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Diagnostic Dilemma: Ocular Features and Treatment Outcome of a Case of Coats-Like Retinitis Pigmentosa

Siow S, Abdullah NA

Cureus, 2024 Oct;16(10):e71695.
PMID: 39552961 DOI: 10.7759/cureus.71695

Coats-like retinitis pigmentosa is a rare disease demonstrating both features of Coats disease and retinitis pigmentosa. We are reporting a case of a 15-year-old female with no known medical illness who presented with a one-year history of nyctalopia and bilateral painless blurred vision. Fundus examination revealed bilateral optic disc swelling, telangiectasia, and bony spicules. Optical coherence tomography and fundus fluorescein angiography showed cystoid macular edema (CMO). The diagnosis of Coats-like retinitis pigmentosa with CMO was made. She received laser indirect ophthalmoscope photocoagulation and intravitreal anti-vascular endothelial growth factor therapy, but her vision remained refractory. Her diagnosis was subsequently revised to bilateral intermediate uveitis causing CMO and her vision improved to periocular steroid injections. This case emphasizes how critical it is to identify symptoms and diagnose the illness as soon as possible because treating related complications on time can save a patient's sight and provide long-term benefits.
Fulltext Reproductive function after treatment of ovarian germ cell malignancy

Abdullah NA, Rushdan MN

Med J Malaysia, 2012 Feb;67(1):71-6.
PMID: 22582552 MyJurnal

This study was undertaken to evaluate the reproductive and oncologic outcomes of patients diagnosed with Ovarian Germ Cell Malignancy (OGCM) who underwent fertility preserving surgery and adjuvant chemotherapy treated in Gynaecology Oncology Unit, Sultanah Bahiyah Hospital, Kedah, Malaysia.
Fulltext The Effect of Individual Factors on the Medication Error

Zyoud AH, Abdullah NA

Glob J Health Sci, 2016 Apr 29;8(12):57756.
PMID: 27357892 DOI: 10.5539/gjhs.v8n12p197

Medication error is a major issue in healthcare industry and significant efforts have been taken in recent years to comprehend factors that influence errors in medication. Therefore, the present study aims to examine individual factors that contribute to medication errors as perceived by nurses. 255 registered nurses working in different Jordanian public hospitals have been chosen as samples to collect the study data from. They were asked to complete a questionnaire to assess the perceived individual factors, specifically, on nursing mathematical calculation skills and training as well as knowledge on medication treatment as factors contributing to medication errors. The current study found that the nurses' mathematical calculation skills, training and their knowledge on medication treatment have significant relationship with medication error. This was proven as the study framework is able to explain 45.6% of the total variance. Consequently, it is recommended that healthcare authorities and hospitals in Jordan should focus on nursing knowledge in medication treatment and the nurses' ability to perform drug calculation in order to improve the medication system in Jordan.
Composition and sources of aliphatic lipids and sterols in sediments of a tropical island, southern South China Sea: preliminary assessment

Mohd Tahir N, Pang SY, Abdullah NA, Suratman S

Environ Monit Assess, 2013 Dec;185(12):10209-16.
PMID: 23856812 DOI: 10.1007/s10661-013-3325-x

Near-shore surface sediment was collected from five stations off Redang Island located on the eastern coast of Peninsular Malaysia. Freeze-dried sediments were Soxhlet extracted and then fractionated using column chromatography into aliphatic and polar fractions. Determination of these fractions was carried out using gas chromatography mass spectrometry. The concentration of total resolved aliphatic hydrocarbons in sediments ranged from 157 to 308 ng/g. The distribution of aliphatic fraction showed the presence of n-alkanes ranging from nC15 to nC33 with a minor odd-to-even predominance exhibiting carbon maximum, depending on station, at nC17, nC26, nC29 or nC31. Calculation of Carbon Preference Index (CPI) for CPI(15-33) gave values ranging from 1.09 to 1.46. n-Alkanol in all sediment exhibits even-to-odd carbon predominance ranging from nC16 to nC28 and maximising at nC22. n-Fatty acids distribution ranged from nC14 to nC24 with a dominant maximum at nC16 and exhibiting high values of short chain fatty acids (≤nC20) to long chain fatty acids (>nC20) ratios. Unsaturated fatty acids, particularly nC16:1 and nC18:1 is also ubiquitous in all samples. Cholesterol is the most abundant compound amongst the sterol group ranging from 42.8 to 62.6% of the total sterols. β-Sitosterol, brassicasterol and stigmasterol, are also present but of relatively lower amount. These observations suggest that the aliphatic lipids and sterols in the study area originate, mainly, from biogenic sources of marine microbial with minor contribution from epiticular waxes of terrestrial plants.
Genetic relationships among five varieties of Curcuma alismatifolia (Zingiberaceae) based on ISSR markers

