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  1. Tan CH, Palasuberniam P, Blanco FB, Tan KY
    Trans R Soc Trop Med Hyg, 2021 01 07;115(1):78-84.
    PMID: 32945886 DOI: 10.1093/trstmh/traa087
    BACKGROUND: The Philippine cobra (Naja philippinensis) and Samar cobra (Naja samarensis) are two WHO Category 1 medically important venomous snakes in the Philippines. Philippine cobra antivenom (PCAV) is the only antivenom available in the country, but its neutralization capacity against the venoms of N. philippinensis and hetero-specific N. samarensis has not been reported. This knowledge gap greatly hinders the optimization of antivenom use in the region.

    METHODS: This study examined the immunological binding and neutralization capacity of PCAV against the two cobra venoms using WHO-recommended protocols.

    RESULTS: In mice, both venoms were highly neurotoxic and lethal with a median lethal dose of 0.18 and 0.20 µg/g, respectively. PCAV exhibited strong and comparable immunoreactivity toward the venoms, indicating conserved venom antigenicity between the two allopatric species. In in vivo assay, PCAV was only moderately effective in neutralizing the toxicity of both venoms. Its potency was even lower against the hetero-specific N. samarensis venom by approximately two-fold compared with its potency against N. philippinensis venom.

    CONCLUSION: The results indicated that PCAV could be used to treat N. samarensis envenomation but at a higher dose, which might increase the risk of hypersensitivity and worsen the shortage of antivenom supply in the field. Antivenom manufacturing should be improved by developing a low-dose, high-efficacy product against cobra envenomation.

  2. Chew SC, Tan CP, Tan CH, Nyam KL
    J Food Sci Technol, 2020 Jul;57(7):2507-2515.
    PMID: 32549601 DOI: 10.1007/s13197-020-04286-9
    This study aimed to investigate the effect of a coffee beverage matrix on the oil release percentage and bioaccessibility of bioactive compounds from microencapsulated refined kenaf seed oil (MRKSO) using an in vitro gastrointestinal digestion model. Refined kenaf seed oil was spray-dried with gum arabic, β-cyclodextrin, and sodium caseinate. Oil release percentage, total phenolic content, radical scavenging activity of DPPH and ABTS, tocopherol and tocotrienol contents, as well as phytosterol content, were measured in the oil released from digested MRKSO along with the coffee matrix and compared to the digested MRKSO without coffee matrix and undigested MRKSO. Refined kenaf seed oil showed a significantly higher oxidative stability index than crude, degummed, and neutralized oil samples. About 91.2 and 94.7% of the oils were released from the digested MRKSO without and with coffee matrix, respectively. Oil released from the digested MRKSO with coffee matrix showed an increase in the total phenolic content (200.5%), DPPH (172.7%), and ABTS (68.1%) values, tocopherol and tocotrienol contents (24.6%), as well as the phytosterol content (62.0%), compared to oil released from the digested MRKSO without coffee matrix. MRKSO was successfully incorporated in the coffee drink and can use as a partial replacement for coffee creamers or supplementation in coffee drinks.
  3. Tang ELH, Tan NH, Fung SY, Tan CH
    Toxicon, 2019 Aug 22;169:91-102.
    PMID: 31445943 DOI: 10.1016/j.toxicon.2019.08.004
    The intraspecific geographical venom variations of Calloselasma rhodostoma from Malaysia (CR-M), Indonesia (CR-I), Thailand (CR-T) and Vietnam (CR-V) were investigated through 1D SDS-PAGE and nano-ESI-LCMS/MS. The venom antigenicity, procoagulant activities and neutralization using Thai C. rhodostoma Monovalent Antivenom (CRMAV) were also investigated. SDS-PAGE patterns of the venoms were relatively similar with minor variations. Proteomic analysis revealed that snake venom metalloproteinases (SVMPs, particularly P-I class), serine proteases (SVSPs) and snaclecs dominated the venom protein composition (68.96-81.80%), followed by L-amino acid oxidase (LAAO) and phospholipase A2 (PLA2) (7.37-11.08% and 5.18-13.81%, respectively), corroborating C. rhodostoma envenoming effects (hemorrhage, consumptive coagulopathy, thrombocytopenia and local tissue necrosis). Other proteins of lower abundances (2.82-9.13%) identified include cysteine-rich secretory proteins (CRISP), phospholipase B, phosphodiesterase, nerve growth factor, 5'-nucleotidase, aminopeptidase and hyaluronidase. All four venoms exhibited strong procoagulant effects which were neutralized by CRMAV to different extents. CRMAV immunoreactivity was high toward venoms of CR-M, CR-I and CR-T but relatively low for CR-V venom. Among the venom samples from different locales, CR-V venom proteome has the smallest SVMP composition while SVSP, PLA2 and phosphodiesterase were more abundant in the venom. These variations in C. rhodostoma venom protein composition could partly explain the differences seen in immunoreactivity. (198 words).
  4. Tang EL, Tan CH, Fung SY, Tan NH
    J Proteomics, 2016 10 04;148:44-56.
    PMID: 27418434 DOI: 10.1016/j.jprot.2016.07.006
    The venom of Malayan pit viper (Calloselasma rhodostoma) is highly toxic but also valuable in drug discovery. However, a comprehensive proteome of the venom that details its toxin composition and abundance is lacking. This study aimed to unravel the venom complexity through a multi-step venomic approach. At least 96 distinct proteins (29 basic, 67 acidic) in 11 families were identified from the venom. The venom consists of mainly snake venom metalloproteinases (SVMP, 41.17% of total venom proteins), within which the P-I (kistomin, 20.4%) and P-II (rhodostoxin, 19.8%) classes predominate. This is followed by C-type lectins (snaclec, 26.3%), snake venom serine protease (SVSP, 14.9%), L-amino acid oxidase (7.0%), phospholipase A2 (4.4%), cysteine-rich secretory protein (2.5%), and five minor toxins (nerve growth factor, neurotrophin, phospholipase B, 5' nucleotidase and phosphodiesterase, totaling 2.6%) not reported in the proteome hitherto. Importantly, all principal hemotoxins unveiled correlate with the syndrome: SVSP ancrod causes venom-induced consumptive coagulopathy, aggravated by thrombocytopenia caused by snaclec rhodocytin, a platelet aggregation inducer, while P-II rhodostoxin mediates hemorrhage, exacerbated by P-I kistomin and snaclec rhodocetin that inhibit platelet plug formation. These toxins exist in multiple isoforms and/or complex subunits, deserving further characterization for the development of an effective, polyspecific regional antivenom.

