Displaying publications 1 - 20 of 248 in total

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  1. Dorai AA, Halim AS, Zulmi W
    Med J Malaysia, 2004 Dec;59 Suppl F:42-6.
    PMID: 15941160
    Reconstructive surgeons often encounter complex soft tissue and skeletal defects following oncological surgery. Soft tissue defects after wide resection in upper extremities posses a difficult challenge to find adequate tissue for reconstructing these defects. Paucity of local tissues dictates the requirement of loco-regional or distant flaps for these complex soft tissue defects which often exposes tendons, bones, nerves and joints. The latissimus dorsi muscle is a near ideal flap for the reconstruction because of the long neurovascular pedicle, ease of mobilization and its expendability. It can be rotated, with or without overlying skin, to cover soft tissue defects of the shoulder arm and elbow. Due to the large size of the muscle, it can be used to resurface the soft tissue defects and cover all major structures. Eleven consecutive cases were reviewed in which latissimus dorsi myocutaneous flap was used to reconstruct soft tissue defects of the upper limb following radical tumor resection. Flap survival was 100% with nominal donor site morbidity.
    Matched MeSH terms: Muscle, Skeletal/blood supply
  2. Jagwani AV, Fathi NQ, Jailani RF, Zakaria AD
    BMJ Case Rep, 2017 Jan 06;2017.
    PMID: 28062430 DOI: 10.1136/bcr-2016-217865
    Polyarteritis nodosa (PAN) is a systemic necrotising vasculitis preferentially targeting medium-sized arteries and not related with glomerulonephritis or small vessel involvement. Clinical manifestations of PAN are multisystem. The gastrointestinal, renal, cardiac, musculoskeletal, skin and central nervous systems may be involved. The aetiology remains unknown, and the ensuing vasculitis may lead to aneurysm formation and thrombosis in any organs of the body with resultant ischaemia. PAN of the intestines is a relatively common manifestation of this disease but rarely causes bowel ischaemia resulting in necrosis. Here we report a case of a young Chinese patient who presented with an acute abdomen requiring surgery and made good recovery post operatively. He remains free of symptoms while on steroid therapy.
    Matched MeSH terms: Cecum/blood supply; Colon/blood supply
  3. Leong BD, Chuah JA, Kumar VM, Mazri MY, Zainal AA
    Singapore Med J, 2008 Nov;49(11):e300-2.
    PMID: 19037533
    True and pseudoaneurysms of the visceral arteries are uncommon. They represent 0.1-0.2 percent of all vascular aneurysms. Visceral artery aneurysms (VAAs) should be treated due to their propensity to rupture and associated high mortality. We describe a 58-year-old man with pseudoaneurysm of the inferior pancreaticoduodenal artery and who presented with post-motor vehicle accident abdominal pain and a pulsatile epigastic mass. Computed tomography (CT) showed a pseudoaneurysm of the visceral artery, and selective mesenteric angiography showed the aneurysm to be arising from the inferior pancreaticoduodenal artery. The aneurysm was successfully treated with endovascular coil embolisation. CT angiogram at one month post-procedure revealed persistent occlusion of the aneurysm. To the best of our knowledge, this is the first reported pseudoaneurysm of inferior pancreaticoduodenal artery secondary to blunt abdominal trauma from a motor vehicle accident and also the first reported VAA from Malaysia.
    Matched MeSH terms: Pancreas/blood supply*
  4. Al-Salahi OS, Kit-Lam C, Majid AM, Al-Suede FS, Mohammed Saghir SA, Abdullah WZ, et al.
    Microvasc Res, 2013 Nov;90:30-9.
    PMID: 23899415 DOI: 10.1016/j.mvr.2013.07.007
