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Liquid chromatography-tandem mass spectroscopic method for the determination of zerumbone in human plasma and its application to pharmacokinetics

Eid EE, Abdul AB, Rasedee A, Suliman FE, Sukari MA, Fatah SA

J Mass Spectrom, 2011 Aug;46(8):772-81.
PMID: 21834015 DOI: 10.1002/jms.1942

A rapid, sensitive, specific and selective LC-MS/MS method for the determination of zerumbone (ZER) in human plasma using 2,4-diamino-6-(4-methoxyphenyl)-1,3,5-triazine (DMTZ) as an internal standard (IS) has been developed and validated. ZER was chromatographed on C8 column using a mobile phase of acetonitrile/water (80:20, v/v) at a flow rate of 0.25 ml min(-1) . Quantitation was achieved using ESI+ interface, employing multiple reaction monitoring (MRM) mode at m/z 219 > 81 and 218 > 134 for ZER and IS, respectively. The calibration standards were linear over a range of 5-3000 ng ml(-1) (r(2)=0.9994) with an LLOQ of 5 ng ml(-1) (RSD %; 11.4% and bias%; 9.5%). Intra- and inter-day precision of ZER assay ranged from 0.18 to 3.56% with accuracy (bias) that varied between -5.09 and 4.3%, demonstrating good precision and accuracy. Recoveries of ZER and the IS from human plasma were above 85%. The developed method was validated for the determination of ZER in rat plasma. Linearity, stability of ZER and the ME on rat plasma were discussed. The applicability of the developed method was demonstrated by measuring ZER in rat plasma samples following intravenous and intraperitoneal administration of ZER prepared in hydroxypropyl-β-cyclodextrin (HPβCD) and sodium carboxymethyl cellulose (CMC), respectively, in 20 mg kg(-1) and this study indicated a clear significant difference (p<0.05) in pharmacokinetic parameters of ZER in ZER/HPβCD complex compared with ZER in CMC preparation.

Matched MeSH terms: Analysis of Variance
Bixa orellana leaves extract inhibits bradykinin-induced inflammation through suppression of nitric oxide production

Yoke Keong Y, Arifah AK, Sukardi S, Roslida AH, Somchit MN, Zuraini A

Med Princ Pract, 2011;20(2):142-6.
PMID: 21252569 DOI: 10.1159/000319907

The present study was conducted to assess the anti-inflammatory effect of a crude aqueous extract of Bixa orellana leaves (AEBO) and to examine the possible involvement of nitric oxide (NO) in its anti-inflammatory mechanism.

Matched MeSH terms: Analysis of Variance
Factors influencing the quality of life in patients with HIV in Malaysia

Hasanah CI, Zaliha AR, Mahiran M

Qual Life Res, 2011 Feb;20(1):91-100.
PMID: 20737215 DOI: 10.1007/s11136-010-9729-y

PURPOSE: The aim of this study was to determine the socio-demographic, clinical and psychological factors influencing the quality of life (QOL) in patients with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS).
METHODS: This was a cross-sectional study on 271 patients with HIV infection attending an HIV clinic in Kota Bharu, Malaysia. Participants completed the Malay version of the Functional Assessment of HIV Infection (FAHI) and Malay Hospital Anxiety Depression Scale (HADS).
RESULTS: The patients functioned satisfactorily in the physical domain. They were mostly impaired in the social domain. Those who acquired the HIV infection via a heterosexual route seemed to have a significantly lower social well-being, while those who acquired HIV via drug injection were not associated with losses in the overall QOL or any of its domains. Non-disclosure paradoxically had a greater effect on social well-being. About 38% had possible anxiety, depression or both, and these emotional disturbances were significantly associated with total FAHI and its five domains.
CONCLUSIONS: Psychological and social well-beings were more affected than physical well-being in out-patients with HIV infection in Kota Bharu, Malaysia. The study suggests that the patients with HIV infection should receive better psycho-education and psychological intervention.
Study site: Infectious Disease clinic, Hospital Raja Perempuan Zainab II, Kota Bharu Kelantan, Malaysia

Matched MeSH terms: Analysis of Variance
Occupational pressure-targeting organisational factors to ameliorate occupational dysfunction