    BIOLOGICAL SIGNIFICANCE: Advents in proteomics and bioinformatics have vigorously propelled the scientific discoveries of toxins from various lineages of venomous snakes. The Malayan pit viper, Calloselasma rhodostoma, is a medically important species in Southeast Asia as its bite can cause envenomation, while the venom is also a source of bioactive compounds for drug discovery. Detailed profiling of the venom, however, is inadequate possibly due to the complex nature of the venom and technical limitation in separating the constituents into details. Integrating a multi-step fractionation method, this study successfully revealed a comprehensive and quantitative profile of the composition of the venom of this medically important venomous snake. The relative abundance of the various venom proteins is determined in a global profile, providing useful information for understanding the pathogenic roles of the different toxins in C. rhodostoma envenomation. Notably, the principal hemotoxins were identified in great details, including the variety of toxin subunits and isoforms. The findings indicate that these toxins are the principal targets for effective antivenom neutralization, and should be addressed in the production of a pan-regional polyspecific antivenom. In addition, minor toxin components not reported previously in the venom were also detected in this study, enriching the current toxin database for the venomous snakes.

  5. Tan TW, Chen BC, Tan HL, Chang CM
    JBI Database System Rev Implement Rep, 2017 Apr;15(4):862-872.
    PMID: 28398972 DOI: 10.11124/JBISRIR-2016-003034
    REVIEW QUESTION/OBJECTIVE: This review aims to determine the best available evidence related to the effectiveness of amylmetacresol and 2,4-dichlorobenzyl alcohol throat lozenges in patients with acute sore throat due to upper respiratory tract infection (URTI). The objective is to examine the analgesic properties of amylmetacresol and 2,4-dichlorobenzyl alcohol (AMC/DCBA) throat lozenge comparing with placebo for the relief of pain in patients with acute sore throat due to URTIs.The review question is:More specifically, the objectives are to.
  6. Tan SH, Habibullah MS, Tan SK, Choon SW
    J Environ Manage, 2017 Dec 01;203(Pt 1):603-611.
    PMID: 28285804 DOI: 10.1016/j.jenvman.2017.02.029
    This study investigates the impact of the aggregate and individual dimensions of environmental performance (EP) on financial performance (FP), based on a dataset covering the travel and tourism industry (airlines, casinos, hotels, and restaurants) across different economic regions over the period 2003-2014. The results reveal that EP positively affects the FP in the hotel industry when aggregate EP is used. When individual dimensions of EP are considered, resource reduction is found to positively (negatively) affect the performance in the hotel (airline) industry, while product innovation positively affects the performance in the restaurant industry. Hence, the trade-off effect seems to be dominant in the airline industry, and the 'heterogeneous resources and reputation-building' hypothesis is evident in both the hotel and restaurant industries. In addition, in general, the findings support the positive moderating effect of slack resources on the relationship between the individual dimensions of EP and FP in the travel and tourism industry, and, hence, are supportive of the slack resources hypothesis. These effects, however, vary depending on the travel and tourism industry under investigation.
  7. Tan BY, Cheah JS, Tan SK, Chew BK
    Med J Malaya, 1970 Jun;24(4):308-10.
    PMID: 4248355
  8. Tan JH, Ng ZQ, Tan HCL, Vendargon S
    BMJ Case Rep, 2018 Jun 27;2018.
    PMID: 29950501 DOI: 10.1136/bcr-2018-224741