    Targeting angiogenesis could be an excellent strategy to combat angiogenesis-dependent pathophysiological conditions such as cancer, rheumatoid arthritis, obesity, systemic lupus erythematosus, psoriasis, proliferative retinopathy and atherosclerosis. Recently a number of clinical investigations are being undertaken to assess the potential therapeutic application of various anti-angiogenic agents. Many of these angiogenesis inhibitors are directed against the functions of endothelial cells, which are considered as the building blocks of blood vessels. Similarly, roots of a traditional medicinal plant, Eurycoma longifolia, can be used as an alternative treatment to prevent and treat the angiogenesis-related diseases. In the present study, antiangiogenic potential of partially purified quassinoid-rich fraction (TAF273) of E. longifolia root extract was evaluated using ex vivo and in vivo angiogenesis models and the anti-angiogenic efficacy of TAF273 was investigated in human umbilical vein endothelial cells (HUVEC). TAF273 caused significant suppression in sprouting of microvessels in rat aorta with IC50 11.5μg/ml. TAF273 (50μg/ml) showed remarkable inhibition (63.13%) of neovascularization in chorioallantoic membrane of chick embryo. Tumor histology also revealed marked reduction in extent of vascularization. In vitro, TAF273 significantly inhibited the major angiogenesis steps such as proliferation, migration and differentiation of HUVECs. Phytochemical analysis revealed high content of quassinoids in TAF273. Specially, HPLC characterization showed that TAF273 is enriched with eurycomanone, 13α(21)-epoxyeurycomanone and eurycomanol. These results demonstrated that the antiangiogenic activity of TAF273 may be due to its inhibitory effect on endothelial cell proliferation, differentiation and migration which could be attributed to the high content of quassinoids in E. longifolia.
    Matched MeSH terms: Chorioallantoic Membrane/blood supply
  5. Aziz ME, Yusof NR, Abdullah MS, Yusof AH, Yusof MI
    Singapore Med J, 2005 Aug;46(8):426-8.
    PMID: 16049615
    Persistent sciatic artery is a very uncommon embryological vascular variant. This case report highlights this rare vascular anomaly, diagnostic difficulty, complication and subsequent treatment in a 43-year-old man who presented with sudden onset of right leg pain for a few hours. He was unable to walk because of pain and numbness. Emergency right lower limb angiogram showed a large aneurysm that was initially thought to arise from the right common femoral artery, associated with thrombus formation within the right popliteal artery. A below knee amputation was performed due to worsening ischaemia of the right leg. The persistent right sciatic artery was later obliterated using percutaneous stenting and endovascular grafting, with deployment of two wallstents.
    Matched MeSH terms: Leg/blood supply*
  6. Halim AS, Yusof I
    J Orthop Surg (Hong Kong), 2004 Jun;12(1):110-3.
    PMID: 15237132
    Management of severe open tibial fracture with neurovascular injury is difficult and controversial. Primary amputation is an acceptable option as salvaging the injured, insensate, and ischaemic limb may result in chronic osteomyelitis and non-functional limb. We report a case of open tibial fracture associated with segmental bone and soft tissue loss, posterior tibial nerve and artery injuries, which was further complicated by chronic osteo-myelitis treated with composite vascularised osteocutaneous fibula and sural nerve graft. Functional outcome of the injured limb at one-year follow-up was satisfactory: the patient was capable of achieving full weightbearing and was able to appreciate crude touch, pain, proprioception, and temperature at the plantar aspect of the foot. There was no pressure sore or ulceration.
    Matched MeSH terms: Fibula/blood supply*
  7. Abu Bakar MR, Abdul Kadir A, Abdul Wahab SZ, Abdul Karim AH, Nik Hussain NH, Mohd Noor N, et al.
    PLoS One, 2015;10(7):e0133514.
    PMID: 26222158 DOI: 10.1371/journal.pone.0133514
    AIM: To compare the mean of anteroposterior (AP) measurements of the uterus in longitudinal and oblique transverse planes, and the pulsatility index (PI) and resistive index (RI) of the uterine artery and superficial skin wound artery between patients taking Channa striatus and placebo.