Taheri S, Abdullah TL, Abdullah NA, Ahmad Z

Genet. Mol. Res., 2012;11(3):3069-76.
PMID: 23007984

The genus Curcuma is a member of the ginger family (Zingiberaceae) that has recently become popular for use as flowering pot plants, both indoors and as patio and landscape plants. We used PCR-based molecular markers (ISSRs) to assess genetic variation and relationships between five varieties of curcuma (Curcuma alismatifolia) cultivated in Malaysia. Sixteen ISSR primers generated 139 amplified fragments, of which 77% had high polymorphism among these varieties. These markers were used to estimate genetic similarity among the varieties using Jaccard's similarity coefficient. The similarity matrix was used to construct a dendrogram, and a principal component plot was developed to examine genetic relationships among varieties. Similarity coefficient values ranged from 0.40 to 0.58 (with a mean of 0.5) among the five varieties. The mean value of number of observed alleles, number of effective alleles, mean Nei's gene diversity, and Shannon's information index were 8.69, 1.48, 0.29, and 0.43, respectively.
Fulltext Ectopic inferior vena cava thrombus secondary to a tubo-ovarian abscess

Koh KS, Abdullah NA, Chong VH

Med J Malaysia, 2014 Dec;69(6):293-5.
PMID: 25934966

Inferior vena cava (IVC) thrombosis typically arises distally from a thrombophlebitic extension in the pelvis or the lower extremities. It may also occur from propagation of an ovarian vein thrombosis as a result of gynaecological disorders such as pelvic inflammatory disease, endometritis or from pelvic surgeries. In this report, we present an interesting case of a tubo-ovarian abscess with an ectopic IVC thrombus. The approach to management in such cases is also highlighted.
Fulltext Survey dataset on presenteeism, job demand and perceived job insecurity: The perspective of diplomatic officers

Mokhtar D, Abdullah NA, Roshaizad NA

Data Brief, 2020 Jun;30:105505.
PMID: 32368580 DOI: 10.1016/j.dib.2020.105505

This data belongs to a sample of 347 diplomatic officers from two different locations which are the National Institute of Public Administration (INTAN) in Johor and Terengganu. This data consists of the demographic characteristics of the sample and three main variables. Each variable has sub-dimension which are (1) presenteeism: ability to complete a task and avoid disturbance, (2) job demand: workload, emotional and cognitive demand, (3) job insecurity: the importance and probability of an event to take place. The data were collected using a cross-sectional questionnaire via paper-and-pencil mode and was analyzed using SPSS version 22. Pearson correlation analyses revealed a significant relationship between avoiding disturbance (sub-dimension of presenteeism) and the probability of an event happening (sub-dimension of job insecurity) and no significant correlation between other variables. Analyses of the data can provide insights into determinants of presenteeism that may be useful for researchers in the field and policymakers that are interested in this area. It may serve as a reference to expand research and to develop interventions to facilitate productivity and well-being in the workplace.
Treatment of Post-traumatic Osteonecrosis in the Distal Tibia With Autologous Bone Grafting: A Case Report

Mazli N, Bajuri MY, Nik Abdullah NA

Cureus, 2023 Nov;15(11):e48214.
PMID: 38050520 DOI: 10.7759/cureus.48214

Osteonecrosis is a disruption of blood supply to the bone which results in bone cell death. Post-traumatic osteonecrosis of distal tibia rarely happens as compared to osteonecrosis which affects other parts of the musculoskeletal system. We report a case of osteonecrosis of distal tibia in an adult male following an open fracture dislocation of the right ankle. Initial surgery of wound debridement with a temporary external fixator was performed for ankle stabilization. The patient underwent internal fixation once the subcutaneous tissue was deemed suitable. A year later, he had worsening ankle pain which affected his daily activities. Magnetic resonance imaging showed osteonecrosis of the distal tibia, osteochondral injury of the medial tibial plafond, and medial talus with lateral ligament complex injuries. Autologous iliac bone grafting was applied to the distal tibia and a cell-free hyaluronic acid-based scaffold (Hyalofast®) was used to address the bone osteonecrosis and osteochondral injury respectively. Visual analog score (VAS), AOFAS hindfoot score, and ankle range of motion improved at three months and significantly increased after six months and one year post-operatively.
A method to improve the prediction performance of cancer-gene association by screening negative training samples through gene network data