    A 72-year-old Chinese man presented with mild symptoms of heart failure. Transthoracic echocardiography showed signs of cardiac tamponade though clinically he was relatively well. The option of pericardiocentesis was not carried out due to a narrow window for aspiration with only a thin layer of effusion seen surrounding the apex and right ventricle on subcostal view.Pericardial window was done via a left anterolateral thoracotomy. Intraoperatively, 500 cm3 of purulent fluid was drained. Microbiology screens were all negative. We present the atypical clinical course of this elderly man presenting with a large pyopericardium.
  9. Tan RZ, Mohd Nor F, Shafie S, Tan LJ
    Forensic Sci Med Pathol, 2019 03;15(1):151-154.
    PMID: 30293222 DOI: 10.1007/s12024-018-0026-3
    Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a gram-negative intracellular bacillus. Tuberculosis, also an infectious disease, is caused by Mycobacterium tuberculosis, an acid fast bacillus. In both diseases, patients commonly present with fever and respiratory symptoms due to sepsis which might lead to respiratory failure or sudden death if left untreated. Not only are these two entities similar in clinical presentation, but the autopsy findings may mimic each other, giving rise to difficulties in determining the cause of death. We report a case of melioidosis and compare it to a typical case of miliary tuberculosis. Similarities between the cases on gross and histopathological examinations are discussed. In such circumstances, microbiological culture of bodily fluids and internal organs should be performed to ascertain the correct cause of death.
  10. Tan SP, Tan EN, Lim QY, Nafiah MA
    J Ethnopharmacol, 2020 May 10;253:112610.
    PMID: 31991202 DOI: 10.1016/j.jep.2020.112610
    ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus acidus (L.) Skeels is not only used for its edible fruits but also used to treat a wide spectrum of diseases such as inflammatory, rheumatism, bronchitis, asthma, respiratory disorder, hepatic diseases and diabetes in India, Asia, the Caribbean region, and Central and South America. This paper aims to discuss the current understanding regarding the traditional uses, phytochemical and pharmacological studies of P. acidus, and their possible research opportunities.

    MATERIALS AND METHODS: All information on P. acidus was collected from various electronic database (ACS, PubMed, Scopus, Web of Science, SciFinder, Science Direct, Google Scholar, Springer, Wiley, Taylor and Mendeley) and also from those published materials (Ph.D. and M.Sc. dissertations and books) by using a combination of various meaningful keywords.

    RESULTS: Phytochemical analyses on barks, leaves, roots and fruits of P. acidus identified triterpene, diterpene, sesquiterpene, and glycosides as predominant classes of bioactive substances found in this plant. P. acidus was reported with various pharmacological activities such as in vivo hepatoprotective and hypoglycemic, in vitro anti-oxidant, α-glucosidase inhibitory, anti-inflammatory and antimicrobial activities. However, none of these studies are with clinical research. Some of the studies were performed with only a single set of experiments or with a high dose of extract, and thus the validity of the experimental data may be questionable. In addition, most of the studies described were without identifying the effective components. Some of the assays were even without a positive control for comparison which makes results questionable.

    CONCLUSION: Although P. acidus has been proven as a valuable medicinal source from its traditional uses. However, the pharmacological experiments conducted were not sufficient to verify its traditional uses. More investigation is required to confirm the traditional claims such as bioassay-guided isolation of bioactive compounds, detailed pharmacological investigations, clinical studies, and its toxicity investigation. Additionally, an experimental design with sufficient data replication, the use of controls and authenticated research materials, and the selection of a rationale dose or concentration for the analysis are keys to providing reproducible experimental data.