    BACKGROUND: Channa striatus, also known as haruan, is a fresh water snakehead fish consumed in many parts of Southeast Asia. Channa striatus is also normally consumed by women postpartum to promote wound healing as well as to reduce post-operative pain.

    METHODOLOGY: This study is a randomised, double blind, placebo-controlled study conducted in women after Lower Segment Caesarean Section (LSCS). Subjects were randomised to either a Channa striatus or a placebo group and were given a daily dosage of 500 mg of Channa striatus extract or 500 mg maltodextrin, respectively, for six weeks post LSCS. The anteroposterior measurements of the uterus in the longitudinal and oblique transverse planes, and the pulsatility index (PI) and resistive index (RI) of the uterine and superficial skin wound arteries were assessed using pelvic Gray-scale ultrasound and Doppler ultrasound at baseline (Day 3) and at two weeks, four weeks and six weeks post-operatively.

    RESULTS: Sixty-six subjects were randomised into the study with 33 in the Channa striatus group and 33 in the placebo group. No significant differences were detected in terms of the pulsatility index (PI) and the resistive index (RI) of the uterine and superficial skin wound arteries between the Channa striatus and placebo groups. However, in the Channa striatus group, the AP measurements of the uterus on the longitudinal and oblique transverse planes were significantly lower compared to the placebo group (p<0.05 and p<0.001, respectively).

    CONCLUSION: Daily intake of Channa striatus extract results in marked differences compared to placebo in terms of uterine involution and recovery in women post LSCS.

    TRIAL REGISTRATION: www.isrctn.com 11960786.

    Matched MeSH terms: Uterus/blood supply*
  8. Ng CT, Fong LY, Tan JJ, Rajab NF, Abas F, Shaari K, et al.
    BMC Complement Altern Med, 2018 Jul 06;18(1):210.
    PMID: 29980198 DOI: 10.1186/s12906-018-2270-1
    BACKGROUND: Clinacanthus nutans (Burm. f.) Lindau. has traditionally been using in South East Asia countries to manage cancer. However, scientific evidence is generally lacking to support this traditional claim. This study aims to investigate the in vitro, ex-vivo and in vivo effects of C. nutans extracts on angiogenesis.

    METHODS: C. nutans leaves was extracted with 50-100% ethanol or deionised water at 1% (w/v). Human umbilical veins endothelial cell (HUVEC) proliferation was examined using MTT assay. The in vitro anti-angiogenic effects of C. nutans were assessed using wound scratch, tube formation and transwell migration assays. The VEGF levels secreted by human oral squamous cell carcinoma (HSC-4) cell and HUVEC permeability were also measured. Besides, the rat aortic ring and chick embryo chorioallantoic membrane (CAM) assays, representing ex vivo and in vivo models, respectively, were performed.

    RESULTS: The MTT assay revealed that water extract of C. nutans leaves exhibited the highest activity, compared to the ethanol extracts. Therefore, the water extract was chosen for subsequent experiments. C. nutans leaf extract significantly suppressed endothelial cell proliferation and migration in both absence and presence of VEGF. However, the water extract failed to suppress HUVEC transmigration, differentiation and permeability. C. nutans water extract also did not suppress HSC-4 cell-induced VEGF production. Importantly, C. nutans water extract significantly abolished the sprouting of vessels in aortic rings as well as in chick embryo CAM.

    CONCLUSION: In conclusion, these findings reveal potential anti-angiogenic effects of C. nutans, providing new evidence for its potential application as an anti-angiogenic agent.

