Publications by authors named "Maha Arafah"

57 Publications

Effect of naked and PEG-coated gold nanoparticles on histopathology and cytokines expression in rat liver and kidneys.

Nanomedicine (Lond) 2020 02 27;15(3):289-302. Epub 2019 Nov 27.

Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.

To compare the effects of 5- and 50-nm naked and PEG-coated gold nanoparticles (AuNP) on proinflammatory cytokines (IL-1β, IL-6, TNF-α) expression and histopathological changes in liver and kidneys of rats. Rats were injected with different nanoparticles and sacrificed after 24 h. Both 5- and 50-nm AuNPs, and 50-nm PEG-AuNPs caused granular clumping of cytoplasm, edema and hydropic dystrophy in hepatic cells. Naked AuNPs of both sizes caused mild shrinkage, whereas 50-nm PEG-AuNPs enlarged the Bowman's space and capsule. Larger nanoparticles produced more profound mRNA expression of cytokines in both the organs. These findings suggest the roles of particle size and coating on immunological response and histopathological changes.
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http://dx.doi.org/10.2217/nnm-2019-0220DOI Listing
February 2020

Toll-like receptor 6 expression, sequence variants, and their association with colorectal cancer risk.

J Cancer 2019 2;10(13):2969-2981. Epub 2019 Jun 2.

Groupe de Recherche en Écologie Buccale, Département de stomatologie, Faculté de Médecine Dentaire, Université Laval, Québec, Québec, Canada.

This is the first study to examine the potential correlation of the rs3796508 and rs5743810 SNPs of the TLR6 gene in patients with colorectal cancer (CRC) in a subset of the Saudi population. TLR6 gene expression was studied by real-time PCR assaysin 10 matching normal and cancer colon tissues. TLR6 expression at the protein level was determined by immunohistochemistry. A case-control search was conductedon 115 case patients and 102 controls. All samples were genotyped with the TaqMan assay for the TLR6 gene. Odds ratios and 95% confidence interval were computed from logistic regression models after adjusting for age, sex, and tumor localization. Our findings showed a decrease in TLR6 expression (p <0.001) in colon cancer tissues when compared to normal colon tissues. Global analysis revealed no significant association between the TLR6 rs3796508 and rs5743810 and CRC in this population. However, the Val/Met genotype of rs3796508 had a significantly higher frequency in the control group than in the cases for the male group (OR= 0.095, and p= 0.03385) or the volunteers aged more than 57 years OR= 0.152; and p= 0.04069, respectively). Two non-synonymous single nucleotide polymorphisms (SNP; S249P and V327M) were common in a few patients and were predicted as damaging by SIFT and Polyphen and were further analyzed for their protein stability and function using advanced bioinformatics tools. The results suggest that TLR6 rs3796508 has a crucial role as a protective factor against colorectal cancer in the older Saudi male population.
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http://dx.doi.org/10.7150/jca.31011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590037PMC
June 2019

The Use of Antifibrotic Recombinant nAG Protein in a Rat Liver Fibrosis Model.

Biomed Res Int 2019 2;2019:9846919. Epub 2019 Jun 2.

Department of Surgery, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.

Objectives: The "nAG" protein is the key protein mediating the regeneration of amputated limbs in salamanders. The senior author (MMA) developed the original hypothesis that since "nAG" is a "regenerative" protein, it must be also an "antifibrotic' protein. The antifibrotic properties were later confirmed in a rabbit skin hypertrophic scar model as well as in a rat spinal cord injury model. The aim of this study is to evaluate the potential therapeutic properties of the nAG protein in a rat liver fibrosis model.

Methodology: Liver fibrosis was induced using intraperitoneal injections of carbon tetrachloride (CCL4). A total of 45 rats were divided equally into 3 groups: Group I (the control group) received normal saline injections for 8 weeks, Group II received CCL4 for 8 weeks, and Group III received CCL4 and nAG for 8 weeks. At the end of the experiment, the serum levels of 6 proteins (hyaluronic acid, PDGF-AB, TIMP-1, laminin, procollagen III N-terminal peptide, and collagen IV-alpha 1 chain) were measured. Liver biopsies were also taken and the stages of live fibrosis were assessed histologically.

Results: The CCL4 treatment resulted in a significant increase in the serum levels of all 6 measured proteins. The nAG treatment significantly reduced these high levels. The degree of liver fibrosis was also significantly reduced in the CCL4/nAG group compared to the CCL4 group.

Conclusions: nAG treatment was able to significantly reduce the serum levels of several protein markers of liver fibrosis and also significantly reduced the histological degree of liver fibrosis.
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http://dx.doi.org/10.1155/2019/9846919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582902PMC
January 2020

Time-Course Evaluation of Iminodipropionitrile-Induced Liver and Kidney Toxicities in Rats: A Biochemical, Molecular and Histopathological Study.

Dose Response 2019 Apr-Jun;17(2):1559325819852233. Epub 2019 May 23.

Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.

Iminodipropionitrile (IDPN) is known to produce axonopathy and vestibular hair cell degeneration. Recent histopathological studies have shown IDPN-induced liver and kidney toxicities in rodents; however, the associated mechanisms are not clearly understood. We investigated the role of proinflammatory cytokines in IDPN-induced liver and kidney toxicities in rats. Rats were treated with saline (control) and IDPN (100 mg/kg, intraperitoneally) daily for 1, 5, and 10 days, respectively. Animals were killed 24 hours after the last dose and liver and kidneys were collected for histopathology and interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α messenger RNA expression analysis. Serum aspartate aminotransferase and alanine aminotransferase activities were significantly increased after 10 doses of IDPN. The level of serum creatinine was initially increased after the first dose of IDPN but subsided on days 5 and 10. Blood urea nitrogen levels were significantly increased on days 5 and 10 following IDPN exposure. Histopathology showed dose-dependent hepatotoxicity in IDPN-treated rats. Iminodipropionitrile-induced expression of proinflammatory cytokines peaked after day 1 in liver and after day 5 in kidneys. In conclusion, repeated exposure of IDPN for 10 days produced significant structural and functional damages in rat liver whereas kidneys showed gradual recovery with time. These findings point toward the role of inflammatory mediators in IDPN-induced toxicity in rats.
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http://dx.doi.org/10.1177/1559325819852233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537673PMC
May 2019

Novel Associations between BRCA1 Variants C.181 T>G (Rs28897672) and Ovarian Crisk in Saudi Females.

