Publications by authors named "Ali Rahim"

13 Publications

  • Page 1 of 1

A 55-Year-Old Male Presenting With a Lower Extremity Rash: A Case of Immunoglobulin A (IgA) Nephropathy.

Cureus 2021 Mar 29;13(3):e14165. Epub 2021 Mar 29.

Internal Medicine, Henry Ford Health System, Detroit, USA.

Immunoglobulin A (IgA) nephropathy, mesangial deposition of IgA in renal parenchyma, typically presents with hematuria and proteinuria. Leukocytoclastic vasculitis (LCV), a small-vessel vasculitis, can present secondary to IgA. We will discuss a case of secondary IgA nephropathy with concomitant LCV in a patient with reactivated hepatitis C. A 55-year-old male with decompensated alcoholic cirrhosis presented for a bilateral lower-extremity rash. The patient was diagnosed with IgA nephropathy, by kidney biopsy, and skin biopsy showing LCV. Further investigation revealed hepatitis C viral load was 275,000. We present a rare presentation of secondary IgA nephropathy with concomitant LCV, which we hypothesize was secondary to reactivation of hepatitis C.
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http://dx.doi.org/10.7759/cureus.14165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080951PMC
March 2021

A prospective randomized trial comparing computerized columnar insulin dosing chart (the Atlanta protocol) versus the joint British diabetes societies for inpatient care protocol in management of hyperglycemia in patients with acute coronary syndrome admitted to cardiac care unit in Alexandria, Egypt.

Diabetes Metab Syndr 2021 May-Jun;15(3):711-718. Epub 2021 Mar 28.

Department of Internal Medicine, Faculty of Medicine, University of Alexandria, Egypt. Electronic address:

Background: Hyperglycemia in acute coronary syndrome (ACS) is linked to raised morbidity and mortality. Insulin administration using insulin infusion protocols (IIP) is the preferred strategy to control hyperglycemia in critically ill patients. To date, no specific IIP has been identified as the most efficient for achieving glycemic control.

Aim: to compare glycemic achievements (safety) (primary objective), and coronary and other clinical outcomes (efficacy) (secondary objective) by hyperglycemia management in Cardiac Care Unit (CCU) using computerized Atlanta Protocol (Group (I)) versus paper-based Joint British Diabetes Societies (JBDS) For Inpatient Care Protocol (Group (II)).

Patients And Methods: The study was done on 100 ACS patients admitted to Alexandria Main University hospital CCU with RBG >180 mg/dL. They were randomized into the 2 groups in a 1:1 ratio. CBG was measured hourly for 72 hours and was managed by IV insulin infusion.

Results: Group (I) showed statistically significant less mean time for target BG achievement (3.52 ± 1.53hours), lower incidence of Level 1 hypoglycemia (2%) than Group (II) (4.76 ± 2.33 hours, 22%, p = 0.013, 0.002 respectively) and statistically significant less mean number of episodes above the glycemic target after its achievement than Group (II) (p < 0.001). Regarding Level 2 hypoglycemia the difference was not significant statistically.

Conclusion: Both protocols successfully maintained target BG level with low incidence of clinically significant hypoglycemia, however, the computerized Atlanta protocol achieved better glycemic outcomes. We recommend the use of the computerized Atlanta protocol in CCU rather than JBDS for Inpatient Care Protocol whenever this is feasible.
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http://dx.doi.org/10.1016/j.dsx.2021.03.024DOI Listing
March 2021

Irinotecan inducing sinus pause bradycardia in a patient with small round cell cancer.

BMJ Case Rep 2020 May 31;13(5). Epub 2020 May 31.

Internal Medicine, Detroit Medical Center, Wayne State University, Detroit, Michigan, USA.

Irinotecan is a novel anticancer drug that has worked wonders in combination with other anticancer drugs. It can be used as a single chemotherapy agent in colonic cancer treatment or in combination with 5-fluorouracil. Irinotecan has been found a better salvage therapy in patients who are resistant to 5-fluorouracil. It is also used in combination with cisplatin and other drugs for cancers such as pleural mesothelioma, Ewing's sarcoma, lung cancer and others, and has helped reduce tumour burden. Irinotecan is generally associated with gastrointestinal side effects including nausea, vomiting and diarrhoea, while cardiovascular toxicity (5%) has been reported mainly as vasodilatation and possible bradycardia with no known incidence. A case was reported in 1998 by Miya of a 65-year-old man with bradycardia which was managed with atropine without modifications in the dosage of irinotecan or in the rate of infusion. We report a case of a patient with small round cell cancer who presented with sinus pause bradycardia after infusion with irinotecan. The patient was managed with atropine during chemotherapy.
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http://dx.doi.org/10.1136/bcr-2019-232053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264695PMC
May 2020

Prevalence of Y chromosome microdeletion in azoospermic infertile males of Iraqi population.

