Carpal tunnel syndrome assessment with diffusion tensor imaging: Value of fractional anisotropy and apparent diffusion coefficient.

OBJECTIVES: To quantitatively assess carpal tunnel syndrome (CTS) with DTI by evaluating two approaches to determine cut-off values. METHODS: In forty patients with CTS diagnosis confirmed by nerve conduction studies (NCs) and 14 healthy subjects (mean age 58.54 and 57.8 years), cross-sectional area (CSA), apparent diffusion coefficient (ADC) and fractional anisotropy (FA) at single and multiple levels with intraobserver agreement were evaluated. RESULTS: Maximum and mean CSA and FA showed significant differences between healthy subjects and patients (12.85 mm2 vs. 28.18 mm2, p < 0.001, and 0.613 vs. 0.524, p=0.007, respectively) (10.12 mm2 vs. 19.9 mm2, p<0.001 and 0.617 vs. 0.54, p=0.003, respectively), but not maximum and mean ADC (p > 0.05). For cut-off values, mean and maximum CSA showed the same sensitivity and specificity (93.3 %). However, mean FA showed better sensitivity than maximum FA (82.6 % vs. 73.9 %), but lower specificity (66.7 % vs. 80 %), and significant correlation for maximum CSA, 97 % (p < 0.01), with good correlation for maximum ADC and FA, 84.5 % (p < 0.01) and 62 % (p=0.056), respectively. CONCLUSIONS: CSA and FA showed significant differences between healthy subjects and patients. Single measurement at maximum CSA is suitable for FA determination. Key Points • DTI showed that FA is stronger than ADC for CTS diagnosis. • Single- and multiple-level approaches were compared to determine FA and ADC. • Single-level evaluation at the thickest MN cross-sectional area is sufficient.

Direct-write three-dimensional nanofabrication of nanopyramids and nanocones on Si by nanotumefaction using a helium ion microscope.

The recently commercialized helium ion microscope (HIM) has already demonstrated its outstanding imaging capabilities in terms of resolution, surface sensitivity, depth of field and ease of charge compensation. Here, we show its exceptional patterning capabilities by fabricating dense lines and three-dimensional (3D) nanostructures on a Si substrate. Small focusing spot size and confined ion-Si interaction volume of a high-energy helium ion beam account for the high resolution in HIM patterning. We demonstrate that a set of resolvable parallel lines with a half pitch as small as 3.5 nm can be achieved. During helium ion bombardment of the Si surface, implantation outperforms milling due to the small mass of the helium ions, which produces tumefaction instead of depression in the Si surface. The Si surface tumefaction is the result of different kinetic processes including diffusion, coalescence and nanobubble formation of the implanted ions, and is found to be very stable structurally at room temperature. Under appropriate conditions, a linear dependence of the surface swollen height on the ion doses can be observed. This relation has enabled us to fabricate nanopyramids and nanocones, thus demonstrating that HIM patterning provides a new 'bottom-up' approach to fabricate 3D nanostructures. This surface tumefaction method is direct, both positioning and height accurate, and free of resist, etch, mode and precursor, and it promises new applications in nanoimprint mold fabrication and photomask clear defect reparation.

Platelet activation: a link between psoriasis per se and subclinical atherosclerosis--a case-control study.