J Med Biochem 2019 Mar 1;38(1):13-21. Epub 2019 Mar 1.

Central Laboratory, Center for Science and Medical Studies for Girls, King Saud University, Riyadh, Saudi Arabia.

Background: Mutations in BRCA1 gene have been implicated in ovarian cancers, and BRCA testing may be conducted in high-risk women. This study was designed to determine the frequency of three single nucleotide polymorphisms (SNPs) variants in BRCA1 gene and BRCA1 expression in Saudi females with ovarian cancer.

Methods: Expression levels of mRNA of BRCA1 gene were studied in 10 ovarian cancer and 10 normal ovarian tissues, by quantitative real time polymerase chain reaction (qPCR). The study also included 28 females who had suffered from ovarian cancer and had been successfully operated upon and 90 healthy females with no history of cancer. Blood was drawn in EDTA tubes and used for extraction of DNA. The genotyping was carried out using Taqman® SNP Genotyping kit by RT-PCR. The variants investigated included c.871 T>C (rs799917), c.1040 G>A (rs4986852), c.181 T>G (rs28897672) in BRCA1 gene.

Results: The c.181 T>G (rs28897672) showed significantly different genotype and allele frequencies between the patients and the control subjects (p value = 0.002 and 0.02, respectively). The genotype TG was significantly protective (OR = 0.36, p value = 0.024). The mRNA expression of BRCA1 gene was found to be low in the ovarian cancer tissues.

Conclusions: This study showed that c.181 T>G in BRCA1 genes is associated with the development of ovarian cancer in Saudis. More studies are needed to unveil other SNPs that may be associated with ovarian cancer and to understand the mechanism(s) involved in reducing the expression of BRCA1 gene in ovarian cancer tissues.
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http://dx.doi.org/10.2478/jomb-2018-0037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298454PMC
March 2019

Idiopathic aggressive myositis ossificans of the hand infiltrating the flexor sheath/checkrein ligament, obliterating the common digital artery, and attenuating the digital nerve: A case report.

Int J Surg Case Rep 2018 22;53:424-428. Epub 2018 Nov 22.

Department of Surgery at King Saud University, Riyadh, Saudi Arabia; King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Electronic address:

Introduction: Myositis ossificans of the hand is extremely rare and tumors do not usually infiltrate adjacent structures. We present a very unusual case with a tumor infiltrating adjacent structures.

Report Of A Case: A 30-year-old female presented with a 5-week history of a painful rapidly-growing mass over the proximal phalanx of the right ring finger. The mass infiltrated the entire flexor sheath over the proximal phalanx as well as the checkrein ligament of the proximal interphalangeal joint. The common digital artery of the 3rd web space was obliterated by the tumor. The radial digital nerve of the ring finger was stretched and attenuated. Total excision was done and histology confirmed the diagnosis of myositis ossificans. No recurrence was seen at the one-year follow-up.

Discussion: Myositis ossificans of the hand is extremely rare. We report our case to document the unique feature of tumor infiltration of adjacent structures. We also document that excision is curative despite the infiltrative nature of the tumor.

Conclusion: Our case is unique because of the infiltrative nature of tumor. There is no indication for amputation even for infiltrative tumors. We demonstrate that complete excision is curative with good regain of function even in infiltrative lesions.
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http://dx.doi.org/10.1016/j.ijscr.2018.11.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262803PMC
November 2018

Potential role of Toll-like receptor 2 expression and polymorphisms in colon cancer susceptibility in the Saudi Arabian population.

Onco Targets Ther 2018 14;11:8127-8141. Epub 2018 Nov 14.

Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia,

Background: Inflammation is a fundamental factor that contributes to the development and progression of several types of cancer including colon cancer. Toll-like receptors () and their signaling pathways have been reported to be associated with chronic inflammation and thereby induced cancer. Our aim was to investigate the expression and polymorphisms of and their association with colon cancer.

Methods: Real-time PCR and immunohistochemistry were used to investigate gene expression and to evaluate the potential risk of predisposition to colon cancer caused by three tagging single-nucleotide polymorphisms (SNPs) on , including rs3804100, rs4696480, and rs3804099. TaqMan assay was conducted on samples from 115 patients with colon cancer and 102 age- and sex-matched normal individuals.

Results: We found that, was highly expressed in epithelial colon cancer cells and both mRNA and protein levels, and significantly decreased in tumor tissues compared to normal tissues. Two of three SNPs increased the risk of colon cancer. However, rs3804099 increased the risk of colon cancer development by more than 3.8- and 5-fold in female patients and patients aged less than 57 years, respectively. The T allele of rs3804100 showed a significant association with patients less than 57 years. In silico analysis of the nucleotide substitution in SNP rs3804100 and rs3804099 determined that 67% and 70% probability of these single nucleotide variants alter splicing phenotypes, rs3804100 more specifically result on activating an additional splice site. Genotype and allele frequencies of rs4696480 were similar between the overall study populations. Thus, rs4696480 appear to be not involved in colon cancer in our study population.

Conclusions: There was a significant link between innate immunity deregulation through disruption of the and potential development of colon cancer. These SNPs can be used as screening markers for predicting colon cancer risk earlier in life to implement necessary prevention.
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http://dx.doi.org/10.2147/OTT.S168478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6241690PMC
November 2018

Correlation between reabsorbed intracytoplasmic proteins in glomerular podocytes and the level of proteinuria in patients with glomerulopathies.

Authors:
Arafah Maha

Ultrastruct Pathol 2018 Nov-Dec;42(6):489-497. Epub 2018 Nov 1.

a Department of Pathology , College of Medicine King Saud University , Riyadh , Kingdom of Saudi Arabia.

