Renoprotective effects of apocynin and/or umbelliferone against acrylamide-induced acute kidney injury in rats: role of the NLRP3 inflammasome and Nrf-2/HO-1 signaling pathways.

Acrylamide (ACR) is a toxic, probably carcinogenic compound commonly found in fried foods and used in the production of many industrial consumer products. ACR-induced acute kidney injury is mediated through several signals. In this research, we investigated, for the first time, the therapeutic effects of phytochemicals apocynin (APO) and/or umbelliferone (UMB) against ACR-induced nephrotoxicity in rats and emphasized the underlying molecular mechanism. To achieve this goal, five groups of rats were randomly assigned: the control group received vehicle (0.5% CMC; 1 ml/rat), ACR (40 mg/kg, i.p.), ACR + APO (100 mg/kg, P.O.), ACR + UMB (50 mg/kg, P.O.), and combination group for 10 days. In ACR-intoxicated rats, there was a significant reduction in weight gain while the levels of blood urea, uric acid, creatinine, and Kim-1 were elevated, indicating renal injury. Histopathological injury was also observed in the kidneys of ACR-intoxicated rats, confirming the biochemical data. Moreover, MDA, TNF-α, and IL-1ß levels were raised; and GSH and SOD levels were decreased. In contrast, treatment with APO, UMB, and their combination significantly reduced the kidney function biomarkers, prevented tissue damage, and decreased inflammatory cytokines and MDA. Mechanistically, it suppressed the expression of NLRP-3, ASC, GSDMD, caspase-1, and IL-1ß, while it upregulated Nrf-2 and HO-1 in the kidneys of ACR-intoxicated rats. In conclusion, APO, UMB, and their combination prevented ACR-induced nephrotoxicity in rats by attenuating oxidative injury and inflammation, suppressing NLRP-3 inflammasome signaling, enhancing antioxidants, and upregulating Nrf-2 and HO-1 in the kidneys of ACR-induced rats.

In Vivo Investigation of the Ameliorating Effect of Tempol against MIA-Induced Knee Osteoarthritis in Rats: Involvement of TGF-ß1/SMAD3/NOX4 Cue.

Osteoarthritis (OA) is a complex disease characterized by structural, functional, and metabolic deteriorations of the whole joint and periarticular tissues. In the current study, we aimed to investigate the possible effects of tempol on knee OA induced by the chemical chondrotoxic monosodium iodoacetate (MIA) which closely mimics both the pain and structural changes associated with human OA. Rats were administrated oral tempol (100 mg/kg) one week post-MIA injection (3 mg/50 µL saline) at the right knee joints for 21 consecutive days. Tempol improved motor performance and debilitated the MIA-related radiological and histological alterations. Moreover, it subsided the knee joint swelling. Tempol decreased the cartilage degradation-related biomarkers as matrix metalloproteinase-13, bone alkaline phosphatase (bone ALP), and fibulin-3. The superoxide dismutase mimetic effect of tempol was accompanied by decreased NADPH oxidase 4 (NOX4), inflammatory mediators, nuclear factor-kappa B (NF-κB), over-released transforming growth factor-ß1 (TGF-ß1). Tempol decreased the expression of chemokine (C-C motif) ligand 2 (CCL2). On the molecular level, tempol reduced the phosphorylated protein levels of p38 mitogen-activated protein kinase (MAPK), and small mother against decapentaplegic 3 homologs (SMAD3). These findings suggest the promising role of tempol in ameliorating MIA-induced knee OA in rats via collateral suppression of the catabolic signaling cascades including TGF-ß1/SMAD3/NOX4, and NOX4/p38MAPK/NF-κB and therefore modulation of oxidative stress, catabolic inflammatory cascades, chondrocyte metabolic homeostasis.

Cilostazol mitigates mesenteric ischemia/reperfusion-induced lung lesion: Contribution of PPAR-γ, NF-κB, and STAT3 crosstalk.