Xu M, Abdullah NA, Md Sabri AQ

Comput Biol Chem, 2024 Feb;108:107997.
PMID: 38154318 DOI: 10.1016/j.compbiolchem.2023.107997

This work focuses on data sampling in cancer-gene association prediction. Currently, researchers are using machine learning methods to predict genes that are more likely to produce cancer-causing mutations. To improve the performance of machine learning models, methods have been proposed, one of which is to improve the quality of the training data. Existing methods focus mainly on positive data, i.e. cancer driver genes, for screening selection. This paper proposes a low-cancer-related gene screening method based on gene network and graph theory algorithms to improve the negative samples selection. Genetic data with low cancer correlation is used as negative training samples. After experimental verification, using the negative samples screened by this method to train the cancer gene classification model can improve prediction performance. The biggest advantage of this method is that it can be easily combined with other methods that focus on enhancing the quality of positive training samples. It has been demonstrated that significant improvement is achieved by combining this method with three state-of-the-arts cancer gene prediction methods.
Fulltext Cryptococcal meningitis in an immunocompetent child: a case report and literature review

Othman N, Abdullah NA, Wahab ZA

Southeast Asian J Trop Med Public Health, 2004 Dec;35(4):930-4.
PMID: 15916093

An immunocompetent 5 year-old girl presented with pyrexia of unknown origin associated with headache. Initial investigations showed leukocytosis and an increased erythrocyte sedimentation rate. A Widal-Weil Felix test, blood film for malarial parasites, mycoplasma IgM antibody, cultures from blood and urine, full blood picture, Mantoux test, and chest x-ray were all negative. A lumbar puncture was done as part of a work-up for pyrexia of unknown origin. Cryptococcus neoformans was seen on India ink examination and confirmed on culture. She was treated with 10 weeks of intravenous amphotericin B and 8 weeks of fluconazole. Further immunological tests did not reveal any defect in the cell-mediated immune system. C. neoformans meningitis may present with non-specific symptoms and should be considered in a work-up for pyrexia of unknown origin.
Exploring alternative approaches to next of kin consenting in the semi-emergency neurosurgical scenario

Zakaria EN, Abdullah NA, Ganesan D

Med J Malaysia, 2024 Nov;79(6):735-742.
PMID: 39614792

INTRODUCTION: Prior to any surgical intervention, obtaining informed consent is necessary. In situations where patients are unable to provide informed consent due to mental incapacity or reduced consciousness, the responsibility falls on surrogate decision-makers, typically family members. This predicament commonly arises during neurosurgical emergencies. Various types of surgical emergencies exist, each with its own classification. In cases of life-threatening neurosurgical emergencies and in the absence of next of kin, two consultants have the authority to decide and grant surgical consent. However, for urgent and semi-emergency surgical cases, obtaining consent from the next of kin is crucial. The conventional requirement for the physical presence of the next of kin at the hospital often causes delays in the procedure. This study aims to explore alternative methods for efficiently and compliantly securing this consent for urgent and semi-emergency neurosurgical cases.
MATERIALS AND METHODS: A prospective, observational crosssectional survey was conducted from 1st May 2022 to 31st December 2022 at the University of Malaya Medical Centre, Kuala Lumpur. This survey included all neurosurgical patients aged 18 and above requiring urgent and semiemergency surgery. The next of kin were interviewed using a standardised questionnaire to obtain their perspectives on the effectiveness of the current consenting process, as well as to explore potential alternative methods for obtaining consent. Data were analysed using IBM SPSS Statistics.
RESULTS: The survey had 103 responses. The analysis revealed that the most common semi-emergency surgical procedures were craniotomy (22 cases) and external ventricular drain insertion (18 cases), followed by burr hole and drainage (14 cases). The most common primary diagnosis that needed urgent intervention was acute hydrocephalus. Interestingly, more than half of the patients (58 cases, 56.3%) had to wait for over 30 minutes to obtain consent from their next of kin prior to surgery. The next of kin interviewed had an age range of 25 to 72 years. The relationships of the next of kin were children (33 subjects), spouses (26 subjects), siblings (25 subjects), and parents (16 subjects) of the patients. Additionally, 96.1% of the respondents owned a smartphone with a mobile internet data connection, and 85.4% had internet connectivity at home. The most preferred method of telecommunication for this exercise was via WhatsApp. An interesting finding was the association between the level of trust in medical professionals and the preferred consent method. It was discovered that individuals who preferred physical consent had lower trust in the hospital and doctors, while those who preferred remote consent had higher trust.
CONCLUSION: The urban Malaysian population are ready to embrace telecommunication for next-of-kin consent in semiemergency neurosurgical scenarios. These findings form a precursor to further studies to develop algorithms for a secure remote digital surgical consenting platform for urgent or semi-emergency surgical cases.
Fulltext Genetic variation in Rhodomyrtus tomentosa (Kemunting) populations from Malaysia as revealed by inter-simple sequence repeat markers