Podocytes can handle proteins when the glomerular filtration barrier is injured with leak of proteins out of the vasculature into the urine. The correlation between the number of podocytes involved in handling leaked proteins, as well as the extent of up-taken proteins in podocytes cytoplasm on one side, and the level of proteinuria in the concerned patients on the other side, is evaluated. A retrospective study of 22 patients with clinical proteinuria caused by various glomerulopathies was retrieved and analyzed. The glomerulopathies in the concerned patients were pathologically diagnosed through microscopic examination of the submitted renal biopsies over a period extending from January, 2013 to December, 2016. Additionally, three cases with protein levels in urine within the acceptable normal range were also analyzed as controls. Electron microscopic examination of the glomerular podocytes in the relevant cases constituted the base for the present study. Among the studied cases, it was noted that the greater the number of glomerular podocytes with reabsorbed proteins within the cytoplasm, the lower the level of proteinuria. Comparatively, cases with fewer numbers of podocytes with reabsorbed proteins disclosed higher levels of proteinuria. The present study might be the first to shed light on the correlation between morphologically recognizable glomerular podocytes with reabsorbed proteins and the level of proteinuria in patients with various glomerulopathies. The current study may constitute a base for the future research work concerned with the structural changes of glomerular podocytes as an adaptive mechanism in cases of proteinuria.
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http://dx.doi.org/10.1080/01913123.2018.1536686DOI Listing
March 2019

IL-17 and colorectal cancer risk in the Middle East: gene polymorphisms and expression.

Cancer Manag Res 2018 5;10:2653-2661. Epub 2018 Sep 5.

Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, College of Medicine, King Saud University, Riyadh, Saudi Arabia,

Background: IL-17 expressed by Th17 cells play a crucial role in tissue inflammation by induction of proinflammatory and neutrophil mobilizing cytokines, and IL-17 polymorphisms are associated with colorectal cancer (CRC).

Objective: We investigated the expression of IL-17 and the association of IL-17 gene polymorphisms with CRC susceptibility in a Middle East population.

Materials And Methods: The study included 117 diagnosed CRC patients and 100 age- and gender-matched healthy controls. IL-17A rs2275913 (G197A) and IL-17F rs763780 (T7488C) single nucleotide polymorphisms, mRNA, and protein levels of IL-17A were assessed.

Results: We observed significant association between rs2275913 in IL-17A and susceptibility to CRC ( = 0.016228). The AG and AA genotypes conferred 2-fold and 2.8-fold, respectively, higher risk of developing CRC compared with individuals having GG genotype. Stratification of the data based on gender and age revealed very strong association of CRC with IL17A rs2275913 only in males and "AG" genotype in patients ≤57 years of age at the time of disease diagnosis. The rs763780 in IL-17F was not linked with CRCs in our cohort. Furthermore, IL-17A mRNA expression in CRCs was significantly elevated compared to adjacent normal tissues, particularly in early stages of disease ( = 0.0005). Strong immunoreactivity to IL-17A protein was observed in 70% of early stage relative to 30% of late-stage tumors.

Conclusion: The IL-17A G197A variant may be utilized as a genetic screening marker in assessing CRC risk, and its expression can be used as a biomarker for early detection of CRC in the Saudi population.
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http://dx.doi.org/10.2147/CMAR.S161248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130533PMC
September 2018

Synergistic Effect of Quercetin and -Lipoic Acid on Aluminium Chloride Induced Neurotoxicity in Rats.

J Toxicol 2018 16;2018:2817036. Epub 2018 May 16.

Department of Biochemistry, College of Science, P.O. Box 22452, King Saud University, Riyadh 11495, Saudi Arabia.

Objectives: The present study was carried out to study the protective effects of quercetin and -lipoic acid alone and in combination against aluminum chloride induced neurotoxicity in rats.

Materials And Methods: The study consisted of eight groups, namely, Group 1: control rats, Group 2: rats receiving aluminium chloride 7 mg/kg body weight intraperitoneal route (i.p) for two weeks, Group 3: rats receiving quercetin 50 mg/kg body weight i.p. for two weeks, Group 4: rats receiving quercetin 50 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks, Group 5: rats receiving -lipoic acid 20 mg/kg body weight i.p. for two weeks, Group 6: rats receiving lipoic acid 20 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks, Group 7: rats receiving -lipoic acid 20 mg/kg body weight and quercetin 50 mg/kg body weight i.p. for two weeks, and Group 8: rats receiving -lipoic acid 20 mg/kg body weight and quercetin 50 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks. The animals were killed after 24 hours of the last dose by cervical dislocation.

Results: Aluminium chloride treatment of rats resulted in significant increases in lipid peroxidation, protein carbonyl levels, and acetylcholine esterase activity in the brain. This was accompanied with significant decreases in reduced glutathione, activities of the glutathione reductase, and superoxide dismutase. Pretreatment of AlCl exposed rats to either quercetin or -lipoic acid also restored altered lipid peroxidation and superoxide dismutase to near normal levels. Quercetin or -lipoic acid pretreatment of AlCl exposed rats improved the protein carbonyl and reduced glutathione, glutathione reductase, and acetylcholine esterase activities in rat brains towards normal levels. Combined pretreatment of AlCl3 exposed rats with quercetin and -lipoic acid resulted in a tendency towards normalization of most of the parameters.

Conclusions: Quercetin and -lipoic acid complemented each other in protecting the rat brain against oxidative stress induced by aluminium chloride.
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http://dx.doi.org/10.1155/2018/2817036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976966PMC
May 2018

High-frequency deregulated expression of Wnt signaling pathway members in breast carcinomas.

Onco Targets Ther 2018 11;11:323-335. Epub 2018 Jan 11.

Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh.

Purpose: Breast carcinoma is the most common malignancy and leading cause of cancer-related deaths in women worldwide including Saudi Arabia. Breast cancer in Saudi women develops at a much early age with median age of onset of 49 years compared to 62 years observed in patients from USA. Aberrations in wingless and integration site growth factor (Wnt) signaling pathway have been pathologically implicated in development of breast cancers and hence its role was examined in Saudi patients.

Materials And Methods: We immunohistochemically examined various components of Wnt signaling pathway including β-catenin, tumor suppressor proteins, adenomatous polyposis coli (APC), and Axin, expression of naturally occurring pathway antagonists such as Dickkopf Wnt signaling pathway inhibitor 3 (DKK3), FRP2, and WIF1, as well as Wnt target cyclin D1 and c-Myc to establish if the pathway is constitutively activated in breast cancers arising in Saudi women.