AIMS: Cilostazol (Cilo), a phosphodiesterase-III inhibitor, has signified its efficacy against different ischemia/reperfusion (IS/RE) models. Nevertheless, it has not fully illuminated its potential effect against intestinal IS/RE-induced lung injury. Consequently, the study was fashioned to evaluate the feasible mechanism of action of Cilo against intestinal IS/RE-induced lung injury. MAIN METHODS: Wistar rats were treated with Cilo (0.1 g/kg, p.o.) or with a vehicle for 14 days prior to IS/RE, induced by clamping of the superior mesenteric artery for 30 min with subsequent clamp removal for 2 h. KEY FINDINGS: The mechanistic study disclosed that Cilo protected the two studied organs, viz., lung, and intestine partially by intensifying the expression/content of PPAR-γ accompanied by reducing the expression/content of NF-қB-p65 and STAT3. In addition to normalizing MDA, iNOS, and NOx, the Cilo antioxidant power was confirmed by intensifying tissues content of the total antioxidant capacity. With regard to the anti-inflammatory effect, Cilo reduced the effects of TNF-α, IL-6, and ICAM-1, which were reflected in MPO activity. Furthermore, Cilo had an anti-apoptotic attribute demonstrated by enhancing Bcl-2 content and lessening caspase-3 level. SIGNIFICANCE: Cilo provided conceivable protective mechanisms to modulate events concomitant with mesenteric IS/RE partly by modulating oxidative stress, inflammation, and apoptosis feasibly via the participation of PPAR-γ, STAT3, and NF-κB p65 signaling pathways.

Dimethyl fumarate and curcumin attenuate hepatic ischemia/reperfusion injury via Nrf2/HO-1 activation and anti-inflammatory properties.

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury occurs in different clinical settings as hepatic transplantation, and different types of shock. I/R injury is the main cause of hepatic damage and failure due to the production of reactive oxygen species (ROS) and inflammatory cytokines. Dimethyl fumarate (DMF), an immunomodulatory drug, activates cellularantioxidantsignaling pathways exerting cytoprotective properties. Curcumin (CUR), a natural phenolic compound, possesses antioxidant and anti-inflammatory properties. METHOD: To study potential protective effects of DMF with CUR against hepatic I/R injury in rats, animals were randomly allocated into seven groups as follows: (1) Sham; (2) DMF (25 mg/Kg, p.o); (3) CUR (400 mg/Kg, p.o.); (4) I/R; (5) DMF + I/R; (6) CUR + I/R; and combination (COM) therapy + I/R. Drugs were given for 14 days before I/R. RESULTS: Compared with I/R group, COM group showed the best amelioration in hepatic injury induced by I/R insult. This was confirmed by a significant reduction in serum ALT and AST activity with improved histopathological results when compared to every single treatment. Hepatic protection afforded by DMF was mediated by activating Nrf2/HO-1 signaling and increasing GSH and TAC contents. CUR treatment improved the inflammatory markers (TNF-α, IL-1ß, Il-6 and iNOS) as well as neutrophilic infiltration assessed as MPO. Moreover, CUR potentiated Nrf2/HO-1 signaling induced by DMF with significant suppression in lipid peroxidation. CONCLUSION: We concluded that combining DMF and CUR has more efficient hepatoprotective effects against hepatic-induced IRI via potentiating antioxidant and anti-inflammatory properties mediated by Nrf2/HO-1 pathway.

New Approach for B-Mode Ultrasound (US) Evaluation of the Plantar Aponeurosis (PA) Thickness in Healthy Subjects.

PURPOSE: To compare ultrasound (US) measurements in the sagittal and axial plane of the plantar aponeurosis (PA) in healthy subjects. MATERIALS AND METHODS: PA thickness was measured in 40 healthy subjects (mean age: 34 years) by two radiologists using US in sagittal, axial medial and axial lateral planes. Subjects were classified according to gender (female and male) and age (18 - 35 versus 50 - 75 years). All measurements were compared and the interobserver agreement was calculated. RESULTS: The PA was medially significantly thicker than laterally (mean ± std 3.1 ±â€Š0.7 mm versus 2.5 ±â€Š0.5 mm respectively, P< 0.001). A significant difference was found between males and females (3.3 ±â€Š0.7 mm versus 2.9 ±â€Š0.6 mm medially and 2.7 ±â€Š0.6 mm versus 2.3 ±â€Š0.4 mm laterally, p < 0.05) and between the older and younger age groups (3.8 ±â€Š0.6 mm versus 2.8 ±â€Š0.4 mm medially and 3.1 ±â€Š0.4 mm versus 2.3 ±â€Š0.4 mm laterally, p < 0.001). Good interobserver agreement was detected (0.74). CONCLUSION: Measurement of central and lateral fascicles of the plantar aponeurosis in both planes (sagittal and axial) is recommended in the daily routine. KEY POINTS: · US examination of the central and lateral fascicles of the PA was feasible.. · PA thickness measurements showed significant differences based on age and gender.. · There was good interobserver correlation between both examiners despite the major difference in experience.. · Scanning of two planes for the PA is recommended in the daily routine.. · PA thickness measurement by US is a fast and reliable method for junior radiologists.. CITATION FORMAT: · Abd Ellah MM, Kremser C, Strobl S et al. New Approach for B-Mode Ultrasound (US) Evaluation of the Plantar Aponeurosis (PA) Thickness in Healthy Subjects. Fortschr Röntgenstr 2019; 191: 333 - 339.