BACKGROUND: Pathomechanisms of both psoriasis and atherosclerosis may involve platelet activation. Activated platelets show increased P-selectin; CD62 expression, and mean platelet volume (MPV). Impaired brachial artery flow-mediated dilatation (FMD) is related to atherosclerosis. OBJECTIVES: To determine the presence of subclinical atherosclerosis in patients with psoriasis (without overt cardiovascular complications or traditional cardiovascular disease risk factors), compared with controls. METHODS: In this case-control study, 25 patients with psoriasis and 25 age- and gender-matched healthy individuals were subjected to assessment of MPV, CD62 expression using flow cytometry, and brachial artery FMD and transthoracic echocardiography by cardiac ultrasound scanner. RESULTS: A statistically highly significant increased CD62 expression, but not MPV, was found in cases compared with controls, and in patients with moderate/severe psoriasis compared with either mild cases or controls (P < 0.001). CD62 expression was statistically significantly positively correlated with the Psoriasis Area and Severity Index (PASI) score (P < 0.001), baseline brachial artery diameter (P = 0.03) but not FMD and aortic root diameter (ARD; P = 0.03). ARD was statistically significantly higher in patients with moderate/severe psoriasis compared with controls (P = 0.017). Stepwise simple linear regression analysis revealed that PASI score was the most important factor affecting CD62 expression (P < 0.001). CONCLUSIONS: Our study showed increased atherosclerosis risk in patients with psoriasis, particularly those with moderate/severe disease, as evidenced by increased expression of platelet CD62 compared with healthy controls. Moreover, we found a positive correlation between CD62 expression and ARD (another possible marker of atherosclerosis), with positive correlation to the PASI score; the most important factor influencing CD62 expression. However, our data on MPV and FMD do not support the use of either value for diagnosing subclinical atherosclerosis in patients with psoriasis in further studies.

Effects of dystocia, fetotomy and caesarian sections on the liver enzymes activities and concentrations of some serum biochemical parameters in dairy cattle.

The aim of the present study was to determine the level of serum liver enzymes, triglyceride and some metabolites in cows with or without difficulties during parturition. The second goal was to compare between the possible effects of caesarian section and fetotomy on these parameters. A total number of 24 native breed cows at full term were included in this study. Out of them, 8 gave normal parturition, 16 cows were admitted with dystocia. The group of dystocia was subdivided into two groups; fetotomy (n=8) and caesarian (n=8) group. In the caesarian group, 4 cows were with uterine torsion. Five blood samples were collected from each cow: directly pre-partum, during and just after delivery and at, 24, 48 and 72 h post-partum. Serum samples were used for determination of aspartate amino transferase (AST), glutamate dehydrogenase (GLDH), gamma glutamyl transferase (gamma-GT), creatine phosphokinase (CK), glucose, total bilirubin, cholesterol and triglyceride. The results showed that AST, GGT, GLDH and CK activities were significantly increased in the group with caesarian sections due to uterine torsion than the control and fetotomy groups. There were insignificant changes in serum GGT and GLDH activities between control, fetotomy and dystocia group without uterine torsion at pre-partum and at 24 and 48 h post-partum. At 72 h post-partum, there was a significant increase in GLDH activity without significant increase in serum GGT activity. The concentrations of cholesterol and triglycerides did not differ in cows with dystocia compared to normal cows. In conclusion, cattle subjected to caesarian section and especially those with uterine torsion are associated with hepatic dysfunction. On the other hand, fetotomy has no effect on hepatocellular damage. The type of parturition has no effect on the bilirubin, cholesterol and triglyceride concentrations just before parturition to the 3rd day post-partum. It is recommended to supply cows with liver supportive therapy after caesarian section with uterine torsion.

Quercetin attenuates di-(2-ethylhexyl) phthalate-induced testicular toxicity in adult rats.

The aim of the present study was to investigate the potential oxidative damage of di-(2-ethylhexyl) phthalate (DEHP) in the rat testis and to further elucidate the potential modulatory effect of quercetin. DEHP was diluted in corn oil and given to rats by oral gavage at doses 0, 300, 600, and 900 mg/kg/day (groups I, III, IV, or V, respectively) for 15 consecutive days. Group VI was pretreated with quercetin (90 mg/kg), 24 h before starting the experiment and then treated with DEHP (900 mg/kg/day) for 15 consecutive days. Group II was treated with quercetin (90 mg/kg/day). The relative testes weight and sperm motility were significantly decreased by treatment with 900 mg/kg of DEHP. Both sperm count and daily sperm production were significantly decreased by DEHP treatment at doses of 600 and 900 mg/kg. Serum testosterone level and prostatic acid phosphatase (ACP) activity and testicular lactate dehydrogenase-X (LDH-X) activity were significantly decreased in animals treated with 900 mg/kg. Serum total ACP activity was significantly increased in animals treated with 600 and 900 mg/kg of DEHP. DEHP treatment induced oxidative stress and histopathological abnormality. These abnormalities were effectively normalized by pretreatment with quercetin except for LDH-X near normalcy. In conclusion, the findings of this study demonstrate that DEHP impairs testicular function at least, in part, by inducing oxidative stress and quercetin has a potent protective effect against DEHP-induced testicular toxicity in rats.

