Study of single nucleotide polymorphism of vascular endothelium factor in patients with differentiated thyroid cancer.

BACKGROUND: Genetic alterations and high levels of the vascular endothelial growth factor (VEGF) are presumptive risk factors for differentiated thyroid cancer (DTC). OBJECTIVE: This work aims to study the presence of - 634G/C polymorphism of vascular endothelial growth factor (rs2010963) and its' serum level in patients with DTC and comparing these results with those of the control subjects. MATERIAL AND METHOD: The study was a retrograde case-control study that included seventy patients with DTCin addition to seventy apparently healthy control subjects. Blood sample was taken and subjected to study of - 634G/C VEGF polymorphism (rs2010963) by real time PCR and measurement of its' plasma level by immunoassay kit (ELISA). RESULTS: Regarding genotyping of VEGFA - 634G/C (rs2010963) polymorphism, there was significant increase in CG and GG genotypes (28.6%, 18.6% respectively) among patients compared to control subjects (20.0%, 4.3% respectively) and significant increase in CC genotype in control subjects (75.7%) compared to patients (52.9%), P = 0.001. The VEGF mean ± SD level was significantly elevated in patients compared to control subjects (1215.81 ± 225.78 versus 307.16 ± 91.81, P = 0.006). Moreover, there was significant increase in VEGF levels in patients with CG and GG genotypes (1295.9 ± 68.74, 1533.08 ± 109.95, respectively) compared to patients with CC genotype (1061 163.25), P = 0.001). CONCLUSION: There was significant increase in GG and CG genotypes in patients with DTC compared to control subjects which may suggest a predisposing role for these genotypes in development of DTC. Moreover, there was significant increase in serum level of vascular endothelial growth factor in patients with GG and CG genotypes which may reflect the mechanism of these genotypes in development of DTC.

Plasma levels of Asymmetric Di Methyl Arginine and endothelial dysfunction in diabetic subjects with neuropathic foot ulcer.

OBJECTIVE: Asymmetric dimethyl arginine (ADMA) is an amino acid that acts as an endogenous competitive inhibitor of Nitric oxide synthase, leading to endothelial dysfunction (ED). The aim of this study was to evaluate the relationship between plasma ADMA (p-ADMA) level and ED in diabetic subjects with neuropathic foot ulcer (NFU), and the possible predictors of p-ADMA level. MATERIALS AND METHODS: 80 diabetic subjects of matched age, sex and BMI were included; 40 with NFU (G1), 20 with peripheral nerve dysfunction (PND) (G2) and 20 without PND (G3), plus 20 matched healthy subjects (G4). Flow-mediated-dilatation (FMD) of brachial artery and Carotid-intima-media-thickness (CIMT) were measured to evaluate ED and subclinical atherosclerosis, respectively. RESULTS: G1&2 had a significantly lower FMD than G3&4 [-5.09 (-22.5 to 22.92), 4.67 (-15 to 23.91) vs. 15.74 (8.33-36.59) and 20.1 (10.0-46.15)%, respectively] (p < 0.001), and higher CIMT [0.9 (0.6-1.5), 0.9 (0.6-1.3) vs. 0.6 (0.5-0.8) and 0.7 (0.5-0.9) cm, respectively] (p < 0.001, r = 0.237, p = 0.034, r = 0.330, p = 0.003, respectively), with no significant correlation with FMD (r = -0.176, p = 0.118). FMD was inversely and strongly related to CIMT (r = -0.520, p < 0.001). p-ADMA levels were significantly higher in uncontrolled hypertensive patients in comparison to controlled and normotensive subjects [717 (286-3611) vs. 648 (335-874) and 686 (526-857) ng/L, respectively] (p = 0.026). Metformin users and hypertensive subjects on ACEIs or ARBs had the lowest p-ADMA levels than the non-users (p < 0.001, p = 0.007, respectively). CONCLUSION: The remarkable ED in diabetic subjects with NFU is unlikely to be due to alteration in p-ADMA. Further studies are needed in order to conclude a causal association between p-ADMA and ED in this group of patients.