    Matched MeSH terms: Chorioallantoic Membrane/blood supply
  9. Yong SJ
    ACS Chem Neurosci, 2021 Feb 17;12(4):573-580.
    PMID: 33538586 DOI: 10.1021/acschemneuro.0c00793
    Long-COVID is a postviral illness that can affect survivors of COVID-19, regardless of initial disease severity or age. Symptoms of long-COVID include fatigue, dyspnea, gastrointestinal and cardiac problems, cognitive impairments, myalgia, and others. While the possible causes of long-COVID include long-term tissue damage, viral persistence, and chronic inflammation, the review proposes, perhaps for the first time, that persistent brainstem dysfunction may also be involved. This hypothesis can be split into two parts. The first is the brainstem tropism and damage in COVID-19. As the brainstem has a relatively high expression of ACE2 receptor compared with other brain regions, SARS-CoV-2 may exhibit tropism therein. Evidence also exists that neuropilin-1, a co-receptor of SARS-CoV-2, may be expressed in the brainstem. Indeed, autopsy studies have found SARS-CoV-2 RNA and proteins in the brainstem. The brainstem is also highly prone to damage from pathological immune or vascular activation, which has also been observed in autopsy of COVID-19 cases. The second part concerns functions of the brainstem that overlap with symptoms of long-COVID. The brainstem contains numerous distinct nuclei and subparts that regulate the respiratory, cardiovascular, gastrointestinal, and neurological processes, which can be linked to long-COVID. As neurons do not readily regenerate, brainstem dysfunction may be long-lasting and, thus, is long-COVID. Indeed, brainstem dysfunction has been implicated in other similar disorders, such as chronic pain and migraine and myalgic encephalomyelitis or chronic fatigue syndrome.
    Matched MeSH terms: Brain Stem/blood supply
  10. Lim CW, Cheng J, Tay ELT, Teo HY, Wong EPY, Yong VKY, et al.
    BMC Ophthalmol, 2018 Dec 10;18(1):315.
    PMID: 30526537 DOI: 10.1186/s12886-018-0976-y
    BACKGROUND: Despite the potential usefulness of optical coherence tomography angiography in retinal and optic disc conditions, the reliability of the imaging modality remains unclear. This study set out to measure the microvascular density of macula and optic disc by mean of optical coherence tomography angiography and report the repeatability of the vessel density measurements.

    METHODS: Cross sectional observational cohort study. Subjects with normal eyes were recruited. Two sets of optical coherence tomography angiography images of macula and optic nerve head were acquired during one visit. Novel in-house developed software was used to count the pixels in each images and to compute the microvessel density of the macula and optic disc. Data were analysed to determine the measurement repeatability.

    RESULTS: A total of 176 eyes from 88 consecutive normal subjects were recruited. For macular images, the mean vessel density at superficial retina, deep retina, outer retina and choriocapillaries segment was OD 0.113 and OS 0.111, OD 0.239 and OS 0.230, OD 0.179 and OS 0.164, OD 0.237 and OS 0.215 respectively. For optic disc images, mean vessel density at vitreoretinal interface, radial peripapillary capillary, superficial nerve head and disc segment at the level of choroid were OD 0.084 and OS 0.085, OD 0.140 and OS 0.138, OD 0.216 and OS 0.209, OD 0.227 and OS 0.236 respectively. The measurement repeatability tests showed that the coefficient of variation of macular scans, for right and left eyes, ranged from 6.4 to 31.1% and 5.3 to 59.4%. Likewise, the coefficient of variation of optic disc scans, for right and left eyes, ranged from 14.3 to 77.4% and 13.5 to 75.3%.

    CONCLUSIONS: Optical coherence tomography angiography is a useful modality to visualise the microvasculature plexus of macula and optic nerve head. The vessel density measurement of macular scan by mean of optical coherence tomography angiography demonstrated good repeatability. The optic disc scan, on the other hand, showed a higher coefficient of variation indicating a lower measurement repeatability than macular scan. Interpretation of optical coherence tomography angiography should take into account test-retest repeatability of the imaging system.

    TRIAL REGISTRATION: National Healthcare Group Domain Specific Review Board ( NHG DSRB ) Singapore. DSRB Reference: 2015/00301.

    Matched MeSH terms: Macula Lutea/blood supply*; Optic Disk/blood supply*
  11. Yip VCH, Wong HT, Yong VKY, Lim BA, Hee OK, Cheng J, et al.
    J Glaucoma, 2019 01;28(1):80-87.
    PMID: 30461553 DOI: 10.1097/IJG.0000000000001125
    AIM: To study the microvascular density of the macular and optic nerve head in healthy and glaucoma subjects using optical coherence tomography angiography.

    METHODOLOGY: We performed a cross-sectional cohort study on healthy subjects and patients with glaucoma. The AngioVue Enhanced Microvascular Imaging System was used to capture the optic nerve head and macula images during one visit. En face segment images of the macular and optic disc were studied in layers. Microvascular density of the optic nerve head and macula were quantified by the number of pixels measured by a novel in-house developed software. Areas under the receiver operating characteristic curves (AUROC) were used to determine the accuracy of differentiating between glaucoma and healthy subjects.