Hue TS, Abdullah TL, Abdullah NA, Sinniah UR

Genet. Mol. Res., 2015;14(4):16827-39.
PMID: 26681029 DOI: 10.4238/2015.December.14.10

Kemunting (Rhodomyrtus tomentosa) from the Myrtaceae family, is native to Malaysia. It is widely used in traditional medicine to treat various illnesses and possesses significant antibacterial properties. In addition, it has great potential as ornamental in landscape design. Genetic variability studies are important for the rational management and conservation of genetic material. In the present study, inter-simple sequence repeat markers were used to assess the genetic diversity of 18 R. tomentosa populations collected from ten states of Peninsular Malaysia. The 11 primers selected generated 173 bands that ranged in size from 1.6 kb to 130 bp, which corresponded to an average of 15.73 bands per primer. Of these bands, 97.69% (169 in total) were polymorphic. High genetic diversity was documented at the species level (H(T) = 0.2705; I = 0.3973; PPB = 97.69%) but there was a low diversity at population level (H(S) = 0.0073; I = 0 .1085; PPB = 20.14%). The high level of genetic differentiation revealed by G(ST) (73%) and analysis of molecular variance (63%), together with the limited gene flow among population (N(m) = 0.1851), suggests that the populations examined are isolated. Results from an unweighted pair group method with arithmetic mean dendrogram and principal coordinate analysis clearly grouped the populations into two geographic groups. This clear grouping can also be demonstrated by the significant Mantel test (r = 0.581, P = 0.001). We recommend that all the R. tomentosa populations be preserved in conservation program.
Fulltext Assessing the genetic relationships of Curcuma alismatifolia varieties using simple sequence repeat markers

Taheri S, Abdullah TL, Abdullah NA, Ahmad Z, Karimi E, Shabanimofrad MR

Genet. Mol. Res., 2014;13(3):7339-46.
PMID: 25222232 DOI: 10.4238/2014.September.5.12

The genus Curcuma is a member of the ginger family (Zingiberaceae) that has recently become popular for use as flowering pot plants, both indoors and as patio and landscape plants. We used PCR-based molecular markers (SSRs) to elucidate genetic variation and relationships between five varieties of Curcuma (Curcuma alismatifolia) cultivated in Malaysia. Of the primers tested, 8 (of 17) SSR primers were selected for their reproducibility and high rates of polymorphism. The number of presumed alleles revealed by the SSR analysis ranged from two to six alleles, with a mean value of 3.25 alleles per locus. The values of HO and HE ranged from 0 to 0.8 (mean value of 0.2) and 0.1837 to 0.7755 (mean value of 0.5102), respectively. Eight SSR primers yielded 26 total amplified fragments and revealed high rates of polymorphism among the varieties studied. The polymorphic information content varied from 0.26 to 0.73. Dice's similarity coefficient was calculated for all pairwise comparisons and used to construct an unweighted pair group method with arithmetic average (UPGMA) dendrogram. Similarity coefficient values from 0.2105 to 0.6667 (with an average of 0.4386) were found among the five varieties examined. A cluster analysis of data using a UPGMA algorithm divided the five varieties/hybrids into 2 groups.
Fulltext An efficient in vitro plantlet regeneration from shoot tip cultures of Curculigo latifolia, a medicinal plant