Gout of hand and wrist: the value of US as compared with DECT.

OBJECTIVES: The purpose of this study was to compare findings of ultrasound (US) with dual-energy CT (DECT) in patients presenting with suspected gouty hand and wrist arthritis. METHODS: This prospective study included 180 patients (136 men and 44 women, age range, 31- 94 years; mean age, 65.9 years) with an initial clinical diagnosis of acute gouty arthritis who underwent DECT and US examination. Intra- and extra-articular findings of each modality were tabulated and calculated with DECT as gold standard. RESULTS: The final diagnosis of gout was positive in 97/180 patients (53.9%) by DECT, an alternative diagnosis confirmed in 83 patients. US showed a sensitivity of 70.1% (extra-articular: 42.5%, p < 0.0001; intra-articular: 80.3%, p = 0.14) and specificity of 51%. The double contour sign (DCS) was present in 58/61 patients with a positive US study for intra-articular gout (95.1%). CONCLUSIONS: Sensitivity of US for diagnosis of gouty arthritis in hand and wrist is limited, particularly with respect to extra-articular urate deposition. The DCS is the most sensitive sign for the assessment of gouty hand and wrist arthritis by US. KEY POINTS: • Sensitivity of US for diagnosis of gouty arthritis in hand and wrist is limited, particularly with respect to extra-articular gouty deposits. • The double contour sign is the most sensitive finding for the assessment of gouty hand and wrist arthritis by US. • Although the sensitivity of US for diagnosis of gouty hand and wrist arthritis is limited, it can be used as a first-line imaging modality in the presence of the DCS.

Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs.

Exosomes have emerged as important mediators of diverse biological functions including tumor suppression, tumor progression, invasion, immune escape and cell-to-cell communication, through the release of molecules such as mRNAs, miRNAs, and proteins. Here, we identified differentially expressed exosomal miRNAs between normal epithelial ovarian cell line and both resistant and sensitive ovarian cancer (OC) cell lines. We found miR-940 as abundant in exosomes from SKOV3-IP1, HeyA8, and HeyA8-MDR cells. The high expression of miR-940 is associated with better survival in patients with ovarian serous cystadenocarcinoma. Ectopic expression of miR-940 inhibited proliferation, colony formation, invasion, and migration and triggered G0/G1 cell cycle arrest and apoptosis in OC cells. Overexpression of miR-940 also inhibited tumor cell growth in vivo. We showed that proto-oncogene tyrosine-protein kinase (SRC) is directly targeted by miR-940 and that miR-940 inhibited SRC expression at mRNA and protein levels. Following this inhibition, the expression of proteins downstream of SRC, such as FAK, paxillin and Akt was also reduced. Collectively, our results suggest that OC cells secrete the tumor-suppressive miR-940 into the extracellular environment via exosomes, to maintain their invasiveness and tumorigenic phenotype.

Exosomes: From Garbage Bins to Promising Therapeutic Targets.