    RESULTS: A total of 24 (32 eyes) glaucoma subjects (57.5±9.5-y old) and 29 (58 eyes) age-matched controls (51.17±13.5-y old) were recruited. Optic disc and macula scans were performed showing a greater mean vessel density (VD) in healthy compared with glaucoma subjects. The control group had higher VD than the glaucoma group at the en face segmented layers of the optic disc (optic nerve head: 0.209±0.05 vs. 0.110±0.048, P<0.001; vitreoretinal interface: 0.086±0.045 vs. 0.052±0.034, P=0.001; radial peripapillary capillary: 0.146±0.040 vs. 0.053±0.036, P<0.001; and choroid: 0.228±0.074 vs. 0.165±0.062, P<0.001). Similarly, the VD at the macula was also greater in controls than glaucoma patients (superficial retina capillary plexus: 0.115±0.016 vs. 0.088±0.027, P<0.001; deep retina capillary plexus: 0.233±0.027 vs. 0.136±0.073, P<0.001; outer retinal capillary plexus: 0.190±0.057 vs. 0.136±0.105, P=0.036; and choriocapillaris: 0.225±0.053 vs. 0.153±0.068, P<0.001. The AUROC was highest for optic disc radial peripapillary capillary (0.96), followed by nerve head (0.92) and optic disc choroid (0.76). At the macula, the AUROC was highest for deep retina (0.86), followed by choroid (0.84), superficial retina (0.81), and outer retina (0.72).

    CONCLUSIONS: Microvascular density of the optic disc and macula in glaucoma patients was reduced compared with healthy controls. VD of both optic disc and macula had a high diagnostic ability in differentiating healthy and glaucoma eyes.

    Matched MeSH terms: Macula Lutea/blood supply*; Optic Disk/blood supply*
  12. Costa H, Xu X, Overbeek G, Vasaikar S, Patro CP, Kostopoulou ON, et al.
    Oncotarget, 2016 Jul 26;7(30):47221-47231.
    PMID: 27363017 DOI: 10.18632/oncotarget.9722
    BACKGROUND: Both arginase (ARG2) and human cytomegalovirus (HCMV) have been implicated in tumorigenesis. However, the role of ARG2 in the pathogenesis of glioblastoma (GBM) and the HCMV effects on ARG2 are unknown. We hypothesize that HCMV may contribute to tumorigenesis by increasing ARG2 expression.

    RESULTS: ARG2 promotes tumorigenesis by increasing cellular proliferation, migration, invasion and vasculogenic mimicry in GBM cells, at least in part due to overexpression of MMP2/9. The nor-NOHA significantly reduced migration and tube formation of ARG2-overexpressing cells. HCMV immediate-early proteins (IE1/2) or its downstream pathways upregulated the expression of ARG2 in U-251 MG cells. Immunostaining of GBM tissue sections confirmed the overexpression of ARG2, consistent with data from subsets of Gene Expression Omnibus. Moreover, higher levels of ARG2 expression tended to be associated with poorer survival in GBM patient by analyzing data from TCGA.

    METHODS: The role of ARG2 in tumorigenesis was examined by proliferation-, migration-, invasion-, wound healing- and tube formation assays using an ARG2-overexpressing cell line and ARG inhibitor, N (omega)-hydroxy-nor-L-arginine (nor-NOHA) and siRNA against ARG2 coupled with functional assays measuring MMP2/9 activity, VEGF levels and nitric oxide synthase activity. Association between HCMV and ARG2 were examined in vitro with 3 different GBM cell lines, and ex vivo with immunostaining on GBM tissue sections. The viral mechanism mediating ARG2 induction was examined by siRNA approach. Correlation between ARG2 expression and patient survival was extrapolated from bioinformatics analysis on data from The Cancer Genome Atlas (TCGA).

    CONCLUSIONS: ARG2 promotes tumorigenesis, and HCMV may contribute to GBM pathogenesis by upregulating ARG2.