Study of Uromodulin Gene Polymorphism in Egyptian Patients with End-Stage Renal Disease.

Uromodulin (UMOD) gene polymorphism has been linked with end-stage renal disease. In this research, we studied the prevalence of UMOD rs42993393 T>C in Egyptian hemodialysis (HD) patients and the blood level of UMOD in those patients. The study was a case-control study and included 100 patients on regular HD and 100 healthy control subjects. The blood samples from the studied groups were subjected to the determination of UMOD blood level and molecular study of UMOD rs42993393 T>C genotype by polymerase chain reaction with restriction fragment length polymorphism. The serum UMOD level was significantly low in patients (38.6 7.6 ng/mL) compared to control subjects (221.3 ± 54.2, P = 0.0001). On the other hand, the UMOD rs42993393T>C was significantly increased in TC in patients (28%, odds ratio 1.3-1.0-2.0) compared to controls (22%, P = 0.03), and there was a significant increase in CC in patients (10%) compared to control subjects (3%; P = 0.0001). The T allele was significantly increased in controls compared to patients with a significant increase in C allele in patients compared to controls (P = 0.01). The present study highlights the prevalence of UMOD gene polymorphism at rs42993393T>C. There was a significant prevalence of C allele and C genotypes in HD patients. This finding may indicate that this allele may be a predisposing genotype for renal failure in susceptible patients. On the other hand, the significant reduction of serum UMOD in patients with end-stage renal disease may be attributed to the reduced functioning renal mass.

MicroRNA-451 as an Early Predictor of Chronic Kidney Disease in Diabetic Nephropathy.

BACKGROUND: Diabetes mellitus is the leading cause of end-stage renal disease worldwide. Microalbuminuria is the cornerstone for the diagnosis of diabetic nephropathy. However, it is an inadequate marker for early diagnosis. MicroRNAs are not only new and promising markers for early diagnosis but also, but they may also play a role in the prevention of disease progression. METHODS: This study included ninety patients with type 2 DM in addition to 30 control subjects. MicroRNA-451 expression in blood and plasma using real-time PCR was evaluated in addition to the classic diabetic nephropathy markers (serum creatinine, urinary albumin, and eGFR). RESULTS: There was a significant difference between the studied groups versus control regarding serum creatinine, eGFR, urinary, and plasma microRNA-451 with p=0.0001. Patients with eGFR 60 ml/min/1.73 m2 showed a significantly higher plasma microRNA-451 (29.6 ± 1.6) and significantly lower urinary microRNA-451 (21 ± 0.9) in comparison to patients with eGFR >60 ml/min/1.73 m2 and p=0.0001. eGFR showed a positive correlation with urinary microRNA-451 and negative correlation with both plasma microRNA-451 and urinary albumin. Both plasma and urinary microRNA-451 are highly sensitive and specific markers for chronicity in diabetic nephropathy patients with sensitivity of 90.9% and 95.5% and specificity of 67.6% and 95.6%, respectively. CONCLUSION: MicroRNA-451 is a promising early biomarker for chronic kidney disease in diabetic nephropathy with high sensitivity and specificity.

The impact of topical phenytoin loaded nanostructured lipid carriers in diabetic foot ulceration.

