Toxic effects of systemic cisplatin on rat eyes and the protective effect of hesperidin against this toxicity

Context: In the present study, cisplatin (CP) induced eye toxicity and the beneficial effect of hesperidin (HP) was investigated.

Methods: Twenty-eight rats were equally divided into four groups; the first group was kept as control. In the second and third group, CP and HP were given at the doses of 7?mg/kg and 50?mg/kg/d, respectively. In the fourth group, CP and HP were given together at the same doses. Tissue samples were collected on day 14 of CP treatment.

Results: The results demonstrated that CP caused a significant increase in thiobarbituric acid reactive substances (TBARS) levels and decrease of glutathione levels and antioxidant enzyme activity (catalase, superoxide dismutase and glutathione peroxidase) in eye tissues compared to other groups, HP prevented these effects of CP. Besides, CP led to histopathological damage in the retina and cornea. On the other hand, HP treatment prevented histopathological effects of CP.

Conclusion: CP had severe dose-limiting toxic effects and HP treatment can be beneficial against the toxic ocular effects of CP. Thus, it appears that co-administration of HP with CP may be a useful approach to attenuate the negative effects of CP on the eye.     

The comparison of the relaxant effects of two methoxylated flavones in rat aortic rings

The vascular effect of salvigenin (6-hydroxyapigenin 6,7,4' -trimethyl ether), a natural flavone, was investigated in comparison with another flavone, 6-hydroxyluteolin 6,7,3',4' -tetramethyl ether in rat aortic rings. Cumulative addition of their increasing concentrations (10(-9)-10(-4)M) produced graded relaxations on rings precontracted with noradrenaline (10(-6) M) and KCl (40 mM). The maximal relaxations induced by flavones were similar, however, based on their pEC50 values salvigenin displayed a higher potency than 6-hydroxyluteolin 6,7,3',4'-tetramethyl ether. Endothelium removal markedly reduced the relaxations to salvigenin while the responses to 6-hydroxyluteolin 6,7,3',4'-tetramethyl ether were partially affected. In addition, a significant decrease was observed in maximal responsiveness and sensitivity to flavones in the presence of L-NOARG, a NO synthase inhibitor. The cyclooxygenase inhibitor indomethacin significantly inhibited the relaxations to salvigenin, but not altered the responses to 6-hydroxyluteolin 6,7,3',4'-tetramethyl ether. Our results provide evidence that salvigenin is an effective flavone in causing vasorelaxation which appears to be mediated by endothelium derived NO and prostacyclin. Whereas, the other flavone, 6-hydroxyluteolin 6,7,3',4'-tetramethyl ether induced relaxant responses are partially endothelium, presumably NO mediated.     

Isolated temporal infarct due traumatic vertebral artery dissecting pseudo-aneurysm: a rare case report

The authors describe a rare case of traumatic vertebral artery dissecting pseudo-aneurysm with temporal lobe infarct in the pre-foramina segment of the left vertebral artery following knife injury of the left anterolateral neck area. A 40 years old man was admitted to the emergency department after a penetrating injury in the left anterolateral neck. On contrast-enhanced CT and Doppler ultrasonography in the neck, a dissecting pseudo-aneurysm of the vertebral artery was revealed.On day 2, MRI scanning revealed an ischemic infarct in the temporal lobe, which can be attributed to vertebral artery injury. The case was treated conservatively and the patient was discharged on the fourth hospital day. Owing to the position of the artery, traumatic vertebral artery dissections are uncommon, and they are linked with a high mortality rate due to aneurismal rupture and embolic impact of the dissections, culminating in stroke in young people. Our findings demonstrate the necessity of imaging in head and neck traumatic injuries to detect vertebral artery injuries far sooner in order to prevent complications.     

Role of carbon dioxide angiography in management of below knee arterial lesions

Introduction

Many practitioners express concern about the adequacy of imaging using CO₂ in the lower extremities, particularly in the distribution of the popliteal artery and below (5). Published results have varied considerably with respect to the validity of imaging this anatomy.

Objectives

Review our experience with CO₂ angiography using CO₂ angioset in evaluation and intervention of below knee arteries.