Results: Cytoplasmic β-catenin, indicative of activation of the pathway, was observed in 24% of cases. Expression of APC and Axin, which are components of β-catenin destruction complex, was lost in 5% and 10% of tumors, respectively. Additionally, Wnt signaling inhibitors DKK3, FRP2, and Wnt inhibitory factor 1 (WIF1) were not expressed in 8%, 14%, and 5% breast tumors, respectively. Overall, accumulation of cytoplasmic β-catenin and downregulation of other Wnt pathway proteins (APC/Axin/DKK3/FRP2/WIF1) were found in approximately half of the breast cancers (47%) in our cohort. Consistent with this, analysis of Wnt target genes demonstrated moderate-to-strong expression of c-Myc in 58% and cyclin D1 in 50% of breast cancers. Deregulation of Wnt pathway was not associated with age of onset of the disease, tumor grade, and triple-negative status of breast cancers.

Conclusions: High level of deregulated expression of Wnt pathway proteins suggests its important role in pathogenesis of breast cancers arising in Saudi women who may benefit from development of therapeutic drugs targeting this pathway.
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http://dx.doi.org/10.2147/OTT.S154395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769582PMC
January 2018

gene polymorphism and colorectal cancer etiology in Saudi population: case-control study.

Onco Targets Ther 2017 14;10:4559-4567. Epub 2017 Sep 14.

Central Laboratory, Female Center for Scientific & Medical Colleges, King Saud University, Riyadh, Saudi Arabia.

Background: Considerable interest is directed toward the enzyme aromatase (CYP19A1) and the development of cancer, due to CYP19A1's role in estrogen biosynthesis. Several cancers display excessive intra-tumor accumulation of estrogens, and aromatase inhibitors are used for treatment. The CYP19A1 gene exhibits polymorphism and mutations that can alter its expression or aromatase activity and influence estrogen production. We designed this study to investigate the link between CYP19A1 polymorphism and susceptibility to colorectal cancer (CRC) development in Saudis.

Patients And Methods: Blood samples from 100 CRC patients and 100 healthy controls were drawn for DNA extractions. Three polymorphic sites, rs4774585, rs936308, and rs4775936, were genotyped using Taqman genotyping by real-time polymerase chain reaction. Allelic and genotype frequencies were calculated and compared in the two groups.

Results: All single nucleotide polymorphisms (SNPs) were polymorphic in Saudis, and comparison of allele frequencies showed several differences when compared to other populations. None of the SNPs were associated with the risk of CRC development in Saudis (>0.05). Some gender and location (colon or rectal) differences were observed.

Discussion: The results of this study highlighted the genetic heterogeneity existing between populations in the prevalence of different SNPs and their relation to disease state. It showed that, although rs4774585, rs936308, and rs4775936 are involved in CRC development in several populations, their role is not significant in the etiology of CRC in Saudis; however, some SNPs do increase susceptibility or resistance to CRC development as judged from the odds ratio. Further large-scale studies are warranted to clarify the role of the CYP19A1 development in CRC.
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http://dx.doi.org/10.2147/OTT.S121557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604566PMC
September 2017

Angiolymphoid hyperplasia with eosinophilia involving the common digital artery of the hand: A case report and classification of upper limb lesions.

Int J Surg Case Rep 2017 10;39:84-87. Epub 2017 Aug 10.

Division of Plastic Surgery, King Saud University, Riyadh, Saudi Arabia.

Introduction: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare benign reactive inflammatory lesion. The usual presentation is a single or multiple skin nodules of the head and neck. Involvement of the hand is very rare and there have been no comprehensive reviews on ALHE of the upper limb. In this paper, we report on a case involving the common digital artery of the hand. We also review the literature and offer two classification systems for upper limb lesions: One according to the primary structure involved, and the other according to the presentation with either single or multiple lesions.

Presentation Of Case: A 32-year old female presented with a slowly growing subcutaneous mass at the second web space of the left hand. The mass was neither tender or mobile. An MRI showed a tri-lobed soft tissue lesion. At the time of surgery, the lesion was found to be within the common digital artery of the second web space. Complete excision was done. Histopathology confirmed the diagnosis of ALHE There has been no recurrence or cold tolerance at final follow-up 1year later.

Discussion: We offer two classification systems for upper limb lesions: One according to the primary structure involved, and the other according to the presentation with either a single or multiple lesions.

Conclusion: A rare case of ALHE of the hand is presented. The literature is reviewed and two classification systems for upper limb lesions are offered and their implications are discussed.
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http://dx.doi.org/10.1016/j.ijscr.2017.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565780PMC
August 2017

Features of nonalcoholic steatohepatitis in severely obese children and adolescents undergoing sleeve gastrectomy.

Surg Obes Relat Dis 2017 Sep 7;13(9):1599-1609. Epub 2017 Apr 7.

College of Education, Texas Tech University, Lubbock, Texas.

Background: Nonalcoholic fatty liver disease (NAFLD) is an underrecognized co-morbidity of obesity. The characteristic features and severity of NAFLD in severe childhood obesity remain unknown.

Objectives: To investigate features of NAFLD in obese children and identify predictors of significant disease.

Setting: Academic center with a standardized pathway for pediatric bariatric surgery and a dedicated multidisciplinary team.

Design: This is a baseline cross-sectional analysis for a data set obtained from a prospective clinical outcome study that included severely obese children (≤14 yr of age) and adolescents (14-21 yr of age) who underwent laparoscopic sleeve gastrectomy between March 2008 and March 2015. Patients with syndromic obesity, history of alcohol intake, parenteral nutrition, liver disease, intake of medications that may affect NAFLD and weight, and insufficient tissue biopsy were excluded. Prevalence and features of nonalcoholic steatohepatitis (NASH) and clinically significant liver fibrosis in different pediatric age groups and noninvasive predictors in severe childhood obesity were evaluated.

Results: The 296 patients in the study group (1:1 sex distribution) had a mean body mass index and age of 48.4±9.8 kg/m and 14.5±3.6 years, respectively. According to histopathology assessment, 225 (76%) patients had NAFLD, of whom 118 patients (39.9% of the total cohort) had NASH. Additionally, 110 (37.2%) had clinically significant (stage 2+) fibrosis and 256 (86.5%) had portal inflammation. Those with NASH were younger than those without NASH (P = .02; prevalence of NASH in children aged≤10 yr = 64.9%) and were more likely to be male (P = .003). Of children aged≤10 years, 60% had clinically significant fibrosis compared with 32% of older patients (P = .03). High-density lipoproteins, triglycerides, glycated hemoglobin, alanine transaminase, and systolic and diastolic blood pressure levels were most predictive of fibrosis. For NASH, triglycerides, homeostatic model assessment of insulin resistance, glycated hemoglobin, alkaline phosphatase, aspartate transaminase, and alanine transaminase were most predictive.