Intercellular communication via cell-released vesicles is a very important process for both normal and tumor cells. Cell communication may involve exosomes, small vesicles of endocytic origin that are released by all types of cells and are found in abundance in body fluids, including blood, saliva, urine, and breast milk. Exosomes have been shown to carry lipids, proteins, mRNAs, non-coding RNAs, and even DNA out of cells. They are more than simply molecular garbage bins, however, in that the molecules they carry can be taken up by other cells. Thus, exosomes transfer biological information to neighboring cells and through this cell-to-cell communication are involved not only in physiological functions such as cell-to-cell communication, but also in the pathogenesis of some diseases, including tumors and neurodegenerative conditions. Our increasing understanding of why cells release exosomes and their role in intercellular communication has revealed the very complex and sophisticated contribution of exosomes to health and disease. The aim of this review is to reveal the emerging roles of exosomes in normal and pathological conditions and describe the controversial biological role of exosomes, as it is now understood, in carcinogenesis. We also summarize what is known about exosome biogenesis, composition, functions, and pathways and discuss the potential clinical applications of exosomes, especially as biomarkers and novel therapeutic agents.

Extensor tendinopathy of the elbow assessed with sonoelastography: histologic correlation.

PURPOSE: To compare agreement between conventional B-mode ultrasound (US) and compression sonoelastography (SEL) of the common extensor tendons of the elbow with histological evaluation. MATERIALS AND METHODS: Twenty-six common extensor tendons were evaluated in 17 cadavers (11 females, median age 85 years and 6 males, median age 80 years). B-mode US was graded into: Grade 1, homogeneous fibrillar pattern; grade 2, hypoechoic areas and/or calcifications <30%; and grade 3 > 30%. SEL was graded into: Grade 1 indicated blue (hardest) to green (hard); grade 2 yellow (soft); and grade 3 red (softest). B-mode US, SEL, and a combined grading score incorporating both were compared to histological findings in 76 biopsies. RESULTS: Histological alterations were detected in 55/76 biopsies. Both modalities showed similar results (sensitivity, specificity, and accuracy 84%, 81%, and 83% for B-mode US versus 85%, 86%, and 86% for SEL, respectively, P > 0.3). However, a combination of both resulted in significant improvement in sensitivity (96%, P < 0.02) without significant change in specificity (81%, P < 0.3), yielding an improved overall accuracy (92%). CONCLUSION: Combined imaging of the extensor tendons with both modalities is superior to either modality alone for predicting the presence of pathologic findings on histology. KEY POINTS: • Combination of B-mode US and SEL proved efficiency in diagnosing lateral epicondylitis. • Combination of B-mode US and SEL in lateral epicondylitis correlates to histology. • Combination of both modalities provides improved sensitivity without loss of specificity.

Sonoelastography of the Common Flexor Tendon of the Elbow with Histologic Agreement: A Cadaveric Study.

Purpose To determine the correlation of the results of conventional B-mode ultrasonography (US) and compression sonoelastography with histologic results in common flexor tendons of the elbow in human cadavers. Materials and Methods Twenty-five common flexor tendons were evaluated in 16 fresh, unembalmed cadavers of 11 women with a median age of 85 years (range, 71-101 years) and five men with a median age of 78 years (range, 70-88 years). Informed consent was provided according to the last will of the donors. B-mode US results were classified as grade 1, normal tendon with homogeneous fibrillar pattern; grade 2, tendon thickening or hypoechoic areas and/or calcifications in less than 30% of the tendon; or grade 3, hypoechoic areas and/or calcifications greater than 30% of the tendon. Sonoelastographic results were grade 1, blue (hardest) to green (hard); grade 2, yellow (soft); and grade 3, red (softest). The intraclass correlation coefficient was calculated to determine agreement with histologic findings for each B-mode US, sonoelastographic, and combined B-mode US and sonoelastographic examination. Histologic results were grade 1, normal, with parallel fibrillar pattern; grade 2, mild tendinopathy, with cellular infiltration, angiogenesis, or fatty vacuoles; or grade 3, severe tendinopathy, with loss of parallel collagen structure and necrosis. Results Histologic alterations were detected in 44% (11 of 25) of biopsy specimens. Intraclass correlation with histologic results was 0.57 for B-mode US, 0.68 for sonoelastography, and 0.84 for the combination of the two approaches. Conclusion The addition of sonoelastography to B-mode US provided statistically significant improvement in correlation with histologic results compared with the use of B-mode US alone (P < .02). © RSNA, 2016 Online supplemental material is available for this article.

Hydroxychloroquine augments early virological response to pegylated interferon plus ribavirin in genotype-4 chronic hepatitis C patients.