J Genet 2020 ;99(0)

Department of Clinical Biochemistry, College of Medicine, University of Kufa, P.O. Box (21), Najaf, Iraq.

In human gamete development, the important period is spermatogenesis, which is organized by specific genes on Y chromosome. In some cases, the infertile men have shown microdeletions on Y chromosome, which seemed as if the structural chromosome variance is linked to the reduction of sperm count. This study aimed to determine the frequency and patterns of Y chromosome microdeletions in azoospermia factor (AZF) of Iraqi infertile males. Here, 90 azoospermic infertile males as a study group and 95 normal fertile males as control group were investigated for the microdeletion of AZF loci using numerous sequence-tagged sites. Of these 90 infertile male patients, 43 (47.8%) demonstrated Y chromosome microdeletions, in which AZFb region was the most deleted section inazoospermia patients (33.3%) followed by deletions in the AZFc region (23%), while there were no microdeletion in the AZFa region. The largest microdeletion involved in both AZFb and AZFc was detected in six azoospermic patients (6.7%). The present study demonstrated a high frequency of Y chromosome microdeletions in the infertile Iraqi patients which is not reported previously. The high frequency of deletions may be due to the association of ethnic and genetic factors. PCR-based Y chromosome screening for microdeletions has a potential to be used in infertility clinics for genetic counselling and assisted reproduction.
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January 2021

Assessing the sustainability of advanced materials using multicriteria decision analysis and the triple bottom line.

Integr Environ Assess Manag 2019 Nov 21;15(6):1021-1028. Epub 2019 Oct 21.

Environmental Laboratory, US Army Engineer Research and Development Center, Vicksburg, Mississippi.

Although advanced materials (AdMs) are beneficial in many applications, questions remain as to whether they are more or less sustainable than the conventional materials that they may replace. Currently, there is no available tool to provide clarity to these questions. Traditional approaches for evaluating the sustainability of a chemical or material are usually not standardized, and as a result, the metrics used in sustainability measurements are subjective and often vary from assessor to assessor. Additionally, sustainability characterizations resulting from these approaches are typically presented qualitatively and are often vaguely drawn, making it difficult to confidently and transparently conclude that 1 material is more sustainable than another. This paper aims to address these gaps by enabling stakeholders involved in the production, use, or governance of AdMs to assess the sustainability of AdMs in a consistent, objective, and quantitative way using a multicriteria decision analysis (MCDA)-based model. The model proposed herein adapts a triple-bottom-line (TBL) framework from the Institution of Chemical Engineers (IChemE) and incorporates criteria weights identified through a stakeholder values assessment conducted by surveying AdM practitioners. Results from the stakeholder values assessment show that the perceived importance of the economic component of the TBL varies the most across stakeholders, and that practitioners providing responses from the perspective of a nongovernmental environmental advocacy group or a regulator of AdMs such as the United States Environmental Protection Agency were more likely to score and weigh economic indicators lower and environmental indicators higher compared to when responding from a business owner perspective. The resulting MCDA-based model allows stakeholders to assess the sustainability of an AdM or AdM-enabled product and compare it to product alternatives, predict how other stakeholders might score a product by identifying the extent to which components of the TBL are valued by other stakeholders, and identify which subcriteria contribute most to an improvement in a product's sustainability score. Integr Environ Assess Manag 2019;00:1-8. © 2019 SETAC.
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http://dx.doi.org/10.1002/ieam.4205DOI Listing
November 2019

Histogram Analysis of Native T Mapping and Its Relationship to Left Ventricular Late Gadolinium Enhancement, Hypertrophy, and Segmental Myocardial Mechanics in Patients With Hypertrophic Cardiomyopathy.

J Magn Reson Imaging 2019 03 24;49(3):668-677. Epub 2018 Aug 24.

Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.

Background: The use of native T mapping for evaluation of hypertrophic cardiomyopathy (HCM) is being explored, and its combination with histogram analysis may benefit the accuracy of such assessments.