Stem cell intervention ameliorates epigallocatechin-3-gallate/lipopolysaccharide-induced hepatotoxicity in mice.

Stem cells are identified as a novel cell therapy for regenerative medicine because of their ability to differentiate into many functional cell types. We have shown earlier a new model of hepatotoxicity in mice by administering (1500 mg/kg) epigallocatechin-3-gallate (EGCG) intragastric (IG) for 5 days after a single intraperitoneal dose (6 mg/kg) of lipopolysaccharide (LPS). In this study, we aimed to study the effect of intrahepatic (IH) injection of mouse embryonic stem cells (MESCs) on the hepatotoxicity induced by EGCG/LPS in mice. Mice were administered EGCG/LPS and rested for 3 days. MESCs were obtained from American Type Culture Collection and cultured in vitro for 4 days. Stem cells were injected IH. Seven days later, a single dose of LPS (6 mg/kg) followed by daily doses of IG administration of EGCG were re-administered for 5 days. At the end of the experiment, blood samples were collected for analysis of biochemical parameters associated with liver. Results showed that the group of mice that were administered MESCs prior to EGCG/LPS showed lower levels of alanine amino transferase, alkaline phosphatase, and bilirubin, higher albumin/globulin ratio, and less remarkable histopathological lesions. Also, that group of mice showed less expression of oxidative stress biomarkers (oxidized low-density lipoprotein Ox.LDL and chemokine CXCL16), less expression of nuclear protein receptors (retinoic acid receptor and retinoid X receptor), and less expression of inflammatory biomarkers (tumor necrosis factor α and transforming growth factor ß1) compared with other groups of mice that were not given MESCs. In conclusion, MESCs can ameliorate EGCG/LPS-induced hepatotoxicity in mice.

Germ cell mutagenicity of topoisomerase I inhibitor topotecan detected in the male mouse-dominant lethal study.

To investigate the ability of topotecan, a topoisomerase I-targeting anticancer drug, to induce dominant lethal mutations in male mouse germ cells, males were treated with single doses of 3, 6 and 12 mg/kg topotecan. Each male was mated at 4-day intervals to virgin females for a total of nine 4-day mating intervals. The two highest doses of topotecan are shown to be mutagenic in post-meiotic cells. The greatest effect occurred in those cells which were in the early-spermatid stage at the time of exposure. Mice treated with 12 mg/kg topotecan showed an additional peak of dominant lethal induction in mature sperm during the first 4-day matings after treatment. The mutagenic effects were directly correlated with free radicals accumulation as an obvious increase in the generation reactive oxygen species and 8-hydroxydeoxyguanosine was noted in animals treated with 6 and 12 mg/kg topotecan. Treatment of male mice with N-acetylcysteine, a free radical scavenger, significantly protected mice from topotecan-induce dominant lethality. Moreover, N-acetylcysteine had no antagonizing effect on topotecan-induce topoisomerase-I inhibition. Our study provides evidence that topotecan is a germ cell mutagen and its effect is more pronounced during the post-meiotic stages through a mechanism that may involves increases in DNA oxidative stress.

Clinical, hematological, and biochemical findings of uterine torsion in buffaloes (Bubalus bubalis).