Loh SY, Than W, Quek KF

J Occup Rehabil, 2011 Dec;21(4):493-500.
PMID: 21365305 DOI: 10.1007/s10926-011-9287-3

INTRODUCTION: Chronic pressure at work has debilitating impact on healthcare employers (e.g. reduced productivity, high costs, poor patient care) and on female healthcare employees (e.g. sickness, dysfunction). This paper highlights relationship at work as the key occupational source of work-stress which is organisational in nature.
METHODS: A cross-sectional study (n = 230) was conducted using the Pressure Management Inventory on several female dominated health professions within a large public hospital. Analysis of variance was used to show relationship between sources and outcome of pressure. Linear regressions were used to predict which sources of pressure (IV) was linked to the outcomes of occupational pressure (DV).
RESULTS: The number one source of occupational pressure is relationships at work (i.e. with supervisors), and not workload. 'Relationship' is also the key predictor of several negative outcomes of pressure at work. Analysis of variance showed significant differences in two sources of pressures, i.e. Workload (P = 0.04) and Home-work balance (P = 0.03).
CONCLUSION: This paper provides insights into the occupational pressure of women health professionals by highlighting the organisational sources of pressure and the implications for preventing occupational dysfunction secondary to stress at work.

Matched MeSH terms: Analysis of Variance
Fulltext Periodic assessment of plasma sFlt-1 and PlGF concentrations and its association with placental morphometry in gestational hypertension (GH) - a prospective follow-up study

Jeevaratnam K, Nadarajah VD, Judson JP, Nalliah S, Abdullah MF

BMC Pregnancy Childbirth, 2010;10:58.
PMID: 20920154 DOI: 10.1186/1471-2393-10-58

Hypertensive disorders in pregnancy contributes to about 12% of maternal deaths in Malaysia and similarly worldwide. Early detection and adequate management are preventable strategies. Biochemical markers of abnormal angiogenesis would be more specific in early detection than routine blood pressure and proteinuria measurements. The aim of this study was to estimate maternal plasma PlGF and sFlt-1 levels in pregnant women with gestational hypertension at three intervals of pregnancy and correlate these biomarker levels with placental morphometry.

Matched MeSH terms: Analysis of Variance
In vitro vascular effects produced by crude aqueous extract of green marine algae, Cladophora patentiramea (Mont.) Kützing, in aorta from normotensive rats

Lim YL, Mok SL

Med Princ Pract, 2010;19(4):260-8.
PMID: 20516701 DOI: 10.1159/000312711

To investigate the antihypertensive activity of aqueous extracts obtained from Malaysian coastal seaweeds and to determine the pharmacological mechanisms of the extracts on rat aorta in vitro.

Matched MeSH terms: Analysis of Variance
Role of supraspinal vasopressin neurones in the effects of atrial natriuretic peptide on sympathetic nerve activity

Yusof AP, Yusoff NH, Suhaimi FW, Coote JH

Auton Neurosci, 2009 Jun 15;148(1-2):50-4.
PMID: 19349212 DOI: 10.1016/j.autneu.2009.03.005

The aim of the present study was to determine if paraventricular-spinal vasopressin neurones participate in the sympatho-inhibitory effects of systemically administered atrial natriuretic peptide (ANP) on renal sympathetic nerve activity (RSNA). Experiments were carried out on male Sprague-Dawley rats anesthetized with 1.3 g/kg urethane. Changes in mean arterial pressure (mm Hg), heart rate (beats per minute) and RSNA (%) were measured following intravenous bolus administration of ANP (250 ng, 500 ng and 5 microg). Intrathecal application of selective V 1a receptor antagonist was performed to test for the involvement of supraspinal vasopressin pathways in mediating the effect on sympathetic outflow evoked by intravenous ANP administration. The results obtained demonstrated that both low and high doses of ANP caused renal sympathoinhibition (250 ng; - 7.5 +/- 1%, 500 ng; - 14.2 +/- 1%, 5 microg; - 16.4 +/- 2%), concomitant with vasodilation and bradycardia. After spinal vasopressin receptor blockade, the inhibitory effects of ANP were prevented and there was a small renal sympatho-excitation (250 ng; + 1.7 +/- 0.2%, 500 ng; + 6.1 +/- 0.03%, 5 microg; + 8.0 +/- 0.03%, P < 0.05). Therefore, the renal sympathetic nerve inhibition elicited by circulating ANP is dependent on the efficacy of a well established supraspinal vasopressin pathway. Since supraspinal vasopressin neurones without exception excite renal sympathetic neurones, it is suggested that ANP elicits this effect by activating cardiac vagal afferents that inhibit the spinally projecting vasopressin neurones at their origin in the paraventricular nucleus of the hypothalamus.