  11. Allotey P, Tan DT, Kirby T, Tan LH
    Health Syst Reform, 2019;5(1):66-77.
    PMID: 30924744 DOI: 10.1080/23288604.2018.1541497
    Community engagement describes a complex political process with dynamic negotiation and renegotiation of power and authority between providers and recipients of health care in order to achieve a shared goal of universal health care coverage. Though examples exist of community engagement projects, there is very little guidance on how to implement and embed community engagement as a concerted, integrated, strategic, and sustained component of health systems. Through a series of case studies, this article explores the factors that enable community engagement particularly with a direct impact on health systems.
  12. Wong SJ, Urlings T, Seng C, Leong S, Tan BS, Tan MH
    Malays Orthop J, 2020 Mar;14(1):42-48.
    PMID: 32296481 DOI: 10.5704/MOJ.2003.007
    Introduction: The management of musculoskeletal tumours is complex and requires a multi-disciplinary approach. Preoperative embolisation can be often employed to reduce intra-operative blood loss and complication rates from surgery. We report our experience with the safety, technical success and efficacy of pre-operative embolisation in musculoskeletal tumours.

    Materials and Methods: Thirteen consecutive patients who underwent pre-operative embolisation of a musculoskeletal tumour followed by surgical intervention at our institution from May 2012 to January 2016 were enrolled into the study. Patient demographics, tumour characteristics, embolisation techniques and type of surgery were recorded. Technical success of embolisation, amount of blood loss during surgery and transfusion requirements were estimated.

    Results: There were five female and eight male patients who underwent pre-operative embolisation during the study period. The age ranged between 16 to 68 years, and the median age was 54. Technical success was achieved in all patients. Mean intra-operative blood loss was 1403ml, with a range of 150ml to 6900ml. Eight patients (62%) required intra-operative blood products of packed red blood cells and fresh frozen plasma. No major complications occurred during embolisation.

    Conclusion: Pre-operative trans-arterial embolisation is feasible and safe for a variety of large and hypervascular musculoskeletal tumours. Our small series suggests that preoperative embolisation could contribute to the reduction of the intra-operative and post-operative blood product transfusion. It should be considered as a pre-operative adjunct for major tumour resections with a high risk of bleeding. The use of the haemoglobin gap complemented the assessment of perioperative blood loss.

  13. Neoh HM, Tan XE, Sapri HF, Tan TL
    Infect Genet Evol, 2019 10;74:103935.
    PMID: 31233781 DOI: 10.1016/j.meegid.2019.103935
    Pulsed-field gel electrophoresis (PFGE) is considered the "gold standard" for bacteria typing. The method involves enzyme restriction of bacteria DNA, separation of the restricted DNA bands using a pulsed-field electrophoresis chamber, followed by clonal assignment of bacteria based on PFGE banding patterns. Various PFGE protocols have been developed for typing different bacteria, leading it to be one of the most widely used methods for phylogenetic studies, food safety surveillance, infection control and outbreak investigations. On the other hand, as PFGE is lengthy and labourious, several PCR-based typing methods can be used as alternatives for research purposes. Recently, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) and whole genome sequencing (WGS) have also been proposed for bacteria typing. In fact, as WGS provides more information, such as antimicrobial resistance and virulence of the tested bacteria in comparison to PFGE, more and more laboratories are currently transitioning from PFGE to WGS for bacteria typing. Nevertheless, PFGE will remain an affordable and relevant technique for small laboratories and hospitals in years to come.
  14. Wong LP, Alias H, Tan YR, Tan KM
    PMID: 34846801 DOI: 10.1111/opn.12436
    BACKGROUND: COVID-19 is a threat to everyone's health and can be especially devastating to older individuals.

    AIM: This study examined the behavioural prevention practices against SARS-CoV-2 infection and the intention to vaccinate among older people when the COVID-19 vaccine is on the verge of becoming available.

    METHOD: A cross-sectional, online survey was conducted between 14th July and 8th October 2020 among the older people in Malaysia. A questionnaire was designed to assess the practice towards measures preventing SARS-CoV-2 infection, and COVID-19 vaccination attitudes and intention. Socio-demographic characteristics, constructs of a health belief model (HBM), the 6-item state version of the State-Trait Anxiety Inventory (STAI-6) were correlates of the main outcomes.

