The efficacy of allicin compared with fluconazole in alleviating systemic Candida albicans infections was evaluated both in vitro and in vivo through a systemic candidiasis mouse model. Determination of in vitro minimum inhibitory concentrations (MICs) for different C. albicans isolates revealed that both allicin and fluconazole showed different MICs that ranged from 0.05 to 12.5 μg mL(-1) and 0.25 to 16 μg mL(-1) , respectively. A time-kill study showed a significant effect of allicin (P<0.01) against C. albicans, comparable to that of fluconazole. Scanning electron microscopy observation revealed that, similar to fluconazole, allicin produced structural destruction of C. albicans cell surface at low MIC and lysis or puncture at high MIC concentrations. Treatment of BALB/c mice systemically infected with C. albicans showed that although the allicin treatment (at 5 mg kg(-1) day(-1) ) was slightly less efficacious than fluconazole treatment in terms of the fungal load reduction and host survival time, it was still effective against C. albicans in terms of mean survival time, which increased from 8.4 to 15.8 days. These results demonstrate the efficacy of anticandidal effects of allicin both in vitro and in an animal model of candidiasis and affirm the potential of allicin as an adjuvant therapy to fluconazole.
Citrin deficiency, aetiologically linked to mutations of SLC25A13 gene, has two clinical phenotypes, namely adult-onset type II citrullinaemia (CTLN2) and neonatal/infantile intrahepatic cholestasis, caused by citrin deficiency (NICCD). Malaysian patients with NICCD, especially of Malay and East Malaysian indigenous descent, have never been reported in the literature. We present the clinical features, biochemical findings and results of molecular analysis in 11 Malaysian children with NICCD. In this case series, all patients manifested prolonged cholestatic jaundice and elevated citrulline levels. The other more variable features included failure to thrive, bleeding diathesis, hypoproteinaemia, abnormal liver enzymes, prolonged coagulation profile, hyperammonaemia, hypergalactosaemia, multiple aminoacidaemia, elevated α-feto protein and urinary orotic acid as well as liver biopsies showing hepatitis and steatosis. DNA analysis of SLC25A13 revealed combinations of 851del4(Ex9), IVS16ins3kb and 1638ins23. Most of our patients recovered completely by the age of 22 months. However, one patient had ongoing symptoms at the time of reporting and one had died of liver failure. Since a small percentage of children with NICCD will develop CTLN2 and the mechanisms leading to this is yet to be defined, ongoing health surveillance into adulthood is essential.
Matched MeSH terms: Genetic Predisposition to Disease
BACKGROUND: Respiratory symptoms including cough, runny nose, sore throat, and fever are the most common clinical manifestations faced by hajj pilgrims in Mecca. The aim of the study was to determine the prevalence of respiratory symptoms among Malaysian hajj pilgrims and the effect of a few protective measures taken by hajj pilgrims to reduce respiratory symptoms.
METHODS: A cross-sectional study was conducted by distributing survey forms to Malaysian hajj pilgrims at transit center before flying back to Malaysia. The recruitment of respondents to the survey was on a voluntary basis.
RESULTS: A total of 387 survey forms were available for analysis. The mean age was 50.4 +/- 11.0 years. The common respiratory symptoms among Malaysian hajj pilgrims were: cough 91.5%, runny nose 79.3%, fever 59.2%, and sore throat 57.1%. The prevalence of hajj pilgrims with triad of cough, subjective fever, and sore throat were 40.1%. The symptoms lasted less than 2 weeks in the majority of cases. Only 3.6% did not suffer from any of these symptoms. Seventy-two percent of hajj pilgrims received influenza vaccination before departure and 72.9% wore facemasks. Influenza vaccination was not associated with any of respiratory symptoms but it was significantly associated with longer duration of sore throat. Wearing masks was significantly associated with sore throat and longer duration of sore throat and fever.
CONCLUSIONS: The prevalence of respiratory symptoms was high among Malaysian hajj pilgrims and the current protective measures seemed inadequate to reduce it. Beside standardization of the term used in hajj studies, more collaborative effort should be taken to reduce respiratory symptoms. The hajj authority should prepare for the challenge of pandemic influenza by providing more healthcare facilities and implementation of more strict measures to reduce the transmission of pandemic influenza strain among hajj pilgrims.