Matched MeSH terms: Analysis of Variance
Cross-cultural differences in infant and toddler sleep

Mindell JA, Sadeh A, Wiegand B, How TH, Goh DY

Sleep Med, 2010 Mar;11(3):274-80.
PMID: 20138578 DOI: 10.1016/j.sleep.2009.04.012

BACKGROUND:
To characterize cross-cultural sleep patterns and sleep problems in a large sample of children ages birth to 36 months in multiple predominantly-Asian (P-A) and predominantly-Caucasian (P-C) countries.

METHODS:
Parents of 29,287 infants and toddlers (predominantly-Asian countries/regions: China, Hong Kong, India, Indonesia, Korea, Japan, Malaysia, Philippines, Singapore, Taiwan, Thailand, Vietnam; predominantly-Caucasian countries: Australia, Canada, New Zealand, United Kingdom, United States) completed an internet-based expanded version of the Brief Infant Sleep Questionnaire.

RESULTS:
Overall, children from P-A countries had significantly later bedtimes, shorter total sleep times, increased parental perception of sleep problems, and were more likely to both bed-share and room-share than children from P-C countries, p

Matched MeSH terms: Analysis of Variance
A comparison between infrared tympanic thermometry, oral and axilla with rectal thermometry in neutropenic adults

Dzarr AA, Kamal M, Baba AA

Eur J Oncol Nurs, 2009 Sep;13(4):250-4.
PMID: 19386547 DOI: 10.1016/j.ejon.2009.03.006

This study assessed the agreement between infrared tympanic membrane (TM), axillary, corrected axillary (+0.5 degrees C), oral, and corrected oral (+0.3 degrees C) to rectal thermometry as reference standard in neutropenic adults. The sensitivity and specificity of the mentioned thermometries in detecting rectal fever (> or =38 degrees C) were also analysed.

Matched MeSH terms: Analysis of Variance
Fulltext Association of colorectal carcinoma with metabolic diseases; experience with 138 cases from Kelantan, Malaysia

Othman NH, Zin AA

Asian Pac J Cancer Prev, 2008 Oct-Dec;9(4):747-51.
PMID: 19256771

OBJECTIVE: Kelantan in Malaysia has a high prevalence of diabetes and colorectal cancer is also on the rise. This study is to determine the association of metabolic diseases, particularly diabetes type 2 [DM2] and hypertension, with colorectal cancer patients in our population.

METHODS: This retrospective study was conducted on all colorectal carcinomas in Hospital Universiti Sains Malaysia (HUSM) in Kelantan from ythe ears 2001-2006. The data were retrieved from the Registry in Pathology laboratory and the clinical details from the patients' clinical records and analyzed using SSPS Version 12.0, with a value of p<0.05 taken to be statistically significant.

RESULTS: 138 CRC cases with complete clinical records were included. The age ranged from 16.0 to 88.0 years, with a mean of 56.9 -/+ SD 15.4. The male 90(65%) to female 48(35%) ratio was 1.7:1.0 and 47.8% were suffering from metabolic diseases; 18(13.0%) with Diabetes Mellitus Type 2(DM2), and 48(34.8%) with hypertension (HT). Diabetes Type 2 and hypertension also demonstrated significant association (p<0.05) with the stage and the site of the cancer. Patients with diabetes type 2 88.8%(16/18) and Hypertension 85.4% (41/48) were strongly associated with cancers located in the distal to transverse colon (p<0.001).

CONCLUSION: There is a high proportion of metabolic diseases; hypertension and diabetes type 2 among colorectal carcinomas seen in Kelantan population. In this preliminary study we noted a strong association of metabolic diseases with the stage and site of the cancer. To reduce CRC incidence, the high prevalence of DM2 in Kelantan needs to be addressed.

Matched MeSH terms: Analysis of Variance
Evaluation of the antinociceptive activity of Ficus deltoidea aqueous extract

Sulaiman MR, Hussain MK, Zakaria ZA, Somchit MN, Moin S, Mohamad AS, et al.