    FINDINGS: The mean score of total preventive measures scores was 13.4 ± 1.7 out of a maximum score of 15, indicating very good prevention practices. By demographics, females, having a tertiary education exhibited higher prevention practices in the univariable analyses. Components of the HBM and being female remain significant correlates of higher prevention practices in multivariable logistic regression analysis (MLRA). A total of 657 (87.1%) participants responded and intend to receive the COVID-19 vaccination. Provider recommendations may improve vaccination uptake (91.6%). MLRA revealed that having a positive vaccination attitude was 16 times more likely to accept the COVID-19 vaccination (OR = 16.10; 95% CI 8.97-28.91). Hearing of someone they know who has COVID-19 serves as a cue to action and significantly influences vaccination (OR = 4.25; 95% CI 1.80-10.03). Participants below 70 years old expressed higher vaccination intention (OR = 2.07; 95% CI 1.19-3.58).

    CONCLUSION: The results provide the first evidence for public authorities to target older people vulnerable to compliance with recommended preventive measures against SARS-CoV-2 infections.

  15. Palasuberniam P, Chan YW, Tan KY, Tan CH
    Front Pharmacol, 2021;12:727756.
    PMID: 35002690 DOI: 10.3389/fphar.2021.727756
    The Samar Cobra, Naja samarensis, is endemic to the southern Philippines and is a WHO-listed Category 1 venomous snake species of medical importance. Envenomation caused by N. samarensis results in neurotoxicity, while there is no species-specific antivenom available for its treatment. The composition and neutralization of N. samarensis venom remain largely unknown to date. This study thus aimed to investigate the venom proteome of N. samarensis for a comprehensive profiling of the venom composition, and to examine the immunorecognition as well as neutralization of its toxins by a hetero-specific antivenom. Applying C18 reverse-phase high-performance liquid chromatography (RP-HPLC) and tandem mass spectrometry (LC-MS/MS), three-finger toxins (3FTx) were shown to dominate the venom proteome by 90.48% of total venom proteins. Other proteins in the venom comprised snake venom metalloproteinases, phospholipases A2, cysteine-rich secretory proteins, venom nerve growth factors, L-amino acid oxidases and vespryn, which were present at much lower abundances. Among all, short-chain alpha-neurotoxins (SαNTX) were the most highly expressed toxin within 3FTx family, constituting 65.87% of the total venom proteins. The SαNTX is the sole neurotoxic component of the venom and has an intravenous median lethal dose (LD50) of 0.18 μg/g in mice. The high abundance and low LD50 support the potent lethal activity of N. samarensis venom. The hetero-specific antivenom, Philippine Cobra Antivenom (PCAV, raised against Naja philippinensis) were immunoreactive toward the venom and its protein fractions, including the principal SαNTX. In efficacy study, PCAV was able to cross-neutralize the lethality of SαNTX albeit the effect was weak with a low potency of 0.20 mg/ml (defined as the amount of toxin completely neutralized per milliliter of the antivenom). With a volume of 5 ml, each vial of PCAV may cross-neutralize approximately 1 mg of the toxin in vivo. The findings support the potential para-specific use of PCAV in treating envenomation caused by N. samarensis while underscoring the need to improve the potency of its neutralization activity, especially against the highly lethal alpha-neurotoxins.
  16. Tan MP, Mohamed Alitheen NB, Tan WS, Yap WB
    Vaccines (Basel), 2022 Dec 01;10(12).
    PMID: 36560475 DOI: 10.3390/vaccines10122066
    The current influenza vaccines only confer protection against the circulating influenza subtypes, therefore universal vaccines are needed to prevent upcoming influenza outbreaks caused by emerging influenza subtypes. The extracellular domain of influenza A M2 protein (M2e) is highly conserved among different subtypes of influenza A viruses, and it is able to elicit protective immunity against the viruses. The influenza nucleoprotein (NP) was used to display the M2e in this study due to its promising T-cell response and adjuvanticity. The M2e gene was fused to the 5'-end of the NP gene and then cloned into pRSET B vector. The DNA sequencing analysis revealed six point mutations in the M2e-NP fusion gene, including one mutation in the M2e peptide and five mutations in the NP. The mutations were reverted using PCR site-directed mutagenesis. The recombinant plasmids (pRSET B-M2e-NP and pRSET B-mM2e-NP) were introduced into Escherichia coli (E. coli) BL21 (DE3) for protein expression. The mutated and non-mutated proteins were subsequently expressed and named mM2e-NP and M2e-NP, respectively. The expression of mM2e-NP and M2e-NP was not affected by the mutations. The binding of anti-M2e antibody to the purified native mM2e-NP and M2e-NP also remained active. However, when the anti-NP antibody was tested, the signal produced by mM2e-NP was very weak. The results implied that the amino acid changes in the NP had adversely impacted on the conformation of mM2e-NP and subsequently affected the antibody binding. In light of the remarkable antibody binding to the M2e-NP fusion protein, this study highly recommends the potential of M2e-NP as a universal influenza vaccine candidate.
  17. Tan WF, Voo SYM, Tan WC, Sandhya R
    Med J Malaysia, 2022 Nov;77(6):669-675.
    PMID: 36448383
    INTRODUCTION: Sweet's syndrome (SS) also known as acute febrile neutrophilic dermatosis, is an uncommon disease characterised by acute onset of tender, violaceous or erythematous, oedematous papules, nodules or plaques, with fever. It is classified into classic, malignancyassociated, and drug-induced subtypes.The aims of this study is to evaluate the subtypes, clinical features, laboratory profiles, and treatment of patients with SS.