Purpose: To investigate the relationship of segmental left ventricular wall thickness (LVWT), myocardial fibrosis, and strain parameters with segmental histogram parameters of native T mapping in HCM patients.

Study Type: Retrospective.

Subjects: Ninety-three HCM patients without previous cardiovascular diseases were included.

Field Strength/sequence: 3.0T cardiac MR. Steady-state free precession cine imaging, modified Look-Locker inversion recovery, phase-sensitive inversion recovery.

Assessment: Images were assessed by three experienced radiologists.

Statistical Tests: Mann-Whitney U-tests, area under the curve (AUC), Spearman's rank correlation, intraclass correlation coefficient, and Bland-Altman test were used for statistical analysis.

Results: A higher LVWT value correlated with higher means, minimums, 10 /25 /50 /75 /90 percentiles, maximums, kurtosis, entropy, and lower SD and energy of T mapping (P < 0.05 for all), with the correlation being stronger for entropy and energy (Spearman's rho = 0.439 and -0.413, respectively) than other parameters. Late gadolinium enhancement positive (LGE+) segments exhibited higher mean, minimum, 10 /25 /50 /75 /90 percentiles, maximum, entropy, and lower energy of T times than late gadolinium enhancement negative (LGE-) segments (P < 0.001 for all). Impaired strain function parameters (peak thickening and thickening rate in radial, circumferential, and longitudinal directions) demonstrated a weak correlation with higher entropy (P < 0.001 for all) and lower energy (P < 0.001 for all).

Data Conclusion: Histogram parameters of native T mapping provide more information than mean T times alone. Among these parameters, entropy and energy may correlate better with LVWT, myocardial late gadolinium enhancement, and strain parameters than mean T times in HCM patients.

Level Of Evidence: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;49:668-677.
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http://dx.doi.org/10.1002/jmri.26272DOI Listing
March 2019

miRNA-221 and miRNA-222 are promising biomarkers for progression of liver fibrosis in HCV Egyptian patients.

Virus Res 2018 07 19;253:135-139. Epub 2018 Jun 19.

Biology Department, American University in Cairo, Cairo, Egypt.

Background: Current methodologies used to determine the progression of hepatic fibrosis rely heavily on liver biopsy, a dangerous and invasive procedure, with semi-subjective analysis of the results of the biopsy. Thus, a new approach is immensely needed for monitoring the progression of liver fibrosis in Hepatitis C virus (HCV) patients.

Aim Of Work: The purpose of this study was to find highly specific and sensitive miRNA biomarkers that can be used to detect different stages of liver fibrosis.

Methodology: The study consisted of 42 cases of chronic hepatitis C (CHC) with early-stage fibrosis, 45 cases of CHC with late-stage fibrosis, and 40 healthy subjects with no CHC or fibrosis as controls. Expression patterns of 5 miRNAs (miR-16, miR-146a, miR-214-5p, miR-221, and miR-222) were analyzed in each group using TaqMan real-time PCR.

Results: Serum levels of miRNA-16, miRNA-146a, miRNA-221, and miRNA-222 were all significantly up-regulated in early and late stages of liver fibrosis. miRNA-222 had the highest sensitivity and specificity values in early and late fibrosis. miRNA-221 had the second highest sensitivity and specificity with the late-stage fibrosis group. Furthermore, miRNA-221 showed significant positive correlations with both miRNA-16 and miRNA-146a in the early- and late-stage fibrosis groups, with the early stage having a stronger correlation.

Conclusions: The results indicated that miRNA-16, miRNA-146a, miRNA-221, and miRNA-222 can be used to detect the presence of liver fibrosis. The high sensitivity and specificity of miRNA-222 and miRNA-221 in late-stage fibrosis indicate promising prognostic biomarkers for HCV-induced liver fibrosis.
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http://dx.doi.org/10.1016/j.virusres.2018.06.007DOI Listing
July 2018

Urinary Neutrophil Gelatinase-Associated Lipocalin in Cirrhotic Patients with Acute Kidney Injury.

Ann Hepatol 2018 July - August ,;17(4):624-630

Hepato-Gastroenterology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt.

Introduction And Aim: It is well known that development of acute kidney injury (AKI) increases mortality in hospitalized cirrhotic patients; therefore many novel markers have been studied for early detection, differential diagnosis and prognosis in cirrhotic patients with AKI. The aim of the current work is to evaluate urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) as a diagnostic biomarker for different causes of acute kidney injury in liver cirrhosis and to assess it as a prognostic marker.