Fitoterapia, 2008 Dec;79(7-8):557-61.
PMID: 18672036 DOI: 10.1016/j.fitote.2008.06.005

The aqueous extract of Ficus deltoidea leaves was evaluated for possible antinociceptive activity in three models of nociception, namely, acetic acid-induced abdominal writhing, formalin and hot plate test. The results of the present study showed that intraperitoneal administration of the F. deltoidea leaves aqueous extract at the dose of 1, 50 and 100 mg/kg, 30 min prior to pain induction produced significant dose-dependent antinociceptive effect in all the models used, which indicating the presence of both central and peripherally mediated activities. Furthermore, the antinociceptive effect of the extract in the formalin and hot plate test was reversed by the non-selective opioid receptor antagonist naloxone suggesting that the endogenous opioid system is involved in its analgesic mechanism of action. Thus, the present results demonstrated that F. deltoidea leaves aqueous extract contains pharmacologically active constituents which possess antinociceptive activity justifying its popular therapeutic use in treating conditions associated with the painful conditions.

Matched MeSH terms: Analysis of Variance
Risk factors for endemic giardiasis: highlighting the possible association of contaminated water and food

Mohammed Mahdy AK, Lim YA, Surin J, Wan KL, Al-Mekhlafi MS

Trans R Soc Trop Med Hyg, 2008 May;102(5):465-70.
PMID: 18377940 DOI: 10.1016/j.trstmh.2008.02.004

This study was conducted to reassess the risk factors for giardiasis in communities of the Orang Asli (indigenous people) in Pahang, Malaysia. Stool samples were collected from 321 individuals (2-76 years old; 160 males, 161 females). Data were collected via laboratory analysis of faecal samples and a pre-tested standard questionnaire. River water samples were tested for Giardia cysts and Cryptosporidium oocysts. The overall prevalence of G. intestinalis infection was 23.7%. Children < or =12 years old had the highest infection rate and have been identified as a high risk group (odds ratio (OR)=6.2, 95% CI 1.5-27.0, P<0.005). The risk of getting giardiasis also appeared to be significantly associated with drinking piped water (OR=5.1, 95% CI 0.06-0.7, P<0.005) and eating raw vegetables (OR=2.4, 95% CI 0.2-0.6, P<0.005). In conclusion, sociodemographic factors have always been associated with the high prevalence of Giardia infections in Malaysia. However, the present study also highlights the need to look into the possibility of other risks such as water and food transmission routes. In future, it is necessary that these two aspects be considered in control strategies.

Matched MeSH terms: Analysis of Variance
Outcome study of first-episode schizophrenia in a developing country: quality of life and antipsychotics

Chee KY

Soc Psychiatry Psychiatr Epidemiol, 2009 Feb;44(2):143-50.
PMID: 18642120 DOI: 10.1007/s00127-008-0415-0

AIM: Quality of life has recently been emphasized in the management of schizophrenia, yet data from developing country is lacking. We explored the differences in subjective quality of life between conventional antipsychotics (CAs) and atypical antipsychotics (AAs).
METHODS: This is a naturalistic study conducted in Kuala Lumpur, Malaysia. Patients with first-episode schizophrenia and related psychosis were recruited from Kuala Lumpur Hospital. WHOQOL-BREF, side effects of medications and other variables were assessed after 1 year of treatment in routine clinical situation.
RESULTS: The study comprised 120 adults. There were no significant statistical differences between groups concerning subjective quality of life, extrapyramidal side effects and employment. Significant less benzhexol usage was reported among AAs (P<0.001) compared to CAs and sulpiride.
CONCLUSION: Patients treated with CAs, sulpiride or AAs experienced similar quality of life, clinical and health outcomes after 1 year commencing treatment. Overall, the results are in line with other major pragmatic clinical trials. This study also found sulpiride cost-effective.