Babaei N, Abdullah NA, Saleh G, Abdullah TL

ScientificWorldJournal, 2014;2014:275028.
PMID: 24723799 DOI: 10.1155/2014/275028

A procedure was developed for in vitro propagation of Curculigo latifolia through shoot tip culture. Direct regeneration and indirect scalp induction of Curculigo latifolia were obtained from shoot tip grown on MS medium supplemented with different concentrations and combinations of thidiazuron and indole-3-butyric acid. Maximum response for direct regeneration in terms of percentage of explants producing shoot, shoot number, and shoot length was obtained on MS medium supplemented with combination of thidiazuron (0.5 mg L(-1)) and indole-3-butyric acid (0.25 mg L(-1)) after both 10 and 14 weeks of cultures. Indole-3-butyric acid in combination with thidiazuron exhibited a synergistic effect on shoot regeneration. The shoot tips were able to induce maximum scalp from basal end of explants on the medium with 2 mg L(-1) thidiazuron. Cultures showed that shoot number, shoot length, and scalp size increased significantly after 14 weeks of culture. Transferring of the shoots onto the MS medium devoid of growth regulators resulted in the highest percentage of root induction and longer roots, while medium supplemented with 0.25 mg L(-1) IBA produced more numbers of roots.
Fulltext Effect of acute gamma irradiation on Curcuma alismatifolia varieties and detection of DNA polymorphism through SSR marker

Taheri S, Abdullah TL, Ahmad Z, Abdullah NA

Biomed Res Int, 2014;2014:631813.
PMID: 24719878 DOI: 10.1155/2014/631813

The effects of eight different doses (0, 10, 20, 25, 35, 40, 60, and 100 Gy) of acute gamma irradiation on 44 (three varieties of Curcuma alismatifolia: Chiang Mai Red, Sweet Pink, Kimono Pink, and one Curcuma hybrid (Doi Tung 554) individual plants were investigated. Radiation sensitivity tests revealed that the LD50 values of the varieties were achieved at 21 Gy for Chiang Mai Red, 23 Gy for Sweet Pink, 25 Gy for Kimono Pink, and 28 Gy for Doi Tung 554. From the analysis of variance (ANOVA), significant variations were observed for vegetative traits, flowering development, and rhizome characteristics among the four varieties of Curcuma alismatifolia and dose levels as well as the dose × variety interaction. In irradiated plants, the leaf length, leaf width, inflorescence length, the number of true flowers, the number of pink bracts, number of shoots, plant height, rhizome size, number of storage roots, and number of new rhizomes decreased significantly (P < 0.05) as the radiation dose increased. The cophenetic correlation coefficient (CCC) between genetic dissimilarity matrix estimated from the morphological characters and the UPGMA clustering method was r = 0.93, showing a proof fit. In terms of genetic variation among the acutely irradiated samples, the number of presumed alleles revealed by simple sequence repeats ranged from two to seven alleles with a mean value of 3.1, 4.5, and 5.3 alleles per locus for radiation doses of 0, 10, and 20 Gy, respectively. The average values of the effective number of alleles, Nei's gene diversity, and Shannon's information index were 2.5-3.2, 0.51-0.66, and 0.9-1.3, respectively. The constructed dendrogram grouped the entities into seven clusters. Principal component analysis (PCA) supported the clustering results. Consequently, it was concluded that irradiation with optimum doses of gamma rays efficiently induces mutations in Curcuma alismatifolia varieties.
The effect of high-fructose intake on the vasopressor response to angiotensin II and adrenergic agonists in Sprague-Dawley rats