Material And Methods: Out of 83 cirrhotic patients with AKI admitted between October 2015 and June 2016; 70 patients were included in this prospective study. Routine laboratory tests, uNGAL and fractional excretion of Na were obtained on admission. End points were death or improvement of kidney function and discharge.

Results: The patients included in our study were 41 males and 29 females with mean age 54.27 ± 6.08 years. HCV was the etiology of cirrhosis in 69 cases while one had combined HBV and HCV infection. More than 50% of patients were classified as Child C. Causes of kidney injury were prerenal, hepatorenal syndrome (HRS) and intrinsic tubular injury (iAKI) in 39 patients (55.7%), 17 patients (24.3%) and 14 patients (20%) respectively. mean value of uNGAL in prerenal, HRS and iAKI was 21.70 ± 7.31, 115.53 ± 68.19 and 240.83 ± 116.94 ng/mg creatinine respectively. MELD above 20 and uNGL above 32 were predictors of mortality.

Conclusion: A single baseline measurement of uNGAL level has the ability to determine type of kidney dysfunction in cirrhotic patients, perhaps accelerating management decisions and improving outcomes.
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http://dx.doi.org/10.5604/01.3001.0012.0931DOI Listing
April 2019

Expression analysis of liver-specific circulating microRNAs in HCV-induced hepatocellular Carcinoma in Egyptian patients.

Cancer Biol Ther 2018 05 16;19(5):400-406. Epub 2018 Feb 16.

a Biology Department , American University in Cairo , Cairo , Egypt.

Objectives: Due to the absence of reliable and accurate biomarkers for the early detection of liver malignancy, circulating microRNAs have recently emerged as great candidates for prompt cancer identification. Therefore, the aim of this study was to investigate the potential of liver-specific circulating microRNAs as an accurate non-invasive diagnostic tool for early diagnosis of hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC).

Methodology: A total of 165 patients were enrolled in this study and categorized into four main groups: 42 chronic hepatitis C (CHC) without cirrhosis, 45 CHC with cirrhosis (LC), 38 HCC with HCV patients, and 40 healthy controls. The expression profiles of seven miRNAs (miR-16, miR-34a, miR-125a, miR-139, miR-145, miR-199a, and miR-221) were analyzed using real-time PCR.

Results: Serum levels of miRNA-125a, miRNA-139, miRNA-145, and miRNA199a were significantly lower (p < 0.01) in HCC than in both CHC and LC groups. On the other hand, no significant difference was shown in the expression of miR-16, miR-34a, and miR-221 between the CHC, LC, and HCC groups. MiR-16, miR-34a, and miR-221 were significantly elevated in the HCC group compared to the control group. MiR-34a showed the highest specificity and sensitivity.

Conclusions: The results indicated that the measurement of serum levels of miR-125a, miR-139, miR-145, and miR-199a can help to differentiate HCC from CHC and LC. Also, miR-16, miR-34a, and miR-221 serum levels would have a prognostic value. MiR-34a had the highest specificity and sensitivity, indicating that it might serve as a novel and potential non-invasive biomarker for HCV-induced HCC.
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http://dx.doi.org/10.1080/15384047.2018.1423922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915034PMC
May 2018

Expression of hnRNPK & Claudin-4 in HCV-Induced Early HCC and Adjacent Liver Tissue.

Open Access Maced J Med Sci 2017 Aug 31;5(5):595-602. Epub 2017 Jul 31.

Department of General Surgery, Theodor Bilharz Research Institute (TBRI), Imbaba, Giza, Egypt.

Background: HCC in Egypt usually occurs in HCV cirrhotic livers with poor prognosis due to late diagnosis. High hnRNPK & low Claudin-4 profiles indicate Epithelial Mesenchymal Transition (EMT), malignant transformation and high-grade tumours.

Aim: We studied the immunohistochemical expression of hnRNPK and Claudin-4 in HCV induced early HCC (eHCC) and adjacent liver tissue in Egyptian patients to improve eHCC detection in cirrhotic livers with better curative therapy options.

Method: We studied the immunohistochemical expression of hnRNPK and Claudin-4 in 100 Egyptian patients resection specimens of HCV induced early HCC (eHCC) and adjacent liver tissue, in order to improve eHCC detection in cirrhotic livers, thus improving their therapeutic options.