Matched MeSH terms: Analysis of Variance
Fulltext Daily supplementation of tocotrienol-rich fraction or alpha-tocopherol did not induce immunomodulatory changes in healthy human volunteers

Radhakrishnan AK, Lee AL, Wong PF, Kaur J, Aung H, Nesaretnam K

Br J Nutr, 2009 Mar;101(6):810-5.
PMID: 18702848 DOI: 10.1017/S0007114508039998

Vitamin E is divided into two subgroups; tocopherols and tocotrienols. Both have protective roles in biological systems. The present study was conducted to compare the effect of short-term supplementation at 200 mg/d of either alpha-tocopherol or a tocotrienol-rich fraction (TRF) from palm oil on immune modulation and plasma vitamin E levels in normal healthy Asian volunteers. In a randomised, double-blind placebo-controlled trial conducted, fifty-three healthy volunteers aged 20-50 years were recruited based on the study's inclusion and exclusion criteria. They were randomly assigned into three groups, i.e. two experimental groups that received daily supplementation at 200 mg of either alpha-tocopherol or the TRF, and the control group that received a placebo. Blood was drawn on days 0, 28 and 56 for several laboratory analyses. Differences in the production of IL-4 or interferon-gamma by concanavalin A-stimulated lymphocytes isolated from these volunteers were not significant (P>0.05). There were no significant differences observed in immune parameters between the healthy volunteers who received daily supplementation with either alpha-tocopherol or the TRF. As these observations were made in the absence of any immunogenic challenge, we feel it would be of benefit to study if there would be any differences observed when an immunogenic challenge such as vaccination were introduced.

Matched MeSH terms: Analysis of Variance
Erythrocyte indicators of oxidative changes in patients with graded traumatic head injury

Nayak CD, Nayak DM, Raja A, Rao A

Neurol India, 2008 3 4;56(1):31-5.
PMID: 18310834

CONTEXT: Acute oxidative stress following a traumatic head injury (HI) has been implicated in inducing severe secondary brain damage and influencing the clinical outcome of HI patients.
AIMS: This study was performed to evaluate and compare the oxidative changes in patients with varying severity of HI in the early posttraumatic period using erythrocyte indicators.
SETTINGS AND DESIGN: Head injury patients were divided into two groups based on their Glasgow Coma Scale (GCS) scores recorded at admission to the hospital on the day of trauma itself. Accordingly, the study included 30 severe HI (SHI, GCS scores 8 or less) and 25 Mild HI (MHI, GCS scores more than 8) patients. Thirty age and sex-matched healthy individuals were included in this comparative study as controls.
MATERIALS AND METHODS: Blood samples were obtained from controls and HI patients (within 24 h of trauma onset). Erythrocyte oxidative changes were studied by estimating thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD) and glutathione reductase (GR).
RESULTS: Erythrocyte TBARS levels were significantly higher and GSH levels were significantly lower in SHI and MHI patients as compared to controls. The SOD activity was significantly increased only in SHI patients and remained unchanged in MHI patients as compared to controls. As compared to MHI patients, erythrocyte TBARS levels were significantly higher, GSH levels were significantly lower and SOD activity was markedly elevated in SHI patients. Erythrocyte GR activity did not show significant changes in both groups of patients as compared to controls.
CONCLUSION: Oxidative stress is evident in both SHI and MHI patients in the early posttraumatic period as reflected by their erythrocyte indicators, but the severity of oxidative stress has varied relatively with the severity of head injury. The present findings provide indications that early oxidative changes could influence the neurological recovery of HI patients.

Matched MeSH terms: Analysis of Variance
The effect of Piper betle and Psidium guajava extracts on the cell-surface hydrophobicity of selected early settlers of dental plaque

Razak FA, Othman RY, Rahim ZH

J Oral Sci, 2006 Jun;48(2):71-5.
PMID: 16858135

The adhesion of early settlers of dental plaque to the tooth surface has a role in the initiation of the development of dental plaque. The hydrophobic surface properties of the bacteria cell wall are indirectly responsible for the adhesion of the bacteria cell to the acquired pellicle on the tooth surfaces. In this study, the effect of aqueous extract of two plants (Psidium guajava and Piper betle) on the cell-surface hydro-phobicity of early settlers of dental plaque was determined in vitro. Hexadecane, a hydrocarbon was used to represent the hydrophobic surface of the teeth in the oral cavity. It was found that treatment of the early plaque settlers with 1 mg/ml extract of Psidium guajava reduced the cell-surface hydrophobicity of Strep. sanguinis, Strep. mitis and Actinomyces sp. by 54.1%, 49.9% and 40.6%, respectively. Treatment of these bacteria with the same concentration of Piper betle however, showed a comparatively lesser effect (< 10%). It was also observed that the anti-adhesive effect of the two extracts on the binding of the early plaque settlers to hexadecane is concentration dependent.

