Displaying all 13 publications

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  1. Samsudin I, Vasikaran SD
    Clin Biochem Rev, 2017 Apr;38(2):59-68.
    PMID: 29332972
    Procalcitonin (PCT), regarded as a biomarker specific for bacterial infections, is used in a variety of clinical settings including primary care, emergency department and intensive care. PCT measurement aids in the diagnosis of sepsis and to guide and monitor antibiotic therapy. This article gives a brief overview of PCT and its use in guiding antibiotic therapy in various clinical settings, as well as its limitations. PCT performance in comparison with other biomarkers of infection in particular CRP is also reviewed. Owing to its greater availability, CRP has been widely used as a biomarker of infection and sepsis. PCT is often reported to be more superior to CRP, being more specific for sepsis and bacterial infection. PCT starts to rise earlier and returns to normal concentration more rapidly than CRP, allowing for an earlier diagnosis and better monitoring of disease progression.
    Matched MeSH terms: Calcitonin
  2. Boo NY, Nor Azlina AA, Rohana J
    Singapore Med J, 2008 Mar;49(3):204-8.
    PMID: 18363001
    This study was designed to determine the sensitivity and specificity of a semi-quantitative procalcitonin (PCT) test kit for the diagnosis of neonatal sepsis.
    Matched MeSH terms: Calcitonin/blood*
  3. Ibrahim N', Mohamad S, Mohamed N, Shuid AN
    Curr Drug Targets, 2013 Dec;14(14):1642-50.
    PMID: 24350807
    Osteoporosis may cause bone fracture even under slight trauma. Osteoporotic fracture has become a major public health problem but until today, the treatments available are not satisfactory. Many pre-clinical testings on animals were done to find new agents that can be sourced from natural products and synthetic drugs for osteoporotic fracture healing. Animal models are more appropriate for fracture healing study than human subject due to several reasons including the ethical issues involved. The bones of rodents are similar to human in term of their morphological change and response to therapy. Small rodents such as rats and mice are suitable animal models for fracture healing studies as they have a similar bone remodeling system to human. To date, there is no specific guideline to carry out fracture healing studies in animal models for the evaluation of new agents. This paper highlights the protocols of various fracture and fixation methods for experimental osteoporotic fracture healing using rodent models.
    Matched MeSH terms: Calcitonin/administration & dosage; Calcitonin/therapeutic use
  4. Mat-Nor MB, Md Ralib A, Abdulah NZ, Pickering JW
    J Crit Care, 2016 Jun;33:245-51.
    PMID: 26851139 DOI: 10.1016/j.jcrc.2016.01.002
    PURPOSE: The purpose of the study was to quantify the ability of procalcitonin (PCT) and interleukin-6 (IL-6) to differentiate noninfectious systemic inflammatory response syndrome (SIRS) and sepsis and to predict hospital mortality.

    MATERIALS: We recruited consecutively adult patients with SIRS admitted to an intensive care unit. They were divided into sepsis and noninfectious SIRS based on clinical assessment with or without positive cultures. Concentrations of PCT and IL-6 were measured daily over the first 3 days.

    RESULTS: A total of 239 patients were recruited, 164 (68.6%) had sepsis, and 68 (28.5%) died in hospital. The PCT levels were higher in sepsis compared with noninfectious SIRS throughout the 3-day period (P < .0001). On admission, PCT concentration was diagnostic of sepsis (area under the curve of 0.63 [0.55-0.71]), and IL-6 was predictive of mortality, (area under the curve of 0.70 [0.62-0.78]). Peak IL-6 concentration improved the risk assessment of Sequential Organ Failure Assessment (SOFA) score for prediction of mortality among those who went on to die by an average of 5% and who did not die by 2%

    CONCLUSIONS: Procalcitonin measured on intensive care unit admission was diagnostic of sepsis, and IL-6 was predictive of mortality. Addition of IL-6 concentration to SOFA score improved risk assessment for prediction of mortality. Future studies should include clinical indices, for example, SOFA score, for prognostic evaluation of biomarkers.