The therapeutic effect of pegylated interferon (peg-IFN) alfa-2a combined with ribavirin (RBV) on chronic hepatitis C Egyptian patients is low and further efforts are required to optimize this therapy for achievement of higher rates of virological response. This study aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) in combination with pegylated interferon plus ribavirin on early virological response (EVR) in chronic hepatitis C Egyptian patients. Naïve 120 Egyptian patients with chronic hepatitis C virus infection were divided into two groups. Group 1 have administered the standard of care therapy (pegylated interferon alfa-2a plus ribavirin) for 12 weeks, (n = 60). Group 2 have administered hydroxychloroquine plus standard of care therapy for 12 weeks, (n = 60). Therapeutics included hydroxychloroquine (200 mg) oral twice daily, peginterferon alfa-2a (160 µg) subcutaneous once weekly and oral weight-based ribavirin (1000-1200 mg/day). Baseline characteristics were similar in the two groups. The percentage of early virological response was significantly more in patients given the triple therapy than in patients given the standard of care [54/60 (90%) vs. 43/60 (71.7%); P = 0.011; respectively]. Biochemical response at week 12 was also significantly higher in patients given the triple therapy compared with the standard of care [58/60 (96.7%) vs. 42/60 (70%); P < 0.001; respectively]. Along the study, the observed adverse events were mild and similar across treatment groups. Addition of hydroxychloroquine to pegylated interferon plus ribavirin improves the rate of early virological and biochemical responses in chronic hepatitis C Egyptian patients without an increase in adverse events. J. Med. Virol. 88:2170-2178, 2016. © 2016 Wiley Periodicals, Inc.

Coadministration of ezetimibe with pegylated interferon plus ribavirin could improve early virological response in chronic hepatitis C obese Egyptian patients.

BACKGROUND: Ezetimibe has been reported to inhibit viral entry and to reduce BMI and has been proposed as a novel therapeutic agent for chronic hepatitis C (CHC), potentiating the effects of pegylated interferon and ribavirin (peg-IFN/RBV). OBJECTIVE: The aim of the study was to assess the effects of ezetimibe coadministration with peg-IFN/RBV combination on the early virological response (EVR) rates in nonobese and obese patients with CHC genotype 4 (CHC-4). PATIENTS AND METHODS: A total of 144 CHC-4 patients were divided into two groups; group 1 included nonobese patients (n=76) and group 2 included obese patients (n=68). Each group was further subclassified into equal control and treated groups. The control groups received peg-IFN/RBV combination for 24 weeks, and the treated groups received peg-IFN/RBV plus ezetimibe for 12 weeks and then only peg-IFN/RBV for the remaining 12 weeks. RESULTS: The study revealed that EVR significantly improved in the obese patients (85.3 vs. 64.7% in the treated and control groups, respectively, at P<0.05) without any significant improvement in the nonobese patients. Biochemical responses (defined as normalization of alanine aminotransferase at week 12) were markedly improved in the treated groups in both the nonobese and obese groups compared with their respective controls. CONCLUSION: The addition of ezetimibe to peg-IFN/RBV combination significantly improves EVR rates in obese patients compared with nonobese patients, and remarkably improves the biochemical responses in both obese and nonobese patients with CHC-4. This may shed light on a new strategy for the treatment of CHC, particularly in obese Egyptian patients.

Lipoic acid attenuates Aroclor 1260-induced hepatotoxicity in adult rats.

The present study was aimed to investigate the mechanistic aspect of Aroclor 1260-induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high-density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase-3 & -9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260-induced liver injury. Lipoic acid could protect rats against Aroclor 1260-induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913-922, 2016.

Meralgia paraesthetica: Ultrasound-guided injection at multiple levels with 12-month follow-up.