The higher field strength magnetic resonance imaging (MRI) such as 3 Tesla (T) and above generates noise that has potential detrimental effects on the hearing. Temporary threshold shifts following MRI examination have been reported for MRI with lower field strength. Such effect, however, have not been reported so far for a 3T MRI. We report a case that exemplifies the possible detrimental effects of a 3 T MRI generated noise on the auditory system. Our patient underwent investigation of his chronic backache in a 3 T MRI unit and developed hearing loss and tinnitus post-MRI examination. Hearing assessment was done using pure tone audiogram, distortion product otoacoustic emission (DPOAE) and brainstem electrical response audiometry (BERA) which revealed a unilateral sensorineural hearing loss which recovered within 3 days. However the tinnitus persisted. This is possibly a case of temporary threshold shift following noise exposure. However a sudden sensorineural hearing loss remains the other possibility.
Transforming growth factor beta-1 (TGF-beta-1) is a multifunctional cytokine involved in the regulation of growth and differentiation of both normal and transformed cells. The main aim of this study was to determine whether TGF-beta-1 or alpha fetoprotein (AFP) or the combination of the two is a better indicator for hepatocellularcarcinoma (HCC). Serum TGF-beta-1 and AFP were measured by ELISA in 40 healthy subjects, 23 patients with hepatocellular carcinoma (HCC), 70 patients with hepatitis B, 26 patients with hepatitis C and 16 patients with liver cirrhosis (LC). Patients with liver diseases showed significantly higher serum TGF-beta-1 values (> 3 fold) compared to control subjects. As for serum AFP, significant elevation was only observed for HCC cases. Serum TGF-beta-1 exhibited higher percent sensitivity compared to serum AFP in all liver diseases. Combination of serum TGF-beta-1 and AFP increased specificities in all cases studied. In conclusion, serum TGF-beta-1 is a more sensitive marker for HCC when compared to serum AFP and its specificity is increased when combined with serum AFP.
We performed a cross-sessional study of all systemic lupus erythematosus (SLE) pregnancies during a 4-year period (2006-2009) to describe the clinical features, maternal and foetal outcomes in our centre. There were 48 pregnancies in 44 women with SLE. Our patients have a mean age of 30.0 years (SD 6.36) and a mean disease duration of 40.67 months (SD 48.23). Our patients have complicated pregnancies: 32.7% have SLE flares, 17.3% have preeclampsia and 48.9% needed caesarean sections. There were 20.0% foetal losses and 17.8% preterm deliveries in our patients. SLE flares contributed to 60.0% of foetal losses in our patients. Lupus pregnancies in our centre generally have a good maternal and foetal outcome comparable to developed countries in Asia. The low incidence of APS, the high usage of hydroxychloroquine and the high SLE remission rate in our patients prior to conceptions contributed to the good outcome.
Recent in vitro and in vivo studies have demonstrated that zerumbone (ZER) possesses anticancer properties. The main objective of this study was to examine the effectiveness of the combination of ZER and cisplatin (CIS) to treat cervical intraepithelial neoplasia (CIN) in vivo. Microculture tetrazolium assay and immunohistochemistry of proliferating cellular nuclear antigen were used to study the antitumor effect of ZER. Prenatally exposed female BALB/c mice were used as a model. The progenies with CIN were injected peritoneally with isotonic sodium chloride solution (positive control), CIS, ZER, and a combination of both compounds. All treated and untreated mice were humanely killed, and serum and cervix were obtained for interleukin 6 analysis and histopathologic studies using hematoxylin and eosin staining, respectively. Zerumbone has revealed an antitumor effect on human cervical cancer cells and downregulates immunoexpression of proliferating cellular nuclear antigen (P < 0.05). In vivo study indicates that ZER at 16 mg/kg and CIS at 10 mg/kg have a regressing effect on CIN. The combination of ZER and CIS also showed similar effectiveness in regressing CIN. Our results indicate that the combination of ZER and CIS has modulated the serum level of interleukin 6 when compared with that in mice treated with isotonic sodium chloride solution (P < 0.05). The effectiveness of combining ZER and CIS could be further explored as a new therapeutic intervention of early precancerous stages of carcinogenesis before the invasive stage begins.