    Matched MeSH terms: Calcitonin/blood*
  5. Shukeri WFWM, Ralib AM, Abdulah NZ, Mat-Nor MB
    J Crit Care, 2018 Feb;43:163-168.
    PMID: 28903084 DOI: 10.1016/j.jcrc.2017.09.009
    PURPOSE: To derive a prediction equation for 30-day mortality in sepsis using a multi-marker approach and compare its performance to the Sequential Organ Failure Assessment (SOFA) score.

    METHODS: This study included 159 septic patients admitted to an intensive care unit. Leukocytes count, procalcitonin (PCT), interleukin-6 (IL-6), and paraoxonase (PON) and arylesterase (ARE) activities of PON-1 were assayed from blood obtained on ICU presentation. Logistic regression was used to derive sepsis mortality score (SMS), a prediction equation describing the relationship between biomarkers and 30-day mortality.

    RESULTS: The 30-day mortality rate was 28.9%. The SMS was [еlogit(p)/(1+еlogit(p))]×100; logit(p)=0.74+(0.004×PCT)+(0.001×IL-6)-(0.025×ARE)-(0.059×leukocytes count). The SMC had higher area under the receiver operating characteristic curve (95% Cl) than SOFA score [0.814 (0.736-0.892) vs. 0.767 (0.677-0.857)], but is not statistically significant. When the SMS was added to the SOFA score, prediction of 30-day mortality improved compared to SOFA score used alone [0.845 (0.777-0.899), p=0.022].

    CONCLUSIONS: A sepsis mortality score using baseline leukocytes count, PCT, IL-6 and ARE was derived, which predicted 30-day mortality with very good performance and added significant prognostic information to SOFA score.