Conclusions: In our setting, 65% of severely obese young children had NASH, and 60% had clinically significant liver fibrosis. Young age, male sex, and features of metabolic syndrome were significantly associated with NASH and liver fibrosis in severely obese pediatric patients.
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http://dx.doi.org/10.1016/j.soard.2017.04.005DOI Listing
September 2017

Toll-like receptor 4 as a predictor of clinical outcomes of estrogen receptor-negative breast cancer in Saudi women.

Onco Targets Ther 2017 24;10:1207-1216. Epub 2017 Feb 24.

Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.

The aim of this study was to investigate the association of the common polymorphisms of Toll-like receptor 4 (TLR-4) with breast cancer development in the Saudi Arabian population. Four TLR-4 polymorphisms (rs2770150, rs10759931, rs10759932, and rs4986790) were studied using 127 breast cancer patients and 117 controls. Relative expression of TLR-4 protein in the breast tumor and the matched normal breast tissues was determined in a large cohort of 70 clinical breast samples in a tissue micro-array format by immunohistochemistry using a specific anti-TLR-4 antibody. Our results demonstrated an increase in TLR-4 expression in estrogen receptor (ER)-, postmenopausal breast cancer patients compared to normal. We also demonstrated that the G allele of single-nucleotide polymorphism was found to be significantly higher in frequency among patients (36.3%) compared to the control group (26.7%), suggesting that this polymorphism is strongly associated with the development of breast cancer in this ethnic population. In addition, the TLR-4 polymorphism was shown to be highly correlated with breast cancer in patients over 48 years of age. The TLR-4 polymorphism was also found to be associated with this malignancy in the ER- patient groups. Our results suggested firstly that the variation in TLR-4 gene expression may influence breast cancer development and secondly a closely linked association between TLR-4 gene polymorphism and ER status. Our study provides support for a better understanding of the implication of TLR-4 polymorphism in breast tumorigenesis and for its eventual use as a cancer biomarker.
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http://dx.doi.org/10.2147/OTT.S112165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338938PMC
February 2017

Dendritic Fibromyxolipoma of the Pyriform Sinus: A Case Report and Review of the Literature.

Case Rep Pathol 2016 18;2016:7289017. Epub 2016 Dec 18.

Section of Anatomic Pathology, Department of Pathology and Laboratory Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Dendritic fibromyxolipoma is a rare and distinctive soft tissue neoplasm that is considered by many authors as a variant of spindle cell lipoma and characterized by the presence of dendritic cytoplasmic processes, plexiform vascular pattern, and keloidal collagen. It has never been reported in the larynx and hypopharynx. Its rarity and the potential to mistake it as a more clinically aggressive myxoid soft tissue neoplasm highlight the importance of its recognition. Here, a case of a dendritic fibromyxolipoma of the pyriform sinus in a 38-year-old male who presented with dysphagia, change of voice, and stridor is reported. A review of the literature, including histopathologic features and differential diagnosis, is also included.
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http://dx.doi.org/10.1155/2016/7289017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5203870PMC
December 2016

Association between polymorphisms and colon cancer susceptibility in Saudi Arabian female patients.

Onco Targets Ther 2017 16;10:1-11. Epub 2016 Dec 16.

Genome Research, Department of Biochemistry, College of Sciences, King Saud University.

Objective: The authors aimed to explore the relationship between the expression/polymorphisms of and susceptibility to colon cancer development in the Saudi Arabian population.

Methods: In total, blood samples from 115 patients with colon cancer and 102 participants without colon cancer were analyzed in this study. Three single-nucleotide polymorphisms (SNPs) were selected from the gene, including two sites within the gene's promoter region (rs352144 and rs187084) and one site in a intron region (rs5743839). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models after adjusting for age, gender, and tumor localization. To investigate the differential expression of in colon cancer, expression was evaluated using quantitative real-time reverse transcription polymerase chain reaction on 40 matched normal and colon tissues.

Results: The authors found that expression was decreased in colon cancer tissues as compared with that in normal tissues. Moreover, significant associations between the rs187084 SNP and colon cancer risk were observed in female patients only. In rs187084, the T allele had a significantly lower frequency (2.8 times) in female cancer patients than in controls (0.27 vs 0.41). The rs352139 and rs352144 SNPs were significantly associated with colon cancer development when the tumor was located in the rectal area.

Conclusion: The findings support the hypothesis that has an anticancer role in colon cancer development. Furthermore, genetic variation may influence colon cancer development, and SNPs in could serve as biomarkers for decision making in the treatment of females with rectal cancer.
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http://dx.doi.org/10.2147/OTT.S106024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5179201PMC
December 2016

Molecular subtypes of breast carcinoma in Saudi Arabia. A retrospective study.

Saudi Med J 2016 May;37(5):506-12

Department of Pathology, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail.

Objectives: To determine the distribution of various molecular subtypes of breast cancer in Saudi Arabia and to assess the association between these subtypes and age at diagnosis, tumor size, histopathological type, grade, presence of carcinoma in-situ, and lymph node status. 

Methods: This observational retrospective study, between January 2010 and  December 2014, was conducted at King Khalid University Hospital, Riyadh, Saudi Arabia. We classified 359 breast cancers into 4 molecular subtypes, using immunohistochemistry: luminal A (estrogen receptor [ER], or progesterone receptor [PR] positive and human epidermal growth factor receptor 2 [HER2] negative), luminal B (ER and/or PR positive and HER2 positive), HER2-positive (ER and PR negative and HER2 positive), and triple negative (ER, PR, and HER2 negative). We evaluated the relationship between these subtypes and clinicopathological features using Chi square test.  

Results: The most prevalent subtype was luminal A (58.5%), followed in descending order of frequency by triple negative (14.8%), luminal B (14.5%), and HER2-positive (12.3%). The average age at diagnosis was 49.8 years, and average tumor size at diagnosis was 3.19 cm.  