Patients and methods

Forty patients with lower limb ischemia were divided into two groups. The 1st group has normal kidney function, subjected to angiography with CO₂ and water soluble contrast media (WSCM) as the reference standard (control). The 2nd group has subjected only to CO₂ angiography due to one or more risk factors related to WSCM. CO₂ angioset is a dedicated CO₂ injection system used in all patients. In the 1st group; imaging findings on CO₂ and WSCM angiography were compared while in the 2nd group; findings were compared with the post procedure clinical and color Doppler findings.

Results

All arterial lesions detected on CO₂ angiography were comparable to those obtained with WSCM in the control group. In the 2nd group; post procedure clinical and Doppler findings correlated well with angiographic findings and angioplasty results. CO₂ angiography images have lower resolution compared to WSCM however, they were reliable for accurate diagnosis and to guide angioplasty.

Conclusion

CO₂ angiography using CO₂ angioset is considered a reliable alternate to WSCM in assessment of below knee arteries and provides a reliable roadmap to interventional procedures.     

Identification of clinical and simple laboratory variables predicting responsible gastrointestinal lesions in patients with iron deficiency anemia

Iron deficiency anemia (IDA) is a frequent disorder. Also, it may be a sign of underlying serious diseases. Iron deficiency points to an occult or frank bleeding lesion when occurred in men or postmenopausal women. In this study, we aimed to evaluate the diagnostic yield of endoscopy in patients with IDA and to define predictive factors of gastrointestinal (GI) lesions causing IDA. Ninety-one patients (77 women, 14 men; mean age: 43 years) who were decided to have esophago-duodenoscopy and/or colonoscopy for iron deficiency anemia were interviewed and responded to a questionnaire that included clinical and biochemical variables. The endoscopic findings were recorded as GI lesions causing IDA or not causing IDA. Endoscopy revealed a source of IDA in 18.6 % of cases. The risk factors for finding GI lesions causing IDA were as follows: male gender (p= 0.004), advanced age (> 50 years) (p= 0.010), weight loss (over 20% of total body weight lost in last 6 month) (p= 0.020), chronic diarrhea (p= 0.006), change of bowel habits (p= 0.043), epigastric tenderness (p= 0.037), raised carcinoembryonic antigen (CEA) level (normal range: 0-7 ng/mL) (p= 0.039), < 10 gr/dl hemoglobin (Hb) level (p=0.054). None of these risk factors had been present in 21 (23%) women younger than 51 years. In this group, no patient had any GI lesion likely to cause IDA (negative predictive value= 100%). In multivariate analysis, advanced age (p=0.017), male gender (p< 0.01) and weight lost (p=0.012) found that associated with GI lesions in all patients. It may be an appropriate clinical approach to consider these risk factors when deciding for gastrointestinal endoscopic evaluation in iron deficiency anemia.     

Childhood apraxia of speech and multiple phonological disorders in Cairo-Egyptian Arabic speaking children: Language, speech, and oro-motor differences

Childhood apraxia of speech is a neurological childhood speech-sound disorder in which the precision and consistency of movements underlying speech are impaired in the absence of neuromuscular deficits. Children with childhood apraxia of speech and those with multiple phonological disorder share some common phonological errors that can be misleading in diagnosis. This study posed a question about a possible significant difference in language, speech and non-speech oral performances between children with childhood apraxia of speech, multiple phonological disorder and normal children that can be used for a differential diagnostic purpose. 30 pre-school children between the ages of 4 and 6 years served as participants. Each of these children represented one of 3 possible subject-groups: Group 1: multiple phonological disorder; Group 2: suspected cases of childhood apraxia of speech; Group 3: control group with no communication disorder. Assessment procedures included: parent interviews; testing of non-speech oral motor skills and testing of speech skills. Data showed that children with suspected childhood apraxia of speech showed significantly lower language score only in their expressive abilities. Non-speech tasks did not identify significant differences between childhood apraxia of speech and multiple phonological disorder groups except for those which required two sequential motor performances. In speech tasks, both consonant and vowel accuracy were significantly lower and inconsistent in childhood apraxia of speech group than in the multiple phonological disorder group. Syllable number, shape and sequence accuracy differed significantly in the childhood apraxia of speech group than the other two groups. In addition, children with childhood apraxia of speech showed greater difficulty in processing prosodic features indicating a clear need to address these variables for differential diagnosis and treatment of children with childhood apraxia of speech.     