OBJECTIVE: The aim of this study is to develop, and characterize nanostructured lipid carriers (NLCs) of phenytoin (PHT) in order to improve its entrapment efficiency and sustained release to improve the healing process. METHODS: Twenty-seven patients with neuropathic diabetic foot ulceration (DFU) were enrolled in this study. Patients were comparable regarding size, grading of ulcer and control of diabetes with no major deformity. All patients were managed by weekly sharp debridement if indicated and offloaded with cast shoes. They were equally divided into three groups: PHT-NLC-hydrogel (0.5%w/v), phenytoin hydrogel (0.5%w/v) and blank hydrogel groups. Changes in wound area were monitored over 2 months. RESULTS: Baseline wound area of PHT-NLC, PHT and blank hydrogels were 5.50 ± 3.66, 3.94 ± 1.86 and 5.36 ± 2.14 cm2, respectively. Ulcers treated with PHT-NLC hydrogel showed smaller wound area compared to control groups (ρ < 0.05). The overall reduction in ulcer size were 95.82 ± 2.22% for PHT-NLC-hydrogel in comparison to 47.10 ± 4.23% and -34.91 ± 28.33% for PHT and blank-hydrogel (ρ < 0.001), respectively. CONCLUSION: PHT-NLC hydrogel speeds up the healing process of the DFU without adverse effects when compared to the positive and negative control hydrogels. Moreover, the study can open a window for topical application of NLCs loaded with PHT in the treatment of numerous dermatological disorders that resist conventional treatment. KEY MESSAGE: The delivery of drug molecules and their localization into the skin is the main purpose of the topical dosage forms. In this manuscript, the impact of topical phenytoin loaded nanostructured lipid carrier in improving wound healing in patients with neuropathic diabetic foot ulceration was investigated. Phenytoin loaded nanostructured lipid carrier dressing was found to be more effective than phenytoin hydrogel at the same concentration in healing of neuropathic diabetic foot ulcer.

Pressure distribution under the contralateral limb in Charcot arthropathy with different walking speeds.

BACKGROUND: The total contact cast has been recognized as the "gold standard" for treatment of Charcot neuro-osteoarthropathy (CN). However, removable cast walkers (RCWs) became an alternative option especially after resolution of the acute stage. RCWs with an elevated sole construction often induce leg length discrepancy (LLD) that could significantly affects plantar pressure (PP) distribution in diabetic patients with neuropathy. AIM: To study the additional effect of walking speed on PP abnormalities induced by LLD. METHOD: The study included 16 patients with diabetes (59±8.8years; 8 men and 8 women), with unilateral CN offloaded by RCW. In-shoe PP distribution was measured using F-scan (Tekscan Inc.), whilst patients walked at their normal speed (53±4 steps/min), versus short slow steps (24±3/min) under the two walking conditions: (1) neglected LLD, and (2) corrected LLD. RESULTS: The greatest reduction in PP was seen during reduction of walking speed, with corrected LLD, followed by corrected LLD with normal walking speed, followed by neglected LLD with slowing of walking speed. The highest PP was found when the patient remain on their normal walking speed and LLD was neglected. CONCLUSION: The contralateral foot of CN offloaded with RCW, is subjected to high pressure loads beneath the hallux, 1st, 2nd, 3rd, and 5th metatarsal heads. As such, care should be taken not only to avoid minor LLD, but to also advise the patient to practice short slow steps while walking, so that pressure overload on contralateral limb and its possible contribution to the development of bilateral Charcot, could be minimized.

Survival without sequelae after prolonged cardiopulmonary resuscitation after electric shock.

"Electrical shock is the physiological reaction or injury caused by electric current passing through the human body. It occurs upon contact of a human body part with any source of electricity that causes a sufficient current through the skin, muscles, or hair causing undesirable effects ranging from simple burns to death." Ventricular fibrillation is believed to be the most common cause of death after electrical shock. "The ideal duration of cardiac resuscitation is unknown. Typically prolonged cardiopulmonary resuscitation is associated with poor neurologic outcomes and reduced long term survival. No consensus statement has been made and traditionally efforts are usually terminated after 15-30 minutes." The case under discussion seems worthy of the somewhat detailed description given. It is for a young man who survived after 65 minutes after electrical shock (ES) after prolonged high-quality cardiopulmonary resuscitation (CPR), multiple defibrillations, and artificial ventilation without any sequelae. Early start of adequate chest compressions and close adherence to advanced cardiac life support protocols played a vital role in successful CPR.