Conclusion: Luminal A tumor was the most common molecular subtype and HER2-positive was the least common. Most lobular carcinomas were luminal A tumors. Human epidermal growth factor receptor 2-positive and triple negative tumors had a higher histologic grade and a larger tumor size at diagnosis, and they were more common in women under 50 years. Carcinoma-in-situ was least common in triple negative tumors. We found no association between lymph node status and molecular subtypes.
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http://dx.doi.org/10.15537/smj.2016.5.15000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880649PMC
May 2016

Expression of nAG and Prod-1 in Terminal Phalanx Amputation Stumps of Adult Mice: An Experimental Model of Bone Regeneration in Higher Vertebrates.

Plast Reconstr Surg 2016 Mar;137(3):879-886

Riyadh, Saudi Arabia From the Department of Surgery, the College of Medicine Research Center, and the Department of Pathology, King Saud University.

Background: nAG and Prod-1 are proteins responsible for the regeneration of completely amputated limbs in salamanders (which are lower vertebrates). The purpose of this study was to introduce an experimental distal phalanx amputation model in mice (which are higher vertebrates) in which nAG and Prod-1 are expressed in the amputation stumps.

Methods: Sixteen mice with amputation of the distal two-thirds of the distal phalanx were used. One hind limb was used and the central three digits were amputated. Injection of nAG and Prod-1 plasmids was performed in the footpad twice weekly in experimental mice (n = 8), and injection of solution only (without the plasmids) was performed twice weekly in control mice (n = 8).

Results: nAG and Prod-1 were expressed in experimental stumps only. This expression results in quicker and more mature bone regeneration in experimental animals, and this was shown using histology and immune stains to osteocalcin (an osteoblast marker). Finally, quantitative mRNA showed a 21-fold increase of osteocalcin in experimental stumps compared with control stumps, and this was statistically significant.

Conclusion: Injection of nAG and Prod-1 into the footpad will result in their expression in the distal amputation stumps, and this will enhance bone regeneration in the model described.
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http://dx.doi.org/10.1097/01.prs.0000479994.27126.4aDOI Listing
March 2016

Malignant Gastric Glomus Tumor: A Case Report and Literature Review of a Rare Entity.

Oman Med J 2016 Jan;31(1):60-4

Department of Histopathology, King Saud University, Riyadh, Saudi Arabia.

A glomus tumor is a mesenchymal neoplasm that usually develops in the peripheral soft tissue, especially in the distal part of the extremities. The subungual zones of the fingers and toes are the most frequent sites of observation. The majority of glomus tumors are entirely benign, and the malignant counterparts are very rare, especially those arising in the visceral organs. We report a case of an extremely rare malignant glomus tumor arising in the stomach of a 53-year-old female admitted to the King Khalid University Hospital, Saudi Arabia. The patient reported a four-month history of pain and fullness in the left hypochondrium. She underwent laparotomy and resection of the gastric mass. The mass was analysed by histopathology. Based on the pathological findings of large tumor size, nuclear atypia, increased mitotic rate, atypical mitosis, the presence of necrosis, and characteristic immunohistochemistry the diagnosis of malignant glomus tumor was rendered. Ultrastructural study confirmed the diagnosis. The patient is well and continues regular follow-up.
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http://dx.doi.org/10.5001/omj.2016.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720945PMC
January 2016

Expression and Polymorphism of Toll-Like Receptor 4 and Effect on NF-κB Mediated Inflammation in Colon Cancer Patients.

PLoS One 2016 15;11(1):e0146333. Epub 2016 Jan 15.

Genome Research Chair, Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia.

Our aim was to evaluate the association between the expression and the polymorphism of TLR4/NF-κB pathways and colon cancer. TLR4 (rs4986790, rs10759932, rs10759931 and rs2770150) were genotyped in blood samples from Colorectal patients and healthy controls. TLR4 and cytokines inflammatory expression were evaluated by real time PCR on 40 matching normal and colon tissues and the protein level by Immunohistochemistry. The high level of TLR4 expression in colon cancer tissues is mainly due to infections by bacteria in the human colon and leads to induction of an acute secretion of inflammatory cytokines mediated by NF-κB. Also, we report here a clear evidence for an association between TLR4 rs10759931 polymorphism (OR = 0.086, CI: 0.04-0.18, P = <0.00001). This polymorphism affects the entire population without being specific to either gender or to any age group. In contrast, the rs2770150 is associated with colon cancer in women aged over 50 years and is closely linked with the decreased levels of female sex hormones during the post-menopausal period (OR = 0.188, CI: 0.074-0.48, P = <0.00084). rs10759932 and rs4986790 appear to have any association with colon cancer. Our data suggest that TLR4 SNPs could possibly serve as biomarkers for decision making in colon cancer treatment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146333PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714746PMC
July 2016

Six Cases of Myofibroma--The Adult Counterpart of Infantile Myofibromatosis: Case Report.

J Hand Surg Am 2016 Feb 22;41(2):251-6. Epub 2015 Dec 22.

Division of Plastic and Hand Surgery, King Saud University, Riyadh, Saudi Arabia; Department of Pathology, King Saud University, Riyadh, Saudi Arabia.

The adult counterpart of infantile myofibromatosis is rare and is known as myofibroma. Cases are rare, and previous ones have been reported as isolated case reports; hence, there has been no consensus regarding the clinical presentation, surgical reconstruction, histological features, and recurrence of hand myofibromas. Over a 10-year period, the senior author treated 6 patients. We review our cases as well as 6 previously reported cases. The presentation is usually a single hand mass in a young adult. The tumor may arise from the lower dermis or from deeper fibrous structures of the hand including the palmar fascia. Tumors that arise from the dermis are best treated by skin excision to ensure complete excision. Histologically, the tumor is composed of highly cellular myofibroblast proliferation and is strongly positive to smooth muscle actin immune stain. The recurrence rate after excision is low.
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http://dx.doi.org/10.1016/j.jhsa.2015.11.011DOI Listing
February 2016

Apelin protect against multiple organ injury following hemorrhagic shock and decrease the inflammatory response.

Int J Appl Basic Med Res 2015 Sep-Dec;5(3):195-9

Department of Pathology, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia.

Introduction: Hemorrhagic shock (HS) result in multiple organ injury and inflammatory response that lead to death. The exact mechanism is not clear. Apelin is an endogenous ligand of orphan G-protein coupled receptor APJ. Apelin has anti-inflammatory effects on the release of inflammatory mediators.