    Matched MeSH terms: Glioblastoma/blood supply
  13. Pue LB, Lo TS, Wu PY
    Int Urogynecol J, 2013 Nov;24(11):1985-7.
    PMID: 23430075 DOI: 10.1007/s00192-013-2060-8
    Vaginal vascular malformation (VVM) is rare. There are, in fact, less than ten cases reported to date. VVM often presents as a mass protruding from the vagina, mimicking pelvic organ prolapse (POP). It can coexist with POP, thereby usually exaggerating the severity of POP. We report a case of VVM in a premenopausal woman who presented as severe POP and urinary incontinence. The diagnosis was confirmed with computed tomography (CT) scan and angiography. The patient underwent conservative management with embolization. These procedures had to be repeated three times in 1.5 years due to lesion recurrence. In mitigation, conservative treatment eliminates the risks associated with surgery, e.g. massive hemorrhage and visceral injuries. It does, however, require a long course of treatment and follow-up.
    Matched MeSH terms: Vagina/blood supply*
  14. Lakhwani MN, Dadlani NI, Wong YC
    ANZ J Surg, 2009 May;79(5):352-7.
    PMID: 19566516 DOI: 10.1111/j.1445-2197.2009.04888.x
    Chronic venous disorders are conditions of increasing prevalence in the developing world, and venous ulceration is the terminal sequel. Currently there are only limited data on all aspects of this from Southeast Asia. The aim of the present study was to assess differences in the demography and outcome between varicose vein surgery (VVS) and the relatively new endovenous laser therapy (EVT) in patients from Penang, Malaysia.
    Matched MeSH terms: Leg/blood supply*
  15. Wong KT
    Neuropathol. Appl. Neurobiol., 2000 Aug;26(4):313-8.
    PMID: 10931364
    Two major epidemics of viral encephalitis occurred in Asia in 1997 and 1998. The first was a re-emergence of neurovirulent strains of enterovirus 71, which caused severe encephalomyelitis in children in Malaysia, Taiwan and Japan, on a background of hand, foot and mouth disease. Necropsy studies of patients who died of enterovirus 71 infection showed severe perivascular cuffing, parenchymal inflammation and neuronophagia in the spinal cord, brainstem and diencephalon, and in focal areas in the cerebellum and cerebrum. Although no viral inclusions were detected, immunohistochemistry showed viral antigen in the neuronal cytoplasm. Inflammation was often more extensive than neuronal infection, suggesting that other factors, in addition to direct viral cytolysis, may be involved in tissue damage. The second epidemic of viral encephalitis was the result of a novel paramyxovirus called Nipah, which mainly involved pig handlers in Malaysia and Singapore. Pathological evidence suggested that the endothelium of small blood vessels in the central nervous system was particularly susceptible to infection. This led to disseminated endothelial damage and syncytium formation, vasculitis, thrombosis, ischaemia and microinfarction. However, there was also evidence of neuronal infection by the virus and this may also have contributed to the neurological dysfunction in Nipah encephalitis. Some patients who seemed to recover from the acute symptoms have been re-admitted with clinical findings suggestive of relapsing encephalitis. As these two epidemics indicate, the emergence and re-emergence of viral encephalitides continue to pose considerable challenges to the neuropathologist, in establishing the diagnosis and unravelling the pathogenesis of the neurological disease.
    Matched MeSH terms: Central Nervous System/blood supply
  16. Singham KT, Wong HO
    Aust N Z J Med, 1979 Apr;9(2):174-6.
    PMID: 287460 DOI: 10.1111/j.1445-5994.1979.tb04323.x
    Findings are reviewed of isolated Patent Ductus Arteriosus after infancy as seen in 181 patients studied at the University Hospital, Kuala Lumpur, during the period 1967 to 1975. The ages of patients ranged from nine months to 54 years. Eighty-two patients underwent cardiac catheterization. More than 50% of patients were above ten years of age; the sex ratio was 1 male: 2.93 females. Thirty-two per cent of the patients had significant effort dyspnoea or were in heart failure. The complications noted were elevated pulmonary vascular resistance, Eisenmenger syndrome, bacterial endocarditis and cardiac failure.
    Matched MeSH terms: Lung/blood supply*
  17. Rasool AH, Ghazali DM, Abdullah H, Halim AS, Wong AR
    Microvasc Res, 2009 Sep;78(2):230-4.
    PMID: 19481100 DOI: 10.1016/j.mvr.2009.05.005