OBJECTIVES: To evaluate the efficacy of ultrasound (US)-guided injections around the lateral femoral cutaneous nerve (LFCN) at different levels in meralgia paraesthetica (MP) patients. METHODS: The study was approved by the university ethics committee and informed oral and written consent were obtained from all patients. Between June 2008 and August 2013, 20 patients with symptoms of MP, including nine men (mean age, 61.33 years) and 11 women (mean age 61.18 years), were treated with US-guided injection of steroids along the LFCN at three different levels in a mean of 2.25 sessions. A visual analogue scale (VAS) was used to measure symptoms before, immediately after and 12 months after treatment. RESULTS: Complete resolution of symptoms was documented in 15/20 patients (mean VAS decreased from 82 to 0), and partial resolution in the remaining five (mean VAS decreased from 92 to 42), which was confirmed at 12-month follow-up. By using the different levels of injection approach overall significantly better symptom relief was obtained (p < 0.05). CONCLUSION: The outcome of US-guided injection along the LFCN can be further improved by injections at different levels (p < 0.05), which was confirmed at 12-month long-term follow-up. KEY POINTS: Meralgia paraesthetica is an entrapment neuropathy of the lateral femoral cutaneous nerve. Ultrasound proved effective in diagnosis and in guiding injection therapy. Injection at the anterior superior iliac spine has been used previously. Multiple injections along the nerve course were used in this study. Long-term follow-up (12 months) confirmed the results.

Mangiferin Mitigates Gastric Ulcer in Ischemia/ Reperfused Rats: Involvement of PPAR-γ, NF-κB and Nrf2/HO-1 Signaling Pathways.

Mangiferin (MF), a xanthonoid from Mangifera indica, has been proved to have antisecretory and antioxidant gastroprotective effects against different gastric ulcer models; however, its molecular mechanism has not been previously elucidated. Therefore, the aim of this study was to test its modulatory effect on several signaling pathways using the ischemia/reperfusion model for the first time. Animals were treated with MF, omeprazole (OMP), and the vehicle. The mechanistic studies revealed that MF mediated its gastroprotective effect partly via inducing the expression of Nrf2, HO-1 and PPAR-γ along with downregulating that of NF-κB. Surprisingly, the effect of MF, especially the high dose, exceeded that mediated by OMP except for Nrf2. The molecular results were reflected on the biomarkers measured, where the antioxidant effect of MF was manifested by increasing total antioxidant capacity and glutathione, besides normalizing malondialdehyde level. Additionally, MF decreased the I/R-induced nitric oxide elevation, an effect that was better than that of OMP. In the serum, MF, dose dependently, enhanced endothelial nitric oxide synthase, while reduced the inducible isoform. Regarding the anti-inflammatory effect of MF, it reduced serum level of IL-1ß and sE-selectin, effects that were mirrored on the tissue level of myeloperoxidase, the neutrophil infiltration marker. In addition, MF possessed an antiapoptotic character evidenced by elevating Bcl-2 level and reducing that of caspase-3 in a dose related order. As a conclusion, the intimated gastroprotective mechanisms of MF are mediated, partially, by modulation of oxidative stress, inflammation and apoptosis possibly via the Nrf2/HO-1, PPAR-γ/NF-κB signaling pathways.

Sonographic cross-sectional area measurement in carpal tunnel syndrome patients: can delta and ratio calculations predict severity compared to nerve conduction studies?

OBJECTIVE: To evaluate the accuracy of two different sonographic median nerve measurement calculations in predicting carpal tunnel syndrome (CTS) severity in a study population with clinically and electrophysiologically confirmed CTS. METHODS: 643 wrists of 427 patients (325 females and 102 males, age range: 17-90 years, mean ± SD: 57.9 ± 14.7) were included with CTS diagnosis based on clinical and nerve conduction studies (NCS). Cross-sectional area (CSA) measurement of the median nerve was performed at the carpal tunnel level (CSAc) and at the pronator quadratus muscle level (CSAp). Two parameters were calculated: delta (∆-CSA), which is the difference between proximal and distal measurements, and ratio (R-CSA), calculated by dividing distal over proximal measurements. RESULTS: Patients were classified into mild, moderate and severe CTS based upon NCS. The mean ∆-CSA (4.2 ± 2.6, 6.95 ± 2.2 and 10.7 ± 4.9 mm(2)) and mean R-CSA (1.5 ± 0.4, 1.95 ± 0.4 and 2.4 ± 0.7) values were significantly different between all groups (p < 0.001). Optimal cut-off values for ∆-CSA and R-CSA were 6 mm(2) and 1.7, respectively, to distinguish mild from moderate disease, and 9 mm(2) and 2.2, respectively, to distinguish moderate from severe disease. CONCLUSION: Threshold values for the calculated sonographic parameters ∆-CSA and R-CSA are useful in predicting CTS severity compared to NCS. KEY POINTS: • Two proposed parameters were calculated (∆-CSA, R-CSA) and compared to NCS. • A defined sonoanatomical proximal landmark was used for the calculation. • Both parameters showed ability to detect CTS severity comparable to NCS. • Cut-off values could be determined for both parameters.