    Matched MeSH terms: Calcitonin/blood*
  6. Kung AW, Pasion EG, Sofiyan M, Lau EM, Tay BK, Lam KS, et al.
    Curr Med Res Opin, 2006 May;22(5):929-37.
    PMID: 16709314 DOI: 10.1185/030079906X104768
    OBJECTIVE: The number of hip fractures is expected to double in the next 20 years, with current estimates that Asia will account for 37% of these cases. As bone mineral density (BMD) may be used as a measure of fracture risk, we sought to compare the effects of teriparatide with salmon calcitonin treatment on changes in BMD, biochemical bone markers, and safety in postmenopausal Asian women with osteoporosis.
    METHODOLOGY: A total of 104 patients (n = 47 teriparatide [20 g/day subcutaneously] and n = 57 calcitonin [100 IU/day subcutaneously]) were enrolled in Hong Kong, Singapore, Philippines, Malaysia, and Thailand. Calcium (> or = 500 mg/day) and vitamin D (200-400 IU/day) supplements were taken throughout the 6-month controlled, randomized study.
    RESULTS: Teriparatide was associated with a 5.03 +/- 4.77% increase in lumbar spine BMD (p < 0.0001, mean +/- SD change from baseline), whereas changes in lumbar spine BMD for patients on calcitonin were not statistically significant (mean change of 0.36 +/- 4.12%, p = 0.16). Comparison of the two groups indicated that teriparatide treatment improved lumbar spine BMD statistically significantly more than calcitonin (p < 0.0001). No statistically significant changes were observed for total hip or femoral neck BMD. Serum bone-specific alkaline phosphatase (BSAP) increased by 55.9% (median change from baseline, p < 0.0001) in the teriparatide group, and remained stable with calcitonin (5.0% change, p = 0.24); osteocalcin increased by 156.15% (median change from baseline, p < 0.0001) with teriparatide, and decreased with calcitonin (-15.25%, p = 0.03). Similar rates of adverse events were observed, with nausea and dizziness the most commonly reported for both groups (teriparatide versus calcitonin, 13.0% versus 23.2% p = 0.21, 10.9% versus 21.4% p = 0.19, respectively). There were no clinically relevant changes observed in laboratory parameters.
    CONCLUSIONS: Both treatments were similarly tolerated, however teriparatide was associated with greater increases in lumbar spine BMD and bone formation markers, demonstrating the unique mechanism of action and safety of this treatment for osteoporosis in these Asian women.
    Matched MeSH terms: Calcitonin/pharmacology; Calcitonin/therapeutic use*
  7. Bador KM, Intan S, Hussin S, Gafor AH
    Lupus, 2012 Oct;21(11):1172-7.
    PMID: 22652631 DOI: 10.1177/0961203312450085
    Previous studies in systemic lupus erythematosus (SLE) patients have produced conflicting results regarding the diagnostic utility of procalcitonin (PCT). The aim of this study was to determine predictive values of PCT and C-reactive protein (CRP) for bacterial infection in SLE patients.
    Matched MeSH terms: Calcitonin/blood*
  8. Huang P, Kuo PH, Lee MT, Chiou LC, Fan PC
    Front Pharmacol, 2018;9:1095.
    PMID: 30319425 DOI: 10.3389/fphar.2018.01095
    Background: Valproic acid (VPA) and topiramate (TPM), initially developed as antiepileptics, are approved for migraine prophylaxis in adults but not children. The differences in their antimigraine mechanism(s) by age remain unclear. Methods: A migraine model induced by intra-cisternal (i.c.) capsaicin instillation in pediatric (4-5 weeks) and adult (8-9 weeks) rats was pretreated with VPA (30, 100 mg/kg) or TPM (10, 30, 100 mg/kg). Noxious meningeal stimulation by the irritant capsaicin triggered trigeminovascular system (TGVS) activation mimicking migraine condition, which were assessed peripherally by the depletion of calcitonin gene-related peptide (CGRP) in sensory nerve fibers of the dura mater, the increased CGRP immunoreactivity at trigeminal ganglia (TG) and centrally by the number of c-Fos-immunoreactive (c-Fos-ir) neurons in the trigeminocervical complex (TCC). Peripherally, CGRP released from dural sensory nerve terminals of TG triggered pain signal transmission in the primary afferent of trigeminal nerve, which in turn caused central sensitization of the TGVS due to TCC activation and hence contributed to migraine. Results: In the VPA-treated group, the central responsiveness expressed by reducing the number of c-Fos-ir neurons, which had been increased by i.c. capsaicin, was significant in pediatric, but not adult, rats. Inversely, VPA was effective in peripheral inhibition of elevated CGRP immunoreactivity in the TG and CGRP depletion in the dura mater of adult, but not pediatric, rats. In TPM group, the central responsiveness was significant in both adult and pediatric groups. Peripherally, TPM significantly inhibited capsaicin-induced CGRP expression of TG in adult, but not pediatric, rats. Interestingly, the capsaicin-induced depletion of CGRP in dura was significantly rescued by TPM at high doses in adults, but at low dose in pediatric group. Conclusion: These results suggest VPA exerted peripheral inhibition in adult, but central suppression in pediatric migraine-rats. In contrast, TPM involves both central and peripheral inhibition of migraine with an optimal therapeutic window in both ages. These findings may clarify the age-dependent anti-migraine mechanism of VPA and TPM, which may guide the development of new pediatric anti-migraine drugs in the future.
    Matched MeSH terms: Calcitonin Gene-Related Peptide
  9. Ahmed S, Ahmed ZA, Rashid NH, Mansoor M, Siddiqui I, Jafri L
    Malays J Pathol, 2021 Dec;43(3):375-380.
    PMID: 34958058
    INTRODUCTION: To evaluate the association of Procalcitonin (PCT) with severity in Coronavirus disease 2019 (COVID-19), hospitalised patients and to test the hypothesis that it is an independent predictor of mortality.

    MATERIALS AND METHODS: This study was conducted at Chemical Pathology, Department of Pathology and Laboratory Medicine and Department of Medicine, Aga Khan University (AKU), Karachi Pakistan. Electronic medical records of all in-patients including both genders and all age groups with documented COVID-19 from March to August 2020 were reviewed and recorded on a pre-structured performa. The subjects were divided into two categories severe and non-severe COVID-19; and survivors and non-survivors. Between-group differences were tested using the Chi-square and Mann-Whitney's U-test. The receiver operating characteristic curve was plotted for serum PCT with severity and mortality. A binary logistic regression was used to identify variables independently associated with mortality. The data was analysed using SPSS.