Targeted Resequencing of 29 Candidate Genes and Mouse Expression Studies Implicate ZIC3 and FOXF1 in Human VATER/VACTERL Association

The VATER/VACTERL association describes the combination of congenital anomalies including vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects. As mutations in ciliary genes were observed in diseases related to VATER/VACTERL, we performed targeted resequencing of 25 ciliary candidate genes as well as disease‐associated genes (FOXF1, HOXD13, PTEN, ZIC3) in 123 patients with VATER/VACTERL or VATER/VACTERL‐like phenotype. We detected no biallelic mutation in any of the 25 ciliary candidate genes; however, identified an identical, probably disease‐causing ZIC3 missense mutation (p.Gly17Cys) in four patients and a FOXF1 de novo mutation (p.Gly220Cys) in a further patient. In situ hybridization analyses in mouse embryos between E9.5 and E14.5 revealed Zic3 expression in limb and prevertebral structures, and Foxf1 expression in esophageal, tracheal, vertebral, anal, and genital tubercle tissues, hence VATER/VACTERL organ systems. These data provide strong evidence that mutations in ZIC3 or FOXF1 contribute to VATER/VACTERL.     

Clinical and pathological correlations of marrow PUMA and P53 expressions in myelodysplastic syndromes

p53 is a key regulator of apoptosis. p53 upregulated modulator of apoptosis (PUMA) is a critical mediator of p53‐dependent and independent apoptosis. The objective of this study was to evaluate the relationship of p53 and PUMA to the prognosis of MDS. Bone marrow biopsies of MDS patients at the time of diagnosis (n = 76) and at the time of transformation (n = 19) were included in the study group. The expression of p53 and PUMA was evaluated using immunohistochemistry. When compared to the control group, both p53 (p < 0.001) and PUMA (p = 0.012) expression levels were significantly higher in MDS group. In MDS group, there was a moderate positive correlation between p53 and PUMA expressions. PUMA expression was not correlated with event free and overall survival. However, overall survival was significantly lower in cases with p53 expression in more than 50% of the cells. There was an increase in PUMA expression in cases that showed transformation as compared to the initial diagnostic bone marrows but was not statistically significant. The correlation that existed between p53 and PUMA was lost in transformed cases. Our results showed that PUMA and p53 expressions are increased in MDS marrows compared to normal marrows. PUMA expression increases further during transformation while the expression of p53 is not significantly altered which suggests that PUMA alterations might be a late event during the evolution of MDS.     

Identification of possible pathogenic pathways in Beh?et's disease using genome-wide association study data from two different populations

Behçet''s disease (BD) is a multi-system inflammatory disorder of unknown etiology. Two recent genome-wide association studies (GWASs) of BD confirmed a strong association with the MHC class I region and identified two non-HLA common genetic variations. In complex diseases, multiple factors may target different sets of genes in the same pathway and thus may cause the same disease phenotype. We therefore hypothesized that identification of disease-associated pathways is critical to elucidate mechanisms underlying BD, and those pathways may be conserved within and across populations. To identify the disease-associated pathways, we developed a novel methodology that combines nominally significant evidence of genetic association with current knowledge of biochemical pathways, protein–protein interaction networks, and functional information of selected SNPs. Using this methodology, we searched for the disease-related pathways in two BD GWASs in Turkish and Japanese case–control groups. We found that 6 of the top 10 identified pathways in both populations were overlapping, even though there were few significantly conserved SNPs/genes within and between populations. The probability of random occurrence of such an event was 2.24E−39. These shared pathways were focal adhesion, MAPK signaling, TGF-β signaling, ECM–receptor interaction, complement and coagulation cascades, and proteasome pathways. Even though each individual has a unique combination of factors involved in their disease development, the targeted pathways are expected to be mostly the same. Hence, the identification of shared pathways between the Turkish and the Japanese patients using GWAS data may help further elucidate the inflammatory mechanisms in BD pathogenesis.