.

Matched MeSH terms: Life Cycle Stages/drug effects*
Fulltext Changing domesticity of Aedes aegypti in northern peninsular Malaysia: reproductive consequences and potential epidemiological implications

Saifur RG, Dieng H, Hassan AA, Salmah MR, Satho T, Miake F, et al.

PLoS One, 2012;7(2):e30919.
PMID: 22363516 DOI: 10.1371/journal.pone.0030919

BACKGROUND: The domestic dengue vector Aedes aegypti mosquitoes breed in indoor containers. However, in northern peninsular Malaysia, they show equal preference for breeding in both indoor and outdoor habitats. To evaluate the epidemiological implications of this peridomestic adaptation, we examined whether Ae. aegypti exhibits decreased survival, gonotrophic activity, and fecundity due to lack of host availability and the changing breeding behavior.
METHODOLOGY/PRINCIPAL FINDINGS: This yearlong field surveillance identified Ae. aegypti breeding in outdoor containers on an enormous scale. Through a sequence of experiments incorporating outdoors and indoors adapting as well as adapted populations, we observed that indoors provided better environment for the survival of Ae. aegypti and the observed death patterns could be explained on the basis of a difference in body size. The duration of gonotrophic period was much shorter in large-bodied females. Fecundity tended to be greater in indoor acclimated females. We also found increased tendency to multiple feeding in outdoors adapted females, which were smaller in size compared to their outdoors breeding counterparts.
CONCLUSION/SIGNIFICANCE: The data presented here suggest that acclimatization of Ae. aegypti to the outdoor environment may not decrease its lifespan or gonotrophic activity but rather increase breeding opportunities (increased number of discarded containers outdoors), the rate of larval development, but small body sizes at emergence. Size is likely to be correlated with disease transmission. In general, small size in Aedes females will favor increased blood-feeding frequency resulting in higher population sizes and disease occurrence.

Matched MeSH terms: Life Cycle Stages/physiology
The anthelmintic efficacy of natural plant cysteine proteinases against two rodent cestodes Hymenolepis diminuta and Hymenolepis microstoma in vitro

Mansur F, Luoga W, Buttle DJ, Duce IR, Lowe A, Behnke JM

Vet Parasitol, 2014 Mar 17;201(1-2):48-58.
PMID: 24462509 DOI: 10.1016/j.vetpar.2013.12.018

Little is known about the efficacy of cysteine proteinases (CP) as anthelmintics for cestode infections. We examined the effects of CPs on two rodent cestodes, Hymenolepis diminuta and H. microstoma in vitro. Our data showed that naturally occurring mixtures of CPs, such as those found in papaya latex, and relatively pure preparations of fruit bromelain, papain and stem bromelain, were active in vitro against both juvenile, artificially excysted scoleces, as well as against adult worms of both rodent cestodes. Significant dose-dependent reduction in motility, ultimately leading to death of the worms, was observed with both species, and against both freshly excysted scoleces and 14-day old pre-adult worms. The most effective was fruit bromelain (after 30 min of incubation of juvenile H. diminuta and H. microstoma IC50=63 and 74 μM, respectively, and for pre-adult worms=199 and 260 μM, respectively). The least effective was stem bromelain (after 30 min of incubation of juvenile H. diminuta and H. microstoma IC50=2855 and 2772 μM, respectively, and for pre-adult worms=1374 and 1332 μM, respectively) and the efficacies of papaya latex supernatant and papain were between these extremes. In all cases these values are higher than those reported previously for efficacy of CPs against intestinal nematodes, and in contrast to nematodes, all CPs were effective against cestodes in the absence of exogenous cysteine in incubation media. The CPs appeared to attack the tegument resulting in generalised erosion mainly on the strobila. The scolex was more resistant to CP attack but nevertheless some damage to the tegument on the scolex was detected.

Matched MeSH terms: Life Cycle Stages/drug effects
Melatonin effects on Plasmodium life cycle: new avenues for therapeutic approach

Srinivasan V, Ahmad AH, Mohamed M, Zakaria R

Recent Pat Endocr Metab Immune Drug Discov, 2012 May;6(2):139-47.
PMID: 22537380

Malaria remains a global health problem affecting more than 515 million people all over the world including Malaysia. It is on the rise, even within unknown regions that previous to this were free of malaria. Although malaria eradication programs carried out by vector control programs are still effective, anti-malarial drugs are also used extensively for curtailing this disease. But resistance to the use of anti-malarial drugs is also increasing on a daily basis. With an increased understanding of mechanisms that cause growth, differentiation and development of malarial parasites in rodents and humans, new avenues of therapeutic approaches for controlling the growth, synchronization and development of malarial parasites are essential. Within this context, the recent discoveries related to IP3 interconnected signalling pathways, the release of Ca2+ from intracellular stores of Plasmodium, ubiquitin protease systems as a signalling pathway, and melatonin influencing the growth and differentiation of malarial parasites by its effects on these signalling pathways have opened new therapeutic avenues for arresting the growth and differentiation of malarial parasites. Indeed, the use of melatonin antagonist, luzindole, has inhibited the melatonin's effect on these signalling pathways and thereby has effectively reduced the growth and differentiation of malarial parasites. As Plasmodium has effective sensors which detect the nocturnal plasma melatonin concentrations, suppression of plasma melatonin levels with the use of bright light during the night or by anti-melatonergic drugs and by using anti-kinase drugs will help in eradicating malaria on a global level. A number of patients have been admitted with regards to the control and management of malarial growth. Patents related to the discovery of serpentine receptors on Plasmodium, essential for modulating intra parasitic melatonin levels, procedures for effective delivery of bright light to suppress plasma melatonin levels and thereby arresting the growth and elimination of malarial parasites from the blood of the host are all cited in the paper. The purpose of the paper is to highlight the importance of melatonin acting as a cue for Plasmodium faciparum growth and to discuss the ways of curbing the effects of melatonin on Plasmodium growth and for arresting its life cycle, as a method of eliminating the parasite from the host.

Matched MeSH terms: Life Cycle Stages/drug effects*

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