A 60-year-old man presented with a 3-month history of nonhealing ulcer over the tip of his right thumb. The ulcer started as a blister over the tip of the thumb that later ruptured and spread proximally to cover the whole pulp area of the thumb. There was no history of trauma, fever, weight loss, or loss of appetite. He is a pensioner and an avid gardener. He has a few cats as pets. The patient initially presented to a private orthopedic surgeon with a nonhealing ulcer of the right thumb. Multiple debridements were unsuccessful in ameliorating the ulcer. Three months after the onset of the initial lesion, multiple painless erythematous nodules had developed on his right arm, and one on the right thigh. All routine blood investigations were nondiagnostic. Swab culture from the ulcer failed to grow any organism and a course of antibiotics did not resolve the problem. Cultures of the biopsy specimen using Sabouraud's dextrose agar and potato carrot medium grew dark brown plaques that microscopically appeared to be branching hyphae. A diagnosis of sporotrichosis of the right upper limb was made and the patient was started on antifungal treatment immediately (T. Itraconazole [Sporanox] 200 mg BD). One month after commencement of antifungal treatment, the ulcer began to dry up and at 3 months all the lesions including the one on the right thigh had healed.
The present study was carried out to evaluate the antinociceptive, anti-inflammatory and antipyretic effects of the aqueous extract of Solanum nigrum leaves using various animal models. The extract, at concentrations of 10, 50 and 100%, was prepared by soaking (1:20; w/v) air-dried powdered leaves (20 g) in distilled water (dH2O) for 72 h. The extract solutions were administered subcutaneously in mice/rats 30 min prior to the tests. The extract exhibited significant (P < 0.05) antinociceptive activity when assessed using the abdominal constriction, hot plate and formalin tests. The extract also produced significant (P < 0.05) anti-inflammatory and antipyretic activities when assessed using the carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests, respectively. Overall, these activities occurred in a concentration-dependent manner, except for the 50% concentration of the extract, which was not effective in the abdominal constriction test. In conclusion, the present study demonstrated that S. nigrum leaves possessed antinociceptive, anti-inflammatory and antipyretic effects and thus supported traditional claims of its medicinal uses.
STUDY OBJECTIVE: To determine if the slope of Phase II and Phase III, and the alpha angle of the expiratory capnographic waveform, as measured via computer-recognizable algorithms, can reflect changes in bronchospasm in acute asthmatic non-intubated patients presenting to the emergency department (ED).
METHODS: In this prospective study carried out in a university hospital ED, 30 patients with acute asthma were monitored with clinical severity scoring and peak flow measurements, and then had a nasal cannula attached for sidestream sampling of expired carbon dioxide. The capnographic waveform was recorded onto a personal computer card for analysis. The patients were treated according to departmental protocols. After treatment, when they had improved enough for discharge, a second set of results was obtained for capnographic waveform recording. The pre-treatment and post-treatment results were then compared with paired-samples t-test analysis.
RESULTS: On the capnographic waveform pre- and post-treatment, there was a significant difference in the slope of Phase III (p < 0.001) and alpha angle (p < 0.001), but not in the Phase II slope (p = 0.35). There was significant change in peak flow meter reading, but it was poorly correlated with all the capnographic indices.
CONCLUSION: The study provides some preliminary data showing that capnographic waveform indices can indicate improvement in airway diameter in acute asthmatics in the ED. Capnographic waveform analysis presents several advantages in that it is effort-independent, and provides continuous monitoring of normal tidal respiration. With further refined studies, it may serve as a new method of monitoring non-intubated asthmatics in the ED.
Study site: Emergency department, Hospital Universiti Sains Malaysia (HUSM), Kubang Kerian, Kelantan, Malaysia
The majority of spinal muscular atrophy (SMA) patients showed homozygous deletion or other mutations of SMN1. However, the genetic etiology of a significant number of SMA patients has not been clarified. Recently, mutation in the gene underlying cat SMA, limb expression 1 (LIX1), has been reported. Similarity in clinical and pathological features of cat and human SMA may give an insight into possible similarity of the genetic etiology.