Abdulla MH, Sattar MA, Abdullah NA, Johns EJ

Pak J Pharm Sci, 2013 Jul;26(4):727-32.
PMID: 23811449

Effect of losartan was assessed on systemic haemodynamic responses to angiotensin II (Ang II) and adrenergic agonists in the model of high-fructose-fed rat. Twenty-four Sprague-Dawley (SD) rats were fed for 8 weeks either 20% fructose solution (FFR) or tap water (C) ad libitum. FFR or C group received losartan (10mg/kg/day p.o.) for 1 week at the end of feeding period (FFR-L and L) respectively, then the vasopressor responses to Ang II, noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) were determined. The responses (%) to NA, PE, ME and Ang II in FFR were lower (P<0.05) than C (FFR vs. C; 22±2 vs. 32±2, 30±3 vs. 40±3, 9±1 vs. 13±1, 10±1 vs. 17±1) respectively. L group had blunted (P<0.05) responses to NA, PE, ME and Ang II compared to C (L vs. C; 26±2 vs. 32±2, 30±3 vs. 40±3, 7±0.7 vs. 13±1, 5±0.4 vs. 17±1) respectively. FFR-L group had aggravated (P<0.05) response to NA and ME, but blunted response to Ang II compared to FFR (FFR-L vs. FFR; 39±3 vs. 22±2, 11±1 vs. 9±1, 3±0.4 vs. 10±1) respectively. Fructose intake for 8 weeks results in smaller vasopressor response to adrenergic agonists and Ang II. Data also demonstrated an important role played by Ang II in the control of systemic haemodynamics in FFR and point to its interaction with adrenergic neurotransmission.
Sustainable complete remission in recurrence yolk sac tumor patient treated with tandem high-dose chemotherapy and autologous stem cell

Abdullah NA, Wang PN, Huang KG, Adlan AS, Casanova J

Eur. J. Gynaecol. Oncol., 2013;34(2):183-5.
PMID: 23781595

A 21-year-old lady diagnosed with Stage 3 ovarian yolk sac tumor (YST) underwent primary cytoreductive fertility sparing surgery, followed by conventional courses of platinum-based chemotherapy and etoposide. Recurrence at cul-da-sac was noted after a short period of remission and secondary debulking performed followed by four cycles of conventional chemotherapy. The patient's disease progressed despite courses of treatments. A joint team management including a hematologist was commenced following the failure of conventional chemotherapies. Two cycles of high-dose chemotherapy (HDCT) with ifosfamide/cisplatin/etoposide (ICE) regimen, followed by autologous stem cell transplantation (ASCT) were given. With this salvage treatment, she remained in complete remission and disease-free for more than 30 months, while maintaining her reproductive function. These approaches appear to be effective as a salvage treatment in selected cases of patients with ovarian germ cell tumor, especially those who failed primary conventional chemotherapy.
Alpha1A- and alpha1D-adrenoceptors are the major functional subtypes of renal alpha1-adrenoceptors in streptozotocin-induced diabetic and normal Sprague-Dawley rats

Armenia, Sattar MA, Abdullah NA, Khan MA, Johns EJ

Auton Autacoid Pharmacol, 2008 Jan;28(1):1-10.
PMID: 18257746 DOI: 10.1111/j.1474-8673.2007.00412.x

1 The present study investigated the effect of streptozotocin-induced diabetes on alpha(1)-adrenoceptor subtypes in rat renal resistance vessels. 2 Studies on renal haemodynamics were carried out 7 days after the last streptozotocin. Changes in renal blood flow were recorded in response to electrical stimulation of the renal nerve (RNS) and a range of adrenergic agonists; noradrenaline (NA), phenylephrine (PE) and methoxamine (MTX), either in the absence or the presence of nitrendipine (Nit), 5-methylurapidil (MEU), chlorethylclonidine (CEC) or BMY 7378. 3 In non-diabetic animals, Nit, MEU and BMY 7378 significantly attenuated renal vasoconstriction induced by adrenergic agonists, while CEC showed a significant accentuation in RNS-induced responses without having a significant effect on responses to adrenergic agonists. In diabetic rats, renal vasoconstriction was also significantly reduced in Nit-, MEU- and BMY 7378-treated groups and CEC potentiated RNS-induced contractions caused a change similar to that observed in non-diabetic rats. BMY 7378 significantly (P < 0.05) attenuated the PE- and MTX-induced vasoconstrictions but did not cause any significant (P > 0.05) alteration in the RNS- and NA-induced responses. 4 The results showed functional co-existence of alpha(1A)- and alpha(1D)-adrenoceptors in the renal vasculature of SD rats irrespective of the presence of diabetes. A possible minor contribution of prejunctional alpha-adrenoceptor subtype has also been suggested in either experimental group, particularly possible functional involvement of alpha(1B)-adrenoceptor subtypes in non-diabetic SD rats.
Influence of cisplatin-induced renal failure on the alpha(1)-adrenoceptor subtype causing vasoconstriction in the kidney of the rat