    Post occlusive skin reactive hyperemia (PORH) is a tool used to assess microcirculation. Endothelial nitric oxide synthase (eNOS) mediates nitric oxide (NO) production; polymorphism of the eNOS gene may affect response to the PORH process. This study aims to determine whether eNOS G894T gene polymorphism affects response to skin PORH. 230 normotensive male and females between 18 and 40 years participated in this cross-sectional study. 170 subjects were of the homozygous GG genotype, whereas 60 were of the GT genotype. Skin PORH was performed by occlusion of the upper arm at 200 mm Hg for 3 min. Skin perfusion and temperature were monitored before, during and after occlusion release using the laser Doppler fluximetry. There were no significant differences between genotypes in their baseline blood pressure, serum cholesterol, BMI and age. Maximum change in perfusion after occlusion release (PORHmax) for the GG and GT genotypes were not significantly different at 50.15+/-1.29 vs. 47.92+/-2.17 AU; ANCOVA, p=0.351. Peak perfusion (PORHpeak) were also not significantly different between the two genotypes (61.23+/-1.36 vs. 57.72+/-2.32 AU; p=0.169). Minimum baseline perfusion were however higher in the GG compared to the GT genotype (10.83+/-0.29 vs. 9.61+/-0.50, p=0.029). We conclude that microvascular reactivity, assessed by change in perfusion after temporary ischemia was not significantly different between the GG and GT genotypes of the eNOS G894T gene. eNOS 894T allele carriers however, have lower baseline perfusion compared to the homozygous G894 allele carrier.
    Matched MeSH terms: Forearm/blood supply; Skin/blood supply*
  18. Marlini M, Mabuchi A, Mallard BL, Hairulhisyam N, Akashi-Takamura S, Harper JL, et al.
    Exp Physiol, 2016 12 01;101(12):1492-1505.
    PMID: 27634415 DOI: 10.1113/EP085727
    NEW FINDINGS: What is the central question of this study? The liver regenerative process is complex and involves a sequence of signalling events, but the possible involvement of structural and haemodynamic changes in vivo during this process has never been explored. What is the main finding and its importance? Normal sinusoidal blood flow and velocity are crucial for a normal regenerative response, and delays in these haemodynamic events resulted in impaired liver regeneration in lipopolysaccharide-insensitive, C3H/HeJ mice. Toll-like receptor 4 signalling is required for restoration of normal liver architecture during the liver regenerative process. Liver regeneration is delayed in mice with a defective Toll-like receptor 4 (TLR4; C3H/HeJ mice) but is normal in TLR4 knockouts (TLR4-/- ). Here, we investigated the possible involvement of structural and haemodynamic changes in vivo in the underlying mechanism. In lipopolysaccharide-sensitive (C3H/HeN and C57BL/6) and lipopolysaccharide-insensitive (C3H/HeJ and TLR4-/- ) mice, a 70% partial hepatectomy (PH) was performed under inhalational anaesthesia. At days 3 and 7 after PH, the hepatic microcirculation was interrogated using intravital microscopy. Delayed liver regeneration was confirmed in C3H/HeJ, but not in C3H/HeN, C57BL/6 (WT) or TLR4-/- mice by liver weight-to-body-weight ratio, the percentage of proliferating cell nuclear antigen (PCNA)-positive cells and mitotic index data. At day 3 after PH, sinusoidal red blood cell velocity increased by 100% in C3H/HeN mice, but by only 40% in C3H/HeJ mice. Estimated sinusoidal blood flow was significantly higher at day 7 after PH in C3H/HeN than in C3H/HeJ mice. The hepatic cord width was significantly larger in C3H/HeN than in C3H/HeJ mice at day 3 and it was significantly larger in TLR4-/- than in C57BL/6 WT mice at day 7 after PH. Hepatocyte nucleus density and functional sinusoidal density was significantly reduced at days 3 and 7 after PH in all mouse strains compared with their zero-time controls. Functional sinusoidal density was significantly lower in C3H/HeJ compared with C3H/HeN mice at day 7 after PH. The present study indicates that altered sinusoidal blood flow and velocity in C3H/HeJ mice may contribute to the observed delay in the regenerative response in these mice. In addition, restoration of normal liver architecture may be delayed in TLR4-/- mice.
    Matched MeSH terms: Liver/blood supply*
  19. Tan JH, Mohamad Y, Tan CLH, Kassim M, Warkentin TE
    J Med Case Rep, 2018 May 19;12(1):131.
    PMID: 29776439 DOI: 10.1186/s13256-018-1684-1
    BACKGROUND: Symmetrical peripheral gangrene is characterized as acral (distal extremity) ischemic limb injury affecting two or more extremities, without large vessel obstruction, typically in a symmetrical fashion. Risk factors include hypotension, disseminated intravascular coagulation, and acute ischemic hepatitis ("shock liver"). In contrast, venous limb gangrene is characterized by acral ischemic injury occurring in a limb with deep vein thrombosis. Both symmetrical peripheral gangrene and venous limb gangrene present as acral limb ischemic necrosis despite presence of arterial pulses. The coexistence of symmetrical peripheral gangrene and venous limb gangrene is rare, with potential to provide pathophysiological insights.