The aim of this study was to investigate uterine torsion in buffaloes, examine factors influencing the outcome of the disease, and to characterize the related alterations in blood constituents. A total of 126 buffaloes with uterine torsion were examined for stage of gestation, duration, degree, site and direction of torsion, as well as the location of the pregnant horn. Methods of correction were documented along with dam and calf survival. Blood samples were obtained from 20 buffaloes with uterine torsion and 10 healthy buffaloes for hematological and biochemical comparisons. Results showed that uterine torsion in buffaloes occurred in multi- (81.7%) and primiparous (18.3%), during late pregnancy (58.4%) and at full term (41.6%), clockwise (96%) and counter- clockwise (4%), at post- (98.4%) and precervical (1.6%), and was of high (52.3%), moderate (31%) and mild (16.7%) degrees. Torsion was predominantly (P=0.01) on same direction of the pregnant horn. Fetal and maternal mortalities occurred in 78.6% and 23.8% of the cases, respectively. The stage of pregnancy, and degree and duration of uterine torsion were major risk factors for fetal mortality (P=0.0001), while the stage of pregnancy and fetal viability were important risk factors for maternal mortality (P<0.05). There were significant (P<0.05) increases in monocytes, albumin, aspartate aminotransferase, creatine phosphokinase, blood urea nitrogen, and phosphorus and decreases in mean corpuscular hemoglobin concentration and globulin in the affected buffaloes. Time of occurrence and duration of torsion affected some of these parameters. Uterine torsion appears to be a serious problem in buffaloes that has certain peculiarities including time of occurrence, site and direction of torsion, and the high mortality rates. Uterine torsion adversely affects liver and kidney functions. Multiparous might be at greater risk of uterine torsion. The stage of pregnancy, as well as degree and duration of uterine torsion are risk factors for fetal and maternal mortalities.

Hesperidin attenuates benzo[alpha] pyrene-induced testicular toxicity in rats via regulation of oxidant/antioxidant balance.

Benzo[alpha]pyrene (BaP) is one of the polycyclic aromatic hydrocarbons, which has shown carcinogenic, teratogenic, and mutagenic potentials. The reproductive toxicity of BaP in male was not well investigated. Thereby, we have addressed in the current study the testicular toxicity of BaP and the postulate whether or not the citrus flavonoid, hesperidin (HDN), could ameliorate such toxicity in male Swiss albino rats. In this sense, animals were challenged with BaP (50 mg/kg/day, orally) for 10 consecutive days. HDN (200 mg/kg/day, orally) was administered ahead of BaP challenge for 10 consecutive days. BaP induced testicular toxicity that was well characterized histologically and biochemically. It decreased the relative testis weight and induced pyknosis and necrobiotic changes as well as chromatolysis in the nuclei of the spermatocytes in the seminiferous tubules. It also markedly deteriorated epididymal function as shown by decreased sperm count, motility, and daily sperm production. The polyaromatic hydrocarbon also reduced the testicular activities of lactate dehydrogenase (LDH-X), superoxide dismutase (SOD), and glutathione-S-transferase (GST). Besides, it decreased the testicular reduced glutathione (GSH) but increased malondialdehyde (MDA) contents. Prior administration of HDN ahead of BaP challenge ameliorated all the histological and biochemical alterations induced by BaP. It improved the epididymal function and mitigated the injurious effects of BaP on the seminiferous tubules. In conclusion, HDN has proven protective effects in BaP-induced testicular toxicity paradigm, and this protection resides, at least in part, on its antioxidant properties.

Nadolol-glibenclamide interaction: relevance to carbohydrate metabolism in hyperglycaemic rats.