Objectives: To examine the protective effects of apelin against multiple organ injury and the possible involvement of inflammatory pathways.

Methodology: Male Sprague-Dawley rats (300-350 g) were subjected to hemorrhage over 60 min to reach a mean arterial blood pressure of 40 mmHg. Then, rats were treated or not with 1 mL of 10 nm/L apelin-13 intraarterially resuscitation was performed in vivo by the reinfusion of the shed blood for 30 min to restore normotension. Blood samples were collected for measurement of tumor necrosis factor (TNF) using ELISA (R and D systems). Biopsies were obtained from organs for light microscopic examination.

Results: HS rats showed significant increase the levels of TNF. Apelin significantly lowered the production of TNF-α. Histological examination of hemorrhagic shocked untreated rats revealed structural damage. Less histological damage was observed in the organs of treated rats. Apelin-treatment decreased the number of inflammatory cells and mitochondrial swollen in cells.

Conclusion: Treatment with apelin before resuscitation protects against multiple organ injury in HS by attenuation the inflammatory response and might be a therapeutic target for HS.
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http://dx.doi.org/10.4103/2229-516X.165377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4606580PMC
November 2015

The Relationship Between Killer Cell Immunoglobulin-Like Receptors and HLA-C Polymorphisms in Colorectal Cancer in a Saudi Population.

Genet Test Mol Biomarkers 2015 Nov 18;19(11):617-22. Epub 2015 Sep 18.

5 Department of Clinical Infection, Microbiology and Immunology, Faculty of Health and Life Sciences, Institute of Global Health, University of Liverpool , Liverpool, United Kingdom .

Aims: We performed an association study to evaluate the contribution of 16 killer cell immunoglobulin-like receptor (KIR) genotype polymorphisms and the HLA-C1 and -C2 ligands in the development of colorectal cancer (CRC) in Saudi Arabian patients.

Methods: A total of 52 patients with different stages of malignant CRC as well as 70 healthy Saudi controls were enrolled at the King Khalid University Hospital.

Results: Our results showed that the frequency of the activating mutations KIR2DS1, 2DS2, 2DS3, 2DS5, and 3DS1 was significantly higher in CRC patients compared to controls. The 3DS1 gene contributed to the highest risk of CRC (odds ratio [OR] = 16.25, p < 0.0001), followed by 2DS1 (OR = 8.6; p < 0.0001). The distributions of HLA-C1 and -C2 ligands were not significantly different between patients and controls. Analyses of different combinations of KIR genes with their HLA-C1 and -C2 ligands show that the frequency of 2DL3 in the presence of its ligand, the allotype C1, was significantly more prevalent in patients compared to controls. In addition, 2DL2 and 2DL3 that were aggregated in combination with the ligand, HLA-C1, were found to be more highly associated mainly with the homozygote HLA-C1/C1 (p = 0.03; OR = 2.6). The activating mutations 2DS1 and 2DS2 when combined with their respective ligands, HLA-C2 and -C1, showed highly significant associations with CRC development.

Conclusion: This study supports a key role for KIR gene mutations in the development of CRC, especially in association with their ligands.
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http://dx.doi.org/10.1089/gtmb.2015.0105DOI Listing
November 2015

The role of Fibroscan in predicting the presence of varices in patients with cirrhosis.

Eur J Gastroenterol Hepatol 2015 Nov;27(11):1307-12

aGastroenterology Unit Department of Medicine, Departments of bMedical Education cPathology, College of Medicine dKing Saud University Liver Disease Research Center, King Saud University, Riyadh eGastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia fDepartment of Tropical Medicine & Gastroenterology, College of Medicine, Assuit University, Asyut, Egypt.

Background/aim: Transient elastography is a relatively new, noninvasive method of measuring liver stiffness. This study aimed to evaluate the diagnostic accuracy of transient elastography and other noninvasive methods for the diagnosis of esophageal varices (EV) in patients with cirrhosis.

Methods: This cross-sectional study graded EV according to size in 145 consecutive patients with cirrhosis who underwent endoscopy, Fibroscan, and other noninvasive diagnostic methods. The accuracy of these diagnostic methods in diagnosing EV was evaluated on the basis of area under receiver operating characteristic (AUROC) curves.

Results: Elastography was successful in 123 patients. Of these, 54.5% had hepatitis C and 10.6% had hepatitis B. EV were absent in 39.8%, small EV was present in 24.4%, and large EV was present in 35.8% of patients. Fibroscan, aspartate aminotransferase-to-platelet ratio index, and international normalized ratio showed low accuracy in diagnosing EV in non-viral-related cirrhosis patients (AUROCs 0.66, 0.68, and 0.67, respectively). Fibroscan and aspartate aminotransferase-to-platelet ratio index were more accurate in measuring EV with a viral etiology (AUROCs 0.704 and 0.703, respectively). A cutoff value of 16.9 kPa was 83.8% sensitive in diagnosing EV in non-viral-cirrhotic patients, whereas a cutoff value of 19.9 kPa was 83.4% sensitive in diagnosing EV in patients with viral hepatitis. Fibroscan was moderately accurate in diagnosing grade I EV and less accurate in diagnosing grades II and III EV in all cirrhotic patients, irrespective of the underlying etiology.

Conclusion: Fibroscan might be useful in predicting the presence of EV in patients with cirrhosis with a viral etiology. However, endoscopy remains the gold standard for EV screening.
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http://dx.doi.org/10.1097/MEG.0000000000000432DOI Listing
November 2015

Expression and new exon mutations of the human Beta defensins and their association on colon cancer development.

PLoS One 2015 3;10(6):e0126868. Epub 2015 Jun 3.

Genome Research Chair, Department of Biochemistry, College of Science King Saud University, Riyadh, Kingdom of Saudi Arabia.