    MATERIALS AND METHODS: We did a retrospective medical record review of all patients with SS from July 2014 to July 2018 at Hospital Queen Elizabeth and Hospital Pulau Pinang, both tertiary hospitals in Malaysia.

    RESULTS: Twenty-nine patients were included. Approximately half of the patients (15) were females with a mean age of onset of 50.93 (± 11.52) years. The most common subtype was classic (62.0%) followed by malignancy-associated (31.0%) and drug-induced (6.9%). Among the patients with the classic subtype, infective-related causes (50.0%) were the most common. Among the patients with malignancy, eight had haematological malignancy and one had a solid tumour. Two-third of the malignancies were diagnosed within a year after the diagnosis of SS. Eight of our patients in Sabah had mycobacterial infections with three having concomitant haematological malignancies. Patients with malignancy-associated SS had lower mean haemoglobin (p=0.018) and mean platelet count (p=0.031). Itch was associated with the presence of pustules (p=0.038). Histopathological examination of all skin lesions showed dermal neutrophilic infiltrates and 25 (86.2%) of them had papillary dermal oedema. The study was limited by its retrospective design. The sample size was small likely due to the uncommon occurrence of this condition.

    CONCLUSION: SS is an uncommon dermatosis with distinctive clinical and histopathological features. Screening for underlying malignancy is essential especially for those who present with anaemia, thrombocytopenia, and pathergy phenomenon. Mycobacterial infection should be considered in this region due to high tuberculosis burden.

  18. Hayati AR, Cheah FC, Tan AE, Tan GC
    Early Hum Dev, 2007 Jan;83(1):41-6.
    PMID: 16750336 DOI: 10.1016/j.earlhumdev.2006.04.002
    BACKGROUND: Septal hypertrophic cardiomyopathy (sHCM) is a characteristic anomaly of the infant of diabetic mother (IDM). Insulin-like growth factor-1 (IGF-1) has been identified as a mediator of tissue overgrowth and we have previously shown that maternal IGF-1 levels were significantly elevated among neonates with asymmetrical sHCM. IGF-1 does not cross the placenta; it exerts physiologic action through binding to the IGF-1 receptor (IGF-1R). Localisation and expression of IGF-1R in term diabetic pregnancies are largely unclear. We have studied IGF-1R in the placentae of diabetic and normal pregnancies and this receptor expression in association with neonates with sHCM.
    METHODS: IGF-1R localization and expression in the placentae of six diabetic pregnancies associated with neonatal sHCM were compared with six each of randomly selected diabetic and normal pregnancies without neonatal sHCM by immunohistochemistry. The staining for IGF-1R in the deciduas, cytotrophoblasts, syncytiotrophoblasts and villous endothelium for these 18 samples were assessed and scored by two pathologists who were blinded to the respective diagnoses.
    RESULTS: Placental IGF-1R staining was negative in the villous endothelium for all three groups. IGF-1R staining was present in deciduas, cytotrophoblasts and syncytiotrophoblasts but the staining was weaker in the entire group of infants with sHCM compared to those without sHCM.
    CONCLUSIONS: IGF-1R is localized in all cell types of the placenta except in villous endothelium. Weaker placental IGF-1R staining in the placentae of diabetic pregnancies associated with sHCM suggests reduced expression of IGF-1R. This may be a down-regulatory response to elevated maternal IGF with neonatal sHCM outcome.
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