Matched MeSH terms: Genetic Predisposition to Disease
Reactive oxygen species (ROS) play an important role in ageing and age-related neurodegenerative changes including Parkinson's disease (PD). PD is characterized by signs of major oxidative stress and mitochondrial damage in the pars compacta of the substantia nigra. Present study was designed to investigate whether the Centella asiatica extract (CAE) would prevent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in aged Sprague-Dawley rats. Adult, male Sprague-dawley rats of 300-350 g were divided into control, C. asiatica alone, MPTP alone (20 mg/kg, for 21 days) and MPTP with C. asiatica (300 mg/kg for 21 days) groups. Effect of aqueous extract of C. asiatica on oxidative biomarker levels in corpus striatum and hippocampus homogenate was examined. MPTP-challenged rats elicited a significant increase in lipid hydroperoxides (LPO) (p < 0.01), protein-carbonyl-content (PCC) (p < 0.01) and xanthine oxidase (XO) (p < 0.01) when compared with control rats. There was a significant decrease in total antioxidants (TA) (p < 0.001), superoxide dismutase (SOD) (p < 0.001), glutathione peroxidase (GPx) (p < 0.01) and catalase (CAT) (p < 0.001) levels with MPTP treatment. Supplementation of CAE reduced LPO and PCC and significantly increased (p < 0.01) TA and antioxidant enzyme levels (p < 0.01) in corpus striatum and hippocampus. These results show that administration of C. asiatica was effective in protecting the brain against neurodegenerative disorders such as Parkinsonism.
Quantitative immunohistochemical methods were used to assess activation of the hypothalamo-hypophyseal-adrenocortical system at the level of its central component - the adenohypophysis - in the growing body during chronic exposure to psychoemotional stressors of different strengths. Sprague-Dawley rats aged 30 days were subjected to "mild" or "severe" immobilization stress for 5 h per day for seven days. Animals were decapitated at the end of the last stress session and the endocrine glands (hypophysis, adrenals) were harvested, weighed, and embedded in paraffin; sections were stained with hematoxylin and eosin, and also immunohistochemically using monoclonal antibodies to adrenocorticotropic hormone (ACTH) and proliferating cell nuclear antigen (PCNA) following by automated image analysis. These studies showed that stress-associated hyperplasia of corticotropocytes in rats of pubertal age was due more to the differentiation of existing immature precursor cells than to cell proliferation.
PURPOSE: The purpose of the study was to determine whether postoperative intra-articular injections of autologous marrow aspirate (MA) and hyaluronic acid (HA) after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring.
METHODS: In a goat model we created a 4-mm full-thickness articular cartilage defect in the stifle joint (equivalent to 1.6 cm in the human knee) and conducted subchondral drilling. The animals were divided into 3 groups: group A (control), no injections; group B (HA), weekly injection of 1 mL of sodium hyaluronate for 3 weeks; and group C (HA + MA), similar to group B but with 2 mL of autologous MA in addition to HA. MA was obtained by bone marrow aspiration, centrifuged, and divided into aliquots for cryopreservation. Fifteen animals were equally divided between the groups and sacrificed 24 weeks after surgery, when the joint was harvested, examined macroscopically and histologically.
RESULTS: Of the 15 animals, 2 from group A had died of non-surgery-related complications and 1 from group C was excluded because of a joint infection. In group A the repair constituted mainly scar tissue, whereas in group B there was less scar tissue, with small amounts of proteoglycan and type II collagen at the osteochondral junction. In contrast, repair cartilage from group C animals showed almost complete coverage of the defect with evidence of hyaline cartilage regeneration. Histology assessed by Gill scoring was significantly better in group C with 1-way analysis of variance yielding an F statistic of 10.611 with a P value of .004, which was highly significant.
CONCLUSIONS: Postoperative intra-articular injections of autologous MA in combination with HA after subchondral drilling resulted in better cartilage repair as assessed histologically by Gill scoring in a goat model.
CLINICAL RELEVANCE: After arthroscopic subchondral drilling, this novel technique may result in better articular cartilage regeneration.
Hypercholesterolaemia, increase in lipid peroxidation and hyperhomocysteinaemia may contribute to the pathogenesis of atherosclerosis. This study was performed to examine the effects of repeatedly heated palm oil mixed with 2% cholesterol diet on atherosclerosis in oestrogen-deficient postmenopausal rats. Ovariectomy causes disruption of tunica intima layer of the rat aorta simulating a postmenopausal condition in females. Twenty-four ovariectomized female Sprague-Dawley rats were divided into four groups. The control group received 2% cholesterol diet without palm oil. A diet with 2% cholesterol content fortified with fresh, once-heated and five-times-heated palm oil was given to the other treatment groups. The rats were sacrificed at the end of 4 months of study and the aortic arch tissue was processed for histomorphometry and electron microscopy. On observation, there was disruption of the intimal layer of the ovariectomized rat aorta. There was no obvious ultrastructural change in the aorta of the rats fed with fresh palm oil. The ultrastructural changes were minimal with once-heated palm oil, in which there was a focal disruption of the endothelial layer. The focal disruption was more pronounced with five-times-heated palm oil. The results of this study show that the ingestion of fresh palm oil may have a protective effect on the aorta but such a protective action may be lost when the palm oil is repeatedly heated. The study may be clinically important for all postmenopausal women who are susceptible to atherosclerosis.