    RESULTS: 336 patients were reviewed as declared COVID-19 positive during the study duration, and 136 were included in the final analysis including 101 males and 35 females. A statistically significant difference in PCT was found between severe and non-severe COVID-19 (p value=0.01); and survivors and nonsurvivors (p value<0.0001). PCT, older age and increased duration of hospital stay were revealed as variables independently associated with mortality. On ROC analysis, an AUC of 0.76 for mortality prediction was generated for PCT.

    CONCLUSION: Baseline serum PCT concentration is a promising predictor of mortality and severity in COVID-19 cases when considered in combination with clinical details and other laboratory tests.

    Matched MeSH terms: Calcitonin Gene-Related Peptide
  10. Omar J, Isa S, Ismail TST, Yaacob NM, Soh NAAC
    Malays J Med Sci, 2019 Jul;26(4):61-69.
    PMID: 31496894 MyJurnal DOI: 10.21315/mjms2019.26.4.7
    Background: As an early recognition of neonatal sepsis is important for triggering the initiation of treatment, this study was thus designed to assess the diagnostic performance and discrimination value of procalcitonin (PCT) in neonatal sepsis cases.

    Methods: This cross-sectional study, which was carried out at the Paediatric Intensive Care Unit of Hospital Universiti Sains Malaysia (HUSM) in Kelantan, Malaysia, had involved 60 neonates admitted for suspected sepsis. Sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV) and the area under receiver operating characteristics curve (AUC) for PCT were determined at initial presentation (0 h) as well as 12 h and 24 h after presentation in comparison to blood culture as the gold standard.

    Results: The study consisted of 27 (45.0%) male and 33 (55.0%) female neonates with a mean (SD) age of 76.8 (48.25) h. At cut-off PCT value of > 2 ng/mL, the sensitivity, specificity, PPV and NPV were 66.7%, 66.7%, 33.3% and 88.9% at 0 h. The respective parameters were 83.3%. 56.3%, 32.3% and 93.1% at 12 h and 83.3%, 52.1%, 30.3% and 92.6% at 24 h. AUC was 71.6%, 76.6% and 71.7% at 0 h, 12 h and 24 h.

    Conclusions: Diagnostic performance and discrimination values of PCT for diagnosis of neonatal sepsis varied with time of obtaining the blood samples. The PCT result at 12 h demonstrates the most optimal diagnostic performance and discrimination values.