Effect of green tea and its polyphenols on mouse liver.

Increased consumption of green tea (GT) without enough scientific data has raised safety concerns. Epigallocatechin 3-gallate (EGCG) is the most prominent polyphenol of GT that has antioxidant activity. However, higher doses of EGCG have been shown to cause liver injury. This study was initiated to determine the effect of GT extracts in a mouse model. We also investigated the effects of EGCG in normal and health-compromised mice. Different doses of GT fractions and EGCG were administered for 5 days to mice. Also, a single dose of lipopolysaccharide (LPS) was combined with EGCG in order to investigate its effect in the presence of fever. Plasma ALT and ALP levels were determined along with liver histopathology. Combining a single high IG dose of EGCG with a single IP dose of LPS initiated liver injury. Furthermore, repeated administration of high IG doses of EGCG showed mild liver injury, but it was augmented under febrile conditions induced by LPS. This study confirms the safety of reasonable consumption of GT over a short term. However, it highlights a caution that high doses of EGCG can lead to mild liver injury, and this may be markedly enhanced under febrile conditions.

Hepatoprotective activity of quercetin against acrylonitrile-induced hepatotoxicity in rats.

Acrylonitrile is a potent hepatotoxic, mutagen, and carcinogen. A role for free radical-mediated lipid peroxidation in the toxicity of acrylonitrile has been suggested. The present study was designed to assess the hepatoprotective effect of quercetin against acrylonitrile-induced hepatotoxicity in rats. Liver damage was induced by oral administration of acrylonitrile (50 mg/kg/day/5 weeks). Acrylonitrile produced a significant elevation of malondialdehyde (138.9%) with a marked decrease in reduced glutathione (72.4%), and enzymatic antioxidants; superoxide dismutase (81%), and glutathione peroxidase (53.2%) in the liver. Serum aspartate aminotransferase, alanine aminotransferases, direct bilirubin, and total bilirubin showed a significant increase in acrylonitrile alone treated rats (115.5%, 110.8%, 1006.8%, and 1000.8%, respectively). Pretreatment with quercetin (70 mg/kg/day/6 weeks) and its coadministration with acrylonitrile prevented acrylonitrile-induced alterations in hepatic lipid peroxides and enzymatic antioxidants as well as serum aminotransferases and bilirubin. Histopathological findings supported the biochemical results. We suggest that querectin possess hepatoprotective effect against acrylonitrile-induced hepatotoxicity through its antioxidant activity.

Protective effect of docosahexaenoic acid against cyclosporine A-induced nephrotoxicity in rats: a possible mechanism of action.

The aim of this experimental study was to investigate whether, and how then, docosahexaenoic acid (DHA) could alleviate the cyclosporine A (CsA)-induced nephrotoxicity. Three main groups of Sprague-Dawley rats were treated orally with CsA (25 mg/kg), DHA (100 mg/kg), and CsA along with DHA. A corresponding control group was also used. DHA administration significantly reduced CsA-induced nephrotoxicity and associated hyperlipidemia and proteinuria as assessed by estimating serum triacylglycerol, serum total cholesterol, serum total protein, serum urea, and creatinine clearance. Furthermore, urinary excretions of protein and N-acetyl-ß-D-glucosaminidase were significantly inhibited following DHA administration. DHA supplementation slightly attenuated the oxidative damage in kidney tissues as evaluated by the levels of thiobarbituric acid-reacting substances and protein carbonyl content in the kidney homogenate, although there were no significant differences between CsA-intoxicated and DHA-treated animals. Moreover, DHA treatment significantly restored total nitric oxide (NO) levels in both renal tissues and urine. This study demonstrates the ability of DHA to ameliorate CsA-induced renal dysfunction, which might be beneficial to enhance the therapeutic index of CsA. The data suggest that the protective potential of DHA in the prevention of CsA nephrotoxicity in rats was mainly associated with the increase of total NO bioavailability in renal tissues. Nevertheless, the exact independent mechanism in which DHA exerts its beneficial effect is yet to be fully elucidated.