Results: Early HCC grade significantly directly correlated with nuclear hnRNPK/5HPFs count and inversely correlated with Claudin-4 expression %, with a converse correlation between hnRNPK and Claudin-4. Moreover in eHCC, combined hnRNPK ≥ 30/5HPFs & Claudin-4 ≥ 40% significantly distinguished low grade eHCC (G1) from high grade eHCC (G2&G3), with sensitivity 97% & specificity 69.7% for hnRNPK ≥ 30/5HPFs, and with sensitivity 70% & specificity 94.3% for Claudin-4 ≥ 40%. Moreover in the adjacent liver, both markers expressions significantly directly correlated with each other and with METAVIR fibrosis score but not with activity. Furthermore, 58% of eHCCs showed hnRNPK ≥ 30 Claudin-4 < 40% profile, indicating EMT type 3, compared to 26% with hnRNPK ≥ 30 Claudin-4 ≤ 10% profile in adjacent cirrhotic/ precirrhotic liver, with significant use of combined hnRNPK ≥ 30/5HPFs & Claudin 4 ≤ 10% as eHCC prediction cut offs in cirrhosis (p < 0.05).

Conclusion: Combination of hnRNPK and Claudin-4 can indicate early HCC development in HCV cirrhotic livers using hnRNPK ≥ 30/5HPFs & Claudin-4 ≤ 10% cut offs. Also, combination of hnRNPK ≥ 30/5HPFs & Claudin-4 ≥ 40% can distinguish low grade eHCC (G1) from high grade eHCC (G2&G3).
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http://dx.doi.org/10.3889/oamjms.2017.092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591587PMC
August 2017

Evaluation of CD44 and CD133 as markers of liver cancer stem cells in Egyptian patients with HCV-induced chronic liver diseases versus hepatocellular carcinoma.

Electron Physician 2017 Jul 25;9(7):4708-4717. Epub 2017 Jul 25.

M.D., Tropical Medicine Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.

Background: Cancer stem cells (CSCs) play a critical role in tumor development, progression, metastasis and recurrence.

Aim: To evaluate hepatic expression of CD44 and CD133 in Egyptian patients with HCV-induced chronic liver diseases and hepatocellular carcinomas (HCCs), and to assess its correlation with inflammatory activity scores, stages of fibrosis (in chronic hepatitis with or without cirrhosis) and grades of HCC.

Methods: This prospective case-control study was conducted on eighty subjects who attended the Tropical Diseases Department, Al-Azhar University Hospital, and in collaboration with Theodor Bilharz Research Institute (2014-2016). They were divided as follows: A) Control healthy group: Ten individuals with serologically negative HCV-Ab and HBsAg, and histopathologically normal liver, B) Seventy patients subdivided into 3 groups; Twenty subjects each, as: HCV-Ab+ non-cirrhotic, HCV-Ab+ cirrhotic and HCC. Necroinflammatory activity and fibrosis in non-neoplastic liver biopsies were scored according to the METAVIR scoring system. CD44 and CD133 immunostaining was evaluated in all groups semi-quantitatively using H score. Statistical analysis was performed by SPSS version 22, using independent-samples t-test.

Results: Our study showed a significant increase of mean CD44 & CD133 expression values with disease progression among the groups (p<0.05). Their expressions increased significantly with the inflammatory activity scores and stages of fibrosis, reaching the highest values in A3F4 score compared to A1F1 (p<0.05). Moreover, there was a significant increase of their expressions across HCC grades (p<0.05), however with no significant correlation with focal lesions size.

Conclusion: CSCs clusters exhibiting CD133+ and/or CD44+ profiles were identified in chronic hepatitis, liver cirrhosis and HCC. CD133 and CD44 expressions significantly corresponded to the increased inflammatory activity, fibrosis stages and higher tumor grades. Therefore, evaluation of CD44 and CD133 expression profiles as CSCs markers in non-neoplastic liver and HCCs can help in development of novel therapeutic agents for HCC targeting and prevention.
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http://dx.doi.org/10.19082/4708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586983PMC
July 2017

Centralized Pan-Middle East Survey on the Under-Treatment of Hypercholesterolemia: Results from the CEPHEUS II Study in Egypt.

Cardiol Ther 2017 Jun 29;6(1):105-120. Epub 2017 Mar 29.