    CASE PRESENTATION: A 42-year-old Chinese man presented with polytrauma (severe head injury, lung contusions, and right femur fracture). Emergency craniotomy and debridement of right thigh wound were performed on presentation. Intraoperative hypotension secondary to bleeding was complicated by transient need for vasopressors and acute liver enzyme elevation indicating shock liver. Beginning on postoperative day 5, he developed an acute platelet count fall (from 559 to 250 × 109/L over 3 days) associated with left iliofemoral deep vein thrombosis that evolved to bilateral lower limb ischemic necrosis; ultimately, the extent of limb ischemic injury was greater in the left (requiring below-knee amputation) versus the right (transmetatarsal amputation). As the presence of deep vein thrombosis is a key feature known to localize microthrombosis and hence ischemic injury in venous limb gangrene, the concurrence of unilateral lower limb deep vein thrombosis in a typical clinical setting of symmetrical peripheral gangrene (hypotension, proximate shock liver, platelet count fall consistent with disseminated intravascular coagulation) helps to explain asymmetric limb injury - manifesting as a greater degree of ischemic necrosis and extent of amputation in the limb affected by deep vein thrombosis - in a patient whose clinical picture otherwise resembled symmetrical peripheral gangrene.

    CONCLUSIONS: Concurrence of unilateral lower limb deep vein thrombosis in a typical clinical setting of symmetrical peripheral gangrene is a potential explanation for greater extent of acral ischemic injury in the limb affected by deep vein thrombosis.

    Matched MeSH terms: Lower Extremity/blood supply*
  20. Loh LN, McCarthy EMC, Narang P, Khan NA, Ward TH
    Traffic, 2017 11;18(11):733-746.
    PMID: 28799243 DOI: 10.1111/tra.12508
    Eukaryotic cells utilize multiple endocytic pathways for specific uptake of ligands or molecules, and these pathways are commonly hijacked by pathogens to enable host cell invasion. Escherichia coli K1, a pathogenic bacterium that causes neonatal meningitis, invades the endothelium of the blood-brain barrier, but the entry route remains unclear. Here, we demonstrate that the bacteria trigger an actin-mediated uptake route, stimulating fluid phase uptake, membrane ruffling and macropinocytosis. The route of uptake requires intact lipid rafts as shown by cholesterol depletion. Using a variety of perturbants we demonstrate that small Rho GTPases and their downstream effectors have a significant effect on bacterial invasion. Furthermore, clathrin-mediated endocytosis appears to play an indirect role in E. coli K1 uptake. The data suggest that the bacteria effect a complex interplay between the Rho GTPases to increase their chances of uptake by macropinocytosis into human brain microvascular endothelial cells.
    Matched MeSH terms: Brain/blood supply
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