The co-occurrence of JAK2 V617F mutation with BCR-ABL reciprocal translocation is uncommon. We report a 60-year-old man who initially presented with phenotype of polycythemia vera (PV), which evolved into chronic myeloid leukemia and back to PV once treatment with imatinib was commenced. JAK2 V617F mutation and BCR-ABL fusion transcripts were detected in the initial sample. However, JAK2 V617F alleles diminished when BCR-ABL mRNA burden increased and reappeared once the patient was commenced on imatinib. The dynamic interaction between JAK2 V617F and BCR-ABL implies that two independent clones exist with the JAK2 V617F clone only achieving clonal dominance when BCR-ABL positive clones are suppressed by imatinib.
CONTEXT:
Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized.
OBJECTIVE:
To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore.
DESIGN:
We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians.
RESULTS:
In Chinese, SNPs in CDKAL1 [odds ratio (OR) = 1.19; P = 2 x 10(-4)], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 x 10(-4)) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 x 10(-4)), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19-1.25; P = 0.003-2.5 x 10(-4)) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 x 10(-4)), CDKN2A/B (OR = 1.16; P = 9 x 10(-5)), HHEX (OR = 1.14; P = 6 x 10(-4)), and KCNQ1 (OR = 1.16-1.20; P = 3 x 10(-4) to 3 x 10(-6)) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry.
CONCLUSIONS:
SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.
Matched MeSH terms: Genetic Predisposition to Disease
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and it is recognized to constitute a heterogenous group of neoplasms. It can be divided into germinal center B-cell-like (GCB) and non-GCB subgroups. The aim of the present study was to evaluate the utility of immunophenotype subgrouping of DLBCL in a cohort of multi-ethnic Asian patients. A total of 84 reconfirmed de novo DLBCL were immunostained for the expression of CD10, BCL-2, BCL-6 and multiple myeloma-1. Thirty-three (39.3%) had the GCB phenotype, and the remainder (60.7%), the non-GCB phenotype. The results concur with most reports using a similar method of stratification. Forty-five patients had complete demographic and phenotype studies and 42 patients did not have rituximab treatment and had sufficient data for survival rate analysis. Similar to other studies, patients with combined low and low-intermediate International Prognostic Index score had better overall survival (P = 0.006). But patients with GCB phenotype did not have better prognosis, and BCL-2 expression was not associated with better prognosis. The expression of BCL-6 was associated with lower overall survival rate (P = 0.038). No apparent difference in overall and disease-free survival was noted between patients with GCB and non-GCB disease. BCL-6 expression by tumor cells appears to be associated with poorer prognosis.
The renin-angiotensin aldosterone system (RAAS) plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT), MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin) of RAAS genes in Malaysian essential hypertensive and type 2 diabetic subjects.
Matched MeSH terms: Genetic Predisposition to Disease
INTRODUCTION: CA15-3 is a well-known tumour marker for breast cancer. Currently it is not recommended for screening or diagnosis of breast cancer and its main application is in monitoring response to treatment in women with metastatic breast cancer. The aim of this study was to correlate serum CA15-3 at presentation with the stage of disease and overall survival in women with breast cancer in the University Malaya Medical Centre.
METHODS: This is a retrospective study of 437 women who had CA15-3 levels determined at initial presentation of breast cancer to UMMC between Jan 1999 and Oct 2003.
RESULTS: Of those patients who were adequately staged, CA15-3 was found to be elevated (defined as >51 U/ml) in 0% of Stage 1, 7.9% of Stage 2, 36.7% of Stage 3 and 68.6% of Stage 4 cases. In a subset of 331 patients with survival data, patients with normal CA15-3 had a 85% five year overall survival rate compared to 38% in their counterparts with elevation of the tumor marker. The level of elevation was also significantly related to survival; patients with values more than 200 U/ml exhibited only a 28% five year survival. The association of elevated CA15-3 at initial presentation with poor outcome was maintained over univariate and multivariate analyses.
CONCLUSION: Estimation of CA15-3 at presentation of breast cancer is important as it is an independent prognostic indicator and may prompt the physician to investigate for metastases if elevated.