Cairo University, Egypt, 12 Dokki Street, Dokki, Giza, Egypt.

Introduction: As part of the CEPHEUS study, CEPHEUS I was conducted in 2010 and 2011 in Cairo and then the CEPHEUS II study was carried out in Alexandria and Delta Regions in Egypt between April 2014 and August 2015 to determine the proportion of dyslipidemic patients on lipid-lowering treatment reaching LDL-C treatment goals.

Methods: We conducted an open-label, observational, multicenter, cross-sectional survey where 90 investigators enrolled 1127 patients receiving lipid-lowering drugs for at least 3 months. After signing informed consent forms, the study questionnaires were completed by patients and investigators. Blood samples were taken for laboratory investigations. Patients with missing LDL-C data were excluded from the analysis and results from 896 patients were analyzed according to European Atherosclerosis Society and EAS/ESC 2011 guidelines.

Results: Out of 896 patients enrolled based on the risk stratification of EAS/ESC 2011 guidelines, 12.4% were classified as low risk, 20.0% as moderate risk, 2.5% as high risk, and 65.2% as very high risk. Achievement goals were 84.7, 44.7, 18.2, and 22.3% for low-risk, moderate-risk, high-risk, and very high risk patients, respectively, with an overall achievement goal of 34.4%. The study population included 50.2% diabetes, 64.4% hypertension, 54.9% metabolic syndrome, 32.2% family history of cardiovascular disease, 23.1% smokers, and 33.8% secondary prevention. Lipid-lowering agents were prescribed as a monotherapy to 90.1% and in combination in 9.9% with goal achievements of 34 and 38%, respectively (p > 0.05). Statins were prescribed to 86.9% of patients. The most frequent prescribed statins were rosuvastatin (47.1%) and atorvastatin (36.0%), followed by simvastatin (9.2%). Treatment goal was achieved in 34.2, 36.0, and 31.7% for rosuvastatin, atorvastatin, and simvastatin, respectively, with no significant difference in achievement goals (p > 0.05).

Conclusions: Hypercholesterolemia is still not being effectively managed in many at-risk patients in Egypt. The majority of patients enrolled in the study were being actively treated with lipid-lowering medications yet the percentage goal achievement was less when compared to CEPHEUS results.
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http://dx.doi.org/10.1007/s40119-017-0089-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446822PMC
June 2017

Gene-environment interactions: neurodegeneration in non-mammals and mammals.

Neurotoxicology 2010 Sep 30;31(5):582-8. Epub 2010 Mar 30.

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.

The understanding of how environmental exposures interact with genetics in central nervous system dysfunction has gained great momentum in the last decade. Seminal findings have been uncovered in both mammalian and non-mammalian model in large result of the extraordinary conservation of both genetic elements and differentiation processes between mammals and non-mammalians. Emerging model organisms, such as the nematode and zebrafish have made it possible to assess the effects of small molecules rapidly, inexpensively, and on a miniaturized scale. By combining the scale and throughput of in vitro screens with the physiological complexity and traditional animal studies, these models are providing relevant information on molecular events in the etiology of neurodegenerative disorders. The utility of these models is largely driven by the functional conservation seen between them and higher organisms, including humans so that knowledge obtained using non-mammalian model systems can often provide a better understanding of equivalent processes, pathways, and mechanisms in man. Understanding the molecular events that trigger neurodegeneration has also greatly relied upon the use of tissue culture models. The purpose of this summary is to provide-state-of-the-art review of recent developments of non-mammalian experimental models and their utility in addressing issues pertinent to neurotoxicity (Caenorhabditis elegans and Danio rerio). The synopses by Aschner and Levin summarize how genetic mutants of these species can be used to complement the understanding of molecular and cellular mechanisms associated with neurobehavioral toxicity and neurodegeneration. Next, studies by Suñol and Olopade detail the predictive value of cultures in assessing neurotoxicity. Suñol and colleagues summarize present novel information strategies based on in vitro toxicity assays that are predictive of cellular effects that can be extrapolated to effects on individuals. Olopade and colleagues describe cellular changes caused by sodium metavanadate (SMV) and demonstrate how rat primary astrocyte cultures can be used as predicitive tools to assess the neuroprotective effects of antidotes on vanadium-induced astrogliosis and demyelination.
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http://dx.doi.org/10.1016/j.neuro.2010.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912949PMC
September 2010