    Matched MeSH terms: Calcitonin
  11. Fan PC, Lai TH, Hor CC, Lee MT, Huang P, Sieghart W, et al.
    Neuropharmacology, 2018 09 15;140:1-13.
    PMID: 30016665 DOI: 10.1016/j.neuropharm.2018.07.017
    Novel treatments against migraine are an urgent medical requirement. The α6 subunit-containing GABAA receptors (α6GABAARs) are expressed in trigeminal ganglia (TG), the hub of the trigeminal vascular system (TGVS) that is involved in the pathogenesis of migraine. Here we reveal an unprecedented role of α6GABAARs in ameliorating TGVS activation using several pharmacological approaches in an animal model mimicking pathological changes in migraine. TGVS activation was induced by intra-cisternal (i.c.) instillation of capsaicin in Wistar rats. Centrally, i.c. capsaicin activated the trigeminal cervical complex (TCC) measured by the increased number of c-Fos-immunoreactive (c-Fos-ir) TCC neurons. Peripherally, it elevated calcitonin gene-related peptide immunoreactivity (CGRP-ir) in TG and depleted CGRP-ir in the dura mater. Pharmacological approaches included a recently identified α6GABAAR-selective positive allosteric modulator (PAM), the pyrazoloquinolinone Compound 6, two α6GABAAR-active PAMs (Ro15-4513 and loreclezole), an α6GABAAR-inactive benzodiazepine (diazepam), an α6GABAAR-selective antagonist (furosemide), and a clinically effective antimigraine agent (topiramate). We examined effects of these compounds on both central and peripheral TGVS responses induced by i.c. capsaicin. Compound 6 (3-10 mg/kg, i.p.) significantly attenuated the TCC neuronal activation and TG CGRP-ir elevation, and dural CGRP depletion induced by capsaicin. All these effects of Compound 6 were mimicked by topiramate, Ro15-4513 and loreclezole, but not by diazepam. The brain-impermeable furosemide antagonized the peripheral, but not central, effects of Compound 6. These results suggest that the α6GABAAR in TG is a novel drug target for TGVS activation and that α6GABAAR-selective PAMs have the potential to be developed as a novel pharmacotherapy for migraine.
    Matched MeSH terms: Calcitonin Gene-Related Peptide/metabolism
  12. Thent ZC, Froemming GRA, Muid S
    Life Sci, 2018 Apr 01;198:1-7.
    PMID: 29432759 DOI: 10.1016/j.lfs.2018.02.013
    Bisphenol A (BPA) (2,2,-bis (hydroxyphenyl) propane), a well-known endocrine disruptor (ED), is the exogenous chemical that mimic the natural endogenous hormone like oestrogen. Due to its extensive exposure to humans, BPA is considered to be a major toxicological agent for general population. Environmental exposure of BPA results in adverse health outcomes including bone loss. BPA disturbs the bone health by decreasing the plasma calcium level and inhibiting the calcitonin secretion. BPA also stimulated differentiation and induced apoptosis in human osteoblasts and osteoclasts. However, little is known about the underlying mechanisms of the untoward effect of BPA against bone metabolism. The present review gives an overview on the possible mechanisms of BPA towards bone loss. The previous literature shows that BPA exerts its toxic effect on bone cells by binding to the oestrogen related receptor-gamma (ERγ), reducing the bone morphogenic protein-2 (BMP-2) and alkaline phosphatase (ALP) activities. BPA interrupts the bone metabolism via RANKL, apoptosis and Wnt/β-catenin signaling pathways. It is, however, still debated on the exact underlying mechanism of BPA against bone health. We summarised the molecular evidences with possible mechanisms of BPA, an old environmental culprit, in bone loss and enlightened the underlying understanding of adverse action of BPA in the society.
    Matched MeSH terms: Calcitonin/antagonists & inhibitors
  13. Jeevaratnam K, Salvage SC, Li M, Huang CL
    Ann N Y Acad Sci, 2018 Dec;1433(1):18-28.
    PMID: 29846007 DOI: 10.1111/nyas.13861
    Alterations in cellular levels of the second messenger 3',5'-cyclic adenosine monophosphate ([cAMP]i ) regulate a wide range of physiologically important cellular signaling processes in numerous cell types. Osteoclasts are terminally differentiated, multinucleated cells specialized for bone resorption. Their systemic regulator, calcitonin, triggers morphometrically and pharmacologically distinct retraction (R) and quiescence (Q) effects on cell-spread area and protrusion-retraction motility, respectively, paralleling its inhibition of bone resorption. Q effects were reproduced by cholera toxin-mediated Gs -protein activation known to increase [cAMP]i , unaccompanied by the [Ca2+ ]i changes contrastingly associated with R effects. We explore a hypothesis implicating cAMP signaling involving guanine nucleotide-exchange activation of the small GTPase Ras-proximate-1 (Rap1) by exchange proteins directly activated by cAMP (Epac). Rap1 activates integrin clustering, cell adhesion to bone matrix, associated cytoskeletal modifications and signaling processes, and transmembrane transduction functions. Epac activation enhanced, whereas Epac inhibition or shRNA-mediated knockdown compromised, the appearance of markers for osteoclast differentiation and motility following stimulation by receptor activator of nuclear factor kappa-Β ligand (RANKL). Deficiencies in talin and Rap1 compromised in vivo bone resorption, producing osteopetrotic phenotypes in genetically modified murine models. Translational implications of an Epac-Rap1 signaling hypothesis in relationship to N-bisphosphonate actions on prenylation and membrane localization of small GTPases are discussed.
    Matched MeSH terms: Calcitonin/metabolism
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