Matched MeSH terms: Analysis of Variance
Role of CD4 and CD8 T-cells in the induction of oral tolerance to Actinomyces viscosus in mice

Sosroseno W, Bird PS, Gemmell E, Seymour GJ

Oral Microbiol. Immunol., 2006 Jun;21(3):151-8.
PMID: 16626371

Mucosal presentation of Actinomyces viscosus results in the induction of antigen specific systemic suppressor cells in mice. The aim of the present study was to determine the phenotype of the suppressor cells responsible for the induction of oral tolerance to low doses of A. viscosus. When CD8 cell-depleted DBA/2 mice were intragastrically immunized and systemically immunized with A. viscosus, the delayed type hypersensitivity response was suppressed but not the levels of antigen specific serum antibodies. Adoptive transfer of orally tolerized CD4(+) cells to CD4(+)-depleted mice resulted in suppression of delayed type hypersensitivity response but not of the levels of antigen specific serum antibodies. In contrast, adoptive transfer of orally immunized CD8(+) cells to CD8(+)-depleted mice resulted in partially suppressed delayed type hypersensitivity response but significantly inhibited the levels of antigen specific serum antibodies. When orally tolerized CD8(+) cells were cocultured with systemically immunized CD8(+) cell-depleted spleen cells, splenic specific antibodies were inhibited. However, no suppression of splenic specific antibodies could be observed in the cultures containing orally tolerized CD4(+) cells and systemically immunized CD4(+) cell-depleted spleen cells. The results of the present study suggest that oral tolerance of humoral and cellular immunity induced by low doses of A. viscosus may be mediated by CD8(+) and CD4(+) cells, respectively.

Matched MeSH terms: Analysis of Variance
Effects of fluoride-modified titanium surfaces on osteoblast proliferation and gene expression

Isa ZM, Schneider GB, Zaharias R, Seabold D, Stanford CM

Int J Oral Maxillofac Implants, 2006 Mar-Apr;21(2):203-11.
PMID: 16634490

PURPOSE: The objective of this study was to test the hypothesis that fluoride-modified titanium surfaces would enhance osteoblast differentiation. Osteoblast growth on a moderately rough etched fluoride-modified titanium surface (alteration in cellular differentiation) was compared to osteoblast growth on the same surface grit-blasted with titanium dioxide. The potential role of nanometer-level alterations on cell shape and subsequent differentiation was then compared.
MATERIALS AND METHODS: Human embryonic palatal mesenchymal (HEPM) cultures were incubated on the respective surfaces for 1, 3, and 7 days, followed by analysis for cell proliferation, alkaline phosphatase (ALP) -specific activity, and mRNA steady-state expression for bone-related genes (ALP, type I collagen, osteocalcin, bone sialoprotein [BSP] II, Cbfa1, and osterix) by real-time polymerase chain reaction (PCR).
RESULTS: The different surfaces did not alter the mRNA expression for ALP, type I collagen, osterix, osteocalcin, or BSP II. However, Cbfa1 expression on the fluoride-modified titanium surface was significantly higher (P < .001) at 1 week. The number of cells on this surface was 20% lower than the number of cells on the surface TiO2-blasted with 25-microm particles but not significantly different from the number of cells on the surface TiO2-blasted with 125-microm particles. Cells grown on all the titanium surfaces expressed similar levels of ALP activity.
CONCLUSIONS: The results indicated that a fluoride-modified surface topography, in synergy with surface roughness, may have a greater influence on the level of expression of Cbfa1 (a key regulator for osteogenesis) than the unmodified titanium surfaces studied.