Khan AH, Sattar MA, Abdullah NA, Johns EJ

Eur J Pharmacol, 2007 Aug 13;569(1-2):110-8.
PMID: 17559832

This study investigated whether the alpha(1)-adrenoceptor subtype(s) mediating the vasoconstrictor actions of the renal sympathetic nerves were altered in rats with cisplatin-induced renal failure. Male Wistar Kyoto rats were used and half received cisplatin (5 mg/kg i.p.) to induce renal failure and were taken for study 7 days later. The renal blood flow reductions caused by electrical renal nerve stimulation and close intra-renal administration of noradrenaline, phenylephrine and methoxamine were determined before and after amlodopine (AMP), 5-methylurapidil (MeU), chloroethylclonidine (CEC) or BMY 7378. Water intake and creatinine clearance were decreased (P<0.05) by 40-50% while fractional excretion of sodium was increased two-fold in the cisplatin treated rats. Mean arterial pressure was higher, 110+/-2 versus 102+/-3 mmHg and renal blood flow was lower, 10.7+/-0.9 versus 18.9+/-0.1 ml/min/kg in the renal failure rats (both P<0.05). AMP, MeU and BMY 7378 decreased (all P<0.05) the adrenergically induced renal vasoconstrictor responses in the renal failure groups by 30 to 50% and in normal rats by 20 to 40%. In the presence of CEC, renal nerve stimulation and noradrenaline and methoxamine induced renal vasoconstrictor responses were enhanced (all P<0.05) in the renal failure but not in the normal rats. These data showed that alpha(1A)- and alpha(1D)-adrenoceptors were the major subtypes in mediating adrenergically induced renal vasoconstriction but there was no substantial shift in subtype in renal failure. The contribution of alpha(1B)-adrenoceptor subtypes either pre- or post-synaptic appeared to be raised in the renal failure rats.
Cisplatin-induced nephrotoxicity causes altered renal hemodynamics in Wistar Kyoto and spontaneously hypertensive rats: role of augmented renal alpha-adrenergic responsiveness

Hye Khan MA, Abdul Sattar M, Abdullah NA, Johns EJ

Exp. Toxicol. Pathol., 2007 Nov;59(3-4):253-60.
PMID: 17764917

The pathogenesis of cisplatin-induced renal failure is related to reduced renal blood flow due to severe tubular damage and enhanced renovascular resistance. It is also known that alpha(1)-adrenoceptors, the major subtype of alpha-adrenoceptors in renal vasculature play the pivotal role in regulating renal hemodynamics. With this background, we have hypothesized that the altered renal hemodynamics and enhanced renovascular resistance in cisplatin-induced renal failure might be caused by the altered alpha-adrenergic responsiveness with a possible involvement of alpha(1)-adrenoceptors in the renal vasculature. In a unique experimental approach with anesthetized rats, this study has therefore examined if there is any shift in the renovascular responsiveness to renal nerve stimulation and a series of alpha-adrenergic agonists in Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats with cisplatin-induced renal failure in comparison with their body weight-matched normal controls. Thirty-two male rats of both WKY (n=16) and SHR (n=16) origin with body weight 236+/-7.9 g received cisplatin (5mg/kg i.p.). The renal failure was confirmed in terms of significantly reduced renal blood flow, reduced creatinine clearance, increased fractional excretion of sodium, increased kidney index (all P<0.05) and tubular damage. After 7 days of cisplatin, the overnight fasted rats were anesthetized (sodium pentobarbitone, 60 mg/kg i.p.) and renal vasoconstrictor experiments were done. The changes in the vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by electrical renal nerve stimulation or intrarenal administration of noradrenaline, phenylephrine and methoxamine. It was observed that in the cisplatin-treated renal failure WKY and SHR rats there were significant (all P<0.05) reductions in the renal blood flow along with significantly (P<0.05) higher renal adrenergic responsiveness as compared with their non-renal failure controls. The data showed that in the renal failure WKY and SHR rats, the altered renal hemodynamics might be caused by an augmented renal adrenergic responsiveness. The results obtained further led us to suggest that the augmented renal adrenergic responsiveness in the cisplatin-induced renal failure rats were possibly mediated by the alpha(1)-adrenoceptors.

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