In the present study, hyperglycaemia was induced by intraperitoneal injection of streptozotocin (65 mg/kg). Treatment with glibenclamide (GB) in a dose of 0.45 or 0.9 mg/kg significantly decreased plasma glucose level in a dose-related manner. Administration of nadolol (ND) in a dose of 5 or 10 mg/kg did not affect plasma glucose level. Combined administration of ND (10 mg/kg) with GB (0.45 or 0.9 mg/kg) potentiated the hypoglycaemic effect of GB, an effect prominent 4 hours post-treatment. In relevance to the effect of ND and GB interactions towards other aspects of carbohydrate metabolism, co-administration of the two drugs [ND (10 mg/kg) + GB (0.9 mg/kg)] failed to alter the increase in plasma insulin level and the decrease in blood pyruvate and lactate levels induced by GB alone. Concerning liver glycogen, concurrent administration of the two drugs showed a synergistic effect upon its content (257%), while it was 186% for GB treatment, and 179% for ND alone compared to the hyperglycaemic control value. The data revealed that ND potentiates the hypoglycaemic effect of GB, so it is very important to consider this potentiation when the usage of the combined drug regimens is recommended.

Influence of p-coumaric acid on doxorubicin-induced oxidative stress in rat's heart.

The therapeutic value of doxorubicin (DOX) as anticancer antibiotic is limited by its cardiotoxicity. The implication of natural phenolic acids in the prevention of many pathologic diseases has been reported. Herein, the ability of p-coumaric (PC) acid, a member of phenolic acids, to protect rat's heart against DOX-induced oxidative stress was investigated. Three main groups of albino rats were used; DOX, PC, and PC plus DOX-receiving animals. Corresponding control animals were also used. DOX was administered i.p. in a single dose of 15mgkg(-1). PC alone, in a dose of 100mgkg(-1), was orally administered for five consecutive days. In PC/DOX group, rats received PC 5 days prior to DOX. DOX-induced high serum levels of lactic dehydrogenase (LDH) and creatine phosphokinase (CPK), were reduced significantly by PC administration, compared to DOX-receiving rats. Pretreatment with PC ameliorated the cardiac content of glutathione (GSH), and superoxide dismutase (SOD) & catalase (CAT) activities, compared to DOX-receiving rats. On the other hand, accumulation of cardiac content of MDA significantly decreased following PC pretreatment, compared to DOX-treated rats. The data presented here indicate that PC protects rats hearts against DOX-induced oxidative stress in the heart. It may be worthy to consider the usefulness of PC as adjuvant therapy in cancer management.

Comparative study of the metabolism of drug substrates by human cytochrome P450 3A4 expressed in bacterial, yeast and human lymphoblastoid cells.

1. The aim was to compare the metabolic activity of human CYP3A4 expressed in bacteria (E. coli), yeast (S. cerevisiae) and human lymphoblastoid cells (hBl), with the native CYP3A4 activity observed in a panel of human livers. 2. Three CYP3A4 substrates were selected for study: dextromethorphan (DEM), midazolam (MDZ) and diazepam (DZ). The substrate metabolism in each of the four systems was characterized by deriving the kinetic parameters K(m) or S(50), V(max) and intrinsic clearance (CL(int)) or maximum clearance (CL(max)) from the kinetic profiles; the latter differing by 100-fold across the three substrates. 3. The K(m) or S(50) for the formation of metabolites 3-methoxymorphinan (MEM), 1'-hydroxymidazolam (1'-OH MDZ) and 3-hydroxydiazepam (3HDZ) compared well in all systems. For CYP3A4-mediated metabolism of DEM, MDZ and DZ, the V(max) for hBl microsomes were generally 2-9-fold higher than the respective yeast and human liver microsomes and E. coli membrane preparations, resulting in greater CL(int) or CL(max). In the case of 3HDZ formation, non-linear kinetics were observed for E. coli, hBl microsomes and human liver microsomes, whereas the kinetics observed for S. cerevisiae were linear. 4. The use of native human liver microsomes for drug metabolic studies will always be preferable. However, owing to the limited availability of human tissues, we find it is reasonable to use any of the recombinant systems described herein, since all three recombinant systems gave good predictions of the native human liver enzyme activities.