Matched MeSH terms: Analysis of Variance
Strategies adopted by the mudskipper Boleophthalmus boddaerti to survive sulfide exposure in normoxia or hypoxia

Ip YK, Kuah SS, Chew SF

Physiol Biochem Zool, 2004 Sep-Oct;77(5):824-37.
PMID: 15547800

The effects of sulfide on the energy metabolism of Boleophthalmus boddaerti in normoxia and hypoxia were examined. The 24-, 48-, and 96-h LC50 values of sulfide for B. boddaerti with body weight ranging from 11.6 to 14.2 g were 0.786, 0.567, and 0.467 mM, respectively. The tolerance of B. boddaerti to sulfide was not due to the presence of a sulfide-insensitive cytochrome c oxidase. There was no accumulation of lactate in the muscle and liver of specimens exposed to sulfide in normoxia. In addition, the levels of ATP, AMP, and energy charge in both the muscle and the liver were unaffected. These results indicate that B. boddaerti was able to sustain the energy supply required for its metabolic needs via mainly aerobic respiration when exposed to sulfide (up to 0.4 mM) in normoxia. Exposure of B. boddaerti simultaneously to hypoxia and 0.2 mM sulfide for 48 h resulted in decreases in the ATP levels in the muscle and liver. However, the energy charge in both tissues remained unchanged, and the level of lactate accumulated in the muscle was too low to have any major contribution to the energy budget of the fish. Our results reveal that B. boddaerti possesses inducible mechanisms to detoxify sulfide in an ample supply or a lack of O2. In normoxia, it detoxified sulfide to sulfate, sulfite, and thiosulfate. There were significant increases in the activities of sulfide oxidase in the muscle and liver of specimens exposed to sulfide, with that in the liver being >13-fold higher than that in the muscle. However, in hypoxia, sulfide oxidase activity in the liver was suppressed in response to environmental sulfide. In such conditions, there were significant increases in the activities of sulfane sulfur-forming enzyme(s) in the muscle and liver that were not observed in specimens exposed to sulfide in normoxia. Correspondingly, there were no changes in the levels of sulfate or sulfite in the muscle or liver. Instead, B. boddaerti detoxified sulfide mainly to sulfane sulfur in hypoxia. In conclusion, B. boddaerti was able to activate different mechanisms to detoxify sulfide, producing different types of detoxification products in normoxia and hypoxia.

Matched MeSH terms: Analysis of Variance
Gene expression profiling of p53(+/-) knockout and wild-type mice following diethylstilbestrol administration

Salleh MN, Ismail P, Abdullah AS, Taufiq-Yap YH, Carmichael P

IUBMB Life, 2004 Jul;56(7):409-16.
PMID: 15545218

Studies with clastogenic carcinogen diethylstilbestrol (DES) resulted in a broad of spectrum of toxic and carcinogenic effects in humans and rodents, but the cellular and molecular mechanism(s) by which it induces cancer is not clear. To identify putative genetic targets for p53 in vivo, we applied the cDNA macroarray gene expression profiles associated with apoptosis by comparing p53+/- knockout mice and wild-type mice on the kidney and uterus of female mice. p53+/- knockout mice and wild-type mice were treated with DES (500 micromole kg(-1)) or vehicle i.p once daily for 4 days. Total RNAs were obtained from kidney and uterus of both control and DES-treated. The signal intensities of individual gene spots on the membrane were quantified and normalized to the expression level of the GAPDH gene as an internal control. Our results demonstrated that 16 genes; bad, bax, bcl-2, bcl-w, bcl-x, caspase-3, caspase-7, caspase-8, c-myc, E124, GADD45, mdm2, NKkappab1, p53, p21, Rb and trail were up-regulated and six genes; caspase-1, caspase-2, DR5, E2F1, FasL and iNOS did not changed in response to DES treatment in wild-type mice compared to p53+/- knockout mice. Most genes are involved in cell cycle regulation, signal transduction, apoptosis, or transcription. The greatest changes were seen in bad, bcl-x, mdm2, p53 and p21 gene expression in wild-type mice compared to p53+/- knockout mice. In comparing p53 and p21 gene expression in wild-type mice and p53+/- knockout mice, there was an 4.4-fold vs. 1.8-fold; 8-fold vs. 5.2-fold for kidney and 16-fold vs. 5.5-fold; 2.1-fold vs. 8.3-fold for uterus samples increase in induction (respectively). RT-PCR and densitometric analysis was used to confirm the biggest changes of p21, p53 and bax genes. Using this approach, we have identified apoptosis associated genes regulated in response to DES and have revealed putative differences between the isogenic parent strain and p53+/- knockout mice, which will contribute to a better understanding of toxicity/carcinogenicity mechanisms in this model.

Matched MeSH terms: Analysis of Variance

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