The development of cancer involves genetic predisposition and a variety of environmental exposures. Genome-wide linkage analyses provide evidence for the significant linkage of many diseases to susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster. Human β-defensins (hBDs) are important molecules of innate immunity. This study was designed to analyze the expression and genetic variations in hBDs (hBD-1, hBD-2, hBD-3 and hBD-4) and their putative association with colon cancer. hBD gene expression and relative protein expression were evaluated by Real-Time polymerase chain reaction (qPCR) and immunohistochemistry, respectively, from 40 normal patients and 40 age-matched patients with colon cancer in Saudi Arabia. In addition, hBD polymorphisms were genotyped by exon sequencing and by promoter methylation. hBD-1, hBD-2, hBD-3 and hBD-4 basal messenger RNA expression was significantly lower in tumor tissues compared with normal tissues. Several insertion mutations were detected in different exons of the analyzed hBDs. However, no methylation in any hBDs promoters was detected because of the limited number of CpG islands in these regions. We demonstrated for the first time a link between hBD expression and colon cancer. This suggests that there is a significant link between innate immunity deregulation through disruption of cationic peptides (hBDs) and the potential development of colon cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126868PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454434PMC
February 2016

Myofibroblast expression in skin wounds is enhanced by collagen III suppression.

Biomed Res Int 2015 19;2015:958695. Epub 2015 Feb 19.

College of Medicine Research Center, King Saud University, P.O. Box 18097, Riyadh 11415, Saudi Arabia.

Generally speaking, the excessive expression of myofibroblasts is associated with excessive collagen production. One exception is seen in patients and animal models of Ehlers-Danlos syndrome type IV in which the COL3A1 gene mutation results in reduced collagen III but with concurrent increased myofibroblast expression. This paradox has not been examined with the use of external drugs/modalities to prevent hypertrophic scars. In this paper, we injected the rabbit ear wound model of hypertrophic scarring with two doses of a protein called nAG, which is known to reduce collagen expression and to suppress hypertrophic scarring in that animal model. The higher nAG dose was associated with significantly less collagen III expression and concurrent higher degree of myofibroblast expression. We concluded that collagen III content of the extracellular matrix may have a direct or an indirect effect on myofibroblast differentiation. However, further research is required to investigate the pathogenesis of this paradoxical phenomenon.
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http://dx.doi.org/10.1155/2015/958695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350964PMC
January 2016

A solitary fibrous tumor of the upper limb.

Saudi Med J 2015 Feb;36(2):236-8

Division of Plastic Surgery, King Saud University, Riyadh, Kingdom of Saudi Arabia. E-mail.

Solitary fibrous tumors (SFT) of the upper limb are extremely rare, and we report this tumor in the arm of a 30-year-old male. He is presented with a 22 cm painless mass. Complete surgical excision was performed. The histological diagnosis of SFT was based on the presence of ectatic blood vessels and positive staining for CD34 and vimentin. He remains disease-free at the 3-year follow-up interval. The report aims to increase the awareness of the criteria for the histological diagnosis of SFT, as well as the principles of their surgical excision and follow-up. 
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http://dx.doi.org/10.15537/smj.2015.2.10524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375705PMC
February 2015

Camel milk attenuates the biochemical and morphological features of diabetic nephropathy: inhibition of Smad1 and collagen type IV synthesis.

Chem Biol Interact 2015 Mar 21;229:100-8. Epub 2015 Jan 21.

Pathology Department, College of Medicine, King Saud University, PO Box 2925, Riyadh 11461, Riyadh, Saudi Arabia.

Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus (DM) that worsens its morbidity and mortality. There is evidence that camel milk (CM) improves the glycemic control in DM but its effect on the renal complications especially the DN remains unclear. Thus the current study aimed to characterize the effects of CM treatment on streptozotocin (STZ)-induced DN. Using STZ-induced diabetes, we investigated the effect of CM treatment on kidney function, proteinuria, renal Smad1, collagen type IV (Col4), blood glucose, insulin resistance (IR), lipid peroxidation, the antioxidant superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH). In addition renal morphology was also examined. The current results showed that rats with untreated diabetes exhibited marked hyperglycemia, IR, high serum urea and creatinine levels, excessive proteinuria, increased renal Smad1 and Col4, glomerular expansion, and extracellular matrix deposition. There was also increased lipid peroxidation products, decreased antioxidant enzyme activity and GSH levels. Camel milk treatment decreased blood glucose, IR, and lipid peroxidation. Superoxide dismutase and CAT expression, CAT activity, and GSH levels were increased. The renoprotective effects of CM were demonstrated by the decreased serum urea and creatinine, proteinuria, Smad1, Col4, and preserved normal tubulo-glomerular morphology. In conclusion, beside its hypoglycemic action, CM attenuates the early changes of DN, decreased renal Smad1 and Col4. This could be attributed to a primary action on the glomerular mesangial cells, or secondarily to the hypoglycemic and antioxidant effects of CM. The protective effects of CM against DN support its use as an adjuvant anti-diabetes therapy.
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http://dx.doi.org/10.1016/j.cbi.2015.01.013DOI Listing
March 2015

Utility of endoscopic ultrasound-guided transbronchial fine-needle cytology in the diagnosis of sarcoidosis: A Saudi experience.

Cytojournal 2014 3;11:31. Epub 2014 Dec 3.

Department of Pulmonary Medicine, King Saud University, King Khalid University Hospital, Riyadh, Saudi Arabia.

Background: Endoscopic ultrasound-guided transbronchial fine-needle aspiration (EBUS-TFNA) is a minimally invasive technique for diagnosis of mediastinal masses/lesions. Although most studies have reported the utility of EBUS-TFNA in malignancy, its use has been extended to the benign conditions as well.

Objective: The present study focused on utility of EBUS in contributing to reach the final diagnosis of sarcoidosis.

Design: From May 2010 to December 2013, 19 of 80 patients who underwent EBUS-TFNA at one center for radiologically suspicious lesions for sarcoidosis, and with no definite histological diagnosis, were included in this retrospective study.

Results: When the histological diagnosis was taken as the gold standard, the sensitivity of EBUS-TFNA was 84.2% and specificity 100% with the positive predictive value of 100. The combined diagnostic sensitivity of EBUS-TFNA and transbronchial lung biopsy was 100%.

Conclusion: EBUS is a valuable, minimally invasive diagnostic modality to support the diagnosis of sarcoidosis in appropriate clinical setting, after conventional work-up - particularly if patients have suspicious radiological findings. This minimally invasive procedure helps in providing a final diagnosis without exposing the patient to the risk of complications from more invasive procedures.
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http://dx.doi.org/10.4103/1742-6413.146118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278100PMC
January 2015